Background: Negative vector orbit is defined as the most anterior globe portion protrudes past the malar eminence. The aim of the study was to evaluate the relationship between negative vector orbit and blow-out fracture location analyzing the distance between the anterior corneal surface and orbital bone with facial soft tissue in medial and orbital floor blow out fractures using orbital computed tomography (CT). Methods: Seventy-seven patients diagnosed with blow-out fractures involving the medial or orbital floor were included. Distances from the anterior cornea to lower lid fat, inferior orbital wall, inferior orbital rim, and anterior cheek mass were measured using orbital CT scans. The proportion of negative vector orbit and measured distanced were compared between medial wall fracture and orbital floor fracture. Medical records including age, sex, concomitant ophthalmic diagnosis, and nature of injury were retrospectively reviewed. Results: Forty-three eyes from 43 patients diagnosed with medial wall fracture and 34 eyes from 34 patients diagnosed with orbital floor fracture were included. There was no significant difference in the distance from the anterior cornea to lower lid fat (P = 0.574), inferior orbital wall (P = 0.494), or orbital rim (P = 0.685). The distance from anterior cornea to anterior cheek mass was significantly different in medial wall fracture (-0.19 +/- 3.49 mm) compared with orbital floor fracture (-1.69 +/- 3.70 mm), P = 0.05. Negative vector orbit was significantly higher in orbital floor fracture patients (24 among 34 patients, 70.6%) compared with those with medial wall fractures (19 among 43 patients, 44.2%) (P = 0.04). Conclusions: Patients presenting with a negative vector orbit relationship when the most anterior portion of globe protruded past the anterior cheek mass and malar eminence were more likely to develop orbital floor fracture than medial wall fracture. (C) 2017 by Mutaz B. Habal, MD.
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Τετάρτη 13 Σεπτεμβρίου 2017
The Americleft Project: A Modification of Asher-McDade Method for Rating Nasolabial Esthetics in Patients With Unilateral Cleft Lip and Palate Using Q-sort.
The purpose of this study was to investigate ways to improve rater reliability and satisfaction in nasolabial esthetic evaluations of patients with complete unilateral cleft lip and palate (UCLP), by modifying the Asher-McDade method with use of Q-sort methodology. Blinded ratings of cropped photographs of one hundred forty-nine 5- to 7-year-old consecutively treated patients with complete UCLP from 4 different centers were used in a rating of frontal and profile nasolabial esthetic outcomes by 6 judges involved in the Americleft Project's intercenter outcome comparisons. Four judges rated in previous studies using the original Asher-McDade approach. For the Q-sort modification, rather than projection of images, each judge had cards with frontal and profile photographs of each patient and rated them on a scale of 1 to 5 for vermillion border, nasolabial frontal, and profile, using the Q-sort method with placement of cards into categories 1 to 5. Inter- and intrarater reliabilities were calculated using the Weighted Kappa (95% confidence interval). For 4 raters, the reliabilities were compared with those in previous studies. There was no significant improvement in inter-rater reliabilities using the new method. Intrarater reliability consistently improved. All raters preferred the Q-sort method with rating cards rather than a PowerPoint of photos, which improved internal consistency in rating compared to previous studies using the original Asher-McDade method. All raters preferred this method because of the ability to continuously compare photos and adjust relative ratings between patients. (C) 2017 by Mutaz B. Habal, MD.
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Does Fat Grafting Influence Postoperative Edema in Orthognathic Surgery?.
Purpose: Autologous fat grafting is a useful adjunctive procedure to orthognathic surgery and may also confer anti-inflammatory properties. The purpose of this study is to answer the clinical question: among patients undergoing orthognathic operations, what are the effects of fat grafting on facial edema (magnitude, duration, and rate of decrease)? Methods: A retrospective cohort study was performed. Three-dimensional photos (Canfield, Fairfield, NJ) from preoperative and a series of postprocedure time-points were analyzed. The data set was divided into a fat-grafted cohort and a non-fat-grafted cohort and later analyzed using paired and unpaired t tests and linear regressions to determine significant correlations. Results: One hundred sixteen pre- and postoperative three-dimensional photo data sets were included. The sample included 29 subjects. The facial volume was analyzed both overall and comparing each subgroup (orthognathic vs. orthognathic + fat grafting group). Postoperative facial volume increase averaged 23.7% for the entire cohort (FG and nFG). By week 12, the swelling decreased about 62% from baseline. In all patients, there was a statistically significant decrease in facial volume with time. In the fat-grafted group, despite adding volume, the facial volume was equal to the non-fat-grafted group at week 1, yet the rate of decrease was faster through week 12. Conclusion: The majority of postoperative facial edema decreases by 12 weeks following orthognathic surgery. In this cohort of patients, despite the addition of volume, concurrent fat grafting lessened postoperative edema, and led to a greater magnitude and speed of resolution. (C) 2017 by Mutaz B. Habal, MD.
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Partial Scalp and Auricula Avulsion in a Child.
No abstract available
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Tear Trough Deformity: Study of Filling Procedures for Its Correction.
The aim of this work is to discuss the anatomy of the tear trough region with relative danger areas, and to describe 2 different options to correct this deformity. The tear trough is a concave deformity of the orbital fat that is noticeable as a result of inherited anatomic differences and aging. However, the periorbital region is a complex area with its own septa and ligaments, fat compartments, muscles, vascularization, and lymphatic drainage and presents anatomic characteristics that must be taken into account in order to achieve good results and avoid complications. The use of hyaluronic acid gel or autologous fat for soft tissue correction is a good option. A total of 96 patients with periorbital hollowing were divided into 2 groups; each group received a different treatment, from December of 2013 to December of 2015, with hyaluronic- or lipo-filling. (C) 2017 by Mutaz B. Habal, MD.
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Stagnant Water Is Bound to Corrupt.
No abstract available
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Interobserver Consistency of Drug-Induced Sleep Endoscopy in Diagnosing Obstructive Sleep Apnea Using a VOTE Classification System.
Objectives: To explore the interobserver consistency of drug-induced sleep endoscopy (DISE) for patients with obstructive sleep apnea syndrome (OSAS) and review the current literature. Methods: In total, 55 patients with an apnea-hypopnea index >5, as determined by on overnight sleep study, were included in this study, 45 males and 10 females, with an average age of 46.87 +/- 10.06 years old (range, 19-71). For all OSAS patients, DISE was performed by the same surgeon, which was recorded digitally. The video recordings of DISE were evaluated independently by 3 experienced surgeons who were asked to note his or her decisions as the pattern, site, and degree of upper airway collapse using a VOTE (velum, oropharynx lateral wall, tongue base, and the epiglottis) classification system. Results: Interobserver consistency in the diagnosis of velum-related obstruction in anteroposterior, lateral, and concentric configurations ranged from poor to good. Only significant interobserver consistency among observers A and B was obtained in the diagnosis of oropharynx-related obstruction in the lateral configuration (concordance 60.0%, kappa: 0.365, P 0.20, all P values
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A Three-Dimensional Study of Midfacial Changes Following Le Fort II Distraction With Zygomatic Repositioning in Syndromic Patients.
Le Fort II distraction with zygomatic repositioning introduced the ability to restore central midfacial height and convexity independent of changes in orbital morphology. This study analyzes midfacial and orbital morphology before and after Le Fort II distraction with zygomatic repositioning. All patients who underwent Le Fort II Distraction with zygomatic repositioning between 2013 and 2015 were included. Two- and 3-dimensional measurements were made using 3dMD Vultus software to assess canthal tilt, nasolabial angle, ratio of midfacial to lower facial height, and absolute change in nasal length. Presence of an open bite and Angle classification were assessed before and after surgery. Four patients underwent segmental midface advancement using Le Fort II distraction with zygomatic repositioning. Associated diagnoses included Apert syndrome, Goldenhar syndrome, and achondroplasia. Changes in facial dimensions included: 3.19[degrees] improvement in canthal tilt (range -4.7[degrees] to 8.4[degrees]), 9[degrees] change in nasolabial angle (range -1.0[degrees] to 19[degrees]), and 0.69 cm increase in absolute nasal length (range 0.2-0.94 cm). Mean ratio of midfacial to lower facial height was 0.79 preoperatively and 0.89 postoperatively. Preoperatively, all patients demonstrated Angle class III with 3 of 4 patients demonstrating anterior open bite. All achieved closure of open bite and demonstrated class I or II occlusion. No complications were observed. Le Fort II distraction with zygomatic repositioning resulted in normalization of midfacial soft tissue landmarks. This form of advancement demonstrates the ability to selectively improve midfacial height and canthal tilt while restoring normal occlusion. (C) 2017 by Mutaz B. Habal, MD.
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Tissue Engineering Strategies for Auricular Reconstruction.
Simulating natural characteristics and aesthetics in reconstructed ears has provided a complex 3-dimensional puzzle for those treating patients with microtia. Costochondral grafts remain the gold standard for autologous reconstruction. However, other options such as Medpor and prosthetics are indicated depending on patient circumstances and personal choice. Research into tissue engineering offers an alternative method to a traditional surgical approach that may reduce donor-site morbidity. However, tissue engineering for microtia reconstruction brings new challenges such as cell sourcing, promotion of chondrogenesis, scaffold vascularization, and prevention of scaffold contraction. Advancements in 3D printing, nanofiber utilization, stem cell technologies, and decellularization techniques have played significant roles in overcoming these challenges. These recent advancements and reports of a successful clinical-scale study in an immunocompetent animal suggest a promising outlook for future clinical application of tissue engineering for auricular reconstruction. (C) 2017 by Mutaz B. Habal, MD.
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Malrotation with midgut volvulus and bowel gangrene in a 45-year-old man
Stephen Akau Kache, Danjuma Sale, Nuhu Yusuf, Jerry Godfrey Makama
Archives of Medicine and Surgery 2017 2(1):29-31
Midgut volvulus due to intestinal malrotation is a rare occurrence in adult life. Malrotation is a congenital, developmental anomaly that results from an arrest of the physiological rotation of the gut through 270°. It is often thought that complications due to it, present themselves early during childhood and rarely occur among adults. However, a few cases have occurred and have been reported among adults. When it does occur in adults, it is often associated with catastrophic consequences. We present the case of a 45-year-old man with malrotation resulting in midgut volvulus. Our patient is a 45-year-old man, who presented with sudden onset of colicky abdominal pain and abdominal swelling of 24 h duration. He had been having recurrent abdominal pain since childhood. Physical examination revealed a patient in shock with markedly distended abdomen and anterior abdominal wall edema. Plain abdominal X-ray showed multiple air-fluid levels with thickened bowel outline. A diagnosis of intestinal obstruction was made. The patient was fully resuscitated and planned for emergency exploratory laparotomy under general anesthesia. Intraoperative findings revealed a 360° clockwise rotation of the small bowel around the mesenteric pedicle of the superior mesenteric artery and vein including about 350 cm of bowel gangrene. Resection and anastomosis were done. The early postoperative period was uneventful. However, he had anastomotic dehiscence on the 5th postoperative day and had to be reoperated but sadly he died 24 h later due to complications of anesthesia. Nonspecific recurrent abdominal complaints in adults of any age should raise suspicion of the possibility of a midgut malrotation or malfixation with or without intermittent volvulus. This case highlights the importance of early diagnosis and treatment.
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Archives of Medicine and Surgery 2017 2(1):29-31
Midgut volvulus due to intestinal malrotation is a rare occurrence in adult life. Malrotation is a congenital, developmental anomaly that results from an arrest of the physiological rotation of the gut through 270°. It is often thought that complications due to it, present themselves early during childhood and rarely occur among adults. However, a few cases have occurred and have been reported among adults. When it does occur in adults, it is often associated with catastrophic consequences. We present the case of a 45-year-old man with malrotation resulting in midgut volvulus. Our patient is a 45-year-old man, who presented with sudden onset of colicky abdominal pain and abdominal swelling of 24 h duration. He had been having recurrent abdominal pain since childhood. Physical examination revealed a patient in shock with markedly distended abdomen and anterior abdominal wall edema. Plain abdominal X-ray showed multiple air-fluid levels with thickened bowel outline. A diagnosis of intestinal obstruction was made. The patient was fully resuscitated and planned for emergency exploratory laparotomy under general anesthesia. Intraoperative findings revealed a 360° clockwise rotation of the small bowel around the mesenteric pedicle of the superior mesenteric artery and vein including about 350 cm of bowel gangrene. Resection and anastomosis were done. The early postoperative period was uneventful. However, he had anastomotic dehiscence on the 5th postoperative day and had to be reoperated but sadly he died 24 h later due to complications of anesthesia. Nonspecific recurrent abdominal complaints in adults of any age should raise suspicion of the possibility of a midgut malrotation or malfixation with or without intermittent volvulus. This case highlights the importance of early diagnosis and treatment.
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Prevalence of obesity and outcome of weight loss on reproduction: A study among women attending infertility clinic in Zaria, Northern Nigeria
Yakubu Aliyu, Adebiyi Gbadebo Adesiyun, Solomon Avidime, Abdullahi Jibril Randawa
Archives of Medicine and Surgery 2017 2(1):3-6
Objective: Obesity is rising in the developing countries because of changing life style, and this has its burden on fertility and its management. This study determined the prevalence of obesity and clinical correlation of obesity with menstrual abnormalities, as well as the rate of spontaneous conception among obese infertile women on nonsurgical weight loss therapy. Methodology: A cross-sectional longitudinal study was done among women that presented with infertility to the gynecology clinic. The main outcomes measured were percentage of infertile women that are obese, menstrual pattern of these women, and spontaneous conception among obese infertile women following weight loss therapy. Results: Of the 205 patients, 68 (33.2%) were found to be obese; there was a significant association between obesity and abnormal menstrual pattern (P = 0.0002). Oligomenorrhea and hypomenorrhea were also found to be significantly associated with obesity (P = 0.009 and P = 0.022, respectively). Following average of 12-month follow up, spontaneous conception among obese infertile women while on weight loss therapy was 21.1%. Conclusion: The prevalence of obesity was high with a significant association between obesity and menstrual abnormalities. Weight loss among obese infertile women led to improvement in spontaneous conception.
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Archives of Medicine and Surgery 2017 2(1):3-6
Objective: Obesity is rising in the developing countries because of changing life style, and this has its burden on fertility and its management. This study determined the prevalence of obesity and clinical correlation of obesity with menstrual abnormalities, as well as the rate of spontaneous conception among obese infertile women on nonsurgical weight loss therapy. Methodology: A cross-sectional longitudinal study was done among women that presented with infertility to the gynecology clinic. The main outcomes measured were percentage of infertile women that are obese, menstrual pattern of these women, and spontaneous conception among obese infertile women following weight loss therapy. Results: Of the 205 patients, 68 (33.2%) were found to be obese; there was a significant association between obesity and abnormal menstrual pattern (P = 0.0002). Oligomenorrhea and hypomenorrhea were also found to be significantly associated with obesity (P = 0.009 and P = 0.022, respectively). Following average of 12-month follow up, spontaneous conception among obese infertile women while on weight loss therapy was 21.1%. Conclusion: The prevalence of obesity was high with a significant association between obesity and menstrual abnormalities. Weight loss among obese infertile women led to improvement in spontaneous conception.
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Does implementation of preanesthesia assessment clinics improve surgical patients care in Nigeria?
Saidu Yusuf Yakubu
Archives of Medicine and Surgery 2017 2(1):20-23
Introduction: Preanesthesia assessment of patients is a major component of the perioperative care of surgical patients. The benefits of outpatient preoperative assessment clinics (PAC) were recognized over 67 years ago. However, these clinics are not used in Nigeria as part of surgical care. Search of the literature did not reveal any hospital in Nigeria that operates PAC, and therefore, its implementation in this country is still in process. This may not be unconnected with scarce financial, material, and human resources. Materials and Methods: This study was a questionnaire survey of the views of anesthetists, surgeons, and hospital administrators in some Nigerian Federal Teaching Hospitals on the usefulness and limitations of PAC. Structured questionnaires were sent to surgeons, anesthetists and Chairmen, Medical Advisory Committees in the selected Hospitalsand the results were analyzed. Results: Respondents indicated the benefits of preanesthesia assessment clinics as decrease in the incidence of surgery delays and cancelations, shorter lengths of hospital stay, improvement in the logistics of preoperative preparation, improved patient knowledge of anesthesia, and preoperative care as well as the role of the anesthetist in surgical care. Limiting factors to successful preanesthesia clinics were lack of cooperation from anesthetists and surgeons, other medical specialists, lack of supporting staff, finance, and appropriate office space. Conclusions: Preanesthesia assessment clinic increases the overall efficiency of the period of stay of the surgical patient in the hospital. Its benefits outweigh its disadvantages, and its successful implementation requires effort, time, money, and close collaboration with hospital administrators.
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Archives of Medicine and Surgery 2017 2(1):20-23
Introduction: Preanesthesia assessment of patients is a major component of the perioperative care of surgical patients. The benefits of outpatient preoperative assessment clinics (PAC) were recognized over 67 years ago. However, these clinics are not used in Nigeria as part of surgical care. Search of the literature did not reveal any hospital in Nigeria that operates PAC, and therefore, its implementation in this country is still in process. This may not be unconnected with scarce financial, material, and human resources. Materials and Methods: This study was a questionnaire survey of the views of anesthetists, surgeons, and hospital administrators in some Nigerian Federal Teaching Hospitals on the usefulness and limitations of PAC. Structured questionnaires were sent to surgeons, anesthetists and Chairmen, Medical Advisory Committees in the selected Hospitalsand the results were analyzed. Results: Respondents indicated the benefits of preanesthesia assessment clinics as decrease in the incidence of surgery delays and cancelations, shorter lengths of hospital stay, improvement in the logistics of preoperative preparation, improved patient knowledge of anesthesia, and preoperative care as well as the role of the anesthetist in surgical care. Limiting factors to successful preanesthesia clinics were lack of cooperation from anesthetists and surgeons, other medical specialists, lack of supporting staff, finance, and appropriate office space. Conclusions: Preanesthesia assessment clinic increases the overall efficiency of the period of stay of the surgical patient in the hospital. Its benefits outweigh its disadvantages, and its successful implementation requires effort, time, money, and close collaboration with hospital administrators.
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Is 5 IU bolus of oxytocin as effective as 10 IU bolus for control of bleeding during cesarean section under spinal anesthesia?
Musa M Yusuf, Elizabeth Ogboli Nwasor, Rabiu I Mohammed
Archives of Medicine and Surgery 2017 2(1):7-11
Aim and Objectives: We sought to compare the hemodynamic effects of 5 international unit (IU) and 10 IU of intravenous (IV) boluses of oxytocin and their efficacy in reducing blood loss during cesarean section and also to determine the incidence of postoperative nausea and vomiting (PONV) and postdural puncture headache (PDPH). Patients and Methods: One hundred and ten parturients of American Society of Anesthesiologists' I and II scheduled for cesarean section under spinal anesthesia were randomized into two groups. Group A (n = 55) received 5 IU IV bolus of oxytocin and Group B (n = 55) received 10 IU IV bolus of oxytocin after delivery. Ten milliliters per kilogram of 0.9% saline was administered to both groups as volume preload. Subarachnoid block was performed with size 24G spinal needles at L2/L3 or L3/L4 intervertebral space with the patients in sitting position. Two milliliters of 0.5% heavy bupivacaine was administered slowly intrathecally. Following delivery of the baby, IV boluses of 5 IU (Group A) or 10 IU (Group B) of oxytocin were administered slowly, and recording of heart rate, systolic, diastolic, and mean arterial blood pressure was done every minute for 5 min after bolus injection. IV infusion of 30 IU of oxytocin in 500 ml of 0.9% saline (60 mU/ml) at a rate of 125 ml/h was continued in both groups till the end of surgery. Estimated blood loss (EBL) was assessed by visual estimation. Patients were monitored continuously until 24 h after surgery to evaluate PDPH and PONV. Results: There were no statistically significant differences in the EBL between the two groups. There was no significant rise in heart rate and no significant decrease in mean arterial blood pressure in Group A compared to Group B. The incidence of PDPH and PONV was also comparable in both groups. Conclusion: Five IU of IV bolus of oxytocin is as effective as 10 IU of IV bolus in reducing blood loss during cesarean section.
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Archives of Medicine and Surgery 2017 2(1):7-11
Aim and Objectives: We sought to compare the hemodynamic effects of 5 international unit (IU) and 10 IU of intravenous (IV) boluses of oxytocin and their efficacy in reducing blood loss during cesarean section and also to determine the incidence of postoperative nausea and vomiting (PONV) and postdural puncture headache (PDPH). Patients and Methods: One hundred and ten parturients of American Society of Anesthesiologists' I and II scheduled for cesarean section under spinal anesthesia were randomized into two groups. Group A (n = 55) received 5 IU IV bolus of oxytocin and Group B (n = 55) received 10 IU IV bolus of oxytocin after delivery. Ten milliliters per kilogram of 0.9% saline was administered to both groups as volume preload. Subarachnoid block was performed with size 24G spinal needles at L2/L3 or L3/L4 intervertebral space with the patients in sitting position. Two milliliters of 0.5% heavy bupivacaine was administered slowly intrathecally. Following delivery of the baby, IV boluses of 5 IU (Group A) or 10 IU (Group B) of oxytocin were administered slowly, and recording of heart rate, systolic, diastolic, and mean arterial blood pressure was done every minute for 5 min after bolus injection. IV infusion of 30 IU of oxytocin in 500 ml of 0.9% saline (60 mU/ml) at a rate of 125 ml/h was continued in both groups till the end of surgery. Estimated blood loss (EBL) was assessed by visual estimation. Patients were monitored continuously until 24 h after surgery to evaluate PDPH and PONV. Results: There were no statistically significant differences in the EBL between the two groups. There was no significant rise in heart rate and no significant decrease in mean arterial blood pressure in Group A compared to Group B. The incidence of PDPH and PONV was also comparable in both groups. Conclusion: Five IU of IV bolus of oxytocin is as effective as 10 IU of IV bolus in reducing blood loss during cesarean section.
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Is acute appendicitis still the most common abdominal surgical emergency
Jerry Godfrey Makama
Archives of Medicine and Surgery 2017 2(1):1-2
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Archives of Medicine and Surgery 2017 2(1):1-2
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Serostatus disclosure to sexual partner by human immunodeficiency virus-positive clients receiving antiretroviral therapy in a tertiary health facility in Northwest Nigeria
Sulaiman Saidu Bashir, Muhammed S Ibrahim, Matthias O Ekpenukpang, Samira G Ahmed
Archives of Medicine and Surgery 2017 2(1):24-28
Background: Disclosure of human immunodeficiency virus (HIV)-positive status to sexual partner is crucial and helpful for treatment adherence, HIV transmission reduction, PMTCT interventions, partner testing and acceptance of referrals for HIV-related care, treatment and support. This study assessed the awareness, practices as well as factors associated with serostatus disclosure among HIV positive clients receiving anti-retroviral treatment in a tertiary health facility in northwest Nigeria. Methodology: A cross-sectional study was conducted among 129 HIV positive clients receiving anti-retroviral therapy selected using a systematic random sampling technique. Data were collected using a structured interviewer-administered questionnaire containing open- and close-ended questions, and analyzed using SPSS Statistics version 21.0. Result: The mean age of respondents was 38.0 ± 10.6 years and most (89.9%) of the respondents were on antiretroviral therapy for more than one year. Majority of the respondents have a positive attitude to serostatus disclosure (67.4%) and have disclosed their serostatus to their partner (79.8%), but only 57.3% did so within one month of knowing their serostatus. Their main reason for disclosure were concern for partner's health (74.6%) while partners' reactions were supportive in 35% and understanding in 21.4% of respondents. Disclosure was high among those currently married (odds ratio = 0.075 96% confidence interval: 0.0230-0.237, P = 0.001) but there was no statistically significant association between disclosure and age, gender, religion, educational status and average monthly income. Conclusion: This study found a good partner disclosure rate of HIV serostatus among PLWHA receiving treatment at Nasara Clinic, ABUTH, and client's marital status as currently married was a significant factor that influenced disclosure rate.
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Archives of Medicine and Surgery 2017 2(1):24-28
Background: Disclosure of human immunodeficiency virus (HIV)-positive status to sexual partner is crucial and helpful for treatment adherence, HIV transmission reduction, PMTCT interventions, partner testing and acceptance of referrals for HIV-related care, treatment and support. This study assessed the awareness, practices as well as factors associated with serostatus disclosure among HIV positive clients receiving anti-retroviral treatment in a tertiary health facility in northwest Nigeria. Methodology: A cross-sectional study was conducted among 129 HIV positive clients receiving anti-retroviral therapy selected using a systematic random sampling technique. Data were collected using a structured interviewer-administered questionnaire containing open- and close-ended questions, and analyzed using SPSS Statistics version 21.0. Result: The mean age of respondents was 38.0 ± 10.6 years and most (89.9%) of the respondents were on antiretroviral therapy for more than one year. Majority of the respondents have a positive attitude to serostatus disclosure (67.4%) and have disclosed their serostatus to their partner (79.8%), but only 57.3% did so within one month of knowing their serostatus. Their main reason for disclosure were concern for partner's health (74.6%) while partners' reactions were supportive in 35% and understanding in 21.4% of respondents. Disclosure was high among those currently married (odds ratio = 0.075 96% confidence interval: 0.0230-0.237, P = 0.001) but there was no statistically significant association between disclosure and age, gender, religion, educational status and average monthly income. Conclusion: This study found a good partner disclosure rate of HIV serostatus among PLWHA receiving treatment at Nasara Clinic, ABUTH, and client's marital status as currently married was a significant factor that influenced disclosure rate.
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Epulis presenting as congenital multiple polypoidal oral mass lesion: A surprising case report
Himanshu Shukla, Chaturbhuj Ramanand Agrawal, Chandra Sarat, Dharma Ram
Archives of Medicine and Surgery 2017 2(1):32-34
A newborn infant with congenital epulis (CE) can be a striking miserable sight for both parents and health care professionals involved in neonatal care. These tumours of the infant mouth can be remarkably large, occupying much of the oral cavity and posing a risk of airway obstruction or interfering with feeding with marked facial deformity. Neumann first described congenital epulis of newborn in 1871. It is most frequently located on the anterior maxillary alveolar ridge with slight female predilection. It clinically appears as a pedunculated protuberant mass. In cases with large lesions, mechanical oral and nasal obstruction can impair fetal deglutition and neonatal respiratory efforts resulting in polyhydramnios prenatally or respiratory impairment postnatally. Histologically Congenital epulis shows characteristic large cells with granular cytoplasm and spindle cells resembling fibroblasts. The exact histogenesis is still uncertain, various theories of origin are epithelial, undifferentiated mesenchymal cells, pericytes, fibroblast, smooth muscle cells and nerve related cells. Herein we report a newborn female child with Multiple Congenital epulis arising from maxilla and mandible with investigation, management and follow-up.
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Archives of Medicine and Surgery 2017 2(1):32-34
A newborn infant with congenital epulis (CE) can be a striking miserable sight for both parents and health care professionals involved in neonatal care. These tumours of the infant mouth can be remarkably large, occupying much of the oral cavity and posing a risk of airway obstruction or interfering with feeding with marked facial deformity. Neumann first described congenital epulis of newborn in 1871. It is most frequently located on the anterior maxillary alveolar ridge with slight female predilection. It clinically appears as a pedunculated protuberant mass. In cases with large lesions, mechanical oral and nasal obstruction can impair fetal deglutition and neonatal respiratory efforts resulting in polyhydramnios prenatally or respiratory impairment postnatally. Histologically Congenital epulis shows characteristic large cells with granular cytoplasm and spindle cells resembling fibroblasts. The exact histogenesis is still uncertain, various theories of origin are epithelial, undifferentiated mesenchymal cells, pericytes, fibroblast, smooth muscle cells and nerve related cells. Herein we report a newborn female child with Multiple Congenital epulis arising from maxilla and mandible with investigation, management and follow-up.
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Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit?
Mohsen Goharinia, Athar Zareei, Mansour Rahimi, Hossein Mirkhani
Research in Pharmaceutical Sciences 2017 12(5):401-408
Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg.day), (4) diabetic + benzbromarone (10 mg/kg.day). Drugs were administered daily and orally from the day after diabetes induction for eight weeks. Thereafter retinal function and structure were evaluated by electroretinography and microscopic studies. Uric acid and oxidative stress biomarkers were measured biochemically. Diabetes significantly increased plasma uric acid and oxidative stress markers and reduced body weight and amplitude of electroretinogram (ERG) b-wave and oscillatory potentials. Treatment of diabetic rats with allopurinol caused a significant increase in the amplitude of ERG b-wave (87%) and decrease in blood sugar (20%), uric acid (49%), and 8-iso-prostaglandin F2a (56%), but had no effect on the number of retinal ganglionic cells and oscillatory potentials. Benzbromarone showed no significant effects on the considered parameters except the reduction of uric acid. Allopurinol improved the b-wave amplitude of diabetic rats. It seems that this beneficial effect is due to the reduction of oxidative stress rather than its effect on plasma uric acid.
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Research in Pharmaceutical Sciences 2017 12(5):401-408
Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg.day), (4) diabetic + benzbromarone (10 mg/kg.day). Drugs were administered daily and orally from the day after diabetes induction for eight weeks. Thereafter retinal function and structure were evaluated by electroretinography and microscopic studies. Uric acid and oxidative stress biomarkers were measured biochemically. Diabetes significantly increased plasma uric acid and oxidative stress markers and reduced body weight and amplitude of electroretinogram (ERG) b-wave and oscillatory potentials. Treatment of diabetic rats with allopurinol caused a significant increase in the amplitude of ERG b-wave (87%) and decrease in blood sugar (20%), uric acid (49%), and 8-iso-prostaglandin F2a (56%), but had no effect on the number of retinal ganglionic cells and oscillatory potentials. Benzbromarone showed no significant effects on the considered parameters except the reduction of uric acid. Allopurinol improved the b-wave amplitude of diabetic rats. It seems that this beneficial effect is due to the reduction of oxidative stress rather than its effect on plasma uric acid.
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Factors affecting liposomes particle size prepared by ethanol injection method
Sherif Shaker, Ahmed Rifaat Gardouh, Mamdouh Mostafa Ghorab
Research in Pharmaceutical Sciences 2017 12(5):346-352
Ethanol injection is one of the techniques frequently used to produce liposomes which favors both simplicity and safety. In this process, an ethanolic solution of lipids is rapidly injected into an aqueous medium through a needle, dispersing the phospholipids throughout the medium and promoting the vesicle formation. Being a critical parameter that determines the fate of liposome and its distribution, we studied different factors affecting the particle size of liposomes including different phospholipid (Phosal® 53 MCT) and cholesterol concentrations and the use of different types of non-ionic surfactants at fixed Phosal® 53 MCT concentration of 50 mg per formulation. Both Phosal® 53 MCT and cholesterol concentration had direct effect on liposomes particle size. Non-ionic surfactants produced liposomes of smaller particle size when compared to conventional liposomes formed using Phosal® 53 MCT 300 mg per formulation only, whereas this effect was diminished when higher Phosal® 53 MCT to cholesterol ratios were used that obviously increased liposomes size. Smaller liposomes sizes were obtained upon using non-ionic surfactants of lower hydrophilic/hydrophobic balance (HLB) as both Tween 80 and Cremophor RH 40 produced liposomes of smaller particle size compared to Poloxamer 407. The smallest liposomes particle size was successfully obtained in the formulation comprising 300 mg Phosal® MCT, 150 mg cholesterol and 50 mg Tween 80.
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Research in Pharmaceutical Sciences 2017 12(5):346-352
Ethanol injection is one of the techniques frequently used to produce liposomes which favors both simplicity and safety. In this process, an ethanolic solution of lipids is rapidly injected into an aqueous medium through a needle, dispersing the phospholipids throughout the medium and promoting the vesicle formation. Being a critical parameter that determines the fate of liposome and its distribution, we studied different factors affecting the particle size of liposomes including different phospholipid (Phosal® 53 MCT) and cholesterol concentrations and the use of different types of non-ionic surfactants at fixed Phosal® 53 MCT concentration of 50 mg per formulation. Both Phosal® 53 MCT and cholesterol concentration had direct effect on liposomes particle size. Non-ionic surfactants produced liposomes of smaller particle size when compared to conventional liposomes formed using Phosal® 53 MCT 300 mg per formulation only, whereas this effect was diminished when higher Phosal® 53 MCT to cholesterol ratios were used that obviously increased liposomes size. Smaller liposomes sizes were obtained upon using non-ionic surfactants of lower hydrophilic/hydrophobic balance (HLB) as both Tween 80 and Cremophor RH 40 produced liposomes of smaller particle size compared to Poloxamer 407. The smallest liposomes particle size was successfully obtained in the formulation comprising 300 mg Phosal® MCT, 150 mg cholesterol and 50 mg Tween 80.
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Facile one-pot four-component synthesis of 3,4-dihydro-2-pyridone derivatives: Novel urease inhibitor scaffold
Arash Modarres Hakimi, Negar Lashgari, Shabnam Mahernia, Ghodsi Mohammadi Ziarani, Massoud Amanlou
Research in Pharmaceutical Sciences 2017 12(5):353-363
In the current study, a series of 3,4-dihydro-2-pyridone derivatives were synthesized in a one-pot four- component reaction of Meldrum's acid, benzaldehyde derivatives, methyl acetoacetate, and ammonium acetate. SiO2-Pr-SO3H was used as an efficient catalyst for the synthesis of the target compounds under solvent-free conditions. The most probable mechanism for this reaction has been discussed. The advantages of this methodology are high product yields, being environmentally benign, short reaction times, and easy handling. Eight 2-pyridinone derivatives were evaluated for their inhibitory activities against Jack bean urease. Molecular docking study of the synthesized compounds was also evaluated. All compounds showed good activities against urease and among them, 4-(4-nitrophenyl)-5-methoxycarbonyl-6-methyl-3,4- dihydropyridone (5a) showed the most potent activity (IC50 = 29.12 µM), more potent than hydroxyurea as the reference drug (IC50 = 100.0 µM). Also, the results from docking studies were in good agreement with those obtained with in vitro assay. According to the docking studies methionine (Met) 637 and nitro phenyl ring cause n-π interaction between lone pair of sulfur atom and π aromatic ring. Moreover, hydrophobic interactions existed between compound 5a and alanine (ALA) 636, ALA 440, and isoleucine 411. The results indicated that the inhibitory activities increased with the increase of electron withdrawing ability of the groups despite a less important role of lipophilicity in increasing the inhibitory activity.
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Research in Pharmaceutical Sciences 2017 12(5):353-363
In the current study, a series of 3,4-dihydro-2-pyridone derivatives were synthesized in a one-pot four- component reaction of Meldrum's acid, benzaldehyde derivatives, methyl acetoacetate, and ammonium acetate. SiO2-Pr-SO3H was used as an efficient catalyst for the synthesis of the target compounds under solvent-free conditions. The most probable mechanism for this reaction has been discussed. The advantages of this methodology are high product yields, being environmentally benign, short reaction times, and easy handling. Eight 2-pyridinone derivatives were evaluated for their inhibitory activities against Jack bean urease. Molecular docking study of the synthesized compounds was also evaluated. All compounds showed good activities against urease and among them, 4-(4-nitrophenyl)-5-methoxycarbonyl-6-methyl-3,4- dihydropyridone (5a) showed the most potent activity (IC50 = 29.12 µM), more potent than hydroxyurea as the reference drug (IC50 = 100.0 µM). Also, the results from docking studies were in good agreement with those obtained with in vitro assay. According to the docking studies methionine (Met) 637 and nitro phenyl ring cause n-π interaction between lone pair of sulfur atom and π aromatic ring. Moreover, hydrophobic interactions existed between compound 5a and alanine (ALA) 636, ALA 440, and isoleucine 411. The results indicated that the inhibitory activities increased with the increase of electron withdrawing ability of the groups despite a less important role of lipophilicity in increasing the inhibitory activity.
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Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice
Akram Ahangarpour, Hamid Heidari, Majid Salehizade Junghani, Reza Absari, Mehdi Khoogar, Ehsan Ghaedi
Research in Pharmaceutical Sciences 2017 12(5):416-424
Type 2 diabetes often leads to dislipidemia and abnormal activity of hepatic enzymes. The purpose of this study was to evaluate the antidiabetic and hypolipidemic properties of Rhus coriaria (R. coriaria) seed extrac on nicotinamide-streptozotocin induced type 2 diabetic mice. In this experimental study, 56 male Naval Medical Research Institute mice (30-35 g) were randomly separated into seven groups: control, diabetic group, diabetic mice treated with glibenclamide (0.25 mg/kg, as standard antidiabetic drug) or R. coriaria seed extract in doses of 200 and 300 mg/kg, and control groups received these two doses of extract orally for 28 days. Induction of diabetes was done by intraperitoneal injection of nicotinamide and streptozotocin. Ultimately, body weight of mice, blood levels of glucose, insulin, hepatic enzymes, leptin, and lipid profile were assayed. After induction of type 2 diabetes, level of glucose, cholesterol, low density lipoprotein, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase increased and level of insulin and high density lipoprotein decreased remarkably. Administration of both doses of extract decreased level of glucose and cholesterol significantly in diabetic mice. LDL level decreased in treated group with dose of 300 mg/kg of the extract. Although usage of the extract improved level of other lipid profiles, insulin and hepatic enzymes, changes weren't significant. This study showed R. coriaria seeds administration has a favorable effect in controlling some blood parameters in type 2 diabetes. Therefore it may be beneficial in the treatment of diabetes.
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Research in Pharmaceutical Sciences 2017 12(5):416-424
Type 2 diabetes often leads to dislipidemia and abnormal activity of hepatic enzymes. The purpose of this study was to evaluate the antidiabetic and hypolipidemic properties of Rhus coriaria (R. coriaria) seed extrac on nicotinamide-streptozotocin induced type 2 diabetic mice. In this experimental study, 56 male Naval Medical Research Institute mice (30-35 g) were randomly separated into seven groups: control, diabetic group, diabetic mice treated with glibenclamide (0.25 mg/kg, as standard antidiabetic drug) or R. coriaria seed extract in doses of 200 and 300 mg/kg, and control groups received these two doses of extract orally for 28 days. Induction of diabetes was done by intraperitoneal injection of nicotinamide and streptozotocin. Ultimately, body weight of mice, blood levels of glucose, insulin, hepatic enzymes, leptin, and lipid profile were assayed. After induction of type 2 diabetes, level of glucose, cholesterol, low density lipoprotein, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase increased and level of insulin and high density lipoprotein decreased remarkably. Administration of both doses of extract decreased level of glucose and cholesterol significantly in diabetic mice. LDL level decreased in treated group with dose of 300 mg/kg of the extract. Although usage of the extract improved level of other lipid profiles, insulin and hepatic enzymes, changes weren't significant. This study showed R. coriaria seeds administration has a favorable effect in controlling some blood parameters in type 2 diabetes. Therefore it may be beneficial in the treatment of diabetes.
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The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line
Rita Arabsolghar, Jamileh Saberzadeh, Forouzan Khodaei, Rozhin Abbasi Borojeni, Marjan Khorsand, Marzieh Rashedinia
Research in Pharmaceutical Sciences 2017 12(5):391-400
Sodium benzoate (SB) is one of the food additives and preservatives that prevent the growth of fungi and bacteria. SB has been shown to improve the symptoms of neurodegenerative disease such as Alzheimer's disease. The aim of this study was to evaluate the effect of SB on the cell survival and cellular antioxidant indices after exposure to aluminum maltolate (Almal) in PC12 cell line as a model of neurotoxicity. The cells exposed to different concentrations of SB (0.125 to 3 mg/mL) in the presence of Almal (500 µM) and cell viability, the level of reactive oxygen species (ROS), glutathione content and catalase activity were measured. The results showed that low concentrations of SB caused an increase in the cell survival, but cell viability was reduced in high concentrations. SB could neither prevent the level of ROS production nor change glutathione content. SB (0.5 mg/mL) significantly increased the catalase enzyme activity as compared to the Almal. This study suggested that SB did not completely protect the cell to aluminum- induced free radicals toxicity. Possibly SB improves the symptoms of neurodegenerative disease by other mechanisms.
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Research in Pharmaceutical Sciences 2017 12(5):391-400
Sodium benzoate (SB) is one of the food additives and preservatives that prevent the growth of fungi and bacteria. SB has been shown to improve the symptoms of neurodegenerative disease such as Alzheimer's disease. The aim of this study was to evaluate the effect of SB on the cell survival and cellular antioxidant indices after exposure to aluminum maltolate (Almal) in PC12 cell line as a model of neurotoxicity. The cells exposed to different concentrations of SB (0.125 to 3 mg/mL) in the presence of Almal (500 µM) and cell viability, the level of reactive oxygen species (ROS), glutathione content and catalase activity were measured. The results showed that low concentrations of SB caused an increase in the cell survival, but cell viability was reduced in high concentrations. SB could neither prevent the level of ROS production nor change glutathione content. SB (0.5 mg/mL) significantly increased the catalase enzyme activity as compared to the Almal. This study suggested that SB did not completely protect the cell to aluminum- induced free radicals toxicity. Possibly SB improves the symptoms of neurodegenerative disease by other mechanisms.
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Isolation of bacteriophages against multidrug resistant Acinetobacter baumannii
Hasan Ghajavand, Bahram Nasr Esfahani, Asghar Havaei, Hossein Fazeli, Reyhaneh Jafari, Sharareh Moghim
Research in Pharmaceutical Sciences 2017 12(5):373-380
Increasing multiple drug resistant (MDR) strains of Acinetobacter baumannii has aggravated curiosity in development of alternative therapy. Bacteriophages are often considered as alternative agents for controlling A. baumannii infections. In the present study two lytic phages for MDR A. baumannii were isolated and their efficacy and host ranges were evaluated. The phages were isolated from hospital wastewater. Electron microscopy revealed that IsfAB78 might belong to Myoviridae and IsfAB39 to Podoviridae. Initial characterization of phages showed that they have narrow host range and failed to infect relative and non- relative bacteria. Both phages decreased the A. baumannii turbidity significantly, indicating that these isolated phages may be considered as candidates for phage therapy.
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Research in Pharmaceutical Sciences 2017 12(5):373-380
Increasing multiple drug resistant (MDR) strains of Acinetobacter baumannii has aggravated curiosity in development of alternative therapy. Bacteriophages are often considered as alternative agents for controlling A. baumannii infections. In the present study two lytic phages for MDR A. baumannii were isolated and their efficacy and host ranges were evaluated. The phages were isolated from hospital wastewater. Electron microscopy revealed that IsfAB78 might belong to Myoviridae and IsfAB39 to Podoviridae. Initial characterization of phages showed that they have narrow host range and failed to infect relative and non- relative bacteria. Both phages decreased the A. baumannii turbidity significantly, indicating that these isolated phages may be considered as candidates for phage therapy.
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Improvement of citral antimicrobial activity by incorporation into nanostructured lipid carriers: A potential application in food stuffs as a natural preservative
Manijeh Mokarizadeh, Hossein Samadi Kafil, Saeed Ghanbarzadeh, Ainaz Alizadeh, Hamed Hamishehkar
Research in Pharmaceutical Sciences 2017 12(5):409-415
At the present time, utilization of essential oils in food preservation to prevent bacterial and fungal growth and improve shelf life and safety of the food products has notably gained increased interest. The aim of the present study was to improve the antimicrobial efficacy of citral as a natural preservative using nanostructured lipid carriers (NLCs). Formulations of NLCs were characterized using particle size analysis and scanning electron microscopy methods. Possible citral-carrier interaction and citral encapsulation efficiency percent (EE%) were assessed by Fourier transform infrared (FTIR) spectroscopy and gas chromatography techniques, respectively. Antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of citral-loaded NLCs were evaluated and compared with the conventional citral emulsion against various gram-positive bacteria (Staphylococcus aureus, Bacillus cereus), gram-negative bacteria (Escherichia coli), and fungi (Candida albicans). Citral-loaded NLCs were spherically shaped nanosized (74.8 nm) particles with narrow size distribution, high EE% (99.84%), and appropriate physical stability during 90 days of storage period. FTIR spectra indicated the interaction between citral and formulation ingredients, which justified the obtained high EE% value. The MIC and MBC values of citral-loaded NLCs were lower than those of citral emulsion for all microorganisms. NLCs formulation showed remarkable capability of encapsulating essential oil and increasing antimicrobial properties to offer effective preservation in food industry.
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Research in Pharmaceutical Sciences 2017 12(5):409-415
At the present time, utilization of essential oils in food preservation to prevent bacterial and fungal growth and improve shelf life and safety of the food products has notably gained increased interest. The aim of the present study was to improve the antimicrobial efficacy of citral as a natural preservative using nanostructured lipid carriers (NLCs). Formulations of NLCs were characterized using particle size analysis and scanning electron microscopy methods. Possible citral-carrier interaction and citral encapsulation efficiency percent (EE%) were assessed by Fourier transform infrared (FTIR) spectroscopy and gas chromatography techniques, respectively. Antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of citral-loaded NLCs were evaluated and compared with the conventional citral emulsion against various gram-positive bacteria (Staphylococcus aureus, Bacillus cereus), gram-negative bacteria (Escherichia coli), and fungi (Candida albicans). Citral-loaded NLCs were spherically shaped nanosized (74.8 nm) particles with narrow size distribution, high EE% (99.84%), and appropriate physical stability during 90 days of storage period. FTIR spectra indicated the interaction between citral and formulation ingredients, which justified the obtained high EE% value. The MIC and MBC values of citral-loaded NLCs were lower than those of citral emulsion for all microorganisms. NLCs formulation showed remarkable capability of encapsulating essential oil and increasing antimicrobial properties to offer effective preservation in food industry.
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Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats
Sri Agus Sudjarwo, Giftania Wardani Sudjarwo, Koerniasari
Research in Pharmaceutical Sciences 2017 12(5):381-390
In recent years, the use of the antioxidant in reducing heavy metal toxicities has increased worldwide. Curcumin has been reported to have a strong antioxidant activity. In this study, we investigated the protective effects of curcumin on lead acetate-induced testicular damage in rats. The sample used 40 male rats divided into 5 groups: negative control (rats were given daily with corn oil); positive control (rats were given daily with lead acetate 50 mg/kg BW orally once in a day for 35 days); and the treatment group (rats were given the curcumin 100 mg, 200 mg, and 400 mg/kg BW orally once in a day for 40 days, and on the 5th day, were given lead acetate 50 mg/kg BW one h after the curcumin administration). After 40 days, levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in testicular tissue, and sperm count, motility and viability in the epididymis were measured in rats. Testis samples were also collected for histopathological studies. Results showed that lead acetate administration significantly decreased the SOD, GPx, and increased MDA levels. Lead acetate also decreased the sperm count, motility, viability, and altered histopathological testis (testicular damage, necrosis of seminiferous tubules and loss of spermatid) compared to the negative control. However, administration of curcumin significantly improved the histopathological in testis, increased the sperm count, motility, viability, and also significantly increased the SOD, GPx, and decreased MDA in testis of lead acetate-treated rats. From the results of this study we concluded that the curcumin could be a potent natural product provide a promising protective effect against lead acetate induced testicular toxicity in rats.
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Research in Pharmaceutical Sciences 2017 12(5):381-390
In recent years, the use of the antioxidant in reducing heavy metal toxicities has increased worldwide. Curcumin has been reported to have a strong antioxidant activity. In this study, we investigated the protective effects of curcumin on lead acetate-induced testicular damage in rats. The sample used 40 male rats divided into 5 groups: negative control (rats were given daily with corn oil); positive control (rats were given daily with lead acetate 50 mg/kg BW orally once in a day for 35 days); and the treatment group (rats were given the curcumin 100 mg, 200 mg, and 400 mg/kg BW orally once in a day for 40 days, and on the 5th day, were given lead acetate 50 mg/kg BW one h after the curcumin administration). After 40 days, levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in testicular tissue, and sperm count, motility and viability in the epididymis were measured in rats. Testis samples were also collected for histopathological studies. Results showed that lead acetate administration significantly decreased the SOD, GPx, and increased MDA levels. Lead acetate also decreased the sperm count, motility, viability, and altered histopathological testis (testicular damage, necrosis of seminiferous tubules and loss of spermatid) compared to the negative control. However, administration of curcumin significantly improved the histopathological in testis, increased the sperm count, motility, viability, and also significantly increased the SOD, GPx, and decreased MDA in testis of lead acetate-treated rats. From the results of this study we concluded that the curcumin could be a potent natural product provide a promising protective effect against lead acetate induced testicular toxicity in rats.
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Docking study, synthesis and antimicrobial evaluation of some novel 4-anilinoquinazoline derivatives
Rezvan Rezaee Nasab, Farshid Hassanzadeh, Ghadam Ali Khodarahmi, Mahboubeh Rostami, Mahmoud Mirzaei, Ali Jahanian-Najafabadi, Mahboubeh Mansourian
Research in Pharmaceutical Sciences 2017 12(5):425-433
A series of novel 4-anilinoquinazoline derivatives were designed and synthesized from benzoic acid through ring closure, chlorination or nucleophilic substitution. The structures of compounds were characterized by IR, 1H-NMR and mass spectroscopy. All synthesized derivatives were screened for their antimicrobial activities against Gram-positive (Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) bacteria and also for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially compound 4c having highest activities against E. coli at 32 μg/mL concentration while the tested compounds did not exhibited remarkable antifungal activities. The potential DNA gyrase inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. All compounds showed good results especially compound 4c which showed the lowest ΔGbind results (-8.16 Kcal/mol).
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Research in Pharmaceutical Sciences 2017 12(5):425-433
A series of novel 4-anilinoquinazoline derivatives were designed and synthesized from benzoic acid through ring closure, chlorination or nucleophilic substitution. The structures of compounds were characterized by IR, 1H-NMR and mass spectroscopy. All synthesized derivatives were screened for their antimicrobial activities against Gram-positive (Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) bacteria and also for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially compound 4c having highest activities against E. coli at 32 μg/mL concentration while the tested compounds did not exhibited remarkable antifungal activities. The potential DNA gyrase inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. All compounds showed good results especially compound 4c which showed the lowest ΔGbind results (-8.16 Kcal/mol).
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Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer
Suyang Guo, Bo Yang, Hongli Liu, Yuzhi Li, Shengze Li, Ling Ma, Jian Liu, Wei Guo
Journal of Cancer Research and Therapeutics 2017 13(4):689-692
Objective: The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Methods: Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. Results: The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21–33.20) mg/mL, 4.78 (0.22–175.20) mg/mL, and 11.56 (2.028–123.66) IU/mL for NRG and 5.64 (0.50–136.80) mg/mL, 22.41 (0.56–588.90) mg/mL, and 25.41 (3.658–3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= –0.13, P = 0.56) was found in the RG patients. Conclusion: Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.
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Journal of Cancer Research and Therapeutics 2017 13(4):689-692
Objective: The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Methods: Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. Results: The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21–33.20) mg/mL, 4.78 (0.22–175.20) mg/mL, and 11.56 (2.028–123.66) IU/mL for NRG and 5.64 (0.50–136.80) mg/mL, 22.41 (0.56–588.90) mg/mL, and 25.41 (3.658–3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= –0.13, P = 0.56) was found in the RG patients. Conclusion: Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.
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Tumour hypoxia: lessons learnt from preclinical imaging
Abstract
Purpose
In tumour, the imbalance between oxygen supply and demand leads to hypoxia, which represents a negative prognostic factor associated with aggressive tumour phenotype and therapy resistance. This review provides an overview of the use of positron emitter-labelled radiopharmaceutical used to image hypoxia in preclinical models of cancer.
Methods
A critical and comprehensive PubMed search was performed identifying articles related to PET imaging for hypoxia assessment in preclinical setting from January 2007 up to January 2017.
Results
We have considered and described a total of 54 original articles, exploring tumour-associated hypoxia in preclinical models. Results underlined the potential application together with the advantages and pitfalls of the use of PET in preclinical research. Multi-target imaging allowed to better define the relationship between hypoxia and other biological hallmarks of tumour; imaging of hypoxia was proved as a useful tool for lesions stratification and response prediction to radiotherapy; however, cutoff indexes were identified in few studies. Hypoxia PET showed remarkable tracer delivery limitations in the study of vascular disrupting agents but suggested the potential use of PET as a marker of response or resistance to anti-angiogenics. Finally, the effect of anaesthesia on tracer kinetics and tumour oxygenation as well as perfusion dependency in tracer uptake should be carefully evaluated to avoid artefactual results.
Conclusions
Preclinical studies highlight the advantages and the limitations of the available hypoxia-radiotracers and their potential usefulness for the evaluation of treatments outcome and radiotherapy planning.
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Economic Burden of Osteoporosis in South Korea: Claim Data of the National Health Insurance Service from 2008 to 2011
Abstract
The purpose of this study was to estimate the current economic burden of osteoporosis in South Korea using national claim data of the Korean National Health Insurance Service (KNHIS) from 2008 to 2011. Patients aged 50 years or older were identified from KNHIS nationwide database for all records of outpatient visits or hospital admissions. Healthcare costs for osteoporotic patients included direct medical costs for hospitalization, outpatient care, and prescription drugs for the year after discharge. Healthcare costs were estimated based on the perspective of KNHIS, and calculated using a bottom-up approach. Between 2008 and 2011, total healthcare costs for osteoporotic patients increased from 3976 million USD to 5126 million USD, with an annual increase of 9.2% which accounted for one-sixth (16.7%) of national healthcare expenditure. Healthcare cost for hospitalization was the highest ($1903 million, 40.0% of total healthcare cost), followed by cost for outpatient care ($1474 million, 31.0%) and cost for prescription drugs ($1379 million, 29.0%). Although total healthcare cost for osteoporotic men was 6 times lower than that for osteoporotic women, the cost per person was 1.5 times higher than that for women. Total healthcare cost for osteoporotic patients without fractures was higher than that for osteoporotic patients with fractures. However, cost per person was the opposite. Osteoporosis entails substantial epidemiologic and economic burden in South Korea. This study provides information about the total healthcare burden, which could be important when determining what attention and awareness osteoporosis should be given in the public health system.
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Bone Phenotype Assessed by HRpQCT and Associations with Fracture Risk in the GLOW Study
Abstract
The epidemiology and pathogenesis of fractures in postmenopausal women has previously been investigated in the Global Longitudinal study of Osteoporosis in Women (GLOW). To date, however, relationships between bone imaging outcomes and fracture have not been studied in this cohort. We examined relationships between high-resolution peripheral quantitative computed tomography (HRpQCT) parameters and fracture in the UK arm of GLOW, performing a cluster analysis to assess if our findings were similar to observations reported from older participants of the Hertfordshire Cohort Study (HCS), and extended the analysis to include tibial measurements. We recorded fracture events and performed HRpQCT of the distal radius and tibia and dual-energy X-ray absorptiometry (DXA) of the hip in 321 women, mean age 70.6 (SD 5.4) years, identifying four clusters at each site. We saw differing relationships at the radius and tibia. Two radial clusters (3 and 4) had a significantly lower hip areal bone mineral density (p < 0.001) compared to Cluster 1; only individuals in Cluster 4 had a significantly higher risk of fracture (p = 0.005). At the tibia, clusters 1, 3 and 4 had lower hip areal bone mineral density (p < 0.001) compared to Cluster 2; individuals in Cluster 3 had a significantly higher risk of fracture (p = 0.009). In GLOW our findings at the radius were very similar to those previously reported in the HCS, suggesting that combining variables derived from HRpQCT may give useful information regarding fracture risk in populations where this modality is available. Further data relating to tibial HRpQCT-phenotype and fractures are provided in this paper, and would benefit from validation in other studies. Differences observed may reflect age differences in the two cohorts.
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Direct Pulp Capping with Calcium Hydroxide, Mineral Trioxide Aggregate, and Biodentine in Permanent Young Teeth with Caries: A Randomized Clinical Trial
Direct pulp capping treatment is intended to preserve pulp vitality, to avoid or retard root canal treatment, and, in cases with an open apex, to allow continued root development. Historically, calcium hydroxide (CH) was the gold standard material, but nowadays calcium silicate materials (CSMs) are displacing CH because of their high bioactivity, biocompatibility, sealing ability, and mechanical properties. However, more randomized clinical trials are needed to confirm the appropriateness of CSMs as replacement materials for CH in direct pulp capping procedures.
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The effects of climate, catchment land use and local factors on the abundance and community structure of sediment ammonia-oxidizing microorganisms in Yangtze lakes
Ammonia-oxidizing archaea (AOA) and bacteria (AOB) play important roles in regulating the nitrification process in lake ecosystems. However, the relative effects of climate, catchment land use and local condit...
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Genetic algorithm with a crossover elitist preservation mechanism for protein–ligand docking
Protein–ligand docking plays an important role in computer-aided pharmaceutical development. Protein–ligand docking can be defined as a search algorithm with a scoring function, whose aim is to determine the c...
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Study on the removal and transport and migration mechanism for As with activated sludge system
In this paper, the removal of As and the transport and migration of As at the process of activated sludge system was studied. The results showed that the activated sludge system has high removal efficiency for...
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Effects of xanthan gum and HPMC on physicochemical and microstructure properties of sponge cakes during storage
Abstract
The effects of xanthan gum (XG) and hydroxypropyl methylcellulose (HPMC) in sponge cakes were studied. Hydrocolloids enhanced the thickening effect in batter that affected the textural attributes of sponge cakes. During storage, the structural changes in XG-cake resulted in higher hardness compared to HPMC-cake. Similar to XG, HPMC also contributed moistness to cake. The moisture loss of cake containing XG was slower than HPMC-cake. FTIR study showed absorption of OH at region of 3600–2900 cm−1 that explained the strong interaction of water in cake containing XG compared to other cake formulations.
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Gelled double emulsions as delivery systems for hydroxytyrosol and n-3 fatty acids in healthy pork patties
Abstract
Structuring of double emulsion offers the possibility to obtain a system with similar consistency to animal fat which is an interesting approach to improve the fat content of meat products. This article examines the suitability of gelled double emulsions (GDE) for use as a delivery system for n-3 PUFAs and hydroxytyrosol (Hxt) in pork patties. Effect of partial (MF/GDE sample) and total (LF/GDE) replacement of pork backfat with GDE with perilla oil (PO) as lipid phase and Hxt (in W1) on pork patty composition and properties was evaluated. Compared with the control sample (NF/CS), the products with PO contained less SFAs and higher proportions of LNA and ALA, and this difference augmented with the level of GDE. Addition of GDE increased Kramer shear force of cooked patties as the higher percentage of fat replaced was used. Oxidative stability of patties can be interpreted in terms of composition and structural factors, especially in relation with the use of GDE as a fat replacer. Products showed oxidation values greater than 1 after 3 days of refrigeration. NF/GDE and MF/GDE, with similar scores, were the most acceptable for the panellists. This technology is suitable for labelling meat products with nutritional and health claims.
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Retrospective cohort study of combined approach for trunk reconstruction using arteriovenous loops and free flaps
Defect reconstruction of the trunk can be performed using microsurgical free flap transplantation. In cases of missing or inappropriate recipient vessels, microsurgical defect reconstruction of the trunk can be achieved by combining free flaps with arteriovenous loops. Here we present our 5-year experience of trunk reconstruction using AV loops and free flaps in a retrospective evaluation. We analyzed 32 cases of trunk reconstruction using a combined approach of free flap transplantation and arteriovenous loops between 2011 and 2016 regarding postoperative complications and perioperative course.
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Investigation of blood perfusion by laser speckle contrast imaging in stretched and rotated skin flaps in a porcine model
Dear Sir,
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Lymphatic vessel density and VEGF-C expression as independent predictors of melanoma metastases: methodological issues
Dear Editor-in-Chief,
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Current status and trends of breast reconstruction in argentina
Over the last decade, there has been an exponential increase in implant-based breast reconstructions correlated with a proportional decrease in autologous reconstruction in the US.1,2 We aimed to determine the breast reconstruction trends in Argentina through a survey of plastic surgeons who were invited to answer a multiple-choice anonymous questionnaire sent through email.
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Effect of distal venous drainage on the survival of four-territory flaps with no pedicle vein: results from a rat model
Venous super-drainage can improve flap survival not only because it prevents congestion, but also because it affects the dominant circulation in multi-territory thin skin flaps. We aimed to evaluate the survival of various flap areas and detect vascular changes in artery-based, four-territory skin flaps after different distal venous drainage procedures.
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Measuring the patient perspective on latissimus dorsi donor site outcomes following breast reconstruction
There is little evidence about the long-term donor site outcome of latissimus dorsi breast reconstruction and no patient-reported outcome measures designed specifically for the procedure.
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The role of ultrasound technology in plastic surgery
The modern medical era is in part characterized by the increased availability of portable imaging devices. Ultrasound devices are used for either high-resolution non-invasive imaging or as a focused acoustic energy source capable of sculpting and shaping tissue. Given the broad scope of the field, plastic and reconstructive surgeons have the unique ability to implement and tailor the use of ultrasound in a variety of clinical situations. This article will review novel uses for ultrasound in the field of plastic surgery.
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Introduction to special section on digital technology and cancer survivorship
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Flared sign of flail mandible on computed tomography: an unstable fracture associated with a compromised airway
A mandibular fracture alone rarely causes a life-threatening injury. The aim of this paper was to emphasise the importance of prompt identification of the radiological signs of a flail mandible in a patient with maxillofacial trauma who eventually needed definitive management of her airway.
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UK temporomandibular joint replacement database: a report on one-year outcomes
Alloplastic temporomandibular joint (TMJ) replacements are increasingly subspecialised, and supraregional centres that treat sufficient numbers to ensure high standards are emerging. Having recently reported the introduction of a national TMJ joint replacement database that is endorsed by the British Association of TMJ Surgeons (BATS), we now present the first-year outcomes. This was a review of all data in the BATS National Case Registration of TMJ Replacement as of June 2014. A total of 252 one-year outcome records were available.
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Survival after surgery for oral cancer: a 30-year experience
Oral squamous cell carcinoma is the most common intraoral malignancy, for which we advocate radical primary resection with adjuvant treatment where indicated. The main aims of this paper are to identify the overall survival of a consecutive series of patients and to relate survival to clinical and pathological factors. Kaplan–Meier curves were produced for site, sex, TNM status, and use of postoperative radiotherapy. The data were analysed using IBM SPSS Statistics for Windows and probabilities of less than 0.05 were accepted as significant.
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Removal of recurrent intraorbital tumour using a system of augmented reality
The most crucial step in the management of pleomorphic adenoma of the lacrimal gland is choosing the optimal approach for excision. We report the successful removal of a recurrent pleomorphic adenoma of the lacrimal gland in a 42-year-old woman using a specific microscope-based system of augmented reality.
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Utility of screening questionnaire and polysomnography to predict postoperative outcomes in children
The prevalence of pediatric obstructive sleep apnea (OSA) has increased concurrently with the increasing prevalence of obesity. We have previously validated a short questionnaire predicting the occurrence of OSA on polysomnography (PSG). This follow-up study assessed the utility of the questionnaire in predicting postoperative outcomes.
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Utility of screening questionnaire and polysomnography to predict postoperative outcomes in children
The prevalence of pediatric obstructive sleep apnea (OSA) has increased concurrently with the increasing prevalence of obesity. We have previously validated a short questionnaire predicting the occurrence of OSA on polysomnography (PSG). This follow-up study assessed the utility of the questionnaire in predicting postoperative outcomes.
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HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
Abstract
Background: Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results.Methods: We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits.Results: A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07–1.29) in Europeans (P = 6.88 × 10–4) and of 1.58 (1.24–2.00) in Asians (P = 2.92 × 10–4) in Model 3. The corresponding OR estimates were 1.30 (1.09–1.55) in Europeans (P = 3.18 × 10–3) and 1.42 (1.11—1.80) in Asians (P = 4.42 × 10–3) in Model 1, and 1.21 (1.11–1.31) in Europeans (P = 3.12 × 10–5) and 1.51 (1.20–1.91) in Asians (P = 7.61 × 10–4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels.Conclusions: Our study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2wb21Cl
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Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care
Abstract
Purpose
Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug–drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations.
Methods
By using the Italian general practice Health Search Database (HSD), we retrospectively selected adult patients with at least one LT4 prescription from 2012 to 2015 and at least 1 year of clinical history recorded. The incident prescription of interacting medications (e.g., proton pump inhibitors, calcium or iron salts) was the index date. Analysis was carried out using a self-controlled study design.
Results
Overall, 3965 users of LT4 formed the study cohort (84.1% women, mean age 56 ± 16.5 years). TSH variability on the entry date was greater among liquid LT4 users than in those prescribed with tablets as shown by the difference between 75th and 25th centile, which were 3.01 and 3.8, respectively. The incidence rate ratio (IRR) for TSH variability did not differ between groups, before and during exposure to DDIs. In contrast, PDDs less likely increased during the exposure to DDI with oral liquid LT4 compared with tablets (IRR = 0.84; 95% CI: 0.77–0.92), especially in patients with post-surgical hypothyroidism (IRR = 0.75; 95% CI: 0.64–0.85).
Conclusions
In clinical practice, the use of oral liquid LT4 is not associated with increased PDDs, compared with tablets formulation, during exposure to DDIs. These results support the need for individualizing LT4 formulation to prescribe, especially in patients with various comorbidities and complex therapeutic regimens.
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Impact of etiology, age and gender on onset and severity of hyponatremia in patients with hypopituitarism: retrospective analysis in a specialised endocrine unit
Abstract
Background
Hyponatremia can unmask hypopituitarism and secondary adrenal insufficiency. This is important, since the need to screen for steroid deficiency, in patients with hyponatremia is often neglected.
Patients and methods
In a retrospective study, twenty-five patients (13f/12m, age 58.9 ± 18.6 years) with hyponatremia (119.7 ± 10.5 mmol/L) were identified among 260 in-patients treated for hypopituitarism in our specialized endocrine unit, over the last decade. We analyzed clinical characteristics, etiology, and severity of hypopituitarism in patients who presented with hyponatremia.
Results
Hyponatremia was recorded in 9.6% of our patients with hypopituitarism. In 80.7% it was the key to diagnosis of hypopituitarism. All patients with hyponatremia were steroid deficient with complete hypopituitarism compared to 75% (steroid deficient) and 60% (complete hypopituitarism) of the patients in the cohort. The most common etiology of hypopituitarism was non-functioning pituitary macro adenoma (NFPA) (n = 128, 49.2%). Patients with hyponatremia were divided into two groups, based on the etiology of hypopituitarism: Group 1. with NFPA n = 15 (5F/10M), mean age 71.47 ± 4.8 years, who were significantly older compared to patients with hyponatremia from other rare causes of hypopituitarism in Group 2. n = 10 (8F/2M), mean age 40.2 ± 15.3 years (p < 0.01), such as: congenital hypopituitarism(n = 2), Sheehan's syndrome (n = 2), intracranial aneurysm (n = 2), lymphocytic hypophysitis (n = 1), traumatic brain injury (n = 1), surgery and radiotherapy for astrocytoma (n = 1), pituitary metastasis from bronchial carcinoma (n = 1). Hyponatremia was more severe in Group 2. compared to Group 1. (113.5 ± 10.9 mmol/L vs. 124.3 ± 8.1 mmol/L, p < 0.01). Older age (p = 0.0001) and number of endocrine deficiencies (p < 0.05) were identified as predictive factors for hyponatremia by multivariate analysis in patients with hypopituitarism.
Conclusion
Hyponatremia is an important presenting feature of pituitary disease and a strong indicator of life-threatening steroid deficiency. Old age and severity of hypopituitarism are major risk factors for hyponatremia. In older patients NFPA is the most common etiology, while other rare causes of hypopituitarism are more prevalent in younger patients with hyponatremia.
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Late-occurring nivolumab-induced cryptogenic organising pneumonia mimicking lung progression in a patient with metastatic non–small cell lung cancer
Metastatic non–small cell lung cancer (NSCLC) care has been transformed these last few years with the approval of programmed death (ligand)–1 (PD(L)1) blockade [1–5] in frontline and after progression on or after platinum-based chemotherapy. Managing immune-related toxicities has become the new field of expertise for oncologists and guidelines of optimal clinical management for PD(L)1 blockade–treated patients are still being established [6–8].
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On the issues of digital competence in educational contexts – a review of literature
Abstract
In this review focus is on how digital competence in educational contexts has been addressed in international research over the last 10 years in terms of policy, organizational infrastructures, strategic leadership as well as teachers and their teaching practices. The analysis shows that although research on digital competence in educational contexts has increased, knowledge on digital competence related to organizational infrastructures and strategic leadership are sparse. The analysis indicated that most research focuses on the specific competence needed by teachers and therefore tends to neglect the influence of broader contextual conditions in the wider school setting. Based on the review, three suggestions for further research can be provided. Firstly, to address research on organizational infrastructures and digital competent leadership. Secondly, to elaborate on theoretical frameworks that can close the gap between research on policy, organizational infrastructures, strategic leadership as well as teachers and their teaching practices. A third suggestion is for researchers to become involved in the development of new approaches that can enhance digital competence in educational contexts. It can be concluded that digital competence might not benefit from being regarded as an isolated phenomena on the level of single actors. Rather, it can be regarded as an organizational task, influenced and driven by several contextual factors embedded within and across a wider school organization.
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Mass. bill to expand access to dentistry picks up steam
Claiming momentum in a fierce policy battle, lawmakers who favor a legal expansion of the scope of dentistry work so that more patients can be served say they are gaining ground on Beacon Hill. "I'm very proud that the fact is the dentists are at the table with us, talking about this," said Rep. William "Smitty" Pignatelli, D-Lenox, who represents many rural communities in Berkshire County, hearing on legislation authorizing a new type of professional, a dental therapist.
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Fabry disease
Fabry disease: A genetic disease caused by a mutation in the GLA gene, resulting in a deficiency of the enzyme alpha-galactosidase A, also known as ceramide trihexosidase. This enzyme is essential to the metabolism of a fat compound known as globotriaosylceramide. Without alpha-galactosidase A, this fatty substance accumulates in the walls of blood vessels, leading to narrowing and decreased blood flow to the tissues normally supplied by these vessels. Small vessels in the skin, kidneys, heart, and nervous system are preferentially affected, impairing function of these organs. Males with Fabry disease are more severely affected than females with it because the gene for Fabry disease is on the X chromosome. Males have only one X, whereas females have a second X and therefore some enzyme activity. Females with partial enzyme activity may not show any symptoms, or may have symptoms as severe as affected males. Diagnosis is made by determining the level of alpha-galactosidase A in blood plasma or through genetic testing. Symptoms may include blood vessel-filled skin lesions known as angiokeratomas over the hips, buttocks, thighs, and lower belly with fever accompanying attacks of pain in the fingers and toes. Potentially life-threatening complications such as stroke, heart failure, and kidney 'failure may also occur. Treatment includes intravenously-administered enzyme replacement therapy with agalsidase beta (brand name: Fabrazyme), which reduces the fat accumulation in many types of cells and tissues. Episodes of pain in the hands and feet may benefit from certain medications. Also known as Anderson-Fabry disease and angiokeratoma corporis diffusum universale.
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Decision-making about healthcare related tests and diagnostic strategies: a qualitative study with experts suggests that test accuracy data alone is rarely sufficient for decision-making
To identify the critical factors that determine recommendations and other decisions about health care related tests and diagnostic strategies (HCTDS).
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Decision-making about healthcare related tests and diagnostic strategies: International guidelines show variability in their approaches.
To describe and compare current practices in developing guidelines about the use of health care related tests and diagnostic strategies (HCTDS)
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Racial and Insurer-Based Disparities of Care Exist Among Thyroid Cancer Patients in the United States
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 351-353.
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Large Retrospective Study Confirms the 2015 American Thyroid Association Guidelines for Classifying Small Thyroid Nodules on Ultrasound
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 344-347.
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Conflicting Occurrence of Thyroid-Stimulating or Blocking Antibodies Is Seen in 4 to 9% of Patients with Autoimmune Thyroid Disease
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 335-337.
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Hypothyroid Symptoms in Pregnant Women Fail to Predict Hypothyroid Status
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 332-334.
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A Deiodinase 2 Polymorphism May Lower Serum T3 and Tissue T3 in Levothyroxine-Treated Patients
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 338-340.
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Moderate-Risk versus High-Risk RET Mutation Does Not Impact Medullary Thyroid Cancer Outcomes in MEN2A Patients
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 348-350.
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Is There a Distinct Pattern of Mutations in Benign Adenomatous Nodules?
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 341-343.
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Does Empathy, a Central Element of the Art of Medicine, Proscribe Using “Good Cancer” Themes in Clinical Practice?
Clinical Thyroidology Sep 2017, Vol. 29, No. 9: 354-357.
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Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications
Summary
Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov, 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21–25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.
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A Randomized Controlled Trial of Green Tea Extract Supplementation and Mammographic Density in Postmenopausal Women at Increased Risk of Breast Cancer
Epidemiological and animal studies suggest a protective role of green tea against breast cancer. However the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50-55 years), GTE supplementation significantly reduced PMD by 4.40% as compared to the placebo with a 1.02% PMD increase from pre- to post-intervention (P = 0.05), but had no effect in older women (P-interaction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-methyltransferase (COMT) genotype or level of body mass index. In conclusion, one-year supplementation with a high dose of EGCG did not have significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted.
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Gene Methylation Biomarkers in Sputum and Plasma as Predictors for Lung Cancer Recurrence
Detection of methylated genes in exfoliated cells from the lungs of smokers provides an assessment of the extent of field cancerization, is a validated biomarker for predicting lung cancer, and provides some discrimination when interrogated in blood. The potential utility of this 8-gene methylation panel for predicting tumor recurrence has not been assessed. The Eastern Cooperative Oncology Group initiated a prevention trial (ECOG-ACRIN5597) that enrolled resected Stage I non-small cell lung cancer patients who were randomized 2:1 to receive selenized yeast versus placebo for four years. We conducted a correlative biomarker study to assess prevalence for methylation of the 8-gene panel in longitudinally collected sputum and blood after tumor resection to determine if selenium alters their methylation profile and whether this panel predicts local and/or distant recurrence. Patients (n=1561) were enrolled into the prevention trial, 565 participated in the biomarker study with 122 recurrences among that group. Assessing the association between recurrence and risk of gene methylation longitudinally for up to 48 months showed a 1.4-fold increase in odds ratio for methylation in sputum in the placebo group independent of location (local or distant). Kaplan Meier curves evaluating the association between number of methylated genes and time to recurrence showed no increased risk in sputum, while a significant hazard ratio of 1.5 was seen in plasma. Methylation detection in sputum and blood is associated with risk for recurrence.
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Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice.
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation and post-weaning. Analyses showed that a post-weaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence. Cox proportional hazards analysis showed that a HF/HS post-weaning diet doubled mammary cancer risk and a HF/HS diet during gestation and post-weaning increased risk 5.5 times. Exposure to a HF/HS diet during gestation, when combined with a post-weaning DR diet, had a protective effect, reducing mammary tumor risk by 86% (HR = 0.142). Serum adipocytokine analysis revealed significant diet-dependent differences in leptin/adiponectin ratio and IGF-1. Flow cytometry analysis of cells isolated from mammary glands from a high tumor incidence group, DR/HF/HF, showed a significant increase in the size of the mammary stem cell compartment compared to a low tumor group, HF/HF/DR. These results indicate that dietary reprogramming induces an expansion of the mammary stem cell compartment during mammary development, increasing likely carcinogen targets and mammary cancer risk.
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Effects of different carrier materials on physicochemical properties of microencapsulated grape skin extract
Abstract
The goal of this study was to investigate the characteristics of grape skin extract (GSE) spray dried with different carriers: maltodextrin (MD), gum Arabic (GA) and skim milk powder (SMP). The grape skin extract was obtained from winery by-product of red grape variety Prokupac (Vitis vinifera L.). The morphology of the powders, their thermal, chemical and physical properties (water activity, bulk and tapped densities, solubility), as well as release studies in different pH conditions were analyzed. Total anthocyanin content and total phenolic content were determined by spectrophotometric methods. MD and GA-based microparticles were non-porous and spherical, while SMP-based ones were irregularly shaped. The process of spray drying Prokupac GSE using these three carriers produced powders with low water activity (0.24–0.28), good powder characteristics, high yields, and solubility higher than 90%. The obtained dissolution/release profiles indicated prolonged release of anthocyanins and phenolic compounds in different mediums, especially from GSE/GA microparticles. These results have shown that grape skin as the main by-product of wine production could be used as a source of natural colorants and bioactive compounds, and microencapsulation as a promising technique for the protection of these compounds, their stabilization in longer periods and prolonged release.
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Outcomes after sofosbuvir-containing regimens for hepatitis C virus in patients with decompensated cirrhosis: a real-world study
Direct-acting antivirals have been used for decompensated cirrhotic patients with hepatitis C virus (HCV) infection. However, the benefits in Chinese patients with decompensated cirrhosis are unclear.
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Early life arsenic exposure, infant and child growth, and morbidity: a systematic review
Abstract
Epidemiological studies have suggested a negative association between early life arsenic exposure and fetal size at birth, and subsequently with child morbidity and growth. However, our understanding of the relationship between arsenic exposure and morbidity and growth is limited. This paper aims to systematically review original human studies with an analytical epidemiological study design that have assessed arsenic exposure in fetal life or early childhood and evaluated the association with one or several of the following outcomes: fetal growth, birth weight or other birth anthropometry, infant and child growth, infectious disease morbidity in infancy and early childhood. A literature search was conducted in PubMed, TOXLINE, Web of Science, SciFinder and Scopus databases filtered for human studies. Based on the predefined eligibility criteria, two authors independently evaluated the studies. A total of 707 studies with morbidity outcomes were identified, of which six studies were eligible and included in this review. For the growth outcomes, a total of 2959 studies were found and nine fulfilled the criteria and were included in the review. A majority of the papers (10/15) emanated from Bangladesh, three from the USA, one from Romania and one from Canada. All included studies on arsenic exposure and morbidity showed an increased risk of respiratory tract infections and diarrhea. The findings in the studies of arsenic exposure and fetal, infant, and child growth were heterogeneous. Arsenic exposure was not associated with fetal growth. There was limited evidence of negative associations between arsenic exposures and birth weight and growth during early childhood. More studies from arsenic-affected low- and middle-income countries are needed to support the generalizability of study findings.
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Pandemics, public health emergencies and antimicrobial resistance - putting the threat in an epidemiologic and risk analysis context
Public health messaging about antimicrobial resistance (AMR) sometimes conveys the problem as an epidemic. We outline why AMR is a serious endemic problem manifested in hospital and community-acquired infections.
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Cancer survival disparities worsening by socio-economic disadvantage over the last 3 decades in new South Wales, Australia
Public concerns are commonly expressed about widening health gaps. This cohort study examines variations and trends in cancer survival by socio-economic disadvantage, geographical remoteness and country of bir...
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A socio-ecological analysis of barriers to the adoption, sustainablity and consistent use of sanitation facilities in rural Ethiopia
Despite evidence showing that access to and use of improved sanitation is associated with healthier households and communities, barriers influencing the adoption and sustainablity of sanitation facilities rema...
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Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b
Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of prima...
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09/13/17 PHD comic: 'Impostor Attack'
| Piled Higher & Deeper by Jorge Cham | www.phdcomics.com | |
 | ||
| title: "Impostor Attack" - originally published 9/13/2017 For the latest news in PHD Comics, CLICK HERE! | ||
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Biodegradable Viral Nanoparticle/Polymer Implants Prepared via Melt-Processing
ACS Nano
DOI: 10.1021/acsnano.7b02786
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Controlling Protein Surface Orientation by Strategic Placement of Oligo-Histidine Tags
ACS Nano
DOI: 10.1021/acsnano.7b03717
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Serum 8-hydroxydeoxyguanosine and aldose reductase C-106T polymorphism in type 2 diabetes mellitus and its relation to complications in Egyptian patients
Abstract
Diabetes mellitus (DM) is an inherited disease, which can affect every organ in the body. 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker for oxidative DNA damage. Occurrence of C-106T polymorphism of the aldose reductase (ALR) gene in type II diabetic patients suffering from diabetic microvascular complications has been reported. The aim of the present work was to assess the association between oxidative stress and C(-106)T ALR gene polymorphism and the incident of type 2 diabetes (T2D) and its complications. The current study was conducted on 200 subjects classified into 150 T2D patients and 50 healthy control subjects. Quantitative determination of human 8-OHdG was done using enzyme-linked immunosorbent assay (ELISA) technique. ALR C(-106)T polymorphism was assessed by PCR/RFLP method. Levels of 8-OHdG were significantly increased in diabetic patients when compared to control subjects and in diabetic patients with complications when compared to those without complications (P < 0.001 or all). CT genotype was associated with susceptibility to development of T2D in Egyptian population. Nevertheless, this association has not been observed in diabetic complications. 8-OHdG level is significantly increased in diabetic group when compared to the control group and in diabetic patients with complications when compared to diabetic patients without complications. C(-106)T gene polymorphisms were associated with susceptibility to development diabetes, but it has no associations in development of complications.
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Phenotypic variation of thymic epithelial cells and partial spontaneous regression in thymoma of a cow
Abstract
Thymoma was recognized in a 12-year-old Holstein dairy cow presenting with no significant clinical signs. The animal was conventionally slaughtered at an abattoir and, on postmortem examination, a spherical tumor mass was found in the anterior region of the mediastinum. Histologically, the tumor was fibrously encapsulated and exhibiting varying-sized cystoid cavities containing serous fluid and necrotic and hemorrhagic foci. No architectural features showing distinct characteristics to a sufficient degree to allow identification of the thymus or other organs could be seen. The tumor showed diffuse solid sheet-like or nodular patterns of proliferation and consisted of a dual cell population: one was neoplastic epithelial cells that were immunohistochemically positive for cytokeratin, and the other was T lymphocytes that exhibited positive immunohistochemical staining with CD3. This finding enabled a diagnosis of mixed thymoma to be made. Neoplastic epithelial cells represented a wide spectrum of phenotypic expression, including (1) spindle shaped cells with a chiasmus-like, interlacing fascicular, or storiform growth pattern; (2) small, round to oval cells with scant cytoplasm showing indistinct boundary of cells; (3) large cells arranged in a solid sheet-like pattern; (4) vacuolated cells similar to signet ring cells; (5) clear cells that had defined cell membranes; and (6) occasional formation of micronodules composed of neoplastic epithelial cells. In addition, some areas of the tumor exhibited features of partial spontaneous regression characterized by collapse or disintegration of tumor tissues in close association with fibrocollagenous connective tissue deposition. Even if the morphology of thymic epithelial cells in thymoma is known to display variable appearance, it is likely to be unusual that, in the current bovine case, such thymic epithelial cells exhibited a wider spectrum of phenotypic expression within a single tumor. This salient histomorphological heterogeneity shown by thymic epithelial cells might have presumably been associated with innate characteristics specific to pluripotent thymic epithelial cells during thymoma tumorigenesis.
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Limited proteolysis as a tool to probe the tertiary conformation of dysferlin and structural consequences of patient missense variant L344P [Molecular Biophysics]
Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair, and underlies a recessive form of inherited muscular dystrophy. Dysferlinopathy is characterized by absence or marked reduction of dysferlin protein, with 43% of reported pathogenic variants being missense variants that span the length of the dysferlin protein. The unique structure of dysferlin, with seven tandem C2-domains separated by linkers, suggest dysferlin may dynamically associate with phospholipid membranes in response to Ca2+ signaling. However, the overall conformation of the dysferlin protein is uncharacterized. To dissect the structural architecture of dysferlin, we have applied the method of limited proteolysis that allows non-specific digestion of unfolded peptides by trypsin. Using five antibodies spanning the dysferlin protein, we identified a highly reproducible jigsaw map of dysferlin fragments protected from digestion. Our data infers a modular architecture of four tertiary domains; 1) C2A which is readily removed as a solo domain, 2) mid-region C2B-C2C-Fer-DysF, commonly excised as an intact module, with sub-digestion to different fragments suggesting several dynamic folding options 3) C-terminal four C2 domain module and 4) calpain-cleaved mini-dysferlinC72, which is particularly resistant to proteolysis. Importantly, we reveal a patient missense variant L344P which largely escapes proteosomal surveillance, shows subtle but clear changes in tertiary conformation. Accompanying evidence from immunohisto-chemistry and flow cytometry, using antibodies with conformationally sensitive epitopes, supports proteolysis data. Collectively, we provide insight into the structural topology of dysferlin and show how a single missense mutation within dysferlin can exert local changes in tertiary conformation.
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The crystal structure of the AhRR/ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription [Gene Regulation]
2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds (TCDDs) are extraordinarily potent environmental toxic pollutants. Most of the TCDD toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription. The control of AhR activation is critical for managing AhR-mediated diseases, but the mechanisms by which AhRR represses AhR activation remain poorly understood, due to the lack of structural information. Here, we determined the structure of the AhRR/ARNT heterodimer by X-ray crystallography, which revealed an asymmetric intertwined domain organization presenting structural features that are both conserved and distinct among bHLH-PAS family members. The structures of AhRR/ARNT and AhR/ARNT were similar in the bHLH-PAS-A region, while the PAS-B of ARNT in the AhRR/ARNT complex exhibited a different domain arrangement in this family reported so far. The structure clearly disclosed that AhRR competitively represses AhR binding to ARNT and target DNA, and further suggested the existence of an AhRR/ARNT-specific repression mechanism. This study provides a structural basis for understanding the mechanism by which AhRR represses AhR-mediated gene transcription.
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Splice variants of cytosolic polyadenylation element binding protein 2 (CPEB2) differentially regulate pathways linked to cancer metastasis [Cell Biology]
The translational regulator cytosolic polyadenylation element binding protein 2 has two isoforms, CPEB2A and CPEB2B, derived by alternative splicing of RNA into a mature form that either includes or excludes exon 4. Previously, we reported that this splicing event is highly dysregulated in aggressive forms of breast cancers, which overexpress CPEB2B. The loss of CPEB2A with a concomitant increase in CPEB2B was also required for breast cancer cells to resist cell death due to detachment (anoikis resistance) and metastasize in vivo. To examine the mechanism by which CPEB2 isoforms mediate opposing effects on cancer-related phenotypes, we used next-generation sequencing of triple-negative breast cancer cells in which the isoforms were specifically downregulated. Downregulation of the CPEB2B isoform inhibited pathways driving the epithelial-to-mesenchymal transition and hypoxic response, whereas downregulation of the CPEB2A isoform did not have this effect. Examining key nodes of these pathways showed that CPEB2B induced the expression of regulatory DNA trans- factors (e.g., HIF1α and TWIST1). Specifically, CPEB2B functioned as a translational activator of TWIST1 and HIF1α. Functional studies showed that specific downregulation of either HIF1α or TWIST1 inhibited the ability of CPEB2B to induce the acquisition of anoikis resistance and drive metastasis. Overall, this study demonstrates that CPEB2 alternative splicing is a major regulator of key cellular pathways linked to anoikis resistance and metastasis.
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BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility [Research]
Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant and carcinogen that is frequently found in particulate matter, with a diameter of ≤2.5 μm (PM2.5). It has been reported to interrupt the normal reproductive system, but the exact molecular basis has not been clearly defined. To understand the underlying mechanisms regarding how BaP exposure disrupts female fertility, we evaluated oocyte quality by assessing the critical regulators and events during oocyte meiotic maturation and fertilization. We found that BaP exposure compromised the mouse oocyte meiotic progression by disrupting normal spindle assembly, chromosome alignment, and kinetochore–microtubule attachment, consequently leading to the generation of aneuploid eggs. In addition, BaP administration significantly decreased the fertilization rate of mouse eggs by reducing the number of sperm binding to the zona pellucida, which was consistent with the premature cleavage of N terminus of zona pellucida sperm–binding protein 2 and precocious exocytosis of ovastacin. Furthermore, BaP exposure interfered with the gamete fusion process by perturbing the localization and protein level of Juno. Notably, we found that BaP exposure induced oxidative stress with an increased level of reactive oxygen species and apoptosis in oocytes and thereby led to the deterioration of critical regulators and events during oocyte meiotic progression and fertilization. Our data document that BaP exposure reduces female fertility via impairing oocyte maturation and fertilization ability induced by oxidative stress and early apoptosis in murine models.—Zhang, M., Miao, Y., Chen, Q., Cai, M., Dong, W., Dai, X., Lu, Y., Zhou, C., Cui, Z., Xiong, B. BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility.
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