Detection and characterization of carbapenem resistant Gram-negative bacilli isolates recovered from hospitalized patients at Soba University Hospital, Sudan

BACKGROUND: Antimicrobial resistance (AMR) poses a complex threat to global health security and universal health coverage. Recently, nosocomial infections with carbapenemase-producing Gram-negative bacilli (GNB) is increasing worldwide. We report the molecular characterization and detection of genes associated with carbapenemase producing Gram negative bacteria isolated from hospitalized patients at Soba University Hospital (SUH) in Khartoum State, Sudan. RESULTS: Between October 2016 and February 2017, a total of 206 GNB clinical specimens were collected from hospitalized patients in SUH. Of 206 carbapenem resistance isolates, 171 (83 %) were confirmed as phenotypically resistant and 121 (58.7 %) isolates harboured one or more carbapenemase genes. New Delhi metallo-β-lactamase (NDM) types were the most predominant genes, blaNDM 107(52 %), followed by blaIMP 7 (3.4 %), blaOXA-48 5(2.4 %) and blaVIM 2 (0.9 %). Co-resistance genes with NDM producing GNB were detected in 87 (81.3 %) of all blaNDM producing isolates. NDM-1 was the most frequent subtype observed in 75 (70 %) blaNDM producing isolates. The highest percentage of resistance was recorded in ampicillin (98 %), cephalexin (93.5 %) amoxicillin clavulanic acid (90 %), cefotaxime (89.7 %), ceftriaxone (88.4 %), ceftazidime (84.2 %), sulfamethoxazole-trimethoprim (78.4 %) and nitrofurantoin (75.2 %), aztreonam (66 %) and temocillin (64 %). A close correlation between phenotypic and carbapenemase genes detection in all GNB was observed. CONCLUSIONS: The frequency of carbapenemase producing bacilli was found to be high in SUH. NDM was found to be the most prevalent carbapenemase gene among clinical isolates. Close surveillance across all hospitals in Sudan is required. The relative distribution of carbapenemase genes among GNB in nosocomial infections in Africa needs to be defined

Toward a conceptual framework of the acceptability of tuberculosis treatment in children using a theory generative approach

To describe an early-stage holistic framework towards evaluating factors that impact the overall acceptability of TB treatment along the TB care cascade in children. We developed a conceptual framework utilising a theory generative approach. Domains were developed through review of existing definitions and analysis of existing qualitative data undertaken in acceptability studies of TB treatment in children. Clarity of domain definitions was achieved through iterative refinement among the research team. Three domains, each comprising several dimensions, were identified to holistically evaluate treatment acceptability: (1) usability, which involves the alignment between the requirements of treatment use and caregivers’ and children’s ability to integrate TB treatment into their everyday routines, (2) receptivity, which describes the end-user’s perception and expectations of treatment and its actual use, and (3) integration, which describes the relationship between available health services and caregivers/children’s capacity to make use of those services. Our framework addresses the gaps in current research which do not account for the influence of caregivers’ and children’s contexts on TB treatment uptake and overall acceptability. This approach may support the development of more standard, holistic measures to improve TB treatment delivery and experiences and future research in children

Actin binding proteins:their ups and downs in metastatic life

In order to metastasize away from the primary tumor site and migrate into adjacent tissues, cancer cells will stimulate cellular motility through the regulation of their cytoskeletal structures. Through the coordinated polymerization of actin filaments, these cells will control the geometry of distinct structures, namely lamella, lamellipodia and filopodia, as well as the more recently characterized invadopodia. Because actin binding proteins play fundamental functions in regulating the dynamics of actin polymerization, they have been at the forefront of cancer research. This review focuses on a subset of actin binding proteins involved in the regulation of these cellular structures and protrusions, and presents some general principles summarizing how these proteins may remodel the structure of actin. The main body of this review aims to provide new insights into how the expression of these actin binding proteins is regulated during carcinogenesis and highlights new mechanisms that may be initiated by the metastatic cells to induce aberrant expression of such proteins. © 2013 Landes Bioscience

CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study

<p>Abstract</p> <p>Background</p> <p>Estrogens, environmental chemicals with carcinogenic potential, as well as oxidative and carbonyl stresses play a very important role in breast cancer (BC) genesis and progression. Therefore, polymorphisms of genes encoding enzymes involved in estrogen biosynthesis pathway and in the metabolic activation of pro-carcinogens to genotoxic intermediates, such as cytochrome P450C17α (CYP17), endogenous free-radical scavenging systems, such as glutathione S-transferase (GSTP1) and paraoxonase 1 (PON1), and anti-glycation defenses, such as glyoxalase I (GLO1), could influence individual susceptibility to BC. In the present case-control study, we investigated the possible association of CYP17 A1A2, GSTP1 ILE105VAL, PON1 Q192R or L55M, and GLO1 A111E polymorphisms with the risk of BC.</p> <p>Methods</p> <p>The above-said five polymorphisms were characterized in 547 patients with BC and in 544 healthy controls by PCR/RFLP methods, using DNA from whole blood. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for BC.</p> <p>Results</p> <p>CYP17 polymorphism had no major effect in BC proneness in the overall population. However, it modified the risk of BC for certain subgroups of patients. In particular, among premenopausal women with the A1A1 genotype, a protective effect of later age at menarche and parity was observed. As to GSTP1 and PON1 192 polymorphisms, the mutant Val and R alleles, respectively, were associated with a decreased risk of developing BC, while polymorphisms in PON1 55 and GLO1 were associated with an increased risk of this neoplasia. However, these findings, while nominally significant, did not withstand correction for multiple testing.</p> <p>Conclusion</p> <p>Genetic polymorphisms in biotransformation enzymes CYP17, GSTP1, PON1 and GLO1 could be associated with the risk for BC. Although significances did not withstand correction for multiple testing, the results of our exploratory analysis warrant further studies on the above mentioned genes and BC.</p

Prevalence of Chlamydia trachomatis infection among women in a Middle Eastern community

BACKGROUND: Common vaginal infections that manifest in women are usually easily diagnosed. However, Chlamydia infection is often asymptomatic, leading to infertility before it is detected. If it occurs in pregnancy, it could lead to significant neonatal morbidity. It may also play a role with other viral infections for e.g. Human Papilloma Virus in the development of cervical cancer. The objective of this study was to determine the prevalence of Chlamydia infection in women undergoing screening for cervical abnormalities as a part of a research project in primary and secondary care institutions in the United Arab Emirates. METHODS: In this cross sectional study married women attending primary and secondary care participating in a large nationwide cervical abnormalities screening survey were offered Chlamydia testing using a commercially available test kit. This kit uses a rapid immunoassay for the direct detection of Chlamydia trachomatis antigen in endocervical swab specimens. As this study was performed in a traditional Islamic country, unmarried women were excluded from testing, as the management of any positive cases would create legal and social problems. All married women consenting to take part in the study were included irrespective of age. RESULTS: Of 1039 women approached over a period of eight months 919 (88.5%) agreed to participate. The number of women in the 16 to 19 years was small (0.01%) and 30% were aged over 40 years. The prevalence of Chlamydia infection in this study was 2.6% (95% confidence interval 1.2–3.3%), which was marginally higher in women screened in secondary care (p = 0.05). CONCLUSION: This is one of the few reports on the prevalence of Chlamydia infection in women from the Middle East. Due to cultural and social constraints this study excluded a large proportion of women aged less than 19 years of age. Hence no direct comparisons on prevalence could be made with studies from the West, which all included younger women at high risk of Chlamydia. However this study emphasizes the importance of cultural factors while interpreting results of studies from different cultures and communities

Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1β, TNF-α, IL-10 and TGF-β) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations

A Cytological Analysis of Wheat Meiosis Targeted by Virus-Induced Gene Silencing (VIGS)

Virus-induced gene silencing (VIGS) is a rapid and cost-effective reverse genetic technology that can be used to assess gene function in wheat. This chapter contains a detailed description of how to target wheat meiotic genes by VIGS. The timing of this technique is critical and has been optimized to silence meiotic genes at peak expression, evidenced by silencing of Triticum aestivum disrupted meiotic cDNA1 (TaDMC1). We also describe cytological techniques that have been adapted for the preparation and analysis of meiocytes in wheat, including fluorescent in situ hybridization (FISH) with directly labeled, synthetic oligonucleotide probes, and immunolocalization on spread material

The association of spinal osteoarthritis with lumbar lordosis

<p>Abstract</p> <p>Background</p> <p>Careful review of published evidence has led to the postulate that the degree of lumbar lordosis may possibly influence the development and progression of spinal osteoarthritis, just as misalignment does in other joints. Spinal degeneration can ensue from the asymmetrical distribution of loads. The resultant lesions lead to a domino- like breakdown of the normal morphology, degenerative instability and deviation from the correct configuration. The aim of this study is to investigate whether a relationship exists between the sagittal alignment of the lumbar spine, as it is expressed by lordosis, and the presence of radiographic osteoarthritis.</p> <p>Methods</p> <p>112 female subjects, aged 40-72 years, were examined in the Outpatients Department of the Orthopedics' Clinic, University Hospital of Heraklion, Crete. Lumbar radiographs were examined on two separate occasions, independently, by two of the authors for the presence of osteoarthritis. Lordosis was measured from the top of L₁to the bottom of L₅as well as from the top of L₁to the top of S₁. Furthermore, the angle between the bottom of L₅to the top of S₁was also measured.</p> <p>Results and discussion</p> <p>49 women were diagnosed with radiographic osteoarthritis of the lumbar spine, while 63 women had no evidence of osteoarthritis and served as controls. The two groups were matched for age and body build, as it is expressed by BMI. No statistically significant differences were found in the lordotic angles between the two groups</p> <p>Conclusions</p> <p>There is no difference in lordosis between those affected with lumbar spine osteoarthritis and those who are disease free. It appears that osteoarthritis is not associated with the degree of lumbar lordosis.</p

Cerebrospinal fluid matrix metalloproteinase-9 increases during treatment of recurrent malignant gliomas

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are enzymes that promote tumor invasion and angiogenesis by enzymatically remodeling the extracellular matrix. MMP-2 and MMP-9 are the most abundant forms of MMPs in malignant gliomas, while a 130 kDa MMP is thought to be MMP-9 complexed to other proteinases. This study determined whether doxycycline can block MMP activity <it>in vitro</it>. We also measured MMP-2 and MMP-9 levels in cerebrospinal fluid (CSF) from patients with recurrent malignant gliomas.</p> <p>Methods</p> <p>To determine whether doxycycline can block MMP activity, we measured the extent of doxycyline-mediated MMP-2 and MMP-9 inhibition <it>in vitro </it>using epidermal growth factor receptor (EGFR) transfected U251 glioma cell lines. MMP activity was measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. In addition, patients underwent lumbar puncture for CSF sampling at baseline, after 6 weeks (1 cycle), and after 12 weeks (2 cycles), while being treated with a novel chemotherapy regimen of irinotecan, thalidomide, and doxycycline designed to block growth/proliferation, angiogenesis, and invasion. Irinotecan was given at 125 mg/m²/week for 4 weeks in 6-week cycles, together with continuous doxycycline at 100 mg twice daily on Day 1 and 50 mg twice daily thereafter. Daily thalidomide dose in our cohort was 400 mg. Tumor progression was monitored by magnetic resonance imaging (MRI).</p> <p>Results</p> <p>Doxycyline <it>in vitro </it>completely abolished MMP-9 activity at 500 μg/ml while there was only 30 to 50% inhibition of MMP-2 activity. Four patients respectively completed 4, 3, 1, and 2 cycles of irinotecan, thalidomide, and doxycycline. Patient enrollment was terminated after one patient developed radiologically defined pulmonary embolism, and another had probable pulmonary embolism. Although CSF MMP-2 and 130 kDa MMP levels were stable, MMP-9 level progressively increased during treatment despite stable MRI.</p> <p>Conclusion</p> <p>Doxycycline can block MMP-2 and MMP-9 activities from glioma cells <it>in vitro</it>. Increased CSF MMP-9 activity could be a biomarker of disease activity in patients with malignant gliomas, before any changes are detectable on MRI.</p