Carotid intima media thickness (CIMT) in adults in the AWI-Gen Nairobi site study: Profiles and predictors / Grosor de la íntima-media carotídea (GIMc) en adultos en el estudio del sitio de AWI-Gen en Nairobi: perfiles y factores predictivos

Background: Carotid intima media thickness (CIMT) is used as a marker of subclinical and asymptomatic atherosclerotic vascular disease. Increased CIMT is associated with future cerebrovascular and cardiovascular events. There is limited data on the profile and correlates of CIMT in Africa. The aim of this study was to describe the profile and correlates of CIMT in apparently normal younger-age adults in an urban setting in Kenya. Methods: This study used population-based data collected from 2003 adults between the ages of 40 and 60 years in two slums of Nairobi as part of a genetic study. CIMT was measured using LOGIQ e (GE Healthcare, CT, USA) ultrasound on both left and right carotid arteries, whereby maximum, mean, and minimum values were recorded. Age- and sex-specific CIMT measurements were calculated and their association with basic sociodemographic, behavioral and body composition indicators were investigated. Results: The median (IQR) CIMT were 0.58 (0.51, 0.66) and 0.59 (0.53, 0.66) in men and women, respectively. About 16% of the study population had CIMT greater than 0.7mm, the cut off for higher CIMT. Nearly 60% had CIMT values ≥75th percentile. Age, current use of alcohol, systolic blood pressure, subcutaneous fat thickness, pulse rate and pulse pressure were found to be the main predictors of CIMT in our study population. Conclusion: This study provided population-based reference values and predictors for CIMT for an adult population living in urban poor settings in Kenya. Future studies need to consider biochemical and genetic predictors of CIMT in this population. (AU)

Antecedentes: El grosor de la íntima-media carotídea (GIMc) se utiliza como marcador de la aterosclerosis subclínica y asintomática. El incremento del GIMc está asociado a episodios cerebrovasculares y cardiovasculares futuros. Existen datos limitados sobre el perfil y la correlación del GIMc en África. El objetivo de este estudio fue describir el perfil y la correlación del GIMc en adultos jóvenes aparentemente normales en un contexto urbano de Kenia. Métodos: Este estudio utilizó datos basados en población de 2.003 adultos con edades comprendidas entre 40 y 60 años en dos suburbios de Nairobi, como parte de un estudio genético. El GIMc se midió utilizando el ecógrafo LOGIQ E (GE Healthcare, CT, EE. UU.) en ambas carótidas, izquierda y derecha, donde se registraron los valores máximo, medio y mínimo. Se calcularon las medidas de GIMc específicas de la edad y el sexo, así como su asociación con los indicadores sociodemográficos, conductuales y corporales básicos. Resultados: Los valores medios (RIC) de GIMc fueron 0,58 (0,51, 0,66) y 0,59 (0,53, 0,66) en hombres y mujeres, respectivamente. Cerca del 16% de la población de estudio tuvo un GIMc superior a 0,7mm, siendo el punto de corte de GIMc elevado. Cerca del 60% reflejó valores de GIMc ≥percentil 75. La edad, el consumo actual de alcohol, la presión arterial sistólica, el grosor de la grasa subcutánea, la frecuencia cardiaca y la presión del pulso fueron los principales factores predictivos de GIMc en la población de nuestro estudio. Conclusión: Este estudio aportó valores de referencia basados en población y factores predictivos de GIMc para una población adulta en un entorno urbano de pocos recursos de Kenia. Los estudios futuros deberán considerar los factores predictivos bioquímicos y genéticos de GIMc en dicha población. (AU)

Carotid intima media thickness (CIMT) in adults in the AWI-Gen Nairobi site study: Profiles and predictors.

BACKGROUND: Carotid intima media thickness (CIMT) is used as a marker of subclinical and asymptomatic atherosclerotic vascular disease. Increased CIMT is associated with future cerebrovascular and cardiovascular events. There is limited data on the profile and correlates of CIMT in Africa. The aim of this study was to describe the profile and correlates of CIMT in apparently normal younger-age adults in an urban setting in Kenya. METHODS: This study used population-based data collected from 2003 adults between the ages of 40 and 60 years in two slums of Nairobi as part of a genetic study. CIMT was measured using LOGIQ e (GE Healthcare, CT, USA) ultrasound on both left and right carotid arteries, whereby maximum, mean, and minimum values were recorded. Age- and sex-specific CIMT measurements were calculated and their association with basic sociodemographic, behavioral and body composition indicators were investigated. RESULTS: The median (IQR) CIMT were 0.58 (0.51, 0.66) and 0.59 (0.53, 0.66) in men and women, respectively. About 16% of the study population had CIMT greater than 0.7mm, the cut off for higher CIMT. Nearly 60% had CIMT values ≥75th percentile. Age, current use of alcohol, systolic blood pressure, subcutaneous fat thickness, pulse rate and pulse pressure were found to be the main predictors of CIMT in our study population. CONCLUSION: This study provided population-based reference values and predictors for CIMT for an adult population living in urban poor settings in Kenya. Future studies need to consider biochemical and genetic predictors of CIMT in this population.

Emergence of Multidrug- and Pandrug- Resistant Pseudomonas aeruginosa from Five Hospitals in Qatar.

BACKGROUND: A global rise in multidrug-resistant (MDR) nosocomial infections has led to a significant increase in morbidity and mortality. MDR Gram-negative bacteria (GNB) are recognised for rapidly developing drug resistance. Despite Pseudomonas aeruginosa being the second most common GNB isolated from healthcare associated infections, the magnitude of MDR P. aeruginosa (MDR-PA) has not been evaluated in Qatar. AIM: To assess the prevalence and antimicrobial susceptibility patterns of MDR-PA from 5 major hospitals in Qatar. METHODS: A total of 2533 P. aeruginosa clinical isolates were collected over a one-year period. MDR-PA was defined as resistance to at least one agent of ≥ 3 antibiotic classes. Clinical and demographic data were collected prospectively. FINDINGS: The overall prevalence of MDR-PA isolates was 8.1% (205/2533); the majority of isolates were from patients exposed to antibiotics during 90 days prior to isolation (85.4 %, 177/205), and the infections were mainly hospital-acquired (95.1%, 195/205) with only 4.9% from the community. The majority of MDR-PA isolates were resistant to cefepime (96.6%, 198/205), ciprofloxacin, piperacillin/tazobactam (91%, 186/205), and meropenem (90%, 184/205). Patient comorbidities with MDR-PA were diabetes mellitus (47.3%, n=97), malignancy (17.1%, n=35), end-stage renal disease (13.7%, n=28) and heart failure (10.7%, n=22). CONCLUSION: There was a significant prevalence of MDR-PA in Qatar, primarily from healthcare facilities and associated with prior antibiotic treatment. There was an alarming level of antimicrobial resistance to carbapenems. Our results are part of a national surveillance of MDR to establish effective containment plans.

Body mass index and wealth index: positively correlated indicators of health and wealth inequalities in Nairobi slums.

INTRODUCTION: Wealth index is a known predictor of body mass index (BMI). Many studies have reported a positive association between BMI and socioeconomic status (SES). However, an in-depth investigation of the relationship between BMI and wealth index is lacking for urban slum settings. OBJECTIVE: To examine the association between BMI and wealth index in an urban slum setting in Nairobi, Kenya. METHODS: A total of 2003 adults between 40 and 60 years of age were included. BMI was derived from direct weight and height measurements. Wealth Index was computed using the standard principal component analysis of household amenities ownership. The relationship between BMI and wealth index was assessed using both linear and logistic regression models. RESULTS: We found that BMI linearly increased across the five quintiles of wealth index in both men and women, after adjusting for potential confounding factors. The prevalence of obesity increased from 10% in the first wealth quintile to 26.2% in the fifth wealth quintile. The average BMI for women entered the overweight category at the second quintile wealth status, or the third quintile for the total population. CONCLUSION: There exists a strong positive relationship between BMI and wealth index in slum settings. Health promotion interventions aimed at reducing obesity may consider using wealth index in priority setting.

Metformin in the Management of Childhood Obesity: A Randomized Control Trial.

BACKGROUND: Childhood obesity-related metabolic derangements are increasing among South Asian populations. Dietary and physical activity plans have limited effect. This study aims to assess the effectiveness of metformin in the management of obesity among 8- to 16-year-old children in Gampaha District of Sri Lanka. MATERIALS AND METHODS: A triple-blinded controlled trial was conducted on 150 obese school children. After 12-hour overnight fast, blood was drawn for fasting blood glucose (FBG) and lipid profile. Anthropometry, fat mass (FM), and blood pressure were measured. BMI and insulin resistance were calculated. Children randomly received either metformin (8-10 years-500 mg 12 hourly; 11-16 years-1 g 12 hourly) or placebo. Anthropometry and blood investigations were repeated at 6 and 12 months. Mean difference in outcome measures, adjusted for baseline values, was compared using ANCOVA. RESULTS: There were 84/150 boys. Metabolic syndrome was present in 25 (16.7%). A statistically significant adjusted mean reduction was observed in the metformin group compared with placebo, in weight (-0.991 vs. 1.394, p = 0.000), BMI/Age-standard deviation score (SDS; -0.287 vs. -0.116, p = 0.000), %FM/Age-SDS (-0.092 vs. 0.016, p = 0.04), systolic blood pressure (SBP; -0.415 vs. 0.015, p = 0.015), total cholesterol (-0.95 vs. -0.7, p = 0.001), low-density lipoprotein (-0.67 vs. -0.45, p = 0.001), and highly sensitive C-reactive protein (-1.36 vs. 0.08, p = 0.013) at 6 months, and in BMI/Age-SDS (-370 vs. -0.222, p = 0.001), WC/Age-SDS (-0.473 vs. -0.337, p = 0.018), SBP (-0.834 vs. -0.477, p = 0.023), and triglycerides (-0.33 vs. -0.14, p = 0.019) at 12 months. CONCLUSIONS: Metformin compared with placebo has beneficial effects on anthropometric and metabolic indicators in the management of childhood obesity.

Synthesis and antitumor activity against HepG-2, PC-3, and HCT-116 cells of some naphthyridine and pyranopyridinecarbonitrile derivatives.

A series of substituted and fused heterocyclic derivatives 2-17 were synthesized using 3,5-bis(4-methoxybenzylidene)-1-propylpiperidin-4-one (1) as starting material. Treatment of 1 with malononitrile or semicarbazide afforded compounds 2 and 3, respectively. Condensation of 1 with ethyl cyanoacetate afforded naphthyridine-3-carbonitrile derivative 4, which reacted with phosphorus pentachloride and phosphoryl chloride to give chloro derivative 5. Treatment of 5 with thiosemicarbazide afforded compound 6. The reaction of 1 with malononitrile gave cyano aminopyrane derivative 7 which was condensed with pyromellitic dianhydride, phthalic anhydride, succinic anhydride, or morpholine in glacial acetic acid to obtain imide derivatives 8-11. Additionally, the reaction of 7 with aromatic aldehydes gave derivatives 12a-12c. Acetylation of 7 with acetic anhydride in boiling acetic acid gave N-acetyl derivative 13 which was cyclized to pyridine derivative 14 by refluxing in dioxane in the presence of triethylamine. Treatment of 7 with hydrazine hydrate gave pyrazolo derivative 15. Finally, the reaction of 7 with triethyl orthoformate in the presence of acetic anhydride gave formimidate 16 which was treated with hydrazine hydrate to form N-amino derivative 17. Some of the synthesized compounds were examined in vitro for their antitumor activity against HepG-2, PC-3, and HCT-116 human carcinoma cell lines using MTT assay.

Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia.

BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) in European population has an incidence of at least 1 in 260 000 live births and is most commonly due to mutations in KCNJ11 and ABCC8. However, data on this condition in other populations are limited. OBJECTIVE: To define the incidence, genetic aetiology, and clinical phenotype of PNDM in Al-Madinah region, northwest Saudi Arabia. METHODS: Patients with PNDM diagnosed between 2001 and 2010 were identified and clinically phenotyped. Sequencing of KCNJ11, ABCC8, and INS were performed initially on all subjects, and EIF2AK3, GLIS3, SLC2A2, SLC19A2, GCK, IPF1, and NEUROD1 genes were sequenced according to the clinical phenotype. RESULTS: In total, 17 patients from 11 consanguineous families were diagnosed with PNDM and the incidence was 1 in 21 196 live births. Six different mutations in four genes were identified, of which two GLIS3 and one SLC2A2 were novel and no patient had KCNJ11, ABCC8, or INS mutations. Fourteen (82.4%) patients had identifiable genetic aetiology and their PNDM was part of known autosomal-recessive syndromes including Wolcott Rallison (41.1%), neonatal diabetes and hypothyroidism (29.4%), Fanconi-Bickel (5.8%), and thiamine-responsive megaloblastic anaemia (5.8%). Two patients with isolated PNDM and one with intermediate developmental delay, epilepsy and neonatal diabetes had no identifiable cause. CONCLUSIONS: Al-Madinah region has the highest reported incidence of PNDM worldwide. In this region with high consanguinity, PNDM has different genetic aetiology and in the majority of cases presents as a part of rare familial autosomal-recessive syndrome rather than in isolation.

Ribonucleotide reductase in Bacillus subtilis--evidence for a Mn-dependent enzyme.

The reduction of 2'-ribonucleotides to 2'-deoxyribonucleotides, a unique step in DNA formation, is catalyzed by ribonucleotide reductase (RRase), an allosterically regulated, cell cycle-dependent enzyme. This work reports a reversible impairment of DNA formation and ribonucleotide reduction upon manganese depletion in Bacillus subtilis demonstrated through in vivo labeling with necleic acid precursors and enzyme assays with ether-permeabilized cells. No deoxyadenosylcobalamin-dependent reduction of ribonucleotides was detected in the cytosol, and the properties of a partially purified enzyme fraction, i.e., sensitivity towards EDTA and hydroxyurea (HU), indicated a metal-dependent type of RRase. The enzyme was enriched by gel filtration on Superose 12 from glycerol- or fumarate-grown cells and submitted to Q-band electron paramagnetic resonance (EPR) spectroscopy for further characterization of the metal center. A distinct Mn(II) signal was obtained in both preparations characteristic of a protein-bound mangaenese in a mononuclear metal center with axial symmetry. The intensity of this Mn signal was not affected by addition of the radical scavenger HU (10 mM) but reduced in the presence of 2.5 mM EDTA. On the basis of these results, we suggest that Bacillus subtilis has a Mn-dependent ribonucleotide reductase.