Proteomic changes upon treatment with semaglutide in individuals with obesity.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.

Reactions of clinical neuropsychologists to the Alzheimer's Association workgroup's draft diagnostic and staging criteria for Alzheimer's disease.

Background: An Alzheimer's Association (AA) workgroup published criteria for the diagnosis and staging of Alzheimer's disease (AD). To date, there have not been empirical investigations of professionals' opinions regarding the AA criteria for AD.

Objective: Our goal was to survey clinical neuropsychologists with expertise in dementia about these criteria.

Sexual dimorphism in lipidomic changes in maternal blood and placenta associated with obesity and gestational diabetes: A discovery study.

Introduction: The placenta uses lipids and other nutrients to support its own metabolism hence impacting the type and amount of these substrates available to the growing fetus. Maternal obesity and gestational diabetes (GDM) can disrupt placental lipid metabolism and thus lead to altered fetal growth contributing to adverse pregnancy outcomes and developmentally programing the offspring for disease in later life. Understanding obesity and GDM driven changes in placental lipid metabolism is thus important.

Dopamine loss alters glutamate synapses and transporters in the medial prefrontal cortex and anxiety-related behaviour in a male MPTP rodent model of Parkinson's disease.

Anxiety is a prominent non-motor symptom of Parkinson's disease (PD). Changes in the B-spectrum recordings in PD patients of the prefrontal cortex correlate with increased anxiety. Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss.

Brown Adipose Tissue Mimicking Head and Neck Cancer on PET Scan in a Patient on GLP-1 Drug.

To report a case of a patient undergoing GLP-1 receptor agonist therapy in which increased FDG uptake in brown adipose tissue (BAT) mimicked metastatic head and neck cancer on PET/CT imaging. A 61-year-old female with Class III obesity presented with a right-sided neck mass after significant weight loss following the use of the GLP-1 receptor agonist, Semaglutide. PET/CT revealed FDG uptake in the right level II lymph node and extensive BAT uptake throughout the neck and mediastinum, complicating the diagnosis.

Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.

In the 'incubation of cocaine craving' model of relapse, rats exhibit progressive intensification (incubation) of cue-induced craving over several weeks of forced abstinence from cocaine self-administration. The expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens core (NAcC) medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity and the expression of incubation depends on ongoing protein translation, and the regulation of translation is altered after incubation of cocaine craving.

Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial.

Objective: To determine whether the relationship between average glucose (AG) levels and hemoglobin A1c (HbA1c) differs across racial/ethnic groups.

Research Design And Methods: We performed a prospective substudy of GRADE, a comparative effectiveness randomized trial conducted in 36 centers in the U.S.

Validation of regression-based change formulae for mild cognitive impairment and Alzheimer's disease.

Introduction: Identification of cognitive decline is critical in older adults at risk for dementia. In a 2020 study reported in , Kiselica and colleagues developed standardized regression-based (SRB) change formulae for the Uniform Data Set 3.0 Neuropsychological Battery in cognitively unimpaired older adults.

Does tolerance to ethanol-induced ataxia explain the sensitized response to ethanol?

Under conditions of repeated exposure to ethanol, a sensitized locomotor stimulant response develops in some strains of mice. It has been hypothesized that the sensitized response is a consequence of tolerance development to the sedative/incoordinating effects of ethanol. Conversely, ethanol-induced sensitization and tolerance may be independent effects of repeated ethanol exposure.

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.

Currently available clinical treatments on alcohol use disorder (AUD) exhibit limited efficacy and new druggable targets are required. One promising approach to discover new molecular treatment targets involves the transcriptomic profiling of brain regions within the addiction neurocircuitry, utilizing animal models and postmortem brain tissue from deceased patients with AUD. Unfortunately, such studies suffer from large heterogeneity and small sample sizes.

Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.

Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.

Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

Background And Aims: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten.

Methods: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion.

Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy.

BCR-ABL1 compound mutations can lead to resistance to ABL1 inhibitors in chronic myeloid leukemia (CML), which could be targeted by combining the ATP-site inhibitor ponatinib and the allosteric inhibitor asciminib. Here, we report the clinical validation of this approach in a CML patient, providing a basis for combination therapy to overcome such resistance.

Sex-Specific Impacts of Early Life Sleep Disruption: Ethanol Seeking, Social Interaction, and Anxiety Are Differentially Altered in Adolescent Prairie Voles.

Early life sleep is important for neuronal development. Using the highly social prairie vole rodent model, we have previously reported that early life sleep disruption (ELSD) during the preweaning period results in interference with social bonding and increases ethanol consumption following a stressor in adulthood. Furthermore, ELSD increases parvalbumin expression and reduces glutamatergic neurotransmission in cortical regions in adult prairie voles.

Management of carcinoid heart disease.

Carcinoid Heart Disease (CaHD) is defined as the constellation of all cardiac manifestations that occur in patients with carcinoid tumors. Cardiac manifestations are generally due to the paraneoplastic effects of vasoactive substances secreted by carcinoid tumors. These primarily cause cardiac valve dysfunction and resultant heart failure.