Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models.

Alzheimer's disease (AD) is the most common form of age-related dementia. In AD, the death of neurons in the central nervous system is associated with the accumulation of toxic amyloid β peptide (Aβ) and mitochondrial dysfunction. Mitochondria are signal transducers of metabolic and biochemical information, and their impairment can compromise cellular function.

The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. : A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II).

Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

Background: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment.

Six-year follow-up and subgroup analyses of a phase 2 trial of venetoclax for del(17p) chronic lymphocytic leukemia.

Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982.

Carob Extract ( L.): Effects on Dyslipidemia and Obesity in a High-Fat Diet-Fed Rat Model.

Dyslipidemia and obesity are recognized as two of the major global health issues and main risk factors for coronary heart disease and cerebrovascular disease. In recent years, carob has shown certain antioxidant and anti-dyslipidemic potential. In this study, Wistar rats were fed with a standard and cholesterol-enriched diet and treated orally with carob extract and simvastatin for four weeks.

Enrichment of Membrane Proteins for Downstream Analysis Using Styrene Maleic Acid Lipid Particles (SMALPs) Extraction.

Integral membrane proteins are an important class of cellular proteins. These take part in key cellular processes such as signaling transducing receptors to transporters, many operating within the plasma membrane. More than half of the FDA-approved protein-targeting drugs operate via interaction with proteins that contain at least one membrane-spanning region, yet the characterization and study of their native interactions with therapeutic agents remains a significant challenge.

Upregulation of Tribbles decreases body weight and increases sleep duration.

Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases act as negative regulators of insulin signalling. Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus.

PERCUTANEOUS DILATATIONAL TRACHEOSTOMY IN COVID-19 PATIENTS IN THE COVID HOSPITAL INTENSIVE CARE UNIT: THE UNIVERSITY CLINICAL CENTER OF VOJVODINA EXPERIENCE.

Patients with acute respiratory distress syndrome due to COVID-19 require intensive care unit (ICU) admission with consecutive endotracheal intubation and invasive mechanical ventilation. In patients with long-term mechanical ventilation, percutaneous dilatational tracheostomy (PDT) may be considered. This retrospective analysis includes clinical data on patients treated at the ICUs of the COVID Hospital of the Clinical Center of Vojvodina in the period from September 3, 2021 to May 1, 2022, and underwent PDT.

Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson's disease.

Parkinson's disease (PD) is characterised by selective death of dopaminergic (DA) neurons in the midbrain and motor function impairment. Gastrointestinal issues often precede motor deficits in PD, indicating that the gut-brain axis is involved in the pathogenesis of this disease. The features of PD include both mitochondrial dysfunction and activation of the unfolded protein response (UPR) in the endoplasmic reticulum (ER).

Increased cysteine metabolism in PINK1 models of Parkinson's disease.

Parkinson's disease (PD), an age-dependent neurodegenerative disease, is characterised by the selective loss of dopaminergic neurons in the substantia nigra (SN). Mitochondrial dysfunction is a hallmark of PD, and mutations in PINK1, a gene necessary for mitochondrial fitness, cause PD. Drosophila melanogaster flies with pink1 mutations exhibit mitochondrial defects and dopaminergic cell loss and are used as a PD model.

[Consensus statement of the Austrian Sleep Medicine Society on the management of residual excessive daytime sleepiness in obstructive sleep apnea].

Background: Six to ten percent of patients with obstructive sleep apnea suffer from residual excessive daytime sleepiness (rEDS) despite adequate nocturnal positive airway pressure therapy or effective alternative treatment. The differential diagnosis of rEDS is an interdisciplinary challenge in clinical practice.

Objectives: Development of a clear guideline for the detection, differential diagnostic considerations, and options for the continuing treatment of rEDS in clinical practice.

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML.

Background/aim: The therapeutic potential of bromodomain and extra-terminal motif (BET) inhibitors in hematological cancers has been well established in preclinical and early-stage clinical trials, although as of yet, no BETtargeting agent has achieved approval. To add insight into potential response to mivebresib (ABBV-075), a broadspectrum BET inhibitor, co-clinical modeling of individual patient biopsies was conducted in the context of a Phase I trial in acute myeloid leukemia (AML).

Materials And Methods: Co-clinical modeling involves taking the patient's biopsy and implanting it in mice with limited passage so that it closely retains the original characteristics of the malignancy and allows comparisons of response between animal model and clinical data.

nicotinic acetylcholine receptor subunits and their native interactions with insecticidal peptide toxins.

nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that represent a target for insecticides. Peptide neurotoxins are known to block nAChRs by binding to their target subunits, however, a better understanding of this mechanism is needed for effective insecticide design. To facilitate the analysis of nAChRs we used a CRISPR/Cas9 strategy to generate null alleles for all ten subunit genes in a common genetic background.

Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia.

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity.

The Role of Socioeconomic Status in Adherence to the Mediterranean Diet and Body Mass Index Change: A Follow-Up Study in the General Population of Southern Croatia.

The Mediterranean diet (MD) is one of the most healthful dietary patterns, beneficial for humans and the environment. However, the MD has recently exhibited a declining trend, especially in younger and less affluent people. This study investigated the association between socioeconomic indicators and adherence to the MD in 4671 adult subjects from Dalmatia, Croatia (age range 18-98 years; 61.

Tracking of Mental Workload with a Mobile EEG Sensor.

The aim of the present investigation was to assess if a mobile electroencephalography (EEG) setup can be used to track mental workload, which is an important aspect of learning performance and motivation and may thus represent a valuable source of information in the evaluation of cognitive training approaches. Twenty five healthy subjects performed a three-level N-back test using a fully mobile setup including tablet-based presentation of the task and EEG data collection with a self-mounted mobile EEG device at two assessment time points. A two-fold analysis approach was chosen including a standard analysis of variance and an artificial neural network to distinguish the levels of cognitive load.

A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a heterogenous malignancy driven by genetic and epigenetic factors. Inhibition of bromodomain and extraterminal (BET) proteins, epigenetic readers that play pivotal roles in the regulation of genes relevant to cancer pathogenesis, constitutes a novel AML treatment approach.

Methods: In this first-in-human study of the pan-BET inhibitor mivebresib as monotherapy (MIV-mono) or in combination with venetoclax (MIV-Ven), the safety profile, efficacy, and pharmacodynamics of mivebresib were determined in patients with relapsed/refractory AML (ClinicalTrials.

Combined Transcriptomic and Proteomic Analysis of Perk Toxicity Pathways.

In , endoplasmic reticulum (ER) stress activates the protein kinase R-like endoplasmic reticulum kinase (dPerk). dPerk can also be activated by defective mitochondria in fly models of Parkinson's disease caused by mutations in or . The Perk branch of the unfolded protein response (UPR) has emerged as a major toxic process in neurodegenerative disorders causing a chronic reduction in vital proteins and neuronal death.

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy.

Venetoclax is approved as monotherapy and in combination with rituximab for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Two Phase 1 studies (M12-175 [NCT01328626]; M13-365 [NCT01682616]) were conducted in which patients who initially responded and then progressed on venetoclax monotherapy could receive added rituximab. Ten patients were evaluated (M12-175, n = 8; M13-365, n = 2), and five (50%) responded again upon addition of rituximab, including three complete and two partial responses.

Alzheimer's and Parkinson's Diseases Predict Different COVID-19 Outcomes: A UK Biobank Study.

In December 2019, a coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began infecting humans, causing a novel disease, coronavirus disease 19 (COVID-19). This was first described in the Wuhan province of the People's Republic of China. SARS-CoV-2 has spread throughout the world, causing a global pandemic.

Links between air pollution and COVID-19 in England.

In December 2019, a novel disease, coronavirus disease 19 (COVID-19), emerged in Wuhan, People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) presumed to have jumped species from another mammal to humans. This virus has caused a rapidly spreading global pandemic.

Five-year surveillance and correlation of antibiotic consumption and resistance of Gram-negative bacteria at an intensive care unit in Serbia.

A surveillance study was performed in an intensive care unit in the largest tertiary health care center in Vojvodina, Serbia from 2014 to 2018. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated using cross-correlation analysis.