Homozygous mutation in SLO3 leads to severe asthenoteratozoospermia due to acrosome hypoplasia and mitochondrial sheath malformations

Background Potassium channels are important for the structure and function of the spermatozoa. As a potassium transporter, the mSlo3 is essential for male fertility as Slo3 knockout male mice were infertile with the series of functional defects in sperm cells. However, no pathogenic variant has been detected in human SLO3 to date. Here we reported a human case with homozygous SLO3 mutation. The function of SLO3 in human sperm and the corresponding assisted reproductive strategy are also investigated. Methods We performed whole-exome sequencing analysis from a large cohort of 105 patients with asthenoteratozoospermia. The effects of the variant were investigated by quantitative RT-PCR, western blotting, and immunofluorescence assays using the patient spermatozoa. Sperm morphological and ultrastructural studies were conducted using haematoxylin and eosin staining, scanning and transmission electron microscopy. Results We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility. This SLO3 variant was rare in human control populations and predicted to be deleterious by multiple bioinformatic tools. Sperm from the individual harbouring the homozygous SLO3 variant exhibited severe morphological abnormalities, such as acrosome hypoplasia, disruption of the mitochondrial sheath, coiled tails, and motility defects. The levels of SLO3 mRNA and protein in spermatozoa from the affected individual were reduced. Furthermore, the acrosome reaction, mitochondrial membrane potential, and membrane potential during capacitation were also afflicted. The levels of acrosome marker glycoproteins and PLCζ1 as well as the mitochondrial sheath protein HSP60 and SLO3 auxiliary subunit LRRC52, were significantly reduced in the spermatozoa from the affected individual. The affected man was sterile due to acrosome and mitochondrial dysfunction; however, intra-cytoplasmic sperm injection successfully rescued this infertile condition. Conclusions SLO3 deficiency seriously impact acrosome formation, mitochondrial sheath assembly, and the function of K+ channels. Our findings provided clinical implications for the genetic and reproductive counselling of affected families.

Post-Operative Neurological Outcome of Intradural Spinal Tumors in Terms of Improvement In Mccormick’s Classification Scheme

OBJECTIVES: To determine the post-operative neurological outcome of intradural spinal tumors in terms of improvement in McCormick classification scheme.METHODOLOGY: Total of 95 patients diagnosed as case of intradural spinal tumor as per operational definition with any McCormick grade were analyzed. After admission and complete neurological examination, pre-operative McCormik’s grades of each patient were determined and followed for one month after surgery. During their stay they were assessed for neurological improvement as per McCormick grade.RESULTS:There were total 95 patients presenting in OPD with the mean age of 45±12.36 years. There were 42% male and 58% female. There were 62% patients who were improved in neurological outcome while 38% patients were not improved. CONCLUSION:Surgical removal of spinal tumor is beneficial to the affected individual and has positive effect on his life.

Why the All-Affected Principle Is Groundless

The all-affected principle is a widely accepted solution to the problem of constituting the demos. Despite its popularity, a basic question in relation to the principle has not received much attention: why does the fact that an individual is affected by a certain decision ground a right to inclusion in democratic decision-making about that matter? An answer to this question must include a reason that explains why an affected individual should be included because she is affected. We identify three such reasons in the literature – to wit, interest protection, self-government and welfare – and show why they all fail. We then propose two alternative reasons, equal relations and fairness, and show why they are also deficient. Surprisingly, the all-affected principle then appears groundless, which supports withholding belief in the all-affected principle or(/and) investing future research in identifying the thus-far unidentified reason why being affected grounds a claim to inclusion.

The Unintended Consequences of Peacebuilding and Peacekeeping Interventions Contributing to the Rise of Violent Extremism

This article uncovers the nexus between the state- and peacebuilding efforts and religious violent extremism. Exploring an exemplary lifestory interview with a directly affected individual, the article makes use of empirical data to inform the current theoretical debates on the subject. The article shows how the inefficient state and peace building efforts unintendedly lead to a rise in religious violent extremism. These errors from the international community in Kosovo became a source of religious violent extremism in the case of Kosovo, as the exemplary lifestory shows.

The Global Recovery: Lessons from the Past

The downturn in global economic activity caused by the COVID-19 pandemic was unique both for its causes and for its severity. Even though, on a global scale, the recent contraction is unprecedented in modern times, it is useful to look at the consequences of large recessions which affected individual countries in the past.

IOT based Patient Monitoring System

Health monitoring is the fundamental issue in this day and age. Because of absence of amazing health monitoring, patient go through from genuine medical problems. There are great deals of IoT gadgets now days to uncover the health of impacted individual over web. Wellbeing specialists are moreover exploiting these splendid contraptions to look out for their patients. With heaps of new medical care innovation new companies, IoT is suddenly changing the medical services industries. Actually in this undertaking, we will make an IoT based patient checking System which reports the patient coronary heart beat rate and assemble temperature and besides transport an email/SMS alert each time these readings go past basic characteristics. Heartbeat charge and inward warmth level readings are recorded over ThingSpeak and Google sheets so that affected individual health can be seen from wherever in the world over through on the web. A furor will in like manner be related so that affected individual can crush it on emergency to send email/SMS to their relatives.

Amyloidogenic proteins and occurrence of different amyloidosis in different animal species

Amyloidosis is a poly-systemic disease caused by extracellular deposition of biologically inactive amyloid proteins, most often in kidneys, liver, nervous system, thyroid, spleen and heart. Depending on the site of production and deposition they can be classified into causing localised (organ-limited) and systemic amyloidosis. Disturbances in functioning of individual organs occur with an increase of the amount of accumulated protein what in turn may lead to the death of the affected individual. The occurrence of amyloidosis has been reported in human, but in animals, the most common form is AA amyloidosis, while AL amyloidosis is the least common. Due to the fact that symptoms of amyloidosis vary and often resemble those occurring in the course of other diseases, it is difficult to diagnose. Treatment of amyloidosis is aimed at improving functioning of the affected organs, yet the disease is incurable.

Food for thought: A dissonance between healthcare utilization costs and research funding for eating disorders in Canada

In this commentary, we present the premise that, in Canada, mental illness research specific to eating disorders is predominantly underfunded, and many Canadians are suffering the consequences of it. We highlight three main drivers underlying this issue: 1) the increasingly common yet potentially life-threatening nature of eating disorders, with an onset usually during adolescence; 2) the challenges and costs to treating eating disorders, with a discussion of current hospital-related costs across Canada; and 3) the glaring discrepancy between the money spent on eating disorder diagnoses/treatment and the funding dollars granted for eating disorder research in Canada (i.e. only $0.70 per affected Canadian in 2018). Research funding per affected individual for other psychiatric and neurodevelopmental conditions are used as comparisons (e.g. $50.17 per affected Canadian with schizophrenia). We suggest that it is time to revolutionize treatment for individuals with eating disorders and use our resources in a more efficient and effective manner, using current neuroimaging and neuromodulation methods as promising examples. We conclude by emphasizing the need for increased research funding in the field of eating disorders in Canada, as the current research-related investments hinder progress in developing neuroscientifically-sound treatments for these populations.

Pixelated vision: Validation of the complaint with no objective findings

Background: We encountered a young female presenting with a complaint of “pixelated vision”. A brief literature search at the time of consultation showed no peer reviewed publications. Our objective was to use an infodemiologic approach to investigate the possible occurrence of an unidentified visual phenomenon.Methods: An Internet search with the metabrowser search engine Dogpile (www.dogpile.com) was conducted on April 24, 2018, using free text words “pixelated” and “vision.” The first 100 results were scanned for forum posts and cross-referenced to minimize duplication.Results: Of the first 100 results, 15 unique posts were identified. The majority of posts were made by the affected individual (n=14, 93%). Sex was female (n=5, 33%), male (n=2, 13%) or unknown (n=8, 53%). Onset was identified as new (n=10, 67%) or chronic (n=5, 33%).Conclusion: The availability and content of these forum postings suggest that pixelated vision is an uncommon, non-pathological visual phenomenon not yet documented in conventional medical literature.

Substance use disorder in anaesthetists: A personal perspective

In this article, I present a firsthand account as an anaesthetist with substance use disorder who has been through rehabilitation and returned to clinical anaesthesia, followed by an overview of substance use disorder in anaesthesia. Substance use disorder is prevalent within the anaesthesia community and can result in tragic consequences, including death in many cases. The incidence is around one to two per 1000 anaesthetist years and this appears to be rising, perhaps mirroring the population-wide increase in substance use disorder as a result of the opioid epidemic. Recognising substance use disorder in a colleague and intervening to try and help them and protect patients can be immensely challenging. Carrying out a successful intervention requires careful planning and coordination in order to protect the affected individual, their colleagues and patients. Returning to clinical anaesthesia following a diagnosis of substance use disorder is also contentious, with the high abstinence rate (relative to the wider substance use disorder population) having to be balanced against the risk of death following relapse. Any return to practice must be well planned and supported, and include appropriate toxicology screening. With such measures, rehabilitation and a return to clinical anaesthesia is possible in certain cases. For the affected individual regaining, then maintaining, their professional identity can be a powerful motivator to remain abstinent. Drug diversion and substance use disorder in anaesthesia is unlikely ever to be fully preventable, but strategies such as biometric dispensing, analysis of unused drugs, random toxicology and ongoing education may help to keep it to a minimum.