All-optical spatiotemporal mapping of ROS dynamics across mitochondrial microdomains in situ.

Hydrogen peroxide (H2O2) functions as a second messenger to signal metabolic distress through highly compartmentalized production in mitochondria. The dynamics of reactive oxygen species (ROS) generation and diffusion between mitochondrial compartments and into the cytosol govern oxidative stress responses and pathology, though these processes remain poorly understood. Here, we couple the H2O2 biosensor, HyPer7, with optogenetic stimulation of the ROS-generating protein KillerRed targeted into multiple mitochondrial microdomains. Single mitochondrial photogeneration of H2O2 demonstrates the spatiotemporal dynamics of ROS diffusion and transient hyperfusion of mitochondria due to ROS. This transient hyperfusion phenotype required mitochondrial fusion but not fission machinery. Measurement of microdomain-specific H2O2 diffusion kinetics reveals directionally selective diffusion through mitochondrial microdomains. All-optical generation and detection of physiologically-relevant concentrations of H2O2 between mitochondrial compartments provide a map of mitochondrial H2O2 diffusion dynamics in situ as a framework to understand the role of ROS in health and disease.

Climate Change and Aging Health in Developing Countries.

The climate of the Earth has changed throughout history. Climate change negatively impacts human rights in a wide range of ways. The study aims to find out the impact of climate change on aging health in developing countries. The study found that public health will be devastated if climate change continues unabated. Countries that are least responsible for global warming are most susceptible to the effects of higher temperatures, such as death and disease. In low- and middle-income countries, disasters are more likely to happen to people aged 60 and over. Although climate change affects all of us, older people are especially at risk from it, as evidenced by a growing body of research. The study also offers countermeasures and suggestions to develop aging health in developing countries affected by climate change.

The Intricate Relationship of Employee Engagement and Lean Approach toward Quality Improvement of the Public Hospitals.

The lean approach is a value-added system that reduces cost and waste to continuously improve the quality performance of the healthcare organization. The present study investigates the relationships of the lean approach with top management team and employee engagement toward quality improvement of the public hospitals in Malaysia. This study used stratified random sampling to collect data from the public hospitals' staff who were directly involved with patient services. In this study, PLS-SEM 3.3.4 was applied to measure the research constructs and hypotheses. The research findings indicate that the lean approach has a significant relationship with the top management team and employee engagement to positively impact the quality improvement of the public hospital. However, research findings also indicate that the top management team has no significant influence on quality improvement in public hospitals, but it has an indirect effect through the lean approach and employee engagement. The findings of the study will provide guidelines on how the lean approach contributes to the body of knowledge and practical implications to continuously improve the quality performance of public healthcare system.

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats.

BACKGROUND: Nowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE. METHODS: Firstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days. RESULTS: The results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress. CONCLUSION: Co-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Congenital colorectal tubular duplication in an infant: A tale of radiological diagnostic challenges.

Enteric duplications (EDs) are rare congenital anomalies that result from defect during embryonic development of the gut. Although EDs can literally occur at any part of the gastrointestinal tract, ileocecal duplication is the commonest type followed by colorectal type. Morphologically, EDs are mostly cystic in nature; tubular duplications are uncommon. We report radiological diagnostic challenges encountered in dealing with a 10 month-old infant who presented with chronic constipation, progressive abdominal distension, and voiding difficulty for several weeks followed by colicky abdominal pain for three days. After a series of radiological procedures, a diagnosis of tubular colorectal duplication was made. The duplicated segment was loaded with impacted feces which exerted pressure effect on the rectum and urinary bladder. The case was treated surgically through laparoscopic procedure that included fenestration and stapling of the duplicated bowel followed by irrigation. Postoperatively, the child was followed up half-yearly for three years and was found to remain symptom-free. This case exemplifies the challenges a radiologist may experience while dealing with a case presenting with features of as acute-on-chronic intestinal obstruction and voiding difficulty.

MR imaging of hypothalamic hamartoma in a patient with gelastic seizures.

Hypothalamic hamartomas (HHs) are non-neoplastic malformations that occur in the region of the hypothalamus. HH is the leading cause of gelastic seizures in children and adolescents, where laughing is characteristically manifested. However, these patients can also experience different forms of complex or generalized tonic-clonic seizures that can obscure the diagnosis of HHs. We present a case of a 10 year-old boy that experienced several seizure types, but was subsequently diagnosed with HH after MR imaging was performed. This case highlights the complementary role of MR imaging in ascertaining seizure etiololgy when the clinical history and EEG findings are non-specific. The importance of early diagnosis with MR imaging is further underscored by the fact that patients diagnosed with HH usually develop drug resistance towards antiepileptic drugs, mandating neurosurgical assessment and intervention.

Wilms tumor presenting as small bowel obstruction in a neonate: A diagnostic challenge.

Wilms tumor is the most common primary malignant renal tumor of childhood which usually presents between 2 and 6 years of age. Its presentation in the neonatal period is extremely rare and presenting with intestinal obstruction is perhaps unknown. We report a 2-day-old baby girl who manifested features of acute upper gastrointestinal obstruction with frequent post-feeding vomiting and abdominal distension. The initial abdominal radiograph showed abnormally displayed small bowel loops to the right hemiabdomen. Subsequent ultrasound and computed tomography scan of the abdomen detected a massive left renal mass. Left-sided nephrectomy was performed, and histopathology demonstrated left-sided Wilms tumor with favorable histology. Post-treatment yearly follow-up for 5 years recorded a disease-free, normally thriving child.

Prediction Model Using Machine Learning for Mortality in Patients with Heart Failure.

Heart Failure (HF) is a major cause of morbidity and mortality in the US. With aging of the US population, the public health burden of HF is enormous. We aimed to develop an ensemble prediction model for 30-day mortality after discharge using machine learning. Using an electronic medical records (EMR) database, all patients with a non-elective HF admission over 10 years (January 2001 - December 2010) within the Montefiore Medical Center (MMC) health system, in the Bronx, New York, were included. We developed an ensemble model for 30-day mortality after discharge and employed discrimination, range of prediction, Brier index and explained variance as metrics in assessing model performance. A total of 7,516 patients were included. The discrimination achieved by the ensemble model was higher 0.83 (95% CI: 0.80 to 0.87) compared to the benchmark model 0.79 (95% CI: 0.75 to 0.84). The ensemble model also exhibited a better range of prediction as well as a favorable profile with respect to the other metrics employed. In conclusion, an ensemble machine learning approach exhibited an improvement in performance compared to the benchmark logistic model in predicting all-cause mortality among HF patients within 30-days of discharge. Machine learning is a promising alternative approach for risk profiling of HF patients, and it enhances individualized patient management.

Integrating DMAIC approach of Lean Six Sigma and theory of constraints toward quality improvement in healthcare.

Healthcare is a unique service industry and it deals with complex tasks. To overcome complex tasks, healthcare organizations need to implement DMAIC (Define, Measure, Analyze, Improve, Control) approach of Lean Six Sigma (LSS) to improve quality performance. Application of DMAIC in a healthcare organization provides guidelines on how to handle a quality service system toward patient satisfaction. This approach also helps healthcare service providers to reduce waste, variation and work imbalance in the service processes. This chapter discusses five phases of DMAIC approach and its integration with the theory of constraints (TOC) for continuous improvements in healthcare performance. The integration of TOC and DMAIC approach would enhance healthcare performance by reducing medical costs, medical errors, administration errors and defects. Moreover, this integration can improve performance in healthcare service processes where it is not possible to reduce bottlenecks.

Effect of Lean Six Sigma on quality performance in Malaysian hospitals.

PURPOSE: The purpose of this paper is to investigate the effects of Lean Six Sigma (LSS) and workforce management on the quality performance of Malaysian hospitals. This paper also investigates the direct and indirect relationships between top management commitment and quality performance of the healthcare organisations in Malaysia. DESIGN/METHODOLOGY/APPROACH: This study applied stratified random sampling to collect data from 15 different hospitals in Peninsular Malaysia. The self-administered survey questionnaires were distributed among 673 hospital staff (i.e. doctors, nurses, pharmacists, and medical laboratory technologists) to obtain 335 useful responses with a 49.47 per cent valid response rate. The research data were analysed based on confirmatory factor analysis and structural equation modelling by using AMOS version 23 software. FINDINGS: The research findings indicated that LSS and workforce management have a significant impact on quality performance of the Malaysian hospitals, whereas senior management commitment was found to have an insignificant relationship with quality performance. The research findings indicate that senior management commitment has no direct significant relationship with quality performance, but it has an indirect significant relationship with quality performance through the mediating effects of LSS and workforce management. RESEARCH LIMITATIONS/IMPLICATIONS: This research focussed solely on healthcare organisations in Malaysia and thus the results might not be applicable for other countries as well as other service organisations. ORIGINALITY/VALUE: This research provides theoretical, methodological, and practical contributions for the LSS approach and the research findings are expected to provide guidelines to enhance the level of quality performance in healthcare organisations in Malaysia as well as other countries.

Primary bone lymphoma: tunisian multicentric retrospective study about 32 cases.

AIM: To report the epidemiologic, clinical features, treatment modalities and prognosis of primary bone lymphomas (PBL) within a retrospective Tunisian series. METHODS: We collected cases of histologically confirmed PBL in 3 medical oncology departments from northern and central Tunisia andwe analyzed their characteristics. RESULTS: From January 1990 to July 2014, we collected 32 patients with histologically proven PBL, having a median age of 53 years. They affected mainly the long bones and diagnosed at early stages. 91% of the PBL were large cell B lymphoma. All patients received CHOP or CHOP-likeChemotherapy (CT), associated to Rituximab in the last 9 cases, with 14/32 patients received loco-regional radiotherapy and one patient had a resection-reconstruction surgery. We observed 90% of objective responses after primary CT.With a median follow-up of 38.5 months (1 to 192), the 5-year overall survival OS rate was 63%.18 patients relapsed and 14 remain alive in complete remission. CONCLUSION: PBL remains a rare disease lately diagnosed in Tunisia. However, most of the patients had early stages tumors. Furthermore, the efficacy of CT and introduction of Rituximab leads to a high rate of complete/objective responses, improving the survival rate.

Selenium-mediated arsenic excretion in mammals: a synchrotron-based study of whole-body distribution and tissue-specific chemistry.

Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers", we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic-selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.

Service quality, patient satisfaction and loyalty in the Bangladesh healthcare sector.

Purpose The purpose of this paper is to investigate service quality, patient satisfaction and loyalty in Bangladesh's healthcare sector. It identifies healthcare quality conformance, patient satisfaction and loyalty based on demographics such as gender, age and marital status. It examines the differences between public and private healthcare sectors regarding service quality, patient satisfaction and loyalty. Design/methodology/approach The authors distributed 450 self-administered questionnaires to hospital patients resulting in 204 useful responses (45.3 per cent response rate). Data were analysed based on reliability analysis, exploratory factor analysis, independent samples t-tests, ANOVA and discriminant analysis using SPSS version 23. Findings Findings indicate that single patients perceive tangibles, reliability, empathy and loyalty higher compared to married patients. Young patients (⩽20 years) have a higher tangibles, empathy and loyalty scores compared to other age groups. The authors observed that private hospital patients perceive healthcare service quality performance higher compared to patients in public hospitals. Research limitations/implications The authors focussed solely on the Bangladesh health sector, so the results might not be applicable to other countries. Originality/value The findings provide guidelines for enhancing service quality, patient satisfaction and loyalty in the Bangladesh healthcare sector and other countries.

Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile.

Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe](-). Previous work has definitively demonstrated the presence of [(GS)2AsSe](-) in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe](-). Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe](-), with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.

Evaluation of the safety and adverse effects of goreisan/wulingsan, a traditional Japanese-chinese herbal formulation (kampo), in a rat model: a toxicological evaluation.

Diarrhea is the second leading cause of death among children less than 5 years of age. Most of these deaths occur in developing countries in the tropical areas of Africa and South Asia. Goreisan/Wulingsan, a formula of Japanese-Chinese medicinal herbs (Kampo), has been used for the treatment of diarrhea and vomiting from ancient times in East Asia. Therefore, we planned a randomized controlled clinical trial of Goreisan/Wulingsan in Bangladeshi children. Although it is believed to be safe in East Asia, information regarding its toxicity on animals is scarce. Since Goreisan/Wulingsan has never been used in Bangladesh, it was necessary to ensure the safety of the formula in an animal experiment. Rats were assigned to a control group (normal saline, n = 4) or various Goreisan/Wulingsan groups (n = 26) receiving doses of 1 to 8 mg/g/day (7.7 to 61.5 times the recommended pediatric dose) over a period of 25 days. Their activities and health conditions were observed until they were sacrificed, after which blood samples were collected for biochemical liver function tests. The kidneys, liver and heart tissue were collected for histopathological study. No lethality was observed during the experiment. All of the rats consumed the doses completely and no constipation was observed, suggesting the absence of any inhibitory effect on intestinal motion. Also, no abnormal neurological activity was detected, nor any significant elevation of AST, ALT or ALP levels, except for AST and ALT at the highest dose of 8 mg/g/day. Histopathological studies of the kidneys, liver and heart tissues revealed no abnormalities. In conclusion, our results showed that Goreisan/Wulingsan is safe for rats, thereby justifying the use of the drug in a human trial.

Detection and molecular characterization of diarrhea causing viruses in single and mixed infections in children: a comparative study between Bangladesh and Turkey.

The incidence and mortality caused by diarrhea differ among countries. The prevalence of different enteric viruses, their molecular characteristics, and infections with multiple viruses might affect the disease incidence and mortality caused by diarrhea. The objective of this study was to determine the distribution and molecular characteristics of enteric viruses in children with diarrhea in Turkey and Bangladesh. A total of 288 stool samples that were negative for group A rotavirus were collected from children aged <5 years with acute diarrhea who presented to hospitals in Turkey and Bangladesh. The samples were screened for human bocavirus (HBoV), astrovirus (HAstV), norovirus (NoV), and adenovirus (AdV). Phylogenetic analyses of the targeted virus genes were performed. In Turkey, viruses were detected in 87/150 samples (58%), which included 69 (79.3%) with single viruses and 18 (20.7%) with multiple viruses. AdV was the most common virus, followed by HBoV. In Bangladesh, viruses were detected in 123/138 samples (89.1%), which included 29 (23.6%) with single viruses and 94 (76.4%) with multiple viruses. NoV GII was the most common, followed by AdV. The dominant genotypes among the virus species were HBoV 2A, HAstV 1, NoV GI type 1, and AdV 40. For NoV GII, the Hunter variant of genotype 4 in Turkey and genotype 17 in Bangladesh were the most common among the sequenced strains. It was concluded that the distribution of the viruses associated with diarrhea in Turkish and Bangladeshi children was different. Enteric viruses and mixed infections were more prevalent in Bangladesh than in Turkey.

Circulating rotaviral RNA in children with rotavirus antigenemia.

BACKGROUND: Rotavirus antigenemia is a common phenomenon in children with rotavirus diarrhea, but information is scarce on aspects of this phenomenon, such as genotype specificity, presence of intact viruses and correlation between genomic RNA and antigen concentration. Such information may help in understanding rotavirus pathogenesis and eventually be useful for diagnosis, treatment and prevention. METHODS AND FINDINGS: Serum samples were collected from children who presented at hospitals with diarrhea. Antigenemia was present in 162/250 (64.8%) samples from children with rotavirus diarrhea. No specific rotavirus genotype was found to be associated with antigenemia. Rotavirus particles could not be found by electron microscopy in concentrated serum from children with high levels of antigenemia. In passaged rotavirus suspension a significant correlation (r=0.9559; P=0.0029) was found between antigen level and viral copy number, but no significant correlation (r=0.001480; P=0.9919) was found between antigenemia level and viral copy number in serum. When intact rotavirus was treated with benzonase endonuclease, genomic double-stranded (ds) RNA was not degraded, but when sera of patients with antigenemia were treated with benzonase endonuclease, genomic dsRNA was degraded, indicating genomic dsRNA was free in sera and not inside virus capsid protein. CONCLUSIONS: Antigenemia is present in a significant number of patients with rotavirus diarrhea. Rotavirus viremia was absent in the children with rotavirus diarrhea who participated in our study, and was not indicated by the presence of antigenemia. The significance of circulating rotavirus antigen and genomic dsRNA in serum of patients with diarrhea deserves further study.

Effects of Lean Six Sigma application in healthcare services: a literature review.

The healthcare organization is the place where defects and mistakes cannot be tolerated. A simple mistake can cost a human life so defects or mistakes must be eliminated in healthcare service processes. A Lean Six Sigma (LSS) approach is the best option in a healthcare environment for dealing with a critical patient. The LSS methodology optimizes the average reduction of a desired process. The expected results can be reductions in several aspects of healthcare such as patient waiting time in emergency departments, lost charges for billing in patient financial services, delinquent medical records, diagnostic result turnaround times, accounts receivable days, patients' length of stay, or medication errors. This paper mainly discusses the effects of the LSS approach in different hospitals around the world according to the literature review. This review also discusses the relationship between LSS as well as their impacts on healthcare services based on literature review.

Detection of human bocavirus in the cerebrospinal fluid of children with encephalitis.

We report 4 children with encephalitis associated with human bocavirus (HBoV) 1 or 2. All children were severely underweight, and 2 died; 1 of them had a matching HBoV2 nucleotide sequence isolated from serum and bocavirus like particles in the cerebrospinal fluid that were observed with electron microscopy. No further pathogens were detected in the cerebrospinal fluid of these patients.