Is birth weight associated with blood pressure among African children and adolescents? A systematic review.

There is substantial evidence of an inverse association between birth weight and later blood pressure (BP) in populations from high-income countries, but whether this applies in low-income countries, where causes of low birth weight are different, is not certain. OBJECTIVE: We conducted a review of the evidence on the relationship between birth weight and BP among African children and adolescents. Medline, EMBASE, Global Health and Web of Science databases were searched for publications to October 2016. Papers reporting the relationship between birth weight and BP among African children and adolescents were assessed. Bibliographies were searched for further relevant publications. Selected papers were summarized following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. In total, 16 papers from 13 studies conducted in nine African countries (Nigeria, Republic of Seychelles, Gambia, Democratic Republic of Congo, Cameroon, South Africa, Algeria, Zimbabwe and Angola) were reviewed. Eight studies were cohorts, while five were cross-sectional. The relationship between birth weight and later BP varied with age of the participants. Studies in neonates showed a consistently positive association, while predominantly inverse associations were seen among children, and studies in adolescents were inconsistent. Based on the limited number of studies identified, the relationship between birth weight and later BP may vary with age in African children and adolescents. Not all studies adequately controlled for confounding, notably gender or age. Whether the inverse relationship between birth weight and BP in later life observed in Western settings is also seen in Africa remains unclear.

Schistosoma mansoni-specific immune responses and allergy in Uganda.

Low allergy-related disease (ARD) prevalence in low-income countries may be partly attributed to helminth infections. In the Schistosoma mansoni (Sm)-endemic Lake Victoria islands (Uganda), we recently observed positive helminth-allergy associations, despite low ARD prevalence. To understand how Sm-induced cytokine and antibody profiles might influence allergic response profiles in this population, we assessed Schistosoma worm (SWA)- and egg antigen (SEA)-specific Th1 (IFN-γ), Th2 (IL-5, IL-13) and regulatory (IL-10) cytokine profiles (n = 407), and total (n = 471), SWA-, SEA- and allergen (house dust mite [HDM] and cockroach)-specific (as)IgE and IgG4 profiles (n = 2117) by ELISA. Wheeze was inversely associated with SWA-specific IFN-γ (P < .001) and IL-10 (P = .058), and SEA-specific IL-5 (P = .004). Conversely, having a detectable asIgE response was positively associated with SWA-specific IL-5 (P = .006) and IL-10 (P < .001). Total, SWA-, SEA- and allergen-specific IgE and IgG4 responses were higher among Sm Kato-Katz positive (SmKK+) and skin prick test (SPT)+ individuals compared to SmKK- and SPT- individuals. However, total and asIgG4/IgE ratios were lower among SPT+ and wheezing individuals. We conclude that, in this population, helminth-induced antibody and cytokine responses may underlie individual positive helminth-atopy associations, while the overall IgG4-IgE balance may contribute to the low overall prevalence of clinical allergies in such settings.

Characterization of plastic and boron carbide additive manufactured neutron collimators.

Additive manufacturing techniques allow for the production of materials with complicated geometries with reduced costs and production time over traditional methods. We have applied this technique to the production of neutron collimators for use in thermal and cold neutron scattering instrumentation directly out of boron carbide. We discuss the design and generation of these collimators. We also provide measurements at neutron scattering beamlines which serve to characterize the performance of these collimators. Additive manufacturing of parts using neutron absorbing material may also find applications in radiography and neutron moderation.

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated.

Helminths are positively associated with atopy and wheeze in Ugandan fishing communities: results from a cross-sectional survey.

BACKGROUND: Parasitic helminths are potent immunomodulators and chronic infections may protect against allergy-related disease and atopy. We conducted a cross-sectional survey to test the hypothesis that in heavily helminth-exposed fishing villages on Lake Victoria, Uganda, helminth infections would be inversely associated with allergy-related conditions. METHODS: A household survey was conducted as baseline to an anthelminthic intervention trial. Outcomes were reported wheeze in last year, atopy assessed both by skin prick test (SPT) and by the measurement of allergen-specific IgE to dust mites and cockroach in plasma. Helminth infections were ascertained by stool, urine and haemoparasitology. Associations were examined using multivariable regression. RESULTS: Two thousand three hundred and sixteen individuals were surveyed. Prevalence of reported wheeze was 2% in under-fives and 5% in participants ≥5 years; 19% had a positive SPT; median Dermatophagoides-specific IgE and cockroach-specific IgE were 1440 and 220 ng/ml, respectively. S. mansoni, N. americanus, S. stercoralis, T. trichiura, M. perstans and A. lumbricoides prevalence was estimated as 51%, 22%, 12%, 10%, 2% and 1%, respectively. S. mansoni was positively associated with Dermatophagoides-specific IgE [adjusted geometric mean ratio (aGMR) (95% confidence interval) 1.64 (1.23, 2.18)]; T. trichiura with SPT [adjusted odds ratio (aOR) 2.08 (1.38, 3.15)]; M. perstans with cockroach-specific IgE [aGMR 2.37 (1.39, 4.06)], A. lumbricoides with wheeze in participants ≥5 years [aOR 6.36 (1.10, 36.63)] and with Dermatophagoides-specific IgE [aGMR 2.34 (1.11, 4.95)]. No inverse associations were observed. CONCLUSIONS: Contrary to our hypothesis, we found little evidence of an inverse relationship between helminths and allergy-related outcomes, but strong evidence that individuals with certain helminths were more prone to atopy in this setting.

The Medical Research Council (UK)/Uganda Virus Research Institute Uganda Research Unit on AIDS--'25 years of research through partnerships'.

For the past 25 years, the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS has conducted research on HIV-1, coinfections and, more recently, on non-communicable diseases. Working with various partners, the research findings of the Unit have contributed to the understanding and control of the HIV epidemic both in Uganda and globally, and informed the future development of biomedical HIV interventions, health policy and practice. In this report, as we celebrate our silver jubilee, we describe some of these achievements and the Unit's multidisciplinary approach to research. We also discuss the future direction of the Unit; an exemplar of a partnership that has been largely funded from the north but led in the south.

Correlation between the temperature dependence of intrinsic MR parameters and thermal dose measured by a rapid chemical shift imaging technique.

In order to investigate simultaneous MR temperature imaging and direct validation of tissue damage during thermal therapy, temperature-dependent signal changes in proton resonance frequency (PRF) shifts, R(2)* values, and T1-weighted amplitudes are measured from one technique in ex vivo tissue. Using a multigradient echo acquisition and the Stieglitz-McBride algorithm, the temperature sensitivity coefficients of these parameters are measured in each tissue at high spatiotemporal resolutions (1.6 x 1.6 x 4 mm 3,≤ 5sec) at the range of 25-61 °C. Non-linear changes in MR parameters are examined and correlated with an Arrhenius rate dose model of thermal damage. Using logistic regression, the probability of changes in these parameters is calculated as a function of thermal dose to determine if changes correspond to thermal damage. Temperature sensitivity of R(2)* and, in some cases, T1-weighted amplitudes are statistically different before and after thermal damage occurred. Significant changes in the slopes of R(2)* as a function of temperature are observed. Logistic regression analysis shows that these changes could be accurately predicted using the Arrhenius rate dose model (Ω = 1.01 ± 0.03), thereby showing that the changes in R(2)* could be direct markers of protein denaturation. Overall, by using a chemical shift imaging technique with simultaneous temperature estimation, R(2)* mapping and T1-W imaging, it is shown that changes in the sensitivity of R(2)* and, to a lesser degree, T1-W amplitudes are measured in ex vivo tissue when thermal damage is expected to occur. These changes could possibly be used for direct validation of thermal damage in contrast to model-based predictions.

A novel COMP mutation in an Inuit patient with pseudoachondroplasia and severe short stature.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia, generally identified clinically at two years of age due to decreased linear growth and a waddling gait. Radiographic features include small and irregular epiphyses, with metaphyseal changes of the long bones and characteristic vertebral changes. Mutations in the COMP gene cause PSACH and some cases of multiple epiphyseal dysplasia. Mutations generally cluster in the calmodulin-like repeat regions of the gene. Mutations in exon 13 (encoding the seventh calmodulin-like repeat) have been associated with severe short stature (-6 SD) in PSACH. We examined an Inuit boy with PSACH and severe short stature. Height essentially remained at -1 SD on the PSACH growth curve (-7.5 SD on a normal growth curve at 10.5 years). Analysis of COMP in our patient revealed a previously undescribed heterozygous A>T substitution in exon 8, at nucleotide 812. This change in the sequence resulted in replacement of a highly conserved and negatively charged aspartic acid with an uncharged, hydrophobic valine at amino acid position 271. Both unaffected parents were negative for this genetic change. This exon encodes the first calmodulin-like repeat, which has not been previously implicated in severe short stature. We propose that this novel missense substitution is responsible for the phenotype of this patient.

Effects of deworming during pregnancy on maternal and perinatal outcomes in Entebbe, Uganda: a randomized controlled trial.

BACKGROUND: Helminth infections during pregnancy may be associated with adverse outcomes, including maternal anemia, low birth weight, and perinatal mortality. Deworming during pregnancy has therefore been strongly advocated, but its benefits have not been rigorously evaluated. METHODS: In Entebbe, Uganda, 2507 pregnant women were recruited to a randomized, double-blind, placebo-controlled trial investigating albendazole and praziquantel in a 2 x 2 factorial design [ISRCTN32849447]. Hematinics and sulphadoxine-pyrimethamine for presumptive treatment of malaria were provided routinely. Maternal and perinatal outcomes were recorded. Analyses were by intention to treat. RESULTS: At enrollment, 68% of women had helminths, 45% had hookworm, 18% had Schistosoma mansoni infection; 40% were anemic (hemoglobin level, <11.2 g/dL). At delivery, 35% were anaemic; there was no overall effect of albendazole (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.79-1.15) or praziquantel (OR, 1.00; 95% CI, 0.83-1.21) on maternal anemia, but there was a suggestion of benefit of albendazole among women with moderate to heavy hookworm (OR, 0.45; 95% CI, 0.21-0.98; P=.15 for interaction). There was no effect of either anthelminthic treatment on mean birth weight (difference in mean associated with albendazole: -0.00 kg; 95% CI, -0.05 to 0.04 kg; difference in mean associated with praziquantel: -0.01 kg; 95% CI, -0.05 to 0.04 kg) or on proportion of low birth weight. Anthelminthic use during pregnancy showed no effect on perinatal mortality or congenital anomalies. CONCLUSIONS: In our study area, where helminth prevalence was high but infection intensity was low, there was no overall effect of anthelminthic use during pregnancy on maternal anemia, birth weight, perinatal mortality, or congenital anomalies. The possible benefit of albendazole against anemia in pregnant women with heavy hookworm infection warrants further investigation.

Adaptation of Western measures of cognition for assessing 5-year-old semi-urban Ugandan children.

BACKGROUND: The majority of available psychometric tests originates from the Western World and was designed to suit the culture, language, and socio-economic status of the respective populations. Few tests have been validated in the developing world despite the growing interest in examining effects of biological and environmental factors on cognitive functioning of children in this setting. AIMS: The present study aimed at translating and adapting Western measures of working memory, general cognitive ability, attention, executive function, and motor ability in order to obtain a cognitive instrument suitable for assessing 5-year-old semi-urban Ugandan children. This population represents a particular assessment challenge as school enrolment is highly variable at this age in this setting and many children are unused to a formal educational setting. METHODS: Measures of the above domains were selected, translated, and modified to suit the local culture, education, and socio-economic background of the target population. The measures were piloted and then administered to semi-urban Ugandan children aged 4;6-5;6, who included children who had started and not yet started school. RESULTS: Analysis of validity and reliability characteristics showed that 8 (at least one from each domain) out of the 11 measures were successfully adapted on the basis that they showed adequate task comprehension, optimum levels of difficulty to demonstrate individual and group differences in abilities, sensitivity to effects of age and education, and good internal as well as test-retest reliability. CONCLUSION: Translation and adaptation are realistic and worthwhile strategies for obtaining valid and reliable cognitive measures in a resource-limited setting.

Central ray deficiency with extensive syndactyly: a dilemma for classification.

Split Hand Foot Malformation (SHFM) (cleft hand/foot, central ray deficiency) is a complex, highly variable anomaly involving the hands and/or feet. A clinical epidemiologic study of split hand/foot (central ray deficiency) of the Manitoba population identified a subset of patients who did not present with either typical or atypical split hand. Clinically, some patients presented with "mitten hand" syndactyly; the deficiency was not recognized before imaging. In this paper, we identify additional similarly affected literature cases, review existing classifications of split hand and syndactyly and attempt to classify these patients. This group presents a challenge for classification and genetic counseling. General classifications permit inclusion of patients with diverse phenotypes; however, details are overlooked. Osseous fusions and disorganization of osseous components complicate classification. Many of these patients had findings that overlapped different subtypes within existing classifications. This cohort highlights the importance of imaging patients with distal limb anomalies. An effective classification scheme should include relevant clinical and radiographic findings in order to assist clinicians following these patients.

Helminths and HIV infection: epidemiological observations on immunological hypotheses.

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection.

Lack of effectiveness of syndromic management in targeting vaginal infections in pregnancy in Entebbe, Uganda.

OBJECTIVES: To measure the prevalence of reproductive tract infections (RTIs) during pregnancy in Entebbe, Uganda, and to evaluate the current syndromic diagnosis and management approach in effectively targeting infections, such as bacterial vaginosis (BV) and trichomoniasis, that are associated with low birth weight and prematurity among newborns. METHODS: We enrolled 250 antenatal clinic attenders. Vaginal swabs and diagnostic tests were performed for BV, Trichomonas vaginalis (TV), candida, Neisseria gonorrhoeae, Chlamydia trachomatis and for HIV-1 and active (TPHA+/RPR+) syphilis infection. Same day treatment was offered for symptoms according to syndromic management guidelines. The treatment actually provided by healthcare workers was documented. Sensitivity, specificity, positive and negative predictive values were used to assess the effectiveness of syndromic management guidelines and practice. RESULTS: The prevalence of infections were: BV 47.7%, TV 17.3%, candida 60.6%, gonorrhoea 4.3%, chlamydia 5.9%, syphilis 1.6%, and HIV 13.1%. In total, 39.7% of women with BV and 30.2% of those with TV were asymptomatic. The sensitivity of syndromic management as applied by health workers in targeting BV and TV was 50.0% and 66.7%, respectively. This would have increased to 60.3% (BV) and 69.8% (TV) had the algorithm been followed exactly. CONCLUSIONS: The prevalence of BV and TV seen in this and other African populations is high. High rates of asymptomatic infection and a tendency of healthcare workers to deviate from management guidelines by following their own personal clinical judgment imply that many vaginal infections remain untreated. Alternative strategies, such as presumptive treatment of BV and TV in pregnancy, should be considered.

Split hand foot malformation (SHFM).

The nomenclature describing the phenotype of missing central rays in the hand and/or foot in the genetics and surgical literature is heterogeneous and confusing. Split hand/foot malformation (SHFM) is the most common term for this phenotype in the genetics community; however, other names such as the offensive 'lobster-claw malformation' and the non-specific 'ectrodactyly' are still utilized to describe this malformation. In this article, we briefly review the nomenclature associated with SHFM and its classifications.

Discrepancies in upper and lower limb patterning in split hand foot malformation.

Discrepancies in upper and lower limb patterning in split hand foot malformation. Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date. Highly variable in presentation, it can occur as an isolated finding or with other anomalies. The genetic heterogeneity and clinical variability make genetic counselling of SHFM families challenging. By establishing genotype/phenotype correlations, one can provide insight into responsible developmental genes and help to direct mapping efforts and target genetic testing, ultimately providing more accurate information for family members. Preaxial involvement of the upper extremities was a significant discriminating limb-specific variable in our analysis of genetically mapped SHFM cases. This finding, which was originally identified through descriptive epidemiology, was subsequently confirmed by discriminant function analysis (p < 0.0001) to be a significant locus discriminator. Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray. These patients' feet, however, tended to show a classical central longitudinal deficiency without a significant preaxial component. This article discusses this discrepant clefting pattern between the upper and lower extremities and proposes potential mechanisms.

The effect of tuberculin skin testing on viral load and anti-mycobacterial immune responses in HIV-1-infected Ugandan adults.

OBJECTIVE: To determine whether tuberculin skin testing (TST) is associated with an increase in human immunodeficiency virus (HIV) viral load, and to examine the effect of TST on anti-mycobacterial immune responses. DESIGN: A nested cohort study of HIV-1-infected adults. METHOD: Forty-two participants (21 TST-positive and 21 TST-negative) from a larger cohort were recruited to the study. Blood was collected for CD4+ T-cell count, whole blood was cultured, and plasma saved for viral load. These measurements were taken before, 3 days after, 3 months after, and 3 months plus 3 days after TST. Cytokine responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis and phytohaemagglutinin (PHA) were examined in the whole blood assay. RESULTS: Twenty-nine participants attended all four visits. No statistically significant change in viral load, CD4+ T-cell count, or cytokine response to PHA was observed at any visit. However, TST was associated with a transient increase in the interferon-gamma response to CFP and a lasting increase in the interleukin-5 response to CFP. CONCLUSION: There appeared to be a systemic effect of TST on the anti-tuberculosis immune response.

Chronic pain and the use of conventional and alternative therapy.

BACKGROUND: Chronic pain is a common problem affecting about half of the general population. This has implications for the utilization of both conventional and alternative health services. OBJECTIVES: The aim of this study was to determine the use of conventional and alternative practitioners and medicines amongst individuals with chronic pain in the community. METHODS: A total of 2422 individuals from a previous population-based survey in the Grampian region of the UK, who agreed to participate in further research, were sent a postal questionnaire. The questionnaire enquired about the presence, type and severity of chronic pain, socio-demographic details, consultations with conventional and alternative practitioners, and the consumption of conventional and alternative medicines. The main outcome measures were the number and frequency of self-reported consultations with GPs, hospital specialists, physical therapists and alternative therapists, and the consumption of prescription, non-prescription and alternative medicines amongst those with chronic pain. RESULTS: Of the 840 individuals reporting chronic pain, 67.2% had seen their GP, 34.0% a hospital specialist, 25.9% a physical therapist and 18.2% an alternative therapist in the preceding year. Prescription medicines had been taken by 58.4%, non-prescription medicines by 57.4% and alternative medicines by 15.7% of individuals with chronic pain. The majority (67.0%) of individuals with chronic pain who sought alternative health care did so in conjunction with conventional health care. Differences in consultations with practitioners and consumption of medicines were found by age, sex, socio-economic status, site of pain and severity of pain. CONCLUSIONS: Individuals with chronic pain consult their GP about their pain more than other practitioners and use conventional medicines more frequently than alternative medicines. Alternative health care is used most commonly in addition to conventional health care, although a small number of individuals with chronic pain use alternative care exclusively. The use of alternative health care amongst those with chronic pain is higher than previously estimated and suggests that the use of these services may be increasing amongst those with chronic pain.

The course of chronic pain in the community: results of a 4-year follow-up study.

Little is known about the course of chronic pain in the community. Such information is needed for the prevention and management of chronic pain. We undertook a 4-year follow-up study of 2184 individuals living in Grampian, UK to describe patterns and predictors of change in chronic pain over time. In October 2000, participants completed a postal questionnaire including case definition questions, the chronic pain grade questionnaire, the SF-36 and socio-demographic questions. Information from this questionnaire was compared to information collected from a similar questionnaire in 1996. A response rate of 83% was achieved for the follow-up study. The overall prevalence of chronic pain (pain or discomfort present either all the time or on and off for 3 months or longer) increased from 45.5% at baseline to 53.8% at follow-up. Seventy-nine percent of those with chronic pain at baseline still had it at follow-up. The average annual incidence was 8.3% and the average annual recovery rate was 5.4%. Individuals in the study samples who are in lowest quartile of SF-36 domains--physical functioning, social functioning and bodily pain at baseline--were more likely to develop chronic pain at follow-up, and respondents who were retired were less likely to develop chronic pain. Individuals in the study samples in the lowest quartile of SF-36 domains, bodily pain and general health at baseline, were less likely to recover from their chronic pain, as were those aged 45-74 compared with those aged 25-34. We concluded that chronic pain is a common, persistent problem in the community with relatively high incidence and low recovery rates. The lack of association between onset or recovery from chronic pain and most traditional socio-demographic factors, highlights the need to broaden the range of factors included in studies of chronic pain aetiology.

Impact of deprivation and rural residence on treatment of colorectal and lung cancer.

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment.