Hospital control and multidrug-resistant pulmonary tuberculosis in female patients, Lima, Peru.

We examined the prevalence of tuberculosis (TB), rate of multidrug-resistant (MDR) TB, and characteristics of TB on a female general medicine ward in Peru. Of 250 patients, 40 (16%) were positive by sputum culture and 27 (11%) by smear, and 8 (3%) had MDRTB. Thirteen (33%) of 40 culture-positive patients had not been suspected of having TB on admission. Six (46%) of 13 patients whose TB was unsuspected on admission had MDRTB, compared with 2 (7%) of 27 suspected cases (p = 0.009). Five (63%) of 8 MDRTB patients were smear positive and therefore highly infective. In developing countries, hospital control, a simple method of reducing the spread of MDRTB, is neglected

Spatial Clustering of Porcine Cysticercosis in Mbulu District, Northern Tanzania

Taenia solium is a tapeworm that causes two different disease conditions. In its adult stage, it inhabits the small intestine of human, a condition known as taeniosis, which is characterised by mild symptoms including abdominal disconfort. In the larval stage, T. solium can infect humans and various animal species, mainly pigs, causing cysticercosis. Taeniosis is acquired through consumption of inadequately cooked infected meat, while cysticercosis is acquired through ingestion of tapeworm eggs in foodstuffs contaminated with faeces from a human tapeworm carrier. Cysticercosis of human central nervous tissues (neurocysticercosis) causes serious syndromes such as epilepsy. Transmission of T. solium is facilitated by several factors such as presence of tapeworm carriers, poor sanitation and poor pig husbandry, which allow pigs to access human faeces. Nevertheless, the role of these factors in parasite transmission may vary with different cultural settings. Following an incidence and a prevalence studies in a rural area of northern Tanzania, there was a significant spatial clustering of porcine cysticerocis, suggesting focal distribution of transmission risk factors, which could be targeted for interventions. The study also revealed that despite the low sensitivity of the lingual examination method to detect porcine cysticercosis, it could highlight the potential ‘hotspots’ of the infection

Transcriptional landscape of the human and fly genomes: Nonlinear and multifunctional modular model of transcriptomes

Regions of the genome not coding for proteins or not involved in cis-acting regulatory activities are frequently viewed as lacking in functional value. However, a number of recent large-scale studies have revealed significant regulated transcription of unannotated portions of a variety of plant and animal genomes, allowing a new appreciation of the widespread transcription of large portions of the genome. High-resolution mapping of the sites of transcription of the human and fly genomes has provided an alternative picture of the extent and organization of transcription and has offered insights for biological functions of some of the newly identified unannotated transcripts. Considerable portions of the unannotated transcription observed are developmental or cell-type-specific parts of protein-coding transcripts, often serving as novel, alternative 5′ transcriptional start sites. These distal 5′ portions are often situated at significant distances from the annotated gene and alternatively join with or ignore portions of other intervening genes to comprise novel unannotated protein-coding transcripts. These data support an interlaced model of the genome in which many regions serve multifunctional purposes and are highly modular in their utilization. This model illustrates the underappreciated organizational complexity of the genome and one of the functional roles of transcription from unannotated portions of the genome. Copyright 2006, Cold Spring Harbor Laboratory Press © 2006 Cold Spring Harbor Laboratory Press

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

Use of Oxfendazole to Control Porcine Cysticercosis in a High-Endemic Area of Mozambique

A randomized controlled field trial to evaluate the effectiveness of a single oral dose of 30 mg/kg of oxfendazole (OFZ) treatment for control of porcine cysticercosis was conducted in 4 rural villages of Angónia district, north-western Mozambique. Two hundred and sixteen piglets aged 4 months were selected and assigned randomly to OFZ treatment or control groups. Fifty-four piglets were treated at 4 months of age (T1), while another 54 piglets were treated at 9 months of age (T2) and these were matched with 108 control pigs from the same litters and raised under the same conditions. Baseline data were collected on the prevalence of porcine cysticercosis using antigen ELISA (Ag-ELISA), as well as knowledge and practices related to Taenia solium transmission based on questionnaire interviews and observations. All animals were followed and re-tested for porcine cysticercosis by Ag-ELISA at 9 and 12 months of age when the study was terminated. Overall prevalence at baseline was 5.1% with no significant difference between groups. At the end of the study, 66.7% of the controls were found positive, whereas 21.4% of the T1 and 9.1% of the T2 pigs were positive, respectively. Incidence rates of porcine cysticercosis were lower in treated pigs as compared to controls. Necropsy of 30 randomly selected animals revealed that viable cysts were present in none (0/8) of T2 pigs, 12.5% (1/8) of T1 pigs and 42.8% (6/14) of control pigs. There was a significant reduction in the risk of T. solium cysticercosis if pigs were treated with OFZ either at 4 months (OR = 0.14; 95% CI: 0.05–0.36) or at 9 months of age (OR = 0.05; 95% CI: 0.02–0.16). Strategic treatment of pigs in endemic areas should be further explored as a means to control T. solium cysticercosis/taeniosis

Taenia solium cysticercosis in Eastern and Southern Africa: an emerging problem in agriculture and public health

Pig production has increased tremendously in Eastern and Southern Africa (ESA), particularly in smallholder rural communities. The increase in pig production has mainly been due to land scarcity, increase in pork consumption in many areas including urban centers, and the recognition by many communities of the fast and greater return of the pig industry, compared with other domesticated livestock industries. Concurrent with the increase in smallholder pig keeping and pork consumption, there have been increasing reports of Taenia solium cysticercosis in pigs and humans in the ESA region, although the problems are under-recognized by all levels in many ESA countries. Having recognizing this, scientists researching T. solium in ESA formed a regional cysticercosis working group (CWGESA) to increase awareness of the problem and enable effective and sustainable control of T. solium. This article summarizes the status of T. solium infections in humans and pigs in the ESA countries and highlights the formation and progress of the CWGESA

Context dependent learning in the serial RT task

This study investigated the development of contextual dependencies for sequential perceptual-motor learning on static features in the learning environment. In three experiments we assessed the effect of manipulating task irrelevant static context features in a serial reaction-time task. Experiment 1 demonstrated impaired performance after simultaneously changing display color, placeholder shape, and placeholder location. Experiment 2 showed that this effect was mainly caused by changing placeholder shape. Finally, Experiment 3 indicated that changing context affected both the application of sequence knowledge and the selection of individual responses. It is proposed either that incidental stimulus features are integrated with a global sequence representation, or that the changed context causes participants to strategically inhibit sequence skills

Neisseria gonorrhoeae Activates the Proteinase Cathepsin B to Mediate the Signaling Activities of the NLRP3 and ASC-Containing Inflammasome

Neisseria gonorrhoeae is a common sexually transmitted pathogen that significantly impacts female fertility, neonatal health, and transmission of HIV worldwide. N. gonorrhoeae usually causes localized inflammation of the urethra and cervix by inducing production of IL-1β and other inflammatory cytokines. Several NLR (Nucleotide binding domain, Leucine Rich Repeat) proteins are implicated in the formation of pro-IL-1β-processing complexes called inflammasomes in response to pathogens. We demonstrate that NLRP3 (cryopyrin,NALP3) is the primary NLR required for IL-1β/IL-18 secretion in response to N. gonorrhoeae in monocytes. We also show that N. gonorrhoeae infection promotes NLRP3-dependent monocytic cell death via pyronecrosis, a recently described pathway with morphological features of necrosis, including release of the strong inflammatory mediator HMBG1. Additionally, N. gonorrhoeae activates the cysteine protease Cathepsin-B as measured by the breakdown of a Cathepsin B substrate. Inhibition of Cathepsin B shows that this protease is an apical controlling step in the downstream activities of NLRP3 including IL-1β production, pyronecrosis, and HMGB1 release. Non-pathogenic Neisseria strains (N. cinerea and N. flavescens) do not activate NLRP3 as robustly as N. gonorrhoeae. Conditioned media from N. gonorrhoeae contains factors capable of initiating the NLRP3 mediated signaling events. Isolated N. gonorrhoeae lipooligosaccharide, a known virulence factor from this bacterium that is elaborated from the bacterium in the form of outer membrane blebs, activates both NLRP3-induced IL-1β secretion and pyronecrosis. Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N. gonorrhoeae

Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3