An aerobic exercise intervention to improve metabolic health among people living with HIV with at-risk alcohol use: the ALIVE-Ex research study protocol.

BACKGROUND: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. METHODS: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention is a moderate intensity aerobic exercise protocol implemented 3 days per week for 10 weeks at the Louisiana State University Health Sciences Center-New Orleans. Participants who have a fasting blood glucose level between 94 and 125 mg/dl will be enrolled in the study. Oral glucose tolerance tests, fitness assessments, and skeletal muscle biopsies will be performed pre- and post-exercise intervention. The primary outcome is to determine whether the exercise protocol improves measures of whole-body glucose-insulin dynamics, cardiorespiratory fitness, and skeletal muscle metabolic and bioenergetic function. Secondary outcomes are to determine whether the exercise intervention improves cognitive function and overall quality of life. Results generated will demonstrate the effect of exercise on glycemic measures in PLWH with subclinical dysglycemia and at-risk alcohol use. CONCLUSIONS: The proposed intervention will also have the potential to be scalable to promote lifestyle changes among PLWH, particularly in underserved communities.

Case report: Homozygous variants of NEB and KLHL40 in two Arab patients with nemaline myopathy.

Objective: Nemaline myopathies are a heterogeneous group of congenital myopathies caused by mutations in different genes associated with the structural and functional proteins of thin muscular filaments. Most patients have congenital onset characterized by hypotonia, respiratory issues, and abnormal deep tendon reflexes, which is a phenotype encountered in a wide spectrum of neuromuscular disorders. Whole-exome sequencing (WES) contributes to a faster diagnosis and facilitates genetic counseling. Methods: Here, we report on two Arab patients from consanguineous families diagnosed with nemaline myopathy of different phenotype spectrum severities. Results: Clinical assessment and particular prenatal history raised suspicion of neuromuscular disease. WES identified homozygous variants in NEB and KLHL40. Muscle biopsy and muscle magnetic resonance imaging studies linked the genetic testing results to the clinical phenotype. The novel variant in the NEB gene resulted in a classical type 2 nemaline myopathy, while the KLHL40 gene variant led to a severe phenotype of nemaline myopathy, type 8. Both patients were identified as having other gene variants with uncertain roles in their complex phenotypes. Conclusions: This study enriches the phenotypic spectrum of nemaline myopathy caused by NEB and KLHL40 variants and highlights the importance of detailed prenatal, neonatal, and infancy assessments of muscular weakness associated with complex systemic features. Variants of uncertain significance in genes associated with nemaline myopathy may be correlated with the phenotype. Early, multidisciplinary intervention can improve the outcome in patients with mild forms of nemaline myopathies. WES is essential for clarifying complex clinical phenotypes encountered in patients from consanguineous families. Targeted carrier screening of extended family members would enable accurate genetic counseling and potential genetic prevention.

An Updated Review on Efficiency of Penthorum chinense Pursh in Traditional Uses, Toxicology, and Clinical Trials.

Traditional Chinese medicines (TCM) play an important role in the control and treatment of several animal diseases. Penthorum chinense Pursh (PCP) is a famous plant for its use in traditional medication practice and therapeutic effects in numerous pathological conditions. In China, PCP is utilized for both food and medication due to numerous bioactivities. PCP is widely administered in prevention and treatment of traumatic injury, edema, and liver diseases with functions of reducing swelling, support diuresis, blood stasis, and mitigation symptoms of excessive alcohol intake. Recently, PCP highlighted for research trials in various fields including pharmacology, pharmacognosy, cosmeceuticals, nutraceuticals, and pharmaceuticals due to medicinal significance with less toxicity and an effective ethnomedicine in veterinary practice. PCP contains diverse important ingredients such as flavonoids, organic acids, coumarins, lignans, polyphenols, and sterols that are important bioactive constituents of PCP exerting the therapeutic benefits and organ-protecting effects. In veterinary, PCP extract, compound, and phytochemicals/biomolecules significantly reversed the liver and kidney injuries, via antioxidation, oxidative stress, apoptosis, mitochondrial signaling pathways, and related genes. PCP water extract and compounds also proved in animal and humans' clinical trial for their hepatoprotective, antiaging, nephroprotective, anti-inflammatory, antidiabetic, antibacterial, antiapoptotic, immune regulation, and antioxidative stress pathways. This updated review spotlighted the current information on efficiency and application of PCP by compiling and reviewing recent publications on animal research. In addition, this review discussed the toxicology, traditional use, comparative, and clinical application of PCP in veterinary practices to authenticate and find out new perspectives on the research and development of this herbal medicine.

Cloud-based healthcare framework for real-time anomaly detection and classification of 1-D ECG signals.

Real-time data collection and pre-processing have enabled the recognition, realization, and prediction of diseases by extracting and analysing the important features of physiological data. In this research, an intelligent end-to-end system for anomaly detection and classification of raw, one-dimensional (1D) electrocardiogram (ECG) signals is given to assess cardiovascular activity automatically. The acquired raw ECG data is pre-processed carefully before storing it in the cloud, and then deeply analyzed for anomaly detection. A deep learning-based auto-encoder(AE) algorithm is applied for the anomaly detection of 1D ECG time-series signals. As a next step, the implemented system identifies it by a multi-label classification algorithm. To improve the classification accuracy and model robustness the improved feature-engineered parameters of the large and diverse datasets have been incorporated. The training has been done using the amazon web service (AWS) machine learning services and cloud-based storage for a unified solution. Multi-class classification of raw ECG signals is challenging due to a large number of possible label combinations and noise susceptibility. To overcome this problem, a performance comparison of a large set of machine algorithms in terms of classification accuracy is presented on an improved feature-engineered dataset. The proposed system reduces the raw signal size up to 95% using wavelet time scattering features to make it less compute-intensive. The results show that among several state-of-the-art techniques, the long short-term memory (LSTM) method has shown 100% classification accuracy, and an F1 score on the three-class test dataset. The ECG signal anomaly detection algorithm shows 98% accuracy using deep LSTM auto-encoders with a reconstructed error threshold of 0.02 in terms of absolute error loss. Our approach provides performance and predictive improvement with an average mean absolute error loss of 0.0072 for normal signals and 0.078 for anomalous signals.

Clinically significant endoscopic findings in a dyspeptic rural population cohort of Sindh, Pakistan: Are we over-investigating?

Objectives: To discuss the clinically significant endoscopic findings of the upper GI tract and their association with different age groups in a dyspeptic rural population of Gadap town, Sindh. Methods: This was a retrospective secondary data analysis of 806 patients conducted in the medical ward of Fatima Hospital, Baqai Medical University from December 2016 to May 2019. It was approved by the University Ethics Committee. Patients' demographics and other data related to the procedure were recovered from patients' records. SPSS version 20 was used for statistical analysis. Results: There were marginally more women suffering from dyspepsia as opposed to men (51.5% vs 48.5% respectively). Majority of the patients were less than 45 years of age, with most procedures being performed as outpatients. Nearly 40% of the patients did not have clinically relevant endoscopic findings. Most common significant finding on endoscopic examination was gastritis followed by hiatal hernia. Conclusion: Normal upper gastrointestinal endoscopy, regardless of age, is a common finding in patients suffering from dyspepsia in our setting. Therefore, in a resource constraint environment like ours, expensive endoscopic procedures should be reserved for those patients who are not responding to medical therapy or those who have alarm symptoms.

COVID-19 lockdown: Online survey of psychosocial factors of adolescents.

BACKGROUND: The coronavirus pandemic has affected more than 14 million people in the world. Adults are somehow able to manage their stress created by the most fearful disease. However, it is the children and adolescents who are most affected by COVID-19 lockdown. AIM: This study aimed to assess the effect of COVID-19 lockdown on adolescent's psychosocial factors. MATERIALS AND METHODS: Using the Google Form link, a questionnaire was developed and an online survey was conducted. This online questionnaire consisted of 40 items assessing personal, social, academic, and family domains related to adolescents. RESULTS: A total of 223 responses were obtained. The results indicate that 6.5% of adolescents experience extreme level of anxiousness, 29.8% become little irritable and angry, affecting their personal/emotional domain. About 12.6% of the adolescents are uncomfortable with social distancing and 48.4% of them greatly miss their friends; 38.1% miss their school and 28.8% are unable to clear their doubts through online teaching. Mathematics was the most uncomfortable subject for them to deal with 49.8%. About 79% of adolescents suffer mildly from family distress, 43.3% (extremely) are eagerly waiting for the lockdown to end. CONCLUSION: Among all four domains, the family domain was the most affected due to COVID-19 lockdown, followed by social, academic, and personal domains.

Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53 ± 9 yr, body mass index: 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.

Upper gastrointestinal endoscopy; A study from a rural population of Sindh, Pakistan.

OBJECTIVE: To discuss common indications and findings on upper gastrointestinal endoscopy as well as to correlate these findings with alarm symptoms in the rural population of Gadap town, Sindh. METHODS: This was a retrospective study on 1288 patients conducted in the medical ward of Fatima Hospital, Baqai Medical University. Patients' demographics and other data related to the procedure were recovered from patients' records. SPSS version 20 was used for statistical analysis. RESULTS: Ratio of male and female patients was approximately 1:1. Majority of the patients were young, and most procedures were done as outpatients without the requirement of conscious sedation. Epigastric pain was the primary indication for upper GI endoscopy (62.6%). One third of the procedures performed did not report any pathological finding. Probability of a positive finding was more likely if a patient presented with dysphagia, heart-burn, hematemesis, vomiting, or for screening endoscopy (for varices). Patients who were diagnosed with esophageal candidiasis, esophageal varices or esophageal growth/ ulcer had reported one or more alarm symptoms in their history. CONCLUSIONS: Upper gastrointestinal endoscopy is a useful test to diagnose disorders of the esophagus, stomach and duodenum. However, it is an expensive procedure and therefore referring physicians should keep appropriate clinical indication and ethical considerations in mind before recommending such an investigation to their patients.

Implementation of the new integrated algorithm for diagnosis of drug-resistant tuberculosis in Karnataka State, India: How well are we doing?

BACKGROUND: As per national policy, all diagnosed tuberculosis patients in India are to be tested using Xpert® MTB/RIF assay at the district level to diagnose rifampicin resistance. Regardless of the result, samples are transported to the reference laboratories for further testing: first-line Line Probe Assay (FL-LPA) for rifampicin-sensitive samples and second-line LPA(SL-LPA) for rifampicin-resistant samples. Based on the results, samples undergo culture and phenotypic drug susceptibility testing. We assessed among patients diagnosed with tuberculosis at 13 selected Xpert laboratories of Karnataka state, India, i) the proportion whose samples reached the reference laboratories and among them, proportion who completed the diagnostic algorithm ii) factors associated with non-reaching and non-completion and iii) the delays involved. METHODS: This was a cohort study involving review of programme records. For each TB patient diagnosed between 1st July and 31st August 2018 at the Xpert laboratory, we tracked the laboratory register at the linked reference laboratory until 30th September (censor date) using Nikshay ID (a unique patient identifier), phone number, name, age and sex. RESULTS: Of 1660 TB patients, 1208(73%) samples reached the reference laboratories and among those reached, 1124(93%) completed the algorithm. Of 1590 rifampicin-sensitive samples, 1170(74%) reached and 1104(94%) completed the algorithm. Of 64 rifampicin-resistant samples, only 35(55%) reached and 17(49%) completed the algorithm. Samples from rifampicin-resistant TB, extra-pulmonary TB and two districts were less likely to reach the reference laboratory. Non-completion was more likely among rifampicin-resistant TB and sputum-negative samples. The median time for conducting and reporting results of Xpert® MTB/RIF was one day, of FL-LPA 5 days and of SL-LPA16 days. CONCLUSION: These findings are encouraging given the complexity of the algorithm. High non-reaching and non-completion rates in rifampicin-resistant patients is a major concern. Future research should focus on understanding the reasons for the gaps identified using qualitative research methods.

Type I Second Degree Atrioventricular Block in a Woman With Remote Repair of a Ventricular Septal Defect.

In a 45-year-old woman with syncope, an electrocardiogram revealed intermittent asymptomatic type I second degree atrioventricular block, right bundle branch block and left anterior fascicular block. An echocardiogram documented concentric left ventricular hypertrophy and right ventricular dilatation and hypokinesia. Because the patient did not have second degree atrioventricular block at the time of an electrophysiological study, the atrioventricular node, the left posterior fascicle, and the His bundle all remain potential sites for the type I second degree atrioventricular block on her initial electrocardiogram.

Atypical Initiation of Typical Atrioventricular Node Reentry Tachycardia With a Ventricular Couplet.

In a woman with sinus rhythm a couplet of ventricular premature complexes is followed by a retrograde P wave. A subsequent couplet of ventricular premature complexes is followed by typical atrioventricular nodal reentrant tachycardia.

Racial Differences in Response to Tilt-Table Testing in Patients Refered.

BACKGROUND: Syncope is a common problem in the general population and results in significant societal and patient costs. Several small studies have demonstrated differences in orthostatic response, and possibly tolerance, between blacks and whites. Based on these observations, we retrospectively reviewed results from our tilt table database to identify potential differences in response to tilt-table testing with regards to race, between black and white patients. METHODS: The reports of 446 tilt-table tests performed on adults, older than 18 years of age, at Boston Medical Center, an urban, tertiary-care, academic hospital, were reviewed. Clinical variables were retrieved from the procedure report. Occurrence of syncope was noted and hemodynamic classification was recorded as neurocardiogenic response, with subcategories of mixed, vasodepressor, or cardio-inhibitory. RESULTS: Of records reviewed, 360 patients (80.7%) identified as white and 86 patients as black (19.3%). There was a significantly lower observed frequency of syncope with a neurocardiogenic response in black vs. white patients (45.5% vs. 60.3%, p=0.015). In addition, significantly fewer black patients demonstrated a mixed neuro-cardiogenic response as compared to white patients (7.0% vs. 15.8%, p=0.038) or cardio-inhibitory response (0% vs. 5.3%, p=0.032). There was no difference in frequency of vasodepressor response in black vs. white patients (39.2 vs.38.4%, p=1.000). CONCLUSIONS: We observed a statistically-significant lower incidence of neurocardiogenic syncope among black patients compared to white patients referred for tilt-table testing for evaluation of syncope.

Use of locally made off-loading techniques for diabetic plantar foot ulcer in Karachi, Pakistan.

The aim of this study was to evaluate the effectiveness of applying locally made pressure off-loading techniques on plantar foot ulcer in individuals with diabetes. This prospective study of 70 diabetic patients was conducted at the foot clinic of Baqai Institute of Diabetology & Endocrinology. Plantar foot ulcer, stages 1A and 2A according to the University of Texas classification, was treated by using three off-loading techniques: modified foot wear (sandal), modified plaster of Paris cast with plywood platform and Scotchcast boot. The outcome was assessed at either complete wound healing (defined as complete epithelialisation) or at 12 weeks, whichever came first. Of the 70 patients, 24 were in modified foot wear group, 23 in modified plaster of Paris cast and 23 in Scotchcast boot group. There was almost equal proportion of patients healed within 12 weeks period treated with these three off-loading techniques, i.e. 22 (95·7%) for modified foot wear group, 19 (95%) for modified plaster cast and 18 (94·7%) for Scotchcast boot group. No significant difference was observed in median healing time and cumulative wound survival at 12 weeks in the three off-loading techniques. Modified foot wear group was the most cost effective ($7) amongst the three off-loading techniques. It is concluded that in this cohort, no significant difference in healing time was observed in the three off-loading techniques, although modified foot wear (sandal) was found to be a more cost-effective treatment modality.

Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis.

BACKGROUND: Flucloxacillin either alone or combined with penicillin V is still the first-line antibiotic drug of choice for the treatment of cellulitis in emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen is their anti-staphylococcal and anti-streptococcal activity. OBJECTIVE: To determine the clinical efficacy, tolerability and safety of oral flucloxacillin alone (monotherapy) compared with a combination of flucloxacillin with penicillin V (dual therapy) in the ED-directed outpatient treatment of cellulitis. METHODS: We searched the following electronic databases: MEDLINE (1950 to August 2011), EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled Trials metaRegister of Clinical Trials (August 2011) and reference lists and websites of potential trials. We performed cross-referencing from the reference lists of major articles on the subject. We imposed no language restriction. RESULTS: Despite a comprehensive literature search to identify relevant studies, no randomized-controlled trials that fulfilled the inclusion criteria were found. CONCLUSIONS: Despite its common use, there are no published randomized-controlled trials comparing flucloxacillin monotherapy with a combination of flucloxacillin and penicillin V in the ED management of cellulitis. We discuss existing European and North American prescribing rationale and current guidelines.

ECG of the month. Irregular rhythm in a 25-year-old man with three prior cardiac operations. Coarse atrial fibrillation with a rapid ventricular response, left anterior fascicular block, left ventricular hypertrophy with repolarization abnormality.

The patient underwent closure of an atrial septal defect at age 3, had a leaking "mitral" valve repaired at age 9, and at age 13 had a "mitral" valve replacement. He began taking warfarin sodium at that time and remained symptom-free until 10 days before his initial visit here when he presented to another hospital with dyspnea and palpitations. Treatment there consisted of lisinopril 10 mg qd, carvedilol 6.25 mg bid, aldactone 25 mg qd, furosemide 40 mg qd, digoxin 0.25 mg qd, and a continuation of warfarin sodium 7.5 mg qd. An echocardiogram showed a left ventricular ejection fraction of 20%. After diuresis, he was referred to our cardiology clinic. On his initial visit here, his heart rate was an irregular 120 beats/min, his blood pressure was 106/77 mmHg, and closing and opening snaps of a normally functioning mechanical mitral valvular prosthesis were heard. He was obese (height, 5' 9"; weight, 272 lbs). An electrocardiogram was recorded (Figure 1).

FibroScore for the non-invasive assessment of liver fibrosis in chronic viral hepatitis.

OBJECTIVE: To evaluate the predictive value of a set of laboratory markers for the assessment of liver fibrosis in chronic viral hepatitis patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Baqai Medical University, Combined Military Hospital, Malir, Karachi, from November 2006 to May 2008. METHODOLOGY: Twenty laboratory parameters were measured in 100 treatment-naïve chronic viral hepatitis patients who also had liver biopsy performed. Descriptive statistics, areas under the ROC's curves, and multivariate logistic regression analysis identified a fibrosis panel, a set of five most useful markers, for the assessment of stages of fibrosis, stage 0 to stage 4. The fibrosis index, FibroScore, consisted of bilirubin, Gamma glutamyl transferase, Hyaluronic acid, alpha 2 macroglobulin, and platelets evaluation. RESULTS: A score of ≥ 0.5 predicted stages 2, 3 and 4, with a sensitivity of 82%, and specificity of 92%. A score ≥ 0.5 for stages 3 and 4 had a sensitivity of 85%, and specificity of 89%. At a score of > 0.80, for stages 3 and 4, the sensitivity was 70%, specificity was 97%, and PPV 87% (there was ≥ 85% possibility of presence of stage 3 or 4). A score of ≤ 0.20 predicted the absence of stages 2, 3, and 4 with a sensitivity of 91%, specificity of 86%, and NPV of 96%. Scores from 0.00 to 0.10 almost certainly ruled out the presence of stages 2-4 (NPV=98%). The areas under the ROC curve were: 0.808 for stage 2; 0.938 for stage 3; and 0.959 for stage 4. CONCLUSION: A combination of 5 markers is very useful in predicting various stages of liver fibrosis, and is helpful in the non-invasive assessment of liver fibrosis in chronic viral hepatitis patients.