Several comorbidities have been shown to be associated with coronavirus disease 2019 (COVID-19) related severity and mortality. However, considerable variation in the prevalence estimates of comorbidities and their effects on COVID-19 morbidity and mortality have been observed in prior studies. This systematic review and meta-analysis aimed to determine geographical, age, and gender related differences in the prevalence of comorbidities and associated severity and mortality rates among COVID-19 patients. We conducted a search using PubMed, Scopus, and EMBASE to include all COVID-19 studies published between January 1st, 2020 to July 24th, 2020 reporting comorbidities with severity or mortality. We included studies reporting the confirmed diagnosis of COVID-19 on human patients that also provided information on comorbidities or disease outcomes. We used DerSimonian and Laird random effects method for calculating estimates. Of 120 studies with 125,446 patients, the most prevalent comorbidity was hypertension (32%), obesity (25%), diabetes (18%), and cardiovascular disease (16%) while chronic kidney or other renal diseases (51%, 44%), cerebrovascular accident (43%, 44%), and cardiovascular disease (44%, 40%) patients had more COVID-19 severity and mortality respectively. Considerable variation in the prevalence of comorbidities and associated disease severity and mortality in different geographic regions was observed. The highest mortality was observed in studies with Latin American and European patients with any medical condition, mostly older adults (≥ 65 years), and predominantly male patients. Although the US studies observed the highest prevalence of comorbidities in COVID-19 patients, the severity of COVID-19 among each comorbid condition was highest in Asian studies whereas the mortality was highest in the European and Latin American countries. Risk stratification and effective control strategies for the COVID-19 should be done according to comorbidities, age, and gender differences specific to geographical location.

Idiopathic normal pressure hydrocephalus (NPH) remains both oversuspected on clinical grounds and underconfirmed when based on immediate and sustained response to cerebrospinal fluid diversion. Poor long-term postshunt benefits and findings of neurodegenerative pathology in most patients with adequate follow-up suggest that hydrocephalic disorders appearing in late adulthood may often result from initially unapparent parenchymal abnormalities. We critically review the NPH literature, highlighting the near universal lack of blinding and controls, absence of specific clinical, imaging, or pathological features, and ongoing dependence for diagnostic confirmation on variable cutoffs of gait response to bedside fluid-drainage testing. We also summarize our long-term institutional experience, in which postshunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimer's disease, dementia with Lewy bodies, and progressive supranuclear palsy). We postulate that previously reported NPH cases with "dual" pathology (ie, developing a "second" disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short-lived, with a consequently unfavorable risk-benefit ratio. Ann Neurol 2017;82:503-513.

Objective Coronavirus disease 2019 (COVID-19) has become a global pandemic and may adversely affect pregnancy outcomes. We estimated the adverse maternal and neonatal characteristics and outcomes among COVID-19 infected women and determined heterogeneity in the estimates and associated factors. Study Designs PubMed search was performed of confirmed COVID-19 pregnant cases and related outcomes were ascertained prior to July 8, 2020, in this systematic review and meta-analysis. Studies reporting premature birth, low birth weight, COVID-19 infection in neonates, or mode of delivery status were included in the study. Two investigators independently performed searches, assessed quality of eligible studies as per the Cochrane handbook recommendations, extracted and reported data according to PRISMA guidelines. Pooled proportions of maternal and neonatal outcomes were estimated using meta-analyses for studies with varying sample sizes while a systematic review with descriptive data analysis was performed for case report studies. Maternal and neonatal outcomes included C-section, premature birth, low birth weight, adverse pregnancy events and COVID transmission in neonates. Results A total of 790 COVID-19 positive females and 548 neonates from 61 studies were analyzed. The rates of C-section, premature birth, low birth weight, and adverse pregnancy events were estimated as 72 %, 23 %, 7 %, and 27 % respectively. In the heterogeneity analysis, the rate of C-section was substantially higher in Chinese studies (91 %) compared to the US (40 %) or European (38 %) studies. The rates of preterm birth and adverse pregnancy events were also lowest in the US studies (12 %, 15 %) compared to Chinese (17 %, 21 %), and European studies (19 %, 19 %). In case reports, the rates of C-section, preterm birth, and low birth weight were estimated as 69 %, 56 %, and 35 %, respectively. Adverse pregnancy outcomes were associated with infection acquired at early gestational ages, more symptomatic presentation, myalgia symptom at presentation, and use of oxygen support therapy. Conclusions Adverse pregnancy outcomes were prevalent in COVID-19 infected females and varied by location, type, and size of the studies. Regular screening and early detection of COVID-19 in pregnant women may provide more favorable outcomes.

Experimental studies in biomedical research frequently pose analytical problems related to small sample size. In such studies, there are conflicting findings regarding the choice of parametric and nonparametric analysis, especially with non-normal data. In such instances, some methodologists questioned the validity of parametric tests and suggested nonparametric tests. In contrast, other methodologists found nonparametric tests to be too conservative and less powerful and thus preferred using parametric tests. Some researchers have recommended using a bootstrap test; however, this method also has small sample size limitation. We used a pooled method in nonparametric bootstrap test that may overcome the problem related with small samples in hypothesis testing. The present study compared nonparametric bootstrap test with pooled resampling method corresponding to parametric, nonparametric, and permutation tests through extensive simulations under various conditions and using real data examples. The nonparametric pooled bootstrap t-test provided equal or greater power for comparing two means as compared with unpaired t-test, Welch t-test, Wilcoxon rank sum test, and permutation test while maintaining type I error probability for any conditions except for Cauchy and extreme variable lognormal distributions. In such cases, we suggest using an exact Wilcoxon rank sum test. Nonparametric bootstrap paired t-test also provided better performance than other alternatives. Nonparametric bootstrap test provided benefit over exact Kruskal-Wallis test. We suggest using nonparametric bootstrap test with pooled resampling method for comparing paired or unpaired means and for validating the one way analysis of variance test results for non-normal data in small sample size studies. Copyright © 2017 John Wiley & Sons, Ltd.

Abstract-Shuffling and freezing while walking can impair function in patients with Parkinson disease (PD). Open-loop devices that provide fixed-velocity visual or auditory cues can improve gait but may be unreliable or exacerbate freezing of gait in some patients. We examined the efficacy of a closedloop, accelerometer-driven, wearable, visual-auditory cueing device in 13 patients with PD with off-state gait impairment at baseline and after 2 weeks of twice daily (30 minute duration) at-home use. We measured gait velocity, stride length, and cadence using a validated electronic gait-analysis system. Subjects underwent standard motor assessment and completed a self-administered Freezing of Gait Questionnaire (FOGQ) (range 0-24; lower is better). After training, device use enhanced walking velocity (61.6 ± 20.1 cm/s to 72.6 ± 26.5 cm/s, p = 0.006) and stride length (74.3 ± 16.4 cm to 84.0 ± 18.5 cm, p = 0.004). Upon device removal, walking velocity (64.5 ± 21.4 cm/s to 75.4 ± 21.5 cm/s, p < 0.001) and stride length (79.0 ± 20.3 cm to 88.8 ± 17.7 cm, p = 0.003) exhibited a greater magnitude of change, suggesting immediate residual benefits. Also upon device removal, nearly 70 percent of subjects improved by at least 20 percent in either walking velocity, stride length, or both. An overall improvement in gait was measured by the FOGQ (14.2 ±1.9 to 12.4 ± 2.5, p = 0.02). Although issues related to compliance and response variability render a definitive interpretation of study outcome difficult, devices using closed-loop sensory feedback appear to be effective and desirable nonpharmacologic interventions to improve walking in selected individuals with PD.

Chronic immune activation that persists despite anti-retroviral therapy (ART) is the strongest predictor of disease progression in HIV infection. Monocyte/macrophages in HIV-infected individuals are known to spontaneously secrete cytokines, although neither the mechanism nor the molecules involved are known. Here we show that overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. The process requires signaling via PD-1H as cytokine secretion could be abrogated by deletion of the cytoplasmic domain. Such overexpression of PD-1H, associated with spontaneous cytokine expression is seen in monocytes from chronically HIV-infected individuals and this correlates with immune activation and CD4 depletion, but not viral load. Moreover, antigen presentation by PD-1H-overexpressing monocytes results in enhanced cytokine secretion by HIV-specific T cells. These results suggest that PD-1H might play a crucial role in modulating immune activation and immune response in HIV infection.

A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.

Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.