Therapeutic potential of Parkin and its regulation in Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the midbrain substantia nigra, resulting in motor and non-motor symptoms. While the exact etiology of PD remains elusive, a growing body of evidence suggests that dysfunction in the parkin protein plays a pivotal role in the pathogenesis of the disease. Parkin is an E3 ubiquitin ligase that ubiquitinates substrate proteins to control a number of crucial cellular processes including protein catabolism, immune response, and cellular apoptosis.

Prevalence and Pathophysiology of Loose Stools and Their Impact on Clinical Severity and Quality of Life in Women With Fecal Incontinence.

Objective: To compare the impact of fecal consistency with anorectal sphincter dysfunctions on clinical severity and quality of life (QoL) in women with fecal incontinence (FI).

Background: FI affects up to 24% of middle-aged women, significantly impacting their QoL. Pathophysiological studies have focused more on sphincter and anorectal dysfunctions than on the role of fecal consistency.

Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants in .

Deep-intronic (DI) variants represent approximately 10%-12% of disease-causing genetic defects in -associated Stargardt disease (STGD1). Although many of these DI variants are amenable to antisense oligonucleotide-based splicing-modulation therapy, no treatment is currently available. These molecules are mostly variant specific, limiting their applicability to a broader patient population.

High-Resolution Melting Assay to Detect the Mutations That Cause the Y132F and G458S Substitutions at the ERG11 Gene Involved in Azole Resistance in Candida parapsilosis.

Background: Candida parapsilosis is a pathogenic yeast that has reduced susceptibility to echinocandins and ranks as the second or third leading cause of candidaemia, depending on the geographical region. This yeast often causes nosocomial infections, which are frequently detected as outbreaks. In recent years, resistance to azoles in C.

Associating structural characteristics to immunomodulating properties of carrot rhamnogalacturonan-I fractions.

Carrot rhamnogalacturonan-I (cRG-I) is a polydisperse polysaccharide with molecular weights of 7-250 kDa. Using size exclusion chromatography cRG-I was fractionated and pooled in fractions (PF1-6). All fractions contained the same RG-I monosaccharides and similar glycosidic linkages although in varying relative amounts.

Molecular mimicry as a mechanism of viral immune evasion and autoimmunity.

Mimicry of host protein structures, or 'molecular mimicry', is a common mechanism employed by viruses to evade the host's immune system. Short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T cells from the host, but the prevalence of such mimics throughout the human virome has not been fully explored. Here we evaluate 134 human-infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the Herpesviridae and Poxviridae families.

Clinically relevant bleeding according to location of metastases in cancer-associated thrombosis.

Background: Patients with cancer-associated thrombosis (CAT) face a heightened risk of clinically relevant bleeding (CRB). However, the relationship between these risks and the location of metastasis remains unclear.

Methods: A single-center, non-interventional study of consecutive patients was conducted between 2007 and 2022, involving patients with CAT (n = 1,277).

Characterisation of C-C Ligand 7 (CCL7) as Asthma Genetic Marker in Pigtailed Monkey.

The pigtailed monkey () is one of the species that have potency like the cynomolgus monkey that is widely used as an animal model for asthma study. The gene has potential as a genetic marker because of the secreted chemokine that plays a role in asthma. The aims of this research are to characterise the gene of pigtailed monkey, compare the structure of their gene with other primate species and determine model 3D structure protein prediction of CCL7 protein.

Clustering for mitigating subject variability in driving fatigue classification using electroencephalography source-space functional connectivity features.

While Electroencephalography (EEG)-based driver fatigue state classification models have demonstrated effectiveness, their real-world application remains uncertain. The substantial variability in EEG signals among individuals poses a challenge in developing a universal model, often necessitating retraining with the introduction of new subjects. However, obtaining sufficient data for retraining, especially fatigue data for new subjects, is impractical in real-world settings.

A Machine Learning Approach to Determine Risk Factors for Respiratory Bacterial/Fungal Coinfection in Critically Ill Patients with Influenza and SARS-CoV-2 Infection: A Spanish Perspective.

: Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. : We conducted a secondary analysis of two prospective multicenter cohort studies with confirmed influenza A (H1N1)pdm09 and COVID-19.

Effects of polystyrene nano- and microplastics on human breast epithelial cells and human breast cancer cells.

The continuous littering of the environment with plastic and the resulting nano- and microplastics produced from various processes are ever-increasing problems. These materials also affect humans, as the absorption and accumulation of nano- and microplastics and their effects on health have thus far been rarely researched, which also applies to cancer. In the present study, the absorption of different sizes of polystyrene (PS) nano- and microplastics (PS particles) into human breast epithelial cells and human breast cancer cells was investigated.

Echocardiographic Phenotype in Severe Aortic Stenosis With and Without Transthyretin Cardiac Amyloidosis: The AMY-TAVI Study.

Aim: The relative apical sparing pattern of left ventricular (LV) longitudinal strain (RELAPS]>1) has been described as a typical sign of cardiac amyloidosis (CA). The objective was to validate this pattern in concomitant CA and aortic stenosis (AS) and to identify new echocardiographic variables suggestive of CA in the presence of AS.

Methods And Results: 324 consecutive patients (age 81.

New model to predict survival in advanced pancreatic ductal adenocarcinoma patients by measuring GGT and LDH levels and monocyte count.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed.

The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning.

Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies.

Exercise as a promoter of neurocognitive improvement in people with psychiatric disorders and comorbid obesity: A randomized controlled trial.

Introduction: The psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity (OB).

Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.

Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families.

The MCIB Model: A Novel Theory for Describing the Spatial Heterogeneity of the Tumor Microenvironment.

The tumor microenvironment (TME) can be regarded as a complex and dynamic microecosystem generated by the interactions of tumor cells, interstitial cells, the extracellular matrix, and their products and plays an important role in the occurrence, progression and metastasis of tumors. In a previous study, we constructed an IEO model (prI-, prE-, and pOst-metastatic niche) according to the chronological sequence of TME development. In this paper, to fill the theoretical gap in spatial heterogeneity in the TME, we defined an MCIB model (Metabolic, Circulatory, Immune, and microBial microenvironment).

Microbiota modulation by teriflunomide therapy in people with multiple sclerosis: An observational case-control study.

Multiple sclerosis (MS) is a chronic immune-mediated and heterogeneous disease characterized by demyelination, axonal damage, and physical and cognitive impairment. Recent studies have highlighted alterations in the microbiota of people with MS (pwMS). However, the intricate nature of the disease and the wide range of treatments available make it challenging to identify specific microbial populations or functions associated with MS symptoms and disease progression.

Differentially expressed lncRNAs in SOD1 mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease.

Amyloid deposition in adults with drug-resistant temporal lobe epilepsy.

Objective: Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE).

Methods: In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old.