Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.

Background: Mutations in the X-linked CDKL5 gene underlie a severe epileptic encephalopathy, CDKL5 deficiency disorder (CDD), characterized by gross motor impairment, autistic features and intellectual disability. Absence of Cdkl5 negatively impacts neuronal proliferation, survival, and maturation in in vitro and in vivo models, resulting in behavioral deficits in the Cdkl5 KO mouse. While there is no targeted therapy for CDD, several studies showed that treatments enabling an increase in brain BDNF levels give rise to structural and behavioral improvements in Cdkl5 KO mice.

The Impact of the Blood-Brain Barrier and Its Dysfunction in Parkinson's Disease: Contributions to Pathogenesis and Progression.

Parkinson's disease (PD) is a brain disorder in which neuronal cells responsible for the release of dopamine, a neurotransmitter that controls movement, are degenerated or impaired in the substantia nigra and basal ganglia. The disease typically affects people over the age of 5 and presents with a variety of motor and nonmotor dysfunctions, which are unique to each person. The impairment of the blood-brain barrier (BBB) and blood retinal barrier (BRB) due to age-related causes such as weakness of tight junctions or rare genetic factors allows several metabolic intermediates to reach and accumulate inside neurons such as Lewy bodies and α-synuclein, disrupting neuronal homeostasis and leading to genetic and epigenetic changes, e.

Attention-aware with stacked embedding for sentiment analysis of student feedback through deep learning techniques.

Automatic polarity prediction is a challenging assessment issue. Even though polarity assessment is a critical topic with many existing applications, it is probably not an easy challenge and faces several difficulties in natural language processing (NLP). Public polling data can give useful information, and polarity assessment or classification of comments on Twitter and Facebook may be an effective approach for gaining a better understanding of user sentiments.

A retrospective analysis of tuberculosis in livestock farmers in Lahore district, Pakistan.

Introduction: Mycobacterium tuberculosis is the main cause of tuberculosis in humans, accounting for numerous illnesses and thousands of fatalities globally. Data regarding the association of various risk factors and TB in livestock farmers in Pakistan is scarce.

Methodology: A retrospective matched case-control study of TB cases was performed in Lahore, Pakistan to investigate the potential risk factors that lead to the development of TB in Pakistani livestock farmers.

Kharadar spontaneous quintuplets reached their adolescence life: A case report.

Quintuplet pregnancies are associated with significant perinatal morbidity and mortality. The spontaneous quintuplets are a rare occurrence, and the survival is extremely rare. The first quintuplets known to survive infancy to adulthood were the Dionne Quintuplets, born in 1934.

Toxicity and bioassimilation of lead and nickel in farm ruminants fed on diversified forage crops grown on contaminated soil.

The cultivation of forage crops on wastewater-irrigated soils, while common in many developing countries, poses significant risks due to heavy metal pollution, particularly Lead (Pb) and Nickel (Ni). This practice, aimed at addressing water scarcity challenges and providing affordable irrigation, was investigated for its ecological and human health implications across three diverse sites (site A, site B, and site C). Our study unveiled increases in Pb concentrations in contaminated soil, cultivated with Sesbania bispinosa showing the highest Pb accumulation.

Burden and factors associated with occupational tuberculosis infection among high-risk workers in Lahore District, Pakistan.

Introduction: The main objective of the study was to estimate the burden of occupational tuberculosis infection in high-risk occupational workers and to identify risk factors associated with the prevalence of Mycobacterium tuberculosis complex (MTBC).

Methodology: An analytical cross-sectional study was conducted among high-risk occupational workers including veterinarians, abattoir workers, animal handlers, livestock farmers, and microbiology laboratory workers. Sputum samples were collected from 100 participants and polymerase chain reaction (PCR) tests were done to diagnose tuberculosis (TB) infection.

Synergy between psychological impact and biochemical manifestation of stress among the COVID-19 pandemic-affected population.

Objective: Due to the COVID-19 pandemic, many countries around the world experienced an unprecedented increase in stress in the general population. Even after normal life has been reestablished, the new normal is punctuated by severely impacted vulnerable groups. Stress-associated symptoms display an intricate relationship with biochemical modulations, which coordinate the stress response.

Diabetic Ketoacidosis Induces Tau Hyperphosphorylation in Rat Brain.

Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear.

Objective: Our objective was to understand how DKA can promote neurodegeneration in AD.

An intelligent diabetes classification and perception framework based on ensemble and deep learning method.

Sugar in the blood can harm individuals and their vital organs, potentially leading to blindness, renal illness, as well as kidney and heart diseases. Globally, diabetic patients face an average annual mortality rate of 38%. This study employs Chi-square, mutual information, and sequential feature selection (SFS) to choose features for training multiple classifiers.

Efficient quality assurance for isocentric stability in stereotactic body radiation therapy using machine learning.

This study aims to predict isocentric stability for stereotactic body radiation therapy (SBRT) treatments using machine learning (ML), covers the challenges of manual assessment and computational time for quality assurance (QA), and supports medical physicists to enhance accuracy. The isocentric parameters for collimator (C), gantry (G), and table (T) tests were conducted with the RUBY phantom during QA using TrueBeam linac for SBRT. This analysis combined statistical features from the IsoCheck EPID software.

Tau and Alzheimer's disease: Past, present and future.

My journey with tau started when in 1974 for the first time I isolated neurofibrillary tangles of paired helical filaments (PHFs) from autopsied Alzheimer's disease (AD) brains and discovered that they were made up of a ~50-70 KDa protein on SDS-polyacrylamide gels. Subsequently my team discovered that this PHF protein and the microtubule-associated factor called tau were one and the same protein. However, we found that tau in neurofibrillary tangles/PHFs in AD brain was abnormally hyperphosphorylated, and unlike normal tau, which promoted the assembly of tubulin into microtubules, the AD-hyperphosphorylated tau inhibited microtubule assembly.

Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective.

Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study.Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2.

Determination of heavy metals (Pb, Cr, As, Hg, and Cd) into the body organs of selected fish, water, sediment, and soil samples from Head Punjnad and Head Taunsa, Punjab, Pakistan.

The present study was conducted on Head Punjnad (HP) and Head Taunsa (HT) to evaluate the contamination of Pb, Cr, As, Hg, and Cd in water, soil, sediment, fish as a whole and fish organs. Fish, water, soil and sediment samples were collected from different sites of HT and HP on a monthly basis for 8 months. Heavy metals in water, soil, and sediment were determined by a polarized Zeeman atomic absorption spectrophotometer and in fish and fish organs by an atomic absorption spectrophotometer.

Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials.

Protein kinases (PKs) have emerged as one of the most intensively investigated drug targets in current pharmacological research, with indications ranging from oncology to neurodegeneration. Tau protein hyperphosphorylation was the first pathological post-translational modification of tau protein described in Alzheimer's disease (AD), highlighting the role of PKs in neurodegeneration. The therapeutic potential of protein kinase inhibitors (PKIs)) and protein phosphatase 2 A (PP2A) activators in AD has recently been explored in several preclinical and clinical studies with variable outcomes.

Administration of vitamin E and C enhances immunological and biochemical responses against toxicity of silver nanoparticles in grass carp (Ctenopharyngodon idella).

The aim of the current study was to evaluate the toxic effect of silver nanoparticles (Ag-NPs) on biochemical biomarkers, immune responses, and the curative potential effects of vitamin C and E on grass carp. Fish (n = 420) with an average initial body weight of 8.045 ± 0.

Two simple assays for assessing the seeding activity of proteopathic tau.

The regional distribution of neurofibrillary tangles of hyperphosphorylated tau aggregates is associated with the progression of Alzheimer's disease (AD). Misfolded proteopathic tau recruits naïve tau and templates its misfolding and aggregation in a prion-like fashion, which is believed to be the molecular basis of propagation of tau pathology. A practical way to assess tau seeding activity is to measure its ability to recruit/bind other tau molecules and to induce tau aggregation.

Long-Term Impact of Multiple Micronutrient Supplementation on Micronutrient Status, Hemoglobin Level, and Growth in Children 24 to 59 Months of Age: A Non-Randomized Community-Based Trial from Pakistan.

Cost-effective interventions are needed to address undernutrition, particularly micronutrient deficiencies, which are common in children under the age of five in low- and middle-income countries. A community-based, non-randomized clinical trial was undertaken in the Kurram district of Khyber Pakhtunkhwa from January 2018 to June 2019, to evaluate the effect of locally produced micronutrient powder (local name: Vita-Mixe) on plasma micronutrient status, hemoglobin level, and anthropometric outcomes. Children aged 24-48 months old were recruited and allocated to the intervention and control arm of the study.

Nano-managing silver and zinc as bio-conservational approach against pathogens of the honey bee.

Herein, silver and zinc oxide Nanoparticles (NPs) were synthesized by using W. coagulant fruit extract as reducing agent and capping agent. The green synthesized NP with distinct properties were used for novel application against fungal and bacterial pathogen of honey bee (A.

Cross-cultural diversity analysis: traditional knowledge and uses of freshwater fish species by indigenous peoples of southern Punjab, Pakistan.

Background: Fisheries have tremendous cultural and educational importance in human societies. The world is undergoing fast environmental and cultural changes, and local knowledge is being lost. Understanding how people interpret environmental change and develop practices in response to such change is essential to comprehend human resource use.

Gut Microbiota and Immunotherapy for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Currently, no effective treatment is available that can slow or halt the progression of the disease. The gut microbiota can modulate the host immune system in the peripheral and central nervous system through the microbiota-gut-brain axis.

Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset and multifactorial nature. A deficit in neurogenesis and synaptic plasticity are considered the early pathological features associated with neurofibrillary tau and amyloid β pathologies and neuroinflammation. The imbalance of neurotrophic factors with an increase in FGF-2 level and a decrease in brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) in the hippocampus, frontal cortex and parietal cortex and disruption of the brain micro-environment are other characteristics of AD.

Crest to Trough Cellular Drifting of Green-Synthesized Zinc Oxide and Silver Nanoparticles.

Green nanotechnology facilitates the blooming of zinc oxide (ZnO) and silver (Ag) nanoparticles (NPs) with distinct flowerlike and spherical morphologies, respectively. The well-characterized NPs with an average size of 35 nm (ZnO) and 25 nm (Ag) were functionalized on the cresty plates for antibacterial inhibition against and , with the flowerlike ZnONPs exhibiting 90.9% inhibition and AgNPs exhibiting 100% inhibition.