Renal phenotype is exacerbated in Os and lpr double mutant mice

Renal phenotype is exacerbated in Os and lpr double mutant mice.BackgroundROP-Os/+ mice are born with oligosyndactyly and oligonephronia and develop renal dysfunction, which includes renal tubular epithelial cell (RTC) Fas-dependent apoptosis and tubular atrophy. MRL/lpr mice harbor a Fas-inactivating mutation and develop glomerulonephritis, whereas mice expressing lpr on a C3H background demonstrate no renal phenotype. We hypothesized that crossing ROP-Os/+ with CH3-lpr/lpr mice would rescue the Os/+ renal phenotype by reducing Fas-dependent RTC apoptosis.MethodsROP-Os/+ mice were intercrossed with C3H-lpr/lpr mice and F2 generation animals were phenotyped by kidney weight, serum creatinine, and albuminuria. Kidney sections were scored for histopathology and apoptosis. Univariate and multivariate analyses were used to examine additive effects of Os and lpr on renal phenotype.ResultsBy 16 weeks, F2Os/+ lpr/lpr mice developed significantly more albuminuria, glomerulosclerosis, and interstitial inflammation compared to Os/++/+ mice. Glomerular cell apoptosis was increased in Os/+ lpr/lpr compared to Os/++/+ mice, with no significant difference in RTC apoptosis. A statistically significant Os-lpr effect on renal phenotype was demonstrated by multivariate analysis, which exceeded the combined independent effects if Os and lpr, indicating a biologic interaction exists between Os and lpr.Conclusion.Os/+mice with a superimposed lpr mutation displayed a more severe renal phenotype, rather than phenotype rescue, suggesting that Fas pathway activation is necessary to delete cells resulting from Os-dependent injury. We further propose that an Os-lpr gene interaction and/or mixed ROP-C3H genetic background regulated the renal phenotype, consistent with the concept that chronic renal disease pathogenesis reflects effects of multiple nephropathy susceptibility alleles

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia

BACKGROUND: Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. METHODS: We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). RESULTS: Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. CONCLUSION AND SIGNIFICANCE: Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population

TRUST IN CROSS-CULTURAL B2B FINANCIAL SERVICE RELATIONSHIPS: THE ROLE OF SHARED VALUES

This is the accepted version of the following article: Houjeir, R. & Brennan, R. J, 'Trust in cross-cultural b2b financial service relationships: The role of shared values', Journal of Financial Services Marketing, June 2016, Vol 21(2): 90-102 The final publication is available at Springer via http://dx.doi.org/10.1057/fsm.2016.4Trust in business-to-business supplier–customer relationships in financial services is an area of considerable research interest. The bulk of prior empirical research in this field has concentrated on trust in business relationships within a Western cultural context. However, shared values are acknowledged to be an important antecedent to trust. The premise of this study is that in circumstances where there are substantial cultural differences between parties to a supplier–customer relationship, these differences will be reflected in shared values, which will in turn be reflected in differences in the nature of trust. A qualitative study was conducted among business bankers and their corporate clients in the context of the United Arab Emirates. In all 170 respondents were interviewed; of these, 160 were paired respondents, that is, where a client and banker from the same business relationship were interviewed (yielding 80 interview dyads). Substantial differences with respect to trust were found between relationships that involved only Emiratis, those that involved Emiratis and non-Emiratis, and those that involved only non-Emiratis. For Emiratis mutual trust is substantially based on family and clan ties and exhibits strongly affective characteristics. For non-Emiratis trust is largely based on business considerations, and exhibits strongly cognitive characteristics.Peer reviewedFinal Accepted Versio

Consumer trust and confidence in the compliance of Islamic banks

Islamic banks compete with traditional (non-Islamic) banks for customers. This article aims to provide insight into why some Muslims choose to bank with Islamic banks in Pakistan, while others do not. Specifically, it addresses the questions: to what extent are trust and confidence active influencers in the decision-making process, are they differentiated or are they one of the same? Also how does the Pakistani collective cultural context further complicate the application of these concepts? For the purposes of this article trust refers to people and their interpersonal or social relations whereas confidence concerns institutions such as banks. Drawing on interviews with Muslim consumers in Pakistan, this study provides further insight into consumer behaviour within financial services and specifically Islamic banking and contributes to our theoretical understanding of the concepts of trust and confidence

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Real-time three-dimensional transthoracic echocardiography in daily practice: initial experience

<p>Abstract</p> <p>Aim of the work</p> <p>To evaluate the feasibility and possible additional value of transthoracic real-time three-dimensional echocardiography (RT3D-TTE) for the assessment of cardiac structures as compared to 2D-TTE.</p> <p>Methods</p> <p>320 patients (mean age 45 ± 8.4 years, 75% males) underwent 2D-TTE and RT3D-TTE using 3DQ-Q lab software for offline analysis. Volume quantification and functional assessment was performed in 90 patients for left ventricle and in 20 patients for right ventricle. Assessment of native (112 patients) and prosthetic (30 patients) valves morphology and functions was performed. RT3D-TTE was performed for evaluation of septal defects in 30 patients and intracardiac masses in 52 patients.</p> <p>Results</p> <p>RT3D-TTE assessment of left ventricle was feasible and reproducible in 86% of patients while for right ventricle, it was (55%). RT3D-TTE could define the surface anatomy of mitral valve optimally (100%), while for aortic and tricuspid was (88% and 81% respectively). Valve area could be planimetered in 100% for the mitral and in 80% for the aortic. RT3D-TTE provided a comprehensive anatomical and functional evaluation of prosthetic valves. RT3D-TTE enface visualization of septal defects allowed optimal assessment of shape, size, area and number of defects and evaluated the outcome post device closure. RT3D-TTE allowed looking inside the intracardiac masses through multiple sectioning, valuable anatomical delineation and volume calculation.</p> <p>Conclusion</p> <p>Our initial experience showed that the use of RT3D-TTE in the assessment of cardiac patients is feasible and allowed detailed anatomical and functional assessment of many cardiac disorders.</p

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised