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Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013-2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity.Regime shifts are increasingly prevalent in the ecological literature. However, definitions vary and detection methods are still developing. Here, we employ a novel statistical algorithm based on the Bayesian online change-point detection framework to simultaneously identify shifts in the mean and (or) variance of time series data. We detected multiple regime shifts in long-term (59-154 years) patterns of coastal Norwegian Atlantic cod (>70% decline) and putative drivers of cod productivity North Atlantic Oscillation (NAO); sea-surface temperature; zooplankton abundance; fishing mortality (F). The consequences of an environmental or climate-related regime shift on cod productivity are accentuated when regime shifts coincide, fishing mortality is high, and populations are small. The analyses suggest that increasing F increasingly sensitized cod in the mid 1970s and late 1990s to regime shifts in NAO, zooplankton abundance, and water temperature. Our work underscores the necessity of accounting for human-induced mortality in regime shift analyses of marine ecosystems.Lyme disease patients would greatly benefit from a timely, sensitive, and specific molecular diagnostic test that can detect the causal agent Borrelia burgdorferi at the onset of symptoms. Currently available diagnostic methods recommended by the Centers for Disease Control and Prevention for Lyme disease involve indirect serological tests that rely on the detection of a host-antibody response, which often takes more than three weeks to develop. With this process, many positive cases are not detected within a timely manner, preventing a complete cure. In this study, we have developed a digital polymerase chain reaction (PCR) assay that detects Lyme disease on clinical presentation with a sensitivity two-fold higher than that of the currently available diagnostic methods, using a cohort of patient samples collected from the Lyme disease endemic state of Connecticut, USA, in 2016-2018. Digital PCR technology was chosen as it is more advanced and sensitive than other PCR techniques in detecting rare targets. The analytical detection sensitivity of this diagnostic assay is approximately three genome copies of B. burgdorferi. The paucity of spirochetes in the bloodstream of Lyme disease patients has hindered the clinical adoption of PCR-based diagnostic tests. However, this drawback was overcome by using a comparatively larger sample volume, applying pre-analytical processing to the blood samples, and implementing a pre-amplification step to enrich for B. burgdorferi-specific gene targets before the patient samples are analyzed via digital PCR technology. Pre-analytical processing of blood samples from acute patients revealed that the best sample type for Lyme disease detection is platelet-rich plasma rather than whole blood. If detected in a timely manner, Lyme disease can be completely cured, thus limiting antibiotic overuse and associated morbidities.In health systems with strongly developed primary care, such as in the Netherlands, effectively engaging primary care professionals (PCPs) in suicide prevention is a key strategy. As part of the national Suicide Prevention Action Network (SUPRANET), a program was offered to PCPs in six regions in the Netherlands in 2017-2018 to more effectively engage them in suicide prevention. This implementation study aimed to evaluate to what extent SUPRANET was helpful in supporting PCPs to apply suicide prevention practices. From March to May 2018, 21 semi-structured interviews have been carried out with PCPs and other non-clinical professionals from SUPRANET regions in the Netherlands. Verbatim transcripts were analysed using the grounded theory approach. Data was structured using the Consolidated Framework for Implementation Research, which enabled identifying facilitating and challenging factors for PCPs to carry out suicide prevention practices. An important challenge included difficulties in assessing suicide risk (intervention characteristics) due to PCPs’ self-perceived incompetence, burdensomeness of suicide and limited time and heavy workload of PCPs. Another important limitation was collaboration with mental health care (outer setting), whereas mental health nurses (inner setting) and SUPRANET (implementation process) were facilitating factors for applying suicide prevention practices. With regard to SUPRANET, especially the training was positively evaluated by PCPs. PCPs expressed a strong need for improving collaboration with specialized mental health care, which was not provided by SUPRANET. Educating PCPs on suicide prevention seems beneficial, but is not sufficient to improve care for suicidal patients. Effective suicide prevention also requires improved liaison between mental health services and primary care, and should therefore be the focus of future suicide prevention strategies aimed at primary care.

Coronavirus disease-19 (COVID-19) has not only spawned a lot of stigma and discrimination towards its survivors but also to their corpses. We aimed to assess the magnitude and correlates of stigma in these survivors, on return to their communities.

This was a cross-sectional, hospital-based, exploratory study conducted by the postgraduate department of psychiatry, in collaboration with the postgraduate department of chest medicine, Govt. medical college, Srinagar. The study was performed among COVID-19 survivors, who attended the outpatient department after their discharge from the hospital. Socio-demographic characteristics were recorded through semi-structured proforma. Stigma was measured by the stigma questionnaire. Data was analyzed using descriptive statistics and regression analysis.

A total of 91 survivors consented to participate in the study. Almost half (46.2%) of them were in the age group of 30-49 years and close to two-thirds (68.1%) were males. About three-fourths (74.7%) were from the urre-integration of these survivors.

Our study results showed high levels of enacted and externalized stigma among COVID-19 survivors. Enacted stigma was more among males and in those who were highly educated. Survivor centered and community-driven anti-stigma programs are the need of the hour to promote the recovery and community re-integration of these survivors.An opaque fetal membrane based on gross appearance is traditionally indicative of histological chorioamnionitis; however, to the best of our knowledge, there is currently no supportive evidence, and its diagnostic efficiency has not yet been scientifically demonstrated. The present study aimed to provide scientific insights into the traditional concept of an opaque fetal membrane based on gross appearance being an indicator of histological chorioamnionitis. We examined the placental pathology after screening of the placental gross appearance and perinatal complications and did not examine uncomplicated deliveries. We investigated the relationship between the presence of an opaque fetal membrane and histological chorioamnionitis (Cohort 1, 571 placentas) or the outcomes of neonates delivered at term (Cohort 2, 409 placentas) at Hamamatsu University School of Medicine between 2010 and 2017. The judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis (Cohort 1). Its sensitivity and specificity were 66.7 and 89.9%, respectively, while positive and negative predictive values were 86.8 and 73.0%, respectively. The judgment of a positive opaque fetal membrane based on gross appearance significantly correlated with chorioamnionitis-related complications in term newborns after adjustments for confounding factors (OR;1.82 [1.07-3.11], P less then 0.05) (Cohort 2). selleckchem A correlation was observed even after adjustments for confounding factors. The present study is the first to demonstrate that the judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis as well as chorioamnionitis-related complications in newborns delivered at term. The present results provide support for the traditionally-described importance of gross inspections for an opaque fetal membrane soon after birth.Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) 9 has been widely used far beyond genome editing. Fusions of deactivated Cas9 (dCas9) to transcription effectors enable interrogation of the epigenome and controlling of gene expression. However, the large transgene size of dCas9-fusion hinders its applications especially in somatic tissues. Here, we develop a robust CRISPR interference (CRISPRi) system by transgenic expression of doxycycline (Dox) inducible dCas9-KRAB in mouse embryonic stem cells (iKRAB ESC). After introduction of specific single-guide RNAs (sgRNAs), the induced dCas9-KRAB efficiently maintains gene inactivation, although it modestly down-regulates the expression of active genes. The proper timing of Dox addition during cell differentiation or reprogramming allows us to study or screen spatiotemporally activated promoters or enhancers and thereby the gene functions. Furthermore, taking the ESC for blastocyst injection, we generate an iKRAB knock-in (KI) mouse model that enables the shutdown of gene expression and loss-of-function (LOF) studies ex vivo and in vivo by a simple transduction of gRNAs. Thus, our inducible CRISPRi ESC line and KI mouse provide versatile and convenient platforms for functional interrogation and high-throughput screens of specific genes and potential regulatory elements in the setting of development or diseases.