Depression in Mexican Americans with diagnosed and undiagnosed diabetes.

BACKGROUND: Depression and diabetes commonly co-occur; however, the strength of the physiological effects of diabetes as mediating factors towards depression is uncertain. METHOD: We analyzed extensive clinical, epidemiological and laboratory data from n = 2081 Mexican Americans aged 35-64 years, recruited from the community as part of the Cameron County Hispanic Cohort (CCHC) divided into three groups: Diagnosed (self-reported) diabetes (DD, n = 335), Undiagnosed diabetes (UD, n = 227) and No diabetes (ND, n = 1519). UD participants denied being diagnosed with diabetes, but on testing met the 2010 American Diabetes Association and World Health Organization definitions of diabetes. Depression was measured using the Center for Epidemiological Studies - Depression (CES-D) scale. Weighted data were analyzed using dimensional and categorical outcomes using univariate and multivariate models. RESULTS: The DD group had significantly higher CES-D scores than both the ND and UD (p ⩽ 0.001) groups, whereas the ND and UD groups did not significantly differ from each other. The DD subjects were more likely to meet the CES-D cut-off score for depression compared to both the ND and UD groups (p = 0.001), respectively. The UD group was also less likely to meet the cut-off score for depression than the ND group (p = 0.003). Our main findings remained significant in models that controlled for socio-demographic and clinical confounders. CONCLUSIONS: Meeting clinical criteria for diabetes was not sufficient for increased depressive symptoms. Our findings suggest that the 'knowing that one is ill' is associated with depressive symptoms in diabetic subjects.

Hepatitis C virus in Mexican Americans: a population-based study reveals relatively high prevalence and negative association with diabetes.

This study aimed to estimate the prevalence and risk factors for hepatitis C virus (HCV) infection in Mexican Americans living in South Texas. We tested plasma for the presence of HCV antibody from the Cameron County Hispanic Cohort (CCHC), a randomized, population-based cohort in an economically disadvantaged Mexican American community on the United States/Mexico border with high rates of chronic disease. A weighted prevalence of HCV antibody of 2·3% [n = 1131, 95% confidence interval (CI) 1·2-3·4] was found. Participants with diabetes had low rates of HCV antibody (0·4%, 95% CI 0·0-0·9) and logistic regression revealed a statistically significant negative association between HCV and diabetes (OR 0·20, 95% CI 0·05-0·77) after adjusting for sociodemographic and clinical factors. This conflicts with reported positive associations of diabetes and HCV infection. No classic risk factors were identified, but important differences between genders emerged in analysis. This population-based study of HCV in Mexican Americans suggests that national studies do not adequately describe the epidemiology of HCV in this border community and that unique risk factors may be involved.

Persisting role of healthcare settings in hepatitis C transmission in Pakistan: cause for concern.

Transmission of hepatitis C (HCV) in Pakistan is a continuing public health problem; 15 years ago it was linked to the practice of reusing therapeutic instruments in healthcare settings. We sought to examine current risk factors for HCV transmission in a hospital population in Karachi, Pakistan. We enrolled 300 laboratory-confirmed HCV-positive participants and 300 laboratory confirmed HCV-negative participants from clinics at Indus Hospital. Independent and significant risk factors for both men and women were: receiving o12 injections in the past year, blood transfusions, having had dental work performed, and delivery in hospital or transfusion for women. Interestingly, being of Mohajir origin or born in Sindh province were protective.Encouragingly, a strong protective effect was observed for those that reported bringing their own needle for injections (59%). The widespread reuse of therapeutic needles in healthcare settings in Karachi remains a major driver of the HCV epidemic.

Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.

Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients. We compared the immune responses of patients who died from Ebola virus disease with those who survived during two large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells, which was indicated by the upregulation of FasL, perforin, CD28 and gamma interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal infection was characterized by impaired humoral responses, with absent specific IgG and barely detectable IgM. Early activation of T cells, indicated by mRNA patterns in peripheral blood mononuclear cells and considerable release of gamma interferon in plasma, was followed in the days preceding death by the disappearance of T cell-related mRNA (including CD3 and CD8). DNA fragmentation in blood leukocytes and release of 41/7 nuclear matrix protein in plasma indicated that massive intravascular apoptosis proceeded relentlessly during the last 5 days of life. Thus, events very early in Ebola virus infection determine the control of viral replication and recovery or catastrophic illness and death.

Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections.

Efforts to solve the epidemiologic puzzle of AIDS in Africa are complicated by the presence of multiple human retroviruses. Simple serologic tests that unambiguously distinguish among infections by these retroviruses are essential. To that end, a partially conserved immunoreactive epitope was identified in the transmembrane glycoproteins of human immunodeficiency viruses (HIV) types 1 and 2. Synthetic peptides derived from these conserved domains were used in sensitive and specific immunoassays that detect antibodies in sera from patients infected with HIV-1 or HIV-2. By making single amino acid substitutions in the HIV-1 peptide, it was possible to demonstrate HIV-1 strain-specific antibody responses to this epitope. Such custom-designed peptides synthesized from this domain are likely to detect newly discovered HIV types, define infection with specific HIV strains, and allow detection of group-common antibodies.

The "how" and "whys" of research: life scientists' views of accountability.

OBJECTIVES: To investigate life scientists' views of accountability and the ethical and societal implications of research. DESIGN: Qualitative focus group and one-on-one interviews. PARTICIPANTS: 45 Stanford University life scientists, including graduate students, postdoctoral fellows and faculty. RESULTS: Two main themes were identified in participants' discussions of accountability: (1) the "how" of science and (2) the "why" of science. The "how" encompassed the internal conduct of research including attributes such as honesty and independence. The "why," or the motivation for conducting research, was two-tiered: first was the desire to positively impact the research community and science itself, and second was an interest in positively impacting the external community, broadly referred to as society. Participants noted that these motivations were influenced by the current systems of publications, grants and funding, thereby supporting a complex notion of boundary-setting between science and non-science. In addition, while all participants recognised the "how" of science and the two tiers of "why," scientists expressed the need to prioritise these domains of accountability. This prioritisation was related to a researcher's position in the academic career trajectory and to the researcher's subsequent "perceived proximity" to scientific or societal concerns. Our findings therefore suggest the need for institutional change to inculcate early-stage researchers with a broader awareness of the implications of their research. The peer review processes for funding and publication could be effective avenues for encouraging scientists to broaden their views of accountability to society.

Uric acid and renal function in multiple sclerosis.

OBJECTIVE: The purpose of this study was to examine the circadian distribution of creatinine and uric acid clearances in subjects with Multiple Sclerosis. MATERIALS AND METHODS: Eleven subjects with MS, 6 women (48+/-7y) and 5 men (58+/-5y) volunteered for this circadian study. Thirteen healthy females (39+/-11y) served as controls. Data of seven healthy male controls (64+/-8 y) were extracted from a similar circadian study conducted previously. Each MS patient, and each male control had blood samples drawn around the clock, at 3h intervals (8/24h), and each collected urines over 3h periods (8/24h). Each female control contributed only one blood sample and one complete 24h urine collection. Blood and urine samples were analyzed for a number of relevant analytes: ELAM, IL-6, NO, insulin, ACTH, aldosterone, cortisol, electrolytes, lymphocytes, monocytes including creatinine and uric acid clearances. Those were standardized to an average body surface area of 1.73 m2. RESULTS: The relevant analytes demonstrated increased synthesis of insulin, IL-6, ELAM, monocytes, and reduced concentrations of serum NO. The creatinine clearances were significantly lower in MS females than in female controls, 63+/-22 vs.108+/-18 ml/min. They were also lower than those of MS males and male controls, 107.8+/-17, 97.5+/-8.2 ml/min. Uric acid clearances in MS females were also lower 6.9+/-2.4 vs. 10.5+/-4.4 ml/min. The uric acid clearance in MS males was higher than in male controls, 7.0+/-4.5 vs. 4.0+/-1.0 ml/min. CONCLUSIONS: The alterations in selected relevant analytes and the reduced creatinine and uric acid clearances in females but not in males, suggest a renal dysfunction in MS females. These observations may contribute to understanding better the mechanism of renal dysfunction in female patients and perhaps this may be an additional factor contributing to greater frequency of MS in females than in male subjects.

Antibody response to serogroup A and C meningococcal polysaccharide vaccines in infants born of mothers vaccinated during pregnancy.

During the large epidemic of serogroups A and C meningococcal disease in Brazil, we studied the immunologic response to meningococcal polysaccharide vaccine in infants born to women vaccinated during pregnancy. Radioimmunoassay serum levels against serogroups A and C polysaccharide were more than threefold higher in vaccinated than in unvaccinated women at delivery. Cord blood levels were also threefold or higher in infants whose mothers were vaccinated while pregnant compared to infants born of unvaccinated mothers. Within 3 mo, the infants' A and C serum antibody levels declined by approximately 80%. When vaccinated at about 6 mo of age, infants born of vaccinated mothers had antibody responses to A and C polysaccharide vaccines indistinguishable from those born of unvaccinated mothers. The response did not vary with the trimester of vaccination. We conclude that the vaccination of pregnant women with groups A and C meningococcal polysaccharide vaccine does not produce immune tolerance in the subsequently born infants.

Epidemiology of emerging/re-emerging antimicrobial-resistant bacterial pathogens.

The rapid global expansion of bacteria resistant to antimicrobials is the most important development over the past year in emerging bacterial diseases. The critical events are the emergence of Staphylococcus aureus with decreased sensitivity to vancomycin, worldwide resistance to penicillin in Streptococcus pneumoniae, and the remorseless progression of multiply-resistant Mycobacterium tuberculosis. Most startling was the isolation from a human in Madagascar of a plague bacillus possessing a plasmid readily transferable to Escherichia coli, which confers multiple antibiotic resistance. The hospital environment continues to see the transmission of resistant organisms, notably vancomycin-resistant enterococci. Finally, as food markets become more open around the world, food-borne outbreaks of E. coli O157 and cholera demonstrate how difficult it can be to establish effective health and safety barriers.

Circadian distribution of iron and ferritin in serum of healthy and type 2 diabetic males.

AIM: We examined the circulating levels of iron and ferritin in serum of seven healthy and three insulin non-dependent diabetic (Type 2) males in order to compare their circadian characteristics. METHODS: Blood samples were collected every 3h over a 24h period and were analyzed for serum iron and ferritin. RESULTS: The mean Fe level was significantly higher in healthy than in diabetic subjects: 80.0 +/- 3.3 vs. 63.0 +/- 3.7 microg/dL. The ferritin level was significantly lower in healthy than in diabetic men: 79.8 +/- 4.7 vs. 186.3 +/- 110.5 microg/L. A significant (p < 0.001) time-effect was found by ANOVA and circadian rhythm was detected at p < 0.001 in all data sets when a 24h cosine was fitted to the normalized data. Acrophases were located in mid to late morning for Fe (11:30, vs. 09:22h) and for ferritin (11:10 vs. 11:46h). DISCUSSION: We concluded that there is significant circadian variation in both serum Fe and ferritin, with predictable peaks in the mid to late morning.

Circadian distribution of hematology variables in subjects with multiple sclerosis.

Hematology variables were measured in blood samples obtained every 3h (8/24h) from 10 multiple sclerosis (MS) patients and 34 healthy subjects and analyzed for circadian characteristics using the population multiple-components method. Red blood cell (RBC) and hemoglobin levels as well as hematocrits exhibited circadian rhythms with minimal amplitudes in healthy individuals and insignificant variability in the smaller group of MS patients. In contrast the total white blood cell (WBC) and platelet counts for MS patients and healthy individuals both showed significant circadian characteristics while the mean 24h WBC and platelet levels did not significantly differ between the two groups. When the different WBC subsets were examined independently, statistically significant circadian rhythms were seen for lymphocytes and eosinophils for both MS patients and healthy individuals and for neutrophils only in the latter. Moreover, the 24h mean levels of lymphocytes, basophils, and eosinophils were significantly higher for the healthy controls while those of monocytes were higher for the MS patients. However, of all the variables tested with significant circadian rhythms in both groups of individuals, only those of lymphocyte numbers exhibited different patterns with somewhat higher amplitude in healthy individuals and a peak level occurring over an hour after that of MS patients. These changes may be the reflection of a disturbance in the regulation of patterns of lymphocyte activity and migration in MS patients. In addition, the elevation in circulating monocytes in MS patients is consistent with the inflammatory nature of the disease.

The Effect of Ignoring Statistical Interactions in Regression Analyses Conducted in Epidemiologic Studies: An Example with Survival Analysis Using Cox Proportional Hazards Regression Model.

OBJECTIVE: To demonstrate the adverse impact of ignoring statistical interactions in regression models used in epidemiologic studies. STUDY DESIGN AND SETTING: Based on different scenarios that involved known values for coefficient of the interaction term in Cox regression models we generated 1000 samples of size 600 each. The simulated samples and a real life data set from the Cameron County Hispanic Cohort were used to evaluate the effect of ignoring statistical interactions in these models. RESULTS: Compared to correctly specified Cox regression models with interaction terms, misspecified models without interaction terms resulted in up to 8.95 fold bias in estimated regression coefficients. Whereas when data were generated from a perfect additive Cox proportional hazards regression model the inclusion of the interaction between the two covariates resulted in only 2% estimated bias in main effect regression coefficients estimates, but did not alter the main findings of no significant interactions. CONCLUSIONS: When the effects are synergic, the failure to account for an interaction effect could lead to bias and misinterpretation of the results, and in some instances to incorrect policy decisions. Best practices in regression analysis must include identification of interactions, including for analysis of data from epidemiologic studies.

HIV-1 and HIV-2 infection associated with AIDS in Abidjan, Côte d'Ivoire.

In September 1987, a seroprevalence study of HIV-1 and HIV-2 infection was conducted among 956 people from different groups in Abidjan, Côte d'Ivoire. Groups examined were hospitalized patients (Internal Medicine and Infectious Disease Departments, Centre Hospitalier Universitaire de Treichville, Abidjan), outpatients at tuberculosis treatment centers, blood donors, women attending an antenatal clinic, and patients attending sexually transmitted disease (STD) clinics. Total HIV infection prevalence ranged from 10% in STD clinic patients and pregnant women to 45% in hospitalized patients on an infectious diseases service. Within groups, HIV-1 infection was 2-6.5 times more prevalent than infection with HIV-2. One-quarter of HIV-seropositive people were serologically reactive to both HIV-1 and HIV-2 on enzyme-linked immunosorbent assay and Western blot. Clinical conditions previously observed in patients with HIV-1 infection were observed in people infected with HIV-2 only, as well as in those with HIV-1 infection and dual serologic reactivity. An isolate of HIV-2 was obtained on culture from a person with wasting disease and chronic fever. The results of this study suggest that infection with HIV-1 and HIV-2 is epidemic in Côte d'Ivoire, and that HIV-2 may be associated with AIDS.

Seroprevalence of HIV-1 and HIV-2 in Guinea Bissau in 1980.

To determine the past prevalence of HIV-1 and HIV-2 in West Africa, we tested 440 serum samples collected in 1980 from people living in rural areas of Guinea Bissau. The sera were screened for antibodies by enzyme immunoassay (EIA) using purified simian immunodeficiency virus (SIV) isolated from rhesus macaque monkeys (SIVmac) and then confirmed by immunoblot and immunofluorescence assays for antibodies to SIV, HIV-2, and HIV-1. Five of the serum samples were repeatedly reactive by all assays to both SIV and HIV-2. None were positive for antibodies to HIV-1 by immunofluorescence, immunoblot or radio-immunoprecipitation (RIP) assays, with the exception of one HIV-2-seropositive samples which reacted with HIV-1 glycoproteins by RIPA. Thus, in 1980, at least 1.4% (six out of 440) of a random sample of people in rural Guinea Bissau had been exposed to a virus highly related to HIV-2 and SIV. One of these subjects may have been dually infected with HIV-1 and HIV-2.

Evaluation of the WHO clinical case definition for AIDS in rural Zaire.

The clinical case definition for AIDS proposed by WHO for use in Africa was evaluated against HIV antibody status in 72 patients in rural Zaire. Twenty-one (29%) of the patients were antibody-positive. For diagnosing anti-HIV seropositivity, the case definition had a sensitivity of 52%, a specificity of 78%, a positive predictive value of 50% and a negative predictive value of 80%. Calculation of the positive predictive value at different levels of prevalence of HIV infection suggests that the case definition operates at maximum reliability in selected high-risk groups. Modifications to the case definition should be evaluated to try and improve its sensitivity and positive predictive value.

PIP: In many areas of Africa where AIDS is endemic, facilities for laboratory diagnosis are too limited to reliably diagnose opportunistic infections. Therefore, the World Health Organization defined a clinical case definition of AIDS in which 2 major signs and at least 1 minor sign must be present to diagnose AIDS. The major signs are: weight loss greater than 10%, diarrhea for more than 1 month, and prolonged fever for more than 1 month. The minor signs are: persistent cough for more than 1 month, generalized pruritic dermatitis, recurrent herpes zoster, oropharyngeal candidiasis, chronic disseminated herpes simplex, and generalized lymphadenopathy. (The presence of Kaposi's sarcoma or cryptococcal meningitis are sufficient by themselves for a diagnosis of AIDS.) 72 patients in 4 hospitals in Equateur Province of Zaire were used to test the reliability of the clinical case definition. 21 (29%) of the patients were HIV seropositive, and 22 (32%) fulfilled the clinical criteria. From these data the sensitivity of the case definition was 52%, specificity was 78%, positive predictive value was 50%, and negative predictive value was 80%. Since positive predictive value rises with prevalence and HIV infection is maximal in the 20-40 age group, restricting the case definition to this age group would increase its predictive value. Exclusion of patients with tuberculosis would reduce the number of false positive results.

Epidemiologic characteristics of infections caused by ampicillin-resistant Hemophilus influenzae.

Hrom February 1974 through May 1975, 58 isolates of ampicillin-resistant Hemophilus influenzae from patients were submitted to the Center for Disease Control from 23 states and the District of Columbia. The epidemiologic characteristics of these widely scattered cases were strikingly similar to those of cases previously reported from individual communities or institutions. Because of the nationwide distribution of resistant isolates and the adverse consequences of ineffective therapy, the use of chloramphenicol is recommended for the initial management of systemic illness definitely or probably due to H. influenzae type b.

Molecular characterization and expression of glycoprotein gene of Hantavirus R22 strain isolated from Rattus norvegicus in China.

A cDNA containing the complete open reading frame of the M genome segment of Hantavirus R22 strain isolated from Rattus norvegicus in China, was amplified by polymerase chain reaction (PCR), and then cloned. The M segment is 3656 nucleotides in length with a predicted region of 3402 bases encoding a precursor glycoprotein of 1134 amino acids subsequently processed into viral glycoproteins 1 and 2 (G1 and G2). A strain comparison between R22 and SR11 (isolated from a rat in Japan), and Hantaan 76-118 (isolated from Apodemus in Korea), and Hallnas B1 (isolated from a bank vole in Sweden) revealed 95%, 74%, and 53% homologies at the deduced amino acid sequence level respectively. This suggests that the rodent host species may be a more important determinant of genetic relationships than geographic proximity. Six potential asparagine linked glycosylation sites (five in G1 and one in G2) were identified, and among them all are conserved in SR11, five in Hantaan virus and four in Hallnas B1 virus. Although different degrees of homology exist among these four viruses at amino acid sequence level, more than 90% of the cysteine residues are conserved, suggesting that structural homology may be very strong between the Hantaviruses. Genetic differences in the M segment genome of R22 and SR11 viruses, within the same serotype viruses, were found as random coding changes; some limited to single amino acids, others in clusters. A recombinant vaccinia virus that contained the fully activated M segment cDNA of R22 was constructed. This recombinant virus expressed two glycoproteins G1 and G2 identical to R22 virus G1 and G2 in molecular weight, cleavage pattern and cellular immunofluorescent patterns.

Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection.

A cloned cDNA (1.65 kb) containing the complete glycoprotein gene of the Josiah strain of Lassa virus was inserted into the thymidine kinase (TK) gene of the New York Board of Health (WYETH) strain of vaccinia virus. The Lassa virus glycoprotein precursor, GPC, and the posttranslational cleavage products, G1 and G2, were shown by Western blot analysis to be properly expressed in cells infected with the recombinant virus. Northern blot hybridization of total cytoplasmic RNA extracted from recombinant virus infected cells demonstrated the presence of RNA transcripts of appropriate size considering the site of transcription initiation from the vaccinia P7.5 promoter, the size of the Lassa glycoprotein gene, and the presumed location of the transcription terminator in the vaccinia thymidine kinase gene. All guinea pigs vaccinated with the recombinant virus survived a lethal challenge infection with Lassa virus, whereas 80% of control animals died. The vaccinated guinea pigs did, however, develop transient, low-grade, fevers and detectable viremias following infection with Lassa virus, indicating that protection was not complete.

Structure, function, and expression of Drosophila melanogaster FMRFamide-related peptides.

In 1977, Price and Greenberg identified the tetrapeptide FMRFamide as a cardioexcitatory molecule from mollusc. Subsequent to this discovery, FMRFamide-related peptides (FaRPs) have been identified in both invertebrates and vertebrates. Peptides in the FaRP family contain a common RFamide C-terminus and act as modulators and messengers of neural and gastrointestinal functions. Like other organisms, Drosophila melanogaster contains several genes that encode for numerous FaRPs. Elucidating the processing and activities of multiple FaRPs encoded in a single precursor is critical to establishing their roles in physiology. In this manuscript, we describe the distribution of FMRFamide immunoreactive materials in the Drosophila central nervous system and gut, and correlate it with the expression of specific FaRPs and their activities. The unique distributions and biological activities of Drosophila FaRPs suggest that the precursors are highly processed and the structurally related peptides are not functionally redundant. The complete distribution of FaRPs in the central nervous system and gut as detected by FMRFamide antisera is not accounted for by the sum of the individual expression patterns of the known Drosophila peptides. Thus, these data suggest that one or more Drosophila FaRPs or structurally related peptides remain to be discovered.