This article reviews advancements in the genetics of malignant hyperthermia, new technologies and approaches for its diagnosis, and the existing limitations of genetic testing for malignant ...hyperthermia. It also reviews the various RYR1-related disorders and phenotypes, such as myopathies, exertional rhabdomyolysis, and bleeding disorders, and examines the connection between these disorders and malignant hyperthermia.
Contract cheating, where students recruit a third party to undertake their assignments, is frequently reported to be increasing, presenting a threat to academic standards and quality. Many incidents ...involve payment of the third party, often a so-called “Essay Mill,” giving contract cheating a commercial aspect. This study synthesized findings from prior research to try and determine how common commercial contract cheating is in Higher Education, and test whether it is increasing. It also sought to evaluate the quality of the research evidence which addresses those questions. Seventy-one samples were identified from 65 studies, going back to 1978. These included 54,514 participants. Contract cheating was self-reported by a historic average of 3.52% of students. The data indicate that contract cheating is increasing; in samples from 2014 to present the percentage of students admitting to paying someone else to undertake their work was 15.7%, potentially representing 31 million students around the world. A significant positive relationship was found between time and the percentage of students admitting to contract cheating. This increase may be due to an overall increase in self-reported cheating generally, rather than contract cheating specifically. Most samples were collected using designs which makes it likely that commercial contract cheating is under-reported, for example using convenience sampling, with a very low response rate and without guarantees of anonymity for participants. Recommendations are made for future studies on academic integrity and contract cheating specifically.
Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed "find-me" signals attract phagocytes toward apoptotic cells, which selectively expose the ...anionic phospholipid phosphatidylserine (PS) and other "eat-me" signals to distinguish healthy from apoptotic cells for phagocytosis. Blebs released by apoptotic cells can deliver find-me signals; however, the mechanism is poorly understood. Here, we demonstrate that apoptotic blebs generated in vivo from mouse thymus attract phagocytes using endogenous chemokines bound to the bleb surface. We show that chemokine binding to apoptotic cells is mediated by PS and that high affinity binding of PS and other anionic phospholipids is a general property of many but not all chemokines. Chemokines are positively charged proteins that also bind to anionic glycosaminoglycans (GAGs) on cell surfaces for presentation to leukocyte G protein-coupled receptors (GPCRs). We found that apoptotic cells down-regulate GAGs as they up-regulate PS on the cell surface and that PS-bound chemokines, unlike GAG-bound chemokines, are able to directly activate chemokine receptors. Thus, we conclude that PS-bound chemokines may serve as find-me signals on apoptotic vesicles acting at cognate chemokine receptors on leukocytes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently ...been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Reck, a GPI-anchored membrane protein, and Gpr124, an orphan GPCR, have been implicated in Wnt7a/Wnt7b signaling in the CNS vasculature. We show here that vascular endothelial cell (EC)-specific ...reduction in Reck impairs CNS angiogenesis and that EC-specific postnatal loss of Reck, combined with loss of Norrin, impairs blood-brain barrier (BBB) maintenance. The most N-terminal domain of Reck binds to the leucine-rich repeat (LRR) and immunoglobulin (Ig) domains of Gpr124, and weakening this interaction by targeted mutagenesis reduces Reck/Gpr124 stimulation of Wnt7a signaling in cell culture and impairs CNS angiogenesis. Finally, a soluble Gpr124(LRR-Ig) probe binds to cells expressing Frizzled, Wnt7a or Wnt7b, and Reck, and a soluble Reck(CC1-5) probe binds to cells expressing Frizzled, Wnt7a or Wnt7b, and Gpr124. These experiments indicate that Reck and Gpr124 are part of the cell surface protein complex that transduces Wnt7a- and Wnt7b-specific signals in mammalian CNS ECs to promote angiogenesis and regulate the BBB.
•Reck promotes mammalian CNS angiogenesis by activating the canonical Wnt pathway•Endothelial Reck regulates blood-brain barrier (BBB) development and maintenance•Reck and Gpr124 genetically and directly interact to stimulate Wnt7a/7b signaling•Reck and Gpr124 form a multi-protein complex with Wnt7a/7b and Frizzled
Cho et al. uncover an essential role for Reck in mammalian CNS angiogenesis and BBB regulation by activating the canonical Wnt pathway. They demonstrate that Reck and Gpr124 are receptor co-factors that assemble into a larger complex with Wnt7a/7b and Frizzled.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Brazil has massive plans for dams in its Amazon region and neighboring countries.•Dam impacts will profoundly affect the economy and environment throughout Amazonia.•Decisions requires timely, ...complete and unbiased assessment of impacts and benefits.•The Madeira EIA excluded important impacts and technical staff were overruled.•EIA and licensing processes need reform to assure independence in many countries.
The Santo Antônio and Jirau dams, under construction on the Madeira River, will have significant impacts, including flooding in Bolivia due to the Jirau reservoir's backwater stretch. The reservoirs eliminate natural ecosystems, and the dams block fish migration affecting both biodiversity and commercial production, especially of the giant catfish of the Madeira River that are important resources in Bolivia and Peru as well as Brazil. Changes in flooding regimes in downstream várzea (floodplain) lakes will also affect fisheries. Mercury methylation and greenhouse-gas emissions are additional problems. The reservoirs form part of a planned series of waterways that, if completed, would open large areas in Bolivian Amazonia to soybeans, thus stimulating deforestation. The dams have significant social impacts, including displacing riverside population and eliminating livelihoods from fishing. Despite the technical staff responsible for environmental licensing having submitted a formal opinion considering these concerns to be exceedingly serious and insufficiently studied to authorize dam construction, political appointees approved the licenses. The Madeira Dams offer important lessons for environmental control in Brazil and in many other countries facing similar challenges.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The sleep of millions has suffered during the global COVID-19 pandemic. Prevalence rates of 20–45% are reported globally for insomnia symptoms during the pandemic. Affected populations include the ...public and health care workers. A sleep deprived society faces the increased burden of COVID-related economic disruption, psychosocial problems, substance abuse, and suicide. Disordered sleep is not expected to disappear with control of infection, making interventions acutely necessary. The question becomes how to manage the sleep dysfunction during and after the pandemic. Depression and anxiety are prominent complaints during pandemic restrictions. Insomnia symptoms and fatigue continue even as mood improves in those who are in recovery from COVID-19 infection. Management of disturbed sleep and mental health is particularly needed in frontline health care workers. This overview describes 53 publications, as of February 2021, on disturbed sleep during the pandemic, treatment studies on COVID-related sleep disturbance, and need to rely on current treatment guidelines for common sleep disorders. The available research during the first year of COVID-19 has generally described symptoms of poor sleep rather than addressing treatment strategies. It covers digital cognitive behavioral therapy for insomnia (CBT-i) for the public and frontline workers, recognizing the need of greater acceptance and efficacy of controlled trials of CBT for affected groups. Recommendations based on a tiered public health model are discussed.
•Global prevalence reports of 20–45% for insomnia symptoms during the COVID-19 pandemic.•Insomnia complaints persist in previously infected patients and in the public after epidemics.•Strategies to improve sleep have been recommended but efficacy awaits further study.•Online digital cognitive behavioral therapy holds promise but acceptance and outcomes need refinement.•As randomized, controlled therapeutic trials are limited for sleep disturbance during COVID-19 and the pandemic, clinicians will need to use their best judgment in application of established treatment guidelines until future clinical research provides direction.•Brief discussion of treatment of obstructive sleep apnea, ICU delirium, and repurposing of medications in COVID-19.•Therapeutic strategies from suicide risk and opioid abuse prevention might offer models to address the global problem for improved sleep.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital ...stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012.
Objectives
To assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset.
Search methods
We searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles.
Selection criteria
We sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months).
Data collection and analysis
Two review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random‐effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.
The primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition.
Main results
We added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).
We assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).
Swallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate‐quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate‐quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD ‐2.9, 95% CI ‐5.65 to ‐0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate‐quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low‐quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD ‐0.66, 95% CI ‐1.01 to ‐0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low‐quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD ‐0.37, 95% CI ‐0.74 to ‐0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low‐quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low‐quality evidence).
Authors' conclusions
Moderate‐ and low‐quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high‐quality trials are needed to test whether specific interventions are effective.
Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health ...risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ∼50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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