The Cost of Antibiotic Mass Drug Administration for Trachoma Control in a Remote Area of South Sudan

Trachoma is one of a group of so-called “neglected tropical diseases” (NTDs) for which safe and effective treatments are available. The International Trachoma Initiative oversees donation of the antibiotic azithromycin to endemic countries. Delivery of this drug to communities affected by trachoma is the responsibility of national programmes and their implementing partners, and should be conducted as part of a comprehensive control strategy termed “SAFE,” which includes trichiasis surgery, health education and water/sanitation interventions. There are little data on how much the different components of a trachoma control programme cost and none from South Sudan. To inform budgeting to scale up control of trachoma, and of other NTDs whose control relies on large-scale mass drug administration (MDA), the present study set out to determine the cost per person treated when antibiotics were delivered through a vertical campaign that covered 94% of the target population in a remote trachoma endemic area of South Sudan. The average economic cost per person treated was USD 1.53, which included all inputs not paid for in cash except for the cost of the donated azithromycin and the opportunity cost of community members attending treatment

The Global Burden of Trachoma: A Review

Trachoma is the commonest infectious cause of blindness worldwide. Recurrent infection of the ocular surface by Chlamydia trachomatis, the causative agent, leads to inturning of the eyelashes (trichiasis) and blinding corneal opacification. Trachoma is endemic in more than 50 countries. It is currently estimated that there are about 1.3 million people blind from the disease and a further 8.2 million have trichiasis. Several estimates for the burden of disease from trachoma have been made, giving quite variable results. The variation is partly because different prevalence data have been used and partly because different sequelae have been included. The most recent estimate from the WHO placed it at around 1.3 million Disability-Adjusted Life Years (DALYs). A key issue in producing a reliable estimate of the global burden of trachoma is the limited amount of reliable survey data from endemic regions

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

Background Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds. Methods The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared. Results Census costs were $103.24 per EA plus initial costs of$108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was$796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than$1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments. Conclusion Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary

Metabolic Impact of Adult-Onset, Isolated, Growth Hormone Deficiency (AOiGHD) Due to Destruction of Pituitary Somatotropes

Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre+/−,iDTR+/− offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre−/−,iDTR+/− mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes

Investigation on synthesis and properties of isosorbide based bis-GMA analogue

The aim of this work was to synthesize and investigate properties of a novel dimethacrylic monomer based on bioderived alicyclic diol—isosorbide. Its potential as a possible substitute of 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BISGMA), widely used in dental restorative materials and suspected for toxicity was assessed. The novel monomer was obtained in a three-step synthesis. First, isosorbide was etherified by a Williamson nucleophilic substitution and subsequently oxidized to isosorbide diglycidyl ether (ISDGE). A triphenyl phosphine catalyzed addition of methacrylic acid to ISDGE resulted in 2,5-bis(2-hydroxy-3-methacryloyloxypropoxy)- 1,4:3,6-dianhydro-sorbitol (ISDGMA). The monomer obtained was photopolymerized using camphorquinone/2-(dimethylamino)ethyl methacrylate initiating system. Next, compositions with triethylene glycol dimethacrylate (TEGDMA) were prepared and polymerized. Double bond conversion, polymerization shrinkage and water sorption of resulting polymers were determined. Selected mechanical (flexular strength and modulus, Brinell hardness) and thermomechanical (DMA analysis) properties were also investigated. BISGMA based materials were prepared as reference for comparison of particular properties

Guidelines for delineation of lymphatic clinical target volumes for high conformal radiotherapy: head and neck region

The success of radiotherapy depends on the accurate delineation of the clinical target volume. The delineation of the lymph node regions has most impact, especially for tumors in the head and neck region. The purpose of this article was the development an atlas for the delineation of the clinical target volume for patients, who should receive radiotherapy for a tumor of the head and neck region. Literature was reviewed for localisations of the adjacent lymph node regions and their lymph drain in dependence of the tumor entity. On this basis the lymph node regions were contoured on transversal CT slices. The probability for involvement was reviewed and a recommendation for the delineation of the CTV was generated

Features, Causes and Consequences of Splanchnic Sequestration of Amino Acid in Old Rats

RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging

Novel ATP-Independent RNA Annealing Activity of the Dengue Virus NS3 Helicase

The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures

Predictors of positive health in disability pensioners: a population-based questionnaire study using Positive Odds Ratio

BACKGROUND: Determinants of ill-health have been studied far more than determinants of good and improving health. Health promotion measures are important even among individuals with chronic diseases. The aim of this study was to find predictors of positive subjective health among disability pensioners (DPs) with musculoskeletal disorders. METHODS: Two questionnaire surveys were performed among 352 DPs with musculoskeletal disorders. Two groups were defined: DPs with positive health and negative health, respectively. In consequence with the health perspective in this study the conception Positive Odds Ratio was defined and used in the logistic regression analyses instead of the commonly used odds ratio. RESULTS: Positive health was associated with age ≥ 55 years, not being an immigrant, not having fibromyalgia as the main diagnosis for granting an early retirement, no regular use of analgesics, a high ADL capacity, a positive subjective health preceding the study period, and good quality of life. CONCLUSION: Positive odds ratio is a concept well adapted to theories of health promotion. It can be used in relation to positive outcomes instead of risks. Suggested health promotion and secondary prevention efforts among individuals with musculoskeletal disorders are 1) to avoid a disability pension for individuals <55 years of age; if necessary, to make sure rehabilitation actions continue, 2) to increase efforts to support immigrants to adjust to circumstances connected to ill-health and retirement, 3) to pay special attention to individuals with fibromyalgia and other general pain disorders, and 4) to strengthen ADL activities to support an independent active life among disability pensioners