Regulation of Dopamine Release by Tonic Activity Patterns in the Striatal Brain Slice.

Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons, which extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs. acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than recordings.

Identification of Protein Networks and Biological Pathways Driving the Progression of Atherosclerosis in Human Carotid Arteries Through Mass Spectrometry-Based Proteomics.

Vulnerable atherosclerotic plaques, especially hemorrhaged lesions, are the major cause of mortalities related to vascular pathologies. The early identification of vulnerable plaques helps to stratify patients at risk of developing acute vascular events. In this study, proteomics analyses of human carotid artery samples collected from patients with atheromatous plaques and complicated lesions, respectively, as well as from healthy controls were performed.

New Antioxidant Caffeate Esters of Fatty Alcohols Identified in .

The stem bark of black locust ( L.) was extracted, and nine antioxidant compounds (-) were detected by high-performance thin-layer chromatography combined with the radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH•) assay, multi-detection, and heated electrospray high-resolution mass spectrometry. For structure elucidation, the methanolic crude extract was fractionated by solid-phase extraction, and the compounds were isolated by reversed-phase high-performance liquid chromatography with diode array detection.

Protection motivation theory and health behaviour: conceptual review, discussion of limitations, and recommendations for best practice and future research.

Protection motivation theory is a pre-eminent health behaviour theory purposed to predict participation in health protection and risk behaviours. It has been widely applied across multiple behaviours, populations and contexts. In this conceptual review, we summarise research applying the theory and identify shortcomings and evidence gaps that limit reported inferences and impede theory and intervention development.

Heme: A link between hemorrhage and retinopathy of prematurity progression.

Neovascularization is implicated in the pathology of retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. In our work, we analyzed how heme released during hemorrhage affects hypoxic response and neovascularization. Our retrospective clinical analysis demonstrated, that hemorrhage was associated with more severe retinal neovascularization in ROP patients.

Relevance of Proteinuria in Kidney Transplant Recipients and Allograft Outcomes.

Background: The onset of proteinuria in renal allograft recipients is frequently associated with an increased risk for both graft failure and mortality. We investigated the risk associated with post-transplant proteinuria and its time-dynamics in a select group treated for biopsy proven antibody-mediated rejection (ABMR).

Methods: Eighty-five patients who underwent transplantation were enrolled in our study and followed up from transplantation until October 31, 2020, death, or the date of the return to dialysis.

Effects of a combined aerobic and core stabilization exercise training program on functional capacity, pain, and health-related quality of life in hemodialysis and kidney transplant patients.

Background: Chronic kidney disease (CKD) poses a significant public health challenge globally while impacting patients' physical function and quality of life. Addressing the issues of physical inactivity and pain management is essential during treatment to improve health-related quality of life. The present study investigated the effect of an aerobic training program with core stabilization exercises for hemodialysis (HD) patients on a transplant waiting list and renal transplant (RTx) patients.

Oleoylethanolamide and Palmitoylethanolamide Enhance IFNβ-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells.

Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are endogenous lipids that act as agonists of the peroxisome proliferator-activated receptor α (PPARα). Recently, an interest in the role of these lipids in malignant tumors has emerged. Nevertheless, the effects of OEA and PEA on human neuroblastoma cells are still not documented.

Deficiencies in the Recognition and Reporting of Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus; A Hungarian Nationwide Analysis.

Recognition of chronic kidney disease (CKD) is crucial in type 2 diabetes mellitus (T2DM). We conducted a nationwide epidemiological study to evaluate T2DM-associated CKD in Hungary between 2016 and 2020. Annual incidence and prevalence rates of registered CKD amongst all pharmacologically treated T2DM patients were analyzed in different age-groups by the central database of the Hungarian Health Insurance Fund Management.

Distinct subsets of anti-pulmonary autoantibodies correlate with disease severity and survival in severe COVID-19 patients.

Autoantibodies targeting the lung tissue were identified in severe COVID-19 patients in this retrospective study. Fifty-three percent of 104 patients developed anti-pulmonary antibodies, the majority of which were IgM class, suggesting that they developed upon infection with SARS-CoV-2. Anti-pulmonary antibodies correlated with worse pulmonary function and a higher risk of multiorgan failure that was further aggravated if 3 or more autoantibody clones were simultaneously present (multi-producers).

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations.

Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

In light chain amyloidosis (LA), the massive glomerular and vascular amyloid deposition leading to interstitial fibrosis/tubular atrophy (IFTA) is thought to be responsible for renal failure. The amyloid deposition in the interstitium and the tubular basement membrane (TBM) has received less attention in the study of LA. We, therefore, collected clinical and laboratory data on patients diagnosed with LA in our Nephrology Department and studied amyloid deposition in the TBM.

Predicting Adolescents' Physical Activity Intentions: Testing an Integrated Social Cognition Model.

Background: Few adolescents meet guideline levels of physical activity associated with good health, highlighting the need for intervention. Interventions promoting adolescents' physical activity should be guided by research applying behavioral theory to identify potentially modifiable correlates and associated processes. We applied an integrated social cognition model to identify theory-based constructs and processes that relate to physical activity intentions in a secondary analysis of two samples of Finnish adolescents using a correlational design.

Cellular FXIII in Human Macrophage-Derived Foam Cells.

Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells.

Hydrogen sulfide as an anti-calcification stratagem in human aortic valve: Altered biogenesis and mitochondrial metabolism of HS lead to HS deficiency in calcific aortic valve disease.

Hydrogen sulfide (HS) was previously revealed to inhibit osteoblastic differentiation of valvular interstitial cells (VICs), a pathological feature in calcific aortic valve disease (CAVD). This study aimed to explore the metabolic control of HS levels in human aortic valves. Lower levels of bioavailable HS and higher levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected in aortic valves of CAVD patients compared to healthy individuals, accompanied by higher expression of cystathionine γ-lyase (CSE) and same expression of cystathionine β-synthase (CBS).

Interactions of reactive sulfur species with metalloproteins.

Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in HS-mediated biological events. RSS (including HS) can exert their biological roles via widespread interactions with metalloproteins. Metalloproteins are essential components along the metabolic route of oxygen in the body, from the transport and storage of O, through cellular respiration, to the maintenance of redox homeostasis by elimination of reactive oxygen species (ROS).

Whole blood transcriptome characterization of young female triathlon athletes following an endurance exercise: a pilot study.

The vast majority of studies focusing on the effects of endurance exercise on hematological parameters and leukocyte gene expression were performed in adult men, so our aim was to investigate these changes in young females. Four young (age 15.3 ± 1.

Overview on hydrogen sulfide-mediated suppression of vascular calcification and hemoglobin/heme-mediated vascular damage in atherosclerosis.

Vulnerable atherosclerotic plaques with hemorrhage considerably contribute to cardiovascular morbidity and mortality. Calcification is the main characteristic of advanced atherosclerotic lesions and calcified aortic valve disease (CAVD). Lyses of red blood cells and hemoglobin (Hb) release occur in human hemorrhagic complicated lesions.

The majority of severe COVID-19 patients develop anti-cardiac autoantibodies.

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens.

Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1.

Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury.

Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.

Oncogenic alterations in human epidermal growth factor receptor 2 (HER2) occur in approximately 2% of patients with non-small cell lung cancer and predominantly affect the tyrosine kinase domain and cluster in exon 20 of the ERBB2 gene. Most clinical-grade tyrosine kinase inhibitors are limited by either insufficient selectivity against wild-type (WT) epidermal growth factor receptor (EGFR), which is a major cause of dose-limiting toxicity or by potency against HER2 exon 20 mutant variants. Here we report the discovery of covalent tyrosine kinase inhibitors that potently inhibit HER2 exon 20 mutants while sparing WT EGFR, which reduce tumor cell survival and proliferation in vitro and result in regressions in preclinical xenograft models of HER2 exon 20 mutant non-small cell lung cancer, concomitant with inhibition of downstream HER2 signaling.

A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System.

Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for diversification of animal models to investigate its pathophysiology, related complications, and to subsequently enable discovery of novel therapeutics.