Alternative reverse genetics system for influenza viruses based on a synthesized swine 45S rRNA promoter

Abstract

We generated an alternative reverse genetics (RG) system based on a synthesized swine 45S rRNA promoter to rescue the H3N2 subtype swine influenza virus. All eight flanking segment cassettes of A/swine/Henan/7/2010 (H3N2) were amplified with ambisense expression elements from RG plasmids. All segments were then recombined with the pHC2014 vector, which contained the synthesized swine 45S rRNA promoter (spol1) and its terminal sequence (t1) in a pcDNA3 backbone. As a result, we obtained a set of RG plasmids carrying the corresponding eight-segment cassettes. We efficiently generated the H3N2 virus after transfection into 293T/PK15, PK15, and 293T cells. The efficiency of spol1-driven influenza virus rescue in PK15 cells was similar to that in 293T cells by titration using the human pol1 RG system. Our approach suggests that an alternative spol1-based RG system can produce influenza viruses.

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Cocaine use is associated with a higher prevalence of elevated ST2 concentrations

Publication date: Available online 23 April 2017
Source:Clinical Biochemistry
Author(s): Xander M.R. van Wijk, Eric Vittinghoff, Alan H.B. Wu, Kara L. Lynch, Elise D. Riley
BackgroundCocaine is a well-known risk factor for acute cardiac events, but the effects in users outside of acute events are less clear. We investigated a possible association between cocaine use and the concentration of a novel biomarker for cardiac stress and heart failure, ST2.MethodsA case-control study was conducted to compare ST2 concentrations by the presence of cocaine in patients presenting for care, but not cardiac care, at an urban safety net hospital.ResultsIn samples taken from 100 cocaine-positive and 100 cocaine-negative patients, the presence of cocaine was associated with ST2 concentrations>35ng/mL. Serum concentrations of benzoylecgonine, a major cocaine metabolite, were significantly correlated with ST2 concentrations.ConclusionsCocaine use is associated with subclinical cardiac stress and damage outside of acute cardiac events. This information could add to better stratification of cocaine users with elevated ST2 concentrations who may be at higher risk for developing heart failure and other cardiac complications.



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Physical performance in newly diagnosed hypothyroidism: a pilot study

Abstract

Objective

Hypothyroidism is complicated by neuromuscular symptoms (myalgias, slowness of movements, and tiredness) and signs (easy fatigability and cramps), which may have a negative impact on general well-being and quality of life. In a pilot, prospective, controlled study, we investigated the features of muscle dysfunction in hypothyroidism by disease questionnaire, biochemical measures, and physical performance tests.

Materials and Methods

Fifty-seven consecutive patients with newly diagnosed hypothyroidism were enrolled, 27 subclinical (S-Hypo) and 30 overt (O-Hypo). A series of 30 euthyroid subjects, with similar demographic characteristics, served as controls. Patients were administered a short disease questionnaire and underwent laboratory exams and standardized physical tests, both at baseline and after restoration of biochemical euthyroidism.

Results

Compared to euthyroid controls, the O-Hypo group showed significantly higher prevalence of neuromuscular symptoms and significantly higher serum creatine phosphokinase (CPK) levels (p value < 0.0001). S-Hypo had slightly higher CPK levels and prevalence of neuromuscular symptoms than controls. Both S-Hypo and O-Hypo patients performed worse than controls in the six-minute walking test. Differences between patients and controls in handgrip strength test and timed chair standing test failed to reach statistical significance (although a trend was noticeable), possibly due to the small sample size. In O-Hypo, an inverse correlation was found between CPK levels and the handgrip strength test (p value < 0.001). Restoration of euthyroidism was associated with normalization of questionnaire responses, six-minute walking test, as well as serum CPK levels.

Conclusion

In addition to neuromuscular symptoms, hypothyroidism is associated with abnormalities of physical performance. The six-minute walking test is the most valuable test to assess this aspect. In the pilot study, levothyroxine therapy could reverse muscle functional abnormalities.

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Jugular vein

Jugular vein: The jugular veins are in the neck and drain blood from the head, brain, face and neck and convey it toward the heart.

The external jugular vein collects most of the blood from the outside of the skull and the deep parts of the face. It lies outside the sternocleidomastoid muscle, passes down the neck and joins the subclavian vein.

The internal jugular vein collects blood from the brain, the outside of the face and the neck. It runs down the inside of the neck outside the internal and common carotid arteries and unites with the subclavian vein to form the innominate vein.

The jugular veins are particularly prominent during congestive heart failure. When the patient is sitting or in a semirecumbent position, the height of the jugular veins and their pulsations provides an estimate of the central venous pressure and gives important information about whether the heart is keeping up with the demands on it or is failing.

The word "jugular" refers to the throat or neck. It derives from the Latin "jugulum" meaning throat or collarbone and the Latin "jugum" meaning yoke. To go for the jugular is to attack a vital part that is particularly vulnerable.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience

Abstract

Purpose

Short-bowel syndrome (SBS) is associated with high morbidity and mortality. We conducted this study to establish the predictors of survival and weaning off parenteral nutrition (PN).

Methods

We reviewed the medical records of 16 SBS infants treated at our institution within a 30-year period. SBS was defined as a residual small-bowel length (RSBL) of <75 cm. Loss of the ileocecal valve (ICV), cholestasis (D-Bil >2.0 mg/dl), enterostomy, and RSBL were all evaluated. Kaplan–Meier analysis was used to analyze the predictors.

Results

The mean RSBL was 34.9 ± 22.9 cm. Six patients died (37.5%) and nine patients were weaned off PN (56.3%). Significant differences were observed in cholestasis (p < 0.03), enterostomy (p < 0.01), an absolute RSBL of <30 cm (p < 0.04), and a percentage of expected RSBL of <10% (p < 0.04) as survival predictors. Significant differences were also observed for cholestasis (p < 0.01), loss of the ICV (p < 0.04), an absolute RSBL of <20 cm (p < 0.01), and a percentage of expected RSBL of <10% (p < 0.03) as predictors of weaning off PN.

Conclusion

These predictors may help us select the optimal treatments for pediatric patients with SBS.

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Senior general surgery residents can be trained to perform focused assessment with sonography for trauma patients accurately

Abstract

Purposes

Researchers studying trauma have found that physicians are able to perform a focused assessment with sonography for trauma (FAST) with minimal training and achieve ideal accuracy. However, there are currently no consensus or standard guidelines regarding the performance of this assessment. The aim of our study was to clarify the value of FAST performed by well-qualified senior general surgery residents in cases of suspected blunt abdominal trauma, which presents an important diagnostic problem in emergency departments.

Methods

This was a retrospective study in the emergency department (ED) of our hospital performed from January 2011 to September 2013. Patients were included if they (1) had undergone a FAST examination performed by qualified residents and (2) had received subsequent formal radiographic or surgical evaluations. The results were compared against subsequent surgical findings or formal Department of Radiology reference standards.

Results

Among the 438 patients enrolled, false-negative results were obtained in 8 and false-positive results in 5. Only one patient was missed and required laparotomy to repair a small intestine perforation. The sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%.

Conclusions

Senior general surgery residents can be trained to perform accurate FAST examinations on trauma patients.

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Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention

Abstract

Purpose

To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies.

Methods

We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model.

Results

The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018).

Conclusions

Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

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The outcomes of pediatric liver retransplantation from a living donor: a 17-year single-center experience

Abstract

Purpose

Liver retransplantation is the only therapeutic option for patients with graft failure after liver transplantation. The aim of this study is to evaluate the outcomes of pediatric retransplantation from living donor at a single center.

Methods

Between December 1998 to August 2015, retransplantation from a living donor was performed for 14 children (<18 years of age) at Kumamoto University Hospital. The characteristics of the retransplantation recipient and the clinicopathological factors between primary transplantation and retransplantation were analyzed to detect the prognostic factors.

Results

In retransplantation, the operative time was longer and the amount of blood loss was greater in comparison to primary transplantation. The 1-, 3-, and 5-year survival rates from the date of retransplantation were 85.7, 85.7, and 78.6%, respectively. The rates of re-laparotomy after primary transplantation, bile leakage and postoperative bleeding after retransplantation were higher than after primary transplantation. Among the three patients who died after retransplantation, the operative time, the rate of re-laparotomy after primary transplantation and the incidence of gastrointestinal complications were higher in comparison to the surviving patients.

Conclusion

Pediatric retransplantation from a living donor is an acceptable procedure that could save the lives of recipients with failing allografts when organs from deceased donors are scarce. To ensure good results, it is essential to make an appropriate assessment of the cardiopulmonary function and the infectious state of the patients before Re-LDLT.

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Immigration and Mental Health

Abstract

Purpose of Review

While the experience of migration and resettlement in a new country is associated with mental health risks, immigrants generally demonstrate better mental health than expected. This review describes patterns in mental health outcomes among immigrants. We discuss a conceptual model of the potential underlying mechanisms that could buffer the stress and disadvantage experienced by this substantial and growing population.

Recent Findings

While epidemiological studies have established a general pattern of lower risk for mental health disorders among first-generation (foreign-born) immigrants in the USA, recent studies highlight how this pattern varies substantially by the intersection of race, ethnicity, national origin, gender, and socioeconomic status. Contextual factors including the family and neighborhood context, an immigrant’s social position, experiences of social support and social exclusion, language competency and ability, and exposure to discrimination and acculturative stress further influence the relationship between immigration and mental health.

Summary

We conclude with an emphasis on social resilience processes, with a focus on how immigrants develop social relations, social capital, and social networks. We recommend future directions for research that prioritize identifying and understanding social adaptation strategies adopted by immigrant groups to cope with immigration stressors.

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Longitudinal Ultrasound Measures of Fetal Growth and Offspring Outcomes

Abstract

Purpose of Review

In this narrative review, we outline recent evidence relating longitudinal ultrasound (US) measurements to offspring outcomes in the perinatal period and in childhood, with an emphasis on the methodological approaches for describing fetal growth.

Recent Findings

The utility of longitudinal ultrasonography (US) to measure fetal growth and determine fetal trajectories is valued in both clinical and research environments. Evidence shows that repeated measures of US throughout pregnancy are useful for distinguishing between a growth-restricted and constitutionally small fetus, the former burdened by adverse clinical outcomes. Fetal growth restriction and small for gestational age are not interchangeable terms, although both can exist in the same individual.

Summary

The application of longitudinal US may have predictive value when determining longer-term health and disease outcomes in offspring born growth-restricted. However, it is important to remember that associations between fetal growth restriction and increased risk for non-communicable diseases are likely modified by postnatal growth.

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The Epidemiology and Prevention of Hepatitis E Virus Infection

Abstract

Purpose of Review

Hepatitis E virus (HEV) infections are a global public health problem. These viruses were originally identified as the cause of large waterborne outbreaks with increased mortality in pregnant women in developing countries in Asia and Africa in 1983. A decade later, locally acquired cases of acute hepatitis were reported in industrialized countries after food-borne transmission from an animal reservoir, especially swine, wild boar, and deer. However, the knowledge about the clinical features of HEV infection, the animal reservoirs, and virus characteristics has expanded substantially in recent years.

Recent Findings

HEV infections in patients who are immunosuppressed after a solid organ transplant and AIDS or cancer chemotherapy frequently develop chronic hepatitis. Some patients with chronic HEV infection develop extra-hepatic manifestations, especially neurologic symptoms. Clinical observations support the effectiveness of ribavirin therapy from chronic HEV. Recent research has found an expanded animal reservoir of Hepeviridae that are human pathogens and strains that are only animal pathogens. A consensus classification of Hepeviridae has been published recently. The risk of transfusion transmission of HEV has been quantified and selected donor screening implemented in two countries in the last few years.

Summary

Recent research has greatly expanded scientific information on the diversity and zoonotic reservoirs of Hepeviridae as well as the epidemiology and clinical features of HEV infection in humans.

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Hepatitis C: Review of the Epidemiology, Clinical Care, and Continued Challenges in the Direct-Acting Antiviral Era

Abstract

Purpose of Review

This review highlights key studies and recently published data, policies, and recommendations related to hepatitis C virus (HCV) epidemiology, transmission, and treatment.

Recent Findings

HCV is a leading cause of liver-related deaths, cirrhosis, and hepatocellular carcinoma. Since 2011 and accelerating since 2013, new, safe, tolerable, and curative therapies have considerably altered clinical and public health frameworks related to the prevention, control, and clinical management of HCV. Nevertheless, there are several populations in the USA that are important to consider because of disparities in HCV prevalence and transmission risk. Adults born during 1945–1965 have an estimated anti-HCV antibody prevalence of ∼3%, which is six times higher than among other adults, are often unaware of their infections, and are at increased risk of having HCV-associated morbidity and mortality from decades of chronic infection. Since the early 2000s, increasing incidence of acute HCV infections among young, white, non-urban people who inject drugs has been reported. Despite promising therapeutic advances, significant challenges remain for reducing HCV-associated morbidity and mortality.

Summary

The high burden of HCV and significant health consequences associated with chronic infection make HCV a critical public health priority. Advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well tolerated, and highly effective; however, benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.

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Social Epidemiology and Global Mental Health: Expanding the Evidence from High-Income to Low- and Middle-Income Countries

Abstract

Purpose of the Review

The vast majority of research on the social determinants of mental health has been generated from high-income country (HIC) populations, even as the greatest health disparities, and greatest disease burden, is observed in lower- and middle-income countries (LMICs). The goal of this review is to examine the evidence base on how key social epidemiology constructs relate to mental health in LMIC contexts. A special focus is on points of departure from the HIC knowledge base, gaps in overall understanding, and opportunities for social epidemiology to make a significant contribution.

Recent Findings

A growing body of literature suggests that there is significant heterogeneity, both in the direction and magnitude, of association between factors such as socioeconomic status, income inequality, gender, and social networks/supports and mental health in LMIC. For example, higher levels of education and being married can be risk factors for worse mental health among women in certain contexts. However, many studies have methodological limitations that make causal inference difficult. Poverty alleviation interventions offer a unique opportunity to examine the impact of improving economic resources and mental health.

Summary

Much remains unknown about the impact of key social factors on mental health in LMIC. Findings from HICs may not apply to LMIC populations, since the meaning and distribution of a given social variable may differ significantly from what is commonly observed in HICs. These points of departure point to opportunities for social epidemiology to make a contribution to the field of global mental health.

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Administrative Claims Data Versus Augmented Pregnancy Data for the Study of Pharmaceutical Treatments in Pregnancy

Abstract

Purpose of Review

Administrative claims databases, which collect reimbursement-related information generated from healthcare encounters, are increasingly used to evaluate medication safety in pregnancy. We reviewed the strengths and limitations of claims-only databases and how other data sources may be used to improve the accuracy and completeness of information critical for studying medication safety in pregnancy.

Recent Findings

Research on medication safety in pregnancy requires information on pregnancy episodes, mother-infant linkage, medication exposure, gestational age, maternal and birth outcomes, confounding factors, and (in some studies) long-term follow-up data. Claims data reliably identifies live births and possibly other pregnancies. It allows mother-infant linkage and has prospectively collected prescription medication information. Its diagnosis and procedure information allows estimation of gestational age. It captures maternal medical conditions but generally has incomplete data on reproductive and lifestyle factors. It has information on certain, typically short-term maternal and infant outcomes that may require chart review confirmation. Other data sources including electronic health records and birth registries can augment claims data or be analyzed alone. Interviews, surveys, or biological samples provide additional information. Nationwide and regional birth and pregnancy registries, such as those in several European and North American countries, generally contain more complete information essential for pregnancy research compared to claims-only databases.

Summary

Claims data offers several advantages in medication safety in pregnancy research. Its limitations can be partially addressed by linking it with other data sources or supplementing with primary data collection. Rigorous assessment of data quality and completeness is recommended regardless of data sources.

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Methodological Challenges in International Comparisons of Perinatal Mortality

Abstract

Purpose of Review

Several prestigious agencies routinely rank countries based on crude perinatal and infant mortality rates, while more recently, international neonatal networks have begun comparing neonatal mortality and morbidity rates among very preterm and very low-birth-weight infants. We discuss the methodologic challenges that compromise such comparisons and potential remedies.

Recent Findings

Crude perinatal mortality rates are biased by international variations in birth registration, especially at the borderline of viability. Such bias is demonstrated by significant differences in crude versus birth weight- and gestational age-specific comparisons of perinatal mortality. Comparisons of neonatal mortality among very preterm and very low-birth-weight infants are plagued by incorrect denominators, and this leads to paradoxical findings.

Summary

A lack of standardization with regard to birth registration and inadequate appreciation of the methods for calculating gestational age-specific mortality rates are responsible for biasing international comparisons of perinatal mortality.

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Epidemiologic Approaches for Studying Assisted Reproductive Technologies: Design, Methods, Analysis, and Interpretation

Abstract

Purpose

While considerable progress has been made since the advent of assisted reproductive technology (ART), the field remains a complex and challenging one for clinicians and researchers alike. This review discusses some of the most salient issues pertaining to the study of ART and whenever possible suggestions on how to address them.

Recent Findings

More than 5 million babies have been born through ART to date, representing up to 4% of all births worldwide. While technologies continue to evolve and demand for treatment grows, it is more important than ever to conduct rigorous and timely research to help guide clinical practice that is safe and effective, and that minimizes potential short- and long-term adverse outcomes to mother and child.

Summary

ART research will require exceedingly more sophisticated research methods, designs, and analyses that are rooted in a reproductive epidemiological framework in order to improve future research and ultimately promote better outcomes for all subfertile couples and their children.

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Modeling and Analysis of the Effect of Dip-Spin Coating Process Parameters on Coating Thickness Using Factorial Design Method

Statistical modeling of the dip-spin coating process to describe colloidal PTFE dispersion coating on the external surface of a small diameter hollow tube was developed by using 24 factorial design with a center point to predict the coating thickness in a range of 4–10 μm. The coating parameters included viscosity, withdrawal rate, spin speed, and immersion time. The adequacy of the predicted model was verified by coefficients of determination and lack-of-fit test. Model accuracy was verified by comparing predicted values with experimental results. The significant interaction effects on the coating thickness were three-way interaction among withdrawal rate, spin speed, and immersion time and two-way interactions between viscosity and withdrawal rate, viscosity and spin speed, and viscosity and immersion time. Cube plot for coating thickness reveals a trend of increasing coating thickness towards high levels of viscosity, withdrawal rate, and immersion time and lower level of spin speed.

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Extra Facial Landmark Localization via Global Shape Reconstruction

Localizing facial landmarks is a popular topic in the field of face analysis. However, problems arose in practical applications such as handling pose variations and partial occlusions while maintaining moderate training model size and computational efficiency still challenges current solutions. In this paper, we present a global shape reconstruction method for locating extra facial landmarks comparing to facial landmarks used in the training phase. In the proposed method, the reduced configuration of facial landmarks is first decomposed into corresponding sparse coefficients. Then explicit face shape correlations are exploited to regress between sparse coefficients of different facial landmark configurations. Finally extra facial landmarks are reconstructed by combining the pretrained shape dictionary and the approximation of sparse coefficients. By applying the proposed method, both the training time and the model size of a class of methods which stack local evidences as an appearance descriptor can be scaled down with only a minor compromise in detection accuracy. Extensive experiments prove that the proposed method is feasible and is able to reconstruct extra facial landmarks even under very asymmetrical face poses.

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Human Papillomavirus Genotype Distribution among Cervical Cancer Patients prior to Brazilian National HPV Immunization Program

To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, ). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, ). The frequency of HPV 16 in PA was higher in younger women (). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions.

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A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical Cutaneous Manifestations

Lyme disease (LD) is a tick-borne illness caused by Borrelia burgdorferi sensu stricto. An 80-year-old female from Pennsylvania, USA, presented to an outside hospital with fever, confusion, lower extremity weakness, and stool incontinence. CT head and MRI spine were unremarkable. An infectious work-up including lumbar puncture was negative. She was transferred to our tertiary care hospital. Patient was noted to have mild unilateral right-sided facial droop and a diffuse macular rash throughout the body. She denied any outdoor activities, tick bites, or previous rash. Intravenous ceftriaxone was started for suspected LD. The patient’s symptoms including facial droop resolved within 24 hours of antibiotic therapy. Polymerase chain reaction of the blood, IgM ELISA, and IgM Western blot testing for LD came back positive a few days after initiation of therapy. She was treated for a total of 21 days for neurological LD with complete symptom resolution. Not all patients have the classic “targetoid” EM rash on initial presentation, rash could develop after neurological manifestations, and prompt initiation of antibiotics without awaiting serology is paramount to making a quick and a full recovery. There should be a high index of suspicion for early disseminated LD, as presentations can be atypical.

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Effectiveness of Information Processing Strategy Training on Academic Task Performance in Children with Learning Disabilities: A Pilot Study

Learning disabilities (LD) can be associated with problems in the four stages of information processing used in learning: input, throughput, output, and feedback. These problems affect the child’s ability to learn and perform activities in daily life, especially during academic activities. This study is a pilot study aimed at investigating the effectiveness of information processing strategy training using a combination of two approaches that address the ability to apply processing strategies during academic activities in children with LD. The two approaches are the Perceive, Recall, Plan, and Perform (PRPP) System of Intervention, which is a strategy training intervention, and the Four-Quadrant Model (4QM) of Facilitated Learning approach, which is a systematic facilitator technique. Twenty children with LD were assigned to two groups: the experimental group and the control group . Children in the experimental group received the intervention twice a week for 6 consecutive weeks. Each treatment session took approximately 50 minutes. Children in the control group received traditional intervention twice a week for 6 consecutive weeks. The results indicated that the combination of the PRPP System of Intervention and the 4QM may improve the participants’ ability to apply information processing strategies during academic activities.

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Modeling of Hydraulic Fracture of Concrete Gravity Dams by Stress-Seepage-Damage Coupling Model

High-pressure hydraulic fracture (HF) is an important part of the safety assessment of high concrete dams. A stress-seepage-damage coupling model based on the finite element method is presented and first applied in HF in concrete dams. The coupling model has the following characteristics: (1) the strain softening behavior of fracture process zone in concrete is considered; (2) the mesh-dependent hardening technique is adopted so that the fracture energy dissipation is not affected by the finite element mesh size; (3) four coupling processes during hydraulic fracture are considered. By the damage model, the crack propagation processes of a 1 : 40 scaled model dam and Koyna dam are simulated. The results are in agreement with experimental and other numerical results, indicating that the damage model can effectively predict the carrying capacity and the crack trajectory of concrete gravity dams. Subsequently, the crack propagation processes of Koyna dam using three notches of different initial lengths are simulated by the damage model and the coupling model. And the influence of HF on the crack propagation path and carrying capacity is studied. The results reveal that HF has a significant influence on the global response of the dam.

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Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds

Blocking the polyol pathway plays an important role preventing diabetic complications. Therefore, aldose reductase (AR) and advanced glycation endproducts (AGEs) formation has significant effect on diabetic complications. Artemisia iwayomogi has long been used as treatment of various diseases in Korea. However, no literatures have reported on AR and AGEs formation inhibitory activities of A. iwayomogi. For these reasons, we aimed to assess that A. iwayomogi had potential as anti-diabetic complications agents. We led to isolation of two coumarins (1 and 2), nine flavonoids (3–11), five caffeoylquinic acids (12–16), three diterpene glycosides (17–19), and one phenolic compound (20) from A. iwayomogi. Among them, hispidulin (4), 6-methoxytricin (6), arteanoflavone (7), quercetin-3-gentiobioside (10), 1,3-di-O-caffeoylquinic acid (13), and suavioside A (18) were first reported on the isolation from A. iwayomogi. Not only two coumarins (1 and 2), nine flavonoids (3–11), and five caffeoylquinic acids (12–16) but also extracts showed significant inhibitor on AR and AGEs formation activities. We analyzed contents of major bioactive compounds in Korea’s various regions of A. iwayomogi. Overall, we selected Yangyang, Gangwon-do, from June, which contained the highest amounts of bioactive compounds, as suitable areas for cultivating A. iwayomogi as preventive or therapeutic agent in the treatment of diabetic complications.

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Evaluation of Quality of Life at Progression in Patients with Soft Tissue Sarcoma

Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year. Understanding quality of life (QoL) and the detrimental impact of disease progression is critical for long-term care and survival. Objectives. The primary objective was to explore the relationship between disease progression and health-related quality of life (HRQoL) using data from Eisai’s study (E7389-G000-309). Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin versus dacarbazine in patients with advanced STS. The QoL analysis was conducted for the baseline and progression populations using the European Organization for Research and Treatment of Cancer 30-item core QoL questionnaire (EORTC QLQ-C30). Results. There were no statistical differences between the two treatment arms at baseline for any domain (; ). Of the 399 patients who experienced disease progression (unadjusted and adjusting for histology), dacarbazine patients had significantly lower Global Health Status, Physical Functioning scores, and significantly worse Nausea and Vomiting, Insomnia, and Appetite Loss (). Conclusions. These results indicate differences in HRQoL overall and at progression between dacarbazine and eribulin patients, with increases in symptom severity observed among dacarbazine patients.

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Entropy Product Formula for Gravitational Instanton

We investigate the entropy product formula for various gravitational instantons. We speculate that due to the mass-independent features of the said instatons they are universal as well as quantized. For isolated Euclidean Schwarzschild black hole, these properties simply fail.

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Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β) signaling pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.

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Factors Affecting Utilization of Voluntary HIV Counseling and Testing Services among Teachers in Awi Zone, Northwest Ethiopia

HIV/AIDS affects the basic educational sector which is the most productive segment of the population and vital to the creation of human capital. The loss of skilled and experienced teachers due to the problem is increasingly compromising the provision of quality education in most African countries. The study was proposed to determine the magnitude of VCT utilization and assess contributing factors that affect VCT service utilization among secondary school teachers in Awi Zone. A cross-sectional study design was conducted among 588 participants in 2014. Self-administered questionnaire was used to collect data. Data was analyzed using SPSS version 16, presented as frequencies and summary statistics, and tested for presence of significant association with odds ratio at 95% CI. More than half (53.6%) of study participants were tested for HIV. Those who had sexual intercourse, had good knowledge about VCT, were divorced/widowed, were in the age group of 20–29 years, and were married utilized VCT services two, three, four, three, and two times better than their counterparts, respectively. Actions targeting unmarried status, increase of educational level, and teachers with age groups above 30 years are necessary to follow their counterparts to utilize VCT service in order to save loss of teachers.

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The Channel Compressive Sensing Estimation for Power Line Based on OMP Algorithm

Power line communication (PLC) can collect information by power line which increases the coverage and connectivity of the smart grid. In this paper, we analyze the transmission characteristics of the power line channel and model it with mathematics channel. The multipath effect of the power line channel is studied with a novel technology named compressive sensing herein. We also proposed a new method to the power line channel estimation based on compressive sensing. We can collect and extract the effective parameters of the power line channel to storage, which only take very little storage space. The simulation results show that the proposed approach can reduce the amount of processing data in the digital signal processing module and decrease the requirement for the hardware.

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Existence and Multiplicity of Positive Solutions for Schrödinger-Kirchhoff-Poisson System with Singularity

We study a singular Schrödinger-Kirchhoff-Poisson system by the variational methods and the Nehari manifold and we prove the existence, uniqueness, and multiplicity of positive solutions of the problem under different conditions.

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Uncertain Decision-Making: A Mathematical Programming Perspective

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Fabricating 90 nm Resolution Structures in Sol-Gel Silica Optical Waveguides for Biosensor Applications

Bragg grating structure in a sol-gel silica waveguide is fabricated on the basis of nanoimprint lithography for biophotonic applications. The process realizes nonstandardized lithography in sol-gel silica at a high resolution for a relatively large area in the range of several micrometers with a resolution in the order of several nanometers. Here we demonstrate structures of 250 and 90 nm resolutions in a sol-gel silica optical waveguide for a large area that is not optimized to date. Bragg grating of a 250 nm periodic structure is realized for a 1 mm long area.

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Contrast-Enhanced Microtomographic Characterisation of Vessels in Native Bone and Engineered Vascularised Grafts Using Ink-Gelatin Perfusion and Phosphotungstic Acid

Objectives. Bone ischemia and necrosis are challenging to treat, requiring investigation of native and engineered bone revascularisation processes through advanced imaging techniques. This study demonstrates an experimental two-step method for precise bone and vessel analysis in native bones or vascularised bone grafts using X-ray microtomography (μCT), without interfering with further histological processing. Methods. Distally ligated epigastric arteries or veins of 6 nude rats were inserted in central channels of porous hydroxyapatite cylinders and these pedicled grafts were implanted subcutaneously. One week later, the rats were perfused with ink-gelatin and euthanised and the femurs, tibias, and grafts were explanted. Samples were scanned using μCT, decalcified, incubated with phosphotungstic acid (PTA) for contrast enhancement, rescanned, and processed histologically. Results. Contrast-enhanced μCT displayed the course and branching of native bone vessels. Histologically, both central (−17%) and epiphyseal vessels (−58%) appeared smaller than in μCT scans. Hydroxyapatite cylinders were thoroughly vascularised but did not display bone formation. Grafts with a central artery had more (+58%) and smaller (−52%) vessel branches compared to grafts with a vein. Conclusions. We present a relatively inexpensive and easy-to-perform two-step method to analyse bone and vessels by μCT, suitable to assess a variety of bone-regenerative strategies.

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An algorithmic framework for frequent intraday pattern recognition and exploitation in forex market

Abstract

We present a knowledge discovery-based framework that is capable of discovering, analyzing and exploiting new intraday price patterns in forex markets, beyond the well-known chart formations of technical analysis. We present a novel pattern recognition algorithm for Pattern Matching, that we successfully used to construct more than 16,000 new intraday price patterns. After processing and analysis, we extracted 3518 chart formations that are capable of predicting the short-term direction of prices. In our experiments, we used forex time series from 8 paired-currencies in various time frames. The system computes the probabilities of events such as "within next 5 periods, price will increase more than 20 pips". Results show that the system is capable of finding patterns whose output signals (tested on unseen data) have predictive accuracy which varies between 60 and 85% depending on the type of pattern. We test the usefulness of the discovered patterns, via implementation of an expert system using a straightforward strategy based on the direction and the accuracy of the pattern predictions. We compare our method against three standard trading techniques plus a "random trader," and we also test against the results presented in two recently published studies. Our framework performs very well against all systems we directly compare , and also, against all other published results.

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Automatic Detection of Lung Cancer Nodules in Computerized Tomography Images

Abstract

Lung cancer is the prime factor in cancer related deaths due to increasing rate of smoking and air pollution. The survival rate of cancer patients increases to 52% if it is localized, and decreases to 4% if it is metastasized. The existing system use simple thresholding approach and pattern recognition method to segment lung and identify nodules in the lung computerized tomography (CT) images. But quality of this process is affected by the image acquisition protocols, scanner types, and inhomogeneity of intensities in the lung region. In order to overcome the drawbacks of the previous process and for separation of nodules from non-nodules, there is a need for an automatic computer aided detection system. This paper proposes an automatic method for detecting nodules from patient lung CT images. In this automatic approach first step is a lung segmentation to differentiate lung and background and make the detection of nodule simple. Then the lung region is segmented by Contextual Clustering based region growing method. Vector quantization method is used to identify the nodules present in the lungs. False positive reduction is done by using various combination of rule based filtering, support vector machine, k-Nearest Neighbours and Random Forest classifier. The performance of this method is evaluated in terms of accuracy, sensitivity and specificity.

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Kaposi Sarcoma Herpesvirus (KSHV) Latency-Associated Nuclear Antigen (LANA) recruits components of the MRN (Mre11-Rad50-NBS1) repair complex to modulate an innate immune signaling pathway and viral latency

by Giuseppe Mariggiò, Sandra Koch, Guigen Zhang, Magdalena Weidner-Glunde, Jessica Rückert, Semra Kati, Susann Santag, Thomas F. Schulz

Kaposi Sarcoma Herpesvirus (KSHV), a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS), Primary Effusion Lymphoma (PEL) and Multicentric Castleman’s Disease (MCD). Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway. Inhibition of NF-κB activation by cytoplasmic LANA is accompanied by increased lytic replication in KSHV-infected cells, suggesting that MRN-dependent NF-κB activation contributes to KSHV latency. Cytoplasmic LANA may therefore support the activation of KSHV lytic replication in part by counteracting the activation of NF-κB in response to cytoplasmic DNA. This would complement the recently described role of cytoplasmic LANA in blocking an interferon response triggered by cGAS and thereby promoting lytic reactivation. Our findings highlight a second point at which cytoplasmic LANA interferes with the innate immune response, as well as the importance of the recently discovered role of cytoplasmic MRN complex members as innate sensors of cytoplasmic DNA for the control of KSHV replication.

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Correction: A Burgeoning Crisis? A Nationwide Assessment of the Geography of Water Affordability in the United States

by Elizabeth A. Mack, Sarah Wrase

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Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF

by Giulia Lombardi, Valentina Di Gregori, Nicolò Girometti, Marina Tadolini, Francesco Bisognin, Paola Dal Monte

Background

Diagnosis of pulmonary (PTB) and extra-pulmonary tuberculosis (EPTB) in smear-negative patients can be difficult. We assessed retrospectively the performance of Xpert MTB/RIF system (Xpert, Cepheid) in diagnosing smear-negative tuberculosis (TB), which represents the most common form of TB in a low incidence setting.

Methods

Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed TB.

Results

386 Mycobacterium tuberculosis (MTB) culture-positive samples were detected out of 5170 specimens tested with smear microscopy, Xpert and culture: 323 were both culture- and Xpert-positive, and 63 culture-positive only. Of these, 234 (60.6%) were smear-negative. In addition Xpert detected 40 probable TB cases, based on clinical findings, which were culture-negative.Compared to culture, Xpert showed an overall sensitivity of 83.7% and a specificity of 99.1%; sensitivity was higher for respiratory samples (86.5%) than for non-respiratory samples (76.8%). Xpert sensitivity for smear-negative culture-confirmed TB was 73.1% and was not influenced by TB localization. As sensitivity of microscopy alone was poor (39.4%), Xpert improved both diagnosis of pulmonary TB (Δ = 36.5%) and extra-pulmonary TB (Δ = 63.4%).

Conclusions

Xpert MTB/RIF is a sensitive method for rapid diagnosis of TB compared to the conventional ZN staining. Xpert can serve as a sensitive and time-saving diagnostic method for microbiological diagnosis of smear-negative TB in countries with a low TB prevalence.

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Correction: Atheists and Agnostics Are More Reflective than Religious Believers: Four Empirical Studies and a Meta-Analysis

by Gordon Pennycook, Robert M. Ross, Derek J. Koehler, Jonathan A. Fugelsang

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NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

by Omar A. Z. Tutakhel, Arthur D. Moes, Marco A. Valdez-Flores, Marleen L. A. Kortenoeven, Mathijs v. D. Vrie, Sabina Jeleń, Robert A. Fenton, Robert Zietse, Joost G. J. Hoenderop, Ewout J. Hoorn, Luuk Hilbrands, René J. M. Bindels

Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics. Our results show that in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus (n = 23), the abundance of both tNCC and pNCC in uEVs is 4–5 fold higher than in CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC prior to treatment with thiazides predicted the blood pressure response to thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and these increases correlate with the blood pressure response to thiazides. This implies that assessment of NCC in uEVs could represent an alternate method to guide anti-hypertensive therapy in kidney transplant recipients.

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Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis

by Satoshi Ito, Tomohisa Nagoshi, Kosuke Minai, Yusuke Kashiwagi, Hiroshi Sekiyama, Akira Yoshii, Haruka Kimura, Yasunori Inoue, Kazuo Ogawa, Toshikazu D. Tanaka, Takayuki Ogawa, Makoto Kawai, Michihiro Yoshimura

Objective

Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether “insulin resistance” is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure.

Methods and results

We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (P Conclusions

Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

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Modulation the alternative splicing of GLA (IVS4+919G>A) in Fabry disease

by Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang

While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA. It could also reverse aberrant GLA splicing in a PP1-dependant manner. Our findings revealed the alternative splicing mechanism of GLA (IVS4+919G>A), and a potential treatment for this specific genetic type of Fabry disease by amiloride in the future.

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Efficacy of fluoride varnishes for preventing enamel demineralization after interproximal enamel reduction. Qualitative and quantitative evaluation

by Ascensión Vicente, Antonio José Ortiz Ruiz, Belén Manuela González Paz, José García López, Luis-Alberto Bravo-González

Objectives

To evaluate quantitatively and qualitatively the changes produced to enamel after interproximal reduction and subjected to demineralization cycles, after applying a fluoride varnish (Profluorid) and a fluoride varnish containing tricalcium phosphate modified by fumaric acid (Clinpro White).

Materials and methods

138 interproximal dental surfaces were divided into six groups: 1) Intact enamel; 2) Intact enamel + demineralization cycles (DC); 3) Interproximal Reduction (IR); 4) IR + DC; 5) IR + Profluorid + DC; 6) IR + Clinpro White + DC. IR was performed with a 0.5 mm cylindrical diamond bur. The weight percentage of calcium (Ca), phosphorous (P) and fluoride (F) were quantified by energy-dispersive X-ray spectrometry (EDX). Samples were examined under scanning electron microscopy (SEM).

Results

The weight percentage of Ca was significantly higher (p0.05). The weight percentage of P was similar among all six groups (p>0.05). F was detected on 65% of Group 6 surfaces. SEM images of Groups 4 and 6 showed signs of demineralization, while Group 5 did not.

Conclusions

Profluorid application acts as a barrier against the demineralization of interproximally reduced enamel.

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Incidence and risk factors for post-penetrating keratoplasty glaucoma: A systematic review and meta-analysis

by Suqian Wu, Jianjiang Xu

Objectives

To establish the incidence and risk factors for post penetrating keratoplasty glaucoma (PKKG).

Methods

Studies published between 1947 and 2016 regarding penetrating keratoplasty (PK) were identified using an electronic search and reviewed. For search purpose, PKKG was defined as ocular hypertension (> 21mmHg) after PK. The incidence and risk factors of PKKG were extracted for all studies. Pooled incidence, odd ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Thirty studies reporting on 27146 patients were included in the analysis of the incidence and risk factors for PKKG. Exact PKKG definitions used in the literature could be classified in to three subgroups: I, ocular hypertension (> 21mmHg) after PK; II, I plus > 4 weeks medical treatment required; III, II plus treatment escalation among patients with preexisting glaucoma. Overall (Definition I) pooled incidence in all studies was 21.5% (95% CI 17.8%, 25.7%). The incidence varied according to different definitions. The highest incidence value was found when only studies using Goldmann tonometer were included (22.5%), while the lowest incidence was found when a strict definition was used and steroid-induced PPKG was excluded (12.1%). The incidence was higher in patients with preexisting glaucoma, bullous keratopathy (BK), aphakia, pseudophakia, failed graft, and surgical indication of trauma. A triple procedure (combined PK with extra capsular cataract extraction and intraocular lens implantation) was not identified as being associated with the increased risk for PKKG.

Conclusions

The overall pooled incidence of PKKG was 21.5%, but it varied according to the criteria used to define the presence of PPKG. Strong risk factors for PKKG included preexisting glaucoma and aphakia, while modest predictors included pseudophakia, regrafting, and preoperative diagnosis like BK and trauma. There may not be sufficient evidence to identify a significant association between a triple procedure and PKKG.

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Suppressors of cytokine signaling in tuberculosis

by Shih-Wei Lee, Chi-Wei Liu, Jia-Ying Hu, Li-Mei Chiang, Chih-Pin Chuu, Lawrence Shih-Hsin Wu, Yung-Hsi Kao

Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection (LTBI), and healthy individuals. Our results showed that active tuberculosis subjects had higher levels of SOCS-3 mRNA, lower expressions of SOCS-2, -4, -5, -6, -7, and cytokine-inducible SH2-containing protein-1 (CIS-1) mRNAs, but not SOCS-1 mRNA than healthy and LTBI subjects. In men, LTBI patients had lower SOCS-3 than healthy subjects, and active TB patients had lower levels of SOCS-4, -5, and CIS-1 mRNAs but higher levels of SOCS-3 mRNA than healthy subjects. In women, LTBI patients had lower SOCS-3 mRNA level than healthy subjects, and active TB patients had lower CIS-1 mRNA level than healthy subjects. In non-aged adults (

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Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a highly conserved genomic structure

by Charlotte Peeters, Vaughn S. Cooper, Philip J. Hatcher, Bart Verheyde, Aurélien Carlier, Peter Vandamme

The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cases has defined strains predisposed to causing infection. Burkholderia multivorans is an important pathogen in people with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired from non-human sources such as the natural environment. This raises the central question of whether the isolation source (CF or environment) or the multilocus sequence type (ST) of B. multivorans better predicts their genomic content and functionality. We identified four pairs of B. multivorans isolates, representing distinct STs and consisting of one CF and one environmental isolate each. All genomes were sequenced using the PacBio SMRT sequencing technology, which resulted in eight high-quality B. multivorans genome assemblies. The present study demonstrated that the genomic structure of the examined B. multivorans STs is highly conserved and that the B. multivorans genomic lineages are defined by their ST. Orthologous protein families were not uniformly distributed among chromosomes, with core orthologs being enriched on the primary chromosome and ST-specific orthologs being enriched on the second and third chromosome. The ST-specific orthologs were enriched in genes involved in defense mechanisms and secondary metabolism, corroborating the strain-specificity of these virulence characteristics. Finally, the same B. multivorans genomic lineages occur in both CF and environmental samples and on different continents, demonstrating their ubiquity and evolutionary persistence.

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Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma

by Johanna Droop, Tibor Szarvas, Wolfgang A. Schulz, Christian Niedworok, Günter Niegisch, Kathrin Scheckenbach, Michèle J. Hoffmann

Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to stratify patients by molecular subtype, thus aiding personalized treatments.

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Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced behavioural sensitisation

by Emilia M. Lefevre, Gregory A. Medley, Timothy Reeks, Suzy Alexander, Thomas H. J. Burne, Darryl W. Eyles

Stress is known to modulate sensitisation to repeated psychostimulant exposure. However, there is no direct evidence linking glucocorticoids and sensitisation achieved by repeated administration of the NMDA receptor antagonist MK-801. We tested the hypothesis that co-administration of RU486, a glucocorticoid receptor (GR) antagonist, prior to repeated daily MK-801 injections would block the expression of locomotor sensitisation due to its dual effects on corticosterone and dopamine. We employed a repeated MK-801 administration locomotor sensitisation paradigm in male Sprague Dawley rats. RU486 or a dimethyl sulfoxide (DMSO) vehicle was co-administered with MK-801 or saline during the induction phase. Subsequent to withdrawal, rats were challenged with MK-801 alone to test for the expression of sensitisation. In a separate cohort of rats, plasma corticosterone levels were quantified from blood samples taken on the 1^st, 4^th and 7^th day of induction and at expression. One day after challenge, nucleus accumbens tissue levels of dopamine and its metabolites DOPAC and HVA were measured. During the induction phase, RU486 progressively enhanced locomotor sensitisation to MK-801. RU486 and MK-801 both showed stimulatory effects on corticosterone levels and this was further augmented when given in combination. Contrary to our hypothesis, RU486 did not block the expression of locomotor sensitisation to MK-801 and actually increased levels of dopamine, DOPAC and HVA in nucleus accumbens tissue. Our results showed that RU486 has augmentative rather than inhibitory effects on MK-801-induced sensitisation. This study indicates a divergent role for glucocorticoids in sensitisation to MK-801 compared to sensitisation with other psychostimulants.

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Cardiovascular safety of tiotropium Respimat vs HandiHaler in the routine clinical practice: A population-based cohort study

by Francesco Trotta, Stefania Spila-Alegiani, Roberto Da Cas, Maja Rajevic, Valentino Conti, Mauro Venegoni, Mariangela Rossi, Giuseppe Traversa

The cardiovascular safety of tiotropium Respimat formulation in the routine clinical practice is still an open issue. Our aim was to compare the risk of acute myocardial infarction and heart rhythm disorders in incident users of either tiotropium Respimat or HandiHaler. The study population comprises patients aged ≥45 years, resident in two Italian regions with a first prescription of tiotropium (HandiHaler or Respimat) between 01/07/2011-30/11/2013. The cohort was identified through the database of prescriptions reimbursed by the Italian National Health Service. Comorbidities and clinical outcomes were obtained from hospital records. The primary outcome was the first hospitalization for acute myocardial infarction and/or for heart rhythm disorders during the exposure period. Hazard ratios were estimated in the propensity score-matched groups through Cox regression. After matching, 31,334 patients with incident prescription of tiotropium were included. The two groups were balanced with regard to baseline characteristics. Similar incidence rates of the primary outcome between Respimat and HandiHaler users were identified (adjusted hazard ratio 1.02, 95% CI 0.82–1.28). No risk difference between Respimat and HandiHaler emerged when considering clinical events separately. This large cohort study showed a comparable acute cardiovascular safety profile of the two tiotropium formulations.

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Prevalence and associated factors of tuberculosis and diabetes mellitus comorbidity: A systematic review

by Mahteme Haile Workneh, Gunnar Aksel Bjune, Solomon Abebe Yimer

Introduction

The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health concern. There is mounting evidence from different countries on the burden of TB and DM comorbidity. The objective of this systematic review was to summarize the existing evidence on prevalence and associated/risk factors of TBDM comorbidity at global and regional levels.

Methods

Ovid Medline, Embase, Global health, Cochrane library, Web of science and Scopus Elsevier databases were searched to identify eligible articles for the systematic review. Data were extracted using standardized excel form and pilot tested. Median with interquartile range (IQR) was used to estimate prevalence of TBDM comorbidity. Associated/risk factors that were identified from individual studies were thematically analyzed and described.

Results

The prevalence of DM among TB patients ranged from 1.9% to 45%. The overall median global prevalence was 16% (IQR 9.0%-25.3%) Similarly, the prevalence of TB among DM patients ranged from 0.38% to 14% and the overall median global prevalence was 4.1% (IQR 1.8%-6.2%). The highest prevalence of DM among TB patients is observed in the studied countries of Asia, North America and Oceania. On the contrary, the prevalence of TB among DM patients is low globally, but relatively higher in the studied countries of Asia and the African continents. Sex, older age, urban residence, tobacco smoking, sedentary lifestyle, poor glycemic control, having family history of DM and TB illness were among the variables identified as associated/risk factors for TBDM comorbidity.

Conclusion

This systematic review revealed that there is a high burden of DM among TB patients at global level. On the contrary, the global prevalence of TB among DM patients is low. Assessing the magnitude and risk/associated factors of TBDM comorbidity at country/local level is crucial before making decisions to undertake TBDM integrated services.

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Correction: Community ART Support Groups in Mozambique: The Potential of Patients as Partners in Care

by Kebba Jobarteh, Ray W. Shiraishi, Inacio Malimane, Paula Samo Gudo, Tom Decroo, Andrew F. Auld, Vania Macome, Aleny Couto

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Correction: Risk factors associated with sexually transmitted infections among HIV infected men who have sex with men

by The PLOS ONE Staff

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Religion and the public ethics of stem-cell research: Attitudes in Europe, Canada and the United States

by Nick Allum, Agnes Allansdottir, George Gaskell, Jürgen Hampel, Jonathan Jackson, Andreea Moldovan, Susanna Priest, Sally Stares, Paul Stoneman

We examine international public opinion towards stem-cell research during the period when the issue was at its most contentious. We draw upon representative sample surveys in Europe and North America, fielded in 2005 and find that the majority of people in Europe, Canada and the United States supported stem-cell research, providing it was tightly regulated, but that there were key differences between the geographical regions in the relative importance of different types of ethical position. In the U.S., moral acceptability was more influential as a driver of support for stem-cell research; in Europe the perceived benefit to society carried more weight; and in Canada the two were almost equally important. We also find that public opinion on stem-cell research was more strongly associated with religious convictions in the U.S. than in Canada and Europe, although many strongly religious citizens in all regions approved of stem-cell research. We conclude that if anything public opinion or ‘public ethics’ are likely to play an increasingly important role in framing policy and regulatory regimes for sensitive technologies in the future.

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Perceived conflict of interest in health science partnerships

by John C. Besley, Aaron M. McCright, Nagwan R. Zahry, Kevin C. Elliott, Norbert E. Kaminski, Joseph D. Martin

University scientists conducting research on topics of potential health concern often want to partner with a range of actors, including government entities, non-governmental organizations, and private enterprises. Such partnerships can provide access to needed resources, including funding. However, those who observe the results of such partnerships may judge those results based on who is involved. This set of studies seeks to assess how people perceive two hypothetical health science research collaborations. In doing so, it also tests the utility of using procedural justice concepts to assess perceptions of research legitimacy as a theoretical way to investigate conflict of interest perceptions. Findings show that including an industry collaborator has clear negative repercussions for how people see a research partnership and that these perceptions shape people’s willingness to see the research as a legitimate source of knowledge. Additional research aimed at further communicating procedures that might mitigate the impact of industry collaboration is suggested.

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Partnering to promote research where it matters

by Michael Eisenstein

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Chromium in Agricultural Soils and Crops: A Review

Abstract

The mobility and distribution of metals in the environment is related not only to their concentration but also to their availability in the environment. Most chromium (Cr) exists in oxidation states ranging from 0 to VI in soils but the most stable and common forms are Cr(0), Cr(III), and Cr(VI) species. Chromium can have positive and negative effects on health, according to the dose, exposure time, and its oxidation state. The last is highly soluble; mobile; and toxic to humans, animals, and plants. On the contrary, Cr(III) has relatively low toxicity and mobility and it is one of the micronutrients needed by humans. In addition, Cr(III) can be absorbed on the surface of clay minerals in precipitates or complexes. Thus, the approaches converting Cr(VI) to Cr(III) in soils and waters have received considerable attention. The Cr(III) compounds are sparingly soluble in water and may be found in water bodies as soluble Cr(III) complexes, while the Cr(VI) compounds are readily soluble in water. Chromium is absorbed by plants through carriers of essential ions such as sulfate. Chromium uptake, accumulation, and translocation, depend on its speciation. Chromium shortage can cause cardiac problems, metabolic dysfunctions, and diabetes. Symptoms of Cr toxicity in plants comprise decrease of germination, reduction of growth, inhibition of enzymatic activities, impairment of photosynthesis and oxidative imbalances. This review provides an overview of the chemical characteristics of Cr, its behavior in the environment, the relationships with plants and aspects of the use of fertilizers.

http://ift.tt/2p8l23B

On the ground in Washington at the March for Science

Thousands rallied and marched in the rain in the US capital to stand up for science and its place in politics

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On the ground in Washington at the March for Science

Thousands rallied and marched in the rain in the US capital to stand up for science and its place in politics

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Mechanisms of Fibroblast Activation in the Remodeling Myocardium

Abstract

Purpose of Review

Activated fibroblasts are critically implicated in repair and remodeling of the injured heart. This manuscript discusses recent progress in the cell biology of fibroblasts in the infarcted and remodeling myocardium, highlighting advances in understanding the origin, function, and mechanisms of activation of these cells.

Recent Findings

Following myocardial injury, fibroblasts undergo activation and myofibroblast transdifferentiation. Recently published studies have suggested that most activated myofibroblasts in the infarcted and pressure-overloaded hearts are derived from resident fibroblast populations. In the healing infarct, fibroblasts undergo dynamic phenotypic alterations in response to changes in the cytokine milieu and in the composition of the extracellular matrix. Fibroblasts do not simply serve as matrix-producing cells, but may also regulate inflammation, modulate cardiomyocyte survival and function, mediate angiogenesis, and contribute to phagocytosis of dead cells.

Summary

In the injured myocardium, fibroblasts are derived predominantly from resident populations and serve a wide range of functions.

http://ift.tt/2p81BYX

Matricellular Proteins and Organ Fibrosis

Abstract

Purpose of Review

This review intends to outline the novel findings on the effects of matricellular proteins in the development of organ fibrosis and present recent advances towards a potential usage of matricellular proteins as markers or targets of therapy for fibrotic diseases.

Recent Findings

Recent studies elucidated the sites of production of different matricellular proteins during fibrosis of several organs, their specific binding receptors, and their effects on different cell types. For some proteins, a differential function between chronic disease and acute injury and a connection to regulation of inflammatory cell subtypes with relevance to fibrosis was established.

Summary

Matricellular proteins have evolved as important mediators in the progression of fibrosis. Several studies have already depicted their potential as biomarkers of the disease stage and evolution in patients, while the evaluation of their utility as therapeutic targets has been limited in animal models of fibrosis. This knowledge should guide future research on the development of drugs to treat fibrosis.

http://ift.tt/2pQByTQ

Pathogenic CD4+ T cells in patients with asthma

Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia.

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Renal-skin syndromes

Abstract

Renal-skin syndroms are a group of genetic disorders with renal and cutaneous manifestations that target molecular components present in both organs. Inherited renal-skin syndromes are mainly associated with defects of cell-matrix adhesion. We provide a non-exhaustive overview of the main molecular players at cell-matrix adhesions in mouse models and in human genetic disorders affecting kidney and skin. Renal and urinary tract involvement is described in all four major epidermolysis bullosa types and, in particular, in junctional subtypes and in recessive dystrophic epidermolysis bullosa. Here, we describe in detail those subtypes for which reno-urinary involvement is a constant and primary feature. Furthermore, complex multiorgan disorders with a predisposition to malignancies or attributable to metabolic defects that involve both kidney and skin are briefly summarized.

http://ift.tt/2p4h3Do

Cell culture: complications due to mechanical release of ATP and activation of purinoceptors

Abstract

There is abundant evidence that ATP (adenosine 5′-triphosphate) is released from a variety of cultured cells in response to mechanical stimulation. The release mechanism involved appears to be a combination of vesicular exocytosis and connexin and pannexin hemichannels. Purinergic receptors on cultured cells mediate both short-term purinergic signalling of secretion and long-term (trophic) signalling such as proliferation, migration, differentiation and apoptosis. We aim in this review to bring to the attention of non-purinergic researchers using tissue culture that the release of ATP in response to mechanical stress evoked by the unavoidable movement of the cells acting on functional purinergic receptors on the culture cells is likely to complicate the interpretation of their data.

http://ift.tt/2pRHoaw

Calpain inhibition prevents flotillin re-ordering and Src family activation during capacitation

Abstract

Prior to fertilization, mammalian sperm undergo several molecular, biochemical and physiological changes in a process termed capacitation. However, the mechanisms explaining the involvement of cytoskeletal remodeling and membrane re-ordering in each process prior to fertilization remain poorly understood. We found that the migration of both flotillin microdomains and Src family kinases towards the apical ridge of guinea pig sperm occurs under capacitating conditions. This re-ordering is associated with spectrin cleavage by calpain. Moreover, Src, Fyn, Lyn and Hck interact with flotillin-1; this interaction increases in a capacitation-dependent manner and the increased autophosphorylation of these kinases is linked to flotillin-1 association. The aforementioned results are prevented by the inhibition of calpain by calpeptin. Thus, spectrin cytoskeleton cleavage during capacitation seems to precede the reorganization of flotillin microdomains and Src family kinases towards the apical ridge of the sperm head in order to initiate the signaling cascade required for proper capacitation and further acrosome reaction. The significance of the Src family kinase reorganization for capacitation is demonstrated by the inhibition of calpain during capacitation also preventing the Src-family-kinase-dependent phosphorylation of FAK at Tyr576/577. Our work further highlights the scaffolding properties of flotillin microdomains and reveals the importance of their large-scale segregation during capacitation.

http://ift.tt/2p49xIs

Is OperaVOX a clinically useful tool for the assessment of voice in a general ENT clinic?

Objective acoustic analysis is a key component of multidimensional voice assessment. OperaVOX is an iOS app which has been shown to be comparable to Multi Dimensional Voice Program for most principal measures ...

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Conservative management of mallet injuries: A national survey of current practice in the UK

Mallet injuries are common, and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding best management and it is unclear whether this uncertainty is reflected in current UK practice.

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Internationally adopted children with cleft lip and/or palate: A retrospective cohort study

The treatment approach for internationally adopted children with cleft lip and/or palate differs from locally born children with cleft lip and/or palate. They are older at initial presentation, may have had treatment abroad of different quality and are establishing new, still fragile relationships with their adoptive parents. The aim of this study was to describe the characteristics and initial care and treatment of this group.

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Delayed Primary Closure of Extensive Wounds Using the TopClosure System and Topical Negative Pressure Therapy

Dear Editor, Extensive skin defects can be a challenging problem for a reconstructive surgeon. Primary closure of such defects is limited by tension and ischemia that develop at the skin edges. In such situation, skin grafting, locoregional, or free flap surgery are often necessary. We want to share our experience in achieving primary closure of extensive wounds with the TopClosure system (IVT Medical Limited, Israel) in combination with negative pressure therapy. The external tissue expansion effect of the TopClosure and the wound contracting ability of negative pressure therapy synergistically facilitates primary closure of extensive defects.

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External Validation of the Breast Reconstruction Risk Assessment Calculator

The Breast reconstruction Risk Assessment (BRA) Score estimates patient-specific risk for post-surgical complications using an individual’s unique combination of pre-operative variables. In this report, we externally validate the BRA Score models for surgical site infection, seroma, and explantation in a large sample of intra-institutional patients who underwent prosthetic breast reconstruction.

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An innovative method of planning and displaying flap volume in DIEP flap breast reconstructions

Determining the ideal volume of the harvested flap in order to achieve symmetry in deep inferior epigastric artery perforator (DIEP) flap breast reconstructions is complex. With preoperative imaging techniques such as 3D stereophotogrammetry and Computed Tomography Angiography (CTA) available nowadays, we can combine information to preoperatively plan the optimal flap volume to be harvested. In this proof-of-concept we investigated whether projection of a virtual flap planning onto the patient's abdomen using a projection method could result in harvesting the correct flap volume.

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A Retrospective Study: Multivariate Logistic Regression Analysis of the Outcomes after Pressure Sores Reconstruction With Fasciocutaneous, Myocutaneous and Perforator Flaps

Despite significant advances in medical care and surgical techniques, pressure sore reconstruction is still prone to elevated rates of complication and recurrence. We conducted a retrospective study to investigate not only complication and recurrence rates following pressure sore reconstruction, but also preoperative risk stratification as well.

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Postoperative outcomes of two- and three-dimensional planning in orthognathic surgery: A comparative study

Compared with conventional two-dimensional (2D) planning, three-dimensional (3D) planning in orthognathic surgery yields more accurate anatomical information and enables the precise positioning of maxillary and mandibular segments, particularly for patients with facial asymmetry. Accordingly, surgical outcomes achieved using 3D planning should be superior. This study determined the differences between the 2D and 3D planning techniques by comparing their surgical outcomes.

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Facial skin rejuvenation by autologous dermal microfat transfer in photoaged patients: clinical evaluation and skin surface digital profilometry analysis

Cumulative, long-term exposure to solar ultraviolet radiation promotes premature skin aging characterized by wrinkle formation and reduced skin elasticity. In this study, we assessed whether microfat transfer could improve dermal and subcutaneous tissue thickness loss associated with photoaging. Twenty one patients affected by facial photoaging (photodamage grade II-IV; age range 35-62 years; 19 females, 2 males; all of Caucasian origin) were treated using minimally-invasive autologous dermal white fat transfer harvested with a recently designed microcannula.

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Solvent-dependent transformation of aflatoxin B 1 in soil

Abstract

To date, all studies of aflatoxin B₁ (AFB₁) transformation in soil or in purified mineral systems have identified aflatoxins B₂ (AFB₂) and G₂ (AFG₂) as the primary transformation products. However, identification in these studies was made using thin layer chromatography which has relatively low resolution, and these studies did not identify a viable mechanism by which such transformations would occur. Further, the use of methanol as the solvent delivery vehicle in these studies may have contributed to formation of artifactual transformation products. In this study, we investigated the role of the solvent vehicle in the transformation of AFB₁ in soil. To do this, we spiked soils with AFB₁ dissolved in water (93:7, water/methanol) or methanol and used HPLC-UV and HPLC-MS to identify the transformation products. Contrasting previous published reports, we did not detect AFB₂ or AFG₂. In an aqueous-soil environment, we identified aflatoxin B_2a (AFB_2a) as the single major transformation product. We propose that AFB_2a is formed from hydrolysis of AFB₁ with the soil acting as an acid catalyst. Alternatively, when methanol was used, we identified methoxy aflatoxin species likely formed via acid-catalyzed addition of methanol to AFB₁. These results suggest that where soil moisture is adequate, AFB₁ is hydrolyzed to AFB_2a and that reactive organic solvents should be avoided when replicating natural conditions to study the fate of AFB₁ in soil.

http://ift.tt/2pRDWN2

Quality and readability of websites for patient information on tonsillectomy and sleep apnea

Tonsillectomy is a common treatment for obstructive sleep apnea (OSA). The Internet allows patients direct access to medical information. Since information on the Internet is largely unregulated, quality and readability are variable. This study evaluates the quality and readability of the most likely visited websites presenting information on sleep apnea and tonsillectomy.

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Actualités en phytothérapie

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Irlande–France

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Note de lecture

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Phytothérapie des caries et abcès dentaires

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Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

Abstract

Introduction

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern.

Objective

We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal–neonatal outcomes after in utero exposure to monotherapy with lamotrigine.

Methods

Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis.

Results

A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62–2.16 and OR 1.25; 95% CI 0.89–1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68–1.03 and OR 0.32; 95% CI 0.26–0.39, respectively).

Conclusion

No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

http://ift.tt/2p86sZV

Stiripentol in the Management of Epilepsy

Abstract

Stiripentol is a structurally unique antiepileptic drug that has several possible mechanisms of action, including diverse effects on the gamma-aminobutyric acid (GABA)-_A receptor and novel inhibition of lactate dehydrogenase. Because of its inhibition of several cytochrome P450 enzymes, it has extensive pharmacokinetic interactions, which often necessitates reduction in doses of certain co-therapies, particularly clobazam. Stiripentol also has a neuroprotective action, by reducing calcium-mediated neurotoxicity. Evidence of its efficacy is most robust for Dravet syndrome, where stiripentol added to clobazam and valproic acid reduces seizure frequency and severity in the majority of cases. Small case series have also suggested benefit for malignant migrating partial seizures in infancy, super-refractory status epilepticus, and intractable focal epilepsy, although larger prospective studies are needed in these disorders.

http://ift.tt/2pQFmVp

Polish Experience of Implementing Vision Zero

Abstract

Purpose of Review

The aim of this study is to present an outline and the principles of Poland's road safety strategic programming as it has developed over the last 25 years since the first Integrated Road Safety System with a strong focus on Sweden's "Vision Zero".

Recent Findings

Countries that have successfully improved road safety have done so by following strategies centred around the idea that people are not infallible and will make mistakes. The human body can only take a limited amount of energy upon impact, so roads, vehicles and road safety programmes must be designed to address this.

Summary

The article gives a summary of Poland's experience of programming preventative measures that have "Vision Zero" as their basis. It evaluates the effectiveness of relevant programmes.

http://ift.tt/2poTLLm

Mesenteric Cystic Teratoma Masquerading as Acute Abdomen

http://ift.tt/2ogeZe3

Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?

Abstract

Purpose

Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies.

Methods

A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test.

Results

One hundred thirty-nine patients with a median age 59 (33–81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. Location: right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03).

Conclusions

In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.

http://ift.tt/2oxIqV4

Dysphagia in a Patient with Cervical Dystonia

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Compression Garments and Recovery from Exercise: A Meta-Analysis

Abstract

Background

Adequate recovery from exercise is essential to maintain performance throughout training and competition. While compression garments (CG) have been demonstrated to accelerate recovery, the literature is clouded by conflicting results and uncertainty over the optimal conditions of use.

Objectives

A meta-analysis was conducted to assess the effects of CG on the recovery of strength, power and endurance performance following an initial bout of resistance, running, or non-load-bearing endurance (metabolic) exercise.

Methods

Change-score data were extracted from 23 peer-reviewed studies on healthy participants. Recovery was quantified by converting into standardized mean effect sizes (ES) [±95% confidence interval (CI)]. The effects of time (0–2, 2–8, 24, >24 h), pressure (<15 vs. ≥15 mmHg) and training status (trained vs. untrained) were also assessed.

Results

CG demonstrated small, very likely benefits [p < 0.001, ES = 0.38 (95% CI 0.25, 0.51)], which were not influenced by pressure (p = 0.06) or training status (p = 0.64). Strength recovery was subject to greater benefits than other outcomes [p < 0.001, ES = 0.62 (95% CI 0.39, 0.84)], displaying large, very likely benefits at 2–8 h [p < 0.001, ES = 1.14 (95% CI 0.72, 1.56)] and >24 h [p < 0.001, ES = 1.03 (95% CI 0.48, 1.57)]. Recovery from using CG was greatest following resistance exercise [p < 0.001, ES = 0.49 (95% CI 0.37, 0.61)], demonstrating the largest, very likely benefits at >24 h [p < 0.001, ES = 1.33 (95% CI 0.80, 1.85)]. Recovery from metabolic exercise (p = 0.01) was significant, although large, very likely benefits emerged only for cycling performance at 24 h post-exercise [p = 0.01, ES = 1.05 (95% CI 0.25, 1.85)].

Conclusion

The largest benefits resulting from CG were for strength recovery from 2 to 8 h and >24 h. Considering exercise modality, compression most effectively enhanced recovery from resistance exercise, particularly at time points >24 h. The use of CG would also be recommended to enhance next-day cycling performance. The benefits of CG in relation to applied pressures and participant training status are unclear and limited by the paucity of reported data.

http://ift.tt/2p2IbT7