The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea

Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea.IS

Quality of Reporting on the Vegetative State in Italian Newspapers. The Case of Eluana Englaro

Background: Media coverage of the vegetative state (VS) includes refutations of the VS diagnosis and describes behaviors inconsistent with VS. We used a quality score to assess the reporting in articles describing the medical characteristics of VS in Italian newspapers. Methodology/Principal Findings: Our search covered a 7-month period from July 1, 2008, to February 28, 2009, using the online searchable databases of four major Italian newspapers: Corriere della Sera, La Repubblica, La Stampa, and Avvenire. Medical reporting was judged as complete if three core VS characteristics were described: patient unawareness of self and the environment, preserved wakefulness (eyes open), and spontaneous respiration (artificial ventilator not needed). We retrieved 2,099 articles, and 967 were dedicated to VS. Of these, 853 (88.2%) were non-medical and mainly focused on describing the political, legal, and ethical aspects of VS. Of the 114 (11.8%) medical articles, 53 (5.5%) discussed other medical problems such as death by dehydration, artificial nutrition, neuroimaging, brain death, or uterine hemorrhage, and 61 (6.3%) described VS. Of these 61, only 18 (1.9%) reported all three CORE characteristics and were judged complete. We found no differences among the four investigated newspapers (Fisher’s exact = 0.798), and incomplete articles were equally distributed between journalistic pieces and expert opinions (x 2 = 1.8854, P = 0.170). Incorrect descriptions of VS were significantly more common among incomplete articles (13 of 43 vs. 1 of 18; Fisher’s exact P = 0.047)

Treatment seeking for alcohol and drug use disorders by immigrants to the Netherlands: Retrospective, population-based, cohort study

Background We compared risks of first contact with services for an alcohol use disorder (AUD) or drug use disorder (DUD) between the largest immigrant groups to the Netherlands and Dutch nationals. We tested the hypothesis that the ethnic pattern for DUD is similar to the previously demonstrated pattern for schizophrenia. Methods Retrospective, population-based cohort study of First Admissions to Dutch psychiatric hospitals during the period 1990-1996 (national data) and First Contacts with inpatient or outpatient centres in Rotterdam for treatment of AUD or DUD during the period 1992-2001 (Rotterdam data). Results In both datasets the risk of service contact for AUD was significantly lower in immigrants from Surinam, Turkey and Morocco than in Dutch nationals. The risk was lower or moderately higher in immigrants from western countries. Analysis of the national data showed that, compared with Dutch males, the risk of first hospital admission for DUD was higher for male immigrants from the Dutch Antilles (RR = 4.6; 95% CI: 4.0-5.3), Surinam (RR = 4.3; 3.94.7) and Morocco (RR = 23; 2.0-2.6), but not for male immigrants from Turkey (RR = 0.9; 0.7-1.1). A similar pattern was found with the Rotterdam data. Female immigrants from Surinam and the Dutch Antilles had a higher risk for DUD according to the national data, but a lower risk according to the Rotterdam data. Female immigrants from Turkey and Morocco had a lower risk (both datasets). Immigrants from western countries had a higher risk for DUD, but many had developed the disorder before emigrating. Conclusion Those immigrant groups in the Netherlands that are at increased risk of schizophrenia appear also at increased risk of developing DUD, but not AUD

Gender-related mental health differences between refugees and non-refugee immigrants - a cross-sectional register-based study

<p>Abstract</p> <p>Background</p> <p>Being an immigrant in a high-income country is a risk factor for severe mental ill health. Studies on mental ill health among immigrants have found significant differences in mental health outcome between immigrants from high income countries and low-income countries. Being an asylum seeker or a refugee is also associated with mental ill health. This study aimed to assess if there is a difference in mental ill health problems between male and female refugee and non-refugee immigrants from six low-income countries in Sweden.</p> <p>Methods</p> <p>A cross-sectional, population-based study design was used comparing refugees with non-refugees. The study size was determined by the number of persons in Sweden fulfilling the inclusion criteria at the time of the study during 2006. Outcome: Mental ill health, as measured with the proxy variable psychotropic drugs purchased. Refugee/Non-refugee: Sweden grants asylum to refugees according to the Geneva Convention and those with a well-grounded fear of death penalty, torture or who need protection due to an internal or external armed conflict or an environmental disaster. The non-refugees were all family members of those granted asylum in Sweden. Covariates: Gender and origin. Potential confounders: Age, marital status, education and duration of stay in Sweden. Background variables were analysed using chi square tests. The association between outcome, exposure and possible confounders was analysed using logistic regression analyses. Multiple logistic regression analysis was used to adjust for potential confounders.</p> <p>Results</p> <p>The study population comprised 43,168 refugees and non-refugees, of whom 20,940 (48.5%) were women and 24,403 (56.5%) were refugees. Gender, age, origin, marital status and education were all associated with the outcome. For female, but not male, refugees there was a significantly higher likelihood of purchasing psychotropic drugs than non-refugees (OR = 1.27, 95% CI = 1.15 - 1.40).</p> <p>Conclusions</p> <p>Female refugees from low-income countries seem to be a risk group among immigrant women from low-income countries, whereas male refugees had the same risk patterns as non-refugee immigrants from low-income countries. This underlines the need for training of clinicians in order to focus on pre-migration stress and the asylum process, among female newcomers.</p

Who uses firearms as a means of suicide? A population study exploring firearm accessibility and method choice

<p>Abstract</p> <p>Background</p> <p>The 1996 Australian National Firearms Agreement introduced strict access limitations. However, reports on the effectiveness of the new legislation are conflicting. This study, accessing all cases of suicide 1997-2004, explores factors which may impact on the choice of firearms as a suicide method, including current licence possession and previous history of legal access.</p> <p>Methods</p> <p>Detailed information on all Queensland suicides (1997-2004) was obtained from the Queensland Suicide Register, with additional details of firearm licence history accessed from the Firearm Registry (Queensland Police Service). Cases were compared against licence history and method choice (firearms or other method). Odds ratios (OR) assessed the risk of firearms suicide and suicide by any method against licence history. A logistic regression was undertaken identifying factors significant in those most likely to use firearms in suicide.</p> <p>Results</p> <p>The rate of suicide using firearms in those with a current license (10.92 per 100,000) far exceeded the rate in those with no license history (1.03 per 100,000). Those with a license history had a far higher rate of suicide (30.41 per 100,000) compared to that of all suicides (15.39 per 100,000). Additionally, a history of firearms licence (current or present) was found to more than double the risk of suicide by any means (OR = 2.09, <it>P </it>< 0.001). The group with the highest risk of selecting firearms to suicide were older males from rural locations.</p> <p>Conclusion</p> <p>Accessibility and familiarity with firearms represent critical elements in determining the choice of method. Further licensing restrictions and the implementation of more stringent secure storage requirements are likely to reduce the overall familiarity with firearms in the community and contribute to reductions in rates of suicide.</p

Synaptic Wnt signaling—a contributor to major psychiatric disorders?

Wnt signaling is a key pathway that helps organize development of the nervous system. It influences cell proliferation, cell fate, and cell migration in the developing nervous system, as well as axon guidance, dendrite development, and synapse formation. Given this wide range of roles, dysregulation of Wnt signaling could have any number of deleterious effects on neural development and thereby contribute in many different ways to the pathogenesis of neurodevelopmental disorders. Some major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders, are coming to be understood as subtle dysregulations of nervous system development, particularly of synapse formation and maintenance. This review will therefore touch on the importance of Wnt signaling to neurodevelopment generally, while focusing on accumulating evidence for a synaptic role of Wnt signaling. These observations will be discussed in the context of current understanding of the neurodevelopmental bases of major psychiatric diseases, spotlighting schizophrenia, bipolar disorder, and autism spectrum disorder. In short, this review will focus on the potential role of synapse formation and maintenance in major psychiatric disorders and summarize evidence that defective Wnt signaling could contribute to their pathogenesis via effects on these late neural differentiation processes

Optimal Forgeries Against Polynomial-Based MACs and GCM

Polynomial-based authentication algorithms, such as GCM and Poly1305, have seen widespread adoption in practice. Due to their importance, a significant amount of attention has been given to understanding and improving both proofs and attacks against such schemes. At EUROCRYPT 2005, Bernstein published the best known analysis of the schemes when instantiated with PRPs, thereby establishing the most lenient limits on the amount of data the schemes can process per key. A long line of work, initiated by Handschuh and Preneel at CRYPTO 2008, finds the best known attacks, advancing our understanding of the fragility of the schemes. Yet surprisingly, no known attacks perform as well as the predicted worst-case attacks allowed by Bernstein\u27s analysis, nor has there been any advancement in proofs improving Bernstein\u27s bounds, and the gap between attacks and analysis is significant. We settle the issue by finding a novel attack against polynomial-based authentication algorithms using PRPs, and combine it with new analysis, to show that Bernstein\u27s bound, and our attacks, are optimal

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome