The neuroprotective effects of cholecystokinin in the brain: antioxidant, anti-inflammatory, cognition, and synaptic plasticity.

Cholecystokinin (CCK) is a major neuropeptide in the brain that functions as a neurotransmitter, hormone, and growth factor. The peptide and its receptors are widely expressed in the brain. CCK signaling modulates synaptic plasticity and can improve or impair memory formation, depending on the brain areas studies and the receptor subtype activated.

The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.

The development of granulomas with central necrosis harboring Mycobacterium tuberculosis (Mtb) is the hallmark of human tuberculosis (TB). New anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ-043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial.

The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif.

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Neuroprotective effects of GLP-1 class drugs in Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate symptoms without halting or delaying disease progression. There is a significant association between PD and type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, and mitochondrial dysfunction.

A standardized carotid endarterectomy care pathway is associated with lower ICU admission rates and a significant reduction in hospital charges.

Background: This study investigated the outcomes before and after initiation of a postoperative care pathway for carotid endarterectomy (CEA) patients.

Methods: A CEA pathway was developed with stakeholders. We compared in-hospital outcomes and charges (USD) for patients undergoing CEA 18 months before (11/2019-04/2021) vs.

Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice.

A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer's disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments.

Non-tuberculous mycobacterial bone and joint infections - a case series from a tertiary referral centre in Australia.

Background: Non-tuberculous mycobacteria (NTM) are rare causes of bone and joint infection (BJI) and there is limited evidence on which to base management decisions. This study describes 1 year of experience from a multi-disciplinary BJI team which collects data on all cases reviewed at a tertiary referral centre in Queensland, Australia.

Methods: The database was interrogated for all cases in which NTM were recovered from operative samples.

Streamlining Preoperative Evaluation for Dialysis Access: A Pilot Study.

Background: Outpatient in-person clinic evaluation is the standard consultation practice for an initial referral for hemodialysis (HD) access. However, most factors predicting the complexity of first-time access surgery can be determined from history rather than physical exam. This study compares the outcomes of patients undergoing first-time arteriovenous fistula creation screened with a standardized preoperative phone interview and no preoperative clinic visit (SPEEDY group) to those opting for a standard in-person clinic visit.

Investigating the treatment shortening potential of a combination of bedaquiline, delamanid and moxifloxacin with and without sutezolid, in a murine tuberculosis model with confirmed drug exposures.

Background: New and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB/c) of Mycobacterium tuberculosis (Mtb) infection.

Methods: Treatment of mice with B25D0.

Endovascular fenestration and stenting for renovisceral malperfusion in a pediatric patient with type II Loeys-Dietz syndrome.

A 16-year-old girl with Loeys-Dietz syndrome presented with an acute, complicated type B aortic dissection (AD) with mesenteric and right renal malperfusion owing to a dynamic obstruction. The anatomy of her AD and her genetic aortography were suboptimal for thoracic endovascular aortic repair. Given the concern for anticipated late aortic degeneration and the need for open aortic repair, she underwent successful transfemoral endovascular septal fenestration with stenting of the fenestration into the superior mesenteric artery and additional stenting of the right renal artery.

Surgical outcomes for occluded venous thoracic outlet syndrome following transaxillary first rib resection.

Objective: Surgical decompression via transaxillary first rib resection (TFRR) is often performed in patients presenting with venous thoracic outlet syndrome (VTOS). We aimed to evaluate the outcomes of TFRR based on chronicity of completely occluded axillosubclavian veins in VTOS.

Methods: We performed a retrospective institutional review of all patients who underwent TFRR for VTOS and had a completely occluded axillosubclavian vein between 2003 and 2022.

Clinical factors associated with ultrashort length of stay in patients undergoing lower extremity bypass for peripheral arterial disease.

Background: Length of stay (LOS) is a major driver of cost and resource utilization following lower extremity bypass (LEB). However, the variable comorbidity burden and mobility status of LEB patients makes implementing enhanced recovery after surgery pathways challenging. The aim of this study was to use a large national database to identify patient factors associated with ultrashort LOS among patients undergoing LEB for peripheral artery disease.

Experiments as Code and its application to VR studies in human-building interaction.

Experiments as Code (ExaC) is a concept for reproducible, auditable, debuggable, reusable, & scalable experiments. Experiments are a crucial tool to understand Human-Building Interactions (HBI) and build a coherent theory around it. However, a common concern for experiments is their auditability and reproducibility.

Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson's and Alzheimer's disease clinical trials: A revolution in the making?

Parkinson's disease (PD) is a complex syndrome for which there is no disease-modifying treatment on the market. However, a group of drugs from the Glucagon-like peptide-1 (GLP-1) class have shown impressive improvements in clinical phase II trials. Exendin-4 (Bydureon), Liraglutide (Victoza, Saxenda) and Lixisenatide (Adlyxin), drugs that are on the market as treatments for diabetes, have shown clear effects in improving motor activity in patients with PD in phase II clinical trials.

A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice.

Background: There are no drugs on the market that can reverse or slow Alzheimer's disease (AD) progression. A protease-resistant Cholecystokinin (CCK) analogue used in this study is based on the basic structure of CCK, which further increases the stability of the peptide fragment and prolongs its half-life in vivo. We observed a neuroprotective effect of CCK-8L in APPswe/PS1dE9 (APP/PS1) AD mice.

The role of strategic visibility in shaping wayfinding behavior in multilevel buildings.

In this paper, we explore the mutual effect of prior background expectations and visibility afforded by the 3D configuration of the physical environment on wayfinding efficiency and strategy in multilevel buildings. We perform new analyses on data from 149 participants who performed six unaided and directed wayfinding tasks in virtual buildings with varying degrees of visibility. Our findings reveal that the interaction between visibility and prior background expectations significantly affects wayfinding efficiency and strategy during between-floor wayfinding tasks.

Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimer's and Parkinson's disease.

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer's disease (AD) and Parkinson's disease (PD). Thus, we review the physiological function and therapeutic potential of CCK.

Liraglutide Reduces Alcohol Consumption, Anxiety, Memory Impairment, and Synapse Loss in Alcohol Dependent Mice.

Glucagon-like peptide 1 (GLP-1) analogues have been commercialized for the management of type 2 diabetes. Recent studies have underscored GLP-1's role as a modulator of alcohol-related behavior. However, the role of the GLP-1 analogue liraglutide on alcohol-withdrawal responses have not been fully elucidated.

O-GlcNAcylation and Its Roles in Neurodegenerative Diseases.

 As a non-classical post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is widely found in human organ systems, particularly in our brains, and is indispensable for healthy cell biology. With the increasing age of the global population, the incidence of neurodegenerative diseases is increasing, too. The common characteristic of these disorders is the aggregation of abnormal proteins in the brain.

The influence of upward social comparison on retail trading behaviour.

Online investing is often facilitated by digital platforms, where the information of peer top performers can be widely accessible and distributed. However, the influence of such information on retail investors' psychology, their trading behaviour and potential risks they may be prone to is poorly understood. We investigate the impact of upward social comparison on risk-taking, trading activity and investor satisfaction using a tailored experiment with 807 experienced retail investors trading on a dynamically evolving simulated stock market, designed to systematically measure various facets of trading activity.

Whole cell hydride Meisenheimer complex biotransformation guided optimization of antimycobacterial benzothiazinones.

Nitrobenzothiazinones (BTZs) are potent active substances against Mycobacterium tuberculosis with currently two investigational drugs in clinical development for the treatment of tuberculosis. BTZs are the first examples for which a metabolic pathway towards transient hydride Meisenheimer complexes (HMC) has been shown in mammals, including humans. In this study, lead optimization efforts on BTZs are guided by the systematic evaluation of the HMC formation propensity combined with multiparameter assessment.

No link between handedness and spatial navigation: evidence from over 400 000 participants in 41 countries.

There is an active debate concerning the association of handedness and spatial ability. Past studies used small sample sizes. Determining the effect of handedness on spatial ability requires a large, cross-cultural sample of participants and a navigation task with real-world validity.