Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity.

The ubiquitin proteasome pathway has been implicated in the pathogenesis of many neurodegenerative diseases, and alterations in two different deubiquitinating enzymes, Uch-L1 and Usp14, result in neurological phenotypes in mice. We identified a new mutation in Uch-L1 and compared the roles of Uch-L1 and Usp14 in the ubiquitin proteasome system. Deficiencies in either Uch-L1 or Usp14 result in decreased levels of ubiquitin, suggesting that they both regulate ubiquitin stability in the nervous system. However, the effect of ubiquitin depletion on viability and onset of symptoms is more severe in the Usp14-deficient mice, and changes in hippocampal synaptic transmission were only observed in Usp14-deficient mice. In addition, while Usp14 appears to function at the proteasome, Uch-L1 deficiency resulted in up-regulation of lysosomal components, indicating that Uch-L1 and Usp14 may differentially affect the ubiquitin proteasome system and synaptic activity by regulating different pools of ubiquitin in the cell.

Weighing Vietnamese children: how accurate are child weights adjusted for estimates of clothing weight?

Children who are weighed for growth monitoring are frequently clothed, especially in the cold weather. Health workers commonly estimate and subtract the weight of these clothes, but the accuracy of these estimates is unknown. We assessed the accuracy of child weights adjusted for estimated clothing typical of hot, cold, and extremely cold ambient temperatures. Trained field workers weighed a sample of 212 children 6 to 42 months old from the ViSION project, adjusted the weights using a job aid describing the weights of common clothing by season and age, and then weighed the clothing to calculate the actual clothing and child weights. Fieldworker estimates of the weight of the clothing that children wore during weighing were remarkably good. In nearly all cases (207 of 212; 97.7%), the difference between the estimated and actual clothing weight was less than the precision of the child scales (+/- 50 g), and most (181 of 212; 84.5%) were within 25 g. Thus, the calculated child weights were, in fact, equivalent to the actual child weights. Using simulations, we found that improperly accounting for clothing weight can overestimate weight-for-age by 0.1 to 0.4 Z score. Accurate weights are possible, even under adverse conditions. Our training methods, clothing album, and job aid might benefit nutrition research and programming in Viet Nam as well as settings with colder climates.

Assessing a computerized routine health information system in Mali using LQAS.

BACKGROUND: Between 1987 and 1998 Save the Children conducted a child survival programme in Mali with the goal of reducing maternal and child morbidity and mortality. An integral part of this programme was a computerized demographic surveillance and health information system (HIS) that gathered data on individuals on an on-going basis. OBJECTIVE: To assess the overall coverage and quality of the data in the HIS, to identify specific health districts that needed improvements in data collection methods, and to determine particular areas of weakness in data collection. METHODS: Random samples of 20 mothers with children <5 years were selected in each of 14 health districts. Mothers were interviewed about pregnancies, live births, deaths of children <5, and children's growth monitoring and immunization status. The Lot Quality Assurance Method (LQAS) was used to identify districts in which records and interview results did not meet predetermined levels of acceptability. Data collected in the interviews were combined to estimate overall coverage and quality. RESULTS: When all variables were analyzed, all 14 lots were rejected, and it was estimated that 52% of all events occurring in the community were registered in ProMIS. Much of this poor performance was due to immunization and growth monitoring data, which were not updated due to printer problems. Coverage of events increased (92%) when immunizations and growth monitoring were excluded, and no lots were rejected. When all variables were analyzed for quality of data recorded, six lots were rejected and the overall estimation was 83%. With immunizations and growth monitoring excluded, overall quality was 86% and no lots were rejected. CONCLUSIONS: The comprehensive computerized HIS did not meet expectations. This may be due, in part, to the ambitious objective of complete and intensive monitoring of a large population without adequate staff and equipment. Future efforts should consider employing a more targeted and streamlined HIS so that data can be more complete and useful.

Effect of improved housing on illness in children under 5 years old in northern Malawi: cross sectional study.

OBJECTIVE: To evaluate the effects of a Habitat for Humanity housing improvement programme in northern Malawi on the prevalence of childhood illnesses. DESIGN: Household based cross sectional study. SETTING: Rural communities centred near the small northern Malawi town of Ekwendeni. SUBJECTS: 318 children under 5 years old. MAIN OUTCOME MEASURES: Prevalence of respiratory, gastrointestinal, and malarial infections according to maternal recall, laboratory, or clinical data. RESULTS: Children living in improved homes were less likely to have respiratory, gastrointestinal, or malarial illnesses (odds ratio 0.56, 95% confidence interval 0.35 to 0.91) after confounding factors were controlled for. The reductions in individual diseases were not significant. CONCLUSION: Improved housing significantly reduced the burden of disease among children under 5 years old.

Early nutrition and later adiposity.

The objective was to review whether nutrition during pregnancy and the first 3 y of life predisposes individuals to be fatter as adults. The roles of undernutrition, overnutrition and breastfeeding were considered. The evidence that poor nutrition in early life is a risk factor for increased fatness later in life is inconclusive. Overnutrition, as proxied by high birthweight or gestational diabetes, on the other hand, is associated with subsequent fatness. Two large, well-conducted studies in developed countries suggest that breastfeeding has a protective effect. Nutrition in early life has a demonstrable but small impact on adult obesity.

Determinants of fasting glucose in young Guatemalan adults.

OBJECTIVE: To examine correlates of fasting glucose, a precursor for type 2 diabetes mellitus, in young adults in Guatemala, a country undergoing an epidemiologic transition. DESIGN: Cross-sectional. METHODS: Anthropometric, lifestyle, dietary, serum lipid, and socioeconomic characteristic data were collected on 189 men and 201 women (mean age 24.4 years) born in four villages in Eastern Guatemala. We used linear regression to identify parsimonious predictive models, including 2-way interactions. RESULTS: In men, mean fasting glucose was 87.3 mg/dL (SD 10.2); our model explained 30% of variance. Body mass index (BMI), abdomen-to-hip ratio (AHR), and total cholesterol showed graded positive effects. BMI and AHR interacted (P<.001); men with high BMI and high AHR had the highest fasting glucose levels. No dietary factors independently predicted fasting glucose. In women, mean fasting glucose was 83.9 mg/dL (SD 8.5); 22% of variance was explained by BMI, energy-adjusted fat intake, physical activity, birth village, and current residence (rural/urban). BMI and fasting glucose were positively related. Urban residence interacted with birth village (P=.06) and physical activity (P=.13). CONCLUSIONS: The major conclusion drawn from this study is that increased adiposity, even among lean individuals, is the largest environmental predictor of fasting glucose. Prevention and control of obesity in young adults in transitioning countries are key strategies for the prevention of diabetes.

Early childhood nutrition, education and fertility milestones in Guatemala.

Data on fertility milestones were collected in 1994 and linked to information collected in a trial conducted in eastern Guatemala between 1969 and 1977, to examine whether early childhood nutrition was associated with the timing of fertility milestones. In the original trial, two pairs of villages were randomly allocated to receive either a high energy, high protein supplement (Atole) or a low energy, no-protein supplement (Fresco). Mean age at follow-up was 23.47 y (n = 240). About 62% of women had experienced first birth (median age at first birth = 19.83 y). The median intervals from menarche to first intercourse and from first intercourse to first birth were 5.67 and 0.95 y; they were 1.68 and 0.06 y shorter, respectively, for the Atole group than for the Fresco group. Women who had received Atole in utero and/or during early childhood experienced earlier milestones even after adjusting for socioeconomic status (SES), education and age at the prior event. Median age at first birth was 1.17 y earlier for the Atole group. Better growth during early childhood (not severely stunted) led to earlier milestones (median age at first birth was 1.04 y earlier), primarily among women with illiterate fathers. Completion of primary school significantly delayed fertility milestones; the median age at first birth was 4.27 y later for those who completed primary school compared with those who did not (P < 0.05). In sum, improved nutrition during early childhood results in earlier fertility milestones, but the effects of schooling in delaying fertility milestones are greater in magnitude. Intervention programs that improve early childhood nutrition should be accompanied by investments in education that ensure that girls complete primary school.

Fatness and body mass index from birth to young adulthood in a rural Guatemalan population.

Body mass index (BMI; wt in kg/ht2 in m) has been proposed as a simple and valid measure for monitoring fatness. Using data from a 25-y longitudinal study of rural Guatemalans, we found that, as children, this population was stunted (mean height-for-age z = -2.6) and had low triceps skinfold thicknesses ( approximately 10% of reference medians), yet had mean BMIs above US reference medians. As young adults, mean BMIs were at the 50th and 20th percentiles for women and men, respectively. BMIs between ages 1 and 5 y were moderately correlated (r = 0.2-0.3) with those in young adulthood. BMI was correlated with subscapular (r = 0.5-0.8) and triceps (r = 0.2-0.7) skinfold thicknesses at all ages and with predicted percentage body fat in adolescence (r = 0.65) and adulthood (r = 0.8). Fatness was highly centralized, with ratios of subscapular to triceps skinfold thicknesses at the 50th-90th percentiles of reference medians at all ages. BMI was a poor indicator of central fat; the correlation between BMI and waist-to-hip ratio in 14-17-y-old males was -0.21). In stunted populations in developing countries, BMI alone should be interpreted with caution. In stunted children, BMIs may be high despite small extremity skinfold thicknesses; BMI alone may overestimate the prevalence of fatness in these children. In adults, measures in addition to BMI may be required to identify centralized adiposity in these populations.

Role of intergenerational effects on linear growth.

Current knowledge on the role of intergenerational effects on linear growth is reviewed on the basis of a literature search and recent findings from an ongoing study in Guatemala. Fourteen studies were identified, most of which examined the intergenerational relationships in birth weight. Overall, for every 100 g increase in maternal birth weight, her child's birth weight increased by 10-20 g. The study samples were primarily from developed countries, and birth weight data were extracted from hospital records and/or birth registries. Among the few studies that examined associations between the adult heights of parents and their offspring, correlation coefficients of 0.42-0.5 were reported. None of the studies examined intergenerational relationships in birth length or linear growth patterns during early childhood, preadolescence and/or adolescence. Prospectively collected data from long-term studies being carried out in rural Guatemala provide the first evidence of intergenerational relationships in birth size in a developing country setting. Data were available for 215 mother-child pairs. Maternal birth size was a significant predictor (P < 0.05) of child's birth size after adjusting for gestational age and sex of the child and other potential confounders. Child's birth weight increased by 29 g/100 g increase in maternal birth weight which is nearly twice that reported in developed countries. Similarly, child's birth length increased by 0.2 cm for every 1 cm increase in mother's birth length. The effect of maternal birth weight remained significant even after adjusting for maternal adult size. More evidence from developing countries will help explain the underlying mechanisms and identify appropriate interventions to prevent growth retardation.

Infant and child growth and fatness and fat distribution in Guatemalan adults.

To examine whether poor growth in utero or young childhood is associated with adult abdominal fatness in a developing country context, the authors analyzed prospectively collected data on 372 female and 161 male Guatemalans measured as children between 1969 and 1977 and remeasured as adults in 1988-1989 (men and women) and 1991-1994 (women only). Childhood stunting (height-for-age z score) was associated with a lower body mass index and percent body fat in men, while no associations were found in women. In both sexes, however, severely stunted children had significantly greater adult abdominal fatness (waist:hip ratio), once overall fatness and confounders were controlled. The adult waist:hip ratio (x100) was increased by 0.65 (95% confidence interval 0.10 to 1.20) in men and 0.29 (95% confidence interval -0.03 to 0.61) in women for each height-for-age z score less at age three. Migration to urban centers was significantly associated with an even greater waist:hip ratio in severely stunted females (p = 0.03). In a subsample of 137 women, short and thin newborns had significantly greater adult abdominal fatness compared with long and thin or short and fat newborns or children who became stunted postnatally. The adult waist:hip ratio (x100) was increased by 1.58 (95% confidence interval 0.35 to 2.81) for each kilogram less birth weight. The authors conclude that, in countries where maternal and child malnutrition exists alongside rapid economic development and urban migration, abdominal obesity and related chronic diseases are likely to increase.

PIP: Being overweight, especially in the abdominal region, is a risk factor for cardiovascular disease, the onset of diabetes in adults, stroke, and mortality. Malnutrition in utero or early childhood may lead to fatness later in life. The authors tested the hypothesis that poor linear growth during childhood predicts fatness and the high-risk fat patterning of young Guatemalan adults. Findings are based upon the analysis of prospectively collected data on 161 male and 372 female Guatemalans measured as children during 1969-77 and remeasured as adults in 1988-89 (men and women) and 1991-94 (women only). Childhood stunting was associated with a lower body mass index (BMI) and percent body fat in men, while no association was found in women. Both male and female severely stunted children had significantly greater adult abdominal fatness, after controlling for overall fatness and confounders. The adult waist:hip ratio was increased by 0.65 in men and 0.29 in women for each height-for-age z score less at age 3. Migration to urban centers was significantly associated with a greater waist:hip ratio in severely stunted females. In a subsample of 137 women, short and thin newborns had significantly greater adult abdominal fatness compared with long and thin or short and fat newborns or children who became stunted postnatally. The adult waist/hip ratio was increased by 1.58 for each kilogram less birth weight. Findings suggest that in countries where maternal and child malnutrition exist in the context of rapid economic development and urban migration, abdominal obesity and related chronic diseases are likely to increase.

Intrauterine growth retardation, body size, body composition and physical performance in adolescence.

Studies about effects of IUGR on growth in childhood as well as on body size, body composition and physical performance in adolescence and adulthood are reviewed. The review is based on 12 studies that distinguished IUGR from other types of low birthweight and compared outcomes of IUGR cases with those of non-IUGR controls. This information is complemented by results of a follow-up study of IUGR cases and controls carried out in Guatemalan adolescents and young adults. In Guatemala as well as in other countries, IUGR newborns showed partial catch-up growth during the first one or two years of life, and then maintained their achieved place in the growth distribution. Guatemalan IUGR cases were shorter, lighter and weaker than non-IUGR controls as adolescents and young adults. The differences in adult body size observed in Guatemala between cases and controls are similar to those found in more affluent countries (i.e. about 5 cm in height and 5 kg in weight).

Dietary management of acute diarrhea with local foods in a Guatemalan rural community.

A community-based, randomized trial was conducted to evaluate a locally available diet for the management of acute diarrhea (n = 99 episodes) in 90 Guatemalan children, 4-42 months of age. The Test Diet (TD), a combination of a semi-solid pap (maize flour, black beans, oil) and a liquid gruel, Incaparina (maize flour, cotton seed flour, sugar), in addition to breast-milk and other home foods (group TD, n = 45 episodes) was offered for 14 d and compared to usual home feeding (group HF, n = 54 episodes). Diarrhea episodes after admission were significantly shorter for group TD (median 2.0 d) than group HF (median 4.4 d, p = 0.003) after adjusting for potential confounders. Weight gains did not differ significantly between groups. We conclude that community-based dietary management of acute childhood diarrhea using energy-dense, locally available foods is feasible and may shorten diarrhea duration. This may encourage mothers to follow recommendations for continued feeding during diarrhea in developing country environments.

Predictive factors of enrollment and adherence in a breast cancer screening program in Barcelona (Spain).

This paper study the predictive factors associated to enrollment and adherence in a breast cancer screening program in Barcelona, Spain; the Program is targeted to women 50-70 years of age who are members of a Health Maintenance Organization. Data were collected by personal interview for the attending women and by telephone in the non-attending group. The questionnaire was focused on knowledge, attitudes and practices related to female cancer prevention and breast cancer risk factors. Data analysis consisted of bivariate and multivariate analysis. Enrolling in a breast cancer screening program was strongly associated with practices related to cancer prevention in the bivariate analysis. Having had a previous mammography was the only behavioral factor that showed an independent relationship with enrollment (OR = 6.45, 95% CI = 3.35-12.42) in the multivariate analysis together with being younger than 55 and having family history of cancer. Adherence was associated with having the best opinion of the program, knowing the preventive role of mammography and performing regular breast self-examination in the bivariate analysis; of these, knowing the preventive role of mammography (OR = 2.66, 95% CI = 1.14-6.18) and performing regular breast self-examination (OR = 1.99, 95% CI = 1.23-3.23) were independently associated in the multivariated analysis. Being a relative of a municipal worker and younger than 55 were also significantly associated with adherence. Getting women to participate in a breast cancer screening program is difficult--mailed invitation letters are not sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Age differences in the impact of nutritional supplementation on growth.

Supplementary feeding programs are common in developing countries. These programs often cannot demonstrate an impact on child growth, however, possibly because they tend to reach older children. This study examines the impact of nutritional supplementation on annual growth rates in length and weight from birth to 7 y of age in 1208 rural Guatemalan children. A series of multiple linear regression models is used to control for initial body size, diarrheal disease, home diet, socioeconomic status and gender. During the first year of life, each 100 kcal/d (418 kJ) of supplement was associated with approximately 9 mm in additional length gain and 350 g in additional weight gain; the benefit decreased to approximately 5 mm in length gain and 250 g in weight gain during the 2nd y of life. Between 24 and 36 mo of age, supplement only had a significant impact on length. There was no impact of nutritional supplementation on growth between 3 and 7 y of age. Patterns were the same if supplement intakes were expressed as a percent of recommended allowances or growth was expressed as a percent of the expected rate. These impacts of nutritional supplementation on growth coincide with the ages when growth velocities, as well as growth deficits, are greatest in this population.

Patterns of linear growth in rural Guatemalan adolescents and children.

Length and weight data from a longitudinal study of rural Guatemalan subjects birth to 7 y of age and height and weight data from a cross-sectional study of the same subjects when they were 11-24.9 y old are compared to reference data for the USA general population and for Mexican-Americans. At birth, the median length of Guatemalan children is at approximately the 16th percentile of the USA reference or approximately 2 cm shorter. By 6 mo of age, Guatemalan children are shorter, on average, than the 5th percentile of the reference curves and, in absolute terms, are approximately 5 cm below the median; by 3 y, the difference increases to approximately 10 cm. As adults, Guatemalans have about the same absolute level of deficit (approximately 13 cm) as they did at age 3 y. If the general USA population is used for comparison, Guatemalans can be said to grow as expected during adolescence, neither recuperating the growth retardation of early childhood nor falling further behind in size. If the Mexican-American sample is selected instead, it would appear that some catch-up in growth occurs in Guatemalan adolescents. Regardless of the choice of reference population, growth is markedly retarded only in early childhood; adolescence is not a period when growth is significantly constrained.

Age at menarche and nutritional supplementation.

Retrospective data on age at menarche were collected for 832 Guatemalans 15-30 y in age to test whether exposure to a high energy and high protein supplement (Atole: 163 kcals/682 kJ and 11.5 g protein per cup or 180 mL) during childhood led to earlier menarche than did exposure to a low energy, no protein supplement (Fresco: 59 kcals/247 kJ in 180 mL). Mean age at menarche was similar in Atole (13.75 +/- 1.22 y; mean +/- SD) and Fresco (13.74 +/- 1.36 y) groups. The corresponding value for immigrants (n = 144), subjects not exposed to the supplements, was 13.55 +/- 1.20 y. Year of birth as well as socioeconomic status (SES) were associated with age at menarche. Age at menarche declined by 0.69 y over the 15-y period and menarche occurred earlier in higher SES households. Significant positive interactions between supplement type and SES and between supplement type and year of birth were found, but plausible explanations for them could not be advanced.

The effects of malnutrition on child mortality in developing countries.

Conventional methods of classifying causes of death suggest that about 70% of the deaths of children (aged 0-4 years) worldwide are due to diarrhoeal illness, acute respiratory infection, malaria, and immunizable diseases. The role of malnutrition in child mortality is not revealed by these conventional methods, despite the long-standing recognition of the synergism between malnutrition and infectious diseases. This paper describes a recently-developed epidemiological method to estimate the percentage of child deaths (aged 6-59 months) which could be attributed to the potentiating effects of malnutrition in infectious disease. The results from 53 developing countries with nationally representative data on child weight-for-age indicate that 56% of child deaths were attributable to malnutrition's potentiating effects, and 83% of these were attributable to mild-to-moderate as opposed to severe malnutrition. For individual countries, malnutrition's total potentiating effects on mortality ranged from 13% to 66%, with at least three-quarters of this arising from mild-to-moderate malnutrition in each case. These results show that malnutrition has a far more powerful impact on child mortality than is generally appreciated, and suggest that strategies involving only the screening and treatment of the severely malnourished will do little to address this impact. The methodology provided in this paper makes it possible to estimate the effects of malnutrition on child mortality in any population for which prevalence data exist.

PIP: Conventional methods of classifying causes of death suggest that about 70% of the deaths of children 0-4 years old worldwide are due to diarrheal illness, acute respiratory infection, malaria, and immunizable diseases. The role of malnutrition in child mortality is not revealed by these conventional methods, despite the long-standing recognition of the synergism between malnutrition and infectious diseases. This paper describes a recently-developed epidemiological method to estimate the percentage of child deaths (ages 6-59 months) which could be attributed to the potentiating effects of malnutrition in infectious disease. The methodology is based on the results of 8 community-based, prospective studies of the relationship between anthropometry and child mortality from the rural areas of Bangladesh, India, Indonesia, Malawi, Papua New Guinea, and Tanzania. These studies suggest that the risk of mortality increases at a compounded rate of 5.9% for each percentage point decline in weight-for-age below the reference point of 90% weight-for-age. Using the relative risk estimates, the standard epidemiological statistic of population-attributable risk (PAR) was used to estimate the percentage of child deaths attributable to malnutrition's potentiating impact on infectious disease. The results from 53 developing countries with nationally representative data on child weight-for-age indicated that 56% of child deaths were attributable to malnutrition's potentiating effects. 83% of these were attributable to mild-to-moderate as opposed to severe malnutrition, with a range of 73-74% in Bangladesh and India to a high of 100% in countries with very low malnutrition prevalences. For individual countries, malnutrition's total potentiating effects on mortality ranged from 13% in Paraguay to 67% in India, with at least 3/4 of this arising from mild-to-moderate malnutrition in each case. The powerful impact of malnutrition on child mortality suggests that strategies involving only the screening and treatment of the severely malnourished are not sufficient.