Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 06/28/17

Τετάρτη 28 Ιουνίου 2017

Bundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day Hospital Readmissions

Abstract

Background.

A streamlined transition from inpatient to outpatient care can decrease 30-day readmissions. Outpatient parenteral antibiotic therapy (OPAT) programs have not reduced readmissions; an OPAT bundle has been suggested to improve outcomes. We implemented a transition-of-care (TOC) OPAT bundle and assessed the effects on all-cause, 30-day hospital readmission.

Methods.

Retrospectively, patients receiving postdischarge intravenous antibiotics were evaluated before and after implementation of a TOC-OPAT program in Bronx, New York, between July, 2015 and February, 2016. Pearson's χ² test was used to compare 30-day readmissions between groups, and logistic regression was used to adjust for covariates. Time from discharge to readmission was analyzed to assess readmission risk, using log-rank test to compare survival curves and Cox proportional hazards model to adjust for covariates. Secondary outcomes, 30-day emergency department (ED) visits, and mortality were analyzed similarly.

Results.

Compared with previous standard care (n = 184), the TOC-OPAT group (n = 146) had significantly lower 30-day readmissions before (13.0% vs 26.1%, P < .01) and after adjustment for covariates (odds ratio [OR] = 0.51; 95% confidence interval [CI], 0.27–0.94; P = .03). In time-dependent analyses, TOC-OPAT patients were at significantly lower risk for readmission (log-rank test, P < .01; hazard ratio = 0.56; 95% CI, 0.32–0.97; P = .04). Propensity-matched sensitivity analysis showed lower readmissions in the TOC-OPAT group (13.6% vs 24.6%, P = .04), which was attenuated after adjustment (OR = 0.51; 95% CI, 0.25–1.05; P = .07). Mortality and ED visits were similar in both groups.

Conclusions.

Our TOC-OPAT patients had reduced 30-day readmissions compared with the previous standard of care. An effective TOC-OPAT bundle can successfully improve patient outcomes in an economically disadvantaged area.

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Pericarditis Associated With Acute Zika Virus Infection in a Returning Traveler

Abstract

Despite the widespread outbreak, few cases of Zika virus associated with cardiac manifestations have been described. We present a case of pericarditis in the setting of an acute, symptomatic Zika virus infection in a traveler returning from St. Thomas. Clinicians should be alert for this potential complication of Zika virus infection.

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Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review

Abstract

Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.

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Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae : A Systematic Review and Meta-Analysis

Abstract

Background.

Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development.

Methods.

We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs).

Results.

Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83–1.37; I² = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25–1.52; I² = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491–2.095; I² = 62.5%; P = .046), compared with the use of empiric carbapenems.

Conclusions.

These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

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Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance

Complete tumor removal and preservation of the facial nerve are essential in parotid gland surgery. A technical adjunct that potentially enhances the contrast between the facial nerve and the adherent tumor ti...

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Financial Incentives for Adherence to Hepatitis C Virus Clinical Care and Treatment: A Randomized Trial of Two Strategies

Abstract

Background.

Although rates of sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in trials and some more "real world" settings, some patients, such as those with substance use disorders, will be challenged to adhere to HCV care.

Methods.

To assess the feasibility of 2 strategies for financially incentivizing adherence to HCV care, patients with a substance use history prescribed 12 weeks of a sofosbuvir-containing regimen were randomized to either fixed or lottery-based monetary incentives for attending clinic appointments, pill count adherence >90%, and SVR achievement. Electronic medication monitoring provided an objective measure of DAA adherence.

Results.

Fifty-nine participants were randomized to the lottery (n = 31) or fixed-incentive (n = 28) arms. All 31 (100%) in the lottery arm and 24 of 28 (86%) in the fixed arm completed 12 weeks of therapy. By intent-to-treat, 93% in the lottery arm and 92% in the fixed arm achieved SVR (estimated difference: 0.5%; 95% confidence interval, −17.5 to 18.8). Overall, 92% of scheduled visits were attended without significant differences between arms. The mean adherence ratio (days with ≥1 bottle opening:monitored days) was 0.91 for lottery and 0.92 for fixed arms.

Conclusions.

In this pilot, fixed- and lottery-based financial incentives were successfully implemented and accepted by patients with a substance use history. High levels of HCV therapy and care adherence, as well as rates of SVR, were observed. Financial incentives may be useful to support treatment adherence in patients with substance use disorders and should be tested in a larger, randomized, controlled trial.

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Antimicrobial Stewardship Lessons From Mupirocin Use and Resistance in Methicillin-Resitant Staphylococcus Aureus

Abstract

Background.

The quantitative relationship between antimicrobial agent consumption and rise or fall of antibiotic resistance has rarely been studied. We began all admission surveillance testing for methicillin-resistant Staphylococcus aureus (MRSA) in August 2005 with subsequent contact isolation and decolonization using nasally applied mupirocin ointment for those colonized. In October 2012, we discontinued decolonization of medical (nonsurgical service) patients.

Methods.

We conducted a retrospective study from 2007 through 2014 of 445680 patients; 35235 were assessed because of mupirocin therapy and positive test results for MRSA. We collected data on those patients receiving 2% mupirocin ointment for decolonization to determine the defined daily doses (DDDs). A nonparametric regression technique was used to quantitate the effect of mupirocin consumption on drug resistance in MRSA.

Results.

Using regressive modeling, we found that, when consumption was consistently >25 DDD/1000 patient-days, there was a statistically significant increase in mupirocin resistance with a correlating positive rate of change. When consumption was ≤25 DDD/1000 patient-days, there was a statistically significant decrease in mupirocin resistance with a correlating negative rate of change. The scatter plot of fitted versus observed mupirocin resistance values showed an R² value of 0.89—a high correlation between mupirocin use and resistance.

Conclusions.

Use of the antimicrobial agent mupirocin for decolonization had a threshold of approximately 25 DDD/1000 patient-days that separated a rise and fall of resistance within the acute-care setting. This has implications for how widely mupirocin can be used for decolonization, as well as for setting consumption thresholds when prescribing antimicrobials as part of stewardship programs.

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Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus

Abstract

Background.

Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV).

Methods.

One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography.

Results.

Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar (P = .03) and added sugar (P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers (P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque (P = .002) and noncalcified plaque (P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A₂), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics.

Conclusions.

We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV.

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Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance

Complete tumor removal and preservation of the facial nerve are essential in parotid gland surgery. A technical adjunct that potentially enhances the contrast between the facial nerve and the adherent tumor ti...

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Air pollution link to premature death is supported by US study

Long term exposure to airborne fine particulate matter (PM2.5) and ozone increases the risk of premature death even at levels below current air quality standards, a US study of 60 million people...

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Acupuncture may reduce symptoms of stress urinary incontinence, study finds

Treating women with stress urinary incontinence with electroacupuncture—passing an electric current between acupuncture needles on the lower back—reduced urine leakage after six weeks, a randomised...

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Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly ...

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The effect of geriatric intervention in frail elderly patients receiving chemotherapy for colorectal cancer: a randomized trial (GERICO)

Better surgical techniques, chemotherapy and biological therapy have improved survival in patients with colorectal cancer (CRC), most markedly in younger patients. About half of patients over 70 years receive ...

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CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) (NCT03001596)

Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadj...

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Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.

Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer.

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Binormal Motion of Curves with Constant Torsion in 3-Spaces

We study curve motion by the binormal flow with curvature and torsion depending velocity and sweeping out immersed surfaces. Using the Gauss-Codazzi equations, we obtain filaments evolving with constant torsion which arise from extremal curves of curvature energy functionals. They are "soliton" solutions in the sense that they evolve without changing shape.

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Babaodan Capsule (八宝丹胶囊) combined with Qingyi Huaji Formula (清胰化积方) in advanced pancreatic cancer—a feasibility study

Abstract

Objective

To observe the clinical effects of Babaodan Capsule (八宝丹, BBD) combined with Qingyi Huaji Formula (清胰化积方, QYHJ) in treating patients with advanced pancreatic cancer.

Methods

Eighty-one patients with advanced pancreatic cancer (from January 1, 2013 to December 31, 2014) were enrolled. Patients were assigned to two groups randomly with a random number table: QYHJ plus BBD group (40 cases) and QYHJ only group (41 cases), and there were no significant differences for other treatment between two groups. The survival and cancer-related symptoms were compared between two groups over two cycles of treatment.

Results

The cancer-related symptoms of patients such as ascites, jaundice, pain, abdominal distension, anorexia and Karnofsky performance status of QYHJ plus BBD group were significantly improved as compared with those of the QYHJ group (P<0.01). In addition, the 1-year survival rate of patients in QYHJ plus BBD group was longer than that in the QYHJ group (65% vs. 33%, respectively, P=0.0023).

Conclusions

BBD with QYHJ is feasible treatment to prolong the survival of patients with advanced pancreatic cancer. However, it deserves to be further investigated in randomized clinical trials.

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Babaodan Capsule (八宝丹胶囊) combined with Qingyi Huaji Formula (清胰化积方) in advanced pancreatic cancer—a feasibility study

Abstract

Objective

To observe the clinical effects of Babaodan Capsule (八宝丹, BBD) combined with Qingyi Huaji Formula (清胰化积方, QYHJ) in treating patients with advanced pancreatic cancer.

Methods

Results

Conclusions

BBD with QYHJ is feasible treatment to prolong the survival of patients with advanced pancreatic cancer. However, it deserves to be further investigated in randomized clinical trials.

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A population level atlas of Mus musculus craniofacial skeleton and automated image-based shape analysis

A population level atlas of Mus musculus craniofacial skeleton and automated image-based shape analysis:

Abstract

Laboratory mice are staples for evo/devo and genetics studies. Inbred strains provide a uniform genetic background to manipulate and understand gene–environment interactions, while their crosses have been instrumental in studies of genetic architecture, integration and modularity, and mapping of complex biological traits. Recently, there have been multiple large-scale studies of laboratory mice to further our understanding of the developmental basis, evolution, and genetic control of shape variation in the craniofacial skeleton (i.e. skull and mandible). These experiments typically use micro-computed tomography (micro-CT) to capture the craniofacial phenotype in 3D and rely on manually annotated anatomical landmarks to conduct statistical shape analysis. Although the common choice for imaging modality and phenotyping provides the potential for collaborative research for even larger studies with more statistical power, the investigator (or lab-specific) nature of the data collection hampers these efforts. Investigators are rightly concerned that subtle differences in how anatomical landmarks were recorded will create systematic bias between studies that will eventually influence scientific findings. Even if researchers are willing to repeat landmark annotation on a combined dataset, different lab practices and software choices may create obstacles for standardization beyond the underlying imaging data. Here, we propose a freely available analysis system that could assist in the standardization of micro-CT studies in the mouse. Our proposal uses best practices developed in biomedical imaging and takes advantage of existing open-source software and imaging formats. Our first contribution is the creation of a synthetic template for the adult mouse craniofacial skeleton from 25 inbred strains and five F1 crosses that are widely used in biological research. The template contains a fully segmented cranium, left and right hemi-mandibles, endocranial space, and the first few cervical vertebrae. We have been using this template in our lab to segment and isolate cranial structures in an automated fashion from a mixed population of mice, including craniofacial mutants, aged 4–12.5 weeks. As a secondary contribution, we demonstrate an application of nearly automated shape analysis, using symmetric diffeomorphic image registration. This approach, which we call diGPA, closely approximates the popular generalized Procrustes analysis (GPA) but negates the collection of anatomical landmarks. We achieve our goals by using the open-source advanced normalization tools (ANT) image quantification library, as well as its associated R library (ANTsR) for statistical image analysis. Finally, we make a plea to investigators to commit to using open imaging standards and software in their labs to the extent possible to increase the potential for data exchange and improve the reproducibility of findings. Future work will incorporate more anatomical detail (such as individual cranial bones, turbinals, dentition, middle ear ossicles) and more diversity into the template.

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The oral proteasome inhibitor ixazomib (Ninlaro®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy.

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma:

Abstract

The oral proteasome inhibitor ixazomib (Ninlaro^®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study). A significantly longer time to progression and favourable hazard ratios for PFS were observed across all prespecified subgroups, including patients with high cytogenetic risk. Overall response was achieved in a significantly higher proportion of patients receiving ixazomib- than placebo-based treatment. Ixazomib had a manageable tolerability profile in patients with MM. Ixazomib is the first orally-administered proteasome inhibitor approved for patients with MM, and in combination with lenalidomide and dexamethasone represents an important new option for use in patients with relapsed and/or refractory MM who have previously received at least one prior therapy.

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The angry chef who's fed up with fad diets - Spectator.co.uk

Spectator.co.uk

The angry chef who's fed up with fad diets
Spectator.co.uk
This character explores these issues in expletive-strewn diatribes, railing against those who sing the physiological virtues of tongue-scrapers and coffee enemas. Warner holds a degree in biochemistry, and has spent 25 years in the food ... He shines a ...

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Clenbuterol hcg nolvadex - Nolvadex sex - Breast cancer drugs like tamoxifen - Track Em Tigers

Track Em Tigers

Clenbuterol hcg nolvadex - Nolvadex sex - Breast cancer drugs like tamoxifen
Track Em Tigers
Side effects of chemotherapy drugs for breast cancer comes to no que tongue and both clinical the something in negatives this and vision stop. thick and by no occurs while confusion leave is resulted and hurting months my of developed said doctors food ...

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Rapid response to clinical symptoms in early psoriatic onycho-pachydermo-periostitis treated with infliximab

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Dermatological learning needs among aboriginal health workers in rural and remote Australia: A cross-sectional survey

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Lepromatous leprosy with Lucio's phenomenon

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Maculopapular type drug eruption caused by garenoxacin mesilate hydrate: A case report and literature review

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Necrobiosis lipoidica following Q-switched laser tattoo removal

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Pyoderma gangrenosum arising during treatment of psoriasis with adalimumab: Effectiveness of ustekinumab

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Febrile headache and leg weakness as the initial symptoms of tickborne encephalitis

Description

A 61-year-old woman presented to the emergency department (ED) with a 1-week fever associated with progressive headache. She also reported weakness and paraesthesias in both legs. In the ED, the patient had normal vital parameters and reported no other medical history. Clinical examination showed a slight neck stiffness; the rest of the examination was normal. Laboratory findings showed a mild inflammatory syndrome. The patient had a lumbar punction; the cerebrospinal fluid (CSF) showed moderate pleocytosis (140 leucocytes/μL with a mononuclear cell dominance). After a normal CT scan, an MRI examination was performed (figures 1and 2). Several days later, intrathecal IgM and IgG antibodies came back positive.

Figure 1

T2-weighted transverse MRI. Localised hyperintense band involving the tegmentum pontis (arrow heads) and the cerebellar vermis (arrow).

Figure 2

Coronal MRI, fluid attenuation inversion recovery...

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Optical Technology Detects Cancer With High Accuracy During Surgery

An intraoperative, multimodal optical cancer detection system can detect brain cancer with high degrees of accuracy, sensitivity, and specificity in real time during surgery, according to a new study. (Source: CancerNetwork)

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Nivolumab Maintained QOL in Advanced Squamous Cell Head and Neck Cancer

Patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with the checkpoint inhibitor nivolumab were able to maintain baseline levels of quality of life. (Source: CancerNetwork)

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Letter to the editor regarding “Blood count values and ratios for predicting sleep apnea in obese children”

We are writing in reference to a study published in your journal titled 'Blood count values and ratios for predicting sleep apnea in obese children' by Erdim I, et al. [1] They concluded that NLR, PLR and RDW were found to be significantly higher in children whose AHI was ≥5 than in children from the other groups. We are very impressed about the study, and enjoyed reading it. It is noteworthy that their article is the first paper to investigate whether various CBC test parameters could provide a method for diagnosing and determining the severity of OSAS in obese children.

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Letter to the editor regarding “Blood count values and ratios for predicting sleep apnea in obese children”

We are writing in reference to a study published in your journal titled 'Blood count values and ratios for predicting sleep apnea in obese children' by Erdim I, et al. [1] They concluded that NLR, PLR and RDW were found to be significantly higher in children whose AHI was ≥5 than in children from the other groups. We are very impressed about the study, and enjoyed reading it. It is noteworthy that their article is the first paper to investigate whether various CBC test parameters could provide a method for diagnosing and determining the severity of OSAS in obese children.

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“The Anatomy of the Medial Antebrachial Cutaneous Nerve and its Significance in Ulnar Nerve Surgery – an Anatomical Study”

During cubital tunnel surgery, the medial antebrachial cutaneous nerve (MACN) may be injured, causing painful scars, neuromas, hypaesthesia or hyperalgesia. As the literature on the anatomy of crossing branches in this area is contradictory, this study aimed to re-examine the anatomy of the MACN in this region.

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Iain Duncan Smith fails to cough up the goods in Radio 2 debut - Telegraph.co.uk

Telegraph.co.uk

Iain Duncan Smith fails to cough up the goods in Radio 2 debut
Telegraph.co.uk
Hearing him doing two hours live on Radio 2, sitting in for Jeremy Vine, coughing away background and foreground, is bound to have the show's seven million listeners sending him syrups, tinctures, lozenges. We worried about Ed Miliband's tonsils last ...

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Necrotising coronaritis with fatal outcome

A 56-year-old woman presented with acute onset of typical chest pain. She was diagnosed with acute coronary syndrome with ST-segment elevation myocardial infarction. Although significant obstructive coronary artery disease was ruled out by coronary angiography, cardiac MRI showed transmural necrosis of the lateral free wall with extensive microvascular obstruction consistent with ischaemic heart disease. Within 48 hours after initial presentation, the patient suddenly arrested due to pulseless electrical activity with futile resuscitation efforts. Autopsy revealed myocardial perforation with extensive haematothorax due to pericardial laceration, caused by the mechanical chest compressions. Eventually, histology identified diffuse necrotising coronary vasculitis as a rare cause of ischaemic heart disease.

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Effects of phylogeny and locomotor style on the allometry of body mass and pelvic dimensions in birds

Abstract

The pelvic girdle provides physical support and attachment for the hind limb musculature. In birds there is variability in pelvic morphology across different orders and this has been used as evidence for various types of locomotion. However, the morphological variation of pelvic bones has yet to be studied systematically in birds. Therefore, we investigated basic allometric relationships among female body mass (as a size proxy) and various pelvic measurements in a phylogenetic context. We also examined in detail the inter-relationships among various pelvic measurements. Also considered were the effects of broader taxonomic relationships at the level of order, with further examination of the influence of style of terrestrial locomotion on the allometric relationships. Positive relationships were initially found among all pelvic linear measurements and female body mass (FBM). The relationships among measures of pelvic width and FBM were isometric, whereas those between pelvic length and FBM showed positive allometry. Also, FBM explained more of the variance in pelvic length than in width. Similarly, the angle of the pelvis had a significant negative relationship, but FBM only explained a very low proportion of the variation in pelvic angles. In general terms, ancova showed that the effect of FBM was smaller than the effect of locomotor style in this species set. Both the synsacrum and pelvic girdle play roles in weight support and therefore scale in proportion to body weight accordingly. All three parts of the pelvis (ilium, ischium and pubis) are attached around the acetabulum and also provide muscle attachment points, so it might be expected for them to scale in a similar manner. Increased angulation of the pelvis is linked to orders which employ their hind limbs in feeding, perching and running, although FBM also explains a very low proportion of the variation in pelvic angle. Muscle attachment and the confines on morphology presented by locomotion explain much of the variation exhibited by the relationships among pelvic measurements.

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Cost analysis of microtia treatment in the Netherlands

Ear reconstruction for microtia is a challenging procedure. Although analyzing aesthetic outcome is crucial, there is a paucity of information with regard to financial aspects of microtia reconstruction. This study was conducted to analyze the costs associated with ear reconstruction with costal cartilage in patients with microtia.

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Bilateral Buccinator Myomucosal Flap Outcomes in Nonsyndromic Patients with Repaired Cleft Palate and Velopharyngeal Insufficiency

The purpose of this study was to assess speech outcomes and complication rate in nonsyndromic repaired cleft palate patients undergoing bilateral buccinator myomucosal flaps for velopharyngeal insufficiency management.

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Clinical, histological and ultrasound follow-up of the breast reconstruction with one-stage muscle sparing “wrap” technique: a single-center experience

Prepectoral implant placement and complete coverage with porcine acellular matrix after mastectomy is a new concept in breast surgery presented in few cases in literature. The aim of this paper is to present our single center experience in one-stage breast reconstruction muscle sparing "wrap" technique by evaluating clinical and aesthetic outcomes, ultrasound and histological examination and patient quality of life.

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The long-term impact of oncoplastic breast conserving surgery using Latissimus Dorsi miniflaps on mammographic surveillance and the detection of local recurrence

Latissimus Dorsi Miniflap is a breast-conserving volume replacement technique for reconstruction of large breast defects. While mammographic features of Mini Flap reconstruction have been described, little is known about the incidence, mode of presentation and size of local recurrence after this procedure. The aim of this study was to investigate the impact of Latissimus Dorsi Miniflap reconstruction on frequency, presentation and detection of local recurrence.

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Interstitial fluid flow-induced growth potential and hyaluronan synthesis of fibroblasts in a fibroblast-populated stretched collagen gel culture

Publication date: Available online 28 June 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Natsumi Saito, Hiroaki Adachi, Hiroshi Tanaka, Satoru Nakata, Norifumi Kawada, Ken Oofusa, Katsutoshi Yoshizato
BackgroundTensioned collagen gels with dermal fibroblasts (DFs) as a dermis model are usually utilized in a static culture (SC) that lacks medium flowing. To make the model closer to its in vivo state, we created a device to perfuse the model with media flowing at a physiological velocity and examined the effects of medium flow (MF) on the cultures.MethodsWe constructed a medium perfusion device for human DF-embedded stretched collagen gels (human dermis model), exposed the model to media that flows upwardly at ~1mL/day, and examined water retention of the gels, cells' growth ability, metabolic activity, expression profiles of nine extracellular matrix (ECM)-related genes. The obtained data were compared with those from the model in SC.ResultsMF increases the gels' water retention and cells' growth potential but had little effect on their metabolic activities. MF robustly enhanced hyaluronan synthase 2 (HAS2) and matrix metalloprotease 1 (MMP1) gene expressions but not of the other genes (MMP2, HYAL1, HYAL2, HYAL3, COL1A1, COL3A1, and CD44). MF significantly increased the amounts of cellular hyaluronan and adenosine triphosphate.ConclusionsThe MF at a physiological speed significantly influences the nature of ECMs and their resident fibroblasts and remodels ECMs by regulating hyaluronan metabolism.General significanceFibroblasts in tensioned collagen gels altered their phenotypes in a MF rate-dependent manner. Collagen gel culture with tension and MF could be utilized as an appropriate in vitro model of interstitial connective tissues to evaluate the pathophysiological significance of mechanosignals generated by fluid flow and cellular/extracellular tension.

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IgG glycan patterns are associated with type 2 diabetes in independent European populations

Publication date: Available online 28 June 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Roosmarijn F.H. Lemmers, Marija Vilaj, Daniel Urda, Felix Agakov, Mirna Šimurina, Lucija Klaric, Igor Rudan, Harry Campbell, Caroline Hayward, Jim F. Wilson, Aloysius G. Lieverse, Olga Gornik, Eric J.G. Sijbrands, Gordan Lauc, Mandy van Hoek
BackgroundType 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.MethodsIn the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.ResultsAfter correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.ConclusionsSeveral IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.General significanceThis work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.

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Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study

Summary

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m²) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

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Lack of effects of a “sobering‘ product, “Eezup!’, on the blood ethanol and congener alcohol concentration

The quest for "sobering" compounds to counteract the effects of alcohol and to alleviate hangover symptoms reaches far back into ancient times. While such a remedy was recommended placing a wreath of parsley on the head, more recent times have seen a popular rise in the use of commercially available "booze busting" products. In Germany, products with names like "Pekasin," "Elektrovid," "Contra," "Stop," "Promill-Ex," "Mobiletten," "Neukamm-Limonade," "Party-Plus," or "Break Down," to name a few [1], each briefly caught the attention of the media, when they were launched on the market and were advertised as new wonder drugs that could sensationally boost the breakdown of alcohol or alleviate hangovers [2].

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Preface to the Special Issue Bioeconomy

Publication date: Available online 28 June 2017
Source:New Biotechnology
Author(s): Alfredo Aguilar, Roland Wohlgemuth, Tomasz Twardowski

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Bio-based Industries Joint Undertaking: The catalyst for sustainable bio-based economic growth in Europe

Publication date: Available online 27 June 2017
Source:New Biotechnology
Author(s): Philippe Mengal, Marcel Wubbolts, Eleni Zika, Ana Ruiz, Dieter Brigitta, Agata Pieniadz, Sarah Black
This article discusses the preparation, structure and objectives of the Bio-based Industries Joint Undertaking (BBI JU). BBI JU is a public-private partnership (PPP) between the European Commission (EC) and the Bio-based Industries Consortium (BIC), the industry-led private not-for-profit organisation representing the private sectors across the bio-based industries. The model of the public-private partnership has been successful as a new approach to supporting research and innovation and de-risking investment in Europe. The BBI JU became a reality in 2014 and represents the largest industrial and economic cooperation endeavour financially ever undertaken in Europe in the area of industrial biotechnologies. It is considered to be one of the most forward-looking initiatives under Horizon 2020 and demonstrates the circular economy in action. The BBI JU will be the catalyst for this strategy to mobilise actors across Europe including large industry, small and medium-sized enterprises (SMEs), all types of research organisations, networks and universities. It will support regions and in doing so, the European Union Member States and associated countries in the implementation of their bioeconomy strategies.

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A Prospective, Randomized Comparison of Lower Eyelid Retraction Repair With Autologous Auricular Cartilage, Bovine Acellular Dermal Matrix (Surgimend), and Porcine Acellular Dermal Matrix (Enduragen) Spacer Grafts.

Purpose: To compare outcomes of lower eyelid retraction repair with 3 types of spacer grafts: autologous auricular cartilage, bovine acellular dermal matrix (Surgimend, Integra, Plainsboro, NJ), porcine acellular dermal matrix (Enduragen, Stryker, Kalamazoo, MI). Methods: A prospective, randomized clinical trial was conducted in patients undergoing lower eyelid retraction repair with spacer graft. Subjects received autologous auricular cartilage, bovine acellular dermal matrix, or porcine acellular dermal matrix between June 2015 and July 2016. Patient demographics, margin to reflex distance 2, conjunctival injection, eyelid swelling, tearing, discomfort, itching, and complications were recorded preoperatively and at postoperative week 1, month 1, month 3, and month 6. Results: Of the 49 randomized lower eyelids (39 patients), 42 eyelids (32 patients) completed the study. The preoperative margin to reflex distance 2, conjunctival injection, eyelid swelling, tearing, discomfort, and itching showed no statistical difference. Postoperative week 1 swelling was statistically significantly higher in auricular cartilage, followed by bovine acellular dermal matrix, then porcine acellular dermal matrix (p = 0.04). The mean postoperative month 6 margin to reflex distance 2 trended toward a better outcome from auricular cartilage over bovine acellular dermal matrix (p = 0.029), but after p was adjusted for multiple pairwise comparisons, this was no longer statistically significant (p = 0.088). All other postoperative 6-month measurements showed no statistical difference. Conclusions: Among patients randomized to 3 types of spacer grafts for lower eyelid retraction repair, outcomes were not statistically significant different when the 3 groups were compared. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Morphometric Analysis of the Orbital Process of the Palatine Bone and its Relationship to Endoscopic Orbital Apex Surgery.

Background: Endoscopic approaches to the orbit improve the ability to directly access apical lesions while minimizing manipulation of normal structures. Inferomedial orbital access is limited by the orbital process of the palatine bone (OPPB) which prevents dissection and retraction in the inferolateral vector. Objective: The objective of this study was to examine the morphometric characteristics of the OPPB and quantify the benefit of complete resection to surgical access. Methods: Morphometric osteologic measurements of the OPPB were performed in 59 human skulls. A radius subtended by the OPPB was calculated to generate a hemispheric dissection corridor achievable by complete resection of the OPPB. Cadaveric and live surgical dissections were then performed on 15 orbits to develop discreet endoscopic surgical landmarks which could be used to both identify the OPPB and verify complete resection. Results: The mean(+/- SD) radius of the OPPB was 0.47 +/- 0.28 cm. Complete OPPB resection provided an additional 0.36 +/- 0.42 cm3 of surgical exposure within the inferomedial apex. Relative to the Caucasian (n = 27) skulls, the radii in the Asian (n = 27) and African (n = 5) skulls were significantly smaller (p

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Ablative Fractional Laser Resurfacing With Laser-Assisted Delivery of 5-Fluorouracil for the Treatment of Cicatricial Ectropion and Periocular Scarring.

Purpose: Cicatricial ectropion and periocular scarring can cause significant functional and cosmetic deficits. Surgical treatments can be associated with recicatrization, donor site morbidity, and textural and pigmentary abnormalities. This case series reports on efficacy and safety of a novel nonsurgical approach to treating cicatricial ectropion using ablative fractional laser resurfacing and laser-assisted delivery of 5-fluorouracil. Methods: A retrospective review was conducted of all patients at a single institution who received >=3 rounds of ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil. Six patients with cicatricial ectropion and periocular scarring secondary to reconstructive surgery, traumatic lacerations, and facial burns were included. Aesthetic and functional improvement were evaluated via fluorescein staining, tear breakup time, external photography, questionnaires gauging dry eye symptoms, and scar appearance. Results: All patients showed functional improvement based on fluorescein staining (mean improvement 6.0 +/- 1.4; p = 0.0007) and other indicators of dry eye. All 4 patients with lagophthalmos improved and 2 showed complete resolution. All patients demonstrated significant cosmetic improvement based on a validated scar assessment questionnaire (mean improvement 37.5 +/- 18.9; p = 0.004), and 5 of 6 patients reported improved satisfaction with scar appearance (mean improvement 19.3 +/- 12.8; p = 0.014). There were no adverse effects reported. Conclusions: Ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil appears to be a safe and effective modality for treating the functional and aesthetic abnormalities associated with periocular scarring, yielding results that are difficult to attain through surgery alone. Optimal management of cicatricial ectropion and periocular scarring often requires multimodality treatment, and ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil may be considered as part of a comprehensive approach to managing periocular scars. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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The Biotechnology and Bioeconomy Landscape in Malaysia

Publication date: Available online 28 June 2017
Source:New Biotechnology
Author(s): Mahaletchumy Arujanan, Muthu Singaram
Since 1990s Malaysia aspired to make biotechnology and bioeconomy as her engines of economic growth to utlise the abundance of natural resources and biodiversity. The public sector plays an integral role in developing the sector and various incentives are in place for the private sector to be actively involved and to forge collaboration with the public sector. The country launched its National Biotechnology Policy in 2005 and later launched its National Bioeconomy Programme in 2010 to become the first country in South East Asia and second in Asia after China to have such an initiative. Malaysia is also very proactive in its biosafety law and regulations and has most of the related legal instrument in place. A lot of success has been recorded since the inception of the National Biotechnology Policy in terms of job creation, contribution to GDP through biobusinesses and investment from foreign companies, but the sector is not spared from challenges too. Due to the nature of the discipline that is multidisciplinary and that requires huge amount of investment, expertise and political will, there are a lot of barriers before the country emerges as a bioeconomy player. This paper discusses the public policies, initiatives and funding mechanisms in place in Malaysia that drive its research, development and commercialisation in the area of biotechnology and bioeconomy. The authors also discuss the challenges faced in Malaysia in implementing the policies.

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Plasma amylase and lipase concentrations in captive black-tailed prairie dogs ( Cynomys ludovicianus )

Abstract

This study was conducted in order to determine plasma amylase and lipase concentrations in captive black-tailed prairie dogs (Cynomys ludovicianus). Twenty-six healthy intact captive prairie dogs of both sexes were studied as part of an overall clinical health evaluation performed under general isoflurane anesthesia. Each animal underwent a complete physical examination, complete blood count, plasma biochemistry, and venous blood gas analysis. Venous blood samples were placed in heparinized blood-collection tubes and submitted for plasma amylase and lipase concentration analyses. The reference interval for amylase was 111.3–499.1 IU/L, and the mean and median plasma amylase concentrations were 323.2 and 341 IU/L, respectively (min = 152 IU/L, max = 481 IU/L). The reference interval for lipase was 25.7–78.4 IU/L, and the mean and median plasma lipase concentrations were both 49.5 IU/L (min = 27 IU/L, max = 80 IU/L). The new data presented in this report can promote better physiological understanding and improve clinical management of this rodent species.

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Primary form of malignant melanoma in an ovarian mature cystic teratoma: case report and literature review

Abstract

Germ cell tumours are a common form of ovarian neoplasm; the most common of which is mature cystic teratoma. However, transformation into malignant melanoma is rare. Here, we present a case of a primary malignant melanoma in an ovarian mature cystic teratoma with literature review. A 63-year-old woman presented at our hospital with abdominal distension and pain. Physical examination showed a mobile, non-tender, abdominopelvic mass. Radiological examination revealed a cystic mass with mixed echogenicity. Histopathological review disclosed a primary malignant melanoma arising in an ovarian mature cystic teratoma. The patient died 28 months after the initial diagnosis. Although it is rare for ovarian neoplasms to transform into malignant melanoma in a mature cystic teratoma, it can happen and physicians should be aware of this exceptional kind of malignancy.

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Clinicopathological impact of CD20 expression in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL)

Abstract

Recognition of BCR/ABL translocation is obligatory in precursor B cell precursor acute lymphoblastic leukemia (BCP-ALL) patients at diagnosis for categorization of patients. The risk stratification of BCP-ALL especially those negative for Philadelphia chromosome is an area of research. The prognostic impact of CD20 expression in childhood BCP-ALL remains controversial. In pediatric patients with BCP-ALL, some studies have demonstrated that CD20 overexpression correlates with bad overall survival, but some others suggest a better outcome. This study aimed to evaluate the efficacy of CD20 expression as a biological marker in BCP-ALL. For 104 children with newly diagnosed BCP-ALL included in this study, CD20 expression was evaluated by flow cytometry. CD20 was positively expressed in 40 (38.5%) of cases. The CD20^positive subgroup had significantly shorter overall survival and disease free survival as compared to the CD20^negative one (P = 0.018; <0.001, respectively). Combined positivity for CD20 and Philadelphia chromosome was detected in 16/40 of studied cases. This patient group had the poorest overall survival and the shortest disease-free survival. In conclusion, CD20 expression at diagnosis in BCP-ALL is a useful biomarker for risk stratification and subsequently in treatment decision especially in Philadelphia negative BCP-ALL.

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Phyllodes tumors are an uncommon differential diagnosis of axillary mass

Abstract

Phyllodes tumors are rare fibroepithelial neoplasm that account for less than 0.5% of all breast tumors and presentation in ectopic breast tissue is even rarer. In this paper, we describe a case of a phyllodes tumor in the ectopic breast tissue of the axilla. A 40-year-old woman presented with a well-circumscribed, firm, and freely mobile mass in the left axilla from 1 year ago. Ultrasound revealed a 5.5 × 4.5 × 4.5 cm homogenous and hypoecho lesion. The histopathologic analysis revealed that it was a benign phyllodes tumor. Phyllodes tumors in ectopic breast tissue may be confirmed to be a diagnostic difficulty, and this concept must be kept in mind while dealing with an axillary mass.

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Diagnostic value of neutrophil-lymphocyte ratio versus C-reactive protein in discrimination between different pathogens causing community-acquired pneumonia

Abstract

Early discrimination of the causative organisms of community-acquired pneumonia (CAP) is important. The aim of the present study is to evaluate neutrophil–lymphocyte ratio (NLR) and derived NLR (dNLR) as adjunct tests to differentiate different types of CAP. NLR, dNLR, and C-reactive protein (CRP) were measured in 187 patients with CAP. Identification of causative organisms was done by direct smears, microbiological cultures, VITEK 2 compact system, and PCR of patient's sputa together with detection of specific IgM antibodies against Chlamydia pneumoniae. There was a significant increase of NLR and CRP values in patients with bacterial pneumonia as compared to patients with TB and patients with atypical pneumonia. NLR and CRP were significantly higher in atypical than TB pneumonia. Although dNLR was significantly higher in both bacterial and atypical than TB pneumonia, it was insignificantly differ between bacterial and atypical pneumonia. For discriminating bacterial CAP from TB, the area under curve (AUC) for NLR was found to be significantly higher than that of CRP at cutoff values of 7.8 for NLR and 172.9 mg/l for CRP. Also, at cutoff values of 6.6 for NLR and 179.1 mg/l for CRP, NLR distinguished bacterial from atypical pneumonia more accurately than CRP (AUC = 0.92 versus 0.74). There was no significant difference in inflammatory marker levels between subcategories of atypical pneumonia except for CRP. There was a significant positive correlation between NLR and CRP in pneumonic patients (r = 0.71, p = 0.000). NLR is easy to be calculated from daily practice and might be used as a surrogate marker to differentiate bacterial CAP from atypical and TB pneumonia as well as atypical from TB pneumonia but could not discriminate the different pathogens causing atypical bacterial pneumonia. dNLR could discriminate TB from both bacterial and atypical pneumonia but could not differentiate bacterial from atypical pneumonia.

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Clinical and paraclinical effects of transportation on miniature and domestic donkeys

Abstract

Transportation of live animals is an inevitable husbandry practice and has been identified as one of the main causes of stress. Miniature donkeys, because of their rarity and entertainment value, occupy a unique place among all domesticated animals in some countries. We hypothesized that transportation stress would produce changes in clinical and biochemical parameters of domestic and miniature donkeys (Equus africanus asinus). Ten clinically healthy donkeys were selected for this study. The overall study population was almost equally subdivided into six subgroups according to the breed (domestics and miniatures), sex (males and non-pregnant non-lactating females) and age (foals and adults). Donkeys up to 2 years of age and over 3 years old were called foals and adults, respectively. Heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were measured before and after transport. Serum concentrations of chloride (Cl⁻), calcium (Ca²⁺), sodium (Na⁺), potassium (K⁺), magnesium (Mg²⁺) and phosphorus (P⁻) were measured. Following the transportation, serum concentrations of Ca²⁺, Na⁺ and K⁺ were significantly reduced in all the donkeys (p < 0.05). There were no significant differences in P⁻, Cl⁻ and Mg²⁺ levels before and after transportation. There were significant decreases in serum concentrations of Ca²⁺ and K⁺ in domestic, female and adult subgroups and in Na⁺ levels in male and foal subgroups. According to the results of this study, transportation generally affects the physiological and biochemical status of domestic and miniature donkeys, regardless of interspecies differences. However, more studies are required to differentiate between the effects of transportation and effects of food and water deprivation during transport.

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RAPD-PCR analysis of Staphylococcus aureus strains isolated from different sources

Abstract

Determination of genetic relationship among Staphylococcus aureus isolates is important for epidemiological surveillance and control of infections caused by this bacterium. The present study was conducted to determine the molecular diversity of S. aureus strains isolated from human, bovine, and food samples using random amplified polymorphic DNA (RAPD)-PCR method. A total of 208 S. aureus strains including 60 human (patients and healthy carriers), 83 bovine milk, and 65 food (pastry and cheese) isolates were assessed. The isolates were confirmed to be methicillin-resistance/susceptible S. aureus (MRSA or MSSA) using common biochemical tests and a species-specific PCR, and finally, they were genetically typed using RAPD-PCR method. Forty-seven RAPD profiles (13, 21, and 15 profiles for isolates from human, bovine, and food samples, respectively) were identified in the examined isolates. Based on these profiles and the constructed dendrogram, all of 208 S. aureus strains were divided into nine major clusters from A to I, at 80% similarity. Some clusters (A, B, C, E, and H) contained S. aureus strains isolated from only one source, while the others (D, F, G, and I) contained isolates from more than one source. The results revealed that although most of S. aureus strains of the same source were placed in certain clusters, there were also some strains of different sources which shared the same RAPD profiles indicating possible transmission of S. aureus strains (especially MRSA ones) among different hosts. Thus, effective hygiene measures should be considered to break transmission chains.

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Infundibulocystic basal cell carcinoma of the eyelid

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Pattern of skin diseases among patients attending an outpatient dermatology clinic in a tertiary hospital in urban Malaysia

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Clinical and dermoscopic features of targetoid haemosiderotic naevus: A peculiar melanoma simulator

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Fibroblast-Like Synoviocyte Mechanosensitivity to Fluid Shear is Modulated by Interleukin-1α

Publication date: Available online 28 June 2017
Source:Journal of Biomechanics
Author(s): Eben G. Estell, Lance A. Murphy, Amy M. Silverstein, Andrea R. Tan, Roshan P. Shah, Gerard A. Ateshian, Clark T Hung
Fibroblast-like synoviocytes (FLS) reside in the synovial membrane of diarthrodial joints and are exposed to a dynamic fluid environment that presents both physical and chemical stimuli. The ability of FLS to sense and respond to these stimuli plays a key role in their normal function, and is implicated in the alterations to function that occur in osteoarthritis (OA). The present work characterizes the response of FLS to fluid flow-induced shear stress via real-time calcium imaging, and tests the hypothesis that this response is modulated by interleukin-1α (IL-1α), a cytokine elevated in OA. FLS demonstrated a robust calcium signaling response to fluid shear that was dose dependent upon stress level and required both external and internal calcium sources. Preconditioning with 10 ng/mL IL-1α for 24 hrs heightened this shear stress response by significantly increasing the percent of responding cells and peak magnitude, while significantly decreasing the time for a peak to occur. Intercellular communication via gap junctions was found to account for a portion of the FLS population response in normal conditions, and was significantly increased by IL-1α preconditioning. IL-1α was also found to significantly increase average length and incidence of the primary cilia, an organelle commonly implicated in shear mechanosensing. These findings suggest that the elevated levels of IL-1α found in the OA environment heighten FLS sensitivity to fluid shear by altering both intercellular communication and individual cell sensitivity, which could affect downstream functions and contribute to progression of the disease state.

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Evaluation of thermal stability of confectionary sunflower protein isolate and its effect on nanoparticulation and particle size of the produced nanoparticles

Abstract

In this study, the effect of different defatting conditions on heat stability of confectionary sunflower protein isolate (SnPI) and the particle size of the produced nanoparticles was investigated. The evaluated factors included temperatures of defatting (40, 50, and 60 °C), time of defatting (2, 6, and 10 h), and the amount of activated carbon (0, 25, and 50% of sample weight). The results of the central composite design showed a significant effect (P < 0.05) among the studied factors, where denaturation temperature and particle size of SnPI nanoparticles were found to be in the ranges of 75.05–89.12 °C and 268–1594 nm, respectively. Moreover, the interaction of activated carbon with temperature and time of defatting proved to be influential factors for the heat stability of confectionary SnPI.

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Ecobiophysical Aspects on Nanosilver Biogenerated from Citrus reticulata Peels, as Potential Biopesticide for Controlling Pathogens and Wetland Plants in Aquatic Media

In recent years, a considerable interest was paid to ecological strategies in management of plant diseases and plant growth. Metallic nanoparticles (MNPs) gained considerable interest as alternative to pesticides due to their interesting properties. Green synthesis of MNPs using plant extracts is very advantageous taking into account the fact that plants are easily available and eco-friendly and possess many phytocompounds that help in bioreduction of metal ions. In this research work, we phytosynthesized AgNPs from aqueous extract of Citrus reticulata peels, with high antioxidant, antibacterial, and antifungal potential. These "green" AgNPs were characterized by modern biophysical methods (absorption and FTIR spectroscopy, AFM, and zeta potential measurements). The nanobioimpact of Citrus-based AgNPs on four invasive wetland plants, Cattail (Typha latifolia), Flowering-rush (Butomus umbellatus), Duckweed (Lemna minor), and Water-pepper (Polygonum hydropiper), was studied by absorption spectroscopy, by monitoring the spectral signature of chlorophyll. The invasive plants exhibited different behavior under AgNP stress. Deep insights were obtained from experiments conducted on biomimetic membranes marked with chlorophyll a. Our results pointed out the potential use of Citrus-based AgNPs as alternative in controlling pathogens in aqueous media and in management of aquatic weeds growth.

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Insomnia and Its Temporal Association with Academic Performance among University Students: A Cross-Sectional Study

Introduction. Studies show that 9.4% to 38.2% of university students are suffering from insomnia. However, research data in developing countries is limited. Thus, the aim of the study was to assess insomnia and its temporal association with academic performance. Methods and Materials. Institution based cross-sectional study was conducted with 388 students at Debre Berhan University. Data were collected at the nine colleges. Logistic and linear regression analysis was performed for modeling insomnia and academic performance with a value threshold of 0.05, respectively. Data were entered using EPI-data version 3.1 and analyzed using SPSS version 20. Results. The prevalence of insomnia was 61.6%. Field of study ( value = 0.01), worshiping frequency ( value = 0.048), marital status ( value = 0.03), and common mental disorder ( value

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Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.

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Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges

Recombinant immunotoxins (RITs) refer to a group of recombinant protein-based therapeutics, which consists of two components: an antibody variable fragment or a specific ligand that allows RITs to bind specifically to target cells and an engineered toxin fragment that kills the target cells upon internalization. To date, over 1,000 RITs have been generated and significant success has been achieved in the therapy of hematological malignancies. However, the immunogenicity and off-target toxicities of RITs remain as significant barriers for their application to solid tumor therapy. A group of RITs have also been generated for the treatment of glioblastoma multiforme, and some have demonstrated evidence of tumor response and an acceptable profile of toxicity and safety in early clinical trials. Different from other solid tumors, how to efficiently deliver the RITs to intracranial tumors is more critical and needs to be solved urgently. In this article, we first review the design and expression of RITs, then summarize the key findings in the preclinical and clinical development of RIT therapy of glioblastoma multiforme, and lastly discuss the specific issues that still remain to forward RIT therapy to clinical practice.

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Clinical Features and Treatments of Syphilitic Uveitis: A Systematic Review and Meta-Analysis

Purpose. To investigate the clinical features and efficacies of treatments for syphilitic uveitis. Methods. PubMed was searched for studies of syphilitic uveitis published between January 1990 and October 2016. The clinical features were summarized and appraised. The pooled success rate was defined as an improved or maintained final visual acuity and was calculated with 95% confidence intervals (CIs). Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were assessed. Results. Thirty-two studies involving 670 patients were analyzed. The most common type of syphilitic uveitis was papillitis. The pooled success rate was 0.91 (95% CI 0.84–0.97) for antibacterial agents alone (15 studies, 286 patients); 0.95 (95% CI 0.91–0.98) for antibacterial agents and systemic corticosteroids combined (11 studies, 245 patients); and 0.91 (95% CI 0.80–0.98) for antibacterial agents, systemic corticosteroids, and other immunosuppressants combined (3 studies, 73 patients). Subgroup analyses revealed no correlations of the efficacy of antibacterial agent monotherapy with study characteristics, such as human immunodeficiency virus coinfection status. Conclusions. This systematic review and meta-analysis revealed the efficacy of antibacterial agents for treating syphilitic uveitis. Coadministration of systemic corticosteroids or immunosuppressants did not elicit further improvements in the clinical outcomes of antibacterial agents.

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Evaluating the TRMM Multisatellite Precipitation Analysis for Extreme Precipitation and Streamflow in Ganjiang River Basin, China

Based on the observed precipitation data and TRMM (Tropical Rainfall Measuring Mission) 3B42 RTV7 and 3B42 V7 precipitation products from 2003 to 2010, the extreme precipitation and streamflow in the Ganjiang River basin were analyzed. The VIC hydrological model was used to simulate the streamflow driven by RTV7/V7 precipitation products in the Ganjiang River basin. The results show that () both of the RTV7 and V7 precipitation products have good applicability in precipitation estimation in the Ganjiang River basin and the correlation between the observed precipitation and RTV7 (V7) was as higher as 0.85 (0.86); () the RTV7/V7 precipitation products can well be used to simulate the streamflow by using the VIC hydrological model and the correlation between the observed streamflow and simulated streamflow driven by RTV7 (V7) products was as high as 0.86 (0.89); () the extreme precipitation varied greatly in the Ganjiang River basin and both of the RTV7 and V7 can capture the pattern of extreme precipitation in the Ganjiang River basin; however, higher extreme precipitation can be found in the northern Ganjiang River basin; () the extreme streamflow simulated driven by RTV7/V7 products agreed well with the observed extreme streamflow in the Ganjiang River basin. This study indicated that the TRMM 3B42 RTV7 and V7 products can be well used in the estimation of extreme precipitation and extreme streamflow.

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NMR Pore Structure and Dynamic Characteristics of Sandstone Caused by Ambient Freeze-Thaw Action

For a deeper understanding of the freeze-thaw weathering effects on the microstructure evolution and deterioration of dynamic mechanical properties of rock, the present paper conducted the nuclear magnetic resonance (NMR) tests and impact loading experiments on sandstone under different freeze-thaw cycles. The results of NMR test show that, with the increase of freeze-thaw cycles, the pores expand and pores size tends to be uniform. The experimental results show that the stress-strain curves all go through four stages, namely, densification, elasticity, yielding, and failure. The densification curve is shorter, and the slope of elasticity curve decreases as the freeze-thaw cycles increase. With increasing freeze-thaw cycles, the dynamic peak stress decreases and energy absorption of sandstone increases. The dynamic failure form is an axial splitting failure, and the fragments increase and the size diminishes with increasing freeze-thaw cycles. The higher the porosity is, the more severe the degradation of dynamic characteristics is. An increase model for the relationships between the porosity or energy absorption and freeze-thaw cycles number was built to reveal the increasing trend with the freeze-thaw cycles increase; meanwhile, a decay model was built to predict the dynamic compressive strength degradation of rock after repeated freeze-thaw cycles.

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A No-Equilibrium Hyperchaotic System and Its Fractional-Order Form

No-equilibrium system with chaotic behavior has attracted considerable attention recently because of its hidden attractor. We study a new four-dimensional system without equilibrium in this work. The new no-equilibrium system exhibits hyperchaos and coexisting attractors. Amplitude control feature of the system is also discovered. The commensurate fractional-order version of the proposed system is studied using numerical simulations. By tuning the commensurate fractional-order, the proposed system displays a wide variety of dynamical behaviors ranging from coexistence of quasiperiodic and chaotic attractors and bistable chaotic attractors to point attractor via transient chaos.

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Optimization of Deacetylation Process for Regenerated Cellulose Hollow Fiber Membranes

Cellulose acetate (CA) hollow fibers were spun from a CA+ Polyvinylpyrrolidone (PVP)/N-methyl-2-pyrrolidone (NMP)/H2O dope solution and regenerated by deacetylation. The complete deacetylation time of 0.5 h was found at a high concentration (0.2 M) NaOH ethanol (96%) solution. The reaction rate of deacetylation with 0.5 M NaOH was faster in a 50% ethanol compared to a 96 vol.% ethanol. The hydrogen bond between CA and tertiary amide group of PVP was confirmed. The deacetylation parameters of NaOH concentration, reaction time, swelling time, and solution were investigated by orthogonal experimental design (OED) method. The degree of cross-linking, the residual acetyl content, and the PVP content in the deacetylated membranes were determined by FTIR analysis. The conjoint analysis in the Statistical Product and Service Solutions (SPSS) software was used to analyze the OED results, and the importance of the deacetylation parameters was sorted as Solution > Swelling time > Reaction time > Concentration. The optimal deacetylation condition of 96 vol.% ethanol solution, swelling time 24 h, the concentration of NaOH (0.075 M), and the reaction time (2 h) were identified. The regenerated cellulose hollow fibers under the optimal deacetylation condition can be further used as precursors for preparation of hollow fiber carbon membranes.

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Clinical Effect of Electroacupuncture on Lung Injury Patients Caused by Severe Acute Pancreatitis

This study aimed to investigate the effects of electroacupuncture at the Lieque, Chize, and Zusanli points in patients with lung injury caused by severe acute pancreatitis. Patients with acute respiratory distress syndrome (ARDS) induced by severe acute pancreatitis (SAP) were randomly divided into three groups based on the treatment: conventional therapy alone (group A), electroacupuncture of nonacupoints with conventional therapy (group B), and electroacupuncture at the Lieque (LU7), Chize (LU5), and Zusanli (ST36) points (group C) once a day for 5 days. Arterial blood samples were obtained for blood gas analysis before electroacupuncture () and 3 () and 5 () days after electroacupuncture. The oxygenation index was significantly higher in all groups at and than that at , while the APACHE-II scores were decreased significantly. The expression of TNF-α was significantly decreased and the IL-10 was significantly increased in all groups at . The oxygenation index at and was significantly higher in group C than that in group B. Electroacupuncture at Lieque, Chize, and Zusanli can lessen the lung injury induced by SAP, and the mechanism may be related to the decreased TNF-α and increased IL-10 value. Clinical Registration Number is ChiCTR-ICR-15006850.

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A Deep Morphological Characterization and Comparison of Different Dental Restorative Materials

Giomer is a relatively new class of restorative material with aesthetics, handling and physical properties of composite resins, and benefits of glass ionomers: high radiopacity, antiplaque effect, fluoride release, and recharge. To verify the superior properties of Giomers, in this study, a deep morphological characterization has been performed with an in vitro comparative study among a Giomer (Beautifil® II by Shofu Dental Corporation, Osaka, Japan), a Compomer (Dyract Extra by Dentsply, Caulk, Germany), glass ionomer cement (Ketac fil plus by 3M ESPE), and a composite resin (Tetric Evoceram by Ivoclar). In particular, mechanical and optical properties and ageing effects have been compared to investigate materials similarities and differences. Indentation tests, UV-Visible spectroscopy, Raman spectroscopy, and weight loss after storage in saliva or sugary drink have been carried out to analyze materials behavior in real conditions. The results confirm the high quality of Giomer material and indicate possible improvements in their usage.

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Corrigendum to “Docetaxel-Induced Systemic Sclerosis with Internal Organ Involvement Masquerading as Congestive Heart Failure”

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Pricing Strategy and Quick Response Adoption System with Strategic Customers

This study determined the competitive advantage of a quick response (QR) system when a firm faces forward-looking customers with heterogeneous and uncertain valuations for a product, uncertain demand, and two selling periods. We identify two classes of pricing strategies, namely, no-price commitment strategy and price commitment strategy. Interestingly, the unique equilibrium is proven to exist if and only if most customers have high tastes on a product's value. We also prove that when customers possess beliefs about the markdown in the second period being smaller enough, a firm obtains a high profit with price commitment; otherwise he obtains a high profit without price commitment. Moreover, we distinguish the competitive advantage of a QR system from two strategies. When a firm uses no-price commitment strategy, the value of QR system in the first period decreases and in the second period increases with customer's strategic behavior. When a firm provides price commitment, the value of QR system in the first period may increase, decrease, or decrease first and then increase with customer's strategic behavior. And the value of QR in the second period under price commitment strategy decreases or rises first and then decreases with customer's strategic behavior.

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Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis

Purpose. To evaluate the capacity of OCT angiography (OCTA) for detecting infraclinical lesions in parafoveal capillaries in diabetic patients without diabetic retinopathy (DR). Methods. This prospective observational cross-sectional case-control study analyzed the superficial and deep capillary plexuses (SCP and DCP) on macular OCTA scans (3 × 3 mm) centered on the fovea. We compared 22 diabetic patients (34 eyes included) without DR diagnosis on color fundus photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes included). Qualitative analysis concerned morphological ischemic capillary alterations. Quantitative analysis measured foveal avascular zone (FAZ) size, parafoveal capillary density, and enlargement coefficient of FAZ between SCP and DCP. Results. Neither the qualitative nor quantitative parameters were significantly different between both groups. No microaneurysms or venous tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ area was 0.322 ± 0.125 mm2 in diabetic patients and 0.285 ± 0.150 mm2 in controls, . On the DCP, the mean FAZ area was 0.444 ± 0.153 mm2 in cases and 0.398 ± 0.138 mm2 in controls, . Conclusion. OCTA did not detect infraclinical qualitative or quantitative differences in parafoveal capillaries of diabetic patients without DR in comparison with nondiabetic controls.

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Common Clinical Characteristics and Rare Medical Problems of Fragile X Syndrome in Thai Patients and Review of the Literature

Background. Clinical characteristics of fragile X syndrome (FXS) have been well documented in Caucasians, whereas in Asians they have rarely been described. Those that have been conducted used small cohorts that utilized DNA for diagnosis and larger cohorts that utilized cytogenetics for diagnosis. This study is to describe clinical characteristics of FXS in a large cohort of Thai patients diagnosed by standard molecular methods. Methods. Seventy-seven index cases and 46 affected relatives diagnosed with FXS were recruited into the study. To determine frequencies of common characteristics of FXS in prepubertal boys, we reviewed 56 unrelated cases aged between 18 and 146 months. To list rare medical problems, we reviewed 75 cases aged between 8 months to 71 years old, including 53 index cases and 22 affected relatives. In addition, we selected 16 clinical studies from various ethnicities for comparison with our findings. Results. In prepubertal boys with FXS, attention deficit and/or hyperactivity, prominent ears, macroorchidism, and elongated face were observed in 96%, 80%, 53%, and 48% of patients, respectively, whereas recognizable X-linked inheritance presented in 11% of patients. IQ scores ranged between 30 and 64 (mean ± SD = , ). We observed clinical findings that rarely or have never been reported, for example, medulloblastoma and tetralogy of Fallot. Conclusion. Attention deficit and/or hyperactivity and prominent ear are the most common behavioral and physical features in prepubertal boys with FXS, respectively. There are differences in frequencies of clinical characteristics observed between ethnicities; however, it is difficult to draw a solid conclusion due to different recruitment criteria and sample sizes within each study.

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Binormal Motion of Curves with Constant Torsion in 3-Spaces

Hepatitis B Vaccination Status among Health Care Workers in a Tertiary Hospital in Ethiopia

Background. Even though health professionals (HPs) need special consideration for hepatitis B virus (HBV) vaccination, this is not widely implemented in low- and middle-income countries. The aim of this study was to determine the vaccination status of health professionals against hepatitis B virus infection, to identify barriers to vaccination and to identify factors associated with vaccination status. Methods. This cross-sectional study was conducted from June 1 to 15, 2016. Data was collected using self-administered questionnaire and analysed using SPSS version 21. A test of association was done using binary logistic regression and P value less than 0.05 was considered statistically significant. Results. Out of 286 HPs included in the study 28.7% received full course vaccination against HBV. The most frequently mentioned reasons for not being vaccinated against HBV are unavailability of the vaccine (58.2%) and its cost (18.5%). Age, marital status, level of education, and type of profession have significant association with vaccination status. Conclusion. HBV coverage among HPs in Gondar University Hospital (GUH) is inadequate. This is mostly due to unavailability of the vaccine and its cost. Vaccination status significantly varies based on level of education, type of profession, age, and marital status. We recommend making vaccines available and accessible.

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Corrigendum to “A Clinical Decision Support System for the Diagnosis, Fracture Risks and Treatment of Osteoporosis”

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Highly Accurate Detection of Cancer In Situ with Intraoperative, Label-Free, Multimodal Optical Spectroscopy

Effectiveness of surgery as a cancer treatment is reduced when all cancer cells are not detected during surgery, leading to recurrences that negatively impact survival. To maximize cancer cell detection during cancer surgery, we designed an in situ intraoperative, label-free, optical cancer detection system that combines intrinsic fluorescence spectroscopy, diffuse reflectance spectroscopy, and Raman spectroscopy. Using this multimodal optical cancer detection system, we found that brain, lung, colon, and skin cancers could be detected in situ during surgery with an accuracy, sensitivity, and specificity of 97%, 100%, and 93%, respectively. This highly sensitive optical molecular imaging approach can profoundly impact a wide range of surgical and noninvasive interventional oncology procedures by improving cancer detection capabilities, thereby reducing cancer burden and improving survival and quality of life. Cancer Res; 77(14); 1–9. ©2017 AACR.

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Human adipose stem cells induced to osteogenic differentiation by an innovative collagen/hydroxylapatite hybrid scaffold [Research]

Novel biomaterials are of paramount importance for bone regrowth. In this study, we investigated human adipose stem cells (hASCs) for osteogenic, osteoconductivity, and osteoinductivity effects of an innovative collagen/hydroxylapatite hybrid scaffold. In hASCs that were grown on this scaffold, osteogenic genes were analyzed for their expression profiles, together with adhesion and extracellular matrix genes. In hASC integrins, basement membrane constituents and collagens were up-regulated, together with cell proliferation. In addition, expression of osteopontin and activated focal adhesion kinase was studied at the protein level. Our in vitro data indicate that hASCs, together with hybrid biomaterial, is an important model of study to investigate in vitro bone induction.—Mazzoni, E., D'Agostino, A., Manfrini, M., Maniero, S., Puozzo, A., Bassi, E., Marsico, S., Fortini, C., Trevisiol, L., Patergnani, S., Tognon, M. Human adipose stem cells induced to osteogenic differentiation by an innovative collagen/hydroxylapatite hybrid scaffold.

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Guanylyl Cyclase Sensitivity to Nitric Oxide is Protected by a Thiol Oxidation-Driven Interaction with Thioredoxin1 [Cell Biology]

Nitric oxide (NO) modulates many physiological events through production of cGMP from its receptor, the NO-sensitive guanylyl cyclase (GC1). NO also appears to function in a cGMP independent manner, via S-nitrosation (SNO), a redox-based modification of cysteine thiols. Previously we have shown that S-nitrosated GC1 (SNO-GC1) is desensitized to NO stimulation following prolonged NO exposure or under oxidative/nitrosative stress. In animal models of nitrate tolerance and angiotensin II-induced hypertension, decreased vasodilation in response to NO correlates with GC1 thiol oxidation, but the physiological mechanism that resensitizes GC1 to NO and restores basal activity is unknown. As GC1 interacts with the oxidoreductase protein disulfide isomerase, we hypothesized that thioredoxin 1 (Trx1), a cytosolic oxidoreductase, could be involved in restoring GC1 basal activity and NO sensitivity, since the Trx/thioredoxin reductase (TrxR) system maintains thiol redox homeostasis. Here, by manipulating activity and levels of the Trx1/TrxR system and by using a Trx1-trap assay, we demonstrate that Trx1 modulates cGMP synthesis through an association between Trx1 and GC1 via a mixed disulfide. A proximity ligation assay confirmed the endogenous Trx1-GC1 complex in cells. Mutational analysis suggested that Cys609 in GC1 is involved in the Trx1-GC1 association and modulation of GC1 activity. Functionally, we established that Trx1 protects GC1 from S-nitrosocysteine induced desensitization. A computational model of Trx1-GC1 interaction illustrates a possible mechanism for Trx1 to maintain basal GC1 activity and prevent/rescue GC1 desensitization to NO. The etiology of some oxidative vascular diseases may very well be explained by the dysfunction of the Trx1-GC1 association.

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The long non-coding RNA GAS5 regulates TGF-{beta}-induced smooth muscle cell differentiation via RNA-Smad binding element [Signal Transduction]

Smooth muscle cell (SMC) differentiation is essential for vascular development, and TGF-β signaling plays a critical role in this process. Although long non-coding RNAs (lncRNAs) regulate various cellular events, their functions in SMC differentiation remain largely unknown. Here, we demonstrate that the lncRNA growth arrest specific 5 (GAS5) suppresses TGF-β/Smad3 signaling in smooth muscle cell differentiation of mesenchymal progenitor cells. We found that forced expression of GAS5 blocked, while knockdown of GAS5 increased, the expression of SMC contractile proteins. Mechanistically, GAS5 competitively bound Smad3 protein via multiple RNA Smad-binding elements (rSBEs), which prevented Smad3 from binding to SBE DNA in TGF-β-responsive SMC gene promoters, resulting in suppression of SMC marker gene transcription and, consequently, in inhibition of TGF-β/Smad3-mediated SMC differentiation. Importantly, other lncRNAs or artificially synthesized RNA molecules that contained rSBEs also effectively inhibited TGF-β/Smad3 signaling, suggesting that lncRNA-rSBE may be a general mechanism used by cells to fine tune Smad3 activity in both basal and TGF-β-stimulated states. Taken together, our results have uncovered a lncRNA-based mechanism that modulates TGF-β/Smad3 signaling during SMC differentiation.

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Τετάρτη 28 Ιουνίου 2017

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