Clinical Utility of Melatonin in Fibromyalgia Diagnosis

       Fibromyalgia syndrome (FMS) is a chronic disease with an unknown etiology, which is characterized by reduced pain threshold (hyperallgesia) & pain with normally innocuous stimuli (allodynia).This diffuse pain is often disease associated  with wide range of  other symptoms including fatigue, sleep disturbance, stiffness& more.FMS often occur concomitantly  with other rheumatologic disease such as rheumatoid arthritis(RA), systemic lupus erthymatosus(SLE).       The pineal hormone melatonin (MT) exerts a variety of effects on the immune system. MT activates immune cells and enhances inflammatory cytokine and nitric oxide production.Methods: We were studied 75 subjects, 55 of subjects were FMS patients defined by the American Colleague of Rheumatology (ACR 2010) criteria. Patients' mean age was 32.5 ± 13.9 years. They were classified into two groups: Group I of 25  primary FMS patients . Group II of 30 secondary FMS patients with other rheumatologic disease such as RA, SLE. Twenty age and sex matched healthy individuals were included in the study as a control group.Results:Mean Melatonin titers were significantly reduced (p<0.0001) in primary FMs patients compared to the controls (21.32vs. 30.9 pg/ml), but they were significantly elevated (p<0.0001) in secondary FMS compared to controls (138.1vs.30.9 pg/ml). Our data imposed that, in 1ry FMS there were negative correlations of MT titers with tender points (r=-0.848**,p<0.0001), sleep disturbance(r=-0.963**, p< 0.0001**), Fatigue (r= -0.972**, p<0.001**), WPI (r= -0,953 **, p<0.0001) and SS (r=-0.901**, p< 0.0001). Conclusions:In primary FMS patients melatonin level is lower than melatonin level in control, but MT level is high in secondary FMS patients. There was a negative correlation between MT with tender points, sleep disturbance, fatigue, SS & WPI. But there was a positive correlation between MT & cognitive symptoms

Myocardial contractility pattern characterization in radiation-induced cardiotoxicity using magnetic resonance imaging: A pilot study with ContractiX

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. Statistical analyses were performed between the sham, 8 weeks post-RT, and 10 weeks post-RT MRI parameters. The results showed that both LVEF and myocardial mass increased post-RT. Peak systolic strain and ContractiX significantly decreased post-RT, with a more relative reduction in ContractiX compared to strain. ContractiX showed an inverse nonlinear relationship with LVEF and continuously decreased with time post-RT. While early diastolic strain rate and mechanical dyssynchrony significantly changed post-RT, ventricular torsion changes were not significant post-RT. In conclusion, ContractiX measured via non-contrast MRI is a sensitive early marker for the detection of subclinical cardiac dysfunction post-RT, and it is superior to other MRI cardiac measures

Obstructive sleep apnoea, positive airway pressure treatment and postoperative delirium: Protocol for a retrospective observational study

INTRODUCTION: Obstructive sleep apnoea (OSA) is common among older surgical patients, and delirium is a frequent and serious postoperative complication. Emerging evidence suggests that OSA increases the risk for postoperative delirium. We hypothesise that OSA is an independent risk factor for postoperative delirium, and that in patients with OSA, perioperative adherence to positive airway pressure (PAP) therapy decreases the incidence of postoperative delirium and its sequelae. The proposed retrospective cohort analysis study will use existing datasets to: (i) describe and compare the incidence of postoperative delirium in surgical patients based on OSA diagnosis and treatment with PAP; (ii) assess whether preoperatively untreated OSA is independently associated with postoperative delirium; and (iii) explore whether preoperatively untreated OSA is independently associated with worse postoperative quality of life (QoL). The findings of this study will inform on the potential utility and approach of an interventional trial aimed at preventing postoperative delirium in patients with diagnosed and undiagnosed OSA. METHODS AND ANALYSIS: Observational data from existing electronic databases will be used, including over 100 000 surgical patients and ~10 000 intensive care unit (ICU) admissions. We will obtain the incidence of postoperative delirium in adults admitted postoperatively to the ICU who underwent structured preoperative assessment, including OSA diagnosis and screening. We will use doubly robust propensity score methods to assess whether untreated OSA independently predicts postoperative delirium. Using similar methodology, we will assess if untreated OSA independently predicts worse postoperative QoL. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Protection Office at Washington University School of Medicine. We will publish the results in a peer-reviewed venue. Because the data are secondary and high risk for reidentification, we will not publicly share the data. Data will be destroyed after 1 year of completion of active Institutional Review Board (IRB) approved projects

Association between preoperative obstructive sleep apnea and preoperative positive airway pressure with postoperative intensive care unit delirium

Importance: Obstructive sleep apnea has been associated with postoperative delirium, which predisposes patients to major adverse outcomes. Positive airway pressure may be an effective intervention to reduce delirium in this population. Objectives: To determine if preoperative obstructive sleep apnea is associated with postoperative incident delirium in the intensive care unit and if preoperative positive airway pressure adherence modifies the association. Design, Setting, and Participants: A retrospective single-center cohort study was conducted at a US tertiary hospital from November 1, 2012, to August 31, 2016, among 7792 patients admitted to an intensive care unit who underwent routine Confusion Assessment Method for the intensive care unit after major surgery. Patients were adults who had undergone a complete preoperative anesthesia assessment, received general anesthesia, underwent at least 1 delirium assessment, were not delirious preoperatively, and had a preoperative intensive care unit stay of less than 6 days. Statistical analysis was conducted from August 20, 2019, to January 11, 2020. Exposures: Self-reported obstructive sleep apnea, billing diagnosis of obstructive sleep apnea, or STOP-BANG (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference and Gender) questionnaire score greater than 4, as well as self-reported use of preoperative positive airway pressure. Main Outcomes and Measures: Delirium within 7 days of surgery. Results: A total of 7792 patients (4562 men; mean [SD] age, 59.2 [15.3] years) met inclusion criteria. Diagnosed or likely obstructive sleep apnea occurred in 2044 patients (26%), and delirium occurred in 3637 patients (47%). The proportion of patients with incident delirium was lower among those with obstructive sleep apnea than those without (897 of 2044 [44%] vs 2740 of 5748 [48%]; unadjusted risk difference, -0.04; 99% credible interval [CrI], -0.07 to -0.00). Positive airway pressure adherence had minimal association with delirium (risk difference, -0.00; 99% CrI, -0.09 to 0.09). Doubly robust confounder adjustment eliminated the association between obstructive sleep apnea and delirium (risk difference, -0.01; 99% CrI, -0.04 to 0.03) and did not change that of preoperative positive airway pressure adherence (risk difference, -0.00, 99% CrI, -0.07 to 0.07). The results were consistent across multiple sensitivity analyses. Conclusions and Relevance: After risk adjustment, this study found no association between obstructive sleep apnea and postoperative delirium in the context of usual care in the intensive care unit, with 99% CrIs excluding clinically meaningful associations. With limited precision, no association was found between positive airway pressure adherence and delirium. Selection bias and measurement error limit the validity and generalizability of these observational associations; however, they suggest that interventions targeting sleep apnea and positive airway pressure are unlikely to have a meaningful association with postoperative intensive care unit delirium

The Relationship of Sperm Motility Pattern and Its Ability to Agglutinate with Vaginal Sperm Selection, Uptake in Sperm Storage Tubules and Competitiveness

To ensure survival, some unique features can be distinguished in birds that help them maintain reproduction. These features include the ability to store sperm for long periods within the utero-vaginal junction, a high sperm concentration per ejaculate, and polyspermy fertilization. Sperm face many challenges prior to fertilization. After copulation, most ejaculated sperm exit the female reproductive tract, and less than 1% continue in an attempt to achieve fertilization. In addition, egg size is substantially larger than sperm size because of the presence of the egg yolk. This results in a large number of sperm penetrating the egg away from the oocyte. These challenges have triggered evolutionary changes to maintain the existence of many species, such as the enormous relative size of the testis, which produces billions of sperm each day, and the ability to store viable sperm for long periods in the oviduct to ensure asynchronous fertilization. This chapter discusses several contemporary and sometimes controversial points regarding sperm behavior and their storage in the oviduct

Rabies virus in slaughtered dogs for meat consumption in Ghana: A potential risk for rabies transmission

Dog-mediated rabies is responsible for approximately 60,000 human deaths annually worldwide. Although dog slaughter for human consumption and its potential risk for rabies transmission has been reported, mainly in some parts of Western Africa and South-East Asia, more information on this and factors that influence dog meat consumption is required for a better understanding from places like Ghana where the practice is common. We tested 144 brain tissues from apparently healthy dogs slaughtered for human consumption for the presence of rabies viruses using a Lyssavirus-specific real-Time RT-PCR. Positive samples were confirmed by virus genome sequencing. We also administered questionnaires to 541 dog owners from three regions in Ghana and evaluated factors that could influence dog meat consumption. We interacted with butchers and observed slaughtering and meat preparation procedures. Three out of 144 (2.1%) brain tissues from apparently healthy dogs tested positive for rabies virus RNA. Two of the viruses with complete genomes were distinct from one another, but both belonged to the Africa 2 lineage. The third virus with a partial genome fragment had high sequence identity to the other two and also belonged to the Africa 2 lineage. Almost half of the study participants practiced dog consumption [49% (265/541)]. Males were almost twice (cOR = 1.72, 95% CI (1.17-2.52), p-value = .006) as likely to consume dog meat compared to females. Likewise, the Frafra tribe from northern Ghana [cOR = 825.1, 95% CI (185.3-3672.9), p-value < .0001] and those with non-specific tribes [cOR = 47.05, 95% CI (10.18-217.41), p-value < .0001] presented with higher odds of dog consumption compared to Ewes. The butchers used bare hands in meat preparation. This study demonstrates the presence of rabies virus RNA in apparently healthy dogs slaughtered for human consumption in Ghana and suggests a potential risk for rabies transmission. Veterinary departments and local assemblies are recommended to monitor and regulate this practice

Gender-Specific HIV Prevention Interventions for Women Who Use Alcohol and Other Drugs: The Evolution of the Science and Future Directions

The use of alcohol and other drugs (AODs) is an important driver of gender disparities in HIV prevalence. Consequently, there is a need for women-specific HIV interventions that are conceptualized to address (1) women’s risk behavior, their roles in sexual relationships, and gender power dynamics, and (2) other issues commonly faced by women who use AODs, such as gender-based violence and victimization. This article presents the evolution of HIV prevention intervention research with women who use AODs. It looks at three generations of women-focused HIV research interventions, including first-generation projects that started in the 1990s, second-generation efforts where projects expanded in scope and included adaptions of evidence-based interventions for global relevance, and finally third-generation projects currently underway that combine biobehavioral methods and are being implemented in real-world settings. Because women who use AODs continue to report risk behaviors related to HIV, emphasis should be placed on training scientists to conduct gender-specific studies, increasing funding for new studies, and advocating to ensure that stigma-free services are available for these at-risk women

ALFRED: an allele frequency resource for research and teaching

ALFRED (http://alfred.med.yale.edu) is a free, web accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Currently, ALFRED has allele frequency tables on over 663 400 polymorphic sites; 170 of them have frequency tables for more than 100 different population samples. In ALFRED, a population may have multiple samples with each ‘sample’ consisting of many individuals on which an allele frequency is based. There are 3566 population samples from 710 different populations with allele frequency tables on at least one polymorphism. Fifty of those population samples have allele frequency data for over 650 000 polymorphisms. Records also have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). The flexible search options and data display and download capabilities available through the web interface allow easy access to the large quantity of high-quality data in ALFRED

Value CMR: Towards a comprehensive, rapid, cost-effective cardiovascular magnetic resonance imaging

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) sequences have been replaced by optimized 3D-cine and 4D-flow sequences, respectively. Furthermore, conventional myocardial tagging has been replaced by fast strain-encoding (SENC) imaging. Finally, T1 and T2 mapping sequences are included in the proposed exam, which allows for myocardial tissue characterization. The proposed rapid exam has been tested in vivo. The proposed exam reduced the scan time from \u3e1 hour with conventional sequences to \u3c20 minutes. Corresponding cardiovascular measurements from the proposed rapid CMR exam showed good agreement with those from conventional sequences and showed that they can differentiate between healthy volunteers and patients. Compared to 2D cine imaging that requires 12-16 separate breath-holds, the implemented 3D-cine sequence allows for whole heart coverage in 1-2 breath-holds. The 4D-flow sequence allows for whole-chest coverage in less than 10 minutes. Finally, SENC imaging reduces scan time to only one slice per heartbeat. In conclusion, the proposed rapid, contrast-free, and comprehensive cardiovascular exam does not require repeated breath-holds or to be supervised by a cardiac imager. These improvements make it tolerable by patients and would help improve cost effectiveness of CMR and increase its adoption in clinical practice

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken