Haemodynamic management of septic shock.

Septic shock is a significant challenge in the management of patients with burns and traumatic injuries when complicated by infection, necessitating prompt and effective haemodynamic support. This review provides a comprehensive overview of current strategies for vasopressor and fluid management in septic shock, with the aim to optimize patient outcomes. With regard to vasopressor management, we elaborate on the pharmacologic profiles and clinical applications of catecholamines, vasopressin derivatives, angiotensin II, and other vasoactive agents.

Targeted Sleep Enhancement Reduces Residual Anxiety Symptoms in Peri-Adolescents Previously Treated for Anxiety Disorders.

Sleep-related problems (SRPs) are a common precursor to anxiety disorders, especially during peri-adolescence, and may be a predictor of treatment response. However, evidence-based anxiety treatments do not alleviate SRPs to a clinically significant degree. The current study examines whether improving sleep in a sample of young adolescents previously treated for anxiety disorders can further reduce anxiety severity.

How does family functioning contribute to child externalizing and internalizing behavior problems after childhood TBI? Evidence from a prospective cohort study.

Background And Objectives: Despite a well-documented association between childhood traumatic brain injury and elevated risk for internalizing and externalizing behavior problems, the mechanisms through which family functioning contributes to individual variation in these behavioral outcomes remains poorly understood. This prospective cohort study aimed to assess the respective contribution of family functioning and child emotion regulation (ER) to post-injury behavior problems at 1-year follow-up, with a specific focus on evaluating the role of ER problems in mediating the effects of familial affective responsiveness and communication on child behavioral outcomes.

Method: The study included 129 participants, comprising 86 children with medically confirmed mild-to-severe TBI, identified from consecutive hospital admissions, and 43 typically developing (TD) control children, of similar age and sex.

Detection of Mismatch Repair Deficiency in Endometrial Cancer: Assessment of IHC, Fragment Length Analysis, and Amplicon Sequencing Based MSI Testing.

Mismatch repair (MMR) deficiency can be indicative of Lynch syndrome (LS) and guide treatment with immune checkpoint inhibitors. Colorectal cancers (CRCs) and endometrial cancers (ECs) are routinely screened to identify LS, primarily using immunohistochemistry (IHC) or microsatellite instability (MSI) testing, but concordance between these methods is variable in ECs. Here, we investigate this variability in 361 ECs from the Ohio OCCPI/OPTEC ( = 196) and Manchester PETALS ( = 165) trials, where concordance between assays differed significantly.

BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees.

Next-generation sequencing is widely applied to the investigation of pedigree data for gene discovery. However, identifying plausible disease-causing variants within a robust statistical framework is challenging. Here, we introduce BICEP: a Bayesian inference tool for rare variant causality evaluation in pedigree-based cohorts.

Targeting macrophage migration inhibitory factor to inhibit T cell immunosuppression in the tumor microenvironment and improve cancer outcomes in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer globally with a 40-50 % survival rate. Although macrophage migration inhibitory factor (MIF) is overexpressed in most solid tumors and promotes tumor growth and invasion, the therapeutic potential of MIF inhibition in HNSCC is yet to be explored. In this study, we investigated the efficacy of CPSI-1306, a small-molecule MIF inhibitor, on HNSCC cell growth and cancer associated signaling pathways in vitro, as well as its impact on T cells in the HNSCC tumor microenvironment in vivo.

Outcomes of Complex Percutaneous Cardiac Interventions in Women.

Complex percutaneous cardiac intervention (PCI) is a growing procedure in modern day cath labs. The treated population is often older, with multiple comorbidities, complex coronary anatomy, left ventricular dysfunction, and possibly concomitant valvular heart disease and/or cardiogenic shock. As such, PCI of bifurcations, chronic total occlusions, and atherectomy coronary interventions are becoming more common.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum.

Effects of PM2.5 exposure during high bushfire smoke days on birthweight and gestational age in Hunter New England, NSW, Australia. A study on pregnant people who smoke and don't smoke.

Australia's 2019/20 bushfire season was one of the most severe on record, from both land mass burned and the economic impact. This extreme weather season allowed the researchers to examine the effect of high PM exposure during high bushfire days on birthweight and gestational age. It is well known that bushfire smoke is harmful to human health.

The integration of human and non-human actors to advance healthcare delivery: unpacking the role of actor-network theory, a systematic literature review.

Background: There is an increasing public, societal and policy imperative for effective integration of healthcare delivery systems. Central to integration in healthcare is a focus on people-centred health, access, patient empowerment, interprofessional teamwork and collaboration between all healthcare stakeholders - difficult to achieve in current silo-driven bureaucratic health organisations. Therefore, actor-network theory (ANT) offers a theoretical approach to understanding the complexities of healthcare delivery by unpacking the type of actor's interplay between social elements and immaterial objects, their interactions, interdependencies and power dynamics.

Two-year trajectories of anhedonia in adolescents at transdiagnostic risk for severe mental illness: Association with clinical symptoms and brain-symptom links.

Anhedonia emerges during adolescence and is characteristic of severe mental illness (SMI). To understand how anhedonia emerges, changes with time, and relates with other symptoms, there is a need to understand patterns of this symptom's course reflecting change or stability-and associations with clinical symptoms and neural reward circuitry in adolescents at risk of SMI. In total, 113 adolescents at low or high familial risk of developing SMI completed clinical measures at up to five time points across 2 years and functional magnetic resonance imaging scanning during a guessing reward task at baseline.

Assessing clinical progression measures in Alzheimer's disease trials: A systematic review and meta-analysis.

Introduction: Assessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment.

Methods: Excluding trials targeting non-cognitive symptoms, we conducted meta-analyses on progression measures from 25 selected RCTs using R version 4.

Si-Linked Glycomimetics through a Stereoselective Silicon Transfer and Anion Addition.

We report a synthesis of silicon-linked glycomimetics, demonstrating unique structural properties and metabolic stability due to the inertness of the C-Si bond. Our method focuses on the stereoselective transfer of silicon and anion addition, revealing that chirality at the silicon atom can be controlled through kinetic resolution. This approach allows for the selective generation of 1,2- and 1,2- isomers via the manipulation of C2-protected silicon ethers and nucleophilic opening of glycal epoxides.

A rapid assessment of depressive and anxious symptoms among university students during the COVID-19 public health emergency: A repeated cross-sectional analysis.

Objectives: To identify potential associations between student characteristics and mental health symptoms during the early parts of the pandemic.

Participants: 3,883 students at a large public university on the West Coast of the United States.

Methods: We conducted a repeated cross-sectional survey to assess health-protective behaviors, mental health, social support, and stigma resistance.

Genetic testing in dementia.

There is growing public awareness and concern regarding dementia risk. In addition, genetic testing is increasingly accessible and is at the point of being integrated into routine clinical practice. As a result, there is a pressing need for treating clinicians to have the appropriate knowledge base to request and consent for diagnostic genetic testing in cognitive clinics.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

Background: Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain.