Peptide SIKVAV-modified chitosan hydrogels promote skin wound healing by accelerating angiogenesis and regulating cytokine secretion.
Skin wound healing is complex and involves the processes of many factors, among which angiogenesis and inflammatory responses play important roles. New blood vessels provide nutrition and oxygen for skin wound repair. Cytokines in skin wounds, which include pro-inflammatory and anti-inflammatory factors, can modulate the inflammatory response. Therefore, treatment strategies that promote angiogenesis and modulate the inflammatory response in skin wounds can accelerate skin wound healing. This study explored the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)-modified chitosan hydrogels in skin wound healing. General observation demonstrated that SIKVAV-modified chitosan hydrogels promoted the contraction of skin wounds compared with the negative and positive controls. Masson's trichrome staining indicated that peptide-modified chitosan hydrogels accelerated the deposition of more collagen fibers in the skin wounds compared with the negative and positive controls. Immunohistochemistry assays showed that more myofibroblasts were deposited and more angiogenesis was found in skin wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. In addition, qRT-PCR assays showed that peptide-modified chitosan hydrogels promoted the expression of TGF-β1 (transforming growth factor-β1) mRNA and inhibited the expression of TNF-α (tumor necrosis factor-α) mRNA and IL-1β (Interleukin-1β) mRNA and IL-6 (Interleukin-6) mRNA in skin wounds. Taken together, these results indicate the potential of SIKVAV-modified chitosan hydrogels in skin wound healing as complex biomaterials.


High and compact formation of baculoviral polyhedrin-induced inclusion body by co-expression of baculoviral FP25 in Escherichia coli.
Previously, we found that baculoviral polyhedrin (Polh) can successfully be used in Escherichia coli as a fusion partner for the expression of special foreign proteins as inclusion bodies, and the resulting, easily isolatable Polh-induced fusion inclusion bodies had almost the same characteristics as the native Polh. Here, we investigated the effects of co-expression of baculoviral FP25 protein on Polh-induced inclusion-body production in an E. coli expression system, as FP25 is known to be involved specifically in polyhedra formation. Using several analytical tools, including SDS-PAGE, pronase proteolysis, solubilization under alkaline conditions, and electron microscopy, we found that co-expressed FP25 was associated with Polh-induced inclusion bodies and that its co-expression led to formation of compact inclusion bodies as well as high production levels. We confirmed that FP25 co-expression induced higher production levels of other heterologous protein, antimicrobial peptide Hal18, fused with aggregation-prone Polh. Therefore, co-expression of baculoviral FP25 can be promisingly used to increase the levels of baculoviral Polh-fused foreign proteins, especially harmful proteins, expressed as inclusion bodies in an E. coli expression system.


AKT in stromal fibroblasts controls invasion of epithelial cells.
The tumour microenvironment has an important role in cancer progression and recent reports have proposed that stromal AKT is activated and regulates tumourigenesis and invasion. We have shown, by immuno-fluorescent analysis of oro-pharyngeal cancer biopsies, an increase in AKT activity in tumour associated stromal fibroblasts compared to normal stromal fibroblasts. Using organotypic raft co-cultures, we show that activation of stromal AKT can induce the invasion of keratinocytes expressing the HPV type 16 E6 and E7 proteins, in a Keratinocyte Growth Factor (KGF) dependent manner. By depleting stromal fibroblasts of each of the three AKT isoforms independently, or through using isoform specific inhibitors, we determined that stromal AKT2 is an essential regulator of invasion and show in oro-pharyngeal cancers that AKT2 specific phosphorylation events are also identified in stromal fibroblasts. Depletion of stromal AKT2 inhibits epithelial invasion through activating a protective pathway counteracting KGF mediated invasions. AKT2 depletion in fibroblasts stimulates the cleavage and release of IL1B from stromal fibroblasts resulting in down-regulation of the KGF receptor (fibroblast growth factor receptor 2B (FGFR2B)) expression in the epithelium. We also show that high IL1B is associated with increased overall survival in a cohort of patients with oro-pharyngeal cancers. Our findings demonstrate the importance of stromal derived growth factors and cytokines in regulating the process of tumour cell invasion.


Substituent and solvent effects on the excited state deactivation channels in anils and boranils.
Differently substituted anils (Schiff bases) and their boranil counterparts lacking the proton-transfer functionality have been studied using stationary and femtosecond time-resolved absorption, fluorescence, and IR techniques, combined with quantum mechanical modelling. Dual fluorescence observed in anils was attributed to excited state intramolecular proton transfer. The rate of this process varies upon changing solvent polarity. In the nitro-substituted anil, proton translocation is accompanied by intramolecular electron transfer coupled with twisting of the nitrophenyl group. The same type of structure is responsible for the emission of the corresponding boranil. A general model was proposed to explain different photophysical responses to different substitution patterns in anils and boranils. It is based on the analysis of changes in the lengths of CN and CC bonds linking the phenyl moieties. The model allows predicting the contributions of different channels that involve torsional dynamics to excited state depopulation.


A Safe and Compliant Noncontact Interactive Approach for Wheeled Walking Aid Robot.
Aiming at promptly and accurately detecting falls and drag-to gaits induced by asynchronous human-robot movement speed during assisted walking, a noncontact interactive approach with generality, compliance and safety is proposed in this paper, and is applied to a wheeled walking aid robot. Firstly, the structure and the functions of the wheeled walking aid robot, including gait rehabilitation robot (GRR) and walking aid robot (WAR) are illustrated, and the characteristic futures of falls and the drag-to gait are shown by experiments. To obtain gait information, a multichannel proximity sensor array is developed, and a two-dimensional gait information detection system is established by combining four proximity sensors groups which are installed in the robot chassis. Additionally, a node-iterative fuzzy Petri net algorithm for abnormal gait recognition is proposed by generating the network trigger mechanism using the fuzzy membership function. It integrates the walking intention direction vector by taking gait deviation, frequency, and torso angle as input parameters of the system. Finally, to improve the compliance of the robot during human-robot interaction, a PID_SC controller is designed by integrating the gait speed compensation, which enables the WAR to track human gait closely. Abnormal gait recognition and assisted walking experiments are carried out respectively. Experimental results show that the proposed algorithm can accurately identify abnormal gaits of different groups of users with different walking habits, and the recognition rate of abnormal gait reaches 91.2%. Results also show that the developed method can guarantee safety in human robot interaction because of user gate follow-up accuracy and compliant movements. The noncontact interactive approach can be applied to robots with similar structure for usage in walking assistance and gait rehabilitation.


From dispositional affect to academic goal attainment: the mediating role of coping.
The purpose of this research was to examine a mediation model in which coping was hypothesized to mediate the relationship between positive and negative dispositional affect and academic goal attainment. At Time 1, a sample of 217 undergraduate students completed measures of dispositional affect and set a personal academic goal. At Time 2, 4 weeks later, they completed a follow-up questionnaire assessing their coping strategies and degree of goal attainment. Results from structural equation modeling revealed that task-oriented coping significantly mediated the relationship between dispositional positive affect and goal attainment. Results also supported disengagement-oriented coping as a mediator in the relationship between dispositional negative affect and goal attainment. These findings highlight the role of coping as an important process in the relationship between dispositional affect and goal attainment.


Nutrition in pregnancy and pathogenic diseases.
A woman's nutritional status should be assessed preconception with the goal of optimizing maternal, fetal, and infant health. Pregnancy-related dietary changes should begin prior to conception, with appropriate modifications across pregnancy and during lactation. The Recommended Dietary Allowances (RDAs) are levels of nutrients recommended by an expert IOM panel based on extensive evaluation of available scientific evidence and mathematically adjusted to meet the needs of 97% of the population.


Heme oxygenase-1 and the vascular bed: from molecular mechanisms to therapeutic opportunities.
Heme oxygenase-1, an enzyme degrading heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to heme release. HO-1 protects endothelial cells from apoptosis, is involved in blood-vessel relaxation regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in blood-vessel formation by means of angiogenesis and vasculogenesis. The latter functions link HO-1 not only to cardiovascular ischemia but also to many other conditions that, like development, wound healing, or cancer, are dependent on neovascularization. The aim of this comprehensive review is to address the mechanisms of HO-1 regulation and function in cardiovascular physiology and pathology and to demonstrate some possible applications of the vast knowledge generated so far. Recent data provide powerful evidence for the involvement of HO-1 in the therapeutic effect of drugs used in cardiovascular diseases. Novel studies open the possibilities of application of HO-1 for gene and cell therapy. Therefore, research in forthcoming years should help to elucidate both the real role of HO-1 in the effect of drugs and the clinical feasibility of HO-1-based cell and gene therapy, creating the effective therapeutic avenues for this refined antioxidant system.


[The pioneers of vascular surgery in Lyon: M. Jaboulay, A. Carrel, E. Villard et R. Leriche].
Lyon was, during about 30 years, French vascular surgery birth place just after our century beginning. At first, Mathieu Jaboulay, the last Hôtel-Dieu chief-surgeon, made up a blood vessel anastomosis by means of a circular eversive suturing. Then, Alexis Carrel improved anastomotic bindings and get on the first organic transplantation. At the same time, Eugène Villard took up again his experimental studies and, since 1811, made them complete by way of accurate histological analysis. At last, René Leriche devoted himself to sympathetic nervous system surgery in order to cure arteritis but without foreseeing by-pass prospects in the future.


DNA methylation biomarkers in stool for early screening of colorectal cancer.
Objective: Detection of aberrant methylated genes in feces has been developed as an early screening method for colorectal cancer. The aim of this study was to probe the methylation status of SEPT9, BMP3, NDRG4, and SDC2 in stool and study whether methylation of these genes is associated with colorectal cancer. Materials and Methods: DNAs were isolated and purified from cancerous and non-cancerous stool samples and colorectal cancer tissue. Gene methylation levels were quantified by methylation-specific PCR on SEPT9, BMP3, NDRG4, and SDC2 and analyzed by a diagnostic model. Results: DNA methylation of SEPT9, NDRG4 and SDC2, but not BMP3, had diagnostic potential for detecting colorectal cancer. Moreover, integration of SEPT9, NDRG4, and SDC2 methylation demonstrated high feasibility for detecting colorectal cancer and adenoma, with better performance on colorectal cancer than adenoma. Conclusion: The methylation of SEPT9, NDRG4, and SDC2 in stool may be a potential biomarker for early screening of colorectal cancer.


Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.
Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11's role in NSCLC and the detailed mechanism behind it. Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial-mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial-mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.


"A tumour registry initiative".
Published literature on epidemiological profile of paediatric brain tumours in India is limited. Aim: To present a retrospective analysis of the histological spectrum of 158 paediatric age group central nervous system tumours operated in a single tertiary care hospital in Coastal South India between January 2015 and December 2021. Retrospective analysis of the data regarding frequencies of various primary brain tumours among 158 paediatric patients (<18 years of age). The tumours were categorised according to the revised 4th edition of World Health Organization (WHO) classification of tumours of the Central Nervous system. Paediatric CNS constituted 8.5% of total intracranial tumours (158/1860) operated in the study period. The mean age of the patients was 10.2 years and a definite male predominance was noted (1.54:1) Astrocytomas, glioneuronal tumours, and neuronal tumours constituted the majority (72/158; 45.6%) followed by embryonal tumours (31/158; 19.6%) and craniopharyngiomas(24/158; 15.4%).Of the glial neoplasms majority were pilocytic and other astrocytic tumours(41.6%), followed by mixed neuroglial tumours (19.4%), diffuse high grade astrocytomas (Grade III/IV) (11.1%), diffuse low -grade astrocytomas (Grade II) (9.7%) and ependymomas (13.8%). Our series also included six meningiomas (3.8%), five germ cell tumours (3.16%), four nerve sheath tumours (2.53%), two choroid plexus tumours (1.26%), two pineal parenchymal tumours (1.26%) and one metastasis from a soft tissue sarcoma from the thigh. Supratentorial tumours (58.2%) were more common than posterior fossa (34.6%) and spinal tumours (7.6%) and visual pathway gliomas accounted for 5.6% of all our tumours. Paediatric central nervous system tumours are more common in boys and in the second decade of life. Astrocytomas are the most common paediatric brain tumours followed by medulloblastomas and craniopharyngiomas. Pediatric tumours affect the supratentorial compartment more often than the infratentorial compartment. The profile of paediatric brain tumours in our series is similar to that reported from other Indian centres as well as most western literature.


Contribution of basic residues of the 70-80-loop to heparin binding and anticoagulant function of activated protein C.
The role of basic residues of the 70-80-loop, Arg(74), Arg(75), and Lys(78) (chymotrypsin numbering) in the catalytic function of activated protein C (APC) was investigated by expressing mutants of protein C in which these residues were replaced with Ala in three separate constructs. Following purification to homogeneity and activation by thrombin, the catalytic properties of the mutants were characterized with respect to their ability to cleave the chromogenic substrate Spectrozyme PCa, react with protein C inhibitor (PCI), and inactivate factor Va. Relative to wild-type APC, the mutants cleaved Spectrozyme PCa with identical or improved catalytic efficiencies. Similarly, PCI inhibited mutants with identical or improved second-order rate constants (k(2)) in the absence of heparin. However, the heparin-catalyzed inhibition of mutants by PCI was impaired approximately 10-fold. Analysis of k(2) values by a ternary complex model revealed that the affinities of mutants for heparin were impaired to a similar extent. Moreover, analysis of the NaCl gradient elution profiles of APC derivatives from Heparin-Sepharose supported this conclusion. An oligosaccharide containing 14 residues efficiently catalyzed the PCI inhibition of APC by a template mechanism. Further studies revealed that the ability of Arg(74) and Arg(75) mutants to inactivate factor Va was markedly impaired. We conclude that basic residues of the 70-80-loop are critical for the catalytic function of APC.


Sulfur amino acid metabolism in Schizosaccharomyces pombe: occurrence of two O-acetylhomoserine sulfhydrylases and the lack of the reverse transsulfuration pathway.
The fission yeast Schizosaccharomyces pombe has a unique organization of sulfur amino acid metabolism: it has two distinct O-acetylhomoserine sulfhydrylases (homocysteine synthases). Similar to Enterobacteriaceae, S. pombe lacks cystathionine beta-synthase and cystathionine gamma-lyase-the enzymes of the reverse transsulfuration pathway, by which methionine is readily metabolized to cysteine-a likely effector in the sulfur metabolite repression system. Consequently no repression of sulfate assimilation is observed when methionine is added to the growth medium.


Atrioesophageal fistula after surgical unipolar radiofrequency atrial ablation for atrial fibrillation.
Atrial fibrillation is the most common arrhythmia in the United States. Procedural treatment options such as the MAZE procedure and radiofrequency ablation are available with reasonable success rates. However, there are risks inherent to these procedures, with atrioesophageal fistula being a rare but devastating complication. We report a patient with atrioesophageal fistula who presented with neurologic symptoms 20 days after her initial MAZE procedure, followed by a quick decline within 24 hours of presentation.


[Implementation of interdisciplinary multimodal pain therapy according to OPS 8‑918 : Recommendations of the ad hoc commission for interdisciplinary multimodal pain therapy of the German Pain Association].
With the implementation of the German diagnosis-related groups (DRG) reimbursement system in hospitals, interdisciplinary multimodal pain therapy was incorporated into the associated catalogue of procedures (OPS 8‑918). Yet, the presented criteria describing the procedure of interdisciplinary multimodal pain therapy are neither precise nor unambiguous. This has led to discrepancies in the interpretation regarding the handling of the procedure-making it difficult for medical services of health insurance companies to evaluate the accordance between the delivered therapy and the required criteria. Since the number of pain units has increased in recent years, the number of examinations by the medical service of health insurance companies has increased. This article, published by the ad hoc commission for interdisciplinary multimodal pain therapy of the German Pain Association, provides specific recommendations for correct implementation of interdisciplinary multimodal pain therapy in routine care. The aim is to achieve a maximum level of accordance between health care providers and the requirements of the medical examiners from health insurance companies. More extensive criteria regarding interdisciplinary multimodal pain treatment in an in-patient setting, especially for patients with chronic and complex pain, are obviously needed. Thus, the authors further discuss specific aspects towards further development of the OPS-code. However, the application of the OPS-code still leaves room regarding treatment intensity and process quality. Therefore, the delivery of pain management in sufficient quantity and quality still remains the responsibility of each health care provider.


Who pays for the state? A reply to Robert Chernomas and Ardeshir Sepehri.
Robert Chernomas and Ardeshir Sepehri indicate that various state-supported transfers that go to the "underclass" are largely paid for by taxation of workers' compensation. Such expenses therefore cannot be considered drains on the social surplus which would otherwise be available to dominant classes in the form of "exploitation." These arguments are criticized on two grounds. First, Chernomas and Sepehri greatly underestimate the total social costs of the existence of an underclass, and this broader array of costs almost certainly impinges on the social surplus even if direct transfer payments do not. Second, they incorrectly identify the empirical target with the relationship of taxation to the social surplus. Even if state revenues take the form of an income tax on ordinary workers, at least some of this taxation should be considered a deduction from social surplus rather than from workers' standard of living (since, in the absence of the taxation, workers' equilibrium wages would not increase by the equivalent of the taxes).


Pigeon navigation: exposure to environmental odours prior to release is sufficient for homeward orientation, but not for homing.
The role of environmental olfactory information in pigeon navigation has been extensively studied by analysing vanishing bearing distributions and homing performances of homing pigeons subjected to manipulation of their olfactory perception and/or the olfactory information they were exposed to during transportation and at the release site. However, their behaviour during the homing flight remains undocumented. In this experiment we report the analysis of tracks of birds made anosmic at the release site by washing their olfactory mucosa with zinc sulfate. We thus can assess the role of local odours at the release site as well as the role of environmental odours perceived on the way, far from the release site. We observed that pigeons transported and kept at the release site in purified air and made anosmic at the release site were unable to orient towards home and were impaired at homing. By contrast, pigeons allowed to smell environmental odours during transportation and at the release site, although made anosmic prior to release, displayed unimpaired homeward orientation, but nevertheless showed impaired homing performance. These results are consistent with the view that local odours at the release site are critical for determining the direction of displacement (olfactory map) and suggest that pigeons consult the olfactory map also during their homing flight in order to be able to find their way home.


US abundance of physicians and international health.
American clinicians with careers encompassing both Third World and underserved American populations would benefit both regions and bring new perspectives to foreign policy and domestic health care problems. Application of the parallel concepts of Community-Oriented Primary Care and Health for All should help contain costs and extend access to appropriate clinical care both in the United States and abroad. As American physicians weigh their short- or long-term career options in the post-Graduate Medical Education National Advisory Council era, there is an urgent need both for a specific US policy on international health and for new partnerships to facilitate careers spanning domestic and Third World areas of need.


Determination of roxatidine in human plasma by liquid chromatography/electrospray mass spectrometry and application to a clinical pharmacokinetic study.
A rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method was developed and validated for the determination of roxatidine in human plasma. Roxatidine was extracted by single liquid-liquid extraction with tert-butyl methyl ether, and the chromatographic separation was performed on a C8 column. The total analytical run time was relatively short (5 min), and the limit of assay quantification was 2 ng/mL using 0.1 mL of human plasma. Roxatidine and the internal standard, propranolol, were monitored in selected ion monitoring (SIM) mode at m/z 307.3 and 260.3, respectively. The standard curve was linear over a concentration range from 2-500 ng/mL, and the correlation coefficients were >0.999. The mean intra- and inter-day assay accuracy ranged from 103.4-108.8% and 102.3-110.0%, respectively, and the mean intra- and inter-day precision was between 3.3-8.8% and 5.3-6.2%, respectively. The developed assay method was successfully applied to a pharmacokinetic study in human volunteers after oral administration of roxatidine acetate hydrochloride at a dose of 75 mg.


Molecular Mechanism in the Development of Pulmonary Fibrosis in Patients with Sarcoidosis.
Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS.


Shorter periconception maternal telomere length and the risk of congenital cardiac outflow defects in the offspring.
Congenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology of COD and enhance telomere length (TL) shortening. We investigated the association between periconception maternal TL and the risk of having a child with COD. From a multicentre case-control trial, 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Relative TL was measured by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios, per standard deviation decrease, between maternal T/S ratio and COD and VSD risk. Adjustments were made for maternal age. Additional adjustments were made in a second model. Shorter maternal relative TL was significantly associated with an OR of 1.29 (95% CI 1.04-1.61), p = .02, for the risk of VSD in offspring, which remained significant after an adjustment for maternal age (adjOR 1.25(95% CI 1.01-1.55), p = .04). No association between maternal TL and the risk of overall COD in offspring was observed. Shorter maternal relative TL is associated with an approximately 1.3-OR for the risk, per SD in relative TL shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.


Sleep quality and job satisfaction of Turkish nurses.
This research was conducted as a descriptive study for the purpose of examining nurses' sleep quality, job satisfaction, and the relationship between them. The research population was comprised of nurses who work at Inönü University Turgut Ozal Medical Center (Turkey) and the research was conducted with a total of 418 nurses. A Personal Information Form, developed by the researchers based on information in the literature, and the Pittsburgh Sleep Quality Index (PSQI) and Short Form Minnesota Satisfaction Questionnaire (MSQ), which have been adapted for Turkish and had validity and reliability studies conducted, were used for data collection in the research. For data analysis, frequency distribution, arithmetic mean, variance analysis (One-Way ANOVA), Tukey test, and Independent Samples t test were used. According to the findings obtained from the research it was determined that nurses' total sleep quality score mean was 7.28 +/- 3.56 and job satisfaction score mean was 48.05 +/- 11.77 and a weak negative correlation was found between the 2 tools (r = -0.25) (P < .05). As the nurses' sleep quality increased (that is, as their sleep quality score mean decreased) their job satisfaction increased (their job satisfaction score mean increased). In general, the results obtained from our research show that nurses' sleep quality is low and their job satisfaction is at a moderate level. In parallel with this, as the nurses' sleep quality decreases their job satisfaction also decreases.


The quest for the holy grail: overcoming challenges in expanding human hematopoietic stem cells for clinical use.
Hematopoietic stem cell (HSC) transplantation has been the golden standard for many hematological disorders. However, the number of HSCs obtained from several sources, including umbilical cord blood (UCB), often is insufficient for transplantation. For decades, maintaining or even expanding HSCs for therapeutic purposes has been a "holy grail" in stem cell biology. Different methods have been proposed to improve the efficiency of cell expansion and enhance homing potential such as co-culture with stromal cells or treatment with specific agents. Recent progress has shown that this is starting to become feasible using serum-free and well-defined media. Some of these protocols to expand HSCs along with genetic modification have been successfully applied in clinical trials and some others are studied in preclinical and clinical studies. However, the main challenges regarding ex vivo expansion of HSCs such as limited growth potential and tendency to differentiate in culture still need improvements. Understanding the biology of blood stem cells, their niche and signaling pathways has provided possibilities to regulate cell fate decisions and manipulate cells to optimize expansion of HSCs in vitro. Here, we review the plethora of HSC expansion protocols that have been proposed and indicate the current state of the art for their clinical application.


A comparison of crossbred and straightbred cow-calf pairs. I. Heterosis effects on total feed efficiency.
Records of 104 crossbred and 33 straightbred individually fed cow-calf units were used to study the effects of heterosis on total cow-calf feed efficiency in the production of weight of calf at weaning, 168 d postweaning, slaughter and in the carcass. The cows were Angus, Hereford, Charolais and reciprocal crosses of these breeds. The calves were straightbred and all possible two-breed backcrosses and three-breed crosses produced from first cross cows. The efficiency of the cow-calf unit was defined as kg of calf produced per kg of total TDN (total digestible nutrients) consumed by the cow-calf pair. Total feed consumed by the cows was for an average period of 315 d, from approximately November 21 to October 2. Total calf TDN consisted of creep to weaning and feed during the postweaning fattening period to slaughter. For all measures of cow-calf unit efficiency studied, the heterosis estimates were small but generally positive, ranging from -.8 to 2.1%. The average advantage of all crosses over the straightbred parents for the conversion of total feed consumed by cow-calf pair to calf weight at weaning was 2%. Heterosis effects, individual and maternal combined, on the average, among two-breed backcrosses and the three-breed crosses were essentially the same. Among the three groups of first-cross cows compared, the study indicated that a slight advantage in total cow-calf efficiency was exhibited by the Angus X Hereford cross.(ABSTRACT TRUNCATED AT 250 WORDS)


Listen to Me! - A Mixed-Methods Study of Thoughts and Attitudes Towards Participation in Pulmonary Telerehabilitation Among People with Severe and Very Severe COPD Who Declined Participation in Pulmonary Rehabilitation.
Pulmonary rehabilitation (PR) is a key standard treatment for people with chronic obstructive pulmonary disease (COPD) with documented effect on symptom relief, improved physical function, and quality of life. However, referral, uptake and adherence rates remain low. Pulmonary telerehabilitation (PTR) is a safe and effective alternative to conventional PR. This study explores associations, thoughts and attitudes towards PTR in patients with COPD who decline referral to outpatient hospital-based routine PR. A mixed-methods study with integration of survey data (n=84) and semi-structured interviews (n=9). We found a significant association between belief of effect of PTR and willingness to participate. Increasing age was significantly associated with reduced odds of daily use of central processing unit (CPU) or tablet. One-third of the participants were undecided about potential participation in PTR. Qualitative findings highlight that participants perceived participating in PTR as more convenient and had preferences for individualized, supervised, and monitored rehabilitation. Those willing to participate in a PTR program believed in the benefits, were comfortable with technological devices, had preferences for exercising at home, and saw opportunities in the social setting. Future PTR programs should include monitoring, preferably managed by a familiar health care professional (HCP).


Computerized audiometry--a facility to prevent hearing damages caused by noise.
A computerized audiometer has been developed to perform pure-tone manual or fixed-frequency Békésy audiometry. A number of statistical evaluation programs are part of the integrated audiometer. It means that even small but statistically certain changes in hearing thresholds can be revealed at an early stage.


Applying principles of behaviour change to reduce SARS-CoV-2 transmission.
Human behaviour is central to transmission of SARS-Cov-2, the virus that causes COVID-19, and changing behaviour is crucial to preventing transmission in the absence of pharmaceutical interventions. Isolation and social distancing measures, including edicts to stay at home, have been brought into place across the globe to reduce transmission of the virus, but at a huge cost to individuals and society. In addition to these measures, we urgently need effective interventions to increase adherence to behaviours that individuals in communities can enact to protect themselves and others: use of tissues to catch expelled droplets from coughs or sneezes, use of face masks as appropriate, hand-washing on all occasions when required, disinfecting objects and surfaces, physical distancing, and not touching one's eyes, nose or mouth. There is an urgent need for direct evidence to inform development of such interventions, but it is possible to make a start by applying behavioural science methods and models.


Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001.
COPD is one of the leading causes of mortality and morbidity in the United States, yet little is known about the prevalence of comorbid conditions and mortality in hospitalized patients with COPD. From the National Hospital Discharge Survey, 1979 to 2001, we evaluated whether or not COPD in adults > or = 25 years old is associated with increased prevalence and in-hospital mortality of several comorbidities. During 1979 to 2001, there were an estimated total of 47,404,700 hospital discharges (8.5% of all hospitalizations in adults > 25 years old) of patients with COPD; 37,540,374 discharges (79.2%) were made with COPD as a secondary diagnosis, and 9,864,278 discharges (20.8%) were made with COPD as the primary diagnosis. The prevalence and in-hospital mortality for pneumonia, congestive heart failure, ischemic heart disease, thoracic malignancies, and respiratory failure were larger in hospital discharges with any mention of COPD. In a nationally representative sample of hospitalizations, any mention of COPD in the discharge diagnosis is associated with higher hospitalization prevalence and in-hospital mortality from other comorbidities. These results highlight the fact that the burden of disease associated with COPD is likely underestimated.


Apparent motion and the Pulfrich effect.
The Pulfrich pendulum effect, obtained by viewing a moving object with a filter over one eye, was examined with target stimuli in apparent, rather than continuous, motion. The filter-induced depth effect persisted until a certain degree of intermittency in the presentations of the target was reached, and then it broke down. The degree of intermittency that could be tolerated before the depth effect broke down increased with the density of the filter. It could be argued that the filter determined a shift in the pairing of successive inputs to the eyes, such that the target position in the unfiltered eye was fused with the preceding target position in the filtered eye. However, it appears that the shifted-pairing effect cannot account for the depth impression seen when the target intermittency is less than about 30 ms. Below this value of intermittency a filter can produce a depth effect even when the delay it introduces is small in comparison to the intermittency of the input. The depth effect seen with intermittencies less than 30 ms appears to be of the same magnitude as that obtained with stimuli in continuous motion. It is concluded that a filter can cause two different kinds of depth shift with apparently moving stimuli.


Confidence intervals for the difference of marginal probabilities in clustered matched-pair binary data.
Although there are several available test statistics to assess the difference of marginal probabilities in clustered matched-pair binary data, associated confidence intervals (CIs) are not readily available. Herein, the construction of corresponding CIs is proposed, and the performance of each CI is investigated. The results from Monte Carlo simulation study indicate that the proposed CIs perform well in maintaining the nominal coverage probability: for small to medium numbers of clusters, the intracluster correlation coefficient-adjusted McNemar statistic and its associated Wald or Score CIs are preferred; however, this statistic becomes conservative when the number of clusters is larger so that alternative statistics and their associated CIs are preferred. In practice, a combination of the intracluster correlation coefficient-adjusted McNemar statistic with an alternative statistic is recommended. To illustrate the practical application, a real clustered matched-pair collection of data is used to illustrate testing the difference of marginal probabilities and constructing the associated CIs.


High resolution 1H detected 1H,13C correlation spectra in MAS solid-state NMR using deuterated proteins with selective 1H,2H isotopic labeling of methyl groups.
MAS solid-state NMR experiments applied to biological solids are still hampered by low sensitivity and resolution. In this work, we employ a deuteration scheme in which individual methyl groups are selectively protonated. This labeling scheme allows the acquisition of proton carbon correlation spectra with a resolution comparable to that in solution-state NMR experiments. We observe an increase in resolution by a factor of 10-15 compared to standard heteronuclear correlation experiments using PMLG for 1H,1H dipolar decoupling in the indirect dimension. At the same time, the full sensitivity of the proton-based experiment is retained. In comparison to the heteronuclear detected version of the experiment, a gain in sensitivity of a factor of approximately 4.7 is achieved.


The fifth sense: Mechanosensory regulation of alpha-actinin-4 and its relevance for cancer metastasis.
Metastatic cancer cells invading through dense tumor stroma experience internal and external forces that are sensed through a variety of mechanosensory proteins that drive adaptations for specific environments. Alpha-actinin-4 (ACTN4) is a member of the α-actinin family of actin crosslinking proteins that is upregulated in several types of cancers. It shares 86% protein similarity with α-actinin-1, another non-muscle ACTN isoform, which appears to have a more modest role, if any, in cancer progression. While they share regulatory mechanisms, such as phosphorylation, calcium binding, phosphatidyl inositol binding, and calpain cleavage, α-actinin-4 exhibits a unique mechanosensory regulation that α-actinin-1 does not. This behavior is mediated, at least in part, by each protein's actin-binding affinity as well as the catch-slip-bond behavior of the actin binding domains. We will discuss currently known modes of ACTN4 regulation, their interactions, and how mechanosensation may provide major therapeutic targeting potential for cancer metastasis.


Multiple sclerosis: improvement of visuoperceptive functions by picoTesla range magnetic fields.
The occurrence of cognitive deficits in multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory" in his patients. Recent studies employing standardized neuropsychological tests have confirmed the high incidence of cognitive deficits in MS patients particularly those with a chronic progressive course of the disease. Visuoperceptive and visuomotor deficits commonly occur in MS patients and are thought to reflect damage to attentional systems due to interruption by demyelinating plaques of nerve conduction along the ascending projections from the brainstem reticular formation to the cortex. Impairment of synaptic conductivity due to serotoninergic depletion (5-HT) may contribute to the emergence of cognitive deficits in MS. The present communication concerns a 36 year old patient with MS in whom external application of picoTesla range magnetic fields (MF) resulted in rapid improvement of symptoms including visuoperceptive functions as demonstrated on various drawing tasks. The report confirms the efficacy of picoTesla range MF in the treatment of MS and demonstrates beneficial effects on cognitive functions as well.


Primary retroperitoneal sarcomas: a multivariate analysis of surgical factors associated with local control.
To define the optimal initial management and the best extent of surgery that would optimize margins on primary retroperitoneal sarcomas (RPS). A total of 382 patients with primary RPS were analyzed. Sixty-five patients had a simple resection of the tumor, 120 patients had a complete compartmental resection (systematic resection of noninvolved contiguous organs), 130 patients had a contiguously involved organ resection, 21 patients had a systematic re-excision, 38 patients had an incomplete gross resection, and eight patients had a biopsy alone. Radiotherapy and chemotherapy were administered to 121 and 145 patients, respectively. One, 3-, and 5-year overall survival (OS) rates were 86% (95% CI, 0.82 to 0.89), 66% (95% CI, 0.61 to 0.71), and 57% (95% CI, 0.51 to 0.62), respectively. Median overall survival was 6 years. In the multivariate analysis, high grade, tumor rupture, gross residual disease, and positive margins were associated with decreased OS. Low grade, no tumor rupture, negative histologic margins, a high number of patients undergoing operation per center, and compartmental resection compared with standard procedures were associated with decreased abdominal recurrences. Compartmental resection is a significant variable, predicting a 3.29-fold lower rate of abdominal recurrence compared with simple complete resection. Complete compartmental surgery without tumor rupture should be performed when possible to achieve clear margins. This surgery should be performed in a high-volume center. The role of adjuvant treatments should be evaluated in a randomized trial in association with this optimal surgery.


One-Dimensional van der Waals Material Tellurium: Raman Spectroscopy under Strain and Magneto-Transport.
Experimental demonstrations of one-dimensional (1D) van der Waals material tellurium (Te) have been presented by Raman spectroscopy under strain and magneto-transport. Raman spectroscopy measurements have been performed under strains along different principle axes. Pronounced strain response along the c-axis is observed due to the strong intrachain covalent bonds, while no strain response is obtained along the a-axis due to the weak interchain van der Waals interaction. Magneto-transport results further verify its anisotropic property, which results in dramatically distinct magneto-resistance behaviors in terms of three different magnetic field directions. Specifically, phase coherence length extracted from weak antilocalization effect, Lϕ ≈ T-0.5, claims its two-dimensional (2D) transport characteristics when an applied magnetic field is perpendicular to the thin film. In contrast, Lϕ ≈ T-0.33 is obtained from universal conductance fluctuations once the magnetic field is along the c-axis of Te, which indicates its nature of 1D transport along the helical atomic chains. Our studies, which are obtained on high quality single crystal Te thin film, appear to serve as strong evidence of its 1D van der Waals structure from experimental perspectives. It is the aim of this paper to address this special concept that differs from the previous well-studied 1D nanowires or 2D van der Waals materials.


First synthesis of 2,3,6,7-tetrabromonaphthalene diimide.
N,N'-Bis(n-octyl)-2,3,6,7-tetrabromonaphthalene diimide (TBNDI) was synthesized by a new imidization reaction and characterized by HRMS, (1)H NMR, (13)C NMR, elemental analyses, FT-IR, UV-vis, and single-crystal X-ray analysis. The TBNDIs are the key precursors for the synthesis of core-tetrasubstituted-naphthalene diimides.


Strategies for the identification of precocity in zebu beef cattle based on mixed nonlinear models and multivariate approach.
The use of mixed nonlinear models reduces the residual variance by including random effects, thereby improving the estimates in growth curves. Therefore, we tested distinct mixed nonlinear models (Richards, Brody, Gompertz, Logistic, and Von Bertalanffy) to model the growth curves of Zebu cattle herds raised on pasture in Brazil. In addition, we evaluated the diversity among breeds using hierarchical cluster multivariate analysis (full linkage) based on asymptotic weight (A), maturity rate (K), absolute growth rate (AGR), and absolute maturity rate (AMR) adjusted to 205, 365, 550, and 730 days of age. Body weight data from 311,834 males and females of Guzerat, Nellore, Tabapuã, and Polled Nellore breeds provided by the Brazilian Association of Zebu Breeders were used. The Brody model considering breed-sex fixed and animal random effects was the most suitable to describe the growth in the four breeds. The Guzerat and Tabapuã males showed increased precocity (higher K values) when compared to polled Nellore and Nellore males, which were characterized by higher A and AMR values. Females were more precocious than males (high K and low A values), particularly within Tabapuã and Guzerat breeds, respectively. Regardless of sex, the highest AGR values were observed from weaning up to 2 years of age in Tabapuã and Guzerat breeds. The cluster analyses revealed two groups: (1) Polled Nellore and Nellore males with high A, AGR_205, AGR_365, AGR_550, and AGR_730 values, represented by large adult animals, and (2) males and females of Guzerat and Tabapuã, characterized as animals of increased precocity. A subgroup encompassing males of Guzerat and Tabapuã was also observed, with intermediate values for all parameters. This information is useful to help breeders and producers in strategies for feeding management and defining the most precocious beef cattle breed to increase the economic gains in pasture-based raising systems.


Brackish habitat dictates cultivable Actinobacterial diversity from marine sponges.
Bacterial communities associated with marine invertebrates such as sponges and ascidians have demonstrated potential as sources of bio-medically relevant small molecules. Metagenomic analysis has shown that many of these invertebrates harbor populations of Actinobacteria, many of which are cultivable. While some populations within invertebrates are transmitted vertically, others are obtained from the environment. We hypothesized that cultivable diversity from sponges living in brackish mangrove habitats have associations with Actinobacterial populations that differ from those found in clear tropical waters. In this study, we analyzed the cultivable Actinobacterial populations from sponges found in these two distinct habitats with the aim of understanding the secondary metabolite potential. Importantly, we wanted to broadly evaluate the potential differences among these groups to guide future Actinobacterial collection strategies for the purposes of drug discovery.


[Functional IgG subclass determinations in patients with suspected humoral immune defects using the LIBA technique].
In patients with recurrent infections, "intrinsic" asthma and lymphoma the specific binding capacity of IgG subclass 2 against pneumococcus was determined by line-immuno-binding-assay (LIBA). The results show that LIBA represents a simple and specific test system suitable as diagnostic parameter in patients with a suspected humoral defect.


HERQ-9 Is a New Multiplex PCR for Differentiation and Quantification of All Nine Human Herpesviruses.
Infections with the nine human herpesviruses (HHVs) are globally prevalent and characterized by lifelong persistence. Reactivations can potentially manifest as life-threatening conditions for which the demonstration of viral DNA is essential. In the present study, we developed HERQ-9, a pan-HHV quantitative PCR designed in triplex reactions to differentiate and quantify each of the HHV-DNAs: (i) herpes simplex viruses 1 and 2 and varicella-zoster virus; (ii) Epstein-Barr virus, human cytomegalovirus, and Kaposi's sarcoma-associated herpesvirus; and (iii) HHV-6A, -6B, and -7. The method was validated with prequantified reference standards as well as with mucocutaneous swabs and cerebrospinal fluid, plasma, and tonsillar tissue samples. Our findings highlight the value of multiplexing in the diagnosis of many unsuspected, yet clinically relevant, herpesviruses. In addition, we report here frequent HHV-DNA co-occurrences in clinical samples, including some previously unknown. HERQ-9 exhibited high specificity and sensitivity (LOD95s of ∼10 to ∼17 copies/reaction), with a dynamic range of 101 to 106 copies/μl. Moreover, it performed accurately in the coamplification of both high- and low-abundance targets in the same reaction. In conclusion, we demonstrated that HERQ-9 is suitable for the diagnosis of a plethora of herpesvirus-related diseases. Besides its significance to clinical management, the method is valuable for the assessment of hitherto-unexplored synergistic effects of herpesvirus coinfections. Furthermore, its high sensitivity enables studies on the human virome, often dealing with minute quantities of persisting HHVs.IMPORTANCE By adulthood, almost all humans become infected by at least one herpesvirus (HHV). The maladies inflicted by these microbes extend beyond the initial infection, as they remain inside our cells for life and can reactivate, causing severe diseases. The diagnosis of active infection by these ubiquitous pathogens includes the detection of DNA with sensitive and specific assays. We developed the first quantitative PCR assay (HERQ-9) designed to identify and quantify each of the nine human herpesviruses. The simultaneous detection of HHVs in the same sample is important since they may act together to induce life-threatening conditions. Moreover, the high sensitivity of our method is of extreme value for assessment of the effects of these viruses persisting in our body and their long-term consequences on our health.


Effects of the treatment with glibenclamide, an ATP-sensitive potassium channel blocker, on intestinal ischemia and reperfusion injury.
Intestinal ischemia and reperfusion injury is dependent on the recruitment and activation of neutrophils. Glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker, has been shown to suppress neutrophil migration and chemotaxis during acute inflammatory responses by a mechanism dependent on its K(ATP) channel blocking activity. In the present study, we evaluated whether the treatment with glibenclamide prevented local, remote and systemic injury following reperfusion of the ischemic superior mesenteric artery in rats. The artery was made ischemic for a period of 30 or 120 min followed by 30 (mild I/R) or 120 (severe I/R) min of reperfusion, respectively. Glibenclamide (0.8 to 20 mg/kg) or vehicle was administered subcutaneously 40 min prior to the reperfusion. Glibenclamide dose-dependently inhibited the reperfusion-associated increase in vascular permeability and neutrophil accumulation in mild I/R. In the severe injury model, glibenclamide inhibited inflammatory parameters, as assessed by Evans blue extravasation, neutrophil influx and haemoglobin content, and the increase in TNF-alpha (tumor necrose factor-alpha) and IL (interleukin)-6 levels in the intestine and lung. The drug did not affect the increase in IL-1beta and IL-10 levels. TEA, a nonselective potassium channel blocker, also inhibited reperfusion injury in both intestine and lungs of animals submitted to mild and severe I/R. Our experiments suggest a role for K(ATP) channels in mediating neutrophil influx and consequent reperfusion-associated injury in rats. The lack of effect of these drugs on the reperfusion-associated hypotension and lethality may limit their usefulness after severe reperfusion injury.


Efficacy of Soft Contact Lenses for Myopia Control: A Systematic Review.
To summarize and analyze critically the scientific evidence focused on the effectiveness of the use of hydrophilic contact lenses (HCLs) in myopia control, as well as their impact on visual quality and the involvement on the accommodative and binocular function. This systematic review was developed selecting all original studies which evaluated HCLs for myopia control with follow-up of at least 1 year. Eligible randomized controlled trials (RCTs) were retrieved from PubMed MEDLINE and Scopus. Methodological quality of the studies was assessed using the Critical Appraisal Skills Programme (CASP) for RCTs. The search provided a total of 276 articles, selecting 13 according to the inclusion and exclusion criteria. The majority of studies evaluating the effectiveness of HCL showed a good efficacy in myopia progression, providing a good quality of vision. The quality of these studies was found to be suitable according to the CASP tool. The accommodative and binocular function with these lenses was evaluated in few studies, reporting a trend to an increase in the accommodative response and exophoria in near vision, while maintaining good level of stereopsis. Aberrometry and pupillometry were only studied in one trial, in which the authors did not find changes in these variables after the use of a myopia control HCL. There is a strong evidence about the effectiveness of different HCLs designs for slowing down myopia progression in children, providing all of them good levels of visual quality. However, there is still poor evidence about changes in accommodation and binocular function, as well as in pupil size and aberrometry with myopia control HCLs, being necessary more studies focused on this issue.


Benzothiazoles: how relevant in cancer drug design strategy?
Heterocyclic compounds, analogs and derivatives have attracted attention due to their diverse biological and pharmacological properties. Benzoheterocycles such as benzothiazoles, benzimidazoles and benzoxazoles are constituents of many bioactive heterocyclic compounds, having wider range of applications. They have been extensively studied for their biological activities, and can serve as unique and versatile scaffolds for drug design. The benzothiazole, in the family of heterocyclic compounds has assumed special significance in synthetic chemistry, pharmaceutical chemistry as well as in clinical applications because of its anti-tumor properties. This review is organized in the following ways. It begins with brief introduction on the chemical diversity of synthetic analogs of benzothiazole. After this, drug design strategy and mechanisms of action through its diverse biological targets in which benzothiazole and its derivatives display their anticancer activity are discussed. It ends with the metabolism pattern of benzothiazole and its analogs. Analysis of the structure-activity relationships (SAR), quantitative structure-activity relationships (QSAR) as well as on docking studies of this family of compounds highlights the potential that may lead to the development of novel anticancer agents. Such relationships will definitely create lot of interest among the researchers to synthesize optimized variety of benzothiazole derivatives and to screen them for their anticancer activity.


Sleep disordered breathing in chronic obstructive pulmonary disease.
We prospectively studied sleep disordered breathing in 50 consecutive patients (39 males) with chronic obstructive pulmonary disease (COPD) with chronic respiratory failure (CRF) (n=33) and without CRF (n=17) by performing polysomnography. Patients with CRF had a lower mean nocturnal oxygen saturation (SaO2 %) (88.6+/-6.7 vs. 96.3+/-0.8; p=0.0001) and a lower minimal nocturnal SaO2 (73.6+/-12.0 vs. 84.3+/-7.3; p=0.002) compared to those without CRF, suggesting that patients with CRF tend to have more severe drops in nocturnal SaO2. Patients with CRF also had a lower FEV1 (% predicted) (p=0.01) and PEFR (% predicted) (p=0.031) compared to those without CRF suggesting an indirect relation to the oxygen saturation. Other pulmonary functions were comparable between both the groups. Among patients with and without CRF, the total sleep time (minutes); the rapid eye movement (REM) stage (% of total sleep time); the non-rapid eye movement (NREM) stage (% of total sleep time) were comparable (p=NS). Only three of the 50 patients with COPD had a significant (>5) apnea-hypopnea index (AHI) (total no. of apneas + total no. of hypopneas/ total sleep time [(hours) = AHI] and these three patients had a mean BMI = 27.7 which was higher than the mean BMI of the whole group (21.1). The AHI was comparable in patients with and without respiratory failure. Multiple regression analysis revealed a positive correlation between AHI and the neck circumference (r=0.41; p=0.005) and BMI (r=0.31; p=NS). There was a small but statistically insignificant negative correlation between AHI and neck length (r= -0.28; p=NS). We conclude that, BMI per se contributes to the AHI and nocturnal desaturation in patients with COPD.


Unified preserving properties of kinetic schemes.
The kinetic theory provides a physical basis for developing multiscale methods for gas flows covering a wide range of flow regimes. A particular challenge for kinetic schemes is whether they can capture the correct hydrodynamic behaviors of the system in the continuum regime (i.e., as the Knudsen number ε≪1) without enforcing kinetic scale resolution. At the current stage, the main approach to analyze such a property is the asymptotic preserving (AP) concept, which aims to show whether a kinetic scheme reduces to a solver for the hydrodynamic equations as ε→0, such as the shock capturing scheme for the Euler equations. However, the detailed asymptotic properties of the kinetic scheme are indistinguishable when ε is small but finite under the AP framework. To distinguish different characteristics of kinetic schemes, in this paper we introduce the concept of unified preserving (UP) aiming at assessing asymptotic orders of a kinetic scheme by employing the modified equation approach and Chapman-Enskon analysis. It is shown that the UP properties of a kinetic scheme generally depend on the spatial and temporal accuracy and closely on the interconnections among three scales (kinetic scale, numerical scale, and hydrodynamic scale) and their corresponding coupled dynamics. Specifically, the numerical resolution and specific discretization of particle transport and collision determine the flow physics of the scheme in different regimes, especially in the near continuum limit. As two examples, the UP methodology is applied to analyze the discrete unified gas-kinetic scheme and a second-order implicit-explicit Runge-Kutta scheme in their asymptotic behaviors in the continuum limit.


[Histomorphology and immunopathology of granulomatous inflammation].
Every inflammation has its morphological substrate, however, not every morphological substrate is specific for a particular disease. On one side, this is due to the limited reaction spectrum of the organism, on the other side, to the fact that completely different etiological agents are able to activate the same pathomechanism. Since this holds true for granuloma formation also, the term "specific inflammation" has to be restricted considerably today. On the other hand, recent progress in the field of mediators of inflammation frequently permits a pathogenetic classification of granulomatous inflammatory processes - even before the etiology has been clarified (e.g. Morbus Boeck). In addition, the possibility to identify "granuloma cells", in particular macrophage- and lymphocyte-subpopulations, in situ by immunohistological means (by monoclonal antibodies to surface markers) expands the scope of conventional histomorphological techniques significantly.


[Local registry of pacemakers implantations: proposals to decrease the infectious risk].
The complications of definitive cardiac stimulation must not be forgotten or sub estimate. The aim of our Registry is to compare the complications of the implantation of a pacemaker in the national and international literature. The assessment of our professional practices has been achieved. We suggest improved procedures. The late complications are not exactly known.


[Analysis of MUT gene mutations and prenatal diagnosis for 20 pedigrees affected with isolated methylmalonic aciduria].
To analyze MUT gene variants among 20 pedigrees affected with isolated methylmalonic aciduria by Sanger sequencing. Peripheral blood samples were collected from the 20 probands and their parents. Following DNA extraction, the coding regions of the MUT gene were subjected to PCR amplification and Sanger sequencing. For 9 pedigrees, chorionic villus sampling was performed for prenatal genetic diagnosis. Nineteen variants were detected in the 20 pedigrees, with the most common ones including c.323G to A (p.Arg108His), c.1106G to A (p.Arg369His), c.729_730insTT(p.D244Lfs*39), and c.1107dupT (p.T370Yfs*22). Three variants were not reported previously, which included a small-scale deletion c.920_923delTCTT (p.F307Sfs*6) and two missense mutations c.419T to C (p.Leu140Pro) and 613G to A (p.Glu205Lys). For 9 pedigrees undergoing prenatal diagnosis, 1 fetus was normal, three were found to carry heterozygous mutations, while the remaining 5 fetuses have carried compound heterozygous mutations or homozygous mutations. Three novel variants of the MUT gene have been identified.


Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis.
We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.


Dysthymia in neurological disorders.
Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders. The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders.


An agonistic TrkB mAb causes sustained TrkB activation, delays RGC death, and protects the retinal structure in optic nerve axotomy and in glaucoma.
Brain-derived neurotrophic factor (BDNF) receptors TrkB and p75(NTR) are expressed in the retina. However, exogenous BDNF does not provide retinal ganglion cells (RGCs) with long-lasting neuroprotection in vivo during optic nerve axotomy or in glaucoma rat models of neurodegeneration. The authors set out to answer the hypothesis that a selective TrkB agonist might afford more efficient neuroprotection. Animal models of acute neurodegeneration (complete optic nerve axotomy) and chronic neurodegeneration (ocular hypertension, glaucoma) were used. After intravitreal delivery of test agents or controls, surviving RGCs were quantified. Transient or sustained activation of TrkB receptors in vivo was quantified by Western blot analysis retinal samples for TrkB-phosphotyrosine. Time-dependent changes to the neuronal retinal layers were quantified longitudinally by Fourier domain-optical coherence tomography. The authors show that a selective TrkB agonist caused long-lived TrkB activation and significantly delayed RGC death in these models of acute and chronic retinal injury in vivo. Importantly, using noninvasive retinal imaging, they also show that a selective TrkB agonist caused preservation of the retinal structure in both animal models, with maintenance of the layers comprising neurons and neuronal fibers. In animal models of acute and chronic neurodegeneration, a TrkB agonist affords long-lasting neuroprotection by causing sustained TrkB activation. The use of structural end points could have prognostic value to evaluate neuroprotection. This work contributes to the understanding of neurotrophic mechanisms underlying RGC death in glaucoma and optic nerve axotomy.


Limitations of learning in the proboscis reflex of the flower visiting syrphid fly Eristalis tenax.
Flower visiting Eristalis hoverflies feed on nectar and pollen and are known to rely on innate colour preferences. In addition to a preference for visiting yellow flowers, the flies possess an innate proboscis reflex elicited by chemical as well as yellow colour stimuli. In this study we show that the flies' proboscis reflex is only triggered by yellow colour stimuli and not altered by conditioning to other colours. Neither in absolute nor in differential conditioning experiments the flies learned to associate other colours than yellow with reward. Even flies that experienced only blue nutrients during the first four days after hatching could not be trained to extend the proboscis towards other colours than yellow. The natural targets of the visually elicited proboscis reflex are yellow pollen and yellow anthers. One consequence of our findings is that flowers might advertise nectar and pollen rewards for Eristalis hoverflies by a yellow colour hue of nectar guides, nectaries, stamens or pollen. Alternatively, flowers might protect their pollen against Eristalis by displaying other pollen colours than yellow or direct flies by yellow pollen-mimicking floral guides towards nectar resources. Testing the proboscis extension of various hoverfly species in the field showed that only Eristalis hoverflies possess the proboscis reflex elicited by yellow colour hues.


A nurse researcher's guide to reflexive interviewing.
In a wider doctoral study related to unfavourable experiences of nursing students studying abroad, the researcher undertook a reflexive interview to reduce the potential for bias. To discuss a method for conducting reflexive interviews and recommend their use to nurse researchers. A reflexive interview was undertaken to reduce bias and pilot an original interview instrument. A senior researcher interviewed the researcher using original questions that would be used to interview participants in the wider doctoral study. The questions required validation and therefore the reflexive interview acted as a pilot. This process acted as a learning opportunity for the researcher, improving interview skills such as keeping in mind the respondent's feelings, paying attention to the ratio of eye-contact to note-taking and consciously slowing the speed of asking questions. Biases were revealed through the listening guide, a reflexive method of analysis underpinned by experiential education. These included the beliefs that sending institutions insufficiently prepare nursing students to study abroad, such trips may not benefit the host locations and students study abroad merely to have an adventure. The reflexive interview exposed implicit biases and enabled the researcher to pilot an original interview instrument. The recommendation for this reflexive method is justified in that it enables introspection, reduces bias and encourages social transformation.


Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.
There is some evidence supporting an association between Cullin-5 (CUL5) and cancer, but no research using pan-cancer analysis has been conducted previously. We therefore investigated the oncogenic role of CUL5 in 33 tumors from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Many cancers reduce CUL5 levels, and the prognosis of certain cancers is vitally linked with CUL5 expression. CUL5 expression is associated with CD8 + T-cell infiltration levels in uveal melanomas and head and neck squamous cell carcinomas, and we observed a positive relationship between CUL5 and Tcm (T central memory) cells, and a negative relationship between T helper (Th) cells and pDC (plasmacytoid DC). CUL5 had negative associations with NK cells, NK CD56bright cells, NK CD56dim cells, Tregs, cytotoxic cells, and Th17 cells. Functions relating to protein processing and ubiquitin were included in the CUL5 functional mechanisms. The top 100 genes that are most strongly related to CUL5 were identified, and enrichment analysis indicated that the biological process with the closest relationship was neddylation, related pathways included the TGF-beta signaling pathway and intracellular receptor signaling pathway. CUL5 is related to biological cell behaviors such as chromosome segregation and positive regulation of chromosome organization. As the first study to perform a pan-cancer analysis of CUL5, the present findings will improve the understanding of the oncogenic role of CUL5 in different tumors.


Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial.
Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators' posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants' posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and social support. Inactive discussion in the Facebook social group might have attributed to the lower effectiveness. Clinicaltrials.gov NCT02007369; https://clinicaltrials.gov/show/NCT02007369 (Archived by WebCite® at http://www.webcitation.org/6c3RbltQG).


Fecal incontinence and rectal prolapse.
The majority of patients who suffer from full-thickness prolapse can be treated successfully and safely. The small proportion who remain incontinent of feces after correction of prolapse may at a later date be helped by postanal repair. If dietary indiscretion and abnormal patterns of defecation are major etiologic factors in this condition, then measures to improve dietary and defectory habits must be instituted mainly to prevent further problems after the deformity has been cured surgically. There seems no doubt that following rectopexy there is an increased tendency to constipation.


Odds, challenges and new approaches in the control of helminthiasis, an Asian study.
The time is passing, and the worms are still a major struggle for local people in Asian countries, especially the less empowered and in a situation of social vulnerability. We are working in the field in Laos, Thailand, and the Philippines where the usual control programs based only on human treatment are partially effective. Areas with mass drug administration could diminish, but not eliminate STHs of endemic areas. The persistence of helminthic NTDs in the environment and animal hosts makes the eradication a very difficult task. Great changes in the landscapes of endemic areas, such as construction of dams, can change the fauna and the lifestyle of local people. Those changes can improve infrastructure, but it can also lead to social vulnerability. The challenge, then, is to conceive new and directed control programs for helminthiasis based on multi- and transdisciplinary approaches diminishing the health gap in a globalized world. In this short review, we summarize the actual scenario concerning the main helminths in Southeast Asia and how an environmental DNA approach and the use of GIS could contribute to surveillance and control programs.


Chiral binaphthyl-derived amine-thiourea organocatalyst-promoted asymmetric Morita-Baylis-Hillman reaction.
[reaction: see text] A new bifunctional binaphthyl-derived amine thiourea organocatalyst has been developed to promote enantioselective Morita-Baylis-Hillman reaction of cyclohexenone with a wide range of aldehydes. The process, catalyzed by the amine thiourea, affords synthetically valuable chiral allylic alcohol building blocks in high yields and high enantioselectivities.


Two-dimensional gel electrophoresis can be used to examine chromatographic effluent fractions from displacement column chromatography.
We show how two-dimensional gel electrophoresis can be used to monitor protein components in effluent fractions from a displacement column. A minor protein in human serum, of interest in studies on psoriasis and highly enriched by using carboxymethyldextrans as displacers on DEAE-Sephacel, was easily detected in the effluent fractions with the two-dimensional gel method because its concentration was sufficiently high and there was no interference by the carboxymethyldextrans or salt.


BoLA class I charge heterogeneity reflects the expression of more than two loci.
Internationally recognized allo-antisera in lymphocyte microcytotoxicity assays are thought to detect allelic products of a single highly polymorphic class I locus. A recent report suggested that two bovine lymphocyte antigen (BoLA) class I loci are expressed at the protein level. However, 1D-IEF analysis of BoLA class I molecules reveals multi-band patterns which cannot be reconciled with the reported number of loci. The aim of this study was to investigate the origins of the charge diversity of BoLA class I molecules observed using 1D-IEF. BoLA class I molecules appear to be glycosylated at a single N-linked position with a complex type carbohydrate moiety which has up to three terminal sialic acid residues. Class I molecules immunoprecipitated from resting bovine PBL are not phosphorylated. Neither modification is responsible for the observed charge heterogeneity. Peptide mapping reveals that different BoLA charge variants have distinct digestion patterns. Furthermore, a number of different polypeptides are associated with each serological specificity. These polypeptides appear to be encoded by different loci which exist in linkage disequilibrium. The number of charge variants with different peptide maps indicates that the BoLA system has a minimum of three class I loci expressed at the protein level.


Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases.
Our previous studies have indicated that chronic treatment with 1-[(2-dimethylamino) ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), an angiotensin-converting enzyme 2 (ACE2) activator, reverses hypertension-induced cardiac and renal fibrosis in spontaneously hypertensive rats (SHRs). Furthermore, XNT prevented pulmonary vascular remodelling and right ventricular hypertrophy and fibrosis in a rat model of monocrotaline-induced pulmonary hypertension. The aim of this study was to determine the mechanisms underlying the protective effects of XNT against cardiac fibrosis. Hydroxyproline assay was used to measure cardiac collagen content in control and XNT-treated (200 ng kg(-1) min(-1) for 28 days) SHRs. Cardiac ACE2 activity and protein levels were determined using the fluorogenic peptide assay and Western blot analysis, respectively. Extracellular signal-regulated kinases (ERKs; p44 and p42) and angiotensin II type 1 (AT(1)) receptor levels were quantified by Western blotting. Cardiac ACE2 protein levels were ∼15% lower in SHRs compared with Wistar-Kyoto control animals (ACE2/glyceraldehyde 3-phosphate dehydrogenase ratio: Wistar-Kyoto, 1.00 ± 0.02 versus SHR, 0.87 ± 0.01). However, treatment of SHRs with XNT completely restored the decreased cardiac ACE2 levels. Also, chronic infusion of XNT significantly increased cardiac ACE2 activity in SHRs. This increase in ACE2 activity was associated with decreased cardiac collagen content. Furthermore, the antifibrotic effect of XNT correlated with increased cardiac angiotensin-(1-7) immunostaining, though no change in cardiac AT(1) protein levels was observed. The beneficial effects of XNT were also accompanied by a reduction in ERK phosphorylation (phospho-ERK/total ERK ratio: Wistar-Kyoto, 1.00 ± 0.04; control SHR, 1.46 ± 0.25; treated SHR, 0.86 ± 0.02). Our observations demonstrate that XNT activates cardiac ACE2 and inhibits fibrosis. These effects are associated with increases in angiotensin-(1-7) and inhibition of cardiac ERK signalling.


Coulomb drag as a probe of the nature of compressible States in a magnetic field.
Magnetodrag reveals the nature of compressible states and the underlying interplay of disorder and interactions. At nu=3/2 clear T(4/3) dependence is observed, which signifies the metallic nature of the N=0 Landau level. In contrast, drag in higher Landau levels reveals an additional contribution, which anomalously grows with decreasing T before turning to zero following a thermal activation law. The anomalous drag is discussed in terms of electron-hole asymmetry arising from disorder and localization, and the crossover to normal drag at high fields as due to screening of disorder.


Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment.
(1) Background: Prostate cancer is the second most common cancer in men, with androgen suppression as the standard treatment. Despite initially responding to castration, most metastatic prostate cancer patients eventually experience progression. In these cases, Radium-223 is the chosen treatment. We hypothesized that the immunophenotype of circulating leukocytes conditions the response to Radium-223 treatment. (2) Material and Methods: In this prospective study, we collected peripheral blood from twelve mCRPC patients and nine healthy donors before (baseline) and during treatment with Radium-223. Immunophenotyping and the percentages of leukocyte-platelet complexes were determined by flow cytometry. The increments or decrements of leukocyte subsets between the baseline and the second Radium-223 injection were also calculated. (3) Results: At baseline, the mCRPC patients had a lower percentages of CD4+ T cells and B cells and higher percentages of NK and neutrophils than the HDs. In addition, they had more OX40+ CD4+ T cells, PD-L1+ CD8low cells, PD-L1+ B cells, PD-L1+ NK cells, and monocyte-platelet complexes than the HDs. Moreover, patients with slow and fast progression had different percentages of PD-L1+ CD8+ T cells. In particular, slow progression patients underwent an increment of PD-L1+ CD8+ T cells after two cycles of Radium-223. (4) Conclusions: The characterization of circulating immune cells before initiating Radium-223 treatment could become a non-invasive indicator of the response.


Preventive effect of fluvastatin on ulcerative colitis-associated carcinogenesis in mice.
An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis (UC), which displays a cycle of recurrence-remission in the colorectal mucosa. Fluvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, is a hypocholesterolemic agent effective in animals and humans. Repeated administration of 3% dextran sulfate sodium subsequent to a single intraperitoneal injection of azoxymethane induces chronic UC resulting in an increased incidence of high-grade dysplasia and submucosal-invasive adenocarcinomas in the mouse colorectum. The effects of fluvastatin as an antioxidant on colorectal carcinogenesis in mice with UC were investigated. Treatment with fluvastatin in mice with UC abolished the anemia caused by colorectal carcinogenesis, and markedly lowered plasma lipid levels resulting in a reduction of colitis and carcinogenesis, shown by inhibition of the decrease in colorectal length, the increased number of foci of gland loss with inflammatory cell infiltration indicating the severity of UC and incidence of colorectal dysplasia, respectively, with a reduction in anti-8-hydroxy-2'-deoxyguanosine (8-OHdG) antibody (a biological marker of in vivo oxidative DNA damage)-positive cells of the colorectal mucosa and the activity of the DNA-synthesizing enzyme thymidine kinase in colorectal tissues.


Slow dynamics and nonergodicity of the bosonic quantum East model in the semiclassical limit.
We study the unitary dynamics of the bosonic quantum East model, a kinetically constrained lattice model which generalizes the quantum East model to arbitrary occupation per site. We consider the semiclassical limit of large (but finite) site occupancy so that the dynamics is approximated by an evolution equation of the Gross-Pitaevskii kind. This allows us to numerically study in detail system sizes of hundreds of sites. Like in the spin-1/2 case, we find two dynamical phases, an active one of fast thermalization and an inactive one of slow relaxation and the absence of ergodicity on numerically accessible timescales. The location of this apparent ergodic to nonergodic transition coincides with the localization transition of the ground state. We further characterize states which are nonergodic on all timescales in the otherwise ergodic regime.


Hiccups associated with reflux esophagitis.
A 67-yr-old man with protracted hiccups, as well as reflux esophagitis and a stricture, was found to have heartburn and water brash only during episodes of hiccups. Intraesophageal pH monitoring showed acid gastroesophageal reflux increased during these episodes and decreased with cessation of hiccups. After all attempts failed to relieve his hiccups, a Nissen fundoplication relieved heartburn, healed the esophagitis, and stopped excessive reflux of acid gastric juice, even though the hiccups persisted. These observations showed that reflux provoked by prolonged hiccups could either have adversely affected preexistent reflux esophagitis and stricture or conceivably could have caused these complications.


Urinary excretion of the enantiomers of 1-methyl-1,2,3,4-tetrahydro-beta-carboline in unequal abundance implies enzymatic metabolism in man.
1-Methyl-1,2,3,4-tetrahydro-beta-carboline, a condensation product of tryptamine and acetaldehyde, is one of the neuropharmacologically active alkaloids in mammals. Its enantiomers excreted in human urine were independently analyzed by gas chromatography-negative ion chemical ionization mass spectrometry. Mass fragmentograms of the racemic 1-methyl-1,2,3,4-tetrahydro-beta-carboline offered two peaks with (S)-(-)- and (R)-(+)-configurations which were eluted in this retention order. When the racemic tetradeuterated 1-methyl-1,2,3,4-tetrahydro-beta-carboline was orally administered to a human subject, the urinary tetradeuterated enantiomers were found to be of unequal abundance. The deuterated (R)-(+)-1-methyl-1,2,3,4-tetrahydro-beta-carboline was predominantly excreted in human urine about 3-times over the deuterated (S)-(-)-one. The stereoselective difference in the urinary excretion of 1-methyl-1,2,3,4-tetrahydro-beta-carboline administered exogenously implies that it is enzymatically metabolized, but not that its biosynthesis is associated with an enzymatic reaction.


Patient portal interventions: a scoping review of functionality, automation used, and therapeutic elements of patient portal interventions.
We sought to understand the objectives, targeted populations, therapeutic elements, and delivery characteristics of patient portal interventions. Following Arksey and O-Malley's methodological framework, we conducted a scoping review of manuscripts published through June 2022 by hand and systematically searching PubMed, PSYCHInfo, Embase, and Web of Science. The search yielded 5403 manuscripts; 248 were selected for full-text review; 81 met the eligibility criteria for examining outcomes of a patient portal intervention. The 81 articles described: trials involving comparison groups (n = 37; 45.7%), quality improvement initiatives (n = 15; 18.5%), pilot studies (n = 7; 8.6%), and single-arm studies (n = 22; 27.2%). Studies were conducted in primary care (n = 33, 40.7%), specialty outpatient (n = 24, 29.6%), or inpatient settings (n = 4, 4.9%)-or they were deployed system wide (n = 9, 11.1%). Interventions targeted specific health conditions (n = 35, 43.2%), promoted preventive services (n = 19, 23.5%), or addressed communication (n = 19, 23.4%); few specifically sought to improve the patient experience (n = 3, 3.7%). About half of the studies (n = 40, 49.4%) relied on human involvement, and about half involved personalized (vs exclusively standardized) elements (n = 42, 51.8%). Interventions commonly collected patient-reported information (n = 36, 44.4%), provided education (n = 35, 43.2%), or deployed preventive service reminders (n = 14, 17.3%). This scoping review finds that most patient portal interventions have delivered education or facilitated collection of patient-reported information. Few interventions have involved pragmatic designs or been deployed system wide. The patient portal is an important tool in real-world efforts to more effectively support patients, but interventions to date rely largely on evidence from consented participants rather than pragmatically implemented systems-level initiatives.


Metagenomic analysis of the intestinal microbiome in goats on cactus and Salicornia-based diets.
The Peruvian coast is characterized by its arid and saline soils, the cactus being an alternative for arid soils and Salicornia for saline soils. Therefore, it is necessary to develop nutrition based on the intestinal microbiota in goats. To identify the intestinal microbiota in goats through a metagenomic analysis. In this study, goats and kids were randomly selected and fed cacti and Salicornia as potential forage species compared to native grass to study the changes in the microbiota using massive sequencing using the 16S rRNA gene as a marker. The sequencing results showed the taxonomic levels of Bacteroidetes and Firmicutes at the phylum level as the most abundant in creole goats' microbiome, varying from 18% to 36% and 47% to 66%, respectively. At the genus level, variants of the genus Ruminococcaceae stand out, related to cellulose degradation, as the most dominant in all samples, followed by Christensenellaceae, Rikenellaceae, and Prevotellaceae. Also, the genus Akkermansia appeared in greater abundance in kids fed with cactus, being necessary for being related to the intestinal mucosa's health and avoiding the adhesion of pathogens to the intestinal epithelium. These microbiota changes based on diets with high fiber content are necessary to understand the adaptation of this species to favorable dietary changes.


Electrically Activated Conductivity and White Light Emission of a Hydrocarbon Nanoring-Iodine Assembly.
Numerous otherwise difficult applications have been realized with materials, the chemical/physical properties of which can be controlled by external stimuli such as heat, pressure, photo-irradiation, and voltage bias. However, the complexity of design and the lack of easy-to-conduct synthetic methods make the creation of on-demand stimuli responsive materials a formidable task. Here we report an electric-stimuli-responsive multifunctional material, [10]CPP-I: crystalline assembly of a hydrocarbon nanoring ([10]cycloparaphenylene: [10]CPP) as an "electro-responsive porous host" and iodine as a "potentially functional molecule". Through applying electric stimulus, [10]CPP-I turned to exhibit two attractive properties: electronic conductivity and white light emission. We revealed that electric stimuli trigger the cascade formation of polyiodide chains inside the [10]CPP assembly through charge transfer, leading to the emergence of these properties. This "responsive porous host" approach is expected to be applicable for different stimuli, and opens the path for devising a generic strategy to the development of stimuli-responsive materials.


[Report of the 2013 data of the Hungarian Vascular Registry].
Nationwide medical databases started to record observations in the 90s. A Hungarian vascular registry was set up in 2002, which processes data of carotid, aneurysm and lower extremity arterial operations. The Hungarian Society for Angiology and Vascular Surgery decided to analyse the data each year. In this article we show the results of the registered carotid, aneurysmal and lower limb operations which were carried out in 2013. Altogether 3916 vascular surgical cases have been registered: 25.36% of cases were related to carotid arteries, 10.11% to aneurysms and 64.53% to lower limb operations. The surgical procedures were acute in 23.9% and they were performed electively in 76.10%. Stent graft implantation was performed in 31.47% of the abdominal aortic aneurysm cases and 68.53% was operated by open surgery. The average maximum diameter of aneurysms was 62.45 ± 12.05 mm. The mortality in aortic aneurysm surgery was 7.57% and 2.06% related to lower extremity surgeries. Carotid surgery has a combined mortality and stroke rate of 2.62%. Registers have been proved to be useful in countries where they are used regularly for decision making. Our best common interest is to maintain a well-established national database.