The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA.

DNA replication stress is characterized by impaired replication fork progression, causing some of the replication forks to collapse and form DNA breaks. It is a primary cause of genomic instability leading to oncogenic transformation. The repair-independent functions of the proteins RAD51 and BRCA2, which are involved in homologous recombination (HR)-mediated DNA repair, are crucial for protecting nascent DNA strands from nuclease-mediated degradation. The BRCA2 and CDKN1A-interacting protein (BCCIP) associates with BRCA2 and RAD51 during HR-mediated DNA repair. Here, we investigated the role of BCCIP during the replication stress response. We find that in the presence of replication stress, BCCIP deficiency increases replication fork stalling and results in DNA double-strand break formation. We show that BCCIP is recruited to stalled replication forks and prevents MRE11 nuclease-mediated degradation of nascent DNA strands.

Comparative Study of Effects of Intraoperative Use of Positive End-Expiratory Pressure, Intermittent Recruitment Maneuver, and Conventional Ventilation on Pulmonary Functions during long-Duration Laparotomy.

BACKGROUND: With an increase in the duration of general anesthesia, there is a gradual deterioration in pulmonary functions. Intraoperative atelectasis is the major cause of deterioration in pulmonary functions. This study was performed to compare and determine the best ventilatory strategy among conventional ventilation, application of positive end-expiratory pressure (PEEP), and intermittent recruitment maneuver. MATERIALS AND METHODS: Seventy-five patients were divided into three groups each of 25 patients. In the first group (zero positive end-expiratory pressure [ZEEP]), we have applied zero PEEP intraoperatively. In the second group (PEEP), we have applied PEEP of 6 cm of H2O. In the third group (intermittent lung recruitment maneuver [IRM]), we have done intermittent recruitment maneuver intraoperatively. Pulmonary functions were analyzed by partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F) and static lung compliance (Cstat). RESULTS: While comparing the mean P/F ratio between the groups, a significant decrease in P/F ratio of the ZEEP group was found from 90 min after induction up till the end (i. e. 24 h after extubation) of our observations as compared to both the PEEP and IRM groups. However, it did not differ (P > 0.05) between the PEEP and IRM groups at all time points on statistical analysis. On comparing the mean of Cstat between the groups, there was a significant decrease in lung compliance of the ZEEP group as compared to both the PEEP and IRM groups at all time points. However, like P/F ratio, compliance was also found to be statistically insignificant between the PEEP and IRM groups. CONCLUSIONS: Pulmonary functions are relatively preserved with application of either PEEP or doing intermittent recruitment maneuver.

Nanotechnology for environmentally sustainable electromobility.

Electric vehicles (EVs) powered by lithium-ion batteries (LIBs) or proton exchange membrane hydrogen fuel cells (PEMFCs) offer important potential climate change mitigation effects when combined with clean energy sources. The development of novel nanomaterials may bring about the next wave of technical improvements for LIBs and PEMFCs. If the next generation of EVs is to lead to not only reduced emissions during use but also environmentally sustainable production chains, the research on nanomaterials for LIBs and PEMFCs should be guided by a life-cycle perspective. In this Analysis, we describe an environmental life-cycle screening framework tailored to assess nanomaterials for electromobility. By applying this framework, we offer an early evaluation of the most promising nanomaterials for LIBs and PEMFCs and their potential contributions to the environmental sustainability of EV life cycles. Potential environmental trade-offs and gaps in nanomaterials research are identified to provide guidance for future nanomaterial developments for electromobility.

Role of surrogate markers in assessment of insulin resistance in females with thyroid disorders.

INTRODUCTION: Thyroid status is known to affect insulin sensitivity although conflicting data have been reported regarding hypothyroid and hyperthyroid states. Assessment of insulin resistance is difficult, therefore we compared homeostasis model assessment (HOMA), glucose to insulin (G:I) ratio, glucose to C-peptide (G:C) ratio and ferritin of hypothyroid and hyperthyroid subjects with euthyroid, euglycemic subjects. METHODS: The study group comprised of 40 hypothyroid, 25 hyperthyroid female subjects and 40 euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, glucose, Insulin, C-peptide and ferritin. Homeostasis model of assessment (HOMA-IR), (G:I), (G:C) and ferritin were employed as surrogate measures to assess the level of insulin resistance. The area under the curves for the surrogate markers was determined from the receiver operating characteristics (ROC) curves for the hypothyroid and hyperthyroid patients. RESULTS: Patients with hypothyroidism demonstrated insulin resistance as observed by the higher HOMA-IR and G:I ratio as compared to the controls whereas insulin resistance was not detected in the hyperthyroid patients in our study. CONCLUSION: Thyroid dysfunction attributes to deranged glucose metabolism. Assessment of the surrogate markers might prove to be beneficial in detecting insulin resistance at the incipient stages and subsequent management.

Awareness about HIV infection among the paramedical staff in a tertiary care hospital in Delhi, India.

In India, acquired immunodeficiency syndrome (AIDS) is a growing epidemic involving all sections of the society. Health care personnel are at increased risk of acquiring blood borne diseases like AIDS, hepatitis, etc. We aimed to assess the level of awareness of HIV infection among the paramedical staff working in a tertiary care hospital. A total number of 207 paramedical staff were asked to complete a questionnaire covering the various aspects of HIV and AIDS which was then critically reviewed. We observed that 57.54% of the staff was aware of the different aspects of HIV infection. Our results highlighted that awareness regarding the different facets of HIV varied among the nurses, lab technicians and support staff. Transmission of blood borne infections through needle stick injury is a harsh reality involving health care personnel. There is an urgent need to teach basic knowledge about HIV infection among high-risk populations.

Hepcidin: a novel peptide hormone regulating iron metabolism.

BACKGROUND: Hepcidin is a low-molecular weight hepatic peptide regulating iron homeostasis. Hepcidin inhibits the cellular efflux of iron by binding to, and inducing the internalization and degradation of, ferroportin, the exclusive iron exporter in iron-transporting cells. It has been recently recognized as a main hormone behind anemia of chronic disease. METHOD: A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/) and the National Library of Medicine (http://www.ncbl.nlm.nih.gov). The data was also assessed from journals and books that published relevant articles in this field. RESULT: Hepcidin regulates iron uptake constantly on a daily basis, to maintain sufficient iron stores for erythropoiesis. Hepcidin, by its iron regulatory action on iron metabolism may be expected to have an important role in immune regulation, inflammatory diseases and malignancies. Hepcidin is the underlying cause of anemia in these clinical settings. CONCLUSION: Hepcidin analysis may prove to be a novel tool for differential diagnosis and monitoring of disorders of iron metabolism, and establishment of therapeutic measures in various disease conditions like hereditary hemochromatosis, anemia associated with chronic kidney disease, rheumatoid arthritis and cancers.

Association of macrovascular complications of type 2 diabetes mellitus with serum magnesium levels.

BACKGROUND: Diabetes mellitus and its complications are a significant cause of morbidity and mortality worldwide. Micronutrients have been evaluated as potential preventive and therapeutic measures in diabetes. The present study evaluated serum magnesium levels in diabetic patients-uncomplicated and those with macrovascular complications. METHOD: This study was done on 150 subjects (60 normal, healthy controls and 90 diabetics). The 90 diabetic patients were selected in the following categories-30 patients without complications (Study Group I), 30 diabetic patients with coronary artery disease (Study Group II) and 30 diabetic patients with peripheral vascular disease (Study Group III). Plasma glucose, glycated hemoglobin and serum magnesium levels were estimated in all the patients. RESULTS: Fasting plasma glucose and glycated hemoglobin levels were significantly higher in all the 3 study groups as compared to the controls, however, serum magnesium levels were significantly lower (p<0.05). In diabetic patients with coronary atherosclerosis or peripheral vascular disease, a significant negative correlation was observed between serum magnesium and fasting plasma glucose and glycated hemoglobin indicating the role of hypomagnesemia in diabetic complications. CONCLUSION: Dietary supplementation with magnesium in addition to classical therapies for diabetes may help in prevention of diabetic complications.

Application of sigma metrics for the assessment of quality assurance in clinical biochemistry laboratory in India: a pilot study.

Ensuring quality of laboratory services is the need of the hour in the field of health care. Keeping in mind the revolution ushered by six sigma concept in corporate world, health care sector may reap the benefits of the same. Six sigma provides a general methodology to describe performance on sigma scale. We aimed to gauge our laboratory performance by sigma metrics. Internal quality control (QC) data was analyzed retrospectively over a period of 6 months from July 2009 to December 2009. Laboratory mean, standard deviation and coefficient of variation were calculated for all the parameters. Sigma was calculated for both the levels of internal QC. Satisfactory sigma values (>6) were elicited for creatinine, triglycerides, SGOT, CPK-Total and Amylase. Blood urea performed poorly on the sigma scale with sigma <3. The findings of our exercise emphasize the need for detailed evaluation and adoption of ameliorative measures in order to effectuate six sigma standards for all the analytical processes.

Potential biochemical markers for preterm labor: a pilot study in north India.

Preterm delivery is a major contributor for neonatal mortality. Intensive research is underway to establish a reliable biomarker that can ascertain the risk of preterm delivery in pregnant women. The aim of our study was to evaluate the role of various biochemical parameters as potential biomarker for risk assessment for preterm labor. Forty women presenting with preterm labor and 40 women who delivered at term were included in the study. Parameters that were evaluated include corticotrophin (ACTH), prolactin, thyroid stimulating hormone (TSH), ferritin and Alkaline Phosphatase (ALP). Serum ACTH, ferritin, ALP and Ferritin/Iron ratio were significantly higher in the subjects who delivered prematurely as compared to the controls. Comparison of sensitivity, specificity, likelihood ratio, positive and negative predictive values for different cut offs for ACTH, ferritin, ALP and ferritin/iron ratio was carried out. Ferritin emerged as the best marker with area under curve of 0.96 as compared to 0.88 for ACTH, 0.825 for ALP and 0.735 for ferritin/iron ratio. Our study establishes the superiority of ferritin as a predictive biomarker for preterm labor as compared to the rest of the parameters evaluated.

Acute presentation of dizziness in vitamin B12 deficient old patient of cardiac disease: a case report.

BACKGROUND: Neuropsychiatric and hematological manifestations of vitamin B12 deficiency are well known. The present report highlights the biochemical basis for the impaired synthesis of DNA and neurological disorders associated with vitamin B12 deficiency. METHODS: We present a case of an old patient who developed acute ataxia, dizziness and imbalance 2 days after pacemaker implantation in a cardiac care unit. RESULTS: On evaluation, the patient was found to have low vitamin B12 levels (121 pmol/l) with raised plasma homocysteine levels (28 µmol/l) and methylmalonic acid levels (17 µmol/l). Neurological examination revealed signs and symptoms of peripheral neuropathy. CT scan of the brain was found to be normal. The usual hematological presentation was absent in this case. The patient responded dramatically to parenteral vitamin B12 supplementation. CONCLUSION: Though frequent, the vitamin B12 deficiency often goes unnoticed in elderly population. So, with this report we emphasize that deficiency of serum vitamin B12 levels should be suspected and evaluated in elderly patients presenting with neuropsychiatric symptoms.

Anti-ceramide antibodies in leprosy: marker for nerve damage?

BACKGROUND: Leprosy is a chronic infectious disease primarily affecting the peripheral nervous system and skin. Multibacillary leprosy is associated with nerve damage which could contribute to myelin alteration. As ceramide is a constituent of myelin sheath, the present study aimed to compare anti-ceramide antibody titre in paucibacillary and multibacillary leprosy patients with controls. METHODOLOGY: Serum levels of anti-ceramide antibody were measured using enzyme-linked immunosorbent assays (ELISA) in 50 leprosy patients (25 paucibacillary and 25 multibacillary) and 25 healthy controls. Results were reported in OD units as mean +/- SD and analyzed by Chi square test (significance at p < 0.05). RESULTS: Patients suffering from multibacillary leprosy had significantly higher anti-ceramide antibody serum levels compared to paucibacillary leprosy patients and healthy controls (p < 0.005). CONCLUSIONS: Since nerve damage is the most debilitating effect of leprosy, the search for a serum marker for assessing nerve damage is required in countries where leprosy is still widespread. In multibacillary leprosy patients, the role of anti-ceramide antibody as a marker for nerve damage should be explored.

NAD(P)H oxidases in coronary artery disease.

Reactive oxygen species (ROS), especially superoxide anion and hydrogen peroxide, are important signaling molecules in cardiovascular cells. ROS participate in growth, apoptosis, and migration of vascular smooth muscle cells, in the modulation of endothelial function, including endothelium-dependent relaxation and expression of proinflammatory phenotype, and in the modification of the extracellular matrix. They have also been linked to hypertension and to pathological states associated with uncontrolled growth and inflammation leading to coronary artery disease (CAD). The NAD(P)H oxidase is a multisubunit enzyme that catalyzes the reduction of molecular oxygen to form superoxide (O2*-). Although first described in phagocytes, NAD(P)H oxidases have also been demonstrated as major sources of superoxide in vascular cells and myocytes. Enhanced superoxide production increases nitric oxide inactivation and leads to an accumulation of peroxynitrites and hydrogen peroxide. An entire new family of NAD(P) H oxidase (Nox) homologs has emerged, which vary widely in cell and tissue distribution as well as in function and regulation. Recent and ongoing research tends to highlight the biochemical characters, activation paradigms, structure, and function of this enzyme. In this review, we provide a brief overview of structural features of NAD(P)H oxidases and then discuss their role in pathophysiology of CAD.

Evaluation of errors in a clinical laboratory: a one-year experience.

BACKGROUND: Efficient laboratory service is the cornerstone of modern health care systems. Scientific innovations have contributed to substantial improvements in the field of laboratory science, but errors still prevail. These errors are classified as preanalytical, analytical and postanalytical, depending upon the time of presentation. METHODS: The data for 67,438 routine venous blood specimens were scrutinized, and errors were documented over the period of 1 year in the clinical biochemistry laboratory of Govind Ballabh Pant Hospital in Delhi, India. RESULTS: Preanalytical errors were most common, with a frequency of 77.1% followed by postanalytical 15% and analytical 7.9%, respectively. CONCLUSIONS: Our study illustrates the importance of proper venipuncture procedures, analytical expertise and correct transcription of numerical data for precise and accurate reporting of results to clinicians. There is an urgent need for close inter-departmental cooperation to meet the goal of ensuring patient well being.

Human and environmental impact assessment of postcombustion CO2 capture focusing on emissions from amine-based scrubbing solvents to air.

Carbon Capture and Storage (CCS) has become a key technology in climate change mitigation programs worldwide. CCS is well-studied in terms of greenhouse gas emission reduction potential and cost of implementation. Impacts on human health and the environment have, however, received considerably less attention. In this work, we present a first assessment of human health and environmental impacts of a postcombustion CO(2) capture facility, focusing on emissions from amine-based scrubbing solvents and their degradation products to air. We develop characterization factors for human toxicity for monoethanolamine (MEA) as these were not yet available. On the basis of the limited information available, our assessment indicates that amine-based scrubbing results in a 10-fold increase in toxic impact on freshwater ecosystems and a minor increase in toxic impacts on terrestrial ecosystems. These increases are attributed to emissions of monoethanolamine. For all other impact categories, i.e., human toxicity, marine ecotoxicity, particulate matter formation, photochemical oxidant formation, and terrestrial acidification, the CO(2) capture facility performs equally well to a conventional NGCC power plant, albeit substantial changes in flue gas composition. The oxidative degradation products of MEA, i.e., formaldehyde, acetaldehyde, and ammonia, do not contribute significantly to total environmental impacts.

Turn Around Time (TAT) as a Benchmark of Laboratory Performance.

Laboratory analytical turnaround time is a reliable indicator of laboratory effectiveness. Our study aimed to evaluate laboratory analytical turnaround time in our laboratory and appraise the contribution of the different phases of analysis towards the same. The turn around time (TAT) for all the samples (both routine and emergency) for the outpatient and hospitalized patients were evaluated for one year. TAT was calculated from sample reception to report dispatch. The average TAT for the clinical biochemistry samples was 5.5 h for routine inpatient samples while the TAT for the outpatient samples was 24 h. The turnaround time for stat samples was 1 h. Pre- and Post-analytical phases were found to contribute approximately 75% to the total TAT. The TAT demonstrates the need for improvement in the pre- and post-analytical periods. We need to tread the middle path to perform optimally according to clinician expectations.

Surrogate markers of insulin resistance: A review.

Insulin resistance is a hallmark of obesity, diabetes, and cardiovascular diseases, and leads to many of the abnormalities associated with metabolic syndrome. Our understanding of insulin resistance has improved tremendously over the years, but certain aspects of its estimation still remain elusive to researchers and clinicians. The quantitative assessment of insulin sensitivity is not routinely used during biochemical investigations for diagnostic purposes, but the emerging importance of insulin resistance has led to its wider application research studies. Evaluation of a number of clinical states where insulin sensitivity is compromised calls for assessment of insulin resistance. Insulin resistance is increasingly being assessed in various disease conditions where it aids in examining their pathogenesis, etiology and consequences. The hyperinsulinemic euglycemic glucose clamp is the gold standard method for the determination of insulin sensitivity, but is impractical as it is labor- and time-intensive. A number of surrogate indices have therefore been employed to simplify and improve the determination of insulin resistance. The object of this review is to highlight various aspects and methodologies for current and upcoming measures of insulin sensitivity/resistance. In-depth knowledge of these markers will help in better understanding and exploitation of the condition.

Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital.

The effect of thyroid status on insulin sensitivity is of great interest but despite various studies there is conflicting data on this subject. The study group comprised of 25 female subjects each with subclinical hypothyroidism, overt hypothyroidism and euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, Insulin and lipid profile. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance. Patients with hypothyroidism demonstrated insulin resistance and dyslipidemia as observed by the higher HOMA-IR and cholesterol and triglyceride levels respectively as compared to the controls. A significantly positive correlation between TSH and HOMA-IR level was also observed in the hypothyroidism group. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. The dyslipidemia and insulin resistance should be managed aggressively to reduce the impending risk.

Fetal intravenous immunoglobulin therapy in rhesus hemolytic disease.

Intrauterine blood transfusion is the mainstay of treatment of fetal rhesus hemolytic anemia with optimal perinatal outcome. Postnatal immunoglobulin therapy has been successfully used in the management of alloimmunized neonates and has shown to decrease the need for exchange transfusion. We report the first case series of fetal immunoglobulin therapy in the antenatal management of severe Rh incompatibility.

Successful pregnancy outcome in Bernard-Soulier syndrome.

Bernard-Soulier syndrome is a rare bleeding disorder, and there is scant literature on the pregnancy outcome in women with this syndrome. Due to the bleeding tendency in this disease, pregnant woman may have ante-, intra- or postpartum complications. We report our experience of managing a pregnant woman with Bernard-Soulier syndrome who had a successful pregnancy outcome, and review the existing literature on pregnancy in women with this syndrome.