GABAergic neurons are susceptible to BAX-dependent apoptosis following isoflurane exposure in the neonatal period.
Exposure to volatile anesthetics during the neonatal period results in acute neuron death. Prior work suggests that apoptosis is the dominant mechanism mediating neuron death. We show that Bax deficiency blocks neuronal death following exposure to isoflurane during the neonatal period. Blocking Bax-mediated neuron death attenuated the neuroinflammatory response of microglia following isoflurane exposure. We find that GABAergic interneurons are disproportionately overrepresented among dying neurons. Despite the increase in neuronal apoptosis induced by isoflurane exposure during the neonatal period, seizure susceptibility, spatial memory retention, and contextual fear memory were unaffected later in life. However, Bax deficiency alone led to mild deficiencies in spatial memory and contextual fear memory, suggesting that normal developmental apoptotic death is important for cognitive function. Collectively, these findings show that while GABAergic neurons in the neonatal brain undergo elevated Bax-dependent apoptotic cell death following exposure to isoflurane, this does not appear to have long-lasting consequences on overall neurological function later in life.


Analysis of the Schizosaccharomyces pombe Cell Cycle.
Schizosaccharomyces pombe cells are rod shaped, and they grow by tip elongation. Growth ceases during mitosis and cell division; therefore, the length of a septated cell is a direct measure of the timing of mitotic commitment, and the length of a wild-type cell is an indicator of its position in the cell cycle. A large number of documented stage-specific changes can be used as landmarks to characterize cell cycle progression under specific experimental conditions. Conditional mutations can permanently or transiently block the cell cycle at almost any stage. Large, synchronously dividing cell populations, essential for the biochemical analysis of cell cycle events, can be generated by induction synchrony (arrest-release of a cell cycle mutant) or selection synchrony (centrifugal elutriation or lactose-gradient centrifugation). Schizosaccharomyces pombe cell cycle studies routinely combine particular markers, mutants, and synchronization procedures to manipulate the cycle. We describe these techniques and list key landmarks in the fission yeast mitotic cell division cycle.


The efficacy of omega-3 supplementation for major depression: a randomized controlled trial.
To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE). Inclusive, double-blind, randomized, controlled, 8-week, parallel-group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini-International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS-SR(30)); the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS). The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR(30) and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR(30) (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS. In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders. controlled-trials.com Identifier: ISRCTN47431149.


[Voice rehabilitation of laryngectomized patients: cultural characteristics in the process].
The objective of this study was to identify the characteristics of the process of vocal rehabilitation among laryngectomees focusing on culture. The study included four laryngectomees who attend the GARPO-Laryngectomees (Support Group For The Rehabilitation of Ostomized Patients--Laryngectomees) and communicate with esophageal or pharyngeal voice. The theme that emerged from the data was "to be born again", in agreement with the cultural value of the voice in our society. The study revealed as well the difficulties of the process, the importance of family participation and the stigma of the altered body image.


Selection and adaptation in human migration.
This article reviews the ways migration shapes human biology. This includes the physiological and genetic, but also socio-cultural aspects such as organization, behavior, and culture. Across disciplines I highlight the multiple levels of cultural and genetic selection whereby individuals and groups adapt to pressures along a migration timeline: the origin, transit, and destination. Generally, the evidence suggests that selective pressures and adaptations occur at the individual, family, and community levels. Consequently, across levels there are negotiations, interactions, and feedbacks that shape migration outcomes and the trajectory of evolutionary change. The rise and persistence of migration-relevant adaptations emerges as a central question, including the maintenance of cumulative culture adaptations, the persistence of "cultures of migration," as well as the individual-level physiological and cognitive adaptations applied to successful transit and settlement in novel environments.


Strong stress-composition coupling in lithium alloy nanoparticles.
The stress inevitably imposed during electrochemical reactions is expected to fundamentally affect the electrochemistry, phase behavior and morphology of electrodes in service. Here, we show a strong stress-composition coupling in lithium binary alloys during the lithiation of tin-tin oxide core-shell nanoparticles. Using in situ graphene liquid cell electron microscopy imaging, we visualise the generation of a non-uniform composition field in the nanoparticles during lithiation. Stress models based on density functional theory calculations show that the composition gradient is proportional to the applied stress. Based on this coupling, we demonstrate that we can directionally control the lithium distribution by applying different stresses to lithium alloy materials. Our results provide insights into stress-lithium electrochemistry coupling at the nanoscale and suggest potential applications of lithium alloy nanoparticles.


The reduction of renogram deconvolution to a direct method of transit time determination.
It is known that the intrarenal mean transit time (MTT) can be determined using renography by first deconvoluing the kidney retention function from the obtained time-activity curve and then integrating the retention function. A direct and approximate calculational method, based on an integral mathematical model, has also been employed to estimate the MTT. In this work it is shown that the direct approximate method is equivalent to the standard deconvolution method applied with the assumption of a time independent retention function. Potential errors incurred using the direct method are thus quantified and assessed over a range of representative decay parameters.


CYP2A6 deletion polymorphism is associated with decreased susceptibility of lung cancer in Asian smokers: a meta-analysis.
Cytochrome P450 2A6 (CYP2A6) is an enzyme involved in the metabolism of some tobacco carcinogens, which is an important risk factor of lung cancer. Among CYP2A6 allelic variants, CYP2A6*4 presents a whole gene deletion that accounts for the majority of poor metabolizer. In this study, a meta-analysis was performed to assess the association between CYP2A6*4 and risk of lung cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 20, 2012. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated in a fixed-effects model and a random-effects model when appropriate. Eight eligible studies with 3,203 lung cancer cases and 2,839 controls were included in this study. Overall, no significant association was observed in CYP2A6*4 with the risk of lung cancer under any genetic model for all samples after correction. However, subgroup analysis showed that significant associations were observed in Asian with pooled OR (95 %CI) of 0.761 (0.672-0.861) for allele comparison, 0.769 (0.668-0.886) for dominant model, and 0.522 (0.359-0.760) for recessive model. Furthermore, after stratifying Asian samples according to smoking status, significant associations were only observed in smokers with pooled OR (95 %CI) of 0.713 (0.607-0.838) for allele comparison, 0.720 (0.596-0.869) for dominant model, and 0.444 (0.275-0.715) for recessive model. This meta-analysis suggests that the CYP2A6*4 polymorphism was associated with susceptibility of lung cancer for smokers in Asian. The whole gene deletion of CYP2A6 might decrease the risk of tobacco-related lung cancer in Asian.


PI3K-PTEN dysregulation leads to mTOR-driven upregulation of the core clock gene BMAL1 in normal and malignant epithelial cells.
Dysfunctional clock signaling is observed in a variety of pathological conditions. Many members of the clock gene family are upregulated in tumor cells. Here, we explored the consequences of a commonly disrupted signaling pathway in head and neck cancer on the regulation of circadian clock genes. PTEN is a key molecular controller of the PI3K signaling, and loss of PTEN function is often observed in a variety of cancers. Our main goal was to determine whether PTEN regulates circadian clock signaling. We found that oxidation-driven loss of PTEN function resulted in the activation of mTOR signaling and activation of the core clock protein BMAL1 (also known as ARNTL). The PTEN-induced BMAL1 upregulation was further confirmed using small interference RNA targeting PTEN, and in vivo conditional depletion of PTEN from the epidermis. We observed that PTEN-driven accumulation of BMAL1 was mTOR-mediated and that administration of Rapamycin, a specific mTOR inhibitor, resulted in in vivo rescue of normal levels of BMAL1. Accumulation of BMAL1 by deletion of PER2, a Period family gene, was also rescued upon in vivo administration of mTOR inhibitor. Notably, BMAL1 regulation requires mTOR regulatory protein Raptor and Rictor. These findings indicate that mTORC1 and mTORC2 complex plays a critical role in controlling BMAL1, establishing a connection between PI3K signaling and the regulation of circadian rhythm, ultimately resulting in deregulated BMAL1 in tumor cells with disrupted PI3K signaling.


Object recognition and location: Which component of object location memory for landmarks is affected by gender? Evidence from four to ten year-old children.
Memory for object location requires at least three processes: object recognition, object location, and object-location binding. Gender-related differences during childhood are still a matter of debate, especially concerning memory for object location, where females are expected to outperform males. Memory for object position is pivotal for spatial navigation and its investigation during childhood is crucial in order to understand the roots of gender-related differences in spatial orientation. Actually, environmental objects, namely landmarks, can be located using egocentric and/or allocentric frames of references, as well as using the spatial translation between them. Here, we investigated gender-related differences during childhood in object recognition and location whenever a shift between egocentric and allocentric frame of reference is required. Sixty-three boys and 44 girls (aged between four and ten years old) were asked to egocentrically learn a path on the Walking Corsi Test enriched with three landmarks. Then, children were asked to recognize (object recognition) the landmarks encountered along the path and locate them (object location) on an allocentric configuration of the spatial array. Girls outperformed boys in locating landmarks, whereas no difference occurred in landmark recognition. These results provide insights into the gender-related differences in location memory of landmarks, suggesting that females are better than males in the object location component well before the age of 13.


Ultrastructural observation of human neutrophils during apoptotic cell death triggered by Entamoeba histolytica.
Neutrophils are important effector cells against protozoan extracellular parasite Entamoeba histolytica, which causes amoebic colitis and liver abscess in human beings. Apoptotic cell death of neutrophils is an important event in the resolution of inflammation and parasite's survival in vivo. This study was undertaken to investigate the ultrastructural aspects of apoptotic cells during neutrophil death triggered by Entamoeba histolytica. Isolated human neutrophils from the peripheral blood were incubated with or without live trophozoites of E. histolytica and examined by transmission electron microscopy (TEM). Neutrophils incubated with E. histolytica were observed to show apoptotic characteristics, such as compaction of the nuclear chromatin and swelling of the nuclear envelop. In contrast, neutrophils incubated in the absence of the amoeba had many protrusions of irregular cell surfaces and heterogenous nuclear chromatin. Therefore, it is suggested that Entamoeba-induced neutrophil apoptosis contribute to prevent unwanted tissue inflammation and damage in the amoeba-invaded lesions in vivo.


Long-term management of ventilated-assisted individuals: the Boston University experience.
In the 4 1/2 years beginning in January 1981, the University Hospital at the Boston University Medical Center admitted 46 ventilator-assisted individuals to its Respiratory Care Center and discharged 38 of them to their homes with ventilators. Of the 46 admitted, 23 had COPD and 23 had neuromuscular or skeletal disorders. All the latter were successfully sent home, and 15 of the 23 with COPD went home. At follow-up in 1985, of the 38 patients managed at home for periods of 1 to 51 months, 30 were surviving and 4 with COPD and 4 with neuromuscular disorders had died. One died immediately after discharge, one who had amyotrophic lateral sclerosis lived 9 months at home before dying, and the other 6 lived at home a year or more before dying. These results were made possible by an inpatient facility that had the goal of improving the quality of life of ventilator-assisted persons. This was done by the use of portable ventilators on motorized wheelchairs, by the use of traditional rehabilitation techniques, and by encouraging and training patients to become independent and responsible for their own personal and respiratory care. The hospital-based Respiratory Care Center is staffed by a team from physical therapy, occupational therapy, respiratory therapy, rehabilitation nursing, social service, psychiatry, rehabilitation medicine, and otolaryngology. A pulmonary physician directs the program and a respiratory nurse specialist is co-director and oversees its daily operation. The rehabilitation process has six stages: Stage 1 is stabilization, Stage II is evaluation, Stage III is rehabilitation planning, Stage IV is rehabilitation training, Stage V is discharge planning.(ABSTRACT TRUNCATED AT 250 WORDS)


Does yohimbine hydrochloride facilitate fear extinction in virtual reality treatment of fear of flying? A randomized placebo-controlled trial.
Research suggests that yohimbine hydrochloride (YOH), a noradrenaline agonist, can facilitate fear extinction. It is thought that the mechanism of enhanced emotional memory is stimulated through elevated noradrenaline levels. This randomized placebo-controlled trial examined the potential exposure-enhancing effects of YOH in a clinical sample of participants meeting DSM-IV criteria for a specific phobia (fear of flying). Sixty-seven participants with fear of flying were randomized to 4 sessions of virtual reality exposure therapy (VRET) combined with YOH (10 mg), or 4 sessions of VRET combined with a placebo. Treatment consisted of 4 weekly 1-hour exposure sessions consisting of two 25-minute virtual flights. At pre- and post- treatment, fear of flying was assessed. The YOH or placebo capsules were administered 1 h prior to exposures. The manipulation of the noradrenaline activity was confirmed by salivary α-amylase (sAA) samples taken pre-, during and post-exposure. Forty-eight participants completed treatment. Manipulation of noradrenaline levels with YOH was successful, with significantly higher levels of sAA in the YOH group when entering exposure. Results showed that both groups improved significantly from pre- to post-treatment with respect to anxiety reduction. However, although the manipulation of noradrenaline activity was successful, there was no evidence that YOH enhanced outcome. Participants improved significantly on anxiety measures independently of drug condition, after 4 sessions of VRET. These data do not support the initial findings of exposure-enhancing effects of YOH in this dosage in clinical populations.


Multigroup discrete ordinates modeling of 125I 6702 seed dose distributions using a broad energy-group cross section representation.
Our purpose in this work is to demonstrate that the efficiency of dose-rate computations in 125I brachytherapy, using multigroup discrete ordinates radiation transport simulations, can be significantly enhanced using broad energy group cross sections without a loss of accuracy. To this end, the DANTSYS multigroup discrete ordinates neutral particle transport code was used to estimate the absorbed dose-rate distributions around an 125I-model 6702 seed in two-dimensional (2-D) cylindrical R-Z geometry for four different problems spanning the geometries found in clinical practice. First, simulations with a high resolution 210 energy groups library were used to analyze the photon flux spectral distribution throughout this set of problems. These distributions were used to design an energy group structure consisting of three broad groups along with suitable weighting functions from which the three-group cross sections were derived. The accuracy of 2-D DANTSYS dose-rate calculations was benchmarked against parallel Monte Carlo simulations. Ray effects were remedied by using the DANTSYS internal first collision source algorithm. It is demonstrated that the 125I primary photon spectrum leads to inappropriate weighting functions. An accuracy of +/-5% is achieved in the four problem geometries considered using geometry-independent three-group libraries derived from either material-specific weighting functions or a single material-independent weighting function. Agreement between Monte Carlo and the three-group DANTSYS calculations, within three standard Monte Carlo deviations, is observed everywhere except for a limited region along the Z axis of rotational symmetry, where ray effects are difficult to mitigate. The three-group DANTSYS calculations are 10-13 times faster than ones with a 210-group cross section library for 125I dosimetry problems. Compared to 2-D EGS4 Monte Carlo calculations, the 3-group DANTSYS simulations are a 100-fold more efficient. Provided that these efficiency gains can be sustained in three-dimensional geometries, the results suggest that discrete ordinates simulations may have the potential to serve as an efficient and accurate dose-calculation algorithm for low-energy brachytherapy treatment planning.


Phenotypic variation in myocardial macrophage populations suggests a role for macrophage activation in SIV-associated cardiac disease.
Cardiac abnormalities are common in HIV-infected individuals, and have been especially well documented as contributors to mortality in HIV-infected children. Underlying pathogenetic mechanisms responsible for myocardial disease in HIV-infection remain imperfectly understood. SIV-infected rhesus monkeys develop a spectrum of cardiac lesions similar to those seen in HIV-infected people, providing an important model for pathogenesis studies. Retrospective analysis of cardiac tissue collected at necropsy from SIV-infected rhesus monkeys was performed to evaluate myocardial macrophage and dendritic cell populations as a function of previously quantitated lymphocytic inflammatory infiltrates and cardiomyocyte degeneration or necrosis. Variations in the size and phenotype of macrophage and dendritic cell populations were examined as possible contributors to the pathogenesis of SIV-associated inflammatory lesions. Macrophages labeling immunohistochemically for CD163 differed substantially from macrophages labeling for HAM56 in overall number, distribution across groups, involvement in inflammatory clusters, correlation with the DC-SIGN(+) subpopulation of macrophages, and correlation with numbers of SIV-infected cells. CD163(+) macrophages occurred in significantly higher numbers in uninflamed hearts from SIV-infected animals than in hearts from SIV-infected animals with myocarditis or uninfected controls (p < 0.01). Numbers of CD163(+) cells correlated positively with numbers of SIV-infected cells (p < 0.05) suggesting that the CD163(+) population was associated with decreased inflammatory infiltration and reduced control of virus within the heart. As CD163 has been associated with nonclassical macrophage activation and an antiinflammatory phenotype, these results suggest that a balance between classical and nonclassical activation may affect levels of inflammatory infiltration and of myocardial virus burden.


Social norms of alcohol, smoking, and marijuana use within a Canadian university setting.
to study actual and perceived substance use in Canadian university students and to compare these rates with US peers. students (N = 1,203) from a large Canadian university. participants were surveyed using items from the National College Health (NCHA) Assessment of the American College Health Association questionnaire. alcohol was the most common substance used (65.8%), followed by marijuana (13.5%) and cigarettes (13.5%). Substance use and norms were significantly less than the NCHA US data. Overall, respondents generally perceived the typical Canadian student to have used all 3 substances. Perceived norms significantly predicted use, with students more likely to use alcohol, cigarettes, or marijuana if they perceived the typical student to use these substances. similar to their US peers, Canadian university students have inaccurate perceptions of peer substance use. These misperceptions may have potentially negative influences on actual substance use and could be a target for intervention. Further research examining the cross-cultural differences for substance abuse is warranted.


Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.
Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates.


Language disturbances after non-thalamic subcortical stroke: a review of the literature.
Language disorders following subcortical non-thalamic stroke show great variability across literature and a well-defined profile in these aphasic disturbances is yet to be established. The lack of recent and consistent literature on the subject complicates the management of subcortical aphasia. The aim of this study is to review the literature describing oral language disturbances following subcortical non-thalamic stoke affecting the basal ganglia and the surrounding white matter. A review of the literature of three databases (PubMed, PsycNet and LLBA), identifying research articles from 1997 to 2015, was completed. The quality of the selected studies was assessed using the Checklist for the assessment of methodological quality. Twenty-two articles met criteria for review and oral language assessment data were extracted for 114 subjects. The results suggest a predominance of deficits in more complex and demanding language levels (ex. discourse, syntax) and in language production (vs comprehension). Rapid recovery is expected, especially for lexical-semantic and receptive deficits. These findings show the importance of a complete oral language evaluation after subcortical stoke and provide recent data relative to expected deficits and recovery to guide clinicians in the management of these patients. They also suggest that a descriptive approach of the deficits may be more efficient and accurate than the use of a traditional classification of aphasia.


Nicotine-mediated signals modulate cell death and survival of T lymphocytes.
The capacity of nicotine to affect the behavior of non-neuronal cells through neuronal nicotinic acetylcholine receptors (nAChRs) has been the subject of considerable recent attention. Previously, we showed that exposure to nicotine activates the nuclear factor of activated T cells (NFAT) transcription factor in lymphocytes and endothelial cells, leading to alterations in cellular growth and vascular endothelial growth factor production. Here, we extend these studies to document effects of nicotine on lymphocyte survival. The data show that nicotine induces paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act both as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other non-neuronal cells. In addition, our results show that, while having overlapping functions, low and high affinity nAChRs also transmit signals that promote distinct outcomes in lymphocytes. The sum of our data suggests that selective modulation of nAChRs might be useful to regulate lymphocyte activation and survival in health and disease.


Reprint of: aromatherapy and massage for antenatal anxiety: its effect on the fetus.
Antenatal anxiety has been linked to maternal hypothalamic-pituitary-adrenal axis changes which can affect fetal development and may have lasting effects on the child's psychological development. Treatments for anxiety have hitherto focused on psychotherapy techniques or antidepressant drugs but these do not always effect long-term improvement. Aromatherapy and massage have successfully been used to produce significantly greater improvement in reduction of anxiety. Midwives may highlight anxiety in some of the mothers in their care and can incorporate the holistic approach of aromatherapy and massage into their practice. However, further research is required to establish the efficacy and cost-effectiveness of aromatherapy and massage in the antenatal period.


[Detection of heterogenicity of the lymphoid populations by measuring the diameter of the cells and cell nuclei].
Some parameters of distribution according to the lymphoid cell and its nuclei size in the peripheral blood, bone marrow, thymus and spleen of healthy rats were studied. A comparative assay revealed population homogeneity for the thymus and bone marrow lymphocytes as well as their mean diameter differences. Mixing of these cell types markedly changed the distribution parameters of newly formed population, as shown on the model of the bone marrow lymphoid reaction caused by migration of thymic lymphocytes after 5-fluorouracil use. Preliminary thymectomy excluded migration and homogeneity of the bone marrow lymphocyte size remained unchanged.


Outcomes of fasciotomy in patients with crush-induced acute kidney injury after Bam earthquake.
INTRODUCTION. Fasciotomy may increase the morbidity and mortality in patients with crush-induced acute kidney injury (AKI), by creating an open wound, increasing the risk of bleeding, coagulopathy, and potentially fatal sepsis. This study evaluates the outcomes of fasciotomy in these patients after Bam earthquake in Iran. MATERIALS AND METHODS. We reviewed medical records of victims of Bam earthquake complicated with crush-induced AKI. Demographic, biochemical, and clinical data of patients who underwent fasciotomy were evaluated and compared with other patients with AKI. RESULTS. Fasciotomy was performed for 70 of 200 patients with crush-induced AKI (35.0%). There were no significant differences regarding sex, age, time under the rubble, and muscle enzymes level between these patients and those without fasciotomy. They did not experience higher rates of disseminated intravascular coagulopathy, sepsis, adult respiratory distress syndrome, amputation, and dialysis session. Neither did they have a longer hospitalization period or higher death rate. CONCLUSIONS. This study showed that fasciotomy did not have any deteriorating effect on morbidity and mortality of patients with crush-induced AKI after Bam earthquake.


Mechanisms, Techniques and Devices of Airborne Virus Detection: A Review.
Airborne viruses, such as COVID-19, cause pandemics all over the world. Virus-containing particles produced by infected individuals are suspended in the air for extended periods, actually resulting in viral aerosols and the spread of infectious diseases. Aerosol collection and detection devices are essential for limiting the spread of airborne virus diseases. This review provides an overview of the primary mechanisms and enhancement techniques for collecting and detecting airborne viruses. Indoor virus detection strategies for scenarios with varying ventilations are also summarized based on the excellent performance of existing advanced comprehensive devices. This review provides guidance for the development of future aerosol detection devices and aids in the control of airborne transmission diseases, such as COVID-19, influenza and other airborne transmission viruses.


Correlating the Morphological Evolution of Individual Catalyst Particles to the Kinetic Behavior of Metallocene-Based Ethylene Polymerization Catalysts.
Kinetics-based differences in the early stage fragmentation of two structurally analogous silica-supported hafnocene- and zirconocene-based catalysts were observed during gas-phase ethylene polymerization at low pressures. A combination of focused ion beam-scanning electron microscopy (FIB-SEM) and nanoscale infrared photoinduced force microscopy (IR PiFM) revealed notable differences in the distribution of the support, polymer, and composite phases between the two catalyst materials. By means of time-resolved probe molecule infrared spectroscopy, correlations between this divergence in morphology and the kinetic behavior of the catalysts' active sites were established. The rate of polymer formation, a property that is inherently related to a catalyst's kinetics and the applied reaction conditions, ultimately governs mass transfer and thus the degree of homogeneity achieved during support fragmentation. In the absence of strong mass transfer limitations, a layer-by-layer mechanism dominates at the level of the individual catalyst support domains under the given experimental conditions.


Effect of coblation polypectomy on estimated blood loss in endoscopic sinus surgery.
We conducted a pilot study comparing estimated blood loss (EBL) using coblation-assisted endoscopic sinus surgery (CAESS) where coblation is used to debulk nasal polyps before microdebridement with a traditional microdebrider technique in chronic rhinosinusitis (CRS) patients with sinonasal polyps undergoing endoscopic sinus surgery (ESS). A retrospective analysis was performed at a tertiary care center on patients with nasal polyposis undergoing ESS between January 2008 and July 2008. The University of Miami CT staging system was used preoperatively to evaluate the extent of sinonasal disease. The duration of surgery, blood loss per minute, total EBL, and demographic data were collected. Twenty-one patients underwent nasal polypectomy/ESS using CAESS and 16 patients underwent nasal polypectomy/ESS using microdebridement. The two groups had comparable University of Miami CT staging scores (p>0.05). The average EBL was 307.1+/-169.8 mL using coblation compared with 627.8+/-424.2 mL using microdebridement (p<0.05). The average duration of surgery using coblation was 116.2+/-41.7 minutes, compared with 125.3+/-48.4 minutes using microdebridement (p>0.05). The average blood loss per minute was 2.8+/-1.7 mL in the coblation group compared with 4.8+/-2.1 mL in the microdebridement group (p<0.05). Subgroup analyses showed a significant decrease in average EBL and EBL/minute to be only significant for revision cases (p<0.05) and not for primary cases (p>0.05). Coblation-assisted nasal polypectomy/ESS is associated with a statistically significant lower EBL and blood loss per minute when compared with traditional microdebridement technique. Coblation represents a new device that can reduce blood loss in patients with nasal polyposis undergoing traditional revision ESS. Further prospective randomized trials are needed to validate these findings.


Deep Learning for Outcome Prediction in Neurosurgery: A Systematic Review of Design, Reporting, and Reproducibility.
Deep learning (DL) is a powerful machine learning technique that has increasingly been used to predict surgical outcomes. However, the large quantity of data required and lack of model interpretability represent substantial barriers to the validity and reproducibility of DL models. The objective of this study was to systematically review the characteristics of DL studies involving neurosurgical outcome prediction and to assess their bias and reporting quality. Literature search using the PubMed, Scopus, and Embase databases identified 1949 records of which 35 studies were included. Of these, 32 (91%) developed and validated a DL model while 3 (9%) validated a pre-existing model. The most commonly represented subspecialty areas were oncology (16 of 35, 46%), spine (8 of 35, 23%), and vascular (6 of 35, 17%). Risk of bias was low in 18 studies (51%), unclear in 5 (14%), and high in 12 (34%), most commonly because of data quality deficiencies. Adherence to transparent reporting of a multivariable prediction model for individual prognosis or diagnosis reporting standards was low, with a median of 12 transparent reporting of a multivariable prediction model for individual prognosis or diagnosis items (39%) per study not reported. Model transparency was severely limited because code was provided in only 3 studies (9%) and final models in 2 (6%). With the exception of public databases, no study data sets were readily available. No studies described DL models as ready for clinical use. The use of DL for neurosurgical outcome prediction remains nascent. Lack of appropriate data sets poses a major concern for bias. Although studies have demonstrated promising results, greater transparency in model development and reporting is needed to facilitate reproducibility and validation.


Protective role of spleen-derived macrophages in lung inflammation, injury, and fibrosis induced by nitrogen mustard.
Nitrogen mustard (NM) is a vesicant that causes lung injury and fibrosis, accompanied by a persistent macrophage inflammatory response. In these studies we analyzed the spleen as a source of these cells. Splenectomized (SPX) and sham control rats were treated intratracheally with NM (0.125 mg/kg) or PBS control. Macrophage responses were analyzed 1-7 days later. Splenectomy resulted in an increase in lung macrophages expressing CCR2, but a decrease in ATR-1α(+) cells, receptors important in bone marrow and spleen monocyte trafficking, respectively. Splenectomy was also associated with an increase in proinflammatory M1 (iNOS(+), CD11b(+)CD43(+)) macrophages in lungs of NM-treated rats, as well as greater upregulation of iNOS and COX-2 mRNA expression. Conversely, a decrease in CD11b(+)CD43(-) M2 macrophages was observed in SPX rats, with no changes in CD68(+), CD163(+), CD206(+), or YM-1(+) M2 macrophages, suggesting distinct origins of M2 subpopulations responding to NM. Macrophage expression of M2 genes including IL-10, ApoE, PTX-2, PTX-3, 5-HT2α, and 5-HT7 was also reduced in NM-treated SPX rats compared with shams, indicating impaired M2 activity. Changes in lung macrophages responding to NM as a consequence of splenectomy were correlated with exacerbated tissue injury and more rapid fibrogenesis. These data demonstrate that the spleen is a source of a subset of M2 macrophages with anti-inflammatory activity; moreover, in their absence, proinflammatory/cytotoxic M1 macrophages predominate in the lung, resulting in heightened pathology. Understanding the origin of macrophages and characterizing their phenotype after vesicant exposure may lead to more targeted therapeutics aimed at reducing toxicity and disease pathogenesis.


Expression cloning of a reserpine-sensitive vesicular monoamine transporter.
A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules.


The role of the anesthesiologist in fast-track surgery: from multimodal analgesia to perioperative medical care.
Improving perioperative efficiency and throughput has become increasingly important in the modern practice of anesthesiology. Fast-track surgery represents a multidisciplinary approach to improving perioperative efficiency by facilitating recovery after both minor (i.e., outpatient) and major (inpatient) surgery procedures. In this article we focus on the expanding role of the anesthesiologist in fast-track surgery. A multidisciplinary group of clinical investigators met at McGill University in the Fall of 2005 to discuss current anesthetic and surgical practices directed at improving the postoperative recovery process. A subgroup of the attendees at this conference was assigned the task of reviewing the peer-reviewed literature on this topic as it related to the role of the anesthesiologist as a perioperative physician. Anesthesiologists as perioperative physicians play a key role in fast-track surgery through their choice of preoperative medication, anesthetics and techniques, use of prophylactic drugs to minimize side effects (e.g., pain, nausea and vomiting, dizziness), as well as the administration of adjunctive drugs to maintain major organ system function during and after surgery. The decisions of the anesthesiologist as a key perioperative physician are of critical importance to the surgical care team in developing a successful fast-track surgery program.


Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from BAL fluid and correlation with lung disease.
To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.


Atypical antipsychotic-like effects of the dopamine D3 receptor agonist, (+)-PD 128,907.
Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3- b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of clozapine. (+)-PD 128,907 blocked stereotypy produced by dizocilpine (MK-801) at 12-fold lower doses than those affecting apomorphine-induced stereotypes in mice and did not produce catalepsy. These effects of (+)-PD 128,907 were stereospecific and were blocked by a D3 antagonist. These data suggest a role for D3 receptors in antipsychotic drug action.


The significance of peroxisome function in chronological aging of Saccharomyces cerevisiae.
We studied the chronological lifespan of glucose-grown Saccharomyces cerevisiae in relation to the function of intact peroxisomes. We analyzed four different peroxisome-deficient (pex) phenotypes. These included Δpex3 cells that lack peroxisomal membranes and in which all peroxisomal proteins are mislocalized together with Δpex6 in which all matrix proteins are mislocalized to the cytosol, whereas membrane proteins are still correctly sorted to peroxisomal ghosts. In addition, we analyzed two mutants in which the peroxisomal location of the β-oxidation machinery is in part disturbed. We analyzed Δpex7 cells that contain virtually normal peroxisomes, except that all matrix proteins that contain a peroxisomal targeting signal type 2 (PTS2, also including thiolase), are mislocalized to the cytosol. In Δpex5 cells, peroxisomes only contain matrix proteins with a PTS2 in conjunction with all proteins containing a peroxisomal targeting signal type 1 (PTS1, including all β-oxidation enzymes except thiolase) are mislocalized to the cytosol. We show that intact peroxisomes are an important factor in yeast chronological aging because all pex mutants showed a reduced chronological lifespan. The strongest reduction was observed in Δpex5 cells. Our data indicate that this is related to the complete inactivation of the peroxisomal β-oxidation pathway in these cells due to the mislocalization of thiolase. Our studies suggest that during chronological aging, peroxisomal β-oxidation contributes to energy generation by the oxidation of fatty acids that are released by degradation of storage materials and recycled cellular components during carbon starvation conditions.


Structural systems biology approach delineate the functional implications of SNPs in exon junction complex interaction network.
In eukaryotes, transcripts that carry premature termination codons (PTC) leading to truncated proteins are degraded by the Nonsense Mediated Decay (NMD) machinery. Missense and nonsense Single Nucleotide Polymorphisms (SNPs) in proteins belonging to Exon junction complex (EJC) and up-frameshift protein (UPF) will compromise NMD leading to the accumulation of truncated proteins in various diseases. The EJC and UPF which are involved in NMD is a good model system to study the effect of SNPs at a system level. Despite the availability of crystal structures, computational tools, and data on mutational and deletion studies, with functional implications, an integrated effort to understand the impact of SNPs at the systems level is lacking. To study the functional consequences of missense SNPs, sequence-based techniques like SIFT and PolyPhen which classify SNPs as deleterious or non-deleterious and structure-based methods like FoldX which calculate the Delta Delta G, (ddGs, ∆∆G) are used. Using FoldX, the ddG for mutations with experimentally validated functional effects is calculated and compared with those calculated for SNPs in the same protein-protein interaction interface. Further, a model is conceived to explain the functional implications of SNPs based on the effects observed for known mutants. The results are visualized in a network format. The effects of nonsense mutations are discerned by comparing with deletion mutation studies and loss of interaction in the crystal structure. The present work not only integrates genomics, proteomics, and classical genetics with 'Structural Biology' but also helps to integrate it into a 'systems-level functional network'.Communicated by Ramaswamy H. Sarma.


Long-lived reactive species on free-radical-damaged proteins.
We have demonstrated two novel reactive species on radical-modified proteins which are relatively long-lived, one oxidizing and one reducing. The two species are reactive with critical biological components, and so may be of physiological and pathological importance. The oxidizing species, which have been identified as protein hydroperoxides, can consume key cellular reductants, such as ascorbate and glutathione. The reducing species can act on both free and metalloprotein forms of copper and iron ions, which participate in radical generation. These findings suggest that proteins may act as traps for the chemical energy released by free radicals, with the capacity to pass it on to other molecules. The long-lived nature of both the reactive moieties indicates that they may be able to diffuse and transfer damaging reactions to distant sites.


Improving our understanding of environmental controls on the distribution of C3 and C4 grasses.
A number of studies have demonstrated the ecological sorting of C3 and C4 grasses along temperature and moisture gradients. However, previous studies of C3 and C4 grass biogeography have often inadvertently compared species in different and relatively unrelated lineages, which are associated with different environmental settings and distinct adaptive traits. Such confounded comparisons of C3 and C4 grasses may bias our understanding of ecological sorting imposed strictly by photosynthetic pathway. Here, we used MaxEnt species distribution modeling in combination with satellite data to understand the functional diversity of C3 and C4 grasses by comparing both large clades and closely related sister taxa. Similar to previous work, we found that C4 grasses showed a preference for regions with higher temperatures and lower precipitation compared with grasses using the C3 pathway. However, air temperature differences were smaller (2 °C vs. 4 °C) and precipitation and % tree cover differences were larger (1783 mm vs. 755 mm, 21.3% vs. 7.7%, respectively) when comparing C3 and C4 grasses within the same clade vs. comparing all C4 and all C3 grasses (i.e., ignoring phylogenetic structure). These results were due to important differences in the environmental preferences of C3 BEP and PACMAD clades (the two main grass clades). Winter precipitation was found to be more important for understanding the distribution and environmental niche of C3 PACMADs in comparison with both C3 BEPs and C4 taxa, for which temperature was much more important. Results comparing closely related C3 -C4 sister taxa supported the patterns derived from our modeling of the larger clade groupings. Our findings, which are novel in comparing the distribution and niches of clades, demonstrate that the evolutionary history of taxa is important for understanding the functional diversity of C3 and C4 grasses, and should have implications for how grasslands will respond to global change.


A wireless multi-channel bioimpedance measurement system for personalized healthcare and lifestyle.
Miniaturized, noninvasive, wearable sensors constitute a fundamental prerequisite for pervasive, predictive, and preventive healthcare systems. In this sense, this paper presents the design, realization, and evaluation of a wireless multi-channel measurement system based on a cost-effective high-performance integrated circuit for electrical bioimpedance (EBI) measurements in the frequency range from 1 kHz to 1 MHz. The resulting on-chip spectrometer provides high measuring EBI capabilities and together with a low-cost, commercially available radio frequency transceiver device. It provides reliable wireless communication, constitutes the basic node to build EBI wireless sensor networks (EBI-WSNs). The proposed EBI-WSN behaves as a high-performance wireless multi-channel EBI spectrometer, where the number of channels is completely scalable and independently configurable to satisfy specific measurement requirements of each individual. A prototype of the EBI node leads to a very small printed circuit board of approximately 8 cm2 including chip-antenna, which can operate several years on one 3-V coin cell battery and make it suitable for long-term preventive healthcare monitoring.


Expression of calcium-binding proteins in the proliferative zones around the corticostriatal junction of rabbits during pre- and postnatal development.
Herein we asked whether cells expressing calcium-binding proteins around the corticostriatal junction are of pallial or subpallial origin. Brains of rabbit embryos between embryonic day E18 and E28 and postnatal day 0-P22 were immunoreacted with monoclonal antibodies raised against calretinin, calbindin and parvalbumin. At E18-E21, calbindin- and calretinin-immunoreactive cells were seen in distinct proliferative zones in the vicinity of the corticostriatal junction. Whereas calbindin-immunoreactive neurons were in the ventricular zone of the ventral pallium (the medial wall of the lateral ventricular angle), calretinin-immunoreactive cells were, nearby, in the subventricular zone of the subpallium at the lateral edge of the lateral ganglionic eminence. From E25 to P22, both calbindin- and calretinin-immunoreactive cells appeared in the pallial ventricular and subventricular zones around the lateral ventricular angle. Some of these cells resembled migratory neuroblasts. Parvalbumin-immunoreactive cells appeared at P5-P10, albeit they were almost negligible in the proliferative zones around the corticostriatal junction and the lateral ventricular angle. The results suggest that a number of the calbindin-expressing neurons that are generated in mid-gestation and postnatally are of pallial origin. They also indicate that only a few of the late-generated calretinin-immunoreactive cells may have a pallial source. The origin of the parvalbumin-immunoreactive cells was not ascertained in the present study.


trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses.
Multiple sequence alignments are central to many areas of bioinformatics. It has been shown that the removal of poorly aligned regions from an alignment increases the quality of subsequent analyses. Such an alignment trimming phase is complicated in large-scale phylogenetic analyses that deal with thousands of alignments. Here, we present trimAl, a tool for automated alignment trimming, which is especially suited for large-scale phylogenetic analyses. trimAl can consider several parameters, alone or in multiple combinations, for selecting the most reliable positions in the alignment. These include the proportion of sequences with a gap, the level of amino acid similarity and, if several alignments for the same set of sequences are provided, the level of consistency across different alignments. Moreover, trimAl can automatically select the parameters to be used in each specific alignment so that the signal-to-noise ratio is optimized. trimAl has been written in C++, it is portable to all platforms. trimAl is freely available for download (http://trimal.cgenomics.org) and can be used online through the Phylemon web server (http://phylemon2.bioinfo.cipf.es/). Supplementary Material is available at http://trimal.cgenomics.org/publications.


Identifying novel drug indications through automated reasoning.
With the large amount of pharmacological and biological knowledge available in literature, finding novel drug indications for existing drugs using in silico approaches has become increasingly feasible. Typical literature-based approaches generate new hypotheses in the form of protein-protein interactions networks by means of linking concepts based on their cooccurrences within abstracts. However, this kind of approaches tends to generate too many hypotheses, and identifying new drug indications from large networks can be a time-consuming process. In this work, we developed a method that acquires the necessary facts from literature and knowledge bases, and identifies new drug indications through automated reasoning. This is achieved by encoding the molecular effects caused by drug-target interactions and links to various diseases and drug mechanism as domain knowledge in AnsProlog, a declarative language that is useful for automated reasoning, including reasoning with incomplete information. Unlike other literature-based approaches, our approach is more fine-grained, especially in identifying indirect relationships for drug indications. To evaluate the capability of our approach in inferring novel drug indications, we applied our method to 943 drugs from DrugBank and asked if any of these drugs have potential anti-cancer activities based on information on their targets and molecular interaction types alone. A total of 507 drugs were found to have the potential to be used for cancer treatments. Among the potential anti-cancer drugs, 67 out of 81 drugs (a recall of 82.7%) are indeed known cancer drugs. In addition, 144 out of 289 drugs (a recall of 49.8%) are non-cancer drugs that are currently tested in clinical trials for cancer treatments. These results suggest that our method is able to infer drug indications (original or alternative) based on their molecular targets and interactions alone and has the potential to discover novel drug indications for existing drugs.


Promoting Inclusion Via Cross-Group Friendship: The Mediating Role of Change in Trust and Sympathy.
To understand the conditions fostering positive outcomes of inclusive schooling, this two-wave study examined the role of individual change in trust and sympathy for adolescents' cross-group friendships and inclusive attitudes toward students with low academic achievement. Cross-group friendships, intergroup trust, intergroup sympathy, and inclusive attitudes were obtained from surveys completed by 1,122 Swiss adolescents (Mage T1 = 11.54 years, Mage T2 = 12.58 years) from 61 school classes. Results from a parallel latent change score model revealed that the number of cross-group friendships positively related to individual change in trust and sympathy; this growing trust and sympathy in turn predicted adolescents' inclusive attitudes. These findings are discussed regarding theories of intergroup contact and inclusive schooling.


The relationship between anxiety, depression and religious coping strategies and erectile dysfunction in Iranian patients with spinal cord injury.
To assess the role of anxiety, depressive mood and religious coping in erectile function among Iranian patients with spinal cord injury (SCI). Brain and Spinal Cord Injury Repair Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. A sample of N=93 men with SCI participated in this cross-sectional study. Levels of anxiety and depressive mood were assessed using the Hospital Anxiety and Depression Scale. Religious coping strategies were measured using the 14-items Brief Coping Questionnaire. Erectile function was assessed using the International Index of Erectile Function. The joint effect of anxiety, depressive mood and religious coping strategies on erectile function was assessed by performing stepwise multiple linear regression analyses. The mean age of the SCI patients was 37.8 years with a mean post-injury time of 4.6 years. Multivariate regression analyses indicated that age (B=-0.27, 95% CI=-0.47 to -0.07), education (B for higher education=0.63, 95% CI=0.24 to 1.02), the American Spinal Injury Association impairment scale (B for complete impairment=-3.36, 95% CI=-3.82 to -2.89), anxiety (B=-3.56, 95% CI=-5.76 to -1.42), positive religious coping (B=0.30, 95% CI=0.03 to 0.57), negative religious coping (B=-0.56, 95% CI=-0.82 to -0.29) and the duration of injury (B=-0.25, 95% CI=-0.22 to -0.29) were all independent factors influencing erectile function in SCI patients. Overall, the results indicated that SCI patients who use positive religious coping strategies had better erectile function compared with individuals who applied negative religious coping strategies. Furthermore, higher levels of anxiety, greater impairment and longer duration of injury turned out to be risk factors for erectile dysfunction.


[Effect of a phosphatidylcholine-enriched diet on the structural and functional parameters of rat liver microsomes].
The authors studied the influence of the diet enriched with phosphatidylcholine on the structural-functional parameters of microsomes: lipid peroxidation activity, the levels of cytochromes b5 and P-450, microviscosity of the lipid phase of the membrane. In experiments in vivo it was found that phosphatidylcholine per se, not combined with antioxidants, did not show antioxidant properties. Biological effects of lecithin could be explained by its role as a catalyst of the monooxygenase system in the liver, based on the correlation (r = +0.8) between the high level of cytochrome b5 and the degree of eximerization of the fluorescent probe pyrene in the microsomes.


Electrical properties of periglomerular cells in the frog olfactory bulb.
Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) preparation to study the basic electrical properties of these inhibitory interneurons. The cells were intracellularly stained with Lucifer Yellow for precise identification. Under current-clamp conditions PG cells showed rich spontaneous excitatory synaptic activity at rest, usually leading to overshooting, TTX-sensitive action potentials. The passive cable properties of the cell membrane have been carefully characterised. Depolarisation of this neurone under voltage-clamp conditions activated a complex pattern of current flow, that has been dissected into its main components. The currents have been isolated resorting to their different kinetic and pharmacological properties. Four main voltage dependent ionic currents have been isolated, two inward currents, I(Na) and I(Ca), and two outward currents carried by potassium ions, one fast transient, I(A)-type and another similar to the delayed rectifier type. These currents have been characterised kinetically and pharmacologically. The functional implications of their properties are discussed.


Hirsutism in Women.
Hirsutism is the excessive growth of terminal hair in a typical male pattern in a female. It is often a sign of excessive androgen levels. Although many conditions can lead to hirsutism, polycystic ovary syndrome and idiopathic hyperandrogenism account for more than 85% of cases. Less common causes include idiopathic hirsutism, nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, medications, hyperprolactinemia, thyroid disorders, and Cushing syndrome. Women with an abnormal hirsutism score based on the Ferriman-Gallwey scoring system should be evaluated for elevated androgen levels. Women with rapid onset of hirsutism over a few months or signs of virilization are at high risk of having an androgen-secreting tumor. Hirsutism may be treated with pharmacologic agents and/or hair removal. Recommended pharmacologic therapies include combined oral contraceptives, finasteride, spironolactone, and topical eflornithine. Because of the length of the hair growth cycle, therapies should be tried for at least six months before switching treatments. Hair removal methods such as shaving, waxing, and plucking may be effective, but their effects are temporary. Photoepilation and electrolysis are somewhat effective for long-term hair removal but are expensive.


Outdoor walking better? environmental elements of cardiorespiratory fitness training trails.
In metropolitan areas where land resources are scarce, trails are a more suitable environment for cardiorespiratory fitness training for modern people. Previous studies have demonstrated that cardiorespiratory fitness is an important factor in assessing individual health and have focused on individual training performance, but the relationship between environment and cardiorespiratory fitness training participants has rarely been investigated. The purpose of this study was to investigate the demands for outdoor cardiorespiratory fitness training and a favorable trail environment by comparing the differences in exercise intensity and perceptions between outdoor and indoor environments. In this study, information on physical data, psychological feedback, and visual atmosphere was collected from nine participants during each phase of moderate intensity cardiorespiratory fitness training in indoor and outdoor environments. The results revealed that outdoor cardiorespiratory fitness training provided participants with lower training intensity during the active exercise phase and higher heart rate during the stretching phase compared to indoor training. The participants paid more attention to the slope, length, pavement, Spaciousness, and width of the trails and the circuitous route. The change of the visual atmosphere and the scenery for the environmental factors were the important factors to motivate the participants to train. The results of the study could assist participants to understand a favorable cardiorespiratory training environment and design a suitable training program, as well as provide a model for trail planning and design for government.


Characterization of monoamine oxidases in mesenchymal stem cells: role in hydrogen peroxide generation and serotonin-dependent apoptosis.
Early death of grafted bone marrow mesenchymal stem cells (MSCs) represents a major limit to their use in cell therapy of solid organs. It is well known that oxidative stress plays a major role in cell death. We have recently shown that the serotonin-degrading enzyme monoamine oxidase A (MAO-A) generates large amount of hydrogen peroxide (H2O2) responsible for cell apoptosis. Hydrogen peroxide generation requires 5-HT internalization into the cell and its degradation by MAO-A. In the present study, we investigated whether MAO-A is expressed in MSCs and we defined its role in serotonin-dependent MSCs apoptosis. RT-PCR analysis and western blots showed that the serotonin transporter (SERT) and the 2 MAO isoenzymes, A and B, are expressed in MSCs. As shown by enzyme assays using [14C]serotonin or [14C]β-phenylethylamine as selective MAO-A or MAO-B substrates, MAO-A is largely predominant in MSCs. Incubation of MSCs with the MAO substrate tyramine led to a time-dependent generation of H2O2 that was prevented by the MAO inhibitor pargyline. Finally, exposure of the cells to serotonin promoted an increase in MSCs apoptosis prevented by pargyline and the SERT inhibitor imipramine. The pro-apoptotic effect of serotonin was associated to a decrease in the expression of the anti-apoptotic factor Bcl-2. In conclusion, these results show for the first time that the 5-HT-degrading enzyme MAO-A is an important source of H2O2 in MSCs and plays a major role in 5-HT-dependent MSCs apoptosis.


Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.
Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.


RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells.
Tick-borne flaviviruses (TBFs) cause thousands of human cases of encephalitis worldwide each year, with some TBF infections progressing to hemorrhagic fever. TBFs are of medical and veterinary importance and strategies to reduce flavivirus transmission by the tick vector may have significant application. Analyses of the proteome of ISE6 cells derived from the black legged tick, Ixodes scapularis infected with the TBF, Langat virus (LGTV), have provided insights into proteins and cellular processes involved with LGTV infection. RNA interference (RNAi)-induced knockdown of transcripts was used to investigate the role of ten tick proteins in the LGTV infection cycle in ISE6 cells. LGTV-infected cells were separately transfected with dsRNA corresponding to each gene of interest and the effect on LGTV genome replication and release of infectious virus was assessed by RT-qPCR and plaque assays, respectively. RNAi-induced knockdown of transcripts for two enzymes that likely function in amino acid, carbohydrate, lipid, terpenoid/polykeytide and vitamin metabolism, and a transcript for one protein of unknown function were associated with decreased replication of the LGTV genome and release of infectious virus from cells. The knockdown of transcripts for five enzymes predicted to function in metabolism, a protein likely associated with folding, sorting and degradation, and a protein of unknown function was associated with a decrease only in the amount of infectious LGTV released from cells. These data suggest tick proteins potentially associated with metabolism and protein processing may be involved in LGTV infection of ISE6 cells. Our study provides information to begin to elucidate the function of these proteins and identify targets for the development of new interventions aimed at controlling the transmission of TBFs.


Predicting in-hospital mortality in ICU patients with sepsis using gradient boosting decision tree.
Sepsis is a leading cause of mortality in the intensive care unit. Early prediction of sepsis can reduce the overall mortality rate and cost of sepsis treatment. Some studies have predicted mortality and development of sepsis using machine learning models. However, there is a gap between the creation of different machine learning algorithms and their implementation in clinical practice.This study utilized data from the Medical Information Mart for Intensive Care III. We established and compared the gradient boosting decision tree (GBDT), logistic regression (LR), k-nearest neighbor (KNN), random forest (RF), and support vector machine (SVM).A total of 3937 sepsis patients were included, with 34.3% mortality in the Medical Information Mart for Intensive Care III group. In our comparison of 5 machine learning models (GBDT, LR, KNN, RF, and SVM), the GBDT model showed the best performance with the highest area under the receiver operating characteristic curve (0.992), recall (94.8%), accuracy (95.4%), and F1 score (0.933). The RF, SVM, and KNN models showed better performance (area under the receiver operating characteristic curve: 0.980, 0.898, and 0.877, respectively) than the LR (0.876).The GBDT model showed better performance than other machine learning models (LR, KNN, RF, and SVM) in predicting the mortality of patients with sepsis in the intensive care unit. This could be used to develop a clinical decision support system in the future.


A new look at radicals in cigarette smoke.
Radicals in cigarette smoke have been proposed to contribute to the harm caused by cigarette smoking. For the first time, using HPLC and high-resolution mass spectrometry analysis of stable radical adducts, we have identified specific radical species in cigarette smoke: 7 acyl and 11 alkylaminocarbonyl radicals. Their combined abundance measured in fresh whole smoke from a single 2R4F cigarette is approximately 225 nmol (1.4 x 10(17) radicals). The fiberglass Cambridge filter pad conventionally employed to separate the gas phase from mainstream smoke was found to reduce the apparent yield of these radicals, introducing artifacts of measurement. The long-accepted steady-state mechanism for the formation of carbon-centered radicals in cigarette smoke involving NO2 chemistry cannot account for these newly identified radicals, and it does not in general appear to be a major source of carbon-centered radicals in fresh mainstream cigarette smoke. Consequently, we suggest that the precise nature of radicals in cigarette smoke warrants reexamination.


Cross-sectional study on medicinal products without commercial interest (MPWCI) in the Spanish market.
To confirm that there is a defined group of products to be protected in the Spanish therapeutic arsenal known as 'medicinal products without commercial interest' (MPWCI) and propose the adoption of legal measures aimed at avoiding, or reducing, the lack of supply of said products. A cross-sectional study of proposed MPWCI based on a survey. The Spanish Agency of Medicines and Medical Devices (AEMPS) was asked for a list of presentations of medicines in order to identify those whose lack could have an impact on welfare. A search on the AEMPS website and a survey conducted among 44 companies belonging to Farmaindustria has allowed for the development of a proposal list of presentations that should continue to be marketed in Spain. Products proposed as MPWCI are old (50% of them have an authorisation of more than 50 years) and are developed by active substances of chemical origin, parenterally administered much more frequently than the rest of the general market (44%vs6.6%, respectively). Unlike oral forms, injectable forms require adequate manufacturing facilities to guarantee the quality and sterility of the product, which naturally increases the cost of the product whose price is low or obsolete. The company experts have not valued the current price revisions as a sufficient enough mechanism to change the consideration of these medicines with respect to the interest on the part of some Marketing Authorisation Holders to maintain their commercialisation. As shown in the results, an upward revision of prices is necessary to contribute to the permanence of these presentations in the market, although some experts do not consider the current price revisions satisfactory enough to maintain these presentations in the market. Therefore, a specific regulation seems necessary to ensure the continuity on the market of these proposed products.


Carbon Fiducial Markers for Tumor Localization in Stereotactic Irradiation of Uveal Melanoma.
The aim of this study was to demonstrate the role of carbon fiducial markers (fiducials) for guiding radiotherapy in the management of uveal melanoma (UM). This is a retrospective interventional case series at a single-center ocular oncology practice. The medical records were reviewed retrospectively for all patients with UM treated with stereotactic radiosurgery using episcleral fiducials. We report our short-term experience with surgical placement of fiducials, UM localization, treatment outcomes, and optimization approaches. We evaluated 11 cases of UM (mean age: 65 years; 64% female). The placed fiducials were numbered from 2 to 4, each secured to the sclera with a surgical microscope or surgical loupes and either 5-0 or 8-0 nylon sutures at 50% scleral depth and 3 mm beyond the tumor margin. Over a median follow-up of 11 months (range: 4.2-43.2 months), no recurrences of intraocular UM were observed. One case of enucleation after stereotactic radiosurgery developed because of radiation-related surface irritation, ocular dryness, and secondary keratopathy. Two patients (18%) with 5-0 nylon sutures required fiducial removal because of suture exposure, successfully accomplished in an outpatient setting. Fiducials represent a viable alternative to tantalum rings for guiding stereotactic radiotherapy to manage UM and provide additional definition of the tumor border with linear orientation that helps optimize targeted radiation delivery. Fiducial placement with a 3-mm margin from the visible tumor border should not result in clinically important radiation dose attenuation at the tumor margins. Anteriorly placed fiducials may cause discomfort, yet they are easily removed in the outpatient setting.


Synovial oedema is a frequent complication in arthroscopic procedures performed with normal saline as the irrigating fluid. The authors have studied the effect of saline solution, Ringer lactate, 5% Dextran and 10% Dextran in normal saline on 12 specimens of human synovial membrane. They found that 10% Dextran in normal saline decreases the water content of the synovium without causing damage, and recommend this solution for procedures lasting longer than 30 minutes.


Mothers Who Use Drugs: Closing the Gaps in Harm Reduction Response Amidst the Dual Epidemics of Overdose and Violence in a Canadian Urban Setting.
Objectives. To identify key gaps in overdose prevention interventions for mothers who use drugs and the paradoxical impact of institutional practices that can increase overdose risk in the context of punitive drug policies and a toxic drug supply. Methods. Semistructured interviews were conducted with 40 women accessing 2 women-only, low-barrier supervised consumption sites in Greater Vancouver, British Columbia, Canada, between 2017 and 2019. Our analysis drew on intersectional understandings of structural, everyday, and symbolic violence. Results. Participants' substance use and overdose risk (e.g., injecting alone) was shaped by fear of institutional and partner scrutiny and loss (or feared loss) of child custody or reunification. Findings indicate that punitive policies and institutional practices that frame women who use drugs as unfit parents continue to negatively shape the lives of women, most significantly among Indigenous participants. Conclusions. Nonpunitive policies, including access to safe, nontoxic drug supplies, are critical first steps to decreasing women's overdose risk alongside gender-specific and culturally informed harm-reduction responses, including community-based, peer-led initiatives to maintain parent-child relationships. (Am J Public Health. 2022;112(S2):S191-S198. https://doi.org/10.2105/AJPH.2022.306776).


MCAK Inhibitors Induce Aneuploidy in Triple Negative Breast Cancer Models.
Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC 50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target. Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype with few treatment options available. Standard of care for TNBC involves the use of taxanes, which are initially effective, but dose limiting toxicities are common, and patients often relapse with resistant tumors. Specific drugs that produce taxane-like effects may be able to improve patient quality of life and prognosis. In this study we identify three novel inhibitors of the Kinesin-13 MCAK. MCAK inhibition induces aneuploidy; similar to cells treated with taxanes. We demonstrate that MCAK is upregulated in TNBC and is associated with poorer prognoses. These MCAK inhibitors reduce the clonogenic survival of TNBC cells, and the most potent of the three inhibitors, C4, sensitizes TNBC cells to taxanes, similar to the effects of MCAK knockdown. This work will expand the field of precision medicine to include aneuploidy-inducing drugs that have the potential to improve patient outcomes.


[Trajan's decision: a neurological point of view].
The emperor of Rome, Marco Ulpio Trajano, ruled the Roman Empire from 98 to 117 AD, being the first emperor of non-Italian origin and the man who took the Empire to its maximum geographical extent. Trajan's death is surrounded by mystery, given Adriano's controversial adoption as his successor just before his death, as well as rumors of poisoning by his wife, Plotina. In addition, despite the limited literary sources available, episodes of «paralysis», «stroke», «dropsy», diarrhea and nonspecific episodes of «illness» have been documented, related to the worsening of his health the months before his death. His special love of wine and life habits related to the personality of the emperor, could be associated with his delicate state of health during the last year of his government, although it is not possible to rule out other pathological processes with neurological involvement associated with the last years of life of the optimus princeps, which could interfere with his last decisions as ruler. In this article, the historical sources available are reviewed in order to analyze, from the neurological point of view, the last moments of the emperor with which Rome reached its maximum military splendor.


Elastic registration for retinal images based on reconstructed vascular trees.
The vascular tree of the retina is likely the most representative and stable feature for eye fundus images in registration. Based on the reconstructed vascular tree, we propose an elastic matching algorithm to register pairs of fundus images. The identified vessels are thinned and approximated using short line segments of equal length that results a set of elements. The set of elements corresponding to one vascular tree are elastically deformed to optimally match the set of elements of another vascular tree, with the guide of an energy function to finally establish pixel relationship between both vascular trees. The mapped positions of pixels in the transformed retinal image are computed to be the sum of their original locations and corresponding displacement vectors. For the purpose of performance comparison, a weak affine model based fast chamfer matching technique is proposed and implemented. Experiment results validated the effectiveness of the elastic matching algorithm and its advantage over the weak affine model for registration of retinal fundus images.


Transforming growth factor-beta inhibits IL-4 and IFN-gamma production by stimulated human T cells.
The present study investigates the effect of transforming growth factor (TGF)-beta on the production of IL-4 and IFN-gamma by the leukemia Th0 type cell line HUT78, by freshly isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-gamma, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-beta 1. TGF-beta 1 also reduced the accumulation of IL-4 and IFN-gamma specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-gamma production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-alpha or granulocyte macrophage colony stimulating factor had no effect. Because IL-2 is an important helper cytokine for the production of IL-4 and IFN-gamma, we investigated whether signal transduction through the IL-2 receptor is impaired by TGF-beta 1. We found that tyrosine phosphorylation in response to IL-2 in HUT78 cells was strongly inhibited by a short preincubation with TGF-beta 1. Evidence for an antagonistic role for TGF-beta 1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-beta 1 mediated inhibition of IL-4 and IFN-gamma production. Similar to its effect on HUT78 cells, TGF-beta 1 also inhibited IL-4 and IFN-gamma production by freshly isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-gamma are both negatively controlled by TGF-beta under conditions where IL-2 production is unaffected by a mechanism which partially involves an inhibition of IL-2/IL-2R signal transduction. These data identify TGF-beta and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-gamma production.


Measuring Implementation of Health Promoting School (HPS) Programs: Development and Psychometric Evaluation of the HPS Implementation Questionnaire.
Implementation of Health Promoting School (HPS) programs can be challenging due to the dynamic school context. Navigating between program fidelity and adaptation, as well as integrating the program, is essential for successful implementation, and consequently, for program effects. As part of an evaluation study in the Netherlands, this study aimed to develop a measurement instrument that differentiates schools according to fidelity, adaptation, and integration of HPS implementation. This study presents the development and psychometric evaluation of the 28-item HPS Implementation Questionnaire, covering 7 dimensions: adherence, dose, participant responsiveness, quality of delivery, program differentiation, adaptation, and integration. The questionnaire, to be filled out by school employees, was developed for primary, secondary, secondary vocational, and special needs education, in close collaboration with experts (n = 54) in school health promotion. Semi-structured interviews aimed at dimension clarification resulted in a list of 58 items. Items were revised, combined, and/or removed based on quantitative and qualitative feedback by the evaluation study's Community of Practice, 2-round expert consultation, and pre-tests. Psychometric evaluation (n = 535 schools), consisting of calculating Cronbach's α and confirmatory factor analysis (CFA), confirmed internal consistency (α > .72) and the 7-dimension framework. The brief yet comprehensive HPS Implementation Questionnaire offers possibilities for research into HPS implementation in various educational sectors and contexts, as well as self-monitoring by individual schools. This study provides first evidence for internal consistency and validity of the questionnaire.


Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet.
The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin and leptin are altered with adiposity and exert antagonistic effects on cancer cell proliferation. We set out to determine whether altering adiposity in vivo via high fat diet (HFD) feeding changed the tumor growth supporting nature of adipose tissue and whether voluntary physical activity (PA) could ameliorate these HFD-dependent effects. We show that conditioned media (CM) created from the adipose tissue of HFD fed animals caused an increase in the proliferation of MCF7 cells compared with cells exposed to CM prepared from the adipose of lean chow diet fed counterparts. This increased proliferation was driven within the MCF7 cells by an HFD-dependent antagonism between AMP-activated protein kinase (AMPK) and protein kinase B (Akt) signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of adiponectin receptor 1 (AdipoR1). PA can ameliorate these proliferative effects of HFD-CM on MCF7 cells, increasing p27(T198) by AMPK, reducing pAkt(T308), and increasing AdipoR1, resulting in cell cycle withdrawal in a manner that depends on the PA intensity. High physical activity (>3 km/day) completely abolished the effects of HFD feeding. In addition, AdipoR1 overexpression mimics the effects of exercise, abolishing the proliferative effects of the HFD-CM on MCF7 cells and further enhancing the antiproliferative effects of PA on the HFD-CM. Thus voluntary PA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients.


Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway.
Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC). To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo. The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis. TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP. TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.


Altered behavior and digestive outcomes in adult male rats primed with minimal colon pain as neonates.
Neonatal colon irritation (CI; pain or inflammation) given for 2 weeks prior to postnatal day 22 (PND22), causes long-lasting functional disorders in rats that can be seen 6 months after the initial insult. This study looked at the effect of varying the frequency and duration of neonatal CI on the rate of growth, digestive outcomes, exploratory activity, and colon and skin sensitivity in adult rats. Male Sprague-Dawley rats were given CI using repeated colorectal distension (CRD) at different time intervals and for varying durations starting at PND 8, 10 or 14. Control rats were handled by the investigator without any intracolonic insertion. Further experiments were done on adult rats. Digestive outcomes (food and water consumption, fecal and urinary outputs) were measured using metabolic cages. Exploratory behavior was measured using digital video tracking in an open field. Cutaneous sensitivity was assessed by measuring the responses to mechanical and heat stimuli applied to the shaved abdomen or hind paws. Visceral sensitivity was measured by recording electromyographic responses, under light isoflurane anesthesia, from the external oblique muscles in response to CRD. No significant weight differences were observed between CI and control rats. Exploratory behavior was reduced in rats with neonatal CI compared to control. Digestive outputs and somatic and visceral sensitivity changed between different treatment groups with earlier and more frequent insults yielding a higher deviation from normal. The diversity of behavioral and digestive symptoms in these rats parallels the diversity of symptoms in patients with functional gastrointestinal disorders and is consistent with global plastic changes affecting more than one system in the organism.


[Effect of tobacco extracts on human gingival fibroblasts' proliferation and fibronectin expression].
To investigate the influence and mechanism of smokeless tobacco (ST) extracts on proliferation and fibronectin expression of human gingival fibroblasts (HGFs) adhered to titanium plates. The cultured primary HGFs with ST of different concentrations for a period of 2h and 2, 4, 6, 8 d was separately conducted; the cell proliferation and the adhesion was assayed using CCK-8 method; enzyme-linked immunosorbent assay was used to determine the content of supernatant fibronectin (FN) at different times. The data was analyzed with SPSS 19.0 software package. With the increase of ST concentration, the cell adherence rate decreased accordingly. With ST concentration of 5.0 g/L and 10 g/L, the adhesion rate was (34.316±7.725)% and (25.478±10.651)%, respectively, which was significantly lower than that of the control group (100%) (P<0.01). Cell proliferation on the titanium plate started at 2 d and 4 d and the cell abundance of the control group was significantly greater than that of ST group (P<0.05) with concentrations of 2.5, 5.0, 10 g/L; The cell abundance of the control group was significantly greater than that of ST group (P<0.05) with concentrations of 0.625-10 g/L on the 6th and 8th day. In 0.625, 1.25, 2.5 g/L ST group, FN concentration was (69.352±31.640), (23.595±8.625) and (7.292±2.865) ng/mL, respectively, which was significantly lower than that of the control group (142.188 ± 28.126) ng/mL (P<0.05). ST can significantly inhibit the proliferation and adhesion of HGFs on pure titanium surface, and the mechanism may be related to decrease of FN secreted by HGFs.


Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation.
Whether or not the muscle bundle within the ligament of Marshall (LOM) can serve as the origin of focal atrial fibrillation (AF) is unknown. A total of 28 consecutive patients with paroxysmal AF underwent balloon-occlusion coronary sinus angiograms to identify the vein of Marshall (VOM). Attempts were then made to advance a 1.5-French electrophysiological catheter into the VOM via the coronary sinus orifice. In 17 of the 28 patients (10 of 17 were men aged 38+/-15 years), cannulation was successful. Double potentials were registered in 8 of these 17 patients. The first potential corresponded with local left atrial activation. The second potential was shorter and narrower than the first. The sequence of activation in the second potential in the VOM was proximal to distal. In 6 patients with direct VOM recordings, we documented that the origin of AF was in the muscle bundle within the LOM. Radiofrequency catheter ablation aimed at the insertion site of the VOM successfully terminated AF in 4 of these 6 patients. (1) It is possible to cannulate and to record electrical potentials from the VOM. (2) The characteristics of the double potentials within the VOM suggest that the second potential is from the muscle bundle (Marshall bundle) within the LOM. (3) The Marshall bundle may be the origin of focal AF in some patients.


[Determining cardiovascular risk in patients with rheumatoid arthritis: waiting for trial outcomes is not recommended].
Cardiovascular risk management is clearly indicated in patients with rheumatoid arthritis (RA) today because this risk is comparable to patients with diabetes. Although formal evidence of cardiovascular endpoint trials with statins and/or antihypertensives is lacking in patients with RA, there are no indications that these drugs will have limited effect. In contrast, there is accumulating evidence as to the efficacy of the use of these drugs in RA that is at least comparable to their effects in the general population. All patients with RA should therefore receive cardiovascular risk-management therapy aimed at powerful suppression of the chronic inflammatory process as well as treatment with statins and/or antihypertensives, if indicated. Obviously, monitoring in the clinical setting is necessary to document if such therapy does indeed reduce cardiovascular disease in patients with RA.


Predictors of GP service use: a community survey of an elderly Australian sample.
As part of a study of an elderly community-dwelling Australian population, predictors of general practitioner (GP) service use were identified. The sample of 897 persons, aged 70 years or older and living in Canberra and Queanbeyan, were interviewed about their health and well-being. Data on the number of GP visits in the following 12-month period were obtained from the Health Insurance Commission. There were important gender differences in the prediction of both contact and volume of service use. Need variables (physical health in men, and disability and anxiety in women) were the most important predictors. Men who were older or who had lower occupational status used more medical services, as did women with less education or higher levels of extraversion. Men with lower social support were less likely to contact a GP, but social support was not related to volume of service use for either men or women. Since at most 21% of the variance in the volume of GP service use could be explained, despite the wide range of predictors considered and the different statistical approaches adopted, better measures of service use and predictors need to be developed.


Early Classification of Time Series by Simultaneously Optimizing the Accuracy and Earliness.
The problem of early classification of time series appears naturally in contexts where the data, of temporal nature, are collected over time, and early class predictions are interesting or even required. The objective is to classify the incoming sequence as soon as possible, while maintaining suitable levels of accuracy in the predictions. Thus, we can say that the problem of early classification consists of optimizing two objectives simultaneously: accuracy and earliness. In this context, we present a method for early classification based on combining a set of probabilistic classifiers together with a stopping rule (SR). This SR will act as a trigger and will tell us when to output a prediction or when to wait for more data, and its main novelty lies in the fact that it is built by explicitly optimizing a cost function based on accuracy and earliness. We have selected a large set of benchmark data sets and four other state-of-the-art early classification methods, and we have evaluated and compared our framework obtaining superior results in terms of both earliness and accuracy.