An international Delphi consensus on patient preparation for metabolic and bariatric surgery.

Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources.

Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing.

Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice.

Cortical norepinephrine-astrocyte signaling critically mediates learned behavior.

Updating behavior based on feedback from the environment is a crucial means by which organisms learn and develop optimal behavioral strategies. Norepinephrine (NE) release from the locus coeruleus (LC) has been shown to mediate learned behaviors such that in a task with graded stimulus uncertainty and performance, a high level of NE released after an unexpected outcome causes improvement in subsequent behavior. Yet, how the transient activity of LC-NE neurons, lasting tens of milliseconds, influences behavior several seconds later, is unclear.

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species.

Long-Term Weight Loss and Comorbidity Resolution of Laparoscopic Sleeve Gastrectomy and Laparoscopic Roux-en-Y Gastric Bypass and the Impact of Preoperative Weight Loss on Overall Outcome.

Background: The impact of preoperative weight loss on long-term weight loss outcomes and comorbidity resolution in both laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are poorly reported. Understanding this relationship is necessary to guide surgeons toward appropriate procedure and patient selection. The present study investigates long-term weight loss outcomes and comorbidity resolution following LSG and LRYGB and investigates the effect of preoperative variables on long-term outcomes.

Synthesis of the bicyclic butenolide core of pallamolide A: a biomimetic approach.

Pallamolide A is a 7,8--labdane terpenoid possessing a unique bicyclo[2.2.2]octane core and a spiro-butenolide moiety.

Predicting Inadequate Weight Loss After Bariatric Surgery: Derivation and Validation of a Four Factor Model.

Introduction: Weight loss following bariatric surgery is variable and predicting inadequate weight loss is required to help select patients for bariatric surgery. The aim of the present study was to determine variables associated with inadequate weight loss and to derive and validate a predictive model.

Methods: All patients who underwent laparoscopic sleeve gastrectomy and Roux-en-Y gastrectomy (2008-2022) in a tertiary referral centre were followed up prospectively.

Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established.

Depletion of follicular B cell-derived antibody secreting cells does not attenuate angiotensin II-induced hypertension or vascular compliance.

Introduction: Marginal zone and follicular B cells are known to contribute to the development of angiotensin II-induced hypertension in mice, but the effector function(s) mediating this effect (e.g., antigen presentation, antibody secretion and/or cytokine production) are unknown.

Optimization of mouse kidney digestion protocols for single-cell applications.

Single-cell technologies such as flow cytometry and single-cell RNA sequencing have allowed for comprehensive characterization of the kidney cellulome. However, there is a disparity in the various protocols for preparing kidney single-cell suspensions. We aimed to address this limitation by characterizing kidney cellular heterogeneity using three previously published single-cell preparation protocols.

Intensive pre-operative information course (IPIC) and pre-operative weight loss results in long-term sustained weight loss following bariatric surgery: 11 years results from a tertiary referral centre.

Introduction: Outcomes of long-term (5-10-year) weight loss have not been investigated thoroughly and the role of pre-operative weight loss on long-term weight loss, among other factors, are unknown. Our regional bariatric service introduced a 12 week intensive pre-operative information course (IPIC) to optimise pre-operative weight loss and provide education prior to bariatric surgery. The present study determines the effect of pre-operative weight loss and an intense pre-operative information course (IPIC), on long-term weight outcomes and sustained weight loss post-bariatric surgery.

Aortic Cellular Heterogeneity in Health and Disease: Novel Insights Into Aortic Diseases From Single-Cell RNA Transcriptomic Data Sets.

Aortic diseases such as atherosclerosis, aortic aneurysms, and aortic stiffening are significant complications that can have significant impact on end-stage cardiovascular disease. With limited pharmacological therapeutic strategies that target the structural changes in the aorta, surgical intervention remains the only option for some patients with these diseases. Although there have been significant contributions to our understanding of the cellular architecture of the diseased aorta, particularly in the context of atherosclerosis, furthering our insight into the cellular drivers of disease is required.

Immune and inflammatory mechanisms in hypertension.

Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression.

Sex-specific effects of a high fat diet on aortic inflammation and dysfunction.

Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. A high fat diet (HFD) is often used to model obesity in mice, but the sex-specific effects of this diet on aortic inflammation and function are unclear. Therefore, we characterized the aortic immune cell profile and function in 6-week-old male and female C57BL/6 mice fed a normal chow diet (NCD) or HFD for 10 weeks.

IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages.

In cardiovascular disease, pathological and protective roles are reported for the Th2 cytokines IL-4 and IL-13, respectively. We hypothesised that differential effects on macrophage function are responsible. Type I and II receptor subunit (IL-2Rγ, IL-4Rα and IL-13Rα1) and M2 marker (MRC-1, CCL18, CCL22) expression was assessed via RT-qPCR in IL-4- and IL-13-treated human primary macrophages.

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Intraepithelial lymphocytes (IELs), including αβ and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/ and a reduced effector and cytotoxic profile, including low expression of granzymes.

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting.

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis.