A study of the effect of sudden cooling on tension development by the anterior byssus retractor muscle of mytilus edulis

The effect of ambient temperature on the ACh-induced tension response of the ABRM of Mytilus edulis was examined. The latter was found to have many temperature dependent variables, these included the latent period, the rate of tension development, maximum tension and the relaxation rate. Pmax was found to show a negative temperature coefficent. K+ contractures also showed a negative temperature co-efficent, Pmax approximately doubling for a 20°C decrease in temperature. The application of a cold shock during an ACh-induced contraction-relaxation cycle resulted in a transient increase in tension, the CIC. The production of a CTC was found to be dependent on the immediate presence of a stimulant, the time of application of the cold shock after the addition of stimulant, muscle length and temperature difference. As the temperature difference (ΔT) between the initial and cold shock solutions increased so the size of the CIC increased. The production of a CIC was found not to be directly related to the ACh or to the active state level yet it did not appear to be a passive phenomenon. A CIC was not produced when cold shock was applied to a muscle at rest or during catchy however, when catch was abolished by the application of relaxant a CIC could once again be elicited. Kinetic analysis of the CIC showed that, however, complex the mechanism two steps appear to be rate limiting, and the increase in tension with increasing AT was probably due to an increase in the availability of activator responsible for its production, rather than a differential effect on one of the rate limiting steps. Although it is conceivable that cold shock may exert a direct effect on the contractile proteins, evidence from the literature, and the experiments reported here, suggest that it is more likely that the CTC results from a transient increase in the level of myoplasmic Ca+2 Pharmacological investigation did not disprove this hypothesis. Of the possible sources of Ca+2 responsible for the CIC membrane associated sites seemed the most likely since under conditions which deplete this site no CIC was observed. Also the involvement of cAMP in the production of the CIC was largely excluded

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and$3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and$8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and$74, respectively, versus $4438 and$102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks

Maternal Knowledge of Stunting in Rural Indonesia

Child undernutrition and stunting remain serious public health problems in Indonesia. According to the Health Belief Model, increasing mothers’ knowledge of stunting is fundamental to establishing accurate threat perceptions predictive of behavior change. The purpose of this study was to increase understanding of factors related to maternal knowledge of stunting in Indonesia by addressing three questions: 1) How familiar with stunting are Indonesian mothers? 2) What antecedent factors do Indonesian mothers associate with stunting? and 3) What health effects do Indonesian mothers associate with stunting? A total of 3,150 mothers participated in structured face-to-face interviews. Study measures targeted four main variables. Mothers were asked: 1) Have you heard of stunting?; 2) Have you heard of shortness?; 3) What causes stunting/shortness?; and 4) What are the effects of stunting? Only 66 (2.1%) mothers reported having heard of, read about, or knew something about stunting. Approximately two-thirds of participants attributed stunting to hereditary factors. Interrupted growth (33.7%), idiocy (13.8%), and easy to get sick (11.8%) were identified as health effects of stunting. Results highlight the need for health promotion and education efforts focused on increasing basic knowledge of stunting, its causes, and its health effects among Indonesian mothers

Increased Maternal Education and Knowledge of Nutrition and Reductions in Poverty are Associated with Dietary Diversity and Meal Frequency in an Observational Study of Indonesian Children

Background: Optimal infant and young child feeding during the first two years of life is essential to optimum child development and health. While the link between feeding practices and child health outcomes is well documented, little is known about the determinants of these feeding practices in Indonesia. The purpose of this study was to better understand factors associated with appropriate child feeding among Indonesian children 6–23 months of age.Methods: Interviewers conducted interviews with 1498 mothers of children 6–23 months of age to identify practices. Measures of feeding practices included dietary diversity, meal frequency, and minimum acceptable diet. Multivariate logistic regression was used to identify factors associated with dietary diversity and separately with meal frequency.Results: After adjusting for covariates, increased maternal education was associated with improved dietary diversity. Age of child [OR=1.11], knowledge of stunting [OR=1.80], and having ever received nutrition information [OR=1.89] were also associated with greater dietary diversity. Wealth [OR=0.86] and age of child [OR=0.92] were inversely associated with meal frequency. Maternal education, age of child, being a male child, knowledge of stunting, and having received nutrition information increased the odds of the child consuming a minimum acceptable diet.Conclusion: Increasing maternal education, knowledge of stunting, and knowledge of nutrition may improve dietary diversity while poverty alleviation has the potential to improve minimum meal frequency. These findings corroborate similar studies and confirm the importance of government efforts that help girls stay in school, improve families’ understanding of nutrition, and reduce poverty

Early Childhood Nutrition Knowledge of Caregivers in Tanzania

Childhood stunting is a pressing health issue in Tanzania and results from chronic infections and inadequate nutrition. Educating caregivers on the nutritional determinants, their consequences, and appropriate solutions may improve nutrition-related practices among caregivers in Tanzania. The purpose of this study was to identify factors associated with Tanzanian caregivers’ knowledge of childhood nutrition practices. Data for this study came from a cross-sectional survey of 4,095 caregivers of children under 24 months living in the Geita, Kagera, Kigoma, Mwanza, and Shinyanga regions of Tanzania. Complete responses relating to demographic and socioeconomic factors, media exposure, and early childhood nutrition knowledge were analyzed using multiple linear regression modeling techniques. Caregivers’ knowledge concerning proper early childhood nutrition practices was found to be significantly related to using a mobile banking account (p<.0001), owning a working radio with batteries (p<.0001), having watched television recently (p<.0001), residing in a southern lake region (p<.0001), affiliating with a Christian faith (p=0.0027), having more children under the age of 5 (p=0.0005), having received advice on maternal nutrition before pregnancy (p<.0001) and having received advice from a community health worker (p=0.0184). Living in a rural environment (p<.0001) and speaking a non-mainstream language (p<0.05) were significantly associated with decreased knowledge. The influences of media and technology, socio-demographic factors and traditional health education may be important in the development of accurate childhood nutrition knowledge among caregivers. These factors may be targeted for future community health worker efforts with vulnerable populations in Tanzania to prevent stunting

Integrated Implementation of Programs Targeting Neglected Tropical Diseases through Preventive Chemotherapy: Proving the Feasibility at National Scale

In 2006, the United States Agency for International Development established the Neglected Tropical Disease (NTD) Control Program to facilitate integration of national programs targeting elimination or control of lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and blinding trachoma. By the end of year 3, 12 countries were supported by this program that focused first on disease mapping where needed, and then on initiating or expanding disease-specific programs in a coordinated/integrated fashion. The number of persons reached each year increased progressively, with a cumulative total during the first three years of 98 million persons receiving 222 million treatments with donated drugs valued at more than $1.4 billion. Geographic coverage increased substantially for all these infections, and the program has supported training of more than 220,000 persons to implement the programs. This current experience of the NTD Control Program demonstrates clearly that an integrated approach to control or eliminate these five neglected diseases can be effective at full national scale

Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma

Purpose: Translocation renal cell carcinoma (tRCC) represents a rare subtype of kidney cancer associated with various TFE3, TFEB, or MITF gene fusions that are not responsive to standard treatments for RCC. Therefore, the identification of new therapeutic targets represents an unmet need for this disease. Experimental Design: We have established and characterized a tRCC patient-derived xenograft, RP-R07, as a novel preclinical model for drug development by using next-generation sequencing and bioinformatics analysis. We then assessed the therapeutic potential of inhibiting the identified pathway using in vitro and in vivo models. Results: The presence of a SFPQ-TFE3 fusion [t(X;1) (p11.2; p34)] with chromosomal break-points was identified by RNA-seq and validated by RT-PCR. TFE3 chromatin immunoprecipitation followed by deep sequencing analysis indicated a strong enrichment for the PI3K/AKT/mTOR pathway. Consistently, miRNA microarray analysis also identified PI3K/AKT/mTOR as a highly enriched pathway in RP-R07. Upregulation of PI3/AKT/mTOR pathway in additional TFE3–tRCC models was confirmed by significantly higher expression of phospho-S6 (P < 0.0001) and phospho-4EBP1 (P < 0.0001) in established tRCC cell lines compared with clear cell RCC cells. Simultaneous vertical targeting of both PI3K/AKT and mTOR axis provided a greater antiproliferative effect both in vitro (P < 0.0001) and in vivo (P < 0.01) compared with single-node inhibition. Knockdown of TFE3 in RP-R07 resulted in decreased expression of IRS-1 and inhibited cell proliferation. Conclusions: These results identify TFE3/IRS-1/PI3K/AKT/mTOR as a potential dysregulated pathway in TFE3–tRCC, and suggest a therapeutic potential of vertical inhibition of this axis by using a dual PI3K/mTOR inhibitor for patients with TFE3–tRCC