Fixed-Dose Versus Off-Label Combination of Isosorbide Dinitrate Plus Hydralazine Hydrochloride: Retrospective Propensity-Matched Analysis in Black Medicare Patients with Heart Failure

Abstract

Introduction

Based upon the findings of the African-American Heart Failure Trial, the US Food and Drug Administration approved the fixed-dose combination of isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HYD) (FDC-ISDN/HYD) as a new drug for treatment of heart failure (HF) in self-identified African Americans. According to the FDA, FDC-ISDN/HYD has no therapeutic equivalent. However, off-label combinations of the separate generic drugs ISDN and HYD (OLC-ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are routinely substituted without any supporting outcome data. We conducted an exploratory retrospective propensity-matched cohort study using Medicare data to determine whether a survival difference exists between these treatments in medication-adherent patients.

Methods

Black Medicare beneficiaries with HF were matched with Medicare Part D data to identify patients with prescriptions to FDC-ISDN/HYD or the off-label combinations. Only patients with 1-year adherence levels ≥80% were included in the analysis. Propensity-matched scoring created two sets of matched cohort pairs on a 1:1 basis, each set comparing FDC-ISDN/HYD with one of the off-label combinations. Kaplan-Meier (KM) survival curves with the log-rank test were then calculated for each pair for the year of medication adherence.

Results

The analysis population was relatively older (77 years) and mainly female (66.7%), with a high burden of comorbid disease. The KM estimates of 1-year survival were 87.9% (95% CI 85.6–89.9%) and 83.0% (95% CI 80.3–85.3%) (log rank p = 0.0024), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISDN+HYD (n = 886 in each group) and 88.2% (95% CI 85.9–90.2%) and 84.8% (95% CI 82.2–87.0%) (log rank p = 0.0320), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISMN+HYD (n = 868 in each group).

Conclusion

The 1-year survival advantage for FDC-ISDN/HYD compared with off-label combinations in adherent black Medicare beneficiaries with HF suggests a genuine difference between these medications and warrants prospective investigation.

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Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases

Abstract

Introduction

Comparative data on the burden of atopic dermatitis (AD) in adults relative to the general population are limited. We performed a large-scale evaluation of the burden of disease among US adults with AD relative to matched non-AD controls, encompassing comorbidities, healthcare resource utilization (HCRU), and costs, using healthcare claims data. The impact of AD disease severity on these outcomes was also evaluated.

Methods

Adult AD patients in the Commercial (n = 83,106), Medicare (n = 31,060), and Medi-Cal (n = 5550) databases were matched (1:1) to non-AD controls by demographic characteristics. AD patients were stratified by disease severity (higher, lower) using treatment as a surrogate measure of severity. The comorbidity burden, HCRU, and costs were evaluated during a 12-month follow-up period.

Results

In the Commercial, Medicare, and Medi-Cal populations, patients with AD had a significantly higher overall comorbidity burden (P < 0.0001), an increased risk of asthma and allergic rhinitis (both P < 0.0001), higher HCRU (P < 0.05), and higher mean total per patient costs (Commercial: US$10,461 versus US$7187; Medicare: US$16,914 versus US$13,714; Medi-Cal; US$19,462 versus US$10,408; all P < 0.0001), compared with matched non-AD controls. Higher disease severity was associated with an increased comorbidity burden (P < 0.0001), HCRU (P < 0.05), and total costs (Commercial: US$14,580 versus US$7192; Medicare: US$21,779 versus US$12,490; Medi-Cal; US$22,123 versus US$16,639; all P < 0.0001) relative to lower severity disease.

Conclusion

In this large-scale, healthcare claims database analysis, AD patients had a significantly higher comorbidity burden, HCRU, and costs compared with matched non-AD controls. Higher disease severity was associated with an even greater comorbidity and economic burden.

Funding

Sanofi and Regeneron Pharmaceuticals, Inc.

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High-resolution cone-beam computed tomography for assessment of bone invasion in oral cancer: Comparison with conventional computed tomography

Abstract

Background

Radiologic assessment of mandibular bone invasion is critical in evaluating the extent of bone resection required in patients with oral cancer. There are a few reports of improved sensitivity with cone-beam CT (CBCT) over conventional CT.

Methods

A prospective cohort study of patients with oral squamous cell carcinomas adjacent to the mandible requiring marginal or segmental mandibular resection was performed. Patients were treated based on clinical assessment and conventional cross-sectional imaging. Patients and surgeons were blinded to the results of CBCT performed preoperatively. Pathologic examination served as the gold standard.

Results

Forty-five patients were included in the study. Thirty-three percent of the patients underwent segmental mandibulectomy and 37% had bone invasion. The sensitivity and specificity of CBCT were 91% and 60%, respectively, compared to 86% and 68% for CT with bone windows.

Conclusion

A CBCT offers marginally improved sensitivity at the cost of reduced specificity for assessment of bone invasion compared to CT.

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High-resolution cone-beam computed tomography for assessment of bone invasion in oral cancer: Comparison with conventional computed tomography

Abstract

Background

Radiologic assessment of mandibular bone invasion is critical in evaluating the extent of bone resection required in patients with oral cancer. There are a few reports of improved sensitivity with cone-beam CT (CBCT) over conventional CT.

Methods

A prospective cohort study of patients with oral squamous cell carcinomas adjacent to the mandible requiring marginal or segmental mandibular resection was performed. Patients were treated based on clinical assessment and conventional cross-sectional imaging. Patients and surgeons were blinded to the results of CBCT performed preoperatively. Pathologic examination served as the gold standard.

Results

Forty-five patients were included in the study. Thirty-three percent of the patients underwent segmental mandibulectomy and 37% had bone invasion. The sensitivity and specificity of CBCT were 91% and 60%, respectively, compared to 86% and 68% for CT with bone windows.

Conclusion

A CBCT offers marginally improved sensitivity at the cost of reduced specificity for assessment of bone invasion compared to CT.

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Clinical Curative Effect and Safety of Balloon Sinuplasty in Children with Chronic Rhinosinusitis

Balloon Sinuplasty for the management of paranasal sinus inflammatory diseases was introduced in otolaryngology in 2005. Over the past decade, evidence strongly supports its safety and efficacy for the treatment of chronic rhinosinusitis (CRS) in adults. Because it requires no bone or tissue removal, this procedure could be suitable in children. We present our initial experience of its use for the treatment of CRS in children.

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How can we improve medical adherence to intranasal corticosteroids in children?

To evaluate the factors which may be related to nonadherence to intranasal corticosteroids (ICS) in the treatment of allergic rhinitis (AR) in children.

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Clinical Curative Effect and Safety of Balloon Sinuplasty in Children with Chronic Rhinosinusitis

Balloon Sinuplasty for the management of paranasal sinus inflammatory diseases was introduced in otolaryngology in 2005. Over the past decade, evidence strongly supports its safety and efficacy for the treatment of chronic rhinosinusitis (CRS) in adults. Because it requires no bone or tissue removal, this procedure could be suitable in children. We present our initial experience of its use for the treatment of CRS in children.

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Misunderstandings and controversies about the insulin-secreting properties of antidiabetic sulfonylureas

Publication date: Available online 12 July 2017
Source:Biochimie
Author(s): Jean-Claude Henquin
After 60 years of use in the treatment of type 2 diabetes, hypoglycemic sulfonylureas remain a recommended option in current therapeutic charts. Their binding to sulfonylurea receptor-1, the regulatory subunit of ATP-sensitive potassium channels in the plasma membrane of pancreatic β-cells, leads to closure of the channels, membrane depolarization and influx of Ca²⁺ through voltage-gated calcium channels. The resulting increase in cytosolic Ca²⁺ triggers exocytosis of insulin granules. Sulfonylureas and glucose thus produce the same triggering signal but, unlike sulfonylureas, glucose does so via acceleration of β-cell metabolism. Glucose metabolism also produces amplifying signals that approximately double the secretory response to triggering Ca²⁺. One persistent misunderstanding about sulfonylureas is the alleged glucose-independence of their effects. It is correct that high concentrations of these drugs can induce insulin secretion in low glucose and cause hypoglycemic episodes in treated patients. Conversely, that untoward effect is erroneously considered as evidence that their therapeutic action is independent of glucose. Another evolving controversy about the action of sulfonylureas in β-cells is whether, like glucose, they also produce intracellular amplifying signals able to augment the efficacy of Ca²⁺ on exocytosis. The aims of this review are to dissipate the misunderstanding and discuss the controversy. Reasons why proposed amplifying effects of sulfonylureas are unlikely to be relevant for their action in vivo will be presented. Possible interactions of sulfonylureas and glucagon-like peptide-1 in β-cells will be discussed. Mechanisms whereby the ambient glucose concentration modulates the insulin-secreting action of therapeutic concentrations of sulfonylureas will be explained.



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Anti-obesogenic effects of WY14643 (PPAR-alpha agonist): Hepatic mitochondrial enhancement and suppressed lipogenic pathway in diet-induced obese mice

Publication date: Available online 12 July 2017
Source:Biochimie
Author(s): Flavia Maria Silva Veiga, Francielle Graus-Nunes, Tamiris Lima Rachid, Aline Barcellos Barreto, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
Non-alcoholic fatty liver disease (NAFLD) presents with growing prevalence worldwide, though its pharmacological treatment remains to be established. This study aimed to evaluate the effects of a PPAR-alpha agonist on liver tissue structure, ultrastructure, and metabolism, focusing on gene and protein expression of de novo lipogenesis and gluconeogenesis pathways, in diet-induced obese mice. Male C57BL/6 mice (three months old) received a control diet (C, 10% of lipids, n = 10) or a high-fat diet (HFD, 50% of lipids, n = 10) for ten weeks. These groups were subdivided to receive the treatment (n = 5 per group): C, C-alpha (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the control diet), HFD and HFD-alpha group (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the HFD). The effects were compared with biometrical, biochemical, molecular biology and transmission electron microscopy (TEM) analyses. HFD showed greater body mass (BM) and insulinemia than C, both of which were tackled by the treatment in the HFD-alpha group. Increased hepatic protein expression of glucose-6-phosphatase, CHREBP and gene expression of PEPCK in HFD points to increased gluconeogenesis. Treatment reduced rescued these parameters in the HFD-alpha group, eliciting a reduced hepatic glucose output, confirmed by the smaller transporter GLUT2 expression in HFD-alpha than in HFD. Conversely, favored de novo lipogenesis was found in the HFD group by the increased expression of PPAR-gamma, and its target gene SREBP-1, FAS and GK when compared to C. The treatment yielded a marked reduction in the expression of all lipogenic factors. TEM analyses showed a greater numerical density of mitochondria per area of tissue in treated than in untreated groups, suggesting an increase in beta-oxidation and the consequent NAFLD control. PPAR-alpha activation reduced BM and treated insulin resistance (IR) and NAFLD by increasing the number of mitochondria and reducing hepatic gluconeogenesis and de novo lipogenesis protein and gene expressions in a murine obesity model.



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Changes in psychosocial and physical working conditions and psychotropic medication in ageing public sector employees: a record-linkage follow-up study

Objectives

To investigate whether changes in psychosocial and physical working conditions are associated with subsequent psychotropic medication in ageing employees.

Methods

Data were from the Helsinki Health Study, a cohort study of Finnish municipal employees, aged 40–60 years at phase 1 (2000–2002). Changes in psychosocial and physical working conditions were measured between phase 1 and phase 2 (2007). Survey data were longitudinally linked to data on prescribed, reimbursed psychotropic medication purchases (Anatomical Therapeutic Chemical) obtained from the registers of the Social Insurance Institution of Finland between the phase 2 survey and December 2013 (N=3587; 80% women). Outcomes were any psychotropic medication; antidepressants (N06A); anxiolytics (N05B); and sedatives and hypnotics (N05C). Cox regression analyses were performed.

Results

During the follow-up, 28% of the participants were prescribed psychotropic medication. Repeated exposures to low job control, high job demands and high physical work load were associated with an increased risk of subsequent antidepressant and anxiolytic medication. Increased and repeated exposure to high physical work load, increased job control and repeated high job demands were associated with subsequent sedative and hypnotic medication. Age and sex-adjusted HR varied from 1.18 to 1.66. Improvement in job control was associated with a lower risk of anxiolytic, but with a higher risk of sedatives and hypnotic medication. Decreased physical work load was associated with a lower risk of antidepressant and anxiolytic medications.

Conclusion

Improvement in working conditions could lower the risk of mental ill-health indicated by psychotropic medication.

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Wealth-related inequality in early uptake of HIV testing among pregnant women: an analysis of data from a national cross-sectional survey, South Africa

Objectives

Wealth-related inequality across the South African antenatal HIV care cascade has not been considered in detail as a potential hindrance to eliminating mother-to-child HIV transmission (EMTCT). We aimed to measure wealth-related inequality in early (before enrolling into antenatal care) uptake of HIV testing and identify the contributing determinants.

Design

Cross-sectional survey.

Settings

South African primary public health facilities in 2012.

Participants

A national-level sample of 8618 pregnant women.

Outcome measures

Wealth-related inequality in early uptake of HIV testing was measured using the Erreygers concentration index (CI) further adjusted for inequality introduced by predicted healthcare need (ie, need-standardised). Determinants contributing to the observed inequality were identified using the Erreygers and Wagstaff decomposition methods.

Results

Participants were aged 13 to 49 years. Antenatal HIV prevalence was 33.2%, of which 43.7% came from the lowest 40% wealth group. A pro-poor wealth-related inequality in early HIV testing was observed. The need-standardised concentration index was –0.030 (95% confidence interval –0.038 to –0.022). The proportion of early HIV testing was significantly better in the lower 40% wealth group compared with the higher 40% wealth group (p value=0.040). The largest contributions to the observed inequality were from underlying inequalities in province (contribution, 65.27%), age (–44.38%), wealth group (24.73%) and transport means (21.61%).

Conclusions

Our results on better early uptake of HIV testing among the poorer subpopulation compared with the richer highlights inequity in uptake of HIV testing in South Africa. This socioeconomic difference could contribute to fast-tracking EMTCT given the high HIV prevalence among the lower wealth group. The high contribution of provinces and age to inequality highlights the need to shift from reliance on national-level estimates alone but identify subregional-specific and age-specific bottlenecks. Future interventions need to be context specific and tailored for specific subpopulations and subregional settings.

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Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study

Introduction

Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research.

Methods and analysis

Using the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population.

Ethics and dissemination

Ethical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.

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A method to assess obstetric outcomes using the 10-Group Classification System: a quantitative descriptive study

Objectives

Internationally, the 10-Group Classification System (TGCS) has been used to report caesarean section rates, but analysis of other outcomes is also recommended. We now aim to present the TGCS as a method to assess outcomes of labour and delivery using routine collection of perinatal information.

Design

This research is a methodological study to describe the use of the TGCS.

Setting

Stavanger University Hospital (SUH), Norway, National Maternity Hospital Dublin, Ireland and Slovenian National Perinatal Database (SLO), Slovenia.

Participants

9848 women from SUH, Norway, 9250 women from National Maternity Hospital Dublin, Ireland and 106 167 women, from SLO, Slovenia.

Main outcome measures

All women were classified according to the TGCS within which caesarean section, oxytocin augmentation, epidural analgesia, operative vaginal deliveries, episiotomy, sphincter rupture, postpartum haemorrhage, blood transfusion, maternal age >35 years, body mass index >30, Apgar score, umbilical cord pH, hypoxic–ischaemic encephalopathy, antepartum and perinatal deaths were incorporated.

Results

There were significant differences in the sizes of the groups of women and the incidences of events and outcomes within the TGCS between the three perinatal databases.

Conclusions

The TGCS is a standardised objective classification system where events and outcomes of labour and delivery can be incorporated. Obstetric core events and outcomes should be agreed and defined to set standards of care. This method provides continuous and available observations from delivery wards, possibly used for further interpretation, questions and international comparisons. The definition of quality may vary in different units and can only be ascertained when all the necessary information is available and considered together.

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Effectiveness of government anti-smoking policy on non-smoking youth in Korea: a 4-year trend analysis of national survey data

Objectives

Since the Health Promotion Act was introduced in Korea in 1995, anti-smoking policies and regulations have undergone numerous revisions, and non-smoking areas have gradually been expanded. The purpose of this study was to examine the impact of a partial legislative ban on adolescent exposure to secondhand smoke using objective urinary cotinine levels in a nationwide representative sample.

Methods

Urine cotinine levels were measured in the Korea National Health and Nutrition Examination Survey from 2008 to 2011. This study was a trend analysis of 4 years of national survey data from 2197 Korean youth aged 10–18 years. Among non-smokers, the 75th percentile urinary cotinine level was estimated. We also considered the number of household smokers.

Results

The 75th percentile urine cotinine level of non-smokers showed a significant decreasing trend from 2008 to 2011, from 15.47 to 5.37 ng/mL, respectively. Urine cotinine did not decline significantly in non-smokers living with smokers during the study period. The results did not show a statistically significant reduction in smoking rate in adolescents from 2008 to 2011, although there was a trend towards a decrease (p=0.081).

Conclusions

Based on urine cotinine levels, government-initiated anti-smoking policies have only been effective among highly exposed non-smoking adolescents during the study period. Further study needs to evaluate whether or not the legislative ban affects domestic smoking exposure.

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Elucidating the information exchange during interfacility care transitions: Insights from a Qualitative Study

Objective

To explore the perceptions of patients, their caregivers and healthcare professionals associated with the exchange of information during transitioning from two acute care hospitals to one rehabilitation hospital.

Design

An exploratory qualitative study using semi-structured interviews and observation.

Participants and setting

Patients over the age of 65 years admitted to an orthopaedic unit for a non-elective admission, their caregivers and healthcare professionals involved in their care. Participating sites included orthopaedic inpatient units from two acute care teaching hospitals and one orthopaedic unit at a rehabilitation hospital in an urban setting.

Findings

Three distinct themes emerged from participants' narrative of their transitional care experience: (1) having no clue what the care plan is, (2) being told and notified about the plan and (3) experiencing challenges absorbing information. Participating patients and their caregivers reported not being engaged in an active discussion with healthcare professionals about their care transition plan. Several healthcare professionals described withholding information within the plan until they themselves were clear about the transition outcomes.

Conclusion

This study highlights the need to increase efforts to ensure that effective information exchanges occur during transition from acute care hospital to rehabilitation settings.

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Efficacy of home-based non-pharmacological interventions for treating depression: a systematic review and network meta-analysis of randomised controlled trials

Objectives

To systematically review and compare the efficacy of all available home-based non-pharmacological treatments of depression.

Design

Systematic review and network meta-analysis of randomised controlled trials.

Data sources

Medline, Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched since inceptions to 7 August 2016.

Eligibility criteria

Randomised controlled trials comparing the efficacy of home-based non-pharmacological interventions with usual care of patients with depression were included in the review.

Main outcomes

Depression symptom scores and disease remission rates at the end of treatment.

Results

Seventeen studies were included in the review. Home-based non-pharmacological interventions were categorised as (1) home-based psychological intervention, (2) home-based exercise intervention, (3) combined home-based psychological intervention with exercise intervention and (4) complementary medicine. Complementary medicine approaches were excluded from the meta-analysis due to heterogeneity. The standardised mean differences of post-treatment depression symptom scores between usual care groups and home-based psychological intervention, home-based exercise intervention and combined home-based psychological intervention with exercise intervention were a'0.57 (95% CI a'0.84 to a'0.31), a'1.03 (95% CI a'2.89 to 0.82) and a'0.78 (95% CI a'1.09 to a'0.47), respectively. These results suggest that only home-based psychological intervention and combined home-based psychological intervention with exercise intervention could significantly decrease depression scores. Compared with usual care groups, the disease remission rate was also significantly higher for home-based psychological intervention (pooled risk ratio=1.53; 95%âCI 1.19 to 1.98) and combined home-based psychological intervention with exercise intervention (pooled risk ratio=3.47; 95%âCI 2.11 to 5.70). Of all the studied interventions, combined home-based psychological intervention with exercise intervention had the highest probability of resulting in disease remission.

Conclusion

Our study confirms the efficacy of home-based psychological intervention and combined home-based psychological intervention with exercise intervention in the treatment of depression. Combined home-based psychological intervention and exercise intervention was the best treatment and should be considered for inclusion in clinical guidelines for managing depression.

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Periconception endogenous and exogenous maternal sex steroid hormones and risk of asthma and allergy in offspring: protocol for a systematic review and meta-analysis

Introduction

Pregnancy is associated with several hormonal changes which influence the developing fetus. Variations in maternal endogenous hormones and prepregnancy use of hormonal preparations have been linked to asthma and allergy in the offspring, but findings are inconsistent. We plan to undertake a systematic review to synthesise the evidence on the association between endogenous and exogenous maternal sex hormones and the risk of asthma and allergy in the offspring.

Methods and analysis

We will search Medline, Embase, Cochrane Library, Institute of Scientific Information Web of Science, Cumulative Index of Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary Medicine Database, Global Health, Psychological Information (PsycINFO), Centre for Agriculture and Bioscience (CAB) International and WHO Global Health Library from inception until 2016 to identify relevant studies on the topic. Additional studies will be identified by searching databases of proceedings of international conferences, contacting international experts in the field and searching the references cited in identified studies. We will include analytical epidemiological studies. Two researchers will independently screen identified studies, undertake data extraction and assess risk of bias in eligible studies, while a third reviewer will arbitrate any disagreement. We will use the Effective Public Health Practice Project tool to assess the risk of bias in the studies. We will perform a random-effects meta-analysis to synthesise the evidence. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the strength and quality of the overall evidence with respect to each outcome.

Ethics and dissemination

Ethical approval is not required since the study is a systematic review of published literature. Our findings will be reported in a peer-reviewed scientific journal.

PROSPERO registration number

CRD42016048324

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Use of a mobile social networking intervention for weight management: a mixed-methods study protocol

Introduction

Obesity and physical inactivity are major societal challenges and significant contributors to the global burden of disease and healthcare costs. Information and communication technologies are increasingly being used in interventions to promote behaviour change in diet and physical activity. In particular, social networking platforms seem promising for the delivery of weight control interventions.

We intend to pilot test an intervention involving the use of a social networking mobile application and tracking devices (Fitbit Flex 2 and Fitbit Aria scale) to promote the social comparison of weight and physical activity, in order to evaluate whether mechanisms of social influence lead to changes in those outcomes over the course of the study.

Methods and analysis

Mixed-methods study involving semi-structured interviews and a pre–post quasi-experimental pilot with one arm, where healthy participants in different body mass index (BMI) categories, aged between 19 and 35 years old, will be subjected to a social networking intervention over a 6-month period. The primary outcome is the average difference in weight before and after the intervention. Secondary outcomes include BMI, number of steps per day, engagement with the intervention, social support and system usability. Semi-structured interviews will assess participants' expectations and perceptions regarding the intervention.

Ethics and dissemination

Ethics approval was granted by Macquarie University's Human Research Ethics Committee for Medical Sciences on 3 November 2016 (ethics reference number 5201600716).

The social network will be moderated by a researcher with clinical expertise, who will monitor and respond to concerns raised by participants. Monitoring will involve daily observation of measures collected by the fitness tracker and the wireless scale, as well as continuous supervision of forum interactions and posts. Additionally, a protocol is in place to monitor for participant misbehaviour and direct participants-in-need to appropriate sources of help.

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Evaluating the importance of policy amenable factors in explaining influenza vaccination: a cross-sectional multinational study

Objectives

Despite continuous efforts to improve influenza vaccination coverage, uptake among high-risk groups remains suboptimal. We aimed to identify policy amenable factors associated with vaccination and to measure their importance in order to assist in the monitoring of vaccination sentiment and the design of communication strategies and interventions to improve vaccination rates.

Setting

The USA, the UK and France.

Participants

A total of 2412 participants were surveyed across the three countries.

Outcome measures

Self-reported influenza vaccination.

Methods

Between March and April 2014, a stratified random sampling strategy was employed with the aim of obtaining nationally representative samples in the USA, the UK and France through online databases and random-digit dialling. Participants were asked about vaccination practices, perceptions and feelings. Multivariable logistic regression was used to identify factors associated with past influenza vaccination.

Results

The models were able to explain 64%–80% of the variance in vaccination behaviour. Overall, sociopsychological variables, which are inherently amenable to policy, were better at explaining past vaccination behaviour than demographic, socioeconomic and health variables. Explanatory variables included social influence (physician), influenza and vaccine risk perceptions and traumatic childhood experiences.

Conclusions

Our results indicate that evidence-based sociopsychological items should be considered for inclusion into national immunisation surveys to gauge the public's views, identify emerging concerns and thus proactively and opportunely address potential barriers and harness vaccination drivers.

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Ventilatory function as a predictor of mortality in lifelong non-smokers: evidence from large British cohort studies

Background

Reduced ventilatory function is an established predictor of all-cause mortality in general population cohorts. We sought to verify this in lifelong non-smokers, among whom confounding by active smoking can be excluded, and investigate associations with circulatory and cancer deaths.

Methods

In UK Biobank, among 149 343 white never-smokers aged 40–69 years at entry, 2401 deaths occurred over a mean of 6.5-year follow-up. In the Health Surveys for England (HSE) 1995, 1996, 2001 and Scottish Health Surveys (SHS) 1998 and 2003 combined, there were 500 deaths among 6579 white never-smokers aged 40–69 years at entry, followed for a mean of 13.9 years. SD (z) scores for forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were derived using Global Lung Initiative 2012 reference equations. These z-scores were related to deaths from all causes, circulatory disease and cancers using proportional hazards models adjusted for age, sex, height, socioeconomic status, region and survey.

Results

In the HSE–SHS data set, decreasing z-scores for FEV1 (zFEV1) and FVC (zFVC) were each associated to a similar degree with increased all-cause mortality (hazard ratios per unit decrement 1.17, 95% CI 1.09 to 1.25 for zFEV1 and 1.19, 95% CI 1.10 to 1.28 for zFVC). This was replicated in Biobank (HRs 1.21, 95% CI 1.17 to 1.26 and 1.24, 1.19 to 1.29, respectively). zFEV1 and zFVC were less strongly associated with mortality from circulatory diseases in HSE–SHS (HR 1.22, 95% CI 1.06 to 1.40 for zFVC) than in Biobank (HR 1.47, 95% CI 1.35 to 1.60 for zFVC). For cancer mortality, HRs were more consistent between cohorts (for zFVC: HRs 1.12, 95% CI 1.01 to 1.24 in HSE–SHS and 1.10, 1.05 to 1.15 in Biobank). The strongest associations were with respiratory mortality (for zFVC: HRs 1.61, 95% CI 1.25 to 2.08 in HSE–SHS and 2.15, 1.77 to 2.61 in Biobank).

Conclusions

Spirometric indices predicted mortality more strongly than systolic blood pressure or body mass index, emphasising the importance of promoting lung health in the general population, even among lifelong non-smokers.

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Measuring patient safety culture in maternal and child health institutions in China: a qualitative study

Introduction

Patient safety culture (PSC) plays a critical role in ensuring safe and quality care. Extensive PSC studies have been undertaken in hospitals. However, little is known about PSC in maternal and child health (MCH) institutions in China, which provide both population-based preventive services as well as individual care for patients.

Objectives

This study aimed to develop a theoretical framework for conceptualising PSC in MCH institutions in China.

Methods

The study was undertaken in six MCH institutions (three in Hebei and three in Beijing). Participants (n=118) were recruited through stratified purposive sampling: 20 managers/administrators, 59 care providers and 39 patients. In-depth interviews were conducted with the participants. The interview data were coded using both inductive (based on the existing PSC theory developed by the Agency for Healthcare Research and Quality) and deductive (open coding arising from data) approaches. A PSC framework was formulated through axial coding that connected initial codes and selective coding that extracted a small number of themes.

Results

The interviewees considered patient safety in relation to six aspects: safety and security in public spaces, safety of medical services, privacy and information security, financial security, psychological safety and gap in services. A 12-dimensional PSC framework was developed, containing 69 items. While the existing PSC theory was confirmed by this study, some new themes emerged from the data. Patients expressed particular concerns about psychological safety and financial security. Defensive medical practices emerged as a PSC dimension that is associated with not only medical safety but also financial security and psychological safety. Patient engagement was also valued by the interviewees, especially the patients, as part of PSC.

Conclusions

Although there are some common features in PSC across different healthcare delivery systems, PSC can also be context specific. In MCH settings in China, the meaning of 'patient safety' goes beyond the traditional definition of patients. General well-being, health and disease prevention are important anchor points for defining PSC in such settings.

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Evaluation of the geriatric co-management for patients with fragility fractures of the proximal femur (Geriatric Fracture Centre (GFC) concept): protocol for a prospective multicentre cohort study

Introduction

Treatment of fractures in the elderly population is a clinical challenge due partly to the presence of comorbidities. In a Geriatric Fracture Centre (GFC), patients are co-managed by a geriatrician in an attempt to improve clinical outcomes and reduce morbidity and mortality. Until now the beneficial effect of orthogeriatric co-management has not been definitively proven. The primary objective of this study is to determine the effect of GFC on predefined major adverse events related to a hip fracture compared to usual care centres (UCC). The secondary objectives include assessments in quality of life, patient-reported outcomes and cost-effectiveness.

Methods and analysis

Two hundred and sixty-six elderly patients diagnosedwith hip fracture and planned to be treated with osteosynthesis or endoprosthesis in either a GFC or UCC study site will be recruited, 133 per type of centre. All procedures and management will be done according to the site's standard of care. Study-related visits will be performed at the following time points: preoperative, intraoperative, discharge from the orthopaedic/trauma department, discharge to definite residential status, 12 weeks and 12 months postsurgery. Data collected include demographics, residential status, adverse events, patient-reported outcomes, fall history, costs and resources related to treatment. The risk of major adverse events at 12 months will be calculated for each centre type; patient-reported outcomes will be analysed by mixed effects regression models to estimate differences in mean scores between baseline and follow-ups whereas cost-effectiveness will be assessed using the incremental cost-effectiveness ratio.

Ethics and dissemination

Ethics approval for this study was granted from the local Ethics Committees or Institutional Review Board from each of the participating sites prior to patient enrolment. The results of this study will be published in peer-reviewed journals and presented at different conferences.

Trial registration number

ClinicalTrials.gov: NCT02297581; pre-results.

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Influences of inorganic and polycyclic aromatic hydrocarbons on the sources of PM2.5 in the Southeast Asian urban sites

Abstract

PM_2.5 released from urban sources and regional biomass fire is of great concern due to the deleterious effect on human health. This study was conducted to determine the chemical compositions andsource apportionment of PM_2.5. Twenty-four-hour PM_2.5 samples were collected at two urban monitoring sites in Kuala Lumpur, Malaysia, from 12 November 2013 to 15 January 2014 using a high volume air sampler (HVS). The source apportionment of PM_2.5 was determined using positive matrix factorization (PMF) version 5.0. Overall, the PM_2.5 mean concentrations ranged from 16 to 55 μg m⁻³ with a mean of 23 ± 9 μg m⁻³. The results of enrichment factor (EF) analysis showed that Zn, Pb, As, Cu, Cr, V, Ni, and Cs mainly originated from non-crustal sources. The dominant polycyclic aromatic hydrocarbons (PAHs) were benzo[b]fluoranthene (B[b]F), benzo[ghi]perylene (B[ghi]P), indeno[1,2,3-cd]pyrene (I[cd]P), benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F). PMF 5.0 results showed that the secondary aerosol coupled with biomass burning was the largest contributor followed by combustion of fuel oil and road dust, soil dust source and sea salt and nitrate aerosol, accounting for 34, 25, 24 and 17% of PM_2.5 mass, respectively. On the other hand, biomass and wood burning (42%) was the predominant source of PAHs followed by combustion of fossil fuel (36%) and natural gas and coal burning (22%). The broad overview of the PM_2.5 sources will help to adopt adequate mitigation measures in the management of future urban air quality in this region.

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Top-down proteomics for the analysis of proteolytic events - methods, applications and perspectives

Publication date: Available online 12 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Andreas Tholey, Alexander Becker
Mass spectrometry based proteomics is an indispensable tool for almost all research areas relevant for the understanding of proteolytic processing, ranging from the identification of substrates, products and cleavage sites up to the analysis of structural features influencing protease activity.The majority of methods for these studies are based on bottom-up proteomics performing analysis at peptide level. As this approach is characterized by a number of pitfalls, e.g. loss of molecular information, there is an ongoing effort to establish top-down proteomics, performing separation and MS analysis both at intact protein level.We briefly introduce major approaches of bottom-up proteomics used in the field of protease research and highlight the shortcomings of these methods. We then discuss the present state-of-the-art of top-down proteomics. Together with the discussion of known challenges we show the potential of this approach and present a number of successful applications of top-down proteomics in protease research. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.



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Parcellation of Macaque Cortex with Anatomical Connectivity Profiles

Abstract

The macaque model has been widely used to investigate the brain mechanisms of specific cognitive functions and psychiatric disorders. However, a detailed functional architecture map of the macaque cortex in vivo is still lacking. Here, we aimed to construct a new macaque cortex atlas based on its anatomical connectivity profiles using in vivo diffusion MRI. First, we defined the macaque cortical seed areas using the NeuroMaps atlas. Then, we applied the anatomical connectivity patterns-based parcellation approach to parcellate the macaque cortex into 80 subareas in each hemisphere, which were approximately symmetric between the two hemispheres. In each hemisphere, we identified 14 subareas in the frontal cortex, 9 subareas in the somatosensory cortex, 13 subareas in the parietal cortex, 16 subareas in the temporal cortex, 16 subareas in the occipital cortex, and 12 subareas in the limbic system. Finally, the graph-based network analyses of the anatomical network based on newly constructed macaque cortex atlas identified seven hub areas including bilateral ventral premotor cortex, bilateral superior parietal lobule, right medial precentral gyrus, and right precuneus. This newly constructed macaque cortex atlas may facilitate studies of the structure and functions of the macaque brain in the future.

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Identification and preliminary characterization of a putative C-type lectin receptor-like protein in the T. cruzi tomato lectin endocytic-enriched proteome

Publication date: Available online 12 July 2017
Source:Microbiological Research
Author(s): Sébastien Brosson, Guy Bottu, Etienne Pays, Sabrina Bousbata, Didier Salmon
Trypanosoma cruzi, the etiological agent of the Chagas' disease in Latin America undergoes a complex life cycle involving two hosts, a mammalian host and a reduviid insect vector (triatomine). In the insect midgut the parasite multiplies as epimastigote forms, which rely on endocytosis for their energy requirement. We recently showed that posttranslational modification of endocytic N-glycoproteins by tomato lectin (TL) binding-N-glycans is crucial for receptor-mediated endocytosis (RME) in epimastigote forms. In an attempt to characterize the endocytic proteome we used a TL affinity chromatography, which significantly enriched glycoproteins of the trypanosomal endocytic pathway. In addition to various lysosomal hydrolases, we found an endosomal C-type lectin-like protein, which displays some structural and topological characteristics of the mammalian lectin receptor superfamily. This lectin encoding a large transmembrane protein of around 375kDa contained three putative extracellular N-terminal C-type lectin domains (CTLD) and located inside the flagellar pocket (FP)/cytostome and endosomal compartments of the insect stage of the parasite and on the surface of the plasma membrane of intracellular amastigote parasites. Noteworthy, this endogenous lectin displayed similar sugar-binding specificity to that of TL and therefore could be important in either the N-glycan mediated endocytosis or parasite adhesion to host cells. We postulated that during the evolution of trypanosomatids, genes encoding lectin harboring 3 CTDLs represent an old acquisition present in free-living, monoxenic and heteroxenic trypanosomatids, which would have been secondarily lost in extracellular parasites from the T. brucei clade.



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The Eating Assessment Tool-10 Predicts Aspiration in Adults with Stable Chronic Obstructive Pulmonary Disease

Abstract

Adults with COPD frequently present with dysphagia, which often leads to clinical complications and hospital admissions. This study investigates the ability of the Eating Assessment Tool (EAT-10) to predict aspiration during objective dysphagia evaluation in adults with stable COPD. Thirty adults (20 male, 10 female; mean age = 69.07 ± 16.82) with stable COPD attended an outpatient dysphagia clinic for a fiberoptic endoscopic evaluation of swallowing (FEES) in an acute teaching hospital (January 2015–November 2016). During evaluations, individuals completed an EAT-10 rating scale followed immediately by a standardised FEES exam. Aspiration status during FEES was rated using the penetration–aspiration scale by clinicians blinded to EAT-10 scores. Data were retrospectively analysed. Significant differences in mean EAT-10 scores were found between aspirators (16.3; SEM = 2.165) and non-aspirators (7.3; SEM = 1.009) (p = 0.000). The EAT-10 predicted aspiration with a high level of accuracy (AUC = 0.88). An EAT-10 cut-off value of >9 presented a sensitivity of 91.67, specificity of 77.78 with positive and negative likelihood ratios of 4.12 and 0.11, respectively. Positive and negative predictive values were 73.30 and 93.30, respectively. Diagnostic odds ratio was 38.50 (p < 0.01, CI 3.75–395.42). EAT-10 is a quick, easy to administer tool, which can accurately predict the presence of aspiration in adults with COPD. The scale can also very accurately exclude the absence of aspiration, helping clinicians to determine the need for onward referral for a comprehensive dysphagia evaluation. This may ultimately reduce clinical complications and hospital admissions resulting from dysphagia in this clinical population.

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Common Vocal Effects and Partial Glottal Vibration in Professional Nonclassical Singers

To multidimensionally investigate common vocal effects in experienced professional nonclassical singers, to examine their mechanism of production and reproducibility, to demonstrate the existence of partial glottal vibration, and to assess the potential of damage to the voice from nonclassical singing.

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Extracellular Matrices for Bone Regeneration: A Literature Review

Tissue Engineering Part A , Vol. 0, No. 0.


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Saccharomyces boulardii : Optimization of simultaneous saccharification and fermentation of cell production in organic and conventional apple substrate pulp

Abstract

A face-centered factorial design was used to study the influence of temperature, cellulase, and pectinase concentration on the production of Saccharomyces boulardii cells during simultaneous saccharification and fermentation of organic and conventional apple substrate pulp. The effects of the variables fermentation temperature (25–35 °C), pectinase concentration (5–25 μL/100 g), and cellulase concentration (4–8 μL/100 g) were analyzed by multiple regression and polynomial models of second order, providing the ideal conditions for yeast cultivation. Cellular production of apple substrates was expressed in log CFU/mL. The optimum condition for temperature was 27.5 °C, and 20 and 5 μL/100 g for pectinase and 8 and 7 μL/100 g for cellulase concentrations for organic and conventional apple pulp, respectively. The observed viability values were in agreement with the predicted values of 8.352 log CFU/mL (organic) and 8.317 log CFU/mL (conventional) apple pulps, thus proving the effectiveness of the models.

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Antioxidant effects of Geranium nepalense ethanol extract on H 2 O 2 -induced cytotoxicity in H9c2, SH-SY5Y, BEAS-2B, and HEK293

Abstract

Oxidative damage leads to many diseases. In this study, we evaluated the antioxidant effects of 70% ethanol extract of Geranium nepalense (GNE) on hydrogen peroxide-induced cytotoxicity in cell lines: H9c2, SH-SY5Y, HEK293, and BEAS-2B. We determined the free radical scavenging activity of GNE using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and superoxide dismutase-like activities, as well as the polyphenol and flavonoid contents of GNE. The results showed that GNE scavenged DPPH and ABTS radicals in a dose-dependent manner. In addition, it contained abundant contents of total polyphenol and flavonoid contents and strongly suppressed cellular reactive oxygen species, thereby protecting H₂O₂-induced cytotoxicity in H9c2, SH-SY5Y, HEK293, and BEAS-2B cell lines. The powerful antioxidant activity exhibited by GNE, both in vitro and in cell systems, was attributed to its free radical scavenging activity. Therefore, GNE may be useful in preventing oxidative stress-induced diseases including Alzheimer's disease, respiratory inflammatory disease, and chronic kidney diseases.

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Sargassum swartzii extracts ameliorate memory functions by neurochemical modulation in a rat model

Abstract

Recently, considerable attention has been paid to drug exploration from natural sources for treating memory loss, a major manifestation of various neurodegenerative diseases. Increasing evidences implicate brain serotonin metabolism in learning and memory, supporting the notion that targeting 5-HT (5-hydroxytryptamine) and its receptors would be beneficial in the treatment of cognitive disorders. In the present study, behavioral and neurochemical effects were examined following administration of Sargassum swartzii extracts in albino Wistar rats. Increase in spatial working memory and recognition memory was exhibited by the seaweed-treated rats as compared to controls. Plasma tryptophan, brain 5-HT, and 5-hydroxyindoleacetic acid levels were measured using HPLC–ECD, and a significant increase in brain 5-HT metabolism was observed in the seaweed-treated rats. The increase in memory functions following repeated administration of S. swartzii extracts is suggested to be due to the increased serotonergic neurotransmission in the brain of seaweed-treated rats.

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Cardio-oncology: Gaps in Knowledge, Goals, Advances, and Educational Efforts

Abstract

Over the past 20 years, cancer treatments have become more effective, leading to significant improvements in survival rates. However, anticancer drugs can have several possible cardiovascular side effects; in particular, the development of left ventricular dysfunction with chemoradiation therapy can negatively affect patients' cardiac outcome, and can limit anticancer treatments. This is an ongoing issue that will continue to persist, due to the ongoing development of new antitumor agents with potential cardiotoxic effects, and the prolonged life expectancy of long-term cancer survivors. Thus, the need for cooperation between oncologists and cardiologists in the management of cancer patients has led to the development of a new medical discipline-cardio-oncology—where the issue of cardiotoxicity is a topic of intense interest and research. However, several issues remain—the proper definition and diagnosis of cardiotoxicity, as well as monitoring and treatment strategies. In this review, the current advances in cardio-oncology, limitations of current approaches, and future research fields will be discussed.

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Introduction to anatomy on Wikipedia

Abstract

Wikipedia (www.wikipedia.com) is the largest encyclopaedia in existence. Of over five million English-language articles, about 6000 relate to Anatomy, which are viewed roughly 30 million times monthly. No work parallels the amount of attention, scope or interdisciplinary layout of Wikipedia, and it offers a unique opportunity to improve the anatomical literacy of the masses. Anatomy on Wikipedia is introduced from an editor's perspective. Article contributors, content, layout and accuracy are discussed, with a view to demystifying editing for anatomy professionals. A final request for edits or on-site feedback from anatomy professionals is made.

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Initial experience of transcatheter closure of subarterial VSD with the Amplatzer duct occluder

The traditional treatment of subarterial ventricular septal defect (VSD) is open heart surgery. This study aimed to evaluate the feasibility, safety and outcome of transcatheter closure with the Amplatzer duct occluder (ADO).

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Silicone tracheobronchial stent: A rare cause for bronchoesophageal fistula and distortion of airway anatomy

Bhupesh Kumar, Ganesh Kumar Munirathinam, Goverdhan Dutt Puri, Anand Kumar Mishra, Virendra Kumar Arya

Annals of Cardiac Anaesthesia 2017 20(3):355-358

Silicone tracheobronchial stents are being increasingly used in a large number of patients for the treatment of tracheal stenosis. One very rare complication due to tracheobronchial stenting is bronchoesophageal fistula (BEF), which has been associated with the use of metallic stents. We report intraoperative management of a patient undergoing repair of a BEF, following previous insertion of a silicone Y-stent that is soft in texture and has not been implicated for this complication till date. In addition, misalignment of this silicone tracheobronchial Y-stent resulted in a tracheal mucosal bulge proximal to the stent that vanished after its removal.

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Risk factors of postcardiotomy ventricular dysfunction in moderate-to-high risk patients undergoing open-heart surgery

Christoph Ellenberger, Tornike Sologashvili, Mustafa Cikirikcioglu, Gabriel Verdon, John Diaper, Tiziano Cassina, Marc Licker

Annals of Cardiac Anaesthesia 2017 20(3):287-296

Introduction: Ventricular dysfunction requiring inotropic support frequently occurs after cardiac surgery, and the associated low cardiac output syndrome largely contributes to postoperative death. We aimed to study the incidence and potential risk factors of postcardiotomy ventricular dysfunction (PCVD) in moderate-to-high risk patients scheduled for open-heart surgery. Methods: Over a 5-year period, we prospectively enrolled 295 consecutive patients undergoing valve replacement for severe aortic stenosis or coronary artery bypass surgery who presented with Bernstein-Parsonnet scores >7. The primary outcome was the occurrence of PCVD as defined by the need for sustained inotropic drug support and by transesophageal echography. The secondary outcomes included in-hospital mortality and the incidence of any major adverse events as well as Intensive Care Unit (ICU) and hospital length of stay. Results: The incidence of PCVD was 28.4%. Patients with PCVD experienced higher in-hospital mortality (12.6% vs. 0.6% in patients without PCVD) with a higher incidence of cardiopulmonary and renal complications as well as a prolonged stay in ICU (median + 2 days). Myocardial infarct occurred more frequently in patients with PCVD than in those without PCVD (19 [30.2%] vs. 12 [7.6%]). By logistic regression analysis, we identified four independent predictors of PCVD: left ventricular ejection fraction <40% (odds ratio [OR] = 6.36; 95% confidence interval [CI], 2.59–15.60), age older than 75 years (OR = 3.35; 95% CI, 1.64–6.81), prolonged aortic clamping time (OR = 3.72; 95% CI, 1.66–8.36), and perioperative bleeding (OR = 2.33; 95% CI, 1.01–5.41). The infusion of glucose-insulin-potassium was associated with lower risk of PCVD (OR = 0.14; 95% CI, 0.06–0.33). Conclusions: This cohort study indicates that age, preoperative ventricular function, myocardial ischemic time, and perioperative bleeding are predictors of PCVD which is associated with poor clinical outcome.

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Methylene blue for post-cardioplumonary bypass vasoplegic syndrome

Neha Pangasa, Rohan Magoon, Vandana Bhardwaj, Amita Sharma, Ameya Karonjkar, Poonam Malhotra Kapoor

Annals of Cardiac Anaesthesia 2017 20(3):381-382



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Idarucizumab (Praxbind) for reversal of pradaxa prior to emergent repair of contained ruptured transverse arch aneurysm

Erol Vahit Belli, Teng Lee

Annals of Cardiac Anaesthesia 2017 20(3):369-371

Idarucizumab before cardiopulmonary bypass was used for the reversal of dabigatran during an emergent frozen elephant trunk repair of a transverse arch aneurysm. Reversal was successful and minimal not massive transfusion was required with no abnormal sequelae seen with use before cardiopulmonary bypass.

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Management of a case of double aortic arch with tracheal compression complicated with postoperative tracheal restenosis

Hemang Gandhi, T Vikram Kumar Naidu, Amit Mishra, Pankaj Garg, Jigar Surti, Visharad Trivedi, Himanshu Acharya

Annals of Cardiac Anaesthesia 2017 20(3):362-364

Tracheal stenosis in association with the double aortic arch (DAA) is uncommon; however, it carries a high risk of morbidity, mortality, and restenosis. Although surgery is the mainstay of managing a case of the DAA with tracheal stenosis, management of tracheal restenosis requires a multidisciplinary approach. In this case report, we present our successful experience in managing a child of DAA with tracheal stenosis who developed tracheal restenosis after sliding tracheoplasty of trachea.

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Propofol versus Ketofol for Sedation of Pediatric Patients Undergoing Transcatheter Pulmonary Valve Implantation: A Double-blind Randomized Study

Rabie Soliman, Mohammed Mofeed, Tarek Momenah

Annals of Cardiac Anaesthesia 2017 20(3):313-317

Objective: The study was done to compare propofol and ketofol for sedation of pediatric patients scheduled for elective pulmonary valve implantation in a catheterization laboratory. Design: This was a double-blind randomized study. Setting: This study was conducted in Prince Sultan Cardiac Centre, Saudi Arabia. Patients and Methods: The study included 60 pediatric patients with pulmonary regurge undergoing pulmonary valve implantation. Intervention: The study included sixty patients, classified into two groups (n = 30). Group A: Propofol was administered as a bolus dose (1–2 mg/kg) and then a continuous infusion of 50–100 μg/kg/min titrated as needed. Group B: Ketofol was administered 1–2 mg/kg and then infusion of 20–60 μg/kg/min. The medication was prepared by the nursing staff and given to anesthetist blindly. Measurements: The monitors included heart rate, mean arterial blood pressure, respiratory rate, temperature, SPO2and PaCO2, Michigan Sedation Score, fentanyl dose, antiemetic medications, and Aldrete score. Main Results: The comparison of heart rate, mean arterial pressure, respiratory rate, temperature, SPO2and PaCO2, Michigan Sedation Score, and Aldrete score were insignificant (P > 0.05). The total fentanyl increased in Group A more than Group B (P = 0.045). The required antiemetic drugs increased in Group A patients more than Group B (P = 0.020). The durations of full recovery and in the postanesthesia care unit were longer in Group A than Group B (P = 0.013, P < 0.001, respectively). Conclusion: The use of propofol and ketofol is safe and effective for sedation of pediatric patients undergoing pulmonary valve implantation in a catheterization laboratory. However, ketofol has many advantages more than the propofol. Ketofol has a rapid onset of sedation, a rapid recovery time, decreased incidence of nausea and vomiting and leads to rapid discharge of patients from the postanesthesia care unit.

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Sugammadex to reverse neuromuscular blockade in a child with a past history of cardiac transplantation

Karen Miller, Brian Hall, Joseph D Tobias

Annals of Cardiac Anaesthesia 2017 20(3):376-378

Sugammadex is a novel agent for the reversal of neuromuscular blockade. The speed and efficacy of reversal with sugammadex are significantly faster than acetylcholinesterase inhibitors, such as neostigmine. Sugammadex also has a limited adverse profile when compared with acetylcholinesterase inhibitors, specifically in regard to the incidence of bradycardia. This adverse effect may be particularly relevant in the setting of a heart transplant recipient with a denervated heart. The authors present a case of an 8-year-old child, status postcardiac transplantation, who required anesthetic care for laparoscopy and lysis of intra-abdominal adhesions. Sugammadex was used to reverse neuromuscular blockade and avoid the potential adverse effects of neostigmine. The unique mechanism of action of sugammadex is discussed, previous reports of its use in this unique patient population are reviewed, and its potential benefits compared to traditional acetylcholinesterase inhibitors are presented.

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Asystole following neuromuscular blockade reversal in cardiac transplant patients

Njinkeng J Nkemngu

Annals of Cardiac Anaesthesia 2017 20(3):385-386



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The blalock and taussig shunt revisited

Usha Kiran, Shivani Aggarwal, Arin Choudhary, B Uma, Poonam Malhotra Kapoor

Annals of Cardiac Anaesthesia 2017 20(3):323-330

The systemic to pulmonary artery shunts are done as palliative procedures for cyanotic congenital heart diseases ranging from simple tetralogy of Fallots (TOFs)/pulmonary atresia (PA) to complex univentricular hearts. They allow growth of pulmonary arteries and maintain regulated blood flow to the lungs till a proper age and body weight suitable for definitive corrective repair is reached. We have reviewed the BT shunt with its anaesthtic considerations and management of associated complications.

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View Point

Prabhat Tewari

Annals of Cardiac Anaesthesia 2017 20(3):285-286



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Interesting images: Multiple coronary artery aneurysms

Jonathon M Howard, Omar Viswanath, Alfredo Armas, Orlando Santana, Gerald P Rosen

Annals of Cardiac Anaesthesia 2017 20(3):331-332

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

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Inadequate venous drainage-transesophageal echocardiography as rescue

Monish S Raut, Arun Maheshwari, Sumir Dubey, Ganesh Shivnani, Sandeep Joshi, Arvind Verma, Swetanka Das

Annals of Cardiac Anaesthesia 2017 20(3):333-334

Malposition of venous cannula can cause inadequate venous drainage during cardiopulmonary bypass. It would be good clinical practice to use TEE to check the position of inferior venous cannula to avoid this problem at the earliest.

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A rare case of acyanotic congenital heart disease, large patent ductus arteriosus with pre-ductal coarctation of descending thoracic aorta with patent ductus arteriosus closure and extra anatomical bypass grafting

Zara Wani, Deepak Tiwari, Rajeev Gehlot, Deepak Kumar, Sushil Chhabra, Meenaxi Sharma

Annals of Cardiac Anaesthesia 2017 20(3):365-368

We report a case of 18-year-old female patient with large patent ductus arteriosus (PDA)-preductal coarctation of descending thoracic aorta. She underwent large PDA closure with a prosthetic graft from ascending aorta to descending thoracic aorta by mid-sternotomy on cardiopulmonary bypass machine under total hypothermic circulatory arrest.

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Is the Intrinsic Genomic Activity of Thyroxine Relevant In Vivo? Effects on Gene Expression in Primary Cerebrocortical and Neuroblastoma Cells

Thyroid , Vol. 0, No. 0.


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Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction [Research]

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell–cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1–mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2–containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1–SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1–VE-cadherin association and promoted VE-cadherin–actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2—via association with ICAM-1—mediates ICAM-1–induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.—Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1–VE-cadherin interaction.

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Circulating RANKL and RANKL/OPG and breast cancer risk by ER and PR subtype: Results from the EPIC cohort

Receptor activator of nuclear factor kappa-B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. <p>A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1976 incident invasive breast cancer cases (estrogen receptor positive (ER+), n=1598), matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an enzyme-linked immunosorbent assay, serum OPG using an electrochemiluminescent assay. Risk ratios (RRs) and 95% confidence intervals (95%CIs) were calculated using conditional logistic regression.</p> <p>Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status (p_het 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer (5th vs. 1st quintile RR 1.28 [95%CI 1.01-1.63]; p_trend 0.20), but not ER- disease. For both ER+ and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR- disease (5^th vs. 1^st quintile RR 0.60 [0.31-1.14]; p_trend 0.03).</p> <p>This study provides the first large-scale prospective data on circulating sRANKL and breast cancer. We observed limited evidence for an association between sRANKL and breast cancer risk.

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Guar and Locust bean gum: Composition, total phenolic content, antioxidant and antinutritional characterisation

Publication date: Available online 12 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Afshan Mumtaz Hamdani, Idrees Ahmed Wani
Guar and locust bean gum are added to various food products because of their ability to modify the texture and rheology. No sufficient data is available about their bioactive roles except that these are physiologically similar to dietary fibre and may be used as low-energy fat replacers. Present study was undertaken to find out the nutraceutical and antinutritional properties of guar and locust bean gum. Antioxidant activity of gums was determined by ferrous ion chelating ability, reducing power, FRAP (ferric reducing antioxidant power) and ABTS (2, 2-azinobis (3-ethylbenzothiazolin-6-sulfonate) scavenging power. Determination of phytic acid, haemagglutinins, terpenoids, saponins and alkaloids was carried out to evaluate their antinutritional activity. Gums showed low antioxidant potential except ferrous ion chelating ability which was significant in both methanolic (65.08–66.82%) and ethanolic (36.46–55.40%) extracts. Gums also exhibited a high DPPH (1,1-diphenyl-2- picrylhydrazyl) radical scavenging activity (11.67–29.78%). Bile acid binding capacity was high i.e., 49.83% (guar gum) and 54.42% (locust bean gum). Tannin and phytic acid content varied from 1.28–3.72 TAE/g and 0.098–0.165mg/g, respectively. Haemagglutinin activity of gums was low (0.066–0.432 HU/mg protein) while the terpenoids, saponins and alkaloids were completely absent. Thus, gums may play beneficial bioactive roles in consumers in addition to conferring desirable organoleptic properties in different food products.

Graphical abstract

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Treatment of refractory and severe hypothyroidism with sublingual levothyroxine in liquid formulation

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The yeast kinesin-5 Cin8 interacts with the microtubule in a noncanonical manner [Enzymology]

Kinesin motors play central roles in establishing and maintaining the mitotic spindle during cell division. Unlike most other kinesins, Cin8, a kinesin-5 motor in Saccharomyces cerevisiae, can move bidirectionally along microtubules, switching directionality according to biochemical conditions, a behavior that remains largely unexplained. To this end, we used biochemical rate and equilibrium constant measurements as well as cryo-electron microscopy methodologies to investigate the microtubule interactions of the Cin8 motor domain. These experiments unexpectedly revealed that, while Cin8 ATPase kinetics fell within measured ranges for kinesins (especially kinesin-5 proteins), approximately four motors can unexpectedly bind each ab-tubulin dimer within the microtubule lattice. This result contrasted with those observations on other known kinesins, which can bind only a single "canonical" site per ab-tubulin dimer. Competition assays with human kinesin-5 (Eg5) only partially abrogated this behavior, indicating that Cin8 binds microtubules not only at the canonical site, but also one or more separate ("noncanonical") sites. Moreover, we found that deleting the large, class-specific insert in the microtubule-binding loop 8 reverts Cin8 to one motor per tubulin in the microtubule. The novel microtubule-binding mode of Cin8 identified here provides a potential explanation for Cin8 clustering along microtubules and potentially may contribute to the mechanism for direction reversal.

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Methionine synthase is localized to the nucleus in Pichia pastoris and Candida albicans and to the cytoplasm in Saccharomyces cerevisiae [Enzymology]

Methionine synthase (MS) catalyzes methylation of homocysteine, the last step in the biosynthesis of methionine, which is essential for the regeneration of tetrahydrofolate and biosynthesis of S-adenosyl methionine. Here, we report that MS is localized to the nucleus of Pichia pastoris and Candida albicans but cytoplasmic in Saccharomyces cerevisiae. P. pastoris strain carrying a deletion of MET6 gene encoding MS (Ppmet6) exhibits methionine as well as adenine auxotrophy indicating that MS is required for methionine as well as adenine biosynthesis. Nuclear localization of P. pastoris MS (PpMS) was abrogated by the deletion of 107 C-terminal amino acids or R742A mutation. In silico analysis of PpMS structure indicated that PpMS may exist in a dimer-like configuration in which R742 of a monomer forms salt-bridge with D113 of another monomer. Biochemical studies indicate that R742A as well as D113R mutations abrogate nuclear localization of PpMS and its ability to reverse methionine auxotrophy of Ppmet6. Thus, association of two PpMS monomers through the interaction of R742 and D113 is essential for catalytic activity and nuclear localization. When PpMS is targeted to cytoplasm employing a heterologous nuclear export signal, it is expressed at very low levels and is unable to reverse methionine and adenine auxotrophy of Ppmet6. Thus, nuclear localization is essential for the stability and function of MS in P. pastoris. We conclude that nuclear localization of MS is a unique feature of respiratory yeasts such as P. pastoris and C. albicans and it may have novel moonlighting functions in the nucleus.

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Inverted stereocontrol of iridoid synthase in snapdragon [Plant Biology]

The natural product class of iridoids, found in various species of flowering plants, harbors astonishing chemical complexity. The discovery of iridoid biosynthetic genes in the medicinal plant Catharanthus roseus has provided insight into the biosynthetic origins of this class of natural product. However, not all iridoids share the exact 5-6 bicyclic ring scaffold of the Catharanthus iridoids. For instance, iridoids in the ornamental flower snapdragon (Antirrhinum majus, Plantaginaceae family) are derived from the C7 epimer of this scaffold. Here we have cloned and characterized the iridoid synthase enzyme from A. majus (AmISY), the enzyme that is responsible for converting 8-oxogeranial into the bicyclic iridoid scaffold in a two-step reduction-cyclization sequence. Chiral analysis of the reaction products reveals that AmISY reduces C7 to generate the opposite stereoconfiguration in comparison to the Catharanthus homologue CrISY. The catalytic activity of AmISY thus explains the biosynthesis of 7-epi-iridoids in Antirrhinum and related genera. However, while the stereoselectivity of the reduction step catalyzed by AmISY is clear, in both AmISY and CrISY the cyclization step produces a diastereomeric mixture. While the reduction of 8-oxogeranial is clearly enzymatically catalyzed, the cyclization step appears to be subject to less stringent enzyme control.

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Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially desaturates trans-retinol to 3,4-dehydroretinol [Metabolism]

Recently zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and that hydroxylation represents only a minor pathway. We show by proteomic analysis that P450 27C1 is localized to human skin, with two proteins of different sizes present, one being a cleavage product of the full-length form. P450 27C1 oxidized alltrans-retinol to 3,4-dehydroretinol, 4-hydroxy (OH) retinol, and 3-OH retinol in a 100:3:2 ratio. Neither 3-OH nor 4-OH retinol was an intermediate in desaturation. No kinetic burst was observed in the steady state; neither the rate of substrate binding or product release was ratelimiting. Ferric P450 27C1 reduction by adrenodoxin (Adx) was 3-fold faster in the presence of the substrate and was ~5-fold faster than the overall turnover. Kinetic isotope effects (KIEs) of 1.5-2.3 (on kcat/Km) were observed with 3,3-, 4,4-, and 3,3,4,4-deuterated retinol. Deuteration at C-4 produced a 4-fold increase in 3- hydroxylation due to metabolic switching, with no observable effect on 4-hydroxylation. Deuteration at C-3 produced a strong KIE for 3-hydroxylation but not 4-hydroxylation. Analysis of the products of deuterated retinol showed a lack of scrambling of a putative allylic radical at C-3 and C-4. We conclude that the most likely catalytic mechanism begins with abstraction of a hydrogen atom from C-4 (or possibly C-3) initiating the desaturation pathway, followed by a sequential abstraction of a hydrogen atom or proton-coupled electron transfer. Adx reduction and hydrogen abstraction both contribute to rate limitation.

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Randomized double blind trial of amitriptyline versus placebo in treatment of chronic laryngopharyngeal neuropathy

A neuropathic etiology has been suggested for patients with chronic laryngopharyngitis symptoms without visible structural pathology. Prior studies have shown that treatment with neuro-modulating medications is beneficial, but it is unknown if this was due to placebo effect. Our objective was to compare the efficacy of amitriptyline versus placebo in treating chronic laryngopharyngeal neuropathy.

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Risk assessment of heavy metals in soil of Tongnan District (Southwest China): evidence from multiple indices with high-spatial-resolution sampling

Abstract

Assessment of heavy metal (HM) pollution in soil is critical for human health, ecological remediation, and soil conservation. In this study, statistical analyses and geochemical approaches such as enrichment factor (EF), the index of geoaccumulation (Igeo), and potential ecological risk index (RI) were used for characterization and risk assessment of soil HMs through a high-spatial-resolution 385 samples from Tongnan District, an important agricultural practice area in Chongqing Municipality in Southwest China. Igeo and EF indicated that Hg and Cd could be considered as low and moderate polluted, respectively, and others HMs were not a major concern. Comprehensive ecological risk information further demonstrated that the HMs have caused a moderate risk. Principal component analysis (PCA) extracted two principal components (PCs) with eigenvalue >1 explaining about 66.1% of the total variance in the HM data sets, demonstrating major source of anthropogenic activity, phosphate fertilizers, vehicle, and pesticides. These multi-index methods have the capacity of HM assessment in soil, which are useful for soil conservation and ecological remediation.

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Occurrence and risk assessment of antidepressants in Huangpu River of Shanghai, China

Abstract

Antidepressants are gaining public attention because of increasing reports of their occurrence in environment and their potential impact on ecosystems and human health. Continuous input of pharmaceuticals into rivers, through psychiatric hospital or wastewater treatment plant (WWTPs) effluent, may cause adverse effects on the aquatic ecosystems of the receiving water bodies. This work investigates the occurrence and sources of 8 antidepressants in main stream and tributaries of Huangpu River in Shanghai. The detected concentrations of the selected antidepressants ranged from low nanogram per liter to 42.9 ng L⁻¹ (fluoxetine) in main stream and ranged from low nanogram per liter to 33.7 ng L⁻¹ (fluoxetine) in tributaries. To study the effect of hospital or wastewater treatment plants (WWTPs) on environment, the upstream and downstream samples were analyzed. Generally, antidepressants had greater concentrations in downstream than that in upstream of the WWTPs or hospitals. It is suggesting that WWTPs and hospitals may introduce pollution into water environment. A preliminary risk assessment was conducted: none of the eight target compounds yielded risk quotient (RQ) values more than 0.1, thus indicating that no adverse effect is expected in water environment. These results will provide background data for future antidepressants pollution control and management in Shanghai, China.

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Experimental investigation of performance and emissions of a VCR diesel engine fuelled with n -butanol diesel blends under varying engine parameters

Abstract

The continuous rise in the cost of fossil fuels as well as in environmental pollution has attracted research in the area of clean alternative fuels for improving the performance and emissions of internal combustion (IC) engines. In the present work, n-butanol is treated as a bio-fuel and investigations have been made to evaluate the feasibility of replacing diesel with a suitable n-butanol-diesel blend. In the current research, an experimental investigation was carried out on a variable compression ratio CI engine with n-butanol-diesel blends (10–25% by volume) to determine the optimum blending ratio and optimum operating parameters of the engine for reduced emissions. The best results of performance and emissions were observed for 20% n-butanol-diesel blend (B20) at a higher compression ratio as compared to diesel while keeping the other parameters unchanged. The observed deterioration in engine performance was within tolerable limits. The reductions in smoke, nitrogen oxides (NO_x ), and carbon monoxide (CO) were observed up to 56.52, 17.19, and 30.43%, respectively, for B20 in comparison to diesel at rated power. However, carbon dioxide (CO₂) and hydrocarbons (HC) were found to be higher by 17.58 and 15.78%, respectively, for B20. It is concluded that n-butanol-diesel blend would be a potential fuel to control emissions from diesel engines.

Graphical abstract

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Soy molasses as a fermentation substrate for the production of biosurfactant using Pseudomonas aeruginosa ATCC 10145

Abstract

Soy molasses is a product co-generated during soybean processing that has high production and low commercial value. Its use has great potential in fermentative processes due to the high concentration of carbohydrates, lipids and proteins. This study investigated the use of Pseudomonas aeruginosa to produce biosurfactants in a soy molasses-based fermentation medium. A central composite design (CCD) was prepared with two variables and three replicates at the central point to optimize the production of biosurfactant. The concentration of soy molasses had values between 29.3 and 170.7 g/L and the initial concentration of microorganism varied between 0.2 and 5.8 g/L. All the experiments were performed in duplicate on a shaker table at 30.0 ± 1.0 °C and 120 rpm for 72 h with samples taken every 12 h. Thus, to validate the experiments, the values of 120 g/L for the initial concentration of soy molasses and 4 g/L for the initial concentration of microorganisms were used. In response, the following values were obtained at 48 h of fermentation: surface tension of 31.9 dyne/cm, emulsifying index of 97.4%, biomass concentration of 11.5 g/L, rhamnose concentration of 6.9 g/L and biosurfactant concentration of 11.70 g/L. Further analysis was carried out for critical micelle concentration (CMC) which was obtained at approximately 80 mg/L. The bands found in Fourier transform infrared spectroscopy analysis had characteristic glycolipids as reported in the literature. These values show a great potential for biosurfactant production using soy molasses as a substrate and bacteria of the species P. aeruginosa.

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Assessment of potential health risk of fluoride consumption through rice, pulses, and vegetables in addition to consumption of fluoride-contaminated drinking water of West Bengal, India

Abstract

A study was conducted in fluoride-affected Bankura and Purulia districts of West Bengal to assess the potential health risk from fluoride exposure among children, teenagers, and adults due to consumption of rice, pulses, and vegetables in addition to drinking water and incidental ingestion of soil by children. Higher mean fluoride contents (13–63 mg/kg dry weight) were observed in radish, carrot, onion bulb, brinjal, potato tuber, cauliflower, cabbage, coriander, and pigeon pea. The combined influence of rice, pulses, and vegetables to cumulative estimated daily intake (EDI) of fluoride for the studied population was found to be 9.5–16%. Results also showed that intake of ivy gourd, broad beans, rice, turnip, fenugreek leaves, mustard, spinach, and amaranth grown in the study area is safe at least for time being. The cumulative EDI values of fluoride (0.06–0.19 mg/kg-day) among different age group of people of the study area were evaluated to be ~10⁴ times higher than those living in the control area; the values for children (0.19 and 0.52 mg/kg-day for CTE and RME scenarios, respectively) were also greater than the "Tolerable Upper Intake Level" value of fluoride. The estimated hazard index (HI) for children (3.2 and 8.7 for CTE and RME scenarios, respectively) living in the two affected districts reveals that they are at high risk of developing dental fluorosis due to the consumption of fluoride-contaminated rice, pulses, and vegetables grown in the study area in addition to the consumption of contaminated drinking water.

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Probiotic characterization of Bacillus subtilis P223 isolated from kimchi

Abstract

Probiotic characteristics of Bacillus subtilis P223 isolated from kimchi were investigated in this study. Spore cells of B. subtilis P223 showed high tolerance to artificial gastric juice (pH 2.5, 0.3% pepsin, 3 h) and bile salts (0.3% oxgall, 24 h). Spore cells of B. subtilis P223 showed more adherence to intestinal cells (HT-29 cells) than vegetative cells. In addition, B. subtilis P223 showed high autoaggregation ability, similar to a commercial strain (Bacillus clausii ATCC 700160). Moreover, its coaggregation abilities with pathogens were strong. The adherence of three pathogens (Salmonella enteritidis ATCC 13076, Listeria monocytogenes ATCC 15313, and Escherichia coli ATCC 25922) to HT-29 cells was inhibited by B. subtilis P223. It was found that B. subtilis P223 could not produce β-glucuronidase, a carcinogenic enzyme. However, it had amylase and protease activities. Antibiotic susceptibility was measured using disk diffusion assay. It was revealed that B. subtilis P223 was only resistant to streptomycin among eight kinds of antibiotics. In addition, B. subtilis P223 showed no hemolysis activity. It did not have enterotoxin genes. Results of this study suggest that B. subtilis P223 isolated from kimchi has potential as a probiotic strain.

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Impact of corona discharge plasma treatment on microbial load and physicochemical and sensory characteristics of semi-dried squid ( Todarodes pacificus )

Abstract

The use of corona discharge plasma jet (CDPJ) for the improvement of the sanitary quality of semi-dried squid was investigated. Microbial contaminants, namely aerobic, coliforms, and molds and yeasts, were detected in the samples. The CDPJ generated using 20 kV DC voltage at 58 kHz frequency was used for the decontamination treatment (1–10 min). The bacterial contaminants and molds and yeasts were inactivated in the range of 1.5–2.1 and at 1.9 log CFU/g, respectively. The inactivation pattern was well fitted to the first-order kinetics model. The CDPJ treatment for 10 min did not exert significant changes (p > 0.05) in VBN and the trimethylamine content of semi-dried squid as compared to untreated controls. On the contrary, significant changes (p < 0.05) in moisture content, water activity, pH, color, and TBARS levels were observed upon plasma exposure. However, the CDPJ-treated samples displayed slightly better sensory properties than the controls in terms of appearance, visual color, and flavor.

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Spent coffee as a rich source of antioxidative compounds

Abstract

Antioxidant activities and major antioxidants were investigated in the methanolic extracts of roasted and spent coffee to evaluate the feasibility of spent coffee as a source of functional ingredients. Phenolic compounds, such as gallic acid, protocatechuic acid, and chlorogenic acid, and nitrogenous compounds, including trigonelline and caffeine, were identified. Caffeine was the most abundant compound, followed by chlorogenic acid. Despite the significant reduction of antioxidants, 2,2,-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was retained in more than 95% of roasted coffee. The retentions of superoxide dismutase (SOD)-like activity and ferric reducing antioxidant power (FRAP) were 65–90 and 46–60%, respectively. Gallic acid had a positive correlation with SOD-like activity, whereas protocatechuic acid positively correlated with FRAP, suggesting that the major compounds contributing to each antioxidant activity are different. These results show that spent coffee can be used as an antioxidant source for functional foods and cosmetic products to improve antioxidant properties.

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Downregulation of USP18 inhibits growth and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma cells by suppressing BCL2L1

Publication date: Available online 12 July 2017
Source:Experimental Cell Research
Author(s): Jing Cai, Tiande Liu, Xiaoliu Jiang, Changkuo Guo, Anwen Liu, Xinlan Xiao
Ubiquitin-specific peptidase 18 (USP18) is closely related with hepatitis B virus (HBV), which has been involved in tumourigenesis. However, there has been little research into the role of USP18 on the progression of hepatocellular carcinoma (HCC), especially in HBV-related HCC. In present study, we found that USP18 expression was aberrantly elevated in HCC tissues than adjacent non-tumour tissues. Importantly, USP18 expression was higher in HBV-related HCC cell lines (HepG2.2.15 and Hep3B) than HBV-unrelated HCC cell lines. Furthermore, knockdown of USP18 significantly suppressed tumor cell proliferation in vitro and tumor growth in vivo, whereas overexpression of USP18 promoted HCC cells growth. Moreover, our experimental data revealed that USP18 silencing obviously blocked cell cycle at G1 phase and increased cell apoptosis. Finally, BCL2L1, a member of BCL2 family protein, was identified as a downstream gene of USP18. Mechanistically, we found that USP18 directly bind to BCL2L1 and positively regulated its expression in HCC cells. Overall, our results suggested that USP18 has a crucial role in regulating diverse aspects of the pathogenesis of HCC, indicating that it might be a potential therapeutic target.



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HAMMOCK: Mill Creek grad, Trickum teacher Fronzak braving summer cancer battle - Gwinnett Prep Sports

HAMMOCK: Mill Creek grad, Trickum teacher Fronzak braving summer cancer battle Gwinnett Prep Sports It took a year for doctor visits to sort out the problem. She began with her primary care doctor, then went to multiple ear, nose and throat doctors and specialists. Her current doctor finally discovered the issue, with the help of her prodding, was ...

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Long Noncoding RNA and Cancer: A New Paradigm

In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 1–17. ©2017 AACR.

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