IJMS, Vol. 18, Pages 1991: Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment

IJMS, Vol. 18, Pages 1991: Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment

International Journal of Molecular Sciences doi: 10.3390/ijms18091991

Authors: Kaoru Toyama Naoki Kiyosawa Kenji Watanabe Hitoshi Ishizuka

Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.

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Bioprospecting of Novel and Bioactive Compounds from Marine Actinomycetes Isolated from South China Sea Sediments

Abstract

Marine actinomycetes are less investigated compared to terrestrial strains as potential sources of natural products. To date, few investigations have been performed on culturable actinomycetes associated with South China Sea sediments. In the present study, twenty-eight actinomycetes were recovered from South China Sea sediments after dereplication by traditional culture-dependent method. The 16S rRNA gene sequences analyses revealed that these strains related to five families and seven genera. Twelve representative strains possessed at least one of the biosynthetic genes coding for polyketide synthase I, II, and nonribosomal peptide synthetase. Four strains had anti-Mycobacterium phlei activities and five strains had activities against methicillin-resistant Staphylococcus aureus. 10 L-scale fermentation of strains Salinispora sp. NHF45, Nocardiopsis sp. NHF48, and Streptomyces sp. NHF86 were carried out for novel and bioactive compounds discovery. Finally, we obtained a novel α-pyrone compound from marine Nocardiopsis sp. NHF48, an analogue of paulomenol from marine Streptomyces sp. NHF86 and a new source of rifamycin B, produced by Salinispora sp. NHF45. The present study concluded that marine actinomycetes, which we isolated from South China Sea sediments, will be a suitable source for the development of novel and bioactive compounds.

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Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands

Abstract

Introduction

The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population.

Materials and methods

A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1–10, 10.1–20, 20.1–50, 50.1–100, and >100 ng/mL and were correlated to the age and presence of cancer.

Results and discussion

Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4–100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level.

Summary

On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. As a result of this research work, it can be concluded that a benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman Islands.

Conclusion

The PSA level can reassure and educate the patients towards the diagnosis of cancer of prostate in Cayman Islands. Benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman.

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Evaluating the impact of a walking program in a disadvantaged area: using the RE-AIM framework by mixed methods

The positive health impact of physical activity (PA) is well known, yet a large proportion of the world's population remains sedentary. General PA programs are common as health promotion initiatives. However, ...

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Effectiveness of a 16-month multi-component and environmental school-based intervention for recovery of poor income overweight/obese children and adolescents: study protocol of the health multipliers program

Excess of weight is a serious public health concern in almost all countries, afflicting people of different ages and socioeconomic backgrounds. Studies have indicated the need for developing treatment strategi...

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Chemotherapy for advanced HER2-negative breast cancer: can one algorithm fit all?

Publication date: Available online 15 September 2017
Source:Cancer Treatment Reviews
Author(s): F. Miglietta, M.V. Dieci, G. Griguolo, V. Guarneri, P.F. Conte
HER2negative (HER2-) metastatic breast cancer (MBC) represents a challenging scenario for clinicians due to its great biological and clinical heterogeneity. Although management of HER2-MBC currently relies on several options, CT still remains a worthwhile strategy to be exploited. However, to date, there is not an univoque algorithm capable of guiding the choice of the proper CT agent/regimen, sequence and duration. Evidence from randomized clinical trials (RCT) and meta-analyses can actually help guiding the decision making process, however the definition of a standard of care for all HER2-MBC patients may be impractical, also in the light of the identification of new promising molecular and immunotherapeutic agents. The purpose of this work is to review available evidence on the role of CT for HER2-MBC with particular emphasis on the need to outline personalized therapeutic strategies for each patient.



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Policies and strategies to facilitate secondary use of research data in the health sciences

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Ethics in Social Networking and Business 2: The Future and Changing Paradigms

The aim of this book is to describe the methodology of conducting the THEDRE research "Traceable Human Experiment Design Research". It applies to Research in Human Centered Informatics (RICH). These are areas of computer research that integrate users to build scientific knowledge and supporting tools for this research. As an example, we can mention the relevant fields such as Information Systems (IS), Human Machine Interfaces Read More...

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Academic Entrepreneurship: How to Bring Your Scientific Discovery to a Successful Commercial Product

The pathway to bringing laboratory discoveries to market is poorly understood and generally new to many academics. This book serves as an easy-to-read roadmap for translating technology to a product launch – guiding university faculty and graduate students on launching a start-up company. •    Addresses a growing trend of academic faculty commercializing their discoveries, especially those supported by the National Science Foundation and National Institutes Read More...

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The muscle regulatory transcription factor MyoD participates with p53 to directly increase the expression of the pro-apoptotic Bcl2 family member PUMA

Abstract

The muscle regulatory transcription factor MyoD is a master regulator of skeletal myoblast differentiation. We have previously reported that MyoD is also necessary for the elevated expression of the pro-apoptotic Bcl2 family member PUMA, and the ensuing apoptosis, that occurs in a subset of myoblasts induced to differentiate. Herein, we report the identification of a functional MyoD binding site within the extended PUMA promoter. In silico analysis of the murine PUMA extended promoter revealed three potential MyoD binding sites within 2 kb of the transcription start site. Expression from a luciferase reporter construct containing this 2 kb fragment was enhanced by activation of MyoD in both myoblasts and fibroblasts and diminished by silencing of MyoD in myoblasts. Experiments utilizing truncated versions of this promoter region revealed that the potential binding site at position − 857 was necessary for expression. Chromatin immunoprecipitation (ChIP) analysis confirmed binding of MyoD to the DNA region encompassing position − 857. The increase in MyoD binding to the PUMA promoter as a consequence of culture in differentiation media (DM) was comparable to the increase in MyoD binding at the myogenin promoter and was diminished in myoblasts silenced for MyoD expression. Finally, ChIP analysis using an antibody specific for the transcription factor p53 demonstrated that, in myoblasts silenced for MyoD expression, p53 binding to the PUMA promoter was diminished in response to culture in DM. These data indicate that MyoD plays a direct role in regulating PUMA expression and reveal functional consequences of MyoD expression on p53 mediated transcription of PUMA.

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Decline patterns and risk assessment of 10 multi-class pesticides in young sprout amaranth ( Amaranthus mangostanus ) under greenhouse growing conditions

Abstract

The present study was designed to investigate the residual decline pattern and the risk assessment of 10 different class pesticides, namely azoxystrobin, boscalid, diazinon, diethofencarb, difenoconazole, etofenprox, flubendiamide, paclobutrazol, and pyraclostrobin in young vegetative amaranth (Amaranthus mangostanus) sprayed once or twice under greenhouse growing conditions. Field-incurred samples, collected at 3, 7, or 10 days after application of both treatments, were extracted and purified with the quick, easy, cheap, effective, rugged, and safe "QuEChERS" citrate-buffered method and analyzed with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) in positive ion mode. The linearity was satisfactory with determination coefficients (R ²) falling between 0.9817 and 0.9999 and limits of detection (LOD) and quantification (LOQ) values of 0.0007 and 0.002 mg/kg, respectively. The mean recovery rate at four spiking levels (equivalent to 5, 10, 50, and 100 × LOQ) ranged from 78.1 to 131.6% with a relative standard deviation (RSD) of < 11%. Substantial differences in the initial deposit between the tested analytes were observed and clearly indicated that the structure, as well as the initial concentration of applied products, greatly affected the residue deposit. From the obtained residual data, the provisional marginal maximum residue limits (MRLs) and the pre-harvest intervals (PHI) were proposed. Risk assessment was evaluated by comparing the theoretical maximum daily intake (TMDI) with the acceptable daily intake (ADI). Herein, the TMDI was lower than the ADI (TMDI/ADI ratio ≤ 80% set by the Korean Ministry of Food and Drug Safety) except for difenoconazole (80.92%, marginally higher), indicating that the vegetative amaranth is not hazardous and can be consumed safely by Korean consumers.

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Association of the Alternative Healthy Eating Index (AHEI-2010) with depression, stress and anxiety among Iranian military personnel

Introduction

Psychological disorders have a major role in the incidence of chronic diseases and may result in reductions in the cost-effectiveness of the Armed Forces. Previous civilian studies have shown a protective association between healthy eating guidelines and mental disorders, but evidence to support this for a military population is limited. The aim of this study was to examine the association of Alternative Healthy Eating Index (AHEI-2010) with depression, stress and anxiety among Iranian military personnel.

Method

A cross-sectional study was conducted on 246 male Army soldiers. Stress, anxiety, depression and dietary intakes were assessed. The association between variables was determined using multivariate logistic regression.

Results

The prevalence of depression, stress and anxiety in study participants was 15.9%, 10.6% and 27.2% respectively. Participants with the highest adherence to the AHEI-2010 had an 80% lower odds of depression than those with the lowest adherence (OR: 0.20; 95% CI 0.04 to 0.78). Such an association was also found between adherences to the AHEI-2010 and anxiety (OR: 0.28; 95% CI 0.05 to 0.95). No significant association between adherence to the AHEI-2010 and stress was found.

Conclusion

An inverse association between adherence to the AHEI-2010 and odds of depression and anxiety was found. Further studies are required to clarify this relationship.

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'Just like a normal pain, what do people with diabetes mellitus experience when having a myocardial infarction: a qualitative study recruited from UK hospitals

Objective

The objective of the study was to investigate the symptoms people with diabetes experience when having a myocardial infarction (MI), their illness narrative and how they present their symptoms to the health service.

Setting

Three London (UK) hospitals (coronary care units and medical wards).

Participants

Patients were recruited with diabetes mellitus (DM) (types 1 and 2) with a clinical presentation of MI (ST elevated MI (STEMI), non-ST elevated MI (NSTEMI), acute MI unspecified and cardiac arrest). A total of 43 participants were recruited, and 39 interviews met the study criteria and were analysed. They were predominantly male (n=30), aged 40–90 years and white British (18/39), and just over a half were from other ethnic groups. The majority had type 2 DM (n=35), 24 had an NSTEMI, 10 had an STEMI and five had other cardiac events.

Definitions of selection/exclusion criteria

A diagnosis of MI and DM and the ability to communicate enough English to complete the interview. Ward staff made a clinical judgement that the participant was post-treatment, clinically stable and well enough to participate.

Methods

A qualitative study using taped and transcribed interviews analysed using a thematic analysis.

Results

While most participants did experience chest pain, it was often not their most striking symptom. As their chest pain did not match their expectations of what a 'heart attack' should be, participants developed narratives to explain these symptoms, including the symptoms being effects of their DM ('hypos'), side effects of medication (oral hypoglycaemics) or symptoms (such as breathlessness and indigestion) related to other comorbidities, often leading to delays in seeking care.

Conclusions

While truly absent chest pain during MI among people with DM was rare in this study, patients' attenuated symptoms often led to delay in seeking attention, and this may result in delays in receiving treatment.

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Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study

Objective

Pharmaceutical treatment of latent tuberculosis infection (LTBI) reduces the risk of progression to active tuberculosis (TB); however, poor adherence tempers the protective effect. We aimed to estimate the health burden of non-adherence, the maximum allowable cost of hypothetical new adherence interventions to be cost-effective and the potential value of existing adherence interventions for patients with low-risk LTBI in Canada.

Design

A microsimulation model of LTBI progression over 25 years.

Setting

General practice in Canada.

Participants

Individuals with LTBI who are initiating drug therapy.

Interventions

A hypothetical intervention with a range of effectiveness was evaluated. Existing drug adherence interventions including peer support, two-way text messaging support, enhanced adherence counselling and adherence incentives were also evaluated.

Primary and secondary outcome measures

Simulation outcomes included healthcare costs, TB incidence, TB deaths and quality-adjusted life years (QALYs). Base case results were interpreted against a willingness-to-pay threshold of $C50 000/QALY.

Results

Compared with current adherence levels, full adherence to LTBI drug therapy could reduce new TB cases from 90.3 cases per 100 000 person-years to 35.9 cases per 100 000 person-years and reduce TB-related deaths from 7.9 deaths per 100 000 person-years to 3.1 deaths per 100 000 person-years. An intervention that increases relative adherence by 40% would bring the population near full adherence to drug therapy and could have a maximum allowable annual cost of approximately $C450 per person to be cost-effective. Based on estimates of effect sizes and costs of existing adherence interventions, we found that they yielded between 900 and 2400 additional QALYs per million people, reduced TB deaths by 5%–25% and were likely to be cost-effective over 25 years.

Conclusion

Full adherence could reduce the number of future TB cases by nearly 60%, offsetting TB-related costs and health burden. Several existing interventions are could be cost-effective to help achieve this goal.

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A protocol of a cross-sectional study evaluating an online tool for early career peer reviewers assessing reports of randomised controlled trials

Introduction

Systematic reviews evaluating the impact of interventions to improve the quality of peer review for biomedical publications highlighted that interventions were limited and have little impact. This study aims to compare the accuracy of early career peer reviewers who use an innovative online tool to the usual peer reviewer process in evaluating the completeness of reporting and switched primary outcomes in completed reports.

Methods and analysis

This is a cross-sectional study of individual two-arm parallel-group randomised controlled trials (RCTs) published in the BioMed Central series medical journals, BMJ, BMJ Open and Annals of Emergency Medicine and indexed with the publication type 'Randomised Controlled Trial'. First, we will develop an online tool and training module based (a) on the Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist and the Explanation and Elaboration document that would be dedicated to junior peer reviewers for assessing the completeness of reporting of key items and (b) the Centre for Evidence-Based Medicine Outcome Monitoring Project process used to identify switched outcomes in completed reports of the primary results of RCTs when initially submitted. Then, we will compare the performance of early career peer reviewers who use the online tool to the usual peer review process in identifying inadequate reporting and switched outcomes in completed reports of RCTs at initial journal submission. The primary outcome will be the mean number of items accurately classified per manuscript. The secondary outcomes will be the mean number of items accurately classified per manuscript for the CONSORT items and the sensitivity, specificity and likelihood ratio to detect the item as adequately reported and to identify a switch in outcomes. We aim to include 120 RCTs and 120 early career peer reviewers.

Ethics and dissemination

The research protocol was approved by the ethics committee of the INSERM Institutional Review Board (21 January 2016). The study is based on voluntary participation and informed written consent.

Trial registration number

NCT03119376.

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Combining CD4 recovery and CD4: CD8 ratio restoration as an indicator for evaluating the outcome of continued antiretroviral therapy: an observational cohort study

Objectives

Immune recovery following highly active antiretroviral therapy (HAART) is commonly assessed by the degree of CD4 reconstitution alone. In this study, we aimed to assess immune recovery by incorporating both CD4 count and CD4:CD8 ratio.

Design

Observational cohort study

Setting and participants

Clinical data from Chinese HIV-positive patients attending the largest HIV service in Hong Kong and who had been on HAART for ≥4 years were accessed.

Main outcome measures

Optimal immune outcome was defined as a combination of a CD4 count ≥500/μL and a CD4:CD8 ratio ≥0.8.

Results

A total of 718 patients were included for analysis (6353 person-years). At the end of year 4, 318 out of 715 patients achieved CD4 ≥500/μL, of which only 33% (105 out of 318) concurrently achieved CD4:CD8 ratio ≥0.8. Patients with a pre-HAART CD8 ≤800/μL (428 out of 704) were more likely to be optimal immune outcome achievers with CD4 ≥500/μL and CD4:CD8 ratio ≥0.8, the association of which was stronger after adjusting for pre-HAART CD4 counts. In a multivariable logistic model, optimal immune outcome was positively associated with male gender, younger pre-HAART age and higher pre-HAART CD4 count, longer duration of HAART and pre-HAART CD8 ≤800/μL. Treatment regimen and cumulative viral loads played no significant role in the pattern of immune recovery.

Conclusions

A combination of CD4 count and CD4:CD8 ratio could be a useful approach for the characterisation of treatment outcome over time, on top of monitoring CD4 count alone.

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Qualitative interview study of parents perspectives, concerns and experiences of the management of lower respiratory tract infections in children in primary care

Objective

To explore parents' perspectives, concerns and experiences of the management of lower respiratory tract infections (LRTIs) in children in primary care.

Design

Qualitative semistructured interview study.

Setting

UK primary care.

Participants

23 parents of children aged 6 months to 10 years presenting with LRTI in primary care.

Method

Thematic analysis of semistructured interviews (either in person or by telephone) conducted with parents to explore their experiences and views on their children being prescribed antibiotics for LRTI.

Results

Four major themes were identified and these are perspectives on: (1) infection, (2) antibiotic use, (3) the general practitioner (GP) appointment and (4) decision making around prescribing. Symptomatic relief was a key concern: the most troublesome symptoms were cough, breathing difficulty, fever and malaise. Many parents were reluctant to use self-care medication, tended to support antibiotic use and believed they are effective for symptoms, illness duration and for preventing complications. However, parental expectations varied from a desire for reassurance and advice to an explicit preference for an antibiotic prescription. These preferences were shaped by: (1) the age of the child, with younger children perceived as more vulnerable because of their greater difficulty in communicating, and concerns about rapid deterioration; (2) the perceived severity of the illness; and (3) disruption to daily routine. When there was disagreement with the GP, parents described feeling dismissed, and they were critical of inconsistent prescribing when they reconsult. When agreement between the parent and the doctor featured, parents described a feeling of relief and legitimation for consulting, feeling reassured that the illness did indeed warrant a doctor's attention.

Conclusion

Symptomatic relief is a major concern for parents. Careful exploration of expectations, and eliciting worries about key symptoms and impact on daily life will be needed to help parents understand when a no antibiotic recommendation or delayed antibiotic recommendation is made.

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Nasotracheal intubation over a bougie vs. non-bougie intubation: a prospective randomised, controlled trial in older children and adults using videolaryngoscopy

Summary

Conventionally, nasotracheal intubation has consisted of blind nasal passage and external manipulation of the tube through the glottis ('conventional technique'), a technique associated with a high incidence of nasal trauma. We evaluated a novel technique for routine asleep (i.e. post-induction) nasotracheal intubation using a bougie ('bougie technique'), which uses a nasopharyngeal airway to guide a paediatric bougie nasotracheally for use as a Seldinger tracheal intubation guide. Two hundred and fifty-seven older children (> 8 years) and adults were randomly assigned to videolaryngoscopy-assisted nasotracheal intubation using either the conventional or the bougie technique. The hypothesis was that the bougie technique would result in less nasopharyngeal trauma. The bougie technique was associated with significantly less nasopharyngeal bleeding than the conventional technique at both 60–90 s (55% vs. 68%; p = 0.033) and 5 min (51% vs. 70%; p = 0.002). The severity of bleeding was also significantly less with the bougie technique, with an OR for active bleeding of 0.42 (95%CI 0.20–0.87; p = 0.020) at 60–90 s and 0.15 (95%CI 0.06–0.37; p < 0.0001) at 5 min. Magill forceps were needed significantly less often with the bougie technique (9% vs. 28%, p = 0.0001) and there was no difference in first attempt and overall success rates between the two techniques (p = 0.133 and p = 0.750, respectively). Not only is nasal intubation over a bougie as successful as the conventional technique, it also significantly decreases both the incidence and severity of nasopharyngeal trauma, as well as the need for the use of Magill forceps.

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Successful twice interrupted therapy of HCV infection in patients with cirrhosis with hepatocellular carcinoma before and after liver transplantation

We are presenting the case study of the patient diagnosed at the age of 37 with liver cirrhosis due to genotype 1b hepatitis C virus infection. At the age of 46, he was diagnosed with hepatocellular carcinoma with subsequent resection of the tumour in May 2015. In December 2015, the treatment was started with ombitasvir, paritaprevir/ritonavir and dasabuvir (3D) with ribavirin (RBV) 1000 mg per day. After 24 days of this treatment, the patient received a deceased donor liver transplantation, followed by 18-day interruption of 3D therapy. Due to the anaemia, RBV dose was reduced to 600 mg per day for the rest of the treatment. At the 11th week of 3D+RBV treatment, there was another 8-day long discontinuation of therapy due to the postoperative wound infection. In total, the patient received 24 weeks of 3D+RBV treatment, achieving sustained virological response at week 24 post-treatment.

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Combined caesarean with splenectomy in pregnancy with portal hypertension: defining plausibility

24-year-old woman at 28 weeks gestation was referred from peripheral hospital with diagnosis of pregnancy with portal hypertension. She had received multiple transfusion for pancytopaenia in the past and had undergone endoscopic sclerotherapy for oesophageal varices. Initially, she was admitted in our hospital at 28 weeks gestation for blood transfusion and was evaluated by multispecialty team of doctors. She was advised splenectomy for transfusion-dependent pancytopaenia secondary to hypersplenism in non-cirrhotic portal hypertension. She was readmitted at 36 weeks gestation. A decision for caesarean was taken owing to failed induction of labour at 38 weeks gestation. She underwent combined caesarean with splenectomy. Mother and child had an uneventful postoperative recovery and were discharged on ninth postoperative day. Preconceptional counselling, treatment of oesophageal varices and multispecialty approach was paramount in the management. Combined caesarean with splenectomy is feasible and cost-effective treatment associated with improved quality of life. Prospective clinical trials are essential to prove safety and efficacy of treatment.

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Renal cell carcinoma with isolated metastasis to sigmoid mesentery: a rare resectable combination

Renal cell carcinoma accounts for 2%–3% of all malignancies in adults. It spreads via direct extension, lymphatic route as well as haematogenous route. Lymph nodes, lungs, bone, liver and brain are the usual sites for its metastatic spread. In the presence of limited metastatic disease with potentially resectable metastases, surgery offers the best chances of cure. In the present case, we describe a case of renal cell carcinoma with a solitary metastasis to the sigmoid mesentery in a patient with Von Hippel-Lindau syndrome. There was no retroperitoneal lymphadenopathy or tumour thrombus in the renal vein. The patient was managed with laparoscopic radical nephrectomy and excision of the sigmoid mesentery mass. At 6 months of follow-up, there is no evidence of recurrent disease.

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Chondromalacia patellae

Chondromalacia patellae: The patellofemoral syndrome (PFS), the most common cause of chronic knee pain. PFS characteristically causes vague discomfort of the inner knee area, aggravated by activity (running, jumping, climbing or descending stairs) or by prolonged sitting with knees in a moderately bent position (the so-called "theater sign" of pain upon arising from a desk or theater seat). The knee may be mildly swollen. If chronic symptoms are ignored, the loss of quadriceps strength may cause the leg to "give out."

PFS is caused by an abnormality in how the kneecap (patella) slides over the lower end of the thigh bone (the femur). Normally, the patella (kneecap) is pulled up over the end of the femur in a straight line by the quadriceps (thigh) muscle. In PFS there is patellar "tracking" toward the lateral (outer) side of the femur. This off-kilter path permits the underside of the patella to grate along the femur leading to chronic inflammation and pain. Females are at greater risk than males for PFS. Knock-kneed and flat-footed runners and persons with an unusually shaped patella are predisposed to PFS.

Initial pain management is icing, anti-inflammatory drugs (for example, ibuprofen or naproxen) and avoiding motions which irritate the kneecap. Treatment and rehabilitation are designed to create a straighter pathway for the patella to follow during quadriceps contraction. Selective strengthening of the inner portion of the quadriceps muscle helps normalize the tracking of the patella. Cardiovascular conditioning can be maintained by stationary bicycling (low resistance but high rpms), pool running, or swimming (flutter kick). Changes in training that may have led to the PFS pain should be reviewed and running shoes examined for proper biomechanical fit to avoid repeating the painful PFS cycle. Occasionally bracing with patellar centering devices is required. Stretching and strengthening the quadriceps and hamstring muscle groups are essential to an effective and lasting rehabilitation of PFS. "Quad sets" are the foundation for such a program and are done by contracting the thigh muscles while the legs are straight and holding the contraction for a count of ten. Sets of 10 contractions are done between 15-20 times per day. Under optimal circumstances, there should be a rapid recovery and return at full functional level to sports.

PFS has also been called "housemaid's knee" and "secretary's knee."

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Architectural delineation and molecular identification of extracellular matrix in ascidian embryos and larvae [RESEARCH ARTICLE]

Jiankai Wei, Guilin Wang, Xiang Li, Ping Ren, Haiyan Yu, and Bo Dong

The extracellular matrix (ECM) not only provides essential physical scaffolding for cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue morphogenesis. In this study, we utilized wheat germ agglutinin (WGA) staining to characterize the ECM architecture in ascidian embryos and larvae. The results showed three distinct populations of ECM presenting in Ciona embryogenesis: the outer layer localized at the surface of embryo, an inner layer of notochord sheath and the apical ECM secreted by the notochord. To further elucidate the precise structure of Ciona embryonic ECM, we employed scanning and transmission electron microscopy, and found that the outer membrane was relatively thick with short fibres, whereas the ECM layer in notochord sheath was not as thick as the outer membrane but more regular arranged; the lumen between notochord cells was hydrostatic and sticky. Then, we used the RNA sequencing data from the embryos and larvae of Ciona savignyi to identify ECM genes and acquire their expression patterns. We identified 115 unigenes as 67 ECM genes, and 77 unigenes showed dynamic expression changes between different stages. Our results reveal the architecture, molecular composition and dynamic expression profile of ECM in ascidian embryogenesis, and may increase understanding of the function of the ECM in chordate development.

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Dlx3b/4b is required for early-born but not later-forming sensory hair cells during zebrafish inner ear development [RESEARCH ARTICLE]

Simone Schwarzer, Sandra Spiess, Michael Brand, and Stefan Hans

Morpholino-mediated knockdown has shown that the homeodomain transcription factors Dlx3b and Dlx4b are essential for proper induction of the otic-epibranchial progenitor domain (OEPD), as well as subsequent formation of sensory hair cells in the developing zebrafish inner ear. However, increasing use of reverse genetic approaches has revealed poor correlation between morpholino-induced and mutant phenotypes. Using CRISPR/Cas9-mediated mutagenesis, we generated a defined deletion eliminating the entire open reading frames of dlx3b and dlx4b (dlx3b/4b) and investigated a potential phenotypic difference between mutants and morpholino-mediated knockdown. Consistent with previous findings obtained by morpholino-mediated knockdown of Dlx3b and Dlx4b, dlx3b/4b mutants display compromised otic induction, the development of smaller otic vesicles and an elimination of all indications of otic specification when combined with loss of foxi1, a second known OEPD competence factor in zebrafish. Furthermore, sensorigenesis is also affected in dlx3b/4b mutants. However, we find that only early-born sensory hair cells (tether cells), that seed and anchor the formation of otoliths, are affected. Later-forming sensory hair cells are present, indicating that two genetically distinct pathways control the development of early-born and later-forming sensory hair cells. Finally, impairment of early-born sensory hair cell formation in dlx3b/4b mutant embryos reverses the common temporal sequence of neuronal and sensory hair cell specification in zebrafish, resembling the order of cell specification in amniotes; Neurog1 expression before Atoh1 expression. We conclude that the Dlx3b/4b-dependent pathway has been either acquired newly in the fish lineage or lost in other vertebrate species during evolution, and that the events during early inner ear development are remarkably similar in fish and amniotes in the absence of this pathway.

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Regulatory RNPs: a novel class of ribonucleoproteins that potentially contribute to ribosome heterogeneity [RESEARCH ARTICLE]

Aaron R. Poole, Ian Vicino, Hironori Adachi, Yi-Tao Yu, and Michael D. Hebert

Many ribonucleoproteins (RNPs), which are comprised of noncoding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here, we provide data that show that these RNAs become part of RNPs we term regulatory RNPs (regRNPs). Most modifications within rRNA (predominantly pseudouridylation and ribose 2'-O-methylation) are conducted by small nucleolar RNPs (snoRNPs), and we provide evidence that the activity of at least some of these snoRNPs is under the control of regRNPs. Because modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides a potential mechanism for how ribosome heterogeneity may be accomplished. This work also provides additional functional connections between the Cajal body and the nucleolus.

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EsGLUT4 and CHHBP are involved in the regulation of glucose homeostasis in the crustacean Eriocheir sinensis [RESEARCH ARTICLE]

Ran Li, Jin-Ze Tian, Mo-Ran Wang, Li-Na Zhu, and Jin-Sheng Sun

Glucose is an essential energy source for both vertebrates and invertebrates. In mammals, glucose uptake is mediated primarily by glucose transporters (GLUTs), members of the major facilitator superfamily (MFS) of passive transporters. Among the GLUTs, GLUT4 is the main glucose transporter in muscles and adipocytes. In skeletal muscle cells, GLUT4 interacts with the lipid raft protein flotillin to transport glucose upon stimulation by insulin. Although several studies have examined GLUT4 function in mammals, few have been performed in crustaceans, which also use glucose as their main energy source. Crustacean hyperglycemic hormone (CHH) is a multifunctional neurohormone found only in arthropods, and one of its roles is to regulate glucose homeostasis. However, the molecular mechanism that underlies CHH regulation and whether GLUT4 is involved in its regulation in crustaceans remain unclear. In the present study, we identified a full-length GLUT4 cDNA sequence (defined herein as EsGLUT4) from the Chinese mitten crab Eriocheir sinensis and analyzed its tissue distribution and cellular localization. By the ForteBio Octet system, two large hydrophilic regions within EsGLUT4 were found to interact with the CHH binding protein (CHHBP), an E. sinensis flotillin-like protein. Interestingly, live-cell imaging indicated that EsGLUT4 and CHHBP responded simultaneously upon stimulation by CHH, resulting in glucose release. In contrast to insulin-dependent GLUT4, however, EsGLUT4 and CHHBP were present within cytoplasmic vesicles, both translocating to the plasma membrane upon CHH stimulation. In conclusion, our results provide new evidence for the involvement of EsGLUT4 and CHHBP in the regulation of glucose homeostasis in crustacean carbohydrate metabolism.

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Phosphorylation of SNAP-23 regulates its dynamic membrane association during mast cell exocytosis [RESEARCH ARTICLE]

Pieu Naskar and Niti Puri

Upon allergen challenge, mast cells (MCs) respond by releasing pre-stored mediators from their secretory granules by the transient mechanism of porosome-mediated cell secretion. The target SNARE SNAP-23 has been shown to be important for MC exocytosis, and our previous studies revealed the presence of one basal (Thr¹⁰²) and two induced (Ser⁹⁵ and Ser¹²⁰) phosphorylation sites in its linker region. To study the role of SNAP-23 phosphorylation in the regulation of exocytosis, green fluorescence protein-tagged wild-type SNAP-23 (GFP-SNAP-23) and its phosphorylation mutants were transfected into rat basophilic leukemia (RBL-2H3) MCs. Studies on GFP-SNAP-23 transfected MCs revealed some dynamic changes in SNAP-23 membrane association. SNAP-23 was associated with plasma membrane in resting MCs, however, on activation a portion of it translocated to cytosol and internal membranes. These internal locations were secretory granule membranes. This dynamic change in the membrane association of SNAP-23 in MCs may be important for mediating internal granule-granule fusions in compound exocytosis. Further studies with SNAP-23 phosphorylation mutants revealed an important role for the phosphorylation at Thr¹⁰² in its initial membrane association, and of induced phosphorylation at Ser⁹⁵ and Ser¹²⁰ in its internal membrane association, during MC exocytosis.

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The probability of wing damage in the dragonfly Sympetrum vulgatum (Anisoptera: Libellulidae): a field study [RESEARCH ARTICLE]

Hamed Rajabi, Veronica Schroeter, Shahab Eshghi, and Stanislav N. Gorb

Dragonfly wings resist millions of cycles of dynamic loading in their lifespan. During their operation, the wings are subjected to relatively high mechanical stresses. They further experience accidental collisions which result from the insects' daily activities, such as foraging, mating and fighting with other individuals. All these factors may lead to irreversible wing damage. Here, for the first time, we collected qualitative and quantitative data to systematically investigate the occurrence of damage in dragonfly wings in nature. The results obtained from the analysis of 119 wings from >30 individual Sympetrum vulgatum (Anisoptera: Libellulidae), collected at the second half of their flight period, indicate a high risk of damage in both fore- and hindwings. Statistical analyses show no significant difference between the extent of damage in fore- and hindwings, or between male and female dragonflies. However, we observe a considerable difference in the probability of damage in different wing regions. The wing damage is found to mainly result from two failure modes: wear and fracture.

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Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection [RESEARCH ARTICLE]

Yuka Matsumoto, Wakana Mochizuki, Shintaro Akiyama, Taichi Matsumoto, Kengo Nozaki, Mamoru Watanabe, and Tetsuya Nakamura

Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans.

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Fat-containing cells are eliminated during Dictyostelium development [RESEARCH ARTICLE]

Jessica M. Kornke and Markus Maniak

Triacylglycerol is a universal storage molecule for metabolic energy in living organisms. However, Dictyostelium amoebae, that have accumulated storage fat from added fatty acids do not progress through the starvation period preceding the development of the durable spore. Mutants deficient in genes of fat metabolism, such as fcsA, encoding a fatty acid activating enzyme, or dgat1 and dgat2, specifying proteins that synthesize triacylglycerol, strongly increase their chances to contribute to the spore fraction of the developing fruiting body, but lose the ability to produce storage fat efficiently. Dictyostelium seipin, an orthologue of a human protein that in patients causes the complete loss of adipose tissue when mutated, does not quantitatively affect fat storage in the amoeba. Dictyostelium seiP knockout mutants have lipid droplets that are enlarged in size but reduced in number. These mutants are as vulnerable as the wild type when exposed to fatty acids during their vegetative growth phase, and do not efficiently enter the spore head in Dictyostelium development.

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Standard metabolic rate predicts growth trajectory of juvenile Chinese crucian carp (Carassius auratus) under changing food availability [RESEARCH ARTICLE]

Ling-Qing Zeng, An-Jie Zhang, Shaun S. Killen, Zhen-Dong Cao, Yu-Xiang Wang, and Shi-Jian Fu

Phenotypic traits vary greatly within populations and can have a significant influence on aspects of performance. The present study aimed to investigate the effects of individual variation in standard metabolic rate (SMR) on growth rate and tolerance to food deprivation in juvenile Chinese crucian carp (Carassius auratus) under varying levels of food availability. To address this issue, 19 high and 16 low SMR individuals were randomly assigned to a satiation diet for 3 weeks, whereas another 20 high and 16 low SMR individuals were assigned to a restricted diet (approximately 50% of satiation) for the same period. Then, all fish were completely food-deprived for another 3 weeks. High SMR individuals showed a higher growth rate when fed to satiation, but this advantage of SMR did not exist in food-restricted fish. This result was related to improved feeding efficiency with decreased food intake in low SMR individuals, due to their low food processing capacity and maintenance costs. High SMR individuals experienced more mass loss during food deprivation as compared to low SMR individuals. Our results here illustrate context-dependent costs and benefits of intraspecific variation in SMR whereby high SMR individuals show increased growth performance under high food availability but had a cost under stressful environments (i.e. food shortage).

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The expression of Ldh-c in the skeletal muscle of plateau pika (Ochotona curzoniae) enhances adaptation to a hypoxic environment [RESEARCH ARTICLE]

Zhi F. An, Deng B. Wei, Lian Wei, Yang Wang, and Lin N. Wei

The plateau pika (Ochotona curzoniae) is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C₄), in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days. Our results showed that after Ldh-c was silenced, the sprint-running ability (swimming time) of the plateau pikas was significant decreased, and the total LDH activities and ATP levels were reduced by 28.21% and 27.88%, respectively. Our results indicated that expression of Ldh-c in the skeletal muscle of plateau pika increased anaerobic glycolysis and enhanced adaptation to highland hypoxic environments.

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PQN-75 is expressed in the pharyngeal gland cells of Caenorhabditis elegans and is dispensable for germline development [RESEARCH ARTICLE]

Jesse D. Rochester, Paige C. Tanner, Catherine S. Sharp, Karolina M. Andralojc, and Dustin L. Updike

In Caenorhabditis elegans, five pharyngeal gland cells reside in the terminal bulb of the pharynx and extend anterior processes to five contact points in the pharyngeal lumen. Pharyngeal gland cells secrete mucin-like proteins thought to facilitate digestion, hatching, molting and assembly of the surface coat of the cuticle, but supporting evidence has been sparse. Here we show pharyngeal gland cell expression of PQN-75, a unique protein containing an N-terminal signal peptide, nucleoporin (Nup)-like phenylalanine/glycine (FG) repeats, and an extensive polyproline repeat domain with similarities to human basic salivary proline-rich pre-protein PRB2. Imaging of C-terminal tagged PQN-75 shows localization throughout pharyngeal gland cell processes but not the pharyngeal lumen; instead, aggregates of PQN-75 are occasionally found throughout the pharynx, suggesting secretion from pharyngeal gland cells into the surrounding pharyngeal muscle. PQN-75 does not affect fertility and brood size in C. elegans but confers some degree of stress resistance and thermotolerance through unknown mechanisms.

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Differential expression of sirtuin 2 and adipocyte maturation restriction: an adaptation process during hypoxia in fish [RESEARCH ARTICLE]

Padmini Ekambaram and Parimala Parasuraman

Sirtuins have received widespread attention due to their diverse physiological role in metabolism. Among sirtuins, SIRT2 is more abundant in adipocytes and exerts effects on adipocyte differentiation, a process which involves conversion of preadipocytes to mature adipocytes orchestrated by adipokines and adipogenic transcription factors. Grey mullet (Mugil cephalus) was chosen as a study organism due to its excellent service as a biomonitor. Adipocytes isolated from natural field conditions were termed as field-hypoxic (Ennore) and -normoxic (Kovalam) based on dissolved oxygen (DO) level in the estuary. A previous study portrayed the hypoxic instance of Ennore estuary (low DO) and grey mullet [HIF1α in adipocytes, brain endothelial cell (EC) and hepatocytes] inhabiting this estuary ( Padmini et al., 2016a, b; Padmini and Tharani, 2015). In this context, fish adipocytes of both conditions were subjected to in vitro hypoxia for 1 h (in the pre/trigassed incubator with the supply of 1% O₂; 94% N₂; 5% CO₂) and were analysed for the expression of adipokines, adipogenic transcription factors and anti-adipogenic markers in fish adipocytes. Elevation of asymmetric dimethylarginine (ADMA), TNFα and leptin along with decreased adiponectin, adipogenic transcription factors and altering sirtuins were observed in test adipocytes and in control adipocytes on in vitro hypoxia. This suggests that adipocytes may follow internal caloric restriction as portrayed from cytomorphological/ultrastructural analysis, limiting adipocyte maturation process, one of the adaptive mechanisms triggered by adipocyte of fish surviving in Ennore estuary. Prolonged exposure to hypoxia (test on in vitro hypoxia for 1 h) showed a drastic alteration in these components leading to both structural and biological fluctuation when compared to limited hypoxic condition (field-hypoxic and control on in vitro hypoxia). Our study concludes that hypoxia may serve as the chief molecular cue in eliciting adipocyte maturation restriction though metabolic reprogramming and it also shows the significance of adipocyte maturation restriction in imparting survival mechanism.

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WASP-Arp2/3-dependent actin polymerization influences fusogen localization during cell-cell fusion in Caenorhabditis elegans embryos [RESEARCH ARTICLE]

Yan Zhang, Yihong Yang, Zhiwen Zhu, and Guangshuo Ou

Cell-cell fusion is essential for development and physiology. Actin polymerization was implicated in the Caenorhabditis elegans fusogen EFF-1 engagement in a reconstituted Drosophila cell culture system, and the actin-binding protein spectraplakin links EFF-1 to the actin cytoskeleton and promotes cell-cell fusions in C. elegans larvae. However, it remains unclear whether and how fusogens and the actin cytoskeleton are coordinated in C. elegans embryos. Here, we used live imaging analysis of GFP knock-in and RNAi embryos to study the embryonic cell-cell fusions in C. elegans. Our results show that the inhibition of WASP-Arp2/3-dependent actin polymerization delays cell-cell fusions. EFF-1 is primarily distributed in intracellular vesicles in embryonic fusing cells, and we find that the perturbation of actin polymerization reduces the number of EFF-1-postive vesicles. Thus, the actin cytoskeleton differently promotes cell-cell fusion by regulating fusogen localization to the fusing plasma membrane in larvae or to intracellular vesicles in embryos.

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An ex vivo model using human peritoneum to explore mesh-tissue integration [METHODS [amp ] TECHNIQUES]

Peter Falk, Fernando Ruiz-Jasbon, Karin Strigard, Ulf Gunnarsson, and Marie-Lois Ivarsson

Biological compatibility, in terms of implantation of foreign mesh material in hernia surgery, still needs experimental investigation. The present study develops an experimental model using human peritoneum to study the integration between tissue and different mesh material. The ex vivo model using peritoneal tissue was studied with different mesh material, and integration was monitored over time using microscopy. The peritoneal model could be kept viable in culture for several weeks. Cell migration was seen after 7-10 days in culture and could be further monitored over several weeks. The use of a human artificial model environment enabling the investigation of tissue/mesh integration has, to our knowledge, not been described previously. This proof-of-concept model was developed for the investigation of peritoneal biology and the integration between tissue and different mesh material. It has the potential to be useful in studies on other important biological mechanisms involving the peritoneum.

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The effects of the exopolysaccharide and growth rate on the morphogenesis of the terrestrial filamentous cyanobacterium Nostoc flagelliforme [RESEARCH ARTICLE]

Lijuan Cui, Haiyan Xu, Zhaoxia Zhu, and Xiang Gao

The terrestrial cyanobacterium Nostoc flagelliforme, which contributes to carbon and nitrogen supplies in arid and semi-arid regions, adopts a filamentous colony form. Owing to its herbal and dietary values, this species has been overexploited. Largely due to the lack of understanding on its morphogenesis, artificial cultivation has not been achieved. Additionally, it may serve as a useful model for recognizing the morphological adaptation of colonial cyanobacteria in terrestrial niches. However, it shows very slow growth in native habitats and is easily disintegrated under laboratory conditions. Thus, a novel experimental system is necessary to explore its morphogenetic mechanism. Liquid-cultured N. flagelliforme has been well developed for exopolysaccharide (EPS) production, in which microscopic colonies (micro-colonies) are generally formed. In this study, we sought to gain some insight into the morphogenesis of N. flagelliforme by examining the effects of two external factors, the EPS and environmental stress-related growth rate, on the morphological shaping of micro-colonies. Our findings indicate that the EPS matrix could act as a basal barrier, leading to the bending of trichomes during their elongation, while very slow growth is conducive to their straight elongation. These findings will guide future cultivation and application of this cyanobacterium for ecological improvement.

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CORRECTION: Surviving murine experimental sepsis affects the function and morphology of the inner ear [CORRECTION]

Natalie Fischer, Nina Maria Mathonia, Georges Hollerich, Julian Veser, Leyla Pinggera, Daniel Dejaco, Rudolf Glueckert, Anneliese Schrott-Fischer, Peter Lackner, Herbert Riechelmann, and Joachim Schmutzhard



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Local Dentist to Offer Free Dental Services

Once again a local dentist is taking one full day to offer free dental services to people in Central New York. The name of the event is called 'Dentistry from the Heart.'

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IJMS, Vol. 18, Pages 1980: The Beneficial Effects of Allicin in Chronic Kidney Disease Are Comparable to Losartan

IJMS, Vol. 18, Pages 1980: The Beneficial Effects of Allicin in Chronic Kidney Disease Are Comparable to Losartan

International Journal of Molecular Sciences doi: 10.3390/ijms18091980

Authors: Ehécatl García Trejo Abraham Arellano Buendía Omegar Sánchez Reyes Fernando García Arroyo Raúl Arguello García María Loredo Mendoza Edilia Tapia Laura Sánchez Lozada Horacio Osorio Alonso

Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex. The levels of angiotensin receptors and endothelial nitric oxide synthase (eNOS) were decreased in the renal cortex from the CKD group. Otherwise, lipid and protein oxidation were higher in the CKD group than in the control group. A disturbance was observed in the expression levels of the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 system (Nrf2/keap1) and the antioxidant enzymes catalase, superoxide dismutase, and heme oxygenase-1. Allicin or losartan treatments relieved renal dysfunction, hypertension, and oxidative stress. In addition, both treatments showed the same efficacy on the expression of angiotensin receptors, the nephrin, Nrf2/keap1 pathway, and eNOS. Further in silico analyses suggest that allicin and losartan could have a common mechanism involving interaction with AT1 receptors. Allicin showed antihypertensive, antioxidant, and nephroprotective effects. The beneficial effects showed by allicin are similar, or even better, than those of losartan. In fact, the effect of allicin on blood pressure and renal function is comparable to reductions seen with losartan, a prescription drug commonly used as a first-line therapy.

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IJMS, Vol. 18, Pages 1984: iTRAQ-Based Quantitative Proteomic Analysis Reveals Cold Responsive Proteins Involved in Leaf Senescence in Upland Cotton (Gossypium hirsutum L.)

IJMS, Vol. 18, Pages 1984: iTRAQ-Based Quantitative Proteomic Analysis Reveals Cold Responsive Proteins Involved in Leaf Senescence in Upland Cotton (Gossypium hirsutum L.)

International Journal of Molecular Sciences doi: 10.3390/ijms18091984

Authors: Xuewei Zheng Shuli Fan Hengling Wei Chengcheng Tao Qiang Ma Qifeng Ma Siping Zhang Hongbin Li Chaoyou Pang Shuxun Yu

Premature leaf senescence occurs in the ultimate phase of the plant, and it occurs through a complex series of actions regulated by stress, hormones and genes. In this study, a proteomic analysis was performed to analyze the factors that could induce premature leaf senescence in two cotton cultivars. We successfully identified 443 differential abundant proteins (DAPs) from 7388 high-confidence proteins at four stages between non-premature senescence (NS) and premature senescence (PS), among which 158 proteins were over-accumulated, 238 proteins were down-accumulated at four stages, and 47 proteins displayed overlapped accumulation. All the DAPs were mapped onto 21 different categories on the basis of a Clusters of Orthologous Groups (COG) analysis, and 9 clusters were based on accumulation. Gene Ontology (GO) enrichment results show that processes related to stress responses, including responses to cold temperatures and responses to hormones, are significantly differentially accumulated. More importantly, the enriched proteins were mapped in The Arabidopsis Information Resource (TAIR), showing that 58 proteins play an active role in abiotic stress, hormone signaling and leaf senescence. Among these proteins, 26 cold-responsive proteins (CRPs) are significantly differentially accumulated. The meteorological data showed that the median temperatures declined at approximately 15 days before the onset of aging, suggesting that a decrease in temperature is tightly linked to an onset of cotton leaf senescence. Because accumulations of H2O2 and increased jasmonic acid (JA) were detected during PS, we speculate that two pathways associated with JA and H2O2 are closely related to premature leaf senescence in cotton.

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Why Vending Machines are Not Bodegas

Technology should be bringing communities together, not creating further divisions. 

-- Read more on ScientificAmerican.com

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Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments

Publication date: Available online 15 September 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Xiaojuan Wang, Jiabao Liu, Pankaj Pandey, Jiabao Chen, Frank R. Fronczek, Stuart Parnham, Xinzhu Qi, Robert J. Doerksen, Daneel Ferreira, Hua Sun, Shuai Li, Mark T. Hamann
BackgroundThe plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential. In this work, the absolute configurations of three highly oxygenated schiartane-type nortriterpenoids were unequivocally assigned using X-ray, ECD, and J-based configuration analysis and HSQC overlay data.MethodsThe ethanol extract of Kadsura longipedunculata Finet et Gagnep was purified by column chromatography using silica, Sephadex LH-20, and ODS as substrates. To help assign the absolute configuration of schiartane-type nortriterpenoids, X-ray diffraction analysis, ECD experiment compared to ab initio computed data, DP4+ analysis, HSQC overlay, NOESY, and J-based configuration analysis were carried out. Hetero- and homo-nuclear coupling constants were extracted from HETLOC experiments.ResultsThree new highly oxygenated triterpenoids, micrandilactone I (1), micrandilactone J (2), and 22, 23-di-epi-micrandilactone J (3) were isolated. Their 2D structures were solved using NMR and HRESIMS data and their absolute configurations were elucidated using X-ray diffraction analysis, ECD experimental results compared to ab initio computed spectra, HSQC overlay, DP4 plus, NOESY, and J-based configuration analysis. Micrandilactone I (1) and 22, 23-di-epi-micrandilactone J (3) showed moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells with cell survival rates of 53.0 and 50.2%, respectively, at 10μM (bicyclol, 49.0%), while micrandilactone J (2) was inactive.General significanceThis is the first comprehensive stereochemical assignment of a non-crystalline schiartane-type nortriterpenoid like 3. This general protocol may contribute towards solving the problems hampering the assignment of the absolute configurations of other members of this class of nortriterpenoids.

Graphical abstract

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Why Vending Machines are Not Bodegas

Technology should be bringing communities together, not creating further divisions. 

-- Read more on ScientificAmerican.com

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Project LifeSkills - a randomized controlled efficacy trial of a culturally tailored, empowerment-based, and group-delivered HIV prevention intervention for young transgender women: study protocol

Transgender women in the U.S. have an alarmingly high incidence rate of HIV infection; condomless anal and vaginal sex is the primary risk behavior driving transmission. Young transgender women are the subpopu...

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A prospective cohort study on ambient air pollution and respiratory morbidities including childhood asthma in adolescents from the western Cape Province: study protocol

There is evidence from existing literature that ambient air pollutant exposure in early childhood likely plays an important role in asthma exacerbation and other respiratory symptoms, with greater effect among...

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The associations between workplace bullying, salivary cortisol, and long-term sickness absence: a longitudinal study

Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absen...

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Body mass index and type 2 diabetes in Thai adults: defining risk thresholds and population impacts

Body mass index (BMI) cut-off values (>25 and >30) that predict diabetes risk have been well validated in Caucasian populations but less so in Asian populations. We aimed to determine the BMI threshold associated...

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Model of ontogenetic variability of the functional state of the organism in different regimes of motor activity

Abstract

This paper analyzes the results of the study of the long-term effect of physical exercising and sports in the age range, including late periods of human ontogeny, from the standpoint of the oxidative stress theory. To study the features of the ontogenetic variability of the functional state of the organism, a comparative study of the indices of the functional state of the organism was carried out under different regimes of motor activity at different age stages of development: in sport veterans who continue active motor activity after the termination of a sports career, in former sportsmen leading a sedentary lifestyle, in individuals engaged in recreational forms of exercise, and in individuals who were never regularly engaged in physical education. The contingent of male subjects of different ages also included former athletes and coaches of national teams for cyclical and game sports that require a predominant endurance. As a result of the study, a model was developed that reflects the features and mechanisms of ontogenetic variability of the functional state of the organism under the influence of different regimes of motor activity.

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Melatonin as a marker of severity of cardiac disorders in developing cachexia syndrome among cancer patients of different age groups

Abstract

We investigated 103 newly diagnosed stage II–IV cancer patients aged 28–78 years before the beginning of their anticancer therapy. The signs of cachexia syndrome were diagnosed and staged (precachexia or fully-fledged cachexia), including the age-related characteristics of subjects, based on the CASCO criteria (2011). It has been established that cardiovascular disorders with comorbid cancer pathologies were significantly more frequently recorded in patients with signs of cachexia syndrome already at its precachexia stage, while the cumulative index of cardiovascular disorders has been found to increase in cancer patients as cachexia progressed and its severity increased. The level of melatonin excretion evaluated by the excreted amount of 6-sulfatoximelatonin (aMT6s), the mean melatonin metabolite, was observed to decrease significantly in cancer patients as the CS manifestations became more advanced. The least changes in the aMT6s levels were observed in patients aged over 60 years who were included in the precachexia group, which might indicate the heterogeneity of the given sample due to the combined manifestation of geriatric syndromes and cancer pathologies. A false-positive precachexia diagnosis is also possible, especially, in elderly and old patients, due to a combination of polygenic metabolic and age-related changes, which are to meet, in sum, the current criteria for CS. Therefore, it is recommended to determine the melatonin excretion indicator as an additional marker in the diagnosis and differential diagnosis of CS with its progression, in particular, in geriatric patients. A significant correlation has been found between the emergence of cardiac pathology and/or a worsening in its course in cancer patients with cachexia symptoms and reduced aMT6s content.

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Study into ratios of mineral metabolism in patients of different age groups suffering from osteoarthritis of the knee

Abstract

A study has been made into indicators of electrolyte composition and phosphatase activity of blood serum, urine, and synovial fluid of the patients belonging to different age groups and going through compensated, subcompensated, and decompensated stages of osteoarthritis of the knee. Changes in parameters of mineral metabolism have been detected related to the progress of the disease. The most obvious alteration was discovered in patients of the second age group having the subcompensated osteoarthritis stage. Elderly patients at the decompensated stage showed shifts of indicators of the bone remodeling.

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Role of ceramide in the aging-related decrease of cardiolipin content in the rat heart

Abstract

Ceramide accumulation and a decrease of cardiolipin level in cardiomyocytes are among the key reasons of mitochondrial dysfunction and the emergence of heart failure. Ceramide has a significant effect on cardiolipin metabolism, and, therefore, the aim of the present study was to assess the role of ceramide in the aging-related decrease of cardiolipin content in the rat heart. Young (sexually mature), adult, and old (3-, 12-, 24-, 30-, and 34-month-old) Wistar male rats were used in the study. A considerable decrease in the content of cardiolipin during aging was accompanied by accumulation of phosphatidic acid, a precursor of cardiolipin. Doxorubicin administration to the rats or the perfusion of an isolated heart with a buffer solution supplemented with C16-ceramide evoked an increase in ceramide levels and a decrease in the level of cardiolipin in the heart of 3-month-old rats. The reduction of ceramide content in the hearts of 24-month-old rats by means of administration of melipramine and zoledronic acid that inhibit acidic sphingomyelinase led to an increase in cardiolipin levels. The results point at a certain contribution of sphingomyelinase-dependent ceramide accumulation to the aging-related decrease of cardiolipin content that can lead to disturbances of cardiac function. Acid sphingomyelinase and cardiolipin metabolism can be important targets in the treatment of aging-related cardiac pathology.

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Content of proinflammatory cytokines, peroxiredoxin-1, and activity of glutathione peroxidase in blood plasma of coronary artery disease patients after coronary artery bypass grafting

Abstract

An examination of a group of 76 CAD patients after coronary artery bypass grafting was performed with the goal to investigate the role of proinflammatory cytokines and enzymes participating in redox regulation in the mechanisms of development of systemic inflammation response and pathogenesis of postpericardiotomy syndrome (PPS). The patients were divided into two groups: the first group was CAD patients that were not diagnosed with PPS based on clinical examination, and the second group was CAD patients diagnosed with PPS. The enhancements of IL-6 and IL-8 production, as well as imbalance in the functions of peroxiredoxin-1 and glutathione peroxidase, was observed in the blood plasma of the patients from both groups. These changes were observed at earlier stages in the patients with PPS, and they were more substantial. The results of this work confirmed the high efficiency of the investigated indicators for prevention and monitoring of the PPS development.

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Analysis of catamnesis of combatants–pensioners of the Ministry of Internal Affairs with mental disorders

Abstract

We analyzed catamnesis of combatants–pensioners of the Ministry of Internal Affairs (MIA) of Russia dismissed due to the presence of mental disorders impeding further serving. It is shown that, within 3 years after the dismissal, a negative clinical dynamics of mental state with disability and formation of concomitant alcohol dependence are noted among combatants. They have some serious social problems, like divorce, and they are involved in unqualified manual work or do not work at all. This requires some improved approaches in providing them with medical, psychological, and social assistance, with regular observation. It was proposed to organize Mental Health Centers in the departmental regional health units of the Ministry of Internal Affairs of Russia on the basis of existing centers of psychophysiological diagnostics for systemic monitoring of the mental state of combatants with mental disorders and improving the quality of provision of medical assistance.

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Emotional burnout syndrome in elderly women–physicians

Abstract

This paper presents the results of a comparative study of the clinical symptoms of emotional burnout syndrome among 84 elderly women working in the specialty of physicians and 48 women who have officially ceased working in this specialty. The findings suggest that emotional burnout syndrome can take place in the elderly and is most closely associated with continued professional activity. The cessation of this working activity leads to stress, often with the subsequent development of posttraumatic stress disorder and stressinduced diseases. However, in this case, the clinical symptoms of emotional burnout syndrome do not disappear but are only transformed with joining of various psychosomatic disorders. Thus, the elderly who suffer from emotional burnout syndrome are a risk group as regards the formation and development of stress-associated diseases and require close attendance within the compulsory program of medical examination.

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Indicators of comorbidity in chronic broncho-obstructive pathology

Abstract

We studied the issue of comorbidity in hospitalized patients with chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA, control group). A correlation and regression analysis has shown a close direct relationship between the comorbidity index and age in patients with chronic broncho-obstructive pathology. By the summary comorbidity index, patients with chronic obstructive pulmonary disease differ significantly more than two times from those of the comparison group. An increase of the comorbidity index with an increase in the severity of chronic obstructive pulmonary disease and the worsening of the forecast mortality within 3 years in COPD compared with bronchial asthma have been revealed.

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Archaic stereotypes and modern approaches in understanding of aging

Abstract

Social sciences are in the process of understanding the place of aged people in society and elaborating an adequate attitude to global aging and the elderly themselves. This appears as a conflict between the archaic stereotypes and new approaches demanded by the changed social and age structure of society. These stereotypes are characteristic not only of the elderly cohort but also of the established scientific institutions and practices. It is necessary to retarget science, media, and social policy to study and implement the potential of postponed aging.

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Aging of dogs and Drosophila as described based on the kinetic theory

Abstract

The goal of this study is to assess the adequacy of models assumed in the kinetic theory of aging of living systems, which is based on the analysis of data obtained on dogs and fruit flies. The mathematical model of the kinetic theory of aging was demonstrated to describe the probability density of death, probability of death, and the average longevity of the biological systems studied. These systems were considered in their natural environments and under conditions of short-term chronic irradiation and elevated temperature in the case of dogs and flies, respectively. The aging kinetic equations and their parameters are represented.

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Endocrinology of cancer and age: Early and late developmental stages

Abstract

Processes essential for hormone-dependent carcinogenesis occur at different developmental stages, even the earliest. Early deviations in the hormone–metabolic status often inversely correlate with the risk of common age-associated noncommunicable diseases, in particular, tumors in hormone-dependent tissues and cardiovascular disorders. Another paradox is the increase in reproductive system tumor incidence at the age associated with lower production of mitogenic hormones. Therefore, one should take into account the production of steroids directly in target tissues and recognize the importance of the progenotoxic effect of estrogens and their derivatives. Another noteworthy aspect is the role of endocrine–genotoxic switchings, which form the so-called basic triad, generated by age-associated endocrine shifts and environmental factors. In addition to the steroid-dependent set of cancer risk factors, attention should be paid to nonsteroid ones (such as those associated with insulin resistance or inflammatory cytokines), since they are tightly connected with the immune system functional state, mild chronic inflammation, obesity phenotype, and pro-/antiinflammatory lipid factor ratio. All these considerations confirm the importance of timely preventive interventions at early and late developmental stages, which are often several decades apart.

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Adaptation to intermittent hypoxia-hyperoxia improves cognitive performance and exercise tolerance in the elderly

Abstract

To maintain physical performance and cognitive functions in the elderly, multimodal training programs (MTP) are used, which are based on physical training, physiotherapy procedures, psychological training, etc. To increase the efficiency of MTP in the elderly, it is suggested to apply a new variant of adaptation to interval normobaric hypoxia, interval hypoxic-hyperoxic training (IHHT). A placebo-controlled clinical trial included 34 patients aged 64–92 years of the day geriatric hospital of the Klagenfurt Clinic (Carinthia, Austria) who were randomized into two groups: experimental (EG), those who received MTP and IHHT, and control (CG), those who passed the course of MTP during the simulation of IHHT procedures. Before and after the rehabilitation course, cognitive functions and exercise endurance of the patients were evaluated using the dementia detection test DemTect, the clock-drawing test, and a 6-minute walk test (6MWT). During the course of IHHT, cognitive capabilities of EG patients significantly improved in comparison with CG patients: the increase in values in the dementia test was +16.7% (in CG +0.39%, p < 0.001), and that in the clock-drawing test was +10.7% (in CG–8%, p = 0.031). The distance covered in the 6-minute test increased in both the groups but significantly more in OG, 24.1% (in CG +10.8%, p = 0.021). Direct significant correlations between increment in exercise tolerance and cognitive tests were revealed. Thus, the inclusion of procedures for adaptation to interval hypoxia-hyperoxia in MTP in the elderly leads to a significant increase in their effectiveness, which is manifested in the improvement of cognitive functions and physical endurance. IHHT procedures are well tolerated and do not cause side effects.

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Apolipoprotein L1 confers pH-switchable ion permeability to phospholipid vesicles [Molecular Bases of Disease]

Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo, we used vesicle-based ion-permeability, direct membrane-association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1. We found that ApoL1 confers chloride-selective permeability to preformed phospholipid vesicles and that this selectivity is strongly pH sensitive, with maximal activity at pH 5 and little activity above pH 7. When ApoL1 and lipid were allowed to interact at low pH and were then brought to neutral pH, chloride permeability was suppressed, and potassium permeability was activated. Both chloride and potassium permeability linearly correlated with the mass of ApoL1 in the reaction mix, and both exhibited lipid selectivity, requiring the presence of negatively charged lipids for activity. Potassium, but not chloride, permease activity required the presence of calcium ions in both the association and activation steps. Direct assessment of ApoL1-lipid associations confirmed that ApoL1 stably associates with phospholipid vesicles, requiring low pH and the presence of negatively charged phospholipids for maximal binding. Intrinsic fluorescence of ApoL1 supported the presence of a significant structural transition when ApoL1 is mixed with lipids at low pH. This pH-switchable ion-selective permeability may explain the different effects of ApoL1 reported in intracellular and plasma membrane environments.

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18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries

Thyroid , Vol. 0, No. 0.


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Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis

Thyroid , Vol. 0, No. 0.


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Comparison of Core-Needle Biopsy and Fine-Needle Aspiration for Evaluating Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: A Propensity Score Analysis

Thyroid , Vol. 0, No. 0.


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Impact of feeding chromium supplemented flaxseed based diet on fatty acid profile, oxidative stability and other functional properties of broiler chicken meat

Abstract

A total of 240 broiler chicken of same hatch with uniform weight were used in a biological experiment with completely randomized design to investigate the effects of incorporating organic chromium (Cr) in flaxseed meal based diet on the fatty acid profile, oxidative stability and functional properties of broiler chicken meat. Five diets were formulated as per the recommendations of BIS (Nutrient requirements for poultry 13: 9863, Bureau of Indian Standards, New Delhi, 1992) in which flaxseed meal was used to replace 10% of soyabean in basal diet and four levels of Cr (0.0, 0.5, 1.0 and 1.5 mg/kg diet) as Cr-picolinate were used. The results revealed that flaxseed feeding significantly increased the percentage of unsaturated fatty acids, including MUFA, PUFA, ω-3, ω-6 fatty acids and ω-3:ω-6 and PUFA:SFA ratios, whereas, significant decline was seen in saturated fatty acids and no effect of Cr was observed on the fatty acid profile of broiler chicken. Flaxseed feeding significantly reduced the cholesterol and fat percentage of meat, whereas, significant progressive reduction was observed with increasing Cr levels. The combination of 10% flaxseed with 1.0 mg Cr/kg diet increased the final pH of broiler meat. The addition of flaxseed significantly reduced water holding capacity, extract release volume and antioxidant potential of broiler meat, whereas, increasing Cr supplementation progressively increased them. Flaxseed feeding significantly increased the drip loss and lipid peroxidation of broiler meat, whereas, Cr supplementation decreased them. It was concluded that inclusion of 10% flaxseed and 1.5 mg Cr/kg diet results in desirable fatty acid profile, oxidative stability and functional properties of broiler chicken meat.

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Radioactive seed migration following parotid gland interstitial brachytherapy

Publication date: Available online 15 September 2017
Source:Brachytherapy
Author(s): Yi Fan, Ming-wei Huang, Yi-jiao Zhao, Hong Gao, Jian-Guo Zhang
PurposeTo evaluate the incidence and associated factors of pulmonary seed migration after parotid brachytherapy using a novel migrated seed detection technique.Methods and MaterialsPatients diagnosed with parotid cancer who underwent permanent parotid brachytherapy from January 2006 to December 2011 were reviewed retrospectively. Head and neck CT scans and chest X-rays were evaluated during routine follow-up. Mimics software and Geomagic Studio software were used for seed reconstruction and migrated seed detection from the original implanted region, respectively. Postimplant dosimetry analysis was performed after seeds migration if the seeds were still in their emitting count. Adverse clinical sequelae from seed embolization to the lung were documented.ResultsThe radioactive seed implants were identified on chest X-rays in 6 patients. The incidence rate of seed migration in 321 parotid brachytherapy patients was 1.87% (6/321) and that of individual seed migration was 0.04% (6/15218 seeds). All migrated seeds were originally from the retromandibular region. No adverse dosimetric consequences were found in the target region. Pulmonary symptoms were not reported by any patient in this study.ConclusionsIn our patient set, migration of radioactive seeds with an initial radioactivity of 0.6–0.7 mCi to the chest following parotid brachytherapy was rare. Late migration of a single seed from the central target region did not affect the dosimetry significantly, and patients did not have severe short-term complications. This study proposed a novel technique to localize the anatomical origin of the migrated seeds during brachytherapy. Our evidence suggested that placement of seeds adjacent to blood vessels was associated with an increased likelihood of seed migration to the lungs.



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Risk Prediction of Cervical Cancer and Precancers by Type-specific Human Papillomavirus: Evidence from a Population-based Cohort Study in China

Risk stratification of human papillomavirus (HPV)-positive women is needed to avoid excessive colposcopy and overtreatment in cervical cancer screening. We aimed to evaluate the predictive value of type-specific HPV in detecting cervical cancer and precancers in a Chinese population-based cohort and provide evidence of HPV genotyping to triage HPV-positive women. We typed all Hybrid Capture 2-positive cytological samples of 1,742 women in Shanxi Province Cervical Cancer Screening Study cohort. Cumulative risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among HPV positive women and cumulative detection rates of CIN2+ among general women by type-specific HPV were estimated during the course of ten-year follow-up. HPV 16 and HPV 52 were most prevalent types among the screening population. Ten-year cumulative risk of CIN2+ was 47.5% (95%CI= 31.6% to 62.3%) for HPV 16 positive women and 46.3% (95%CI= 15.3% to 75.4%) for HPV 31 positive women. Ten-year cumulative risks of CIN2+ among HPV 58, 39, 33, 18 and 52 positive women ranged from 34.3% to 12.0% in a decreasing order. CIN2+ risks were found to be positively associated with infection times of the same genotypes of HPV 16, 31, 33 and 58 (all ptrend<0.001). Cumulative detection rates of CIN2+ within ten years were predominantly contributed by HPV 16, 31 and 58. Our results support the risk-based management of HPV positive women using HPV genotyping, and also indicate the significance of including HPV 31 and 58 apart from commonly acknowledged HPV 16 and HPV 18 in achieving better risk stratification.

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These Unprecedented Times

Telemedicine and e-Health Sep 2017, Vol. 23, No. 9: 697-698.


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Functionalized poly(3-hydroxybutyric acid) bodies as new in vitro biocatalysts

Publication date: Available online 15 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Benjamin Stenger, Adrian Gerber, Rita Bernhardt, Frank Hannemann
Cytochromes P450 play a key role in the drug and steroid metabolism in the human body. This leads to a high interest in this class of proteins. Mammalian cytochromes P450 are rather delicate. Due to their localization in the mitochondrial or microsomal membrane, they tend to aggregate during expression and purification and to convert to an inactive form so that they have to be purified and stored in complex buffers. The complex buffers and low storage temperatures, however, limit the feasibility of fast, automated screening of the corresponding cytochrome P450-effector interactions, which are necessary to study substrate-protein and inhibitor-protein interactions. Here, we present the production and isolation of functionalized poly(3-hydroxybutyrate) granules (PHB bodies) from Bacillus megaterium MS941 strain. In contrast to the expression in Escherichia coli, where mammalian cytochromes P450 are associated to the cell membrane, when CYP11A1 is heterologously expressed in Bacillus megaterium, it is located on the PHB bodies. The surface of these particles provides a matrix for immobilization and stabilization of the CYP11A1 during the storage of the protein and substrate conversion. It was demonstrated that the PHB polymer basis is inert concerning the performed conversion. Immobilization of the CYP11A1 onto the PHB bodies allows freeze-drying of the complex without significant decrease of the CYP11A1 activity. This is the first lyophilization of a mammalian cytochrome P450, which allows storage over more than 18days at 4°C instead of storage at −80°C. In addition, we were able to immobilize the cytochrome P450 on the PHB bodies in vitro. In this case the expression of the protein is separated from the production of the immobilization matrix, which widens the application of this method. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.



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Dangling regimes after free flap reconstruction of the lower limb; further evidence is required

We read with interest the recent systematic review by McGhee et al.1 on flap survival and morbidity following early post-operative rehabilitation after lower limb free flap reconstruction, where it was concluded that post-operative dangling confers physiological benefit in flap healing.

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Peripheral T-cell lymphomas:focusing on novel agents in relapsed and refractory disease

Peripheral T-cell non-Hodgkin lymphomas (PTCL) are a heterogeneous group of mature T-cell neoplasms, mostly of nodal origin, generally associated with a poor prognosis and displaying a wide geographical heterogeneity, accounting for 5% to 10% of all aggressive lymphomas in Europe and in the United States, whereas being most widely represented (up to roughly 20%) in Asia, where some peculiar forms of disease (adult T-cell leukemia/lymphoma, ATLL; or neoplasms of the NK/T-cell origin) are prevalent [1–3].

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