Childhood mistreatment (CM) has been associated with adult posttraumatic disorder (PTSD) and substance use disorders (SUDs) in the general population. Few studies have examined the role of PTSD in the CM-SUD association among Latinx. This cross-sectional study evaluated a theory-driven conceptual model with a specific focus on the impact of perceived discrimination, which may interfere with these associations.

Using a nationally representative sample and structural equation modeling (SEM), the study evaluated the mediation of PTSD in the CM-SUD link, adjusting for or omitting discrimination and other sociodemographic variables that are known predictors of Latinx behavioral health. Multi-subsample analyses were then conducted to review nativity differences (US-born=924.43% and immigrant=1630.57%).

The fully specified final model (model 1, covariates adjusted) failed to show a significant mediation of PTSD in the tested link, but a direct detrimental effect group of discrimination, for all Latinx. The medtraumatic exposure occurred. This unexpected finding challenges theories explaining the CM-SUD connection, suggesting possible model misspecifications of parametric SES; namely, omitting the unique impact of perceived discrimination in Latinx can lead to biased results. From a clinical standpoint, both trauma and discrimination must be addressed when assessing Latinx behavioral health.

Cancer patients are prone to infections, but the mortality of fatal infections remains unclear. find more Understanding the patterns of fatal infections in patients with cancer is imperative. In this study, we report the characteristics, incidence, and predictive risk factors of fatal infections among a population-based cancer cohort.

A total of 8,471,051 patients diagnosed with cancer between 1975 and 2016 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) program. The primary outcome was dying from fatal infections. Mortality rates and standardized mortality ratios (SMRs) adjusted for age, sex, race, and calendar year were calculated to characterize the relative risks of dying from fatal infections and to compare with the general population. Furthermore, cumulative mortality rates and the Cox regression models were applied to identify predictive risk factors of fatal infections.

In cancer patients, the mortality rate of fatal infections was 260.1/100,000 person-years, nencer patients were at high risks of dying from infectious diseases. Certain groups of cancer patients, including those aged between 20 and 39 or > 80 years, as well as those receiving chemotherapy, should be sensitized to the risk of fatal infections.

80 years, as well as those receiving chemotherapy, should be sensitized to the risk of fatal infections.The desensitization of G protein-coupled receptors (GPCRs), which involves rapid loss of responsiveness due to repeated or chronic exposure to agonists, can occur through various mechanisms at different levels of signaling pathways. In this review, the mechanisms of GPCR desensitization are classified according to their occurrence at the receptor level and downstream to the receptor. The desensitization at the receptor level occurs in a phosphorylation-dependent manner, wherein the activated receptors are phosphorylated by GPCR kinases (GRKs), thereby increasing their affinities for arrestins. Arrestins bind to receptors through the cavity on the cytoplasmic region of heptahelical domains and interfere with the binding and activation of G-protein. Diverse mechanisms are involved in the desensitization that occurs downstream of the receptor. Some of these include the sequestration of G proteins, such as Gq and Gi/o by GRK2/3 and deubiquitinated arrestins, respectively. Mechanistically, GRK2/3 attenuates GPCR signaling by sequestering the Gα subunits of the Gq family and Gβγ via regulators of G protein signaling and pleckstrin homology domains, respectively. Moreover, studies on Gi/o-coupled D2-like receptors have reported that arrestins are deubiquitinated under desensitization condition and form a stable complex with Gβγ, thereby preventing them from coupling with Gα and the receptor, eventually leading to receptor signaling inhibition. Notably, the desensitization mechanism that involves arrestin deubiquitination is interesting; however, this is a new mechanism and needs to be explored further.Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.