Physical fitness in northern European youth: reference values from the Latvian Physical Health in Youth Study.
Physical fitness has the potential to be used as a key health determinant in youth. The aim of this study was to establish age- and sex-stratified reference values for health-related physical fitness in Latvian school-age children and to identify notable sex differences. Physical fitness was assessed using the EUROFIT test battery. Data were gathered from schoolchildren aged between 6 and 17 years (n = 10,464) by a medical team using standardised methods (EUROFIT battery). Fitness levels, stratified by chronological age and sex, were computed as mean ± SD. Each test was also analysed for differences between males and females in each age group. Boys performed better than girls in muscular endurance and strength, cardiorespiratory endurance, and speed-agility fitness tests. Girls had better flexibility than boys (p < 0.001). There was also a more pronounced improvement in physical fitness scores with age in boys compared with girls. Physical fitness reference values were developed for Latvian children and adolescents. These reference values will permit comparisons between students during physical education lessons and provide a baseline against which progress in physical fitness among northern European youths can be compared.


Growth, growth hormone (GH)-binding protein, and GH receptors are differentially regulated by peak and trough components of the GH secretory pattern in the rat.
Body growth, GH secretory pattern, hepatic GH receptor (GHR), and plasma GH-binding protein (GHBP) levels are all sexually dimorphic in the rat. Male rats grow faster than females, and in GH-deficient animals, GH therapy is more effective when given in a pulsatile pattern rather than a continuous infusion. This contrasts with GHBP and hepatic GHR levels, which are lower in males than in females and raised by continuous but not pulsatile GH therapy. One possible explanation is that growth is primarily regulated by GH pulses, whereas GHR and GHBP are regulated mostly by the trough levels (which are lower in males than in females). To test this hypothesis directly, GH-deficient dwarf rats were given patterned iv infusions of hGH in which the relative contributions of the peak and trough components of the GH pattern were systematically varied, independently of dose, and their effects on weight and length gain, plasma GHBP, and hepatic GHR binding were measured. We found that the dose-response curves for GH given by pulsatile vs. continuous infusion were significantly nonparallel, and that growth was primarily stimulated by the pulsatile component of a mixed GH infusion pattern; doubling the GH dose by adding a continuous (c) infusion to a series of pulses (p) neither enhanced nor inhibited weight gain (36 micrograms hGH/day pulses (36p) vs. 36 micrograms hGH/day pulses + 36 micrograms hGH/day continuously (36p + 36c):0.9 +/- 0.2 g/day vs. 1.1 +/- 0.2 g/day), whereas doubling the GH dose by adding a pulsatile component significantly enhanced growth (72p:2.1 +/- 0.2 g/day, P < 0.01). Conversely, hepatic GHR and plasma GHBP levels were highly sensitive to the continuous element of the mixed infusion pattern and were totally unaffected by varying the pulsatile component over a wide range of doses. These results strongly suggest that growth and hepatic GHR/plasma GHBP respond differentially to the peak and trough components of the GH secretion pattern in the rat.


Chitin synthetase distribution on the yeast plasma membrane.
Purified, intact yeast plasma membranes were allowed to synthesize chitin, and the nascent chains of polysaccharide were observed either by the fluorescence produced with a brightener or by autoradiography. By both methods, it was concluded that the newly formed chitin emerged at many sites on each membrane. Thus, the synthetase that catalyzes chitin formation has a similar distribution. Since chitin synthetase is found mainly in a zymogen form, these results confirm the hypothesis that initiation of the chitinous primary septum of Saccharomyces occurs by localized activation of the uniformly distributed zymogen.


Calibration drift in regression and machine learning models for acute kidney injury.
Predictive analytics create opportunities to incorporate personalized risk estimates into clinical decision support. Models must be well calibrated to support decision-making, yet calibration deteriorates over time. This study explored the influence of modeling methods on performance drift and connected observed drift with data shifts in the patient population. Using 2003 admissions to Department of Veterans Affairs hospitals nationwide, we developed 7 parallel models for hospital-acquired acute kidney injury using common regression and machine learning methods, validating each over 9 subsequent years. Discrimination was maintained for all models. Calibration declined as all models increasingly overpredicted risk. However, the random forest and neural network models maintained calibration across ranges of probability, capturing more admissions than did the regression models. The magnitude of overprediction increased over time for the regression models while remaining stable and small for the machine learning models. Changes in the rate of acute kidney injury were strongly linked to increasing overprediction, while changes in predictor-outcome associations corresponded with diverging patterns of calibration drift across methods. Efficient and effective updating protocols will be essential for maintaining accuracy of, user confidence in, and safety of personalized risk predictions to support decision-making. Model updating protocols should be tailored to account for variations in calibration drift across methods and respond to periods of rapid performance drift rather than be limited to regularly scheduled annual or biannual intervals.


Total vascular exclusion for hepatic resection in cirrhotic patients. Application of venovenous bypass.
Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes.


Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial.
Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.


Youth Access to Cigarettes Across Seven European Countries: A Mixed-Methods Study.
Despite widespread age-of-sale restrictions on tobacco, adolescents continue to obtain cigarettes and experiment with smoking. This mixed-methods study aimed to understand how European adolescents access cigarettes and how the policy context may influence this process, using a realist evaluation approach. This is the first study to assess access to cigarettes across various European contexts. A survey of 4104 students was combined with qualitative data from focus groups among 319 adolescents aged 14-19 across seven European countries. Data were synthesized to explore mechanisms via which young people obtain cigarettes despite age-of-sale restrictions. While purchasing cigarettes from supermarkets was widely regarded as difficult, many participants purchased cigarettes from noncompliant retailers (often in smaller shops or cafes). Other contra-mechanisms included circumventing age checks, proxy purchases, and/or social sources. Dominant forms of access differed across the seven contexts, with direct purchases more common where perceived enforcement was low (eg, Belgium) and proxy purchases more important where perceived enforcement of age-of-sale laws was high (eg, Finland). The effectiveness of age-of-sale restrictions in reducing youth access appears to be influenced by a range of contextual factors including retailer compliance, the availability of vending machines, and the specific minimum age-of-sale. Our findings illustrate the relevance of programme theory in understanding the contra-mechanisms that undermine the effectiveness of age-of-sale laws in discouraging youth smoking. Young people's access to cigarettes could be further limited by addressing these contra-mechanisms, including an increase in the legal sales age (particularly in Belgium), banning vending machines, and strengthening enforcement. Despite widespread implementation of age-of-sale laws, a substantial proportion of minors continue to access cigarettes. Young people use a number of contra-mechanisms to circumvent age-of-sale restrictions. These include accessing cigarettes via social sources, proxy sales or by circumventing age checks. Our findings show that in contexts where perceived enforcement of age-of-sale restrictions is high, young people are more reliant on irregular forms of access such as proxy sales. Young people's access to cigarettes may be further reduced by policy interventions that address these contra-mechanisms-for example, banning vending machines, strengthening enforcement of age-of-sale laws, and increasing the minimum age-of-sale.


A spin label study of the membranolytic effects of crystalline monosodium urate monohydrate.
The nature of the membranolytic interaction between monosodium urate monohydrate (MSUM) crystals and phospholipid membranes was studied using electron spin resonance. Two spin probe molecules were incorporated into intact human erythrocytes and incubated with MSUM crystals. The apparent increased fluidity of 5-doxyl stearic acid incorporated erythrocytes after a 2 h incubation with MSUM was probably due to an electrostatically induced redistribution of probe from the outer more rigid layer to the fluid inner leaflet via a flip-flop mechanism. It was suggested that the MSUM induced redistribution of cationic amphiphilic probe population in the whole erythrocyte was also due to an electrostatic interaction between negatively charged MSUM crystals and positively charged probe. Possible mechanisms of MSUM induced membranolysis are discussed.


Evaluating artificial intelligence software for delineating hemorrhage extent on CT brain imaging in stroke: AI delineation of ICH on CT.
The extent and distribution of intracranial hemorrhage (ICH) directly affects clinical management. Artificial intelligence (AI) software can detect and may delineate ICH extent on brain CT. We evaluated e-ASPECTS software (Brainomix Ltd.) performance for ICH delineation. We qualitatively assessed software delineation of ICH on CT using patients from six stroke trials. We assessed hemorrhage delineation in five compartments: lobar, deep, posterior fossa, intraventricular, extra-axial. We categorized delineation as excellent, good, moderate, or poor. We assessed quality of software delineation with number of affected compartments in univariate analysis (Kruskall-Wallis test) and ICH location using logistic regression (dependent variable: dichotomous delineation categories 'excellent-good' versus 'moderate-poor'), and report odds ratios (OR) and 95 % confidence intervals (95 %CI). From 651 patients with ICH (median age 75 years, 53 % male), we included 628 with assessable CTs. Software delineation of ICH extent was 'excellent' in 189/628 (30 %), 'good' in 255/628 (41 %), 'moderate' in 127/628 (20 %), and 'poor' in 57/628 cases (9 %). The quality of software delineation of ICH was better when fewer compartments were affected (Z = 3.61-6.27; p = 0.0063). Software delineation of ICH extent was more likely to be 'excellent-good' quality when lobar alone (OR = 1.56, 95 %CI = 0.97-2.53) but 'moderate-poor' with any intraventricular (OR = 0.56, 95 %CI = 0.39-0.81, p = 0.002) or any extra-axial (OR = 0.41, 95 %CI = 0.27-0.62, p<0.001) extension. Delineation of ICH extent on stroke CT scans by AI software was excellent or good in 71 % of cases but was more likely to over- or under-estimate extent when ICH was either more extensive, intraventricular, or extra-axial.


Palliative Radiation Therapy: Knowledge and Referrals Among Primary Care Providers.
Cancer is a leading cause of death worldwide. Many individuals have significant symptoms related to this disease. Palliative radiation therapy (PRT) can relieve symptoms at the end of life for those with metastatic cancer. PRT is underused in treating patients with symptomatic cancer at the end of life, particularly in rural and remote settings, despite the evidence that supports it. The purpose of this evidence-based practice study is to (a) assess the knowledge of rural primary care providers about PRT, (b) disseminate evidence on the indications for PRT, and


The Bacillus subtilis yabQ gene is essential for formation of the spore cortex.
An extensive screening for transcripts with probes specific for the genes in a 108 kb region from rrnO to spo0H of the Bacillus subtilis chromosome led to identification of an operon, yabP--yabQ--divIC--yabR, the expression of which was initiated at the second hour of sporulation and in a sigma(E)-dependent manner. Among three y genes in the operon, deletion of the yabQ gene, which is predicted to encode a protein product of 468 residues with five membrane-spanning domains, resulted in a large decrease in numbers of chloroform-, lysozyme- and heat-resistant spores, compared to findings with the wild-type strain. Electron microscopy revealed that development of the spore cortex was blocked in the yabQ mutant. In addition, although the spore coat was visible, the inner coat layer of the mutant seemed partially detached from the outer coat. In sporangia of the strains harbouring an in-frame fusion of the green fluorescent protein gene to yabQ, fluorescence was detected around the forespore. This localization did not depend on SpoIVA or on CotE functions, both of which determine proper localization of coat proteins and cortex formation. The yabQ deletion did not affect expression of genes involved in cortex synthesis. These results suggest that the YabQ protein localizes in the membrane of the forespore and plays an important role in cortex formation.


Development of a 3D coupled physical-biogeochemical model for the Marseille coastal area (NW Mediterranean Sea): what complexity is required in the coastal zone?
Terrestrial inputs (natural and anthropogenic) from rivers, the atmosphere and physical processes strongly impact the functioning of coastal pelagic ecosystems. The objective of this study was to develop a tool for the examination of these impacts on the Marseille coastal area, which experiences inputs from the Rhone River and high rates of atmospheric deposition. Therefore, a new 3D coupled physical/biogeochemical model was developed. Two versions of the biogeochemical model were tested, one model considering only the carbon (C) and nitrogen (N) cycles and a second model that also considers the phosphorus (P) cycle. Realistic simulations were performed for a period of 5 years (2007-2011). The model accuracy assessment showed that both versions of the model were able of capturing the seasonal changes and spatial characteristics of the ecosystem. The model also reproduced upwelling events and the intrusion of Rhone River water into the Bay of Marseille well. Those processes appeared to greatly impact this coastal oligotrophic area because they induced strong increases in chlorophyll-a concentrations in the surface layer. The model with the C, N and P cycles better reproduced the chlorophyll-a concentrations at the surface than did the model without the P cycle, especially for the Rhone River water. Nevertheless, the chlorophyll-a concentrations at depth were better represented by the model without the P cycle. Therefore, the complexity of the biogeochemical model introduced errors into the model results, but it also improved model results during specific events. Finally, this study suggested that in coastal oligotrophic areas, improvements in the description and quantification of the hydrodynamics and the terrestrial inputs should be preferred over increasing the complexity of the biogeochemical model.


Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.
Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.


[Computer-assisted audiometry].
A computer audiometer has been designed on the computer using program "Audiometry". No special devices are needed. This computer audiometric complex can perform all kinds of behavioral audiometry: tonal threshold, suprathreshold, speech and in a free sound field.


Multiple nuclear gene phylogenetic analysis of the evolution of dioecy and sex chromosomes in the genus Silene.
In the plant genus Silene, separate sexes and sex chromosomes are believed to have evolved twice. Silene species that are wholly or largely hermaphroditic are assumed to represent the ancestral state from which dioecy evolved. This assumption is important for choice of outgroup species for inferring the genetic and chromosomal changes involved in the evolution of dioecy, but is mainly based on data from a single locus (ITS). To establish the order of events more clearly, and inform outgroup choice, we therefore carried out (i) multi-nuclear-gene phylogenetic analyses of 14 Silene species (including 7 hermaphrodite or gynodioecious species), representing species from both Silene clades with dioecious members, plus a more distantly related outgroup, and (ii) a BayesTraits character analysis of the evolution of dioecy. We confirm two origins of dioecy within this genus in agreement with recent work on comparing sex chromosomes from both clades with dioecious species. We conclude that sex chromosomes evolved after the origin of Silene and within a clade that includes only S. latifolia and its closest relatives. We estimate that sex chromosomes emerged soon after the split with the ancestor of S. viscosa, the probable closest non-dioecious S. latifolia relative among the species included in our study.


Partial recovery of alcohol dependence-related deficits in sleep evoked potentials following 12 months of abstinence.
Stimuli presented during sleep can produce an evoked EEG delta wave referred to as a K-complex. These responses occur when large numbers of cortical cells burst fire in a synchronized manner. Large amplitude synchronized scalp responses require that the CNS contain large numbers of healthy neurons that are interconnected with highly functional white matter pathways. The P2, N550, and P900 components of the evoked K-complex are sensitive measures of normal healthy brain aging, showing a decrease in amplitude with age. N550 and P900 amplitudes are also reduced in recently detoxified alcoholics, most dramatically over frontal scalp regions. The present study tested the hypothesis that the amplitude of K-complex related evoked potential components would increase with prolonged abstinence. Fifteen alcoholics (12 men) were studied twice, separated by a 12 month period, during which time they were followed with monthly phone calls. Subjects were aged between 38 and 60 years at their first study. They had on average a 29.3 ± 6.7 year drinking history and had been abstinent for between 54 and 405 days at initial testing. Evoked K-complexes were identified in the EEG and averaged to enable measurement of the P2, N550 and P900 peaks. Data were collected from seven scalp sites (FP1, FP2, Fz, FCz, Cz, CPz, and Pz). N550 and P900 amplitudes were significantly higher after 12 months of abstinence and an improvement of at least 5 μV occurred in 12 of the 15 subjects. N550 and P900 also showed highly significant site by night interactions with the largest increases occurring over prefrontal and frontal sites. The data indicate that the sleep evoked response may provide a sensitive marker of brain recovery with abstinence from alcohol.


Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants.
Persistent patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Prostaglandin synthetase inhibitors such as indomethacin promote PDA closure but also have potential side effects. The effect of the prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA would be exposed to indomethacin, warrants particular scrutiny. To determine the effect of prophylactic indomethacin on mortality and morbidity in preterm infants. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 5, 2010), MEDLINE, EMBASE and CINAHL (until April 2010), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared prophylactic indomethacin versus placebo or no drug in preterm infants. The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two review authors. Nineteen eligible trials in which 2872 infants participated were identified. Most participants were very low birth weight, but the largest single trial restricted participation to extremely low birth weight infants (N = 1202). The trials were generally of good quality.The incidence of symptomatic PDA [typical relative risk (RR) 0.44, 95% confidence interval (CI) 0.38 to 0.50] and PDA surgical ligation (typical RR 0.51, 95% CI 0.37,0.71) was significantly lower in treated infants. Prophylactic indomethacin also significantly reduced the incidence of severe intraventricular haemorrhage (typical RR 0.66, 95% CI 0.53 to 0.82). Meta-analyses found no evidence of an effect on mortality (typical RR 0.96, 95% CI 0.81 to 1.12) or on a composite of death or severe neurodevelopmental disability assessed at 18 to 36 months old (typical RR 1.02, 95% CI 0.90, 1.15). Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment.


Riboflavin-Ultraviolet A Corneal Cross-linking for Keratoconus.
To evaluate the safety, efficacy of riboflavin-ultraviolet A irradiation (UVA) corneal cross-linking and present refractive changes induced by the treatment in cases of keratoconus. The study includes 15 eyes of 9 patients with keratoconus with an average keratometric (K) reading less than 54 D and minimal corneal thickness greater than 420 microns. The corneal epithelium was removed manually within the central 8.5 mm diameter area and the cornea was soaked with riboflavin eye drops (0.1% in 20% dextran tau-500) for 30 minutes followed by exposure to UVA radiation (365 nm, 3 mW/cm(2)) for 30 minutes. During the follow-up period, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, slit lamp examination and topographic changes were recorded at the first week, first month, 3 and 6 months. There was statistically significant improvement of UCVA from a preoperative mean of 0.11 +/- 0.07 (range 0.05-0.3) to a postoperative mean of 0.15 +/- 0.06 (range 0.1-0.3) (P < 0.05). None of the eyes lost lines of preoperative UCVA but 1 eye lost 1 line of preoperative BSCVA. The preoperative mean K of 49.97 +/- 2.81 D (range 47.20-51.75) changed to 48.34 +/- 2.64 D (range 45.75-50.40). This decrease in K readings was statistically significant (P < 0.05). All eyes developed minimal faint stromal haze that cleared in 14 eyes within 1 month. In only 1 eye, this resulted in a very faint corneal scar. Other sight threatening complications were not encountered in this series. Progression of the original disease was not seen in any of the treated eyes within 6 months of follow-up. Riboflavin-UVA corneal cross-linking is a safe and promising method for keratoconus. Larger studies with longer follow up are recommended.


Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function.
Recent studies suggest that women are at greater risk for Alzheimer's disease than men and that estrogen replacement can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that the increased risk for Alzheimer's-related dementia is due, in part, to the loss of ovarian function in postmenopausal women and to the effects that decreased levels of ovarian hormones have on basal forebrain cholinergic function. In the present study, the effects of aging and ovariectomy on cholinergic neurons in the rat basal forebrain were examined to determine (1) whether aging differentially affects cholinergic neurons in the basal forebrain of males vs females, and (2) whether long-term loss of ovarian function produces deficits in basal forebrain cholinergic function beyond those associated with aging and sex. In part I of the study, gonadally intact male and female rats were sacrificed at 13, 19, and 25 months of age and the effects of aging on cholinergic neurons in the medial septum (MS) and nucleus basalis magnocellularis (NBM) were compared. In part II of the study, female rats were ovariectomized at 13 months of age and then sacrificed 3 and 6 months later along with gonadally intact, age-matched controls. Adjacent sections through the MS and NBM were processed for either immunocytochemical detection of choline acetyltransferase (ChAT) and p75NTR-like immunoreactivity or for in situ hybridization detection and quantification of ChAT and trkA mRNA. Results from part I revealed no significant effects of age on the relative size or density of cholinergic neurons in the MS and NBM of gonadally intact animals. Likewise, no significant effects on the relative numbers of cholinergic neurons expressing p75NTR protein were detected. However, a significant decrease in trkA mRNA was detected in the MS of gonadally intact females, but not males, between 13 and 25 months of age. No significant effects of aging on ChAT mRNA were detected. Results from part II revealed significant decreases in both ChAT and trkA mRNA in the MS and NBM of female rats sacrificed 6 months, but not 3 months, following ovariectomy relative to age-matched, gonadally intact controls. Short-term estrogen replacement initiated 6 months following ovariectomy and administered for 3 days prior to sacrifice partially restored ChAT mRNA levels in the MS and trkA mRNA levels in the NBM. These findings suggest that ovarian hormones play a role in maintaining normal levels of ChAT and trkA expression in the MS and NBM. The fact that ChAT mRNA was decreased in the MS and NBM at 6 months following ovariectomy suggests that long-term loss of ovarian function produces a decrease in the functional status of basal forebrain cholinergic neurons projecting to the hippocampus and cortex. In addition, we hypothesize that the decreases in trkA mRNA detected both in the MS as a function of aging, and in the MS and NBM in response to ovariectomy, reflect decreases in the production of high affinity nerve growth factor (NGF) receptors, and a decrease in the responsiveness of the cholinergic neurons to endogenous NGF. This, in turn, may increase the susceptibility of the cholinergic neurons to the effects of aging and disease and thereby contribute to basal forebrain cholinergic decline. We conclude that long-term loss of ovarian function combined with aging has a negative impact on basal forebrain cholinergic neurons. These effects may contribute to the risk and severity of cognitive decline associated with aging and Alzheimer's disease in postmenopausal women.


Challenges in Management of Tracheobronchial Foreign Bodies with Delayed Presentation: An Institutional Experience.
Introduction Airway foreign bodies are emergencies involving multidisciplinary departments like Pediatrics, Aneasthesiology and Otorhinolaryngology. It is always a challenge to diagnose and manage patients who present late to our emergencies. Objective In the present study, we aim to analyze the various challenges faced during the management of tracheobronchial foreign bodies with delayed presentation. Methods A retrospective hospital record-based analysis of patients who presented to us with tracheobronchial foreign bodies from January 2017 to February 2020 was performed. All patients until the age of 16 years old were included in the present study. We assessed the demographics, preoperative, intraoperative and postoperative data of the patients. Results Seventeen patients were analyzed in the study. Among these, 44.4% of the patients had delayed presentation (> 1 month). The majority of the patients had an organic foreign body (Supari or betel nut). All patients underwent rigid bronchoscopy, followed by optical forceps-assisted removal of the foreign body. A total of 82% of the patients had granulations around the foreign body. Conclusion Management of delayed presentation tracheobronchial foreign body is a big challenge for Otorhinolaryngologists. The key factors for preventing complications in the definitive management of tracheobronchial foreign bodies are preoperative planning, multi-discipline teamwork, surgeon expertise and technique.


Histone modification pattern evolution after yeast gene duplication.
Gene duplication and subsequent functional divergence especially expression divergence have been widely considered as main sources for evolutionary innovations. Many studies evidenced that genetic regulatory network evolved rapidly shortly after gene duplication, thus leading to accelerated expression divergence and diversification. However, little is known whether epigenetic factors have mediated the evolution of expression regulation since gene duplication. In this study, we conducted detailed analyses on yeast histone modification (HM), the major epigenetics type in this organism, as well as other available functional genomics data to address this issue. Duplicate genes, on average, share more common HM-code patterns than random singleton pairs in their promoters and open reading frames (ORF). Though HM-code divergence between duplicates in both promoter and ORF regions increase with their sequence divergence, the HM-code in ORF region evolves slower than that in promoter region, probably owing to the functional constraints imposed on protein sequences. After excluding the confounding effect of sequence divergence (or evolutionary time), we found the evidence supporting the notion that in yeast, the HM-code may co-evolve with cis- and trans-regulatory factors. Moreover, we observed that deletion of some yeast HM-related enzymes increases the expression divergence between duplicate genes, yet the effect is lower than the case of transcription factor (TF) deletion or environmental stresses. Our analyses demonstrate that after gene duplication, yeast histone modification profile between duplicates diverged with evolutionary time, similar to genetic regulatory elements. Moreover, we found the evidence of the co-evolution between genetic and epigenetic elements since gene duplication, together contributing to the expression divergence between duplicate genes.


Rheumatoid Arthritis in the View of Osteoimmunology.
Rheumatoid arthritis is characterized by synovial inflammation and irreversible bone erosions, both highlighting the immense reciprocal relationship between the immune and bone systems, designed osteoimmunology two decades ago. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the articular bone erosions. The main triggers of this local bone resorption are autoantibodies directed against citrullinated proteins, as well as pro-inflammatory cytokines and the receptor activator of nuclear factor-κB ligand, that regulate both the formation and activity of the osteoclast, as well as immune cell functions. In addition, local bone loss is due to the suppression of osteoblast-mediated bone formation and repair by inflammatory cytokines. Similarly, inflammation affects systemic bone remodeling in rheumatoid arthritis with the net increase in bone resorption, leading to systemic osteoporosis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of systemic and local bone loss in rheumatoid arthritis.


Monoclonal antibodies can precipitate low-density lipoprotein. I. Characterization and use in determining apolipoprotein B.
We produced 20 mouse monoclonal antibodies against human plasma low-density lipoprotein (LDL). Individually they failed to precipitate LDL in agarose gel by the double-immunodiffusion technique; collectively they did, or as few as two combined monoclonal antibodies could do so. To mimic polyclonal antibodies in determination of apolipoprotein B (apo B) by radial immunodiffusion, a combination of four particular monoclonal antibodies (clones A, B, C, and D) was necessary. We characterized these four clones with respect to temperature dependency, affinity, total binding to 125I-labeled LDL, and specificity to the different species of apolipoprotein B. Two monoclonal antibodies (B and C) bound 100% of 125I-labeled LDL; clones A and D bound 80% and 87%, respectively. All four clones bound maximally to LDL at 4 degrees C. The affinity constants for clones A, B, C, and D were 0.6, 2.1, 3.8, and 2.3 X 10(9) L/mol, respectively. By the Western blotting technique, the four monoclonal antibodies all reacted with the species B-100 and B-74 of apolipoprotein B, and to various degrees with B-48 and B-26. Radial immunodiffusion (chi) and direct enzyme-linked immunosorbent assay (y) with a mixture of the four monoclonal antibodies gave almost identical results for 70 patients: y = 0.921 chi-2.58; r = 0.933.


Developing leaders' strategic thinking through global work experience: the moderating role of cultural distance.
To respond to the challenge of how organizations can develop leaders who can think strategically, we investigate the relation of leaders' global work experiences--that is, those experiences that require the role incumbent to transcend national boundaries--to their competency in strategic thinking. We further examine whether leaders' exposure to a country whose culture is quite distinct from the culture of their own country (i.e., one that is culturally distant) moderates these relationships. Our analyses of 231 upper level leaders reveals that the time they have spent in global work experiences positively relates to their strategic thinking competency, particularly for leaders who have had exposure to a more culturally distant country. We discuss these findings in light of the research on international work experiences and leader development.


Baseline data of a population-based cohort of patients with diabetes in Switzerland (CoDiab-VD).
To describe a population-based sample of patients with diabetes and the quality of their care in the canton of Vaud, Switzerland, as a baseline measure for the evaluation of the "Programme cantonal Diabète". We conducted a self-administered paper-based questionnaire survey. Non-institutionalised adult (aged ≥18 years) patients with diabetes diagnosed for at least 1 year and residing in the canton of Vaud were recruited by community pharmacies. Women with gestational diabetes, people with obvious cognitive impairment or people not sufficiently fluent in French were excluded. Primary outcomes were recommended processes-of-care and outcomes of care (glycosylated haemoglobin [HbA1c], generic and disease-specific health-related quality of life (HRQoL), overall care score in relation to the Chronic Care Model). Other measures included diabetes education, self-management support and self-efficacy, health status, health behaviour and demographics. A total of 519 patients with diabetes were included. Whereas the mean HbA1c level was 7.3% (n = 177, 95% confidence interval 7.1-7.5), diabetes-specific processes-of-care and influenza vaccination were reported by less than two-thirds of the patients. Physical activity and diet recommendations results mirrored patients' difficulties with their management in daily life and diabetes-specific HRQoL was worst in the dimensions relative to diet (eating and drinking) and sex life. A minority of patients reported ever having participated in diabetes education courses (32.8%). Overall, patients were satisfied with their care and the support they received. This study provides a broad picture of the experiences of people living with diabetes in the canton of Vaud. It shall guide the development of targeted interventions within the "Programme cantonal Diabète".


GmMs1 encodes a kinesin-like protein essential for male fertility in soybean (Glycine max L.).
The application of heterosis is a promising approach for greatly increasing yield in soybean (Glycine max L.). Nuclear male sterility is essential for hybrid seed production and the utilization of heterosis. Here we report the cloning of the gene underlying the soybean male-sterile mutant ms-1, which has been widely used for recurrent selection in soybean breeding programs. We initially delimited the ms1 locus to a 16.15 kb region on chromosome 13, based on SLAF_BSA sequencing followed by genotyping of an F2 population segregating for the locus. Compared with the same region in fertile plants, the mutant region lacks a sequence of approximately 38.7 kb containing five protein-coding genes, including an ortholog of the kinesin-like protein gene NACK2, named GmMs1. The GmMs1 knockout plants generated via CRISPR/Cas-mediated gene editing displayed a complete male-sterile phenotype. Metabolic profiling showed that fertile anthers accumulated starch and sucrose normally, whereas sterile anthers had higher anthocyanin levels and lower flavonoid levels and lower antioxidant enzyme activities. These results provide insights into the molecular mechanisms governing male sterility and demonstrate that GmMs1 could be used to create male-sterile lines through targeted mutagenesis. These findings pave the way for designing seed production technology and an intelligent male-sterile line system to utilize heterosis in soybean.


Defective Autophagy and Mitophagy in Aging and Alzheimer's Disease.
Aging is the time-dependent process that all living organisms go through characterized by declining physiological function due to alterations in metabolic and molecular pathways. Many decades of research have been devoted to uncovering the cellular changes and progression of aging and have revealed that not all organisms with the same chronological age exhibit the same age-related declines in physiological function. In assessing biological age, factors such as epigenetic changes, telomere length, oxidative damage, and mitochondrial dysfunction in rescue mechanisms such as autophagy all play major roles. Recent studies have focused on autophagy dysfunction in aging, particularly on mitophagy due to its major role in energy generation and reactive oxidative species generation of mitochondria. Mitophagy has been implicated in playing a role in the pathogenesis of many age-related diseases, including Alzheimer's disease (AD), Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The purpose of our article is to highlight the mechanisms of autophagy and mitophagy and how defects in these pathways contribute to the physiological markers of aging and AD. This article also discusses how mitochondrial dysfunction, abnormal mitochondrial dynamics, impaired biogenesis, and defective mitophagy are related to aging and AD progression. This article highlights recent studies of amyloid beta and phosphorylated tau in relation to autophagy and mitophagy in AD.


[Perfusion management in liver transplantation].
Veno-venous bypass (VVB) with a Biopump centrifugal pump (Biomedicus, USA) was used in 36 patients with liver diseases during orthotopic transplantation of the liver. Volume rate of perfusion (VR), systolic, diastolic, and mean arterial pressure (AP), and central venous pressure (CVP) were monitored. VR during liver-free period was 850-1350 (1064.2 +/- 87.5) ml/min in femoral-axillary bypass and 1700-3500 (2630.5 +/- 112.3) ml/min in femoral-porto-axillary bypass. A trend to a decrease of the mean AP to 65 mm Hg was observed at the end of liver-free period (p < 0.05), while CVP decreased to 2 mm Hg (p < 0.05); there was a trend to a moderate tachycardia. No significant shifts in acid-base balance, oxygen balance, and blood electrolytes were observed during the liver-free period. Maximum blood loss occurred during the liver-free period and reperfusion of the transplant. Blood loss was evaluated by the amount of washed autoerythrocytes obtained after processing of collected blood in the Cell-Saver device. VVB had a favorable impact on the course of orthotopic transplantation of the liver, maintaining stable hemodynamic and biochemical parameters and preventing ischemia of the abdominal organs. Preservation of autoerythrocytes by the Cell-Saver device minimized the need in donor erythrocytes, thus ruling out the complications associated with homologous blood transfusion.


Mitochondrial Glutathione: Recent Insights and Role in Disease.
Mitochondria are the main source of reactive oxygen species (ROS), most of them deriving from the mitochondrial respiratory chain. Among the numerous enzymatic and non-enzymatic antioxidant systems present in mitochondria, mitochondrial glutathione (mGSH) emerges as the main line of defense for maintaining the appropriate mitochondrial redox environment. mGSH's ability to act directly or as a co-factor in reactions catalyzed by other mitochondrial enzymes makes its presence essential to avoid or to repair oxidative modifications that can lead to mitochondrial dysfunction and subsequently to cell death. Since mitochondrial redox disorders play a central part in many diseases, harboring optimal levels of mGSH is vitally important. In this review, we will highlight the participation of mGSH as a contributor to disease progression in pathologies as diverse as Alzheimer's disease, alcoholic and non-alcoholic steatohepatitis, or diabetic nephropathy. Furthermore, the involvement of mitochondrial ROS in the signaling of new prescribed drugs and in other pathologies (or in other unmet medical needs, such as gender differences or coronavirus disease of 2019 (COVID-19) treatment) is still being revealed; guaranteeing that research on mGSH will be an interesting topic for years to come.


WHEN SHOULD BE CONVERTED LAPAROSCOPIC SLEEVE GASTRECTOMY TO LAPAROSCOPIC ROUX-EN-Y GASTRIC BYPASS DUE TO GASTROESOPHAGEAL REFLUX?
Gastroesophageal reflux (GER) is one of the most common indications for conversion of sleeve gastrectomy (LSG) to laparoscopic Roux-en-Y gastric bypass (LRYGBP). Objective evaluations are necessary in order to choose the best definitive treatment for these patients. To present and describe the findings of the objective studies for gastroesophageal reflux disease performed before LSG conversion to LRYGBP in order to support the indication for surgery. Thirty-nine non-responder patients to proton pump inhibitors treatment after LSG were included in this prospective study. They did not present GER symptoms, esophagitis or hiatal hernia before LSG. Endoscopy, radiology, manometry, 24 h pH monitoring were performed. The mean time of appearance of reflux symptoms was 26.8+24.08 months (8-71). Erosive esophagitis was found in 33/39 symptomatic patients (84.6%) and Barrett´s esophagus in five. (12.8%). Manometry and acid reflux test were performed in 38/39 patients. Defective lower esophageal sphincter function was observed independent the grade of esophagitis or Barrett´s esophagus. Pathologic acid reflux with elevated DeMeester´s scores and % of time pH<4 was detected in all these patients. more significant in those with severe esophagitis and Barrett´s esophagus. Radiologic sleeve abnormalities were observed in 35 patients, mainly cardia dilatation (n=18) and hiatal hernia (n=11). Middle gastric stricture was observed in only six patients. Patients with reflux symptoms and esophagitis or Barrett´s esophagus after SG present defective lower esophageal sphincter function and increased acid reflux. These conditions support the indication of conversion to LRYGBP.


Age at initial consultation for craniosynostosis: comparison across different patient characteristics.
The severity and dysmorphology that results from the premature fusion of one or more cranial sutures is not uniform. Less striking phenotypes may be more easily missed on routine screening, possibly leading to delayed diagnosis and treatment. The purpose of this study was to compare the age at initial presentation for the different forms of craniosynostosis. The authors reviewed the records of all patients who underwent open craniofacial repair of craniosynostosis at a single institution from 1996 to 2009. Relationships between type of suture fusion and age at initial consultation were compared. Two hundred eleven patients (136 males, 75 females) were identified. Indications included sagittal (n = 96), metopic (n = 39), unicoronal (n = 33), bicoronal (n = 24), multisutural (n = 15), bilambdoidal (n = 3), and unilambdoidal (n = 1) synostoses. Seventeen patients (8.1%) had a craniosynostosis syndrome and 5 (2.4%) had a syndrome or disorder not typically associated with craniosynostosis [X-linked hypophosphatemic rickets (n = 3), achondroplasia (n = 1), and Beckwith Wiedemann (n = 1)]. Median age at initial consultation was 4.1 months; there was no gender difference. Patients with X-linked hypophosphatemic rickets presented at a significantly older age than nonsyndromic patients or those with a known craniosynostosis syndrome. Those with multisutural synostosis presented at a significantly older age than patients with sagittal or bicoronal synostosis. Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. The latter group of patients may especially benefit from routine surveillance for craniosynostosis given their advanced age at diagnosis.


Risk stratification for COVID-19 hospitalization: a multivariable model based on gradient-boosting decision trees.
The COVID-19 pandemic has led to an increased demand for health care resources and, in some cases, shortage of medical equipment and staff. Our objective was to develop and validate a multivariable model to predict risk of hospitalization for patients infected with SARS-CoV-2. We used routinely collected health records in a patient cohort to develop and validate our prediction model. This cohort included adult patients (age ≥ 18 yr) from Ontario, Canada, who tested positive for SARS-CoV-2 ribonucleic acid by polymerase chain reaction between Feb. 2 and Oct. 5, 2020, and were followed up through Nov. 5, 2020. Patients living in long-term care facilities were excluded, as they were all assumed to be at high risk of hospitalization for COVID-19. Risk of hospitalization within 30 days of diagnosis of SARS-CoV-2 infection was estimated via gradient-boosting decision trees, and variable importance examined via Shapley values. We built a gradient-boosting model using the Extreme Gradient Boosting (XGBoost) algorithm and compared its performance against 4 empirical rules commonly used for risk stratifications based on age and number of comorbidities. The cohort included 36 323 patients with 2583 hospitalizations (7.1%). Hospitalized patients had a higher median age (64 yr v. 43 yr), were more likely to be male (56.3% v. 47.3%) and had a higher median number of comorbidities (3, interquartile range [IQR] 2-6 v. 1, IQR 0-3) than nonhospitalized patients. Patients were split into development (n = 29 058, 80.0%) and held-out validation (n = 7265, 20.0%) cohorts. The gradient-boosting model achieved high discrimination (development cohort: area under the receiver operating characteristic curve across the 5 folds of 0.852; validation cohort: 0.8475) and strong calibration (slope = 1.01, intercept = -0.01). The patients who scored at the top 10% captured 47.4% of hospitalizations, and those who scored at the top 30% captured 80.6%. We developed and validated an accurate risk stratification model using routinely collected health administrative data. We envision that modelling such risk stratification based on routinely collected health data could support management of COVID-19 on a population health level.


[Advanced Digestive Cancer in Super Elderly Patients More Than 85 Years Old - Two Cases That Required Major Invasive Surgery].
Case 1 involved an 87-year-old woman. She had increased serum amylase levels, and intraductal papillary mucinous adenocarcinoma( IPMC)in the accessory pancreatic duct was diagnosed following various medical examinations. Radical surgery is possible for such a lesion when there are no issues detected following evaluation. The patient and her family decided that she should undergo surgery; therefore, pancreatoduodenectomy was performed for Stage III IPMC. Various morbidities required medical treatment, but she was finally discharged from hospital 89 days after surgery. She has had no recurrence 2 years and 11 months after surgery. Case 2 involved a 90-year-old man. He had liver dysfunction, and progressive hepatocellular carcinoma( HCC)was diagnosed based on computed tomography(CT)findings. The tumor size reduced to around 10 cm with enforced 2 degrees TACE. The patient and his family chose for him to undergo radical surgery; therefore, right trisegmentectomy of the liver was performed for Stage III HCC. He was discharged from the hospital 22 days after surgery, and has had no recurrence for the past 1.6 years. More careful examination and a general assessment are necessary to make decisions on surgical indications in super elderly patients.


Intractable Epilepsy and Progressive Cognitive Decline in a Young Man.
A young man with normal neurodevelopment presented with 3 years of medically refractory, progressive epilepsy and myoclonus. Initial examination included neuroimaging, electroencephalography, and biochemical analyses, all of which were unremarkable except for mildly enlarged ventricles. Over the following year, the patient experienced rapid cognitive decline with new-onset recurrent visual hallucinations and progressive lethargy. Results of subsequent electroencephalography and brain imaging were unchanged, and a fluorodeoxyglucose F 18 positron emission tomographic scan was normal.


Phase-field simulations at the atomic scale in comparison to molecular dynamics.
Early solidification is investigated using two different simulation techniques: the molecular dynamics (MD) and the phase-field (PF) methods. While the first describes the evolution of a system on the basis of motion equations of particles, the second grounds on the evolution of continuous local order parameter field. The aim of this study is to probe the ability of the mesoscopic phase-field method to make predictions of growth velocity at the nanoscopic length scale. For this purpose the isothermal growth of a spherical crystalline cluster embedded in a melt is considered. The system in study is Ni modeled with the embedded atom method (EAM). The bulk and interfacial properties required in the PF method are obtained from MD simulations. Also the initial configuration obtained from MD data is used in the PF as input. Results for the evolution of the cluster volume at high and moderate undercooling are presented.


Improving fiber-optic laser beam delivery by incorporating GRADIUM optics.
The performance of a fiber-optic laser beam delivery system strongly depends on the fiber and the optics used to image the fiber face on the workpiece. We have compared off-the-shelf homogenous (BK7) and GRADIUM (axial-gradient) singlets to determine what improvement the GRADIUM offers in practice to the typical laser user. The realized benefit for this application, although significant, is much smaller than would be realized by a conventional imaging application. The figure of merit for laser-based materials processing is the 86% energy-enclosure radius, which is not directly supported by commercial ray-tracing software. Therefore empirical rules of thumb are presented to understand when GRADIUM (or any other well-corrected optics) will yield meaningful improvements to the beam delivery system.


Patterns in Follow-Up Imaging Usage for Pediatric Patients with Whiplash-Associated Disorder.
A clinical concern exists that pediatric patients with whiplash-associated disorder (WAD) might have missed structural injuries or, alternatively, subsequently develop structural injuries over time, despite initially negative imaging findings. The primary objective of this study is to assess follow-up imaging usage for pediatric patients presenting with WAD. A retrospective review of 444 pediatric patients presenting to a level 1 pediatric trauma hospital from January 1, 2010 to December 31, 2019 was performed. Imaging was reviewed at the initial encounter and the 3- and 6-month follow-up appointments. At the initial evaluation, children aged <6 years were more likely to receive radiographs (P = 0.007) and magnetic resonance imaging (P = 0.048) than were children aged 6-11 and 12-18 years. At the 3- and 6-month follow-up appointments, persistent neck pain was rare, representing <15% of patients at either time. Regardless of pain persistence, 80.2% of patients seen at the 3-month follow-up and 100% of patients at the 6-month follow-up underwent additional imaging studies. At the 3-month follow-up, children with persistent neck pain were more likely to undergo magnetic resonance imaging than were patients without persistent pain (P < 0.001). Also, patients with persistent neck pain were also more likely to not undergo any imaging evaluation (P = 0.002). Follow-up imaging studies did not reveal new structural injuries at either time point. Follow-up imaging for pediatric patients with low-grade WAD did not identify new structural pathology-in patients with or without persistent neck pain.


Thermoresponsive shear-thinning hydrogel (T-STH) hemostats for minimally invasive treatment of external hemorrhages.
Hemorrhage is the leading cause of death following battlefield injuries. Although several hemostats are commercially available, they do not meet all the necessary requirements to stop bleeding in combat injuries. Here, we engineer thermoresponsive shear-thinning hydrogels (T-STH) composed of a thermoresponsive polymer, poly(N-isopropyl acrylamide) (p(NIPAM)), and hemostatic silicate nanodisks, LAPONITE®, as minimally invasive injectable hemostatic agents. Our T-STH is a physiologically stable hydrogel that can be easily injected through a syringe and needle and exhibits rapid mechanical recovery. Additionally, it demonstrates temperature-dependent blood coagulation owing to the phase transition of p(NIPAM). It decreases in vitro blood clotting times over 50% at physiological temperatures compared to room temperature. Furthermore, it significantly prevents blood loss in an ex vivo bleeding model at different blood flow rates (1 mL min-1 and 5 mL min-1) by forming a wound plug. More importantly, our T-STH is comparable to a commercially available hemostat, Floseal, in terms of blood loss and blood clotting time in an in vivo rat liver bleeding model. Furthermore, once the hemorrhage is stabilized, our T-STH can be easily removed using a cold saline wash without any rebleeding or leaving any residues. Taken together, our T-STH can be used as a first aid hemostat to treat external hemorrhages in emergency situations.


Salmonella Typhimurium outbreak associated with frozen tomato cubes at a restaurant in western Finland, January to February 2021.
Several individuals reported gastrointestinal symptoms following meals consumed in late January 2021 at a restaurant in western Finland. We conducted a retrospective cohort study and defined a case as a person who ate at the lunch restaurant between 27 and 29 January 2021 and had stomach pain, vomiting or diarrhoea and/or a laboratory-confirmed Salmonella Typhimurium infection within 2 weeks after the exposure. We collected faecal and food samples for microbiological analysis. Salmonella isolates were characterised in detail using whole genome sequencing (WGS) and cluster analysis by core genome multilocus sequence typing (cgMLST). Altogether, 393 meals were sold and 101 people (who ate 142 meals) participated in the cohort study. There were 49 cases; 23 were laboratory-confirmed infections with a multidrug-resistant S. Typhimurium. The S. Typhimurium isolates from cases and frozen tomato cubes used uncooked in salads were closely related and clustered together in cgMLST comparison. These salads were consumed by 76% of the cases. Based on the cgMLST clustering, they were the suggested source of the outbreak. Statistical association was not significant between eating the salads and being a case. Following the outbreak investigation, the producer decided to recommend cooking of their frozen tomato products before consumption.


A Transgenic Mouse Line Expressing the Red Fluorescent Protein tdTomato in GABAergic Neurons.
GABAergic inhibitory neurons are a large population of neurons in the central nervous system (CNS) of mammals and crucially contribute to the function of the circuitry of the brain. To identify specific cell types and investigate their functions labelling of cell populations by transgenic expression of fluorescent proteins is a powerful approach. While a number of mouse lines expressing the green fluorescent protein (GFP) in different subpopulations of GABAergic cells are available, GFP expressing mouse lines are not suitable for either crossbreeding to other mouse lines expressing GFP in other cell types or for Ca2+-imaging using the superior green Ca2+-indicator dyes. Therefore, we have generated a novel transgenic mouse line expressing the red fluorescent protein tdTomato in GABAergic neurons using a bacterial artificial chromosome based strategy and inserting the tdTomato open reading frame at the start codon within exon 1 of the GAD2 gene encoding glutamic acid decarboxylase 65 (GAD65). TdTomato expression was observed in all expected brain regions; however, the fluorescence intensity was highest in the olfactory bulb and the striatum. Robust expression was also observed in cortical and hippocampal neurons, Purkinje cells in the cerebellum, amacrine cells in the retina as well as in cells migrating along the rostral migratory stream. In cortex, hippocampus, olfactory bulb and brainstem, 80% to 90% of neurons expressing endogenous GAD65 also expressed the fluorescent protein. Moreover, almost all tdTomato-expressing cells coexpressed GAD65, indicating that indeed only GABAergic neurons are labelled by tdTomato expression. This mouse line with its unique spectral properties for labelling GABAergic neurons will therefore be a valuable new tool for research addressing this fascinating cell type.


Waldenström's macroglobulinemia: incidence patterns in the United States, 1988-1994.
There are few data describing the epidemiologic aspects of Waldenström's macroglobulinemia (WM), a rare lymphoplasmaproliferative disorder. The authors evaluated the incidence of WM reported in 11 population-based cancer registries in the U.S. A total of 624 cases were diagnosed between January 1, 1988 (when WM became reportable) and December 31, 1994. Age-adjusted incidence rates for WM (per 1 million person-years at risk) were 3.4 among males and 1.7 among females. The rates increased sharply with age, from 0.1 at age < 45 years to 36.3 at age 75+ years (males) and from 0.1 at age < 45 years to 16.4 at age 75+ years (females). The rates for WM were comparable to those for hairy cell leukemia, but considerably lower than those for multiple myeloma or chronic lymphocytic leukemia. Some geographic variation was evident, with age-adjusted rates among white males ranging from 2.2-7.8 across registries. There was no significant change in rates over the 7-year study period (P > 0.05). The markedly higher rates for WM among whites than blacks stand in contrast to multiple myeloma, which occurs twice as often among blacks. This survey provides new data regarding the incidence patterns of WM in the U.S. However, further epidemiologic studies with biomarkers are needed to define the environmental, genetic, immunologic, and viral determinants of this rare but distinctive disorder.


Discrimination of early HCC using single cell nucleus image and visualization of feature distribution in whole slide images.
Among hepatocellular carcinoma (HCC), early HCC such as well-differentiated hepatocellular carcinoma is more difficult to distinguish from non-cancer than other cancers. In particular, very well-differentiated hepatocellular carcinoma is even more difficult to distinguish, and it is difficult for pathologists to distinguish between cancer and non-cancer from a single nucleus image. If a function to distinguish cancer with a single cell nucleus image is realized, it may be possible to find new features related to nuclei that are useful for differentiating early HCC. The function will also be very helpful in needle biopsy where the area that can be observed is limited.In this study, we investigated the potential to discriminate cancer/non-cancer from an image of a single hepatocyte nucleus using CNN. The results indicated that discrimination was achievable with a correct rate of around 70%.The probability of cancer/non-cancer was visualized on WSI. The visualization results indicated a difference between cancerous and non-cancerous areas in 71% of the cases, which will help pathologists distinguish region of interest. Grouping sections with similar features also proved useful in improving accuracy and visualization results.


New synthesis of substituted pyrrolo[1,2-alpha][1,3]diazepine and its pharmacological activity.
A facile route for the synthesis of the substituted pyrrolo[1,2-alpha][1,3]diazepine nucleus from readily available starting material is reported. The compound was tested for antimalarial activity in mice, antineoplastic activity in mice, acute hypotensive activity in rats and dogs, effect on cholesterol-lipoprotein levels in rats, anti-inflammatory activity in rats, antiviral activity in mice, CNS depressant or stimulant activity in mice, diuretic activity in fasted rats, and antidiabetic activity in rats. Hypotensive activity of relatively short duration was observed in rats. The compound lacked positive pharmacological activity in the remaining tests.


Ocean sprawl facilitates dispersal and connectivity of protected species.
Highly connected networks generally improve resilience in complex systems. We present a novel application of this paradigm and investigated the potential for anthropogenic structures in the ocean to enhance connectivity of a protected species threatened by human pressures and climate change. Biophysical dispersal models of a protected coral species simulated potential connectivity between oil and gas installations across the North Sea but also metapopulation outcomes for naturally occurring corals downstream. Network analyses illustrated how just a single generation of virtual larvae released from these installations could create a highly connected anthropogenic system, with larvae becoming competent to settle over a range of natural deep-sea, shelf and fjord coral ecosystems including a marine protected area. These results provide the first study showing that a system of anthropogenic structures can have international conservation significance by creating ecologically connected networks and by acting as stepping stones for cross-border interconnection to natural populations.


The concentration of liquor outlets in an economically disadvantaged city in the northeastern United States.
This study reports data from a mapping analysis designed to assess the extent to which liquor outlets concentrate in certain neighborhoods within one economically disadvantaged midsized city in New Jersey. Four neighborhoods, which occupy one-quarter of the residential land mass of the city and which are home to one-quarter of its population, were found to contain over half of its retail liquor outlets. Three of these neighborhoods are very poor and have large minority populations. The neighborhood with the highest concentration of outlets, however, has one of the lowest levels of poverty in the city and is ethnically quite diverse.


The pathogenesis of fraud in medical science.
Using a recent case of research fraud as a basis, this article examines the pathogenesis of fraud in medical science and suggests some remedies. Among causative factors are the "pre-med syndrome," the extraordinary size of science (which makes supervision of young investigators difficult), and competition, both professional and economic. Remedies include more careful selection of personnel, reduction of excessively large research groups, and closer examination of work at all levels--the laboratory, the academic department, and the institution. Each institution should have in place mechanisms to investigate research fraud when it is uncovered.


Research on a collaborative evolution model of multi-airport route network considering subsidy strategies.
To efficiently utilize subsidy strategies for optimizing multi-airport route networks and promoting collaborative development among multiple airports, we delve into the tripartite strategic interactions between passengers, airlines and airports. A dual-layer game-theoretic model is constructed to optimize subsidy strategies, facilitating a synergistic alignment between multi-airport positioning and route networks. In the upper-layer game-theoretic model, Fermi rules are employed to analyze the interplay between pricing strategies of distinct airline brands and passenger travel preferences, aiding in determining optimal pricing strategies for airlines. The lower-layer game-theoretic model introduces an asymmetric stochastic best response equilibrium (QRE) model, drawing insights from optimal airline pricing and the impact of airport subsidies on airline route adjustments to formulate effective multi-airport subsidy strategies. The results reveal that: (ⅰ) Airline revenues display varying peaks based on travel distances, with optimal fare discount intervals clustering between 0.6 and 0.9, contingent upon travel distances and passenger rationality; (ⅱ) dynamic monopolistic intervals and inefficient ranges characterize airport subsidy strategies due to diverse competitive strategies employed by rivals; (ⅲ) targeted airport subsidy strategies can enhance inter-airport route coordination in alignment with their functional positioning. This research provides decision-making insights into collaborative airport group development, encompassing airport subsidy strategies and considerations for airline pricing.


[Group therapy following lung transplantation -- first experiences with a theme-centered "life management group"].
Lung transplantation is a drastic life event that usually takes place in the preterminal phase of a lung disease. Although a lung transplantation increases the quality of life considerably, patients still face a range of physical and psychosocial strains. This article presents experiences made with a "Life Management Group" for lung transplantation patients. The aim of the eight group meetings was to encourage the sharing of experiences between patients and to support them in their active and competent realizations of desires and plans. Physical health, self-identity of lung transplant recipients, growing problems financing medical treatment and the forming of doctor-patient-relationships were the important issues. Patients were able to reach a higher level of self efficiency; they could use active coping strategies and develop their social networks. Positive experiences were made with the implementation of group therapy for lung transplantation patients. Lung transplant recipients have to deal with specific problems of identity. On the other hand, there are growing health-economic questions also from the patient's point of view.


[Melatonin inhibits the proliferation of pituitary prolactin-secreting tumor by suppressing the enhancer elements mutation of PRL gene in the rat].
In order to investigate the molecular mechanisms of the inhibition of the proliferation of 17-beta-estradiol (E(2))-induced pituitary prolactin-secreting tumor (prolactinoma) by melatonin (MLT) in the rat, we examined the inhibitory effects of MLT on the proliferation of E(2)-induced prolactinoma of the rat and the suppressing effects of MLT on the enhancer elements mutation of PRL gene in vivo and in vitro. The results showed that the weights of prolactinomas in MLT groups, in which 0.25 mg or 0.50 mg per day per rat of MLT was administered subcutaneously at 18:00, were decreased significantly. Out of the dosage of MLT, such as 0.05, 1.00 mg and 2.00 mg per day per rat, the antitumor action of MLT is less or disappointing. Polymerase chain reaction (PCR) and DNA sequencing showed five mutations in the enhancer elements of PRL gene in prolactinoma, such as -1885 point mutation (C --> G), -1857 - -1855 substitution (ACA --> G), -1792 - -1791 insertion G, -1383 - -1382 insertion (GGTGTGTG), -1265 - -1250 deletion (GTGTGTGTGTGTGTGT). Excluding of -1885 point mutation (C --> G), the mutation in the prolactinoma treated with 0.25 mg per day per rat MLT was decreased, such as -1792 - -1791 without insertion of G, -1856 - -1855 deletion AC, -1385 - -1384 deletion TG, -1250 - -1253 deletion GTGT. Firefly luciferase reporter gene systems showed that the luminosity of enhancer elements-luciferase reporter fusion gene in normal pituitary, prolactinoma treated without or with 0.25 mg per day per rat MLT were (13448.17+/-3012.74), (161831.67+/-60996.01), and (10212.17+/-634.71) OD units. Compared with the normal pituitary, the activity of PRL gene enhancer elements in prolactinoma was increased by 11 times (P<0.001). Compared with the prolactinoma, the activity of PRL gene enhancer elements in prolactinoma treated with MLT was decreased by 93.69% (P<0.001). Analysis of the space structure of PRL gene enhancer elements showed that the bending index in prolactinoma was higher than that in prolactinoma treated with MLT, which was higher than that in the normal pituitary. These results demonstrate that one of the important molecular mechanisms of MLT inhibiting the proliferation of prolactinoma is related to the reduction of enhancer elements mutation of PRL gene. These data also suggest that MLT-induced attenuation of enhancer elements mutation of PRL gene is involved in decreasing the bending index and attenuating the higher expression of PRL gene.


T17b murine embryonal endothelial progenitor cells can be induced towards both proliferation and differentiation in a fibrin matrix.
Endothelial progenitor cells (EPC) may enhance blood vessel formation in a variety of clinical settings such as ischaemia and tumour angiogenesis as well as in tissue-engineered matrices. In the present study, we cultured a murine endothelial progenitor cell line, T17b, in vitro in cell culture as well as in an FDA-approved fibrin matrix and investigated cell proliferation, differentiation and secretion patterns of the angiogenic growth factor VEGF under hypoxia and differentiation. We show that T17b EPC remain viable for at least 8 days in the fibrin matrix where they proliferate and form clusters including lumen-like structures. Proliferation in fibrin clots overlayed with basal medium (BM) was confirmed morphologically and immunohistochemically by positive Ki67 staining, indicating mitotic activity. Significant cell proliferation and Ki-67 expression were absent when cells were incubated with dibutyryl-cAMP and retinoic acid (RA). Incubation with dibutyryl-cAMP and RA stimulated the expression of the EPC differentiation markers von Willebrand Factor (vWF) and VEGF receptor 2 (VEGFR-2), indicating successful differentiation in the fibrin clot. EPC differentiation induced by dibutyryl-cAMP and RA was confirmed in 2-D chamber slide cultures by positive vWF immunostaining, which was absent in BM controls. EPC chamber slides also displayed positive vWF staining when exposed to hypoxia under BM conditions, indicating EPC activation and differentiation could also be induced by hypoxia. Taken together, T17b EPC secrete increased levels of VEGF when submitted to either hypoxia or differentiation and can be differentiated into mature endothelial cells not only in cell and matrigel cultures but also in a fibrin matrix that is FDA approved for clinical application.


Emergency Department Prescribing Patterns for Pharyngitis in Children.
Pharyngitis is commonly diagnosed in the emergency department (ED) and accounts for substantial antibiotic burden in pediatrics. This study describes ED patterns of group A streptococcal (GAS) pharyngitis diagnosis and antibiotic prescribing patterns. This was a secondary data analysis of the National Hospital Ambulatory Medical Care Survey. Diagnosis and antibiotic treatment for GAS and non-GAS (viral) pharyngitis were reported in all ages and specifically examined in children <3 years of age from 2010 to 2015. GAS pharyngitis was diagnosed in 29% of visits for children with pharyngitis; however, 60% of patients with any pharyngitis received antibiotics. Twenty percent of children <3 years were diagnosed with GAS pharyngitis, yet over half were given antibiotics. Broad-spectrum antibiotics were commonly prescribed. Antibiotic treatment of pharyngitis, including broad-spectrum antibiotics, remains high when compared with the known prevalence of GAS pharyngitis. Diagnosis and treatment of GAS pharyngitis in patients <3 years persists despite recommendations against testing.


The roles of extracellular DNA in the structural integrity of extracellular polymeric substance and bacterial biofilm development.
Bacteria adhere to natural and engineered surfaces and develop into mature biofilms encased in self-produced extracellular polymeric substances (EPSs). EPS consists of polysaccharides, proteins, metabolites and extracellular DNA (eDNA). Extracellular DNA release by bacteria is mediated by both quorum-sensing (QS)-dependent and -independent mechanisms. Quorum-sensing-independent mechanisms are responsible for basal levels of eDNA release, whereas QS-dependent mechanisms control the production of prophages, phenazines and proteins involved in cell lysis and subsequent release of elevated amounts of eDNA. Extracellular DNA binds with other biopolymers such as polysaccharides, proteins or metabolites like phenazines, thereby providing structural integrity to EPS. Extracellular DNA promotes attractive acid-base interactions between bacterial cells and between bacteria and surfaces. It therefore plays an essential structural role in stabilising biofilms and protecting bacterial cells from physical and chemical challenges. Accordingly, with current knowledge, it becomes clear that targeting and destroying eDNA in bacterial EPS is a promising strategy for treatment of bacterial-associated infections in a medical context and biofilm control on surfaces to prevent biocorrison in an engineering context. In contrast, the addition of DNA can be applied to engineering of biofilms for beneficial purposes such as remediation of environmental pollutants and electricity or fuel production in bioelectrochemical systems or bioreactors.


Sex-based differences in clinical features, management, and 28-day and 7-year prognosis of first acute myocardial infarction. RESCATE II study.
To analyze sex-based differences in clinical characteristics, management, and 28-day and 7-year prognosis after a first myocardial infarction. Between 2001 and 2003, 2042 first myocardial infarction patients were consecutively registered in 6 Spanish hospitals. Clinical characteristics, management, and 28-day case-fatality were prospectively recorded. Seven-year vital status was also ascertained by data linkage with the National Mortality Index. The registry included 449 women and 1593 men with a first myocardial infarction. Compared with men, women were older, had a higher prevalence of hypertension and diabetes, and were more likely to receive angiotensin-converting enzyme (ACE) inhibitors but were less likely to receive beta-blockers or thrombolysis. No differences were observed in use of invasive procedures. More women had non-ST-segment elevation and unclassified myocardial infarction than men (37.9% vs 31.3% and 9.8% vs 6.1%, respectively; both P<.001). Case-fatality at 28 days was similar in women and men (5.57% vs 4.46%; P=.39). After multivariate adjustment, the odds ratio of 28-day mortality for men was 1.06 (95% confidence interval: 0.49-2.27; P=.883) compared with women. After multivariate adjustment, men had higher 7-year mortality than women, hazard ratio 1.93 (95% confidence interval: 1.46-2.56; P<.001). There are demographic and clinical differences between men and women with a first myocardial infarction. The short-term prognosis of a first myocardial infarction in this century is similar in both sexes. However, the long-term vital prognosis after a first myocardial infarction is worse in men than in women. These results are observed in both ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction events.


Subcellular Localization of GUS- and GFP-Tagged Proteins in Onion Epidermal Cells.
INTRODUCTIONRecombinant tags (i.e., reporter proteins) offer an excellent alternative to antibodies for determining the subcellular localization of proteins. The most user-friendly tags are the ß-glucuronidase (GUS) reporter enzyme from Escherichia coli and fluorescent proteins derived primarily from the green fluorescent protein (GFP) of the jellyfish Aequorea victoria. GUS is useful primarily as a tag to address nuclear localization, whereas GFP is more versatile. Moreover, GFP is detectable directly in living cells, whereas GUS is only detected indirectly by staining of fixed tissue. This may lead to artifacts or it may obscure problems with protein solubility. In this protocol, protein localization is routinely assayed after particle-mediated transient transformation of onion epidermal cells. With this method it can be determined rapidly whether a given fusion protein is active, and preliminary targeting data can be obtained.


Scopolamine-induced alterations in predatory behaviour pattern in cats.
Predatory behaviour in its full pattern (i.e., following the mouse, killing it and consuming the carcass) was tested in semi-natural conditions in cats. Consumption of minced horse meat was tested as well. Centrally acting scopolamine hydrobromide injected i.p. did not suppress predatory motivation, since following the prey and killing it were preserved. The executory phase of predation (i.e., the killing grip) was severely disturbed and the consumption of the mouse as well as meat was totally inhibited. Peripherally acting scopolamine methylnitrate administered into another group of cats under the same conditions generally did not affect predatory pattern, though meat and mouse consumption was disturbed to some extent. It is concluded that central muscarinic involvement in predatory behaviour in cats is limited to sensorimotor control of jaw movements.


Temporal Changes in the Cross-Sectional Associations between Cannabis Use, Suicidal Ideation, and Depression in a Nationally Representative Sample of Canadian Adults in 2012 Compared to 2002.
With the recent legalization of nonmedical cannabis in Canada, it is important to document previous associations between cannabis use and major depressive episode and suicidal ideation, as well as the extent to which these associations have changed over time. This study uses pooled data from the 2002 and 2012 Canadian Community Health Survey's Mental Health Component, which are repeated cross-sectional surveys of nationally representative samples of Canadians 15 to 60 years of age (n = 43,466). Binary logistic regression was performed, applying weighting and bootstrapping, to examine the association between at least monthly use of cannabis and past 12-month suicidal ideation and major depressive episode (MDE). At least monthly nonmedical cannabis use was associated with an increased odds of MDE and suicidal ideation, and both associations strengthened in 2012 compared to 2002. Canadians using cannabis at least once a month in 2012 had 1.59 (95% confidence interval [CI], 1.11 to 2.27) times the odds of experiencing suicidal ideation and 1.55 (95% CI, 1.12 to 2.13) times the odds of experiencing MDE compared to those who used cannabis at least once a month in 2002. This temporal change remained after controlling for other substance use. Monthly cannabis use was consistently related to both suicidal ideation and MDE, and these associations were stronger in 2012 compared to 2002. The findings of this study provide a baseline for the association between cannabis use and suicide and depression in the Canadian population that should be reevaluated now that nonmedical cannabis has been legalized.


Phenotypic plasticity of the basidiomata of Thelephora sp. (Thelephoraceae) in tropical forest habitats.
Phenotypic plasticity in macroscopic fungi has been poorly studied in comparison to plants or animals and only general aspects of these changes have been described. In this work, the phenotypic variation in the basidiomata of Thelephora sp. (Thelephoraceae) was examined, as well as some aspects of its ecology and habitat, using 24 specimens collected in the tropical forests of the Chamela Biological Station, Jalisco, Mexico. Our observations showed that this taxon has clavarioid basidiomata that can become resupinate during development and growth if they are in contact with rocks, litter or live plants, establishing in the latter only an epiphytic relationship. This tropical species may form groups of up to 139 basidiomata over an area of 32.2m2, and in both types of vegetation (tropical sub-evergreen and deciduous forest) were primarily located on steep (>20 degree) South-facing slopes. It is found under closed canopy in both tropical forests, but its presence in sub-evergreen forests is greater than expected.


Practitioner Review: Cognitive bias modification for mental health problems in children and adolescents: a meta-analysis.
Despite accumulating research and bold claims about the efficacy of cognitive bias modification (CBM) for young populations, no meta-analysis has attempted to synthesize the research literature so far. We examined whether there was empirical evidence for the clinical efficacy of CBM interventions in youths, while also considering the methodological quality of this evidence. Studies were identified through systematic searches in bibliographical databases (PubMed, PsychInfo, Cochrane Library and EMBASE to June 2014). We included randomized controlled trials of CBM interventions, and considered both clinical outcomes and targeted biases. We examined the quality of the trials, as well as potential publication bias and possible moderators. We identified 23 trials that reported on four types of outcomes: mental health, anxiety, depression and bias. Effect sizes were small and nonsignificant for all symptom outcomes considered. We found a moderate significant effect size for bias outcomes (Hedges' g of 0.53), with significant heterogeneity. There were no differences between types of CBM interventions, or between one versus multiple-session applications. A small but significant effect size for mental health problems arose when the intervention was delivered in schools. The quality of almost all of the included studies was suboptimal and the vast majority did not include information needed for allowing quality assessment. We conducted the first meta-analysis of CBM interventions for children and adolescents and found no effects for mental health outcomes, but we did find moderate and significant effects on the targeted biases. Our results cast serious doubts on CBM interventions having any clinical utility for nonadult populations. Demand characteristics might play an important part in CBM research.


Improved management of community-acquired pneumonia in the emergency department.
To determine the impact of implementing clinical practice guidelines (CPGs) in the treatment of community-acquired pneumonia (CAP) in the emergency department (ED) by analyzing case management decisions (admission or discharge, appropriateness and timeliness of antibiotic therapy, complementary tests) and the consequent results (clinical stabilization time, length of hospital stay, re-admission to ED and mortality). A prospective, observational, descriptive, comparative study carried out from 1st January 2008 to 1st August 2009 in two phases: before and after the implementation of the "Management of CAP in ED" SEMES-SEPAR (Spanish Society of Emergency Medicine - Spanish Society of Pneumology and Thoracic Surgery) clinical practice guidelines from 2008. Two hundred adult patients treated in the ED with a diagnosis of CAP were included in the study, both in the pre-intervention and post-intervention groups. The application of the guidelines increased the administration of early and appropriate antibiotic therapy (P<.001) and shortened both the total antibiotic therapy (P<.001) and the intravenous antibiotic therapy (P=.042) times. Time to clinical stabilization (P=.027), length of hospital stay (1.14 days, P=.01), intra-hospital mortality (P=.004) and total 30-day mortality (P=.044) were all reduced. Assessment with the Pneumonia Severity Index (PSI) and biomarkers aided in appropriate decision-making concerning admission/discharge (P<.001). The implementation of the SEMES-SEPAR 2008 guidelines, along with the use of PSI and biomarkers, significantly improved the entire treatment process of CAP. This benefitted both patients and the system by reducing mortality and improving the results of other patient management factors.


Reliability and validity of a risk assessment tool for patients with kidney failure.
Reliable and valid tools are needed to assist nurses to prospectively identify high-risk patients with kidney failure. Early identification of high-risk patients permits targeting of nursing interventions and resources to improve quality and cost outcomes. A 16-item risk assessment tool Risk for Outcomes Adverse to Dialysis (ROAD), was developed based on a comprehensive review of the literature on risk factors associated with adverse outcomes with kidney failure Reliability and validity of the ROAD was tested on a random sample of 253 participants in the Anemia Management Demonstration Project. High risk scores on the ROAD were significantly associated with hospitalization 1 to 6 months following risk assessment and inversely correlated with physical and mental components of quality of life. The results indicate that the ROAD provides a useful tool to identify patients on hemodialysis at risk of poor outcomes.


From fenfluramine racemate to d-fenfluramine. Specificity and potency of the effects on the serotoninergic system and food intake.
Experiments using the binding of various ligands for monoamines to rat brain membranes and synaptosomal preparations for studying monoamine uptake and release have shown that d-fenfluramine is more potent than the l isomer in inhibiting 5-HT uptake, whereas d-norfenfluramine preferentially releases 5-HT from a reserpine-insensitive compartment. Studies on brain monoamine metabolism in intact animals have shown that the d and l isomers of fenfluramine at relatively low doses have a specific action on brain 5-HT and catecholamines, respectively. Based on the different ability of metergoline and ritanserin to displace 5-HT2 binding to rat brain membranes and to antagonize d-fenfluramine's anorexia, evidence has been provided that d-fenfluramine preferentially uses 5-HT1 sites in the rat brain to cause anorexia in this animal species. Finally, characteristics, regional distribution, and pharmacological characterization of a high-affinity [3H]d-fenfluramine binding to rat brain membranes have been described. This binding appears to be different from 5-HT uptake sites ([3H]imipramine binding) and 5-HT receptors and is not regionally related to the endogenous levels of 5-HT in the rat brain. It is, however, preferentially displaced by some agents using 5-HT to cause anorexia in rats, raising the possibility that it is somewhat related to 5-HT mechanisms involved in feeding control.


Angioplasty of below-the-elbow arteries in critical hand ischaemia.
Critical hand ischaemia (CHI) due to pure below-the-elbow (BTE) artery obstruction is a disabling disease and there is still no consensus concerning the most appropriate revascularisation strategy. The aim of this study was to assess the feasibility, safety and outcomes of percutaneous transluminal angioplasty (PTA) in the treatment of CHI due to pure BTE artery disease. Twenty-eight patients (age 62 ± 11 years; three females) with a total of 34 hands affected by CHI (one pain at rest; 18 non-healing ulcer; 15 gangrene) due to pure BTE artery disease underwent PTA. Most of the patients were males with a long history of diabetes mellitus, end-stage renal disease (ESRD) on haemodialysis and systemic atherosclerosis. The interosseous artery was free of disease in all cases, whereas the radial and ulnar arteries were simultaneously involved in 31/34 hands with long stenosis/occlusions (91%; mean length 155 ± 64 mm). The technical success rate was 82% (28/34), with only three minor complications. In the three cases with a functioning radial arteriovenous fistula, we successfully treated the ulnar artery. PTA was unsuccessful in 18% (6/34) hands due to inability to cross severely calcified lesions. The hand-healing rate was 65% (22/34). The predictors of hand healing were PTA technical success (odds ratio (OR) 0.5, confidence interval (CI) 0.28-0.88; p ≤ 0.0001) and digital run-off (OR 0.37, CI 0.19-0.71; p ≤ 0.003). The mean follow-up period was 13 ± 9 months. Six patients (18%) underwent secondary procedures due to symptomatic restenosis. In all these cases, a successful re-PTA was performed at a mean 6 months after the index procedure, and there were no major procedure-related events. Ten patients (36%) died during follow-up. Angioplasty of BTE vessels for CHI is a feasible and safe procedure with acceptable rates of technical success and hand healing. Poor digital run-off due to obstructive disease of the digital vessels can reduce the hand-healing rate after a successful PTA. Pure isolated BTE vessel disease seems to characterise patients with ESRD and diabetes mellitus.


[Sensitivity of malaria mosquito larvae to bacterial insecticides in relation to handling].
The conditions for cultivation of malaria mosquito larvae were found to exert a great impact on their sensitivity to bactoculicide. Elevating keeping temperatures for An. sacharovi and An. pulcherrimus by 10-11 degrees C causes 2-4-fold increases in LC50. There are virtually no impacts of larval population during their development or temperature-population density relationships. Ten-fold increases in larval population density under which An. stephensi larvae have been grown result in 3-fold decreases in LC50. There are no impacts of temperatures and temperature-population density relationships either. There are also great larval species-specific differences in their sensitivity to bactoculicide.


Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter.
The effect of nucleoside on Na+ reabsorption via Na+/nucleoside cotransporter in cultured rat epididymal epithelia was studied by short-circuit current (Isc) technique. Guanosine added apically stimulated Isc in a dose-dependent manner, with a median effective concentration (EC50) of 7 +/- 2 microM (mean +/- SEM). Removal of Na+ from the apical bathing solution or pretreatment with a nonspecific Na+/nucleoside cotransporter inhibitor, phloridzin, completely blocked the Isc response to guanosine. Moreover, the guanosine response was abolished by pretreatment of the tissue with ouabain, a Na+/K+-ATPase inhibitor, suggesting the involvement of Na+/nucleoside cotransporter on the apical side and Na+/K+-ATPase on the basolateral side in Na+ reabsorption. In contrast, the Isc response to guanosine was not affected after desensitization of purinoceptors by ATP. Addition of the Na+/K+/2Cl- symport inhibitor bumetanide to the basolateral side or the nonspecific Cl- channel blocker diphenylamine-2-carboxylate to the apical side showed no effect on the Isc response to guanosine, excluding stimulation of Cl- secretion by guanosine as the cause of the guanosine-induced Isc. The Isc response to purine nucleoside (guanosine and inosine) was much higher than that to pyrimidine nucleoside (thymidine and cytidine). Consistent with substrate specificity, results of reverse transcription-polymerase chain reaction revealed mRNA for concentrative nucleoside transporter (CNT2), which is a purine nucleoside-selective Na+/nucleoside cotransporter in the epididymis, but not for CNT1. It is suggested that the Na+/nucleoside cotransporter (i.e., CNT2) may be one of the elements involved in Na+ and fluid reabsorption in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa.