Effects of Dietary Fatty Acids in Pancreatic Beta Cell Metabolism, Implications in Homeostasis.
Fatty acids are involved in several metabolic processes, including the development of metabolic and cardiovascular diseases. In recent years a disease that has received escalated interest is type 2 diabetes (T2D). Many contributing factors including a high-caloric diet rich in dietary saturated fats have been broadly characterized as triggers of T2D. Insulin resistance resulting from a high saturated fat diet leads to alterations in lipid cellular intake and accumulation which generate lipotoxic conditions, a key phenomenon in the metabolism of β-cells. Alternatively, unsaturated fatty acids have been described to show opposite effects in pancreatic β-cells. The purpose of this work is to perform a critical analysis of the complex role of saturated and unsaturated fatty acids in β-cell metabolism. We discuss the diverse effects main dietary fatty acids have upon pancreatic β-cell metabolism as a key factor to maintain homeostasis by focusing in the cellular and molecular mechanisms involved in the development and progression of T2D. For instance, modifications in protein homeostasis as well as the intracellular management of lipid metabolism which are associated with inflammatory pathways. These conditions initiate critical metabolic rearrangements, that in turn have repercussions on insulin β-cell metabolism. This review allows an integral and broad understanding of different functions of fatty acids inside β-cells, being important metabolites for novel therapeutic targets in T2D treatment.


Zinc dependency as a cause of chronic diarrhea in variant acrodermatitis enteropathica.
Two siblings with chronic diarrhea, growth failure, mood changes, and occasional cheilosis responded repeatedly to treatment with either pharmacologic doses of zinc or pancreatin (Viokase), and their symptoms were exacerbated after withdrawal of therapy. Pancreatic exocrine deficiency was ruled out in both cases. Proteolytic activity was 20% of normal in one infant tested. Plasma zinc concentration was normal. Plasma picolinic acid concentration was low in these two patients and in one previously reported patient (mean 3.6, normal 12.4 +/- 3.3 mumoles/liter). This is a characteristic shared with acrodermatitis enteropathica. The response to Viokase may be due to its content of picolinic acid and/or zinc or the correction of a deficiency of carboxypeptidase, a zinc-requiring enzyme.


The impact of hemodialysis schedules on the day of the week of hospitalization for cardiovascular and infectious diseases, over a period of 20 years.
There have been no studies as yet that have evaluated how hemodialysis (HD) schedules affect the day of the week of hospitalization for cardiovascular diseases (CVDs) and infectious diseases (IDs), over a period of time. Herein, we performed a retrospective observational cohort study (1995-2014) evaluating 11,111 hospitalizations in 1,953 patients with end-stage renal disease, receiving HD 3 times a week (following either a Monday-Wednesday-Friday [MWF] schedule or a Tuesday-Thursday-Saturday [TTS] schedule) or receiving frequent HD (FHD) at least 4 times a week. Overall, hospitalization rates for CVDs and IDs were the highest on Monday in the MWF schedule and Tuesday in the TTS schedule compared to the average rates for all the days of the week. When generalized estimating equations (GEEs) were used in conjunction with robust variance estimators of each type of CVD, the risk for pulmonary edema was found to be significantly higher on Sunday and Monday in the MWF schedule and Monday and Tuesday in the TTS schedule. For both cerebrovascular and ischemic heart disease, the risks were significantly higher on Tuesday in the MWF schedule and Wednesday in the TTS schedule. Moreover, there were significant differences in the day of the week risks among the various CVD types. On trend analysis, the overall hospitalization rate for CVDs on the first HD day did not decrease (P = 0.2); however, the hospitalization rate for IDs on the first HD day significantly decreased (P = 0.02) over a span of 20 years. When GEEs were used in the case of FHD patients with severe heart failure, the hospitalization rate on the first HD day (Monday) significantly decreased after FHD initiation (P = 0.04). It was found that HD schedules affected the day of the week of hospitalization for CVDs. FHD may lower the day of the week risk.


Unsupervised learning of disentangled representations in deep restricted kernel machines with orthogonality constraints.
We introduce Constr-DRKM, a deep kernel method for the unsupervised learning of disentangled data representations. We propose augmenting the original deep restricted kernel machine formulation for kernel PCA by orthogonality constraints on the latent variables to promote disentanglement and to make it possible to carry out optimization without first defining a stabilized objective. After discussing a number of algorithms for end-to-end training, we quantitatively evaluate the proposed method's effectiveness in disentangled feature learning. We demonstrate on four benchmark datasets that this approach performs similarly overall to β-VAE on several disentanglement metrics when few training points are available while being less sensitive to randomness and hyperparameter selection than β-VAE. We also present a deterministic initialization of Constr-DRKM's training algorithm that significantly improves the reproducibility of the results. Finally, we empirically evaluate and discuss the role of the number of layers in the proposed methodology, examining the influence of each principal component in every layer and showing that components in lower layers act as local feature detectors capturing the broad trends of the data distribution, while components in deeper layers use the representation learned by previous layers and more accurately reproduce higher-level features.


Reversible myocardial dysfunction: basics and evaluation.
Large areas of non-functional but viable myocardium with reversible dysfunction are commonly seen in patients with acute myocardial infarction. Both reperfusion of acutely ischemic myocardium and chronic myocardial ischemia may produce a reversible forms of ventricular dysfunction. The two main conditions that lead to reversible myocardial dysfunction are stunned myocardium and hibernating myocardium. Myocardial stunning represents post-ischemic myocardial dysfunction that persists despite restoration of normal flow, with gradual return of contractile function. Hibernating myocardium is a state of persistently impaired myocardial function at rest due to reduced coronary blood flow owing to residual stenosis that can be restored toward normal by revascularization. The success of the revascularization procedures depends on the presence of amount of dysfunctional but viable myocardium. The basics and evaluation of reversible myocardial dysfunction are reviewed.


[Evidence of Physical Training Programs for Fall Prevention in Seniors].
Evidence of Physical Training Programs for Fall Prevention in Seniors Abstract. It has been shown that physical exercise reduced fall risk by 23-42% in community-dwelling adults aged 65+. This is particularly true for physical exercises with functional, balance and strength components. Growing evidence shows that functional training is particularly effective in reducing fall risk. Functional training is composed by exercises which reflect activities of daily life, supported by weights and other aids.


Mobile phone use among e-cyclists at red traffic lights: An observation study in a city of China.
The observation study sought to explore the influencing factors associated with mobile phone use when e-cyclists were waiting for red lights at intersections, which provided a theoretical foundation for solving the potential traffic threat and developing management plans for e-cyclists. Data regarding e-cyclists were collected through camera conducted at the entrance of multiple intersections in Zhenjiang, China in July 2020. The data was reviewed by playing frame by frame. A statistical analysis was performed with the statistical package SPSS software. After conducting univariate logistic analysis on study variables, the multivariate analysis was adopted based on the binary logit regression model. Among the 1166 e-cyclists observed, 15.01% (n = 175) e-cyclists had operated their mobile phones while waiting for red lights. Young e-cyclists, delivery cyclists were more likely to be involved with mobile phone use. Furthermore, mobile phone use was more observed at intersections in suburban areas and with long waiting time. E-cyclists, who was carrying a child, rarely used mobile phone. All intersections during off-peak times showed an increase in mobile phone use. The results also show that neither e-cyclists themselves nor traffic managers are aware of the risks of mobile phone use and the impact on traffic safety while waiting for a red light. The findings of this research revealed the factors influencing mobile phone use of e-cyclists while waiting for a red light, and indicated that education and behavioral intervention need to be strengthened to improve riding safety at intersections. These results will be helpful in developing programs of electric bicycle management.


Dislocation of the elbow: a retrospective multicentre study of 86 patients.
The objective of this retrospective multicentre cohort study was to prospectively assess the long-term functional outcomes of simple and complex elbow dislocations.We analysed the hospital and outpatient records of 86 patients between 01.03.1999 and 25.02.2009 with an elbow dislocation. After a mean follow-up of 3.3 years, all patients were re-examined at the outpatient clinic for measurement of different outcomes.The mean range of motion was ROM 135.5 degrees . The Mayo elbow performance index (MEPI) scored an average of 91.9 (87.5% of the patients were rated excellent or good). The average Quick disabilities of the arm, shoulder and hand (Quick- DASH) score was 9.7, the sports/music score 11.5 and work score 6.1. The Oxford function score was 75.7, Oxford pain score 75.2 and Oxford social-psychological score 73.9.Elbow dislocation is a mild disease and generally, the outcome is excellent. Functional results might improve with early active movements.


Cost-effectiveness of pembrolizumab versus brentuximab vedotin for patients with relapsed or refractory classical Hodgkin's lymphoma: a United States payer perspective.
Patients with classical Hodgkin's lymphoma (cHL) who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) have limited treatment options and generally a poor prognosis. Pembrolizumab was recently approved in the US for the treatment of such patients having demonstrated clinical benefit and tolerability in relapsed/refractory cHL; however, the cost-effectiveness of pembrolizumab in this population is currently unknown. A three-state Markov model (progression-free [PF], progressed disease, and death) was developed to assess the cost-effectiveness of pembrolizumab (200 mg) vs brentuximab vedotin (BV; 1.8 mg/kg) in patients with relapsed/refractory cHL after ASCT who have not received BV post-ASCT over a 20-year time horizon from a US payer perspective. PF survival was modeled using a naïve indirect treatment comparison of data from KEYNOTE-087 and the SG035-003 trial. Post-progression survival was modeled using data from published literature. Costs (drug acquisition and administration, disease management, subsequent treatment, and adverse events) and outcomes were discounted at an annual rate of 3.0%. Uncertainty surrounding cost-effectiveness was assessed via probabilistic, deterministic, and scenario analyses. In the base case, pembrolizumab was predicted to yield an additional 0.574 life-years (LYs) and 0.500 quality-adjusted life-years (QALYs) vs BV and cost savings of $63,278. Drug acquisition costs were the biggest driver of incremental costs between strategies. Pembrolizumab had a 99.6% probability of being cost-effective compared with BV at a willingness-to-pay threshold of $20,000/QALY and dominated BV in all scenarios tested. The analysis was subject to potential bias due to the use of a naïve indirect treatment comparison and, given the current immaturity of OS in KEYNOTE-087, PPS was assumed equivalent across both treatments. Pembrolizumab is a cost-effective alternative to BV for patients with relapsed/refractory cHL after ASCT.


Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors.
Human immunodeficiency virus-1 (HIV-1) is the most frequent cause of dementia in adults under 40. We sought to use gene delivery to protect from HIV-1-related neuron loss. Because HIV-1 envelope (Env) gp120 elicits oxidant stress and apoptosis in cultured neurons, we established reproducible parameters of Env-mediated neurotoxicity in vivo, then tested neuroprotection using gene delivery of antioxidant enzymes. We injected 100-500 ng mul(-1)gp120 stereotaxically into rat caudate-putamens (CP) and assayed brains for apoptosis by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) 6-h to 14-day post-injection. Peak apoptosis occurred 1 day after injection of 250 and 500 ng microl(-1)gp120. TUNEL-positive cells mostly expressed neuronal markers (NeuroTrace), although some expressed CD68 and so were most likely microglial cells. Finally, we compared neuroprotection from gp120-induced apoptosis provided by localized and generalized intra-central nervous system (CNS) gene delivery. Recombinant SV40 vectors carrying Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) were injected into the CP, where gp120 was administered 4-24 weeks later. Alternatively, we inoculated the vector into the lateral ventricle (LV), with or without prior intraperitoneal (i.p.) administration of mannitol. Intracerebral injection of SV(SOD1) or SV(GPx1) significantly protected neurons from gp120-induced apoptosis throughout the 24-week study. Intraventricular vector administration protected from gp120 neurotoxicity comparably, particularly if preceded by mannitol i.p. Thus, HIV-1 gp120 is neurotoxic in vivo, and intracerebral or intra-ventricular administration of rSV40 vectors carrying antioxidant enzymes is neuroprotective. These findings suggest the potential utility of both localized and widespread gene delivery in treating neuroAIDS and other CNS diseases characterized by excessive oxidative stress.


Gender Differences of Arterial Stiffness and Arterial Age in Smokers.
The present study aimed to find gender differences for arterial stiffness and arterial aging in smokers. A total of 147 smokers (71 male and 76 female, matched for age) were explored using an Arteriograph in a cross-sectional survey. Pulse wave velocity (PWV), arterial age (AA), brachial and aortic augmentation index (AixBrach, AixAo), and blood pressure variables were assessed. Data about smoking intensity, such as the number of cigarettes smoked daily, smoking period, and smoking pack years (SPY) were used. No significant differences were found for PWV, AA, AixBrach and AixAo. Significant correlations were found between SPY and PWV, augmentation indices, and AA, respectively. The cut-off values for SPY were higher for an increased arterial stiffness in male compared to female smokers (18.5 and 7.5 pack year, respectively). SPY is significantly associated with an increased arterial stiffness in smokers regardless of gender, and with an increased SBPAo only in female smokers. The results of our study indicate gender differences for arterial stiffness and arterial age in smokers.


The possible mechanism of rhapontigenin influencing antifungal activity on Candida albicans.
Rhapontigenin, an aglycone of rhapontin, was produced by biotransformation and we investigated its antifungal activity against Candida albicans, one of the most important opportunistic fungal pathogens. Rhapontigenin is found to have, in vitro, inhibitory activity with a minimal inhibitory concentration (MIC) value against all test isolates of 128-256 μg/ml. We detected increased reactive oxygen species (ROS) levels in yeast cultures treated with rhapontigenin at the MIC. Rhapontigenin inhibited DNA, RNA, and protein synthesis, especially RNA synthesis, and induced morphological changes and apoptosis of C. albicans. The apoptotic effect of rhapontigenin on C. albicans at subinhibitory concentrations was higher in the stationary growth phase than in the exponential phase, while the opposite results were noted with amphotericin B. The mechanism of antifungal activity of rhapontigenin may be associated with the generation of ROS that might induce apoptosis and it may also involve the inhibition of ergosterol biosynthesis.


Evaluation of culture media for Paenibacillus larvae applied to studies of antimicrobial activity.
This study was conducted to compare different liquid culture media for Paenibacillus larvae growth in order to find the best one to be used in studies on activity of antimicrobial substances, such as essential oils. P. larvae presented poor growth in usual broths such as Mueller-Hinton, commonly employed in antimicrobial activity assays. Growth in liquid media was evaluated using Paenibacillus larvae strains isolated from hives located in different geographical zones. The MYT medium (Mueller-Hinton broth, yeast extract and thiamine) was selected out of the eight liquid media analyzed, as it proved to be the most adequate due to its higher absorbance at 620 nm. The following mean values were obtained from the four P. larvae strains: 0.227 +/- 0.016 for the Cobo strain, 0.279 +/- 0.015 for La Plata strain, 0.758 +/- 0.020 for Mechongué strain and 0.244 +/- 0.0079 for Sierra de los Padres strain, respectively.


Influence of Cone-beam Computed Tomography on Endodontic Retreatment Strategies among General Dental Practitioners and Endodontists.
Treatment options for endodontic failure include nonsurgical or surgical endodontic retreatment, intentional replantation, and extraction with or without replacement of the tooth. The aim of the present study was to determine the impact of cone-beam computed tomographic (CBCT) imaging on clinical decision making among general dental practitioners and endodontists after failed root canal treatment. A second objective was to assess the self-reported level of difficulty in making a treatment choice before and after viewing a preoperative CBCT scan. Eight patients with endodontically treated teeth diagnosed as symptomatic apical periodontitis, acute apical abscess, or chronic apical abscess were selected. In the first session, the examiners were given the details of each case, including any relevant radiographs, and were asked to choose 1 of the proposed treatment alternatives and assess the difficulty of making a decision. One month later, the examiners reviewed randomly the same 8 cases with the additional information from the CBCT data. The examiners altered their treatment plan after viewing the CBCT scan in 49.8% of the cases. A significant difference in the treatment plan between the 2 imaging modalities was recorded for endodontists and general practitioners (P < .05). After CBCT evaluation, neither group altered their self-reported level of difficulty when choosing a treatment plan (P = .0524). The extraction option rose significantly to 20% after viewing the CBCT scan (P < .05). CBCT imaging directly influences endodontic retreatment strategies among general dental practitioners and endodontists.


Extremely low-frequency magnetic fields effects on the snail single neurons.
The aim of present work is to explore the influence of extremely low-frequency electromagnetic fields (8.34 and 217 Hz) utilized in cell phones on habituation of the mollusk single neuron to intracellular stimuli. The isolated nervous system of the mollusk Helix Pomatia was used in the experiments. Helmholtz coils were used to expose brain ganglia to the low-frequency electromagnetic fields. Peak values of the extremely low-frequency fields were between 1 and 6 mT. Neuron electrophysiology was investigated using a standard microelectrode technique. Exposure of the neuron to the low-frequency electromagnetic fields caused dehabituation to intracellular stimulus. The effect was proportional to the magnetic induction peak value. The observed dehabituation occurs by degradation of the signal to noise ratio and by alteration of the neuron's normal function.


Metabolite Transporter PEG344 Is Required for Full Virulence of Hypervirulent Klebsiella pneumoniae Strain hvKP1 after Pulmonary but Not Subcutaneous Challenge.
Hypervirulent Klebsiella pneumoniae (hvKP) is an emerging pathotype that is capable of causing tissue-invasive and organ- and life-threatening infections in healthy individuals from the community. Knowledge on the virulence factors specific to hvKP is limited. In this report, we describe a new factor (PEG344) that increases the virulence of hvKP strain hvKP1. peg-344 is present on the hvKP1 virulence plasmid, is broadly prevalent among hvKP strains, and has increased RNA abundance when grown in human ascites. An isogenic derivative of hvKP1 (hvKP1Δpeg-344) was constructed and compared with its wild-type parent strain in in vitro, ex vivo, and infection model studies. Both survival and competition experiments with outbred CD1 mice demonstrated that PEG344 was required for full virulence after pulmonary challenge but, interestingly, not after subcutaneous challenge. In silico analysis suggested that PEG344 serves as an inner membrane transporter. Compared to hvKP1, a small but significant decrease in the growth/survival of hvKP1Δpeg-344 was observed in human ascites, but resistance to the bactericidal activity of complement was similar. These data suggested that PEG344 may transport an unidentified growth factor present in ascites. The data presented are important since they expand our limited knowledge base on virulence factors unique to hvKP, which is needed to lay the groundwork for translational approaches to prevent or treat these devastating infections.


Detection of a resistance gradient to Passion fruit woodiness virus and selection of 'yellow' passion fruit plants under field conditions.
Productivity of 'yellow' passion fruit (Passiflora edulis Sims. f. flavicarpa O. Deg.) is reduced by infection with Cowpea aphid-borne mosaic virus (CABMV). We examined resistance in 72 yellow passion fruit plants grown from open-pollinated commercial seed. Plants were mechanically inoculated with CABMV virus and maintained in the field in order to select contrasting genotypes for resistance. Isolates were obtained from symptomatic leaves of yellow passion fruit plants from field production in Livramento de Nossa Senhora, Bahia state and were characterized by sequencing the viral coat protein gene. Severity of leaf symptoms of the disease, evaluated through a global leaf disease index, was measured during the eighth month of growth. Morpho-agronomic variables of fruit were evaluated from months 10 to 12. Significant linear regressions between the quantification of the leaf symptoms and the morpho-agronomic characteristics related to productivity were detected (5.17% <or= R(2) <or= 11%; 0.002 <or= p <or= 0.028). Based on evaluations of fruit productivity, severity of leaf symptoms of the disease, and the application of a selection index of 10%, four contrasting groups of 'yellow' passion fruit plants considered as "resistant", "mildly resistant", "susceptible" and "extremely susceptible" in their reaction to CABMV (0.0001 < p < 0.024) were selected. These plants could be useful for genetic studies and for breeding yellow passion fruit plants resistant to this disease.


Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo.
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.


Eliciting possible reaction equations and metabolic pathways involving orphan metabolites.
The development of metabolomics has resulted in the discovery of an increasing number of orphan metabolites, which are defined as compounds that are known to be present in living organisms but whose synthetic/degradation pathways are unknown. In this paper, we describe a procedure for identifying possible products and/or precursors of such orphan metabolites and for suggesting complete reaction equations and the corresponding EC (Enzyme Commission) number simultaneously. Chemical structure comparison is performed for a pair of compounds consisting of a reported substrate and its corresponding product and also for pairs of randomly selected compounds. Possible combinations of compounds registered in the KEGG database were used for generating putative enzyme reaction equations, which resulted in 77% of the reported equations being generated, as most of the remainder represent classes of compounds, rather than specific compounds, or contain Markush structures. The quality was checked using chemical structure comparison and the random-tree method, which gave 98% accuracy in suggesting EC subsubclasses for reported equations in cross-validation tests. The equations generated in this study can be seen using the Web-based program GREP (Generator of Reaction Equations & Pathways; http://bisscat.org/GREP/ ). The usefulness of our method for constructing possible metabolic pathways was demonstrated by mapping the generated equations for several groups of compounds, such as the betalain alkaloids. The possible development of our method so that alternative substrates for reported enzymes can be found and for annotating enzyme functions in genomic research is also discussed.


Isolation and characterization of salt-soluble, unsheared chromatin.
From rat liver nuclei depending on the extraction time, 10 to 20% of total chromatin has been extracted with a solution containing 0.1 M ammonium sulfate, 2 mM MnCl2, 0.1 M Tris-HCl, pH 7.9. We term this chromatin chromatin S. It has a protein: DNA ratio of 1.3, the full amount of the 5 histones in an undegraded state, and a RNA: DNA ratio of approximately 0.2. Its nonhistone protein pattern, obtained by gel electrophoresis exhibits a rich spectrum of proteins in a broad range of molecular weights. Electrophoretic analysis of the DNA fragments obtained by micrococcus nuclease digestion of chromatin S yields the same digestion pattern as that of nuclei. Thus, chromatin S fulfils an essential criterion of unsheared chromatin. In contrast to other chromatin preparations described so far, this chromatin is soluble at a salt concentration of 0.1 M ammonium sulfate. We have shown previously that it exhibits a compact conformation, low intrinsic viscosity and low radius of gyration obtained by light scattering measurements. Its mean molecular weight was determined to be nearly 10(8).


Exploring the Structure and Interrelations of Time-Stable Psychological Resilience, Psychological Vulnerability, and Social Cohesion.
The current study explores the relationship between three constructs of high relevance in the context of adversities which have, however, not yet been systematically linked on the level of psychological dispositions: psychological vulnerability, psychological resilience, and social cohesion. Based on previous theoretical and empirical frameworks, a collection of trait questionnaires was assessed in a Berlin sample of 3,522 subjects between 18 and 65 years of age. Using a confirmatory factor analytical approach, we found no support for a simple three-factor structure. Results from exploratory structural analyses suggest that instead of psychological resilience and psychological vulnerability constituting two separate factors, respective indicators load on one bipolar latent factor. Interestingly, some psychological resilience indicators contributed to an additional specific latent factor, which may be interpreted as adaptive capacities, that is, abilities to adapt to changes or adjust to consequences of adversities. Furthermore, instead of evidence for one single social cohesion factor on the psychological level, indicators of perceived social support and loneliness formed another specific factor of social belonging, while indicators of prosocial competencies were found to form yet another distinct factor, which was positively associated to the other social factors, adaptive capacities and social belonging. Our results suggest that social cohesion is composed of different independent psychological components, such as trust, social belonging, and social skills. Furthermore, our findings highlight the importance of social capacities and belonging for psychological resilience and suggest that decreasing loneliness and increasing social skills should therefore represent a valuable intervention strategy to foster adaptive capacities.


Investigation of inflammatory and allergic responses to common mold species: Results from in vitro experiments, from a mouse model of asthma, and from a group of asthmatic patients.
Most studies on molds focus on Alternaria alternata and Aspergillus fumigatus. Here, we report on inflammatory and allergenic properties of more typical indoor species Aspergillus versicolor, P. chrysogenum, C. cladosporioïdes, and C. sphaerospermum that were compared to A. alternata and A. fumigatus. In a mouse model, after intranasal instillation, A. alternaria, A. versicolor, and C. sphaerospermum induced the early recruitment of neutrophils and the strong expression of inflammatory markers in the bronchoalveolar lavages fluids. A. fumigatus also induced the early accumulation of neutrophils but with lower levels of inflammatory markers. Chronic treatment induced variable response according to species: P. chrysogenum and A. fumigatus appeared strong pro-allergenic inducers compared to A. alternata and C. sphaerospermum while A. versicolor and C. cladosporioides induced a mixed pro-allergenic/pro-inflammatory response. In mold-sensitized asthmatics, mold-specific Immunoglobulin E (IgE) were detected with an in-house dot-blot assay. A. fumigatus and A. alternata were the most frequent sensitizers. Altogether, P. chrysogenum, P. brevicompactum, C. sphaerospermum, and C. cladosporïoides were the "major sensitizer" (defined as the strongest response against a single mold species) for almost 30% of the asthmatics. These results show that, not only A. alternata and A. fumigatus, but also indoor species have strong inflammatory and allergic properties and a harmful potency.


The psychopharmacological treatment of obsessive-compulsive disorder: a review.
This article reviews the literature concerning obsessive-compulsive disorder (OCD) and its treatment with drugs. We survey the differential diagnosis of OCD and the problems involved in evaluating its severity in a research setting. Pharmacological treatment of OCD has usually involved antidepressants, especially clomipramine, with equivocal but nevertheless encouraging success. Anxiolytic and neuroleptics have also been tried, but the results are inconsistent. We discuss the implications of these findings for treatment of patients with OCD and for future research.


[Experimental and clinical studies on esophago-gastric hemodynamics before and after devascularization for esophageal varices].
Esophago-gastric hemodynamics subsequent to devascularization was studied in a view of changes in mucosal blood flow and tissue oxygen tension (PtO2). Thirty-four mongrel dogs (26 normal dogs and 8 portal hypertensive dogs) were used in experimental studies, and mucosal blood flow was determined by means of hydrogen gas clearance. Remarkable reduction of a 73% in gastric cardia was recognized on normal dogs just after extended devascularization, and those dogs died of severe gastric necrosis within 4 days after surgery. Reduction of a 28.5% in the cardia was found by the devascularization on portal hypertensive dogs produced by a whole liver compression. These portal hypertensive dogs survived for 2 weeks after surgery, and then mucosal blood flows were returned to the previous levels. Liver cirrhosis (10 cases) with esophageal varices were used for clinical studies. Gastric hemodynamics was measured by PtO2 before and after devascularization. Reduction of a 25.7% in the cardia was recognized on cirrhotic patients. These results suggest that influences of extended devascularization on esophago-gastric hemodynamics would be a small in cirrhotic patients with esophageal varices.


The effect of dietary Laminaria-derived laminarin and fucoidan on nutrient digestibility, nitrogen utilisation, intestinal microflora and volatile fatty acid concentration in pigs.
In experiment 1, 30 boars were assigned to one of five treatments (n = 6): T1, 0 g kg(-1) seaweed extract (SWE); T2, 0.7 g kg(-1) SWE; T3, 1.4 g kg(-1) SWE; T4, 2.8 g kg(-1) SWE and T5, 5.6 g kg(-1) SWE. The extract contained laminarin and fucoidan only and was extracted from Laminaria spp. In experiment 2, 28 boars were assigned, in a 2 x 2 factorial to one of four treatments (n = 7): T1, control; T2, control plus 300 mg laminarin; T3, control plus 240 mg fucoidan; T4, control plus 300 mg laminarin and 240 mg fucoidan kg(-1) diet. In experiment 1 there was a response to SWE on colonic Bifidobacterium spp. (P < 0.01 quadratic), Enterobacterium spp. (quadratic P < 0.05) and on caecal Enterobacterium spp. (quadratic P < 0.05). In experiment 2 there was an interaction (P < 0.05) between laminarin and fucoidan supplementation on Enterobacterium spp. in the proximal and distal colon. Pigs offered laminarin had reduced Enterobacterium spp. compared with pigs offered the control diet. However, the combination of laminarin and fucoidan had increased Enterobacterium spp. compared with alone. Pigs offered diets containing fucoidan had increased Lactobacilli spp. in the proximal colon (P < 0.05) and distal colon (P < 0.001) compared with non-fucoidan diets. Overall, the reductions in intestinal Enterobacterium spp. and increases in Lactobacilli spp. obtained suggest that laminarin and fucoidan may provide a dietary means to improve gut health in pigs.


Rapid and sensitive multiresidue analysis of pesticides in tobacco using low pressure and traditional gas chromatography tandem mass spectrometry.
Public exposure to pesticide residues through the main/side-stream smoke of tobacco (Nicotiana tabacum L.) is an international concern. This article reports optimization and validation of large-scale multiresidue analysis methods involving low pressure and traditional gas chromatography tandem mass spectrometry in compliance with the guidance residue levels (GRLs) of Cooperative Centre for Scientific Research Relative to Tobacco (CORESTA). Analysis by low pressure GC-MS/MS offered three times rapid turn around time over the traditional GC-MS/MS with limits of quantifications (LOQs) less than 2μg/L for all the 259 test compounds and the recoveries in the range of 70-118% (±20%) at 10 and 20μg/kg levels of fortification.


[Clinical analysis of immunotherapy rechallenge in advanced gastric cancer].
Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.


Transient synovitis: is there a need to aspirate hip joint effusions?
There is debate as to the optimal management of children with hip joint effusions especially regarding the decision to aspirate. The objective of this study was to determine whether there is a need to aspirate hip joint effusions detected on ultrasound in patients with clinical transient synovitis (TS) and to identify the natural history of these effusions. Twenty-five children with proven hip joint effusions were followed up sequentially by clinical and radiological examination until symptom free. The mean age was 6 years with equal right/left distribution. No child underwent hip aspiration and no cases of sepsis were missed. The median size of hip effusion detected on ultrasound at presentation was 9 mm. At 7 days 60% (15/25) of patients had a normal clinical examination with no detectable effusion on ultrasound. At 14 days 16% (4/25) had an effusion detectable on ultrasound but they were all pain and limp free and their effusions were reducing in size. These results support the known benign nature of TS and that it will settle with conservative treatment.


Divergent haplotypes and human history as revealed in a worldwide survey of X-linked DNA sequence variation.
The population genetic history of a 10.1-kbp noncoding region of the human X chromosome was studied using the males of the HGDP-CEPH Human Genome Diversity Panel (672 individuals from 52 populations). The geographic distribution of patterns of variation was roughly consistent with previous studies, with the major exception that 1 highly divergent haplotype (haplotype X, hX) was observed at low frequency in widely scattered non-African populations and not at all observed in sub-Saharan African populations. Microsatellite (short tandem repeat) variation within the sequenced region was low among copies of hX, even though the estimated time of ancestry of hX and other sequences was 1.44 Myr. The estimated age of the common ancestor of all hX copies was 5,230 years (95% consistency index: 2,000-75,480 years). To further address the presence of hX in Africa, additional samples from Chad and Tanzania were screened. Five additional copies of hX were observed, consistent with a history in which hX was present in Africa prior to the migration of modern humans out of Africa and with eastern Africa being the source of non-African modern human populations. Taken together, these features of hX-that it is much older than other haplotypes and uncommon and patchily distributed throughout Africa, Europe, and Asia-present a cautionary tale for interpretations of human history.


Substance P enhanced titanium particles-induced RANKL expression in fibroblasts from periprosthetic membrane.
Aseptic loosening remains the primary cause of failure in total joint arthroplasty. Implant-derived particles are thought to be a main cause of osteolysis that leads to the failure. Substance P (SP) immunoreactive nerve fibers have been detected in the periprosthetic membrane of aseptic loose hip prostheses. We isolated fibroblasts from periprosthetic membrane. Fibroblasts were examined by real-time RT-PCR and enzyme-linked immunosorbent assay for expression of the receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase (COX)-1, and COX-2. Experiments were performed in the presence and absence of titanium particles, SP and NS-398 (a selective COX-2 inhibitor). Titanium particles or SP stimulated RANKL and COX-2 expression in fibroblasts, whereas NS-398 inhibited RANKL production, suggesting a COX-2-mediated event. Moreover, SP enhanced COX-2 and RANKL expression by titanium particles-stimulated fibroblasts. Thus, SP and titanium particles acted synergistically to increase RANKL expression.


Decomposition of organochlorine compounds in flue gas from municipal solid waste incinerators using natural and activated acid clays.
High-temperature particle control (HTPC) using a ceramic filter is a dust collection method without inefficient cooling and reheating of flue gas treatment; thus, its use is expected to improve the energy recovery efficiency of municipal solid waste incinerators (MSWIs). However there are concerns regarding de novo synthesis and a decrease in the adsorptive removal efficiency of dioxins (DXNs) at approximately 300 degrees C. In this study, the effect of natural and activated acid clays on the decomposition of monochlorobenzene (MCB), one of the organochlorine compounds in MSW flue gas, was investigated. From the results of MCB removal tests at 30-300 degrees C, the clays were classified as adsorption, decomposition, and low removal types. More than half of the clays (four kinds of natural acid clays and two kinds of activated acid clays) were of the decomposition type. In addition, the presence of Cl atoms detached from MCB was confirmed by washing the clay used in the MCB removal test at 300 degrees C. Activated acid clay was expected to have high dechlorination performance because of its proton-rich-composition, but only two clays were classed as decomposition type. Conversely, all the natural acid clays used in this work were of the decomposition type, which contained relatively higher di- and trivalent metal oxides such as Al2O3, Fe2O3, MgO, and CaO. These metal oxides might contribute to the catalytic dechlorination of MCB at 300 degrees C. Therefore, natural and activated acid clays can be used as alternatives for activated carbon at 300 degrees C to remove organochloride compounds such as DXNs. Their utilization is expected to mitigate the latent risks related to the adoption of HTPC, and also to contribute to the improvement of energy recovery efficiency of MSWI. Implications: The effect of natural and activated acid clays on MCB decomposition was investigated to evaluate their suitability as materials for the removal of organochlorine compounds, such as DXNs, from MSWI flue gas at approximately 300 degrees C. More than half of the clays used in this study showed the decomposition characteristics of MCB. The presence of Cl atoms in the clay used in the MCB removal test at 300 degrees C proved the occurrence of MCB decomposition. The results of this study suggest a novel flue gas treatment method to establish high-energy efficient MSWI systems.


Complexity of spontaneous BOLD activity in default mode network is correlated with cognitive function in normal male elderly: a multiscale entropy analysis.
The nonlinear properties of spontaneous fluctuations in blood oxygen level-dependent (BOLD) signals remain unexplored. We test the hypothesis that complexity of BOLD activity is reduced with aging and is correlated with cognitive performance in the elderly. A total of 99 normal older and 56 younger male subjects were included. Cognitive function was assessed using Cognitive Abilities Screening Instrument and Wechsler Digit Span Task. We employed a complexity measure, multiscale entropy (MSE) analysis, and investigated appropriate parameters for MSE calculation from relatively short BOLD signals. We then compared the complexity of BOLD signals between the younger and older groups, and examined the correlation between cognitive test scores and complexity of BOLD signals in various brain regions. Compared with the younger group, older subjects had the most significant reductions in MSE of BOLD signals in posterior cingulate gyrus and hippocampal cortex. For older subjects, MSE of BOLD signals from default mode network areas, including hippocampal cortex, cingulate cortex, superior and middle frontal gyrus, and middle temporal gyrus, were found to be positively correlated with major cognitive functions, such as attention, orientation, short-term memory, mental manipulation, and language. MSE from subcortical regions, such as amygdala and putamen, were found to be positively correlated with abstract thinking and list-generating fluency, respectively. Our findings confirmed the hypothesis that complexity of BOLD activity was correlated with aging and cognitive performance based on MSE analysis, and may provide insights on how dynamics of spontaneous brain activity relates to aging and cognitive function in specific brain regions.


Aspartate kinase involved in 4-hydroxy-3-nitrosobenzamide biosynthesis in Streptomyces murayamaensis.
Streptomyces murayamensis carries two aspartate kinase (AK) genes: one for the biosynthesis of lysine, threonine, and methionine, and the other (nspJ) contained in the biosynthetic gene cluster for the secondary metabolite, 4-hydroxy-3-nitrosobenzamide, for catalyzing the first reaction. AKs involved in the biosynthesis of amino acids are often regulated allosterically by the end products. In the present study, we characterized NspJ to investigate whether AKs involved in secondary metabolism were also allosterically regulated. NspJ was in α2β2 and (α2β2)2 heterooligomeric forms, and was insensitive to all the compounds tested including lysine, threonine, and methionine. The reduction in the activity following the removal of ammonium sulfate, which induced subunit dissociation, suggests that the β subunit may be involved in stabilizing the structure of the α subunit in order to exhibit its activity. This study has provided the first example of a feedback-insensitive α2β2-type AK, which is involved in the secondary metabolism.


Novel diesel-oil-degrading bacteria and fungi from the Ecuadorian Amazon rainforest.
Isolating new diesel-oil-degrading microorganisms from crude-oil contaminated sites and evaluating their degradation capacities are vitally important in the remediation of oil-polluted environments and crude-oil exploitation. In this research, new hydrocarbon-degrading bacteria and fungi were isolated from the crude-oil contaminated soil of the oil-fields in the Amazon rainforest of north-east Ecuador by using a soil enrichment technique. Degradation analysis was tracked by gas chromatography and a flame ionization detector. Under laboratory conditions, maximum degradability of the total n-alkanes reached up to 77.34 and 62.62 removal ratios after 30 days of incubation for the evaporated diesel oil by fungi (isolate-1) and bacteria (isolate-1), respectively. The 16S/18S rDNA sequence analysis indicated that the microorganisms were most closely (99-100%) related to Bacillus cereus (isolate-1), Bacillus thuringiensis (isolate-2), Geomyces pannorum (isolate-1), and Geomyces sp. (isolate-2). Therefore, these strains enable the degradation of hydrocarbons as the sole carbon source, and these findings will benefit these strains in the remediation of oil-polluted environments and oil exploitation.


The temporal effect of intra-articular ozone injections on pain in knee osteoarthritis.
Osteoarthritis (OA) is a most common orthopaedic condition, often complicated by inflammatory features. A systematic search in PubMed, Embase, Google Scholar and Scopus databases (to January 2019) was performed to define the effect obtained in patients with OA of the knee by injections of ozone, on pain and physical function. Six RCTs and 353 patients were included. Recently, an increasing number of physicians have used ozone therapy to alleviate the symptoms of acute and chronic OA of the knee. Ozone can allow greater mobility of the knee joint, pain relief and decrease in effusion. The volume and concentration of ozone injected are different in the various treatment protocols published. The action of ozone is unclear, but it is a promising therapeutic modality capable of impacting, favourably, function and quality of life. The lack of a clear protocol of use is a major limitation, and to date there is no clear evidence of long-term efficacy.


Dimerization between aequorea fluorescent proteins does not affect interaction between tagged estrogen receptors in living cells.
Forster resonance energy transfer (FRET) detection of protein interaction in living cells is commonly measured following the expression of interacting proteins genetically fused to the cyan (CFP) and yellow (YFP) derivatives of the Aequorea victoria fluorescent protein (FP). These FPs can dimerize at mM concentrations, which may introduce artifacts into the measurement of interaction between proteins that are fused with the FPs. Here, FRET analysis of the interaction between estrogen receptors (alpha isoform, ERalpha) labeled with "wild-type" CFP and YFP is compared with that of ERalpha labeled with "monomeric" A206K mutants of CFP and YFP. The intracellular equilibrium dissociation constant for the hormone-induced ERalpha-ERalpha interaction is similar for ERalpha labeled with wild-type or monomeric FPs. However, the measurement of energy transfer measured for ERalpha-ERalpha interaction in each cell is less consistent with the monomeric FPs. Thus, dimerization of the FPs does not affect the kinetics of ERalpha-ERalpha interaction but, when brought close together via ERalpha-ERalpha interaction, FP dimerization modestly improves FRET measurement.


Current management of acute diarrhoeas. Use and abuse of drug therapy.
Acute diarrhoeas in infants and children should be regarded as a protective physiological response of the gastrointestinal tract to flush out harmful organisms and toxins, thus limiting the morbidity from this illness. The approach to therapy of acute diarrhoeas must be physiological rather than pharmacological. Prevention and early correction of acute dehydration with oral rehydration is the most physiological approach to the successful management of acute diarrhoeas, which generally have a self-limited course. The use of antidiarrhoeal drugs is limited to a few isolated cases. These may include the short term administration of antimicrobials in selected cases of acute diarrhoea caused by entero-pathogens where antimicrobials are proven to be efficacious. Antisecretory drugs which are devoid of unwanted side effects may be tried in persistent cases of acute diarrhoeas, but kaolin-pectin mixtures and antimotility drugs should be avoided for infants and children. Generally, the management of acute diarrhoea is simply to stop the dehydration rather than the diarrhoea, not with drug therapy but with oral rehydration therapy.


Pheromone-based action thresholds for control of the swede midge, Contarinia nasturtii (Diptera: Cecidomyiidae), and residual insecticide efficacy in cole crops.
The swede midge, Contarinia nasturtii (Kieffer), is an invasive gall midge causing economic damage to cole crops (Brassica oleracea L.) and other crucifers in eastern Canada and United States. An effective decision-making tool for timing insecticide applications is a critical part of an integrated pest management program against C. nasturtii. Experiments were undertaken over 2 yr and at three locations in southern Ontario to develop pheromone-based action thresholds for C. nasturtii in cabbage and broccoli. An economic comparison between action threshold and calendar insecticide regimes was undertaken. The threshold approach was both economically viable and successful at minimizing swede midge damage for cabbage, and an action threshold of five males per trap per day with a minimum 7 d retreatment interval successfully reduced damage to acceptable levels. However, this approach was not successful with broccoli, which, unlike cabbage, is susceptible to damage by C. nasturtii through all plant stages, including heading. Acetamiprid and lambda-cyhalothrin both demonstrated approximately 7 d residual activity against C. nasturtii. Registration labels for both insecticides specify a minimum 7 d retreatment interval, which is supported by residual efficacy results. More effective insecticidal products may have longer residual efficacy and improve efficacy of the action threshold approach for broccoli and cabbage.


A protected biotin containing deoxycytidine building block for solid phase synthesis of biotinylated oligonucleotides.
The synthesis of a modified 2'-deoxycytidine-3'-O-phosphoramidite carrying an N-t-butylbenzoyl protected biotin on a long polar spacer arm attached to the 4-N position is described. The presence of the bulky lipophilic t-butylbenzoyl protecting group enables the direct solid phase synthesis of biotinylated oligoribonucleotides and a variety of analogues in high yield without modification of the biotin moiety. Biotinylated antisense oligonucleotides incorporating this new derivative allow convenient isolation and purification of ribonucleic acid-protein complexes. The kinetics of biotin binding to streptavidin agarose is facilitated by the long polar spacer arm.


Bridge Damage Identification Using Deep Neural Networks on Time-Frequency Signals Representation.
For the purpose of maintaining and prolonging the service life of civil constructions, structural damage must be closely monitored. Monitoring the incidence, formation, and spread of damage is crucial to ensure a structure's ongoing performance. This research proposes a unique approach for multiclass damage detection using acceleration responses based on synchrosqueezing transform (SST) together with deep learning algorithms. In particular, our pipeline is able to classify correctly the time series representing the responses of accelerometers placed on a bridge, which are classified with respect to different types of damage scenarios applied to the bridge. Using benchmark data from the Z24 bridge for multiclass classification for different damage situations, the suggested method is validated. This dataset includes labeled accelerometer measurements from a real-world bridge that has been gradually damaged by various conditions. The findings demonstrate that the suggested approach is successful in exploiting pre-trained 2D convolutional neural networks, obtaining a high classification accuracy that can be further boosted by the application of simple voting methods.


Complex integrons containing qnrB4-ampC (bla(DHA-1)) in plasmids of multidrug-resistant Citrobacter freundii from wastewater.
Microbial populations in wastewater treatment plants (WWTPs) are increasingly being recognized as environmental reservoirs of antibiotic resistance genes. PCR amplicons for plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS were recorded in samples from a WWTP in Vancouver, British Columbia. Six strains of ciprofloxacin-resistant Citrobacter freundii were isolated and found to carry mutations in gyrA and parC, as well as multiple plasmid-borne resistance genes, collectively including qnrB; aac(6')-Ib-cr; β-lactamase-encoding genes from molecular classes A (blaTEM-1), C (ampC), D (blaOXA-1, blaOXA-10); and genes for resistance to 5 other types of antibiotics. In 3 strains, large (>60 kb) plasmids carried qnrB4 and ampC as part of a complex integron in a 14 kb arrangement that has been reported worldwide but, until recently, only among pathogenic strains of Klebsiella. Analysis of single-nucleotide polymorphisms in the qnrB4-ampC regions infers 2 introductions into the WWTP environment. These results suggest recent passage of plasmid-borne fluoroquinolone and β-lactam resistance genes from pathogens to bacteria that may be indigenous inhabitants of WWTPs, thus contributing to an environmental pool of antibiotic resistance.


[Effects of microRNA-373 on the proliferation and invasiveness of breast carcinoma and its mechanisms].
Objective: To explore the effects of microRNA (miR)-373 on proliferation and invasion of breast cancer cells and its mechanisms. Methods: Breast carcinoma tissues and its corresponding normal tissues (80 cases) were obtained from the First Affiliated Hospital of Zhengzhou University from 2010 to 2014. Quantitative real-time (RT)-PCR was used to detect the expression of miR-373 of breast carcinoma tissues and its corresponding normal tissues. The cellula experiment was divided into three groups: the normal control group, the miR-373 mimic group and the miR-373 inhibitor group. The proliferation was detected by Cell Counting Kit.8 (CCK-8) method and the invasion and migration were detected by Transwell method. Effect of miR-373 on cell apoptosis was determined by Flow Cytometry. Results: Expression of miR-373 in breast cancer tissue was significant lower than the normal breast tissues (0.21±0.09 vs 0.98±0.23, P<0.001); expression of miR-373 contributed to the inhibition of Bcl-6 expression. The apoptosis rate in miR-373 was higher than normal control group (18.29%±0.29% vs 4.91%±0.31%), cell proliferation, cell invasion and cell migration were lower than normal control group [(0.69±0.11) vs (1.25±0.12) (the fifth day), (30.50±0.20) vs (66.50±0.42), (29.50±0.21) vs (48.50±0.31), all P<0.05]. Conclusion: miR-373 plays a suppressive role in proliferation and invasion of breast carcinoma, and the downregulation of miR-373 promotes the invasion of breast cancer which may mediate by the increased expression of Bcl-6.


Stress-responsive HILPDA is necessary for thermoregulation during fasting.
Hypoxia-inducible lipid droplet-associated protein (HILPDA) has been shown to localize to lipid droplets in nutrient-responsive cell types such as hepatocytes and adipocytes. However, its role in the control of whole-body homeostasis is not known. We sought to measure cell-intrinsic and systemic stress responses in a mouse strain harboring whole-body Hilpda deficiency. We generated a genetically engineered mouse model of whole-body HILPDA deficiency by replacing the coding Hilpda exon with luciferase. We subjected the knockout animals to environmental stresses and measured whole-animal metabolic and behavioral parameters. Brown adipocyte precursors were isolated and differentiated in vitro to quantify the impact of HILPDA ablation in lipid storage and mobilization in these cells. HILPDA-knockout animals are viable and fertile, but show reduced ambulatory activity and oxygen consumption at regular housing conditions. Acclimatization at thermoneutral conditions abolished the phenotypic differences observed at 22°C. When fasted, HILPDA KO mice are unable to maintain body temperature and become hypothermic at 22°C, without apparent abnormalities in blood chemistry parameters or tissue triglyceride content. HILPDA expression was upregulated during adipocyte differentiation and activation in vitro; however, it was not required for lipid droplet formation in brown adipocytes. We conclude that HILPDA is necessary for efficient fuel utilization suggesting a homeostatic role for Hilpda in sub-optimal environments.


[Spinal intradural tumors].
Spinal intradural tumors are uncommon lesions but may cause significant morbidity. In establishing the differential diagnosis for a spinal lesion, location, age, and the patient's clinical presentation are important. Magnetic resonance imaging plays a central role in the visualization of spinal tumors, easily allowing tumors to be classified as extradural, intradural extramedullary, or intramedullary which is very useful in tumor characterization. We describe intradural tumors; the majority is extramedullary, with nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Ependymomas and astrocytomas comprise the majority of this group. Typical imaging features of both intradural extramedullary and intramedullary tumors are described.


Genome-wide characterization of the Rab gene family in Gossypium by comparative analysis.
Rab protein family is the largest subfamily of small G protein family. As one of the most important families in plant, Rab family plays an important role in the process of plant growth and development. So far, the identification of 57 members of the Rab family in Arabidopsis has been completed. In cotton, the relevant family has not been reported. Here, we identified 87, 169, 136, 80 Rabs in the four sequenced cotton species, G. raimondii (D5), G. hirsutum acc. TM-1 (AD1), G. barbadense acc. 3-79 (AD2) and G. arboreum (A2), respectively. Biological information analysis showed that the number of amino acid is 200-300 aa among Rab family members in G. raimondii and the protein molecular weight is between 20 and 30 kDa, which is consistent with the characterization of the Rab protein itself. 87 GrRabs in G. raimondii are divided into eight groups. In each group, intron numbers and subcellular localization of Rab protein are basically the same. We mapped the distribution of GrRab genes on 13 chromosomes of G. raimondii except two genes. Among the 87 GrRabs in G. raimondii, we identified 60 pairs of GrRabs formed in whole genome duplication. Among all the gene pairs, the Ka/Ks values were less than 1. This indicates that it is the results of the purification selection and will help maintain the conservation of gene in structure and function. Further, 4 of the 87 GrRabs showed tandem duplication. They were GrRabA2a vs GrRabD1a and GrRabA2h vs GrRabD1b respectively. Expression patterns analysis of 169 GhRabs in G. hirsutum acc. TM-1 indicates that most Rab family members play a certain role in different tissues/organs and different growth stages of cotton, implying their potential function in the polar growth of pollen tube, root hair and fiber cell, as well as improving stress and disease tolerance. The systematic investigation of Rab genes in cotton will lay a foundation for understanding the functional roles of different Rab members in the polar growth and stress tolerance.


Diversifying Food Systems in the Pursuit of Sustainable Food Production and Healthy Diets.
Increasing demand for nutritious, safe, and healthy food because of a growing population, and the pledge to maintain biodiversity and other resources, pose a major challenge to agriculture that is already threatened by a changing climate. Diverse and healthy diets, largely based on plant-derived food, may reduce diet-related illnesses. Investments in plant sciences will be necessary to design diverse cropping systems balancing productivity, sustainability, and nutritional quality. Cultivar diversity and nutritional quality are crucial. We call for better cooperation between food and medical scientists, food sector industries, breeders, and farmers to develop diversified and nutritious cultivars that reduce soil degradation and dependence on external inputs, such as fertilizers and pesticides, and to increase adaptation to climate change and resistance to emerging pests.


Cytopathological and chemico-physical analyses of smears of mucosa surrounding oral piercing.
The aim of this comparative study was to analyze cytopathologically and chemico-physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back-scattered) scanning electron microscope (SEM) and X-ray microanalysis to study piercing fragments. Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X-ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.


Blood and urinary zinc changes after a glucose challenge in early and late pregnancies.
This study was undertaken to investigate the effect of pregnancy and glucose loading on zinc metabolism. In a completely random design with repeated measures, 18 non-pregnant women, 16 early-pregnant women (13-17 wk), and 16 late-pregnant women (28-34 wk) had blood collected at 0, 30, 60, 120, and 180 min after ingesting 100 g glucose to evaluate changes in variables of Zn nutriture. Fasting plasma Zn concentrations decreased significantly as pregnancy progressed. Late-pregnant women had significantly higher erythrocyte Zn levels and greater 24-h urinary Zn and glucose excretions. Erythrocyte Zn responses to glucose loading were unaffected by gestational age. Plasma Zn after a glucose load in nonpregnant women exhibited a curvilinear response whereas pregnant women showed no change. This lack of response by pregnant women may be related to their lower plasma Zn concentrations. Plasma Zn in pregnant women may not be as readily available to assist in glucose utilization.


An Imaging and Histological Study on Intrahepatic Microvascular Passage of Contrast Materials in Rat Liver.
Background. Lipiodol has been applied for decades in transarterial chemoembolization to treat liver malignancies, but its intrahepatic pathway through arterioportal shunt (APS) in the liver has not been histologically revealed. This rodent experiment was conducted to provide evidence for the pathway of Lipiodol delivered through the hepatic artery (HA) but found in the portal vein (PV) and to elucidate the observed unidirectional APS. Methods. Thirty rats were divided into 5 groups receiving systemic or local arterial infusion of red-stained iodized oil (RIO) or its hydrosoluble substitute barium sulfate suspension (BSS), or infusion of BSS via the PV, monitored by real-time digital radiography. Histomorphology of serial frozen and paraffin sections was performed and quantified. Results. After HA infusion, RIO and BSS appeared extensively in PV lumens with peribiliary vascular plexus (PVP) identified as the responsible anastomotic channel. After PV infusion, BSS appeared predominantly in the PV and surrounding sinusoids and to a much lesser extent in the PVP and HA (P < 0.001). Fluid mechanics well explains the one-way-valve phenomenon of APS. Conclusions. Intravascularly injected rat livers provide histomorphologic evidences: (1) the PVP exists in between the HA and PV, which is responsible to the APS of Lipiodol; and (2) the intrahepatic vascular inflow appears HA-PVP-PV unidirectional without a physical one-way valve, which can be postulated by the fluid mechanics.


MIL-103, a 3-D lanthanide-based metal organic framework with large one-dimensional tunnels and a high surface area.
A lanthanide-based metal organic framework, formulated Tb(C27H15O6)(H2O).2C6H11OH, has been solvothermally synthesized using the extended rigid tritopic ligand 1,3,5-tribenzoate. Included free solvent could be removed upon heating, and the resulting material presents large 1-D micropores (free diameter = 10 A) and a high surface area (SLangmuir > 1000 m2.g-1).


Antifouling Biomimetic Liquid-Infused Stainless Steel: Application to Dairy Industrial Processing.
Fouling is a widespread and costly issue, faced by all food-processing industries. Particularly, in the dairy sector, where thermal treatments are mandatory to ensure product safety, heat-induced fouling represents up to 80% of the total production costs. Significant environmental impacts, due the massive consumption of water and energy, are also to deplore. Fouling control solutions are thus desperately needed, as they would lead to substantial financial gains as well as tremendous progress toward eco-responsible processes. This work aims at presenting a novel and very promising dairy fouling-mitigation strategy, inspired by nature, and to test its antifouling performances in real industrial conditions. Slippery liquid-infused surfaces were successfully designed directly on food grade stainless steel, via femtosecond laser ablation, followed by fluorosilanization and impregnation with an inert perfluorinated oil. Resulting hydrophobic surfaces (water contact angle of 112°) exhibited an extremely slippery nature (contact angle hysteresis of 0.6°). Outstanding fouling-release performances were obtained for these liquid-infused surfaces as absolutely no trace of dairy deposit was found after 90 min of pasteurization test in pilot-scale equipment followed by a short water rinse.


Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf Signaling.
Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively promoted by bacterial determinants during infection. Using Mycobacterium marinum-infected zebrafish as a model, we identify the enzyme proximal cyclopropane synthase of alpha-mycolates (PcaA) as an important bacterial determinant of granuloma-associated angiogenesis. cis-Cyclopropanation of mycobacterial mycolic acids by pcaA drives the activation of host Vegf signaling within granuloma macrophages. Cyclopropanation of the mycobacterial cell wall glycolipid trehalose dimycolate is both required and sufficient to induce robust host angiogenesis. Inducible genetic inhibition of angiogenesis and Vegf signaling during granuloma formation results in bacterial growth deficits. Together, these data reveal a mechanism by which PcaA-mediated cis-cyclopropanation of mycolic acids promotes bacterial growth and dissemination in vivo by eliciting granuloma vascularization and suggest potential approaches for host-directed therapies.


Intestinal permeability in non-alcoholic fatty liver disease: the gut-liver axis.
The gut-liver axis model has helped to explain the liver steatosis (NAFLD) and steatohepatitis (NASH) etiopathogenesis. The discovery of a key role for an altered intestinal permeability (IP) in this pathophysioligcal framework has closed the link between gut lumen antigenic/toxic substances and systemic and liver inflammation in NAFLD and obesity, metabolic syndrome. Recent evidence from the literature show how IP can be modulated by several non-pharmacological and pharmacological agents and be the target for future preventive and curative treatment of NAFLD and NASH. In this review we describe the concept of IP, its ultrastructural basis, its role in the NALFD pathophysiology and emerging evidence on non-pharmacological and pharmacological agents able to favourably modulate it.


Age differences and longitudinal change in the effects of data collection mode on self-reports of psychosocial functioning.
The current study investigated age differences and longitudinal change in mode effects, wherein individuals report less negative and more positive psychosocial functioning with data collection modes that have greater (vs. less) direct contact with interviewers (e.g., in-person interviews vs. telephone interviews). Using 2 longitudinal datasets, the Later Life Study of Social Exchanges (LLSSE) and Swedish Adoption/Twin Study of Aging (SATSA), we tested how mode effects may vary with cohort (baseline age differences) and maturational development (longitudinal change). In Study 1, LLSSE participants (65-90 years old) completed in-person and telephone interviews assessing negative and positive aspects of psychosocial functioning across 2 years. The data collection mode with greater direct contact with interviewers (in-person interviews) was associated with reporting less negative and more positive psychosocial functioning compared to the mode with less direct contact (telephone interviews). These mode effects were more pronounced with older baseline age, but only for the negative psychosocial measures. Mode effects also became stronger over time for reports of negative affect. In Study 2, SATSA participants (38-86 years old) completed mailed questionnaires and questionnaires collected in-person that assessed depressive symptoms and positive affect across 18 years. Consistent with Study 1, participants reported fewer depressive symptoms and more positive affect with greater (vs. less) direct contact with interviewers (questionnaires collected in-person vs. mailed questionnaires). For reports of depressive symptoms, but not positive affect, mode effects were more pronounced with age and time. Together, the results underscore how mode effects may contribute to inconsistent findings in the socioemotional aging literature.


Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism.
Mammalian acetylcholinesterase (AChE) is well-studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa Analysis of WT and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 Å resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Because of the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases.


Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d-Peptides for Selectively Inhibiting Ovarian Cancer Cells.
Cancer is a major public health concern requiring novel treatment approaches. Enzyme-instructed self-assembly (EISA) provides a unique approach for selectively inhibiting cancer cells. However, the structure and activity correlation of EISA remains to be explored. This study investigates new EISA substrates of alkaline phosphatase (ALP) to hinder ovarian cancer cells. Analogues 2-8 were synthesized by modifying the amino acid residues of a potent EISA substrate 1 that effectively inhibits the growth of OVSAHO, a high-grade serous ovarian cancer (HGSOC) cell line. The efficacy of 2-8 against OVSAHO was assessed, along with the combination of substrate 1 with clinically used drugs. The results reveal that substrate 1 displays the highest cytotoxicity against OVSAHO cells, with an IC50 of around 8 μM. However, there was limited synergism observed between substrate 1 and the tested clinically used drugs. These findings indicate that EISA likely operates through a distinct mechanism that necessitates further elucidation.


Practical management of recurrent urinary tract infections in premenopausal women.
Recurrent urinary tract infections (UTIs) are a major healthcare concern for premenopausal, healthy, sexually active women. A practical approach to the management and prevention of recurrent UTIs should be simple, practical, and cost effective. Low-dose or postcoital antimicrobial therapy can be effective for women with constellations of many recurrent UTIs, but for women with 2 to 4 UTIs per year, the most cost-effective and empowering management strategy is patient-initiated antimicrobial treatment.


Activation of Melatonin Receptors by Ramelteon Induces Cardioprotection by Postconditioning in the Rat Heart.
Activation of melatonin receptors protects the heart against ischemia-reperfusion injury. Ramelteon, a clinically used drug for insomnia, acts via activation of melatonin receptors. We investigated whether ramelteon induces acute infarct size reduction by postconditioning. Male Wistar rats were randomized to 6 groups. Hearts were treated with melatonin and ramelteon at the beginning of reperfusion. The melatonin receptor inhibitor luzindole was administered with and without melatonin and ramelteon, respectively. Ramelteon reduced infarct size to the same extent as melatonin. Both effects were completely abolished by luzindole. The results show for the first time that ramelteon induces cardioprotection by postconditioning.


Quantitative analysis of chondroitin sulfate isomers in intervertebral disk chondrocyte culture using capillary electrophoresis.
Chondroitin sulfate (CS) isomers, 6-sulfate (CS6) and 4-sulfate (CS4), change their ratio to each other in cartilaginous tissues with aging. In this study, a quantitative measurement method of CS6 and CS4 was developed, using capillary electrophoresis (CE). Various buffer solutions, pH, and digestion times were studied, and the use of 0.1 M Tris-HCl at pH of 8.0 allowed the isolation of CS6 and CS4 from CS most efficiently when combined with chondrotinase ABC at a concentration of 1 mU/microg of the substrate during a 3 hr digestion period. Amounts of newly synthesized CS6 and CS4 in the intervertebral disk chondrocyte three-dimensional culture were quantified by this method after the proteoglycans were extracted by equilibrium density centrifugation.


Self-reported methods of cessation of adult male child abusers: a pilot study.
This pilot study explored the pre-arrest self-selected cessation attempts of sexual offenders (N = 109) who abused children and often others. Four participants were dropped because of invalid responding (N = 104). While 74.3% of sample participants reported attempts to decrease or stop their sexual offending prior to arrest, 56% out of 100 who responded to the cessation question reported that they were able to do so. Self-efficacy was examined as a potential predictive variable of cessation attempts and success of attempts; however, no relationship was found between self-efficacy and attempts. Practice and research implications are discussed.


A national quitline service and its promotion in the mass media: modelling the health gain, health equity and cost-utility.
Mass media campaigns and quitlines are both important distinct components of tobacco control programmes around the world. But when used as an integrated package, the effectiveness and cost-effectiveness are not well described. We therefore aimed to estimate the health gain, health equity impacts and cost-utility of the package of a national quitline service and its promotion in the mass media. We adapted an established Markov and multistate life-table macro-simulation model. The population was all New Zealand adults in 2011. Effect sizes and intervention costs were based on past New Zealand quitline data. Health system costs were from a national data set linking individual health events to costs. The 1-year operation of the existing intervention package of mass media promotion and quitline service was found to be net cost saving to the health sector for all age groups, sexes and ethnic groups (saving $NZ84 million; 95%uncertainty interval 60-115 million in the base-case model). It also produced greater per capita health gains for Māori (indigenous) than non-Māori (2.2 vs 0.73 quality-adjusted life-years (QALYs) per 1000 population, respectively). The net cost saving of the intervention was maintained in all sensitivity and scenario analyses for example at a discount rate of 6% and when the intervention effect size was quartered (given the possibility of residual confounding in our estimates of smoking cessation). Running the intervention for 20 years would generate an estimated 54 000 QALYs and $NZ1.10 billion (US$0.74 billion) in cost savings. The package of a quitline service and its promotion in the mass media appears to be an effective means to generate health gain, address health inequalities and save health system costs. Nevertheless, the role of this intervention needs to be compared with other tobacco control and health sector interventions, some of which may be even more cost saving.


Cervical mediastinoscopy and anterior mediastinotomy in superior vena cava obstruction.
There is general agreement regarding the diagnostic efficacy of cervical mediastinoscopy (CMDS) and anterior mediastinotomy (AMDT) on patients with superior vena cava obstruction (SVCO), but controversy exists concerning the safety of these two diagnostic methods on that particular subset of patients. The purpose of the present study is to evaluate the safety and diagnostic efficacy of CMDS and AMDT in patients with SVCO. During the last 28 years, 39 consecutive patients with SVCO underwent biopsy of mediastinal lesions by CMDS (n = 18) or AMDT (n = 19) or both these techniques (n = 2). The medical records of all patients were reviewed, and demographic data, operative notes, perioperative complications, outcome, and histologic diagnoses were examined. The findings were compared with those of 367 patients without SVCO who underwent biopsy of mediastinal lesions during the same period of time. An up-to-date English-language literature search was performed. The sensitivity of CMDS and/or AMDT in detecting malignancies in 39 patients with SVCO was 97.4%, specificity was 100%, and diagnostic accuracy was 97.4%. There was no in-hospital mortality, while morbidity consisted of five major complications and one minor complication, including two major hemorrhages and two airway obstructions. These patients, compared to those without SVCO, showed significantly higher postoperative morbidity (p < 0.001) and had a higher rate of malignancy (p < 0.001). Among 280 patients of the literature review, major hemorrhage was recorded in eight cases and airway obstruction in none. CMDS and AMDT are effective methods to establish a histologic diagnosis in patients with SVCO. Although their mortality is negligible, they are accompanied by a significantly higher morbidity compared to patients without SVCO. Airway obstruction is a life-threatening complication that can occur in these patients. In our series, patients with SVCO had a higher rate of malignancy compared to patients without SVCO.


The Role of Peritoneal Immunity in Peritoneal Endometriosis and Related Infertility.
Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms.


Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients-Real-World Data From Hungary.
Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.


The Mortality Rate of 100% Service-Connected U.S. Veterans.
Previously, it was unknown if 100% service-connected U.S. veterans have a diminished mortality. However, it is widely documented that this patient population experiences worse health due to their military service, so it is logical that their mortality will be diminished due to their worse health. This research study helped address an apparent gap in the literature regarding the mortality of 100% service-connected U.S. veterans. The objective of this research study was to answer the question, what is the average age at death of 100% service-connected U.S. veterans? This research study is a pilot study designed to help answer this initial question. This is important because it will help determine if the mortality of this U.S. veteran population is reduced due to their military service.


Implementing Transitions of Care Services in a Primary Care Clinic: Role of the Pharmacist.
IntroductionPharmacists in primary care clinics improve medication adherence and reduce medication errors but these require further investigation to determine its potential impact on health care readmission rates. Methods: This review assessed the addition of a clinical pharmacist to the primary care provider's transitions of care appointment. The primary outcome of this review was the change in acute health care encounters (hospital readmissions and/or Emergency Department visits) in the 6-month period before to the 6 months following initial clinical pharmacist intervention. Each patient served as their own control. Secondary outcomes included the number and types of pharmacist interventions, percentage of pharmacist recommendations accepted, number and categories of drug-related problems (DRPs), nonadherence reasons, 30-day hospital readmission rate, 30-day Emergency Department (ED) rate, time to first hospital readmission, time to first ED readmission, and preventable readmission rate. Results: The total number of combined acute health care encounters in 6 months decreased by 15% from 280 at baseline to 238 after pharmacist intervention (P = .087) for the 206 patients included in the final analysis. The 30-day hospital readmission rate was 9.7% and the median time between first hospital readmission was 54.5 days (IQR 63.5). We identified a total number of 310 DRPs with a mean of 1.5 DRPs (SD 1.3) identified per patient. The providers accepted 88% of the pharmacists' recommendations. Conclusions: Clinical pharmacists embedded in a primary care setting demonstrated improved patient care during transitions of care by identifying and resolving drug-related problems, with a trend in decreasing acute health care utilization.


Perioperative anaesthetic care of the cat undergoing dental and oral procedures: key considerations.
Anaesthesia for dental and oral procedures in cats can be challenging and many factors need to be taken into consideration. Often it is older patients requiring these procedures and, while old age itself is not a contraindication for general anaesthesia, older patients tend to have limited homeostatic reserves and are, therefore, more prone to anaesthesia-induced insults of vital organs. Most sedative and anaesthetic agents have cardiovascular side effects, which may result in detrimental consequences in older patients in which organ reserves are likely reduced. The need for good patient assessment and management during the entire perianaesthetic period cannot be overemphasised. This article describes how both anaesthetic protocol and intravenous fluid therapy should be tailored to the individual cat's needs. Application of a multimodal analgesic protocol (the combination of different analgesic agents) and a balanced anaesthetic technique incorporating local nerve blocks is highly recommended and a particular focus of the review. The use of local anaesthetic agents for the latter not only provides optimal pre-emptive analgesia, but also reduces the amount of anaesthetic agents needed to maintain an adequate level of anaesthesia and, therefore, limits their side effects. Other key aspects of perianaesthetic care of the feline dental and oral patient include airway protection, monitoring and maintenance of body temperature, eye protection, and analgesia extending well into the post-anaesthetic period. The authors draw on their clinical experience and the referenced literature to provide a practical overview of this critical but often-overlooked aspect of feline dentistry.


HOTAIR Competitively Binds MiRNA330 as a Molecular Sponge to Increase the Resistance of Gastric Cancer to Trastuzumab.
HOTAIR, one of the most widely studied long non-coding RNAs in tumors, is closely related to tumor proliferation, migration, invasion and chemoresistance. Here, we studied the mechanism behind proliferation and chemoresistance processes. A total of 75 samples were collected from patients who underwent surgical resection of their gastric cancer and received trastuzumab treatment. Primary cells were isolated and cultured. We also developed a cell line overexpressing HOTAIR by constructing a lentiviral vector. These cell lines were studied using an array of established biomolecular methods. We found that HOTAIR levels were inversely associated with sensitivity to trastuzumab in gastric cancer and that overexpression of HOTAIR can promote the proliferation and invasion of gastric cancer cells. The sensitivity of cells overexpressing HOTAIR to two different types of human epidermal growth factor receptor 2 (HER2) inhibitors (trastuzumab and afatinib) showed that overexpression of HOTAIR is specific for trastuzumab resistance. Furthermore, luciferase reporter gene assay and western blot assay showed that there is a HOTAIR-miRNA330-ERBB4 competitive endogenous RNA regulatory network with miRNA330 as the core. HOTAIR can not only promote tumor proliferation but also enhance the resistance of tumor cells to drugs. Our experimental data not only showed strong expression of HOTAIR in gastric cancer, but also that strong expression of HOTAIR caused the sensitivity of gastric cancer cells to trastuzumab, which is a useful reference for postoperative medication.


Liver-specific deletion of 3-hydroxy-3-methylglutaryl coenzyme A reductase causes hepatic steatosis and death.
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) catalyzes the rate-limiting step in cholesterol biosynthesis and has proven to be an effective target of lipid-lowering drugs, statins. The aim of this study was to understand the role of hepatic HMGCR in vivo. To disrupt the HMGCR gene in liver, we generated mice homozygous for a floxed HMGCR allele and heterozygous for a transgene encoding Cre recombinase under the control of the albumin promoter (liver-specific HMGCR knockout mice). Ninety-six percent of male and 71% of female mice died by 6 weeks of age, probably as a result of liver failure or hypoglycemia. At 5 weeks of age, liver-specific HMGCR knockout mice showed severe hepatic steatosis with apoptotic cells, hypercholesterolemia, and hypoglycemia. The hepatic steatosis and death were completely reversed by providing the animals with mevalonate, indicating its essential role in normal liver function. There was a modest decrease in hepatic cholesterol synthesis in liver-specific HMGCR knockout mice. Instead, they showed a robust increase in the fatty acid synthesis, independent of sterol regulatory element binding protein-1c. Hepatocyte HMGCR is essential for the survival of mice, and its abrogation elicits hepatic steatosis with jaundice and hypoglycemia.


Thermodynamics of the QCD plasma and the large-N limit.
The equilibrium thermodynamic properties of the SU(N) plasma are studied nonperturbatively in the large-N limit, via high-precision lattice simulations at temperatures from 0.8T(c) to 3.4T(c) (T(c) being the critical deconfinement temperature). Our results for SU(N) Yang-Mills theories with N=3, 4, 5, 6, and 8 colors show a very mild dependence on N, supporting the idea that the QCD plasma could be described by models based on the large-N limit. We compare our data with various theoretical descriptions, including, in particular, the improved holographic QCD model proposed by Kiritsis and collaborators. We also comment on the relevance of an AdS/CFT description in a phenomenologically interesting temperature range where the system, while still strongly coupled, becomes approximately scale invariant. Finally, we extrapolate our results to the N --> infinity limit.


Natural progression of calciphylaxis in a patient on haemodialysis.
A 40 year old patient with end-stage renal disease developed features of calciphylaxis and tumoral calcification after four and half years on regular haemodialysis. The patient had hyperphosphatemia, with high calcium-phosphate index and radiological evidence of hyperparathyroidism before the onset of symptoms. Conservative management was without success and the patient developed florid symptoms. Parathyroidectomy was delayed due to unavoidable circumstances. When it was eventually performed there was a prompt regression of the calcific masses, but not of the vascular calcifications. The natural progression of the disease and its regression by parathyroidectomy provides an interesting insight into this phenomenon, the full blown picture of which is rarely seen these days.


Patient smoking cessation--treatment strategies.
Smoking is one of the major health issues of our century. It is clearly a detrimental health behavior that costs millions of dollars annually and undisputed morbidity and mortality. There is considerable interest among health care providers in assisting smokers in the cessation of this destructive personal habit. This article covers indirect measures (including environmental strategies) and direct measures to influence the smoking behavior of patients. Direct measures covered include the most appropriate delivery of anti-smoking information, an evaluation of legitimate and organized smoking cessation resources, and tips on assisting patients with their smoking cessation and cessation maintenance efforts. Through an understanding of the individual patient, his or her unique history and needs, and the basic design of the most popular smoking cessation strategies, the clinician can most effectively assist patients in the initiation, development and maintenance of patient cigarette smoking cessation efforts.