Association of various reproductive rights, domestic violence and marital rape with depression among Pakistani women

<p>Abstract</p> <p>Background</p> <p>Depression among women is common in developing countries. Gender inequality can contribute to women's risk for depression. Lack of reproductive and sexual rights is an important marker of gender inequality and women do not have the freedom to express their reproductive and sexual needs in many parts of the world. Therefore we designed this study to determine the association of depression with lack of various reproductive rights and domestic violence among married women in Karachi, Pakistan.</p> <p>Methods</p> <p>A case-control study with 152 cases and 152 controls, which included women 15-48 years, recruited from two teaching hospitals from 1^stJune 2007 through 31^stAugust 2007. The SRQ was administered to all subjects. A cut off score of 8 was used to confirm cases of depression diagnosed by physicians, and to exclude cases of depression from the controls. Self-administered questionnaire was used to assess the risk factors.</p> <p>Results</p> <p>61% of the cases and 43% of the controls were ever abused by spouse and the frequency of marital rape was 33% in cases and 13% in controls. After adjusting for the effects of other variables in the model, less than 18 years of age at marriage (OR 2.00; 95% CI = 1.07, 3.7), decision for marriage by parents (OR 3.51; 95% CI = 1.67, 7.37), abuse by in laws (OR 4.91; 95% CI = 2.66, 9.06), ≤ 3 hours per day spent with husband (OR 2.33; 95% CI = 1.34, 4.08), frequency of intercourse ≤ 2 times per week (OR 1.85; 95% CI = 1.06, 3.22) and marital rape (OR 3.03; 95% CI = 1.50, 6.11) were associated with depression among women.</p> <p>Conclusion</p> <p>In our study depression in married women was associated with younger age at marriage, lack of autonomy in marriage decisions, marital rape and domestic abuse by in-laws. Efforts should be directed towards creating awareness about the reproductive and sexual rights of women in Pakistan. Physicians should be trained to screen and identify women who may be at risk for psychological distress as a result of denial of reproductive rights so that they can support positive mental health outcomes through individual, family or marital counseling.</p

Evolution records a Mx tape for anti-viral immunity

Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and species-specific susceptibility to viral infection

Campylobacter jejuni:A brief overview on pathogenicity-associated factors and disease-mediating mechanisms

Campylobacter jejuni has long been recognized as a cause of bacterial food-borne illness, and surprisingly, it remains the most prevalent bacterial food-borne pathogen in the industrial world to date. Natural reservoirs for this Gram-negative, spiral-shaped bacterium are wild birds, whose intestines offer a suitable biological niche for the survival and dissemination of C. jejuni Chickens become colonized shortly after birth and are the most important source for human infection. In the last decade, effective intervention strategies to limit infections caused by this elusive pathogen were hindered mainly because of a paucity in understanding the virulence mechanisms of C. jejuni and in part, unavailability of an adequate animal model for the disease. However, recent developments in deciphering molecular mechanisms of virulence of C. jejuni made it clear that C. jejuni is a unique pathogen, being able to execute N-linked glycosylation of more than 30 proteins related to colonization, adherence, and invasion. Moreover, the flagellum is not only depicted to facilitate motility but as well secretion of Campylobacter invasive antigens (Cia). The only toxin of C. jejuni, the so-called cytolethal distending toxin (CdtA,B,C), seems to be important for cell cycle control and induction of host cell apoptosis and has been recognized as a major pathogenicity-associated factor. In contrast to other diarrhoea-causing bacteria, no other classical virulence factors have yet been identified in C. jejuni. Instead, host factors seem to play a major role for pathogenesis of campylobacteriosis of man. Indeed, several lines of evidence suggest exploitation of different adaptation strategies by this pathogen depending on its requirement, whether to establish itself in the natural avian reservoir or during the course of human infection. (C) 2009 Elsevier GmbH. All rights reserved

Epidemiological Association of Different Campylobacter jejuni Groups with Metabolism-Associated Genetic Markers ▿ †

In this study, multilocus sequence typing (MLST) was combined with the genetic detection of six genetic markers, ansB, dmsA, ggt, cj1585c, cjj81176-1367/71 (cj1365c), and the two-gene marker tlp7 (cj0951c plus cj0952c), to assess if their presence correlated with different C. jejuni clonal groups. Using a collection of 266 C. jejuni isolates from (in decreasing order of sample size) humans, chickens, cattle, and turkeys, it was further investigated whether the resulting genotypes correlated with the isolation source. We found combinations of the six marker genes to be mutually exclusive, and their patterns of presence or absence correlated to some degree with animal source. Together with MLST results, the obtained genotypes could be segregated into six groups. An association was identified for ansB, dmsA, and ggt with the MLST-clonal complexes (MLST-CC) 22, 42, 45, and 283, which formed the most prominent group, in which chickens were the most prevalent animal source. Two other groups, characterized by the presence of cj1585c, cjj81176-1367/71, and the two-gene marker tlp7, associated with either MLST-CC 21 or 61, were overrepresented in isolates of bovine origin. Mutually exclusive marker gene combinations were observed for ansB, dmsA, and ggt, typically found in CC 45 and the related CC 22, 42, and 283, whereas the other three marker genes were found mostly in CC 21, 48, and 206. The presence of the two-gene marker tlp7, which is typical for MLST 21 and 53 as well as for MLST-CC 61, strongly correlates with a bovine host; this is interpreted as an example of host adaptation. In cases of C. jejuni outbreaks, these genetic markers could be helpful for more effective source tracking

The Campylobacter jejuni Cj0268c protein is required for adhesion and invasion in vitro.

Adherence of Campylobacter jejuni to its particular host cells is mediated by several pathogen proteins. We screened a transposon-based mutant library of C. jejuni in order to identify clones with an invasion deficient phenotype towards Caco2 cells and detected a mutant with the transposon insertion in gene cj0268c. In vitro characterization of a generated non-random mutant, the mutant complemented with an intact copy of cj0268c and parental strain NCTC 11168 confirmed the relevance of Cj0268c in the invasion process, in particular regarding adherence to host cells. Whereas Cj0268c does not impact autoagglutination or motility of C. jejuni, heterologous expression in E. coli strain DH5α enhanced the potential of the complemented E. coli strain to adhere to Caco2 cells significantly and, thus, indicates that Cj0268c does not need to interact with other C. jejuni proteins to develop its adherence-mediating phenotype. Flow cytometric measurements of E. coli expressing Cj0268c indicate a localization of the protein in the periplasmic space with no access of its C-terminus to the bacterial surface. Since a respective knockout mutant possesses clearly reduced resistance to Triton X-100 treatment, Cj0268c contributes to the stability of the bacterial cell wall. Finally, we could show that the presence of cj0268c seems to be ubiquitous in isolates of C. jejuni and does not correlate with specific clonal groups regarding pathogenicity or pathogen metabolism

Impact of Campylobacter jejuni cj0268c knockout mutation on intestinal colonization, translocation, and induction of immunopathology in gnotobiotic IL-10 deficient mice.

BACKGROUND: Although Campylobacter jejuni infections have a high prevalence worldwide and represent a significant socioeconomic burden, the underlying molecular mechanisms of induced intestinal immunopathology are still not well understood. We have recently generated a C. jejuni mutant strain NCTC11168::cj0268c, which has been shown to be involved in cellular adhesion and invasion. The immunopathological impact of this gene, however, has not been investigated in vivo so far. METHODOLOGY/PRINCIPAL FINDINGS: Gnotobiotic IL-10 deficient mice were generated by quintuple antibiotic treatment and perorally infected with C. jejuni mutant strain NCTC11168::cj0268c, its complemented version (NCTC11168::cj0268c-comp-cj0268c), or the parental strain NCTC11168. Kinetic analyses of fecal pathogen loads until day 6 post infection (p.i.) revealed that knockout of cj0268c did not compromise intestinal C. jejuni colonization capacities. Whereas animals irrespective of the analysed C. jejuni strain developed similar clinical symptoms of campylobacteriosis (i.e. enteritis), mice infected with the NCTC11168::cj0268c mutant strain displayed significant longer small as well as large intestinal lengths indicative for less distinct C. jejuni induced pathology when compared to infected control groups at day 6 p.i. This was further supported by significantly lower apoptotic and T cell numbers in the colonic mucosa and lamina propria, which were paralleled by lower intestinal IFN-γ and IL-6 concentrations at day 6 following knockout mutant NCTC11168::cj0268c as compared to parental strain infection. Remarkably, less intestinal immunopathology was accompanied by lower IFN-γ secretion in ex vivo biopsies taken from mesenteric lymphnodes of NCTC11168::cj0268c infected mice versus controls. CONCLUSION/SIGNIFICANCE: We here for the first time show that the cj0268c gene is involved in mediating C. jejuni induced immunopathogenesis in vivo. Future studies will provide further deep insights into the immunological and molecular interplays between C. jejuni and innate immunity in human campylobacteriosis

Gentamicin protection assays.

<p>1. wild type strain NCTC 11168, 2. mutant strain NCTC 11168::<i>cj0268c</i>, 3. complemented mutant NCTC 11168::<i>cj0268c</i>-comp-<i>cj0268c</i>. Gentamicin protection assays with the strains under investigation using (a) Caco2 cells and (b) PCC-cells. The assays on Caco2 cells with the parental strain, the knockout mutant and the complemented knockout mutant confirmed the infection-deficient phenotype to be due to the functional loss of <i>cj0268c.</i> Four independent experiments have been carried out, respectively. The standard deviations are indicated. (a) Taking the number of <i>C. jejuni</i> wild type strain NCTC 11168 colonies recovered as 100%, the mean value of <i>cj0268c</i>-mutant colonies (NCTC 11168::<i>cj0268c</i>) accounted for 62% (±2.41), whereas the percentage of obtained colonies from the complemented strain (NCTC 11168::<i>cj0268c</i>-comp-<i>cj0268c)</i> was 93% (±2.04). Since the <i>P</i>-value for the mutant was less than 0.001, the reduced invasion capacity was significant. (b) The relevance of <i>cj0268c</i> for invasion is not restricted to human cells, since it could also be shown for the invasion of PCC-cells. Compared to the invasion capacity of parental strain NCTC 11168 (100%), the percentage of colonies obtained from mutant strain NCTC 11168::<i>cj0268c was</i> only 62% (±2.36, P<0.0007). However, complementation of the mutant strain with <i>cj0268c</i> restored the infectivity of NCTC 11168::<i>cj0268c</i>-comp-<i>cj0268c</i> which was similar to that of the parental strain (96%, ±4.96).</p

Resistance to Triton X-100.

<p>(1) Parental strain NCTC 11168, (2) <i>cj0268c</i> knockout mutant (NCTC 11168::<i>cj0268c</i>), (3) complemented knockout mutant (NCTC 11168::<i>cj0268c-</i>comp-<i>cj0268c</i>). The numbers of colonies of the respective fourth dilution plated onto blood agar are shown. The <i>cj0268c</i> knockout mutant shows a clearly diminished resistance to Triton X-100. When defining the number of wild type colonies as 100%, the mean value of colonies recovered from the corresponding <i>cj0268c</i>-mutant was 21.3% (±9.02, P<0.0039). After complementation of the mutant with an intact copy of <i>cj0268c</i> the percentage of colonies obtained increased to 91.3%.</p