Detection of Schistosoma DNA in genital specimens and urine: A comparison between five female African study populations originating from S. haematobium and/or S. mansoni endemic areas.

Female Genital Schistosomiasis (FGS) is a neglected disease affecting millions, however challenging to diagnose. This explorative descriptive study compares Schistosoma real-time PCR analysis of cervico-vaginal lavages (CVL) with corresponding urine and stool samples of 933 women from five different previously described study populations. Sampling included 310 women from an S. mansoni endemic region in Mwanza, Tanzania and 112 women from a nearby S. haematobium endemic region. Findings were compared with samples collected from S. haematobium endemic regions in South Africa from 394 women and from 117 women from Madagascar of which 79 were urine pre-selected microscopy positive cases from highly-endemic communities and 38 were urine microscopy negatives from a low-endemic community. As anticipated, urine and stool microscopy and gynecological investigations varied substantially between study populations; however, the same Schistosoma real-time PCR was performed in one reference laboratory. Schistosoma DNA was detected in 13% (120/933) of the CVL, ranging from 3% in the S. mansoni Tanzanian endemic region to 61% in the pre-selected Malagasy urine microscopy positive cases. Detectable Schistosoma DNA in CVL was associated with Schistosoma DNA in urine but not with microscopic detection of eggs in urine or by cytological examination. This study confirmed real-time PCR for the detection of Schistosoma DNA in gynecological samples to be a valuable diagnostic tool to study the distribution of FGS within schistosomiasis endemic areas.

The ripple effect: why promoting female leadership in global health matters.

Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field.

Les positions de dirigeant dans la santé du monde sont largement orientées vers les hommes et ce déséquilibre est encore plus prononcé dans les pays à revenu faible et moyen. La sous-représentation des femmes en termes de dirigeant menace l'égalité des genres et a également un impact sur l'amélioration de l'état de santé des femmes dans le monde. Dans cette perspective, nous affirmons que la promotion et la rétention des femmes au sein du leadership de la santé dans le monde a un effet d'entraînement qui peut aboutir à une amélioration de l'état de santé dans le monde. Nous présentons des solutions pragmatiques et réalisables pour promouvoir et retenir des leaders féminins en matière de santé dans le monde.

Los puestos directivos en materia de salud mundial se asignan de manera desproporcionada a los hombres; este desequilibrio es aun más notorio en los países de ingresos bajos y medianos. La subrepresentación de las mujeres en los cargos de responsabilidad pone en peligro la equidad entre los hombres y las mujeres y tiene además repercusiones en los resultados de salud de las mujeres en el mundo. En el presente artículo de opinión, se sostiene que promover a las mujeres a las funciones directivas relacionadas con la salud mundial y facilitar su permanencia en ellas genera una reacción en cadena que puede dar lugar a mejores resultados de salud a escala mundial. Se proponen soluciones viables y prácticas encaminadas a estimular la presencia de las mujeres en los cargos de responsabilidad en materia de salud mundial y a respaldar su permanencia en esta actividad.

'Cough-triggered' tuberculosis screening among adults with diabetes in Tanzania.

AIMS: Diabetes increases the risk of tuberculosis and the prevalence of diabetes is rising in tuberculosis-endemic regions such as sub-Saharan Africa. Resource-appropriate strategies for tuberculosis case finding among African adults with diabetes are needed. The aims of this study were to determine prevalence of tuberculosis and evaluate one screening strategy among adult Tanzanians with diabetes. METHODS: In this prospective cohort study, we evaluated a 'cough-triggered' strategy for tuberculosis case finding among adults with diabetes at our zonal hospital in Tanzania. All adults with diabetes and cough underwent further tuberculosis symptom assessment, and those with productive cough had sputum collected for microscopy and Mycobacterium tuberculosis culture. RESULTS: Between September 2011 and March 2012, 700 adults with diabetes attended our hospital. A total of 693 were enrolled, 121/693 (17.5%) had cough and 32/693 (4.6%) had at least two of the classic symptoms of tuberculosis. Of note, 87/121 (71.9%) of patients with cough could not produce sputum spontaneously. Nine patients were diagnosed with tuberculosis for a prevalence of 1299/100 000 (1.3%), sevenfold greater than the national average. CONCLUSIONS: Tuberculosis is common among Tanzanian adults with diabetes, but tuberculosis case finding is challenging because of the high prevalence of non-productive cough. This low-cost, 'cough-triggered' tuberculosis case-finding strategy may serve as a reasonable first step for improving tuberculosis screening among adults with diabetes in sub-Saharan Africa.

Predictors of tuberculosis in first 6 months after initiation of antiretroviral therapy: a case-control study.

SETTING: In Africa, 10% of human immunodeficiency virus (HIV) infected adults starting antiretroviral therapy (ART) die within the first year, and tuberculosis (TB) is the leading cause of death. OBJECTIVE: To investigate the predictors of ART-associated TB at an adult HIV clinic in Tanzania. DESIGN: In this nested case-control study, adults starting ART were screened for TB according to the World Health Organization protocol. Those not diagnosed with TB were observed for 6 months. Patients diagnosed with TB were defined as cases, and controls were selected from among the patients who did not develop TB using incidence density matching. RESULTS: Among the 2514 HIV-positive adults in our cohort, 72 (3%) were diagnosed with TB during the first 6 months of ART. By multivariate analysis, baseline characteristics predictive of TB were cough, fever and night sweats; 76% (55/72) of the cases had at least one of these symptoms at the time of starting ART. CONCLUSION: Overall, 75% of the patients who developed TB during the first 6 months of ART had TB symptoms at the time of starting ART. Improved TB diagnostics and/or better strategies for empirical anti-tuberculosis treatment are needed for patients with symptoms of TB at ART initiation.

Gross motor profile in rett syndrome as determined by video analysis.

Movement impairment is a fundamental but variable component of the Rett syndrome phenotype. This study used video supplemented by parent report data to describe the gross motor profile in females with Rett syndrome (n=99) and to investigate the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis enabled the calculation of general and complex gross motor skills scores. Most subjects were able to sit, slightly less than half were able to walk and a minority were able to transfer without assistance. General gross motor skills declined with age and were poorer in those who had surgically treated scoliosis but not conservatively managed scoliosis. Complex gross motor skills did not decline with age and were better in those without scoliosis. Those with a p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills overall than those with a p.R270X or large deletion mutation. Motor scores were not related to the frequency of hand stereotypies. This information is useful for the clinician and family when planning support strategies and interventions.

Chromatin structure and DNA double-strand break responses in cancer progression and therapy.

Defects in the detection and repair of DNA double-strand breaks (DSBs) have been causatively linked to tumourigenesis. Moreover, inhibition of DNA damage responses (DDR) can increase the efficacy of cancer therapies that rely on generation of damaged DNA. DDR must occur within the context of chromatin, and there have been significant advances in recent years in understanding how the modulation and manipulation of chromatin contribute to this activity. One particular covalent modification of a histone variant--the phosphorylation of H2AX--has been investigated in great detail and has been shown to have important roles in DNA DSB responses and in preventing tumourigenesis. These studies are reviewed here in the context of their relevance to cancer therapy and diagnostics. In addition, there is emerging evidence for contributions by proteins involved in mediating higher order structure to DNA DSB responses. The contributions of a subset of these proteins--linker histones and high-mobility group box (HMGB) proteins--to DDR and their potential significance in tumourigenesis are discussed.

The contribution of the budding yeast histone H2A C-terminal tail to DNA-damage responses.

The cellular response to DNA damage involves extensive interaction with and manipulation of chromatin. This includes the detection and repair of the DNA lesion, but there are also transcriptional responses to DNA damage, involving the up- or down-regulation of numerous genes. Therefore changes to chromatin structure, including covalent modification of histone proteins, are known to occur during DNA-damage responses. One of the most well characterized DNA-damage-responsive chromatin modification events is the phosphorylation of the SQ motif found in the C-terminal tail of histone H2A or the H2AX variant in higher eukaryotes. In the budding yeast, a number of additional residues in this region of histone H2A that contribute to the cellular response to DNA damage have been identified, providing an insight into the nature and complexity of the DNA-damage histone code.

Benefits of an education programme on the self-management of aerosol and airway clearance treatments for children with cystic fibrosis.

Adherence to recommended aerosol medicines and airway clearance techniques (ACT) for children with cystic fibrosis (CF) requires self-management skills. A multi-centre, randomized, controlled trial was conducted to investigate the effectiveness of a self-management education programme called 'Airways' for six- to 11-year old children with CF and their caregivers. Assessments were conducted immediately before and after the intervention period, and six and 12 months after the post-intervention assessment. The pen and paper education programme was completed by the child and caregiver together at home. Participants in the intervention and control groups had similar baseline characteristics. A per-protocol analysis was conducted and for variables that changed significantly, an additional intention-to-treat analysis was performed that included data from participants in the intervention group who withdrew from the study during the intervention period. The intervention group increased the percentage of prescribed aerosols taken (P < 0.001) and this was maintained at 12-month follow-up (P < 0.001). There was no change in the percentage of prescribed ACT performed, although when the child was unwell, caregivers in the intervention group increased the frequency and/or duration of ACT (P = 0.028) in the per-protocol analysis but not in the intention-to-treat analysis. Children in the intervention group increased their knowledge of ACT (P < 0.001) which was maintained at 12-month follow-up (P < 0.001) and felt more positively about their chest treatment regimens immediately following the intervention (P = 0.017) but not at 12-month follow-up. There were no significant changes in the control group for these variables over time. No significant changes occurred in the caregivers' reports of self-management behaviours and self-efficacy in either group. The positive results suggest that 'Airways' is a valuable educational tool for primary school-aged children with CF and their caregiver.

A role for Saccharomyces cerevisiae histone H2A in DNA repair.

Histone proteins associate with and compact eukaryotic nuclear DNA to form chromatin. The basic unit of chromatin is the nucleosome, which is made up of 146 base pairs of DNA wrapped around two of each of four core histones, H2A, H2B, H3 and H4. Chromatin structure and its regulation are important in transcription and DNA replication. We therefore thought that DNA-damage signalling and repair components might also modulate chromatin structure. Here we have characterized a conserved motif in the carboxy terminus of the core histone H2A from Saccharomyces cerevisiae that contains a consensus phosphorylation site for phosphatidylinositol-3-OH kinase related kinases (PIKKs). This motif is important for survival in the presence of agents that generate DNA double-strand breaks, and the phosphorylation of this motif in response to DNA damage is dependent on the PIKK family member Mec1. The motif is not necessary for Mec1-dependent cell-cycle or transcriptional responses to DNA damage, but is required for efficient DNA double-strand break repair by non-homologous end joining. In addition, the motif has a role in determining higher order chromatin structure. Thus, phosphorylation of a core histone in response to DNA damage may cause an alteration of chromatin structure that facilitates DNA repair.

Involvement of DNA end-binding protein Ku in Ty element retrotransposition.

Saccharomyces cerevisiae Ty elements are retrotransposons whose life cycles are strikingly similar to those of retroviruses. They transpose via an RNA intermediate that is converted to linear double-stranded cDNA and then inserted into the host genome. Although Ty integration is mediated by the element-encoded integrase, it has been proposed that host factors are involved in this process. Here, we show that the DNA end-binding protein Ku, which functions in DNA double-strand break repair, potentiates retrotransposition. Specifically, by using a galactose-inducible Ty1 system, we found that in vivo, Ty1 retrotransposition rates were substantially reduced in the absence of Ku. In contrast, this phenotype was not observed with yeast strains containing mutations in other genes that are involved in DNA repair. We present evidence that Ku associates with Ty1 viruslike particles both in vitro and in vivo. These results provide an additional role for Ku and suggest that it might function in the life cycles of retroelements in other systems.

Effect of neck rotation on the timing and pattern of infant tidal breathing.

While neck flexion and extension are known to influence the patency of the upper airway, far less information is available regarding the effects of neck rotation. The effect of neck rotation on respiratory rate (RR), expiratory time (tE), and phase angle (phi) was assessed in 17 healthy infants aged between 1 and 4 months. An inclinometer was used to measure neck rotation and uncalibrated Respiratory inductive Plethysmography to measure the dependent variables while the infants were in natural, quiet sleep. Baseline measurements were made with the head positioned centrally (0 degree rotation); further measurement positions included 30 degrees, 60 degrees, 90 degrees rotation, and repeat measurement at 0 degree (0r degree) in randomized order. Mean RR, tE, and phi were determined for each infant in each position. Using the paired t-test, RR at 0 degree rotation was significantly higher than that at 0r degree rotation (mean difference, 5 bpm; 95% CI, 2.1, 8.1; P = 0.0023); mean tE at 0 degree rotation was significantly shorter than at 0r degree rotation (mean difference, -0.18s; 95% CI, -0.27, -0.07; P = 0.002); whereas phi remained similar (mean difference, 10 degrees; 95% CI, -2.2, 22.3; P = 0.10. These changes probably reflect the slowing of metabolism that occurs after the onset of quiet sleep, and they emphasize the importance of randomization. Measurements at 0r degree were randomized and hence were most likely to reflect the true basal condition of the infant with the head in a neutral position. Consequently, these data, rather than those collected at 0 degree at the onset of quiet sleep, were used for comparisons with all subsequent positional changes. When comparing the positions whose order was randomized, neck rotation did not significantly affect RR (P = 0.445), tE (P = 0.272), or phi (P = 0.169). However, two infants demonstrated marked changes in respiratory pattern with decreases in RR and increases in tE at 90 degrees rotation, suggesting that some infants may be susceptible to obstruction in this position.

Genetic analysis of growth inhibition by GAL4-L kappa B-alpha in Saccharomyces cerevisiae.

I kappa B proteins bind to and regulate Rel/NF- kappa B transcription factors. We showed previously that a fusion protein (GAL4-p40) containing the DNA-binding domain of GAL4 and sequences of chicken l kappa B-alpha (p40) inhibits growth in the yeast Saccharomyces cerevisiae. We now show that p40 must be bound to DNA to inhibit yeast growth, p40 proteins, bound to DNA either as GAL4 or LEXA fusion proteins, inhibit yeast growth. In contrast, p40 proteins that cannot bind to DNA, such as full-length p40, a GAL4-l kappa B fusion protein containing a mutant GAL4 DNA-binding domain, and a fusion protein (GAD-p40) containing the transcriptional activation domain of GAL4 fused to p40, each failed to inhibit cell growth. As with GAL4-VP16, GAL4-p40 needs a functional cellular ADA2 gene to exert its growth-inhibitory effect in S. cerevisiae. Using a high copy suppression strategy, we have isolated three S. cerevisiae genes that restore normal growth to yeast expressing GAL4-p40 or LEXA-p40. We have termed these rescuing genes collectively as SIK genes, for "Suppressors of 1 kappa B." Expression of the SIK genes specifically suppresses the growth-inhibitory activity of GAL4-p40 and LEXA-p40 because SIK gene expression cannot block GAL4-VP16-mediated growth inhibition in S. cerevisiae. SIK1 encodes a novel protein that contains a COOH-terminal repeat that has been found in many microtubule-binding proteins. SIK2 encodes NH2-terminal acetyltransferase, and SIK3 encodes the yeast ribosomal S4 protein. None of the SIK proteins binds directly to p40 sequences in vitro, suggesting that the SIK proteins are likely to act downstream of the direct point of growth inhibition by GAL4-p40. Our results may be useful for devising strategies for identifying vertebrate inhibitors of l kappa B proteins and of other proteins that inhibit growth in S. cerevisiae.

T-cell receptor alpha and beta chain gene expression in cells infiltrating human cardiac allografts.

Intragraft T-cell receptor (TCR) alpha and beta chain variable region gene expression was analyzed in human cardiac allograft biopsies by reverse transcription polymerase chain reaction. Rearranged TCR alpha and beta chain gene transcripts were detected in all biopsies examined (N = 23), indicating the presence of T cells bearing the alpha/beta TCR even in the absence of microscopically apparent leukocyte infiltration. In this analysis, a broad TCR alpha/beta repertoire in actively rejecting lesions was demonstrated, whereas fewer TCR alpha and beta chain gene families were detected in nonrejecting lesions. The number of expressed TCR V beta chain gene families typically was two- to sixfold higher than that of V alpha chain families in all biopsies tested. This asymmetric relation was present throughout the histologic grading spectrum of the biopsies. Based on these data, the TCR repertoire is heterogenous even in the early stages of mononuclear cell infiltration of the allograft. Also based on the data, the presence of T cells in grafts with minimal cellular infiltrates is not a specific marker of subsequent rejection episode, because T cells were identified in all allograft biopsies.

Effect of intervention on development of hip posture in very preterm babies.

Preterm babies are physiologically hypotonic, which causes their posture to be flattened when lying in the prone position. This flattened posture may persist beyond term. In a prospective, randomised, controlled, double blind trial of postural support carried out on 45 babies born at less than 33 weeks of gestation, we showed that infants positioned with specific hip support during the period of intensive care had significantly fewer features of flattened posture at the age equivalent to term.

Prosthodontic rehabilitation for glossectomy patients.

Patients with oral carcinomas often have resection of the tongue, the floor of the mouth, or the bone of the mandible. Postoperatively, these patients encounter chewing, swallowing, and speech problems. Oral rehabilitation through prosthetic management can aid in alleviating these problems. Designs of the prosthesis vary according to patient needs. A "snap-on" tongue prosthesis or palatal augmentation prosthesis can be constructed. Total glossectomy patients require prosthetic intervention on a mandibular framework. Partial glossectomy patients require prosthetic augmentation on a maxillary framework. Through prosthetic management of this type, articulation and resonance are improved, food is more easily directed into the esophagus, tissues are protected and socialization is enhanced through improved appearance.