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is a world-wide parasite, with an estimated prevalence of approximately 30%. Toxoplasmosis is a severe disease in the immunocompromised, but few symptoms are exhibited by patients with an intact immune system, making this parasite a worldwide burden. Currently, few drugs exist in treating acute toxoplasmosis and no drugs exist to eliminate the bradyzoite of . Effective therapies against acute and chronic toxoplasmosis are urgently needed to reduce the burden of this disease. This review aims to give a summary of recent findings in the bradyzoite form of and the implication of these findings on drug development. A thorough search of PubMed and Google Scholar databases was used to identify studies within the past 10 years that illustrate targetable key elements in the differentiation and formation of the bradyzoite form of

BackgroundAdvanced cardiovascular life support (ACLS) for cardiac arrest is a cornerstone of emergency care and yet remains poorly studied in low- and middle-income countries. We characterised the clinical epidemiology and outcomes of cardiac arrest and ACLS in an ED in central Haiti, a lower middle-income country with a nascent emergency care system.MethodsWe conducted a prospective observational study of adult and paediatric patients who suffered cardiac arrest in an academic hospital ED in central Haiti from January 2019 to August 2020. Patients were identified prospectively at the time of clinical care. Data on demographics, comorbidities, clinical presentation, management with or without ACLS and outcomes were extracted from patient charts using a standardised form and analysed in SAS V.9.4. The primary outcome was survival to 24 hours after arrest.ResultsWe identified 161 patients who suffered cardiac arrest in the ED. The mean age was 45 years; 55.9% were female, and 82.6% were aged >18. Common presenting diagnoses were pneumonia (16.1%), sepsis (14.9%), congestive heart failure/cardiogenic shock (11.2%) and cerebrovascular accident (10.6%). Few patients were on cardiac or oxygen saturation monitors (23.1%; 63.5%) prior to arrest. 43 (27%) patients received ACLS (two patients missing data). Among these, 58.1% had initial rhythm assessed, and 2/25 (8%) patients had shockable rhythms. The median time to arrest was 23.6 hours. Sustained return of spontaneous circulation was achieved in two patients (4.7%). Among patients for whom ACLS was not initiated, the majority were due to poor prognosis (66.4%) or irreversible cause (22.4%) in the setting of available resources. One patient survived to 24 hours; none survived to hospital discharge.ConclusionIn this lower middle-income setting, cardiac arrest in the ED was associated with poor survival despite ACLS. Survival may be impacted by limited resources for prearrest monitoring as well as for ongoing critical care.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.

This paper describes how a successful pilot project for a first-year support strategy designed to help at risk students develop self-management and problem-solving capabilities was expanded into a much larger project, at a regional university with a diverse student cohort. The whole-of-institution project included the implementation of the strategy across several schools and disciplines. The strategy involved students who had failed or barely passed an early assessment item filling out a reflective workbook and participating in an intensive academic planning discussion with their tutor. Its use was found to be highly effective in the areas of retention and academic performance in most of the units in which it was implemented. Much of its success hinged, however, on the commitment and enthusiasm of participating teaching staff. [Author abstract]

Obesity negatively affects children's health because of its associations with cardiovascular disease risk factors, type 2 diabetes, asthma, fatty liver disease, victimization stemming from social stigma and bullying, and poor mental health (e.g., anxiety and depression). Children who have overweight or obesity in early childhood are approximately four times as likely to have overweight or obesity in young adulthood as their normal weight peers. Obesity prevalence is especially high among children from low-income families. In 2010, the overall upward trend in obesity prevalence turned downward among children aged 2-4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), a program of the US Department of Agriculture; prevalence decreased significantly in all racial/ethnic groups and in 34 of the 56 WIC state or territory agencies during 2010-2014. These findings indicate statistically significant decreases in obesity prevalence during 2010-2016 among children aged 2-4 years enrolled in WIC in 41 (73%) of 56 WIC state or territory agencies.

Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst‐lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1RC/RC mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin‐1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin‐1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin‐1 function with probenecid can be used to attenuate ADPKD development. Renal function in male and female Pkd1RC/RC and control mice was monitored between 9 and 20 months of age. To test the therapeutic effects of probenecid (a uricosuric agent and a pannexin‐1 blocker), osmotic minipumps were implanted in male and female Pkd1RC/RC mice, and probenecid or vehicle was administered for 42 days until 1 year of age. Probenecid treatment improved glomerular filtration rates and slowed renal cyst formation in male mice (as shown in histopathology). The mechanistic effects of probenecid on sodium reabsorption and fluid transport were tested on polarized mpkCCDcl4 cells subjected to short‐circuit current measurements, and in 3D cysts grown in Matrigel. In the mpkCCDcl4 epithelial cell line, probenecid elicited higher ENaC currents and attenuated in vitro cyst formation, indicating lower sodium and less fluid retention in the cysts. Our studies open new avenues of research into targeting pannexin‐1 in ADPKD pathology. Probenecid inhibits pannexin‐mediated ATP release into ADPKD cysts.

The etiology of the rapidly evolving prevalence of pediatric obesity and diabetes is largely, if not entirely, due to the accessibility and affordability of whole foods and a lack of physical activity. Another likely large factor is health literacy. There is a lack of understanding that overconsumption of highly processed foods and a lack of exercise can lead to diseases even in childhood. Although the etiology of pediatric obesity is vastly multifactorial, diet is a crucial contributing factor, and this is the foundation of our research. This study investigates and compares the proposed efficacy of utilizing carnivore or ketogenic-like diets in treating pediatric obesity and other comorbidities. Current standard guidelines include recommending diets low in protein and high in vegetables, whereas participants implementing our proposed diets would prioritize protein intake. Although there are limited long-term data regarding carnivore or ketogenic-like diets, our research suggests that even short-term application of such a lifestyle will treat and likely prevent many cases of pediatric obesity. Regular physical activity is also encouraged to maximize the benefits of these diets, along with maintaining a mindful diet after the eventual cessation of these treatment diets. These diets have been shown to treat many conditions and show great promise in being realistic alternatives and preventative mechanisms to combat the epidemic of pediatric obesity.

Transitional living service (TLS) programmes for adults with an acquired brain injury are considered an important part of rehabilitation. However, considerable variability exists in the design and structure of these services, with limited research to guide the development of a programme based on best evidence. A scoping literature review was completed to answer the question ‘What is known about TLS programmes for adults with an acquired brain injury?’ Four electronic databases were systematically searched, followed by a grey literature search (from 1996 to 2015). 3183 articles were screened and 13 articles were included in the final review. Themes that emerged from the literature include the types of residents using TLS programmes, the subjective experience of residents and staff, intervention approaches, programme staffing, and programme outcomes. The research reviewed supports the use of TLS programmes to maximise functional independence and community integration of individuals with an acquired brain injury. Clinical practise recommendations were developed to help support implementation of TLS programmes based on best evidence, these included: to use multiple outcome measures, implement collaborative goal setting, support generalisation of skills learnt in the TLS to the home environment and for eligibility criteria for these programmes to include individuals across all phases of recovery.

Toxoplasma gondii is an intracellular obligate parasite of phylum Apicomplexa. Toxoplasma is able to infect any nucleated cell including up to one third of the world’s population. Within its hosts, the asexual life cycle of Toxoplasma consists of two distinct forms; a rapidly growing form called tachyzoite and a latent cyst encapsulated form called bradyzoite. Although tachyzoites can be removed by the host’s immune system, parasites can convert to bradyzoites thereby evading the host’s immune response. If the host’s immune system becomes weakened, bradyzoites are able to reconvert to tachyzoites. Taken together, these observations suggest Toxoplasma contains intricate gene regulation mechanisms that could be shared by other intracellular parasites. MicroRNAs (miRNAs) are crucial genetic effectors involved in numerous gene regulation mechanisms in eukaryotes. Although a post-transcriptional gene silencing can be observed in Toxoplasma the roles and functions of Tg-miRNAs are still elusive. In this work an engineered dual luciferase reporter system was used to examine and standardize the ability of long and short double-stranded RNA to control gene expression in Toxoplasma. The effects of endogenous Tg-miRNAs were also evaluated based on (i) their abundance and (ii) the number of binding sites within a transcript. Tg-miRNA effectiveness can be altered by use of miRNA mimics and inhibitors. Also a genetic knockdown system that exploits and directs Tg-miRNAs for loss-of-function analysis of essential and non-essential genes was developed. To further our understanding of miRNA induced gene silencing on parasite cell biology, a model gene target was selected for the most abundant Tg-miR-60a. The locus of the Ubiquitin-like protease 1 (Ulp1) contains the highest number of predicted Tg-miR-60a binding sites. The antisense RNA expresses a likely precursor of Tg-miR-60a suggesting TgUlp1 expression could be self-regulating. Ulp1 activity is required for the first and last step in the SUMOylation pathway. TgUlp1 is able to compliment the function of yeast Ulp1 and exhibits cleavage activity in vitro. Knockout of TgUlp1 is detrimental to parasite egress and survival. Since a miR-60a inhibitor or antisense RNA can alter TgUlp1 expression and activity, a TgUlp1-SF line was created to study the effects of miR-60a and its effects on total protein SUMOylation to demonstrate the importance of proper gene regulation by miRNAs. Furthermore, Toxoplasma Argonaute, the core protein of RNA-induced gene silencing that is required for a gene silencing effect, is expressed as two isoforms from the same locus, suggesting alternative translational starts sites. Overall, this dissertation reveals the importance of proper gene regulation directed by non-coding RNAs in Toxoplasma that could lead to the development of anti-Toxoplasma therapeutic.