Recent US Case of Variant Creutzfeldt-Jakob Disease—Global Implications

Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient’s exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD.     

Implementing rapid testing for tuberculosis in Mozambique

Problem

In Mozambique, pulmonary tuberculosis is primarily diagnosed with sputum smear microscopy. However this method has low sensitivity, especially in people infected with human immunodeficiency virus (HIV). Patients are seldom tested for drug-resistant tuberculosis.

Approach

The national tuberculosis programme and Health Alliance International introduced rapid testing of smear-negative sputum samples. Samples were tested using a polymerase-chain-reaction-based assay that detects Mycobacterium tuberculosis deoxyribonucleic acid and a mutation indicating rifampicin resistance; Xpert® MTB/RIF (Xpert®). Four machines were deployed in four public hospitals along with a sputum transportation system to transfer samples from selected health centres. Laboratory technicians were trained to operate the machines and clinicians taught to interpret the results.

Local setting

In 2012, Mozambique had an estimated 140 000 new tuberculosis cases, only 34% of which were diagnosed and treated. Of tuberculosis patients, 58% are HIV-infected.

Relevant changes

From 2012–2013, 1558 people were newly diagnosed with tuberculosis using sputum smears at intervention sites. Xpert® detected M. tuberculosis in an additional 1081 sputum smear-negative individuals, an increase of 69%. Rifampicin resistance was detected in 58/1081 (5%) of the samples. However, treatment was started in only 82% of patients diagnosed by microscopy and 67% of patients diagnosed with the rapid test. Twelve of 16 Xpert® modules failed calibration within 15 months of implementation.

Lessons learnt

Using rapid tests to diagnose tuberculosis is promising but logistically challenging. More affordable and durable platforms are needed. All patients diagnosed with tuberculosis need to start and complete treatment, including those who have drug resistant strains.     

Violence exposures by school children in Brazil: results from the National Adolescent School-based Health Survey (PeNSE)

This article presents the main results of the National Adolescent School-based Health Survey (PeNSE). A questionnaire was applied to a sample of 60,973 students of the 9th year of Junior high school in public and private schools of the Brazilian state capitals and the Federal District, between March and June 2009. The prevalence and confidence interval of 95% (CI 95%) of the violence situations involving adolescents were analyzed. The following situations were identified: lack of safety on the way home-school (6.4%; CI95%: 6.1%-6.8%) and at school (5.5%; CI95%: 5.2%-5.8%); involving fights with physical aggression (12.9%; CI95%: 12.4%-13.4%), with knife (6.1%; CI95%: 5.7%-6.4%) or fire arm (4.0%; CI95%: 3.7%-4.3%); physical aggression by family member (9.5%; CI95%: 9.1%-9.9%). Violence situations were more prevalent among male students. There were great variations among the cities studied. Adolescents are exposed to different violence manifestations in the institutions that supposedly must assure their protection and healthy development: school and the home. These results aim to support health promotion measures and prevention of these risk factors.     

Child's play: Harnessing play and curiosity motives to improve child handwashing in a humanitarian setting

In humanitarian emergency settings there is need for low cost and rapidly deployable interventions to protect vulnerable children, in- and out-of-school, from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but interventions specifically targeting children's handwashing behaviour in humanitarian settings have not been tested. Traditional children's handwashing promotion interventions have been school-focused, resource-intensive and reliant on health-based messaging. However, recent research from non-humanitarian settings and targeting adults suggests that theory-based behaviour change interventions targeting specific motives may be more effective than traditional handwashing interventions. In this proof-of-concept study we test, for the first time, the distribution of a modified soap bar, designed to appeal to the motives of play and curiosity, in a household-level, rapidly deployable, handwashing promotion intervention for older children in a humanitarian setting - an internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks within the camp, one was assigned to intervention and one to control. 40 households from each assigned block were then randomly chosen for inclusion in the study and the practice of handwashing with soap at key times was measured at baseline and four weeks after intervention delivery. Children in intervention households received transparent soaps with embedded toys, delivered within a short, fun, and interactive household session with minimal, non-health-based, messaging. The control group received plain soap delivered in a short standard, health-based, hygiene promotion session. At the 4-week follow-up, children in the intervention group were 4 times more likely to wash their hands with soap after key handwashing occasions than expected in the counterfactual (if there had been no intervention) based on the comparison to children in the control group (adjusted RR?=?3.94, 95% CI 1.59–9.79). We show that distributing soaps with toys embedded inside, in a rapidly deployable intervention, can improve child handwashing behaviour in a humanitarian emergency context. Further studies are needed to determine the longer-term behavioural and health impact of such an intervention when delivered at a greater scale in a humanitarian context.     

Circadian changes of intraocular pressure and ocular perfusion pressure after timolol or latanoprost in Caucasians with normal-tension glaucoma

Purpose To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG). Patients and methods In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 – IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight. Results Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it. Conclusions Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.     

Microtox solid phase test: Effect of diluent used in toxicity test

Microtox solid phase test is an acute toxicity test for solid matrices based on inhibition of natural bioluminescence of the marine bacterium Vibrio fischeri. Protocols developed to overcome the effects of confounding factors are proposed in the literature that differs by important practical and methodological issues. This work focused on diluents used for sediment resuspension and dilution. Two artificial seawaters, one natural seawater and two phosphate buffer solutions, were compared. The results showed that toxicity data obtained using different diluents were not comparable and that test sensitivity is highest using 0.1M phosphate buffer solution. The effects of medium on test organism were also investigated, in order to verify the capacity of media to maintain bioluminescence. The results underlined the importance of pH and Eh to explain the observed differences in toxicity.     

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain

Introduction: The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis.

Objectives: The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated.

Methods: Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography.

Results: TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets.

Discussion: Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.     

Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols

Purpose

At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure–activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.

Methods

The effects of two catechins, (?)-epigallocatechin-3-gallate (EGCG) and (?)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.

Results

At resting tension, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01–10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.

Conclusions

Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.     

Baseline Results from Hawaii's Nā Mikimiki Project: A Physical Activity Intervention Tailored to Multiethnic Postpartum Women

During the postpartum period, ethnic minority women have higher rates of inactivity/under-activity than white women. The Nā Mikimiki (“the active ones”) Project is designed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old. The study was designed to test, via a randomized controlled trial, the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website materials-only condition. Healthy, underactive women (mean age = 32 ± 5.6 years) with a baby (mean age = 5.7 ± 2.8 months) were enrolled from 2008–2009 (N = 278). Of the total sample, 84% were ethnic minority women, predominantly Asian–American and Native Hawaiian. Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition, ethnicity, infant's age, maternal body mass index, or maternal employment. Women had high scores on perceived benefits, self-efficacy, and environmental support for exercise but low scores on social support for exercise. This multiethnic sample's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women. The Nā Mikimiki Project's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women.     

Synthesis of variously substituted 1,8-naphthyridine derivatives and evaluation of their antimycobacterial activity

A series of 1,8-naphthyridine derivatives variously substituted in the 2, 3, 4 and 7 positions were synthesized for in vitro evaluation of antimycobacterial activity in accordance with an international program with the tuberculosis antimicrobial acquisition and coordinating facility (TAACF). Several compounds 4, 8, 12, 14, 19, 29 and 30, when tested at a concentration of 6.25 microg/ml against Mycobacterium tuberculosis H37Rv, showed an interesting activity with % inhibition in the range 38-96%. The most effective substituent in position 2, 4 or 7 of the 1,8-naphthyridine nucleus seem to be the piperidinyl group.