Eph receptors are the largest family of receptor tyrosine kinases and mediate a myriad of essential processes in humans from embryonic development to adult tissue homeostasis through interactions ...with membrane-bound ephrin ligands. The ubiquitous expression of Eph receptors and ephrin ligands among the cellular players of the immune system underscores the importance of these molecules in orchestrating an optimal immune response. This review provides an overview of the various roles of Eph receptors and ephrin ligands in immune cell development, activation, and migration. We also discuss the role of Eph receptors in disease pathogenesis as well as the implications of Eph receptors as future immunotherapy targets. Given the diverse and critical roles of Eph receptors and ephrin ligands throughout the immune system during both resting and activated states, this review aims to highlight the critical yet underappreciated roles of this family of signaling molecules in the immune system.
Introduction
Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The ...beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.
Methods
EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference.
Results
Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46–0.87
I
2
34%,
p
= 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23–0.68,
I
2
= 0%,
p
= 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD −2.39 95% CI −4.86 to 0.08
I
2
= 0%,
p
= 0.06) or change in 6MWT distance (WMD 9.06 95% CI −35.68, 53.81
I
2
= 88%,
p
= 0.69) was observed.
Conclusions
Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.
Reproduction is required for the survival of all mammalian species, and thousands of essential 'sex' genes are conserved through evolution. Basic research helps to define these genes and the ...mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care.
Highlights • PAR-1 knockdown neuronal and astrocytes cells are negative for TUNEL-positive cells. • PAR-1 knockdown results in 70% reduction of dying neurons with improved neurological deficits. • ...Knockdown or inhibition of PAR-1 would provide neuroprotection in the brain from ischemic injury.
Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of ...global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.
The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.
Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.
Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?
This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.
Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between ...anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.
Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.
Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.
Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.
Although male factors account for approximately 50% of all infertility, the mechanisms underlying their origin are unknown. Currently, clinicians rely primarily on semen analyses to predict male ...reproductive potential and chart treatment success. Even when invasive procedures are performed, the causes of male factor infertility frequently remain elusive. Recently, the advent of new technologies has spurred the search for novel male infertility biomarkers, and the detection of genes, proteins, or metabolites unique to the infertile male holds much promise. The concept that a cost-effective, noninvasive, and accurate set of biomarkers can be identified to diagnose male factor infertility is tantalizing. This review focuses on the various methodologies used in the discovery of novel biomarkers along with their findings. Specific attention is paid to recent advances in the fields of genetics, proteomics, and metabolomics.
The combination of a chromium(III) salophen bromide complex and tetrabutylammonium bromide is shown to catalyze the reaction between terminal epoxides and carbon dioxide at ambient temperature and 1 ...bar carbon dioxide pressure and between internal epoxides and carbon dioxide at 80 °C and 10 bar carbon dioxide pressure to form cyclic carbonates. The optimal conditions involve the use of 1.5–2.5 mol % of both the chromium(III) salophen bromide complex and tetrabutylammonium bromide and result in the formation of cyclic carbonates in 57–92% isolated yields after a reaction time of 24 h. Under these conditions, no polycarbonate formation is observed except when cyclohexene oxide is used as substrate. The reactions were found to proceed with retention of epoxide stereochemistry. A study of the reaction kinetics revealed that the chromium(III) complex and tetrabutylammonium bromide react together to form a six-coordinate anionic chromium complex which is the actual catalyst, and a catalytic cycle is proposed which explains the experimentally observed results.
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