Status of insecticide resistance and its biochemical and molecular mechanisms in Anopheles stephensi (Diptera: Culicidae) from Afghanistan.

BACKGROUND: Insecticide resistance of Anopheles stephensi, the main malaria vector in eastern Afghanistan, has been reported previously. This study describes the biochemical and molecular mechanisms of resistance to facilitate effective vector control and insecticide resistance management. METHODS: Mosquito larvae were collected from the provinces of Kunar, Laghman and Nangarhar from 2014 to 2017. The susceptibility of the reared 3-4 days old adults was tested with deltamethrin 0.05%, bendiocarb 0.1%, malathion 5%, permethrin 0.75% and DDT 4%. Cytochrome P450 content and general esterase, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were measured in the three field populations and the results were compared with those of the laboratory susceptible An. stephensi Beech strain. Two separate allele-specific PCR assays were used to identify L1014, L1014F and L1014S mutations in the voltage gated sodium channel gene of An. stephensi. Probit analysis, ANOVA and Hardy-Weinberg equilibrium were used to analyse bioassay, biochemical assay and gene frequency data respectively. RESULTS: The population of An. stephensi from Kunar was susceptible to bendiocarb, apart from this, all populations were resistant to all the other insecticides tested. The differences between all values for cytochrome P450s, general esterases, GSTs and AChE inhibition rates in the Kunar, Laghman and Nangarhar populations were statistically significant when compared to the Beech strain, excluding GST activities between Kunar and Beech due to the high standard deviation in Kunar. The three different sodium channel alleles [L1014 (wild type), L1014F (kdr west) and L1014S (kdr east)] were all segregated in the Afghan populations. The frequencies of kdr east mutation were 22.9%, 32.7% and 35% in Kunar, Laghman and Nangarhar populations respectively. Kdr west was at the lowest frequency of 4.44%. CONCLUSIONS: Resistance to different groups of insecticides in the field populations of An. stephensi from Kunar, Laghman and Nangarhar Provinces of Afghanistan is caused by a range of metabolic and site insensitivity mechanisms, including esterases, cytochrome P450s and GSTs combined with AChE and sodium channel target site insensitivity. The intensity and frequency of these mechanisms are increasing in these populations, calling for urgent reorientation of vector control programmes and implementation of insecticide resistance management strategies.

Targeted volumetric single-molecule localization microscopy of defined presynaptic structures in brain sections.

Revealing the molecular organization of anatomically precisely defined brain regions is necessary for refined understanding of synaptic plasticity. Although three-dimensional (3D) single-molecule localization microscopy can provide the required resolution, imaging more than a few micrometers deep into tissue remains challenging. To quantify presynaptic active zones (AZ) of entire, large, conditional detonator hippocampal mossy fiber (MF) boutons with diameters as large as 10 µm, we developed a method for targeted volumetric direct stochastic optical reconstruction microscopy (dSTORM). An optimized protocol for fast repeated axial scanning and efficient sequential labeling of the AZ scaffold Bassoon and membrane bound GFP with Alexa Fluor 647 enabled 3D-dSTORM imaging of 25 µm thick mouse brain sections and assignment of AZs to specific neuronal substructures. Quantitative data analysis revealed large differences in Bassoon cluster size and density for distinct hippocampal regions with largest clusters in MF boutons.

Regulation of platelet guanylyl cyclase by collagen: evidence that Glycoprotein VI mediates platelet nitric oxide synthesis in response to collagen.

The molecular regulation of nitric oxide synthase (NOS) in blood platelets is an uncharacterised area of platelet biology. We investigated the mechanism of collagen-stimulated NO synthesis in platelets. Our aim was to identify the key collagen receptor and downstream signalling mechanisms linking collagen to NOS activation. Collagen and the GpVI-specific platelet activator collagen-related peptide (CRP-XL) stimulated NO synthesis, as evidenced by increased [(3)H]L-citrulline production, and cyclic GMP (cGMP) formation. After platelet activation by collagen and CRP-XL was normalised, we found no differences in NOS activation or cGMP formation in response to these agonists. Blocking the interaction of collagen with integrin alpha(2)beta(1), a second collagen receptor, failed to affect NOS activation by collagen. These data indicate that collagen-induced NO synthesis is linked to GpVI activation. cGMP formation in response to collagen and CRP-XL required increased intracellular Ca(2+), Src family kinases, phosphatidylinositol 3-kinase (PI3-K) and protein kinase C. By comparison, Gp VI-independent cGMP formation induced by thrombin was Src kinase-dependent, but was independent of PI3-K and PKC. Thus the mechanisms of collagen- and CRP-XL-induced NOS activation were identical, but distinct from that of thrombin. Platelet activation in response to collagen leads to secretion of adenosine diphosphate (ADP) and thromboxane A(2) (TxA(2)). Our results demonstrate that collagen-stimulated cGMP synthesis was enhanced significantly by platelet-derived ADP and TxA(2). These results reveal that collagen stimulates platelet NOS activation through a specific Ca(2+)-dependent GpVI receptor signalling cascade, and demonstrate that collagen-induced cGMP accrual requires the release of secondary platelet agonists.

The effect of interpersonal psychotherapy on marriage adaptive and postpartum depression in isfahan.

BACKGROUND: Regarding high prevalence and injurious consequences of postpartum depression, the aim of the present work is the study of the effect rate of interpersonal psychotherapy on marriage adaptive and postpartum in women. METHOD: The present study is semi-empiric, and included control group and pre- and post-test groups. Thirty-two women suffering from postpartum depression were selected from among female referents to counseling centers and clinics in Esfahan city by purposive sampling and were placed in two groups (control and test) randomly case group participated in a 10-weeks marriage interpersonal psychotherapy meetings. Beck II depression questionnaire and marriage adaptive scale were completed by two groups at pre-test and post-test steps. Collected data were analyzed using SPSS software and multivariable covariance analysis. RESULTS: The scores of average of depression and marriage adaptive post-test in test group was significantly less than that in the control group (P < 0.0005). CONCLUSIONS: The findings of this research confirm marriage interpersonal psychotherapy on the depression recovery and the increasing marriage satisfaction of women suffering from postpartum depression.

Effectiveness of Attribution Retraining on Women's Depression and Anxiety After Miscarriage.

BACKGROUND: Given miscarriage psychological consequences on the women health, the aim of the present study is the survey of effectiveness rate of attributive retraining interventions on women depression and anxiety reducing after miscarriage. METHODS: The present study is semi-empiric and it's made using control group, pre- and post-test execution and follow-up. Thirty-two women, who had recent experience of miscarriage, were selected among female referents to obstetricians and clinics in Esfahan city by accessible sampling and then they were placed on two groups, case and control, randomly. Case group participated in 6 weekly sessions for attributive retraining interventions and both groups completed hospital depression and anxiety questionnaire on three steps: Pre-test, post-test, and follow-up. Collected data were analyzed statistically, using Statistical Package for the Social Sciences (SPSS) software and variance by repeated measuring. RESULTS: Obtained results show that average post-test and follow-up scores of depression and anxiety in case group is less than average post-test scores in control group, significantly (P < 0.0005). CONCLUSIONS: The findings of this research, "Attributive Retraining Effectiveness on Women's Depression and Anxiety Reducing after Miscarriage," were confirmed.