LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies

Loss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

"Begging the Question"-Does Toxocara Infection/Exposure Associate with Multiple Sclerosis-Risk?

Although the cause of multiple sclerosis (MS) is unclear, infectious agents, including some parasitic roundworms (nematodes), have been proposed as possible risk factors or contributors. Here, we conducted a systematic review and meta-analysis of published observational studies to evaluate whether there is a possible association between infection with, or exposure to, one or more members of the genus Toxocara (phylum Nematoda; superfamily Ascaridoidea) and MS. We undertook a search of public literature databases to identify relevant studies and then used a random-effects meta-analysis model to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). This search identified six of a total of 1371 articles that were relevant to the topic; these published studies involved totals of 473 MS patients and 647 control subjects. Anti-Toxocara IgG serum antibodies were detected in 62 MS patients and 37 controls, resulting in respective seroprevalences of 13.1% (95% CI: 8.2–20.3) and 4.8% (95% CI: 2.5–9.2), indicating an association (pooled OR, 3.01; 95% CI: 1.46–6.21). Because of the publication bias identified (six eligible studies), well-designed and -controlled studies are required in the future to rigorously test the hypothesis that Toxocara infection/exposure has an association with MS

Psychological disorders among inhabint residing in poor social district of Gorgan, Iran

Background and Objective: Normal psychological behaviour is one of the general concept of health. This study was carried out to evalute psychological disorders among inhabint residing in poor social district of Gorgan, Iran. Materials and Methods: This cross-sectional study was done on 376 subjects (188 males and 188 females) with simple random sampling method. Data were gathered using the general health questionnaire (GHQ-28). Data was analyzed by SPSS-16, Kruskal–Wallis and Pearson tests. Results: The prevalence of psychological disorders was 37% (33.5% in men, 40.4% in women), depression was 24.45% (22.5% in men and 26.4% in women) and anxiety was 31.6% (31.2% in men, 32% in women). Social affairs disorder 21% (19.2% in men, 22.7% in women) and psychosomatic disorders in 28.5% (22% of men, 35% of women). The relationship between psychological disorder with economic level and family size was significant (P<0.05). Conclusion: This study showed that 37% of inhabint residing in poor social district of Gorgan, Northern Iran had psychological disorders

SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-analysis

OBJECTIVES: COVID-19 has been arguably the most important public health concern worldwide in 2020, and efforts are now escalating to suppress or eliminate its spread. In this study we undertook a meta-analysis to estimate the global and regional seroprevalence rates in humans of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to assess whether seroprevalence is associated with geographical, climatic and/or sociodemographic factors. METHODS: We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv databases for preprints or peer-reviewed articles (up to 14 August 2020). Study eligibility criteria were population-based studies describing the prevalence of anti-SARS-CoV-2 (IgG and/or IgM) serum antibodies. Participants were people from different socioeconomic and ethnic backgrounds (from the general population), whose prior COVID-19 status was unknown and who were tested for the presence of anti-SARS-CoV-2 serum antibodies. We used a random-effects model to estimate pooled seroprevalence, and then extrapolated the findings to the global population (for 2020). Subgroup and meta-regression analyses explored potential sources of heterogeneity in the data, and relationships between seroprevalence and sociodemographic, geographical and/or climatic factors. RESULTS: In total, 47 studies involving 399 265 people from 23 countries met the inclusion criteria. Heterogeneity (I2 = 99.4%, p < 0.001) was seen among studies; SARS-CoV-2 seroprevalence in the general population varied from 0.37% to 22.1%, with a pooled estimate of 3.38% (95%CI 3.05-3.72%; 15 879/399 265). On a regional level, seroprevalence varied from 1.45% (0.95-1.94%, South America) to 5.27% (3.97-6.57%, Northern Europe), although some variation appeared to relate to the serological assay used. The findings suggested an association of seroprevalence with income levels, human development indices, geographic latitudes and/or climate. Extrapolating to the 2020 world population, we estimated that 263.5 million individuals had been exposed or infected at the time of this study. CONCLUSIONS: This study showed that SARS-CoV-2 seroprevalence varied markedly among geographic regions, as might be expected early in a pandemic. Longitudinal surveys to continually monitor seroprevalence around the globe will be critical to support prevention and control efforts, and might indicate levels of endemic stability or instability in particular countries and regions

Seroprevalence estimates for toxocariasis in people worldwide: A systematic review and meta-analysis

BACKGROUND: Human toxocariasis is an important neglected disease. We performed a systematic review and meta-analysis study to estimate the global and regional prevalence of anti-Toxocara serum antibodies (referred to as 'T-seroprevalence') in human populations around the world. METHODS: We searched five international databases (PubMed, EMBASE, Web of Science, SciELO and Scopus) for seroprevalence studies published from 1 January 1980 to 15 March 2019. We used random effect models to calculate the overall T-seroprevalence (with 95% CIs) in all six WHO regions and worldwide. We also conducted subgroup and linear meta-regression analyses to evaluate the impact of socio-demographic, geographical and climatic parameters on seroprevalence. RESULTS: We identified 250 eligible studies (253 datasets) comprising 265,327 participants in 71 countries for inclusion in the present meta-analysis. The estimated global T-seroprevalence rate was 19.0% (95%CI, 16.6-21.4%; 62,927/265,327); seroprevalence was highest in the African region (37.7%; 25.7-50.6%) and lowest in the Eastern Mediterranean region (8.2%; 5.1-12.0%). The pooled seroprevalence for other WHO regions was 34.1% (20.2-49.4%) in the South-East Asia; 24.2% (16.0-33.5%) in the Western Pacific; 22.8% (19.7-26.0%) in the American; and 10.5% (8.5-12.8%) in the European regions. A significantly higher T-seroprevalence was associated with a lower income level; lower human development index (HDI); lower latitude; higher humidity; higher temperature; and higher precipitation (P-value < 0.001). Potential risk factors associated with seropositivity to Toxocara included male gender; living in a rural area; young age; close contact with dogs, cats or soil; consumption of raw meat; and the drinking of untreated water. CONCLUSIONS: The present findings indicate high levels of infection with, or exposure to Toxocara spp. in many countries, which calls for increased attention to human toxocariasis and improved measures to prevent adverse health risks of this disease

Global Prevalence Estimates of Toxascaris leonina Infection in Dogs and Cats

Toxascaris leonina is an ascaridoid nematode of dogs and cats; this parasite affects the health of these animals. This study estimated the global prevalence of Ta. leonina infection in dogs and cats using random effects meta-analysis as well as subgroup, meta-regression and heterogeneity analyses. The data were stratified according to geographical region, the type of dogs and cats and environmental variables. A quantitative analysis of 135 published studies, involving 119,317 dogs and 25,364 cats, estimated prevalence rates of Ta. leonina in dogs and cats at 2.9% and 3.4%, respectively. Prevalence was highest in the Eastern Mediterranean region (7.2% for dogs and 10.0% for cats) and was significantly higher in stray dogs (7.0% vs. 1.5%) and stray cats (7.5% vs. 1.8%) than in pets. The findings indicate that, worldwide, ~26 million dogs and ~23 million cats are infected with Ta. leonina; these animals would shed substantial numbers of Ta. leonina eggs into the environment each year and might represent reservoirs of infection to other accidental or paratenic hosts. It is important that populations of dogs and cats as well as other canids and felids be monitored and dewormed for Ta. leonina and (other) zoonotic helminths

Acute Toxoplasma infection in pregnant women worldwide: A systematic review and meta-analysis

BACKGROUND: Acute Toxoplasma infection (ATI) during pregnancy, if left untreated, can cause severe adverse outcomes for the fetus and newborn. Here, we undertook a meta-analysis to estimate the worldwide prevalence of ATI in pregnant women. METHODS: We searched international databases for studies published between January 1988 and November 2018. We included population-based cross-sectional and prospective cohort studies that reported the prevalence of ATI in pregnant women. Data were synthesized using a random effect model to calculate the overall prevalence of ATI (with a 95% CI) in six WHO regions and globally. We also performed linear meta-regression analyses to investigate associations of maternal, socio-demographic, geographical and climate parameters with the prevalence of ATI. RESULTS: In total, 217 studies comprising 902,228 pregnant women across 74 countries were included in the meta-analysis. The overall prevalence of ATI in pregnant women globally was 1.1% (95% CI: 0.9-1.2%). In studies where more strict criteria for ATI were used, the overall prevalence was 0.6% (95% CI: 0.4-0.7%). The prevalence was highest in the Eastern Mediterranean region (2.5%; 95%CI: 1.7-3.4%) and lowest in the European region (0.5%; 95% CI: 0.4-0.7%). A significantly higher prevalence of ATI was found in countries with lower income levels (P = 0.027), lower human development indices (P = 0.04), higher temperatures (P = 0.02) and lower latitudes (P = 0.005) and longitudes (P = 0.02). CONCLUSIONS: The risk of acquiring ATI during gestation is clinically important and preventive measures to avoid exposure of pregnant women to Toxoplasma infection should be strictly applied