THE GUT-BRAIN AXIS: IMPLICATIONS FOR NEUROLOGICAL DISORDERS, MENTAL HEALTH, AND IMMUNE FUNCTION.

A gut-brain axis (GBA) has a long history of conceptual development. Intestinal dysbiosis has now been recognized as a key player in the development of adult neurodevelopmental disorders, obesity, and inflammatory bowel disease. Recent developments in metagenomics suggest those nutrition and gut microbiotas (GM) are important regulators of the gut-brain communication pathways that cause neurodevelopmental and psychiatric problems in adulthood. Intestinal dysbiosis and neurodevelopmental disease outcomes in preterm newborns are being linked by recent research. Recent clinical investigations demonstrate that in critical care units, intestinal dysbiosis occurs before late-onset newborn sepsis and necrotizing enterocolitis. Strong epidemiologic data also shows a connection between necrotizing enterocolitis and extremely low birth weight babies' long-term psychomotor impairments and late-onset neonatal sepsis. The GBA theory suggests that intestinal bacteria may indirectly affect preterm newborns' developing brains. In this review, we emphasize the structure and function of the GBA and discuss how immune-microbial dysfunction in the gut affects the transmission of stress signals to the brain. Preterm babies who are exposed to these signals develop neurologic disorders. Understanding neuronal and humoral communication through the GBA may provide insight into therapeutic and nutritional strategies that may enhance the results of very low-birth-weight babies.

Short term outcome of patients attending a renal-immunology clinic in central India.

Background: : Glomerular diseases (GDs) and other renal immunologic diseases are an important cause of morbidity and mortality. Providing a single point of service in collaboration with various specialists at a renal immunology clinic for such patients is not novel, but outcomes have not been reported. Here, we report the short-term outcome of Indian patients attending our clinic. Methods: : This single-center prospective cohort study enrolled biopsy-proven immunologically-mediated adults with renal diseases between April 2018 and December 2019, and followed them for six months. The primary end point for the analysis was an incidence of end-stage renal disease (ESRD) or loss of >50% estimated glomerular filtration rate (eGFR) and patient survival at six months. Secondary endpoints were the rate of complete or partial remission, and impact of demographic factors. Results: : Ninety two patients underwent renal biopsy for suspected immunological renal diseases. Fourteen (15.2%) cases were excluded for nonimmune etiologies, whereas 78 (84.7%) confirmed cases of immune etiology were included. Most common primary GD (n = 51) (93.5%) was membranous nephropathy (n = 20) (25.6%), whereas lupus nephritis was the most common (n = 8) (29.6%) secondary GD. Overall, 10 (12.8%) patients reached renal endpoint of ESRD or >50% fall in eGFR. Focal segmental glomerulosclerosis (FSGS) (27%) patients had worst renal outcome. Patient survival was 94.8%. Thirty patients (38.4%) achieved complete, whereas 24 each (30.7%) achieved partial remission and remained resistant to disease specific therapies, respectively. Univariate analysis identified hypertension, severity of hypertension, and resistance to achieve proteinuria remission as significantly associated (P < 0.001) factors with poor renal outcome. Conclusions: : The present study shows that short term renal outcome of Indian patients with renal immune diseases remains poor. FSGS remains the GD with the worst renal outcome. Hypertension, its severity, failure to achieve proteinuria remission were significantly associated with poor renal outcomes.

Gendered differences in relative ACE2 expression in the nasal epithelium.

Gendered differences in relative ACE2 expression in the nasal epithelium.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Retinal Haemorrhage in Newborns in Tertiary Care Hospital.

Background Retinal haemorrhage in new-born is a clinically common neonatal fundus condition. Although, it usually does not affect the development of visual function, entities like macular haemorrhages may lead to amblyopia causing deterioration of visual function. Such scenario leads to downgrade in quality of life of the affected child. Objective To explore the underlying clinical factors associated with retinal haemorrhage in term new-borns. Method A cross sectional study was conducted involving 136 term neonates admitted in the neonatal intensive care unit of Dhulikhel Hospital. Fundus examination was performed within 2 weeks of delivery. Retinal haemorrhage was graded according to their location in three retinal zones. Result Out of 136 cases examined, 44 (32.35%) of the cases had one of the eyes with retinal haemorrhage. Where grade 1 retinal haemorrhage was accounted in majority of the cases. Birth weight, gestational age, mode of delivery, poor Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score in 1 and 5 minutes, birth asphyxia, neonatal sepsis and heavy work in antenatal period had statistically significant correlation with occurrence of retinal haemorrhage. Conclusion Our results suggest that spontaneous vaginal delivery, larger birth weight, higher gestational age, birth asphyxia, low Appearance, Pulse, Grimace, Activity, and Respiration score, are risk factors for occurrence of neonatal retinal haemorrhage. It is recommended that in neonates with above high-risk factors should undergo targeted fundus screening for early identification and needful interventions.

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Blended programmatic assessment for competency based curricula.

The uncertainty in all spheres of higher education due to the COVID-19 pandemic has had an unprecedented impact on teaching-learning and assessments in medical colleges across the globe. The conventional ways of assessment are now neither possible nor practical for certifying medical graduates. This has necessitated thoughtful considerations in making adjustments to the assessment system, with most institutions transitioning to online assessments that so far have remained underutilized. Programmatic assessment encourages the deliberate and longitudinal use of diverse assessment methods to maximize learning and assessment and at present can be utilized optimally as it ensures the collection of multiple low-stake assessment data which can be aggregated for high-stake pass/fail decisions by making use of every opportunity for formative feedback to improve performance. Though efforts have been made to introduce programmatic assessment in the competency-based undergraduate curriculum, transitioning to online assessment can be a potential opportunity if the basic tenets of programmatic assessment, choice of online assessment tools, strategies, good practices of online assessments and challenges are understood and explored explicitly for designing and implementing online assessments. This paper explores the possibility of introducing online assessment with face-to-face assessment and structuring a blended programmatic assessment in competency-based medical education.

Observational study to compare the effect of altitude on cardiopulmonary reserves of different individuals staying more than 6 weeks at 10,000 ft and 15,000 ft.

BACKGROUND: The variation in heights beyond high altitude has different effects on the cardiorespiratory profile of individuals because of variation in oxygen density with every thousand feet. This study was planned to analyze and compare the effects of difference in altitudes on cardiorespiratory profile from anesthesiologist's point of view. METHODS: A multicenter observational study was done involving two different groups of 600 patients at 10,000 ft (Group A) and 15,000 ft (Group B). Observation and comparison of oxygen saturation, 6-min walk test, and breath holding time was carried out. RESULTS: Fifty-five percent of subjects in Group A had oxygen saturation of more than 93% in comparison to 5.5% in Group B. This was statistically significant (P < 0.001). Two percent of subjects in Group A in comparison to 63.5% of Group B had oxygen saturation of less than 88% (P < 0.001). Percentage increase of more than 15% of heart rate was found to be statistically significant in all the age groups. Overall, 3.8% of individuals in Group A had breath holding time less than 15 s in comparison to 16.6% of individuals in Group B (P value < 0.001). CONCLUSION: The study demonstrates that there is a significant fall in oxygen saturation, significant rise in the heart rate in 6-min walk test, and significant fall in the breath holding time in the group located at 15,000 ft. Heights beyond 10,000 ft should be restricted to life and limb saving surgeries, and logistics should be focused more on "scoop and run" than "stay and play" policy.

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies.

BACKGROUND: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. METHODS: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. CONCLUSIONS: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

Neoadjuvant chemoradiation versus adjuvant chemotherapy for locally advanced adenocarcinoma of the rectosigmoid junction.

AIM: The optimal treatment approach for adenocarcinoma of the rectosigmoid junction remains unclear. The aim of this work was to compare outcomes of neoadjuvant chemoradiation (NCR) and adjuvant chemotherapy (AC) treatment for cancer of the rectosigmoid junction. METHOD: This was a nationwide, retrospective cohort study (2004-2015) using hospital-based cancer outcomes data (National Cancer Database). All patients who underwent resection with curative intent for locally advanced [American Joint Committee on Cancer (AJCC) Stages II and III] adenocarcinoma of the rectosigmoid junction were included. Exclusion criteria were age less than 18 or over 75 years, Charlson-Deyo score > 2, AJCC Stages I and IV and unstaged tumours. Treatment with NCR was compared with treatment with AC, the primary outcome being overall survival. Other end-points were resection margin status, the presence of lymphovascular invasion and postoperative length of stay. RESULTS: A total of 2828 patients were included in this study, of whom 1701 (59.7%) received NCR. NCR was more frequently utilized in patients who were black (10.3% vs 7.6%, P < 0.05) and underwent treatment at academic institutions (37.9% vs 22.5%, P < 0.05). Treatment with NCR did not differentially influence survival following risk adjustment (hazard ratio 1.17, CI 0.98-1.40; P = 0.085). NCR was independently associated with a decreased likelihood of a positive resection margin (OR 0.44, CI 0.33-0.58; P < 0.001) and lymphovascular invasion (OR 0.51, CI 0.40-0.67; P < 0.001). However, treatment with NCR was associated with the need for prolonged hospitalization compared with AC (7.3 days vs 6.5 days; P = 0.015). The study was limited by its retrospective design, external validity and risk of tumour misclassification. CONCLUSION: NCR currently seems to be favoured over AC for the management of locally advanced adenocarcinoma of the rectosigmoid junction. This approach may not be justified as NCR is associated with prolonged hospitalization needs without a clear survival benefit when compared with AC. Prospective studies are warranted to definitively compare outcomes of NCR and AC in this patient population.

Association between prenatal immune phenotyping and cord blood leukocyte telomere length in the PRISM pregnancy cohort.

BACKGROUND: Environmental exposures including air pollutants, toxic metals, and psychosocial stress have been associated with shorter telomere length (TL) in newborns. These exposures have in turn been linked to an enhanced inflammatory immune response. Increased inflammation during pregnancy may be a central biological pathway linking environmental factors with reduced TL at birth. Approaches that more comprehensively characterize the prenatal inflammatory milieu rather than targeting specific individual cytokines in relation to newborn TL may better elucidate inflammatory mechanisms. METHODS: Analyses included 129 mother-child dyads enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured 92 inflammation related proteins during pregnancy in maternal serum using the Olink protein array and quantified cord blood relative leukocyte TL (rLTL) via qPCR. We leveraged a tree-based machine learning algorithm to select the most important inflammatory related proteins jointly associated with rLTL. We then evaluated the combined association between the selected proteins with rLTL using Bayesian Weighted Quantile Sum (BWQS) Regression. Analyses were adjusted for gestational week of serum collection, maternal race/ethnicity, age, and education, and fetal sex. We evaluated major biological function of the identified proteins by using the UniProtKB, a centralized repository of curated functional information. RESULTS: Three proteins were negatively and linearly associated with rLTL (CASP8 ß: -0.22 p = 0.008, BNGF ß: -0.43 p = 0.033, TRANCE ß: 0.38 p = 0.004). Results from BWQS regression showed a significant overall decrease in rLTL (ß: -0.26 95%CrI: -0.43, -0.07) per quartile increase of the mixture, with CASP8 contributing the greatest weight (CASP8 50%; BNGF 27%, and TRANCE 23%). The identified proteins were involved in the regulation of apoptotic processes and cell proliferation. CONCLUSIONS: This proteomics approach identifies novel maternal prenatal inflammatory protein biomarkers associated with shortened rLTL in newborns.

The power of subjectivity in competency-based assessment.

With the introduction of competency-based undergraduate curriculum in India, a paradigm shift in the assessment methods and tools will be the need of the hour. Competencies are complex combinations of various attributes, many of which being not assessable by objective methods. Assessment of affective and communication domains has always been neglected for want of objective methods. Areas like professionalism, ethics, altruism, and communication-so vital for being an Indian Medical Graduate, can be assessed longitudinally applying subjective means only. Though subjectivity has often been questioned as being biased, it has been proven time and again that a subjective assessment in expert hands gives comparable results as that of any objective assessment. By insisting on objectivity, we may compromise the validity of the assessment and deprive the students of enriched subjective feedback and judgement also. This review highlights the importance of subjective assessment in competency-based assessment and ways and means of improving the rigor of subjective assessment, with particular emphasis on the development and use of rubrics.

Risk of Diabetic Foot in Diabetic Patients with Peripheral Arterial Disease.

Background The prevalence of peripheral arterial disease is higher in diabetic patients. And 11.6% of the patients with diabetic foot ulcer have associated peripheral arterial disease. Objective The main objective of the study is to assess the risk of diabetic foot in diabetic patients with peripheral arterial disease. Method This was a case control study conducted in Bir Hospital, National Academy of Medical Sciences (NAMS). The sample size was 173 out of which cases (diabetic foot) and unmatched controls (diabetics without diabetic foot) were divided in the ratio of 1:2. The Odds Ratio (OR) of peripheral arterial disease in diabetic foot was calculated. The study was conducted after taking ethical clearance from Institutional Review Board of National Academy of Medical Sciences. Result There were 173 participants enrolled in the study. Four were excluded, 55 participants were cases of diabetic foot (cases) and 114 participants were diabetics without diabetic foot (controls). The odds of diabetic foot in patients with peripheral arterial disease was 4.12, p < 0.001. Conclusion The risk of diabetic foot in diabetic patients with peripheral arterial disease was higher as compared to diabetic patients without peripheral arterial disease.

Risk Factors Associated with Ninety Day Readmission in Chronic Obstructive Pulmonary Disease Exacerbation at a Tertiary Care Hospital: A retrospective cohort study.

Background Chronic obstructive pulmonary disease (COPD) exacerbation is a leading cause of frequent hospital admission. Globally, several studies have reported potential risk factors associated with COPD exacerbations which are largely unknown in Nepalese health care setting. Objective To identify the risk factors associated with hospital readmission within ninety days of discharge in acute COPD exacerbation. Method This is a hospital based retrospective cohort study conducted at Tribhuvan University Teaching Hospital. COPD patients admitted in respiratory ward from August 2019 to November 2019 were followed up till 90 days after discharge. Logistic regression analysis was performed at 95% Confidence Interval (CI) to identify risk factors for readmission in COPD exacerbation. Statistical analysis was performed using SPSS version 20.0. Result Of total 86 patients hospitalized for COPD, 42 (48.8%) had at least one subsequent readmission during post-discharge follow-up period of 90 days. Mean age of patients was 70.55±10.98 years. There were 45 (52.3%) males. Logistic regression analysis revealed preadmission domiciliary oxygen use (Odds Ratio (OR) 2.93; 95% CI 1.195- 7.202; p=0.019), admission in intensive care unit (ICU) (OR 3.060; 95% CI 1.145- 8.179; p=0.026), previous hospital admission for COPD exacerbation (OR 3.230; 95% CI 1.219-8.556; p=0.018), age (OR 0.946; 95% CI 0.905-0.988; p=0.012) and duration of hospital stay (OR 0.901; 95% CI 0.819-0.992; p=0.034) were independently associated with ninety day readmission in COPD patients. Conclusion Five clinical factors were found to be independently associated with COPD readmission in this study. Large multi-centre study at various health care levels is recommended to validate the potential risk factors in different populations and health care settings in Nepal.

Neonatal Arrhythmia.

Arrhythmias are seldom observed in the newborn period and rarely lead to serious consequences. Because they may be a continuation of fetal arrhythmias, newborn arrhythmias are different from those occurring at later ages. Here we describe a case of a newborn presented with tachycardia at birth. A female baby of 1950 grams born by emergency cesarean section for fetal distress at 36 weeks of gestation. Fetal tachycardia of 251 bpm was detected prenatally. Electrocardiography showed supraventricular tachycardia (SVT). Hematological and biochemical tests done were within normal limits. Echocardiography revealed normal anatomy with severe tachycardia, dilated chambers with moderate to severe TR with moderately reduced ventricle function. For persisting SVT intravenous adenosine was administered with no significant decrease in heart rate, then continuous intravenous amiodarone infusion was started resulting in a transient decrease in heart rate, however again increased, hence baby was started on intravenous digoxin which responded well. Repeated echocardiography showed normal cardiac chambers and function. Baby was discharged on maintenance oral digoxin and was gradually weaned and stopped after 12 months of age. Neonatal arrhythmias is not an uncommon condition in newborns, however it should be early recognized and evaluated for a better outcome of the baby. Although the frequency of arrhythmias in the newborn period is not high, SVT are the most frequently observed arrhythmias in this period.

Monitoring Iodine Deficiency in a District Hospital, Nepal.

Background Iodine deficiency possesses serious threat to pregnant women and infants. During pregnancy, iodine deficiency can result in stillbirth while in infants it can lead to impaired brain development. Objective This study was conducted to assess the status of iodine deficiency among pregnant women and infants. Method Ninety seven pregnant women seeking antenatal check-up (ANC) from Chautara Hospital Sindhupalchowk were included to analyze urine iodine. Thirty one mothers and their children were followed-up for their clinical status. Additionally, the infants were assessed for their urine iodine excretion and the mothers were assessed for their awareness about iodine and iodine deficiency disorder (IDD). Result Urinary iodine excretion revealed 25.2% of pregnant women and 20% children below one year of age had insufficient iodine intake while 42.9% of pregnant women and 24% children had iodine level above normal. Almost all households were found using iodized salt, 80% respondents had heard about iodized salt, 13% mothers were aware of benefits of iodized salt, 41.9% had knowledge of iodine deficiency diseases and 38.4% cognized the source of iodine. Conclusion Though awareness about iodine and iodine deficiency disorder was satisfactory, pregnant women and children were at risk of iodine deficiency and excessive iodine disorder. Therefore, to improve health of pregnant women and newborn, their nutrition must be prioritized which ultimately will help reduce morbidity and mortality.

Online Learning in the Face of COVID-19 Pandemic: Assessment of Students' Satisfaction at Chitwan Medical College of Nepal.

Background Online learning can play a vital role in the process of teaching and learning during Corona Virus Disease 2019 (COVID-19) pandemic. However, learners' satisfaction is extremely important in effective implementation of the online learning, especially at institutions where it is newly adopted. Objective To assess satisfaction towards online learning and its predictors among students at Chitwan Medical College, Bharatpur. Method A web-based cross-sectional survey was undertaken among 434 undergraduate and postgraduate students from various academic programs who had participated in the online classes started during this COVID-19 pandemic. A structured questionnaire consisting of 31 items (5-point Likert scale) covering four major student satisfaction domains (learners' dimensions, technological characteristics, instructors' characteristics and course management and coordination) was distributed to the students using Google Form. Result More than half (53.5%) of the students were satisfied with the online learning, while 29.7% gave neutral views. Bivariate analyses found that all four domains scores were positively correlated with each other as well as with the students' overall satisfaction towards learning. In multivariate analysis, female gender [aOR: 2.72, p = 0.013], WiFi as internet modality for learning [aOR: 3.36, p = 0.001) and learners' dimension score [aOR: 1.27, p<0.001] were the significant predictors of students' satisfaction. Conclusion Although recently adopted, the satisfaction of the students towards online classes appears good, and prioritizing the identified predictors and working on the weak links could assist in enhancing students' satisfaction and better outcomes.

Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.

Exploring Campylobacter seasonality across Europe using The European Surveillance System (TESSy), 2008 to 2016.

BackgroundCampylobacteriosis is the most commonly reported food-borne infection in the European Union, with an annual number of cases estimated at around 9 million. In many countries, campylobacteriosis has a striking seasonal peak during early/mid-summer. In the early 2000s, several publications reported on campylobacteriosis seasonality across Europe and associations with temperature and precipitation. Subsequently, many European countries have introduced new measures against this food-borne disease.AimTo examine how the seasonality of campylobacteriosis varied across Europe from 2008-16, to explore associations with temperature and precipitation, and to compare these results with previous studies. We also sought to assess the utility of the European Surveillance System TESSy for cross-European seasonal analysis of campylobacteriosis.MethodsWard's Minimum Variance Clustering was used to group countries with similar seasonal patterns of campylobacteriosis. A two-stage multivariate meta-analysis methodology was used to explore associations with temperature and precipitation.ResultsNordic countries had a pronounced seasonal campylobacteriosis peak in mid- to late summer (weeks 29-32), while most other European countries had a less pronounced peak earlier in the year. The United Kingdom, Ireland, Hungary and Slovakia had a slightly earlier peak (week 24). Campylobacteriosis cases were positively associated with temperature and, to a lesser degree, precipitation.ConclusionAcross Europe, the strength and timing of campylobacteriosis peaks have remained similar to those observed previously. In addition, TESSy is a useful resource for cross-European seasonal analysis of infectious diseases such as campylobacteriosis, but its utility depends upon each country's reporting infrastructure.