A multi-defense strategy: Enhancing bactericidal activity of a medical grade polymer with a nitric oxide donor and surface-immobilized quaternary ammonium compound.
Although the use of biomedical devices in hospital-based care is inevitable, unfortunately, it is also one of the leading causes of the nosocomial infections, and thus demands development of novel antimicrobial materials for medical device fabrication. In the current study, a multi-defense mechanism against Gram-positive and Gram-negative bacteria is demonstrated by combining a nitric oxide (NO) releasing agent with a quaternary ammonium antimicrobial that can be covalently grafted to medical devices. Antibacterial polymeric composites were fabricated by incorporating an NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) in CarboSil® polymer and top coated with surface immobilized benzophenone based quaternary ammonium antimicrobial (BPAM) small molecule. The results suggest that SNAP and BPAM individually have a different degree of toxicity towards Gram-positive and Gram-negative bacteria, while the SNAP-BPAM combination is effective in reducing both types of adhered viable bacteria equally well. SNAP-BPAM combinations reduced the adhered viable Pseudomonas aeruginosa by 99.0% and Staphylococcus aureus by 99.98% as compared to the control CarboSil films. Agar diffusion tests demonstrate that the diffusive nature of NO kills bacteria beyond the direct point of contact which the non-leaching BPAM cannot achieve alone. This is important for potential application in biofilm eradication. The live-dead bacteria staining shows that the SNAP-BPAM combination has more attached dead bacteria (than live) as compared to the controls. The SNAP-BPAM films have increased hydrophilicity and higher NO flux as compared to the SNAP films useful for preventing blood protein and bacterial adhesion. Overall the combination of SNAP and BPAM imparts different attributes to the polymeric composite that can be used in the fabrication of antimicrobial surfaces for various medical device applications. A significant increase in the biomedical device related infections (BDRIs), inability of the currently existing antimicrobial strategies to combat them and a proportional rise in the associated morbidity demands development of novel antimicrobial surfaces. Some of the major challenges associated with the currently used therapeutics are: antibiotic resistance and cytotoxicity. In the current study, engineered polymeric composites with multi-defense mechanism were fabricated to kill bacteria via both active and passive mode. This was done by incorporating a nitric oxide (NO) donor S-nitroso-N-acetypenicillamine (SNAP) in a medical grade polymer (CarboSil®) and a benzophenone based quaternary ammonium antimicrobial small molecule (BPAM) was surface immobilized as the top layer. The developed biomaterial was tested with Gram-positive and Gram-negative strains and was found to be effective against both the strains resulting in up to 99.98% reduction in viable bacterial count. This preventative strategy can be used to fabricate implantable biomedical devices (such as catheters, stents, extracorporeal circuits) to not only significantly limit biofilm formation but also to reduce the antibiotic dose which are usually given post infections.


Association between highly active antiretroviral therapy and selected cardiovascular disease risk factors in sub-Saharan Africa: a systematic review and meta-analysis protocol.
The increasing highly active antiretroviral therapy (HAART) coverage in sub-Saharan Africa (SSA) has been associated with increasing cardiovascular disease (CVD) incidence. However, the epidemiology of the association between HAART and CVD risk factors in SSA is sparse. We aim to assess the extent to which HAART is associated with selected cardiovascular risk factors (hypertension, diabetes, dyslipidaemia and metabolic syndrome) in SSA. This will be a systematic review and meta-analysis of published studies on the association between HAART and CVD risk factors retrieved from Medline, Embase, Popline, Africa-Wide Information, African Index Medicus and the Cochrane library databases. Studies will be screened for eligibility according to the selection criteria by two independent reviewers. Eligible studies will be assessed for the quality of their evidence and risk of bias using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Health Institute and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with respect to the measured outcomes (hypertension, diabetes, dyslipidaemia and metabolic syndrome). A data abstraction form will be produced on Epi info V.7 and data analysis done on STATA V.14 statistical software. Summary estimates of measures of effects for the association between HAART use and the outcomes will be derived. Random effects meta-analyses will be performed and I2 statistic used to assess for heterogeneity between studies with respect to measured parameters. Qualitative synthesis will be used where data is insufficient to produce quantitative synthesis. The protocol has been reviewed by the Research Governance & Integrity Office of the Research Ethics Committee of the London School of Hygiene and Tropical Medicine and confirmed as not requiring ethical approval. The findings of this study will be made widely available especially to national HIV/AIDS committees formulating HIV/AIDS guidelines for their respective settings. CRD42016042306; Pre-results.


Engaging cultural resources to promote mental health in Dutch LSES neighborhoods: study of a community-based participatory media project.
Community-based participatory media projects form a promising new strategy for mental health promotion that can help address the mental health-gap identified by the World Health Organization. (2008b) mhGAP, Mental Health Gap Action Programme: Scaling Up Care for Mental, Neurological and Substance Use Disorders. World Health Organization, Geneva. In this article we present an ethnographic study about a participatory media project that was developed to promote mental health in selected Dutch low socio-economic status neighborhoods. Through narrowcastings (group film viewings), participant observation and interviews we mapped the ways in which the media project effected and facilitated the collective sense-making process of the audience with regard to sources of stress impacting mental health and opportunities for action. These determinants of mental health are shaped by cultural dimensions, since the cultural context shapes everyday experiences of stress as well as the resources and skills to manage them. Our analysis shows that the media project engaged cultural resources to challenge stressful social scripts. We conclude that more attention should be paid to cultural narratives in a community to understand how health promotion strategies can support social resilience.


Association of the wild-type A/A genotype of MBL2 codon 54 with asthma in a North Indian population.
High serum MBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene polymorphisms thus control the serum levels of MBL as well as C3a and C5a. This is the first case-control study conducted in India, investigating the role of MBL2 codon 54 A/B polymorphism in asthma pathogenesis. A case-control study was performed with a total of 992 adult subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The MBL2 codon 54 A/B polymorphism was genotyped by PCR-RFLP. Statistical analysis for the codon 54 polymorphism revealed that the wild (A) allele was significantly associated with asthma with OR=1.9, 95% CI (1.4-2.4), and p< 0.001. The MBL2 codon 54 A/B polymorphism is significantly associated with asthma and its phenotypic traits as the wild (A/A) genotype confers a significant risk towards the disease in the studied North Indian population.


Ldlr-/-.Leiden mice develop neurodegeneration, age-dependent astrogliosis and obesity-induced changes in microglia immunophenotype which are partly reversed by complement component 5 neutralizing antibody.
Obesity has been linked to vascular dysfunction, cognitive impairment and neurodegenerative diseases. However, experimental models that recapitulate brain pathology in relation to obesity and vascular dysfunction are still lacking. In this study we performed the histological and histochemical characterization of brains from Ldlr-/-.Leiden mice, an established model for obesity and associated vascular disease. First, HFD-fed 18 week-old and 50 week-old Ldlr-/-.Leiden male mice were compared with age-matched C57BL/6J mice. We then assessed the effect of high-fat diet (HFD)-induced obesity on brain pathology in Ldlr-/-.Leiden mice and tested whether a treatment with an anti-complement component 5 antibody, a terminal complement pathway inhibitor recently shown to reduce vascular disease, can attenuate neurodegeneration and neuroinflammation. Histological analyses were complemented with Next Generation Sequencing (NGS) analyses of the hippocampus to unravel molecular pathways underlying brain histopathology. We show that chow-fed Ldlr-/-.Leiden mice have more severe neurodegeneration and show an age-dependent astrogliosis that is not observed in age-matched C57BL/6J controls. This was substantiated by pathway enrichment analysis using the NGS data which showed that oxidative phosphorylation, EIF2 signaling and mitochondrial dysfunction pathways, all associated with neurodegeneration, were significantly altered in the hippocampus of Ldlr-/-.Leiden mice compared with C57BL/6J controls. Obesity-inducing HFD-feeding did not aggravate neurodegeneration and astrogliosis in Ldlr-/-.Leiden mice. However, brains from HFD-fed Ldlr-/-.Leiden mice showed reduced IBA-1 immunoreactivity and increased CD68 immunoreactivity compared with chow-fed Ldlr-/-.Leiden mice, indicating alteration of microglial immunophenotype by HFD feeding. The systemic administration of an anti-C5 treatment partially restored the HFD effect on microglial immunophenotype. In addition, NGS data of hippocampi from Ldlr-/-.Leiden mice showed that HFD feeding affected multiple molecular pathways relative to chow-fed controls: HFD notably inactivated synaptogenesis and activated neuroinflammation pathways. The anti-C5 treatment restored the HFD-induced effect on molecular pathways to a large extent. This study shows that the Ldlr-/-.Leiden mouse model is suitable to study brain histopathology and associated biological processes in a context of obesity and provides evidence of the potential therapeutic value of anti-complement therapy against obesity-induced neuroinflammation.


Propofol requirement for induction of unconsciousness is reduced in patients with Parkinson's disease: a case control study.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85-2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53-2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.).


New Curcumin-Loaded Chitosan Nanocapsules: In Vivo Evaluation.
The medicinal applications of curcumin, the major component of Curcuma longa, are limited by its poor solubility and low oral bioavailability. In order to overcome this limitation, a method to produce nanocapsules of chitosan loaded with curcumin was developed. Three different molecular weight and deacetylation degree chitosan polymers were used in the formulation in order to prepare curcumin-loaded nanocapsules (mass ratio 1 : 1.4). The best results were achieved using chitosan-Bi with a molecular weight of 710 000 Da. A bimodal distribution was observed in samples; moreover, chitosan-Bi produced the lowest particle size (197 nm). The entrapment efficacy of all chitosan nanocapsules produced reached values between 75 and 92 %. Their rate of drug release at different pH levels (2.0 and 7.4) showed a fast onset of curcumin release. Swiss mice were used to determine oral and total bioavailability of the new curcumin-loaded nanocapsules. Remarkably, the bioavailability of curcumin nanoformulated increased 9-fold compared with no formulated curcumin. These nanocapsules have the ability to cross the blood-brain barrier, and its production is an easy to scale-up procedure using nontoxic materials.


Less radiation, better images.
It is explained in this paper that the use of fast film-screen combinations, despite their greater intrinsic unsharpness, can lead to much better image quality in the case of involuntary movements of the organs to be visualized. It is also demonstrated that in such cases the use of a large focus with high ratings can be preferable. Also discussed is the possible value of the modern intensifying screens, in which compounds of the group of the so-called 'rare earths' are contained in the luminescent layer.


[Endogenous protective effects of arachidonic acid epoxygenase metabolites, epoxyeicosatrienoic acids, in cardiovascular system].
The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.


Anemia predicts lower white matter volume and cognitive performance in sickle and non-sickle cell anemia syndrome.
Severe chronic anemia is an independent predictor of overt stroke, white matter damage, and cognitive dysfunction in the elderly. Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype. We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD). In the current study, we investigated whether patients with non-sickle anemia also have lower WM volumes and cognitive dysfunction. Magnetic Resonance Imaging was performed on 52 clinically asymptomatic SCD patients (age = 21.4 ± 7.7; F = 27, M = 25; hemoglobin = 9.6 ± 1.6 g/dL), 26 non-sickle anemic patients (age = 23.9 ± 7.9; F = 14, M = 12; hemoglobin = 10.8 ± 2.5 g/dL) and 40 control subjects (age = 27.7 ± 11.3; F = 28, M = 12; hemoglobin = 13.4 ± 1.3 g/dL). Voxel-wise changes in WM brain volumes were compared to hemoglobin levels to identify brain regions that are vulnerable to anemia. White matter volume was diffusely lower in deep, watershed areas proportionally to anemia severity. After controlling for age, sex, and hemoglobin level, brain volumes were independent of disease. WM volume loss was associated with lower Full Scale Intelligence Quotient (FSIQ; P = .0048; r2 = .18) and an abnormal burden of silent cerebral infarctions (P = .029) in males, but not in females. Hemoglobin count and cognitive measures were similar between subjects with and without white-matter hyperintensities. The spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia. Neurocognitive consequences of WM volume changes and silent cerebral infarction were strongly sexually dimorphic. Understanding the possible neurological consequences of chronic anemia may help inform our current clinical practices.


Hyperspectral Classification of Cyperus esculentus Clones and Morphologically Similar Weeds.
Cyperus esculentus (yellow nutsedge) is one of the world's worst weeds as it can cause great damage to crops and crop production. To eradicate C. esculentus, early detection is key-a challenging task as it is often confused with other Cyperaceae and displays wide genetic variability. In this study, the objective was to classify C. esculentus clones and morphologically similar weeds. Hyperspectral reflectance between 500 and 800 nm was tested as a measure to discriminate between (I) C. esculentus and morphologically similar Cyperaceae weeds, and between (II) different clonal populations of C. esculentus using three classification models: random forest (RF), regularized logistic regression (RLR) and partial least squares-discriminant analysis (PLS-DA). RLR performed better than RF and PLS-DA, and was able to adequately classify the samples. The possibility of creating an affordable multispectral sensing tool, for precise in-field recognition of C. esculentus plants based on fewer spectral bands, was tested. Results of this study were compared against simulated results from a commercially available multispectral camera with four spectral bands. The model created with customized bands performed almost equally well as the original PLS-DA or RLR model, and much better than the model describing multispectral image data from a commercially available camera. These results open up the opportunity to develop a dedicated robust tool for C. esculentus recognition based on four spectral bands and an appropriate classification model.


Evaluation of postural stability in youth athletes: the relationship between two rating systems.
The Balance Error Scoring System (BESS) has been documented as a useful way to evaluate postural control following sport-related concussions sustained by youth athletes. However, limitations have been reported with its use due to the reliance on visual observation as the primary measurement outcome. The primary purpose of this study was to examine the correlation between the modified BESS (mBESS) as rated by a clinician and a simultaneous analysis performed by an integrated video-force plate system. The secondary purpose was to assess if a history of prior concussion affected postural control. A group of healthy youth athletes (n = 398; mean age 13.7 ± 2.4 years) completed the mBESS while simultaneously undergoing an integrated video-force plate evaluation to measure postural stability. Spearman rank-order correlations were used to determine the strength of correlation between the 2 rating systems. In addition, performance on the mBESS between those with and without a history of concussion was compared using univariate ANCOVAs. A moderately high correlation was found during single-leg stance (ρ = -0.64, p < .001), while a weak correlation was found during tandem stance (ρ = -0.30, p < .001). No postural control differences were found between groups with and without a concussion history. The video-force plate rating system correlates well with the clinician rating during the single-leg stance of the mBESS, but not during double-leg or tandem stances. A history of concussion did not affect mBESS scores.


Influenza vaccination for healthy children.
Influenza virus infections cause vaccine-preventable but uncontrolled epidemic disease in the United States. Population dynamics dictate that the burden of disease will increase dramatically over the next 20 years if new strategies are not implemented. New weapons for the diagnosis, treatment and prevention of influenza are now available and should be implemented immediately. The impact of disease in children has been largely overlooked. Control measures should be focused on the prevention of disease in children, who have the highest annual attack rates. The new live attenuated nasal spray influenza vaccine is particularly effective in healthy children who would benefit most from universal immunization.


Semiparametric animal models via penalized splines as alternatives to models with contemporary groups.
Contemporary groups (CG) are used in genetic evaluation to account for systematic environmental effects of management, nutritional level, or any other differentially expressed group effect; however, because the functional form of the distribution of those effects is unknown, CG serve as an approximation to a time-varying mean. Conversely, in semiparametric models, there is no need to assume any functional form for the time-varying effects. In this research, we present a semiparametric animal model (AMS) using the covariate day of birth (DOB) by means of penalized splines (P-splines), as an alternative to fitting CG. In the AMS, the functionality of the data on DOB is expressed by means of a Basic segmented polynomial line (B-spline) basis, and proper covariance matrices are used to reflect the serial correlation among the points of support (or knots) at different times. Three different covariance matrices that reflect either short- or long-range dependences among knots are discussed. Different models were fitted to birth weight data from Polled Hereford calves. Models compared were an animal model with CG, an animal model with CG and the covariate DOB nested within CG (CG + DOB), and P-splines with the first difference penalty matrix and three different AMS with 20, 40, 60, 80, or 120 knots. Models were compared using a modified Akaike information criterion (AICC), which was calculated as a byproduct of the estimation of variance components by REML using the expectation maximization algorithm. All three AMS had smaller (better) values of AICC than the regular model with CG, while producing almost the same ranking of predicted breeding values and similar average predicted error variance. In all AMS, the inference and all measures of comparison were similar when the number of knots was equal > or = 40. The model CG + DOB had analogous performance to the AMS, but at the expense of using more parameters. It is concluded that the use of penalized regression splines using a B-spline basis with proper covariance matrices is a competitive method to the fitting of CG into animal models for genetic evaluation, without having to assume any functional form for the covariate DOB.


The impact of changing neonatal respiratory management on extracorporeal membrane oxygenation utilization.
The introduction of inhaled nitric oxide (INO) and high-frequency oscillatory ventilation (HFV) has had a profound effect on the use of extracorporeal membrane oxygenation (ECMO) for respiratory failure in neonates without congenital diaphragmatic hernia (CDH). The purpose of this study was to evaluate the changes in the demographics and outcome of non-CDH neonates who underwent ECMO for hypoxemic respiratory failure. All neonates (non-CDH and noncardiac) who underwent ECMO between January 1, 1989 and January 1, 2001 were reviewed. Patients were separated into 3, 4-year periods for comparison (period A, 1989 through 1992; B, 1993 through 1996; C, 1997 through 2000). Data were examined by analysis of variance and contingency table analysis. There was a progressive decline in the total number of neonates requiring ECMO over time (period A, 172; B, 114; C, 56; P <.01). The utilization of pre-ECMO alternate respiratory therapies such as INO (period A, 0%; B, 23%; C, 98%; P <.01) and HFV (period A, 9%; B, 61%; C, 89%; P <.01) have increased significantly associated with an increase in the age of ECMO initiation (Period A, 40.5 hours; B, 58.3 hours; C, 68.5 hours; P <.01). The length of ECMO run also has increased (period A, 154.7 hours; B, 193.0 hours; C, 174.5 hours; P <.01), but the overall mortality rate has remained unchanged. With the increasing use of INO and HFO, the absolute number of non-CDH, noncardiac neonates with hypoxemic respiratory failure requiring ECMO has decreased. Initiation of ECMO has become progressively later likely because of the use of these rescue therapies, but the overall mortality rate remains unchanged despite this delay.


How well do different measurement modalities estimate the number of vasomotor symptoms? Findings from the Study of Women's Health Across the Nation FLASHES Study.
Studies of vasomotor symptoms (VMS) typically measure VMS via daily diaries completed at the end of the day. VMS can also be measured via diaries completed throughout the day or via physiological monitors-modalities with lower recall demands. We examined the degree of correspondence between three VMS measurement modalities: retrospective end-of-day/morning diaries, prospective reporting, and physiological monitoring. We determined whether discrepancies between measurement modalities varied by participant characteristics. Twenty-five African-American women and 27 white women from the Pittsburgh site of the Study of Women's Health Across the Nation who were experiencing VMS, had intact uterus and ovaries, and were free of medications affecting VMS underwent 4 days of ambulatory VMS and Actiwatch monitoring. VMS were recalled in end-of-day and morning diaries, reported prospectively during the day, and measured physiologically via a hot flash monitor. Associations between anxiety, sleep, or race/ethnicity and VMS measurement modality difference scores were examined using generalized estimating equations. Women underestimated the number of daytime VMS at the end of the day as compared with VMS that were prospectively reported or physiologically measured throughout the day. This pattern was particularly pronounced among African-American women (b [SE] = -3.01 [0.93], P = 0.001) and women with higher anxiety (b [SE] = -3.13 [1.53], P = 0.04). For nighttime VMS, women overestimated the number of VMS in the morning upon waking as compared with prospective measures, particularly if they had poorer sleep (higher wakening after sleep onset: b [SE] = 0.03 [0.008], P = 0.001). Different measurement modalities yield different VMS estimates. Negative affect, sleep, and race/ethnicity may affect the recall of VMS.


Early bone formation adjacent to rough and turned endosseous implant surfaces. An experimental study in the dog.
To validate a proposed model (Berglundh et al. 2003) and to evaluate the rate and degree of osseointegration at turned (T) and sand blasted and acid etched (SLA) implant surfaces during early phases of healing. The devices used for the study of early healing had a geometry that corresponded to that of a solid screw implant with either a SLA or a T surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound chamber. Twenty Labrador dogs received totally 160 experimental devices to allow the evaluation of healing between 2 h and 12 weeks. Both ground and decalcified sections were prepared from mesial/distal and buccal/lingual device sites. Histometric and morphometric analyses of the ground sections and morphometric analysis of the tissue components in decalcified sections were performed. The ground sections provided an overview of the various phases of tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling for both SLA and T surfaces. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but on the SLA surface woven bone was also found at a distance from the parent bone. Parallel-fibered and/or lamellar bone as well as bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more bone-to-device contact, more initial woven bone and earlier lamellar bone formation was found than in the T chambers. Osseointegration represents a dynamic process both during its establishment and its maintenance. While healing showed similar characteristics with resorptive and appositional events for both SLA and T surfaces, the rate and degree of osseointegration were superior for the SLA compared with the T chambers.


Regular Physical Activity as a Potential Risk Factor for Erosive Lesions in Adolescents.
Tooth erosion is becoming an increasingly common dental problem among teenagers. The study aimed to determine risk factors for erosive lesions in young sports professionals. Participants were 155 students-102 physically active and 53 controls. The method included dental examination (including Basic Erosive Wear Examination) and a questionnaire concerning sports activity, dietary and hygienic habits. The sporting activity significantly correlated with erosive lesions (RSpearman = 0.344). The regression model incorporating the kind of sports activity, special diet and (non-)drinking water was statistically significant (p = 0.922 for the Hosmer-Lemeshow test) and strong enough to predict erosive lesions in young athletes (AUC = 0.758). Water sports professionals were almost 14 times more likely to suffer from erosive lesions than control students. Drinking water as the main beverage decreased the odds by about 70%. The graphical interpretation of multidimensional correspondence analysis confirms the predictive value of these factors. The kind of sports activity adjusted by the main beverage and a special diet was the best variable to predict erosive lesions among teenagers. Early proper diagnosis with defined risk factors leads to better prevention and successful treatment.


Thirty years of human infections caused by Yersinia enterocolitica in northern Spain: 1985-2014.
Yersinia enterocolitica infection is a zoonosis with worldwide distribution, gastroenteritis being by far the most common clinical manifestation of human infection. In Gipuzkoa, northern Spain, human Y. enterocolitica infections increased from the mid-1980s to the beginning of the 21st century (from 7·9 to 23·2 annual episodes per 100 000 population) to decrease to 7·2 annual episodes per 100 000 population in the last years of the study. The hospital admission rate due to yersiniosis during the last 15 years of the study was 7·3%. More than 99% of isolates were serotype O:3. Infection affected mainly children under 5 years of age (average rate: 140 episodes per 100 000 population). The incidence in adults was low but hospitalisation increased with age, exceeding 50% in people over 64 years old.


Partial EMT in Squamous Cell Carcinoma: A Snapshot.
In the process of cancer EMT, some subgroups of cancer cells simultaneously exhibit both mesenchymal and epithelial characteristics, a phenomenon termed partial EMT (pEMT). pEMT is a plastic state in which cells coexpress epithelial and mesenchymal markers. In squamous cell carcinoma (SCC), pEMT is regulated, and the phenotype is maintained via the HIPPO pathway, NOTCH pathway and TGF-β pathways and by microRNAs, lncRNAs and the cancer microenvironment (CME); thus, SCC exhibits aggressive tumorigenic properties and high stemness, which leads collective migration and therapy resistance. Few studies have reported therapeutic interventions to address cells that have undergone pEMT, and this approach may be an effective way to inhibit the plasticity, drug resistance and metastatic potential of SCC.


Senhance robotic radical prostatectomy: A single-centre, 3-year experience.
Senhance Surgical System is a novel robotic platform used in University Hospital Centre Zagreb since February 2019. In this study, we present our 3-year experience with this platform. Data were prospectively collected for 200 patients who underwent extraperitoneal robotic radical prostatectomy (RRP) from May 2019 to March 2022. The median age of the patients was 65 years, and the prostate-specific antigen was 6.9 ng/mL. Clinically, most of the patients had T1c stage. The estimated blood loss was 250 mL, and there were 6 conversions to laparoscopic and 2 to open prostatectomy. There were 15 early postoperative complications, 11 Clavien-Dindo classification grade I, 3 grade II and 1 grade IV. Functional outcomes in the first 150 patients: 140 patients (93.3%) had good urinary control. Thirteen patients underwent additional oncological treatment. RRP performed with the Senhance robotic platform is a feasible and safe procedure with good initial results.


Anthocyanins as inflammatory modulators and the role of the gut microbiota.
The health benefits of consuming fruits that are rich in polyphenols, especially anthocyanins, have been the focus of recent in vitro and in vivo investigations. Thus, greater attention is being directed to the reduction of the inflammatory process associated with the intestinal microbiota and the mechanism underlying these effects because the microbiota has been closely associated with the metabolism of these compounds in the gastrointestinal tract. Further interest lies in the ability of these metabolites to modulate the growth of specific intestinal bacteria. Thus, this review examines studies involving the action of the anthocyanins that are present in many fruits and their effect in the modulating the inflammatory process associated with the interaction between the host and the gut microbiota. The findings of both in vitro and in vivo studies suggest a potential antiinflammatory effect of these compounds, which seem to inhibit activation of the signaling pathway mediated by the transcription factor NFκB. This effect is associated with modulation of a beneficial gut microbiota, particularly an increase in Bifidobacterium strains.


A Comparative Study of Retrorectus Mesh Placement Versus Properitoneal Mesh Placement in Open Repairs of Ventral Hernias.
Background Ventral hernias affect millions of patients each year. Surgery is the main line of management and various techniques have been advocated; however, mesh repair has become the norm and different approaches have been described regarding the plane of mesh fixation, but none of them are standardized. Open repair is commonly practiced, and the two most commonly performed methods are retrorectus and properitoneal mesh placement. Objectives To compare the postoperative outcomes between the retrorectus plane and the properitoneal plane of fixation of mesh in open ventral hernia repair. Methods Between September 2018 and August 2020, 56 patients with midline ventral hernia admitted to Ramaiah Hospital, Bengaluru were chosen for this prospective comparative study. Group A had 28 patients who underwent open retrorectus mesh repair and 28 patients in Group B underwent open properitoneal mesh repair. The postoperative outcomes were studied in terms of operating time, postoperative complications, and early recurrence at the end of six months and 24 months post-surgery. Results The operative time for retrorectus mesh placement was significantly lower than properitoneal mesh placement. The latter had a higher complication rate overall with an incidence of 18%, with seroma being the most common complication; however, the difference in complication rates was not statistically significant. Skin necrosis was identical in both groups and 0% of cases in both groups had SSI or mesh infection. Three patients (10.71%) in the retrorectus group and two patients (7.10%) in the properitoneal group developed recurrence at 24 months follow-up. Conclusion Retrorectus mesh repair and properitoneal mesh repair in open ventral abdominal hernias have equally good postoperative outcomes.


Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae.
Inverted DNA repeats are an at-risk motif for genetic instability that can induce both deletions and recombination in yeast. We investigated the role of the length of inverted repeats and size of the DNA separating the repeats for deletion and recombination. Stimulation of both deletion and recombination was directly related to the size of inverted repeats and inversely related to the size of intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted repeats, increased intra- and interchromosomal recombination in the adjacent region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin of replication in the spacer reduced both rates of deletion and recombination. These results support a model in which the stimulation of deletion and recombination by inverted repeats is initiated by a secondary structure formed between single-stranded DNA of inverted repeats during replication.


Upper gastrointestinal hemorrhage caused by superwarfarin poisoning.
Superwarfarins are a class of rodenticides. Gastrointestinal hemorrhage is a fatal complication of superwarfarin poisoning, requiring immediate treatment. Here, we report a 55-year-old woman with tardive upper gastrointestinal hemorrhage caused by superwarfarin poisoning after endoscopic cold mucosal biopsy.


A Pattern-Based Approach for Detecting Pneumatic Failures on Temporary Immersion Bioreactors.
Temporary Immersion Bioreactors (TIBs) are used for increasing plant quality and plant multiplication rates. These TIBs are actioned by mean of a pneumatic system. A failure in the pneumatic system could produce severe damages into the TIB. Consequently, the whole biological process would be aborted, increasing the production cost. Therefore, an important task is to detect failures on a temporary immersion bioreactor system. In this paper, we propose to approach this task using a contrast pattern based classifier. We show that our proposal, for detecting pneumatic failures in a TIB, outperforms other approaches reported in the literature. In addition, we introduce a feature representation based on the differences among feature values. Additionally, we collected a new pineapple micropropagation database for detecting four new types of pneumatic failures on TIBs. Finally, we provide an analysis of our experimental results together with experts in both biotechnology and pneumatic devices.


Input-output organization of jaw movement-related areas in monkey frontal cortex.
The brain mechanisms underlying mastication are not fully understood. To address this issue, we analyzed the distribution patterns of cortico-striatal and cortico-brainstem axon terminals and the origin of thalamocortical and intracortical fibers by injecting anterograde/retrograde tracers into physiologically and morphologically defined jaw movement-related cortical areas. Four areas were identified in the macaque monkey: the primary and supplementary orofacial motor areas (MIoro and SMAoro) and the principal and deep parts of the cortical masticatory area (CMaAp and CMaAd), where intracortical microstimulation produced single twitch-like or rhythmic jaw movements, respectively. Tracer injections into these areas labeled terminals in the ipsilateral putamen in a topographic fashion (MIoro vs. SMAoro and CMaAp vs. CMaAd), in the lateral reticular formation and trigeminal sensory nuclei contralaterally (MIoro and CMaAp) or bilaterally (SMAoro) in a complex manner of segregation vs. overlap, and in the medial parabranchial and Kölliker-Fuse nuclei contralaterally (CMaAd). The MIoro and CMaAp received thalamic projections from the ventrolateral and ventroposterolateral nuclei, the SMAoro from the ventroanterior and ventrolateral nuclei, and the CMaAd from the ventroposteromedial nucleus. The MIoro, SMAoro, CMaAp, and CMaAd received intracortical projections from the ventral premotor cortex and primary somatosensory cortex, the ventral premotor cortex and rostral cingulate motor area, the ventral premotor cortex and area 7b, and various sensory areas. In addition, the MIoro and CMaAp received projections from the three other jaw movement-related areas. Our results suggest that the four jaw movement-related cortical areas may play important roles in the formation of distinctive masticatory patterns.


[Survival of patients with gastric cancer treated with intra-lymph nodal injection of activated carbon particles absorbed mitomycin C].
We studied the efficacy of the intra-lymph nodal injection of the activated carbon particle absorbed mitomycin C (MMC-CH40) for gastric cancer. Ninety-five patients with gastric cancer underwent gastrectomy with D1 or D2 lymph node dissection. Of these, 38 patients were treated with intra-lymph nodal injection of MMC-CH 40 (MMC-CH 40 group). The other 57 patients were classified into the control group. The survival of MMC-CH group was significantly higher than that of the control group using generalized Wilcoxon method. However, since the percentage of stage IV was higher in the control group than in MMC-CH 40 group, the survivals of subgroups of stage I-III were compared. Although the percentage of the early gastric cancer was higher in the control group of stage I-III (n = 35) than in the MMC-CH group of stage I-III (n = 38), the survival curves of MMC-CH group were higher than in the control group. The difference in survival between the two groups was significant at 8 months after surgery. These results indicate that this new therapy improves survival in patients with stage I-III gastric cancer.


Delayed treatment of tuberculosis patients in rural areas of Yogyakarta province, Indonesia.
In year 2000, the entire population in Indonesia was 201 million and 57.6 percent of that was living in rural areas. This paper reports analyses that address to what extent the rural structure influence the way TB patients seek care prior to diagnosis by a DOTS facility. We documented healthcare utilization pattern of smear positive TB patients prior to diagnosis and treatment by DOTS services (health centre, chest clinic, public and private hospital) in Yogyakarta province. We calculated the delay in treatment as the number of weeks between the onset of symptoms and the start of DOTS treatment. Statistical analysis was carried out with Epi Info version 3.3 (October 5, 2004). The only factor which was significantly associated with total delay was urban-rural setting (p = < 0.0001). The median total delay for TB patients in urban districts was 8 (1st Quartile = 4; 3rd Quartile = 12) weeks compared to 12 (1st Quartile = 7; 3rd Quartile = 23) weeks for patients in rural districts. Multivariate analysis suggested no confounding between individual factors and urban-rural setting remained as the main factor for total delay (p = < 0.0001). Primary health centre was the first choice provider for most (38.7%) of these TB patients. Urban-rural setting was also the only factor which was significantly associated with choice of first provider (p = 0.03). Improving access to DOTS services in rural areas is an area of vital importance in aiming to make progress toward achieving TB control targets in Indonesia.


Menière's disease: role of antibodies against basement membrane antigens.
Recently, high levels of anti-collagen II (CII) antibodies have been found in a significant percentage of patients with Menière's disease (MD). An immune response against other collagens (C) present in the basal membranes has also been suggested by the presence of anti-CIV and anti-laminin antibodies in a number of instances of progressive systemic sclerosis (PSS) and Raynaud's phenomenon (RP). The aim of the present study was to measure the levels and frequency of anti-CI, -CII, -CIV, -CV, and anti-laminin antibodies by enzyme-linked immunosorbent assay (ELISA) in 45 patients affected by MD, 24 patients with PSS, 24 patients with RP, and 25 normal subjects. Immunoglobulin G (IgG) anti-CII antibodies were detected in 15.5% of MD sera, and 6.6% of MD sera were positive on CV, 11.1% were positive on laminin, 4.4% were positive on CI, and 4.4% were positive on CIV. A low incidence of anti-CI, -CII, -CIV, -CV, and antilaminin antibodies was found. Positive sera did not react on immunoblot with peptides obtained by cyanogen bromide (CNBr) digestion of CII. These results contrast with those of Yoo, et al.; differences in the washing procedure used and in the ethnic background of the patients may explain this divergence. Our results would seem to indicate that autoimmune responses do not play a role in the pathogenesis of MD.


Computed tomographic imaging of cerebral venous thrombosis.
Cerebral venous thrombosis (CVT) is an entity which is not rare and can have devastating consequences if not diagnosed and treated in a timely manner. Although, the gold standard for diagnosing this entity is a catheter angiogram, magnetic resonance venography, by virtue of its non-invasiveness and detailed demonstration of the cerebral venous structures, has become the diagnostic modality of choice for this entity. However, in a resource-strapped country like Pakistan, CT scan remains the primary first (and sometimes the only) diagnostic modality used in patients with neurological problems. Therefore, it is important to recognize the signs of cerebral venous thrombosis on CT scan in order to initiate timely therapy. These CT findings of CVT are discussed in this paper. The CT findings of CVT have been divided into direct and indirect findings and the same have been described for noncontrast and postcontrast CT scans separately. A brief discussion of CT venography, which has come around as a promising tool for diagnosing CVT as a result of newer innovations in CT technology, is also included here.


Left ventricular pseudoaneurysm by cardiac CT angiography.
Although left ventricular (LV) pseudoaneurysm is seen infrequently, it should be recognized and distinguished from the common type of left ventricular aneurysm. The diagnosis can be difficult and the lesions are prone to rupture, thus the condition is associated with a high rate of morbidity and mortality. LV pseudoaneurysms are the result of a contained rupture of the free wall of the myocardium, with the containment being provided by adherent pericardium or scar tissue. Among patients dying of infarction, 17% have been found to have ruptured the heart through the infarcted area. Rupture of the free wall is four to five times more common than septal rupture and is usually immediately fatal. We present images of a LV pseudoaneurysm in a patient with a past history of coronary bypass grafting who underwent computed tomographic angiography for evaluation of his bypass vessels.


Major alkaloids of Glaucium flavum Grantz, population Ghom.
Glaucium flavum Grantz, population Ghom, contains 1.24% dicentrine, 0.89% bulbocapnine, and 0.05% salutaridine in dry aerial parts and root of the flowering plant. These alkaloids were detected for the first time in the Glaucium genus.


Nodular fasciitis of the male breast: a case report.
A case of nodular fasciitis is reported that involved the breast parenchyma of a 40-year-old man. The differential diagnosis of nodular fasciitis in the male breast mainly includes fibromatosis and myofibroblastoma. However, other benign and malignant spindle cell lesions of the breast, such as pseudoangiomatous stromal hyperplasia and especially spindle cell metaplastic carcinoma and fibrosarcoma, may enter the differential. The classic histomorphologic features and immunohistochemical findings are helpful in arriving at the correct diagnosis. The patient underwent a total excision of the lesion and is free of disease after 14 months. To our knowledge, this is the first reported case of a lesion of this type in the male breast.


Antidiabetic and gastric emptying inhibitory effect of herbal Melia azedarach leaf extract in rodent models of diabetes type 2 mellitus.
Diabetes type 2 is associated with impaired insulin production and increased insulin resistance. Treatment with antidiabetic drugs and insulin strives for normalizing glucose homeostasis. In Ethiopian traditional medicine, plant extracts of Melia azedarach are used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects of M. azedarach leaf extracts in diabetic type 2 experimental animals. In this study, mice were injected with Melia extract intraperitoneally. Plasma glucose was studied by using tail vein sampling in acute experiments over 4 h and chronic experiments over 21 days with concurrent insulin and body weight assessments. Glucose tolerance was studied by using intraperitoneal glucose (2 mg/g) tolerance test over 120 min. Gastric emptying of a metabolically inert meal was studied by the gastric retention of a radioactive marker over 20 min. Melia extracts displayed acute, dose-dependent antidiabetic effects in ob/ob mice similar to glibenclamide (p<0.05-0.001). Long-term administration of Melia extract reduced plasma glucose (p<0.001) and insulin (p<0.01-0.001) levels over 21 days, concurrent with body weight loss. Glucose tolerance test showed reduced basal glucose levels (p<0.05-0.01), but no difference was found in glucose disposal after long-term treatment with Melia extract. In addition, the Melia extract at 400 mg/kg slowed gastric emptying rate of normal Sprague-Dawley (p<0.001) and diabetic Goto-Kakizaki rats (p<0.001) compared with controls. It is concluded that the M. azedarach leaf extract elicits diabetic activity through a multitargeted action. Primarily an increased insulin-sensitizing effect is at hand, resulting in blood glucose reduction and improved peripheral glucose disposal, but also through reduced gastric emptying and decreased insulin demand.


Lessons from the Field Beyond the Numbers: Narratives of Professionals on Women who Experienced Severe Maternal Morbidity.
Several factors might affect the health and the quality of life of women who had a severe maternal morbidity (SMM) or a maternal near-miss (MNM) episode. The objective of the present study was to explore the perspectives of the professionals on the repercussions of SMM or of MNM after interviewing women who survived such episodes. Selected cases that captured the attention of professionals were reported. The professionals built individually 10 narratives, which were analyzed with the technique of content analysis. According to the perspectives of the professionals, women surviving a severe maternal condition and their families experienced clinical and psychosocial consequences. Some cases portrayed the intense psychological distress in mourning for the loss of the fetus or of their reproductive capacity and changes in family dynamics generating emotional overload, depression, and gender violence. The analysis of narratives may offer an idea on the complexity of the perception of care by professionals and on the need for an interdisciplinary follow-up of women surviving an SMM or an MNM episode.


Reanalysis of EphA3 Knock-In Double Maps in Mouse Suggests That Stochasticity in Topographic Map Formation Acts at the Retina Rather than between Competing Mechanisms at the Colliculus.
It has been suggested that stochasticity acts in the formation of topographically ordered maps in the visual system through the opposing chemoaffinity and neural activity forces acting on the innervating nerve fibers being held in an unstable equilibrium. Evidence comes from the Islet2-EphA3 knock-in mouse, in which ∼50% of the retinal ganglion cells, distributed across the retina, acquire the EphA3 receptor, thus having an enhanced density of EphA which specifies retinotopic order along the rostrocaudal (RC) axis of the colliculus. Sampling EphA3 knock-in maps in heterozygotes at different positions along the mediolateral (ML) extent of the colliculus had found single 1D maps [as in wild types (WTs)], double maps (as in homozygous knock-ins) or both single and double maps. We constructed full 2D maps from the same mouse dataset. We found either single maps or maps where the visual field projects rostrally, with a part-projection more caudally to form a double map, the extent and location of this duplication varying considerably. Contrary to previous analyses, there was no strict demarcation between heterozygous and homozygous maps. These maps were replicated in a computational model where, as the level of EphA3 was increased, there was a smooth transition from single to double maps. Our results suggest that the diversity in these retinotopic maps has its origin in a variability over the retina in the effective amount of EphA3, such as through variability in gene expression or the proportion of EphA3+ retinal ganglion cells, rather than the result of competing mechanisms acting at the colliculus.


Broadband infrared photoluminescence in silicon nanowires with high density stacking faults.
Making silicon an efficient light-emitting material is an important goal of silicon photonics. Here we report the observation of broadband sub-bandgap photoluminescence in silicon nanowires with a high density of stacking faults. The photoluminescence becomes stronger and exhibits a blue shift under higher laser powers. The super-linear dependence on excitation intensity indicates a strong competition between radiative and defect-related non-radiative channels, and the spectral blue shift is ascribed to the band filling effect in the heterostructures of wurtzite silicon and cubic silicon created by stacking faults.


Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults.
To investigate different proxies of brain and cognitive reserve as potential mediators of the effect of cortical thinning on cognition in healthy middle-aged adults. Eighty-two middle-aged individuals were included (mean(SD) age=45.1(3.9)years). Cortical thickness was calculated for multiple brain regions using FreeSurfer. Cognitive measures sensitive to early cognitive decline were selected, including Block Design from the Wechsler Adult Intelligence Scale-III (WAIS-III), Judgment of Line Orientation Test (JLOT), Color Trails Test (CTT), and first learning trial of TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). Brain reserve was operationalized as total intracranial volume (TIV); and cognitive reserve was estimated by means of Years of Education, WAIS-III Vocabulary subtest, WAIS-III Information subtest, and a Cognitive Reserve Questionnaire (CRQ). Mediation effects were investigated with multiple linear regression and bootstrapping analysis. Information and Vocabulary showed the greatest mediation capacity. All the observed mediations were positive indicating that higher levels of reserve attenuate the effect of reduced cortical thickness on cognition. Information, Vocabulary and TIV buffered the effect of frontal thinning on Block Design; Vocabulary and Years of Education buffered the effect of frontal thinning on JLOT; and CRQ buffered the effect of temporal thinning on CTT. Higher reserve buffers the effect of cortical thinning on cognition in healthy middle-aged adults. The investigated proxies might be underpinned by slightly different neural networks. Advancing in the understanding of the influences of reserve in healthy middle-aged adults is crucial to facilitate early interventions.


Life Cycle of Peanut (Arachis hypogaea L.) Plant in Vitro.
Alteration of generations in peanut plants was examined by the culturing of seeds. Flowers were induced in more than 50% of the seed cultures in vitro. Benzyl aminopurine stimulated the rate of flower induction most among the factors examined. Development of pegs was stimulated by gibberellic acid given after flowering. Dark culture allowed the development of ovaries in pegs to immature seeds and then to mature seeds; with this, the life cycle of the peanut plant was complete. Mature seeds excised from the original cultures germinated normally in vitro, and the cotyledonary nodes proliferated multiple shoots on shoot-forming medium. Alteration of generations and the in vitro omission of certain steps of the life cycle in plants are discussed.


Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²⁺ balance protein levels.
Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX.


[Quantification of left-to-right shunt in atrial septal defect using oximetry, isotopes, and Doppler echocardiography. Is there a method of reference?].
Determination of pulmonary to systemic blood flow ratio (QP/QS) is considered to be important for the management of patients with atrial septal defect. The QP/QS provides information on shunt severity and is usually determined by three methods: oximetry, first-pass radionuclide angiocardiography and Doppler echocardiography. The aim of the present study was to assess the accuracy and concordance level of these three methods in QP/QS quantification in atrial septal defects. Sixty-four adult atrial septal defects patients in whom QP/QS was determined by these three methods with a 6 month interval were studied. Nuclear and echocardiographic post-surgical studies were repeated in 36 patients. QP/QS values determined by the three techniques had a low correlation between them: oximetry (r = 0.52; SEE = 0.74); radionuclide angiocardiography (r = 0.40; SEE = 0.79) and Doppler echocardiography (r = 0.72; SEE = 0.57). Radionuclide angiocardiography underestimated QP/QS > 3 (-0.61 +/- 1.21; p < 0.01). Only in 33% of studies there concordance (differences < 0.5) among the three methods and in 58% between two methods. Right ventricular dilatation and tricuspid regurgitation influenced radionuclide accuracy. Nevertheless, the correlation between this technique and echocardiography was satisfactory when the 36 post-surgical were included (r = 0.75); both techniques agreed in the diagnosis of the two cases with residual post-surgical shunt. Inter-method disparity in QP/QS quantification is high and no method can be used as a gold standard; clinical decisions therefore based on QP/QS quantification by one technique alone are ill-advised.


Stimulatory and inhibitory effects of substance P on rat submandibular secretion.
Intravenous infusions of the undecapeptide substance P caused a moderate but transient secretory response from the rat submandibular gland. The electrolyte composition of the saliva elicited by this peptide was qualitatively similar to that of the secretion induced by parasympathomimetic agents. Substance P inhibited the secretory response to acetylcholine and isoproterenol, but did not modify the binding of specific ligands to glandular autonomic receptors. It is concluded that this naturally occurring peptide plays a role in the physiologic regulation of salivary secretions, which involves both direct stimulatory effects and a modulating action on the effect of autonomic neurotransmitters on the salivary gland cells. The latter may involve similar effects of substance P and the neurotransmitters on a metabolic pathway localized beyond receptor activation.


[Sulfasalazine in rheumatoid arthritis].
Sulfasalazine (SLZ) is now a second-line treatment in rheumatoid arthritis (RA), as well as in psoriatic arthritis and ankylosing spondylitis. 54 patients with active RA were treated with enteric coated SLZ (2 g daily) in a 24-week open study. Clinical and laboratory parameters of disease activity were monitored initially and thereafter at 2-week intervals for the first 2 months, and then at 4-week intervals until the end of the 24-week study. There was significant clinical improvement at the end, as shown by scores for joint pain (Ritchie), grip strength and morning stiffness (p less than 0.0001, less than 0.0001 and less than 0.01, respectively, by paired t test). Clinical improvement was accompanied by significant decrease in erythrocyte sedimentation rate and increase in hemoglobin (p less than 0.002 and less than 0.016, respectively). There was improvement in some cases as early as 3 weeks after starting therapy. The drop-out rate was significant: 19/54 (35%), most (13) due to side-effects, mainly gastrointestinal; none of the side-effects were serious. Our results, similar to those of other studies, indicate that despite the high rate of side effects, SLZ is an effective, second-line drug for RA.


Colorectal Cancer-Derived Small Extracellular Vesicles Promote Tumor Immune Evasion by Upregulating PD-L1 Expression in Tumor-Associated Macrophages.
Tumor-associated macrophages (TAMs) are one of the most abundant cell types in colorectal cancer (CRC) tumor microenvironment (TME). Recent studies observed complicated "cross-talks" between cancer cells and macrophages in TME. However, the underlying mechanisms are still poorly elucidated. Here, PD-L1 levels are very low in CRC cells but highly abundant in TAMs, and a specific PD-L1+CD206+ macrophage subpopulation are identified, which is induced by tumor cells and associated with a poor prognosis. Mechanistic investigations reveal that CRC cells can secrete small extracellular vesicles (sEVs) taken up by macrophages that induce M2 like polarization and PD-L1 expression, resulting in increased PD-L1+CD206+ macrophage abundance and decreased T cell activity in CRC TME. sEV-derived miR-21-5p and miR-200a are identified as key signaling molecules mediating the regulatory effects of CRC on macrophages. Further studies reveal that CRC-derived miR-21-5p and miR-200a synergistically induces macrophage M2 like polarization and PD-L1 expression by regulating the PTEN/AKT and SCOS1/STAT1 pathways, resulting in decreased CD8+ T cell activity and increased tumor growth. This study suggests that inhibiting the secretion of specific sEV-miRNAs from CRC and targeting PD-L1 in TAMs may serve as novel methods for CRC treatment as well as a sensitization method for anti-PD-L1 therapy in CRC.


A new case of 13q12.2q13.1 microdeletion syndrome contributes to phenotype delineation.
A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely, KATNAL1, LINC00426, and HMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified a de novo microdeletion at 13q12.2q13.1 spanning 3-3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.


How families cope with diabetes in adolescence. An approach and case analyses.
In this paper we describe our newly constructed Family Coping Coding System. This scheme was constructed to identify family coping strategies that involve appraisal, problem solving, and emotion management dimensions. We discuss the theoretical rationale, meanings and reliability of the coping codes, and illustrate them through excerpts drawn from family discussions of a recent stressful situation (the onset of a chronic or acute illness in an adolescent member). Finally, we consider the clinical research relevance of this new assessment technique, exemplifying this potential with respect to medical compliance. We present analyses of two families with diabetic adolescents who strikingly differ with respect to compliance, and explore which family coping strategies may be predictive of an adolescent's favorable or problematic compliance to diabetes management.


[Airway Management Utilizing an air-Q blocker in a Patient with Motor Neuron Disease and Soft Palate Paralysis].
A 67-year-old woman suffering from hoarseness or dysphagia was diagnosed with motor neuron disease. She was scheduled for laparoscopic cholecystectomy under general anesthesia for suspected gallbladder cancer. She was concerned about the exacerbation of her hoarseness or dysphagia from tracheal intubation. We therefore decided to perform airway management by using supraglottic device air-Q blocker, through which a gastric tube could be inserted. We first passed the gastric tube through the outer blocker hole and inserted it into the esophagus using Magill forceps. The air-Q blocker was placed position under the guidance of a McGrath videolaryngoscope. Sealing pressure was over 20 cmH2O and mechanical ventilation was performed uneventfully during artificial pneumoperitoneum. We were able to deflate the stomach and perform tracheal suction via the inner hole of the air-Q. Following the operation, the patient developed neither hoarseness nor pharyngeal pain.


Pre-Test and Post-Test Applications to Shape the Education of Phlebotomists in A Quality Management Program: An Experience in a Training Hospital.
After the introduction of modern laboratory instruments and information systems, preanalytic phase is the new field of battle. Errors in preanalytical phase account for approximately half of total errors in clinical laboratory. The objective of this study was to share an experience of an education program that was believed to be successful in decreasing the number of rejected samples received from the Emergency Department (ED). An education program about laboratory procedures, quality requirements in the laboratory, patient and health-care worker safety was planned by the quality team to be performed on 36 people who were responsible for sample collection in the ED. A questionary which included 11 questions about the preanalytic phase was applied to all the attendees before and after training. The number of rejected samples per million was discovered with right proportion account over the number of accepted and rejected samples to laboratory after and before the training period. Most of the attendees were nurses (n: 22/55%), with over 12 years of experience in general and 2-4 years experience in the ED. Knowledge level of the attendees was calculated before training as 58.9% and after training as 91.8%. While the total rate of sample rejection before training was 2.35% (sigma value 3.37-3.50), the rate after training was 1.56% (sigma value 3.62-3.75). Increasing the knowledge of staff has a direct positive impact on the preanalytic phase. The application of a pre-test was observed to be a feasible tool to shape group specific education programs.


Femtosecond and picosecond fluorescence of native bacteriorhodopsin and a nonisomerizing analog.
The spectrally and temporally resolved fluorescence properties of native bacteriorhodopsin (bR) and bR reconstituted with a nonisomerizing analog of the retinal Schiff base (bR5.12) are examined. The first attempt to experimentally monitor the excited state relaxation processes in both type of pigments using ultrafast fluorescence spectroscopy is reported. The fluorescence is emitted from retinal molecules in an all-trans configuration. Substantial energy relaxation involves very fast intramolecular and intermolecular vibrational modes and these are shown to occur on a time scale faster than isomerization. The possible contribution of dielectric interaction between the retinal Schiff base and the protein environment for the excited state energy relaxation is discussed.


Effects of acute aerobic exercise on high-molecular-weight adiponectin.
Few studies have reported the response of high-molecular-weight (HMW) adiponectin to acute aerobic exercise. The purpose of this study was to investigate the influence of acute aerobic exercise on HMW adiponectin in healthy men. Eight healthy men (age, 24.9 +/- 1.8 yr; BMI, 21.9 +/- 0.5 kg x m) participated in this study. They performed two trials. Trial 1 [exercise trial (EX)] consisted of 60-min stationary cycle exercise (50% peak oxygen uptake) followed by 30-min rest. Trial 2 [control trial (CON)] was 90-min rest. Blood samples were drawn to assess hormones (catecholamine and insulin), metabolites (free fatty acid [FFA], glycerol, and glucose), and total and HMW adiponectin concentration. There were significant trial x group interactions in serum FFA and glycerol concentrations (P < 0.05). Serum FFA and glycerol concentrations were higher in EX than in CON (P < 0.05). There were significant trial x group interactions in plasma insulin and glucose concentration (P < 0.05). Plasma insulin and glucose concentrations were lower in EX than in CON (P < 0.05). Total adiponectin, HMW adiponectin concentration, and the ratio of HMW to total adiponectin concentration, however, were unchanged during aerobic exercise and postexercise. Also, those changes did not differ between EX and CON. Our results indicate that total adiponectin and HMW adiponectin concentrations are not regulated by the change of hormones or metabolites during acute moderate-intensity aerobic exercise and postexercise in healthy young men.


Aripiprazole in an adult with Asperger disorder.
To report a case of aripiprazole-responsive adult Asperger disorder. A 34-year-old white man with lifelong, disabling Asperger disorder and a 20-year history of failed psychotherapeutic and pharmacologic interventions was prescribed aripiprazole, with dramatic symptomatic improvement. Multiple prior pharmacologic efforts over several years aimed predominantly at altering serotonin and dopamine neurotransmission resulted in treatment failure due to intolerable adverse effects, exacerbation of underlying symptoms, or nonresponse. Aripiprazole, with a complex profile of neurotransmitter affinities, has produced significant core symptom changes. Improved sociability; increased self-awareness; reduced rigidity, anxiety, and irritability; and reduced preoccupation with circumscribed esoteric interests are among the effects noted. Previously intractable Asperger disorder symptoms in a 34-year-old man were ameliorated with aripiprazole.


B cell aplasia and hypogammaglobulinemia after carbamazepine treatment.
Although immunosuppressive effects of antiepileptic drug are well known, serious complications of antiepileptic drug are rare. We report a case of hypogammaglobulinemia associated with aplasia of B lymphocytes after carbamazepine treatment. Despite repeated intravenous immunoglobulin replacement therapy, this condition persisted for more than three months. The present case suggested that routine monitoring of the blood cell count and serum levels of immunoglobulin are important in patients treated with carbamazepine, and a lymphocyte subpopulation study is valuable in cases of hypogammaglobulinemia.


Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs.
To assess safety and efficacy of repeated B-cell depletion with rituximab in patients with rheumatoid arthritis (RA). Thirty-seven patients with refractory RA entered into a programme of repeated B-lymphocyte depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti-CD20 monoclonal antibody, rituximab, have been observed over periods of >5 yrs (n = 22) or 3-5 yrs (n = 14). Twenty two subjects have been followed up for >5 yrs. Average duration of benefit per cycle was 15 months (maximum 43 months), and time to re-treatment 20 months. Nineteen patients remain on the programme. Patients were withdrawn for lack of efficacy (n = 5), hypersensitivity infusion reaction (n = 1), brevity of response (n = 8), or occurrence of adverse respiratory events (n = 1). Sixteen major lower respiratory events occurred during the 180 patient-yrs of follow-up. Of these only one had low IgG. In patients receiving rituximab +/- cyclophosphamide (cy) carcinomata have developed as follows: breast (3, +cy), ovary (1, +cy), transitional cell (1, +cy), and renal cell (1, -cy). Falls in total immunoglobulin levels to below the normal range occurred in 12 patients for IgM (undetectable levels in three after repeated cycles), seven for IgG and one for IgA, not taking into account patients who started off with low immunoglobulin levels before the first cycle. Repeated B-lymphocyte depletion over a 5-yr period appears to be an acceptable and relatively well-tolerated therapy in RA with a relatively high rate of continuation. Long-term effects on immunoglobulin levels require surveillance.


Impact of mail order pharmacy use and travel time to pharmacy on viral suppression among people living with HIV.
This study aimed to evaluate the impact of mail order pharmacy services and travel time to pharmacy on HIV viral suppression rates among people living with HIV. For adult patients receiving HIV care from 2010 to 2015 at an urban HIV care clinic, we collected demographics, pharmacy type, viral load, and patient home and pharmacy address. We geocoded addresses and measured travel time to pharmacy by car and public transportation. No difference was observed in recent viral suppression rates based on pharmacy type (p = 0.41), distance to pharmacy (p = 0.16), or travel time to pharmacy by car (p = 0.20) or public transportation (p = 0.15). The only factors significantly associated with sustained viral suppression were number of doses per day of antiretroviral therapy, with patients prescribed twice daily regimens less likely to be virally suppressed than those prescribed once daily regimens (aOR 0.4, 95% CI, [0.1, 0.6]) and average household income in patients' zip code, with patients living in zip codes with average household income <$40,000 per year less likely to be virally suppressed than those living in zip codes with average income >$55,000 per year (aOR 0.2. 95% CI, [0.1, 0.7]).


Clionapyrrolidine A--a metabolite from the encrusting and excavating sponge Cliona tenuis that kills coral tissue upon contact.
The Caribbean encrusting and excavating sponge Cliona tenuis successfully competes for space with reef corals by undermining, killing, and displacing live coral tissue at rates of up to 20 cm per year. The crude extract from this sponge, along with the more polar partitions, kills coral tissue and lowers the photosynthetic potential of coral zooxanthellae. We used a bioassay-guided fractionation of the extract to identify the compound(s) responsible. The crude extract, the aqueous partition, and compound 1, herein named clionapyrrolidine A [(-)-(5S)-2-imino-1-methylpyrrolidine-5-carboxylic acid], when incorporated into gels at close to natural volumetric concentrations, killed coral tissue when brought into forced contact with live coral for periods of 1-4 days. This is the first report of a pure chemical produced by a sponge that kills coral tissue upon direct contact. The results are consistent with the localized coral death that occurs when C. tenuis-colonized coral fragments are thrown forcibly against live coral during storms. However, healed C. tenuis fragments placed directly onto live coral were killed readily by coral defenses, and fragments placed in close proximity to coral did not have any effect on the adjacent coral tissue. Solutions of clionapyrrolidine A in sea water were only slightly toxic against live coral. Hence, the coral death naturally brought about by C. tenuis when undermining live coral does not occur through external release of allelochemicals; below-polyp mechanisms must be explored further. N-acetylhomoagmatine (2), originally isolated from Cliona celata from the Northeastern Atlantic, was also assayed for comparison purposes because of its structural similarity to siphonodictidine, a toxic compound produced by a coral excavating sponge of the genus Aka. The lack of activity of N-acetylhomoagmatine at close to natural concentrations seems to indicate that the guanidine moiety, which is also present in siphonodictidine, is not a sufficiently strong structural motif for activity against corals.


The muscle thin filament as a classical cooperative/allosteric regulatory system.
It is generally accepted that the regulation of muscle contraction involves cooperative and allosteric interactions among the protein components, actin, myosin, tropomyosin and troponin. But, as yet, the individual role of each component has not been clearly identified. Here we compare the properties of the components of the muscle regulatory system with the corresponding components of two systems, hemoglobin and aspartate transcarbamylase, that are well described by the classical Monod, Wyman and Changeux (MWC) model. The analogy indicates that actin is the catalytic subunit, tropomyosin is the regulatory subunit and troponin in the absence and presence of Ca2+ is the allosteric inhibitor and activator, respectively. The analogy additionally indicates that the substrate is myosin-ATP (or myosin-ADP-Pi) rather than ATP. Also, in contrast to other MWC systems, the activating ligand for actin-tropomyosin is a myosin-nucleotide intermediate or product that binds tightly to actin, rather than the substrate which binds weakly. This tightly bound intermediate switches the system from the off-state to the on-state (T to R-state in MWC nomenclature) in a concerted transition, affecting n actin subunits, allowing force to be developed.


Influence of the number of motile spermatozoa inseminated and of their morphology on the success of intrauterine insemination.
Although intrauterine insemination (IUI) is one of the most common assisted reproductive technology methods in the world, the relative influence of various semen characteristics on the likelihood of a successful outcome is controversial. The aim of our study was to assess the results of IUI as a function of both the number of motile spermatozoa inseminated (NMSI) and the percentage of morphologically normal spermatozoa after preparation. This was a retrospective study of 889 couples who underwent 2564 IUI cycles of ovarian stimulation with HMG or recombinant FSH in our centre between January 1991 and December 2000. A total of 331 clinical pregnancies were obtained, for a pregnancy rate/cycle of 12.91%. When the NMSI was < 1 x 10(6), the pregnancy rate/cycle was significantly lower (3.13%) than in any of the subgroups with NMSI > or = 2 x 10(6). Sperm morphology, assessed before or after preparation, was not in itself a significant factor that affected the likelihood of IUI success. Nonetheless, when the post-migration rate of normal sperm was < 30%, the pregnancy rate/cycle was 5.43% when NMSI was < 5 x 10(6) and 18.42% when NMSI was > or = 5 x 10(6) (P = 0.008). Pregnancy rates did not differ significantly according to NMSI when the percentage of normal sperm after preparation was > or = 30%, or according to percentage of normal sperm when the NMSI was > or = 5 x 10(6). Our results show that a minimum of 5 x 10(6) motile spermatozoa should be inseminated when the normal morphology of the sperm after preparation is < 30%; the quantity compensates at least in part for the defective quality. If this threshold of NMSI cannot be obtained, IVF should be recommended.


Assessment of spray drift potential reduction for hollow-cone nozzles: Part 1. Classification using indirect methods.
Spray drift is one of the main pollution sources identified when pesticides are sprayed on crops. In this work, in order to simplify the evaluation of hollow-cone nozzles according to their drift potential reduction, several models commonly used were tested by three indirect methods: phase Doppler particle analyser (PDPA) and two different wind tunnels. The main aim of this study is then to classify for the first time these hollow-cone nozzle models all of them used in tree crop spraying (3D crops). A comparison between these indirect methods to assess their suitability and to provide guidelines for a spray drift classification of hollow-cone nozzles was carried out. The results show that, in general terms, all methods allow hollow-cone nozzle classifications according to their drift potential reduction (DPR) with a similar trend. Among all the parameters determined with the PDPA, the V100 parameter performed best in differentiating the tested nozzles among drift reduction classes. In the wind tunnel, similar values were obtained for both sedimenting and airborne drift depositions. The V100 parameter displayed a high correlation (up to R2 = 0.948) with the drift potential tested with the wind tunnel. It is concluded that in general, the evaluated indirect methods provide equivalent classification results. Additional studies with a greater variety of nozzle types are required to achieve a proposal of harmonized methodology for testing hollow-cone nozzles.


[Comparison of the effects of diflunisal, ibuprofen and placebo in chronic polyarthritis].
Diflunisal, a new nonsteroidal, Aspirin-like anti-inflammatory agent has been compared with Ibuprofen und Placebo in a six-week double-blind randomized crossover controlled study in 24 patients with rheumatoid arthritis. There was a statistically significant improvement for all variables while on Diflunisal and Ibuprofen. Adverse reactions were seen in each of the three treatment groups. Clinical determinations and physiological examinations gave no indication of any potential harm from therapy with Diflunisal.


[A survey about the competences required by primary health physicians in Chile].
Primary health care is considering the cornerstone of health care in Chile. Its efficiency is strongly influenced by the quality and competences of physicians that are responsible for health care at this level. To define the features and competences that should have primary care physicians. A group of experts that could be physicians or other professionals working in primary health care were invited to answer electronically a structured questionnaire containing a list of 71 competences, for a basic and an expert level of physician, using the Delphi method. Competences were classifying as "desirable" or "indispensable". If there was lack of consensus in the importance given to a specific competence, the researchers defined its importance. Thirty-eight professionals (50% physicians) were inviting to participate and 16 answered the questionnaire. The competence profile defined for basic physicians has 13 knowledge items, 24 skills and 16 attitudes. The figures for advanced physicians are 29 knowledge items, 37 skills and 20 attitudes. This list of competences should been considered by medical schools to adapt undergraduate training of future physicians.


Meta-analysis of diazotrophic signatures across terrestrial ecosystems at the continental scale.
Biological nitrogen fixation performed by diazotrophs forms a cornerstone of Earth's terrestrial ecosystem productivity. However, the composition, diversity and distribution of soil diazotrophs are poorly understood across different soil ecosystems. Furthermore, the biological potential of the key diazotroph species in relation to key environmental parameters is unknown. To address this, we used meta-analysis approach to merge together 39 independent diazotroph amplicon sequencing (nifH gene) datasets consisting of 1988 independent soil samples. We then employed multiple statistical analyses and machine-learning approaches to compare diazotroph community differences and indicator species between terrestrial ecosystems on a global scale. The distribution, composition and structure of diazotroph communities varied across seven different terrestrial ecosystems, with community composition exhibiting an especially clear effect. The Cyanobacteria were the most abundant taxa in crust ecosystems (accounting for ~45% of diazotrophs), while other terrestrial ecosystems were dominated by Proteobacteria, including Alpha-, Beta- and Gamma-Proteobacteria (accounting for ~70% of diazotrophs). Farmland ecosystems harboured the highest and crust ecosystems the lowest alpha and phylogenetic diversities. Azospirillum zeae, Skermanella aerolata and four Bradyrhizobium species were identified as key indicator species of potential diazotroph activity. Overall, diazotroph abundances and distribution were affected by multiple environmental parameters, including soil pH, nitrogen, organic carbon, C:N ratio and annual mean precipitation and temperature. Together, our findings suggest that based on the relative abundance and diversity of nifH marker gene, diazotrophs have adapted to a range of environmental niches globally.


Inorganic mercury and methylmercury in placentas of Swedish women.
We determined levels of inorganic mercury (I-Hg) and methylmercury in placentas from 119 Swedish women, not selected with respect to high exposure of mercury. Our objective was to relate placental Hg species with maternal and fetal blood concentrations and to evaluate possible associations with selenium. We performed the analyses using automated alkaline solubilization/reduction and cold-vapor atomic fluorescence spectrophotometry. I-Hg levels in placenta increased with an increasing number of maternal dental amalgam fillings (p < 0.001). Despite placental accumulation (median, 1.3 microg/kg; range, 0.18-6.7 microg/kg wet weight), a substantial fraction of maternal blood I-Hg, probably as Hg(0), reached the fetus. Although MeHg transferred easily to the fetus, it also accumulated in the placenta. On average, 60% of placental Hg was in the form of MeHg. The median concentration was 1.8 microg/kg (range, 0-6.2 microg/kg wet weight), more than twice the maternal blood concentration. We found significant associations between MeHg and selenium in both maternal and umbilical cord blood but not in the placenta. The associations were particularly obvious in freshwater fish consumers, probably reflecting that fish is a source of both MeHg and selenium. We found no correlations between I-Hg and selenium. This study increases the understanding of Hg, in its different forms, in human placenta and how they are related to maternal and fetal exposure.


Chia Oil-Enriched Restructured Pork Effects on Oxidative and Inflammatory Status of Aged Rats Fed High Cholesterol/High Fat Diets.
Chia oil has the highest recognized α-linolenic acid (ALA) content. ALA is associated with beneficial changes in plasma lipids and the prevention of cardiovascular diseases. Present article aims to analyze the effect of Chia oil-enriched restructured pork (RP) on aged rats in a nonalcoholic steatohepatitis (NASH) model. Groups of six male Wistar rats (1-year old) were fed the experimental diets: control RP diet (C) noncholesterol high saturated; cholesterol-enriched high-saturated fat/high-cholesterol control RP diet (HC) with added cholesterol and cholic acid; and Chia oil- or Hydroxytyrosol RP cholesterol-enriched high-saturated fat/high cholesterol (CHIA and HxT). Total cholesterol, hepatosomatic index, Nrf2, antioxidant, and inflammation markers were determined. CHIA reduced the hypercholesterolemic effect by lowering levels similar to C; also, ameliorated redox index. CHIA, despite high polyunsaturated fatty acids (PUFA) content, reduced thiobarbituric acid reactive substances (TBARS) and induced the lowest SOD protein synthesis but not a reduction on its activity. Chia oil activated the Nrf2 to arrest the pro-oxidative response to cholesterol and aging. Endothelial nitric oxide synthase (eNOS) system was lower in HxT than in CHIA, suggesting its antiatherogenic activity and related protective effect against high PUFA. Increase in tumor necrosis factor alpha (TNFα) was partially blocked by CHIA. Chia oil has the ability to prevent oxidative damage and modify the inflammatory response, suggesting adequate regulation of the antioxidant system. Results stress the importance of incorporating ALA into the diet.


Performance of a deep neural network at detecting North Atlantic right whale upcalls.
Passive acoustics provides a powerful tool for monitoring the endangered North Atlantic right whale (Eubalaena glacialis), but robust detection algorithms are needed to handle diverse and variable acoustic conditions and differences in recording techniques and equipment. This paper investigates the potential of deep neural networks (DNNs) for addressing this need. ResNet, an architecture commonly used for image recognition, was trained to recognize the time-frequency representation of the characteristic North Atlantic right whale upcall. The network was trained on several thousand examples recorded at various locations in the Gulf of St. Lawrence in 2018 and 2019, using different equipment and deployment techniques. Used as a detection algorithm on fifty 30-min recordings from the years 2015-2017 containing over one thousand upcalls, the network achieved recalls up to 80% while maintaining a precision of 90%. Importantly, the performance of the network improved as more variance was introduced into the training dataset, whereas the opposite trend was observed using a conventional linear discriminant analysis approach. This study demonstrates that DNNs can be trained to identify North Atlantic right whale upcalls under diverse and variable conditions with a performance that compares favorably to that of existing algorithms.


When should a new test become the current reference standard?
The evaluation of claims that a new diagnostic test is better than the current gold standard test is hindered by the lack of a perfect reference judge. However, this problem may be sidestepped by focusing on the clinical consequences of the decision rather than on estimation of accuracy. Consequences can be assessed by use of a "fair umpire" test that is not perfect yet can discriminate between disease and nondisease cases and is not biased in favor of 1 test. This article discusses 3 principles to aid judgments about the value of new tests. First, the consequences are best examined in cases with disagreement between the current and new tests. Second, resolving these disagreements requires a fair, but not necessarily perfect, umpire test. Finally, umpire tests include consequences, such as prognosis and response to treatment, as well as causal exposures and other test results.


Estrogenic effects of an antiestrogen, MER-25, on eating and body weight in rats.
Ethamoxytriphetol, MER-25, which acts as an estrogen antagonist on other estrogen-sensitive behaviors and in peripheral tissues, was found to be fully estrogenic with respect to eating behavior and body weight regulation. The MER-25 causes decreases in eating and weight gain that are not due to toxicity, as indicated by its failure to induce a learned aversion to saccharin and by its failure to alter spontaneous activity. Estradiol benzoate (EB) and MER-25 similarly affect eating and body weight in gonadectomized rats: Both cause a transient decrease in food intake and a permanent decrease in body weight relative to controls; the eating and body weight effects of both MER-25 and EB are attenuated by progesterone; and both MER-25 and EB affect females more than males. Because of its full estrogenicity, MER-25 fails to antagonize the effects of EB on eating and body weight while simultaneously antagonizing effects of EB on sexual behavior, the uterus, and the vagina. The results indicate that the systems mediating the effects of estrogens on eating and body weight differ biochemically from other behavioral and somatic estrogen-sensitive systems.


The uncertain fate of otolaryngology in sleep medicine.
Since 2011, otolaryngologists have been required to complete a 1-year fellowship in sleep medicine in order to be eligible for the ABOto Sleep Medicine Certification Examination (ASMCE). Resultantly, the number of sleep medicine board-certified otolaryngologists has plunged since that time. This push toward extinction comes at a time when otolaryngologists have been cast into the spotlight for the diagnosis and treatment of obstructive sleep apnea, the prevailing disorder in sleep medicine. To reverse the trajectory of this subspecialty, 2 changes need to occur: increase the exposure to sleep medicine/surgery during residency and improve access to sleep medicine fellowships featuring a strong otolaryngology presence.


Transport coefficients of aqueous dodecyltrimethylammonium bromide solutions: comparison between experiments, analytical calculations and numerical simulations.
We study dynamical properties of ionic species in aqueous solutions of dodecyltrimethylammonium bromide, for several concentrations below and above the critical micellar concentration (cmc). New experimental determinations of the electrical conductivity are given which are compared to results obtained from an analytical transport theory; transport coefficients of ions in these solutions above the cmc are also computed from Brownian dynamics simulations. Analytical calculations as well as the simulation treat the solution within the framework of the continuous solvent model. Above the cmc, three ionic species are considered: the monomer surfactant, the micelle and the counterion. The analytical transport theory describes the structural properties of the electrolyte solution within the mean spherical approximation and assumes that the dominant forces which determine the deviations of transport processes from the ideal behavior (i.e., without any interactions between ions) are hydrodynamic interactions and electrostatic relaxation forces. In the simulations, both direct interactions and hydrodynamic interactions between solutes are taken into account. The interaction potential is modeled by pairwise repulsive 1/r(12) interactions and Coulomb interactions. The input parameters of the simulation (radii and self-diffusion coefficients of ions at infinite dilution) are partially obtained from the analytical transport theory which fits the experimental determinations of the electrical conductivity. Both the electrical conductivity of the solution and the self-diffusion coefficients of each species computed from Brownian dynamics are compared to available experimental data. In every case, the influence of hydrodynamic interactions (HIs) on the transport coefficients is investigated. It is shown that HIs are crucial to obtain agreement with experiments. In particular, the self-diffusion coefficient of the micelle, which is the largest and most charged species in the present system, is enhanced when HIs are included whereas the diffusion coefficients of the monomer and the counterion are roughly not influenced by HIs.


Differentiation of RNP- and SM-antibody subsets in SLE and MCTD patients by a new ELISA using recombinant antigens.
Connective tissue diseases often have overlapping clinical features and laboratory abnormalities. The distinctiveness of mixed connective tissue disease (MCTD) as an entity is of scientific interest and practical importance. In order to discriminate between MCTD and SLE patients we used a newly developed, commercially not available ELISA with recombinant antigen expressed in Baculovirus infected cells. This ELISA detects antibodies against RNP and Sm in complex as well as the subsets U1-snRNP 68 kDa, RNP-A, RNP-C (RNP), Sm-BB' and SS-D. We analyzed 66 RNP-positive consecutive patients prediagnosed as SLE or MCTD/overlap-syndrome. 45/66 patients were found to be U1-snRNP-68 kDa positive (27 SLE, 18 MCTD), 51/66 RNP-A [36,15] and 44/66 RNP-C [31,13]. 35/66 had antibodies against Sm-BB' (30 SLE, 5 MCTD), 10/66 against Sm-D (all SLE). 28/66 were found to be U1-snRNP-68 kDa and Sm-BB' positive (23 SLE, 5 MCTD), while 8/66 where U1-snRNP-68 kDa and Sm-D positive (all SLE). The combination of antibodies against 68 kDa, Aand C was exclusively observed in 6 MCTD patients, while the combination against 68 kDa, A, C, Sm-BB' and Sm-D was restricted to 8 patients with SLE. The antibody combination to 68 kDa, A, C and Sm-BB' was also found in 11/20 SLE patients with major organ involvement. In SLE and MCTD, determination of subsets of antibodies against Ul-snRNP-68 kDa and Sm-complex allows a differentiation of patient subgroups with more definite diagnoses and potential prognostic impact.