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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 55 records · Page 3Linked to original sources

An association between chronic undernutrition and educational test scores in Vietnamese children.

OBJECTIVE: To examine the association between results of educational tests and the anthropometric status of schoolchildren. DESIGN: Cross-sectional data collected during the baseline survey of a randomised trial. SETTING: Eighty-one primary schools in three districts of northern Vietnam. SUBJECTS: A total of 3055 schoolchildren enrolled in class 3 and born in 1990. MAIN OUTCOME MEASURES: Tests of mathematics and Vietnamese language developed not to show floor or ceiling effects, and Z-scores of height-for-age, weight-for-age and weight-for-height. RESULTS: After controlling for age, sex, district and school the results of test scores in both mathematics and Vietnamese were significantly negatively correlated with Z-scores of height-for-age (P<0.001) and weight-for-age (P<0.001), but not with weight-for-height (P=0.75). CONCLUSIONS: A cross-sectional negative association was observed in Vietnamese primary school children between indicators of chronic undernutrition and tests of educational achievement. SPONSORSHIP: The study was funded by donors to the Partnership for Child Development including the Rockefeller Foundation and the World Bank.

Anthropometry↗

Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data.

In this paper, remotely sensed (RS) satellite sensor environmental data, using logistic regression, are used to develop prediction maps of the probability of having infection prevalence exceeding 50%, and warranting mass treatment according to World Health Organization (WHO) guidelines. The model was developed using data from one area of coastal Tanzania and validated with independent data from different areas of the country. Receiver operating characteristic (ROC) analysis was used to evaluate the model's predictive performance. The model allows reasonable discrimination between high and low prevalence schools, at least within those geographical areas in which they were originally developed, and performs reasonably well in other coastal areas, but performs poorly by comparison in the Great Lakes area of Tanzania. These results may be explained by reference to an ecological zone map based on RS-derived environmental data. This map suggests that areas where the model reliably predicts a high prevalence of schistosomiasis fall within the same ecological zone, which has common intermediate-host snail species responsible for transmission. By contrast, the model's performance is poor near Lake Victoria, which is in a different ecological zone with different snail species. The ecological map can potentially define a template for those areas where existing models can be applied, and highlight areas where further data and models are required. The developed model was then used to provide estimates of the number of schoolchildren at risk of high prevalence and associated programme costs.

Adolescent↗

Community perception of school-based delivery of anthelmintics in Ghana and Tanzania.

This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children. Over 90% of parents in both Ghana and Tanzania indicated a willingness to pay for the continuation of drug treatment. The evaluation also highlighted areas that are critical to programme effectiveness, such as communication between schools and parents, the issue of collaboration between the health and education sectors, parents' perception of the importance of helminth infection as a serious and chronic health problem (compared with more acute and life threatening illnesses such as malaria), and who should pay for treatment of side-effects.

Adult↗

Anaemia in schoolchildren in eight countries in Africa and Asia.

OBJECTIVE: To report on the haemoglobin concentrations and prevalence of anaemia in schoolchildren in eight countries in Africa and Asia. DESIGN: Blood samples were collected during surveys of the health of schoolchildren as a part of programmes to develop school-based health services. SETTING: Rural schools in Ghana, Indonesia, Kenya, Malawi, Mali, Mozambique, Tanzania and Vietnam. SUBJECTS: Nearly 14 000 children enrolled in basic education in three age ranges (7-11 years, 12-14 years and > or =15 years) which reflect the new UNICEF/WHO thresholds to define anaemia. RESULTS: Anaemia was found to be a severe public health problem (defined as >40% anaemic) in five African countries for children aged 7-11 years and in four of the same countries for children aged 12-14 years. Anaemia was not a public health problem in the children studied in the two Asian countries. More boys than girls were anaemic, and children who enrolled late in school were more likely to be anaemic than children who enrolled closer to the correct age. The implications of the four new thresholds defining anaemia for school-age children are examined. CONCLUSIONS: Anaemia is a significant problem in schoolchildren in sub-Saharan Africa. School-based health services which provide treatments for simple conditions that cause blood loss, such as worms, followed by multiple micronutrient supplements including iron, have the potential to provide relief from a large burden of anaemia.

Adolescent↗

Comparison of PCR to histology for the diagnosis of invasive candidiasis in a murine model.

The ability of a PCR method to diagnose invasive candidiasis in comparison to histology was determined using a murine model. One hundred and sixty mice were divided into 16 groups of 10 mice each. One group served as a negative control while 15 groups were infected with Candida albicans. Of the infected groups, 14 (A1-A7 and B1-B7) received fluconazole treatment. Surviving animals of group A1 were killed on day 3, and animals of successive groups were sacrificed every other day thereafter. Fluconazole treatment was stopped in the corresponding B group. All surviving mice were killed on day 43. One hundred and thirty-eight mice were evaluable. Yeast were seen in the kidney specimens of 77 mice; 66/77 of these, plus an additional 7 histologically-negative mice, were positive by PCR. The sensitivity and specificity of the PCR test compared with histology were 85.71% and 88.52%, respectively. In combination with blood cultures, PCR could be a useful diagnostic tool for invasive candidiasis in clinical settings.

Animals↗

Circadian clock-regulated expression of phytochrome and cryptochrome genes in Arabidopsis.

Many physiological and biochemical processes in plants exhibit endogenous rhythms with a period of about 24 h. Endogenous oscillators called circadian clocks regulate these rhythms. The circadian clocks are synchronized to the periodic environmental changes (e.g. day/night cycles) by specific stimuli; among these, the most important is the light. Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. In this work, we analyzed the spatial, temporal, and long-term light-regulated expression patterns of the Arabidopsis phytochrome (PHYA to PHYE) and cryptochrome (CRY1 and CRY2) promoters fused to the luciferase (LUC(+)) reporter gene. The results revealed new details of the tissue-specific expression and light regulation of the PHYC and CRY1 and 2 promoters. More importantly, the data obtained demonstrate that the activities of the promoter::LUC(+) constructs, with the exception of PHYC::LUC(+), display circadian oscillations under constant conditions. In addition, it is shown by measuring the mRNA abundance of PHY and CRY genes under constant light conditions that the circadian control is also maintained at the level of mRNA accumulation. These observations indicate that the plant circadian clock controls the expression of these photoreceptors, revealing the formation of a new regulatory loop that could modulate gating and resetting of the circadian clock.

Arabidopsis↗

Lipopolysaccharide-induced activation of beta2-integrin function in macrophages requires Irak kinase activity, p38 mitogen- activated protein kinase, and the Rap1 GTPase.

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, is a potent activator of macrophages. Besides inducing many transcriptional pathways, LPS also elicits rapid morphological changes such as cell spreading. Here we have investigated the signaling pathway that controls macrophage beta2-integrin-dependent spreading in response to LPS. We show that inhibition of the adapter protein MyD88, the interleukin-1 receptor-associated kinase Irak, the p38 mitogen-activated protein kinase, or the Ras-like GTPase Rap1 blocks LPS-induced spreading. In addition, Irak activates p38 and stimulates p38-dependent spreading. The activation of p38 by Irak requires Irak's kinase activity. We find that p38 controls spreading independently of its role in transcription but rather through activation of Rap1. Together, our results suggest that beta2-integrin-dependent spreading of macrophages in response to LPS is controlled by a linear signaling pathway via MyD88, Irak, p38, and Rap1.

Adaptor Proteins, Signal Transducing↗

Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter.

In the absence of vasopressin, medullary thick ascending limb cells express a K(+)-independent, furosemide-sensitive Na(+)-Cl(-) cotransporter that is inhibited by hypertonicity. The murine renal specific Na(+)-K(+)-2 Cl(-) cotransporter gene (SLC12A1) gives rise to six alternatively spliced isoforms. Three feature a long COOH-terminal domain that encodes the butmetanide-sensitive Na(+)-K(+)-2 Cl(-) cotransporter (BSC1-9/NKCC2), and three with a short COOH-terminal domain, known as mBSC1-A4, B4, or F4 (19). Here we have determined the functional characteristics of mBSC1-A4, as expressed in Xenopus laevis oocytes. When incubated at normal oocyte osmolarity (approximately 200 mosmol/kgH(2)O), mBSC1-4-injected oocytes do not express significant Na(+) uptake over H(2)O-injected controls, and immunohistochemical analysis shows that the majority of mBSC1-4 protein is in the oocyte cytoplasm and not at the plasma membrane. In contrast, when mBSC1-4 oocytes are exposed to hypotonicity (approximately 100 mosmol/kgH(2)O), a significant increase in Na(+) uptake but not in (86)Rb(+) uptake is observed. The increased Na(+) uptake is Cl(-) dependent, furosemide sensitive, and cAMP sensitive but K(+) independent. Sodium uptake increases with decreasing osmolarity between 120 and 70 mosmol/kgH(2)O (r = 0.95, P < 0.01). Immunohistochemical analysis shows that in hypotonic conditions mBSC1-A4 protein is expressed in the plasma membrane. These studies indicate that the mBSC1-A4 isoform of the SLC12A1 gene encodes a hypotonically activated, cAMP- and furosemide-sensitive Na(+)-Cl(-) cotransporter. Thus it is possible that alternative splicing of the BSC1 gene could provide the molecular mechanism enabling the Na(+)-Cl(-)-to-Na(+)-K(+)-2Cl(-) switching in thick ascending limb cells.

1-Methyl-3-isobutylxanthine↗

Improving understanding of research consent disclosures among persons with mental illness.

OBJECTIVE: The objective of this study was to evaluate alternative procedures for improving the understanding of research consent disclosures by persons who have mental illness. METHODS: Three groups participated in the study: persons with schizophrenia (N=79), persons with depression (N=82), and a healthy control group (N=80). The participants were guided through an informed consent process in which two factors were manipulated. One was the structure of the disclosure form; either a typical disclosure form involving standard dense text was used, or a graphically enhanced form was used. The other was the interpersonal process: the presence or absence of a third-party facilitator, with iterative feedback given to participants for whom a facilitator was not present. Participants' understanding of the disclosure was assessed with the use of recall tests that involved paraphrasing and recognition tests that involved multiple choice. RESULTS: The mean understanding scores did not differ significantly between the depression and control groups, and the mean scores of the schizophrenia group were significantly lower than those of the other two groups. Neither the graphically enhanced consent disclosure form nor the presence of a third-party facilitator was associated with improved understanding. The use of iterative feedback was associated with improvement in comprehension scores in all groups. CONCLUSIONS: The use of a feedback procedure in the consent disclosure process during the recruitment of persons who are mentally ill may be a valuable safeguard for ensuring adequate understanding and appropriate participation in research.

Adult↗

Analysis of R-Ras signalling pathways.

R-Ras has a high degree of sequence homology to Ras and to other members of the Ras subfamily including Rap, TC21 and M-Ras. Activated versions of Ras and TC21 are highly transforming in a variety of cell lines and mutated forms of both proteins have been found in human tumours. R-Ras interacts with many of the same proteins as Ras and TC21, including c-Raf1, and can induce transformed foci, although this activity is weak compared to Ras and appears to be cell-type specific. Here, we have investigated R-Ras signalling pathways in a variety of cell types. We find that microinjection of activated R-Ras into quiescent fibroblasts stimulates cell cycle progression through G(1) phase and subsequent DNA synthesis. However, unlike Ras, R-Ras does not activate the ERK MAP kinase pathway nor does it activate the JNK or p38/Mpk2 MAP kinase pathways. Microinjection of R-Ras into PC12 cells does not induce terminal differentiation, but instead causes extensive cell spreading, consistent with R-Ras having a role in integrin activation. Finally, in a macrophage cell line, R-Ras activates the alpha(M)beta(2) integrin via the small GTPase Rap1, leading to phagocytosis of opsonized red blood cells, whereas Ras does not. These results indicate that R-Ras has an important role in the regulation of cell growth and adhesion, but that this is mediated through downstream signals distinct from those used by Ras.

3T3 Cells↗

Epidemiology of intestinal helminth infestations among schoolchildren in southern Uganda.

OBJECTIVE: To determine the prevalence and intensity of intestinal helminth species among school children in southern Uganda. DESIGN: A cross-sectional survey using a randomly selected sample. SETTING: Eighteen districts of southern Uganda. SUBJECT: Two thousand and four school children aged two to twenty years (93.3%, aged 5-10 years) selected from classes 1 and 2 in 26 randomly selected primary schools. RESULTS: Overall, 55.9% of children were infected with either hookworm, Ascanis lumbricoides or Trichuris trichiura. The prevalence of A. lumbricoides was 17.5% ( range 0-66.7% by school), T. trichiura was 7.3% (0-45.0%) and hookworm 44.5% (15.6-86.0%). The prevalence of A. lumbricoides and T. trichiura was greatest in western districts while hookworm infection was more evenly distributed across the country. CONCLUSION: Mass antihelminthic treatment of school children was warranted in 13 of the 18 districts as more than 50% of the children were infected with an intestinal nematode. It is likely that pre-school children are similarly infected.

Adolescent↗

Conditional circadian regulation of PHYTOCHROME A gene expression.

The phytochrome photoreceptors and the circadian clock control many of the same developmental processes, in all organs and throughout the growth of Arabidopsis plants. Phytochrome A (phyA) provides light input signals to entrain the circadian clock. The clock is known to rhythmically regulate its light input pathway, so we tested rhythmic regulation of phyA, using transgenic plants carrying a PHYA promoter fusion to the luciferase reporter (PHYA:LUC). We provide the first images of LUC activity with subcellular resolution in intact tissue. PHYA transcription and the accumulation of all three PHYA mRNAs were indeed clock controlled. PHYA is expressed throughout the seedling, so we tested whether circadian rhythms were observed in all PHYA-expressing organs and whether the rhythms were autonomously controlled by each organ. In contrast to our previous results using other clock controlled genes, the rhythmic pattern of PHYA expression varied markedly among isolated organs and between isolated organs and intact plants. High-amplitude rhythms were maintained for many days in isolated leaves in darkness, whereas the leaves of intact plants rapidly lost rhythmicity. Wounding the leaves of intact plants had no effect. The rhythmic pattern of PHYA expression is not organ autonomous but depends upon the physical continuity or isolation of the rhythmic tissues, consistent with the presence of a transmitted signal that controls the overt expression of circadian rhythms without necessarily affecting the underlying clock. A circadian system might be present in most, if not all, plant cells, but its effect on intracellular rhythms can be controlled by supracellular signaling.

Arabidopsis↗

The ELF3 zeitnehmer regulates light signalling to the circadian clock.

The circadian system regulates 24-hour biological rhythms and seasonal rhythms, such as flowering. Long-day flowering plants like Arabidopsis thaliana, measure day length with a rhythm that is not reset at lights-off, whereas short-day plants measure night length on the basis of circadian rhythm of light sensitivity that is set from dusk, early flowering 3 (elf3) mutants of Arabidopsis are aphotoperiodic and exhibit light-conditional arrhythmias. Here we show that the elf3-7 mutant retains oscillator function in the light but blunts circadian gating of CAB gene activation, indicating that deregulated phototransduction may mask rhythmicity. Furthermore, elf3 mutations confer the resetting pattern of short-day photoperiodism, indicating that gating of phototransduction may control resetting. Temperature entrainment can bypass the requirement for normal ELF3 function for the oscillator and partially restore rhythmic CAB expression. Therefore, ELF3 specifically affects light input to the oscillator, similar to its function in gating CAB activation, allowing oscillator progression past a light-sensitive phase in the subjective evening. ELF3 provides experimental demonstration of the zeitnehmer ('time-taker') concept.

Arabidopsis↗

Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16.

We have identified a rapid protein phosphorylation event at residue serine 16 of stathmin using two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization mass spectrometry in combination with post-source decay analysis, which is induced by the epidermal growth factor receptor. Phosphorylation is specifically mediated by the small GTPases Rac and Cdc42 and their common downstream target, the serine/threonine kinase p65PAK. Both GTPases have previously been shown to regulate the dynamics of actin polymerization. Because stathmin destabilizes microtubules, and this process is inhibited by phosphorylation at residue 16, Rac and Cdc42 can potentially regulate both F-actin and microtubule dynamics.

Cell Line↗

The health of enrolled and non enrolled children of school age in Tanga, Tanzania.

The health of 227 children enrolled at primary school was compared with that of 214 non enrolled children living in rural Tanga, Tanzania. No consistent difference was observed with respect to prevalence and intensity of parasitic infection (hookworm, T. trichiura, A. lumbricoides, S. haematobium and P. falciparum). Since enrolled children were as commonly and as heavily infected as non enrolled children, treatment of enrolled children would be effective in reducing transmission throughout the total population. Non enrolled children were more stunted (P=0.0001) and wasted (P=0.0001) than enrolled children and also tended to be more anaemic (P=0.080) showing that poor nutrition is not only associated with delayed enrolment but continues to be associated with non enrolment throughout the school age years. Given that treatment has the greatest impact on the most malnourished children, additional measures to extend treatment to non enrolled children would be justified.

Animals↗