Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials.

Aims/hypothesis: Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

Classification of Predictors of Rapid Development of Kidney Failure and Short-Term Changes in Concentration of Circulating Proteins.

Objective: Limited knowledge exists regarding short-term changes/increases in concentrations of circulating proteins (referred here as deltas) and rapid development of kidney failure (rapid KF) in diabetes mellitus.

Research Design And Methods: Concentrations of 452 circulating proteins were measured by OLINK proteomics platform at baseline and after a median interval of 3-4 years in 106 individuals with type 1 and 77 with type 2 diabetes in two case-control studies. During 10-year follow-up, 31 and 26 individuals, respectively, developed rapid KF.

Structural mechanisms of SLF1 interactions with Histone H4 and RAD18 at the stalled replication fork.

DNA damage that obstructs the replication machinery poses a significant threat to genome stability. Replication-coupled repair mechanisms safeguard stalled replication forks by coordinating proteins involved in the DNA damage response (DDR) and replication. SLF1 (SMC5-SMC6 complex localization factor 1) is crucial for facilitating the recruitment of the SMC5/6 complex to damage sites through interactions with SLF2, RAD18, and nucleosomes.

Meta-analytical evidence for frequency-dependent selection across the tree of life.

Explaining the maintenance of genetic variation in fitness-related traits within populations is a fundamental challenge in ecology and evolutionary biology. Frequency-dependent selection (FDS) is one mechanism that can maintain such variation, especially when selection favours rare variants (negative FDS). However, our general knowledge about the occurrence of FDS, its strength and direction remain fragmented, limiting general inferences about this important evolutionary process.

The Wnt signaling pathway in major depressive disorder: A systematic review of human studies.

Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential factor in the pathogenesis of MDD. Known for its role in intercellular communication, cell proliferation, and fate, Wnt signaling has been implicated in diverse biological phenomena associated with MDD, spanning neurodevelopmental to neurodegenerative processes. In this systematic review, we summarize the functional differences in protein and gene expression of the Wnt signaling pathway, and targeted genetic association studies, to provide an integrated synthesis of available human data examining Wnt signaling in MDD.

Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

Background: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD.

SmartFSCV: An Artificial Intelligence Enabled Miniaturised FSCV Device Targeting Serotonin.

Dynamically monitoring serotonin in real-time within target brain regions would significantly improve the diagnostic and therapeutic approaches to a variety of neurological and psychiatric disorders. Current systems for measuring serotonin lack immediacy and portability and are bulky and expensive. We present a new miniaturised device, named SmartFSCV, designed to monitor dynamic changes of serotonin using fast-scan cyclic voltammetry (FSCV).

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD.

Predator mass mortality events restructure food webs through trophic decoupling.

Predators have a key role in structuring ecosystems. However, predator loss is accelerating globally, and predator mass-mortality events (MMEs)-rapid large-scale die-offs-are now emblematic of the Anthropocene epoch. Owing to their rare and unpredictable nature, we lack an understanding of how MMEs immediately impact ecosystems.

Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression.

Objective: We conducted an open-label clinical trial ("Bio-K") using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission. Here, we report the clinical efficacy and side effect outcomes of Bio-K.

Methods: Across 4 US sites, 75 patients ages 18-65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period.

Perception towards palliative care among patients with pulmonary hypertension in malaysia: a correlation with disease status.

Objectives: This study aimed to describe the perception of Malaysian patients with pulmonary hypertension towards palliative care and their receptivity towards palliative care.

Methods: This was a cross-sectional, single-centre study conducted via questionnaire. Patients aged 18 years old and above, who were diagnosed with non-curable pulmonary hypertension were recruited and given the assessment tool - perceptions of palliative care instrument electronically.

Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.

Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone.

Interactions between fitness components across the life cycle constrain competitor coexistence.

Numerous mechanisms can promote competitor coexistence. Yet, these mechanisms are often considered in isolation from one another. Consequently, whether multiple mechanisms shaping coexistence combine to promote or constrain species coexistence remains an open question.

High frequency deep brain stimulation can mitigate the acute effects of cocaine administration on tonic dopamine levels in the rat nucleus accumbens.

Cocaine's addictive properties stem from its capacity to increase tonic extracellular dopamine levels in the nucleus accumbens (NAc). The ventral tegmental area (VTA) is a principal source of NAc dopamine. To investigate how high frequency stimulation (HFS) of the rodent VTA or nucleus accumbens core (NAcc) modulates the acute effects of cocaine administration on NAcc tonic dopamine levels multiple-cyclic square wave voltammetry (M-CSWV) was used.

The importance of targeting multiple risk markers in patients with type 2 diabetes: A post-hoc study from the CANVAS programme.

Aims: To investigate the extent to which improvements in multiple cardiovascular risk markers are associated with a lower risk of cardiovascular and kidney outcomes in patients with type 2 diabetes and high cardiovascular risk participating in the CANVAS programme.

Materials And Methods: Clinically relevant improvements in cardiovascular risk factors were defined as a reduction in glycated haemoglobin ≥1.0%, systolic blood pressure ≥10 mmHg, body weight ≥3 kg, urinary-albumin-creatinine ratio ≥30%, uric acid ≥0.

Perceptions of employability related to severity of hypernasality: a pilot study.

The primary aim of this investigation was to evaluate listener auditory-perceptual assessment of employability for individuals with hypernasal speech. Using an online survey platform, listeners with managerial experience evaluated speech samples from individuals with varying hypernasal resonance disorder severity to determine auditory-perceptual judgements regarding intelligence and employability. Speech samples of individuals with hypernasal speech were rated lower on scales of intelligence and employability, and more likely to be selected for jobs with infrequent rates of communication and lower levels of responsibility.

Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania.

Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM- (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito-, n = 289) mitochondrial electron transport chain (ETC) activity.

Initiation of the SGLT2 inhibitor canagliflozin to prevent kidney and heart failure outcomes guided by HbA1c, albuminuria, and predicted risk of kidney failure.

Background: Sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of kidney and heart failure events independent of glycemic effects. We assessed whether initiation of the SGLT2 inhibitor canagliflozin guided by multivariable predicted risk based on clinical characteristics and novel biomarkers is more efficient to prevent clinical outcomes compared to a strategy guided by HbA1c or urinary-albumin-creatinine ratio (UACR) alone.

Methods: We performed a post-hoc analysis of the CANVAS trial including 3713 patients with available biomarker measurements.

Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial.

Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression.

Prediction of the Effects of Liraglutide on Kidney and Cardiovascular Outcomes Based on Short-Term Changes in Multiple Risk Markers.

The LEADER trial demonstrated that the glucagon-like peptide-1 receptor agonist (GLP1-RA) liraglutide reduces kidney and cardiovascular (CV) risk in patients with type 2 diabetes. We previously developed a Parameter Response Efficacy (PRE) score that translates multiple short-term risk marker changes, from baseline to first available follow-up measurement, into a predicted long-term drug effect on clinical outcomes. The objective of this study was to assess the accuracy of the PRE score in predicting the efficacy of liraglutide in reducing the risk of kidney and CV outcomes.

Neurocognitive effects of repeated ketamine infusions in comorbid posttraumatic stress disorder and major depressive disorder.

Background: The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine's potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect.