Genetic and environmental risk factors for sexual distress and its association with female sexual dysfunction

A. Burri, Q. Rahman and T. Spector (2011). Genetic and environmental risk factors for sexual distress and its association with female sexual dysfunction. Psychological Medicine, 41, pp 2435-2445. Copyright © Cambridge University Press 2011. http://dx.doi.org/10.1017/S003329171100049

Collecting close-contact social mixing data with contact diaries: reporting errors and biases

The analysis of contact networks plays a major role to understanding the dynamics of disease spread. Empirical contact data is often collected using contact diaries. Such studies rely on self-reported perceptions of contacts, and arrangements for validation are usually not made. Our study was based on a complete network study design that allowed for the analysis of reporting accuracy in contact diary studies. We collected contact data of the employees of three research groups over a period of 1 work week. We found that more than one third of all reported contacts were only reported by one out of the two involved contact partners. Non-reporting is most frequent in cases of short, non-intense contact. We estimated that the probability of forgetting a contact of ⩽5 min duration is greater than 50%. Furthermore, the number of forgotten contacts appears to be proportional to the total number of contact

Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).

BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense

Quantification of mechanical forces and physiological processes involved in pollen tube growth using microfluidics and microrobotics

Pollen tubes face many obstacles on their way to the ovule. They have to decide whether to navigate around cells or penetrate the cell wall and grow through it or even within it. Besides chemical sensing, which directs the pollen tubes on their path to the ovule, this involves mechanosensing to determine the optimal strategy in specific situations. Mechanical cues then need to be translated into physiological signals, which eventually lead to changes in the growth behavior of the pollen tube. To study these events, we have developed a system to directly quantify the forces involved in pollen tube navigation. We combined a lab-on-a-chip device with a microelectromechanical systems-based force sensor to mimic the pollen tube's journey from stigma to ovary in vitro. A force-sensing plate creates a mechanical obstacle for the pollen tube to either circumvent or attempt to penetrate while measuring the involved forces in real time. The change of growth behavior and intracellular signaling activities can be observed with a fluorescence microscope

Clinical study on the melarsoprol-related encephalopathic syndrome: risk factors and HLA association

Melarsoprol administration for the treatment of late-stage human African trypanosomiasis (HAT) is associated with the development of an unpredictable and badly characterized encephalopathic syndrome (ES), probably of immune origin, that kills approximately 50% of those affected. We investigated the characteristics and clinical risk factors for ES, as well as the association between the Human Leukocyte Antigen (HLA) complex and the risk for ES in a case-control study. Late-stage Gambiense HAT patients treated with melarsoprol and developing ES (69 cases) were compared to patients not suffering from the syndrome (207 controls). Patients were enrolled in six HAT treatment centres in Angola and in the Democratic Republic of Congo. Standardized clinical data was obtained from all participants before melarsoprol was initiated. Class I (HLA-A, HLA-B, HLA-Cw) and II (HLA-DR) alleles were determined by PCR-SSOP methods in 62 ES cases and 189 controls. The principal ES pattern consisted in convulsions followed by a coma, whereas ES with exclusively mental changes was not observed. Oedema, bone pain, apathy, and a depressed humour were associated with a higher risk of ES, while abdominal pain, coma, respiratory distress, and a Babinski sign were associated with higher ES-associated mortality. Haplotype C*14/B*15 was associated with an elevated risk for ES (OR: 6.64; p-value: 0.008). Haplotypes A*23/C*14, A*23/B*15 and DR*07/B*58 also showed a weaker association with ES. This result supports the hypothesis that a genetically determined peculiar type of immune response confers susceptibility for ES

Development of Sample-Adaptable Holders for Lightsheet Microscopy.

Multi-user core microscopy facilities are often faced with the challenge to adapt or modify existing instruments. This is essential in order to fulfill the requirements of the user community, who wants to image a wide range of model organisms with varying stains and sample thicknesses. In recent years, lightsheet microscopy has turned into an invaluable tool for both live and cleared sample imaging of many different specimens. This brought up new challenges in terms of sample mounting as the classical approach of attachment onto a coverslip cannot be universally applied. Here we describe the development of a diversified holder which extends the range of samples which can be imaged on a Zeiss Lightsheet microscope Z1. We focus on mounting strategies of cleared specimens; however, the holder and mounting strategy can be applied to live specimens too. The proposed methodology provides very high flexibility along with numerous possibilities for adaptation based on imaging specimen size, condition and available clearing reagents. Moreover, the described mounting strategies can be applied to other light sheet microscopes that can mount 1 mL syringes

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Feasibility and acceptability of a strategy deploying multiple first-line artemisinin-based combination therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso

(1) Background: Effective malaria case management relies on World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs), but partial resistance to artemisinin has emerged and is spreading, threatening malaria control and elimination efforts. The strategy of deploying multiple first-line therapies (MFT) may help mitigate this threat and extend the therapeutic life of current ACTs. (2) Methods: A district-wide pilot quasi-experimental study was conducted, deploying three different ACTs at the public health facility (PHF) level for uncomplicated malaria treatment from December 2019 to December 2020 in the health district (HD) of Kaya, Burkina Faso. Mixed methods, including household and health facility-based quantitative and qualitative surveys, were used to evaluate the pilot programme. (3) Results: A total of 2008 suspected malaria patients were surveyed at PHFs, of which 79.1% were tested by rapid diagnostic test (RDT) with 65.5% positivity rate. In total, 86.1% of the confirmed cases received the appropriate ACT according to the MFT strategy. The adherence level did not differ by study segment (p = 0.19). Overall, the compliance level of health workers (HWs) with MFT strategy was 72.7% (95% CI: 69.7-75.5). The odds of using PHF as the first source of care increased after the intervention (aOR = 1.6; 95% CI, 1.3-1.9), and the reported adherence to the 3-day treatment regimen was 82.1%; (95% CI: 79.6-84.3). Qualitative results showed a high acceptance of the MFT strategy with positive opinions from all stakeholders. (4) Conclusions: Implementing an MFT strategy is operationally feasible and acceptable by stakeholders in the health systems in Burkina Faso. This study provides evidence to support the simultaneous use of multiple first-line artemisinin combination therapies in malaria-endemic countries such as Burkina Faso

What is the clinical relevance of different lung compartments?

The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense

A new initiative for the development of new diagnostic tests for human African trypanosomiasis

Human African trypanosomiasis is a threat to millions of people living in sub-Saharan countries and is fatal unless treated. At present, the serological and parasitological tests used in the field for diagnosis of sleeping sickness have low specificity and sensitivity. There is clearly an urgent need for accurate tools for both diagnosis and staging of the disease. The Foundation for Innovative New Diagnostics and the World Health Organization have announced that they will collaborate to develop and evaluate new diagnostic tests for human African trypanosomiasis