Reliability of the cervical vertebrae maturation (CVM) method

OBJECTIVE To assess the reliability of the cervical vertebrae maturation method (CVM). BACKGROUND Skeletal maturity estimation can influence the manner and time of orthodontic treatment. The CVM method evaluates skeletal growth on the basis of the changes in the morphology of cervical vertebrae C2, C3, C4 during growth. These vertebrae are visible on a lateral cephalogram, so the method does not require an additional radiograph. METHODS In this website based study, 10 orthodontists with a long clinical practice (3 routinely using the method - "Routine user - RU" and 7 with less experience in the CVM method - "Non-Routine user - nonRU") rated twice cervical vertebrae maturation with the CVM method on 50 cropped scans of lateral cephalograms of children in circumpubertal age (for boys: 11.5 to 15.5 years; for girls: 10 to 14 years). Kappa statistics (with lower limits of 95% confidence intervals (CI)) and proportion of complete agreement on staging was used to evaluate intra- and inter-assessor agreement. RESULTS The mean weighted kappa for intra-assessor agreement was 0.44 (range: 0.30-0.64; range of lower limits of 95% CI: 0.12-0.48) and for inter-assessor agreement was 0.28 (range: -0.01-0.58; range of lower limits of 95% CI: -0.14-0.42). The mean proportion of identical scores assigned by the same assessor was 55.2 %(range: 44-74 %) and for different pairs of assessors was 42 % (range: 16-68 %). CONCLUSIONS The reliability of the CVM method is questionable and if orthodontic treatment should be initiated relative to the maximum growth, the use of additional biologic indicators should be considered (Tab. 4, Fig. 1, Ref. 24).

High intratumoral levels of FoxP3+ lymphocytes are associated with better prognosis in primary resected esophageal adenocarcinomas.

Background: Tumor infiltrating T-lymphocytes (TILs) have been shown to play an important prognostic role in many carcinomas. The identification of prognostic relevant morphological or molecular factors is a major area of interest in the diagnostic process and for the treatment of highly aggressive esophageal adenocarcinoma. Studies about the impact of TILs in this tumor have not shown completely congruent results yet. We present a comprehensive study about the clinical and pathological impact of TIL in esophageal adenocarcinomas. Methods: A next generation tissue microarray (TMA) of 117 primary resected esophageal adenocarcinomas was analyzed for CD3+, CD8+ and FoxP3+ TIL using immunohistochemistry. The TMA contained three cores of the tumor center and the tumor periphery per each case. Slides were scanned with a high-resolution scanner (ScanScope CS; Aperio) and an image analysis software (Aperio Image Scope) was used to determine the TIL counts. The results were correlated with clinicopathological parameters. Results: CD3+, CD8+ and FoxP3+ TIL counts showed a significant correlation among each other (p<0.001 each, range: 0.27-0.77). TIL counts were categorized as high and low levels, according to the median. Tumors with high FoxP3+ intratumoral lymphocyte counts were more frequently of lower pT category (p<0.001) and without lymph node metastasis (p=0.04). High levels of FoxP3+ lymphocytes in the tumor center and the periphery were also associated with better prognosis (p<0.001 and p=0.041, respectively) in univariate analysis. A similar prognostic impact was seen for high levels of CD3+ and CD8+ TIL in the tumor center, but not in the periphery (p=0.047 and p=0.011, respectively). In multivariate analysis high central FoxP3+TIL levels were an independent prognostic factor (HR=0.4; p=0.023) which was similar to a combination score of CD3+/CD8+/FoxP3+ TIL (HR=0.54; p=0.027) or CD8+/Foxp3+ TIL (HR=0.052; p=0.020) and superior to pT- and pN category (p>0.05 each). Conclusion: This study demonstrates a significant beneficial prognostic impact of high TIL counts in the tumor center of esophageal adenocarcinomas, in particular with regards to the subpopulation of FoxP3+ and CD8+ T-regulatory cells. The determination of intratumoral lymphocytic counts and application of TIL scores can improve prognostic accuracy of pathologic reports of these tumors and may be helpful for better risk stratification of esophageal adenocarcinoma patients.

The influence of different fever definitions on the rate of fever in neutropenia diagnosed in children with cancer

BACKGROUND The temperature limit defining fever (TLDF) is based on scarce evidence. This study aimed to determine the rate of fever in neutropenia (FN) episodes additionally diagnosed by lower versus standard TLDF. METHODS In a single center using a high TLDF (39.0°C tympanic temperature, LimitStandard), pediatric patients treated with chemotherapy for cancer were observed prospectively. Results of all temperature measurements and CBCs were recorded. The application of lower TLDFs (LimitLow; range, 37.5°C to 38.9°C) versus LimitStandard was simulated in silicon, resulting in three types of FN: simultaneous FN, diagnosed at both limits within 1 hour; earlier FN, diagnosed >1hour earlier at LimitLow; and additional FN, not diagnosed at LimitStandard. RESULTS In 39 patients, 8896 temperature measurements and 1873 CBCs were recorded during 289 months of chemotherapy. Virtually applying LimitStandard resulted in 34 FN diagnoses. The predefined relevantly (≥15%) increased FN rate was reached at LimitLow 38.4°C, with total 44 FN, 23 simultaneous, 11 earlier, and 10 additional (Poisson rate ratioAdditional/Standard, 0.29; 95% lower confidence bound, 0.16). Virtually applying 37.5°C as LimitLow led to earlier FN diagnosis (median, 4.5 hours; 95% CI, 1.0 to 20.8), and to 53 additional FN diagnosed. In 51 (96%) of them, spontaneous defervescence without specific therapy was observed in reality. CONCLUSION Lower TLDFs led to many additional FN diagnoses, implying overtreatment because spontaneous defervescence was observed in the vast majority. Lower TLDFs led as well to relevantly earlier diagnosis in a minority of FN episodes. The question if the high TLDF is not only efficacious but as well safe remains open.

Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency.

The congenital form of thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13. Some, but not all, congenital TTP patients manifest renal insufficiency in addition to microangiopathic hemolysis and thrombocytopenia. We included 32 congenital TTP patients in the present study, which was designed to assess whether congenital TTP patients with renal insufficiency have predisposing mutations in complement regulatory genes, as found in many patients with atypical hemolytic uremic syndrome (aHUS). In 13 patients with severe renal insufficiency, six candidate complement or complement regulatory genes were sequenced and 11 missense mutations were identified. One of these missense mutations, C3:p.K155Q mutation, is a rare mutation located in the macroglobulin-like 2 domain of C3, where other mutations predisposing for aHUS cluster. Several of the common missense mutations identified in our study have been reported to increase disease-risk for aHUS, but were not more common in patients with as compared to those without renal insufficiency. Taken together, our results show that the majority of the congenital TTP patients with renal insufficiency studied do not carry rare genetic mutations in complement or complement regulatory genes.

Complete genome of a Puumala virus strain from Central Europe

Puumala virus (PUUV) is one of the predominant hantavirus species in Europe causing mild to moderate cases of haemorrhagic fever with renal syndrome. Parts of Lower Saxony in north-western Germany are endemic for PUUV infections. In this study, the complete PUUV genome sequence of a bank vole-derived tissue sample from the 2007 outbreak was determined by a combined primer-walking and RNA ligation strategy. The S, M and L genome segments were 1,828, 3,680 and 6,550 nucleotides in length, respectively. Sliding-window analyses of the nucleotide sequences of all available complete PUUV genomes indicated a non-homogenous distribution of variability with hypervariable regions located at the 3′-ends of the S and M segments. The overall similarity of the coding genome regions to the other PUUV strains ranged between 80.1 and 84.7 % at the level of the nucleotide sequence and between 89.5 and 98.1 % for the deduced amino acid sequences. In comparison to the phylogenetic trees of the complete coding sequences, trees based on partial segments revealed a general drop in phylogenetic support and a lower resolution. The Astrup strain S and M segment sequences showed the highest similarity to sequences of strains from geographically close sites in the Osnabrück Hills region. In conclusion, a primer-walking-mediated strategy resulted in the determination of the first complete nucleotide sequence of a PUUV strain from Central Europe. Different levels of variability along the genome provide the opportunity to choose regions for analyses according to the particular research question, e.g., large-scale phylogenetics or within-host evolution.

Genetic mechanisms of Na+, K+-ATPase regulation in hypertension

The spontaneously hypertensive rat (SHR) is a model of essential hypertension. During the early development of hypertension, the SHR demonstrates increased proximal tubule (PT) Na+ reabsorption. I hypothesized that the increased PT Na+ reabsorption exhibited by the young SHR was due to altered sub-cellular distribution of Na+, K +-ATPase compared to the normotensive Wistar Kyoto (WKY). The hypothesis is supported, herein, by observations of greater Na+, K +-ATPase α 1 abundance in PT plasma membrane and lower abundance in late endosomes of 4wk SHR despite no difference in total PT α 1 abundance. There is a greater amount of Ser-18 unphosphorylated α 1 in the 4wk SHR PT. Total PT Na+, K+-ATPase γ abundance is greater in SHR at 4wk and 16wk but γ abundance in plasma membrane is greater only at 4wk. The phosphatase, calcineurin, was chosen for study because it is involved in the stimulation of Na+, K +-ATPase. No difference in calcineurin coding sequence, expression, or activity was observed in SHR. Gene expression arrays were next used to find candidate genes involved in the regulation of Na+, K +-ATPase. The first candidate analyzed was soluble epoxide hydrolase (sEH). The gene encoding sEH (EPHX2) showed lower expression in SHR. There was also a reduction in sEH protein abundance but there was no correlation between protein abundance and blood pressure in F2 progeny. Two EPHX2 alleles were identified, an ancestral allele and a variant allele containing four polymorphisms. sEH activity was greater in animals carrying the variant allele but the inheritance of the variant allele did not correlate with blood pressure. Gene expression arrays also led to the examination of genes involved in redox balance/Na+, K+-ATPase regulation. A pattern of lower expression of genes involved in reactive radical detoxification in SHR was discerned. Six transcription factor binding sites were identified that occurred more often in these genes. Three transcription factors that bind to the HNF1 site were expressed at lower levels in SHR. This points to the HNF1 transcriptional complex as an important trans-acting regulator of a wide range of genes involved in altered redox balance in SHR. ^

Ontogenetic Effects of Hatching Plasticity in the Spotted Salamander (Ambystoma maculatum) due to Egg and Larval Predators

The ability to respond plastically to the environment has allowed amphibians to evolve a response to spatial and temporal variation in predation threat (Benard 2004). Embroys exposed to egg predation are expected to hatch out earlier than their conspecifics. Larval predation can induce a suite of phenotypic changes including growing a larger tail area. When presented with cues from both egg and larval predators, embryos are expected to respond to the egg predator by hatching out earlier because the egg predator presents an immediate threat. However, hatching early may be costly in the larval environment in terms of development, morphology, and/or behavior. We created a laboratory experiment in which we exposed clutches of spotted salamander (Ambystoma maculatum) eggs to both egg (caddisfly larvae) and larval (A. opacum) predators to test this hypothesis. We recorded hatching time and stage and took developmental and morphological data of the animals a week after hatching. Larvae were entered into lethal predation trials with a larval predatory sunfish (Lepomis sp.) in order to study behavior. We found that animals exposed to the egg predator cues hatched out earlier and at earlier developmental stages than conspecifics regardless of whether there was a larval predator present. Animals exposed to larval predator cues grew relatively larger tails and survived longer in the lethal predation trials. However the group exposed to both predators showed a cost of early hatching in terms of lower tail area and shorter survival time in predation trials. The morphological and developmental effects measured of hatching plasticity were transient as there were no developmental or morphological differences between the treatment groups at metamorphosis. Hatching plasticity may be transient but it is important to the development and survival of many amphibians.

Characterization of Staphylococcus aureus adhesins important for respiratory tract infection

Staphylococcus aureus is a leading cause of lower respiratory tract infections in both adult and pediatric populations. In the past two decades, reports have described emergent incidence of severe necrotizing pneumonia in previously healthy individuals, frequently caused by antibiotic resistant strains. Additionally, S. aureus remains the most common cause of ventilator-associated pneumonia, contributing morbidity and mortality in intensive care units. As treatment of infection is made more difficult by the resistance to multiple antibiotics including vancomycin, there is a pressing need for novel strategies to prevent and treat S. aureus infections. Targeting essential mechanisms that promote infection such as adhesion, colonization, invasion, evasion of immune system and signaling may lead to inhibition of pathogenic surge. Staphylococcal adhesins of the MSCRAMM family (microbial surface components recognizing adherent matrix molecules) represent viable targets for such investigations. Understanding the molecular mechanism of binding is the first step toward the development of such therapies. Analysis of bacterial strains isolated from patients with staphylococcal pneumonia show increased expression of protein A, SdrD, SdrC and ClfB, cell surface proteins members of the MSCRAMM family. In this study the interaction of these MSCRAMMs with candidate ligands has been examined. We found that SdrD mediates S. aureus adherence to the lung epithelial cell line A549. Consistently, bacteria expressing SdrD have increased persistence in the lungs of infected mice after bronchoalveolar lavage in comparison with bacteria lacking this protein. Inhibition studies revealed that bacterial attachment can be abolished using neutralizing antibodies against SdrD. Using phage display, neurexin β isoforms were identified as SdrC binding partners. Previous reports postulated that MSCRAMMS bind their ligands by a 'dock, lock and latch' mechanism of interaction. Our data suggested that ClfB, an MSCRAMM responsible for nasal colonization, binds cytokeratin 10 by a 'dock and lock' variant of this model, in which the 'latching' event is not necessary. In summary, we have characterized aspects of molecular interaction between several MSCRAMMS and host components. We hope that continued delineation of these interactions will lead to identification of novel therapeutic targets or preventive strategies against S. aureus infections. ^

Comparison of compliance and immune response of drug users on the standard and accelerated hepatitis B vaccine schedules - Houston, Texas

Despite the availability of hepatitis B vaccine for over two decades, drug users and other high-risk adult populations have experienced low vaccine coverage. Poor compliance has limited efforts to reduce transmission of hepatitis B infection in this population. Evidence suggests that immunological response in drug users is impaired compared to the general population, both in terms of lower seroprotection rates and antibodies levels.^ The current study investigated the effectiveness of the multi-dose hepatitis B vaccine and compared the effect of the standard and accelerated vaccine schedules in a not-in-treatment, drug-using adult population in the city of Houston, USA.^ A population of drug-users from two communities in Houston, susceptible to hepatitis B, was sampled by outreach workers and referral methodology. Subjects were randomized either to the standard hepatitis vaccine schedule (0, 1-, 6-month) or to an accelerated schedule (0, 1-, 2-month). Antibody levels were detected through laboratory analyses at various time-points. The participants were followed for two years and seroconversion rates were calculated to determine immune response.^ A four percent difference in the overall compliance rate was observed between the standard (73%) and accelerated schedules (77%). Logistic regression analyses showed that drug users living on the streets were twice as likely to not complete all three vaccine doses (p=0.028), and current speedball use was also associated with non-completion (p=0.002). Completion of all three vaccinations in the multivariate analysis was also correlated with older age. Drug users on the accelerated schedule were 26% more likely to achieve completion, although this factor was marginally significant (p=0.085).^ Cumulative adequate protective response was gained by 65% of the HBV susceptible subgroup by 12-months and was identical for both the standard and accelerated schedules. Excess protective response (>=100 mIU/mL) occurred with greater frequency at the later period for the standard schedule (36% at 12-months compared to 14% at six months), while the greater proportion of excess protective response for the accelerated schedule occurred earlier (34% at 6 months compared to 18% at 12-months). Seroconversion at the adequate protective response level of 10 mIU/mL was reached by the accelerated schedule group at a quicker rate (62% vs. 49%), and with a higher mean titer (104.8 vs. 64.3 mIU/mL), when measured at six months. Multivariate analyses indicated a 63% increased risk of non-response for older age and confirmed the existence of an accelerating decline in immune response to vaccination manifesting after 40 years (p=0.001). Injecting more than daily was also highly associated with the risk of non-response (p=0.016).^ The substantial increase in the seroprotection rate at six months may be worth the trade-off against the faster antibody titer decrease and is recommended for enhancing compliance and seroconversion. Utilization of the accelerated schedule with the primary objective of increasing compliance and seroconversion rates during the six months after the first dose may confer early protective immunity and reduce the HBV vulnerability of drug users who continue, or have recently initiated, increased high risk drug use and sexual behaviors.^

The influence of socioeconomic status on the relationship between diabetes and amputations: A systematic review of the literature

This paper synthesizes the current knowledge available regarding the impact of socioeconomic status on diabetes and amputations. In September 2009, searches in the OVID Medline and PubMed databases were performed using keywords associated with race/ethnicity, educational level, insurance status, veteran status, low income, diabetes, and lower extremity amputation. Articles published between 1996 and the search date were used. The pertinent articles were analyzed, summarized, and synthesized. ^ The majority of the articles agreed that African American, American Indian, and Latino minorities experience significantly higher rates of diabetes-related lower extremity amputation (LEA) when compared to whites. Few articles suggested that the disparity experienced by minorities and others of low SES was due to biology; most articles link it to a combination of lower income, lower educational attainment, uninsured or underinsured status, and a greater prevalence of detrimental health behaviors such as smoking. These, in turn, are linked to decreased knowledge of self-care, delayed health care seeking, delayed diagnoses and treatment, discrimination, and low quality health care. Interventions focused on patient education, established regimens of treatment, foot care, and control of diabetes have been shown to be effective, although none have lowered the rate of diabetes-related LEA to rates found in the general population.^

Findings of the University of Texas Health Science Center at San Antonio's Dental School pilot mobile van program in Laredo, Texas

Lack of access to oral health care frequently affects those of lower socio-economic level; individuals in this group experience more dental decay, and the caries experience is more likely to be untreated. Inadequate dental care access may be attributed to exclusion that is due to income, geography, age, race or ethnicity. Objective: The present study aims were to: (1) determine how oral disease prevalence and access to dental services in four US-Mexico Border unincorporated low socioeconomic settlements identified as colonias compare to each other and Laredo, Texas, and (2) determine if insurance status affects dental care access and/or disease prevalence. Methods: A secondary analysis of data from a retrospective chart review of 672 patients attending a Mobile Dental Van Program in the Webb County colonias. Demographic information, (ethnicity, age, gender, insurance coverage and colonia site), dental visits within past year, insurance status, presence of dental sealants, prevalence of untreated dental decay (caries), and presence of gum disease (gingivitis and periodontitis) were extracted. Pearson's chi-square tests (χ2) were computed to compare the prevalence of these outcomes between colonias and Laredo and their potential association with insurance status. Results: For 6 - 11 year olds, dental visits in the past year were lower for colonias (39%), than Laredo (58.5%) (p<0.002). Caries prevalence was higher for colonias (56.6%), than Laredo (37.1%) (p<0.001). Gum disease prevalence was higher in colonias (73%), than in Laredo (21.4%) (p<0.001). No significant differences were noted for caries (χ2=1.73; p<0.188) and gum disease (χ2=0.0098; p<0.921) by patient's insurance status. For adults 36 - 64 years of age, dental visits in the past year were lower in colonias (22.4%), than Laredo (36.3%) (p<0.001). Caries prevalence was higher for colonias (78.3%), than Laredo (54.0%) (p<0.001). Gum disease prevalence was also higher among colonias (91.3%) than Laredo (61.3%) (p<0.001). No significant differences were noted for caries (χ2=0.0010; p<0.975) and gum disease (χ2=0.0607; p<0.805) by patient's insurance status. Conclusion: Colonia residents seeking dental care at a Mobile Dental Van Program in Webb County have significantly higher prevalence of oral disease regardless of insurance status.^

A qualitative and quantitative assessment of cancer patients' perceptions of barriers to treatment

This study examined barriers that cancer patients experience in obtaining treatment. The principal aim of the study was to conduct a comprehensive quantitative and qualitative assessment of barriers to cancer treatment for Texas cancer patients. The three specific aims of the study were to: (1) conduct a review and critique of published and unpublished research on barriers to cancer treatment; (2) conduct focus groups for the qualitative assessment of cancer patients' perceived barriers to cancer treatment; and (3) survey a representative sample of cancer patients regarding perceived barriers to treatment. The study was guided by the Aday and Andersen access framework of predisposing, enabling, and need determinants of care-seeking.^ To address the first specific aim, a total of 732 abstracts were examined, from which 154 articles were selected for review. Of these 154 articles, 57 that related directly to research on barriers to cancer treatment were chosen for subsequent analysis. Criteria were applied to each article to evaluate the strength of the study design, sampling and measurement procedures. The major barriers that were consistently documented to influence whether or not cancer patients sought or continued required treatment included problems with communication between the patient and provider, lack of information on side effects, the cost of treatment and associated difficulties in obtaining and maintaining insurance coverage, and the absence of formal and informal networks of social support. Access barriers were generally greater for older, minority women, and patients of lower socioeconomic status.^ To address the second specific aim, a total of eight focus groups (n = 44) were conducted across the State of Texas with cancer patients identified by the Texas Community Oncology Network, American Cancer Society, and community health centers. One important finding was that cost is the greatest hurdle that patients face. Another finding was that with the health care/insurance crisis, an increasing number of physicians are working with their patients to develop individually-tailored payment plans. For people in rural areas, travel to treatment sites is a major barrier due to the travel costs as well as work time forfeited by patients and their family members. A third major finding was the patients' family and church play important roles in providing social and emotional support for cancer patients.^ To address the third aim, a total of 910 cancer patients were surveyed during October and November, 1993. Approximately 65% of the cancer patients responded to the survey. The findings showed that the major barriers to treatment included costs of medications and diagnostic tests, transportation, lack of social support, problems understanding the written information regarding their disease as well as losing coverage or having higher premiums or copayments once they were diagnosed (particularly among blacks).^ Significant differences in reported barriers were found between racial groups. The minority respondents (i.e., blacks and Hispanics) tended to experience more barriers to treatment compared to the white respondents. More specifically, Hispanics were more likely to report transportation as a barrier to treatment than both white and blacks. Future research is needed to better understand the problems that minority cancer patients experience in receiving treatment. (Abstract shortened by UMI.) ^

ASSOCIATIONS AND INTERRELATIONSHIPS OF SOCIOECONOMIC STATUS, BEHAVIORAL FACTORS AND BIOLOGICAL FACTORS WITH BIRTH WEIGHT

Although the influences of socioeconomic, behavioral and biological factors on birth weight have been extensively studied, most studies have been limited to clinical populations. This study examines such relationships in a national probability sample, the National Health and Nutrition Examination Survey of 1971-1974. The study sample consisted of 2161 white children and 812 black children, aged 1 to 5 years. Analyses were performed on a subsample consisting of 753 white and 138 black children whose mothers were also selected into the survey. Detailed analyses examined interrelationships among socio-economic, behavioral and biological factors by means of multiple regression and partial correlation procedures in the white population. These analyses were not carried out among blacks because of an observed clustering bias introduced in the black subsample that hampered generalization to the US population.^ The results among the whites indicated that the biological factors of maternal height, maternal weight, maternal size (weight/height('2)), maternal age and sex of child were independently related to birth weight and were also interrelated with socioeconomic factors such as family income, education of the mother and education of the head of the household. The joint effect was significantly associated with birth weight.^ Mothers' dietary practices represented the behavioral factors. Selected nutrients from the mothers' 24-hour dietary recall were used to develop indices of dietary quality. Dietary quality was significantly interrelated with socioeconomic status, biological factors and birth weight.^ The findings of this study suggest that smaller, younger mothers of lower socioeconomic status and female children were significantly associated with lower birth weight. The findings also suggest that dietary quality is a mediating factor among socioeconomic status and biological factors in that mothers with more financial and educational resources have better dietary practices. Such mothers may also practice other health behaviors that would prevent having a low birthweight baby. This dissertation contributes primarily to the further conceptualization and empirical testing of the interrelationships among socioeconomic, behavioral and biological factors with respect to birth weight. ^

THE EVALUATION OF PUBLIC HEALTH COMPONENTS OF INTERNATIONAL DISASTER RELIEF OPERATIONS: INDOCHINESE REFUGEES IN THAILAND, 1979-1982

Refugee populations suffer poor health status and yet the activities of refugee relief agencies in the public health sector have not been subjected previously to comprehensive evaluation. The purpose of this study was to examine the effectiveness and cost of the major public health service inputs of the international relief operation for Indochinese refugees in Thailand coordinated by the United Nations High Commissioner for Refugees (UNHCR). The investigator collected data from surveillance reports and agency records pertaining to 11 old refugee camps administered by the Government of Thailand Ministry of Interior (MOI) since an earlier refugee influx, and five new Khmer holding centers administered directly by UNHCR, from November, 1979, to March, 1982.^ Generous international funding permitted UNHCR to maintain a higher level of public health service inputs than refugees usually enjoyed in their countries of origin or than Thais around them enjoyed. Annual per capita expenditure for public health inputs averaged approximately US$151. Indochinese refugees in Thailand, for the most part, had access to adequate general food rations, to supplementary feeding programs, and to preventive health measures, and enjoyed high-quality medical services. Old refugee camps administered by MOI consistently received public health inputs of lower quantity and quality compared with new UNHCR-administered holding centers, despite comparable per capita expenditure after both types of camps had stabilized (static phase).^ Mortality and morbidity rates among new Khmer refugees were catastrophic during the emergency and transition phases of camp development. Health status in the refugee population during the static phase, however, was similar to, or better than, health status in the refugees' countries of origin or the Thai communities surrounding the camps. During the static phase, mortality and morbidity generally remained stable at roughly the same low levels in both types of camps.^ Furthermore, the results of multiple regression analyses demonstrated that combined public health inputs accounted for from one to 23 per cent of the variation in refugee mortality and morbidity. The direction of associations between some public health inputs and specific health outcome variables demonstrated no clear pattern. ^

Inhibitor of cytochrome c messenger RNA -protein interaction in stimulated rat skeletal muscle

The purpose of this work was to examine the possible mechanisms for the regulation of cytochrome c gene expression in response to increased contractile activity in rat skeletal muscle. The working hypothesis was that increased contractile activity enhances cytochrome c gene expression through a cis-element. A 110% increase in cytochrome c mRNA concentration was observed in tibialis anterior (TA) muscle after 9 days of chronic stimulation. Similar difference (120%) exists between soleus (SO) muscle of higher contractile activity and white vastus lateralis (WV) muscle of lower contractile activity. These results suggest that the endogenous cytochrome c gene expression is regulated by contractile activity. Cytochrome c-reporter genes were injected into skeletal muscles to identify the cis-element that is responsible for the regulation. Although the data was inconclusive, part of it suggested the importance of the 3$\sp\prime$-untranslated region (3$\sp\prime$-UTR) in mediating the response to increased contractile activity.^ RNA gel mobility shift (GMSA) and ultraviolet (UV) cross-linking assays revealed specific RNA-protein interaction in a 50-nucleotide region of the 3$\sp\prime$-UTR in unstimulated TA muscle. Computer analysis predicted a stem-loop structure of 17 nucleotides, which provides a structural basis for RNA-protein interaction. These 17 nucleotides are 100% conserved among rat, mouse and human cytochrome c genes and their 13 pseudogenes, suggesting a functional role for this region. The RNA-protein interaction was significantly less in highly active SO muscle than in inactive WV muscle and was dramatically decreased in stimulated TA muscle due to a protein inhibitor(s) associated with ribosome. It is possible that cytochrome c mRNAs undergoing translation are subject to a compartmentalized regulatory influence.^ The conclusion from these results is that increases in contractile activity induce or activate a protein inhibitor(s) associated with ribosome in rat skeletal muscle. The inhibitor decreases RNA-protein interaction in the 3$\sp\prime$-UTR of cytochrome c mRNA, which may result in increased mRNA stability and/or translation. ^