A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.

Study Question: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?

Summary Answer: Our findings revealed a significant association between SPGF and the gene and identified three novel genes (, , and ) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.

What Is Known Already: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants.

Dosimetric study of bevel factors in IOERT with mobile linacs: Towards a unified code of practice.

Background: Dosimetry in intraoperative electron radiotherapy (IOERT) poses distinct challenges, especially with inclined applicators deviating from international protocols. Ion recombination in ionization chambers, electron beam degradation due to scattering in cylindrical applicators, coupled with a lack of a well-defined beam quality surrogate, complicate output factor determination with ionization chambers. Synthetic diamond-based detectors, offer potential solutions; however, their suitability requires further exploration.

Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.

Background: The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

Real-Time Monitoring of Particle Size in Emulsion Polymerization: Simultaneous Turbidity and Photon Density Wave Spectroscopy.

Particle size evolution in seeded semibatch emulsion polymerization is monitored by two real-time monitoring techniques: online turbidity spectroscopy (TUS) and inline photon density wave spectroscopy (PDWS). An automatic dilution system that withdraws a sample from the reactor and upon dilution transfers to the measurement cell is used for the online TUS analysis. A PDWS probe is immersed in the reactor and collects inline the scattered light directly from the reacting latex.

Disproportionate infection, hospitalisation and death from COVID-19 in ethnic minority groups and Indigenous Peoples: an application of the Priority Public Health Conditions analytical framework.

The COVID-19 pandemic has resulted in disproportionate consequences for ethnic minority groups and Indigenous Peoples. We present an application of the Priority Public Health Conditions (PPHC) framework from the World Health Organisation (WHO), to explicitly address COVID-19 and other respiratory viruses of pandemic potential. This application is supported by evidence that ethnic minority groups were more likely to be infected, implying differential exposure (PPHC level two), be more vulnerable to severe disease once infected (PPHC level three) and have poorer health outcomes following infection (PPHC level four).

Dual effect of cardiac FKBP12.6 overexpression on excitation-contraction coupling and the incidence of ventricular arrhythmia depending on its expression level.

FKBP12.6, a binding protein to the immunosuppressant FK506, which also binds the ryanodine receptor (RyR2) in the heart, has been proposed to regulate RyR2 function and to have antiarrhythmic properties. However, the level of FKBP12.

A snapshot of the transcriptome of Medicago truncatula (Fabales: Fabaceae) shoots and roots in response to an arbuscular mycorrhizal fungus and the pea aphid (Acyrthosiphon pisum) (Hemiptera: Aphididae).

Plants simultaneously interact with belowground symbionts such as arbuscular mycorrhizal (AM) fungi and aboveground antagonists such as aphids. Generally, plants gain access to valuable resources including nutrients and water through the AM symbiosis and are more resistant to pests. Nevertheless, aphids' performance improves on mycorrhizal plants, and it remains unclear whether a more nutritious food source and/or attenuated defenses are the contributing factors.

Medical consultation in ulcerative colitis: Key elements for improvement.

Ulcerative colitis (UC) is a chronic inflammatory disease with a high impact. In order to improve patient outcomes, the clinician-patient relationship in daily practice is critical. Clinical guidelines provide a framework for UC diagnosis and treatment.

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.

Primary health care as a platform for addressing racial discrimination to "leave no one behind" and reduce health inequities.

The health inequities faced by populations experiencing racial discrimination, including indigenous peoples and people of African descent, Roma, and other ethnic minorities, are an issue of global concern. Health systems have an important role to play in tackling these health inequities. Health systems based on comprehensive Primary Health Care (PHC) are best placed to tackle health inequities because PHC encompasses a whole-of-society approach to health.

Opportunities to tackle structural racism and ethnicity-based discrimination in recovering and rebuilding from the COVID-19 pandemic.

The impact of COVID-19 has been disproportionately felt by populations experiencing structural racial- and ethnicity-based discrimination. Here, we describe opportunities for COVID-19 response and recovery efforts to help build more equal and resilient societies, through investments in: (i) interventions focused on explicitly addressing racial and ethnicity-based discrimination; (ii) interventions supporting the delivery of universal services, and in ways that address compounding and intersecting drivers of exclusion and marginalization; and (iii) cross-cutting enabling measures, such as participatory mechanisms and data disaggregation.

Heart failure in mice induces a dysfunction of the sinus node associated with reduced CaMKII signaling.

Dysfunction of the sinoatrial node (SAN), the natural heart pacemaker, is common in heart failure (HF) patients. SAN spontaneous activity relies on various ion currents in the plasma membrane (voltage clock), but intracellular Ca2+ ([Ca2+]i) release via ryanodine receptor 2 (RYR2; Ca2+ clock) plays an important synergetic role. Whereas remodeling of voltage-clock components has been revealed in HF, less is known about possible alterations to the Ca2+ clock.

Phytohormone Profile of in Response to Mycorrhizal Fungi, Aphids, and Gibberellic Acid.

Although gibberellic acid (GA) is widely used in agriculture, it is unclear whether exogenous GA makes aphid-infested, mycorrhizal plants more susceptible to herbivory. This study investigates the role of GA in modulating defenses in barrel medic plants () that are infested with pea aphids () and colonized by the beneficial symbiont . Mock- and -inoculated potted plants were grown in a topsoil: sand mix for 42 days and were treated with GA or solvent.

Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.

Background: The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects.

Methods: To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice.

Patient Journey in Atopic Dermatitis: The Real-World Scenario.

Introduction: The diagnosis and management of atopic dermatitis (AD) is extensively addressed in detailed clinical guidelines. However, the high heterogeneity regarding presentation and progression and the increasingly broad therapeutic landscape suggest a complex real-world scenario, leading to multiple trajectories of AD patients.

Methods: Using a Delphi methodology for assessing the degree of consensus, we explored the views of a panel of dermatologists regarding the patients' trajectory through the diagnosis (block 1), treatment (block 2), and long-term management (block 3) of AD.

Adherence improvement in patients with ulcerative colitis: a multidisciplinary consensus document.

Objectives: a) to analyze the evidence available about poor adherence/non-adherence, including prevalences, associated factors, and interventions in ulcerative colitis (UC) patients; b) to provide a framework to improve poor adherence/non-adherence.

Methods: a qualitative approach was used. A literature review was performed using Medline.

Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA.

Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain.

Background: To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective.

Methods: A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis.

Update on the Safety Profile of Tofacitinib in Rheumatoid Arthritis from Clinical Trials to Real-World Studies: A Narrative Review.

Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6-24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF.

Gaps between research and recommendations in rheumatoid arthritis.

Objectives: To identify recommendations on the diagnosis and management of rheumatoid arthritis (RA) supported by low recommendation grades, to study the causes of this low grading, and to propose solutions.

Methods: A group of six rheumatologists, with extensive experience in the development of systematic reviews, reviewed national and international RA recommendations and practice guidelines. They identified all recommendations with a low level of evidence or recommendation grade (levels equivalent to 4, 5, or grades C or D of the Oxford Levels of Evidence), classified them by areas (diagnosis, follow-up, treatment, others), and analyzed plausible causes of low graduation.

Worldwide survey on key indicators for public cord blood banking technologies: By the World Marrow Donor Association Cord Blood Working Group.

The Cord Blood Working Group of the World Marrow Donor Association created a survey for cord blood banks (CBBs) aimed to identify and understand the main technical procedures currently used by public CBBs worldwide regarding cord blood units (CBUs) available for unrelated hematopoietic stem cell transplantation. These technical procedures include CBU collection, (pre-) processing, packaging, testing, storage, and transport. The survey was an online survey created with SurveyGizmo and was completed individually by each CBB at the end of 2017.

Consensus document on the management preferences of patients with ulcerative colitis: points to consider and recommendations.

Background And Aims: Our objective was to define, describe and organize (on the basis of consensus) the patient's preferences in the management of ulcerative colitis (UC), in order to further incorporate them in daily practice and improve patients satisfaction, adherence to the treatment and quality of care.

Methods: Qualitative study. A narrative literature review in Medline using Mesh and free-text terms was conducted to identify articles on UC patient preferences as well as clinical scenarios that may influence the preferences.

Disease features associated with a low disease impact in patients with psoriatic arthritis: results of a cross-sectional multicenter study.

Background: Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients' lives. The objective of the study was to describe the demographic and clinical characteristics of PsA patients with a low disease impact and to analyze predictive factors for that state.

Methods: Post hoc analysis of a cross-sectional multicenter study that included 223 consecutive patients.

Delphi-based recommendations for the management of cardiovascular comorbidities in patients with psoriatic arthritis and moderate-to-severe psoriasis.

The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (n = 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree).