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Non-nucleoside reverse transcriptase inhibitors are the prime members of antiretroviral therapy that are presently employed for the management of the human immunodeficiency virus. It uses an enzyme i.e., reverse transcriptase to convert its ribonucleic acid into reverse transcription; these agents impede the function of reverse transcriptase and reverse transcription counter human immunodeficiency virus from replicating. Efavirenz is the first-generation non-nucleoside reverse transcriptase inhibitor agent. Similar to the other non-nucleoside reverse transcriptase inhibitor agents; it is prescribed with other inhibitors in combination for regimens antiretroviral therapy. To enhance survival and avoid aggressive infections in patients affected with human immunodeficiency virus infection, adequate antiretroviral therapy is the most significant treatment. Accordingly, the development and validation of such therapeutic agents are challenging work for the analysts. Therefore, the proposed review integrally addresses the analytical reports of efavirenz recorded in the literature databases like Scopus, Web of Science, Google Scholar, Pub-Med, and through many other sources. It has been remarked that for the development of efavirenz many analytical techniques were used for addressing the qualitative and quantitative estimation of efavirenz from various pharmaceutical and biological matrices. This review plan to review the stereochemistry, mechanism of action, resistance, pharmacokinetics, pharmacodynamics, safety and adverse reaction, and various analytical approaches assessed for the same. The hyphenated and chromatographic techniques are frequently used for analysis of cited drug.

Neutrophils are vital to both the inflammatory cascade and tissue repair after an injury. Neutrophil heterogeneity is well established but there is less evidence for significant, different functional roles for neutrophil subsets. OLFM4 (Olfactomedin-4) is expressed by a subset of neutrophils, and high expression of OLFM4 is associated with worse outcomes in patients with sepsis and acute respiratory distress syndrome. We hypothesized that an increased number of OLFM4(+) neutrophils would occur in trauma patients with worse clinical outcomes. To test this, we prospectively enrolled patients who suffered a blunt traumatic injury. Blood was collected at the time of admission, Day 3, and Day 7 and analyzed for the percentage of neutrophils expressing OLFM4. We found that a subset of patients who suffered blunt traumatic injury upregulated their percentage of OLFM4(+) neutrophils. Those who upregulated their OLFM4 had an increased length of stay, days in the ICU, and ventilator days. A majority of these patients also suffered from hemorrhagic shock. To establish a potential role for OLFM4(+) neutrophils, we used a murine model of hemorrhagic shock because mice also express OLFM4 in a subset of neutrophils. These studies demonstrated that wild type mice had higher concentrations of cytokines in the plasma and myeloperoxidase in the lungs compared with OLFM4-null mice. In addition, we used an anti-OLFM4 antibody, which when given to wild type mice led to the reduction of myeloperoxidase in the lungs of mice. These findings suggest that OLFM4(+) neutrophils are a unique subset of neutrophils that affect the inflammatory response after tissue injury.

Background and Aims: Mass Drug Administration (MDA) coverage remains an important indicator in elimination of Lymphatic Filariasis (LF), especially in context of recent changes in programme strategies in India, such as incorporation of Ivermectin and involvement of urban Accredited Social Health Activists (ASHAs). This study aimed at assessing the coverage and compliance with MDA of Filariasis as well as exploring perspective of beneficiaries for non-consumption in selected slum area of Nagpur city. Methods: Mixed-method study design comprising of quantitative assessment of MDA coverage, followed by qualitative method to explore the reasons of non-compliance was used in selected slum areas of Nagpur city. Using cluster sampling, 240 households were selected and house-to-house visits were made to interview the eligible participants. In-depth interviews were conducted among selected non-compliant participants. Statistical Analysis: Multivariable logistic regression analysis to identify the factors associated with non-consumption. Thematic analysis was done to obtain the reasons of non-consumption as perceived by the beneficiaries. Results: Among the 1096 individuals studied, distribution and consumption coverage were 55.2% and 48.5%, respectively. Effective supervised consumption was further low (28.9%). Coverage compliance gap (CCG) was 12.1%. Male sex and younger age (2-5 years) were significant socio-demographic determinants of non-consumption. No repeat visit to houses left in first round, fear of side effects, pill burden, poor understanding about the need were important reasons as revealed by qualitative inquiry. Conclusion: Effective pre-campaign awareness, incorporation of context specific drug delivery strategies and strengthening monitoring system are essential for successful MDA implementation.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases., Central Illustration, Highlights • The burden of CVD, in number of DALYs and deaths, continues to increase globally. • CVD burden attributable to modifiable risk factors continues to increase globally. • Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.

With the goal of safety and efficiency in health care delivery, enhanced recovery protocols (ERPs) continue to gain traction throughout various surgical disciplines, including in pediatric scoliosis surgery. The growing body of literature reporting decreased length of stay and cost with no change in readmissions or complications has brought these protocols to the forefront. The key components of ERPs include preoperative patient counseling, perioperative pain management, and early patient mobilization. In this review, the authors aim to describe the foundational history and major components of ERPs following pediatric spine deformity surgery. [ Orthopedics . 2020;43(5):e338–e344.]

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

INTRODUCTION There is lack of reliable mortality estimates in India about maternal, neonatal and infant deaths. As we move towards achieving the targets under Sustainable Development Goals, information on cause of death is essential to prioritize our resources and planning. Therefore, the present study describes the causes and characteristics of neonatal, post-neonatal and maternal deaths in India. METHODS The study analysed nationwide District-Level Household Survey-4 conducted by the Ministry of Health and Family Welfare, Government of India, in 2014. The household questionnaire collected information on the socio-economic characteristics of the household and deaths within the household, including neonatal, post-neonatal, maternal and adult deaths. RESULTS Of 1324 neonatal deaths, 46% occurred at home and 73% in the first week of life. Among 2032 post-neonatal deaths reported, 70% occurred at home. Birth injuries, low birth weight and neonatal infections were the leading causes of neonatal deaths. Acute respiratory infection was the most common cause of post-neonatal deaths, whereas excessive bleeding and pregnancy-induced hypertension were the common causes of maternal deaths. Nearly 39% of neonatal and 50% of post-neonatal deaths were either classified as others or could not be ascertained. Household characteristics such as use of unclean fuel, poor sanitation, poor drinking water source, type of house (kachha) and below poverty line family are associated with mortality. CONCLUSION A high proportion of avoidable deaths still occur at home. These findings indicate the need for an efficient ambulance transport system, promoting health-seeking behaviour, better knowledge of danger signs and strengthening community-facility linkages. A more accurate verbal autopsy tool and proper administration of the tool are required to accurately ascertain cause of death and reduce the number of deaths that are assigned an ill-defined cause.

Background Tuberculosis causes more deaths than any other infectious disease worldwide, with pulmonary tuberculosis being the most common form. Standard first‐line treatment for drug‐sensitive pulmonary tuberculosis for six months comprises isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for two months, followed by HRE (in areas of high TB drug resistance) or HR, given over a four‐month continuation phase. Many people do not complete this full course. Shortened treatment regimens that are equally effective and safe could improve treatment success. Objectives To evaluate the efficacy and safety of shortened treatment regimens versus the standard six‐month treatment regimen for individuals with drug‐sensitive pulmonary tuberculosis. Search methods We searched the following databases up to 10 July 2019: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE (PubMed); Embase; the Latin American Caribbean Health Sciences Literature (LILACS); Science Citation Index‐Expanded; Indian Medlars Center; and the South Asian Database of Controlled Clinical Trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, the Clinical Trials Unit of the International Union Against Tuberculosis and Lung Disease, the UK Medical Research Council Clinical Trials Unit, and the Clinical Trials Registry India for ongoing trials. We checked the reference lists of identified articles to find additional relevant studies. Selection criteria We searched for randomized controlled trials (RCTs) or quasi‐RCTs that compared shorter‐duration regimens (less than six months) versus the standard six‐month regimen for people of all ages, irrespective of HIV status, who were newly diagnosed with pulmonary tuberculosis by positive sputum culture or GeneXpert, and with presumed or proven drug‐sensitive tuberculosis. The primary outcome of interest was relapse within two years of completion of anti‐tuberculosis treatment (ATT). Data collection and analysis Two review authors independently selected trials, extracted data, and assessed risk of bias for the included trials. For dichotomous outcomes, we used risk ratios (RRs) with 95% confidence intervals (CIs). When appropriate, we pooled data from the included trials in meta‐analyses. We assessed the certainty of evidence using the GRADE approach. Main results We included five randomized trials that compared fluoroquinolone‐containing four‐month ATT regimens versus standard six‐month ATT regimens and recruited 5825 adults with newly diagnosed drug‐sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three were multi‐country trials that included a total of 572 HIV‐positive people. These trials excluded children, pregnant or lactating women, people with serious comorbid conditions, and those with diabetes mellitus. Four trials had multiple treatment arms. Moxifloxacin replaced ethambutol in standard four‐month, daily or thrice‐weekly ATT regimens in two trials; moxifloxacin replaced isoniazid in four‐month ATT regimens in two trials, was given daily in one trial, and was given with rifapentine instead of rifampicin daily for two months and twice weekly for two months in one trial. Moxifloxacin was added to standard ATT drugs for three to four months in one ongoing trial that reported interim results. Gatifloxacin replaced ethambutol in standard ATT regimens given daily or thrice weekly for four months in two trials. Follow‐up ranged from 12 months to 24 months after treatment completion for the majority of participants. Moxifloxacin‐containing four‐month ATT regimens Moxifloxacin‐containing four‐month ATT regimens that replaced ethambutol or isoniazid probably increased the proportions who experienced relapse after successful treatment compared to standard ATT regimens (RR 3.56, 95% CI 2.37 to 5.37; 2265 participants, 3 trials; moderate‐certainty evidence). For death from any cause, there was probably little or no difference between the two regimens (2760 participants, 3 trials; moderate‐certainty evidence). Treatment failure was rare, and there was probably little or no difference in proportions with treatment failure between ATT regimens (2282 participants, 3 trials; moderate‐certainty evidence). None of the participants given moxifloxacin‐containing regimens developed resistance to rifampicin, and these regimens may not increase the risk of acquired resistance (2282 participants, 3 trials; low‐certainty evidence). Severe adverse events were probably little or no different with moxifloxacin‐containing four‐month regimens that replaced ethambutol or isoniazid, and with three‐ to four‐month regimens that augmented standard ATT with moxifloxacin, when compared to standard six‐month ATT regimens (3548 participants, 4 trials; moderate‐certainty evidence). Gatifloxacin‐containing four‐month ATT regimens Gatifloxacin‐containing four‐month ATT regimens that replaced ethambutol probably increased relapse compared to standard six‐month ATT regimens in adults with drug‐sensitive pulmonary tuberculosis (RR 2.11, 95% CI 1.56 to 2.84; 1633 participants, 2 trials; moderate‐certainty evidence). The four‐month regimen probably made little or no difference in death compared to the six‐month regimen (1886 participants, 2 trials; moderate‐certainty evidence). Treatment failure was uncommon and was probably little or no different between the four‐month and six‐month regimens (1657 participants, 2 trials; moderate‐certainty evidence). Acquired resistance to isoniazid or rifampicin was not detected in those given the gatifloxacin‐containing shortened ATT regimen, but we are uncertain whether acquired drug resistance is any different in the four‐ and six‐month regimens (429 participants, 1 trial; very low‐certainty evidence). Serious adverse events were probably no different with either regimen (1993 participants, 2 trials; moderate‐certainty evidence). Authors' conclusions Evidence to date does not support the use of shortened ATT regimens in adults with newly diagnosed drug‐sensitive pulmonary tuberculosis. Four‐month ATT regimens that replace ethambutol with moxifloxacin or gatifloxacin, or isoniazid with moxifloxacin, increase relapse substantially compared to standard six‐month ATT regimens, although treatment success and serious adverse events are little or no different. The results of six large ongoing trials will help inform decisions on whether shortened ATT regimens can replace standard six‐month ATT regimens. 9 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (10 Jul, 2019) were included, Plain language summary Shorter treatment regimens for people with pulmonary tuberculosis What was the aim of this review? The aim of this Cochrane Review was to find out if the duration of anti‐tuberculosis treatment (ATT) for people with newly diagnosed drug‐sensitive pulmonary tuberculosis can be shortened to less than six months. Cochrane Review authors collected and analysed all relevant studies to answer this question and found five relevant studies. Key messages Shortened ATT regimens probably make little or no difference in death, treatment failure, or serious adverse events compared to six‐month ATT regimens, but they probably increase relapse of tuberculosis. Six large ongoing trials are studying this question. What was studied in the review? Tuberculosis is an infectious disease, and tuberculosis affecting the lungs (pulmonary tuberculosis) is the most common presentation of tuberculosis in adults. Tuberculosis is a major public health problem worldwide, and among infectious diseases, it is the leading cause of death. People with pulmonary tuberculosis are currently treated with a six‐month combination of drugs that include isoniazid, rifampicin, ethambutol, and pyrazinamide for two months, followed by isoniazid and rifampicin (with or without ethambutol) for four months. Many people do not finish the treatment or they take the drugs irregularly because of the long treatment duration, or because of drug side effects. Incomplete or irregular treatment can lead to treatment failure and can increase disease relapse. Such treatment can also lead to drug resistance. If newer drug combinations given for less than six months are found to be as effective and safe as the currently recommended six‐month ATT regimens, more people might be adherent and might complete treatment. This could help reduce drug resistance and could help to stop tuberculosis infection worldwide. What are the main results of the review? The five included trials studied 5825 adults with newly diagnosed drug‐sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three trials included 572 HIV‐positive people, but all excluded people with other serious comorbid conditions and those with diabetes mellitus. This reduced the applicability of study results. All were funded by government or international agencies. Four studies replaced isoniazid or ethambutol with moxifloxacin or gatifloxacin in four‐month ATT regimens. Follow‐up was provided for 12 months to 24 months after treatment completion. In one ongoing study, moxifloxacin was added to four‐month ATT, but study authors provided only interim results. This review shows the following when four‐month ATT regimens are compared to standard six‐month ATT regimens. • Relapse after successful treatment is probably increased (moderate‐certainty evidence). • Death from any cause, treatment failure, and serious adverse events are probably little or no different (moderate‐certainty evidence). • Drug resistance may not be increased with moxifloxacin‐containing four‐month regimens (low‐certainty evidence), but we are uncertain whether this applies to gatifloxacin‐containing regimens (very low‐certainty evidence). How up‐to‐date is this review? The review authors searched for available studies up to 10 July 2019.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease associated with high mortality worldwide. Increases in iron levels have been reported in diabetic rat kidneys as well as in human urine of patients with diabetes. In addition, a low-iron diet or iron chelators delay the progression of DN in patients with diabetes and in animal models of diabetes. Possible maladaptive mechanisms of organ damage by tissue iron accumulation have not been well studied. We recently reported that iron induced the retinal renin-angiotensin system (RAS) and accelerated the progression of diabetic retinopathy. However, whether iron regulates the systemic RAS is unknown. To explore if iron alters the expression of intrarenal RAS and its role in the progression of DN, we used the high Fe iron (HFE) knockout mouse, a genetic model of systemic iron overload. We found that diabetes upregulated the expression of iron regulatory proteins and augmented tissue iron accumulation in the kidneys of both type 1 and type 2 diabetic mouse models. Iron accumulation in the kidneys of HFE knockout mice was associated with increase in serum and intrarenal renin expression. Induction of diabetes in HFE knockout mice using streptozotocin caused a much higher accumulation of renal iron and accelerated the progression of nephropathy compared with diabetic wild-type mice. Treatment of diabetic mice with the iron chelator deferiprone reversed the renin upregulation and reduced kidney injury. Thus, our results establish a new link between renal iron and RAS activity. Exploring the mechanisms of iron-induced RAS activation further may have a significant therapeutic impact on hypertension and DN.

Levetiracetam is an anti-epileptic that works at the synapse and binds synapse vesicle protein 2A, thereby controlling the release of neurotransmitters. Its side effects mainly include somnolence, headache, fatigue, dizziness, vomiting, and behavioral alterations. Rhabdomyolysis is a rare adverse effect of levetiracetam. The underlying pathophysiology of this adverse effect is unknown. Our patient is a 42-year-old male who was brought to the hospital with a complaint of generalized tonic-clonic seizures and urinary incontinence. His symptoms were caused by hyponatremia. Levetiracetam was started for seizure prevention along with management for hyponatremia. His creatine phosphokinase levels increased on the third day of admission to 30,000 U/L. Four days after the discontinuation of levetiracetam and with the institution of supportive therapy, the patient's rhabdomyolysis resolved.

A high-throughput Coulter counter for point-of-care (POC) applications has been developed, which measures the concentration and size distribution of cells in suspension at a single cell resolution. Vertical channels (silicon-based through-holes), instead of conventional planar ones, were employed to achieve a higher density of sensing channels for a high-throughput operation. The crosstalk from the multiple sensing channels was minimized by potentiometric measurement based on a three-electrode configuration, decoupling the neighboring channels electrically. The through-hole array and potentiometric sensing increased throughput up to 8000 cells/s in the prototype (designed with four channels). To secure the sensitivity over a wide range of cell sizes in a limited setting (a portable device powered by a battery power

Background With an estimated 65 million Diabetes Mellitus (DM) patients, India ranks second in the world in terms of DM burden. The emphasis of current medical practice has been on pharmacotherapy but, despite the best combination therapies, acheiving glycaemic control (reduction of blood sugar to desirable levels) is a challenge. ‘Integrated Naturopathy and Yoga’(INY) is an alternative system of medicine that lays emphasis on the role of diet and physical exercise. We assessed the short term effect of INY as an adjunct to pharmacotherapy on glycaemic control among type 2 DM patients. Methods In this prospective cohort study with a 3 month follow-up, DM patients consecutively admitted to a hospital in India from May-October 2014 for either 15 or 30 days were offered INY - a package of vegetarian diet with no added oil, sugar and salt, yoga-based exercise, patient counselling and rest. A ‘favourable outcome’ was defined as glycaemic control (glycosylated hemoglobin (HbA1c)

Measures to assess kidney function and injury in the diabetic population are currently either inadequate or manifest late in the progressive phase, leading to extensive irreversible damage. Recent efforts to identify novel biomarkers in the diabetic population have been evolving either to detect early kidney injury or repair that ultimately lead to progression of diabetic kidney disease. Emerging roles of urinary biomarkers have proven beneficial due to the ability to standardize the various markers to creatinine or peptides already present in the urine. The role of neutrophil gelatinase-associated lipoprotein, kidney injury molecule-1 and podocin derivatives have gained enormous significance in the process of early identification of kidney injury in the diabetic population. The recent identification of various novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney diseases has garnered much attention. This article will discuss the evolution of novel biomarker...

Background: Homeopathy is a complementary medicine widely used around the world. Despite extensive use of homeopathy for cancer and other serious conditions with reported success, clinical and laboratory research has been equivocal, and no rigorous research has been done on cancer. In 1999, the US National Cancer Institute evaluated the effects of homeopathic treatment of cancer from a clinic in India and has released a request for protocols to conduct further research into this treatment. Therefore, the authors conducted a series of carefully controlled laboratory studies evaluating the effects of commonly used homeopathic remedies in cell and animal models of prostate cancer. Study Design: One hundred male Copenhagen rats were randomly assigned to either treatment or control groups after inoculation with prostate tumor cells. Methods: Prostate tumor cells DU-145, LNCaP, and MAT-LyLu were exposed to 5 homeopathic remedies. Male Copenhagen rats were injected with MAT-LyLu cells and exposed to the same homeopathic remedies for 5 weeks. In vitro outcomes included tumor cell viability and apoptosis gene expression. In vivo outcomes included tumor incidence, volume, weight, total mortality, proliferating cell nuclear antigen (PCNA) expression, apoptotic cell death (terminal deoxynucleotidyl transferase mediated d-uridine triphosphate nick end labeling), and gene expression (rAPO-multiprobe). Results: There were no effects on cell viability or gene expression in 3 prostate cell lines with any remedies at any exposure time. There was a 23% reduction in tumor incidence (P < .0001), and for animals with tumors, there was a 38% reduction in tumor volume in homeopathy-treated animals versus controls (P < .02). At time of killing, experimental animals with tumors had a 13% lower average tumor weight (P < .05). Tumors in these treated animals showed a 19% increase in apoptotic cell death (P < .05) and reduced PCNA-positive cells. Conclusions: The findings indicate that selected homeopathic remedies for the present study have no direct cellular anticancer effects but appear to significantly slow the progression of cancer and reduce cancer incidence and mortality in Copenhagen rats injected with MAT-LyLu prostate cancer cells.

Wound healing involves inflammation, cell proliferation, matrix deposition, and tissue remodeling. Interaction of different cells, extracellular matrix proteins, and their receptors are mediated by cytokines and growth factors during wound healing. In this study, we have evaluated the effect of arnebin-1, a natural product isolated from Arnebia nobilis, on normal and impaired wound healing in cutaneous punch wound model. Arnebin-1 was applied topically daily on wounds of hydrocortisone-treated or untreated animals. Arnebin-1 significantly accelerated healing of wounds with or without hydrocortisone treatment as revealed by a reduction in the wound width and gap length compared with controls. Arnebin-1 treatment promoted the cell proliferation, migration, and vessel formation to form a thick granulation tissue and re-epithelialization of the wounds. An increase in the synthesis of collagen, fibronectin and transforming growth factor-β1 was seen in arnebin-1-treated wounds compared with the untreated control. As transforming growth factor-β1 is known to enhance wound healing, and associated with the wound healing defect in hydrocortisone-treated wounds, the enhanced expression of transforming growth factor-β1 at both translational and transcriptional level by arnebin-1 may be responsible for the enhancement of wound healing during normal and impaired wound repair. These studies suggest that arnebin-1 could be developed as a potent therapeutic agent for wound healing in steroid-impaired wounds.

The implementation of cellular manufacturing can be carried out through the creation of manufacturing cells (i.e., groups of dissimilar machines dedicated to a set of part types that are placed in close proximity to one another) or virtual cells (i.e., the dedication of specific machines within the current departments to a prespecified set of part types). Typically, the former involves the reorganization of the shop floor and provides the operational benefit of reduced materials handling. On the other hand, the latter configuration is simpler to implement and easier to reconfigure in light of product demand changes, but it may not offer the same operational benefits. In this paper, we propose and validate analytical approximations for comparing the performance of virtual cells and multistage flow shops. Using these approximations and hypothetical data, we identify some key factors that influence the implementation of virtual cells in a multistage flow shop environment. We conclude with an application of our approximations to industrial data.

Purpose: We studied the role of p53 tumor suppressor gene alteration in prostate cancer progression by demonstrating a difference in abnormal p53 findings between early and hormone refractory disease.Materials and Methods: The study included p53 immunohistochemistry of 26 archival transurethral resection specimens from patients with radiation recurrent and hormone refractory disease, 27 untreated primary tumors and 8 untreated metastatic lesions. p53 mutation analysis of tumor deoxyribonucleic acid (DNA) from microdissected specimens was done by cold single strand conformational polymorphism and DNA sequencing.Results: Elevated p53 protein was present in 16 of 17 hormone refractory specimens (94 percent), 4 of 8 untreated metastatic tumors (50 percent) and 6 of 27 primary untreated tumors (22 percent). DNA analysis of representative specimens with elevated p53 confirmed p53 gene alterations in 9 of 11 cases (82 percent).Conclusions: Our study revealed a clear progression of increased p53 alteratio...

Hypertension and diabetes are the two significant cardiovascular risk factors that contribute to the development and progression of chronic kidney disease (CKD). Hypertension is present in >50 % of those with estimated glomerular filtration rate (eGFR)

Diabetes is associated with an increased pro-oxidative and pro-inflammatory state that conveys an increased risk for cardiovascular end points such as cerebrovascular disease, ischemic heart disease, congestive heart failure, peripheral vascular disease, and chronic kidney disease (CKD). Both prediabetes and diabetes predispose to development of the cardiorenal metabolic syndrome, which is constituted by a group of interactive maladaptive factors including insulin resistance, hypertension, metabolic dyslipidemia, obesity, microalbuminuria and/or reduced renal function. In this regard, the presence of insulin resistance, hypertension, and visceral adiposity, independent of the presence of diabetes, leads to an increased risk for kidney disease and progressive loss of renal function. Whether there is a direct cause and effect relationship between the insulin resistance and obesity, the cardiorenal syndrome, and progressive kidney disease or just the presence of known risk factors for initiation and progression of CKD (i.e. hypertension and diabetes mellitus), is unknown. However, there is growing evidence that suggests that the obesity and insulin resistance directly contribute to CKD.

Orthostatic hypertension (OHT) is a clinically important problem increasingly recognized in persons with borderline hypertension, diabetes mellitus, and autonomic neuropathies, and in the elderly. Moreover, the association of OHT with progression of target end-organ damage, especially coronary heart disease and chronic kidney disease (CKD), and the attendant increased cardiovascular disease (CVD) and CKD risk, is gaining attention but is still underappreciated. There are various mechanisms that contribute to the development of OHT: excessive vascular adrenergic sensitivity, baroreceptor reflex abnormalities, and inappropriate activation of the renin-angiotensin-aldosterone system, which are also mechanisms that lead to cardiorenal metabolic disease (CRS). While the evidence is compelling for the clinical importance of OHT, more investigation is needed to evaluate the effects of OHT on CKD and CVD. The notion that the development of OHT is a risk factor for the development of CRS raises the need for further clinical and investigational attention to this clinical dilemma.

One of the most critical disadvantages of knowledge based systems is their slow execution speed. Knowledge based systems run about ten to one hundred times slower than traditional (procedural) information systems. This has generally limited their application environments and constrained the development of hybrid systems requiring both traditional and knowledge based approaches. This paper presents a framework for modularizing PROLOG knowledge bases such that the inferencing process to execute a goal is localized to an independent module consisting of only a subset of the knowledge base. Note that the motivation for modularization in a knowledge based system is quite different from the motivations for modularization in a traditional system. The presented modularization approach is expected to contribute to the development of more efficient knowledge based systems and more effective hybrid systems requiring both knowledge based and traditional approaches.

The metabolic syndrome is a constellation of metabolic and vascular abnormalities that include insulin resistance with compensatory hyperinsulinemia, central or visceral obesity, hypertension, dyslipidemia, microalbuminuria, and oxidative stress as well as prothrombotic and inflammatory abnormalities that contribute to a hypercoagulable state and systemic endothelial dysfunction. Visceral adipose tissue is now known to secrete into the circulation a number of protein and nonprotein factors that regulate glucose metabolism in traditional insulin-sensitive tissue as well as nontraditional insulin-sensitive tissue including cardiovascular tissue. Collectively, this constellation of factors that lead to metabolic dysregulation contributes to a substantial risk for adverse cardiovascular and renal outcomes. The development of a particularly resistant form of hypertension in these individuals can be attributed to a number of factors including vasoconstriction from increased sympathetic activation, proinflammatory cytokines, and inappropriate activation of the renin-angiotensin-aldosterone system. The management of hypertension in such patients can be challenging and generally requires nonpharmacologic as well as pharmacologic interventions.

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. In the present study, we have investigated the effect of picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.

Hemochromatosis is a highly prevalent genetic disease associated with excessive iron accumulation in a variety of tissues in an age-dependent manner. In a majority of patients (>85%) with hemochromatosis, mutations in the iron-regulatory gene HFE are the cause. Iron, when present in excess, is an inducer of oxidative stress and suppresses mitochondrial function. Patients with hemochromatosis show evidence of colonic inflammation. Further, some studies have shown increased risk for colon cancer associated with genetic mutations known to cause hemochromatosis. Based on these findings in the literature, we hypothesized that hemochromatosis is an important determinant of disease progression in patients with colitis and colon cancer. We tested this hypothesis by comparing progression of experimentally induced colitis and colon cancer between wild type mice and Hfe-null mice, a model for hemochromatosis. We also compared the transcriptome profile between wild type and Hfe-null colonic epithelial cells. In addition, we analyzed fecal bacteria in wild type mice and Hfe-null mice because colonic microbiome is an important determinant of colonic inflammation and colon cancer. With dextran sulfate sodium-induced colitis, Hfe-null mice suffered more weight loss and exhibited more severe bleeding and diarrhea scores than wild type mice. With ApcMin-driven colon and intestinal cancer, Hfe-null mice had more polyps in the small intestine and colon than wild type mice. Transcriptome analysis showed that Hfe-null colonic epithelial cells, compared to wild type cells, had increased expression of the cytokines Ccl3 and Ccl5 and the interferon-stimulated gene 15 (ISG15 or Usp18), which are all known to promote inflammation and cancer. Hfe-null colonic epithelial cells also had decreased expression of Erdr1 (erythroid differentiation regulator 1), whose expression is known to suppress tumor cell proliferation, invasion, migration and metastasis. Analysis of fecal microbiome indicated that the prevalence of Bacteroidetes and Firmicutes decreased while that of Proteobacteria increased in Hfe-null mice compared to wild type mice, a finding particularly striking in male mice. These studies demonstrate that hemochromatosis enhances the progression of colonic inflammation and colon carcinogenesis. This conclusion is further supported by xenograft studies using the colon cancer cell line HCT116 with and without shRNA-induced downregulation of HFE. When HFE was silenced, there was a significant increase in the growth of HCT116 cells in mouse xenografts, demonstrating that inactivation of HFE promotes colon cancer progression. Based on these data, we conclude that the iron-overload disease hemochromatosis is a promoter of disease progression in colitis and colon cancer, and that use of iron chelators might have a logical basis for inclusion in therapeutic modalities in the treatment of colonic inflammation and colon cancer. Citation Format: Vadivel Ganapathy, Ashish Gurav, Jaya P. Gnanaprakasam, Ellappan Babu, Yangzom D. Bhutia, Cynthia Reinoso Webb, Matthew B. Grisham. The iron-overload genetic disease hemochromatosis potentiates colonic inflammation and colon carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1557. doi:10.1158/1538-7445.AM2015-1557

Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.

Inflammatory cytokines interleukin 1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) have been recognized as important mediators of pathophysiological and immunological events associated with shock. These inflammatory events after hemorrhage and resuscitation are characterized by the activation of transcription regulators such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Curcumin, an anti-inflammatory remedy used in Indian medicine, is known to suppress NF-kappaB and AP-1 activation and also to reduce ischemia-reperfusion injuries in animal models. Therefore, the aim of this study was to determine whether administration of curcumin before hemorrhagic shock has any salutary effects on cytokines and the redox-sensitive transcription factors NF-kappaB and AP-1. mRNA levels of IL-1alpha, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha were determined by reverse transcriptase-polymerase chain reaction in rat livers collected at 2 and 24 h after hemorrhage/resuscitation. The effect of curcumin on the activation of NF-kappaB and AP-1 was determined by electrophoretic mobility shift assays. Significant increases in the levels of liver cytokines IL-1alpha, IL-1beta, IL-2, IL-6, and IL-10 were observed in the 2-h posthemorrhage/resuscitation group compared with sham animals. In contrast, oral administration of curcumin for 7 days followed by hemorrhage/resuscitation regimen resulted in significant restoration of these cytokines to depleted levels, and, in fact, IL-1beta levels were lower than sham levels. Also, the 24-h postresuscitation group showed similar patterns with some exceptions. NF-kappaB and AP-1 were differentially activated at 2 and 24 h posthemorrhage and were inhibited by curcumin pretreatment. Serum aspartate transaminase estimates indicate decreased liver injury in curcumin-pretreated hemorrhage animals. These results suggest that protection against hemorrhage/resuscitation injury by curcumin pretreatment may result from the inactivation of transcription factors involved and regulation of cytokines to beneficial levels.

Wound healing is a complicated biological process, which involves interactions of multiple cell types, various growth factors, their mediators and the extracellular matrix proteins. In this study, we evaluated the effects of shikonin analogue 93/637 (SA), derived from the plant Arnebia nobilis, on normal and hydrocortisone-induced impaired healing in full thickness cutaneous punch wounds in rats. SA (0.1%) was applied topically daily as an ointment in polyethylene glycol base on wounds. SA treatment significantly accelerated healing of wounds, as measured by wound contraction compared to controls in hydrocortisone-impaired animals. SA treatment promoted formation of granulation tissue including cell migration and neovascularization, collagenization and reepithelialization. The expression of basic fibroblast growth factor (bFGF) was higher as revealed by immunohistochemistry in treated wounds compared to controls. However, the expression of transforming growth factor-β1 was not affected by SA treatment. Since bFGF is known to accelerate wound healing, the increased expression of bFGF by SA may be partly responsible for the enhancement of wound healing. These studies suggest that SA could be further studied for clinical use to enhance wound healing.

In this paper, detection of QRS complex in Electrocardiogram (ECG) signal based on Autocorrelation and Hilbert transform (HT) is proposed. The autocorrelation method is used to determine the duration of one cardiac cycle of ECG signal and HT method is applied to detect the R-peaks point in ECG signal. The proposed algorithm is evaluated on MIT-BIH arrhythmia database and achieves a detection error rate of 0.12%, sensitivity of 99.93% and positive prediction of 99.95%. The proposed method shows better performance as compared to other two established techniques like Pan-Tompkins method and the technique that uses the Difference Operation Method (DOM).

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

Ultrasonic guided waves are fast emerging as a reliable tool for continuous structural health monitoring. Their multi-modal nature along with their long range propagation characteristics offer several possibilities for interrogating structures. Transducers commonly used to generate guided waves in structures excite multiple modes at any frequency; their complex scattering and reflection from defects and boundaries often complicates the extraction of useful information. Often it is desirable to control the guided wave modes propagating in a structure to take advantage of their unique properties for different applications. Earlier attempts at guided wave mode control involved developing fixed wavelength linear and annular array transducers. Their only disadvantage is that the transducer is limited to a particular wavelength and a change in wavelength necessitates a change in the transducer. In this paper, we propose the development of an annular array transducer that can generate mode controlled omnidirectional guided waves by independently controlling the amplitude and phase of the array elements. A simplified actuator model that approximates the transducer loading on the structure to a constant pressure load under the array elements is assumed and an optimization problem is set up to compute the excitation voltage and phase of the elements. A five element annular array transducer is designed utilizing 1?3 type piezocomposite materials. The theoretical computations are experimentally verified on an aluminum plate like structure by exciting A0 and S0 guided wave modes.

Ultrasonic guided wave tomography utilizes an array of permanently mounted transducers to detect and image defects like corrosion, cracks and delamination in structures. It is critical for successful tomography imaging to avoid the influences from external environmental conditions like water loading and changes in temperature. Water loading is particularly challenging as it affects the guided wave propagation in the structure. However, by taking advantage of the physical properties of guided waves it is possible to reduce its effect on the tomography images. Modal points on the dispersion curves can be found that have low out-of-plane displacement in their wave structure and hence no leakage into the liquid on the structure. In this paper, the omnidirectional excitation of desired guided wave modes with annular array transducers is discussed. Guided wave tomography of a steel plate like structure with a corrosion defect is studied under water loading conditions. The influence of water loading is overcome by exciting symmetric guided wave modes (S1) in the structure. Utilizing guided wave mode control it is shown that the defects in the structure can be easily discriminated from any artifacts in the images due to the liquid layer.

The structure, composition, electronic and optical properties of dip-coated CdS in the as-deposited condition and following rapid thermal annealing have been investigated. It has been shown that oxygen incorporated in the CdS film can be leached out following rapid thermal annealing. Strongly oriented CdS films with resistivity = 0.16 Ω cm and free electron concentration = 2.65 × 1017 cm−3 have been grown. Thin film heterojunction devices fabricated by non-aqueous electrodeposition of CdTe on a glass-ITO-CdS cathode have been shown to exhibit good rectification behaviour and photovoltaic activity.

For structural health monitoring applications, ultrasonic guided wave mode control is critical for obtaining simple signals that can be easily analyzed as well as special modes and frequencies for improved sensitivity to certain defects. This paper discusses the development of an annular array transducer for omnidirectional guided wave mode control in plate like structures. Using a flexible piezoelectric material like polyvinlydine fluoride (PVDF), annular array transducers that are low cost, low profile and conformable to the structure can be made rapidly. Two different array patterns, namely ones of comb and inter-digital (IDT) type, are studied. The loadings of these transducers on a structure differ from one another and hence so do their source influences. An axi-symmetric finite element modeling is employed to study the surface displacement pattern of these two transducer configurations. The source influence of the transducer configurations is studied experimentally by exciting an anti-symmetric (A1) and a symmetric (S1) type guided wave mode in a steel plate. It was observed that IDT type transducers were able to couple well to the guided wave modes at the wavelengths that they are designed for. The comb type transducers have a weak coupling to symmetric guided wave modes at frequencies where the wave structure has high in-plane displacement and negligible out-of-plane displacement on the surface of the structure.

Although research has suggested a number of desirable characteristics for on-line help systems, traditional design approaches have resulted in software containing many inadequacies and limitations. Here the deficiencies of current help systems are discussed and an expert system design approach to on-line help is outlined. The main components of such an expert help system are introduced.

Background Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. Methods/Design A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c