Dohertyconrad0278

The exotic invasive tiger mosquito, Aedes albopictus, appeared in southern Switzerland in 2003. The spread of the mosquito has been surveyed constantly since then, and an integrated vector management (IVM) has been implemented to control its numbers. The control measures focus on the aquatic phase of the mosquito with removal of breeding sites and applications of larvicides in public areas whereas private areas are reached through extensive public information campaigns. Here, we evaluated the efficacy of the IVM.

Since all the municipalities with Ae. albopictus in southern Switzerland are currently implementing the IVM, Italian municipalities just across the Swiss-Italian border, where Ae. albopictus is present but no coordinated intervention programme is in place, served as control. Ovitraps and adult female traps were used to measure mosquito abundance in 2019. Generalised mixed-effects models were used to model the numbers of Ae. BTK inhibitor chemical structure albopictus eggs and adult females collected. These numbers of Ae. albopict defined control measures. With the constant implementation of an IVM, it appears possible to contain the numbers of Ae. albopictus at a manageable level, reducing the nuisance for the human population and the risk of arbovirus epidemics.

The results of the survey strongly support the efficacy of the IVM programme implemented in southern Switzerland compared to municipalities without defined control measures. With the constant implementation of an IVM, it appears possible to contain the numbers of Ae. albopictus at a manageable level, reducing the nuisance for the human population and the risk of arbovirus epidemics.We reported a patient with unresectable hepatocellular carcinoma (HCC) who initially received 15 cycles of atezolizumab plus bevacizumab combination and had best tumor response of partial response, but later experienced disease progression. After subsequent surgical resection, the patient enjoyed long-term disease-free status at the last follow-up 19 months after surgery. By investigating paired tumor tissues (pretreatment and post-progression samples) with immunohistochemistry, multiplex immunofluorescence, RNA sequencing, and DNA sequencing, we explored the dynamic changes in the tumor microenvironment (TME) and potential mechanisms underlying acquired resistance to the combination. In the post-progression HCC tissue compared with the baseline tissue, the expression of PD-L1 in tumor-infiltrating immune cells and the abundance of CD8+ T cells in the tumor area had decreased, and an immune-excluded TME had emerged. Transcriptomic analysis revealed a gene expression signature representing progenitor/hepatoblast features in the post-progression tumor tissue, with an increased expression of imprinted genes and decreased expression of cytochrome P450 family genes. Finally, tumor mutational burden and MHC class I expression in tumor cells were both increased in the post-progression tissue, suggesting that neoantigen depletion or loss-of-antigen presentation were unlikely causes of acquired resistance in this patient. Atezolizumab plus bevacizumab combination therapy enabled our patient to receive hepatectomy and achieve long-term remission. A comparison of paired tumor tissues suggested that immune-excluded TME and tumor dedifferentiation may have contributed to acquired resistance to the combination.Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54-3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53-3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41-7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.

Many shift workers suffer from sleep issues, which negatively affect quality of life and performance. Scientifically evaluated, structured programs for prevention and treatment are scarce. We developed an anonymous online cognitive behavioral therapy for insomnia (CBT-I) program. After successful completion of a feasibility study, we now start this prospective, randomized, controlled superiority trial to compare outcomes of two parallel groups, namely an intervention group and a waiting-list control-group. Additionally, we will compare these outcomes to those of a face-to-face CBT-I outpatient sample.

Collaborating companies will offer our anonymous online intervention to their shift-working employees. Company physicians and counseling services will screen those interested for inclusion and exclusion criteria. Participants will receive access to our online service, where they will complete psychometric assessment and receive random assignment to either the intervention group or the waiting-list control grpiness.

The online intervention allows shift workers to follow a CBT-I program independently of their working schedule and location. Forthcoming results might contribute to further improvement of prevention and therapy of sleep issues in shift workers.

German Clinical Trials Register DRKS DRKS00017777 . Registered on 14 January 2020-retrospectively registered.

German Clinical Trials Register DRKS DRKS00017777 . Registered on 14 January 2020-retrospectively registered.

Accumulating evidence indicated that necroptosis plays an essential role in the pathogenesis of inflammatory bowel disease (IBD). The O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) of necroptotic signal molecule receptor-interacting serine-threonine kinase 3 (RIPK3) was reported to exert a protective effect in gut inflammation. Our recent study suggested traditional Chinese herbal formula Wu-Mei-Wan (WMW) as an effective prescription in mouse colitis. However, the potential mechanisms are not fully understood. Considering the crucial role of necroptosis in the pathogenesis of IBD, therefore, this study was designed to explain whether the anti-colitis effect of WMW is mediated by modulating necroptosis and its related mechanisms.

The protective effects of WMW on colitis have been determined by detecting colitis mice body weight, disease activity index (DAI), survival rate and colon length. Colonic inflammation was examined by inflammatory cells infiltration and local cytokines levels. After then, wg of RIPK3 and MLKL, which led to the inhibition of necroptosis. Additionally, docking analysis demonstrated that hesperidin, coptisine and ginsenoside Rb1 may exert a major role in the regulation on OGT and OGA activities by WMW.

Our work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation.

Our work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation.

Aedes albopictus is the primary vector of dengue fever in China. This mosquito species has a wide distribution range in China and can be found in the tropical climate zones of southern provinces through to temperate climate zones of northern provinces. Insecticides are an important control method, especially during outbreaks of dengue fever, but increasing insecticide resistance raises the risk of failure to control vector-borne diseases. Knockdown resistance (kdr) caused by point mutations in the voltage-gated sodium channel (VGSC) gene is a key mechanism that confers resistance to pyrethroids. In this study we explored the characteristics and possible evolutionary trend of kdr mutation in Ae. albopictus based on analysis of the kdr mutations in field populations of mosquitoes in China.

A total of 1549 adult Ae. albopictus were collected from 18 sites in China from 2017 to 2019 and 50 individuals from three sites in the 1990s. A fragment of approximately 350bp from part of the S6 segment in the VGSC genefield populations of Ae. albopictus in China. Two novel mutant alleles, F1534W/TGG and F1534R/CGC, were detected in this study. The 1534 kdr mutation appeared in the population of Ae. albopictus no later than the 1990s. The F1534 mutation rate was positively correlated with AAT, while the I1532 mutation rate was negatively correlated with AAT. These results indicate that iInsecticide usage should be carefully managed to slow down the spread of highly resistant Ae. albopictus populations, especially in the areas with higher AAT.Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures and developmental delay. DEEs are primarily attributed to genetic causes and an increasing number of cases have been correlated with variants in ion channel genes. In this study, we report a child with an early severe DEE. Whole exome sequencing showed a de novo heterozygous variant (c.4873-4881 duplication) in the SCN8A gene and an inherited heterozygous variant (c.952G > A) in the CACNA1H gene encoding for Nav1.6 voltage-gated sodium and Cav3.2 voltage-gated calcium channels, respectively. In vitro functional analysis of human Nav1.6 and Cav3.2 channel variants revealed mild but significant alterations of their gating properties that were in general consistent with a gain- and loss-of-channel function, respectively. Although additional studies will be required to confirm the actual pathogenic involvement of SCN8A and CACNA1H, these findings add to the notion that rare ion channel variants may contribute to the etiology of DEEs.

Metabolic reprogramming is a central feature in many cancer subtypes and a hallmark of cancer. Many therapeutic strategies attempt to exploit this feature, often having unintended side effects on normal metabolic programs and limited efficacy due to integrative nature of metabolic substrate sourcing. Although the initiating oncogenic lesion may vary, tumor cells in lymphoid malignancies often share similar environments and potentially similar metabolic profiles. We examined cells from mouse models of MYC-, RAS-, and BCR-ABL-driven lymphoid malignancies and find a convergence on de novo lipogenesis. We explore the potential role of MYC in mediating lipogenesis by

C glucose tracing and untargeted metabolic profiling. Inhibition of lipogenesis leads to cell death both in vitro and in vivo and does not induce cell death of normal splenocytes.

We analyzed RNA-seq data sets for common metabolic convergence in lymphoma and leukemia. Using in vitro cell lines derived in from conditional MYC, RAS, and BCR-ABL trand progression in vivo in transplanted lymphoma cell lines. We also observe delayed progression of T-ALL in a primary transgenic mouse model upon TOFA administration. In a panel of human cell lines, we demonstrate sensitivity to TOFA treatment as a metabolic liability due to the general convergence on de novo lipogenesis in lymphoid malignancies driven by MYC, RAS, or BCR-ABL. Importantly, cell death was not significantly observed in non-malignant cells in vivo.

These studies suggest that de novo lipogenesis may be a common survival strategy for many lymphoid malignancies and may be a clinically exploitable metabolic liability.

This study does not include any clinical interventions on human subjects.

This study does not include any clinical interventions on human subjects.