Effects of Different Irrigation Solutions and Protocols on Mineral Content and Ultrastructure of Root Canal Dentine.
The aim of this study was to evaluate the effect of different irrigating solutions and irrigation protocols on the chemical and physical structure of root dentin. Thirty extracted single-rooted human teeth were selected and then distributed into the following treatment groups (n=10): G1, saline solution (0.9% NaCl); G2, 2.5% NaOCl + 17% EDTA + 2.5% NaOCl; G3, 2.5% NaOCl + 9% Etidronate (HEBP) + 2.5% NaOCl; G4, mixture of 5% NaOCl + 18% HEBP; G5, 2.5% NaOCl + 17% EDTA + 0.9% NaCl, and G6, 2.5% NaOCl + 9% HEBP + 0.9% NaCl. The ultrastructure of dentin was characterized through scanning electron microscopy (SEM) and energy dispersive x-ray spectrometry (EDS) determined the chemical composition in terms of the calcium (Ca), phosphorus (P), magnesium (Mg) and potassium (K) content and the Ca/P ratio; and the crystalline phase was analyzed by x-ray diffraction (XRD). A descriptive analysis was performed on the ultrastructure and the crystallography data of dentin. Data analysis included a chemical composition analysis of variance (one-way ANOVA) and a subsequent multiple comparison test (Tukey's test). Except for the control group, all groups showed morphological changes upon visualization with SEM. For EDS, G2 and G5 showed significant mineral loss and changes in the Ca/P ratio (P<0.05); the highest values of Ca and P were observed in G3, G4 and G6. All the irrigating solutions and irrigation protocols tested promoted changes in the morphology and physical and chemical composition of the dentin. However, no significant differences were observed crystallographically.


Effects of urbanization and climate change on stream health in north-central Texas.
Estimation of stream health involves the analysis of changes in aquatic species, riparian vegetation, microinvertebrates, and channel degradation due to hydrologic changes occurring from anthropogenic activities. In this study, we quantified stream health changes arising from urbanization and climate change using a combination of the widely accepted Indicators of Hydrologic Alteration (IHA) and Dundee Hydrologic Regime Assessment Method (DHRAM) on a rapidly urbanized watershed in the Dallas-Fort Worth metropolitan area in Texas. Historical flow data were split into pre-alteration and post-alteration periods. The influence of climate change on stream health was analyzed by dividing the precipitation data into three groups of dry, average, and wet conditions based on recorded annual precipitation. Hydrologic indicators were evaluated for all three of the climate scenarios to estimate the stream health changes brought about by climate change. The effect of urbanization on stream health was analyzed for a specific subwatershed where urbanization occurred dramatically but no stream flow data were available using the widely used watershed-scale Soil and Water Assessment Tool (SWAT) model. The results of this study identify negative impacts to stream health with increasing urbanization and indicate that dry weather has more impact on stream health than wet weather. The IHA-DHRAM approach and SWAT model prove to be useful tools to estimate stream health at the watershed scale.


Effectiveness of paliperidone long-acting injection in clinical practice.
The efficacy of the long-acting injectable formulation of the antipsychotic paliperidone (paliperidone palmitate) has been investigated in randomized controlled trials. Due to the nature of study designs, these may not be representative of usual clinical practice. The aim of this study was to assess the clinical effectiveness of the long-acting injectable antipsychotic paliperidone palmitate using treatment continuation at 1 year as an outcome. Patients were initiated on paliperidone palmitate prior to December 2014 in a single health board in Wales (UK). Demographic factors that may have influenced outcome, including diagnosis, age at initiation, sex, inpatient or outpatient status on initiation, were analysed to assess whether they influenced patient outcome. For patients completing 1 year of treatment, inpatient stay in the 12 months prior to and following paliperidone palmitate initiation was compared. Data were available for 64 patients; 41 had a diagnosis of schizophrenia and 7 had previously received clozapine. Continuation rates at 6 and 12 months were 69% and 63% respectively. Treatment continuation was not associated with demographic factors. For continuers, mean inpatient stay pre- and post-initiation was 83.2 ± 105.3 and 73.5 ± 103.3 days respectively (p = 0.61). The most common reason for discontinuation was lack of effect (n = 9). The proportion of patients remaining on treatment was comparable to that reported in other naturalistic studies. Prescribing for indications outside the product licence was relatively common, but did not appear to influence outcome, although the number of patients in each group was small. Treatment continuation at 6 months appeared to be a predictor of longer-term outcome.


The Impact of COVID-19 and Vaccine on the Human Nervous System.
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has precipitated a global health crisis of unprecedented proportions. Due to its severe impact, multiple COVID-19 vaccines are being developed, approved, and manufactured rapidly. However, some serious adverse events (AEs) were reported after the application of them, significantly increasing concerns about the safety and efficacy of the vaccines and doubts about the necessity of vaccination. Particularly, previous vaccination campaigns have shown us that partial vaccination can induce neurologic AEs. Herein, we discuss in depth the involvement of the nervous system during SARS-CoV-2 infection or after vaccination. On the one hand, COVID-19 could pose an enormous threat to human neurological health through direct infection and indirect neurotoxicity effects. On the other hand, our review indicated that only a few serious neurological AEs following vaccination occurred and among which headache was the most common. Moreover, some neurological AEs do not seem to be related to vaccination. Of course, the causal relationships between several vaccines and AEs are considered plausible, and it is not doubtful that these AEs should be taken seriously by clinicians in assessing the potential risks and benefits of vaccinations in special populations. Nevertheless, in the case of the rapid spread of COVID-19, the potential side effects of vaccination on the nervous system should be compared with adverse COVID-19 outcomes rather than being considered alone. Thus, it is obviously a wise option to be vaccinated instead of suffering from serious adverse symptoms of virus infection.


The protective role of the Mediterranean diet on the prevalence of metabolic syndrome in a population of Greek obese subjects.
Obesity is a rapidly expanding epidemic in Western societies, with rates of more than 30% across Europe, and it is associated with an increased risk of metabolic disturbances. Previous reports have documented an association of reduced physical activity and abstinence from the traditional Mediterranean diet (MD) with increased mortality rate and prevalence of obesity in a population of Greek subjects. The aim of the present study was to evaluate and analyze the dietary habits in a population of Greek overweight and obese subjects and to investigate the potential associations between those patterns and the prevalence of metabolic syndrome components. The study recruited 226 consecutive adult (30 men, 169 women) overweight or obese (body mass index >25 kg/m(2)) individuals attending the Metabolic Diseases Unit. Medical history, dietary history, and anthropometric parameters were recorded during the first visit. Fasting blood samples were collected for biochemistry assaying. According to the nutrient intake history and Mediterranean Diet Scale (MDS), participants were divided into 3 groups: those adhering to the MD and those not following the MD, who were further subdivided into the high-carbohydrate (HC) and high-fat (HF) diet groups according to the source of maximum energy intake. Adherence to the MD was associated with a lower prevalence of metabolic syndrome (27.3%, 69.2%, and 60.4% in MD, HC, and HF respectively, p = 0.006), lower low-density lipoprotein cholesterol (p = 0.009, MD vs. HF), and lower postchallenge glucose values (p = 0.028, MD vs. HF). Adherence to the MD seems to be declining among Greek overweight and obese subjects, a phenomenon that is associated with an increase in the prevalence of the metabolic syndrome.


Emergency clinicians' perceived self-efficacy in the care of intoxicated women victims of violence.
Previous research has identified perceived self-efficacy to be a vital component of clinicians' positive attitudes towards caring for intoxicated patients and women who have been assaulted. To date, little is known about the perceived self-efficacy and influences among emergency clinicians towards intoxicated women victims of violence. Using mixed methods, 179 emergency clinicians were surveyed and 22 emergency clinicians were interviewed in South Australia about their education/training, their awareness and use of best practice guidelines and tools, and their perceived self-efficacy toward treating intoxicated women victims of violence. There were statistically significant relationships between use of best practice tools (n = 32) and knowledge (χ2 = 6.52; p = .02) and confidence (χ2 = 6.52; p = .02) treating women victims of violence. There were also statistically significant relationships between previous alcohol and other drug education/training and knowledge (n = 43), skills and confidence treating both intoxicated patients (χ2 = 7.85; p = .01) and women victims of violence (χ2 = 11.63; p < .01). The interviews identified four themes about confidence, knowledge and use of research evidence, education and training, and resources. Emergency clinicians reported low levels of perceived self-efficacy, and infrequent use of guidelines and tools to support the care of intoxicated women victims of violence. Participants wanted more knowledge and education/training in caring for intoxicated women who have been assaulted, as they felt lacking in these skills.


Effects of saturation and contrast polarity on the figure-ground organization of color on gray.
Poorly saturated colors are closer to a pure gray than strongly saturated ones and, therefore, appear less "colorful."Color saturation is effectively manipulated in the visual arts for balancing conflicting sensations and moods and for inducing the perception of relative distance in the pictorial plane. While perceptual science has proven quite clearly that the luminance contrast of any hue acts as a self-sufficient cue to relative depth in visual images, the role of color saturation in such figure-ground organization has remained unclear. We presented configurations of colored inducers on gray "test" backgrounds to human observers. Luminance and saturation of the inducers was uniform on each trial, but varied across trials. We ran two separate experimental tasks. In the relative background brightness task, perceptual judgments indicated whether the apparent brightness of the gray test background contrasted with, assimilated to, or appeared equal (no effect) to that of a comparison background with the same luminance contrast. Contrast polarity and its interaction with color saturation affected response proportions for contrast, assimilation and no effect. In the figure-ground task, perceptual judgments indicated whether the inducers appeared to lie in front of, behind, or in the same depth with the background. Strongly saturated inducers produced significantly larger proportions of foreground effects indicating that these inducers stand out as figure against the background. Weakly saturated inducers produced significantly larger proportions of background effects, indicating that these inducers are perceived as lying behind the backgrounds. We infer that color saturation modulates figure-ground organization, both directly by determining relative inducer depth, and indirectly, and in interaction with contrast polarity, by affecting apparent background brightness. The results point toward a hitherto undocumented functional role of color saturation in the genesis of form, and in particular figure-ground percepts in the absence of chromatostereopsis.


Mechanism of altered glomerular hemodynamics during chronic sodium depletion.
Chronic sodium depletion in the rat is associated with decreased nephron filtration rate (SNGFR), nephron plasma flow (rpf), and a reduction in the glomerular permeability coefficient (LpA). This study was designed to determine whether the reduction in LpA could be acutely reversed with volume repletion and whether administration of angiotensin I converting enzyme inhibitor will restore LpA to normal values in the sodium-depleted rat. Measurements were performed in Munich-Wistar rats employing micropuncture techniques to assess the effects of acute volume repletion, 3-5 days of oral converting enzyme inhibitor (CEI) (30 mg . kg body wt-1 . day-1), and longer term (13-18 days) treatment with CEI begun just before or after initial volume depletion. Volume repletion in chronic sodium-depleted rats restored LpA to normal control values within a 60-min period, and values for glomerular dynamics were not different from a group of normal NaCl-intake rats to which the same treatment was applied. Both short-term and long-term CEI treatment during sodium depletion resulted in restoration of rpf to values not different from those with normal NaCl intake. However, only long-term but not short-term CEI treatment restored LpA to normal values. These studies suggest that intrarenal angiotensin II may mediate this reduction in LpA during chronic sodium depletion, but an effect of adrenergic nerve activity has not been excluded.


Analysis of Agreement Between Computed Tomography Measurements of Glenoid Bone Defects in Anterior Shoulder Instability With and Without Comparison With the Contralateral Shoulder.
Computed tomography (CT) is frequently used to diagnose glenoid bone defects in anterior shoulder instability. The assessment of glenoid defects on 2-dimensional (2D) and 3-dimensional (3D) CT scans has been reported with and without a comparative study of the contralateral shoulder; however, no previous studies have analyzed if these 4 methods agree. To estimate agreement between CT assessments of glenoid defects by examination of the affected shoulder alone and by comparison with the contralateral side on both 2D and 3D CT scans. Cohort study (diagnosis); Level of evidence, 2. A total of 200 prospectively enlisted patients affected by unilateral anterior shoulder instability underwent CT of both shoulders. The area of the missing glenoid was calculated on 4 sets of CT scans (2D and 3D CT images with and without comparison with the contralateral shoulder) by using the circle method. Agreement between the 4 measurements in quantifying the bone defect was estimated according to the Bland-Altman method. Agreement between the 4 measurements in assessing the presence and type of defect (fracture or erosion) was analyzed with κ statistics. Analysis of agreement between CT measurements in quantifying glenoid bone defects showed that the mean difference between the 4 measures was less than 1% of the area of the inferior glenoid in each pairwise comparison. Limits of agreement were always below the established acceptable limit of 5%. The assessment of the presence and type of bone defect showed strong to near-complete agreement between the 4 measurement methods. CT assessments of glenoid bone defects with and without comparison with the contralateral shoulder showed very good agreement in identifying the size, presence, and type of defect in patients with anterior shoulder instability on both 2D and 3D CT scans.


Empirical comparison of univariate and multivariate meta-analyses in Cochrane Pregnancy and Childbirth reviews with multiple binary outcomes.
Multivariate meta-analysis (MVMA) jointly synthesizes effects for multiple correlated outcomes. The MVMA model is potentially more difficult and time-consuming to apply than univariate models, so if its use makes little difference to parameter estimates, it could be argued that it is redundant. We assessed the applicability and impact of MVMA in Cochrane Pregnancy and Childbirth (CPCB) systematic reviews. We applied MVMA to CPCB reviews published between 2011 and 2013 with two or more binary outcomes with at least three studies and compared findings with results of univariate meta-analyses. Univariate random effects meta-analysis models were fitted using restricted maximum likelihood estimation (REML). Eighty CPCB reviews were published. MVMA could not be applied in 70 of these reviews. MVMA was not feasible in three of the remaining 10 reviews because the appropriate models failed to converge. Estimates from MVMA agreed with those of univariate analyses in most of the other seven reviews. Statistical significance changed in two reviews: In one, this was due to a very small change in P value; in the other, the MVMA result for one outcome suggested that previous univariate results may be vulnerable to small-study effects and that the certainty of clinical conclusions needs consideration. MVMA methods can be applied only in a minority of reviews of interventions in pregnancy and childbirth and can be difficult to apply because of missing correlations or lack of convergence. Nevertheless, clinical and/or statistical conclusions from MVMA may occasionally differ from those from univariate analyses.


[Effect of salt-restriction on blood pressure. A review over epidemiological studies and a meta-analysis of clinically controlled studies].
Cross-section regression analyses of some of the world's populations suggest a direct linear relationship between mean blood pressure and mean salt-intake. Since such investigations have hitherto been partly based on information about dietary salt intake, which is a questionable measure, we performed an analysis including 28 male populations and an analysis including 21 female populations solely based on 24 hour sodium urinary excretion. The regression analysis confirmed that a direct linear relationship between blood pressure and 24 hour sodium urinary excretion existed, since the blood pressure in a population was about 7 mmHg/6 mmHg higher than in a population which consumed 100 mmol less salt. We were, however, not able to correct for confounders. This was done in the recently published "Intersalt" study in which the linear relationship between median blood pressure and median salt intake disappeared after correction for weight and alcohol intake. From the regression coefficients from "Intersalt" it can be deduced that a reduction in salt intake from 150 mmol to 75 mmol may reduce blood pressure by 1.6/0.05 mmHg. Most epidemiological studies have not been able to demonstrate a correlation between salt intake and blood pressure within population. Still, on the basis of uncontrolled clinical studies it has been claimed that salt-restriction may reduce blood pressure. Consequently we also performed a meta-analysis of 15 controlled clinical trials dealing with the effect of salt-restriction on blood pressure within a population. This meta-analysis including 704 patients showed that a reduction in average salt intake from 150 mmol to 75 mmol may reduce blood pressure by 2.4/1.4 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of pulmonary pleomorphic carcinoma treated with S-1 following radiotherapy].
Pleomorphic carcinoma is a rare malignancy of the lung. Here we present a 68-year-old man who was admitted to our hospital for examination of an abnormal radiogram of the chest. The radiogram revealed a large mass in the right lung field. A chest computed tomographic (CT) scan demonstrated a nonsegmentalmass like consolidation. Percutaneous CT-guided fine-needle needle biopsy from the lung was performed, and the specimen demonstrated pulmonary pleomorphic carcinoma. The patient was initially treated with two courses of cisplatin (CDDP) and docetaxel (DOC), and still showed progressive disease (PD). Therefore, we administered S-1 following radiotherapy. The chest CT revealed partial response after 4 months. We experienced a pulmonary pleomorphic carcinoma which showed a response to salvage chemotherapy with S-1.


[Guillain-Barre syndrome in the paediatric age: epidemiological, clinical and therapeutic profile in a hospital in El Salvador].
Guillain-Barre syndrome (GBS) is an acute polyradiculoneuropathy with, in most cases, an autoimmune aetiology. It manifests as a flaccid motor paralysis, of a distal ascending type, accompanied by areflexia with or without sensory alterations. To determine the clinical and therapeutic epidemiological profile of patients diagnosed as suffering from GBS who were attended at the Benjamin Bloom Children's Hospital in El Salvador, between 1st January 1997 and 31st December 2004. We performed an observation-based, descriptive, cross-sectional study that included 414 cases. The following data were evaluated: age distribution, sex, age, history of infections, clinical manifestations, results of the lumbar puncture, electrophysiological studies and treatment that was received. A predominance of males was observed, together with a more frequent presentation in school-age children. The number of cases increased in the third quarter of each of the years included in the study. The most prevalent event in the history of infections was acute respiratory infection. And the most frequent clinical presentation was ascending weakness. Albuminocytological dissociation was detected in 88% of patients who had undergone lumbar puncture. Acute inflammatory demyelinating polyneuropathy predominated in 88.3% of cases. Sixty per cent of patients had to be admitted to the intensive care unit. In most cases treatment consisted in intravenous administration of immunoglobulin. Complications occurred in 30.5% of cases and the mortality rate was 2.9%. GBS occurs predominantly in the rainiest season of the year, which is related to an increase in the number of infections in the upper respiratory tract and gastroenteric infections that give rise to a predisposition to present secular outbreaks of the disease.


Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism.
Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center.


Effects of dietary rhIGF-I in neonatal calves on the appearance of glucose, insulin, D-xylose, globulins and gamma-glutamyl transferase in blood.
Cow colostrum is rich in insulin-like growth factors IGF-I and II, thus the dietary effects of recombinant human (rh) rhIGF-I on the newborn were of interest. The objective of this study was to examine the effect of dietary IGF-I upon selected blood components and gut absorptive development. Calves were blocked by birth weight and fed two times per d for a total of four times with the initial restricted diet. The initial feeding was 1.5 l and the remaining three feedings were at 2 l with one of three experimental diets; 1) milk replacer plus isolated colostrum derived globulins (MR-), 2) same as 1 above plus 750 ng/ml rhIGF-I (MR+), 3) pooled cow colostrum (COL). Thereafter, all animals received only milk replacer at 5% of body weight (BW)/feeding two times per d with only treatment 2 having continued addition of 750 ng/ml rhIGF-I until experimental completion at 6 to 7 d after birth. At feeding three, animals were fed D-xylose (0.5 g/kg BW) and 5,000 U of bovine kidney membrane gamma-glutamyl transferase as indicators of gut absorptive capacity. Colostrum-fed animals received 5,000 U of natural occurring gamma-glutamyl transferase activity in the 1.5 l first feeding. Blood samples taken over time were collected and saved as frozen plasma. All diets were analyzed for nutrient composition and endogenous levels of test hormones. Colostrum fed calves had greater globulin concentration (P < 0.01) than MR- or MR+ fed calves. Recombinant hIGF-I feeding had no effect (MR- vs. MR+) upon total protein, albumin or globulin blood levels. Absorption of colostrum gamma-glutamyl transferase at first feeding resulted in a peak total blood U of 4.5% of that fed. Although enzyme absorption was greatly reduced by the third feeding (0.5% of total fed), MR+ fed calves exhibited no significant difference in enzyme absorption when compared with the controls (MR- vs. MR+). However, pharmacokinetic analysis of D-xylose absorption at the third feeding showed diet effect upon absorption of D-xylose. Dietary rhIGF-I may change development or activity of sugar transporters and also may alter absorption of macromolecules (closure) in neonatal calves.


Generalization of sensory auditory learning to top-down skills in a randomized controlled trial.
Research has shown that auditory training improves auditory sensory skills; however, it is unclear whether this improvement is transferred to top-down skills, such as memory, attention, and language, and whether it depends on group characteristics in regard to memory and attention skills. The primary goal of this research was to investigate the generalization of learning from auditory sensory skills to top-down skills such as memory, attention, and language. We also aimed to compare whether this generalization process occurs in the same way among typically developing children and children with speech sound disorder. This study was a randomized controlled trial. Typically developing 7- to 12-yr-old children and children with speech sound disorder were separated into four groups: a trained control group (TDT; n = 10, age 9.6 ± 2.0 yr), a nontrained control group (TDNT; n = 11, age 8.2 ± 1.6 yr), a trained study group (SSDT; n = 10, age 7.7 ± 1.2 yr), and a nontrained study group (SSDNT; n = 8, age 8.6 ± 1.2 yr). Both trained groups underwent a computerized, nonverbal auditory training that focused on frequency discrimination, ordering, and backward-masking tasks. The training consisted of twelve 45 min sessions, once a week, for a total of 9 hr of training, approximately. Near-transfer (Gap-In-Noise [GIN] and Frequency Pattern Test) and far-transfer measures (auditory and visual sustained attention tests, phonological working memory and language tests) were applied before and after training. The results were analyzed using a 2 × 2 × 2 mixed-model analysis of variance with the group and training as the between-group variables and the period as the within-group variable. The significance threshold was p ≤ 0.05. There was a group × period × training interaction for GIN [F(1.35) = 7.18, p = 0.011], indicating a significant threshold reduction only for the TDT group (Tukey multiple comparisons). There was a significant group × period interaction [F(1.35) = 5.52, p = 0.025] and a training × period interaction for visual reaction time [F(1.35) = 4.20, p = 0.048], indicating improvement in the SSDT group and worsening in both nontrained groups. There was also a significant group × training × period interaction [F(1.35) = 4.27, p = 0.046] for the auditory false alarms, with a significant improvement after training only for the SSDT group. Analysis of variance also revealed that all groups exhibited approximately the same level of gains for all measures, except for GIN [F(3,38) = 4.261, p = 0.011] and visual response time [F(3.38) = 4.069, p = 0.014]. After training, the TDT group demonstrated a significant improvement for GIN and the SSDT exhibited the same for sustained attention, indicating learning generalization from an auditory sensory training to a top-down skill. For the other measures, all groups exhibited approximately the same level of gains, indicating the presence of a test-retest effect. Our findings also show that the memory span was not related to the learning generalization process given that the SSDT exhibited a more pronounced gain in attention skills after the sensory training.


The energetic cost of mounting an immune response for Pallas's long-tongued bat (Glossophaga soricina).
The acute phase response (APR) is the first line of defense of the vertebrate immune system against pathogens. Mounting an immune response is believed to be energetically costly but direct measures of metabolic rate during immune challenges contradict this assumption. The energetic cost of APR for birds is higher than for rodents, suggesting that this response is less expensive for mammals. However, the particularly large increase in metabolic rate after APR activation for a piscivorous bat (Myotis vivesi) suggests that immune response might be unusually costly for bats. Here we quantified the energetic cost and body mass change associated with APR for the nectarivorous Pallas's long-tongued bat (Glossophaga soricina). Activation of the APR resulted in a short-term decrease in body mass and an increase in resting metabolic rate (RMR) with a total energy cost of only 2% of the total energy expenditure estimated for G. soricina. This increase in RMR was far from the large increase measured for piscivorous bats; rather, it was similar to the highest values reported for birds. Overall, our results suggest that the costs of APR for bats may vary interspecifically. Measurement of the energy cost of vertebrate immune response is limited to a few species and further work is warranted to evaluate its significance for an animal's energy budget.


Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations.
Rationale: Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Objectives: We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort. Methods: We used sputum samples from 102 patients hospitalized because of AECOPD. All subjects were followed for 1 year after discharge. The microbiome profile was assessed through sequencing of 16S rRNA gene. Microbiome analyses were performed according to 1-year mortality status. To investigate the effect of α-diversity measures and taxon features on time to death, we applied Cox proportional hazards regression models and obtained hazard ratios (HRs) associated with these variables. Measurements and Main Results: We observed significantly lower values of α-diversity (richness, Shannon index, evenness, and Faith's Phylogenetic Diversity) among nonsurvivors (n = 19, 18.6%) than survivors (n = 83, 81.4%). β-Diversity analysis also demonstrated significant differences between both groups (adjusted permutational multivariate ANOVA, P = 0.010). The survivors had a higher relative abundance of Veillonella; in contrast, nonsurvivors had a higher abundance of Staphylococcus. The adjusted HRs for 1-year mortality increased significantly with decreasing α-diversity. We also observed lower survival among patients in whom sputum samples were negative for Veillonella (HR, 13.5; 95% confidence interval, 4.2-43.9; P < 0.001) or positive for Staphylococcus (HR, 7.3; 95% confidence interval, 1.6-33.2; P = 0.01). Conclusions: The microbiome profile of sputum in AECOPD is associated with 1-year mortality and may be used to identify subjects with a poor prognosis at the time of hospitalization.


Using Lipoamidase as a Novel Probe To Interrogate the Importance of Lipoylation in Plasmodium falciparum.
Lipoate is a redox active cofactor that is covalently bound to key enzymes of oxidative metabolism. Plasmodium falciparum is auxotrophic for lipoate during the intraerythrocytic stages, but it is not known whether lipoate attachment to protein is required or whether attachment is required in a specific subcellular compartment of the parasite. To address these questions, we used an enzyme called lipoamidase (Lpa) as a probe of lipoate metabolism. Lpa was first described in Enterococcus faecalis, and it specifically cleaves protein-bound lipoate, inactivating enzymes requiring this cofactor. Enzymatically active Lpa could be expressed in the cytosol of P. falciparum without any effect on protein lipoylation or parasite growth. Similarly, Lpa could be expressed in the apicoplast, and although protein lipoylation was reduced, parasite growth was not inhibited. By contrast, while an inactive mutant of Lpa could be expressed in the mitochondrion, the active enzyme could not. We designed an attenuated mutant of Lpa and found that this enzyme could be expressed in the parasite mitochondrion, but only in conjunction with a chemical bypass system. These studies suggest that acetyl-CoA production and a cryptic function of the H protein are both required for parasite survival. Our study validates Lpa as a novel probe of metabolism that can be used in other systems and provides new insight into key aspects of mitochondrial metabolism that are responsible for lipoate auxotrophy in malaria parasites.IMPORTANCE Lipoate is an essential cofactor for a small number of enzymes that are important for central metabolism. Malaria parasites require lipoate scavenged from the human host for growth and survival; however, it is not known why this cofactor is so important. To address this question, we designed a probe of lipoate activity based on the bacterial enzyme lipoamidase (Lpa). Expression of this probe in different subcellular locations allowed us to define the mitochondrion as the compartment housing essential lipoate metabolism. To gain further insight into the specific uses of lipoate in the mitochondrion, we designed a series of catalytically attenuated probes and employed the probes in conjunction with a chemical bypass system. These studies suggest that two lipoylated proteins are required for parasite survival. We were able to express Lpa with different catalytic abilities in different subcellular compartments and driven by different promoters, demonstrating the versatility of this tool and suggesting that it can be used as a probe of lipoate metabolism in other organisms.


Soybean seed coat chitinase as a defense protein against the stored product pest Callosobruchus maculatus.
Chitinases (EC 184.108.40.206) are enzymes involved in the breaking of the β-1,4-glycosidic linkages of chitin. In insects, chitin is present mainly in the cuticle and in peritrophic membranes and peritrophic gel. Enzymes with the potential to damage peritrophic membranes and gel, such as chitinase, have been associated with plant defense systems. Identification and characterization of seed coat chitinase as a plant defense molecule may indicate a more effective target for manipulation strategies, which may lead to the prevention of consumption of embryonic tissues by larvae and consequently minimization of seed damage. We studied the efficiency of soybean seed coat chitinase as a defense molecule against the insect Callosobruchus maculatus. The seed coat chitinase was isolated and identified by mass spectrometry, immunoreacted with an anti-chitinase antibody and shown to have activity against chitin azure and 4-methylumbelliferyl β-D-N,N',N''-triacetylchitotrioside. A chitinase fraction incorporated in artificial cotyledons at 0.1% reduced larval survival by approximately 77%, and at 0.5%, the reduction in larval mass was 60%. Fluorescein isothiocyanate (FITC)-labeled chitinase was detected in the guts and feces of larvae. At 25% in thick artificial seed coats, chitinase showed a high toxicity to larvae, with mortality of 90% and a reduction of larval mass of 87%. Seed coat chitinase is an important seed defense molecule not only in the cotyledons but also in seed coats, acting as part of the array of defense mechanisms against Callosobruchus maculatus. © 2017 Society of Chemical Industry.


Treatment of miller type I and II gingival recession defects using three-dimensional porcine collagen matrix with coronally advanced flap: A randomized clinical split-mouth trial (a 1-year follow-up).
The main goal of periodontal plastic surgery is obtaining complete root coverage (CRC) and an optimal appearance. The aim of this study was to evaluate the effectiveness of a three-dimensional porcine collagen matrix (PCM) with coronally advanced flap (CAF) in treating of Miller type I and II gingival recession (GR). Twenty patients were enrolled in this study, presenting 40 Miller type I and II GR. Patients were randomized into test group (PCM + CAF) and control group [connective tissue graft (CTG + CAF)]. Clinical parameters such as recession depth (RD), probing depth, clinical attachment level (CAL), and width of keratinized gingiva (WKG) were evaluated at baseline and 12 months later. Root coverage percentage (RC%) and CRC were assessed at 12 months post surgically. Statistical analysis was performed using independent t-test for intergroup comparison. Statistical significance was set at 0.05. The mean RD at 12 months was 0.20 mm for the test group and 0.12 mm for the control group, whereas the mean RC% was 94.22% for PCM + CAF and 96.48% for CTG + CAF. CRC was higher in CTG + CAF with 80%. CAL gain was 2.05 and 2.07 mm in the test and control sites, respectively. The gain of WKG was 1.35 and 1.30 mm in the test and control sites, respectively. Patient esthetic satisfaction at 12 months post surgically in both groups was equivalent. Within the limits of this study, using of PCM + CAF in treating GR is a successful and effective treatment option and could serve as an alternative to CTGs.


The Evolution of Polymorphic Hybrid Incompatibilities in House Mice.
Resolving the mechanistic and genetic bases of reproductive barriers between species is essential to understanding the evolutionary forces that shape speciation. Intrinsic hybrid incompatibilities are often treated as fixed between species, yet there can be considerable variation in the strength of reproductive isolation between populations. The extent and causes of this variation remain poorly understood in most systems. We investigated the genetic basis of variable hybrid male sterility (HMS) between two recently diverged subspecies of house mice, Mus musculus domesticus and Mus musculus musculus We found that polymorphic HMS has a surprisingly complex genetic basis, with contributions from at least five autosomal loci segregating between two closely related wild-derived strains of M. m. musculus One of the HMS-linked regions on chromosome 4 also showed extensive introgression among inbred laboratory strains and transmission ratio distortion (TRD) in hybrid crosses. Using additional crosses and whole genome sequencing of sperm pools, we showed that TRD was limited to hybrid crosses and was not due to differences in sperm motility between M. m. musculus strains. Based on these results, we argue that TRD likely reflects additional incompatibilities that reduce hybrid embryonic viability. In some common inbred strains of mice, selection against deleterious interactions appears to have unexpectedly driven introgression at loci involved in epistatic hybrid incompatibilities. The highly variable genetic basis to F1 hybrid incompatibilities between closely related mouse lineages argues that a thorough dissection of reproductive isolation will require much more extensive sampling of natural variation than has been commonly utilized in mice and other model systems.


Oxygen uptake, plasma catecholamines and cardiac output during neurolept-nitrous oxide and halothane anaesthesias.
Cardiac output, oxygen uptake and plasma catecholamines were studied in patients both awake and during anaesthesia prior to and during upper abdominal surgery. Two different forms of anaesthesia were used: neurolept-nitrous oxide (NLA) and halothane (HALO) anaesthesia. Oxygen uptake was determined by using a masspectrometer, and cardiac output was measured according to the Fick principle. Plasma catecholamines were analysed by high performance liquid chromatography. Cardiac output fell by 40% during NLA and by 30% during HALO. Concomitantly, the oxygen uptake fell by 40% and 35%, respectively. A linear relationship between cardiac output and oxygen uptake could be established both in the awake state and during anaesthesia, with no significant change in the slope or position of the regression line when anaesthesia was commenced. Ventricular filling pressures fell during both anaesthetic procedures. Adrenaline fell to half the plasma concentrations seen in normal subjects under resting conditions, while noradrenaline returned to normal from an initially 30-40% increased value. Surgery caused no significant changes in either cardiac output or oxygen uptake, whereas plasma adrenaline increased by 20 times and noradrenaline by 60-90%. The findings suggest that the reduced oxygen uptake during anaesthesia causes the fall in cardiac output rather than any cardiodepressant action of the anaesthetic. It is possible that the anaesthetic depresses whole-body metabolism by either blocking the effects of catecholamines or interfering with cellular metabolism.


An alternative splicing form of phosphatidylserine-specific phospholipase A1 that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans.
Phosphatidylserine-specific phospholipase A1 (PS-PLA1), which acts specifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to hydrolyze fatty acids at the sn-1 position of these phospholipids, was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In this study we isolated and sequenced cDNA clones encoding human PS-PLA1, which showed 80% homology with rat PS-PLA1 at the amino acid level. In addition to an mRNA encoding a 456-amino acid product (PS-PLA1), an mRNA with four extra bases inserted at the boundary of the exon-intron junction was detected in human tissues and various human cell lines. This mRNA is most probably produced via an alternative use of the 5'-splicing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS-PLA1DeltaC) that lacks two-thirds of the C-terminal domain of PS-PLA1. Unlike PS-PLA1, PS-PLA1DeltaC hydrolyzed exclusively lyso-PS but not PS appreciably. Any other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives were not hydrolyzed at all. These data demonstrated that PS-PLA1DeltaC exhibits lyso-PS-specific lysophospholipase activity and that the C-terminal domain of PS-PLA1 is responsible for recognizing diacylphospholipids. In addition, human PS-PLA1 gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).


Perceived control is significantly associated with psychological adaptation in individuals with known or suspected inborn errors of immunity.
Inborn errors of immunity (IEIs) are rare genetic disorders characterized by increased susceptibility to infection and immune system dysregulation. Despite the significant physical toll of IEIs, there is less information on clinical and patient-reported biopsychosocial outcomes and how these individuals psychologically adapt. We invited adults with IEIs or suspected IEIs (sIEIs) enrolled on a protocol at the National Institutes of Health to complete a cross-sectional survey measuring patient-reported biopsychosocial outcomes, psychological adaptation, and perceived control. We received responses from 312 individuals. Levels of adaptation to illness were similar to previously published cohorts of individuals with chronic health conditions. Participants reported significantly increased levels of anxiety, pain, sleep disturbance, and fatigue and significantly lower levels of physical functioning compared to the general population (p < 0.05). Multiple linear regression analysis indicated that perceived present control was significantly positively associated with adaptation (β = 0.26, p < 0.05). We found that perceived present control was significantly associated with psychological adaptation. Individuals with sIEIs in our sample struggled with poorer biopsychosocial outcomes than the general population, although these may not ultimately be directly related to psychological adaptation. Interventions to increase perceived control may be beneficial to this patient population. Clinicians should also consider screening and management for psychological and physical concerns including anxiety, depression, sleep disturbance, pain, and fatigue.


Myofibrillogenesis in the developing zebrafish heart: A functional study of tnnt2.
Various hypotheses have been proposed to explain the molecule processes of sarcomere assembly, partially due to the lack of systematic genetic studies of sarcomeric genes in an in vivo model. Towards the goal of developing zebrafish as a vertebrate model for this purpose, we characterized myofibrillogenesis in a developing zebrafish heart and went on to examine the functions of cardiac troponin T (tnnt2). We found that sarcomere assembly in zebrafish heart was initiated from a non-striated actin filament network at the perimembrane region, whereas sarcomeric myosin is independently assembled into thick filaments of variable length before integrating into the thin filament network. Compared to Z-discs that are initially aligned to form shorter periodic dots and expanded longitudinally at a later time, M-lines assemble later and have a constant length. Depletion of full-length tnnt2 disrupted the striation of thin filaments and Z-bodies, which sequentially affects the striation of thick filaments and M-lines. Conversely, truncation of a C-terminal troponin complex-binding domain did not affect the striation of these sarcomere sub-structures, but resulted in reduced cardiomyocyte size. In summary, our data indicates that zebrafish are a valuable in vivo model for studying both myofibrillogenesis and sarcomere-based cardiac diseases.


Regulation of insulin secretion by energy metabolism in pancreatic B-cell mitochondria. Studies with a non-metabolizable leucine analogue.
In mouse pancreatic islets the kinetics of insulin secretion and O2 uptake in response to the non-metabolizable leucine analogue (+/-)-BCH (2-endo- aminonorbornane -2-carboxylic acid) were compared. In addition, the fuel-mobilizing effect of (+/-)-BCH was studied with a mitochondrial fraction from islets. (1) Within 2 min 20 mM-(+/-)-BCH markedly enhanced insulin release or O2 consumption by islets respiring in the absence of exogenous fuels. During prolonged exposure to 20 mM-(+/-)-BCH secretion declined more rapidly than O2 uptake. (2) L-Glutamine (10 mM) prevented the decrease of both insulin release and O2 uptake of islets exposed to 20mM-(+/-)-BCH. During the second phase of insulin release in response to 20 mM-(+/-)-BCH + 10 mM-L-glutamine, kinetics of secretion and respiration correlated closely. (3) Initial peaks were consistently seen in the (+/-)-BCH-induced secretory profiles, but never in the respiratory profiles. (4) In contrast with L-glycerol 3-phosphate, L-malate or pyruvate, L-glutamine or L-glutamate maintained low rates of oxidative phosphorylation in B-cell mitochondria. The effects of L-glutamine or L-glutamate were potentiated severalfold by (+/-)-BCH. (5) The effects of other branched-chain amino acids on oxidative phosphorylation resembled their effects on insulin release, redox state of nicotinamide nucleotides and glutamate dehydrogenase activity. (6) The results support the view that (+/-)-BCH stimulates insulin secretion via a primary enhancement of hydrogen supply to the respiratory chain of B-cell mitochondria.


New findings in a patient with I-cell disease.
A case of I-cell disease showing some previously undescribed features is reported. The diagnosis was confirmed on the basis of lysosomal enzyme activity. The radiogram showed metaphyseal radiolucent bands not yet described and extensive epiphyseal stippling. The electronmicroscopical findings clearly demonstrated the presence of abnormal inclusion bodies in absorptive cells and in cells of the lamina propria of the small intestine. Immunological investigation revealed and increased absolute number of both B and T lymphocytes. The B cells, unlike the T cells, showed cytoplasmic vacuoles on phase contrast microscopy. The immune response to antigenic challenge was impaired, as assessed by specific antibody production and in vitro lymphocyte transformation testing.


[Microcirculation in diabetes: implications for chronic complications and treatment of the disease].
Diabetic microangiopathy is responsible for an important rate of morbidity and mortality related to the disease. Endothelial damage seems to be the triggering factor in the pathogenesis of microvascular complications. Diabetes mellitus and other metabolic diseases are associated to endothelial dysfunction, the most precocious known marker of atherosclerosis. Changes on microvascular reactivity are present in patients with diabetes mellitus, as well as in individuals with risk factors for this disease. Evaluation of endothelial and microvascular functions is possible using different invasive or preferentially non-invasive methods. Adequate control of diabetes mellitus might postpone or perhaps even prevent the microvascular disease. Microvascular dysfunction, when seen only by changes on microvascular reactivity, could be ameliorated with correction of risk factors or drug treatment.


Comparing the effectiveness of using generic and specific search terms in electronic databases to identify health outcomes for a systematic review: a prospective comparative study of literature search methods.
To compare the effectiveness of systematic review literature searches that use either generic or specific terms for health outcomes. Prospective comparative study of two electronic literature search strategies. The 'generic' search included general terms for health such as 'adolescent health', 'health status', 'morbidity', etc. The 'specific' search focused on terms for a range of specific illnesses, such as 'headache', 'epilepsy', 'diabetes mellitus', etc. The authors searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Education Resources Information Center for studies published in English between 1992 and April 2010. Number and proportion of studies included in the systematic review that were identified from each search. The two searches tended to identify different studies. Of 41 studies included in the final review, only three (7%) were identified by both search strategies, 21 (51%) were identified by the generic search only and 17 (41%) were identified by the specific search only. 5 of the 41 studies were also identified through manual searching methods. Studies identified by the two ELS differed in terms of reported health outcomes, while each ELS uniquely identified some of the review's higher quality studies. Electronic literature searches (ELS) are a vital stage in conducting systematic reviews and therefore have an important role in attempts to inform and improve policy and practice with the best available evidence. While the use of both generic and specific health terms is conventional for many reviewers and information scientists, there are also reviews that rely solely on either generic or specific terms. Based on the findings, reliance on only the generic or specific approach could increase the risk of systematic reviews missing important evidence and, consequently, misinforming decision makers. However, future research should test the generalisability of these findings.


An Analytic Gabor Feedforward Network for Single-Sample and Pose-Invariant Face Recognition.
Gabor magnitude is known to be among the most discriminative representations for face images due to its space- frequency co-localization property. However, such property causes adverse effects even when the images are acquired under moderate head pose variations. To address this pose sensitivity issue and other moderate imaging variations, we propose an analytic Gabor feedforward network which can absorb such moderate changes. Essentially, the network works directly on the raw face images and produces directionally projected Gabor magnitude features at the hidden layer. Subsequently, several sets of magnitude features obtained from various orientations and scales are fused at the output layer for final classification decision. The network model is analytically trained using a single sample per identity. The obtained solution is globally optimal with respect to the classification total error rate. Our empirical experiments conducted on five face data sets (six subsets) from the public domain show encouraging results in terms of identification accuracy and computational efficiency.


Thrombolytic and anticoagulant efficiencies of purified fibrinolytic enzyme produced from Cochliobolus hawaiiensis under solid-state fermentation.
Cochliobolus hawaiiensis Alcorn Assiut University Mycological Centre 8606 was chosen from the screened 20 fungal species as the potent producer of fibrinolytic enzyme on skimmed-milk agar plates. The greatest enzyme yield was attained when the submerged fermentation (SmF) conditions were optimized, and it was around (39.7 U/mg protein). Moreover, upon optimization of fibrinolytic enzyme production under solid-state fermentation (SSF), the maximum productivity of fibrinolytic enzyme was greatly increased recorded a bout (405 U/mg protein) on sugarcane bagasse, incubation period of 5 days, moisture level of 100%, initial pH of salt basal medium 7.8, incubation temperature at 35°C, and supplementation of the salt basal medium with corn steep liquor (80%, v/v). The yield of fibrinolytic enzyme by C. hawaiiensis under SSF was higher than that of SmF with about 10.20-fold. The purification procedures of fibrinolytic enzyme by ammonium sulfate (70%), gel filtration, and ion-exchange columns chromatography caused a great increase in its specific activity to 2581.6 U/mg protein with an overall yield of 55.89%, 6.37 purification fold and molecular weight of 35 kDa. Maximal activity was recorded at pH 7 and 37°C. Significant pH stability was recorded at pH 6.6-7.2, and thermal stability was recorded at 33-41°C. The enzyme showed the highest affinity toward fibrin, with Vmax of 240 U/mL and an apparent Km value of 47.61 mmol. Mg2+ and Ca2+ moderately induced fibrinolytic activity, whereas Cu2+ and Zn2+ greatly suppressed the enzyme activity. The produced enzyme is categorized as serine protease and non-metalloprotease. The purified fibrinolytic enzyme showed efficient thrombolytic and antiplatelet aggregation activities by completely prevention and dissolution of the blood clot which confirmed by microscopic examination and amelioration of blood coagulation assays. These findings suggested that the produced fibrinolytic enzyme is a promising agent in management of blood coagulation disorders.


Endoplasmic reticulum stress in the heart.
Over the last decade, it has become clear that the accumulation of misfolded proteins contributes to a number of neurodegenerative, immune, and endocrine pathologies, as well as other age-related illnesses. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to vascular and cardiac diseases. In large part, the misfolding of proteins takes place during synthesis on free ribosomes in the cytoplasm or on endoplasmic reticulum ribosomes. In fact, even under optimal conditions, approximately 30% of all newly synthesized proteins are rapidly degraded, most likely because of improper folding. Accordingly, stresses that perturb the folding of proteins during or soon after synthesis can lead to the accumulation of misfolded proteins and to potential cellular dysfunction and pathological consequences. To avert such outcomes, cells have developed elaborate protein quality-control systems for detecting misfolded proteins and making appropriate adjustments to the machinery responsible for protein synthesis and/or degradation. Important contributors to protein quality control include cytosolic and organelle-targeted molecular chaperones, which help fold and stabilize proteins from unfolding, and the ubiquitin proteasome system, which degrades terminally misfolded proteins. Both of these systems play important roles in cardiovascular biology. The focus of this review is the endoplasmic reticulum stress response, a protein quality-control and signal-transduction system that has not been well studied in the context of cardiovascular biology but that could be important for vascular and cardiac health and disease.


Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities.
Alzheimer's disease (AD) can be diagnosed with a considerable degree of accuracy. In some centers, clinical diagnosis predicts the autopsy diagnosis with 90% certainty in series reported from academic centers. The characteristic histopathologic changes at autopsy include neurofibrillary tangles, neuritic plaques, neuronal loss, and amyloid angiopathy. Mutations on chromosomes 21, 14, and 1 cause familial AD. Risk factors for AD include advanced age, lower intelligence, small head size, and history of head trauma; female gender may confer additional risks. Susceptibility genes do not cause the disease by themselves but, in combination with other genes or epigenetic factors, modulate the age of onset and increase the probability of developing AD. Among several putative susceptibility genes (on chromosomes 19, 12, and 6), the role of apolipoprotein E (ApoE) on chromosome 19 has been repeatedly confirmed. Protective factors include ApoE-2 genotype, history of estrogen replacement therapy in postmenopausal women, higher educational level, and history of use of nonsteroidal anti-inflammatory agents. The most proximal brain events associated with the clinical expression of dementia are progressive neuronal dysfunction and loss of neurons in specific regions of the brain. Although the cascade of antecedent events leading to the final common path of neurodegeneration must be determined in greater detail, the accumulation of stable amyloid is increasingly widely accepted as a central pathogenetic event. All mutations known to cause AD increase the production of beta-amyloid peptide. This protein is derived from amyloid precursor protein and, when aggregated in a beta-pleated sheet configuration, is neurotoxic and forms the core of neuritic plaques. Nerve cell loss in selected nuclei leads to neurochemical deficiencies, and the combination of neuronal loss and neurotransmitter deficits leads to the appearance of the dementia syndrome. The destructive aspects include neurochemical deficits that disrupt cell-to-cell communications, abnormal synthesis and accumulation of cytoskeletal proteins (e.g., tau), loss of synapses, pruning of dendrites, damage through oxidative metabolism, and cell death. The concepts of cognitive reserve and symptom thresholds may explain the effects of education, intelligence, and brain size on the occurrence and timing of AD symptoms. Advances in understanding the pathogenetic cascade of events that characterize AD provide a framework for early detection and therapeutic interventions, including transmitter replacement therapies, antioxidants, anti-inflammatory agents, estrogens, nerve growth factor, and drugs that prevent amyloid formation in the brain.


Prophylaxis for ribavirin-related anemia using eicosapentaenoic acid in chronic hepatitis C patients.
Ribavirin-related anemia is a serious side-effect of the pegylated interferon and ribavirin therapy used for hepatitis C, and may be cause for a reduction in ribavirin dose or even cessation of treatment. The aim of this study was to evaluate the prophylactic effects of oral eicosapentaenoic acid (EPA) supplementation on ribavirin-induced hemolytic anemia in pediatric and young adult patients. Twelve chronic hepatitis C patients ranging in age from 3 to 21 years (mean, 13.9 ± 5.1 years) who received pegylated interferon α-2b and ribavirin combination therapy were randomized to either the control group (n = 6) or EPA group (n = 6). Blood samples were collected before, and at 4, 8, and 16 weeks after treatment to measure clinical laboratory parameters. The reduction in hemoglobin levels of the EPA group was significantly ameliorated at 8 and 16 weeks when compared to the control group (P < 0.05). There was no significant difference in plasma ribavirin concentrations between the two groups during the treatment. However, one patient in the control group had a reduction in ribavirin dose. EPA supplementation prevented ribavirin-induced hemolytic anemia during combination therapy with pegylated interferon α-2b and ribavirin in pediatric and young adult patients.


Paternal age is affected by genetic abnormalities, perinatal complications and mental health of the offspring.
Infertility and fecundity problems concern 10-18% of partners in their reproductive years compromising around one million females and males in Poland. Research and analysis of factors that affect male fertility are limited, especially, regarding the age of the father and determining the age at which quality of semen decreases. Age of the father has greater impact than maternal age, on cases of sporadic autosomal dominant congenital diseases such as Apert, Crouzon, Pfeiffer, Noonan and Costello syndromes, multiple endocrine neoplasia (types 2A and 2B) and achondroplasia. However, there are only a few reports taking paternal advanced age into consideration for pre-mature birth, low Apgar scores or admission to a neonatal intensive care department. Paternal age increases the frequency of congenital diseases such as heart malformations as well as oral, palate and lip cleft. Moreover, mental disorders (autism, schizophrenia, bipolar disorder, low IQ level as well as ADHD) also occur more frequently in advanced father's age. Advanced paternal age is defined differently in every research. It depends on disorders in offspring we are talking about. Paternal age has an impact on child's health and development and it is as significant as maternal age, when it comes to reproductive matters.


Embryo-derived platelet activating factor.
Platelet-activating factor (PAF) is secreted by the preimplantation embryo of a number of species. The role of this secretion is yet to be fully elucidated. Evidence to date indicates that it has an important function as an autocrine stimulant of embryonic metabolism, growth and viability. Production of PAF by embryos appears to be severely compromised in vitro. This may be a major cause of reduced embryo viability following embryo culture and it may also help to explain the controversy in the literature regarding the production of PAF by embryos. PAF also alters several aspects of maternal physiology during early pregnancy including endometrial prostaglandin secretion. The significance of these changes remains to be defined.


Giant beaver palaeoecology inferred from stable isotopes.
This is a multi-individual (n = 11), stable carbon and nitrogen isotope study of bone collagen (δ13Ccol and δ15Ncol) from the giant beaver (genus Castoroides). The now-extinct giant beaver was once one of the most widespread Pleistocene megafauna in North America. We confirm that Castoroides consumed a diet of predominantly submerged aquatic macrophytes. These dietary preferences rendered the giant beaver highly dependent on wetland habitat for survival. Castoroides' δ13Ccol and δ15Ncol do not support the hypothesis that the giant beaver consumed trees or woody plants, which suggests that it did not share the same behaviours as Castor (i.e., tree-cutting and harvesting). The onset of warmer, more arid conditions likely contributed to the extinction of Castoroides. Six new radiocarbon dates help establish the chronology of the northward dispersal of the giant beaver in Beringia, indicating a correlation with ice sheet retreat.


Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways.
TBX1 is the major candidate gene for DiGeorge syndrome (DGS). Mouse studies have shown that the Tbx1 gene is haploinsufficient, as expected for a DGS candidate gene, and that it is required for the development of pharyngeal arches and pouches, as predicted by the DGS clinical phenotype. However, a detailed analysis of the cardiovascular phenotype associated with Tbx1 mutations has not been reported. Here we show that Tbx1 deficiency causes a number of distinct vascular and heart defects, suggesting multiple roles in cardiovascular development - specifically formation and growth of the pharyngeal arch arteries, growth and septation of the outflow tract of the heart, interventricular septation, and conal alignment. Comparison of phenotype and gene expression using a Tbx1-lacZ reporter allele supports a cell-autonomous function in the growth of the pharyngeal apparatus, and a cell non-autonomous function in the growth and early remodeling of the pharyngeal arch arteries. Our data do not support a direct role of neural crest cells in the pathogenesis of the Tbx1 mutant phenotype; however, these cells, and the cranial nerves, are misdirected. We hypothesize that this is due to the lack of a guidance role from the pouch endoderm, which is missing in these mutants.


Increased risk of OGTT-induced hypoglycemia after gastric bypass in severely obese patients with normal glucose tolerance.
Hypoglycemic episodes are described after bariatric surgery. To report the prevalence of hypoglycemia after a 75 g oral glucose load (OGTT) after Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (LAGB), and to identify predicting factors. Bariatric surgery referral center. Prospective cohort of 351 consecutive patients before and 12 months after bariatric surgery, on whom an OGTT was performed. The main outcome measure was postchallenge hypoglycemia (PCHy), defined as a 120 minute plasma glucose value<2.8 mmol/L (50.4 mg/dL). Only patients with an RYGB presented with PCHy. It occurred in 23 patients or a prevalence of 10.4% after an RYGB. The OR was 25.5 (95% CI 3.4-191; P<.001) compared with before surgery. Patients with PCHy after surgery had a lower glycated hemoglobin (HbA1c), and a lower 2-hour postchallenge value before surgery. Before surgery, patients with normal glucose tolerance had an increased risk of PCHy after surgery (OR 8.6, 95% CI 2.0-37.6; P< .001). The prevalence of OGTT-induced hypoglycemia is increased 25.5 times, 12 months after an RYGB. This is not observed after a gastric banding.


Minimally Invasive Spine Surgery: The Learning Curve of a Single Surgeon.
Retrospective cohort study. The learning curve associated with the implementation of minimally invasive spinal surgery (MIS) has been the center of attention in numerous publications. So far, these studies referred to a single MIS procedure. In our view, minimally invasive surgical skills are acquired simultaneously through a variety of procedures that share common features. The aim of this study was to analyze the skills progression of a single surgeon implementing diverse minimally invasive techniques. We retrospectively collected all patients who underwent spinal surgery for thoracic or lumbar pathology by a single surgeon between 2012 and 2015 at a single institute. Both minimally invasive as well as open surgical techniques were analyzed; these groups were compared on the basis of surgical indications and outcomes. Skills progression analysis in reference to minimally invasive technique was performed. A total of 230 patients met the inclusion criteria for this study. MIS group included higher percentage of lumbar discectomy and the open-surgery group included higher percentage of tumor resection surgery. Learning curve evaluation demonstrated increased surgical complexity, evaluated by number of levels treated, over the 4-year period, which corresponded with decreased complication rates. A gradual increase in surgical complexity over 4 years, together with careful patient selection, enables the surgeon to maintain the rate of complication within acceptable limits. The main challenge facing the MIS community is constructing an education program for MIS surgeons in order to reduce the learning curve-induced complications. Advancement of educational aids for MIS surgical skill improvement, including spine models, virtual and augmented reality aids and surgical simulators may reduce the learning curve of spine surgeons.


Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure.
Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.


Sclerosing Perivascular Epithelioid Cell Tumor of the Lung: A Case Report with Cytologic Findings.
Benign perivascular epithelioid cell tumor (PEComa) of the lung is a rare benign neoplasm, a sclerosing variant of which is even rarer. We present a case of 51-year-old man who was diagnosed with benign sclerosing PEComa by percutaneous fine needle aspiration cytology and biopsy. The aspirate revealed a few cell clusters composed of bland-looking polygonal or spindle cells with fine granular or clear cytoplasm. Occasional fine vessel-like structures with surrounding hyalinized materials were seen. The patient later underwent wedge resection of the lung. The histopathological study of the resected specimen revealed sheets of polygonal cells with clear vacuolated cytoplasm, variably sized thin blood vessels, and densely hyalinized stroma. In immunohistochemical studies, reactivity of tumor cells for human melanoma black 45 and Melan-A further supported the diagnosis of benign sclerosing PEComa. To the best of our knowledge, this is the first case of benign sclerosing PEComa described in lung.


Protein kinase regulation of cardiac phosphorylase activity and contractility.
The relationship between cAMP-dependent protein kinase activity and epinephrine-produced activation of phosphorylase and increase in contractility was investigated in the intact working rat heart. Epinephrine was administered as a bolus into the superior vena cava of open-chest preparations and the hearts were rapidly frozen. cAMP increased within 5 s and returned to control within 20-30 s. Protein kinase and phosphorylase kinase activity ratios increased transiently with the same time course as that for cAMP. The phosphorylase activity ratio and the rate of left ventricular pressure development increased maximally within 15 s and returned to control in 30-60 s. Continuous infusion of epinephrine caused a sustained elevation of the protein kinase. Free catalytic protein kinase activity increased proportionately with the dose of epinephrine. The beta-adrenergic blocking agent, practolol, had no effect on the basal levels of the five parameters studied, but did prevent the epinephrine-produced increases. The results suggest that the time course of cAMP-dependent protein kinase activation is appropriate if this enzyme is to play a role in the catecholamine-induced increase in both glycogenolysis and contractility in the in vivo heart.


Cyclooxygenase and thromboxane/prostaglandin receptor contribute to aortic endothelium-dependent dysfunction in aging female spontaneously hypertensive rats.
Cyclooxygenase (COX)-derived vasoconstrictory prostanoids contribute to impaired endothelium-dependent vasorelaxation in aging male (m) spontaneously hypertensive rats (SHR); however, vasomotor responses in aging female (f) SHR and sex differences in aging SHR are unknown. Examining mechanisms governing dysfunction in aging fSHR will contribute to understanding sex-dependent vascular complications in advanced hypertension. Aortic endothelium-dependent relaxation dose responses (ACh) of 16- and 30-wk-old mSHR and fSHR and normotensive Wistar-Kyoto rats were examined in the absence (no drug control) and presence of COX inhibition [indomethacin (Indo)] and thromboxane/prostaglandin receptor inhibition (SQ-29548). No drug control-treated 16-wk mSHR exhibited considerable blunting of the peak relaxation response to ACh (e.g., 77 +/- 4% relaxation to 10(-5) mol/l) vs. Wistar-Kyoto controls (89 +/- 6%), and greater dysfunction occurred in 30-wk mSHR (63 +/- 2%). Interestingly, ACh relaxations of fSHR were unimpaired at 16 wk (101 +/- 2% to 10(-5) mol/l), but blunted in 30 wk (76 +/- 4%). Indo and SQ-29548 restored robust ACh vasorelaxation in all groups (e.g., 113 +/- 3 and 112 +/- 3%, respectively, in Indo- and SQ-29548-treated 30-wk fSHR). Aortic COX-1 protein expression was elevated by 75% in 30-wk vs. 16-wk fSHR, whereas group-averaged ACh-stimulated aortic PGI(2) release (assessed as 6- keto-PGF(1alpha)) was 30% greater in 30-wk vs. 16-wk fSHR (9,926 +/- 890 vs. 7,621 +/- 690 pg.ml(-1).mg dry wt(-1)), although this did not reach significance (P = 0.0758). Dramatic deterioration of endothelium-dependent vasomotor function in fSHR across this age range involves COX and thromboxane/prostaglandin receptor, supporting a mechanism of impairment similar to that which occurs in aging mSHR.


Augmentation of syngeneic tumor-specific immunity by semiallogeneic cell hybrids.
Hybrid cell lines were established from fusions between lipopolysaccharide- (LPS) stimulated C57BL/6J spleen cells and MPC-11 tumor cells (45.6TG1.7, abbreviated M45), and were tested for their ability to immunize semiallogeneic mice against a parental tumor challenge. These hybrids were tumorigenic in syngeneic (BALB/c X C57BL/6J) F1 (CB6F1) mice but did not grow in semiallogeneic (BALB/c X A/J) F1 (CAF1) mice. All hybrids express both parental major histocompatibility antigens (H-2b and H-2d) as detected by indirect immunofluorescence and by their ability to function as either stimulators or targets for allogeneic cytotoxic lymphocytes (CTL). M45 tumor-associated antigens (TAA) were expressed on the hybrid surface as shown by their ability to act as either stimulators or targets for syngeneic CTL specific for M45 TAA. Immunization of semiallogeneic CAF1 mice with the hybrids i.p. followed by a challenge with M45 tumor cells resulted in extended survival when compared to untreated mice or animals immunized i.p. with M45 tumor cells. This immunity was specific and was not due to an allogeneic effect; immunization with an unrelated H-2bd tumor, 70Z/3, or H-2bd B6D2F1 spleen cells or with semiallogeneic spleen cells plus M45 did not protect mice from M45 challenge. Interestingly, prophylactic priming with semiallogeneic hybrid tumor cells or parental myeloma cells led to M45-specific CTL and "help" for an in vitro CTL response; however, the degree of CTL priming by hybrid tumors was not augmented when compared to the level of CTL achieved with parental tumor alone. Hence, stimulation of CTL activity per se by hybrid tumor cells cannot explain the protective effect of hybrid tumor immunization. These studies nevertheless confirm that semiallogeneic hybrids, which we show express TAA and alloantigens, can be used to immunize mice against a lethal syngeneic myeloma tumor challenge.


[Spatial frequency characteristics of the receptive fields of neurons of the lateral suprasylvian area of the cerebral cortex in the cat].
Two-dimensional spatial-frequency characteristics of the receptive fields of 46 neurons in the lateral suprasylvian area were analyzed in awake cats. Extreme spatial frequencies were disposed in the range less than 1.5 cycle/deg. Spatial-frequency bands were measured for 21 neurons, their mean value was 1.47 +/- 0.5 octaves. 17 neurons had inhibitory characteristics if testing gratings were of nonoptimal orientations. For 6 neurons the inhibitory characteristics measured with nonoptimal orientations were in form of a narrow band with mean value of 1.47 +/- 0.6 octaves.


MicroRNA-1205 Regulation of FRYL in Prostate Cancer.
High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors in vivo. To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced in vitro and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.


The central laboratory: who needs it?
A central lab can provide substantial savings in personnel and procurement costs while promoting improvements in service. Activities integral to this process are coordinating purchasing, implementing common processes, identifying key facilities, and using a common management information system.


The longitudinal validity of proxy-reported CHU9D.
The Child Health Utility 9D (CHU9D) currently represents the only preference-based health-related quality-of-life instrument designed exclusively from its inception for application with children. The objective of this study was to examine the construct validity and responsiveness of the proxy-reported (parent) CHU9D in a mental health setting using utility weights derived from an adult and adolescent population, respectively. The discriminant validity and convergent validity were examined using the mental health-specific 'The Strengths and Difficulties Questionnaire' (SDQ) and the generic KIDSCREEN-27. Responsiveness was assessed by examining the floor-ceiling effects, the magnitude of change over time, and the ability to differentiate between improvement and no improvement. The study included 396 children with mental health problems. CHU9D showed good construct validity, with correlation coefficients ranging between 0.329 and 0.571 for SDQ Impact score and KIDSCREEN-27 Psychological Well-being. CHU9D was able to distinguish between groups of children with different levels of mental health problems (p < 0.001). The absolute magnitudes of the group mean differences were larger using adolescent weights. No evidence of a floor/ceiling effect was found at the baseline. A standardized response mean of 0.634-0.654 was found for the children who experienced clinically significant improvements. CHU9D was able to discriminate between children who experienced positive and no health improvements (p < 0.001). This study provides the first evidence on responsiveness for CHU9D in a mental health context. The findings demonstrate that CHU9D is an appropriate HRQOL measure for use in mental health trials. Furthermore, the results show that the preference weights generated from an adolescent population resulted in the larger mean differences between groups.


Compliance to clinical guidelines determines outcome in glutaric aciduria type I in the era of newborn screening.
We report on a 4.5-year-old patient diagnosed with Glutaric aciduria type I (GAI), an autosomal recessive inborn error of lysine, hydroxylysine and tryptophan metabolism. Enzymatic assay in cultivated skin fibroblasts revealed complete absence of glutaryl-CoA dehydrogenase activity. All 11 Exons of the GCDH-Gen were sequenced and homozygosity for a yet undescribed mutation was identified. The patient was treated following the recently published guidelines for GA-I. Following this treatment regimen, the child developed normally without any manifest clinical crises. Our patient provides evidence that early commencement and strict adherence to treatment improves clinical outcome even in patients with complete absence of enzyme activity.


The role of epigenetics in kidney malignancies.
Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.


Tooth Fairy guilty of favouritism!
To determine the proportion of children visited by the Tooth Fairy, the child-related factors that influence the likelihood of her visit, and the parent-related variables that affect the amount of money the Tooth Fairy leaves. Cross-sectional questionnaire study. Zürich, Switzerland. 3617 parents of children (mean age of children, 6.8 years; 51.9% girls) who had lost at least one deciduous tooth received a self-developed questionnaire; 1274 questionnaires were returned (35.2%). Primary outcome variables were the Tooth Fairy's visit after tooth loss and the amount of money given in case of a visit. Child- and parent-related variables were assessed as predictors of the main outcomes. Most parents (71.0%) reported that the Tooth Fairy visited their child. She usually exchanged the lost tooth for money (55.8% of visits) or placed money next to the tooth (40.7%); rarely did she take the tooth without pecuniary substitution. The Tooth Fairy left an average of 7.20 Swiss francs (approximately AU$9.45). The Tooth Fairy favoured visiting for the teeth of older children (odds ratio [OR], per year, 1.87; 95% CI, 1.09-3.21), of boys (OR, 2.65; 95% CI, 1.09-6.42), and of children who believed in her (OR, 4.12; 95% CI, 1.77-9.64). The amount of money was influenced by maternal, but not paternal socio-demographic factors, including level of education (OR, per level, 0.78; 95% CI, 0.66-0.92) and country of origin (OR, Western countries v non-Western countries, 2.35; 95% CI, 1.20-4.62). The Tooth Fairy does not visit all children after tooth loss, displaying clear preferences in her choice of business partners. The odds of a visit are dramatically increased if she is believed in, and the value of a deciduous tooth is influenced by socio-demographic factors.


Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms.
Human umbilical vein endothelial cell attachment, spreading and migration on collagen and vitronectin are mediated by integrins alpha 2 beta 1 and alpha v beta 3, respectively, and these events take place in the absence of cytokines, growth factors, or chemoattractants. Cell attachment and spreading on these ligands occur in the absence of extracellular calcium, as does migration on collagen. In contrast, vitronectin-mediated migration is absolutely dependent on the presence of extracellular calcium. Cell contact with immobilized vitronectin or anti-alpha v beta 3 mAbs promotes a measurable rise in [Ca2+]i which requires an extracellular calcium source, whereas collagen, or anti-alpha 2 beta 1 mAbs fail to promote this signaling event. In fact, vitronectin-mediated migration and the rise in intracellular calcium showed the same dose dependence on extracellular calcium. While vitronectin and collagen differ in their ability to induce a calcium influx both ligands or antibodies to their respective integrins promote an equivalent increase in intracellular pH consistent with activation of the Na/H antiporter an event independent of extracellular calcium. These results support two salient conclusions. Firstly, collagen and vitronectin, through their respective integrins, promote distinct intracellular signaling events. Secondly, the alpha v beta 3 specific influx of calcium is not required for cell spreading yet appears to facilitate cellular migration on vitronectin.


Arsenic in drinking water and acute coronary syndrome in Zrenjanin municipality, Serbia.
Arsenic is constantly present in drinking water supply systems of Zrenjanin municipality across decades. It presents a great public health problem in Serbia, but its relationship with acute coronary syndrome (ACS) has not been studied previously. The aims of this study were to assess the incidence of ACS in two areas from Zrenjanin municipality consuming different levels of arsenic in drinking water, and to explore the association between arsenic exposure and the probability of fatal outcome of ACS. The research was a registry-based ecological study of two populations consuming water with different arsenic levels, based on current guidelines (10 μg/L). Median arsenic in the area above national standard was 80 μg/L; median arsenic in the other area was 1 μg/L. Newly diagnosed cases of ACS were obtained from the National Registry for Acute Coronary Syndrome from 2006 to 2010. The two populations were comparable by age, gender, and prevalence of risk factors for ACS. Standardized incidence rates (SIR) of ACS were higher for people consuming arsenic above standard (average five-year SIR was 237.00 per 100.000; 95% CI=214.93-260.74), in comparison to people consuming arsenic within limits (average SIR=124.40 per 100.000; 95% CI=96.00-158.56). Exposure to arsenic above limits was insignificantly associated with fatal outcome of ACS for the whole population, men and women. Consumption of arsenic above national standards was associated with higher risk for the occurrence of acute coronary syndrome and with insignificantly higher probability of fatal outcome of ACS in Zrenjanin municipality.


Recurrent malignant peripheral nerve sheath tumor presenting as an asymptomatic intravenous thrombus extending to the heart: a case report.
Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart. A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation. In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.


Effective Connectivity Modeling for fMRI: Six Issues and Possible Solutions Using Linear Dynamic Systems.
Analysis of directionally specific or causal interactions between regions in functional magnetic resonance imaging (fMRI) data has proliferated. Here we identify six issues with existing effective connectivity methods that need to be addressed. The issues are discussed within the framework of linear dynamic systems for fMRI (LDSf). The first concerns the use of deterministic models to identify inter-regional effective connectivity. We show that deterministic dynamics are incapable of identifying the trial-to-trial variability typically investigated as the marker of connectivity while stochastic models can capture this variability. The second concerns the simplistic (constant) connectivity modeled by most methods. Connectivity parameters of the LDSf model can vary at the same timescale as the input data. Further, extending LDSf to mixtures of multiple models provides more robust connectivity variation. The third concerns the correct identification of the network itself including the number and anatomical origin of the network nodes. Augmentation of the LDSf state space can identify additional nodes of a network. The fourth concerns the locus of the signal used as a "node" in a network. A novel extension LDSf incorporating sparse canonical correlations can select most relevant voxels from an anatomically defined region based on connectivity. The fifth concerns connection interpretation. Individual parameter differences have received most attention. We present alternative network descriptors of connectivity changes which consider the whole network. The sixth concerns the temporal resolution of fMRI data relative to the timescale of the inter-regional interactions in the brain. LDSf includes an "instantaneous" connection term to capture connectivity occurring at timescales faster than the data resolution. The LDS framework can also be extended to statistically combine fMRI and EEG data. The LDSf framework is a promising foundation for effective connectivity analysis.


A new method for second toe flap revascularization in plantar dominant artery pattern - dorsal metatarsal artery interpositional graf.
Toe transfer to hand is a viable option for patients, which can provide functionally useful digits. Harvesting of the second toe is still accepted as a demanding surgical procedure. The major questions before this transfer are the location and the dominance of the arterial anatomy of the second toe. The authors present the incidence of patients with a dominant plantar artery system and a description of a versatile technique that can be used for toe transfers in these patients. The study was designed retrospectively. Toe to hand transfers performed between 2010 and 2018 were reviewed. The patients with a dominant plantar arterial system were included in this study. The dorsalis pedis arterial graft technique described by the authors was used in all cases with a dominant plantar system. All of transfers were done by the senior author. All cases followed up at least one year post-operatively. The survival of the transferred finger was examined in the follow-ups. Eleven toe to hand transplantation cases in nine traumatic patients were included in this series. The reason for the operation was trauma in all patients. Second toe transfer was performed in all of the cases. Plantar dominant arterial system was seen in 3 of the 9 patients. Dorsal arterial system was dominant in the remaining six patients. Dorsalis pedis arterial graft technique was used in these four cases. All of the toes survived, and reexploration was needed in 2 cases because of venous insufficiency. Mean follow-up time was 16.4 months. This is the first study to recommend the use of dorsalis pedis as an arterial graft instead of vein grafts. This surgical method described will make these rarely performed transfers easier and affect the success rates positively.


Amycolatopsis methanolica sp. nov., a facultatively methylotrophic actinomycete.
The generic position of a gram-positive, facultatively methylotrophic actinomycete known as Nocardia sp. strain 239 was determined by comparing reverse transcriptase sequences of 16S rRNA. The assignment of the organism to the genus Amycolatopsis was strongly supported by chemotaxonomic and morphological data. A comparison with the type strains of validly described Amycolatopsis species showed that the organism formed the nucleus of a new species. The name proposed for this new species is Amycolatopsis methanolica. The organism has been deposited in the National Collection of Industrial Bacteria as NCIB 11946.


Familial concordance of dietary fat practices and intake.
This study examined parent and child dietary fat practices and child dietary fat intake. High- and low-fat practices and percentage of kilocalories from fat were obtained from food records completed by 132 students in the 4th to 6th grades. Parents completed three scales: meat modifications (MMOD); fat substitutions (FSUB); and fruit, juice, and vegetable practices (FJVP). A parent low-fat practices (PLFP) scale was created with the items matching the child low-fat practices (LFPs). Parent PLFP, FSUB, and FJVP were significantly correlated with child LFPs. Parent LFP was a significant predictor of child LFP. Family intervention programs targeting dietary fat behaviors should encourage use of low-fat dietary behaviors.


Do the structural changes defined by the electron density topology necessarily affect the picture of the bonding?
The analysis of domain averaged Fermi holes (DAFH) was applied to the elucidation of the nature of the bonding interactions in supported metal carbonyls, where multicenter bonding of the bridging ligands and direct metal-metal bonds are considered as possible alternatives. The main focus is directed on the detailed scrutiny of the possible impact of the changes in the topology of electron density induced by the systematic variation of the geometry of the studied carbonyls on the picture of the bonding provided by the visual description in terms of DAFH analysis. It has been shown that irrespective of the dramatic changes in the topology of electron density exemplified by the existence and/or the lack of direct metal-metal bond path, the DAFH picture of the bonding remains practically unaffected and in all cases consistently suggests that the bonding of the bridging ligands exhibits the typical features of delocalized 3c-2e bonding.