Hydrogen tunneling in enzyme reactions.

Primary and secondary protium-to-tritium (H/T) and deuterium-to-tritium (D/T) kinetic isotope effects for the catalytic oxidation of benzyl alcohol to benzaldehyde by yeast alcohol dehydrogenase (YADH) at 25 degrees Celsius have been determined. Previous studies showed that this reaction is nearly or fully rate limited by the hydrogen-transfer step. Semiclassical mass considerations that do not include tunneling effects would predict that kH/kT = (kD/kT)3.26, where kH, kD, and kT are the rate constants for the reaction of protium, deuterium, and tritium derivatives, respectively. Significant deviations from this relation have now been observed for both primary and especially secondary effects, such that experimental H/T ratios are much greater than those calculated from the above expression. These deviations also hold in the temperature range from 0 to 40 degrees Celsius. Such deviations were previously predicted to result from a reaction coordinate containing a significant contribution from hydrogen tunneling.

Tuberculosis: commentary on a reemergent killer.

Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model.

Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran.

OBJECTIVE: To use a range of existing information sources to develop a national snapshot of the burden of road traffic injuries in one developing country-Iran. METHODS: The distribution of deaths was estimated by using data from the national death registration system, hospital admissions and outpatient visits from a time-limited hospital registry in 12 of 30 provinces, and injuries that received no institutional care using the 2000 demographic and health survey. Results were extrapolated to national annual incidence of health burden differentiated by age, sex, external cause, nature of injuries and institutional care. RESULTS: In 2005, 30,721 Iranians died annually in road traffic crashes and over one million were injured. The death rate (44 per 100,000) is the highest of any country in the world for which reliable estimates are available. Road traffic injuries are the third leading cause of death in Iran. While young adults are at high risk in non-fatal crashes, the elderly have the highest total death rates, largely due to pedestrian crashes. While car occupants lead the death count, motorized two-wheeler riders dominate hospital admissions, outpatient visits and health burden. CONCLUSIONS: Reliable estimates of the burden of road traffic injuries are an essential input for rational priority setting. Most low income countries are unlikely to have national injury surveillance systems for several decades. Thus national estimates of the burden of injuries should be built by collating information from all existing information sources by appropriately correcting for source specific shortcomings.

Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors.

The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates of oral conditions for the period of 1990 to 2015. Since death as a direct result of oral diseases is rare, DALY estimates were based on years lived with disability, which are estimated only on those persons with unmet need for dental care. We used our data to assess progress toward the Federation Dental International, World Health Organization, and International Association for Dental Research's oral health goals of reducing the level of oral diseases and minimizing their impact by 2020. Oral health has not improved in the last 25 y, and oral conditions remained a major public health challenge all over the world in 2015. Due to demographic changes, including population growth and aging, the cumulative burden of oral conditions dramatically increased between 1990 and 2015. The number of people with untreated oral conditions rose from 2.5 billion in 1990 to 3.5 billion in 2015, with a 64% increase in DALYs due to oral conditions throughout the world. Clearly, oral diseases are highly prevalent in the globe, posing a very serious public health challenge to policy makers. Greater efforts and potentially different approaches are needed if the oral health goal of reducing the level of oral diseases and minimizing their impact is to be achieved by 2020. Despite some challenges with current measurement methodologies for oral diseases, measurable specific oral health goals should be developed to advance global public health.

Geochemical and Microbial Community Attributes in Relation to Hyporheic Zone Geological Facies.

The hyporheic zone (HZ) is the active ecotone between the surface stream and groundwater, where exchanges of nutrients and organic carbon have been shown to stimulate microbial activity and transformations of carbon and nitrogen. To examine the relationship between sediment texture, biogeochemistry, and biological activity in the Columbia River HZ, the grain size distributions for sediment samples were characterized to define geological facies, and the relationships among physical properties of the facies, physicochemical attributes of the local environment, and the structure and activity of associated microbial communities were examined. Mud and sand content and the presence of microbial heterotrophic and nitrifying communities partially explained the variability in many biogeochemical attributes such as C:N ratio and %TOC. Microbial community analysis revealed a high relative abundance of putative ammonia-oxidizing Thaumarchaeota and nitrite-oxidizing Nitrospirae. Network analysis showed negative relationships between sets of co-varying organisms and sand and mud contents, and positive relationships with total organic carbon. Our results indicate grain size distribution is a good predictor of biogeochemical properties, and that subsets of the overall microbial community respond to different sediment texture. Relationships between facies and hydrobiogeochemical properties enable facies-based conditional simulation/mapping of these properties to inform multiscale modeling of hyporheic exchange and biogeochemical processes.

Global burden of untreated caries: a systematic review and metaregression.

We aimed to consolidate all epidemiologic data about untreated caries and subsequently generate internally consistent prevalence and incidence estimates for all countries, 20 age groups, and both sexes for 1990 and 2010. The systematic search of the literature yielded 18,311 unique citations. After screening titles and abstracts, we excluded 10,461 citations as clearly irrelevant to this systematic review, leaving 1,682 for full-text review. Furthermore, 1,373 publications were excluded following the validity assessment. Overall, 192 studies of 1,502,260 children aged 1 to 14 y in 74 countries and 186 studies of 3,265,546 individuals aged 5 y or older in 67 countries were included in separate metaregressions for untreated caries in deciduous and permanent teeth, respectively, using modeling resources from the Global Burden of Disease 2010 study. In 2010, untreated caries in permanent teeth was the most prevalent condition worldwide, affecting 2.4 billion people, and untreated caries in deciduous teeth was the 10th-most prevalent condition, affecting 621 million children worldwide. The global age-standardized prevalence and incidence of untreated caries remained static between 1990 and 2010. There is evidence that the burden of untreated caries is shifting from children to adults, with 3 peaks in prevalence at ages 6, 25, and 70 y. Also, there were considerable variations in prevalence and incidence between regions and countries. Policy makers need to be aware of a predictable increasing burden of untreated caries due to population growth and longevity and a significant decrease in the prevalence of total tooth loss throughout the world from 1990 to 2010.

An ecological interdependence of diet and disease? A study of infection in one tribe consuming two different diets.

The nature and incidence of infections were studied in two groups of Turkana living in the same area but eating different diets; one consumed milk only and the other a combination of fish and milk. The only apparent and significant nutritional difference between the two groups was mild iron deficiency in the milk drinkers. Episodes of fever, symptomatic infection with malaria and brucellosis, molluscum contagiosum and common warts, episodes of diarrhea, and serological evidence of infection with Entamoeba histolytica were significantly increased in Turkana eating fish. We suggest that this phenomenon may result from a disruption of a long-standing ecological compromise between the all-milk diet of the Turkana and the pathogenic organisms.

Parotid enlargement, forehead edema, and suppression of malaria as nutritional consequences of ascariasis.

Bilateral painless enlargement of the parotids, a curiously localized edema of the forehead and relative freedom from malaria were striking findings in children of Anjouan but not of Grande Comore, two neighboring islands of the Comorro group in the Indian Ocean. Compared with those of Grande Comore, Anjouan children were heavily infested with Ascaris lumbricoides. We suggest that the clinical findings may be the nutritional consequence of severe ascariasis and that the low incidence of malaria in Anjouan children may be an example of the delicate ecological balance between the host, the Ascaris, and the plasmoidum.

The infant mortality rate, life expectancy at birth, and a linear index of mortality as measures of general health status.

The infant mortality rate is not a good indicator of overall mortality or health status. Based on new empirical life tables from the UN Population Division, it can only predict life expectancy with 95% confidence to within a 14-year range. Two infant mortality rates must be nearly 80 units apart to be 95% confident that life expectancy in the two communities is different. Life expectancy itself is not an ideal general measure of mortality, because it implicitly weights deaths at different ages in an inconsistent fashion. A measure of potential years of life lost is preferable because it is ethically more consistent.

PIP: This paper re-assesses the use of the infant mortality rate and the life expectancy at birth as indexes for general mortality in developing countries, and then suggests and alternative, called the linear index of mortality or LIM. The infant mortality rate is not a good indicator of overall mortality or health status because it is sensitive to socioeconomic changes, in particular to maternal education. Based on new empirical life tables from the UN Population Division, it can only predict life expectancy with 95% confidence to within a 14-year range. Life expectancy itself is not an ideal general measure of mortality because it implicitly weights deaths at different ages in a inconsistent way. The linear index of mortality (LIM) is a measure of potential years of life lost. By weighting the number of deaths in each age group by 100 minus the age of death, a composite index of general mortality can be calculated that is linear, uniform and ethically consistent. Using UN empirical life tables for 20 developing countries, it is possible from the LIM to get an idea how much the difference between high and low mortality countries is due to differences in infant, child and adult mortality. This kind of comparison is impossible with life expectancy because it is non-linear. The relationship between the natural log of life expectancy and LIM is linear. Alternative health status measures like LIM need to be developed, in order to make our statistical perception of the world's nations consistent with our ethical conception of how health should be measured.

Laparoscopic suture hysteropexy for uterine prolapse.

OBJECTIVE: Vaginal hysterectomy remains the accepted surgical treatment for women with uterine prolapse. The Manchester repair is favored in women wishing uterine preservation. Vaginal hysterectomy alone fails to address the pathologic cause of the uterine prolapse. The Manchester repair has a high failure rate and may cause difficulty sampling the cervix and uterus in the future. The laparoscopic suture hysteropexy offers physiologic repair of uterine prolapse. METHOD: At the laparoscopic suture hysteropexy, the pouch of Douglas is closed and the uterosacral ligaments are plicated and reattached to the cervix. RESULTS: Forty-three women with symptomatic uterine prolapse were prospectively evaluated and underwent laparoscopic suture hysteropexy with a mean follow-up of 12 +/- 7 months (range 6-32). The mean operating time for the laparoscopic suture hysteropexy alone was 42 +/- 15 minutes (range 22-121), and the mean blood loss was less than 50 mL. On review, 35 women (81%) had no symptoms of prolapse and 34 (79%) had no objective evidence of uterine prolapse. Two women subsequently completed term pregnancies and were without prolapse. Both underwent elective cesarean delivery. CONCLUSION: The laparoscopic suture hysteropexy is effective and safe in the management of symptomatic uterine prolapse. The result is physiologically correct, without disfiguring the cervix. This may be an appropriate procedure for women with uterine prolapse wishing uterine preservation.

Iliococcygeus or sacrospinous fixation for vaginal vault prolapse.

OBJECTIVE: To compare iliococcygeus (prespinous) and sacrospinous fixation for vaginal vault prolapse. METHODS: Between 1994 and 1998, 78 women underwent sacrospinous colpopexy and 50 underwent iliococcygeus fixation for the management of symptomatic vaginal vault prolapse. A matched case-control study was designed to compare the two approaches. The matched variables included age, parity, body mass index, degree of vault prolapse, menopause, sexual activity, constipation, previous prolapse or continence surgery, stress incontinence, and length of review. Thirty-six matched pairs were isolated, resulting in a study with a power of 50% to detect a 20% difference in the success rates between the two groups. RESULTS: The subjective success rate for the iliococcygeus group was 91%; it was 94% for the sacrospinous group (P =.73). The objective success rate was 53% and 67% (P =.36), and the patient satisfaction with surgery was 78 of 100 and 91 of 100 (P =.01) on a visual analogue scale. The mean length of postoperative follow-up was 21 months for the iliococcygeus group and 19 months for the sacrospinous group (P =.52). The recovery time was 54 days in the iliococcygeus group and 39 days in the sacrospinous group (P =.04). No significant difference was seen in the incidence of postoperative cystoceles or damage to the pudendal neurovascular bundle. CONCLUSION: Sacrospinous and iliococcygeus fixation are equally effective procedures for vaginal vault prolapse and have similar rates of postoperative cystocele, buttock pain, and hemorrhage requiring transfusion. The sacrospinous ligament fixation should not be discarded in favor of the iliococcygeus fixation in the management of vaginal vault prolapse.

Epidemiology of participation: an Australian community study.

STUDY OBJECTIVE: To determine the levels of participation in social and civic community life in a metropolitan region, and to assess differential levels of participation according to demographic, socioeconomic and health status. To contribute to policy debates on community participation, social capital and health using these empirical data. DESIGN: Cross sectional, postal, self completed survey on health and participation. SETTING: Random sample of the population from the western suburbs of Adelaide, the capital city of South Australia, a population of approximately 210 000. PARTICIPANTS: 2542 respondents from a sample of 4000 people aged 18 years and over who were registered on the electoral roll. MAIN RESULTS: The response rate to the survey was 63.6% (n=2542). Six indices of participation, on range of social and civic activities, with a number of items in each, were created. Levels of participation were highest in the informal social activities index (46.7-83.7% for individual items), and lowest in the index of civic activities of a collective nature (2.4-5.9% for individual items). Low levels of involvement in social and civic activities were reported more frequently by people of low income and low education levels. CONCLUSIONS: Levels of participation in social and civic community life in an urban setting are significantly influenced by individual socioeconomic status, health and other demographic characteristics. An understanding of the pattern of participation is important to inform social and health policy making. Increasing levels of participation will reduce social exclusion and is likely to improve the overall quality of community life.

Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine.

Understanding DALYs (disability-adjusted life years).

The measurement unit disability-adjusted life years (DALYs), used in recent years to quantify the burden of diseases, injuries and risk factors on human populations, is grounded on cogent economic and ethical principles and can guide policies toward delivering more cost-effective and equitable health care. DALYs follow from a fairness principle that treats 'like as like' within an information set comprising the health conditions of individuals, differentiated solely by age and sex. The particular health state weights used to account for non-fatal health outcomes are derived through the application of various forms of the person trade-off.

Modeling the effects of health on economic growth.

This paper investigates the effects of health indicators such as adult survival rates (ASR) on GDP growth rates at 5-year intervals in several countries. Panel data were analyzed on GDP series based on purchasing power adjustments and on exchange rates. First, we developed a framework for modeling the inter-relationships between GDP growth rates and explanatory variables by re-examining the life expectancy-income relationship. Second, models for growth rates were estimated taking into account the interaction between ASR and lagged GDP level; issues of endogeneity and reverse causality were addressed. Lastly, we computed confidence intervals for the effect of ASR on growth rate and applied a test for parameter stability. The results showed positive effects of ASR on GDP growth rates in low-income countries.

A critical review of international mortality data.

Mortality data have become increasingly important not only in health related studies but also in development studies as a whole. The demand for data on life expectancy and the infant mortality rate is met by five publications-the UN Demographic Yearbook, World Population Prospects, World Development Report, World Population Trends and Policies Monitoring Report, and World Population. Within these statistical publications, life expectancy and the infant mortality rate are available for nearly every country each year. However, recent empirical information on mortality in most developing exists only for a handful of countries. The estimates published in the World Development Report and World Population Prospects are based on old empirical data updated with assumed rates of improvement in mortality. Neither of these sources provide technical notes explaining the original data source, estimation technique, and updating model used. Fortunately, two sources, the World Population Trends and Policies Monitoring Report and World Population, publish only empirically based data clearly identifying source, year of applicability, and estimation technique. The work in the World Development Report and the World Population Prospects could be made more useful if they provided adequate technical documentation for each estimate. At present, the Monitoring Report and World Population are the only appropriate sources for quantitative analysis of mortality or of change in mortality.

In search of a contemporary theory for understanding mortality change.

This paper represents a speculative approach to the question of changing mortality levels in human populations. The surprising resilience and reluctance of mortality declines to respond to powerful countervailing is considered. A more integrated approach is proposed to examine the interactive roles of income, technology and behavior in relation to life expectancy. The paper concludes by a discussion of the relevance of the accumulation of health assets to national mortality levels.

A critical re-examination of the economics of blindness prevention under the Onchocerciasis Control Programme.

This article is a critical re-examination of the recent cost-effectiveness analysis of the Onchocerciasis Control Programme (OCP) in West Africa, undertaken by Prost and Prescott in 1984. We use the same approach, namely, measuring effectiveness of the programme by the number of healthy years of life added by the prevention of blindness. This work focuses on certain technical aspects of the data used for estimating parameter values in the cost-effectiveness calculations. Through examination of available data and the relationships between certain key variables, we estimate values that differ substantially from Prost and Prescott for the population at risk, the incidence and prevalence of onchocercal blindness, and the years of healthy life lost due to blindness. Our final results suggest that depending on the discount rate that the OCP is 7-40 times more costly as measured by discounted years of productive life added than measles immunisation. These results are in contradiction to Prost and Prescott's estimation that the OCP was more cost-effective than measles immunisation. We, however, feel that our results do not demonstrate that OCP is an inefficient use of resources. Rather, they call into question the methods used and the relevance of comparing measles immunisation and onchocerciasis control. In a subsequent article, we hope to deal directly with these conceptual problems by presenting separate humanitarian and economic cost-effectiveness measures.