3,977 research outputs found
Chronic kidney disease in patients admitted to the medical ward of Mbarara Regional Referral Hospital in southwestern Uganda: Prevalence and associated factors
Background: In tropical Africa, although chronic kidney disease (CKD) is common, there are few data about its’ prevalence among patients admitted to a general medical ward. Aim: We proposed to determine the prevalence of CKD among patients admitted to a general medical ward in Uganda. Methods: We conducted a cross sectional study consecutively enrolling adults admitted to the medical ward of Mbarara Regional Referral Hospital over three months. We collected socio-demographic and clinical data including presenting symptoms, history of diabetes, hypertension, and use of nephrotoxic medication. Consenting patients provided spot morning urine specimen for measurement of urine albumin and we also drew patients’ blood for measurement of markers of renal function, complete blood count, hepatitis B surface antigen, and HIV. We also performed renal sonography for all included patients. We defined CKD as a glomerular filtration rate (eGFR) less than 60ml/min/1.73m².We used logistic regression to assess for factors associated with CKD. Results: Of the 372 patients enrolled, 57 (15.3%) had CKD. Body swelling (OR=2.79, 95% CI 1.53-5.07; p=0.001), active urine sediment (OR=3.13, 95% CI 1.64-6.41; p=0.016), microalbuminuria (OR=1.92, 95% CI 1.07-3.43; p=0.028), history of hypertension (OR=3.65, 95% CI 1.69-7.90; p=0.001), and high blood pressure (OR=3.34, 95% CI 1.33-8.40; p=0.010) were independently associated with CKD. Conclusion: Chronic kidney disease is common with hypertension as the etiology and associated with body swelling, active urine sediment and microalbuminuria among patients admitted to a general medical ward in southwestern Uganda. Screening for CKD of patients at risk should be prioritized in general medical wards.Key words: Chronic kidney disease, epidemiology, nephrotoxicity, poor resource setting, Ugand
Association between Intraoperative Bactibilia and Postoperative Septic Complications in Biliary Tract Surgery
Background: The present study intended to clarify the role of biliary bacteria in the development of postoperative septic complications in patients undergoing biliary operations and need for antibiotic prophylaxis.Patient and methods: A total of 121 patients with various biliary tract diseases underwent various surgical interventions. The relation between contaminated ductal bile and postoperative septic complications was analyzed prospectively.Results: 42/121 patients were bile culture positive (B+) while 79/121 patients were bile culture negative (B-).14 patients in B (+) group developed septic complications compared to only 3 patients in B (-) group (P = 0.0001). In B (+) group, bacteria found in ductal bile were also detected in infected sites of 85% of patients with septic complications. In B (+) group postoperative antibiotic modification significantly (p=0.001) reduced infectious complications.Conclusion: Infected bile plays a critical role in development of post operative septic complications. Hence patients with risk factors for bactibilia should receive prophylactic antibiotics covering endogenous gram negative organisms which should be modified in postoperative phase according to the results of sensitivity. However this issue requires further investigations by studies conducted on similar lines
Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc-mediated response to hyperosmolarity
Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified. The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes. Based on microarray studies we chose two tyrosine-kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc phosphorylation and generated single and double knock-out mutants to them. Transcriptional regulation of STATc and STATc dependent genes was disturbed in pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2 resulted in diminished or completely abolished increased transcription of STATc dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ. Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-) cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced phosphorylation was mirrored by a significant delay in nuclear translocation of GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747. Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo. Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an, as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and hence its inhibition, and that Pyk3 is involved in the regulation of STATc by either directly or indirectly activating it. Our results add further complexities to the regulation of STATc, which presumably ensure its optimal activation in response to different environmental cues
Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid
BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio
Relationship between PPI and baseline startle response
Prepulse inhibition (PPI) of the startle response to a sudden noise is the reduction in startle observed when the noise is preceded shortly by a mild sensory event, which is often a tone. A part of the literature is based on the assumption that PPI is independent of the baseline startle. A simple model is presented and experimental validation provided. The model is based on the commonly accepted observation that the neuronal circuit of PPI differs from that of startle. But, by using a common output, the measures of both phenomena become linked to each other. But, how can we interpret the numerous experimental data showing PPI to be independent of the startle level? It is suggested that in a number of such cases the baseline startle would have been stabilized by a ceiling effect in the startle/PPI neuronal networks. Reducing the startle level, for example in a PPI evaluation procedure, may disclose properties of startle masked by this ceiling effect. Disclosure of habituation to the startle eliciting noise produced an increase of PPI along its initial measurements. Taken together, even if the neuronal process that sustains startle and PPI are distinct, separating them experimentally requires careful parametric methods and caution in the interpretation of the corresponding observations
Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.
Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9)), and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9)). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements
Does Practice Make Perfect?
Extensive literature supports the correlation between surgical volume and improved clinical outcome in the management of various cancers. It is this evidence that has catalysed the creation of centres of excellence. However, on closer inspection, many of these studies are poor quality, low weight and use vastly heterogenous end points in assessment of both volume and outcome. We critically appraise the English language literature published over the last ten years pertaining to the volume outcome relationship in the context of cancer care. Future balanced unbiased studies may enable equipoise in planning international cancer management strategies
Estimation of Fracture Toughness of Anisotropic Rocks by Semi-Circular Bend (SCB) Tests Under Water Vapor Pressure
In order to investigate the influence of water vapor pressure in the surrounding environment on mode I fracture toughness (KIc) of rocks, semi-circular bend (SCB) tests under various water vapor pressures were conducted. Water vapor is one of the most effective agents which promote stress corrosion of rocks. The range of water vapor pressure used was 10−2 to 103 Pa, and two anisotropic rock types, African granodiorite and Korean granite, were used in this work. The measurement of elastic wave velocity and observation of thin sections of these rocks were performed to investigate the microstructures of the rocks. It was found that the distribution of inherent microcracks and grains have a preferred orientation. Two types of specimens in different orientations, namely Type-1 and Type-3, were prepared based on the anisotropy identified by the differences in the elastic wave velocity. KIc of both rock types was dependent on the water vapor pressure in the surrounding environment and decreased with increasing water vapor pressure. It was found that the degree of the dependence is influenced by the orientation and density of inherent microcracks. The experimental results also showed that KIc depended on the material anisotropy. A fracture process was discussed on the basis of the geometry of fractures within fractured specimens visualized by the X-ray computed tomography (CT) method. It was concluded that the dominant factor causing the anisotropy of KIc is the distribution of grains rather than inherent microcracks in these rocks
Socioeconomic disparities in breast cancer survival: relation to stage at diagnosis, treatment and race
<p>Abstract</p> <p>Background</p> <p>Previous studies have documented lower breast cancer survival among women with lower socioeconomic status (SES) in the United States. In this study, I examined the extent to which socioeconomic disparity in breast cancer survival was explained by stage at diagnosis, treatment, race and rural/urban residence using the Surveillance, Epidemiology, and End Results (SEER) data.</p> <p>Methods</p> <p>Women diagnosed with breast cancer during 1998-2002 in the 13 SEER cancer registry areas were followed-up to the end of 2005. The association between an area-based measure of SES and cause-specific five-year survival was estimated using Cox regression models. Six models were used to assess the extent to which SES differences in survival were explained by clinical and demographical factors. The base model estimated the hazard ratio (HR) by SES only and then additional adjustments were made sequentially for: 1) age and year of diagnosis; 2) stage at diagnosis; 3) first course treatment; 4) race; and 5) rural/urban residence.</p> <p>Results</p> <p>An inverse association was found between SES and risk of dying from breast cancer (p < 0.0001). As area-level SES falls, HR rises (1.00 → 1.05 → 1.23 → 1.31) with the two lowest SES groups having statistically higher HRs. This SES differential completely disappeared after full adjustment for clinical and demographical factors (p = 0.20).</p> <p>Conclusion</p> <p>Stage at diagnosis, first course treatment and race explained most of the socioeconomic disparity in breast cancer survival. Targeted interventions to increase breast cancer screening and treatment coverage in patients with lower SES could reduce much of socioeconomic disparity.</p
Structural and Biochemical Characterization of SrcA, a Multi-Cargo Type III Secretion Chaperone in Salmonella Required for Pathogenic Association with a Host
Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2) is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 Å revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS
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