Efficacy and Safety of Shatavari Root Extract for the Management of Menopausal Symptoms: A Double-Blind, Multicenter, Randomized Controlled Trial.

Background Menopause is a physiological state that occurs in all women and refers to the halt of the reproductive phase. The cessation of the reproductive phase occurs through various stages and presents different symptoms such as hot flashes, night sweats, insomnia, anxiety, depression, and irritability. Such pre- and post-menopausal symptoms may affect the daily activities and production capacities of women, impacting the quality of life (QoL) of women. Hormone replacement therapy (HRT) is primarily used to manage menopausal symptoms. However, various side effects have been reported related to HRT. Therefore, women are choosing alternative medicine such as Ayurveda that can benefit them with less or no adverse effects. Shatavari (Asparagus racemosus) is known in Ayurveda as an effective medicinal plant source for various women's health remedies since ancient times. This study aimed to evaluate the safety and efficacy of the Ayurvedic Shatavari formulation on menopausal symptoms compared to the placebo. Methodology This is a randomized, double-blinded, multicenter, placebo-controlled, clinical study. Altogether, 70 patients were randomized to two groups, i.e., the test group (active group) and the placebo group (microcrystalline cellulose), with 35 participants in each group. Results The study outcomes showed a positive and significant effect of the active test ingredient over the placebo in terms of reduction in hot flashes, night sweats, insomnia, anxiety, nervousness, vaginal dryness, and loss of libido. The Utian QoL improved significantly in the test group compared to the placebo group. No significant adverse events were recorded in the test group, suggesting the safety of this formulation. Conclusions The test compound could be a safe alternative to modern drugs. The findings of this study support the traditional use of Shatavari. Further clinical and pharmacological studies with longer duration and larger and more diverse sample sizes are required to understand the generalized effect of Shatavari root extract in menopausal women.

Effect of yoga on adipokine levels among overweight and obese people: A systematic review.

BACKGROUND: Adipokines have an important role in the pathophysiology of overweight and obesity and associated inflammatory diseases. OBJECTIVE: The present review aims to evaluate the role of Yoga on adipokines among people with overweight and obesity. METHODS: Authors performed a systematic search for relevant research studies as per the PRISMA guidelines in Google Scholar, Medline/Pubmed, Scopus, Web of Science, PsychInfo electronic databases. Two independent authors conducted the selection of articles, data extraction, assessment of the risk of bias for individual studies. Any disagreements were resolved by discussion with the third author. RESULTS: Eight randomized trials and four uncontrolled trials involving a total of 1054 participants were included. Yoga with varying frequencies was administered for different durations. The studied adipokines among overweight and obese were leptin, adiponectin, interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), chemerin, visfatin, plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta (TGF-ß). The methodological quality of the included studies was low to moderate on the Cochrane risk of bias tool and Newcastle-Ottawa Quality Assessment Scale. The higher the frequency and duration of Yoga practice, the more significant changes in the adipokine levels were seen. CONCLUSION: The present review indicates that Yoga practices positively impacts adipokines among people with overweight and obesity. However, the present study precludes the generalizability of results due to the methodological heterogeneity, the type of Yoga intervention, and settings.

Formulation and evaluation of Ocimum sanctum Linn containing carboxymethylcellulose and sorbitol based hydrogel.

It is of interest to formulate a hydrogel consisting of Ocimum sanctum Linn, sorbitol, and carboxymethyl cellulose and to evaluate the physical properties of the hydrogel. The hydrogel was prepared by dissolving Ocimum sanctum Linn extract into the mixture containing sorbitol and carboxymethyl cellulose. The formulation was further evaluated for its swelling index, contact angle, in -vitro release properties, and surface analysis using atomic force microscopy. The swelling index showed a significant increase in weight from 1st hr to the 84th hour which is 11.1% and 15.8% respectively. The contact angle test showed a value of 72.81° and 75.99° respectively. In vitro drug release showed a burst release till the 6th day followed by a sustained release till the 20th day. Atomic force microscopy revealed smooth and consistent surface topography with a mean size of 51µm in diameter which depicts that the particles are well dispersed throughout the hydrogel matrix. Data show that hydrogel containing Ocimum sanctum Linn extract, sorbitol, and carboxymethyl cellulose could be an efficient economic primeval substitute that is non-toxic, natural, and structured for clinical application.

Formulation and evaluation of a novel herbal trio gel containing flax seed extract, carbopol and carboxymethyl cellulose.

It is of interest to formulate and evaluate herbal trio gel containing brown flax seed extract, carbopol, and carboxymethyl cellulose and to assess the antimicrobial, anti-inflammatory activity along with quality analysis using SEM and FTIR. The brown flax seeds were grinded into a fine powder and supercritical fluid was prepared which was mixed with CMC and carbopol. The formulation was checked for antimicrobial, anti-inflammatory activity, surface characteristics with SEM and FTIR. The results revealed that the activity of the trio gel was efficacious in hampering the growth of black pigmented anaerobes. The highest zone of inhibition for novel herbal trio gel was recorded at 100 µL measuring 14mm and for the standard chlorhexidine gel it was recorded at 100 µL measuring 23mm in diameter. The results proved that the zone of inhibition of novel herbal trio gel had a decent difference to that of standard chlorhexidine gel. The anti-inflammatory activity showed significant activity at 20 µL which accounted for 53% for the novel herbal trio gel and for the standard diclofenac gel it showed highest activity at 20 µL which accounted for 60%. However, there was not much difference between the herbal trio gel and standard diclofenac gel. SEM observations revealed that the components used in formulation of this trio gel have been bonded well to each other and exhibited appreciable surface characteristics. The lattice of the trio gel has been very well exhibited in SEM analysis. FTIR revealed high peaks showing the different components present in the trio gel. Within the limitations of the study, the results of our study concluded that novel herbal trio gel containing Linum usitatissimum extract, sorbitol, and carboxymethyl cellulose could be an efficient economic primeval substitute that is non-toxic, natural, and structured for clinical application.

Cardiac arrest: An interdisciplinary scoping review of clinical literature from 2020.

Objectives: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct an annual search of peer-reviewed literature relevant to cardiac arrest. Now in its third year, the goals of the review are to highlight annual updates in the interdisciplinary world of clinical cardiac arrest research with a focus on clinically relevant and impactful clinical and population-level studies from 2020. Methods: A search of PubMed using keywords related to clinical research in cardiac arrest was conducted. Titles and abstracts were screened for relevance and sorted into 7 categories: Epidemiology & Public Health Initiatives; Prehospital Resuscitation, Technology & Care; In-Hospital Resuscitation & Post-Arrest Care; Prognostication & Outcomes; Pediatrics; Interdisciplinary Guidelines & Reviews; and a new section dedicated to the coronavirus disease 2019 (COVID-19) pandemic. Screened manuscripts underwent standardized scoring of methodological quality and impact on the respective fields by reviewer teams lead by a subject matter expert editor. Articles scoring higher than 99 percentiles by category were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. Results: A total of 3594 articles were identified on initial search; of these, 1026 were scored after screening for relevance and deduplication, and 51 underwent full critique. The leading category was Prehospital Resuscitation, Technology & Care representing 35% (18/51) of fully reviewed articles. Four COVID-19 related articles were included for formal review that was attributed to a relative lack of high-quality data concerning cardiac arrest and COVID-19 specifically by the end of the 2020 calendar year. No significant differences between editor and reviewer scoring were found among review articles (P = 0.697). Among original research articles, section editors scored a median 1 point (interquartile range, 0-3; P < 0.01) less than reviewers. Conclusions: Several clinically relevant studies have added to the evidence base for the management of cardiac arrest patients including methods for prognostication of neurologic outcome following arrest, airway management strategy, timing of coronary intervention, and methods to improve expeditious performance of key components of resuscitation such as chest compressions in adults and children.

A Comprehensive Biological and Synthetic Perspective on 2-Deoxy-d-Glucose (2-DG), A Sweet Molecule with Therapeutic and Diagnostic Potentials.

Glucose, the primary substrate for ATP synthesis, is catabolized during glycolysis to generate ATP and precursors for the synthesis of other vital biomolecules. Opportunistic viruses and cancer cells often hijack this metabolic machinery to obtain energy and components needed for their replication and proliferation. One way to halt such energy-dependent processes is by interfering with the glycolytic pathway. 2-Deoxy-d-glucose (2-DG) is a synthetic glucose analogue that can inhibit key enzymes in the glycolytic pathway. The efficacy of 2-DG has been reported across an array of diseases and disorders, thereby demonstrating its broad therapeutic potential. Recent approval of 2-DG in India as a therapeutic approach for the management of the COVID-19 pandemic has brought renewed attention to this molecule. The purpose of this perspective is to present updated therapeutic avenues as well as a variety of chemical synthetic strategies for this medically useful sugar derivative, 2-DG.

A review on ozone therapy in periodontitis.

The biologic process of osseointegration (bone to implant interface), in which the implant forms an intimate relationship with the bone, provides the foundation for modern dental implants. Osseointegration necessitates a varying length of healing time. Despite the high success and survival rates of dental implants, problems do occur, necessitating ongoing periodontal and prosthodontic care. This failure frequently results in "peri-implantitis," which affects the soft and hard tissues surrounding the osseointegrated implants, resulting in the formation of a peri implant pocket and bone loss. Decontamination is a difficult feature of surgical regenerative therapy for peri-implantitis that has an impact on its success. Because microbial biofilms play such a significant part in the aetiology of peri-implant illnesses, it has long been assumed that eliminating microbial pathogens would be beneficial.

Radio-Morphometric Analysis of Sella Turcica in Relation to Age and Gender in Sri Ganganagar Population: A Prospective Cephalometric Study.

Background Sella turcica (ST) is a crucial structure that is morphologically situated in the median position and is well-utilised in cephalometrics. This saddle-shaped sella constitutes a significant radiographic landmark for various related analyses. Therefore, studying its varying dimensions in different populations is of utmost importance. This paper evaluates and compares the linear dimensions and morphological variations of ST in different facial skeletal classes in relation to age and gender using lateral cephalograms in the Sri Ganganagar population. Methodology The study population was selected through simple random sampling from the accessible population of the Sri Ganganagar district. A total of 180 participants of both genders were selected from patients who visited the outpatient clinic of the Department of Oral Medicine and Radiology of Surendra Dental College and Research Institute in Sri Ganganagar. These samples were equally divided into three age groups. Apart from typical morphology, five possible variations of ST were determined. The area of ST on the lateral cephalogram was also evaluated. The extent of ST was calculated from the tubercle portion to the top of the dorsal side. The relative deepness of the sella was assessed by making a tangent across the innermost point of the sella. SPSS software was utilised for statistical analysis and related inferences. Results In the study sample (n = 180), 50% were men and 50% were women. The sample was divided into three equal groups based on age: Group I (n = 60; 33.33%) consisted of participants aged 15-20; Group II (n = 60; 33.33%) consisted of participants aged 21-25; and Group III (n = 60; 33.33%) consisted of participants aged 26-30. Conclusions The anteroposterior diameter of the sella structure is strongly related to age progression with no significant gender correlation. The most common shape of ST other than the normal one was oblique. Additionally, skeletal relationships showed a significant relationship with the shape of ST in the study population.

In vivo imaging of immediate early gene expression dynamics segregates neuronal ensemble of memories of dual events.

Identification of neurons undergoing plasticity in response to external stimuli is one of the pertinent problems in neuroscience. Immediate early genes (IEGs) are widely used as a marker for neuronal plasticity. Here, we model the dynamics of IEG expression as a consecutive, irreversible first-order reaction with a limiting substrate. First, we develop an analytical framework to show that such a model, together with two-photon in vivo imaging of IEG expression, can be used to identify distinct neuronal subsets representing multiple memories. Using the above combination, we show that the expression kinetics, rather than intensity threshold, can be used to identify neuronal ensembles responding to the presentation of two events in vivo. The analytical expression allowed us to segregate the neurons based on their temporal response to one specific behavioural event, thereby improving the ability to detect plasticity related neurons. We image the retrosplenial cortex (RSc) of cfos-GFP transgenic mice to follow the dynamics of cellular changes resulting from contextual fear conditioning behaviour, enabling us to establish a representation of context in RSc at the cellular scale following memory acquisition. Thus, we obtain a general method that distinguishes neurons that took part in multiple temporally separated events by measuring fluorescence of individual neurons in live mice.

Designing and validation of a yoga-based module for obesity with metabolic comorbidities.

OBJECTIVES: Obesity is a condition of increased adipose tissue in the body, which is commonly associated with various comorbidities like diabetes, hypertension, arthritis, back pain, and many others. Yoga modules have been designed and validated for obesity; however, we couldn't find any specific module for metabolic syndrome, a condition which includes obesity, diabetes mellitus type 2 and/or hypertension together. Keeping this in view, our study aimed to develop and validate a specific generic yoga-based intervention module for metabolic syndrome patients. MATERIALS AND METHODS: A yoga module was designed based on traditional and contemporary yoga literature as well as published studies. We derived the yoga practices for the module, from these yoga texts and research evidence were already available. The yoga module was sent to 40 yoga experts for their validation. RESULTS: Twenty-two experts gave their opinion on the usefulness of a yoga module for patients with metabolic syndrome with some suggestions. Of these experts, 73% were males, and 27% were females. Yoga therapy practices with content validity ratio (CVR) >0.08 were included in the final module. In total, 86% (31 of 36 items) of the items in the initial module were retained. CONCLUSION: A specific yoga-based module for metabolic syndrome was designed and validated by experts. Further studies are needed to confirm the efficacy and clinical utility of the module.Additional clinical validation is suggested.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Faculty's perspective on skill assessment in undergraduate medical education: Qualitative online forum study.

BACKGROUND: India is at the nascent stage of competency-based medical education. Faculties trained in medical education are the main driving force for change. The present study explores the perception of faculties about the current practices and problems in medical/dental/nursing undergraduate assessment, barriers to adoption of best practices, and solutions for addressing them. METHODOLOGY: A qualitative study was designed and data collected through an asynchronous online discussion forum. A group of 31 health professionals (FAIMER fellows selected on the basis of active participation in department of medical education of respective colleges) participated in the forum. An open-ended topic guide with prompts was designed. The forum was initiated by release of discussion topics (threads) at the start of the month and remained in forum throughout the month. Researchers moderated and recorded day-to-day events. All online forum data were coded line by line and analyzed using conventional content analysis. RESULTS: Four categories generated were: (1) Low utility of current skill assessment system due to low validity and reliability; (2) Barrier in adopting newer assessment tool due to the absence of felt need of faculties and students, mistaken beliefs, and limited resources; (3) Poor implementation of newer assessment tools such as formatives and objective structured clinical examination with no blueprinting; and (4) Solutions proposed were regular formative assessment, criterion-based examination, quality-assured faculty development programs, and administrative support. CONCLUSIONS: Barriers in adopting newer assessment tools are related to the faculty's perception and resource constraint. This can be addressed by quality-assured faculty development programs and effective implementation of competency-based education.

Cardiac arrest: An interdisciplinary review of the literature from 2018.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest (CA). The goals of the review are to illustrate best practices and help reduce knowledge silos by disseminating clinically relevant advances in the field of CA across disciplines. METHODS: An electronic search of PubMed using keywords related to CA was conducted. Title and abstracts retrieved by these searches were screened for relevancy, separated by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and importance. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors and reviewer scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 9119 articles were identified on initial search; of these, 1214 were scored after screening for relevance and deduplication, and 80 underwent full critique. Prognostication & Outcomes category comprised 25% and Epidemiology & Public Health 17.5% of fully reviewed articles. There were no differences between editor and reviewer scoring. CONCLUSIONS: The total number of articles demonstrates the need for an accessible source summarizing high-quality research findings to serve as a high-yield reference for clinicians and scientists seeking to absorb the ever-growing body of CA-related literature. This may promote further development of the unique and interdisciplinary field of CA medicine.

Cardiac arrest: An interdisciplinary scoping review of the literature from 2019.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest. Now in its second year, the goals of the review are to illustrate best practices in research and help reduce compartmentalization of knowledge by disseminating clinically relevant advances in the field of cardiac arrest across disciplines. METHODS: An electronic search of PubMed using keywords related to cardiac arrest was conducted. Title and abstracts retrieved by these searches were screened for relevance, classified by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and impact on the categorized fields of study by reviewer teams lead by a subject-matter expert editor. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 3348 articles were identified on initial search; of these, 1364 were scored after screening for relevance and deduplication, and forty-five underwent full critique. Epidemiology & Public Health represented 24% of fully reviewed articles with Prehospital Resuscitation, Technology & Care, and In-Hospital Resuscitation & Post-Arrest Care Categories both representing 20% of fully reviewed articles. There were no significant differences between editor and reviewer scoring. CONCLUSIONS: The sheer number of articles screened is a testament to the need for an accessible source calling attention to high-quality and impactful research and serving as a high-yield reference for clinicians and scientists seeking to follow the ever-growing body of cardiac arrest-related literature. This will promote further development of the unique and interdisciplinary field of cardiac arrest medicine.

Utilization of ICDS program by adolescent girls and implementation barriers in Urban Rishikesh, India.

CONTEXT: Adolescent girls are at higher risk of mortality and morbidity due to childbirth. Government of India therefore initiated Adolescent girls' scheme since year 2000. However, since its inception program received various setbacks. AIMS: This study was carried out to assess the utilization of ICDS program for adolescent girls through Anganwadi centers (AWC) and implementation barrier from providers point of view. Also study assessed gaps in knowledge, attitude, and practice of anemia. SETTINGS AND DESIGN: Mixed-method sequential explanatory approach was adopted. Quantitative data was collected by community-based cross-sectional survey in Urban Rishikesh, Uttarakhand. This was followed by in-depth interview of Anganwadi worker (AWW). METHODS AND MATERIALS: Twenty adolescent girls from each of 20 clusters were selected by cluster sampling. Data was collected by structured validated questionnaire using Epicollect 5. AWWs were interviewed with help of interview guide. STATISTICAL ANALYSIS: Variables were described as proportion and mean. The interview transcript was analyzed using content analysis. RESULTS: Out of 400 adolescent girls, 10% were school dropouts and 59% were undernourished. Seven percent had ever visited AWC in last year. The main reason for nonutilization was unawareness. 38% had knowledge regarding symptoms of anemia. AWW faces problems due to nonavailability of iron tablet, untrained for health education sessions, and service not meeting demand of beneficiaries. CONCLUSIONS: Poor utilization of ICDS services by adolescent girls due to unawareness. There is gap in knowledge regarding anemia among adolescent girls. Adolescent girls' scheme is not as per felt need of beneficiary and poorly implemented.

The Association of Health Literacy With Preventable Emergency Department Visits: A Cross-sectional Study.

BACKGROUND: Policymakers argue that emergency department (ED) visits for conditions preventable with high-quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor, and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high-quality ambulatory care is unknown. OBJECTIVE: The objective was to determine the association of health literacy with preventable ED visits. METHODS: We conducted an observational cross-sectional study of potentially preventable ED visits (outcome) among adults (≥18 years old) in an ED serving an urban community. We assessed health literacy (predictor) through structured interviews with the Rapid Estimate of Adult Literacy in Medicine (REALM). We recorded age, sex, race, employment, payer, marital and health status, and number of comorbidities through structured interviews or electronic record review. We identified potentially preventable ED visits in the 2 years before the index ED visit by applying Agency for Healthcare Research and Quality technical specifications to identify ambulatory care sensitive conditions using ED discharge diagnoses in hospital administrative data. We used Poisson regression to evaluate the number of preventable ED visits among patients with limited (REALM < 61) versus adequate (REALM ≥ 61) health literacy after adjusting for covariates. RESULTS: Of 1,201 participants, 709 (59%) were female, 370 (31%) were African American, mean age was 41.6 years, and 394 (33%) had limited health literacy. Of 4,444 total ED visits, 423 (9.5%) were potentially preventable. Of these, 260 (61%) resulted in hospital admission and 163 (39%) were treat and release. After covariates were adjusted for, patients with limited literacy had 2.3 (95% confidence interval [CI] = 1.7-3.1) times the number of potentially preventable ED visits resulting in hospital admission compared to individuals with adequate health literacy, 1.4 (95% CI = 1.0-2.0) times the number of treat-and-release visits, and 1.9 (95% CI = 1.5-2.4) times the number of total preventable ED visits. CONCLUSIONS: Our results suggest that the ED may be an important site to deploy universal literacy-sensitive precautions and to test literacy-sensitive interventions with the goal of reducing the burden of potentially preventable ED visits on patients and the healthcare system.

Managing GIST in the imatinib era: optimization of adjuvant therapy.

We reviewed studies evaluating the clinical benefits of 1 year or more of adjuvant imatinib therapy in patients with gastrointestinal stromal tumor (GIST). Data from the Scandinavian Sarcoma Group (SSG) XVIII/AIO Phase III trial of 1 year versus 3 years of adjuvant imatinib support the use of 3 years as standard of care in patients who are at high risk for GIST recurrence following resection. Although adjuvant imatinib therapy prolonged recurrence-free survival in the evaluated trials, overall survival was not significantly increased except in the SSG XVIII/AIO trial. The optimal duration of therapy, and whether high-risk patients should use adjuvant imatinib continuously, remains unknown. The importance of risk assessment, risk stratification and GIST genotype in patient selection is also discussed.

Association of IL-1ß +3954 C/T and IL-10-1082 G/A cytokine gene polymorphisms with susceptibility to tuberculosis.

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL-1ß and IL-10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene-gene interactions. The genotype and allele frequencies of IL-1ß +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059-0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526-5.696) genotypes of IL-10-1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1-3.35) genotype in IL-1ß and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225-9.702) genotype in IL-10 were at increased risk of developing tuberculosis. MDR tests revealed high-risk genotypes in IL-1ß and IL-10 based on the association model. Our results demonstrate that the polymorphisms of IL-1ß and IL-10 genes may be valuable markers to predict the risk for the development of TB in household contacts.

Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination.

Abro1 (also known as KIAA0157) is a scaffold protein that recruits polypeptides to assemble the BRISC (BRCC36-containing isopeptidase complex) deubiquitinating (DUB) enzyme. The four subunits of BRISC enzyme include Abro1, NBA1, BRE, and BRCC36 proteins. The DUB activity of the BRISC enzyme is exclusively directed against Lys63-linked polyubiquitin that does not have a proteolytic role but regulates protein function. In this report, we identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. Abro1 was predominantly expressed in the heart and its protein level was regulated following experimentally induced myocardial ischemia/reperfusion (MI/R) injury. Furthermore, in patients with coronary artery disease (CAD), there was a dramatic increase in Abro1 protein level in the myocardial infarction (MI) area. Increase in Abro1 leads to a significant reduction in Lys63-linked ubiquitination of specific protein targets. Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury. Additionally, overexpression of Abro1 in a heterologous system provided significant protection against oxidative stress-induced apoptosis. In conclusion, our results demonstrate that Abro1 protein level substantially increases in myocardial injury and coronary artery disease and this up-regulation is part of a novel cardioprotective mechanism. In addition, our data suggest a potential new link between Lys63-specific ubiquitination, its modulation by the BRISC DUB enzyme, and the development and progression of heart disease.

THAP5 is a DNA-binding transcriptional repressor that is regulated in melanoma cells during DNA damage-induced cell death.

THAP5 was originally isolated as a specific interactor and substrate of the mitochondrial pro-apoptotic Omi/HtrA2 protease. It is a human zinc finger protein characterized by a restricted pattern of expression and the lack of orthologs in mouse and rat. The biological function of THAP5 is unknown but our previous studies suggest it could regulate G2/M transition in kidney cells and could be involved in human cardiomyocyte cell death associated with coronary artery disease (CAD). In this report, we expanded our studies on the properties and function of THAP5 in human melanoma cells. THAP5 was expressed in primary human melanocytes as well as in all melanoma cell lines that were tested. THAP5 protein level was significantly induced by UV irradiation or cisplatin treatment, conditions known to cause DNA damage. The induction of THAP5 correlated with a significant increase in apoptotic cell death. In addition, we show that THAP5 is a nuclear protein that could recognize and bind a specific DNA motif. THAP5 could also repress the transcription of a reporter gene in a heterologous system. Our work suggests that THAP5 is a DNA-binding protein and a transcriptional repressor. Furthermore, THAP5 has a pro-apoptotic function and it was induced in melanoma cells under conditions that promoted cell death.