Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review.

Introduction: Without disease-modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near-total failure rate in clinical trials suggests that more disease-modifying therapies are on the horizon. In this review, we assess the late-stage pipeline of disease-modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms-groups of candidates that share an underlying biological mechanism of action and general disease target.

Ankle and foot deformities and malformations in proximal femoral focal deficiency.

Purpose: To describe foot abnormalities in proximal femoral focal deficiency and their correlation to the severity.

Methods: Eighty-nine extremities in 87 patients were evaluated between 1996 and 2020 clinically and radiologically. Fibula length, ankle shape, tarsal coalitions, and the number of foot rays were recorded.

Adiposity and body fat distribution based on skinfold thicknesses and body circumferences in Czech preschool children, secular changes.

Background: The long-standing widespread prevalence of obesity includes issues of its evaluation. Nutritional status may be assessed using various tools and methods; among others simple anthropometric measurements are well established. Widely used body mass index (BMI), presents an obstacle of needing to calculate a standard deviation score (SD) for correct use in the child population.

Oxidative DNA Damage and Arterial Hypertension in Light of Current ESC Guidelines.

A new insight into oxidative stress is based on oxidative deoxyribonucleic acid (DNA) damage. DNA is the pivotal biopolymer for life and health. Arterial hypertension (HT) is a globally common disease and a major risk factor for numerous cardiovascular (CV) conditions and non-cardiac complications, making it a significant health and socio-economic problem.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and complex or multivessel coronary disease (TCW): an international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial.

Background: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative.

Surface-functionalized PAN fiber membranes for the sensitive detection of airborne specific markers.

PAN fibers are characterized by having a large surface-to-volume ratio and small pores, which are beneficial for applications in filtration and specific molecular detection systems. Naturally, larger items are filtered, and a lower ratio between specific and nonspecific binding is expected since small pores do not allow larger elements to penetrate through membranes; thus, nonspecific binding is enhanced. We prepared and tested fiber membranes (diameter cca 700 nm) functionalized with a specific antibody to prove that even microscopic systems such as bacteria could be specifically identified.

Paragangliomas and syringomyelia in Tetralogy of Fallot-A case report and literature review.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, paragangliomas, and syringomyelia are uncommon diseases. Furthermore, in the absence of any genetic link and with less than five reported adult patients surviving unrepaired rare form of Tetralogy of Fallot, our case shows noteworthiness. The possibility of definitive treatment of these conditions is rendered unsafe due to this persistent defect.

Cardiac Conduction System as an OAR in Radiation Therapy: Doses to SA/AV Nodes and Their Reduction.

Purpose: Despite advancements in radiation techniques, concerns persist regarding the adverse effects of radiation therapy, particularly cardiotoxicity or radiation-induced heart disease. Recently, arrhythmogenic toxicity has come to the forefront-the impact of radiation therapy on the cardiac conduction system. Our objective was to conduct a dosimetric study and subsequently investigate the feasibility of optimizing the sinoatrial (SA) and atrioventricular (AV) nodes as organs at risk (OARs) in proton radiation therapy for non-small cell lung cancer with N3 disease.

Comparative cytogenetics of three Zoraptera species as a basis for understanding chromosomal evolution in Polyneoptera insects.

Zoraptera (also called "angel insects") is one of the most unexplored insect orders. However, it holds promise for understanding the evolution of insect karyotypes and genome organization given its status as an early branching group of Polyneoptera and Pterygota (winged insects) during the Paleozoic. Here, we provide karyotype descriptions of three Zorapteran species: (2n♂; ♀ = 42; 42), (2n♂; ♀ = 43; 44) and (2n♂; ♀ = 36; 36).

Selected Papers from the pHealth 2022 Conference, Oslo, Norway, 8-10 November 2022.

This Special Issue of the Journal of Personalized Medicine presents extended versions of selected contributions to pHealth 2022, the 19th International Conference on Wearable Micro and Nano Technologies for Personalized Health, held on 8-10 November 2022 in Oslo, Norway [...

Taxonomic reintroduction of (Taphrinales, Ascomycota) associated with as one of five well defined European species colonizing alders.

Phylogenetic analysis of four DNA regions (ITS, LSU, mtSSU and ) supported the existence of five European species which colonise in Europe. In addition to previously well-defined species, is, for the first time recognised, by molecular study as a species related to . Analysis of publicly available sequences of barcoding regions suggested that is only associated with and no other species colonize this host tree.

Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study.

Background: Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.

Methods: We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia.

Phlebotomine sand flies (Diptera: Psychodidae) of Bosnia and Herzegovina: distribution, ecology and environmental preferences.

Sand flies (Diptera: Phlebotominae) are the principal vectors for the protozoan parasites Leishmania spp. and for phleboviruses. The sand fly fauna on the Balkan Peninsula, including Bosnia and Herzegovina (BIH), is diverse and the circulation of Leishmania infantum as well as phleboviruses has been proven.

A cross-sectional study on phlebotomine sand flies in relation to disease transmission in the Republic of Kosovo.

Sand flies (Diptera: Psychodidae: Phlebotominae) are blood-feeding insects that transmit the protozoan parasites Leishmania spp. and various arboviruses. The Balkan region, including the Republic of Kosovo, harbours a diverse sand fly fauna.

Loneliness, cerebrovascular and Alzheimer's disease pathology, and cognition.

Introduction: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited.

Methods: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression.

Error in jump height estimation using the flight time method: simulation of the effect of ankle position between takeoff and landing.

During vertical jump evaluations in which jump height is estimated from flight time (FT), the jumper must maintain the same body posture between vertical takeoff and landing. As maintaining identical posture is rare during takeoff and landing between different jump attempts and in different individuals, we simulated the effect of changes in ankle position from takeoff to landing in vertical jumping to determine the range of errors that might occur in real-life scenarios. Our simulations account for changes in center of mass position during takeoff and landing, changes in ankle position, different subject statures (1.

Flat feet occurrence among young school-age children and its association with body mass index values.

A sedentary lifestyle, characterised by a lack of physical activity, negatively influences Body Mass Index (BMI). BMI may be related to the prevalence of flat feet. This study aims to observe the occurrence of flat feet in young children and determine its association with BMI.

Discovery of highly potent SARS-CoV-2 nsp14 methyltransferase inhibitors based on adenosine 5'-carboxamides.

The emergence of SARS-CoV-2, the causative agent of COVID-19, has highlighted the need for advanced antiviral strategies. Targeting the coronaviral methyltransferase nsp14, which is essential for RNA capping, offers a promising approach for the development of small-molecule inhibitors. We designed and synthesized a series of adenosine 5'-carboxamide derivatives as potential nsp14 inhibitors and identified coumarin analogs to be particularly effective.