Persistence of onchocerciasis and associated dermatologic and ophthalmic pathologies after 27 years of ivermectin mass drug administration in the middle belt of Ghana

Objectives: There is a pressing need to regularly evaluate the progress of onchocerciasis elimination programmes to timely identify and mitigate potential risks hindering the reaching of the 2030 targets proposed by the World Health Organization (WHO) in its roadmap on neglected tropical diseases (NTDs). We determined the prevalence of onchocerciasis and associated dermatological and ophthalmological manifestations in six endemic communities in the Bono Region of Ghana after 27 years of ivermectin mass treatment. Methods: In a cross-sectional study, 564 participants aged ≥5 years were enrolled (49.1% females), with a median age of 26 (range: 5–89) years. In 54% and 47%, skin-snip microscopy and Ov16 rapid diagnostic tests were performed, respectively. Skin disease was determined using the WHO Skin NTD App. Visual function assessments included tests of visual acuity. Results: The overall microfilarial prevalence was 12.5% (38/305) and Ov16 seroprevalence was 24.2% (64/265). Severe itching was recorded in 24.3%, acute papular onchodermatitis in 52.8%, chronic papular onchodermatitis in 12.5%, lichenified onchodermatitis in 0.7%, skin atrophy in 11.3%, depigmentation in 1.7% and palpable nodules in 5.3%. Of the 301 persons in which visual acuity was examined, 17% were visually impaired and 5.3% were blind and 47.3% presented with cataract. Chronic papular onchodermatitis, lichenified onchodermatitis, depigmentation and visual impairment were significantly associated with the presence of skin microfilariae and Ov16 seropositivity. Conclusions: The persistence of Onchocerca volvulus infection and onchocerciasis-associated dermatological and ophthalmological pathologies after prolonged treatment is of concern. There is a need to include morbidity management in onchocerciasis elimination programmes and understand better patterns of treatment coverage, adherence and actual intake of ivermectin

Positive deviance control-case life history: a method to develop grounded hypotheses about successful long-term avoidance of infection

<p>Abstract</p> <p>Background</p> <p>Prevalence rates for long-term injection drug users in some localities surpass 60% for HIV and 80% for HCV. We describe methods for developing grounded hypotheses about how some injectors avoid infection with either virus.</p> <p>Methods</p> <p>Subjects: 25 drug injectors who have injected drugs 8 – 15 years in New York City. 17 remain without antibody to either HIV or HCV; 3 are double-positives; and 5 are positive for HCV but not HIV. "Staying Safe" methodology compares serostatus groups using detailed biographical timelines and narratives; and information about how subjects maintain access to physical resources and social support; their strategies and tactics to remain safe; how they handle problems of addiction and demands by drug dealers and other drug users; and how their behaviors and strategies do or do not become socially-embedded practices. Grounded theory and life-history analysis techniques compare and contrast doubly-uninfected with those infected with both viruses or only with HCV.</p> <p>Results</p> <p>Themes and initial hypotheses emerging from analyses included two master hypotheses that, if confirmed, should help shape preventive interventions: 1) Staying uninfected is not simply a question of social structure or social position. It involves agency by drug injectors, including sustained hard work and adaptation to changing circumstances. 2) Multiple intentionalities contribute to remaining uninfected. These conscious goals include balancing one's need for drugs and one's income; developing ways to avoid drug withdrawal sickness; avoiding situations where other drug users importune you to share drugs; and avoiding HIV (and perhaps HCV) infection. Thus, focusing on a single goal in prevention might be sub-optimal.</p> <p>Other hypotheses specify mechanisms of enacting these intentionalities. One example is finding ways to avoid extreme social ostracism.</p> <p>Conclusion</p> <p>We have identified strategies and tactics that some doubly-uninfected IDUs have developed to stay safe. Staying Safe methodology develops grounded hypotheses. These can be tested through cohort studies of incidence and prevention trials of hypothesis-based programs to help drug injectors make their injection and sexual careers safer for themselves and others. This positive deviance control-case life history method might be used to study avoiding other infections like genital herpes among sex workers.</p

Error mapping controller: a closed loop neuroprosthesis controlled by artificial neural networks

BACKGROUND: The design of an optimal neuroprostheses controller and its clinical use presents several challenges. First, the physiological system is characterized by highly inter-subjects varying properties and also by non stationary behaviour with time, due to conditioning level and fatigue. Secondly, the easiness to use in routine clinical practice requires experienced operators. Therefore, feedback controllers, avoiding long setting procedures, are required. METHODS: The error mapping controller (EMC) here proposed uses artificial neural networks (ANNs) both for the design of an inverse model and of a feedback controller. A neuromuscular model is used to validate the performance of the controllers in simulations. The EMC performance is compared to a Proportional Integral Derivative (PID) included in an anti wind-up scheme (called PIDAW) and to a controller with an ANN as inverse model and a PID in the feedback loop (NEUROPID). In addition tests on the EMC robustness in response to variations of the Plant parameters and to mechanical disturbances are carried out. RESULTS: The EMC shows improvements with respect to the other controllers in tracking accuracy, capability to prolong exercise managing fatigue, robustness to parameter variations and resistance to mechanical disturbances. CONCLUSION: Different from the other controllers, the EMC is capable of balancing between tracking accuracy and mapping of fatigue during the exercise. In this way, it avoids overstressing muscles and allows a considerable prolongation of the movement. The collection of the training sets does not require any particular experimental setting and can be introduced in routine clinical practice

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

A needle in the haystack – the dire straits of needle exchange in Hungary

Abstract Background The two largest needle exchange programs (NEPs) in Hungary were forced to close down in the second half of 2014 due to extreme political attacks and related lack of government funding. The closures occurred against a background of rapid expansion in Hungary of injectable new psychoactive substances, which are associated with very frequent injecting episodes and syringe sharing. The aim of our analysis was to predict how the overall Hungarian NEP syringe supply was affected by the closures. Methods We analyzed all registry data from all NEPs in Hungary for all years of standardized NEP data collection protocols currently in use (2008–2014) concerning 22 949 client enrollments, 9 211 new clients, 228 167 client contacts, 3 160 560 distributed syringes, and 2 077 676 collected syringes. Results We found that while the combined share of the two now closed NEPs decreased over time, even in their partial year 2014 they still distributed and collected about half of all syringes, and attended to over half of all clients and client contacts in Hungary. The number of distributed syringes per PWID (WHO minimum target = 100) was 81 in 2014 in Hungary, but 39 without the two now closed NEPs. Conclusions There is a high probability that the combination of decreased NEP coverage and the increased injection risk of new psychoactive substances may lead in Hungary to a public health disaster similar to the HIV outbreaks in Romania and Greece. This can be avoided only by an immediate change in the attitude of the Hungarian government towards harm reduction

Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance

OBJECTIVE: The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Whilst the effect of these neuropeptides on individual aspects of energy homeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following ICV administration of 1nmol and 3nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight food deprived rats received an ICV injection of the anorectic peptides α-MSH, corticotrophin releasing factor (CRF) or neuromedin U (NMU). RESULTS: Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity whilst NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. Alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3nmol of the peptide. CONCLUSION: We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has demonstrated the interrelated effects of these neuropeotides on activity, energy expenditure and food intake thus facilitating comparison between the different hypothalamic systems

Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age

<p>Abstract</p> <p>Background</p> <p>The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a <it>Schistosoma haematobium </it>endemic area and further investigated the relationship between the cytokine responses and infection intensity.</p> <p>Methods</p> <p>Schistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to <it>S. haematobium </it>infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with <it>S. haematobium </it>egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches.</p> <p>Results</p> <p>Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other.</p> <p>Conclusion</p> <p>Taken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.</p

Hacking into bacterial biofilms: a new therapeutic challenge

Microbiologists have extensively worked during the past decade on a particular phase of the bacterial cell cycle known as biofilm, in which single-celled individuals gather together to form a sedentary but dynamic community within a complex structure, displaying spatial and functional heterogeneity. In response to the perception of environmental signals by sensing systems, appropriate responses are triggered, leading to biofilm formation. This process involves various molecular systems that enable bacteria to identify appropriate surfaces on which to anchor themselves, to stick to those surfaces and to each other, to construct multicellular communities several hundreds of micrometers thick, and to detach from the community. The biofilm microbial community is a unique, highly competitive, and crowded environment facilitating microevolutionary processes and horizontal gene transfer between distantly related microorganisms. It is governed by social rules, based on the production and use of "public" goods, with actors and recipients. Biofilms constitute a unique shield against external aggressions, including drug treatment and immune reactions. Biofilm-associated infections in humans have therefore generated major problems for the diagnosis and treatment of diseases. Improvements in our understanding of biofilms have led to innovative research designed to interfere with this process

Neurogenic bladder: etiology and assessment

A review of the various causes of neurologic impairment to the lower urinary tract in children was the aim of this presentation. The emphasis was on diagnosis, pathophysiology, and treatment that strive to maintain as normal a function as possible in order to achieve eventual urinary continence and health of the upper urinary tract. The latest principles based on the most up to date evidence are promulgated but with an eye towards historical prospective. The reader should gain an adequate understanding of various disorders that comprise this condition and feel comfortable with proposing options for management when faced with the responsibility of caring for an affected child