Haematologic Indices in Pulmonary Tuberculosis with or without HIV Co-Infection in South Eastern Nigeria

To evaluate the changes in haematologic indices in patients with pulmonary tuberculosis (PTB) with or without Human Immune Deficiency Virus (HIV) co-infection in South Eastern Nigeria. The study population included 116 subjects (60 = males; 56 = females), recruited from 2 study centers: mile 4 Hospital Abakaliki Ebonyi State and Nnamdi Azikiwe University, Teaching  Hospital Nnewi, Anambra State, both in Nigeria. PTB + HIV (n = 20); PTB infection ( n = 27) and HIV sereopositive (n = 28). The PTB and HIV negative; control subjects were 41 (n = 41). Blood samples collected from subjects in Ethylene diamine tetra acetic acid (EDTA) container were used for the analysis of the Haemtological cells count,  packed cell volume (PCV) and Haemoglobin estimation using routine methods as described (Dacie and Lewis, 1984). HIV screening was done with Stat pak kit and confirmatory test by Western blot method. Erythrocyte sedimentation rate (ESR) was by Westergren method. Haemoglobin estimation (Hb), packed cell volume (PCV) values were significantly lower in patients with PTB (11.27±1.62 g/dl, 0.35±0.04 l/l) compared with control values (13.67±1.46 g/dl 0.41 ± 0.05 l/l) (p < 0.05). Patients with HIV seropositive showed significantly low PCV values of (0.36 ± 0.04 l/l) compared with the control subjects (0.41 ± 0.05 l/l) (p < 0.05). PTB patients showed higher TWBC counts (6062.5 ± 1481.83109/l) when compared those with HIV infection (3841.38±735.58 x 109/l) as well as normal control value (4363.64±551.66 x 109/l) (p < 0.05). Male and female values compared in this work showed no significant difference (p > 0.05). The results showed that the effect of PTB and HIV infection have caused some haematological deregulation. It also showed that sex has little or no effect on the studied parameters. Keywords: Pulmonary tuberculosis (PTB); Human ImmunoDeficiency Virus (HIV) and Hematologic Indice

Reduced serum tetanus antibody titre in HIV infected subjects with malaria co-infection in a malaria endemic area of Nigeria

Tetanus infection is widespread and difficult to completely eradicate. Thus the present study was designed to assess the tetanus antibody titre in HIV infected subjects in relation to the presence or absence of malaria parasitaemia. 107 subjects consisting of asymptomatic group (asymptomatic HIV, n=17 and asymptomatic HIV-Malaria co-infection, n=17), symptomatic group (symptomatic HIV, n=18 and symptomatic HIV-Malaria co-infection, n=17), and control group (control without malaria, n=19 and control with malaria, n=19) participated in the study. Blood sample collected from the participants were used for the determination of packed cell volume, CD4+ T cell count, malaria parasite, HIV seropositivity and tetanus antibody titre using standard laboratory methods. The tetanus antibody titre was significantly reduced in symptomatic HIV infected subjects with malaria co-infection compared with symptomatic HIV infected subjects without malaria (

Mode of onset of type 2 diabetes from normal or impaired glucose tolerance

Wartości stężenia glukozy na czczo (FPG, fasting plasma glucose) wskazują, jakie jest ryzyko wystąpienia cukrzycy typu 2. Nie wiadomo, czy hiperglikemia rozwija się stopniowo, czy też narasta skokowo. W grupie mężczyzn i nieciężarnych kobiet w wieku 35&#8211;64 lat, biorących udział w badaniu populacyjnym Mexico City Diabetes Study, podczas doustnego testu tolerancji glukozy (OGTT, oral glucose tolerace test) sprawdzano stężenie glukozy i insuliny w surowicy. Testy te przeprowadzono w czasie badania wstępnego (n = 2279) oraz po 3,25 (n = 1740) i 7 latach (n = 1711) obserwacji. Wśród osób z prawidłową tolerancją glukozy (NGT, normal glucose tolerance) w czasie wszystkich trzech badań (osoby niechorujące, n = 911) wartość FPG wzrosła nieznacznie (0,23 &plusmn; 0,79 mmol/l, średnia &plusmn; SD; p < 0,0001) w okresie 7 lat. Natomiast wystąpienie cukrzycy wśród osób z NGT (n = 98) poprzedzał znaczny wzrost FPG, niezależnie od czasu zachorowania (3,06 &plusmn; 2,57 i 2,94 &plusmn; 3,11 mmol/l, odpowiednio w 3,25. i 7. roku obserwacji; p < 0,0001 vs. osoby niechorujące). Podobnie u osób z upośledzoną tolerancją glukozy, które zachorowały na cukrzycę (n = 75), wartość FPG wzrosła o 3,14 &plusmn; 3,83 i 3,12 &plusmn; 3,61 mmol/l (p < 0,0001 vs. osoby niechorujące). U 3/4 osób, które zachorowały na cukrzycę, obserwowano wzrost FPG powyżej 90. percentyla rozkładu wzrostu glikemii u osób niechorujących na cukrzycę. U osób, które zachorowały na cukrzycę, stwierdzono wyższe wyjściowe wartości wskaźnika masy ciała (BMI, body mass index) (30,4 &plusmn; 4,9 vs. 27,3 &plusmn; 4,0 kg/m2; p < 0,001) i insulinemii na czczo (120 &plusmn; 78 vs. 84 &plusmn; 84 pmol/l; p < 0,02) niż u osób niechorujących, mimo że nie zaobserwowano zmian żadnego z tych parametrów przed zachorowaniem. Przeciwnie, zmiany stężenia insuliny, w stosunku do wcześniejszych oznaczeń, w 2. godzinie testu tolerancji glukozy wykazywały istotną statystycznie odwrotną zależność (p < 0,0001) z odpowiadającymi zmianami w FPG. W czasie 3-letniej obserwacji stwierdzono, iż początek cukrzycy charakteryzuje się częściej skokowym niż stopniowym wzrostem glikemii, co można w pewnym stopniu wyjaśnić zmniejszeniem uwalniania insuliny w odpowiedzi na stymulację glukozą.Fasting plasma glucose concentrations (FPG) predict development of type 2 diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or as a step increase is not known. We measured plasma glucose and insulin levels during oral glucose testing in 35-to 64-year-old men and nonpregnant women from a population-based survey (Mexico City Diabetes Study) at baseline (n = 2,279) and after 3.25 (n = 1,740) and 7 years (n = 1,711) of follow-up. In subjects with normal glucose tolerance (NGT) on all three occasions (nonconverters; n = 911), FPG increased only slightly (0.23 &#177; 0.79 mmol/l, mean &#177; &#177; SD; P < 0.0001) over 7 years. In contrast, conversion to diabetes among NGT subjects (n = 98) was marked by a large step-up in FPG regardless of time of conversion (3.06 &#177; 2.57 and 2.94 &#177; 3.11 mmol/l, respectively, at 3.25 and 7 years; P < 0.0001 vs. nonconverters). Likewise, in subjects who converted to diabetes from impaired glucose tolerance (n = 75), FPG rose by 3.14 &#177; 3.83 and 3.12 &#177; 3.61 mmol/l (P < 0.0001 vs. nonconverters). Three-quarters of converters had increments in FPG above the 90th percentile of the corresponding increments in nonconverters. Converters had higher baseline BMI (30.4 &#177; &#177; 4.9 vs. 27.3 &#177; 4.0 kg/m2; P < 0.001) and fasting plasma insulin values (120 &#177; 78 vs. 84 &#177; 84 pmol/l; P < 0.02) than nonconverters; however, no consistent change in either parameter had occurred before conversion. In contrast, changes in 2-h postglucose insulin levels between time of conversion and preceding measurement were significantly (P < < 0.0001) related to the corresponding changes in FPG in an inverse manner. We conclude that, within a 3-year time frame, the onset of diabetes is very often rapid rather than gradual and is in part explained by a fall in glucose-stimulated insulin response

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

Background High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). Methods Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. Results Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness &lt; 65 \u3bcm (odds ratio = 1.32 per each 10 \u3bcmol/L mannose change [95% confidence interval, 1.05\u20131.65]) and was an independent predictor of death (hazard ratio for mannose 65vs &lt; 84.6 \u3bcmol/L: 4.0(95%CI, 1.4\u201311.3), p = 0.006)

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML

Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes

Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 × 10−5], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes

13C-direct detected NMR experiments for the sequential J-based resonance assignment of RNA oligonucleotides

We present here a set of 13C-direct detected NMR experiments to facilitate the resonance assignment of RNA oligonucleotides. Three experiments have been developed: (1) the (H)CC-TOCSY-experiment utilizing a virtual decoupling scheme to assign the intraresidual ribose 13C-spins, (2) the (H)CPC-experiment that correlates each phosphorus with the C4′ nuclei of adjacent nucleotides via J(C,P) couplings and (3) the (H)CPC-CCH-TOCSY-experiment that correlates the phosphorus nuclei with the respective C1′,H1′ ribose signals. The experiments were applied to two RNA hairpin structures. The current set of 13C-direct detected experiments allows direct and unambiguous assignment of the majority of the hetero nuclei and the identification of the individual ribose moieties following their sequential assignment. Thus, 13C-direct detected NMR methods constitute useful complements to the conventional 1H-detected approach for the resonance assignment of oligonucleotides that is often hindered by the limited chemical shift dispersion. The developed methods can also be applied to large deuterated RNAs

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p < 0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml(3)) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100-200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p < or = 0.001) were more likely to be adherent.These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence