Significance of biological resource collection and tumor tissue bank creation.
Progress in the molecular oncology of gastrointestinal carcinomas depends on high quality cancer tissues for research. Recent acceleration on new technological platforms as well as the "omics" revolution increases the demands on tissues and peripheral blood for research at the DNA, mRNA and protein levels. Tissue bank creation emerges as a priority. Tumor tissue banks are facilities that are organized to collect, store and distribute samples of tumor and normal tissue for further use in basic and translational cancer research. The samples are generally obtained immediately after excision, prior to fixation, to ensure optimal preservation of proteins and nucleic acids. It is possible for surgeons or pathologists to collect fresh tissue prospectively during their routine dissection procedures. Most tissue banks are "project-driven" tumor banks, which are specialized collections of tumor samples on which their research is based. Systematic collection of all available tumor tissue is much rarer. High quality tissue banks need the collaboration of clinicians and basic scientists, but also the informed consent of patients and ethical approval. Through the standard operation procedure, snap frozen fresh tissue collection, storage and quality control for cryopreserved tissues are the pivotal factors on tissue bank construction and maintaining. The purpose of the tissue bank creation is enhancing the quality and speed on both the basic and translational research on gastrointestinal cancer. The quality assurance and quality control are handled based on reviewing HE staining slides or touch imprint cytology by pathologists.


Effects of manual lymph drainage for abdomen on the brain activity of subjects with psychological stress.
[Purpose] The present study investigated the effects of manual lymph drainage for abdomen on electroencephalography in subjects with psychological stress. [Subjects and Methods] Twenty-eight subjects were randomly allocated to undergo a 20-min session of either manual lymph drainage or abdominal massage on a bed. [Results] Analysis of electroencephalograms from the manual lymph drainage group showed a significant increase in relaxation, manifested as an increase in average absolute, relative alpha activity and a decrease in relative gamma activity. [Conclusion] Our results suggest that the application of manual lymph drainage from the abdomen provides acute neural effects that increase relaxation in subjects with psychological stress.


Time Period of Treatment's Effect on the Association Between Race and Survival in Patients With Malignant Colorectal Adenocarcinoma.
Colorectal cancer is one of the most common malignancies diagnosed in the United States, with 126,240 new cases diagnosed in 2020. Past studies have shown that disparities may exist between certain patient populations, but it is unknown how they are affected over time as treatments evolve. The purpose of this study was to determine whether the decade of treatment modifies the association between race and five-year survival in adults diagnosed and treated for malignant colorectal adenocarcinomas since the 1970s. This was a non-concurrent retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The inclusion criteria involved patients with primary malignant colorectal adenocarcinoma between the years 1975 and 2018. Exclusion criteria included previous malignancies or missing information on any of the variables. The exposure variable was the patient's race, and the main outcome variable was average five-year survival rates. The effect modifier was the time period in which the patient received treatment. The covariates of the study included age, sex, Hispanic status, surgical intervention recommendation, and disease stage. Unadjusted and adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using Cox regression models. As the interaction term between race/ethnicity and year of diagnosis was statistically significant, the data were stratified according to year of diagnosis. Black patients in both time periods had a higher mortality rate from malignant colorectal carcinoma after adjustment for the covariates (1975-1990: HR 1.10, 95% CI 1.06-1.15; 1991-2018: HR 1.19, 95% CI 1.16-1.23) when compared with White patients. American Indian, Alaskan Native, and Asian patients were found to have lower mortality in both time periods when compared with White patients (1975-1990: HR 0.90, 95% CI 0.85-0.95; 1991-2018: HR 0.93, 95% CI 0.89-0.96). Our data found that despite the evolution in the standard of care treatment for malignant colorectal adenocarcinoma since the year 1975, Black patients had lower five-year survival rates when compared with their White counterparts as well as increased rates of being diagnosed with this disease. Overall, addressing these disparities in colorectal cancer outcomes is critical for improving public health and reducing healthcare costs.


A γ-amino acid that favors 12/10-helical secondary structure in α/γ-peptides.
H-bonded helices in conventional peptides (containing exclusively homochiral α-amino acid residues) feature a uniform H-bonding directionality, N-terminal side C═O to C-terminal side NH. In contrast, heterochiral α-peptides can form helices in which the H-bond directionality alternates along the backbone because neighboring amide groups are oriented in opposite directions. Alternating H-bond directions are seen also in helices formed by unnatural peptidic backbones, e.g., those containing β- or γ-amino acid residues. In the present study, we used NMR spectroscopy and crystallography to evaluate the conformational preferences of the novel γ-amino acid (1R,2R,3S)-2-(1-aminopropyl)-cyclohexanecarboxylic acid (APCH), which is constrained by a six-membered ring across its Cα-Cβ bond. These studies were made possible by the development of a stereoselective synthesis of N-protected APCH. APCH strongly enforces the α/γ-peptide 12/10-helical secondary structure, which features alternating H-bond directionality. Thus, APCH residues appear to have a conformational propensity distinct from those of other cyclically constrained γ-amino acid residues.


Radiomic analysis identifies tumor subtypes associated with distinct molecular and microenvironmental factors in head and neck squamous cell carcinoma.
To identify whether radiomic features from pre-treatment computed tomography (CT) scans can predict molecular differences between head and neck squamous cell carcinoma (HNSCC) using The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 77 patients from the TCIA with HNSCC had imaging suitable for analysis. Radiomic features were extracted and unsupervised consensus clustering was performed to identify subtypes. Genomic data was extracted from the matched patients in the TCGA database. We explored relationships between radiomic features and molecular profiles of tumors, including the tumor immune microenvironment. A machine learning method was used to build a model predictive of CD8 + T-cells. An independent cohort of 83 HNSCC patients was used to validate the radiomic clusters. We initially extracted 104 two-dimensional radiomic features, and after feature stability tests and removal of volume dependent features, reduced this to 67 features for subsequent analysis. Consensus clustering based on these features resulted in two distinct clusters. The radiomic clusters differed by primary tumor subsite (p = 0.0096), HPV status (p = 0.0127), methylation-based clustering results (p = 0.0025), and tumor immune microenvironment. A random forest model using radiomic features predicted CD8 + T-cells independent of HPV status with R2 = 0.30 (p < 0.0001) on cross validation. Consensus clustering on the validation cohort resulted in two distinct clusters that differ in tumor subsite (p = 1.3 × 10-7) and HPV status (p = 4.0 × 10-7). Radiomic analysis can identify biologic features of tumors such as HPV status and T-cell infiltration and may be able to provide other information in the near future to help with patient stratification.


Unconventional Surface Critical Behavior Induced by a Quantum Phase Transition from the Two-Dimensional Affleck-Kennedy-Lieb-Tasaki Phase to a Néel-Ordered Phase.
A symmetry-protected topological phase has nontrivial surface states in the presence of certain symmetries, which can either be gapless or be degenerate. In this work, we study the physical consequence of such gapless surface states at the bulk quantum phase transition (QPT) that spontaneously breaks these symmetries. The two-dimensional Affleck-Kennedy-Lieb-Tasaki phase on a square lattice and its QPTs to Néel ordered phases are realized with the spin-1/2 Heisenberg model on a decorated square lattice. With large-scale quantum Monte Carlo simulations, we show that even though the bulk QPTs are governed by the conventional Landau phase transition theory, the gapless surface states induce unconventional universality classes of the surface critical behavior.


Carotid intima media thickness as a measure of cardiovascular disease burden in nigerian africans with hypertension and diabetes mellitus.
As part of a larger study of cardiovascular risk factors in nonhypertensive type 2 diabetes patients, we subjected a cohort of diabetics to B mode ultrasonography of the carotid artery to measure the intima media thickness (IMT) and compared it with values in hypertensives and apparently normal controls matched reasonably for gender and age. All groups were comparable in terms of age and gender representation. The mean (SD) of carotid IMT right and left was 0.94 mm (0.12), 0.94 mm (0.16); 0.93 mm (0.21), 0.93 mm (0.15); 0.91 mm (0.17), 0.91 mm (0.13) for diabetic, hypertensive, and normal groups, respectively. There was a nonsignificant tendency to raised IMT for the disease groups from the normal ones. Diabetic and hypertensive Nigerians are equally burdened by cardiovascular disease risk factors. Apparently normal subjects have a reasonable degree of burden suggesting the need to evaluate them for other traditional and emerging risk factors.


Characterizing affect dynamics with a damped linear oscillator model: Theoretical considerations and recommendations for individual-level applications.
People show stable differences in the way their affect fluctuates over time. Within the general framework of dynamical systems, the damped linear oscillator (DLO) model has been proposed as a useful approach to study affect dynamics. The DLO model can be applied to repeated measures provided by a single individual, and the resulting parameters can capture relevant features of the person's affect dynamics. Focusing on negative affect, we provide an accessible interpretation of the DLO model parameters in terms of emotional lability, resilience, and vulnerability. We conducted a Monte Carlo study to test the DLO model performance under different empirically relevant conditions in terms of individual characteristics and sampling scheme. We used state-space models in continuous time. The results show that, under certain conditions, the DLO model is able to accurately and efficiently recover the parameters underlying the affective dynamics of a single individual. We discuss the results and the theoretical and practical implications of using this model, illustrate how to use it for studying psychological phenomena at the individual level, and provide specific recommendations on how to collect data for this purpose. We also provide a tutorial website and computer code in R to implement this approach. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


An ex-vivo experimental study on optimization of bipolar radiofrequency liver ablation using perfusion-cooled electrodes.
To determine optimal parameters for bipolar radiofrequency ablation (RFA) using perfusion-cooled electrodes to create a large ablation volume in ex vivo bovine liver. Three sets of RF experiments were performed using a 200-Watt generator and two 15-gauge perfusion-cooled or internally cooled electrodes in ex vivo bovine livers. In the first set of experiments, to find the ideal inter-electrode distance for creating large coagulation necrosis, 30 ablation lesions were created by bipolar RFAs at inter-electrode spacings of 3 cm, 4 cm, and 5 cm. In the second set of experiments, to explore the ideal duration of RF application, bipolar RFAs were performed for 10 min and 20 min. In the first and second experiments, 10 lesions were made for each condition with infusion of 6% hypertonic saline (HS) at 2 ml/min. In the third set of experiments, 10 ablation lesions were created by bipolar RFAs using internally cooled electrodes without HS infusion. The mean volume of those ablation lesions was then compared to that of the lesions created by bipolar RFA using perfusion-cooled electrodes in the second experiments. Tissue impedance, dimension, and shape of the ablated areas were compared in each condition. In the first set of experiments, bipolar RFA created a homogeneous oval or spherical-shaped ablation area between the electrodes at 3-5 cm spacing, but showed a more spherical-shaped lesion at 3 cm inter-electrode spacing than at 4 cm and 5 cm spacing. In the second set of experiments, RF energy delivered for 20 min created a larger dimension of coagulation necrosis than energy delivered for 10 min: 107.6 +/- 34 cm3 versus 59.5 +/- 27 cm3 (P<0.05). In addition, the mean volume of ablation regions obtained with bipolar RFA using the internally cooled electrode was 47.5+/- 17 cm3, which was significantly less than that with bipolar RFA using perfusion-cooled electrodes (P <0.05). Bipolar RFA using perfusion-cooled electrodes achieves homogeneous areas of coagulation necrosis between two electrodes, preferably at 3 or 4 cm inter-electrode distance for 20 min, and is better in creating large coagulation necrosis than bipolar RFA using internally cooled electrodes.


Ongoing multistate outbreak of Escherichia coli serotype O157:H7 infections associated with consumption of fresh spinach--United States, September 2006.
On September 13, 2006, CDC officials were alerted by epidemiologists in Wisconsin and Oregon that fresh spinach was the suspected source of small clusters of Escherichia coli serotype O157:H7 infections in those states. On the same day, New Mexico epidemiologists contacted Wisconsin and Oregon epidemiologists about a cluster of E. coli O157:H7 infections in New Mexico associated with fresh spinach consumption. Wisconsin public health officials had first reported a cluster of E. coli O157:H7 infections to CDC on September 8. On September 12, CDC PulseNet had confirmed that the E. coli O157:H7 strains from infected patients in Wisconsin had matching pulsed-field gel electrophoresis (PFGE) patterns and identified the same pattern in patient isolates from other states. This report describes the joint investigation and outbreak-control measures undertaken by state public health officials, CDC, and the Food and Drug Administration (FDA). This investigation and additional case finding are ongoing.


Measurement of tumor necrosis factor alpha mRNA in small numbers of cells by quantitative polymerase chain reaction.
We have developed a method to quantitate TNF alpha-mRNA in small numbers of cells by reverse transcription followed by competitive polymerase chain reaction (RT-PCR). RT-PCR allowed the accurate quantitation of TNF alpha-mRNA over a 1000-fold range of concentration. The recovery of RNA isolated from 1000 to 10,000 cells was optimized by reducing sample volumes and by adding 1 microgram yeast RNA. Using these modifications we accurately measured TNF alpha-mRNA in as little as 10,000 U937 cells by RT-PCR. Then we measured TNF alpha-mRNA in lamina propria mononuclear cells isolated from uninflamed and inflamed colonic mucosa from patients with inflammatory bowel disease (IBD). A 9-fold increase (5.4 copies per cell) was found in mononuclear cells from the gut of the inflamed regions compared to those cells from the uninflamed regions (0.6 copies per cell). These findings demonstrated the utility of this method in measuring differences of expression of the TNF-alpha gene in small number of cells isolated from tissues.


Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial.
In a previous phase II trial, circadian (chronomodulated) delivery of fluorouracil (5-FU), folinic acid (FA; leucovorin), and oxaliplatin (1-OHP; a new platinum complex with no renal and minor hematologic toxic effects) produced an objective response rate of 58% in 93 patients with metastatic colorectal cancer. To determine whether chronomodulated drug delivery affects therapeutic activity, we again tested this regimen in another trial in patients with previously untreated metastatic colorectal cancer, this time comparing chronomodulated with constant-rate drug delivery. Seven European centers participated in this trial. Ninety-two patients with metastatic colorectal cancer were enrolled and assigned to a treatment schedule by central randomization. Treatment courses consisted of the daily administration of 5-FU (600 mg/m2 per day), FA (300 mg/m2 per day), and 1-OHP (20 mg/m2 per day) for 5 days and were repeated every 21 days (16-day intermission) in ambulatory patients with the use of a programmable in-time pump. Drug delivery was kept constant over a 5-day period in schedule A (47 patients). It was chronomodulated in schedule B (maximum delivery of 5-FU and FA infusions at 0400 hours and maximum delivery of 1-OHP at 1600 hours; 45 patients). A risk of partial chemical inactivation of 1-OHP by its 2-hour exposure to the basic pH of the 5-FU solution in the catheter was documented in schedule A. Severe stomatitis (grade 3 or 4, World Health Organization [WHO] grading system), the dose-limiting toxic effect of 5-FU, occurred in five times as many patients on schedule A than on schedule B (89% versus 18%; chi 2 = 46; P < .001). The cumulative dose-limiting toxicity of schedule B was peripheral sensitive neuropathy (WHO grade 2). This side effect was reversible following 1-OHP withdrawal. Higher doses of 5-FU were administered in schedule B (median: 700 mg/m2 per day) compared with schedule A (median: 500 mg/m2 per day) (P < .0001; Mann-Whitney U test). On schedule B, 24 of 45 patients (53%; 95% confidence interval [CI] = 38%-68%) exhibited an objective response compared with 15 of 47 patients (32%; 95% CI = 18%-46%) on schedule A (chi 2 = 4.3; P = .038). The median progression-free survival was, respectively, 11 and 8 months (P = .19; logrank). The median survival was 19 months (95% CI = 14.8-23.2) on schedule B and 14.9 months (95% CI = 12.1-17.8) on schedule A (P = .03; logrank). This ambulatory treatment modality was both more effective and less toxic if drug delivery was chronomodulated rather than constant over time. The respective roles of 1-OHP dose and schedule and circadian peak time of drug delivery are being investigated with regard to the high activity of this three-drug, chronomodulated chemotherapeutic regimen.


Dietary fiber is positively associated with cognitive control among prepubertal children.
Converging evidence now indicates that aerobic fitness and adiposity are key correlates of childhood cognitive function and brain health. However, the evidence relating dietary intake to executive function/cognitive control remains limited. The current study assessed cross-sectional associations between performance on an attentional inhibition task and dietary fatty acids (FAs), fiber, and overall diet quality among children aged 7-9 y (n = 65). Attentional inhibition was assessed by using a modified flanker task. Three-day food records were used to conduct nutrient-level analyses and to calculate diet quality (Healthy Eating Index-2005) scores. Bivariate correlations revealed that socioeconomic status and sex were not related to task performance or diet measures. However, age, intelligence quotient (IQ), pubertal staging, maximal oxygen uptake (V̇O2max), and percentage of fat mass (%fat mass) correlated with task accuracy. Hierarchical regression models were used to determine the relation between diet variables and task accuracy and reaction time across both congruent and incongruent trials of the flanker task. After adjustment of confounding variables (age, IQ, pubertal staging, V̇O2max, and %fat mass), congruent accuracy was positively associated with insoluble fiber (β = 0.26, P = 0.03) and total dietary fiber (β = 0.23, P = 0.05). Incongruent response accuracy was positively associated with insoluble fiber (β = 0.35, P < 0.01), pectins (β = 0.25, P = 0.04), and total dietary fiber (β = 0.32, P < 0.01). Higher diet quality was related to lower accuracy interference (β = -0.26, P = 0.03), whereas higher total FA intake was related to greater accuracy interference (β = 0.24, P = 0.04). No statistically significant associations were observed between diet variables and reaction time measures. These results demonstrate that children's diet quality, specifically dietary fiber, is an important correlate of performance on a cognitive task requiring variable amounts of cognitive control.


Establishment and rapid detection of a heterozygous missense mutation in the CACNA1F gene by ARMS technique with double-base mismatched primers.
Retinitis pigmentosa (RP) is a retinal degenerative disorder that often causes complete blindness. Mutations of more than 50 genes have been identified as associated with RP, including the CACNA1F gene. In a recent study, by employing next-generation sequencing, we identified a novel mutation in the CACNA1F gene. In this study, we used the amplification refractory mutation system (ARMS) and identified a single nucleotide change c.1555C>T in exon 13 of the CACNA1F gene, leading to the substitution of arginine by tryptophan (p.R519W) in a Chinese individual affected by RP. This study actually confirms this novel mutation, and establishes the ARMS technique for the detection of mutations in RP.


Diagnosis of acute acquired toxoplasmosis with the enzyme-labelled antigen reversed immunoassay for immunoglobulin M antibodies.
The reversed enzyme-labelled antigen immunoassay (R-EIA), based on the capture of serum immunoglobulin M antibodies (IgM) and subsequent addition of Toxoplasma gondii soluble antigen tagged with peroxidase and substrate, was evaluated comparatively with the IgM-indirect immunofluorescence test (IgM-IIF) for the detection of anti-toxoplasma IgM antibodies in sera from individuals with diagnosed acute acquired toxoplasmosis. Additional serum groups from normal healthy individuals and sera presenting possible nonspecific reactivities were also evaluated. Complete specificity of R-EIA was shown. There was no correlation between the magnitude of R-EIA results and IgM-IIF titers, but a positive (although not linear) correlation was found between R-EIA and the IgM-IIF titers obtained after adsorption of sera with Staphylococcus aureus protein A. Direct labelling of the antigen by a simple coupling technique facilitated the assay standardization and improved its signal-to-noise ratio.


Ergonomic Considerations in the Incidence of CTS in College of Dentistry, King Khalid University, Abha - Kingdom of Saudi Arabia.
Ergonomics in dentistry poses some challenges to dentists and may require considerable concentration and attention to detail. This research enables early recognition and prevention of common ergonomic-related conditions, such as carpel tunnel syndrome, back pain and neck pain. The purpose of this study was to determine the prevalence of ergonomic-related problems concerning carpel tunnel syndrome (CTS) and to know the efficacy of independent and combined clinical tests used in diagnosing it. Initially the participants were instructed to complete a self-administered questionnaire regarding the severity of symptoms of their hands on a hand-wrist diagram and a visual analogue scale. The principle investigator evaluated all questionnaires independently and four clinical tests were used on both hands in a systematic (non-randomised) order for subjects who had symptoms. Those with residual symptoms that exceeded beyond 1 min interval were identified and controlled for the statistical analyses. The most common symptom noted in the study group was tingling and numbness of fingers (66.46%) followed by neck pain (66.34%). 29.26% of subjects reported moderate difficulty in typing and driving vehicles, whereas 26.82% subjects felt moderate difficulty in grasping and carrying shopping bags. 61.94% of subjects with symptoms spent more than 1 h daily of their free time on mobile phones or other smart devices. Individually, in our study the Tinsel's sign stood out as ineffective in ruling out CTS when compared with Phalen's test. Combination tests like Phalen's test and compression tests are confirmatory to CTS diagnosis and 66.34 % of the research group were hence diagnosed for CTS. A positive criteria for CTS, neck and shoulder pain is identified in our study as being due to long-term use of mobile devices. Further, combination tests like Phalen's with pressure provocation tests proved accurate in conforming CTS. Future research is needed to confirm the diagnostic utility of these independent and combined clinical tests in less prevalent settings, including general dental practitioners and occupational worksites. The current study is registered in King Khalid University, College of dentistry ethical committee SRC/REG/2016-17/107.


Preventing postpartum depression: review and recommendations.
Nearly 20 % of mothers will experience an episode of major or minor depression within the first 3 months postpartum, making it the most common complication of childbearing. Postpartum depression (PPD) is significantly undertreated, and because prospective mothers are especially motivated for self-care, a focus on the prevention of PPD holds promise of clinical efficacy. This study is a qualitative review of existing approaches to prevent PPD. A PubMed search identified studies of methods of PPD prevention. The search was limited to peer-reviewed, published, English-language, randomized controlled trials (RCTs) of biological, psychological, and psychosocial interventions. Eighty articles were initially identified, and 45 were found to meet inclusion criteria. Eight RCTs of biological interventions were identified and 37 RCTs of psychological or psychosocial interventions. Results were mixed, with 20 studies showing clear positive effects of an intervention and 25 showing no effect. Studies differed widely in screening, population, measurement, and intervention. Among biological studies, anti-depressants and nutrients provided the most evidence of successful intervention. Among psychological and psychosocial studies, 13/17 successful trials targeted an at-risk population, and 4/7 trials using interpersonal therapy demonstrated success of the intervention versus control, with a further two small studies showing trends toward statistical significance. Existing approaches to the prevention of PPD vary widely, and given the current literature, it is not possible to identify one approach that is superior to others. Interpersonal therapy trials and trials that targeted an at-risk population appear to hold the most promise for further study.


Linking disaster resilience and urban sustainability: a glocal approach for future cities.
Resilience and sustainability will be two primary objectives of future cities. The violent consequences of extreme natural events and the environmental, social and economic burden of contemporary cities make the concepts of resilience and sustainability extremely relevant. In this paper we analyse the various definitions of resilience and sustainability applied to urban systems and propose a synthesis, based on similarities between the two concepts. According to the proposed approach, catastrophic events and the subsequent transformations occurring in urban systems represent a moment in the city life cycle to be seen in terms of the complex sustainability framework. Hence, resilience is seen as a requirement for urban system sustainability. In addition, resilience should be evaluated not only for single cities, with their physical and social systems, but also on a global scale, taking into account the complex and dynamic relationships connecting contemporary cities.


"What else to say?"-Primary health care in times of COVID-19 from the perspective of German general practitioners: An exploratory analysis of the open text field in the PRICOV-19 study.
The international collaboration study PRICOV-19 -Primary Health Care in times of COVID-19 aims to assess the impact of the COVID-19 pandemic on the organisation of primary health care. The German part focuses on the subjective perceptions of general practitioners on primary health care and the impact of political measures during the second wave of the COVID-19 pandemic. Within this survey, the "open text field" of the questionnaire was utilised remarkably frequently and extensively by the respondents. It became clear that the content that was named needed to be analysed in an exploratory manner. Accordingly, this paper addresses the following question: What preoccupies general practitioners in Germany during COVID-19 that we have not yet asked them enough? The data collection took place throughout Germany from 01.02.2021 to 28.02.2021with a quantitative online questionnaire consisting of 53 items arranged across six topics as well as an "open text field" for further comments. The questionnaire's open text field was analysed following the premises of the qualitative content analysis. The topics discussed by the respondents were: insufficient support from health policies, not being prioritised and involved in the vaccination strategy, feeling insufficient prepared, that infrastructural changes and financial concerns threatened the practice, and perceiving the own role as important, as well as that health policies affected the wellbeing of the respondents. One of the main points was the way general practitioners were not sufficiently acknowledged for their contribution to ensuring high-quality care during the pandemic. German general practitioners perceived their work and role as highly relevant during the COVID-19 pandemic. In controversy with their perception, they described political conditions in which they were the ones who contributed significantly to the fight against the pandemic but were not given enough recognition.


Occupational accidents and injuries in Thailand.
The Workers' Compensation Fund (WCF) represents only a limited fraction of work-related injuries in the Thai workforce. This cross-sectional study examined 258,986 records from the Thai National Injury Surveillance (NIS) system collected during 2001-2004, focusing on 17,538 injuries coded as work-related. NIS records provided information generally not represented in WCF statistics, such as construction and agriculture. The reported mechanisms in 129 work-related fatalities were particularly informative, including electrical current (27%), transport accidents (20%), and falls (15%). Mortality in transport accidents was dramatically higher when seat belts or motorcycle helmets were not used, whether work-related or not. The findings emphasize the need to use multiple sources of information for a complete picture of work-related injuries in Thailand, and possibly in other countries. The mechanisms of fatal injury indicate areas where focused efforts are warranted.


The causes and consequences of pest population variability in agricultural landscapes.
Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, the need for long-term pest population data across many farms has prevented researchers from exploring the drivers and implications of pest population variability (PV). Here, we demonstrate the critical importance of PV for sustainable farming by analyzing 13 years of pest densities across >1300 Spanish olive groves and vineyards. Variable populations were more likely to cause major yield losses, but also occasionally created temporal windows when densities fell below insecticide spray thresholds. Importantly, environmental factors regulating pest variability were very distinct from factors regulating mean density, suggesting variability needs to be uniquely managed. Finally, we found diversifying landscapes may be a win-win situation for conservation and farmers, as diversified landscapes promote less abundant and less variable pest populations. Therefore, we encourage agricultural stakeholders to increase the complexity of the landscapes surrounding their farms through conserving/restoring natural habitat and/or diversifying crops.


[A view on providing care in the field of medicines in Slovakia - the pharmacist and the patient].
The paper deals with the evaluation of care provided in a public pharmacy in terms of achieving patient / customer satisfaction. Expectations and opinions of patients are also confronted with the assumptions of pharmacists. Up to 82% of patients confirmed their satisfaction with the care given to them by the pharmacist. A key factor of patient satisfaction has proved particularly professional and human approach of pharmacist. 73.6% of patients in the survey accepted pharmacist as an expert on drugs. Pharmacist self-evaluation was more negative. Monitoring and evaluation of patient satisfaction with care delivered in the pharmacy is essential for the improvement of the quality of the health system and the implementation of pharmaceutical care focussed on the patient. The real application of pharmaceutical care in the practice currently lacks the necessary conditions and support.


Characterization and use of laser-based lysis for cell analysis on-chip.
We demonstrate the use of a pulsed laser microbeam for cell lysis followed by electrophoretic separation of cellular analytes in a microfluidic device. The influence of pulse energy and laser focal point within the microchannel on the threshold for plasma formation was measured. The thickness of the poly(dimethylsiloxane) (PDMS) layer through which the beam travelled was a critical determinant of the threshold energy. An effective optical path length, Leff, for the laser beam can be used to predict the threshold for optical breakdown at different microchannel locations. A key benefit of laser-based cell lysis is the very limited zone (less than 5 microm) of lysis. A second asset is the rapid cell lysis times (approx. microseconds). These features enable two analytes, fluorescein and Oregon Green, from a cell to be electrophoretically separated in the channel in which cell lysis occurred. The resolution and efficiency of the separation of the cellular analytes are similar to those of standards demonstrating the feasibility of using a pulsed laser microbeam in single-cell analysis.


[Prevalence of active pulmonary tuberculosis among household contacts of recently diagnosed pulmonary tuberculosis patients with positive sputum-smear].
To describe the prevalence of pulmonary tuberculosis (TB) among household contacts of patients recently diagnosed as pulmonary TB. Newly diagnosed pulmonary TB cases in 2006 were used as index cases for searching more active TB cases. All the household contacts were identified and examined with purified protein derivative, chest X-ray and sputum-smear for three times. The prevalence of active TB infection among household contacts was calculated and compared against demographic characteristics. A total of 1386 newly diagnosed active TB cases were reported and their 5392 household contacts were screened. The overall prevalence of active pulmonary TB among household contacts was 3.76%, but significantly higher in the age groups of <15 years or > or =55 years than the other age groups (chi2 = 15.381, P < 0.01). The rate of active pulmonary TB in household contacts was significantly associated with the amount of bacteria discharged from index cases (r = 0.998, P < 0.01). Through contact tracing, every 100 index cases could contribute in finding 15 more new active TB cases among household contacts. Our results showed that this program could increase the identification of active pulmonary TB case through tracking down the household contacts of newly diagnosed TB cases.


Incorporating robotic surgery into the management of ovarian cancer after neoadjuvant chemotherapy.
With the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III-IV ovarian cancer. All patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III-IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III-IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery. A total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24-88), 78% had stage III disease, and the median follow-up time was 37 months (5.6-91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10-1250 mL), and the median hospital stay was 1 day. Robotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.


Effects of different nitrogen doses and cultivars on fermentation quality and nutritive value of Italian ryegrass (Lolium multiflorum Lam.) silages.
The fermentation profile and silage quality of 3 Italian ryegrass (Lolium multiflorum Lam.) cultivars (cvs. Devis, Hellen, and Trinova) treated with 5 nitrogen doses (0, 50, 100, 150, and 200 kg/ha) were evaluated. The experiment was laid out in split plot in randomized complete block design with three replications. Annual ryegrass cultivars used in this study have been commonly grown in Turkey. Nitrogen doses were set in main plot and cultivars in split plot in the field. Plants were harvested at full-flowering stage with dry matter content about 220 g/kg for first cutting and 260 g/kg for second cutting. Harvested plants were chopped theoretically into 2 to 3 cm lengths for ensiling. Chopped fresh materials were ensilaged by compressing in 2 L plastic jars about 3±0.1 kg. Effects of N doses on dry matter, neutral detergent fiber, acid detergent fiber, dry matter digestibility, relative feed value, crude protein, pH, ammonia nitrogen, lactic acid, acetic acid, and lactic acid/acetic acid were statistically significant while water soluble carbohydrate, ash and organic matter were not statistically different. Ammonia nitrogen, crude protein, ash, organic matter, lactic acid, and lactic acid/acetic acid were affected by cultivars, but the other parameters were not. Increasing nitrogen applications positively affected the chemical composition of annual ryegrass silage. The significant increase in protein content was remarkable, however, silage fermentation properties were adversely affected by the increasing nitrogen dose. It can be recommended 150 kg/ha nitrogen dose for annual ryegrass harvested at full blooming stage. Even though the silage fermentation properties of the used cultivars were similar, cv. Devis gave better results than the others in terms of silage pH and relative feed value.


Streamer initiation in atmospheric pressure gas discharges by direct particle simulation.
A two-dimensional particle code that simulates electrical breakdown of gases by modeling avalanche evolution from the initial ion-electron pair up to the development of a streamer is presented. Trajectories of individual particles are followed, the self-field is included consistently and collision processes are accurately modeled using experimentally determined cross sections. It is emphasized that the tadpolelike structure of well-formed streamer heads is present throughout the avalanche phase, and that the transition to the self-similar evolution characteristic of the streamer phase merely reflects the continued development of this structure. The importance of this for conventional fluid simulations of streamers, where the initial conditions for the streamer are taken to be a structureless Gaussian concentration of neutral plasma with significant density, is discussed. In the (realistic) situation where several avalanches are present simultaneously the large self-fields that rapidly develop lead to a strong interaction between them, in accord with the standard "cartoon" of streamer evolution.


Associations of intracompartmental leg pressures and radiographic findings in congenital talipes equinovarus.
The etiopathogenesis of congenital talipes equinovarus remains mysterious. The authors investigated the role of increased intracompartmental leg pressures as a causal relationship with this deformity by measuring the pressures in 25 children aged between 6 months and 1 year with unilateral talipes equinivarus before surgical release. The deep posterior intracompartmental pressure in the leg with talipes equinovarus was greater than the other compartments, and the deep and superficial posterior intracompartmental pressures were also significantly higher than those of the contralateral normal sides (p < 0.05). There were linear correlations between the posterior intracompartmental pressure of affected legs and the Kite index, tibiocalcaneal angle and talo-first metatarsal angle of the affected legs. Deep posterior intracompartmental pressure is a strong predictor of abnormality in the Kite index. The present study showed a probable causal relationship between increased deep posterior intracompartmental pressure and etiopathogenesis of talipes equinovarus.


Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer.
We previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP. Microarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo. The downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155. Bmi-1 was proven to induce the expression of miR-27a and miR-155 and thus promote tumor metastasis and chemoresistance by targeting RKIP in GC. Overall, miR-27a and miR-155 might be promising targets for the screening, diagnosis, prognosis, treatment and disease monitoring of GC.


Primary palliative care for heart failure: what is it? How do we implement it?
Heart failure (HF) is a chronic and progressive illness, which affects a growing number of adults, and is associated with a high morbidity and mortality, as well as significant physical and psychological symptom burden on both patients with HF and their families. Palliative care is the multidisciplinary specialty focused on optimizing quality of life and reducing suffering for patients and families facing serious illness, regardless of prognosis. Palliative care can be delivered as (1) specialist palliative care in which a palliative care specialist with subspecialty palliative care training consults or co-manages patients to address palliative needs alongside clinicians who manage the underlying illness or (2) as primary palliative care in which the primary clinician (such as the internist, cardiologist, cardiology nurse, or HF specialist) caring for the patient with HF provides the essential palliative domains. In this paper, we describe the key domains of primary palliative care for patients with HF and offer some specific ways in which primary palliative care and specialist palliative care can be offered in this population. Although there is little research on HF primary palliative care, primary palliative care in HF offers a key opportunity to ensure that this population receives high-quality palliative care in spite of the growing numbers of patients with HF as well as the limited number of specialist palliative care providers.


Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of an N-arylbenzimidazole ligand's rescue of Parkinson's-associated cell toxicity.
The development of phenotypic models of Parkinson's disease (PD) has enabled screening and identification of phenotypically active small molecules that restore complex biological pathways affected by PD toxicity. While these phenotypic screening platforms are powerful, they do not inherently enable direct identification of the cellular targets of promising lead compounds. To overcome this, chemoproteomic platforms like Thermal Proteome Profiling (TPP) and Stability of Proteins from Rates of Oxidation (SPROX) can be implemented to reveal protein targets of biologically active small molecules. Here we utilize both of these chemoproteomic strategies to identify targets of an N-arylbenzimidazole compound, NAB2, which was previously identified for its ability to restore viability in cellular models of PD-associated α-synuclein toxicity. The combined results from our TPP and SPROX analyses of NAB2 and the proteins in a neuroblastoma-derived SHSY5Y cell lysate reveal a previously unrecognized protein target of NAB2. This newly recognized target, Rab1a, is a small GTPase that acts as a molecular switch to regulate ER-to-Golgi trafficking, a process that is disrupted by α-synuclein toxicity and restored by NAB2 treatment. Further validation reveals that NAB2 binds to Rab1a with selectivity for its GDP-bound form and that NAB2 treatment phenocopies Rab1a overexpression in alleviation of α-synuclein toxicity. Finally, we conduct a preliminary investigation into the relationship between Rab1a and the E3 ubiquitin ligase, Nedd4, a previously identified NAB2 target. Together, these efforts expand our understanding of the mechanism of NAB2 in the alleviation of α-synuclein toxicity and reinforce the utility of chemoproteomic identification of the targets of phenotypically active small molecules that regulate complex biological pathways.


The Impact of Caesarean Section on the Risk of Childhood Overweight and Obesity: New Evidence from a Contemporary Cohort Study.
Caesarean section (CS) rates are increasing globally and exceed 50% in some countries. Childhood obesity has been linked to CS via lack of exposure to vaginal microflora although the literature is inconsistent. We investigated the association between CS birth and the risk of childhood obesity using the nationally representative Growing-Up-in-Ireland (GUI) cohort. The GUI study recruited randomly 11134 infants. The exposure was categorised into normal vaginal birth (VD) [reference], assisted VD, elective (planned) CS and emergency (unplanned) CS. The primary outcome measure was obesity defined according to the International Obesity Taskforce criteria. Statistical analysis included multinomial logistic regression with adjustment for potential confounders. Infants delivered by elective CS had an adjusted relative risk ratio (aRRR) = 1.32; [95% confidence interval (CI) 1.01-1.74] of being obese at age three years. This association was attenuated when macrosomic children were excluded (aRRR = 0.99; [95% CI 0.67-1.45]). Infants delivered by emergency CS had an increased risk of obesity aRRR = 1.56; [95% CI 1.20-2.03]; this association remained after excluding macrosomic children. We found insufficient evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora.


[Arsenic metabolism in purple nonsulfur bacteria].
To elucidate the arsenic metabolic pathway of purple nonsulfur bacteria (PNSB). We investigated the distribution within their genomes, organization, composition, arrangement, core genes and coding proteins of arsenic gene clusters found in complete genome from 17 strains of PNSB by comparing the genomes analysis, and studied the arsenic metabolism in 3 members of PNSB under anaerobic conditions by UV-Vis and HPLC-ICP-MS. Arsenate reduction and arsenite methylation pathways mediated by ars operon are the dominating arsenic metabolic processes. The arsenic gene clusters differ vastly in composition and arrangement. Some members of PNSB evolved two independently families of arsenate reduction genes (arsC). The cells of Rhodopseudomonas palustris CQV97, Rhodobacter azotoformans 134K20 and Rhodobacter capsulatus XJ-1 could reduce As (V) to As (III), whereas As (III) could not be transformed back to As (V). Higher concentration phosphate competitively inhibited arsenate toxicity to cells. Our investigations shed light on the evolution and functional implications in arsenic gene clusters of PNSB, and support the notion that arsenate reduction and arsenite methylation appears to be the dominant process in PNSB.


A new function for lactate in the toad Bufo marinus.
In the amphibian Bufo marinus, progressive hypoxia below a critical PO2 elicits a transient 50% increase in O2 consumption that coincides with the onset of lactate formation. The present study was designed to test the hypothesis that lactate causes the observed rise in metabolic rate. Arterial bolus infusions of pH-neutral sodium lactate solutions (4 mmol/kg body wt) in toads maintained under hypoxia actually elicit a similar increase in metabolic rate. The application of adrenergic antagonists (bretylium tosylate, phentolamine, propranolol, and reserpine) inhibits this response, suggesting that catecholamines are involved. Moreover, animals injected with lactate move to a cooler environment (behavioral hypothermia), a behavioral response that is beneficial during hypoxia. We hypothesize that, in accordance with Cannon's concept of an emergency response, lactate may function as an alarm signal during hypoxia. However, the signal function of lactate is observed in animals both under hypoxia and under normoxia and should thus be considered in future studies whenever elevated lactate levels are present, e.g., during and after exercise.


Morse potential specific heat with applications: an integral equations theory based.
The specific heat in its molar form or mass form is a significant thermal property in the study of the thermal capacity of the described system. There are two basic methods for the determination of the molar specific heat capacity, one of them is the experimental procedure and the other is the theoretical procedure. The present study deals with finding a formula of the molar specific heat capacity using the theory of the integral equations for Morse interaction which is a very important potential for the study of the general oscillations in the quantum mechanics. We use the approximation (Mean-Spherical) for finding the total energy of the compositions described by Morse interaction. We find two formulas of the heat capacity, one at a constant pressure and the other at a constant volume. We conclude that the Morse molar specific heat is temperature dependent via the inverse square low with respect to temperature. Besides, we find that the Morse molar specific heat is proportional to the square of the Morse interaction well depth. Also, we find that the Morse molar specific heat depends on the particles' diameter, the bond distance of Morse interaction, the width parameter of Morse interaction, and the volumetric density of the system. We apply the formula of the specific heat for finding the specific heat of the vibrational part for two dimer which are the lithium and caesium dimers and for the hydrogen fluoride, hydrogen chloride, nitrogen, and hydrogen molecules.


Impact of sepsis bundle strategy on outcomes of patients suffering from severe sepsis and septic shock in china.
It is well known that poor sepsis outcomes are related to delays in diagnosis and treatment. The aim of this study was to compare the mortality rate between two groups of patients, one group presenting before and one group presenting after implementation of the Surviving Sepsis Campaign (SSC) sepsis performance improvement bundles in the Emergency Department (ED). This was a prospective study. The studied population included severe sepsis and septic shock patients entered in the SSC database who were admitted to the ED between June 2008 and December 2009. Patients were divided into two groups based on when they presented to the ED. Key treatment interventions, admission to the intensive care unit, and in-hospital mortality were compared. In addition, a survey was completed by the treating physicians to identify reasons for failures to comply with indicators. One hundred ninety-five (195) patients with severe sepsis and septic shock were enrolled in the study. Mortality was significantly higher at 44.8% in the baseline group (Group 1) compared to 31.6% in the group studied after the SSC protocol was instituted (Group 2) (p < 0.05). Compliance with all elements of the sepsis resuscitation bundle was 1% in Group 1 and 9% in Group 2 (p < 0.05). Compliance with all elements of the management bundle was 1% in Group 1 and 12.8% in Group 2. The most frequently reported reasons by physicians for failure to comply with the bundles were: "did not think it was needed" and "unsure of reason." The results revealed a significant drop in mortality after implementing the SSC protocol and sepsis performance improvement bundles in the ED. The barriers to implementing sepsis guidelines are knowledge, attitude, and behavioral barriers.


Clinical applications of lactate dehydrogenase isoenzymes.
A quantitative electrophoretic test for the determination of lactate dehydrogenase isoenzymes was applied to the analysis of human tissues, cells and fluids in order to obtain their normal isoenzyme patterns and to form a reference record. The same test was employed in the analysis of serum samples from patients with defined pathological conditions. The abnormal serum isoenzyme patterns were correlated with the tissue patterns, thus indicating the origin of the abnormality. This type of correlation, together with the clear demonstration of the actual isoenzymes and their quantitation, improves diagnostic discrimination and enhances the early detection of a biochemical abnormality that aids in the prevention of disease.


[African horse sickness and equine encephalosis: must Switzerland get prepared].
African horse sickness (AHS) of equines is partly transmitted by the same culicoides species as Bluetongue (BT) disease in even-toed ungulates. Horses normally get seriously sick, with a high case fatality rate. Equine Encephalosis is another, but less-known viral disease of equines, caused by viruses of the same genus as BT and AHS. Like BT of serotype 8 in 2006, both diseases could theoretically be introduced to Europe anytime and spread rapidly then. After the lessons learnt from the most recent bluetongue outbreaks in Europe, the regulations and AHS-contingency plans in force must be updated. All stakeholders must be aware of the risks and take own measures to prevent a possible emergence of the diseases, and be prepared in case of an outbreak.


Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution.
Although rhinitis is among the most common diseases worldwide, rhinitis prevalence in the general adult population is unclear and definitions differ widely. To summarize the literature on rhinitis prevalence in the general adult population and to assess: (1) the prevalence according to different rhinitis definitions overall and in different regions of the world, and (2) the evolution of rhinitis prevalence over time. We conducted an extensive literature review of publications including rhinitis prevalence using Pubmed and Scopus databases up to October 2020. We classified the definitions into three categories: unspecified rhinitis, allergic rhinitis (AR), and nonallergic rhinitis (NAR). Among 5878 articles screened, 184 articles were included, presenting 156 different definitions of rhinitis. Rhinitis prevalence ranged from 1% to 63%. The overall median prevalences of unspecified rhinitis, AR and NAR were 29.4%, 18.1% and 12.0%, and they varied according to the geographical location. Rhinitis prevalence tended to increase over time. This review highlights the great heterogeneity of the definitions. The majority of studies had focused on AR, while only a few epidemiological data exist on NAR. We found geographical variability in rhinitis prevalence. Most of studies reported an increase of rhinitis prevalence over the last decades.


A retrospective study of the occurrence of chronic superficial keratitis in 308 German Shepherd dogs: 1999-2010.
Chronic Superficial Keratitis (CSK) is an autoimmune mediated inflammation of the cornea, that is usually bilateral but often with nonsymmetrical manifestation. The aim of this study was to determine the occurrence and appearance of clinical symptoms of CSK in German Shepherd dogs in Poland and Slovakia. CSK was diagnosed in 308 German Shepherds for a period of 11 years (from 1999 to 2010). The highest incidence of the CSK (p < 0.001) in Slovakia and in Poland was in dogs between the ages of 5-8 years. This study found similarity in gender ratio of affected patients with CSK in two neighboring countries. This disease occurs most often in males, with almost identical frequency in both countries, Slovakia 65.63% and Poland 61.32%, respectively. The incidence of depigmentation and thickening of the external surface of the third eyelid together with CSK was observed in 69.19% of dogs in Poland and in 63.15% of dogs in Slovakia. CSK is often recognized in advanced stage-affected areas with inflammatory process by CSK, obtained frequently from 2 to 3 quadrants.


Analytic description of competitive grain growth.
We describe an analytic model for polycrystalline thin film growth based on competition between grains with conic geometries. This model is valid for all film thicknesses and is verified using level set simulations in 2+1 dimensions. We study the effects of nonuniform initial grain distributions on growth statistics. These results provide a possible explanation for discrepancies between experimentally measured and theoretical scaling laws.


[A qualitative research on the psychological experience of hospitalized patients with acute myocardial infarction].
To observe the psychological experience of patients with acute myocardial infarction (AMI) during hospitalization. From November 2012 to February 2013, semi-structured interviews were conducted in 10 patients with AMI in the Cardiovascular Department of First Affiliated Hospital of Henan University of Science and Technology. Grounded theory approach was performed to analyze the collected data. The 6 themes and 3 secondary themes during their hospitalization were: helplessness and dependence when AMI was diagnosed fear of immediate death induced by AMI, confusion on various problems such as operation time, excretory after PCI and limited knowledge details, the feel of safety after PCI, the fear of AMI, and the worry about overtreatment. Hospitalized AMI patients have complicated psychological responses. Medical staff should provide targeted strategies and timely communication with AMI patients to reduce their psychological burden.


Influence of cyclopentadienyl ring-tilt on electron-transfer reactions: redox-induced reactivity of strained [2] and [3]ruthenocenophanes.
In contrast to ruthenocene [Ru(η(5) -C5 H5 )2 ] and dimethylruthenocene [Ru(η(5) -C5 H4 Me)2 ] (7), chemical oxidation of highly strained, ring-tilted [2]ruthenocenophane [Ru(η(5) -C5 H4 )2 (CH2 )2 ] (5) and slightly strained [3]ruthenocenophane [Ru(η(5) -C5 H4 )2 (CH2 )3 ] (6) with cationic oxidants containing the non-coordinating [B(C6 F5 )4 ](-) anion was found to afford stable and isolable metalmetal bonded dicationic dimer salts [Ru(η(5) -C5 H4 )2 (CH2 )2 ]2 [B(C6 F5 )4 ]2 (8) and [Ru(η(5) -C5 H4 )2 (CH2 )3 ]2 [B(C6 F5 )4 ]2 (17), respectively. Cyclic voltammetry and DFT studies indicated that the oxidation potential, propensity for dimerization, and strength of the resulting RuRu bond is strongly dependent on the degree of tilt present in 5 and 6 and thereby degree of exposure of the Ru center. Cleavage of the RuRu bond in 8 was achieved through reaction with the radical source [(CH3 )2 NC(S)SSC(S)N(CH3 )2 ] (thiram), affording unusual dimer [(CH3 )2 NCS2 Ru(η(5) -C5 H4 )(η(3) -C5 H4 )C2 H4 ]2 [B(C6 F5 )4 ]2 (9) through a haptotropic η(5) -η(3) ring-slippage followed by an apparent [2+2] cyclodimerization of the cyclopentadienyl ligand. Analogs of possible intermediates in the reaction pathway [C6 H5 ERu(η(5) -C5 H4 )2 C2 H4 ][B(C6 F5 )4 ] [E=S (15) or Se (16)] were synthesized through reaction of 8 with C6 H5 EEC6 H5 (E=S or Se).


Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD.
Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory airway disease often associated with cigarette smoke (CS) exposure. The disease is increasing in global prevalence and there is no effective therapy. A major step forward would be to understand the disease pathogenesis. The ATP-P2X7 pathway plays a dominant role in murine models of CS induced airway inflammation, and markers of activation of this axis are upregulated in patients with COPD. This strongly suggests that the axis could be important in the pathogenesis of COPD. The aim of this study was to perform a detailed characterisation of the signalling pathway components involved in the CS-driven, P2X7 dependent airway inflammation. We used a murine model system, bioassays and a range of genetically modified mice to better understand this complex signalling pathway. The inflammasome-associated proteins NALP3 and ASC, but not IPAF and AIM2, are required for CS-induced IL-1β/IL-18 release, but not IL-1α. This was associated with a partial decrease in lung tissue caspase 1 activity and BALF neutrophilia. Mice missing caspase 1/11 or caspase 11 had markedly attenuated levels of all three cytokines and neutrophilia. Finally the mechanism by which these inflammatory proteins are involved in the CS-induced neutrophilia appeared to be via the induction of proteins involved in neutrophil transmigration e.g. E-Selectin. This data indicates a key role for the P2X7-NALP3/ASC-caspase1/11-IL-1β/IL-18 axis in CS induced airway inflammation, highlighting this pathway as a possible therapeutic target for the treatment of COPD.


Parallel MR imaging.
Parallel imaging is a robust method for accelerating the acquisition of magnetic resonance imaging (MRI) data, and has made possible many new applications of MR imaging. Parallel imaging works by acquiring a reduced amount of k-space data with an array of receiver coils. These undersampled data can be acquired more quickly, but the undersampling leads to aliased images. One of several parallel imaging algorithms can then be used to reconstruct artifact-free images from either the aliased images (SENSE-type reconstruction) or from the undersampled data (GRAPPA-type reconstruction). The advantages of parallel imaging in a clinical setting include faster image acquisition, which can be used, for instance, to shorten breath-hold times resulting in fewer motion-corrupted examinations. In this article the basic concepts behind parallel imaging are introduced. The relationship between undersampling and aliasing is discussed and two commonly used parallel imaging methods, SENSE and GRAPPA, are explained in detail. Examples of artifacts arising from parallel imaging are shown and ways to detect and mitigate these artifacts are described. Finally, several current applications of parallel imaging are presented and recent advancements and promising research in parallel imaging are briefly reviewed.


Shivering endurance and fatigue during cold water immersion in humans.
An important component of survival time during cold exposure is shivering endurance. Nine male and three female healthy and fit subjects [mean (SD) age 24.8 (6.3) years, body mass 71.7 (13.2) kg, height 1.75 (0.10) m, body fat 22.7 (7.4)%] were immersed to the upper chest level in cold water for periods ranging from 105 to 388 min on two occasions to test a prediction of shivering endurance. The water was cooled from 20 to 8 degrees C during the first 15 min of immersion and subsequently rewarmed (<20 degrees C) to elicit a near constant submaximal shivering response. The data were divided according to moderate (M) and high (H) levels of shivering intensity. Respective mean total immersion times were 250 (75) and 199 (80) min ( P=0.086) at different average shivering intensities of 61 (10) and 69 (8)% relative to maximal shivering ( P<0.001). Blood plasma glucose concentration increased during the immersion [from 3.44 (0.54) pre- to 3.94 (0.60) mmol x l(-1) post-immersion ( P=0.037)] and levels were higher during M ( P=0.012). When compared to a model prediction of shivering endurance, shivering activity continued well beyond the predicted endurance times in 18 out of the 24 trials. The average rates of oxygen consumption over the entire immersion period were lower ( P=0.002) during M [0.93 (0.20) l x min(-1)] compared to H [1.05 (0.21) l x min(-1)), and while these rates did not change during the last 90 min of immersion, there was an increase in fat oxidation. There were no trial differences in the average esophageal (T(es)) and mean skin temperatures during the entire immersion period (36.0 and 18.0 degrees C, respectively), yet T(es) decreased ( P=0.003) approximately 0.4 degrees C during the last 90 min of immersion. When the shivering intensity was normalized to account for this decrease, a significant downward trend of approximately 17% x h(-1) in the normalized shivering intensity was found after the predicted end of shivering endurance. These results suggest that shivering drive, and not shivering intensity per se, decreased during the latter stages of the immersion. Underlying mechanisms such as fatigue and habituation for this diminishing cold sensitivity are discussed.


Human Listeriosis Presenting as Breast Abscess: Report of a Rare Case.
An abscess is defined as a collection of pus in various tissues of the body including skin and other organs. Abscesses most commonly are formed on the skin under the armpits, groin areas, and rectal areas. Most abscesses involve microbial infections with few remaining sterile. The treatment of abscesses includes both medical and surgical intervention. In the era of multidrug resistance, isolation and identification of the causative microbe and testing for antimicrobial susceptible patterns assume greater significance for the better management of patients, thereby reducing the resultant morbidity and mortality. Listeria spp. are a group of aerobic and non-spore forming gram-positive bacilli. They are present in the environment, soil, and water. Listeria spp. have also been noted to be present as a normal intestinal flora of animals. They are known for their ability to thrive under both cold and hot environmental conditions. Human infections with Listeria spp. have not been frequently reported, mostly because of the difficulty in laboratory identification and complex clinical presentations. In humans, Listeria spp. have been frequently responsible for food poisoning and neonatal meningitis. Although not considered as a classic pathogen, Listeria spp. are associated with infections in elderly people, pregnant women, newborns, and persons with weakened immune systems. This report presents a case of breast abscess caused by Listeria spp. in a young lactating female belonging to rural India.


Carbenicillin inactivation of aminoglycosides in patients with severe renal failure.
Carbenicillin appears to produce clinically important inactivation of aminoglycoside antibiotics in patients with severe renal failure. If combination carbenicillin/aminoglycoside therapy is used in patients with severe renal failure, the dose of carbenicillin must be adjusted to renal function and serum levels of both drugs should be monitored. Even with therapeutic serum carbenicillin levels (100-200 mug/ml), large doses of aminoglycosides may be required to achieve therapeutic serum levels and this may increase the risk of toxicity.


Tumor in the Crossfire: Inhibiting TGF-β to Enhance Cancer Immunotherapy.
Cancer immunotherapy using monoclonal antibodies targeting immune checkpoints has undoubtedly revolutionized the cancer treatment landscape in the last decade. Immune checkpoint inhibitors can elicit long-lasting, previously unheard-of responses in a number of tumor entities. Yet, even in such tumors as metastatic melanoma and non-small cell-lung cancer, in which immune checkpoint inhibition has become the first-line treatment of choice, only a minority of patients will benefit considerably from these treatments. This has been attributed to a number of factors, including an immune-suppressive tumor microenvironment (TME). Using different modalities to break these barriers is of utmost importance to expand the population of patients that benefit from immune checkpoint inhibition. The multifunctional cytokine transforming growth factor-β (TGF-β) has long been recognized as an immune-suppressive factor in the TME. A considerable number of drugs have been developed to target TGF-β, yet most of these have since been discontinued. The combination of anti-TGF-β agents with immune checkpoint inhibitors now has the potential to revive this target as a viable immunomodulatory therapeutic approach. Currently, a limited number of small molecular inhibitor and monoclonal antibody candidates that target TGF-β are in clinical development in combination with the following immune checkpoint inhibitors: SRK 181, an antibody inhibiting the activation of latent TGF-β1; NIS 793, a monoclonal antibody targeting TGF-β; and SHR 1701, a fusion protein consisting of an anti-PD-L1 monoclonal antibody fused with the extracellular domain of human TGF-β receptor II. Several small molecular inhibitors are also in development and are briefly reviewed: LY364947, a pyrazole-based small molecular inhibitor of the serine-threonine kinase activity of TGFβRI; SB-431542, an inhibitor targeting several TGF-β superfamily Type I activin receptor-like kinases as well as TGF-β1-induced nuclear Smad3 localization; and galunisertib, an oral small molecular inhibitor of the TGFβRI kinase. One of the most advanced agents in this area is bintrafusp alfa, a bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II fused to a human IgG1 mAb blocking PD-L1. Bintrafusp alfa is currently in advanced clinical development and as an agent in this space with the most clinical experience, is a focused highlight of this review.


Role of RIPK3‑CaMKII‑mPTP signaling pathway‑mediated necroptosis in cardiovascular diseases (Review).
Necroptosis, which is distinct from apoptosis and necrosis, serves a crucial role in ontogeny and the maintenance of homeostasis. In the last decade, it has been demonstrated that the pathogenesis of cardiovascular diseases is also linked to necroptosis. Receptor interaction protein kinase (RIPK) 1, RIPK3 and mixed lineage kinase domain‑like protein serve vital roles in necroptosis. In addition to the aforementioned necroptosis‑related components, calcium/calmodulin‑dependent protein kinase II (CaMKII) has been identified as a novel substrate for RIPK3 that promotes the opening of the mitochondrial permeability transition pore (mPTP), and thus, mediates necroptosis of myocardial cells through the RIPK3‑CaMKII‑mPTP signaling pathway. The present review provides an overview of the current knowledge of the RIPK3‑CaMKII‑mPTP‑mediated necroptosis signaling pathway in cardiovascular diseases, focusing on the role of the RIPK3‑CaMKII‑mPTP signaling pathway in acute myocardial infarction, ischemia‑reperfusion injury, heart failure, abdominal aortic aneurysm, atherosclerosis, diabetic cardiomyopathy, hypertrophic cardiomyopathy, atrial fibrillation, and the cardiotoxicity associated with antitumor drugs and other chemicals. Finally, the present review discusses the research status of drugs targeting the RIPK3‑CaMKII‑mPTP signaling pathway.


Parallel Coupling of Ion Mobility Spectrometry and Ion Trap Mass Spectrometry for the Real-Time Alarm Triggering and Identification of Hazardous Chemical Leakages.
Hazardous chemical leakages involved in chemical terrorist attacks and chemical industrial accidents have been posing severe threats to human health and the environment. Vehicle-mounted mass spectrometry (MS) has been developed for continuous, on-road measurements to map the spatial and temporal distributions of hazardous chemicals. However, the detection of chemicals with small temporal scales and spatial scales is always challenging. In this study, a parallel coupling apparatus combining the techniques of ion mobility spectrometry and ion trap MS (p-IMS-ITMS) was developed to improve the detection rate and the time response capability of a stand-alone ITMS system for short time-span chemical tracking. A workflow was also proposed along with the apparatus, where the ITMS system can be triggered, as chemical suspects were discovered with the IMS system. The sampling positions of the ITMS system were investigated and optimized. In addition, a strategy was proposed to diminish the time span of samples from 1.5 to 0.5 s for evaluating the performances of the p-IMS-ITMS system. The detection rate of the stand-alone ITMS system was measured to be only 9.5, 32, and 87.5% for the time span of 0.5, 1, and 1.5 s, respectively. By comparison, the detection rates of the p-IMS-ITMS system were 99.5, 100, and 100%, where the detection rate was increased by a factor of 10 for 0.5 s time span. Moreover, the addition of an IMS system could provide temporal patterns of hazardous chemicals with a resolution of 33 ms. Finally, the potential of the p-IMS-ITMS system for environmental navigation monitoring and assessment was further demonstrated by detecting the leakages of dimethyl methyl phosphonate and dipropylene glycol monomethyl ether.


Preparation of biodegradable gelatin/PVA porous scaffolds for skin regeneration.
Porous scaffolds composed of gelatin/poly (vinyl alcohol), (Gel/PVA), were prepared using combination of freeze gelation and freeze drying methods. The effect of polymer concentration, gelatin/PVA ratio, and glutaraldehyde/gelatin ratio (GA/Gel) was investigated on morphology of pores, swelling ratio, biodegradation, and skin cell culture. At optimum preparation conditions the scaffolds had uniform pore size distributions showing high swelling ratio of 23.6. The scaffolds were of biodegradable nature and almost degraded in 28 days. Human dermal fibroblast cells (HDF) were cultured on the scaffolds and MTS assay was conducted to evaluate the influence of PVA on growth and proliferation of the cells.


The routine bridling of nasojejunal tubes is a safe and effective method of reducing dislodgement in the intensive care unit.
To determine if the routine bridling of nasoenteric feeding tubes in the intensive care unit is a low-morbidity, cost-effective method of decreasing tube dislodgement. Data were prospectively collected from 62 consecutive bridled patients and compared with that from 172 consecutive unbridled patients for differences in tube dislodgement, nasal ulceration, and estimated cost. Bridled patients demonstrated significantly less tube dislodgement (6.5% vs 32.6%, P < .0001). Bridling resulted in 4 cases of nasal ulceration per 800 tube feeding days, all of which were associated with red rubber catheter bridles. Conversion to 1/8-in umbilical tape bridles eliminated ulceration and further reduced dislodgement from 10% to 4.8%. Implementation of bridling saved an estimated $4038 over 3 months. Nasal bridling is a simple, cost-effective practice that may reduce the rate of nasoenteric tube dislodgement. The use of 1/8-in umbilical tape may be more effective and safer than 8-Fr red rubber catheters for this purpose.


[What is cytochrome P-450? Enzyme forms of cytochrome P-450--extent of knowledge].
The submitted review summarizes contemporary knowledge of the enzyme P 450, the importance of which in human metabolic processes has been beyond doubt for a long time. The existence of various forms of the enzyme (there is a number of enzymatic forms of this haemoprotein which does not differ only as regards the structure of the alipoprotein but also as regards some physical and chemical properties) was proved in many prokaryotic and eukaryotic organisms. It played a special role in herbivores. New forms were detected which can be induced e. g. by polycyclic hydrocarbons, barbiturates, steroids, ethanol (1), hypolipidaemic substances and some antibiotics. Also other regulating factors are known. The clinical use of P 450 is complicated so far by the great genetically conditioned multiplicity of its forms in man. However, a number of very promising and important applications are foreseen.


Prevention & women's health: making the health care system more responsive to women. Grantmakers In Health.
This report is the first in a series of programs made possible by a grant to Grantmakers In Health (GIH) from The Commonwealth Fund to bring grantmakers together with experts in policy, practice, and research to exchange information and ideas about key health issues facing the nation. On May 10, 1999, GIH convened a small group of grantmakers along with experts in community health, research, and government for an Issue Dialogue on prevention and women's health. Intended to both share lessons learned and stimulate new ideas, the Issue Dialogue proved to be a lively and insightful forum on the challenges and opportunities in funding projects in this area. This Issue Brief brings together key points from the day's discussion with factual information on women's health and grantmaker activities drawn from a background paper prepared for Dialogue participants.


Demonstration of highly specific and sensitive antibodies to a naturally occurring tetrahydroisoquinoline alkaloid, salsolidine.
1. We report for the first time on the production and characterization of antibodies against a naturally occurring tetrahydroisoquinoline, namely salsolidine (6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline). 2. Immunogen synthesis was carried out by coupling the hapten salsolidine to bovine serum albumin (BSA) as carrier protein on the basis of reductive amination. 3. By immunization of rabbits with salsolidine-BSA conjugate antisalsolidine antibodies were produced. 4. At a final dilution of 1:1700 the highest-titre antiserum bound 35% of 0.21 pmol [3H]salsolidine. This antiserum was used to develop a radioimmunoassay for salsolidine. 5. Cross-reactivity studies revealed a high specificity of the antiserum to the hapten. 6. The antibodies had a high affinity to salsolidine (Ka = 1.5 x 10(9) M-1). 7. Standard curves covered a measuring range of 0.5-70 pmol/tube and the detection limit was found to be 0.27 pmol/tube.


From earth's primitive atmosphere to chiral peptides--the origin of precursors for life.
To re-enact the long way to the origin of life with today's chemical methods, many steps have to be investigated in the light of a primordial scenario deduced from geochemical research. After the formation of our planet and its atmosphere, prebiotic chemical evolution started its course with the formation of the first building blocks for the formation of biomolecules. In the case of proteins, those building blocks were amino acids that had to be formed in the primitive atmosphere, and then had to react to peptides and proteins as the main pillar of first life. In this paper, we describe the processes in the primordial atmosphere according to contemporary geochemical knowledge leading to the synthesis of amino acids until the formation of homochiral peptides, and, thus, show a plausible pathway towards the origin of life.


Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022.
Bronchiolitis obliterans (BO) is a rare and irreversible chronic respiratory disease. The diagnosis of BO is challenging, and there still needs to be specific therapies and uniform treatment guidelines available. Research on BO has grown steadily over the past 20 years, and with the continued interest of researchers in this area, a bibliometric study of BO becomes necessary. This topic aims to assess the current state of research in BO over the last 2 decades and to identify research hotspots and emerging directions. Information on BO-related articles were obtained from the Science Citation Index Expand of the Web of Science Core Collection (WOSCC [SCI-E]) database. Citespace (6.1.R6), VOSviewer (1.6.18), and the online bibliometrics website (https://bibliometric.com/) were used for bibliometric analysis mainly to include country/region, institution, author, journal, keywords, and references and to construct visual knowledge network diagrams. A total of 4153 publications from the WOSCC [SCI-E] database were included in this study. Most publications come from the United States, Japan, and Germany, which collaborate relatively more frequently. Research institutions in the United States, especially the University of Washington, published the largest number of BO-related articles. Regarding authors, Vos, R is the most productive author, while Verleden, GM is the most influential in BO. In addition, JOURNAL OF HEART AND LUNG TRANSPLANTATION is the journal with the most published articles. The most cited article is Estenne M, 2002. Based on the clustering analysis of keywords and references, the diagnosis of bronchiolitis obliterans syndrome (BOS), treatment of BOS, and risk factors of BO are the current research hotspots and future research trends. We analyzed the publication trends in BO by bibliometrics and mapped the knowledge network of major contributing countries/regions, institutions, authors, and journals. Current research hotspots were found based on the main keywords and references. The outcome may help researchers identify potential collaborators, collaborating institutions, and hot fronts in BO to enhance collaboration on critical issues and improve the diagnosis and treatment of BO.


RIG-I-like receptors: Molecular mechanism of activation and signaling.
During RNA viral infection, RIG-I-like receptors (RLRs) recognize the intracellular pathogenic RNA species derived from viral replication and activate antiviral innate immune response by stimulating type 1 interferon expression. Three RLR members, namely, RIG-I, MDA5, and LGP2 are homologous and belong to a subgroup of superfamily 2 Helicase/ATPase that is preferably activated by double-stranded RNA. RLRs are significantly different in gene architecture, RNA ligand preference, activation, and molecular functions. As switchable macromolecular sensors, RLRs' activities are tightly regulated by RNA ligands, ATP, posttranslational modifications, and cellular cofactors. We provide a comprehensive review of the structure and function of the RLRs and summarize the molecular understanding of sensing and signaling events during the RLR activation process. The key roles RLR signaling play in both anti-infection and immune disease conditions highlight the therapeutic potential in targeting this important molecular pathway.


Multi organ failure following intravenous gasoline for suicide: a case report.
Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of necrotic tissues, at the operation room. He was intubated and mechanically ventilated because of acute lung injury. He developed acute kidney injury after 2 days. These symptoms seem to be due to extravasation of gasoline from vessels which lead to inflammation, cell damage and organ failure. The patient developed multi organ failure which unfortunately did not respond to our treatment and he died at day 21. Management of gasoline intoxication depends on the rout of exposure. Like other types of toxications, intravenous toxication has pulmonary involvement, however in this case we had multiple organ involvement. It seems that in such cases we should consider early end organ targeted therapy to stop the future organ failure.


The vibrational dependence of dissociative recombination: rate constants for N2 (+).
Dissociative recombination rate constants are reported with electron temperature dependent uncertainties for the lowest 5 vibrational levels of the N2 (+) ground state. The rate constants are determined from ab initio calculations of potential curves, electronic widths, quantum defects, and cross sections. At 100 K electron temperature, the rate constants overlap with the exception of the third vibrational level. At and above 300 K, the rate constants for excited vibrational levels are significantly smaller than that for the ground level. It is shown that any experimentally determined total rate constant at 300 K electron temperature that is smaller than 2.0 × 10(-7) cm(3)/s is likely to be for ions that have a substantially excited vibrational population. Using the vibrational level specific rate constants, the total rate constant is in very good agreement with that for an excited vibrational distribution found in a storage ring experiment. It is also shown that a prior analysis of a laser induced fluorescence experiment is quantitatively flawed due to the need to account for reactions with unknown rate constants. Two prior calculations of the dissociative recombination rate constant are shown to be inconsistent with the cross sections upon which they are based. The rate constants calculated here contribute to the resolution of a 30 year old disagreement between modeled and observed N2 (+) ionospheric densities.


CDK redundancy guarantees cell cycle progression in Rb-negative tumor cells independently of their p16 status.
A high percentage of tumor cells bear mutations in the Rb tumor suppressor gene. They have high levels of the cdk inhibitor p16(ink4a) and no cyclin D/cdk4-6 complexes. Although p16 is known not to arrest the proliferation of Rb-negative cells, it is not known whether its presence affects how their cycle progresses, how E2F-dependent transcription is modulated, and whether and how Rb-related proteins are inactivated. We have assessed the relevance of p16(ink4a) for cell cycle progression of these cells. Using SaOS2 osteosarcoma cells as a model, we find that downregulation of p16(ink4a) by RNAi and reconstitution of active cyclin D/cdk4 complexes does not affect progression of the cycle of these cells or expression of E2F-dependent genes. Rb-negative tumor cells can functionally inactivate Rb-related proteins in G(1)/S transition independently of their p16(ink4a) status. Furthermore, Rb-negative tumor cells do not arrest when cdk1, cdk2 or cdk3 are inhibited by RNAi, independently of their p16(ink4a) status, and combined inhibition of these cdks is also not enough to arrest their cell cycle. However, cell cycle progression of Rb-negative tumor cells is sensitive to complete cdk inhibition, as it is arrested by the chemical cdk inhibitor roscovitine and the biological cdk inhibitor p27. These results suggest that, despite their lack of cyclin D-containing complexes, Rb-negative tumor cells, like normal untransformed cells, take advantage of the high degree of redundancy of cdks for their cell cycle progression.


Correlates of Human Papillomavirus Vaccination and Association with HPV-16 and HPV-18 DNA Detection in Young Women.
Background: Despite a reduction in the prevalence of vaccine-preventable types of human papillomavirus (HPV), attributed to increased HPV vaccine uptake, HPV continues to be a major cause of cancer in the United States. Methods: We assessed factors associated with self-reported HPV vaccine uptake, HPV vaccination effectiveness, using DNA testing to assess HPV types 16 and/or 18 (HPV 16/18) positivity, and patterns of HPV vaccination in 375 women aged 21-29 years who were eligible to receive catch-up vaccination, using baseline data collected from March 2012 to December 2014 from a randomized controlled trial evaluating a novel approach to cervical cancer screening. Results: More than half (n = 228, 60.8%) of participants reported receipt of at least one HPV vaccine dose and 16 (4.3%) tested positive for HPV 16/18 at baseline. College-educated participants were four times more likely to have been vaccinated than those reporting high school education or less. 56.5% of HPV-vaccinated participants reported first dose after age 18 and 68.4% after first vaginal intercourse. Women vaccinated after age 18 and women vaccinated after first vaginal intercourse were somewhat more likely to be infected with HPV 16/18 infection compared with women vaccinated earlier, but these associations did not reach statistical significance. Conclusions: HPV vaccination is common among college-educated women in the catch-up population but less common among those without college education. Contrary to current guidelines, catch-up females frequently obtain HPV vaccination after age 18 and first vaginal intercourse. Women without a college education represent an ideal population for targeted HPV vaccination efforts that emphasize vaccination before sexual debut.


Valbenazine for the treatment of tardive dyskinesia.
Tardive dyskinesia (TD) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for TD is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of TD. Areas covered: An overview of TD, unmet medical needs and current treatment guidelines are presented. The background, chemistry and clinical development of valbenazine to treat TD is detailed. A competitive market is developing as the treatment gap is identified and potential therapies are discussed in context of a broader market overview. Expert opinion: Antipsychotic use is growing among adults and children in the U.S. Consequently, prevalence of TD is expected to rise. Cessation of antipsychotics is often not possible as the psychiatric condition may deteriorate. Increasing doses of an antipsychotic to suppress involuntary movements is not sustainable long term as underlying TD worsens and movements typically recur. There were no FDA approved treatments for TD. The approval of valbenazine to treat TD is a critical step in addressing this gap in neurologic care.


Functional evaluation of the porcine heterograft in the mitral position.
In vivo function of glutaraldehyde-fixed porcine heterografts used for mitral valve replacement was evaluated by cardiac catheterization in 14 of our first 33 patients who have undergone mitral valve replacement with this prosthesis. Diastolic gradients were present in each patient. Average mean diastolic gradient was 6.5 mm Hg for the group, and average end-diastolic gradient was 3.0 mm Hg. Calculated mitral valve orifice areas ranged from 0.92 cm2 to 3.39 cm2, the average being 2.15 cm2. With rapid pacing (heart rate approximately 140), average mean gradient increased by 6 mm Hg. No patient had mitral regurgitation. Two patients had calculated mitral valve areas of 1 cm2 or less; one of these was found at postmortem examination to have thrombus adherent to the ventricular aspect of 2 of the 3 valve leaflets, rendering them immobile.


All-cause and cause-specific mortality by socioeconomic status among employed persons in 27 US states, 1984-1997.
We investigated mortality differences according to socioeconomic status (SES) for employed persons in 27 states during 1984-1997. SES was determined for persons aged 35-64 years according to the "usual occupation" listed on their death certificates. We used US Census denominator data. For all-cause mortality, rate ratios from lowest to highest SES quartile for men and women were 2.02, 1.69, 1.25, and 1.00 and 1.29, 1.01, 1.07, and 1.00, respectively. Percentage of all deaths attributable to being in the lowest 3 SES quartiles was 27%. Inverse SES gradients were strong for most major causes of death except breast cancer and colorectal cancer. Heart disease mortality for highest and lowest SES quartiles dropped 45% and 25%, respectively, between 1984 and 1997. Mortality differences by SES were sustained through the 1990s and are increasing for men.


Representing consumer interests: imbalanced markets, health planning, and the HSAs.
The health planning legislation of 1974, establishing HSAs, represented an important attempt to break recurring patterns of decision making in public choices. One widely heralded strategy for controlling contemporary medical care--consumer involvement through accountability, representation, and participation--is flawed by failure to recognize that political markets are always imbalanced because of unequal interests and disproportionate resources. How can we represent broad, diffuse interests when all the incentives point to domination by a minority of intensely interested producers? Solutions favored at the local level may not best serve the entire nation; they cannot mirror the full spectrum of constituencies. Adjustment of mechanisms both internal to HSAs and external to them are suggested--yet, even so, their mandate reaches beyond possibility of accomplishment.


Urgent action needed to address key worker housing crisis.
We report this week that a group of nurses living in a block of flats in south east London faced with a 20% rent hike have been given just 8 weeks to pay up or move out.