Postpartum intrauterine contraceptive device use and its associated factors in Ethiopia: systematic review and meta-analysis.

BACKGROUND: The intrauterine contraceptive device, a type of long-acting reversible contraception, is one of the most effective and safe contraceptive methods. In Ethiopia, intrauterine contraceptive device is little known and practised to delay pregnancy. Therefore, this study aimed to assess post-partum intrauterine contraceptive device utilisation and its associated factors among women in Ethiopia. METHOD: In the current meta-analysis, variables were searched from different electronic database systems, including PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Data were extracted using a standardised data collection measurement tool. The data were also analysed by using STATA 16 statistical software. I2 tests assessed heterogeneity between the studies. A random-effect model was used to forecast the pooled utilisation of postpartum intrauterine contraceptive device. RESULTS: Twelve full-article studies were included. The pooled prevalence of post-partum intrauterine contraceptive device among women in Ethiopia was 21.63%. Occupation (OR = 4.44, 95% CI, 2.24-8.81), educational level of college and above (OR = 5.93, 95% CI, 2.55-13.8), antenatal care (OR = 2.09, 95% CI, 1.4-3.12), age (OR = 4.8, 95% CI, 2.3-10.04), good knowledge (OR = 4.16, 95% CI, 1.65-10.49), counseling (OR = 3.05, 95%CI, 1.41-6.63), husband support (OR = 11.48, 95% CI, 6.05-21.79) and awareness about IUCD (OR = 3.86, 95% CI, 1.46-10.2) were positively associated with utilization of postpartum intrauterine contraception device. CONCLUSIONS: Utilisation of post-partum intrauterine contraceptive device was significantly low. Scaling up women's educational status and ANC use has paramount importance in increasing post-partum IUD use, which further improves maternal and child health in general. This finding may be useful in both reproductive health promotion at an individual level and policy-making regarding this issue.

Family planning (FP) is widely recognised as a life-saving and health-improving intervention for women and children. An IUCD is a small, "T-shaped" intrauterine contraceptive device inserted into a woman's uterus. It is also referred to as an IUD, a loop, or a coil. Post-partum IUCD is an intrauterine contraceptive device inserted during the post-partum period. Although several primary studies have been conducted in various regions of Ethiopia, there is no nationally representative evidence on the PPIUCD utilisation and the pooled effects of its determinants in Ethiopia. In this review, some of the factors associated with the post-partum intrauterine contraceptive device were pooled quantitatively, and some were not because of inconsistent classification (grouping) of the exposures concerning the outcome (post-partum intrauterine contraceptive device).This systematic review and meta-analysis used the following electronic database; PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature to search the primary articles. A total of 12 primary studies assessing the utilisation of postpartum intrauterine contraceptive device (PPIUCD) were included based on study eligibility criteria.And also, in this study we found that the pooled prevalence of post-partum intrauterine contraceptive device among women in Ethiopia was 21.63%. Occupation, educational status, good knowledge, husband support, age, counselling, antenatal care follow-up, and awareness about IUCD were factors that affect the use of post-partum intrauterine contraceptive devices.This systematic review and meta-analysis report that utilisation of post-partum intrauterine contraceptive device was significantly low. Therefore, scaling up women's educational status, and ANC use has paramount importance in increasing post-partum IUD use, which further improves maternal and child health in general. Beside this health professional also should be give health education and promotion about the importance of PPIUCD.

Building resilience to El Niño-related drought: experiences in early warning and early action from Nicaragua and Ethiopia.

Forecast-based drought early warning/early action has been hampered by both inadequate decision-making frameworks and a lack of appropriate funding mechanisms. Rural communities in Nicaragua and Ethiopia that have participated in resilience-building interventions of varying durations demonstrate the value of community-based actions informed by early warning, forecasts and drought management advice, both before and during the agricultural season. While drought affected all crops negatively, participants were better able to mitigate impacts, were more organised in accessing relief and recovered more effectively. These results are consistent with other research on the cost/benefit of anticipatory actions, use of climate services and appropriate drought management advice. They also confirm the importance of embedding short-term early action in long-term resilience-building. Despite this, formal systems, national and local, remain essentially unimplemented. Systems being developed at global level now need to be operationalised and translated into effective local drought management standard operating procedures for the most vulnerable.

Rad51 inhibition is an effective means of targeting DNA repair in glioma models and CD133+ tumor-derived cells.

High grade gliomas (HGGs) are characterized by resistance to radiotherapy and chemotherapy. Targeting Rad51-dependent homologous recombination repair may be an effective target for chemo- and radiosensitization. In this study we assessed the role of Rad51-dependent repair on sensitivity to radiation and temozolomide (TMZ) as single agents or in combination. Repair protein levels in established glioma cell lines, early passage glioblastoma multiforme (GBM) cell lines, and normal human astrocytes (NHAs) were measured using western blot. Viability and clonogenic survival assays were used to measure the effects of Rad51 knockdown with radiation (XR) and TMZ. Immunocytochemistry was used to evaluate kinetics of Rad51 and γ-H2AX repair foci. Immunohistochemistry was used to assess Rad51 protein levels in glioma specimens. Repair proteins including Rad51 are upregulated in HGG cells compared with NHA. Established glioma cell lines show a dose-dependent increase in Rad51 foci formation after XR and TMZ. Rad51 levels are inversely correlated with radiosensitivity, and downregulation markedly increases the cytotoxicity of TMZ. Rad51 knockdown also promotes more residual γ-H2AX foci 24 h after combined treatment. Newly established GBM cell lines also have high Rad51 levels and are extremely sensitive to Rad51 knockdown. Clinical samples from recently resected gliomas of varying grades demonstrate that Rad51 levels do not correlate with tumor grade. Rad51-dependent repair makes a significant contribution to DNA repair in glioma cells and contributes to resistance to both XR and TMZ. Agents targeting Rad51-dependent repair would be effective adjuvants in standard combination regimens.

BRCA1 and BRCA2 heterozygosity in embryonic stem cells reduces radiation-induced Rad51 focus formation but is not associated with radiosensitivity.

PURPOSE: The breast cancer susceptibility genes BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2) encode proteins involved in double-strand break (DSB) repair, whose functions include facilitating homologous recombination through interactions with Rad51, the human homologue of bacterial RecA. Homozygous deficiency inhibits Rad51 focus formation and enhances radiosensitivity, but the effects of heterozygosity have not been investigated in detail. The purpose of this work was to examine the effect of heterozygosity on Rad51 activation and clonogenicity following X-irradiation (XR). MATERIALS AND METHODS: We used quantitative assessment of immunofluorescent foci to assess Rad51 activation in wild type mouse embryonic fibroblasts (MEF) and in paired mutant and wild type BRCA1 and BRCA2 embryonic stem cells (ES cells). We measured radiosensitivity in the same cell lines using clonogenic survival assays. RESULTS: ES cells exhibit higher numbers of cells with Rad51 foci post radiation than MEF, likely due to differences in cell cycle distribution. Compared to wild type cells, BRCA1 and BRCA2 heterozygous ES cells demonstrate lower numbers of Rad51 foci per nucleus 4 and 24 hours post radiation. This was not associated with significantly enhanced radiosensitivity. CONCLUSIONS: BRCA1/2 heterozygosity in ES cells is associated with a subtle reduction in Rad51 foci formation that is not associated with increased XR induced cytotoxicity.

Effect of a thrombin receptor (protease-activated receptor 1, PAR-1) gene polymorphism in chronic hepatitis C liver fibrosis.

BACKGROUND AND AIM: Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease-activated receptor 1 (PAR-1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR-1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C. METHODS: Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (-1426C/T), 13 bp repeat of preceding -506 5'-CGGCCGCGGGAAG-3' sequence (-506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon-2 start site (IVS-14A/T). A total of 287 European and 90 Brazilian patients were studied. RESULTS: 1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype (P = 0.06) and an association between genotype CC and slow fibrosis (P = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT (P = 0.003) and CC (P = 0.007). There was a significant association between TT and fast fibrosis (P = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC (P = 0.03). Analysis of -506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS-14A/T showed no difference between genotypes. CONCLUSION: In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.

TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan.

Immune responses to microorganisms in the gastrointestinal tract must be carefully controlled to avoid disease. Helicobacter are Gram-negative bacteria which cause persistent infection and, in a minority of hosts, peptic ulceration or gastric cancer. Lymphocyte responses are important determinants of the outcome of infection. Therefore, it is important to identify the genetic determinants of lymphocyte responses to this mucosal pathogen. Using a (C57BL/6xBALB/c) F2 mouse model of Helicobacter infection, we mapped a region of linkage for lymphoproliferation to chromosome 9. Analysis of candidate genes in this region revealed variation of DNA sequence and gene expression in the TLR9 gene between C57BL/6 and BALB/c mouse strains. Reporter assays demonstrated higher levels of TLR9 transcriptional activity and increased NF-kappaB activation associated with the C57BL/6 TLR9 promoter and coding sequences. The importance of TLR9 in the control of lymphocyte responses was confirmed by demonstrating that lymphoproliferation and IFN-gamma secretion was diminished in the TLR9-/- mouse. Furthermore, neutrophil infiltration of the gastric epithelium is reduced in the absence of TLR9. Regulation of TLR9 expression and signalling therefore appears to play an important role in the control of lymphocyte responses to Helicobacter and potentially other luminal microorganisms.

Helicobacter infection in the surfactant protein D-deficient mouse.

BACKGROUND: Surfactant protein D (SP-D), a component of innate immunity, is expressed in the gastric mucosa and is up-regulated in the presence of Helicobacter infection. SP-D binds to Helicobacter in vitro, suggesting the involvement of SP-D in Helicobacter-induced immune responses. The aim of this study was to determine the role of SP-D in gastric epithelial defense in vivo. METHODS: Specific pathogen-free SP-D-deficient mice (SP-D(-/-)) and C57BL/6 wild-type controls were challenged by gavage with different doses of Helicobacter felis, a mouse-adapted Helicobacter strain. Mice were assessed for colonization rates and density of infection. Inflammatory responses were measured by neutrophil counting and T-cell responses by proliferation assays on spleen cells stimulated with H. felis sonicate. The in vitro effect of SP-D on Helicobacter uptake by monocyte-derived dendritic cells was assessed by confocal microscopy and FACS analyses. RESULTS: SP-D(-/-) mice were more susceptible to low-dose infectious challenge than C57BL/6 controls (p = .02). The density of colonization was higher in the SP-D(-/-) infected mice. Neutrophil infiltrates were lower in the SP-D(-/-) mice, particularly in the acid-secreting regions of the stomach. T-cell proliferative responses to Helicobacter antigen were reduced in SP-D(-/-) mice (p = .001) after 12 weeks infection. In vitro uptake of Helicobacter by dendritic cells was significantly enhanced in the presence of SP-D (p = .001). CONCLUSION: In the absence of SP-D, Helicobacter uptake by dendritic cells is impaired. This provides an explanation for the diminished inflammation and immune responses in the SP-D(-/-) mice.

Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D.

Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.

Helicobacter pylori flagellar hook-filament transition is controlled by a FliK functional homolog encoded by the gene HP0906.

Helicobacter pylori is a human gastric pathogen which is dependent on motility for infection. The H. pylori genome encodes a near-complete complement of flagellar proteins compared to model enteric bacteria. One of the few flagellar genes not annotated in H. pylori is that encoding FliK, a hook length control protein whose absence leads to a polyhook phenotype in Salmonella enterica. We investigated the role of the H. pylori gene HP0906 in flagellar biogenesis because of linkage to other flagellar genes, because of its transcriptional regulation pattern, and because of the properties of an ortholog in Campylobacter jejuni (N. Kamal and C. W. Penn, unpublished data). A nonpolar mutation of HP0906 in strain CCUG 17874 was generated by insertion of a chloramphenicol resistance marker. Cells of the mutant were almost completely nonmotile but produced sheathed, undulating polyhook structures at the cell pole. Expression of HP0906 in a Salmonella fliK mutant restored motility, confirming that HP0906 is the H. pylori fliK gene. Mutation of HP0906 caused a dramatic reduction in H. pylori flagellin protein production and a significant increase in production of the hook protein FlgE. The HP0906 mutant showed increased transcription of the flgE and flaB genes relative to the wild type, down-regulation of flaA transcription, and no significant change in transcription of the flagellar intermediate class genes flgM, fliD, and flhA. We conclude that the H. pylori HP0906 gene product is the hook length control protein FliK and that its function is required for turning off the sigma(54) regulon during progression of the flagellar gene expression cascade.

HP0958 is an essential motility gene in Helicobacter pylori.

Motility is an essential colonization factor for the human gastric pathogen Helicobacter pylori. The H. pylori genome encodes most known flagellar proteins, although a number of key transcription regulators, chaperones, and structural proteins have not yet been identified. Using recently published yeast two-hybrid data we identified HP0958 as a potential motility-associated protein due to its strong interactions with RpoN (sigma(54)) and FliH, a flagellar ATPase regulator. HP0958 exhibits no sequence similarity to any published flagellar genes but contains a carboxy-terminal zinc finger domain that could function in nucleic acid or protein binding. We created a HP0958 mutant by inserting a chloramphenicol resistance marker into the gene using a PCR-based allelic exchange method and the resultant mutant was non-motile as measured by a BacTracker instrument. Electron microscopic analysis revealed that the HP0958 mutant cells were aflagellate and Western blot analysis revealed a dramatic reduction in flagellin and hook protein production. The HP0958 mutant also showed decreased transcription of flgE, flaB and flaA as well as the checkpoint genes flhA and flhF. Expression of flgM was increased relative to the wild-type and both rpoN and fliA (sigma(28)) expression were unchanged. We conclude that HP0958 is essential for normal motility and flagella production, and represents a novel flagellar component in the epsilon proteobacteria.

Chemotactic response of Helicobacter pylori to human plasma and bile.

To clarify further the role of chemotaxis in Helicobacter pylori colonization, the in vitro bacterium response to human plasma and bile (secretions containing chemoeffector compounds that are present in the gastric mucus layer) was examined. Human plasma, after dilution to 1 % (v/v) with buffer, was found to be a chemoattractant for the motile bacillus. Human gall-bladder bile, after dilution to 2 % (v/v) with buffer, was found to be a chemorepellent, but did not cause the motility of the bacillus to be diminished after prolonged exposure. The basis of the chemoattractant effect of plasma was explored by examining how urea and 12 amino acids found in plasma affected the taxis of H. pylori. Urea and the amino acids histidine, glutamine, glycine and arginine were the strongest chemoattractants. Other amino acids were chemoattractants, with the exceptions of aspartic and glutamic acids, which were chemorepellents. The basis of the chemorepellent effect of bile was explored by examining how the six most abundant conjugated bile acids in human bile affected the taxis of H. pylori. All the bile acids were chemorepellents, with the greatest effects being demonstrated by taurocholic and taurodeoxycholic acids. The implications of these findings for H. pylori colonization of gastric epithelium are discussed.

How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.

BACKGROUND: Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment. METHODS: Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach. RESULTS: H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8. CONCLUSIONS: Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.