Prevalence of Undiagnosed Depression among Persons with Hypertension and Associated Risk Factors: A Cross-Sectional Study in Urban Nepal

BackgroundDespite an increasing number of studies exploring prevalence of depression among hypertensive patients in high income countries, limited data is available from low and middle income countries, particularly Nepal. Our aim was to investigate the prevalence of undiagnosed (sub clinical) depression and associated risk factors among hypertensive patients attending a tertiary health care clinic in Nepal.MethodsThe study was based on a cross-sectional study design, with 321 hypertensive patients attending the Out-Patient Department of a central hospital in Nepal. Blood measure was recorded via a mercury column sphygmomanometer. Depression levels were assessed using the Beck Depression Inventory-Ia (BDI) scale. Demographics and risk factors were assessed.ResultThe proportion of participants with undiagnosed depression was 15%. Multivariable analyses demonstrated an increase in BDI scores with increased aging. Approximately a 1 point increase in the BDI score was observed for each additional decade of aging in hypertensive patients. Additional factors associated with increased risk of depression included being female (4.28 point BDI score increase), smoking (5.61 point BDI score increase), being hypertensive with no hypertensive medication (4.46 point BDI score increase) and being illiterate (4.46 point BDI score increase).ConclusionsAmong persons with hypertension in outpatient settings in Nepal, demographic (age, sex, education), behavioural (smoking,) and adherence factors (anti-hypertensive medication) were associated with undiagnosed depression. Screening programs in Nepal may assist early intervention in hypertensive patients with sub clinical depression.     

T-Cell Regulation in Lepromatous Leprosy

Regulatory T (T_reg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25⁺ cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients'' skin lesions. Depletion of CD25⁺ cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25⁺ cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25⁺ cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25⁺ T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25⁺ cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25⁺ cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3⁺ CD8⁺CD25⁺ T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68⁺CD163⁺ as well as FoxP3⁺ cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25⁺ T_reg cells play a role in M. leprae-Th1 unresponsiveness in LL.     

Evolutionary Divergence of TNL Disease-Resistant Proteins in Soybean (<Emphasis Type="Italic">Glycine max</Emphasis>) and Common Bean (<Emphasis Type="Italic">Phaseolus vulgaris</Emphasis>)

Disease-resistant genes (R genes) encode proteins that are involved in protecting plants from their pathogens and pests. Availability of complete genome sequences from soybean and common bean allowed us to perform a genome-wide identification and analysis of the Toll interleukin-1 receptor-like nucleotide-binding site leucine-rich repeat (TNL) proteins. Hidden Markov model (HMM) profiling of all protein sequences resulted in the identification of 117 and 77 regular TNL genes in soybean and common bean, respectively. We also identified TNL gene homologs with unique domains, and signal peptides as well as nuclear localization signals. The TNL genes in soybean formed 28 clusters located on 10 of the 20 chromosomes, with the majority found on chromosome 3, 6 and 16. Similarly, the TNL genes in common bean formed 14 clusters located on five of the 11 chromosomes, with the majority found on chromosome 10. Phylogenetic analyses of the TNL genes from Arabidopsis, soybean and common bean revealed less divergence within legumes relative to the divergence between legumes and Arabidopsis. Syntenic blocks were found between chromosomes Pv10 and Gm03, Pv07 and Gm10, as well as Pv01 and Gm14. The gene expression data revealed basal level expression and tissue specificity, while analysis of available microRNA data showed 37 predicted microRNA families involved in targeting the identified TNL genes in soybean and common bean.     

Complete genome sequence of Serratia plymuthica strain AS12

A plant-associated member of the family Enterobacteriaceae, Serratia plymuthica strain AS12 was isolated from rapeseed roots. It is of scientific interest because it promotes plant growth and inhibits plant pathogens. The genome of S. plymuthica AS12 comprises a 5,443,009 bp long circular chromosome, which consists of 4,952 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome was sequenced within the 2010 DOE-JGI Community Sequencing Program (CSP2010) as part of the project entitled "Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens".     

Transcriptional Regulation,Metal Binding Properties and Structure of Pden1597, an Unusual Zinc Transport Protein from Paracoccus denitrificans

ATP-binding cassette (ABC) transporters of the cluster 9 family are ubiquitous among bacteria and essential for acquiring Zn²⁺ and Mn²⁺ from the environment or, in the case of pathogens, from the host. These rely on a substrate-binding protein (SBP) to coordinate the relevant metal with high affinity and specificity and subsequently release it to a membrane permease for translocation into the cytoplasm. Although a number of cluster 9 SBP structures have been determined, the structural attributes conferring Zn²⁺ or Mn²⁺ specificity remain ambiguous. Here we describe the gene expression profile, in vitro metal binding properties, and crystal structure of a new cluster 9 SBP from Paracoccus denitrificans we have called AztC. Although all of our results strongly indicate Zn²⁺ over Mn²⁺ specificity, the Zn²⁺ ion is coordinated by a conserved Asp residue only observed to date as a metal ligand in Mn²⁺-specific SBPs. The unusual sequence properties of this protein are shared among close homologues, including members from the human pathogens Klebsiella pneumonia and Enterobacter aerogenes, and would seem to suggest a subclass of Zn²⁺-specific transporters among the cluster 9 family. In any case, the unusual coordination environment of AztC expands the already considerable range of those available to Zn²⁺-specific SBPs and highlights the presence of a His-rich loop as the most reliable indicator of Zn²⁺ specificity.     

Extended spectrum beta-lactamase and metallo beta-lactamase production among <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> isolated from different clinical samples in a tertiary care hospital in Kathmandu,Nepal

Background

Extended spectrum beta-lactamase (ESBL) and metallo beta-lactamase (MBL) production in Klebsiella pneumoniae and Escherichia coli are the commonest modes of drug resistance among these commonly isolated bacteria from clinical specimens. So the main purpose of our study was to determine the burden of ESBL and MBL production in E. coli and K. pneumoniae isolated from clinical samples. Further, the antimicrobial susceptibility patterns of E. coli and K. pneumoniae were also determined.

Methods

A cross-sectional study was conducted at Om Hospital and Research Centre, Kathmandu, Nepal by using the E. coli and K. pneumoniae isolated from different clinical samples (urine, pus, body fluids, sputum, blood) from May 2015 to December 2015. Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion technique. Extended spectrum beta-lactamase production was detected by combined disc method using ceftazidime and ceftazidime/clavulanic acid discs and cefotaxime and cefotaxime/clavulanic acid discs. Similarly, metallo beta-lactamase production was detected by combined disc assay using imipenem and imipenem/ethylenediaminetetracetate discs. Bacteria showing resistance to at least three different classes of antibiotics were considered multidrug resistant (MDR).

Results

Of total 1568 different clinical samples processed, 268 (17.1%) samples were culture positive. Among which, E. coli and K. pneumoniae were isolated from 138 (51.5%) and 39 (14.6%) samples respectively. Of the total isolates 61 (34.5%) were ESBL producers and 7 (4%) isolates were found to be MBL producers. High rates of ESBL production (35.9%) was noted among the clinical isolates from outpatients, however no MBL producing strains were isolated from outpatients. Among 138 E. coli and 39 K. pneumoniae, 73 (52.9%) E. coli and 23 (59%) K. pneumoniae were multidrug resistant. The lowest rates of resistance was seen toward imipenem followed by piperacillin/tazobactam, amikacin and cefoperazone/sulbactam.

Conclusions

High rate of ESBL production was found in the E. coli and K. pneumoniae isolated from outpatients suggesting the dissemination of ESBL producing isolates in community. This is very serious issue and can’t be neglected. Regular monitoring of rates of ESBL and MBL production along with multidrug resistance among clinical isolates is very necessary.

     

Sulfhydryl-reagent alteration of soybean resistance to the cabbage looper, Trichoplusia ni

The hypothesis that the sulfhydryl reagent, N-ethylmaleimide, would function as an elicitor of alterable resistance in soybean (Glycine max) plants to Trichoplusia ni herbivory was tested experimentally under greenhouse conditions. This elicitory chemical, which allows receptor thiols to add across its carbon-carbon double bond, altered the resistance in one or more leaves of plants at one or more intervals after treatment; and thus yielded results supporting the hypothesis. Leaf dipping and soil application were both effective methods of treatment. Results support the interpretation that an elicitor may function in intact plants by altering the integrity of sulfhydryl groups in receptor macromolecules which are also involved in signaling a change in the plant's biosynthesis of characteristic defensive compounds such as phenylpropanoids including antifeedant and antibiotic flavonoids. Induced feeding non-preference by T. ni was highly correlated positively with the amount of glyceollins in the leaf.     

An endoplasmic reticulum stress regulator,Tmbim6, modulates secretory stage of mice molar

To understand the role of endoplasmic reticulum (ER)-stress in mice molar development, we studied Tmbim6 that antagonizes the unfolded protein response, using Tmbim6 knockout (KO) mice and in vitro organ cultivation with knocking down using small interfering RNA. During molar development, Tmbim6 is expressed in developing tooth at E14–E16, postnatal0 (PN0), and PN6. Mineral content in Tmbim6 KO enamel was reduced while dentin was slightly increased revealing ultrastructural changes in pattern formation of both enamel and dentin. Moreover, odontoblast differentiation was altered with increased Dspp expression at PN0 followed by altered AMELX localizations at PN5. These results were confirmed by in vitro organ cultivation and showed altered Bmp signaling, proliferation, and actin rearrangement in the presumptive ameloblast and odontoblasts that followed the altered expression of differentiation and ER stress-related signaling molecules at E16.5. Overall, ER stress modulated by Tmbim6 would play important roles in patterned dental hard tissue formation in mice molar within a limited period of development.     

Health risk assessment of atmospheric polycyclic aromatic hydrocarbons over the Central Himalayas

Carcinogenic risk assessments of polycyclic aromatic hydrocarbons (PAHs) in four sites from the Central Himalayas (Bode, Lumbini, Pokhara, and Dhunche) were performed. Lifetime Average Daily Dose (LADD), Lifetime lung cancer risk (LLCR) and Incremental lifetime cancer risk (ILCR) were calculated in order to evaluate the cancer risk. PAHs levels were converted to BaP equivalent concentrations (B[a]Peq), and models of health risk assessment were applied. B[a]Peq concentrations exceeded the standard limited value (1 ng/m³) in all the four sites. The human health risk assessment (HHRA) demonstrated high carcinogenic risk on residents of Bode and Lumbini. Further, LLCR in all sites were over the acceptable range (1.15E-03, 7.90E-04, 1.40E-04 and 9.96E-05, respectively); however, ILCR ranking exhibited acceptable range in Lumbini, Pokhara, and Dhunche (7.10E-06, 1.26E-06, and 8.95E-07). The risk variation among the sites is due to the difference in pollution status. The study shows health risk due to atmospheric PAHs via inhalation prevails all the seasons throughout, differing only seasonally; nevertheless, the concentration and carcinogenic risk decreased remarkably from south-north transect of the central Himalaya. Keeping some uncertainties aside, this study provides noble insights and helps to formulate new advance assessment on the carcinogenic risk of atmospheric PAHs over the Central Himalayas.