Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension.

Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH) and it is predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD free diet for 5 weeks and followed by Su5416 administration and hypoxia (10%) for 3 weeks, a standard experimental model of PAH.

Inclisiran, Reasons for a Novel Agent in a Crowded Therapeutic Field.

Purpose Of The Review: A significant number of patients fail to achieve target LDL cholesterol (LDL-C) levels. This review aims to explore why inclisiran, a novel class of LLT, should be considered a valuable addition to the current treatment options.

Recent Findings: Inclisiran is a small interfering RNA (siRNA) that targets PCSK9 synthesis specifically in the hepatocytes.

Oocyte maturation defect in women undergoing IVF: contributing factors and effects on mature sibling oocyte outcomes.

Purpose: This study aimed to identify demographic and clinical factors associated with low maturation rates and to investigate if the rate of immature oocytes impacts the outcomes of mature sibling oocytes.

Methods: Women undergoing their first IVF-ICSI cycle between 2018 and 2022 at a fertility clinic were included. Cycles were classified into five groups according to the proportion of Metaphase II stage oocytes (MII): Null (0% MII, n = 46), Poor (1-25% MII, n = 44), Low (26-50% MII, n = 453), Acceptable (51-75% MII, n = 1641), and Optimal (76-100% MII, n = 2642).

Patient-reported outcome measures to assess mental and physical health status, functionality, and quality of life in patients with major depression or schizophrenia.

Background: Patient-reported outcomes measures (PROMs) are standardized self-administered tools that assess the patient's opinion on the level of health, quality of life, and disability among other aspects. The objective of this study was to gather information on physical and mental health in patients with major mental illness using PROMs.

Methods: This was an observational, naturalistic, prospective study carried out in adult stabilized outpatients attended at nine Adult Mental Health Centers in Barcelona, Spain.

Examining the learning curves in robotic cardiac surgery wet lab simulation training.

Background: Simulation-based training has gained distinction in cardiothoracic surgery, as robotic-assisted cardiac procedures evolve. Despite the increasing use of wet lab simulators, the effectiveness of these training methods and skill acquisition rates remain poorly understood.

Objective: This study aimed to compare learning curves and assess the robotic cardiac surgical skill acquisition rate for cardiac and noncardiac surgeons who had no robotic experience in a wet lab simulation setting.

Mechanism of syncope: role of ambulatory blood pressure monitoring and cardiovascular autonomic function assessment.

Background And Aims: Identifying the haemodynamic mechanism of autonomic syncope is the essential pre-requisite for effective and personalized therapy aimed at preventing recurrences. The present study assessed the diagnostic efficacy of a two-step assessment.

Methods: Multicentre prospective, cross-sectional, observational study.

RAD51 testing in patients with early HER2-negative breast cancer and homologous recombination deficiency: post-hoc analysis of the GeparOla trial.

Purpose: The randomized GeparOla trial reported comparable pathological complete response (pCR) rates with neoadjuvant containing olaparib vs. carboplatin treatment. Here, we evaluate the association between functional homologous repair deficiency (HRD) by RAD51 foci and pCR, and the potential of improving patient selection by combining RAD51 and stromal tumor infiltrating lymphocytes (sTILs).

Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs.

Features related to the presence of internet gaming disorder and their impact on the treatment outcomes.

Background And Aims: Internet gaming disorder (IGD) is a highly engrossing activity with the individual spending up to 10 h per day gaming, this causes issues in accomplishing their tasks and personal goals. Also, to generate in them increased anxiety, impulsivity and lack of social skills, this impacts the good personal development and individual's quality of life. Therefore, it is vital to better understand, in terms of treatment, which factors are associated with therapeutic outcomes (largely to achieve control over the use of video games and the lack of relapses) following a standardized Cognitive Behavioral Therapy (CBT) protocol.

Transformational Teacher Leadership and Physical Education Students' Intention to be Active: The Mediating Roles of Motor Self-Efficacy and Enjoyment.

Previous research has highlighted positive associations between physical education (PE) teachers' transformational leadership and their adolescent students' intentions to be active. However, no prior investigators have addressed mediating variables of students' motor self-efficacy and enjoyment. Our aim in this study was to re-analyze the relationships between teachers' transformational leadership style and PE students' intentions to be active, while also examining the roles of motor self-efficacy and enjoyment as potential mediators in these relationships.

Aminoalkylation of Alkenes Enabled by Triple Radical Sorting.

The direct synthesis of C(sp)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp-rich molecules from commercial feedstocks, such as alkenes.

Response of Amblyseius swirskii to deltamethrin.

Background: The rising demand for environmentally friendly pest control highlights the importance of understanding the interaction between natural enemies and pesticides. Amblyseius swirskii, a predatory mite extensively used in biocontrol, plays a crucial role in managing pest populations in agricultural systems. Integrating this mite with selective pesticide use within integrated pest management (IPM) would significantly advance pest control and may reduce pesticide residues in the environment and agricultural produce.

Biomarkers.

Background: biomarkers are essential in order to make a diagnosis with a high level of accuracy in patients with cognitive and behavior complaints. However, molecular imaging biomarkers not always provide an answer in daily clinical practice.

Methods: retrospective and descriptive study in patients with Amyloid PET (APscans) implemented according to rational use of this technic, between January 2019-November 2023 in Neurology Department, Infanta Leonor Hospital, Madrid, Spain.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Neurofilament light chain (NfL) is a fluid biomarker of axonal damage reported to be elevated in cases with dementia, and particularly in FTD. In this study we evaluate the performance of a recently developed NfL assay to be analyzed through the Lumipulse chemiluminescent platform, which is frequently available in clinical settings for the study of AD core biomarkers.

Method: We evaluated CSF NfL levels using the Lumipulse G600II platform (Fujirebio, Iberia) in 70 cases, including 33 patients with AD (supported by CSF biomarkers consistent with an A+T+(N)+ classification scheme), 26 with confirmed FTD (typical phenotype and CSF with a A-T- profile), and 11 controls.

Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Alzheimer's Disease (AD) has a long preclinical stage, in which brain metabolic alterations precede the symptoms onset. Therefore, an early and proper diagnosis of AD is essential for prevention and therapeutic evaluation. Current diagnosis and staging procedures rely on neuroimaging techniques, such as positron emission tomography (PET), which require intensity normalization to ensure the correct interpretation of the data.

Biomarkers.

Background: A key neuropathological feature in the early stages of Alzheimer's disease (AD) involves hippocampal dysfunction arising from the accumulation of amyloid-β (Aβ). Previously, our laboratory identified a shift in the synaptic plasticity long term potentiation (LTP)/long term depression (LTD) induction threshold, leading to memory deficits in a non-transgenic murine model of early AD generated by intracerebroventricular (icv.) injections Aβ oligomers (oAβ), one of the most predominant pathogenetic factors in initial stages of the disease.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common neuropathologic finding at advanced age that associates with hippocampal sclerosis (HS) and is often comorbid with AD pathology. Neuroimaging measurements of LATE-NC-associated limbic degeneration have been proposed as indirect biomarkers, but molecular-specific biomarkers for LATE-NC are still lacking. Here we used combined ante-mortem blood and MRI data to study TDP-43 levels in plasma-derived small extracellular vesicles (sEV-TDP-43) and hippocampal volume (HV) in relation to LATE-NC and HS at autopsy.

Biomarkers.

Background: Beyond dementia syndromes, cognitive symptoms are highly prevalent in Parkinson's disease (PD), often manifesting as mild cognitive impairment (MCI). Yet, their detection and characterization remain suboptimal because standard approaches rely on subjective impressions derived from lengthy, univariate tests. Here we introduce a novel approach to detect cognitive symptom severity and identify MCI in PD using fully automated word property analyses on brief verbal fluency tasks.

Biomarkers.

Background: Understanding the genetic etiology of Alzheimer's disease (AD) has been a major focus of research in neurodegenerative diseases. Amid the three common allelic variants of the apolipoprotein E (APOE) gene in humans, called APOE ε2, ε3 and ε4, the ε4 allele is the most common genetic risk factor for late-onset AD, being found in 20% of the world population.

Method: We used Event-Related Potentials (ERP) and Event-Related Spectral Perturbation (ERSP) as features for classification of apolipoprotein E ϵ4 (APOE ε4) allele carriers in AD patients and healthy controls.

Biomarkers.

Background: Detecting Alzheimer's disease (AD) biological hallmarks before clinical symptoms emerge is now possible with available blood-based biomarkers. However, the rate of cognitive decline varies among individuals at risk of AD, and accurate prognostic blood-based biomarkers are lacking. Our goal is to identify plasma proteins predictive of fast cognitive decline in asymptomatic individuals at risk of AD.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: Recent reports support the use of plasma biomarkers of neurodegeneration and neuroinflammation, as determined through ultrasensitive single molecular arrays (SIMOA), to screen and diagnose patients with dementia. However, their translation to clinical settings requires further studies.

Methods: We evaluated plasma samples from 186 individuals including 72 patients with AD (supported by CSF biomarkers consistent with an A+T+N+ classification scheme), 44 with confirmed FTD, 48 cognitively intact nonagenarians, and 22 controls (ages 40-83 years).

Biomarkers.

Background: Changes in Amyloid-β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.

Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three-stage analytical approach (discovery, replication, and meta-analysis).