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Background. Spinal cord injuries typically result in a range of negative health outcomes and health states, which impacts overall functioning, health and well-being. It remains important to establish the prevalence (burden) of health outcomes to help with the development of optimal treatment strategies. Objectives. To determine the prevalence and treatment rates of secondary health conditions (SHCs) and mental health states in persons with long-term spinal cord injury (SCI) receiving public compared with private healthcare services in South Africa. Methods. A cross-sectional survey included 200 community-dwelling persons with long-term SCI, 60% with paraplegia, 53% with complete injuries and 156 from the public and 44 from private healthcare sectors. The following modules of the International Spinal Cord Injury (InSCI) community survey were used: (i) demographic and injury characteristics; (ii) SHCs and treatment rates; and (iii) vitality and emotional well-being. All statistical analyses were stratified according to healthcare sector. Results. Pain (47% v. 57), sexual dysfunction (59% v. 41%) and muscle spasms (54% v. 43%) were the most common SHCs in both cohorts, and the period prevalence was significantly higher for sleeping problems (41% v. 25%), sexual dysfunction (59% v. 41%) and contractures (42% v. 20%) in the public compared with the private cohort. Persons with SCI in the private cohort received treatment more often for sleeping problems (100% v. 45%), autonomic dysreflexia (75% v. 27%) and pain (56% v. 33%) than their counterparts with public insurance. Negative mental health states were prevalent in both groups. Conclusion. SHCs and negative mental health were common in persons with SCI in South Africa, while those with public insurance reporter a higher occurrence of sleep problems and contractures, as well as lower treatment rates. Overall, a need exists to better support persons with SCI in the long-term context to facilitate improved functioning and wellbeing.

Background. Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown.Objectives. To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients.Methods. Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital.Results. A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge.Conclusion. Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

Fistula-in-ano is a debilitating disease affecting anorectal region. It is an abnormal tract lined with fibrous tissue and unhealthy granulation tissue. It usually begins from a perianal abscess caused by cryptoglandular infection. The abscess burst spontaneously and forms fistula-in-ano. It may also seen in association with other diseases like Crohn’s disease, lymphogranuloma venereum, actinomycosis, malignancy and TB. It is distressing to the patient and the surgeon due to its recurrent nature and the complications like postoperative incontinence. The disease can be classified as low anal and high anal fistulae on the basis of its internal opening. Perianal subcutaneous fistula is included under low anal fistula. Generally, the modern treatment measures for fistula-in-ano include fistulectomy, fistulotomy, advancement flaps, fistula clip closure, LIFT technique, VAAFT procedure, anal fistula plug repair, fibrin glue and seton technique. The prime aim of the treatment is to eradicate the tract and drain the site of infection while preserving anal continence. In Ayurveda, Fistula-in-ano can be correlated with Bhagandara on the basis of signs and symptoms. Since it is difficult to treat, Acharya Susruta considered it as one among Ashtamahagada. He described the treatment as Shastra Karma, Kshara Karma, Agni Karma. In the present case study, a 35-year old male patient visited the OPD with perianal subcutaneous fistula was selected for Agnikarma after fistulotomy to reduce the treatment period and to improve the quality of living. Daily dressing was done with Jathyadi ghrta and the patient was cured within 21 days of intervention. The follow up was done for next 3 months and no complications were noted.

U.S. immigration law has excluded noncitizens likely to become a “public charge” since 1882. When the Trump administration proposed a new Rule expanding the interpretation of that exclusion in 2018, over 55,000 people wrote public comments. These comments, overwhelmingly opposed to the change, are the subject of Rachel Fabi and Lauren Zahn’s insightful article in this issue of The Journal of Law, Medicine, and Ethics. The themes they identify resonate with the history of the public charge exclusion, which has always reflected a tension between two aims of American governance — to provide for those in need of assistance, and to shape the nation’s citizenry according to ideals of self-sufficiency.

Oral Squamous Cell Carcinoma (OSCC), a grave debilitating disease besides causing structural abnormalities, it harms patient’s quality of life as well. Several pathological parameters can predict the survival and prognosis of OSCC. Cell Cannibalism (CC), a distinctive morphological feature have already been explored and proved in various malignancies. However, cannibalistic cells are often ignored during routine histopathological assessment of head and neck OSCC and have not been extensively studied. The authors present a case report of a 64-year-old, female, OSCC patient with uncontrolled diabetics, in which we observed many cannibalistic cells on slide evaluation. On further examination a Histologic Tumour Thickness (HTT) of 8 mm and a depth of invasion of 6 mm was noted, which again can foretell an adverse prognosis. Subsequently, patient was referred and managed at a cancer center but a regular postoperative evaluation was scheduled in the institute for better patient care. Interpreting and understanding these risk factors and being more empathetic towards the patient, will not only help in postoperative evaluation but also ensure a better quality of life thereafter.

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprosthetic joint infection operated with one- or two-stage replacement during which cefepime (2g)-daptomycin (10mg/kg) combination was administered intravenously as intraoperative empirical antibiotic treatment. Three biopsies (two bones and one synovial membrane) were taken from each patient just before the insertion of the new implant. Eighteen adults of median age 68 years were included. Knee was involved in 10 patients (55.6%) and surgery consisted in one-/two-stage replacement in 11/7 patients. A tourniquet was used during the intervention in the 10 patients with knee prosthesis. Among 54 tissue samples, cefepime and daptomycin were detected respectively in 35 (64.8%) and 21 (38.9%) cases (P=0.01). A total of 17 bacteria dominated by staphylococci (n=14) were identified in 10 patients; tissue inhibitory quotient calculated in 51 samples was >1 in 22 cases (43.1%) for cefepime and in 16 cases (31.4%) for daptomycin. The proportion of tissue samples with detectable antibiotic was significantly higher in hip versus knee prosthesis (P=0.03). The present study suggests that intraoperative empirical administration of cefepime-daptomycin combination during septic prosthetic joint replacement results in a high proportion of tissue samples in which at least one of the two antibiotics was not detected or at a low concentration despite satisfactory concomitant blood serum concentrations.

Novel red emitting europium doped Cerium phosphate nanocrystals were synthesized by microwave assisted sol gel method. X-ray powder diffraction analysis identified the monoclinic structure of synthesized samples. The morphology of the samples were found to beconstructed from elongated spheres and is explained with the help of TEM analysis. Intense orange red emission on excitation with Ce4+ - O2-charge transfer band is established by photoluminescence analysis. The effect of annealing on the efficiency of excitation with Ce4+ - O2-charge transfer band is demonstrated and is explained in association with the concentration of surface Ce4+. Chromaticity coordinates indicate good colour purity of the sample. All the results indicated that microwave assisted method is suitable for synthesizing red emitting CePO4:Eu phosphors and become a potential candidate for optoelectronic and biological applications.

The relationship between adiposity and metabolic health is well established. However, very little is known about the fat depot, known as paracardial fat (pCF), located superior to and surrounding the heart. Here, we show that pCF remodels with aging and a high-fat diet and that the size and function of this depot are controlled by alcohol dehydrogenase 1 (ADH1), an enzyme that oxidizes retinol into retinaldehyde. Elderly individuals and individuals with obesity have low ADH1 expression in pCF, and in mice, genetic ablation of Adh1 is sufficient to drive pCF accumulation, dysfunction, and global impairments in metabolic flexibility. Metabolomics analysis revealed that pCF controlled the levels of circulating metabolites affecting fatty acid biosynthesis. Also, surgical removal of the pCF depot was sufficient to rescue the impairments in cardiometabolic flexibility and fitness observed in Adh1-deficient mice. Furthermore, treatment with retinaldehyde prevented pCF remodeling in these animals. Mechanistically, we found that the ADH1/retinaldehyde pathway works by driving PGC-1α nuclear translocation and promoting mitochondrial fusion and biogenesis in the pCF depot. Together, these data demonstrate that pCF is a critical regulator of cardiometabolic fitness and that retinaldehyde and its generating enzyme ADH1 act as critical regulators of adipocyte remodeling in the pCF depot.

Objectives Gold standard cause of death data is critically important to improve verbal autopsy (VA) methods in diagnosing cause of death where civil and vital registration systems are inadequate or poor. As part of a three-country research study—Improving Methods to Measure Comparable Mortality by Cause (IMMCMC) study—data were collected on clinicopathological criteria-based gold standard cause of death from hospital record reviews with matched VAs. The purpose of this data note is to make accessible a de-identified format of these gold standard VAs for interested researchers to improve the diagnostic accuracy of VA methods. Data description The study was conducted between 2011 and 2014 in the Philippines, Bangladesh, and Papua New Guinea. Gold standard diagnoses of underlying causes of death for deaths occurring in hospital were matched to VAs conducted using a standardized VA questionnaire developed by the Population Health Metrics Consortium. 3512 deaths were collected in total, comprised of 2491 adults (12 years and older), 320 children (28 days to 12 years), and 702 neonates (0–27 days).

When presented with a choice, organisms need to assimilate internal information with external stimuli and past experiences to rapidly and flexibly optimize decisions on a moment-to-moment basis. We hypothesized that increasing hunger intensity would curb expression of social behaviors such as mating or territorial aggression; we further hypothesized social interactions, reciprocally, would influence food consumption. We assessed competition between these motivations from both perspectives of mice within a resident-intruder paradigm. We found that as hunger state escalated, resident animal social interactions with either a female or male intruder decreased. Furthermore, intense hunger states, especially those evoked via AgRP photoactivation, fundamentally altered sequences of behavioral choice; effects dependent on food availibility. Additionally, female, but not male, intrusion attenuated resident mouse feeding. Lastly, we noted environmental context-dependent gating of food intake in intruding mice, suggesting a dynamic influence of context cues on the expression of feeding behaviors.

Background Recent economic growth in Papua New Guinea (PNG) would suggest that the country may be experiencing an epidemiological transition, characterized by a reduction in infectious diseases and a growing burden from non-communicable diseases (NCDs). However, data on cause-specific mortality in PNG are very sparse, and the extent of the transition within the country is poorly understood. Methods Mortality surveillance was established in four small populations across PNG: West Hiri in Central Province, Asaro Valley in Eastern Highlands Province, Hides in Hela Province and Karkar Island in Madang Province. Verbal autopsies (VAs) were conducted on all deaths identified, and causes of death were assigned by SmartVA and classified into five broad disease categories: endemic NCDs; emerging NCDs; endemic infections; emerging infections; and injuries. Results from previous PNG VA studies, using different VA methods and spanning the years 1970 to 2001, are also presented here. Results A total of 868 deaths among adolescents and adults were identified and assigned a cause of death. NCDs made up the majority of all deaths (40.4%), with the endemic NCD of chronic respiratory disease responsible for the largest proportion of deaths (10.5%), followed by the emerging NCD of diabetes (6.2%). Emerging infectious diseases outnumbered endemic infectious diseases (11.9% versus 9.5%). The distribution of causes of death differed across the four sites, with emerging NCDs and emerging infections highest at the site that is most socioeconomically developed, West Hiri. Comparing the 1970–2001 VA series with the present study suggests a large decrease in endemic infections. Conclusions Our results indicate immediate priorities for health service planning and for strengthening of vital registration systems, to more usefully serve the needs of health priority setting.

Mutations in LMNA encoding lamin A/C and EMD encoding emerin cause cardiomyopathy and muscular dystrophy. Lmna null mice develop these disorders and have a lifespan of 7–8 weeks. Emd null mice show no overt pathology and have normal skeletal muscle but with regeneration defects. We generated mice with germline deletions of both Lmna and Emd to determine the effects of combined loss of the encoded proteins. Mice without lamin A/C and emerin are born at the expected Mendelian ratio, are grossly normal at birth but have shorter lifespans than those lacking only lamin A/C. However, there are no major differences between these mice with regards to left ventricular function, heart ultrastructure or electrocardiographic parameters except for slower heart rates in the mice lacking both lamin A/C and emerin. Skeletal muscle is similarly affected in both of these mice. Lmna+/− mice also lacking emerin live to at least 1 year and have no significant differences in growth, heart or skeletal muscle compared to Lmna+/− mice. Deletion of the mouse gene encoding lamina-associated protein 1 leads to prenatal death; however, mice with heterozygous deletion of this gene lacking both lamin A/C and emerin are born at the expected Mendelian ratio but had a shorter lifespan than those only lacking lamin A/C and emerin. These results show that mice with combined deficiencies of three interacting nuclear envelope proteins have normal embryonic development and that early postnatal defects are primarily driven by loss of lamin A/C or lamina-associated polypeptide 1 rather than emerin.

Introduction: Metabolic disorders like hypoglycaemia and hyperglycaemia are much common in neonates as compared to any other age groups. Infants are born with a blood glucose concentration of 60 to 70% of the maternal levels and it falls during the first 24 hours. Transient low blood glucose levels are common after birth as the glucose supply to neonates changes from a continuous transplacental supply from the mother to an intermittent supply from feeds. Aim: To find out the correlation between glucose levels in cord blood and capillary blood of neonates using glucometer soon after birth and to determine the prevalence of hypoglycaemia and hyperglycaemia among the study population. Materials and Methods: The study was a hospital based cross-sectional study and the study population included 1100 newborns who satisfied inclusion criteria. The glucose measurements were obtained using standard equipments and procedures. Data coded and entered into Microsoft excel, then analysed using SPSS software. Results: Results showed that there was a significant correlation between cord blood glucose and capillary blood glucose values (Pearson correlation coefficient r=0.894, p

Background Recently, a new algorithm for automatic computer certification of verbal autopsy data named InSilicoVA was published. The authors presented their algorithm as a statistical method and assessed its performance using a single set of model predictors and one age group. Methods We perform a standard procedure for analyzing the predictive accuracy of verbal autopsy classification methods using the same data and the publicly available implementation of the algorithm released by the authors. We extend the original analysis to include children and neonates, instead of only adults, and test accuracy using different sets of predictors, including the set used in the original paper and a set that matches the released software. Results The population-level performance (i.e., predictive accuracy) of the algorithm varied from 2.1 to 37.6% when trained on data preprocessed similarly as in the original study. When trained on data that matched the software default format, the performance ranged from −11.5 to 17.5%. When using the default training data provided, the performance ranged from −59.4 to −38.5%. Overall, the InSilicoVA predictive accuracy was found to be 11.6–8.2 percentage points lower than that of an alternative algorithm. Additionally, the sensitivity for InSilicoVA was consistently lower than that for an alternative diagnostic algorithm (Tariff 2.0), although the specificity was comparable. Conclusions The default format and training data provided by the software lead to results that are at best suboptimal, with poor cause-of-death predictive performance. This method is likely to generate erroneous cause of death predictions and, even if properly configured, is not as accurate as alternative automated diagnostic methods.

A woven coronary artery is a rare congenital vascular variation that involves the separation of the artery into several thin channels, which later merge distally to form a single lumen. This mesh of intertwining small vessels may occur anywhere along the vessel and may be present in multiple coronaries. Although generally a benign incidental finding, there have been reported cases of associated ischemia, thrombus and atherosclerotic plaque formation and complications with cardiac intervention procedures. In this review, we have analyzed and compiled all the reported data pertaining to woven coronary arteries and highlighted its relevance to clinical practice.

The relationship of QRS morphology with cardiac structure and function in patients with heart failure is uncertain.Patients with a clinical diagnosis of heart failure and objective evidence of cardiac dysfunction [either a left ventricular ejection fraction (LVEF)50 % or an amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml] who had been investigated by cardiac magnetic resonance imaging (CMRI) were identified. QRS duration ≥120 ms was grouped morphologically as left (LBBB), right bundle branch block (RBBB) or indeterminate.Of 877 patients, 320 (36 %) had QRS ≥ 120 ms. Compared to patients with LBBB, those with RBBB had a lower median [inter-quartile range (IQR)] right ventricular (RV) ejection fraction [RBBB: 46 (37-57); LBBB: 52 (42-61) %; p = 0.014], greater median (IQR) RV mass [RBBB: 53 (42-73); LBBB: 45 (36-56) g; p 0.001], higher median (IQR) plasma NT-proBNP [RBBB: 2013 (659-3573); LBBB: 1159 (589-2207) pg/ml, p = 0.026], more signs of peripheral congestion and higher prevalence of atrial fibrillation but had similar LVEF. During a median follow-up of 1302 days (IQR: 742-2237), 311 patients died. Compared with patients who had QRS 120 ms, those with RBBB [HR 1.98, 95 % CI (1.37-2.86); p 0.001] had a higher mortality. Age and NT-proBNP were the strongest independent predictors of mortality; neither QRS nor CMRI variables improved prediction.In patients with heart failure and QRS ≥ 120 ms, RBBB is associated with more severe RV dysfunction and congestion and a worse prognosis. However, neither QRS morphology nor CMRI data provide independent prognostic information in a multivariable analysis including NT-proBNP.

Cardiomyopathy frequently complicates sepsis and is associated with increased mortality. Increased cardiac oxidative stress and mitochondrial dysfunction have been observed during sepsis, but the mechanisms responsible for these abnormalities have not been determined. We hypothesized that NADPH oxidase 2 (NOX2) activation could be responsible for sepsis-induced oxidative stress and cardiomyopathy. Treatment of isolated adult mouse cardiomyocytes with low concentrations of the endotoxin lipopolysaccharide (LPS) increased total cellular reactive oxygen species (ROS) and mitochondrial superoxide. Elevated mitochondrial superoxide was accompanied by depolarization of the mitochondrial inner membrane potential, an indication of mitochondrial dysfunction, and mitochondrial calcium overload. NOX2 inhibition decreased LPS-induced superoxide and prevented mitochondrial dysfunction. Further, cardiomyocytes from mice with genetic ablation of NOX2 did not have LPS-induced superoxide or mitochondrial dysfunction. LPS decreased contractility and calcium transient amplitude in isolated cardiomyocytes, and these abnormalities were prevented by inhibition of NOX2. LPS decreased systolic function in mice, measured by echocardiography. NOX2 inhibition was cardioprotective in 2 mouse models of sepsis, preserving systolic function after LPS injection or cecal ligation and puncture (CLP). These data show that inhibition of NOX2 decreases oxidative stress, preserves intracellular calcium handling and mitochondrial function, and alleviates sepsis-induced systolic dysfunction in vivo. Thus, NOX2 is a potential target for pharmacotherapy of sepsis-induced cardiomyopathy.

Background:\ud \ud The pulmonary artery (PA) distends as pressure increases.\ud \ud Hypothesis:\ud \ud The ratio of PA to aortic (Ao) diameter may be an indicator of pulmonary hypertension and consequently carry prognostic information in patients with chronic heart failure (HF).\ud \ud Methods:\ud \ud Patients with chronic HF and control subjects undergoing cardiac magnetic resonance imaging were evaluated. The main PA diameter and the transverse axial Ao diameter at the level of bifurcation of the main PA were measured. The maximum diameter of both vessels was measured throughout the cardiac cycle and the PA/Ao ratio was calculated.\ud \ud Results:\ud \ud A total of 384 patients (mean age, 69 years; mean left ventricular ejection fraction, 40%; median NT-proBNP, 1010 ng/L [interquartile range, 448–2262 ng/L]) and 38 controls were included. Controls and patients with chronic HF had similar maximum Ao and PA diameters and PA/Ao ratio. During a median follow-up of 1759 days (interquartile range, 998–2269 days), 181 patients with HF were hospitalized for HF or died. Neither PA diameter nor PA/Ao ratio predicted outcome in univariable analysis. In a multivariable model, only age and NT-proBNP were independent predictors of adverse events.\ud \ud Conclusions:\ud \ud The PA/Ao ratio is not a useful method to stratify prognosis in patients with HF.

International audience; Cardiomyopathy caused by lamin A/C gene mutations (LMNA cardiomyopathy) is characterized by increased myocardial fibrosis, which impairs left ventricular relaxation and predisposes to heart failure, and cardiac conduction abnormalities. While we previously discovered abnormally elevated extracellular signal-regulated kinase 1/2 (ERK1/2) activities in heart in LMNA cardiomyopathy, its role on the development of myocardial fibrosis remains unclear. We now showed that transforming growth factor (TGF)-β/Smad signaling participates in the activation of ERK1/2 signaling in LMNA cardiomyopathy. ERK1/2 acts on connective tissue growth factor (CTGF/CCN2) expression to mediate the myocardial fibrosis and left ventricular dysfunction. Studies in vivo demonstrate that inhibiting CTGF/CCN2 using a specific antibody decreases myocardial fibrosis and improves the left ventricular dysfunction. Together, these findings show that cardiac ERK1/2 activity is modulated in part by TGF-β/Smad signaling, leading to altered activation of CTGF/CCN2 to mediate fibrosis and alter cardiac function. This identifies a novel mechanism in the development of LMNA cardiomyopathy.

The solid-phase synthesis, structural characterization, and biological evaluation of a small library of cancer-targeting peptides have been determined in HepG2 hepatoblastoma cells. These peptides are based on the highly specific Pep42 motif, which has been shown to target the glucose-regulated protein 78 receptors overexpressed and exclusively localized on the cell surface of tumors. In this study, Pep42 was designed to contain varying lengths (3-12) of poly(arginine) sequences to assess their influence on peptide structure and biology. Peptides were effectively synthesized by 9-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis, in which the use of a poly(ethylene glycol) resin provided good yields (14-46%) and crude purities >95% as analyzed by liquid chromatography-mass spectrometry. Peptide structure and biophysical properties were investigated using circular dichroism spectroscopy. Interestingly, peptides displayed secondary structures that were contingent on solvent and length of the poly(arginine) sequences. Peptides exhibited helical and turn conformations, while retaining significant thermal stability. Structure-activity relationship studies conducted by flow cytometry and confocal microscopy revealed that the poly(arginine) derived Pep42 sequences maintained glucose-regulated protein 78 binding on HepG2 cells while exhibiting cell translocation activity that was contingent on the length of the poly(arginine) strand. In single dose (0.15 mM) and dose-response (0-1.5 mM) cell viability assays, peptides were found to be nontoxic in human HepG2 liver cancer cells, illustrating their potential as safe cancer-targeting delivery agents.

Background A Centenarian is a person who attains and lives beyond the age of 100. Four percent of centenarians die from cancer. It is therefore important to understand which cancers affect them in order to devise better methods to prevent and treat them. The aim of this study was to investigate the top cancers that affect centenarians. Material/Method We identified 1385 cases with the Surveillance Epidemiology and End Result (SEER) database. Our study included centenarians age 100–115 years diagnosed with the 5 most common cancers between 1973 and 2007 in the United States. Observed survival (OS) was calculated for each cancer type. The Kaplan-Meier (KM) method was used to calculate OS at 1-month intervals for the first 40 months after diagnosis using SEER*Stat version 7.04. A log rank test was performed on KM survival output and a Cox proportional hazard model was used to calculate hazard ratios. All statistical analyses were performed with 95% confidence intervals with significance determined at P

Importance US health care spending has continued to increase, and now accounts for more than 17% of the US economy. Despite the size and growth of this spending, little is known about how spending on each condition varies by age and across time. Objective To systematically and comprehensively estimate US spending on personal health care and public health, according to condition, age and sex group, and type of care. Design and Setting Government budgets, insurance claims, facility surveys, household surveys, and official US records from 1996 through 2013 were collected and combined. In total, 183 sources of data were used to estimate spending for 155 conditions (including cancer, which was disaggregated into 29 conditions). For each record, spending was extracted, along with the age and sex of the patient, and the type of care. Spending was adjusted to reflect the health condition treated, rather than the primary diagnosis. Exposures Encounter with US health care system. Main Outcomes and Measures National spending estimates stratified by condition, age and sex group, and type of care. Results From 1996 through 2013, $30.1 trillion of personal health care spending was disaggregated by 155 conditions, age and sex group, and type of care. Among these 155 conditions, diabetes had the highest health care spending in 2013, with an estimated $101.4 billion (uncertainty interval [UI], $96.7 billion-$106.5 billion) in spending, including 57.6% (UI, 53.8%-62.1%) spent on pharmaceuticals and 23.5% (UI, 21.7%-25.7%) spent on ambulatory care. Ischemic heart disease accounted for the second-highest amount of health care spending in 2013, with estimated spending of $88.1 billion (UI, $82.7 billion-$92.9 billion), and low back and neck pain accounted for the third-highest amount, with estimated health care spending of $87.6 billion (UI, $67.5 billion-$94.1 billion). The conditions with the highest spending levels varied by age, sex, type of care, and year. Personal health care spending increased for 143 of the 155 conditions from 1996 through 2013. Spending on low back and neck pain and on diabetes increased the most over the 18 years, by an estimated $57.2 billion (UI, $47.4 billion-$64.4 billion) and $64.4 billion (UI, $57.8 billion-$70.7 billion), respectively. From 1996 through 2013, spending on emergency care and retail pharmaceuticals increased at the fastest rates (6.4% [UI, 6.4%-6.4%] and 5.6% [UI, 5.6%-5.6%] annual growth rate, respectively), which were higher than annual rates for spending on inpatient care (2.8% [UI, 2.8%–2.8%] and nursing facility care (2.5% [UI, 2.5%-2.5%]). Conclusions and Relevance Modeled estimates of US spending on personal health care and public health showed substantial increases from 1996 through 2013; with spending on diabetes, ischemic heart disease, and low back and neck pain accounting for the highest amounts of spending by disease category. The rate of change in annual spending varied considerably among different conditions and types of care. This information may have implications for efforts to control US health care spending.

The health care delivery system has undergone dramatic shifts in care settings in the recent past. More patients are receiving professional home care following discharge from hospitals, skilled-care facilities and rehabilitation centers. Home care has become an integral part of patient recovery especially among the long stay patients. Skilled nursing care delivered in the patient's home may prevent, foresee or limit costly readmissions back to hospitals. There are few other adverse events which are likely to happen at hospital settings like patient fall, developing HAI etc can be totally prevented in a home environment by one to one care which unloads the financial burden on both sides. There have been number of studies undertaken and many literatures are available on hospital readmission rates for reference. Nonetheless not much focus has been given to this particular area i.e. readmission of patients to hospitals while they are being taken care at home settings. Hence this study helps in understanding the readmission rates in home-based care. The study duration was from Jan 2018 – June 2018 to Jan 2019- June 2019. This was a comparative study and the study group was critically ill patients who were admitted during this time at Health care at home (HCAH), India.

Background: Incidents of fall remains the major cause of accidental and unintended injury in health care setups. Caring for patients at homecare setting comes with its own challenges and concerns. Methods: The incidents of fall reported over past 18 months in patients availing home care services from Healthcare at home from February 2018 to August 2019 was analysed to identify various risk factors involved in fall and suggestions for fall prevention were laid out in the study. Results: The fall percentage reported was 1.29% of patients served by HCAH during this tenure. The incident of fall was higher in rehabilitation services and lower in nursing services. The results show that prevalence of falling was higher among women than men between the age of 65-84 years. The highest number of falls was reported in patients suffering from neuro disorders, most of the incidents resulted due to external factors where more emphasis needs to be given on creating safe environment in the patient's home. Conclusion: Providing clinical care at home environment even makes it more difficult to control certain factors such as adequate space in the room for safe mobilization or unavailability of grab bars or presence of slippery floors or poor lightening are the majorly contributing to incidents like falls. Thus, identifying underlying risk while admitting the patient in homecare becomes the primary responsibility of the care provider.

The emergence of a novel strain of coronavirus in the Arabian Peninsula raised a global health concern in 2012, partly because the majority of human infections were fatal and partly due to its presumed animal origin. An urgent meeting of scientific and public health experts was convened by WHO in January 2013 in view of the limited knowledge available on the epidemiological and natural history of infection with this novel virus. The meeting reviewed current evidence and identified critical knowledge gaps to improve better understanding of the public health risk associated with the virus so as to improve preparedness and to safeguard and protect global health.

Heart failure is a complex disease in which a careful clinical examination and the measurement of cardiac function may not always be sufficient for making a correct diagnosis. Measuring plasma levels of natriuretic peptides may assist in this process, also offering a good tool for accurate risk stratification. Other alternative biomarkers may give insight into the different pathways of heart failure genesis and pathophysiology, and may help to identify those patients with overt heart failure and a more adverse outcome, or distinguish between those at risk of developing heart failure. Despite a high number of potentially useful biomarkers, only a few will likely be introduced routinely into clinical practice. However, a multi-marker approach might increase the diagnostic accuracy and it might identify different phenotypes of heart failure patients who might benefit from individualized therapy in the future.

The new one-pot method is found to be general and greener as it avoids the use of environmentally harmful POCl3 and strong alkali required for the previously reported method.

A catalyst, ligand and solvent free method for double heteroarylation of N, O and S nucleophiles has been developed for the first time leading towards the synthesis of compounds containing an indole ring fused with pyrrolo-, furo- and thieno[2,3-b]quinoxaline moieties. This general and greener approach afforded novel compounds of medicinal importance.

Quality problem. The gap between evidence-based guidelines and practice of care is reflected, in low- and middle-income countries, by high rates of maternal and child mortality and limited effectiveness of large-scale programing to decrease those rates. Choice of solution. We designed a phased, rapid, national scale-up quality improvement (QI) intervention to accelerate the achievement of Millennium Development Goal Four in Ghana. Our intervention promoted systems thinking, active participation of managers and frontline providers, generation and testing of local change ideas using iterative learning from transparent district and local data, local ownership and sustainability. Implementation. After 50 months of implementation, we have completed two prototype learning phases and have begun regional spread phases to all health facilities in all 38 districts of the three northernmost regions and all 29 Catholic hospitals in the remaining regions of the country. To accelerate the spread of improvement, we developed ‘change packages’ of rigorously tested process changes along the continuum of care from pregnancy to age 5 in both inpatient and outpatient settings. Lessons learned. The primary successes for the project so far include broad and deep adoption of QI by local stakeholders for improving system performance, widespread capacitation of leaders, managers and frontline providers in QI methods, incorporation of local ideas into change packages and successful scale-up to approximately 25% of the country’s districts in 3 years. Implementation challenges include variable leadership uptake and commitment at the district level, delays due to recruiting and scheduling barriers, weak data systems and repeated QI training due to high staff turnover.

Toussaintine A (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-2,7-dione), toussaintine B (N-cinnamoyl-5,6-dehydro-4,7-dihydroxyindolidin-2-one), toussaintine C (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-7-one), toussaintine D (N-cinnamoyl-2-amino-4-hydroxy-7-oxo-2,3,8,9-tetrahydrobenzofuran) and toussaintine E (N-cinnamoyl-1-acetoxymethyl-2-amino-1-hydroxycyclox-5-en-4-one) were isolated as antibacterial and antifungal constituents of the leaves of Toussaintia orientalis Verdc. (Annonaceae) and their structures established from analysis of spectroscopic data. The compounds belong to a series of variously cyclized aminocinnamoyl tetraketide derivatives, showing the importance of rarely occurring Annonaceae species as sources of structurally diverse natural products.

In non-endemic areas, malaria is mainly an imported disease. This article reports a case of transfusion-related Plasmodium falciparum malaria in a non-endemic area. Despite initial clinical signs consistent with malaria, the diagnosis was not elicited because of the absence of any identified epidemiological risk factors. The case indicates that transfusion-transmitted malaria still occurs in non-endemic countries. The role of laboratory testing to prevent and diagnose transfusion-transmitted malaria in non-endemic malaria countries is crucial.

Suppression Subtractive Hybridization was employed in order to identify the differentially expressed genes in the hepatopancreas of white spot syndrome virus infected Fenneropenaeus indicus. A forward subtracted cDNA library generated 356 clones following a white spot syndrome virus infection. A total of 345 clones with more than 100 nucleotides were selected for further analysis using bioinformatics tools after vector screening. Twenty-three contigs and 111 singletons were generated from a total of 134 consensuses. The consensuses, on a sequence homology search using BLASTX (NCBI), revealed that 74 (55%) of them had no significant match to reported sequences in the database, suggesting that they were found for the first time and are probably associated with shrimp immune function. Out of the remaining 60 (45%) consensuses, 43 had significant homology to known protein sequences in the database while 17 consensuses are homologous to unknown proteins in the database which are considered novel. The most abundant genes in the subtracted library were antimicrobial peptides accounting for 56 clones; among which one is a member of SNF2 family of proteins and another belonged to PfP1 family of proteins on analysis using Antimicrobial peptide predictor software. The other predicted genes in the subtracted library include signal transduction molecules (GTPase, Serine threonine kinase, Armadillo repeats etc), antioxidant enzymes (Cytochrome oxidase, Monomeric sarcosine oxidase and Catalase), active transporters (Nuclear Localization Signal [NLS], calcium ATPase, sodium glutamate symporter, Store-Operated Calcium Entry [SOCE] and ribonucleoprotein [RNP]) contributing to 19, 14 and 5 clones respectively. Three clones are homologous to reverse transcriptase; a first time report in shrimp and one each belong to cell adhesion molecule and Proteinase. InterProScan at EMBL, when used for an integrated search at PROSITE predicted; signal sequences and transmembrane regions for 13 clones. This is the first report on the differential gene expression in WSSV-infected F. indicus. The high expression of immune related genes in response to virus infection in shrimp will provide a new insight into the crustacean innate immunity. Further work on the functionality of the unknown genes in shrimps will give an overview on the role of the differentially expressed genes during viral infection and increase our understanding for developing antiviral measures by making use of the shrimp defense mechanism.

In traditional African communities, repellent volatiles from certain plants generated by direct burning or by thermal expulsion have played an important role in protecting households against vectors of malaria and other diseases. Previous research on volatile constituents of plants has shown that some are good sources of potent mosquito repellents. In this bioprospecting initiative, the essential oil of leaves of the tree, Suregada zanzibariensis Verdc. (Angiospermae: Euphobiaceae) was tested against the mosquito, Anopheles gambiae s.s. Giles (Diptera: Culicidae) and found to be repellent. Gas chromatography (GC), GC-linked mass spectrometry (GC-MS) and, where possible, GC-co-injections with authentic compounds, led to the identification of about 34 compounds in the essential oil. About 56% of the constituents were terpenoid ketones, mostly methyl ketones. Phenylacetaldehyde (14.4%), artemisia ketone (10.1%), (1S)-(-)-verbenone (12.1%) and geranyl acetone (9.4%) were the main constituents. Apart from phenylacetaldehyde, repellent activities of the other main constituents were higher than that of the essential oil. The blends of the main constituents in proportions found in the essential oil were more repellent to An. gambiae s.s. than was the parent oil (p < 0.05), and the presence of artemisia ketone in the blend caused a significant increase in the repellency of the resulting blend. These results suggested that blends of some terpenoid ketones can serve as effective An. gambiae s.s. mosquito repellents.

Cyclo[EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER(+) human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep might form a dynamically stable putative Type I beta-turn, and thus be biologically active without additional amino acids. The studies presented in this paper were performed to determine whether TOVN and other small analogs of AFPep would inhibit estrogen-stimulated cancer growth and exhibit a broad effective-dose range. These peptides contained nine or fewer amino acids, and were designed to bracket or include the putative pharmacophoric region (TOVN) of AFPep. Biological activities of these peptides were evaluated using an immature mouse uterine growth inhibition assay, a T47D breast cancer cell proliferation assay, and an MCF-7 breast cancer xenograft assay. TOVN had very weak antiestrogenic activity in comparison to AFPep's activity, whereas TOVNO had antiestrogenic and anticancer activities similar to AFPep. OVNO, which does not form a putative Type I beta-turn, had virtually no antiestrogenic and anticancer activities. A putative proteolytic cleavage product of AFPep, TOVNOGNEK, significantly inhibited E(2)-stimulated growth in vivo and in vitro over a wider dose range than AFPep or TOVNO. We conclude that TOVNO has anticancer potential, that TOVNOGNEK is as effective as AFPep in suppressing growth of human breast cancer cells, and that it does so over a broader effective-dose range.

Ectoine, a cyclic tetrahydropyrimidine (2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid), is a natural compound, which serves as a protective substance in many bacterial cells. In this study, the putative ectABC gene cluster from Bacillus halodurans was heterologously expressed in E. coli and the production of ectoine was confirmed by HPLC analysis. The activity of the enzymes coded by the ectA, B and C genes were found to be higher in induced transgenic cells compared to the uninduced cells. Phylogenetic analysis revealed sequence identities ranging from 36-73% for ectA gene, 55-81% for ectB gene and 55-80% for ectC gene indicating that the enzymes are evolutionarily well conserved.

The work was aimed to study the microbial quality of the seafood sold in the domestic markets and incidence of Vibrio parahaemolyticus. Samples comprising of shellfish, finfish, and cephalopods were collected from various fish markets in and around Cochin. Presumed V. parahaemolyticus were identified by standard biochemical tests, and further confirmed by polymerase chain reaction targeting species-specific tl gene (450 bp). About 81% of the samples were found to exceed the limits specified for total plate count while total presumptive V. parahaemolyticus count was above the limit in 71% of the samples ranging from 5.5 × 105 to 9.7 × 107 and 0.31 × 102 to 7.8 × 106 cfu/g, respectively. Pathogenicity of the identified isolates was confirmed by Kanagawa phenomenon and urease activity. A total of 10% of the isolates exhibited weak haemolysis on Wagatsuma agar, and 1% of the isolates showed urease activity using Christensen’s urea agar. Random amplified polymorphic DNA analysis revealed two major clusters based on the species rather than seasonality. The gel pattern revealed 8–10 bands ranging from 0.45 to 3.0 kb. Antibiogram results revealed 85% of the strains sensitive to chloramphenicol and nitrofurantoin. Multiple antibiotic resistance index was found to be 0.4 thus suggesting the risk potential involved in consuming seafoods. The present study has clearly demonstrated the need to adopt seafood safety measures for the products meant for human consumption.

The rosane diterpenoids hugorosenone [3beta-hydroxyrosa-1(10),15-dien-2-one], 18-hydroxyhugorosenone and 18-hydroxy-3-deoxyhugorosenone, and 12-hydroxy-13-methylpodocarpa-8,11,13-trien-3-one were isolated as antifungal constituents of H. castaneifolia Engl. root bark, together with the previously reported di-podocarpanoids hugonone A and hugonone B that were weakly active, and 1(10),15-rosadiene-2beta,3beta-diol (hugorosenol), 4alpha-methoxyhimachal-10-en-5beta-ol (hugonianene B) and 2-hydroxyhenpentacont-2-enal, and the known compounds tetracosyl-(E)-ferrulate and caryophyllene oxide, all of which were inactive. Hugorosenone also exhibited activity against Anopheles gambiae mosquito larvae. Structural determination was achieved based on spectroscopic data.

Xylan is the major hemicellulose in dicot wood. Unraveling genes involved in the biosynthesis of xylan will be of importance in understanding the process of wood formation. In this report, we investigated the possible role of poplar GT47C, a glycosyltransferase belonging to family GT47, in the biosynthesis of xylan. PoGT47C from the hybrid poplar Populus alba x tremula exhibits 84% sequence similarity to Fragile fiber8 (FRA8), which is involved in the biosynthesis of glucuronoxylan in Arabidopsis. Phylogenetic analysis of glycosyltransferase family GT47 in the Populus trichocarpa genome revealed that GT47C is the only close homolog of FRA8. In situ hybridization showed that the PoGT47C gene was expressed in developing primary xylem, secondary xylem and phloem fibers of stems, and in developing secondary xylem of roots. Sequence analysis suggests that PoGT47C is a type II membrane protein, and study of the subcellular localization demonstrated that fluorescent protein-tagged PoGT47C was located in the Golgi. Immunolocalization with a xylan monoclonal antibody LM10 revealed a nearly complete loss of xylan signals in the secondary walls of fibers and vessels in the Arabidopsis fra8 mutant. Expression of PoGT47C in the fra8 mutant restored the secondary wall thickness and xylan content to the wild-type level. Together, these results suggest that PoGT47C is functionally conserved with FRA8 and it is probably involved in xylan synthesis during wood formation.

Heart failure in pregnancy is rare, but usually ascribed to peripartum cardiomyopathy in the absence of other possible diagnoses. However, heart failure can develop solely due to a tachycardia, so-called 'tachycardia-induced cardiomyopathy'. The incidence of tachycardia-induced cardiomyopathy in pregnancy is unknown, but it is a treatable and potentially reversible cause of heart failure. Clinically, tachycardia-induced cardiomyopathy during pregnancy might present in a similar manner, but its management has to be individualized according to the arrhythmic substrate and usually involve multidisciplinary input from specialists in obstetrics, cardiac electrophysiology and heart failure.

Petroleum ether, dichloromethane, and ethanolic extracts of the stem bark and leaves of Uvaria scheffleri Diels (Annonaceae) exhibited antifungal activity against Aspergillus niger (wild strain), Aspergillus fumigatus (wild strain), and a Penicillium species (wild strain). The ethanol extract of the stem bark was also active against Candida albicans (Strain H6392). The dichloromethane extract of the leaves showed the highest antifungal activity and in addition it showed antibacterial activity against Staphylococcus aureus (NCTC 6571). Fractionation of the dichloromethane extract of the leaves yielded nine known compounds. They included a 1 : 1 mixture of stigmasterol (1) and β-sitosterol (2), which showed antifungal activity against Candida albicans. Others were 3-farnesylindole (3), 2′,6′-dihydroxy-3′,4′-dimethoxy-chalcone (4), 2′-hydroxy-3′,4′,6′-trimethoxychalcone (5), 5-hydroxy-7,8-dimethoxyflavanone (6), 5,7,8-trimethoxyflavanone (7), and a 3 : 2 mixture of 2′,6′-dihydroxy-4′-methoxychalcone (8) and ...

Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino- l -gulitol ( l -guloDNJ) and 1,5-dideoxy-1,5-imino- l -talitol ( l -taloDNJ) are reported, from d -mannose and d -fructose, respectively. The key steps in both syntheses involved reductive aminative cyclizations. Thus, l -guloDNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl- d -mannononitrile with LiAlH4 in DME to give the protected azasugar which upon hydrolysis with HCl afforded crystalline l -guloDNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β- d -ribohexulofuranose obtained from d -fructose in six steps, followed by treatment with HCl, afforded l -taloDNJ as an HCl salt in ∼10% overall yield.

Surfactin is a lipopeptide, composed of one β-hydroxy fatty acid, a long fatty acid moiety, and seven amino acids. In this study, the biosurfactant biosynthesis genes; 4′-pantetheinyl transferase (sfp), phosphopantetheinyl transferase (sfpO), and surfactin synthetase (srfA) have been characterized from the marine sponge-associated Bacillus licheniformis NIOT-06 from the Andaman and Nicobar Islands. The purified recombinant biosurfactant revealed excellent emulsification activity with crude oil and kerosene. Reverse-phase high-performance liquid chromatography resolved the purified recombinant biosurfactant into several fractions and one of which had significant surface tension reducing property. Fourier transform infrared spectroscopy spectrum also revealed the presence of C–N–N, alkenes, and N–H as the functional groups, and a similar overlapping pattern was observed with that of standard lipopeptide surfactin. The diversity and phylogeny of sfp, sfpO, and srfA gene sequences were compared with other eubacteria. The sfp, sfpO, and srfA gene sequences obtained from Bacillus licheniformis NIOT-06 were diverse and appeared to be partially conserved when compared with the GenBank reported sequences of several eubacteria.