Secretion of extracellular vesicles (EVs), a process common to eukaryotes, archae, and bacteria, represents a secretory pathway that allows cell-free intercellular communication. Microbial EVs ...package diverse proteins and influence the host-pathogen interaction, but the mechanisms underlying EV production in Gram-positive bacteria are poorly understood. Here we show that EVs purified from community-associated methicillin-resistant Staphylococcus aureus package cytosolic, surface, and secreted proteins, including cytolysins. Staphylococcal alpha-type phenol-soluble modulins promote EV biogenesis by disrupting the cytoplasmic membrane; whereas, peptidoglycan cross-linking and autolysin activity modulate EV production by altering the permeability of the cell wall. We demonstrate that EVs purified from a S. aureus mutant that is genetically engineered to express detoxified cytolysins are immunogenic in mice, elicit cytolysin-neutralizing antibodies, and protect the animals in a lethal sepsis model. Our study reveals mechanisms underlying S. aureus EV production and highlights the usefulness of EVs as a S. aureus vaccine platform.
This meta‐analysis investigated the effects of learning video games on mathematics achievement of PreK‐12th‐grade students compared with traditional classroom instructional methods. Results from the ...24 collected studies showed heterogeneity among effect sizes, both in magnitude and direction. Using a random effects model, a small but marginally significant overall effect (
d¯RE=0.13,p=.02) suggested that mathematics video games contributed to higher learning gains as compared with traditional instructional methods. In addition, moderator analyses were mixed in terms of statistical significance and explored effect‐size heterogeneity across effects using grade level, instrument type, length of game‐based intervention, country, publication type, and study year characteristics. Overall findings indicate that video games are a slightly effective instructional strategy for teaching mathematics across PreK‐12th‐grade levels.
Lay Description
What is already known about this topic:
Math video games are gaining increased popularity in the classroom.
Research on the effectiveness of math video games in PreK‐12 education is inconsistent.
More empirical studies on math video games are needed.
What this paper adds:
This meta‐analysis focused on math video games versus traditional classroom instruction.
The targeted learner audience was PreK‐12 students.
The target learning outcome was mathematics achievement.
Results indicate that video games contribute to higher learning gains compared with traditional instruction.
Publication year and type influenced the strength of the video‐gaming intervention effect.
Implications for practice and/or policy:
Video games are an effective instructional strategy for teaching mathematics across PreK‐12th grades.
Having more teaching instruction/intervention that includes video games might increase students' math achievement.
Peroral endoscopic myotomy (POEM) is a relatively novel minimally invasive technique that is used to treat achalasia and other esophageal motility disorders. We systematically reviewed the medical ...literature in order to evaluate the safety and efficacy of POEM.
We performed a comprehensive review and meta-analysis of studies published up to March 2016 that reported on clinical outcomes of POEM. Five databases were searched: MEDLINE, EMBASE, Ovid, CINAHL, and Cochrane.
A total of 36 studies involving 2373 patients were included in the review. Clinical success (Eckardt score ≤ 3) was achieved in 98 % (95 % confidence interval CI 97 % - 100 %) of patients after the procedure. The mean Eckardt score decreased from 6.9 ± 0.15 preoperatively to 0.77 ± 0.10, 1.0 ± 0.10, and 1.0 ± 0.08 within 1, 6, and 12 months of treatment. In addition, there were significant decreases in the average lower esophageal sphincter pressure, integrated relaxation pressure, and the average heights of the barium column following a timed barium esophagogram after the procedure. After a mean follow-up of 8 months post-procedure, the rates of symptomatic gastroesophageal reflux, esophagitis on esophagogastroduodenoscopy, and abnormal acid exposure were 8.5 % (95 %CI 4.9 % - 13 %), 13 % (95 %CI 5.0 % - 23 %), and 47 % (95 %CI 21 % - 74 %), respectively.
POEM appears to be safe and effective based on the large body of current evidence, and warrants consideration as first-line therapy when an expert operator is available.
Central diabetes insipidus (CDI) is characterized by hypotonic polyuria due to impairment of AVP secretion from the posterior pituitary. In clinical practice, it needs to be distinguished from renal ...resistance to the antidiuretic effects of AVP (nephrogenic DI), and abnormalities of thirst appreciation (primary polydipsia). As nephrogenic diabetes insipidus is rare in adults, unless they are treated with lithium salts, the practical challenge is how to differentiate between CDI and clinical disorders of excess thirst. The differential diagnosis is usually straight forward, but the recommended gold standard test, the water deprivation test, is not without interpretative pitfalls. The addition of the measurement of plasma AVP concentrations improves diagnostic accuracy, but the radioimmunoassay for AVP is technically difficult, and is only available in a few specialized centres. More recently, the measurement of plasma copeptin concentrations has been claimed to provide a reliable alternative to measurement of plasma AVP, without the sampling handling challenges. In addition, the measurement of thirst ratings can help the differentiation between CDI and primary polydipsia. Once the diagnosis of CDI is biochemically certain, investigations to determine the cause of AVP deficiency are needed. In this review, we will outline the diagnostic approach to polyuria, revisit the caveats of the water deprivation test and review recent data on value of adding AVP/copeptin measurement. We will also discuss treatment strategies for CDI, with analysis of potential complications of treatment.
Abstract Hyponatremia is a serious, but often overlooked, electrolyte imbalance that has been independently associated with a wide range of deleterious changes involving many different body systems. ...Untreated acute hyponatremia can cause substantial morbidity and mortality as a result of osmotically induced cerebral edema, and excessively rapid correction of chronic hyponatremia can cause severe neurologic impairment and death as a result of osmotic demyelination. The diverse etiologies and comorbidities associated with hyponatremia pose substantial challenges in managing this disorder. In 2007, a panel of experts in hyponatremia convened to develop the Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations that defined strategies for clinicians caring for patients with hyponatremia. In the 6 years since the publication of that document, the field has seen several notable developments, including new evidence on morbidities and complications associated with hyponatremia, the importance of treating mild to moderate hyponatremia, and the efficacy and safety of vasopressin receptor antagonist therapy for hyponatremic patients. Therefore, additional guidance was deemed necessary and a panel of hyponatremia experts (which included all of the original panel members) was convened to update the previous recommendations for optimal current management of this disorder. The updated expert panel recommendations in this document represent recommended approaches for multiple etiologies of hyponatremia that are based on both consensus opinions of experts in hyponatremia and the most recent published data in this field.
Mutualistic and commensal interactions can have significant positive impacts on animal fitness and survival. However, behavioural interactions between pelagic animals living in offshore oceanic ...environments are little studied. Parasites can negatively effect the fitness of their hosts by draining resources and diverting energy from growth, reproduction, and other bodily functions. Pelagic fishes are hosts to a diverse array of parasites, however their environment provides few options for removal. Here we provide records of scraping behaviour of several pelagic teleost species, a behaviour that is likely used for parasite removal. These records span three ocean basins and, to the best of our knowledge, include the first records of scraping interactions involving tunas, blue sharks, and mako sharks as well as the first records of intraspecific scraping. We found that scrapers preferred scraping their head, eyes, gill cover, and lateral surfaces, areas where parasites are commonly found and where damage would likely have a substantial impact on fitness. Scraper species varied in their scraping preferences with tunas scraping mostly on the posterior caudal margins of sharks and occasionally conspecifics, while rainbow runner scraped in more varied locations on both sharks and conspecifics. Lengths of scrapers and scrapees were positively correlated and fish scraping on sharks were larger than those scraping on conspecifics, suggesting that risk of predation may be a limiting factor. We show that pelagic teleosts prefer to scrape on sharks rather than conspecifics or other teleosts and suggest that this behaviour may have a positive impact on teleost fitness by reducing parasite loads. The decline of shark populations in the global ocean and the reduction in mean size of many species may limit these interactions, eroding possible fitness benefits associated with this behaviour, and consequently placing more pressure on already highly targeted and vulnerable species.
Obesity is a worsening pandemic with numerous related comorbid illnesses. Conservative management including lifestyle modification and medications have limited efficacy. In contradistinction, ...bariatric surgery is effective, however, with substantial cost and non-negligible morbidity and mortality. As such, a small percentage of eligible patients undergo surgery. Over the past decade, endoscopic bariatric and metabolic therapies have been introduced as a less invasive option for the treatment of obesity and its related comorbid illnesses. This article reviews major endoscopic bariatric and metabolic therapies, their surgical analogues, and proposed mechanisms of action. Clinical trial data for each device also are discussed.
Background
Bariatric surgery is endorsed by multiple societies as the most effective treatment for obesity. Psychosocial functioning has also been noted to improve for most patients after bariatric ...surgery. However, some studies have shown an increase in post-operative suicide risk. The aim of this study was to review the published literature and evaluate the association of bariatric surgery with suicide events and suicide/self-harm attempts in patients who have undergone weight loss surgery.
Methods
MEDLINE and Embase were searched from inception through January 2018 for retrospective or prospective studies reporting mortality outcomes and self-harm or suicide rates after bariatric procedures. The primary outcome was the pooled event rate with 95% confidence interval (95% CI) for suicide. Secondary outcomes were suicide/self-harm attempts after bariatric surgery compared to same population prior to surgery and to matched control subjects, with the respective calculated odds ratios (OR) and 95% CI.
Results
From 227 citations, 32 studies with 148,643 subjects were eligible for inclusion. The patients were predominantly females (76.9%). Roux-en-Y gastric bypass (RYGB) was the most commonly performed procedure (58.9%). The post-bariatric suicide event rate was 2.7/1000 patients (95% CI 0.0019–0.0038), while the suicide/self-harm attempt event rate was 17/1000 patients (95% CI 0.01–0.03). The self-harm/suicide attempt risk was higher after bariatric surgery within the same population with OR of 1.9 (95% CI 1.23–2.95), and compared to matched control subjects, OR 3.8 (95% CI, 2.19–6.59).
Conclusions
Post-bariatric surgery patients had higher self-harm/suicide attempt risk compared to age-, sex-, and BMI-matched controls. Various pre- and post-surgical psychosocial, pharmacokinetic, physiologic, and medical factors may be involved.
Background
EUS-guided gastroenterostomy (EUS-GE) is a novel procedure for palliation of malignant gastric outlet obstruction (GOO); however, data comparing EUS-GE to enteral stent placement are ...limited. We aimed to compare clinical outcomes between EUS-GE and enteral stent placement in the palliation of malignant GOO.
Methods
Retrospective analysis of a prospectively collected database on patients who underwent EUS-GE or enteral stent placement for palliation of malignant GOO from 2014 to 2017 was conducted. Primary outcome was the rate of stent failure requiring repeat intervention. Secondary outcomes included technical and clinical success, time to repeat intervention, length of hospital stay, and adverse events.
Results
A total of 100 consecutive patients (mean age 65.9 ± 11.9 years, 44.0% female) were identified, of which 78 underwent enteral stent placement, and 22 underwent EUS-GE. Rate of stent failure requiring repeat intervention was higher in the enteral stent group than the EUS-GE group (32.0% vs. 8.3%,
p
= 0.021). Technical success was achieved in 100% in both groups. Higher initial clinical success was attained in the EUS-GE group than the enteral stent group (95.8% vs. 76.3%,
p
= 0.042). Mean length of hospital stay following stent placement was similar between groups (
p
= 0.821). The enteral stent group trended towards increased adverse events (40.2% vs. 20.8%,
p
= 0.098). Kaplan–Meier analysis showed decreased stent function in the enteral stent group (
p
= 0.013).
Conclusion
Compared to enteral stent placement, EUS-GE has a higher rate of initial clinical success and lower rate of stent failure requiring repeat intervention. EUS-GE may be offered for selected patients with malignant GOO in centers with extensive experience.
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