The impact of contract service policy and doctor communication skills on rural patient-doctor trust relationship in the village clinics of three counties.
Trust is regarded as the cornerstone of the doctor-patient relationship in the world of medicine; it determines the decisions patients make when choosing doctors and influences patients' compliance with recommended treatments. In China, patient-doctor trust acts as a thermometer measuring harmony in the doctor-patient relationship. The objective of this study is to explore the relationship between the contract service and patient-doctor trust-building in 25 village clinics of rural China. The research was carried out in village clinics in rural China. A simple random sampling method was used to choose clinics and subjects. Based on feasibility and financial support, we chose three counties as our study settings: Dafeng District, Jiangsu Province; Yinan County, Shandong Province; and Wufeng Tujia Autonomous County, Hubei Province. Twenty-five village clinics and 574 subjects were selected in the three areas from the contract service and patient list. Descriptive statistics, t-tests, MANOVA, SEM, and multiple regression statistical analysis were employed to analyze the data. Statistical analysis showed that contract service directly and indirectly influenced patient-doctor trust-building in village clinics. The patient perception of doctor communication skills was a mediator in the relationship between contract service policy and patient-doctor trust-building. Building patient-doctor trust is important in developing and enhancing rural health. The policy of contract service plays a significant role in building relationships. Well-developed communication skills of doctors contribute to the implementation of the contract service policy and to establishing patient-doctor trust.


Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence.
Males and females show differences in the prevalence of many major diseases that have important inflammatory components to their etiology. These gender-specific diseases, which include autoimmune diseases, hepatocellular carcinoma, diabetes, and osteoporosis, are largely considered to reflect the actions of sex hormones on the susceptibility to inflammatory stimuli. However, inflammation reflects a balance between pro- and anti-inflammatory signals, and investigation of gender-specific responses to the latter has been neglected. Glucocorticoids are the primary physiological anti-inflammatory hormones in mammals, and synthetic derivatives of these hormones are prescribed as anti-inflammatory agents, irrespective of patient gender. We explored the possibility that sexually dimorphic actions of glucocorticoid regulation of gene expression may contribute to the dimorphic basis of inflammatory disease by evaluating the rat liver, a classic glucocorticoid-responsive organ. Surprisingly, glucocorticoid administration expanded the set of hepatic sexually dimorphic genes. Eight distinct patterns of glucocorticoid-regulated gene expression were identified, which included sex-specific genes. Our experiments also defined specific genes with altered expression in response to glucocorticoid treatment in both sexes, but in opposite directions. Pathway analysis identified sex-specific glucocorticoid-regulated gene expression in several canonical pathways involved in susceptibility to and progression of diseases with gender differences in prevalence. Moreover, a comparison of the number of genes involved in inflammatory disorders between sexes revealed 84 additional glucocorticoid-responsive genes in the male, suggesting that the anti-inflammatory actions of glucocorticoids are more effective in males. These gender-specific actions of glucocorticoids in liver were substantiated in vivo with a sepsis model of systemic inflammation.


Bringing it to the next level: how to make your EMR implementation a success.
Electronic medical records (EMRs) are the wave of the future. Is your practice ready to join in? This article will guide you through the steps to take to determine what EMRs can do for you and how you can start the process. Establishing goals and policies as well as providing adequate training are just as important in transitioning from paper records as the hardware and software of the system you choose.


Trends in Mood and Anxiety Symptoms and Suicide-Related Outcomes Among U.S. Undergraduates, 2007-2018: Evidence From Two National Surveys.
Past work has evidenced increased utilization of mental health services on college campuses, as well as rising rates of mood and suicide-related pathology in adolescents and young adults in recent years. We examined whether such findings are reflective of large-scale, nationwide trends in college student mental health in the past decade. We examined trends in mood, anxiety, and suicide-related outcomes among U.S. college students from 2007 to 2018 across two large national datasets: (1) the National College Health Assessment (n = 610,543; mean age = 21.25 years; 67.7% female; and 72.0% white) and (2) the Healthy Minds Study (n = 177,692; 86% students aged 18-22 years; 57% female; and 74% white). Participants, randomly selected by their educational institution, completed self-report measures of past-year mood, anxiety, nonsuicidal self-injury, and suicidal thoughts and behaviors. In both samples, rates of depression, anxiety, nonsuicidal self-injury, suicidal ideation, and suicide attempts markedly increased over the assessed years, with rates doubling over the period in many cases. Anger, low flourishing, and suicide plans, each assessed in only one dataset, also exhibited upward trends. Findings demonstrate a broad worsening of mental health among U.S. college students over the past decade, a concerning result meriting further attention and intervention.


Resistance of Trichostrongylus colubriformis to levamisole and morantel: differences in relation to selection history.
Two field strains of Trichostrongylus colubriformis were tested by in vitro and in vivo methods for resistance to morantel, levamisole and thiabendazole and compared with an anthelmintic-naive laboratory-passaged strain (McM). One field strain (TAS) was isolated from a dairy goat herd which had experienced severe helminthiasis despite intensive anthelmintic usage. The other (BCK) was isolated from sheep which had been treated solely with levamisole over a 6-year period. The BCK strain had very high levels of both levamisole and morantel resistance. In contrast the TAS strain was resistant to morantel but highly susceptible to levamisole. This finding is contrary to the expectation that selection with morantel automatically confers resistance to levamisole, the converse of which was shown to apply in the BCK strain. Although the TAS strain was exposed to levamisole prior to isolation, examination of the drug's pharmacokinetics in goats indicated that it exerted little if any anthelmintic effect, and therefore selection pressure, on the parasite population. This study suggests that the mechanism of levamisole resistance covers a wide spectrum, and embraces that for morantel. It also suggests that in order to conserve the effectiveness of the levamisole/morantel group of broad spectrum anthelmintics, morantel should be used to the exclusion of levamisole until resistance is detected, at which time levamisole may be introduced to re-establish high levels of control.


Diagnosis and management of ureteral complications following renal transplantation.
When compared with maintenance dialysis, renal transplantation affords patients with end-stage renal disease better long-term survival and a better quality of life. Approximately 9% of patients will develop a major urologic complication following kidney transplantation. Ureteral complications are most common and include obstruction (intrinsic and extrinsic), urine leak and vesicoureteral reflux. Ureterovesical anastomotic strictures result from technical error or ureteral ischemia. Balloon dilation or endoureterotomy may be considered for short, low-grade strictures, but open reconstruction is associated with higher success rates. Urine leak usually occurs in the early postoperative period. Nearly 60% of patients can be successfully managed with a pelvic drain and urinary decompression (nephrostomy tube, ureteral stent, and indwelling bladder catheter). Proximal, large-volume, or leaks that persist despite urinary diversion, require open repair. Vesicoureteral reflux is common following transplantation. Patients with recurrent pyelonephritis despite antimicrobial prophylaxis require surgical treatment. Deflux injection may be considered in recipients with low-grade disease. Grade IV and V reflux are best managed with open reconstruction.


The effect of adrenal steroids, corticotropin, and growth hormone on resistance to experimental infections.
Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone in depressing resistance to these infections. Cortisone, hydrocortisone, corticosterone, and corticotropin did not alter significantly the titers of influenza virus attained in the murine lungs during the first 2 days after infection, but cortisone and hydrocortisone markedly delayed the rate at which virus titers declined during the subsequent 6 days. Corticosterone and corticotropin delayed the rate at which the titers declined but slightly, and growth hormone had no apparent effect, as compared with controls. Growth hormone did not overcome the effect of cortisone and hydrocortisone on viral titers. No detectable antibody was found as late as 6 days after infection, in controls or in hormone-treated animals.


The trichorhinophalangeal syndrome with repeated dislocation of the patella.
The trichorhinophalangeal syndrome associated with laxity of the skin and joints has been mistaken for Ehlers-Danlos syndrome (Jones 1988). We report a case of the trichorhinophalangeal syndrome which we mistook for the Larsen syndrome. Literature and published photographs of the Larsen syndrome are reviewed to highlight the similarities between these two entities. These observations may be of value in the genetic mapping of the Larsen syndrome, which perhaps is a contiguous gene syndrome.


Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients.
Epidermoid carcinoma of the anal canal is an uncommon disease, and most institutions have only a small series of patients. The current study of a large series of patients treated with radiation therapy in a single institution evaluates the outcome, prognostic factors, and the late complications for these patients. From 1972 to 1991, 270 patients with anal canal epidermoid carcinoma without evident distant metastasis were irradiated with curative intent in the Radiotherapy Department of Tenon Hospital. The sex ratio was 1 man/5.7 women, with a mean age of 67.5 years. The histology included 59.6% well-differentiated epidermoid carcinoma, 32.2% moderately or poorly differentiated epidermoid carcinoma, and 8.2% cloacogenic. The T-classification was: T1: 8.5%; T2: 51.1%; T3: 30.4%; T4: 10%. Abnormal inguinal lymph nodes were present in 12.5% of the patients. Patients were irradiated by external beam. They received a first course of photon irradiation consisting of (mostly 18 mV or 25 mVl; some Co60 or 6 mV) 40-45 Gy (box technique) in the pelvis for 4-5 weeks. After a rest of 4-6 weeks, a second course of 15-20 gy in 2 weeks was given through a perineal field by an electron beam of suitable energy. When rectal involvement was important, a four-field, small box technique was used. Fourteen patients were given a booster irradiation of 30 Gy by interstitial brachytherapy (Iridium 192 sources), and four patients were treated with interstitial brachytherapy alone, to a mean dose of 62.5 Gy. At 5 and 10 years, determinate survival rates were: T1: 86% and 86%; T2: 86.2% and 82.5%; T3: 60.1% and 56.8%; T4: 45% and 45%, respectively. The overall local control rate was 80%. The overall anal conservation rate was 67%. In 154 patients (57%), the anus had maintained its normal function. At 5 and 10 years, determinate survival was 76% and 73.7%, respectively, for N0 and 53.5 and 53.5% for clinically involved inguinal lymph nodes. According to the log-rank test, survival comparisons between T2 and T3 classifications and of tumor sizes less than or equal to 4 cm in length and greater than or equal to 5 cm in length were significant (P = 0.0001 and P < 0.0001, respectively). The presence of clinical abnormal inguinal lymph nodes had a significant negative influence on survival rates (P = 0.047). Multivariate analysis indicated that T-classification and tumor size in centimeters were the only predictive variables. Nonpredictive variables included nodal status, histology, age, total dose, overall treatment time, and irradiation technique. The grade 3 complication rate requiring surgical treatment was 27/270 (10%), considering all patients (27/190 represents a 14% rate for patients who had local tumor control after radiation therapy alone without secondary salvage amputation). There was no significant relationship between complication rate and the aforementioned variables. Because of the homogeneity of the irradiation doses, no significant relationship was found between dose, local control rate, or complication rate. After radiation therapy, recognizing the distinction between tumor sizes of less than or equal to 4 cm in length and more than 4 cm in length (which is not considered in TNM Classification criteria [International Union Against Cancer, 1987]) could help to improve treatment strategies. For tumors more than 4 cm in length and/or with clinically involved lymph nodes, the treatment should be more extensive with combined chemotherapy and radiation therapy, but the increased local control with the addition of cytotoxic chemotherapy to irradiation has not been proven.


Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.
A recent randomised, double-blind, placebo controlled study conducted by our research group, provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure. Compared to placebo, 8 weeks of curcumin supplementation was associated with elevations in urinary thromboxane B2 (p<0.05), and substance P (p<0.001); while placebo supplementation was associated with reductions in aldosterone (p<0.05) and cortisol (p<0.05). Higher baseline plasma endothelin-1 (rs=-0.587; p<0.01) and leptin (rs=-0.470; p<0.05) in curcumin-treated individuals was associated with greater reductions in IDS-SR30 score after 8 weeks of treatment. Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action. Plasma concentrations of leptin and endothelin-1 seem to have particular relevance to treatment outcome. Further investigations using larger samples sizes are required to elucidate these findings, as the multiple statistical comparisons completed in this study increased the risk of type I errors.


Shortcomings of vitamin D-based model simulations of seasonal influenza.
Seasonal variation in serum concentration of the vitamin D metabolite 25(OH) vitamin D [25(OH)D], which contributes to host immune function, has been hypothesized to be the underlying source of observed influenza seasonality in temperate regions. The objective of this study was to determine whether observed 25(OH)D levels could be used to simulate observed influenza infection rates. Data of mean and variance in 25(OH)D serum levels by month were obtained from the Health Professionals Follow-up Study and used to parameterize an individual-based model of influenza transmission dynamics in two regions of the United States. Simulations were compared with observed daily influenza excess mortality data. Best-fitting simulations could reproduce the observed seasonal cycle of influenza; however, these best-fit simulations were shown to be highly sensitive to stochastic processes within the model and were unable consistently to reproduce observed seasonal patterns. In this respect the simulations with the vitamin D forced model were inferior to similar modeling efforts using absolute humidity and the school calendar as seasonal forcing variables. These model results indicate it is unlikely that seasonal variations in vitamin D levels principally determine the seasonality of influenza in temperate regions.


High HIV Prevalence and Risk Among Male Clients of Female Sex Workers in Hanoi and Ho Chi Minh City, Vietnam.
In Vietnam's concentrated HIV epidemic, female sex workers (FSWs) are at increased risk for acquiring and transmitting HIV, largely through their male clients. A high proportion of males in Vietnam report being clients of FSWs. Studying HIV-related risk factors and prevalence among male clients is important, particularly given the potential for male clients to be a 'bridge' of HIV transmission to the more general population or to sex workers. Time-location sampling was used to identify FSW in Hanoi and Ho Chi Minh City, Vietnam's largest cities, in 2013-2014. Recruited FSWs were asked to refer one male client to the study. Demographic and risk behavior data were collected from FSWs and male clients by administered questionnaires. Biologic specimens collected from male clients were tested for HIV and opiates. Sampling weights, calculated based on the FSWs probability of being selected for enrolment, were applied to prevalence estimates for both FSWs and male clients. Logistic regression models were developed to obtain odds ratios for HIV infection among male clients. A total of 804 male clients were enrolled. Overall, HIV prevalence among male clients was 10.2%; HIV prevalence was 20.7% (95% confidence interval (CI) 15.0-27.9%) among those reporting a history of illegal drug use and 32.4% (95% CI 20.2-47.7%) among those with opioids detected in urine. HIV prevalence among male clients did not differ across 'bridging' categories defined by condom use with FSWs and regular partners over the previous 6 months. HIV among male clients was associated with a reported history of illegal drug use (OR 3.76; 95% CI 1.87-7.56), current opioid use (OR 2.55; 95% CI 1.02-6.36), and being referred by an FSW who self-reported as HIV-positive (OR 5.37; 95% CI 1.46-19.75). Self-reported HIV prevalence among enrolled FSWs was 2.8%. Based on HIV test results of male clients and self-reported status from FSWs, an estimated 12.1% of male client-FSW pairs were sero-discordant. These results indicate high HIV prevalence among male clients of FSWs, particularly among those with a history of drug use. Programs to expand HIV testing, drug-use harm reduction, and HIV treatment for HIV-infected male clients of FSWs should be considered as key interventions for controlling the HIV epidemic in Vietnam.


Guided self-help as the first step for bulimic symptoms: implementation of a stepped-care model within specialized psychiatry.
This study describes the implementation and effectiveness of the first step, guided self-help (GSH), in a clinical setting, of a stepped-care model of cognitive behavior therapy for patients with bulimic symptoms. Eighty-nine patients participated. In the intent to-treat analyses, the effect sizes were small to moderate (0.25-0.66). However, the effect sizes were substantially larger (0.44-1.66) for the patients who completed all the GSH sessions (45%). The majority of noncompleters stayed within psychiatric services. Supplementary treatments were mostly directed towards comorbid conditions, especially depression. Those discontinuing treatment in advance where characterized by more lifetime diagnoses and higher ratings on the restraint subscale of the EDE-Q. GSH within specialized psychiatry might be effective for about 30% of the patients. There is no indication of patients losing their confidence in psychiatric services by being offered GSH as the first treatment.


Impact of ADCY9 Genotype on Response to Anacetrapib.
Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by ADCY9 genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib through Lipid-Modification) demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with preexisting atherosclerotic vascular disease. In the present study, we examined the impact of ADCY9 genotype on response to anacetrapib in the REVEAL trial. Individuals with stable atherosclerotic vascular disease who were treated with intensive atorvastatin therapy received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization, or presumed ischemic stroke) and the interaction with ADCY9 rs1967309 genotype. Among 19 210 genotyped individuals of European ancestry, 2504 (13.0%) had a first major vascular event during 4 years median follow-up: 1216 (12.6%) among anacetrapib-allocated participants and 1288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by ADCY9 genotype: hazard ratio (HR) = 0.92 (95% CI, 0.81-1.05) for GG; HR = 0.94 (95% CI, 0.84-1.06) for AG; and HR = 0.93 (95% CI, 0.76-1.13) for AA genotype carriers, respectively; genotypic P for interaction = 0.96. Furthermore, there were no associations between ADCY9 genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib. The REVEAL trial is the single largest study to date evaluating the ADCY9 pharmacogenetic interaction. It provides no support for the hypothesis that ADCY9 genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib. URL: https://www. gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.


Listeria monocytogenes impairs SUMOylation for efficient infection.
During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation and escape from host immune responses. Post-translational modifications are unique mechanisms that allow cells to rapidly, locally and specifically modify activity or interactions of key proteins. Some of these modifications, including phosphorylation and ubiquitylation, can be induced by pathogens. However, the effects of pathogenic bacteria on SUMOylation, an essential post-translational modification in eukaryotic cells, remain largely unknown. Here we show that infection with Listeria monocytogenes leads to a decrease in the levels of cellular SUMO-conjugated proteins. This event is triggered by the bacterial virulence factor listeriolysin O (LLO), which induces a proteasome-independent degradation of Ubc9, an essential enzyme of the SUMOylation machinery, and a proteasome-dependent degradation of some SUMOylated proteins. The effect of LLO on Ubc9 is dependent on the pore-forming capacity of the toxin and is shared by other bacterial pore-forming toxins like perfringolysin O (PFO) and pneumolysin (PLY). Ubc9 degradation was also observed in vivo in infected mice. Furthermore, we show that SUMO overexpression impairs bacterial infection. Together, our results reveal that Listeria, and probably other pathogens, dampen the host response by decreasing the SUMOylation level of proteins critical for infection.


Mosquito biology. Evolution of sexual traits influencing vectorial capacity in anopheline mosquitoes.
The availability of genome sequences from 16 anopheline species provides unprecedented opportunities to study the evolution of reproductive traits relevant for malaria transmission. In Anopheles gambiae, a likely candidate for sexual selection is male 20-hydroxyecdysone (20E). Sexual transfer of this steroid hormone as part of a mating plug dramatically changes female physiological processes intimately tied to vectorial capacity. By combining phenotypic studies with ancestral state reconstructions and phylogenetic analyses, we show that mating plug transfer and male 20E synthesis are both derived characters that have coevolved in anophelines, driving the adaptation of a female 20E-interacting protein that promotes oogenesis via mechanisms also favoring Plasmodium survival. Our data reveal coevolutionary dynamics of reproductive traits between the sexes likely to have shaped the ability of anophelines to transmit malaria.


Eyes as fenestrations to the ears: a novel mechanism for high-frequency and ultrasonic hearing.
Intense airborne ultrasound has been associated with hearing loss, tinnitus, and various nonauditory subjective effects, such as headaches, dizziness, and fullness in the ear. Yet, when people detect ultrasonic components in music, ultrasound adds to the pleasantness of the perception and evokes changes in the brain as measured in electroencephalograms, behavior, and imaging. How does the airborne ultrasound get into the ear to create such polar-opposite human effects? Surprisingly, ultrasound passes first through the eyes; thus, the eye becomes but another window into the inner ear.


Sitter Reduction Through Mobile Video Monitoring: A Nurse-Driven Sitter Protocol and Administrative Oversight.
This article describes the implementation of a mobile video monitoring program, combined with a nursing-driven sitter protocol and administrative oversight, resulting in a significant return on investment over a 2-year period. Program implementation, structures, and processes are described. Financial and quality outcomes are summarized and compared to national benchmarks.


Clinician Diagnoses of Failure to Thrive Before and After Switch to World Health Organization Growth Curves.
To evaluate change in the incidence of failure to thrive (FTT) based on selected growth percentile criteria and diagnostic codes before and after a switch in growth curves. We performed a retrospective cohort study of children 2 to 24 months of age in a large primary care network that switched its default growth curve from the Centers for Disease Control and Prevention (CDC) reference to the World Health Organization (WHO) standards in 2012. We compared the incidence of FTT defined by growth percentile criteria (using the default growth curve at the time of each measurement) and by International Classification of Diseases, Ninth Revision, codes in the 3 years before and after the CDC-WHO switch using an interrupted time series analysis. We performed these analyses stratified by age group (≤6 months and >6-24 months). We evaluated 83,299 children. Among those ≤6 months, increases in FTT incidence were found in both growth-percentile and clinician-diagnosis criteria at the CDC-WHO switch (P < .05). Among those >6 to 24 months, decreases in FTT incidence were found by growth-percentile criteria at the CDC-WHO switch (P < .05), but no significant changes were found in FTT incidence by diagnostic codes. When switching from the CDC to the WHO growth curves, changes in the incidence of FTT by growth-percentile and clinician-diagnosis criteria differed for younger versus older infants. Factors beyond growth likely influence the decision to diagnose a child as having FTT and may differ in younger compared to older infants.


Density dependent structural phase transition for confined copper: origin of the layering.
Confinement presents the opportunity for novel structural transition scenarios not observed in three-dimensional systems. Here, we report a comprehensive molecular dynamic (MD) study of the structural phase transition induced by density for an ordinary metal copper (Cu) confined between two parallel panel walls. At 4.19 g cm-3 < ρ < 4.66 g cm-3, a notable structural phase transition occurs between the triangle unit cell structure and quasi-square unit cell structure upon densification. Both the bond order parameter (BOP) and angular distribution function (ADF) can provide evidence for the transition. We highlight the fact that when the sole decrease of the atom distance cannot adapt to the further densification, the system starts to adjust the neighboring bond angle and promote the layering transition, thus inducing the structural phase transition. At the metastable coexistence zone, the viscosity exhibits a remarkable drop and the diffusion coefficient shows a notable increase, both facilitating the accomplishment of the structural transition. Our results will trigger more interest on the phase transition under confinement in a metallic system.


Mechanism for the hydrolysis of a sulfur-sulfur bond based on the crystal structure of the thiosulfohydrolase SoxB.
SoxB is an essential component of the bacterial Sox sulfur oxidation pathway. SoxB contains a di-manganese(II) site and is proposed to catalyze the release of sulfate from a protein-bound cysteine S-thiosulfonate. A direct assay for SoxB activity is described. The structure of recombinant Thermus thermophilus SoxB was determined by x-ray crystallography to a resolution of 1.5 A. Structures were also determined for SoxB in complex with the substrate analogue thiosulfate and in complex with the product sulfate. A mechanistic model for SoxB is proposed based on these structures.


The effectiveness of anti-illicit-drug public-service announcements: a systematic review and meta-analysis.
Anti-illicit-drug public-service announcements (PSAs) have become a cornerstone of drug policy in the USA. However, studies of the effectiveness of these interventions have not been subjected to a systematic evaluation. The authors searched 10 electronic databases along with major conference abstract databases (from inception until 15 February 2010) for all articles and abstracts that evaluated the effectiveness of anti-illicit-drug PSAs. The authors evaluated all studies that assessed intention to use illicit drugs and/or levels of illicit-drug use after exposure to PSAs, and conducted meta-analyses of these studies. The authors identified seven randomised trials (n=5428) and four observational trials (n=17 404). Only one randomised trial showed a statistically significant benefit of PSAs on intention to use illicit drugs, and two found evidence that PSAs significantly increased intention to use drugs. A meta-analysis of eligible randomised trials demonstrated no significant effect. Observational studies showed evidence of both harmful and beneficial effects. Existing evidence suggests that the dissemination of anti-illicit-drug PSAs may have a limited impact on the intention to use illicit drugs or the patterns of illicit-drug use among target populations.


Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): ability to predict cancer progression and decision-making regarding adjuvant therapy after radical prostatectomy.
The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.


DeNTNet: Deep Neural Transfer Network for the detection of periodontal bone loss using panoramic dental radiographs.
In this study, a deep learning-based method for developing an automated diagnostic support system that detects periodontal bone loss in the panoramic dental radiographs is proposed. The presented method called DeNTNet not only detects lesions but also provides the corresponding teeth numbers of the lesion according to dental federation notation. DeNTNet applies deep convolutional neural networks(CNNs) using transfer learning and clinical prior knowledge to overcome the morphological variation of the lesions and imbalanced training dataset. With 12,179 panoramic dental radiographs annotated by experienced dental clinicians, DeNTNet was trained, validated, and tested using 11,189, 190, and 800 panoramic dental radiographs, respectively. Each experimental model was subjected to comparative study to demonstrate the validity of each phase of the proposed method. When compared to the dental clinicians, DeNTNet achieved the F1 score of 0.75 on the test set, whereas the average performance of dental clinicians was 0.69.


Current insights into inherited bone marrow failure syndromes.
Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.


Infant mortality: explaining black/white disparities in Wisconsin.
Understanding the factors contributing to black/white disparities in infant mortality rates in Wisconsin is a prerequisite to decreasing these disparities and improving birth outcomes. We examined multiple determinants of infant mortality to understand the impact of specific risk factors on the infant mortality rates of blacks and whites in Wisconsin. We used the Wisconsin Interactive Statistics on Health database to examine infant mortality data for the 5-year time period, 1998-2002 (N=32,166 black infant births; 272,559 white infant births). We conducted a bivariate analysis of relative risks (RR) of infant mortality (black vs. white) using specific variables available in the database. We then examined the relationship between infant mortality rate and selected risk factors using regression analyses. Unadjusted, black infants were 3.0 times more likely to die during their first year of life, compared with white infants. Adjusting for gestational age black infants were only 1.9 times more likely to die. The risk was further reduced, after adjusting for birth weight, to 1.3. However, stratifying and adjusting for 8 other multiple variables accounted for some, but not all of the disparity. Black infants who had the same risk profile as white infants still had a 2-fold excess risk of death. In addition, simultaneously controlling for 4 of the 8 risk factors (maternal age, maternal education, adequacy of prenatal care received, and region of the state) also reduced, but did not eliminate, this excess risk (RR was still 2.2 for black infants). Independent of maternal age and region of the state, adequate prenatal care and higher levels of education are significant indicators of the racial disparity between whites and blacks. These results suggest that, within a given racial group, increasing access to prenatal care and increasing maternal educational attainment will improve infant mortality rates but will not eliminate the black/white disparity in infant mortality. In fact, these interventions may actually widen the disparity in infant mortality rate between blacks and whites, especially if funds and programs are applied equally throughout the population, rather than targeted to high-risk individuals, who lag significantly behind the majority population. The Wisconsin white population, which has already attained an infant mortality rate of 4.5 per 1,000 live births, will continue to have greatest benefit from these programs compared to blacks who have a rate of 19.2 in 2004; thus, the disparity is not eliminated and the gap widens probably due to differential uptake of health messages secondary to health literacy issues. Further research is needed to fully understand the additional, more difficult to measure factors that contribute significantly to infant mortality, especially among black women.


Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients.
Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients. We recorded haemodynamics in supine VVS and healthy volunteers (aged 15-27 years), challenged with graded lower body negative pressure (LBNP) (-15, -30, -45 mm Hg each for 5 min, then -60 mm Hg for a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA. Controls endured 25.9±4.0 min of LBNP during Saline+PE compared with 11.6±1.4 min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2 min compared with 22.6±1.6 min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored. We conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide.


The effect of interconnections on gas adsorption in materials with spherical mesopores: A Monte Carlo simulation study.
Gas adsorption is a standard method for measuring pore-size distributions of nanoporous materials. This method is often based on assuming the pores as separate entities of a certain simple shape: slit-like, cylindrical, or spherical. Here, we study the effect of interconnections on gas adsorption in materials with spherical pores, such as three-dimensionally ordered mesoporous (3DOm) carbons. We consider interconnected systems with two, four, and six windows of various sizes. We propose a simple method based on the integration of solid-fluid interactions to take into account these windows. We used Monte Carlo simulations to model argon adsorption at the normal boiling point and obtained adsorption isotherms for the range of systems. For a system with two windows, we obtained a remarkably smooth transition from the spherical to cylindrical isotherm. Depending on the size and number of windows, our system resembles both spherical and cylindrical pores. These windows can drastically shift the point of capillary condensation and result in pore-size distributions that are very different from the ones based on a spherical pore model. Our results can be further used for modeling fluids in a system of interconnected pores using Monte Carlo and density functional theory methods.


Saturated Fats Versus Polyunsaturated Fats Versus Carbohydrates for Cardiovascular Disease Prevention and Treatment.
The effects of saturated fatty acids (SFAs) on cardiovascular disease (CVD) risk are modulated by the nutrients that replace them and their food matrices. Replacement of SFAs with polyunsaturated fatty acids has been associated with reduced CVD risk, although there is heterogeneity in both fatty acid categories. In contrast, replacement of SFAs with carbohydrates, particularly sugar, has been associated with no improvement or even a worsening of CVD risk, at least in part through effects on atherogenic dyslipidemia, a cluster of traits including small, dense low-density lipoprotein particles. The effects of dietary SFAs on insulin sensitivity, inflammation, vascular function, and thrombosis are less clear. There is growing evidence that SFAs in the context of dairy foods, particularly fermented dairy products, have neutral or inverse associations with CVD. Overall dietary patterns emphasizing vegetables, fish, nuts, and whole versus processed grains form the basis of heart-healthy eating and should supersede a focus on macronutrient composition.


The effectiveness of low-level laser therapy for nonspecific chronic low back pain: a systematic review and meta-analysis.
In recent decades, low-level laser therapy (LLLT) has been widely used to relieve pain caused by different musculoskeletal disorders. Though widely used, its reported therapeutic outcomes are varied and conflicting. Results similarly conflict regarding its usage in patients with nonspecific chronic low back pain (NSCLBP). This study investigated the efficacy of low-level laser therapy (LLLT) for the treatment of NSCLBP by a systematic literature search with meta-analyses on selected studies. MEDLINE, EMBASE, ISI Web of Science and Cochrane Library were systematically searched from January 2000 to November 2014. Included studies were randomized controlled trials (RCTs) written in English that compared LLLT with placebo treatment in NSCLBP patients. The efficacy effect size was estimated by the weighted mean difference (WMD). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)). Of 221 studies, seven RCTs (one triple-blind, four double-blind, one single-blind, one not mentioning blinding, totaling 394 patients) met the criteria for inclusion. Based on five studies, the WMD in visual analog scale (VAS) pain outcome score after treatment was significantly lower in the LLLT group compared with placebo (WMD = -13.57 [95 % CI = -17.42, -9.72], I(2) = 0 %). No significant treatment effect was identified for disability scores or spinal range of motion outcomes. Our findings indicate that LLLT is an effective method for relieving pain in NSCLBP patients. However, there is still a lack of evidence supporting its effect on function.


Induction of pluripotency in bone marrow mononuclear cells via polyketal nanoparticle-mediated delivery of mature microRNAs.
Since the successful generation of induced pluripotent stem cells (iPSC) from adult somatic cells using integrating-viral methods, various methods have been tried for iPSC generation using non-viral and non-integrating technique for clinical applications. Recently, various non-viral approaches such as protein, mRNA, microRNA, and small molecule transduction were developed to avoid genomic integration and generate stem cell-like cells from mouse and human fibroblasts. Despite these successes, there has been no successful generation of iPSC from bone marrow (BM)-derived hematopoietic cells derived using non-viral methods to date. Previous reports demonstrate the ability of polymeric micro and nanoparticles made from polyketals to deliver various molecules to macrophages. MicroRNA-loaded nanoparticles were created using the polyketal polymer PK3 (PK3-miR) and delivered to somatic cells for 6 days, resulting in the formation of colonies. Isolated cells from these colonies were assayed and substantial induction of the pluripotency markers Oct4, Sox2, and Nanog were detected. Moreover, colonies transferred to feeder layers also stained positive for pluripotency markers including SSEA-1. Here, we demonstrate successful activation of pluripotency-associated genes in mouse BM-mononuclear cells using embryonic stem cell (ESC)-specific microRNAs encapsulated in the acid sensitive polyketal PK3. These reprogramming results demonstrate that a polyketal-microRNA delivery vehicle can be used to generate various reprogrammed cells without permanent genetic manipulation in an efficient manner.


SYBR Green II Dye-Based Real-Time Assay for Measuring Inhibitor Activity Against HIV-1 Reverse Transcriptase.
There are arrays of in vitro assays to quantify the activity of HIV-1 reverse transcriptase (HIV-1 RT). These assays utilize either chemically customized/labelled nucleotides, or TaqMan probes, or radiolabeled nucleotides/primers. Although several real-time PCR assays exist commercially for measuring the RT activity, which are usually used for quantifying the viral titres, these assays are not optimized for measuring the inhibitory concentrations (IC50) of HIV-1 RT inhibitors. Moreover, a recently established inorganic pyrophosphate-coupled enzyme assay cannot be employed for studying nonphosphorylated nucleoside reverse transcriptase inhibitors (NRTIs). In the present study, we have developed a novel one-step assay with native nucleotide substrates and SYBR Green II dye to determine IC50 values of triphosphorylated NRTIs against HIV-1 RT. Using exact batches of wild-type and mutant RT, and triphosphorylated NRTIs, we showed that our method gave IC50 values for inhibitors similar to that of an earlier published colorimetric assay with BrdUTP substrate (CABS). Our assay should be suitable for high-throughput screening of antiretroviral drugs and could also be suitable for studying drug resistance profiles. Additionally, we also used our assay to study inhibition by AZT in its nonphosphorylated form by supplementing the reaction mixture with necessary kinases and ATP.


Prospective study of risk factors for conjunctival bacterial contamination in patients undergoing intraocular surgery.
To determine whether a patient's age, gender, local or systemic risk factors affect the rate of preoperative bacterial contamination. Consecutive 1,474 patients undergoing intraocular surgery were enrolled in this prospective masked study. Past medical history was noted and examinations were performed. The patients were divided into four groups: a control group (without local or systemic risk factors), those with local risk factors (chronic use of topical medications, contact lens wear, blepharitis, chronic eyelid or conjunctival inflammation), those with systemic risk factors (immunosuppression, diabetes, autoimmune conditions, and asthma), and those with both. Conjunctival cultures were obtained before surgery. Among the 1,474 patients, 914 bacteria were isolated from 214 (14.9%) patients. Advanced age was associated with a higher rate of positive conjunctival cultures (p<0.005). No statistical difference was found with regard to gender (p=0.7173). Among the 282 patients in the control group, 14 (5%) had a positive conjunctival culture. Compared to the control group, positive conjunctival cultures were found in 118 out of 503 patients (23.5%) with local risk factors (p<0.0001), 65 out of 545 patients (11.9%) with systemic risk factors (p=0.0019), and 22 out of 144 (15.3%) with both (p=0.0006). Two patients developed postoperative endophthalmitis (0.14%), one with both local risk and systemic factors and the other with a systemic risk factor. Patients with local or systemic risk factors or advanced age were found to have a higher rate of bacterial conjunctival contamination before intraocular surgery.


Unique sleep-stage transitions determined by obstructive sleep apnea severity, age and gender.
In obstructive sleep apnea, patients' sleep is fragmented leading to excessive daytime sleepiness and co-morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two-step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two-step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep-states for power-laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake-state durations followed a power-law distribution, while sleep-state durations were characterized by an exponential distribution. Sleep-stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea-related clinical outcomes like arterial hypertension and daytime sleepiness.


Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women.
The purpose of the present study was twofold: first, to describe changes of Health-Related Quality of Life (HRQoL) during the adjuvant treatment among postmenopausal women with breast cancer; second, in the same population to identify the best predictors of Overall Quality of Life (QoL) after treatment, from perceived functioning, symptoms, emotional distress and clinical/demographic variables measured at baseline. The study group was 150 women (> or = 55 years of age) scheduled for adjuvant chemotherapy (CT, n=75) or radiotherapy (RT, n=75). They were examined before (baseline), during and after completing the treatment. Data about QoL, perceived functioning, symptoms and emotional distress were collected with the European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30, BR23 and Hospital Anxiety and Depression Scale (HADS) questionnaires. The general finding was that the adjuvant treatments were associated with decrease in overall QoL, physical and role functioning, anxiety and body image, as well as with increase in fatigue, dyspnoea, pain, nausea/vomiting, constipation and systemic therapy side effects measured over time. For women receiving CT, better emotional functioning and less pain at baseline predicted better overall QoL at the end of the treatment. For women receiving RT, better physical and emotional functioning, less breast symptoms and lower tumour stage at baseline predicted better overall QoL at the end of the treatment.


Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review.
Objective To characterize the prospective controlled clinical studies for all novel drugs that were initially approved by the Food and Drug Administration on the basis of limited evidence.Design Systematic review.Data sources Drugs@FDA database and PubMed.Study inclusion All prospective controlled clinical studies published after approval for all novel drugs initially approved by the FDA between 2005 and 2012 on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease as primary endpoints, or both. Results Between 2005 and 2012 the FDA approved 117 novel drugs for 123 indications on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease, or both (single surrogate trials). We identified 758 published controlled studies over a median of 5.5 years (interquartile range 3.4-8.2) after approval, most of which (554 of 758; 73.1%) were studies for indications approved on the basis of surrogate markers of disease. Most postapproval studies used active comparators-67 of 77 (87.0%) indications approved on the basis of single pivotal trials, 365 of 554 (65.9%) approvals based on surrogate marker trials, and 100 of 127 (78.7%) approvals based on single surrogate trials-and examined surrogate markers of efficacy as primary endpoints-51 of 77 (66.2%), 512 of 554 (92.4%), and 110 of 127 (86.6%), respectively. Overall, no postapproval studies were identified for 43 of the 123 (35.0%) approved indications. The median total number of postapproval studies identified was 1 (interquartile range 0-2) for indications approved on the basis of a single pivotal trial, 3 (1-8) for indications approved on the basis of pivotal trials that used surrogate markers of disease as primary endpoints, and 1 (0-2) for single surrogate trial approvals, and the median aggregate number of patients enrolled in postapproval studies was 90 (0-509), 533 (122-3633), and 38 (0-666), respectively. The proportion of approved indications with one or more randomized, controlled, double blind study using a clinical outcome for the primary endpoint that was published after approval and showed superior efficacy was 18.2% (6 of 33), 2.0% (1 of 49), and 4.9% (2 of 41), respectively.Conclusions The quantity and quality of postapproval clinical evidence varied substantially for novel drugs first approved by the FDA on the basis of limited evidence, with few controlled studies published after approval that confirmed efficacy using clinical outcomes for the original FDA approved indication.


Comparison of penetrating and nonpenetrating captive bolt methods in horned goats.
OBJECTIVE To use MRI and CT to compare the amount of tissue damage (soft tissue and bone) to the heads of goats after administration of a nonpenetrating or penetrating captive bolt. ANIMALS Cadavers of twelve 1- to 5-year-old mixed-breed goats that had been euthanized with an overdose of pentobarbital as part of an unrelated study. PROCEDURES Cadavers were randomly assigned to receive a nonpenetrating (n = 6) or penetrating (6) captive bolt. The head of 1 cadaver was imaged via CT and MRI. The muzzle of a device designed to administer either a penetrating or nonpenetrating captive bolt was then placed flush on the dorsal midline of each head at the level of the external occipital protuberance (poll) and aimed downward toward the cranialmost portion of the intermandibular space, and the assigned bolt was administered. Heads were removed, and CT and MRI of each head were performed. After imaging, each skull was transected along the sagittal plane to permit gross evaluation of central nervous tissue and obtain digital photographic images. In addition, 1 head that received a nonpenetrating captive bolt was further evaluated via blunt dissection and removal of adnexa from the external surface of the calvarium. RESULTS MRI, CT, and dissection of skulls revealed severe skeletal and soft tissue damage after impact with the penetrating and nonpenetrating captive bolts. CONCLUSIONS AND CLINICAL RELEVANCE The nonpenetrating captive bolt appeared to cause damage similar to that of the penetrating captive bolt in the cranium and soft tissues of the head in caprine cadavers. This damage suggested that administration of a nonpenetrating captive bolt as described here may be an acceptable method of euthanasia in goats.


What happens inside a fuel cell? Developing an experimental functional map of fuel cell performance.
Fuel cell performance is determined by the complex interplay of mass transport, energy transfer and electrochemical processes. The convolution of these processes leads to spatial heterogeneity in the way that fuel cells perform, particularly due to reactant consumption, water management and the design of fluid-flow plates. It is therefore unlikely that any bulk measurement made on a fuel cell will accurately represent performance at all parts of the cell. The ability to make spatially resolved measurements in a fuel cell provides one of the most useful ways in which to monitor and optimise performance. This Minireview explores a range of in situ techniques being used to study fuel cells and describes the use of novel experimental techniques that the authors have used to develop an 'experimental functional map' of fuel cell performance. These techniques include the mapping of current density, electrochemical impedance, electrolyte conductivity, contact resistance and CO poisoning distribution within working PEFCs, as well as mapping the flow of reactant in gas channels using laser Doppler anemometry (LDA). For the high-temperature solid oxide fuel cell (SOFC), temperature mapping, reference electrode placement and the use of Raman spectroscopy are described along with methods to map the microstructural features of electrodes. The combination of these techniques, applied across a range of fuel cell operating conditions, allows a unique picture of the internal workings of fuel cells to be obtained and have been used to validate both numerical and analytical models.


Many QTLs with minor additive effects are associated with a large difference in growth between two selection lines in chickens.
Two growth-selected lines in chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age. After more than 40 generations of selection they show a nine-fold difference in body weight at selection age and large differences in growth rate, appetite, fat deposition and metabolic characteristics. We have generated a large intercross between these lines comprising more than 800 F2 birds. QTL mapping revealed 13 loci affecting growth. The most striking observation was that the allele in the high weight line in all cases was associated with enhanced growth, but each locus explained only a small proportion of the phenotypic variance using a standard QTL model (1.3-3.1%). This result is in sharp contrast to our previous study where we reported that the two-fold difference in adult body size between the red junglefowl and White Leghorn domestic chickens is explained by a small number of QTLs with large additive effects. Furthermore, no QTLs for anorexia or antibody response were detected despite large differences for these traits between the founder lines. The result is an excellent example where a large phenotypic difference between populations occurs in the apparent absence of any single locus with large phenotypic effects. The study underscores the need for powerful experimental designs in genetic studies of multifactorial traits. No QTL at all would have reached genome-wide significance using a less powerful design (e.g. approx. 200 F2 individuals) regardless of the nine-fold phenotypic difference between the founder lines for the selected trait.


Neurogenesis of neural crest-derived periodontal ligament stem cells by EGF and bFGF.
Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells, the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor, and basic fibroblast growth factor. Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy. A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein, demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole-cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na(+) ) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine.


Changes in chemical permeation of disposable latex, nitrile, and vinyl gloves exposed to simulated movement.
Glove movement can affect chemical permeation of organic compounds through polymer glove products. However, conflicting reports make it difficult to compare the effects of movement on chemical permeation through commonly available glove types. The aim of this study was to evaluate the effect of movement on chemical permeation of an organic solvent through disposable latex, nitrile, and vinyl gloves. Simulated whole-glove permeation testing was conducted using ethyl alcohol and a previously designed permeation test system. With exposure to movement, a significant decrease (p ≤ 0.001) in breakthrough time (BT) was observed for the latex (-23%) and nitrile gloves (-31%). With exposure to movement, only the nitrile glove exhibited a significant increase (p ≤ 0.001) in steady-state permeation rate (+47%) and cumulative permeation at 30 min (+111%). Even though the nitrile glove provided optimum chemical resistance against ethyl alcohol, it was most affected by movement. With exposure to movement, the latex glove was an equivalent option for overall worker protection, because it was less affected by movement and the permeation rate was lower than that of the nitrile glove. In contrast, the vinyl glove was the least affected by movement, but did not provide adequate chemical resistance to ethyl alcohol in comparison with the nitrile and latex gloves. Glove selection should take movement and polymer type into account. Some glove polymer types are less affected by movement, most notably the latex glove in this test. With nitrile gloves, at least a factor of three should be used when attempting to assign a protection factor when repetitive hand motions are anticipated. Ultimately, the latex gloves outperformed nitrile and vinyl in these tests, which evaluated the effect of movement on chemical permeation. Future research should aim to resolve some of the observed discrepancies in test results with latex and vinyl gloves.


In situ Materials Characterization using the Tissue Diagnostic Instrument.
An understanding of the mechanical behavior of polymers is critical towards the design, implementation, and quality control of such materials. Yet experiments and method for the characterization of material properties of polymers remain challenging due the need to reconcile constitutive assumptions with experimental conditions. Well-established modes of mechanical testing, such as unconfined compression or uniaxial tension, require samples with specific geometries and carefully controlled orientations. Moreover, producing specimens that conform to such specifications often requires a considerable amount of sample material. In this study we validate a micromechanical indentation device, the Tissue Diagnostic Instrument (TDI), which implements a cyclic indentation method to determine the material properties of polymers and elastomeric materials. Measurements using the TDI require little or no sample preparation, and they allow the testing of sample materials in situ. In order to validate the use of the TDI, we compared measurements of modulus determined by the TDI to those obtained by unconfined compression tests and by uniaxial tension tests within the limit of small stresses and strains. The results show that the TDI measurements were significantly correlated with both unconfined compression (p<0.001; r(2) = 0.92) and uniaxial tension tests (p<0.001; r(2)=0.87). Moreover, the measurements across all three modes of testing were statistically indistinguishable from each other (p=0.92; ANOVA) and demonstrate that TDI measurements can provide a surrogate for the conventional methods of mechanical characterization.


Effect of hypokalaemia on the ouabain-sensitive sodium transport and the ouabain-binding capacity in human erythrocytes.
1. The sodium content, the ouabain-sensitive sodium efflux and efflux rate constant and the ouabain-binding capacity were measured in the erythrocytes of 53 patients with hypokalaemia and in 37 healthy controls. The sodium content alone was measured in a further 57 patients with hypokalaemia. 2. In the patients with hypokalaemia there was an increase in the average sodium content of the erythrocytes, which was entirely due to a reduction in the ouabain-sensitive efflux rate constant. 3. The ratio of the ouabain-sensitive efflux rate constant to the number of sodium pumps was decreased in the patients with hypokalaemia, and was directly related to the plasma potassium. 4. Many patients with moderate hypokalaemia had normal erythrocyte sodium and potassium contents and normal ouabain-sensitive efflux rate constant. These patients had an increased number of sodium pumps, which compensated for the inhibitory effect of hypokalaemia on each sodium pump. 5. This increase in the number of sodium pumps was common even in patients who had probably had hypokalaemia for less than 2 weeks. This finding suggests that there are latent sodium pumps within the circulating erythrocytes.


Genome-wide identification, characterization and phylogenetic analysis of 50 catfish ATP-binding cassette (ABC) transporter genes.
Although a large set of full-length transcripts was recently assembled in catfish, annotation of large gene families, especially those with duplications, is still a great challenge. Most often, complexities in annotation cause mis-identification and thereby much confusion in the scientific literature. As such, detailed phylogenetic analysis and/or orthology analysis are required for annotation of genes involved in gene families. The ATP-binding cassette (ABC) transporter gene superfamily is a large gene family that encodes membrane proteins that transport a diverse set of substrates across membranes, playing important roles in protecting organisms from diverse environment. In this work, we identified a set of 50 ABC transporters in catfish genome. Phylogenetic analysis allowed their identification and annotation into seven subfamilies, including 9 ABCA genes, 12 ABCB genes, 12 ABCC genes, 5 ABCD genes, 2 ABCE genes, 4 ABCF genes and 6 ABCG genes. Most ABC transporters are conserved among vertebrates, though cases of recent gene duplications and gene losses do exist. Gene duplications in catfish were found for ABCA1, ABCB3, ABCB6, ABCC5, ABCD3, ABCE1, ABCF2 and ABCG2. The whole set of catfish ABC transporters provide the essential genomic resources for future biochemical, toxicological and physiological studies of ABC drug efflux transporters. The establishment of orthologies should allow functional inferences with the information from model species, though the function of lineage-specific genes can be distinct because of specific living environment with different selection pressure.


Exploring the Use of a General Equilibrium Method to Assess the Value of a Malaria Vaccine: An Application to Ghana.
Background. Malaria is an important health and economic burden in sub-Saharan Africa. Conventional economic evaluations typically consider only direct costs to the health care system and government budgets. This paper quantifies the potential impact of malaria vaccination on the wider economy, using Ghana as an example. Methods. We used a computable general equilibrium model of the Ghanaian economy to estimate the macroeconomic impact of malaria vaccination in children under the age of 5, with a vaccine efficacy of 50% against clinical malaria and 20% against malaria mortality. The model considered changes in demography and labor productivity, and projected gross domestic product (GDP) over a time frame of 30 years. Vaccine coverage ranging from 20% to 100% was compared with a baseline with no vaccination. Results. Malaria vaccination with 100% coverage was projected to increase the GDP of Ghana over 30 years by US$6.93 billion (in 2015 prices) above the baseline without vaccination, equivalent to an increase in annual GDP growth of 0.5%. Projected GDP per capita would increase in the first year due to immediate reductions in time lost from work by adults caring for children with malaria, then decrease for several years as reductions in child mortality increase the number of dependent children, then show a sustained increase after Year 11 due to long-term productivity improvements in adults resulting from fewer malaria episodes in childhood. Conclusion. Investing in improving childhood health by vaccinating against malaria could result in substantial long-term macroeconomic benefits when these children enter the workforce as adults. These macroeconomic benefits are not captured by conventional economic evaluations and constitute an important potential benefit of vaccination.


Sleep apnea syndrome in Parkinson's disease. A case-control study in 49 patients.
In PD, the impact of nocturnal respiration on sleep continuity and architecture has not been systematically investigated by polysomnography (PSG). We performed a case-control study with retrospective analysis of PSG data of 49 PD patients. After classifying the PD patients according to their apnea/hypopnea index (AHI), they were matched with 49 controls in terms of age, gender, and AHI. There were 21 PD patients (43%) who had sleep apnea syndrome (SAS), classified as mild (AHI, 5-15) in 10 patients, moderate (AHI, >15-30) in 4 patients, and severe (AHI, > 30) in 7 patients. PD patients had more deep sleep (P = 0.02) and more nocturnal awakenings (P < 0.001) than the controls. Their body mass index (BMI) was lower (P = 0.04), and they maintained a more favorable respiratory profile, with higher mean and minimal oxygen saturation values (P = 0.006 and 0.01, respectively). These differences were preserved when only considering PD patients with AHI > 15. PD patients had less obstructive sleep apneas (P = 0.035), independently from the factor AHI. Only the respiratory changes of 4 PD patients with BMI > 27 and AHI > 15 (8%) approximated those seen in the controls. At an early or middle stage of the disease, non-obese PD patients frequently have AHI values suggesting SAS, however, without the oxygen desaturation profile of SAS. Longitudinal studies of patients with such "abortive" SAS are warranted to establish if this finding reflects benign nocturnal respiratory muscle dyskinesia or constitutes a precursor sign of dysautonomia in PD.


Atypical desquamation in a 2.5-year-old boy with Kawasaki disease: A case report.
Kawasaki disease (KD) is a vasculitis that mostly affects children under 5 years of age. This article presents a 2.5-year-old boy who presented with 6 days of fever, generalized maculopapular rash, bilateral non-exudative conjunctivitis, cracked lips, right cervical lymphadenopathy, erythematous extremities, and perianal desquamation. Laboratory studies showed leukocytosis and sterile pyuria. Because diagnosis of KD was proved, oral acetylsalicylic acid with the anti-inflammatory dose and intravenous immunoglobulin were started for him. On the seventh day of admission time, he developed desquamation and erythema on the site of his right cervical lymphadenopathy as well as periungual scaling. About three weeks after starting the treatment, scaling of the cervical lymphadenopathy and periungual area stopped. Echocardiography was performed for him three times: at the time of diagnosis, four weeks, and 6 months later and revealed normal coronary arteries. We report this sign, desquamation on the site of cervical lymphadenopathy, as a new finding.


Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum.
The pathogenic potential of Fusobacterium nucleatum and its significance in the development of periodontal diseases, as well as in infections in other organs, have gained new interest for several reasons. First, this bacterium has the potential to be pathogenic because of its number and frequency in periodontal lesions, its production of tissue irritants, its synergism with other bacteria in mixed infections, and its ability to form aggregates with other suspected pathogens in periodontal disease and thus act as a bridge between early and late colonizers on the tooth surface. Second, of the microbial species that are statistically associated with periodontal disease, F. nucleatum is the most common in clinical infections of other body sites. Third, during the past few years, new techniques have made it possible to obtain more information about F. nucleatum on the genetic level, thereby also gaining better knowledge of the structure and functions of the outer membrane proteins (OMPs). OMPs are of great interest with respect to coaggregation, cell nutrition, and antibiotic susceptibility. This review covers what is known to date about F. nucleatum in general, such as taxonomy and biology, with special emphasis on its pathogenic potential. Its possible relationship to other periodontal bacteria in the development of periodontal diseases and the possible roles played by OMPs are considered.


Tauopathy with paired helical filaments in an aged chimpanzee.
An enigmatic feature of age-related neurodegenerative diseases is that they seldom, if ever, are fully manifested in nonhuman species under natural conditions. The neurodegenerative tauopathies are typified by the intracellular aggregation of hyperphosphorylated microtubule-associated protein tau (MAPT) and the dysfunction and death of affected neurons. We document the first case of tauopathy with paired helical filaments in an aged chimpanzee (Pan troglodytes). Pathologic forms of tau in neuronal somata, neuropil threads, and plaque-like clusters of neurites were histologically identified throughout the neocortex and, to a lesser degree, in allocortical and subcortical structures. Ultrastructurally, the neurofibrillary tangles consisted of tau-immunoreactive paired helical filaments with a diameter and helical periodicity indistinguishable from those seen in Alzheimer's disease. A moderate degree of Abeta deposition was present in the cerebral vasculature and, less frequently, in senile plaques. Sequencing of the exons and flanking intronic regions in the genomic MAPT locus disclosed no mutations that are associated with the known human hereditary tauopathies, nor any polymorphisms of obvious functional significance. Although the lesion profile in this chimpanzee differed somewhat from that in Alzheimer's disease, the copresence of paired helical filaments and Abeta-amyloidosis indicates that the molecular mechanisms for the pathogenesis of the two canonical Alzheimer lesions--neurofibrillary tangles and senile plaques--are present in aged chimpanzees.


Unilamellar vesicles from amphiphilic graphene quantum dots.
Graphene quantum dots (GQDs) have attracted considerable interest due to their unique physicochemical properties and various applications. For the first time it is shown that GQDs surface-functionalized with hydrocarbon chains (i.e., amphiphilic GQDs) self-assemble into unilamellar spherical vesicles in aqueous solution. The amphiphilic GQD vesicles exhibit multicolor luminescence that can be readily exploited for membrane studies by fluorescence spectroscopy and microscopy. The GQD vesicles were used for microscopic analysis of membrane interactions and disruption by the peptide beta-amyloid.


Neural Markers of Speech Comprehension: Measuring EEG Tracking of Linguistic Speech Representations, Controlling the Speech Acoustics.
When listening to speech, our brain responses time lock to acoustic events in the stimulus. Recent studies have also reported that cortical responses track linguistic representations of speech. However, tracking of these representations is often described without controlling for acoustic properties. Therefore, the response to these linguistic representations might reflect unaccounted acoustic processing rather than language processing. Here, we evaluated the potential of several recently proposed linguistic representations as neural markers of speech comprehension. To do so, we investigated EEG responses to audiobook speech of 29 participants (22 females). We examined whether these representations contribute unique information over and beyond acoustic neural tracking and each other. Indeed, not all of these linguistic representations were significantly tracked after controlling for acoustic properties. However, phoneme surprisal, cohort entropy, word surprisal, and word frequency were all significantly tracked over and beyond acoustic properties. We also tested the generality of the associated responses by training on one story and testing on another. In general, the linguistic representations are tracked similarly across different stories spoken by different readers. These results suggests that these representations characterize the processing of the linguistic content of speech.SIGNIFICANCE STATEMENT For clinical applications, it would be desirable to develop a neural marker of speech comprehension derived from neural responses to continuous speech. Such a measure would allow for behavior-free evaluation of speech understanding; this would open doors toward better quantification of speech understanding in populations from whom obtaining behavioral measures may be difficult, such as young children or people with cognitive impairments, to allow better targeted interventions and better fitting of hearing devices.


Enzootic transmission of Babesia divergens among cottontail rabbits on Nantucket Island, Massachusetts.
Specific ticks seem to locally serve as vector for characteristic microbial assemblages (guilds) comprising spirochetes, piroplasms, ehrlichiae, and arboviruses. Borrelia andersoni and Anaplasma phagocytophilum are intensely transmitted between cottontail rabbits. To test the hypothesis that a piroplasm may also be maintained in rabbits, we sampled these hosts from Nantucket Island, Massachusetts and tested their blood and tissues by a polymerase chain reaction for evidence of infection. Surprisingly, the agent of bovine redwater and of European human babesiosis, Babesia divergens, was detected in 16% of the rabbits sampled during 1998-2002 (> 99% sequence similarity in the 18S ribosomal DNA). The vector of B. divergens on Nantucket appears to be Ixodes dentatus, a rabbit- and bird-feeding tick that may feed on humans. Although the risk of human infection appears to be minimal, an autochthonously acquired Kentucky case due to this rabbit agent was recently reported. Physicians should entertain the diagnosis of babesiosis due to B. divergens for severe hemolytic febrile syndromes in American patients exposed to sites where rabbits are common.


Below-the-Knee Retrograde Access for Peripheral Interventions: A Systematic Review.
To investigate the hypothesis that interventions involving retrograde below-the-knee (BTK) vessel punctures have an acceptably low complication rate and high procedural success. A systematic review was performed of the MEDLINE and Scopus databases for articles describing the results of BTK retrograde access for peripheral interventions. Outcome measures were access success, procedure success, and complications. A predefined subgroup analysis was performed of prospective studies to reduce the influence of possible reporting bias on outcomes. Nineteen articles, including 3 prospective studies, were selected, including a total of 1905 interventions in 1395 patients (mean age 69.5 years; 918 men). The BTK vessels were punctured in 1168 (61.3%) of these interventions. Access was successful in 94.0% of BTK attempts, 86.0% of all lesions were successfully crossed using a retrograde access, and 84.0% of interventions achieved technical success. Forty-eight (4.1%) distal access site complications were reported. Vessel perforations were seen in 13 (1.1%) interventions, vasospasm in 5 (0.4%), and acute distal occlusions in 5 (0.4%). Predefined subgroup analysis of prospective studies showed similar results (p=0.24). A retrograde approach to facilitate peripheral endovascular interventions is a safe and successful technique and should be considered when an antegrade approach is not possible or fails to cross the lesion. Because of missing data on long-term outcomes and methodological shortcomings, real world data of retrograde access in nonexpert centers remains necessary before this technique can be advised to all interventionists dealing with peripheral artery disease.


Exploiting symmetry properties of the discretizable molecular distance geometry problem.
The Discretizable Molecular Distance Geometry Problem (DMDGP) involves a subset of instances of the distance geometry problem for which some assumptions allowing for discretization are satisfied. The search domain for the DMDGP is a binary tree that can be efficiently explored by employing a Branch & Prune (BP) algorithm. We showed in recent works that this binary tree may contain several symmetries, which are directly related to the total number of solutions of DMDGP instances. In this paper, we study the possibility of exploiting these symmetries for speeding up the solution of DMDGPs, and propose an extension of the BP algorithm that we named symmetry-driven BP (symBP). Computational experiments on artificial and protein instances are presented.


Linking the Price of Cancer Drug Treatments to Their Clinical Value.
Appropriate pricing of medications is one of the ultimate goals for decision makers, but reliable data on the risk/benefit ratio are often lacking when a Marketing Authorization Application is submitted. Here we propose a method to consistently evaluate price adequacy, which we applied to six anticancer medications approved in Italy in recent years. We obtained ratios of cost per survival per day (cost/survival/day) by dividing the total costs of evaluated medications for the median survival gain in days. Each cost/survival/day corresponds to a crude score, with 0 assigned to a cost/survival/day ≥€586. The maximum price considered as adequate was €91 cost/survival/day (score 75) while a score of 100 corresponded to a cost/survival/day ≤€11, based on the thresholds set by the British National Health System (NHS) and the "willingness-to-pay" of the Italian NHS. Crude scores were then adjusted using correction factors for efficacy, safety, quality of life, and prevalence of disease. None of the analyzed medications (abiraterone, afatinib, aflibercept, bevacizumab, dabrafenib, and ipilimumab) achieved a final score of 75, corresponding to adequate pricing. The final score for afatinib was the highest with 55 points. Prices of all the other drugs resulted in being inadequate, with negative final scores for bevacizumab, dabrafenib, and ipilimumab. This method may be considered a tool for the evaluation of appropriateness of price proposed at negotiation and could represent a reliable resource for decision-making. Furthermore, this analysis suggests that most recently approved cancer drugs in Italy do not fulfill price adequacy.


Prevalence and risk factors for betaherpesvirus DNAemia in children >3 weeks and <2 years of age admitted to a large referral hospital in sub-Saharan Africa.
Betaherpesviruses are established causes of morbidity and mortality in immunosuppressed patient groups but have been little studied in sub-Saharan Africa, the epicenter of the human immunodeficiency virus (HIV) pandemic. In this region, primary infections with human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) type 6 are endemic in infancy, but the clinical impact of these infections among pediatric inpatient groups is poorly characterized and assumptive, based largely on data from Western populations. We used TaqMan polymerase chain reaction to screen sera from a group of 303 pediatric inpatients aged between 3 weeks and 2 years, at the University Teaching Hospital in Lusaka, Zambia. We report the prevalence of DNAemia and viral loads within this patient group, and evaluate possible clinical associations/risk factors for betaherpesvirus infections in these hospitalized children. We detected betaherpesvirus DNAemia in 59.1% (179/303) of children. HCMV was the most prevalent (41.3%), followed by HHV-6B (20.5%), HHV-7 (20.1%), and HHV-6A (0.3%). HIV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.37-3.90; P = .002), being underweight (OR, 1.82; 95% CI, 1.06-3.12; P = .03), and an admission diagnosis of suspected meningitis (OR, 5.72; 95% CI, 1.07-30.5; P = .041) were independently associated with an increased odds of HCMV DNAemia. Conversely, HHV-6B and HHV-7 DNAemia were not associated with HIV, underweight, or admission diagnosis. Median HCMV viral load was moderately but significantly higher in HIV-infected children. Highly prevalent HCMV DNAemia was independently associated with HIV infection and being underweight across all age groups, and was also associated with meningitis, with previously underappreciated implications for the health and development of African children.


Does bilevel positive airway pressure improve outcome of acute respiratory failure after open-heart surgery?
Respiratory failure is of concern in the postoperative period after cardiac surgeries. Invasive ventilation (intermittent positive pressure ventilation [IPPV]) carries the risks and complications of intubation and mechanical ventilation (MV). Noninvasive positive pressure ventilation (NIPPV) is an alternative method and as effective as IPPV in treating insufficiency of respiration with less complications and minimal effects on respiratory and hemodynamic parameters next to open-heart surgery. This is a prospective, randomized and controlled study. Forty-four patients scheduled for cardiac surgery were divided into two equal groups: Group I (IPPV) and Group II (NIPPV). Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), oxygen saturation (SpO2), arterial blood gas, weaning time, reintubation, tracheotomy rate, MV time, postoperative hospital stay, and ventilator-associated pneumonia during the period of hospital stay were recorded. There was statistically significant difference in HR between groups with higher in Group I at 30 and 60 min and at 12 and 24 h. According to MAP, it started to increase significantly at hypoxemia, 15 min, 30 min, 4 h, 12 h, and at 24 h which was higher in Group I also. RR, PaO2, and PaCO2showed significant higher in Group II at 15, 30, and 60 min and 4 h. According to pH, there was a significant difference between groups at 15, 30, and 60 min and at 4, 12, and 24 h postoperatively. SpO2showed higher significant values in Group I at 15 and 30 min and at 12 h postoperatively. Duration of postoperative supportive ventilation was higher in Group I than that of Group II with statistically significant difference. Complications were statistically insignificant between Group I and Group II. Our study showed superiority of invasive over noninvasive mode of ventilator support. However, NIPPV (bilevel positive airway pressure) was proved to be a safe method.


What midlife women want from gynecologists: a survey of patients in specialty and private practices.
This study characterized the self-reported reason for a gynecology visit among midlife women in three different practice settings. We hypothesized that women seeking specialty care were more likely to report nonvasomotor symptoms potentially related to the menopausal transition. Participants were 625 women aged 40-60 seen by gynecologists at three sites: an urban, academic, gynecologic menopause practice (Midlife Practice, or MLP) and urban (site A) and suburban (site B) locations of a general, nonacademic obstetrics and gynecology practice. Participants completed a self-report questionnaire asking them to choose and weigh the reason for their visit as "very much," "somewhat," or "not at all" for 15 common gynecologic and menopausal concerns. Demographic questions included age, self-rated health status, race/ethnicity, difficulty of paying for basics, and education. Comparisons between the three groups were made using parametric and nonparametric tests as appropriate. The main outcome measure was the response to the reason for participants' visit compared across the three sites. Women presenting to the MLP were significantly older and more likely to report vasomotor symptoms (VMS), moodiness, sexual problems, sleep problems, and weight and to learn more about menopause. When "very much" and "somewhat" reasons were combined, nearly 80% of the MLP responses listed sleep problems, 60% listed vaginal dryness or low desire, 34% listed weight gain, and 30.7% listed mood. Midlife women seeking care in a menopause gynecology practice had significantly more visits for vasomotor and nonvasomotor concerns than did women seeing general gynecologists. Women sought care for a broad range of concerns that are not typically in gynecologists' scope of practice, including sleep disturbances, moodiness, and weight management.


Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial.
The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes. As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549. 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA1c, blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07). Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant. National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA.


A novel role for uroguanylin in the regulation of sodium balance.
Uroguanylin is a peptide hormone that regulates sodium excretion by the kidney when excess NaCl is consumed. A new study demonstrates that mice deficient in uroguanylin have blunted urinary sodium excretion responses to oral sodium loads in addition to elevated blood pressure (see related article beginning on page 1244). A physiological role for uroguanylin is discussed, linking the intestine and kidney in an endocrine axis for the maintenance of sodium balance.