Validity of the concept of minor depression in a developing country setting

Evidence for validity of the diagnostic construct of minor depressive disorder comes primarily from reports on subthreshold depressive states rather than minor depressive disorder per se. We report on the prevalence, impact, and sociodemographic correlates of minor depressive disorder in a developing country setting as further validation of this diagnostic construct. Diagnostic assessment of 1714 adults of an island population in Ethiopia was carried out using the Composite International Diagnostic Interview. The lifetime prevalence of minor depressive disorder was 20.5% (95% confidence interval 18.6, 22.5%). One-third of cases had sought help and expressed suicidal ideation. Being divorced/widowed, middle-aged, and having somatic pain were independently associated with having minor depressive disorder. Only being divorced/widowed was a shared risk factor for both minor depressive disorder and bereavement. Minor depressive disorder seems to be a useful and valid diagnostic construct with particular clinical significance in this and, possibly, similar developing country settings.     

The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding

OBJECTIVE—The G-protein–coupled receptor GPR40 is expressed in pancreatic β-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid–amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS itself. However, the role of GPR40 in the long-term effects of fatty acids on insulin secretion remains controversial. This study aimed to test the hypothesis that GPR40 plays a role in insulin secretion after high-fat feeding.RESEARCH DESIGN AND METHODS—GPR40 knockout (KO) mice on a C57BL/6 background and their wild-type (WT) littermates were fed a high-fat diet (HFD) for 11 weeks. Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period.RESULTS—GPR40 KO mice had fasting hyperglycemia. They became as obese, glucose intolerant, and insulin resistant as their WT littermates given HFD and developed a similar degree of liver steatosis. Their fasting blood glucose levels increased earlier than those of control mice during the course of the HFD. The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice.CONCLUSIONS—GPR40 plays a role not only in fatty acid modulation of insulin secretion, but also in GSIS after high-fat feeding. These observations raise doubts on the validity of a therapeutic approach based on GPR40 antagonism for the treatment of type 2 diabetes.Fatty acids do not initiate insulin release in the absence of glucose, but they potentiate glucose-induced insulin secretion (GSIS) upon acute exposure. Their mechanisms of action are, however, incompletely understood. The discovery of GPR40 as a G-protein–coupled receptor highly expressed in pancreatic β-cells and activated by long-chain fatty acids (1–4) has enabled the identification of a novel mechanism of action of fatty acids on insulin secretion. Loss of function of GPR40 via small interfering RNA (2,5–7), antisense oligonucleotides (8), pharmacological inhibitors (9), or gene deletion in the mouse (10,11) partially suppresses fatty acid potentiation of GSIS in vitro. We (10) and others (11) have shown that whole-body GPR40 knockout (KO) mice have normal glucose tolerance and unaltered insulin secretion in response to glucose in vivo and in vitro, but that isolated islets from these mice secrete less insulin in response to fatty acids. Furthermore, insulin secretion induced by Intralipid in vivo is reduced in GPR40 KO mice, demonstrating a physiological role for GPR40 in fatty acid–potentiation of GSIS (10).GPR40 has received considerable attention as a potential therapeutic target in type 2 diabetes (12–15). Surprisingly, whether an agonist or antagonist should be developed as a therapeutic agent remains debated (13,15). This uncertainty stems, in part, from conflicting reports regarding the role of GPR40 in β-cell function (10,11). Steneberg et al. (11) found that islets isolated from GPR40 KO mice were protected from the inhibitory effects of prolonged fatty acid exposure on GSIS, in contrast to our findings in a different line of GPR40 KO mice (10) and a recent study using GPR40 agonists (16). Steneberg et al. (11) further showed that GPR40 KO mice were protected from high-fat diet (HFD)-induced insulin resistance, glucose intolerance, and hepatic steatosis. Given these discrepancies and the importance of determining whether an agonist or antagonist approach should be pursued for drug development, the present study was designed to test the hypothesis that GPR40 contributes to the enhancement of insulin secretion after HFD. Specifically, we sought to examine whether GPR40 KO mice are more susceptible to HFD-induced hyperglycemia and, if so, whether this is due to changes in insulin secretion in vivo or associated with changes in the expression of genes controlling fatty acid metabolism in islets.     

Determinants of Incomplete Childhood Vaccination among Children Aged 12–23 Months in Gambela Region,Southwest Ethiopia: A Case Control Study

BackgroundChildhood vaccination is considered as one of the most cost-effective public health interventions. With an increasing dropout rate from vaccination, the factors for incomplete vaccination are not well explored. The objective of this study was to identify determinants of incomplete childhood vaccination.MethodCommunity based case-control study was conducted from March 1–30, 2018. Cases were children who missed at least one dose of routine vaccine while controls were children who completed all recommended doses. Face-to-face interviews were used to collect data. Multivariable logistic regression was performed in order to identify determinants with 95% CI and a p-value of <0.05.ResultA total of 93 cases and 185 controls were participated in the study. Not attending postnatal care [AOR=2.16, 95% CI: 1.08–4.28], household not visited by health workers [AOR=3.99, 95% CI: 2.13–7.48], postponing vaccination schedules [AOR = 6.15, 95% CI: 3.08–12.27], caretakers who had misconception of vaccination [AOR = 2.90, 95% CI: 1.53–5.52], unsatisfied care takers [AOR=1.970, 95% CI:1.04–3.74] and poor knowledge about vaccines [AOR = 2.33, 95% CI: 1.19–4.59] were determinants of incomplete childhood vaccination.ConclusionFailure to attend postnatal care, postponing vaccination schedules, having misconception for vaccine contraindication, households not visited by health workers, caretakers who had poor knowledge about vaccines and unsatisfied caretakers were determinants of incomplete childhood vaccination. Based on the finding, it is recommended that health education should be improved to decrease caretakers'' misconception, poor knowledge and postponement of the vaccine schedule. It is also recommended to increase health workers household visit.     

Conventional cytogenetics in myelofibrosis: literature review and discussion

The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include −7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ‘favorable’ or ‘unfavorable’. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1-positive or PDGFRB-rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q).     

Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty‐two patients (～24%) required transfusions at diagnosis whereas 22 (～9%) became transfusion‐dependent and 170 remained transfusion‐independent during the first year postdiagnosis; after a median follow‐up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS‐ and karyotype‐independent prognostic weight of transfusion status. Among IPSS intermediate‐1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate‐2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

Maternal rubella-specific antibody prevalence in Ethiopian infants

In countries with a high transmission rate of rubella the optimal age for universal rubella vaccination of infants is critically dependent upon the rate of loss of maternal antibodies. Few studies have investigated the decay characteristics of such antibodies. Mother:infant pairs were recruited at the Ethio-Swedish Children's Hospital, Addis Ababa, in 1994/95. Rubella antibody levels, determined by radial haemolysis, were available for analysis from 1542 infants aged 0-12 months, with 942 repeat measures, and from 846 mothers. Decay in seropositivity was well described by a delayed exponential function. The proportion seropositive at age 6, 9, or 12 months was 6-13%, 1-4%, or 0-1%, respectively, dependent upon assay cutoff level. Only infant age and mother's antibody level were important predictors of seropositivity. Results suggest that the success of vaccination at age 9 months or above would be little affected by residual maternal antibodies.     

Screening of some medicinal plants of Ethiopia for their anti-microbial properties and chemical profiles

In the indigenous health care delivery system of Ethiopia, numerous plant species are used to treat diseases of infectious origin. Regardless of the number of species, if any of such claims could be verified scientifically, the potential significance for the improvement of the health care services would be substantial. The objective of this study was, therefore, to determine the presence of anti-microbial activity in the crude extracts of some of the commonly used medicinal plants as well as to identify the class of compounds in the plants that were subjected to such screening. Thus, the crude methanol, petroleum ether and aqueous extracts of 67 plant species were subjected to preliminary screening against 10 strains of bacterial species and 6 fungal strains using the agar dilution method. A sample concentration of 250-2000 microg/ml and 500-4000 microg/ml were used for the bacterial and fungal pathogens, respectively. The results indicated that 44 different plant species exhibited activity against one or more of the bacteria while one species, viz., Albizzia gummifera showed activity against all the 10 bacteria at different gradient of dilution. Twenty three species inhibited or retarded growth of one or more organisms at dilution as low as 250 microg/ml. Extracts of same plants species were also tested against six different fungal pathogenic agents of which eight species showed growth inhibition against one or more of the organisms. Trichila emetica and Dovyalis abyssinica, which inhibited growth of four and five fungal strains at 100 microg/ml concentration, respectively, were the most promising plants. Chemical screening conducted on the extracts of all the plants showed the presence of several secondary metabolites, mainly, polyphenols, alkaloids, tannins sterols/terpenes, saponins and glycosides. The plants containing more of these metabolites demonstrated stronger anti-microbial properties stressing the need for further investigations using fractionated extracts and purified chemical components.     

An in-vivo study of falciparum malaria sensitivity to Chloroquine in unstable malaria endemic area of central Ethiopia

The role of Chloroquine as a first line drug to treat P. falciparum is almost universally becoming questionable. This study was conducted in one of the country's unstable malaria endemic area, North Shoa with the objective of assessing the in-vivo treatment efficacy of Chloroquine to falciparum malaria using the standard WHO 14 days treatment response monitoring guideline. A total of 427 patients were followed among which 87.8% showed treatment failure. This was more pronounced in children than in adults (Chi-square for trend = 8.16; P < 0.01). Clinical presentation with high grade fever on day 0 was found to be more predictive of treatment failure in children (OR = 2.06; 95% CI = 1.26, 3.36; P < 0.005). Tendency to remain febrile on subsequent follow up days was also more observed in children compared to adults. Treatment failure was further associated with high Parasite Density Index (PDI) on day 0 in all age groups (OR = 1.99; 95% CI = 1.04, 3.83; P < 0.05). Supplemented with large scale sensitivity studies, it is high time that switch to alternate drugs needs due consideration by policy makers.     

Sequential assignments of polymers by 2D NMR techniques: application to stereochemical configuration assignment of poly(acrylic acid)

Two-dimensional heteronuclear single quantum coherence — total correlation spectroscopy (2D HSQC-TOCSY) was used to make end-to-end sequential assignments and determine stereochemical configuration at the triad, tetrad and pentad levels of poly(acrylic acid). The pseudo three-dimensional experiment allows heteronuclear (¹³C-¹H) as well as homonuclear (¹H-¹H) corelations in a single 2D NMR experiment. The stereochemical configuration assignment is based on sequential identification of neighboring species. For example, a mmr tetrad resonance (methylene-¹³C) is determined by its correlations to the mm and mr triad resonances (methine) that constitute it. Hence, it is independent of chemical shift and peak intensity estimates that are requisites of the conventional method. This self-consistent technique enables absolute assignments of all magnetically unique tetrads and some of the pentad resonances. In addition, some resonances in the methylene and methine regions that have been difficult to characterize by conventional techniques were unequivocally assigned to endgroup resonances and other polymerization by-products of the low-molecular-weight poly(acrylic acid).     

Low Urinary Iodine Concentration Is Associated with Increased Risk for Elevated Plasma Glucose in Females: An Analysis of NHANES 2011–12

Iodine intake in the US has declined in recent years. Iodine insufficiency increases the risk for inadequate thyroid hormone production and there is growing evidence that sub-clinical hypothyroidism may be disruptive to metabolic health, including insulin resistance (IR). We investigated the association between urinary iodine concentrations (UIC), a measurement of iodine status, and IR in adults. Data from 1286 US adults (≥20 years) in the NHANES 2011–2012 were analyzed. Two subgroups (low = UIC < 100 µg/L and normal = UIC ≥ 100 µg/L) were compared for markers of IR, including fasting plasma glucose (FPG) and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1C). Chi-square test, both linear and logistic regression models were used. In males, there were no significant associations between UIC and markers of IR; however, females with normal UIC had greater risks for elevated HOMA-IR (AOR = 0.56, 95% CI= 0.32–0.99) and HbA1C (AOR = 0.56, 95% CI = 0.34–0.90), while females with low UIC had a greater risk for FPG ≥ 5.6 mmol/L (AOR = 1.73, 95% CI = 1.09–2.72). Results only partially support our hypothesis that UIC is associated with the odds of IR in adults. The finding of an increased risk for elevated FPG, a marker of prediabetes, in female adults with low iodine status requires further investigation.