TNF-α -308 G>A polymorphism and weight gain in patients with schizophrenia under long-term clozapine, risperidone or olanzapine treatment.
Atypical or second-generation antipsychotics (SGAs) are associated with excessive body weight gain (BWG) and other components of metabolic syndrome. Among all SGAs, clozapine and olanzapine are known to cause the most significant weight gain, followed by risperidone and quetiapine. The genetic variant of tumor necrosis factor α (TNF-α), -308 G>A polymorphism (rs1800629), has been implicated in clozapine-induced BWG in several studies. We hypothesized that TNF-α -308 G>A polymorphism has a general effect on SGA-induced BWG. The present study was conducted to examine the association between TNF-α -308 G>A polymorphism and BWG during treatment for schizophrenia using a variety of second generation antipsychotics (SGAs). A total of 500 patients with schizophrenia treated with clozapine (n=275), olanzapine (n=79) or risperidone (n=146) for an average of 49.9 months were recruited. Subjects with an increase in weight of more than 7% from the baseline before the current SGA treatment to the weight at the survey point were defined as having BWG. The association between TNF-α -308 G>A polymorphism and BWG was studied, and the effect of non-genetic factors such as baseline BMI, SGA treatment duration and SGA type on the association was controlled by logistic regression. The results revealed that there was no significant association between BWG and TNF-α -308 G>A polymorphism (GG/GA/AA or GG/GA+AA) in each separate SGA group or collectively. These findings suggest that TNF-α -308 G>A polymorphism does not play a major role in SGA-induced weight gain.


Optimal Allocation of Nursing Resources: An Interview With Robyn Begley, DNP, RN, NEA-BC; Pamela F. Cipriano, PhD, RN, NEA-BC, FAAN; and Todd Nelson, FHFMA, MBA.
Appropriate nurse staffing to provide high-quality care was a hot topic before the pandemic challenged healthcare organizations across the nation. In a report released earlier this year, the subject is explored by 3 coauthors: Robyn Begley, DNP, RN, NEA-BC, chief executive officer of American Organization for Nursing Leadership and chief nursing officer of the American Hospital Association; Pamela F. Cipriano, PhD, RN, NEA-BC, FAAN, University of Virginia School of Nursing Sadie Heath Cabaniss professor and dean and former president of the American Nurses Association; and Todd Nelson, FHFMA, MBA, Healthcare Financial Management Association director of partnership relationships and chief partnership executive. The report was excerpted in the June issue of Nurse Leader and can be read in full at the Healthcare Financial Management Association website. The authors delve into the report's insights, generated by questions from Terese Hudson Thrall, managing editor at the American Organization for Nursing Leadership.


Application of ultra-high performance supercritical fluid chromatography for the determination of carotenoids in dietary supplements.
A quick and simple ultra-high performance supercritical fluid chromatography-photodiode array detector method was developed and validated for the simultaneous determination of 9 carotenoids in dietary supplements. The influences of stationary phase, co-solvent, pressure, temperature and flow rate on the separation of carotenoids were evaluated. The separation of the carotenoids was carried out using an Acquity UPC(2) HSS C18 SB column (150mm×3.0mm, 1.8μm) by gradient elution with carbon dioxide and a 1:2 (v:v) methanol/ethanol mixture. The column temperature was set to 35°C and the backpressure was 15.2MPa. Under these conditions, 9 carotenoids and the internal standard, β-apo-8'-carotenal, were successfully separated within 10min. The correlation coefficients (R(2)) of the calibration curves were all above 0.997, the limits of detection for the 9 carotenoids were in the range of 0.33-1.08μg/mL, and the limits of quantification were in the range of 1.09-3.58μg/mL. The mean recoveries were from 93.4% to 109.5% at different spiking levels, and the relative standard deviations were between 0.8% and 6.0%. This method was successfully applied to the determination of 9 carotenoids in commercial dietary supplements.


[Target organs involvement in arterial hypertension. The role of heredity and environment (study of twins)].
To elucidate relationship between hereditary and environmental factors in development of target organ damage in hypertension. The state of myocardium, central nervous system, blood vessels (including funduscopic examination) was assessed in 64 pairs of mono- and dizygous hypertensive twins (mean age 57.2+/-3.2 years) and clinical and genetic analysis of qualitative and quantitative signs was carried out. Hypertensive twins had similar qualitative features of target organs involvement irrespective of duration of hypertension. Concordance of signs of target organ damage in homozygous twins was more than twice higher than that of same signs in dizygous twin pairs. Left ventricular myocardial mass and intima-media thickness were mainly determined by hereditary factors. Their contribution into overall phenotypic variability of a sign exceeded 70%.


Expert Opinion on Dose Regimen and Therapeutic Drug Monitoring for Long-Term Use of Dalbavancin: Expert Review Panel.
Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment. A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used. After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation. These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings.


Assessment of instructors' readiness for implementing e-learning in continuing medical education in Iran.
E-learning provides new levels of flexibility in learning and teaching. This contribution of e-learning is dependent on the levels of readiness in several critical factors particularly in an educational organization. The purpose of this study was to assess instructors' readiness and to identify the most important factors that affect their readiness in e-learning in CME programs in order to use the effective opportunities that facilitate e-learning in CME programs. A 5-point Likert scale instrument consisting of two domains (technical and pedagogical) was constructed according to four subdomains (knowledge, attitude, skills, and habits) and distributed to 70 faculty members. A factor analysis was employed to extract significant factors. The results revealed that the mean of readiness on e-learning for faculty members was 3.25 ± 0.58 in technical and 3.37 ± 0.49 in pedagogical domains on a 5-point Likert scale (1-5). The factors such as "familiarity with learning management system," "willingness to teach by adopting a new technology," "willingness to use e-learning as a viable alternative," "ability to deliver e-material and to provide e-content for teaching," and "being accustomed to the virtual environment and utilization of the computer and the internet" were extracted on technical readiness domain. In addition, the pedagogical readiness factors were: "familiarity with online teaching principle and method," "willingness to use technology in instruction and material development," "ability to design content for e-material and online course evaluation," and "being accustomed to providing information back up regularly and employing eclectic methods and multiple approaches in teaching." The findings of this study suggest that training should be offered to instructors on a continuous, rather than a one-off basis so that their IT knowledge and skills are upgraded over time. In addition, results indicate that pedagogical innovations are required to develop and implement an effectiveness e-learning program.


Association of SARS-CoV-2 presence in sewage with public adherence to precautionary measures and reported COVID-19 prevalence in Tehran.
Compared to the growing body of literature on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and quantification in sewage, there are limited studies reporting on correlations between the viral loads in sewage and the prevalence of infected patients. The present work is a part of the regular monitoring effort for SARS-CoV-2 in wastewater influents from seven wastewater treatment plants (WWTPs) in Tehran, Iran, starting from late September 2020 until early April 2021. These facilities cover ~64% of the metropolis serving >5000,000 M individuals. The study set out to track the trends in the prevalence of COVID-19 in the community using wastewater based epidemiology (WBE) and to investigate whether these measurements correlate with officially reported infections in the population. Composite sewage samples collected over 16 h were enriched by polyethylene glycol precipitation and the corresponding threshold cycle (Ct) profiles for CDC 'N' and 'ORF1ab' assays were derived through real time RT-qPCR. Monte Carlo simulation model was employed to provide estimates of the disease prevalence in the study area. RNA from SARS-CoV-2 was detectable in 100% ('N' assay) and 81% ('ORF1ab' assay) of totally 91 sewage samples, with viral loads ranging from 40 to 45,000 gene copies/L. The outbreak of COVID-19 positively correlated (R2 = 0.80) with the measured viral load in sewage samples. Furthermore, sewage SARS-CoV-2 RNA loads preceded infections in the population by 1 to 2 days, which were in line with public adherence with and support for government instructions to contain the pandemic. Given the transient presence of human host-restricted infections such as SARS-CoV-2, these results provide evidence for assessment of the effectiveness of coordinated efforts that specifically address public health responses based on wastewater-based disease surveillance against not only COVID-19 but also for future infectious outbreaks.


Effects of Psychological and Social Work Factors on Self-Reported Sleep Disturbance and Difficulties Initiating Sleep.
This prospective cohort study examined previously underexplored relations between psychological/social work factors and troubled sleep in order to provide practical information about specific, modifiable factors at work. A comprehensive evaluation of a range of psychological/social work factors was obtained by several designs; i.e., cross-sectional analyses at baseline and follow-up, prospective analyses with baseline predictors (T1), prospective analyses with average exposure across waves as predictor ([T1 + T2] / 2), and prospective analyses with change in exposure from baseline to follow-up as predictor. Participants consisted of a sample of Norwegian employees from a broad spectrum of occupations, who completed a questionnaire at two points in time, approximately two years apart. Cross-sectional analyses at T1 comprised 7,459 participants, cross-sectional analyses at T2 included 6,688 participants. Prospective analyses comprised a sample 5,070 of participants who responded at both T1 and T2. Univariable and multivariable ordinal logistic regressions were performed. Thirteen psychological/social work factors and two aspects of troubled sleep, namely difficulties initiating sleep and disturbed sleep, were studied. Ordinal logistic regressions revealed statistically significant associations for all psychological and social work factors in at least one of the analyses. Psychological and social work factors predicted sleep problems in the short term as well as the long term. All work factors investigated showed statistically significant associations with both sleep items, however quantitative job demands, decision control, role conflict, and support from superior were the most robust predictors and may therefore be suitable targets of interventions aimed at improving employee sleep.


Small-molecule drugs development for Alzheimer's disease.
Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder with no effective therapeutic drugs currently. The complicated pathophysiology of AD is not well understood, although beta-amyloid (Aβ) cascade and hyperphosphorylated tau protein were regarded as the two main causes of AD. Other mechanisms, such as oxidative stress, deficiency of central cholinergic neurotransmitters, mitochondrial dysfunction, and inflammation, were also proposed and studied as targets in AD. This review aims to summarize the small-molecule drugs that were developed based on the pathogenesis and gives a deeper understanding of the AD. We hope that it could help scientists find new and better treatments to gradually conquer the problems related to AD in future.


Mutations of tumor necrosis factor alpha-responsive serine residues within the C-terminal transactivation domain of human transcription factor REL enhance its in vitro transforming ability.
The human c-rel gene (REL), encoding an NF-kappaB transcription factor, is amplified or mutated in several human B-cell lymphomas and can transform chicken lymphoid cells in vitro. We have previously shown that certain deletions of C-terminal transactivation sequences enhance REL's transforming ability in chicken spleen cells. In this report, we have analysed the effect of single amino-acid changes at select serine residues in the C-terminal transactivation domain on REL's transforming ability. Mutation of either of two TNFalpha-inducible serine residues (Ser460 and Ser471) to nonphosphorylatable residues (alanine, asparagine, phenylalanine) made REL more efficient at transforming chicken spleen cells in vitro. In contrast, mutation of Ser471 to a phosphorylation mimetic aspartate residue impaired REL's transforming ability, even though it increased REL's inherent transactivation ability as a GAL4-fusion protein. Alanine mutations of several other serine residues within the transactivation domain did not substantially affect REL's transforming ability. Transactivation by GAL4-REL fusion proteins containing either transformation enhancing or nonenhancing mutations at serine residues was generally similar to wild-type GAL4-REL. However, more transforming mutants with mutations at either Ser460 or Ser471 differed from wild-type REL in their ability to transactivate certain kappaB-site reporter genes. In particular, the SOD2 promoter, encoding manganese superoxide dismutase, was activated less strongly by the more transforming REL mutant REL-S471N in transient assays, but REL-S471N-transformed chicken spleen cells had increased levels of MnSOD protein as compared to wild-type REL-transformed cells. Taken together, our results show that mutations of certain serine residues can enhance REL's transforming ability in vitro and suggest that these mutations increase REL-mediated transformation by altering REL's ability to modulate the expression of select target genes. Furthermore, phosphorylation of Ser471 may be involved in REL-mediated modulation of transformation-specific target gene expression. Lastly, these results suggest that similar mutations in the REL transactivation domain contribute to the development of certain human B-cell lymphomas.


Preeclampsia and the risk of cardiovascular disease later in life--A review of the evidence.
The aim of the literature review was to explore and quantify the risks associated with preeclampsia (PET) and the incidence of cardiovascular disease (CVD) namely myocardial infarction and stroke in later life. Four databases used were searched: Ovid Medline, maternal and child health, Google Scholar and CINAHL with limits on years (2003-current), English language and full text. Any studies that included preeclampsia during pregnancy and where long term follow-up data were collected. Studies with longitudinal follow-up, cohort studies, females aged 18 years or over and those that included preeclampsia at any gestation in pregnancy were included while randomised controlled trials, short follow-up (i.e. not longitudinal) and studies pre-pregnancy or postpartum (within 6 weeks of birth) were excluded. Seven studies with over 4.93 million participants were identified as meeting the inclusion criteria. These studies demonstrated that PET is a strong marker of future CVD and a history of PET significantly increases the risk of hypertension later in life and subsequently increases the risk of other cardiovascular events in particular ischemic heart disease and stroke (both fatal and non-fatal). Early identification of CVD risk factors is an important public health issue and there needs to be greater awareness of hypertension and PET in pregnancy by both healthcare professionals and pregnant women. The evidence from the literature clearly demonstrates that PET is a risk factor for future CVD and the challenge will be to educate healthcare professionals in particular midwives, nurses, obstetricians and General Practitioners as well as the women with PET so that they can be involved in the long term management of CVD risk factors.


Catalytic, Regioselective 1,4-Fluorodifunctionalization of Dienes.
A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp3 )-F and C(sp3 )-CF3 groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.


STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion.
Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloid-derived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). Mechanistic analyses reveal that STING represses NPC-derived MDSC induction by enhancing SOCS1 expression in both tumor cells and MDSCs. SOCS1 physically interacts with STAT3 through its SH2 domain to prevent STAT3 phosphorylation and dimerization, resulting in reduced MDSC induction via inhibition of GM-CSF and IL-6 production. Notably, reduced tumoral STING expression was found to be significantly associated with a poor prognosis for NPC patients. Our findings reveal a novel mechanism linking STING to tumor microenvironmental cytokine production and MDSC induction.


Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review.
The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon, beginning with precancerous conditions. Among these, adenoma is a direct precursor, because of the dysplastic nature of its cells. However, gastric adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common precancerous condition, in which intestinal metaplasia often occurs. Carcinoma develops in CAG through stages of hyperplasia and dysplasia involving both metaplastic and non-metaplastic glands. Molecular alterations, including replication error and p53 and APC gene mutation and aneuploidy have been found in some of these conditions, confirming their role in carcinogenesis. Carcinomas of the stomach are heterogeneous in cellular composition. Both intestinal and gastric types of cells are found in all types of tumors, indicating the unique characteristics of gastric cancer. Many molecular lesions have been found in gastric carcinomas. Basic changes involve replication errors, telomerase activity, and aberrant CD44 transcripts. Many other changes often show differences in the frequency of their occurrence between the two major histological types of gastric carcinoma: well differentiated versus poorly differentiated, or intestinal type versus diffuse type. The timing and frequency of these changes in the stomach differ from the timing and frequency in colonic carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic research as well as clinical management. To obtain correlation with molecular alterations, the need for detailed pathologic classification of gastric carcinoma is recognized, taking into account its biologic behavior and grades of cell differentiation.The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinomas are unique in their heterogeneity in both cellular composition and molecular changes.


Further evidence for a membrane potential-dependent shape transformation of the human erythrocyte membrane.
The influence of various factors (pH, temperature, sodium gluconate) on the ionic strength-dependent stomatocyte-discocyte-echinocyte transformation of the human erythrocyte membrane was investigated. The results give further evidence for a correlation between shape of erythrocyte membrane and the transmembrane potential of the cells.


Distribution and decline of human pathogenic bacteria in soil after application in irrigation water and the potential for soil-splash-mediated dispersal onto fresh produce.
To improve our understanding of the survival and splash-mediated transfer of zoonotic agents and faecal indicator bacteria introduced into soils used for crop cultivation via contaminated irrigation waters. Zoonotic agents and an Escherichia coli marker bacterium were inoculated into borehole water, which was applied to two different soil types in early-, mid- and late summer. Decline of the zoonotic agents was influenced by soil type. Marker bacteria applied to columns of two soil types in irrigation water did not concentrate at the surface of the soils. Decline of zoonotic agents at the surface was influenced by soil type and environmental conditions. Typically, declines were rapid and bacteria were not detectable after 5 weeks. Selective agar strips were used to determine that the impact of water drops 24-87 μl could splash marker bacteria from soil surfaces horizontal distances of at least 25 cm and heights of 20 cm. Soil splash created by rain-sized water droplets can transfer enteric bacteria from soil to ready-to-eat crops. Persistence of zoonotic agents was reduced at the hottest part of the growing season when irrigation is most likely. Soil splash can cause crop contamination. We report the penetration depths and seasonally influenced declines of bacteria applied in irrigation water into two soil types.


Detergent-induced changes in the mapping of certain enzymes in various cell types of Rita rita. I. Opercular epidermis.
The different cell types in the opercular epidermis of Rita rita when exposed to a synthetic detergent, dodecylbenzene sodium sulfonate in the concentration of 6.9 mg liter-1 (96-hr LC50 of the detergent), had a gradual decrease in the activity of various enzymes responsible for different metabolic processes occurring inside the cell. After a certain period of detergent exposure, the activities of all the enzymes in these cells are completely inhibited.


ECG pattern recognition and classification using non-linear transformations and neural networks: a review.
The most widely used signal in clinical practice is the ECG. ECG conveys information regarding the electrical function of the heart, by altering the shape of its constituent waves, namely the P, QRS, and T waves. Thus, the required tasks of ECG processing are the reliable recognition of these waves, and the accurate measurement of clinically important parameters measured from the temporal distribution of the ECG constituent waves. In this paper, we shall review some current trends on ECG pattern recognition. In particular, we shall review non-linear transformations of the ECG, the use of principal component analysis (linear and non-linear), ways to map the transformed data into n-dimensional spaces, and the use of neural networks (NN) based techniques for ECG pattern recognition and classification. The problems we shall deal with are the QRS/PVC recognition and classification, the recognition of ischemic beats and episodes, and the detection of atrial fibrillation. Finally, a generalised approach to the classification problems in n-dimensional spaces will be presented using among others NN, radial basis function networks (RBFN) and non-linear principal component analysis (NLPCA) techniques. The performance measures of the sensitivity and specificity of these algorithms will also be presented using as training and testing data sets from the MIT-BIH and the European ST-T databases.


Chitin microparticles for the control of intestinal inflammation.
Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known. In this study chitin microparticles (CMPs) or phosphate-buffered saline (PBS) were orally administered to acute and chronic colitis models every 3 days for 6 consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, coculture study, and enteric bacterial analysis in dextran sodium sulfate (DSS)-induced colitis or T-cell receptor alpha (TCRα) knockout chronic colitis models. Histologically, chitin-treated mice showed significantly suppressed colitis as compared with PBS-treated mice in both animal models. The production of interferon-gamma (IFN-γ) was upregulated in the mucosa of chitin-treated mice compared with control mice. The major source of IFN-γ-producing cells was CD4+ T cells. In mouse dendritic cells (DCs) we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced a 7-fold higher amount of IFN-γ in the culture supernatant after being cocultured with DCs and chitin as compared with the control. Proliferation of carboxyfluorescein succinimidyl ester (CFSE)(low) CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared with the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased interleukin (IL)-10-producing cells in noninflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa. CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon.


The Peruvian brothel as sexual dispensary and social arena.
This ethnographic description of a Peruvian brothel suggests that the organization of the brothel is determined to a considerable extent by social considerations as well as sexual needs. The authors describe a temporal arrangement that provides for a separation and differential treatment of two social groupings or classes that patronize the brothel. The wealthier and older clients are provided with sexual services within a setting that might be described as a "macho theater" in which social needs are also allowed expression. The less wealthy classes are served in almost purely biological fashion and can ill-afford within this setting the "macho" practices provided to other more wealthy clients.


Primary non-Hodgkin lymphoma of the vulva.
We report a rare case of non-Hodgkin lymphoma located in the vulva. The diagnosis was supported by the cytological anomalies in material obtained by fine needle aspiration. The tumor was removed with wide excision, and the patient was alive and in good health ten months after surgery.


Telecommunication technologies in high-tech homecare.
The future of critical care nursing will be dependent upon the subspecialty's ability to prepare the high-tech homecare nurse for practice in the next millennium. Client self-management of highly complex interventional therapies will be enabled by the high-tech homecare nurse, who will facilitate the transitioning of critical care nursing to the home setting. Rapidly evolving technologic capabilities will be managed by the high-tech homecare nurse, who will assist in the development of a seamless health care delivery system, where quality of care is maintained in settings beyond the traditional boundaries of the intensive care unit.


Metabolomic differences of exhaled breath condensate among children with and without asthma.
There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community. One hundred and sixty-five Asian children (92 stable asthma and 73 non-asthmatic controls) participating in a population-based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance-based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis. EBC metabolomic signature (lactate, formate, butyrate, and isobutyrate) had an area under the receiver operator characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P < .001) and FEV1 /FVC % predicted (AUC = 0.569; P < .001). The AUC for EBC metabolomic signature was 0.745 in the validation set, which was slightly but not significantly lower than in the testing set (P = .282). We further extrapolated two potentially involved metabolic pathways, including pyruvate (P = 1.67 × 10-3 ; impact: 0.14) and methane (P = 1.89 × 10-3 ; impact: 0.15), as the most likely divergent metabolisms between children with and without asthma. This study provided evidence supporting the role of EBC metabolomic signature to discriminate stable asthma in Asian children in the community, with a discriminative property outperforming conventional clinical tests such as FeNO or spirometry.


Isolation of cold-adapted nitrate-reducing fungi that have potential to increase nitrate removal in woodchip bioreactors.
The aim of this study was to obtain cold-adapted denitrifying fungi that could be used for bioaugmentation in woodchip bioreactors to remove nitrate from agricultural subsurface drainage water. We isolated a total of 91 nitrate-reducing fungal strains belonging to Ascomycota and Mucoromycota from agricultural soil and a woodchip bioreactor under relatively cold conditions (5 and 15°C). When these strains were incubated with 15 N-labelled nitrate, 29 N2 was frequently produced, suggesting the occurrence of co-denitrification (microbially mediated nitrosation). Two strains also produced 30 N2 , indicating their ability to reduce N2 O. Of the 91 nitrate-reducing fungal strains, fungal nitrite reductase gene (nirK) and cytochrome P450 nitric oxide reductase gene (p450nor) were detected by PCR in 34 (37%) and 11 (12%) strains, respectively. Eight strains possessed both nirK and p450nor, further verifying their denitrification capability. In addition, most strains degraded cellulose under denitrification condition. Diverse nitrate-reducing fungi were isolated from soil and a woodchip bioreactor. These fungi reduced nitrate to gaseous N forms at relatively low temperatures. These cold-adapted, cellulose-degrading and nitrate-reducing fungi could support themselves and other denitrifiers in woodchip bioreactors. The cold-adapted, cellulose-degrading and nitrate-reducing fungi isolated in this study could be useful to enhance nitrate removal in woodchip bioreactors under low-temperature conditions.


Cyclooxygenase-2 inhibitor delays fracture healing in rats.
Cyclooxigenase-2 (COX-2) inhibitors have been reported to delay fracture healing. To investigate the major inhibitory period of COX-2 inhibitors in fracture healing, we administrated etodolac, a COX-2-specific inhibitor, to a rat fracture model by altering the period of administration from early to late. After closed fractures had been created at the middle of the femoral shafts in 12-week-old Wister rats, a standardized dose of etodolac was administrated in three ways: group I received it for 3 weeks, group II for just the first week after operation, and group III for just the third (final) week. Group IV was the vehicle control group. Bone maturation was estimated by radiographic scoring system, and mechanically by a three-point bending test. In both the radiographic and mechanical studies, groups I and II showed lower scores than group IV, indicating that even a short period of administration of a COX-2-specific inhibitor in the early phase of fracture healing creates a risk of delayed healing. blacksquare, square, filled.


Outcomes of Autologous Stem Cell Transplant Consolidation in Primary Central Nervous System Lymphoma: A Mayo Clinic Experience.
A paucity of randomized phase III clinical trials in primary central nervous system lymphoma (PCNSL) has resulted in no uniform consensus on the optimal strategy for consolidation and conditioning regimens for autologous stem cell transplant (ASCT). The past 2 decades have witnessed a preference for thiotepa (TT)-based conditioning regimens due to superior central nervous system penetration. We retrospectively evaluated outcomes of patients with PCNSL who underwent ASCT at Mayo Clinic, Rochester over the past 2 decades, and the impact of TT-based conditioning regimens. Fifty-six patients underwent transplant for PCNSL, with 25 and 31 patients receiving BEAM (non-thiotepa) and carmustine (BCNU)/TT-based conditioning, respectively. All patients received high-dose methotrexate-based induction therapy. While the BCNU/TT group had higher risk disease features such as high International Extranodal Lymphoma Study Group prognostic score, elevated cerebrospinal fluid protein, and older patient population, there was no significant difference at 2 years post-transplant in progression-free survival (BEAM 68.0% [46.1% to 82.5%] versus BCNU/TT, 65.5% [45.2% to 79.8%], P = .99) or overall survival (OS) (84.0% [62.8% to 93.7%] in the BEAM group versus 81.6% [61.3% to 91.9%] in the BCNU/TT group, P = .95). Disease response status before transplant significantly affected the outcomes as those in complete remission had an OS at 2 years post-transplant of 94.7% (68.1% to 99.2%) in the BEAM group and 90.5% (67.0% to 97.5%) in the BCNU/TT group compared with those in partial response, 57.1% (17.2% to 83.7%) in BCNU/TT group and 50.0% (11.1% to 80.4%) in the BEAM group, respectively (P < .0001). Our retrospective cohort adds to the currently available literature and identifies the disease status before transplant as a significant factor affecting survival.


Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1.
There is currently substantial interest in the regulation of cell function by mammalian target of rapamycin (mTOR), especially effects linked to the rapamycin-sensitive mTOR complex 1 (mTORC1). Rapamycin induces G(1) arrest and blocks proliferation of many tumor cells, suggesting that the inhibition of mTORC1 signaling may be useful in cancer therapy. In MCF7 breast adenocarcinoma cells, rapamycin decreases levels of cyclin D1, without affecting cytoplasmic levels of its mRNA. In some cell-types, rapamycin does not affect cyclin D1 levels, whereas the starvation for leucine (which impairs mTORC1 signaling more profoundly than rapamycin) does. This pattern correlates with the behavior of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, an mTORC1 target that regulates translation initiation). siRNA-mediated knock-down of 4E-BP1 abrogates the effect of rapamycin on cyclin D1 expression and increases the polysomal association of the cyclin D1 mRNA. Our data identify 4E-BP1 as a key regulator of cyclin D1 expression, indicate that this effect is not mediated through the changes in cytoplasmic levels of cyclin D1 mRNA and suggest that, in some cell types, interfering with the amino acid input to mTORC1, rather than using rapamycin, may inhibit proliferation.


Stimulation of antibodies to Epstein-Barr virus (EBV) in acute viral infections.
Acute and convalescent sera from 77 patients with serologically confirmed influenza, measles and adenovirus infections and from 36 healthy controls were tested for the level of antibodies to Epstein-Barr (EB) virus. In the three groups of patients significantly higher titers of antibodies to EB viral capsid antigen (VCA) were found as compared to the controls. In 19 patients twofold or higher rise in antibody titers between the first and second blood sample was demonstrated. It is suggested that in patients with influenza, measles or adenovirus infections, involvement of lymphocytes leads to reactivation of EB virus and antibody formation is stimulated.


X-ray structure of a compound of cobalt with uridine 5'-monophosphate. Evidence for metal-phosphate bonding only.
An X-ray study of the crystal structure of a cobalt(II) complex with uridine 5'-monophosphate shows it to contain polymeric chains of composition [Co2(H2O)4 (5'-UMP)2]n. The cobalt atoms do not bind to the pyrimidine base moiety; instead each metal atom is octahedrally coordinated to four phosphate groups and two water molecules. Managanese(II) forms a similar compound.


Scipion Flexibility Hub: an integrative framework for advanced analysis of conformational heterogeneity in cryoEM.
Understanding how structure and function meet to drive biological processes is progressively shifting the cryoEM field towards a more advanced analysis of macromolecular flexibility. Thanks to techniques such as single-particle analysis and electron tomography, it is possible to image a macromolecule in different states, information that can subsequently be extracted through advanced image-processing methods to build a richer approximation of a conformational landscape. However, the interoperability of all of these algorithms remains a challenging task that is left to users, preventing them from defining a single flexible workflow in which conformational information can be addressed by different algorithms. Therefore, in this work, a new framework integrated into Scipion is proposed called the Flexibility Hub. This framework automatically handles intercommunication between different heterogeneity software, simplifying the task of combining the software into workflows in which the quality and the amount of information extracted from flexibility analysis is maximized.


Relation between polymer transitions and the extensional viscosity of dough systems during thermal stabilization assessed by lubricated squeezing flow.
Polymer transitions occurring during the thermal processing of dough are defining the rheological behaviour of solidifying dough. Yeast, an essential ingredient in breadmaking, plays an important role in this transformation process, but its impact on the transitional behavior of the polymers remains unknown. Therefore, the aim of this study was to elucidate the impact of hydrothermally induced polymer transitions on the elongational rheological behavior of dough under process-relevant strain-strain-rate combinations transitions in dependence of the presence of yeast. Using elongational rheology together with DSC, TD-NMR and microscopy, yeast-induced degradation on the microstructural level (average decrease of protein strand length of 46%) and microstructural level were shown to affect the course of the starch gelatinization process and the functionality of gluten while baking. These findings can be used to relate oven rise performance to fundamental rheological behavior based on occurring phase transitions, leading to a more comprehensive process understanding.


Effect of K+ on the membrane functions of an alkalophilic Bacillus.
We have examined the involvement of K+ in the membrane functions of a facultatively alkalophilic Bacillus at neutral and alkaline pH. The effects of K+ on membrane functions, such as maintenance of the membrane potential, leucine uptake and respiratory activity, were dependent on the external pH. K+ uptake, which induced alkalinization of the cytoplasm, is suggested to be electrogenic at neutral pH and 'electroneutral' at alkaline pH, resulting in a similar level of net accumulation. We suggest that the bacterial membrane is highly permeable to K+ at neutral pH, compared to alkaline pH, which results in a pH-dependent effect of K+ on the above membrane functions.


Nasopharyngeal angiofibroma: a concise classification system and appropriate treatment options.
To describe a clear and simplified classification system for juvenile nasopharyngeal angiofibroma (JNA), and to describe suitable management options. Retrospective medical record review. The clinical and imaging materials of 51 cases of JNA diagnosed at our hospital between 1981 and 2011 were collected and studied. Based on our experiences, we prefer to divide JNAs into three types. Type I includes JNAs fundamentally localized to the nasal cavity, paranasal sinus, nasopharynx, or pterygopalatine fossa. Type II is a JNA extending into the infratemporal fossa, cheek region, or orbital cavity, with anterior and/or minimal middle cranial fossa extension but intact dura mater. Type III is a calabash-like massive tumor lobe in the middle cranial fossa. The management and prognosis for the three types of JNA were compared and evaluated. Among cases of type I JNA (n=16), the entire mass was removed by the initial operation in 15 cases and by a repeat operation in 1 case. Among cases of type II JNA (n=29), the entire mass was removed by the first operation in 24 cases and by repeat operation in 5 cases. In cases of type III JNA (n=6), the huge calabash-like lobe in the middle cranial fossa could not be completely excised; 4 cases underwent radiotherapy and 2 cases were lost to follow-up. 1) The transnasal cavity approach with endoscopic guidance is suitable for type I JNA resection. 2) The transantral-infratemporal fossa-nasal cavity combined approach is reliable for resection of a type II JNA, which extends into the deep anterior cranial fossa and/or minimally into the middle cranial fossa, with intact dura mater. 3) The complete removal of a type III JNA is difficult, even through a combined extracranial and intracranial approach. Radiotherapy is useful for treating the residual intracranial tumor. The successful or failed experiences of 6 typical cases prove that this revised classification system is reasonable and reliable.


In vivo test of a radiography-based navigation system for control of derotational osteotomies.
Malalignment of the femur is a frequently encountered problem in orthopaedics entailing manifold consequences for the affected patients. Corrective osteotomies, necessary to restore the physiological and anatomical relationships, face great challenges due to no existing reliable gold standard for intraoperative control of torsional malalignment. The aim of this study was to test a novel radiography-based navigation tool for control of derotational osteotomies in a clinical environment. In a first-and preliminary-case-controlled study on 12 patients (level 3 of evidence), the achieved torsional correction measured with implementation of the navigation tool was compared with measurements from pre- and postoperative computed tomography (CT) scans. The navigation tool was able to acquire and process all relevant data and capture possible malrotation during surgery with only little deviations of 1.61° ± 0.86° (mean ± standard deviation) from the measurements based on CT scans. Next, the system will be used to assist surgeons for more precise treatment avoiding maltorsion after derotational osteotomies.


K+ conduction description from the low frequency impedance and admittance of squid axon.
The form of power spectra of K+ conduction fluctuations in patches of squid axon suggested that K+ conduction kinetics are higher than first order (Fishman, Moore & Poussart, 1975, J. Membrane Biol. 24:305). To obtain an alternative description of ion conduction kinetics consistent with spontaneous fluctuations, the complex impedance and admittance of squid (Loligo pealei) axon were measured at low frequencies (1-1000 Hz) with a four electrode system using white Gaussian noise as a stochastic perturbation. As predicted from the spontaneous noise measurements, a low frequency impedance feature is observed between 1 and 30 Hz which is voltage and temperature dependent, disappears after substantial reduction in [Ki+], and is unaffected by the state of Na+ conduction or active transport. These measurements confirm and constitute strong support for the patch noise measurements and interpretations. The linearized Hodgkin-Huxley (HH) equations do not produce the low frequency feature since first order ion conduction kinetics are assumed. Computation of diffusion polarization effects associated with the axon sheath gives a qualitative account of the low frequency feature, but the potential dependence is opposite to that of the data. Thus, K+ conduction kinetics in the axon are not adequately described by a single first order process. In addition, significant changes in HH parameter values were required to describe the usual impedance (resonance) feature in Loligo pealei axon data.


Brain development and the immune system: an introduction to inflammatory and infectious diseases of the child's brain.
A short overview of the specificities of immune response within the brain is given as an introduction to subsequent chapters on infectious and inflammatory diseases of the child's brain. The blood-brain barrier starts developing during vascular proliferation of the developing brain during neurogenesis but maturation is not completed until several weeks after birth, and varies in different parts of the brain. The development of postcapillary venules in which cell recruitment occurs seems to be completed at birth. Brain macrophages are detected in brain tissue from the 8th to 12th week of gestation and then exert an important role during neuroblast selection and differentiation, as astrocytes and macrophages acquire the ability to secrete soluble substances. From the third trimester, the fetal brain is able to generate an inflammatory reaction and toll-like receptors can be detected on the surface of fetal neurons and glial cells. Innate immunity maturation occurs within weeks after birth. Although neonates lack preexisting immunological memory and have a small number of immune cells in peripheral lymphoid tissues, they are competent to develop a mature T-cell response, they have a strong CD8 cytotoxic function, and dendritic cells are fully competent.


Willingness to pay for community based health insurance scheme and factors associated with it among households in rural community of South West Shoa Zone, Ethiopia.
Out-of-pocket payments are the major significant barrier in achieving universal health coverage, particularly in developing countries' rural communities. In 2011, the Ethiopian government launched a pilot community-based health insurance (CBHI) scheme with the goal of increasing access to modern health care services and providing financial security to households in the informal sector and rural areas. The main objective of this study is to estimate willingness to pay (WTP) for CBHI scheme and factors that influence it among rural households in the South West Shoa Zone. A household-level cross-sectional study was conducted to examine the WTP for the CBHI scheme and factors associated with it in rural communities of South West Shoa Zone. The study used a sample of 400 rural households. Systematic random sampling was employed during household selection, and double-bounded contingent valuation method was used to estimate WTP for the CBHI scheme. About 65 percent of the households are willing to pay for CBHI scheme. Moreover, the study found that the households were willing to pay 255.55 Birr per year on average. The result of the study also revealed that amount of bid, household income, family size, household head's education, household health status, membership to community-based health insurance scheme, membership in any association, and awareness about the scheme are factors that are significantly associated with WTP for the scheme. Households are willing to pay a higher price than the policy price. Therefore, setting a new premium that reflects households' willingness to pay is highly valuable to policymakers. Social capital and awareness about CBHI scheme play an important role in influencing WTP. Thus, the study suggests that local communities need to strengthen their social cohesion and solidarity. It is also necessary to create awareness about the CBHI's benefits.


[Rapid determination of ceftriaxone in mixed saliva of practically healthy subjects and patients with infectious and somatic pathologies].
A method for spectroscopic determination of ceftriaxone in saliva of healthy subjects and patients with upper respiratory tract infections was developed. The concentration range is 1-50 mcg/ml. The method is express and simple, and can be used to determine ceftriaxone in clinical tests and pharmacokinetic studies. Possible determination of ceftriaxone in aqueous solutions was demonstrated which is useful in analysis of drugs.


Estimation of the genetically significant dose from diagnostic X-ray procedures in the Islamic Republic of Iran.
The genetically significant dose from diagnostic X-ray sources has been estimated. Age and sex distribution was based on a survey of 13,100 patients. Dosimetry was performed on patients and on an equivalent-man Rando phantom. Child-expectancy factors were estimated from the census results of fertility and mortality rates. The GSD value for the diagnostic procedures to the Iranian population was estimated to be 9.2 mrem/yr in 1980.


[Visceral leishmaniasis in infants without bioptic demonstration of the parasite. Presentation of 3 cases].
The Authors describe three infants with visceral leishmaniasis in whom bioptic research (in marrow, spleen and liver) has not demonstrated presence of leishmania. They remark this unusual aspect of visceral leishmaniasis in infant and debate the epidemiological, diagnostic, and therapeutic aspects of these cases.


Rapid quantitative assessment of fungiform papillae density in the human tongue.
Fungiform papillae density, which can be used in a variety of circumstances as an indicator of taste function [L.M. Bartoshuk, V.B. Duffy, I.J. Miller, PTC/PROP tasting: anatomy, psychophysics and sex effects, Physiol. Behav. 56 (1994) 1165-1171; I.J. Miller, F.E. Reedy, Variation in human taste bud density and taste intensity perception, Physiol. Behav. 47 (1990) 1213-1219; J.R. Zuniga, N. Chen, C.L. Phillips, Chemosensory and somatosensory regeneration after lingual nerve repair in humans, J. Oral Maxillofac. Surg. 55 (1997) 2-13], was measured on the dorsal surface of the anterior tongue of living humans using a digital camera and a videomicroscope. Both procedures provided similar results, with the camera providing a more rapid, portable and flexible imaging procedure. Subsequently, the camera was successfully used to identify small regions of the anterior tongue which provide reliable measures of fungiform papillae density that correlate highly with the total number of fungiform papillae on the anterior tongue.


Differences in the effects of orthodontic treatment on airway-craniocervical functional environment in adult and adolescent patients with skeletal class II high-angle: a retrospective pilot study.
This retrospective cohort study aimed to compare the change in upper airway and craniocervical posture after orthodontic treatment between adolescent and adult patients with Class II high-angle malocclusion. A total of 12 adolescent (mean ± standard deviation age = 13.0 ± 2.0 years) and 12 adult patients with Class II high-angle malocclusion (mean ± standard deviation age = 23.7 ± 6.4 years) were selected in this study. The lateral cephalograms and cone beam computed tomography images of adolescent and adult patients were taken before and after treatment, which can be employed to evaluate the variables of craniofacial morphology, upper airway, and craniocervical posture through paired t tests, respectively. An independent sample t test was performed to observe the differences between two groups after orthodontic intervention. For adults and adolescents, the correlation between craniofacial morphology, upper airway, and craniocervical posture was determined through Pearson correlation analysis. In all subjects, the improvements in vertical and sagittal facial morphology after treatment were observed. Anterior and inferior movements of the hyoid bone, an increase of upper airway dimension, posterior tipping of the head and a reduction of cervical inclination in the lower and middle segments post-treatment were identified in adolescence (P < 0.05). Adults displayed anterior movements of the hyoid bone, whereas no significant difference was observed in upper airway dimension and craniocervical posture (P < 0.05). Notable differences were identified in the change of hyoid position and airway volume between two groups (P > 0.05). Mandibular plane inclination, growth pattern, occlusal plane inclination, and chin position were all significantly correlated with craniocervical posture in adolescent patients. Besides, the mandibular growth pattern and chin position in adult patients were significantly correlated with craniocervical posture (P < 0.05). Orthodontic treatment is capable of enhancing the facial profile of patients with skeletal class II high-angle while improving their upper airway morphology and craniocervical posture, where adolescents and adults differ substantially in that the former exhibit a more favorable alteration in the airway-craniocervical functional environment.


Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias.
Determining the percentage of peripheral blood (PB) and bone marrow (BM) blasts is important for diagnosing and classifying acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Although most patients with acute leukemia or MDS have a higher percentage of BM blasts than PB blasts, the relative proportion is reversed in some patients. We explored the clinical relevance of this phenomenon in MDS (n = 446), AML (n = 1314), and acute lymphoblastic leukemia (ALL) (n = 385). Among patients with MDS or ALL, but not AML, having a higher blast percentage in PB than in BM was associated with significantly shorter survival. In multivariate analyses, these associations were independent of other relevant predictors, including cytogenetic status. Our findings suggest that MDS and ALL patients who have a higher percentage of PB blasts than BM blasts have more aggressive disease. These data also suggest that MDS classification schemes should take into account the percentage of blasts in PB differently from the percentage of blasts in BM.


Diagnosis and management of post-cholecystectomy symptoms: the place of endoscopy and retrograde choledochopancreatography.
Endoscopic retrograde choledochopancreatography (ERCP) was employed in 52 patients symptomatic after cholecystectomy in whom barium meal studies and intravenous cholangiography had failed to yield a diagnosis. Cannulation of the papilla of Vater was carried out in 50 of the patients in a mean time of 10 min. Diagnostic information demonstrating a pathological lesion or a normal biliary and pancreatic ductal system was obtained by means of endoscopy and ERCP in 48 cases. There were no serious complications. A pathological lesion was demonstrated in all but one of the patients presenting with jaundice, cholangitis or pancreatitis but the diagnostic yield was not as high in patients with vague upper abdominal symptoms. Endoscopy and ERCP are the investigative procedures of first choice in complex post-cholecystectomy cases in whom intravenous cholangiography fails, gives incomplete information or suggests normality in the face of continuing symptoms or clinical evidence of residual biliary disease.


Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease.
Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 +/- 7 to 87 +/- 7 ml and decreased systemic vascular resistance from 1,573 +/- 199 to 1,319 +/- 180 dynes.s.cm-5 (both, p less than 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p less than 0.05). Myocardial lactate consumption was maintained (21 +/- 8 vs 19 +/- 11 X 10(-3) mEq/min, p is not significant at p less than or equal to 0.05 level) at a lower arterial lactate concentration (0.72 +/- 0.09 to 0.47 +/- 0.08 mEq/liter, p less than 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease.


Two-stage phase II survival trial design.
Recently, molecularly targeted agents and immunotherapy have been advanced for the treatment of relapse or refractory cancer patients, where disease progression-free survival or event-free survival is often a primary endpoint for the trial design. However, methods to evaluate two-stage single-arm phase II trials with a time-to-event endpoint are currently processed under an exponential distribution, which limits application of real trial designs. In this paper, we developed an optimal two-stage design, which is applied to the four commonly used parametric survival distributions. The proposed method has advantages compared with existing methods in that the choice of underlying survival model is more flexible and the power of the study is more adequately addressed. Therefore, the proposed two-stage design can be routinely used for single-arm phase II trial designs with a time-to-event endpoint as a complement to the commonly used Simon's two-stage design for the binary outcome.


Seasonal acclimatization to temperature in monk parakeets.
Metabolism and insulation of monk parakeets were determined in summer and compared with previously reported winter values. Fasting levels of metabolism were the same in winter and summer during the daytime: nighttime values were significantly lower in winter (6.11 versus 8.20 Wkg-1). Evaporative water loss at 20-30° C was significantly lower in winter (2.24 versus 3.05 mg H2O g-1 h-1). Winter birds were better able to maintain body temperature (Tb) independent of ambient temperature (Ta) below 20° C than were summer birds. Coefficients of dry heat transfer determined for Tb-Ta gradients greater than 10° C were not significantly different for the two seasons. Similarly, the slope of the line relating oxygen consumption to Ta below thermal neutrality (i.e. thermal conductance) was the same in winter and summer birds, indicating no seasonal change in overall body insulation. Literature review revealed a relation between seasonal change in fasting metabolic rate (FMR) and body size in birds. Winter FMR as a fraction of summer FMR is inversely, related to body mass (Mb) by the equation; winter FMR/summer FMR=1.49 Mb -0.077 where Mb is in grams. Thus, in small birds FMR is higher in winter than summer, while for large birds (>200 g) the converse is true.


The secret of health in daily cuisine: typical healthy vegetables in local markets in central Myanmar.
Central Myanmar is located in the Indo-Burma biodiversity hotspot, and the Bamar people are the main ethnic group, which settled there over 1000 years ago. Despite being the core region of the country, central Myanmar has been ignored in previous ethnobotanical studies. Local healthy foods and knowledge are regarded as treasures for resource development and pharmaceutical drug discovery, and market surveys are a good strategy in ethnobotanical research. Thus, we collected and documented typical vegetables and local knowledge in local markets and then analysed the diversity and local knowledge of these vegetables. Observations and interviews were used in the field study, and 10 markets and fairs were selected in central Myanmar. A total of 277 vegetable stalls or shops were visited. We compared the local knowledge we collected with selected important and typical herbal books on traditional Myanmar medicine. Quantitative analysis, including frequency of citation (FC), relative frequency of citation (RFC) and use value (UV), was used to assess the diversity and local knowledge of these vegetables. A total of 132 plant taxa from 47 botanical families and 116 genera were collected. Most (106 taxa, 80.3%) of these vegetables were cited by the informants as functional foods that had health benefits, while others were regarded as merely "good for health". The main health function of the vegetables was treating digestive problems. Sixty-four species were recorded in selected herbal books on traditional Myanmar medicine, and forty-seven taxa were not recorded in these books but were nonetheless used as healthy vegetables by local people. Twenty-eight species of vegetables were collected from wild places. The diversity and local knowledge of healthy vegetables in central Myanmar were rich. Nevertheless, the diversity of wild vegetables was seemingly relatively low. The possible reason was that we counted only the vegetables that were from entirely wild sources as "wild vegetables". The most frequently cited vegetables were commonly cultivated species, which reflects the fact that plants cultivated on a large scale comprise the major source of vegetables. Some lesser known vegetables could reflect the unique food culture of local people, but most of these were cited only a few times by the interviewees, which caused low UV and RFC rankings for them in the league table. In addition, future research should pay more attention to the food safety of these vegetables.


Automated analysis of written language in the three variants of primary progressive aphasia.
Despite the important role of written language in everyday life, abnormalities in functional written communication have been sparsely investigated in primary progressive aphasia. Prior studies have analysed written language separately in each of the three variants of primary progressive aphasia-but have rarely compared them to each other or to spoken language. Manual analysis of written language can be a time-consuming process. We therefore developed a program that quantifies content units and total units in written or transcribed language samples. We analysed written and spoken descriptions of the Western Aphasia Battery picnic scene, based on a predefined content unit corpus. We calculated the ratio of content units to units as a measure of content density. Our cohort included 115 participants (20 controls for written, 20 controls for spoken, 28 participants with nonfluent variant primary progressive aphasia, 30 for logopenic variant and 17 for semantic variant). Our program identified content units with a validity of 99.7% (95%CI 99.5-99.8). All patients wrote fewer units than controls (P < 0.001). Patients with the logopenic variant (P = 0.013) and the semantic variant (0.004) wrote fewer content units than controls. The content unit-to-unit ratio was higher in the nonfluent and semantic variants than controls (P = 0.019), but no difference in the logopenic variant (P = 0.962). Participants with the logopenic (P < 0.001) and semantic (P = 0.04) variants produced fewer content units in written compared to spoken descriptions. All variants produced fewer units in written samples compared to spoken (P < 0.001). However, due to a relatively smaller decrease in written content units, we observed a larger content unit-to-unit ratio in writing over speech (P < 0.001). Written and spoken content units (r = 0.5, P = 0.009) and total units (r = 0.64, P < 0.001) were significantly correlated in patients with nonfluent variant, but this was not the case for logopenic or semantic. Considering all patients with primary progressive aphasia, fewer content units were produced in those with greater aphasia severity (Progressive Aphasia Severity Scale Sum of Boxes, r = -0.24, P = 0.04) and dementia severity (Clinical Dementia Rating scale Sum of Boxes, r = -0.34, P = 0.004). In conclusion, we observed reduced written content in patients with primary progressive aphasia compared to controls, with a preference for content over non-content units in patients with the nonfluent and semantic variants. We observed a similar 'telegraphic' style in both language modalities in patients with the nonfluent variant. Lastly, we show how our program provides a time-efficient tool, which could enable feedback and tracking of writing as an important feature of language and cognition.


The Bacterial Hydrophobin BslA is a Switchable Ellipsoidal Janus Nanocolloid.
BslA is an amphiphilic protein that forms a highly hydrophobic coat around Bacillus subtilis biofilms, shielding the bacterial community from external aqueous solution. It has a unique structure featuring a distinct partition between hydrophilic and hydrophobic surfaces. This surface property is reminiscent of synthesized Janus colloids. By investigating the behavior of BslA variants at water-cyclohexane interfaces through a set of multiscale simulations informed by experimental data, we show that BslA indeed represents a biological example of an ellipsoidal Janus nanoparticle, whose surface interactions are, moreover, readily switchable. BslA contains a local conformational toggle, which controls its global affinity for, and orientation at, water-oil interfaces. This adaptability, together with single-point mutations, enables the fine-tuning of its solvent and interfacial interactions, and suggests that BslA could be a basis for biotechnological applications.


Characterization of a Novel Chromosome-Encoded AmpC β-Lactamase Gene, bla PRC-1, in an Isolate of a Newly Classified Pseudomonas Species, Pseudomonas wenzhouensis A20, From Animal Farm Sewage.
In this work, we characterized a novel chromosome-encoded AmpC β-lactamase gene, bla PRC-1, in an isolate of a newly classified Pseudomonas species designated Pseudomonas wenzhouensis A20, which was isolated from sewage discharged from an animal farm in Wenzhou, China. Susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis were performed to determine the function and enzymatic properties of the β-lactamase. Sequencing and comparative genomic analysis were conducted to clarify the phylogenetic relationship and genetic context of the bla PRC-1 gene. PRC-1 is a 379-amino acid AmpC β-lactamase with a molecular weight of 41.48 kDa and a predicted pI of 6.44, sharing the highest amino acid identity (57.7%) with the functionally characterized AmpC β-lactamase PDC-211 (ARX71249). bla PRC-1 confers resistance to many β-lactam antibiotics, including penicillins (penicillin G, amoxicillin, and amoxicillin-clavulanic acid) and cephalosporins (cefazolin, ceftriaxone, and cefotaxime). The kinetic properties of PRC-1 were compatible with those of a typical class C β-lactamase showing hydrolytic activities against β-lactam antibiotics, and the hydrolytic activity was strongly inhibited by avibactam. The genetic context of bla PRC-1 was relatively conserved, and no mobile genetic element was predicted in its surrounding region. Identification of a novel β-lactamase gene in an unusual environmental bacterium reveals that there might be numerous unknown resistance mechanisms in bacterial populations, which may pose potential risks to human health due to universal horizontal gene transfer between microorganisms. It is therefore of great value to carry out extensive research on the mechanism of antibiotic resistance.


The experiences of nurses implementing the Modified Early Warning Score and a 24-hour on-call Mobile Intensive Care Nurse: An exploratory study.
To explore experiences of nurses implementing and using the Modified Early Warning Score (MEWS) and a Mobile Intensive Care Nurse (MICN) providing 24-hour on-call nursing support. To secure patient safety in hospital wards, nurses may increase the quality of care using a tool to detect the failure of vital functions. Possibilities for support can be provided through on-call supervision from a qualified team or nurse. This exploratory qualitative investigation used focus group interviews with nurses from two wards of a university hospital in Norway. A purposive sample of seven registered nurses was interviewed in focus groups. A semi-structured guide and an inductive thematic analysis were used to identify interview themes. Three themes emerged: (1) experiences with the early recognition of deterioration using the MEWS, (2) supportive collaboration and knowledge transfer between nurses and (3) a "new" precise language using the score for communicating with physicians. The use of scores and support were perceived as improving care for deteriorating patients and for supporting the collaboration of nurses with other professionals. In our study, nurses described increased confidence in the recognition of deteriorating patients and in the management of such situations. The non-critical attitude, supportive communication and interactive learning according to the MICN were essential elements for success.


Sensitivity to stimulus onset and offset in the S-cone pathway.
Previous work [Vassilev, capital A, Cyrillic., Mihaylova, M., Racheva, K., Zlatkova, M., & Anderson, R. S. (2003). Spatial summation of S-cone ON and OFF signals: Effects of retinal eccentricity. Vision Research, 43, 2875-2884; Vassilev, A., Zlatkova, M., Krumov, A., & Schaumberger, M. (2000). Spatial summation of blue-on yellow light increments and decrements in human vision. Vision Research, 40, 989-1000] has shown that spatial summation of brief S-cone selective stimuli depends on their polarity, increments or decrements, suggesting involvement of S-ON and OFF pathways, respectively. This assumption was tested in two experiments using a modified two-color threshold method of Stiles to selectively stimulate the S-cones. In the first experiment we measured detection threshold for small 100ms S-cone selective increments and decrements presented within three types of temporal window, rectangular, ramp onset/rapid offset and rapid onset/ramp offset. The ramp-onset threshold was higher than the ramp-offset threshold regardless of stimulus sign. In the second experiment we measured reaction time (RT) with near-threshold stimuli spatially coincident with the background to avoid spatial contrast. RT distribution for S-cone selective 500ms increments and decrements was unimodal and followed stimulus onset. An increase of stimulus duration to 1000 and 2000ms resulted in the appearance of responses following stimulus offset. The results suggest that, for brief S-cone selective increments or decrements, the human visual system is more sensitive to stimulus onset than to stimulus offset. Only for longer stimuli is the offset important, probably due to slow adaptation at a postreceptoral level.


Preparation and property of a biantenna macromolecule based on polysialic acid.
Polysialic acid (PSA), an acidic polysaccharide usually exists as a double-chain structure on cell adhesion molecules in vertebrates. The available PSA produced from Escherichia coli fermentation, however, is monochain PSA. In this work, a biomimetic biantenna type PSA (biPSA) was synthesized in vitro under mild conditions, and the terminal nonreducing ends of sialic acid residue were retained. The structure of biPSA was characterized through infrared spectroscopy, and NMR, and the double-chain structure of biPSA was confirmed by the doubled molecular weight and particle size of biPSA. Analysis through circular dichroism, isothermal titration calorimetry, and thermostability experiments revealed that the obtained biPSA was more stable in aqueous solution than PSA, especially after complexation with Ca2+, which increased the variation in enthalpy and entropy. However, the addition of Cu2+ had a negligible effect on configuration of PSA and biPSA. The addition of Ca2+ promoted cell proliferation in a culture of microglia BV-2 cells with biPSA in medium. By contrast, the addition of Cu2+ had toxic effects. Supplementation with biPSA can maintain cell viability for a longer period than supplementation with monochain PSA. This work indicates that biPSA is a potential substitute for monochain PSA in practical applications.


The Effects of Exercise in Patients with Sarcopenia.
The aim of this study was to assess the effects of different types of exercise interventions for treating sarcopenia compared to no specific treatment, a minimal intervention (e.g., education), or another active treatment (nutritional supplements). A review was conducted of the recent English literature searching PubMed and ScienceDirect databases. Ten randomized controlled trials (RCTs) were included in this review, presenting the results of 671 sarcopenic patients. The exercise interventions were resistance training (four studies), a multimodal program (five studies, encompassing resistance training and additional exercises such as aerobic exercises, flexibility, balance and strength training), and a whole body vibration program (one study). Results show that exercise interventions could have beneficial effects in improving muscle mass, muscle strength, and physical performance in 3 months of intervention. Resistance training, added to an adequate nutrition and aerobic exercise, appeared to deliver the most positive outcome after 3 months of intervention. Types of exercise and dose-response parameters of exercise eliciting improvement warrant further investigation. Due to the significant heterogeneity in clinical trials, the current evidence provides limited guidance. Well-designed studies evaluating exercise interventions are needed before treatment guidelines can be developed.


Neck dissection with harmonic instruments and electrocautery: a prospective comparative study.
Harmonic instruments are becoming popular in head and neck surgeries. In this prospective, randomized study, the efficacy of the harmonic instruments and electrosurgical technique is compared. A total of 48 patients undergoing unilateral neck dissection were divided into two groups. In one group, surgery was performed using conventional hemostatic instruments while in the other, only harmonic instruments were used. The two techniques were then compared with regard to intra- and post-operative blood loss, complications in operating time, drain, tracheotomy and nasogastric tube duration, and post-operative hospital stay. Differences in operative time (P = 0.647), total suction drainage (P = 0.362) and time that drains (P = 0.404), nasogastric tube (P = 0.378), and tracheotomy (P = 0.052) were kept in place and proved not significant. The average blood loss during surgery was significantly greater in the CH group (P = 0.003) as the number of hemoclips and resorbable ligature used (P = 0.002). In contrast to what has been reported up to now, our study did not reveal a net advantage in the use of harmonic instruments with respect to classical instruments in terms of surgical outcome. On the contrary, harmonic tools had a higher complication rate (i.e., salivary fistula and lymphatic leak) probably due to the decreased ability of this instruments to permanently close glandular structures and lymphatic ducts. In these cases, a closure technique such as electrocautery or classic knot-tying should be used.


Obesity and the risk of primary liver cancer: A systematic review and meta-analysis.
In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer. This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords "obesity," "overweight," "body mass index (BMI)," "body weight," "liver," "cancer," "hepatocellular carcinoma," "liver cancer," "risk," and "mortality." Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included. A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancerrelated mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50-1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02-1.81), 1.77 (95% CI, 1.56-2.01), and 3.08 (95% CI, 1.21-7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14-2.27, I2=80%). High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.


Determination of Oseltamivir in Human Plasma by HPLC-MS/MS.
A procedure for the determination of oseltamivir in human plasma by high-performance liquid chromatography( tandem mass spectrometry (HPLC-MS/MS) was proposed and validated. Arapid and easy-to-use method of liquid(liquid extraction with ethyl acetate using venlafaxine as an internal standard was used during sample preparation. The addition of benzoic acid to aqueous acetonitrile solutions of the analyte was shown to prevent its oxidative degradation. The detection limit and limit of quantitation were 0.08 and 0.30 ng/mL, respectively; the calibration range, 0.3-200 ng/mL (R 2 = 0.9937); the total analysis time, 3.2 min. The within- and between-run accuracy ranged from 97 to 105%. The precision was <10%. The proposed procedure was characterized by selective determination of the analyte, the absence of significant matrix effects, the ability to dilute samples with high analyte concentrations, and satisfactory extraction recovery (≥89%). The analyte was stable when stored in plasma samples (4 h at room temperature, 31 d at (80°C, after three freeze(thaw cycles) and extracts under autosampler storage conditions (24 h at 15°C). The procedure was successfully used for oseltamivir quantitation in actual plasma samples from healthy volunteers obtained during a bioequivalence study of the new generic drug.


A new technique for beta attenuation studies in neutron activation foils using 4πß-γ coincidence system.
Foil activation method is an accurate method for neutron fluence rate measurements. In this, the inactive foils are activated and the induced activity is then measured and correlated to the neutron fluence rate through the cross section for the reaction, number of atoms and time of irradiation. To evaluate this induced activity, gamma-ray spectrometers are generally used. If the neutron fluence rate is very low of the order of 1-10(3) n cm(-2) s(-1), a 4πβ flow-type proportional counter with 100 % efficiency is the most suitable detector for measuring the low induced activity. But this method poses a serious problem of beta self-attenuation in the foils. A detailed investigation of the beta attenuation of different activation foils such as gold, manganese, cobalt, magnesium and aluminium by empirical equations as well as with a new experimental method using 4πβ-γ coincidence counter and 4πβ flow-type proportional counter is discussed in this paper.


Spatial heterogeneity in post-dispersal predation on Prunus and Uvularia seeds.
We investigated effects of seed density, distance from parent, and habitat (woods, open field) on post-dispersal predation risk (chiefly by rodents) for seeds of Prunus virginiana (Rosaceae). Additional study of the habitat effect (woods, open field, treefall gap) was made with seeds of Prunus avium (Rosaceae) and Uvularia grandiflora (Liliaceae). Density of Prunus seeds (range 2-40 seeds/group) did not affect predation risk for individual seeds. Distance from parent plants did influence predation risk, which was greatest directly beneath parents. This distance effect primarily comprised a sharp drop in risk within 2 m of parents, a distance too small to generate a "spacing rule" for conspecifics.We found that habitat strongly influenced predation intensity. Rates of removal of Prunus seeds were higher in woods than in open fields, except when overall predation intensity was very low and no pattern could be discerned. Prunus seed removal rates were higher in closed woods than in treefall gaps. Consequently, a Prunus seed will more likely escape predation if dispersed to an open site. In contrast, Uvularia seed removal rates were higher in open fields than in woods but did not differ between closed woods and tree-fall gaps.Predation intensity was spatially patchy between and within experimental arrays, but was consistent over time at some specific points in space, possibly reflecting home ranges of seed predators.


Adenosine effects on hormone-stimulated steroidogenesis in isolated bovine adrenal zona fasciculata cells.
In isolated bovine adrenal zona fasciculata cells, the use of adenosine deaminase to remove endogenous adenosine had no effect on basal or angiotensin II-stimulated steroidogenesis but enhanced ACTH1-24-stimulated steroidogenesis over the entire dose response range without appreciable change in potency of ACTH1-24. 8-Phenyl-theophylline, an adenosine antagonist, mimicked all of the actions of adenosine deaminase. High concentrations (greater than 1 microM) of N6-phenylisopropyl-adenosine (PIA) increased basal, angiotensin II and cyclic AMP-stimulated steroidogenesis, whilst inhibiting the ACTH1-24-stimulated condition. PIA also increased the potency of angiotensin II approx 20-fold. These observations are consistent with the possibility that adenosine exerts effects on two different signalling systems within zona fasciculata cells.


c-Src-mediated phosphorylation of AP-2 reveals a general mechanism for receptors internalizing through the clathrin pathway.
Clathrin-mediated endocytosis is a complex process regulated at many different levels. We showed previously that activation of the angiotensin type 1 receptor (AT1R), which belongs to the G protein-coupled receptor (GPCR) family, leads to c-Src-dependent tyrosine phosphorylation of beta2-adaptin, a subunit of the clathrin adaptor AP-2. The phosphorylation of beta2-adaptin on tyrosine residue 737 (Y737) negatively regulates its interaction with betaarrestin, another important clathrin adaptor for GPCR internalization. Here we sought to determine whether AP-2 phosphorylation represents a general mechanism for different receptors internalizing through the clathrin pathway. Using a specifically designed antibody against the phosphorylated form of Y737 on beta2-adaptin, we demonstrate that this residue is phosphorylated by AT1R in different cell types like HEK293, COS-7 and vascular smooth muscle cells. Using RNA interference approaches, we reveal that this agonist-mediated event is both betaarrestin- and c-Src-dependent, and that it occurs at the plasma membrane in clathrin-coated vesicles (CCVs). We further show that this is not only a common event employed by other GPCRs like the beta2-adrenergic, vasopressin V2, bradykinin type 2, platelet-activating factor and endothelin A receptors but that the epidermal growth factor receptor is capable of eliciting the phosphorylation of AP-2 in CCVs. Our results imply that tyrosine phosphorylation of Y737 on beta2-adaptin is a common regulatory mechanism employed by different receptors undergoing clathrin-dependent endocytosis, and suggest a wider function for this event than originally anticipated.


In vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination against Listeria monocytogenes.
The in vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination was determined against seven strains of Listeria monocytogenes by the killing curve method. Amoxicillin plus gentamicin was the most rapidly bactericidal combination, whereas trimethoprim-sulfamethoxazole was less bactericidal at 6 h but as bactericidal at 24 h. The combination of trimethoprim-sulfamethoxazole with either amoxicillin, ciprofloxacin or rifampicin did not result in antagonism, but the combinations were no more active than trimethoprim-sulfamethoxazole alone. The interaction of amoxicillin with rifampin was fairly antagonistic (1 log10 difference). The combination of amoxicillin and ciprofloxacin, although producing antagonism during the first 6 h, was more active at 24 h than amoxicillin alone and prevented the regrowth observed with ciprofloxacin alone. Ciprofloxacin and rifampicin interacted antagonistically during the first 6 h, and the combination was not very bactericidal (3 log10) but prevented the emergence of mutants, as observed with each drug alone, when used at concentrations greater than the MICs for the strain tested. These regimens merit evaluation in in vivo models of Listeria monocytogenes meningitis.


1:1 atrial-flutter. Prevalence and clinical characteristics.
Little is known about the epidemiology of 1:1 atrial flutter (AFL). Our objectives were to determine its prevalence and predisposing conditions. 1037 patients aged 16 to 93 years (mean 64±12) were consecutively referred for AFL ablation. 791 had heart disease (HD). Patients admitted with 1/1 AFL were collected. Patients were followed 3±3 years. 1:1 AFL-related tachycardiomyopathy was found in 85 patients, 59 men (69%) with a mean age of 59±12 years. The prevalence was 8%. They were compared to 952 patients, 741 men (78%, 0.04), with a mean age of 65±12 years (0.002) without 1:1 AFL. Factors favoring 1:1 AFL was the absence of HD (35 vs 23%, 0.006), the history of AF (42 vs 30.5%)(0.025) and the use of class I antiarrhythmic drugs (34 vs 13%)(p<0.0001), while use of amiodarone or beta blockers was less frequent in patients with 1:1 AFL (5, 3.5%) than in patients without 1:1 AFL (25, 15%) (p<0.0001, 0.03). The failure of ablation (9.4 vs 11%), ablation-related complications (2.3 vs 1.4%), risk of subsequent atrial fibrillation (AF) (20 vs 24%), risk of AFL recurrences (19 vs 13%) and risk of cardiac death (5 vs 6%) were similar in patients with and without 1:1 AFL. The prevalence of 1:1 AFL in patients admitted for AFL ablation was 8%. These patients were younger, had less frequent HD, had more frequent history of AF and received more frequently class I antiarrhythmic drugs than patients without 1:1 AFL. Their prognosis was similar to patients without 1:1 AFL.


Predictive potential of SARS-CoV-2 RNA concentration in wastewater to assess the dynamics of COVID-19 clinical outcomes and infections.
Coronavirus disease 2019 - caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -, has triggered a worldwide pandemic resulting in 665 million infections and over 6.5 million deaths as of December 15, 2022. The development of different epidemiological tools have helped predict new outbreaks and assess the behavior of clinical variables in different health contexts. In this study, we aimed to monitor concentrations of SARS-CoV-2 in wastewater as a tool to predict the progression of clinical variables during Waves 3, 5, and 6 of the pandemic in the Spanish city of Xátiva from September 2020 to March 2022. We estimated SARS-CoV-2 RNA concentrations in 195 wastewater samples using the RT-PCR Diagnostic Panel validated by the Center for Disease Control and Prevention. We also compared the trends of several clinical variables (14-day cumulative incidence, positive cases, hospital cases and stays, critical cases and stays, primary care visits, and deaths) for each study wave against wastewater SARS-CoV-2 RNA concentrations using Pearson's product-moment correlations, a two-sided Mann-Whitney U test, and a cross-correlation analysis. We found strong correlations between SARS-CoV-2 concentrations with 14-day cumulative incidence and positive cases over time. Wastewater RNA concentrations showed strong correlations with these variables one and two weeks in advance. There were significant correlations with hospitalizations and critical care during Wave 3 and Wave 6; cross-correlations were stronger for hospitalization stays one week before during Wave 6. No association between vaccination percentages and wastewater viral concentrations was observed. Our findings support wastewater SARS-CoV-2 concentrations as a potential surveillance tool to anticipate infection and epidemiological data such as 14-day cumulative incidence, hospitalizations, and critical care stays. Public health authorities could use this epidemiological tool on a similar population as an aid for health care decision-making during an epidemic outbreak.


Physical activity and cardiometabolic risk factors in individuals with spinal cord injury: a systematic review and meta-analysis.
Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 μU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO2) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 μU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.


Role of mast cells and pro-inflammatory mediators on the intestinal secretion induced by cholera toxin.
Recent data suggest that diarrhea caused by Vibrio cholerae involves a pro-inflammatory mediators release, such as cytokines, prostaglandin and nitric oxide. The aim of this study was to investigate the role of mast cells and their mediators in the intestinal secretion induced by cholera toxin. We examined the dose responses, time course and role of mast cells and pro-inflammatory mediators in cholera toxin intestinal secretory response, in vivo. Cholera toxin caused a dose-dependent secretion, in ligated small intestine loops, at 18 h. Rats treated with 48/80 compound or ketotifen had a significant decrease in the intestinal secretory response. Cholera toxin secretion was significantly reduced by an unspecific histamine/serotonin receptor antagonist, histamine receptor antagonist, phospholipase A2 and cyclooxygenase inhibitors, platelet-activating factor (PAF) receptor antagonists and TNF-alpha synthesis blockers. On the other hand, pretreatment with a specific serotonin receptor antagonist and lipoxygenase inhibitors failed to block this effect. Analysis of the intestinal fluid from rats injected with cholera toxin, revealed that cholera toxin induces the release of IL-1beta and TNF-alpha into fluid. The data suggest that, at least in part, mast cells are involved in cholera toxin-induced secretion, as well as point to the importance of histamine, prostaglandins, PAF, IL-1beta and TNF-alpha in this process.


Electromyographic analysis of specific exercises for scapular control in early phases of shoulder rehabilitation.
Restoration of control of dynamic scapular motion by specific activation of the serratus anterior and lower trapezius muscles is an important part of functional rehabilitation. This study evaluated activation of those muscles in specific exercises. Specific exercises will activate key scapular-stabilizing muscles in clinically significant amplitudes and patterns. Controlled laboratory study. Muscle activation amplitudes and patterns were evaluated in the serratus anterior, upper trapezius, lower trapezius, anterior deltoid, and posterior deltoid muscles with electromyography in symptomatic (n = 18) and asymptomatic (n = 21) subjects as they executed the low row, inferior glide, lawnmower, and robbery exercises. There were no significant differences in muscle activation amplitude between groups. Muscle activation was moderate across all of the exercises and varied slightly with the specific exercise. The serratus anterior and lower trapezius were activated between 15% and 30% in all exercises. Upper trapezius activation was high (21%-36%) in the dynamic exercises (lawnmower and robbery). Serratus anterior was activated first in the low row and last in the lawnmower and robbery. The upper trapezius and lower trapezius were activated first in the lawnmower and robbery. These specific exercises activate key scapular-stabilizing muscles at amplitudes that are known to increase muscle strength. These exercises can be used as part of a comprehensive rehabilitation program for restoration of shoulder function. They activate the serratus anterior and lower trapezius-key muscles in dynamic shoulder control-while variably activating the upper trapezius. Activation patterns depended on scapular position resulting in variability of amplitude and activation sequencing between exercises. Inferior glide and low row can be performed early in rehabilitation because of their limited range of motion, while lawnmower and robbery, which require larger movements, can be instituted later in the sequence.


Corrosive esophagitis in children. Assessment by the esophagogram.
The roentgenograms of 27 children aged 10 months to 13 years with endoscopically confirmed corrosive esophagitis were reviewed. The initial barium esophagogram showed 19 to have strictures. The length and irregularity of the strictures were recorded and related to the severity of the illness and the treatment required. In the remaining eight patients, the initial study gave normal results, but two were later shown to have developed strictures.