Virtual reality (VR)-based environmental enrichment in older adults with mild cognitive impairment (MCI) and mild dementia

Background: Despite an alarming rise in the global prevalence of dementia, the available modalities for improving cognition and mental wellbeing of dementia patients remain limited. Environmental enrichment is an experimental paradigm that has shown promising anti-depressive and memory-enhancing effects in pre-clinical studies. However, its clinical utility has remained limited due to the lack of effective implementation strategies.Objective: The primary objective of this study was to evaluate the usability (tolerability and interactivity) of a long-term virtual reality (VR)- based environmental enrichment training program in older adults with mild cognitive impairment (MCI) and mild dementia. A secondary objective was to assess the effect of VR-based environmental enrichment on stabilization of cognitive functioning and improvement of mental wellbeing in older adults with MCI and mild dementia.Methods: A total of seven participants (four patients with MCI and three with mild dementia) received biweekly VR-based environmental enrichment over a course of 6 months. The tolerability and interactivity of the participants in the VR training was serially assessed via virtual reality sickness questionnaire (VRSQ) and recording of input-error ratio. Cognitive functioning was assessed through Montreal cognitive assessment (MoCA) before and after the study. Mental wellbeing was assessed through Warwick-Edinburgh Mental Well Being Scale (WEMWBS).Results: VR-based environmental enrichment was well-tolerated by the patients with significant decrease in VRSQ scores (p \u3c 0.01) and input-error ratio (p \u3c 0.001) overtime. VR training was also effective in stabilization of MoCA scores over the course of therapy (non-significant difference in the MoCA scores before and after the therapy) and was associated with a trend (p \u3c 0.1) towards improvement in WEMWBS scores between the first and the last assessments. Qualitative observations by the care-givers further corroborated a noticeable improvement in mental wellbeing of patients.Conclusions: This pilot study shows that VR can be a feasible, tolerable, and potentially effective tool in long-term support of older adults with MCI and mild dementia

Human west nile virus disease outbreak in Pakistan, 2015–2016

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus(JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Extrapulmonary tuberculosis among females in South Asia—gap analysis

The percentage of extrapulmonary tuberculosis (EPTB) among new and relapse tuberculosis cases in South Asia (Afghanistan, Pakistan, India, and Bangladesh) ranged from 19% to 23% in 2014. While tuberculosis was reportedly more prevalent in males, a higher preponderance of EPTB was observed in females. National tuberculosis control programs are highly focused on pulmonary tuberculosis. This creates gaps in the surveillance, diagnosis, and study of EPTB among females, which is especially pronounced in the South Asian setting. We have reviewed recently published literatures from January 2010 to June 2016 reporting EPTB in females with a view to evaluate the current epidemiology, risk factors, diagnostic modalities, and treatment outcomes. We report significant gaps in the surveillance of EPTB among women in South Asia, emphasizing the need for greater focus on EPTB in females to overcome current surveillance and knowledge gaps

Distinct microRNA signature in human serum and germline after childhood trauma

Traumatic experiences during childhood can persistently alter mental and physical health in humans and have been implicated in transmission of symptoms to the progeny in animal models. Molecular evidence from these models implicates epigenetic/non-genetic factors, such as microRNAs (miRNAs), in the expression of trauma-induced symptoms and their transmission to the offspring. To confirm these findings in humans, we assembled three cohorts of subjects exposed to childhood trauma and examined selected miRNAs linked to psychological and pathophysiological manifestations of childhood trauma. Children aged 7-12 years (n = 72, control n = 30) exposed to paternal loss and maternal separation (PLMS) exhibited increase in two miRNAs, miR-16 and miR-375 in serum and reduced level of high-density lipoproteins (HDL) compared to control children. Comparable miRNA changes were observed in serum of adult men aged 18-25 years (n = 13, control n = 17) who had been exposed to PLMS at a young age. Finally, the same miRNAs were altered in sperm of adult men aged 21-50 years (n = 23, control n = 35) exposed to two or more significant traumatic events in childhood, assessed retrospectively using the standardized childhood trauma questionnaire (CTQ). In vitro experiments show that regulation of these miRNA involves the HDL receptor SRB-1, suggesting a link between trauma-associated miRNAs and metabolic alterations

Data_Sheet_1_Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016.XLSX

<p>Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.</p