Timbral influences on vocal pitch-matching accuracy.
The purpose of this study was to investigate how vocal fundamental frequency control was influenced by the timbre of target auditory stimuli. Nineteen female participants were asked to vocally reproduce the pitch of target tones, which consisted of female, male, violin, and clarinet timbres at three different fundamental frequencies. Results revealed that the participants were significantly more accurate at matching the pitch of female target tones compared to the instrumental timbres. This was interpreted as being due to an effect of spectral similarity of the female timbre to that of the female participants. The results of this study support the hypothesis of a perceptual integrality between timbre and pitch, and that stimulus timbre can influence the accuracy of vocal reproduction.


Nonlinear immunofluorescent assay for androgenic hormones based on resonant structures.
We report for the first time the use of two photon fluorescence as detection method of affinity binding reactions. We use a resonant grating waveguide structure as platform enhancement for detecting the interaction between fluorescent labeled Boldenone, a non-natural androgenic hormone, and a specific anti-anabolic antibody. We were able to detect a surface coverage of approximately 0.7 ng/mm(2).


Trends in Survival Based on Treatment Modality in Non-Small Cell Lung Cancer Patients: A Population-Based Study.
Objectives: We examined the trends in survival based on treatment modality among non-small cell lung cancer (NSCLC) patients in the province of Ontario, Canada, from 2007 to 2015. Methods: We investigated the trends in survival based on treatment modality. Results: Among 56,417 identified patients, the mean age at diagnosis was 70.1 years (SD = 10.7). Treatment modalities varied significantly over time (p<.001). Overall, 23.0% of patients received surgical treatments. We observed more than 20% increase in five-year survival rates for all surgical groups over time. Conclusions: Patients undergoing sublobar/lobar resections had higher survival rate.


The Care of Children With Cancer During the COVID-19 Pandemic.
The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.


Is interviewer support associated with the reduced reluctance and enhanced informativeness of alleged child abuse victims?
Child maltreatment victims are often reluctant to report abuse when formally interviewed. Evidence-based guidelines like the National Institute of Child Health and Human Development Standard Investigative Interview Protocol do not adequately address such reluctance because they are focused on cognitive rather than socioemotional strategies. The present study was designed to determine whether the Revised National Institute of Child Health and Human Development Protocol, which emphasizes supportive interviewing more than the standard protocol does, might predict increases in the overall informativeness and reductions in the reluctance of alleged victims. A total of 254 interviews, 166 using the revised protocol and 88 using the standard protocol, were conducted with 4.06- to 13.98-year-old children (M = 9.20, SD = 2.49) who disclosed multiple incidents of physical abuse by their parents and were thus expected to be more reluctant than victims of extrafamilial abuse. We coded indices of interviewer support and question types, children's reluctance, and informativeness in each utterance during the substantive phases of the interviews. The Revised Protocol was associated with better interviewer support and questioning as well as reduced reluctance and increased informativeness on the part of the children. These findings document the value of training interviewers to attend to the socioemotional needs of suspected abuse victims during investigative interviews. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Active site cysteine is protonated in the PAD4 Michaelis complex: evidence from Born-Oppenheimer ab initio QM/MM molecular dynamics simulations.
The protein arginine deiminase 4 (PAD4) catalyzes the citrullination of the peptidylarginine and plays a critical role in rheumatoid arthritis (RA) and gene regulation. Understanding its catalytic mechanism is not only of fundamental importance but also of significant medical interest for the rational design of new inhibitors. By employing on-the-fly Born-Oppenheimer ab initio QM/MM molecular dynamics simulations, we have demonstrated that it is unlikely for the active site cysteine and histidine to exist as a thiolate-imidazolium ion pair in the PAD4 Michaelis reactant complex. Instead, a substrate-assisted proton transfer mechanism for the deimination reaction step has been characterized: both Cys645 and His471 in the PAD4 active site are neutral prior to the reaction; the deprotonation of Cys645 by the substrate arginine occurs in concert with the nucleophilic addition of the Cys thiolate to Czeta of the substrate, and leads to a covalent tetrahedral intermediate; then, the Czeta-Neta1 bond cleaves and the resulted ammonia is displaced by a solvent water molecule. The initial deprotonation and nucleophilic attack step is found to be rate-determining. The computed free energy barrier with B3LYP(6-31G*) QM/MM MD simulations and umbrella sampling is 20.9 kcal.mol(-1), consistent with the experimental kinetic data. During the deimination, His471 plays an important role in stabilizing the transition state through the formation of the hydrogen bond with the guanidinium group. Our current studies further demonstrated the viability and strength of the ab initio QM/MM molecular dynamics approach in simulating enzyme reactions.


The SOCRATES curriculum: an innovative integration of technology and theory in medical education.
This article describes the pilot study of an innovative medical school curriculum module that utilizes a modified problem-based learning (PBL) approach to teach medical students about management of diabetes mellitus. The PBL-based curriculum incorporated computer simulations and analysis of videotaped patient encounters in addition to independent study and group discussion. At the conclusion of the study, student knowledge and clinical decision-making skills were evaluated via questionnaires and examinations. Twenty-three students completed the workshop and all evaluation assessments. Students performed well on the case-study examinations (mean score of 3.39 out of 4) but not on the short answer essay examination, which assessed basic knowledge. Students rated the quality and appeal of the activities using Likert-type scales. In general, students perceived the activities as very worthwhile, with reasonable complexity and adequate time devoted to each activity. Students were very positive about the workshop and preceptor; 15 of the 16 items used to rate workshop appeal yielded mean scores greater than 4 (on a scale of 1 to 5, with 5 being the highest). The results of the pilot study suggest future enhancements that would further improve the outcomes of the training.


[Risperidone in the early treatment of first-episode psychosis: a two-year follow-up study].
The main goals of any antipsychotic pharmacological treatment are the improvement of negative, positive, behavioral, affective and cognitive symptoms related to psychotic disorders, a good side-effects profile and again an improvement in patients quality of life and social - environmental relationships. The development of new atypical antipsychotic drugs has opened new therapeutical bias. Nevertheless only a few clinical studies have been developed studying new atypical antipsychotic role on first psychotic episodes. We developed an open, observational, multicenter and prospective study in order to evaluate effectiveness, tolerability and security of early treatment with risperidone in patients affected by a first psychotic episode (DSM IV diagnostic criteria) and the long-term effect of this treatment on the clinical evolution of these patients. We recruited 436 patients (age 18-65) who had never before received any antipsychotic drug. The most prevalent diagnosis was schizophrenia and other psychotic disorders no substance abuse related (90.6%). The average dosage of risperidone used during this study was 5.12 mg/d and most of the patients remained on risperidone monotherapy. We observed a statistically significant improvement in psychopathological scale PANSS (total; positive, negative and general subescales), Global Activity Scale (EEAG) and Clinical Global Impression Scale (CGI) scores from first month treatment on. This improvement was maintained during the two-year follow up period. We also observed an improvement in Young Mania Scale and Hamilton Depression Scale scores sustained from first month up to the end of the study. The number of patients hospitalized importantly decreased and most of them (95.9%) were ambulatory patients at the end of the study. We also observed a decrease on UKU neurological side-effects scale scores (including parkinsonism) from sixth month up to the end of the study and from basal to final evaluation. Other side effects related were amenorrhea (2.1%) and weight gain (1.6%). Investigators' opinion about risperidone efficacy and tolerability was good or very good in 84.4% and 91.6% respectively. This study concludes that risperidone is an effective, well tolerated an secure antipsychotic drug in the treatment of patients with a first psychotic episode, and in our opinion is a first rank therapeutical alternative in these kind of patients.


Evaluation of sleep-disordered breathing and its relationship with respiratory parameters in children with mucopolysaccharidosis Type IVA and VI.
The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = -0.594, p = .009; r = -0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.


Creating a geospatial database of risks and resources to explore urban adolescent substance use.
This article illustrates the methodology of creating a comprehensive geospatial database in order to systematically understand the social ecology of risk and protection for urban youth. The challenges and future opportunities involved with this complex work were reviewed, and specific examples were provided to guide researchers. Data were collected from a Washington, DC adolescent substance abuse treatment sample to construct a geospatial database to evaluate urban youths' social environmental risk and resources. A geographic information systems (GIS) approach was adopted to integrate a large array of variables at different levels of geography. For example, risk factors included proximity to crime hotspots, and other known potential establishments with negative influence (such as liquor stores). We also used GIS to assess the subjects' accessibility to protective resources such as public libraries, recreational, parks, and police stations. Unique to our method was the collecting and mapping of each teen's activity locations (places they typically frequent). These data form "risk and protection exposure" estimates for each teen. Finally, we illustrated the specific methods for creating a dynamic geospatial database for urban youth and present future analytical approaches and challenges with these type of data.


High Resolution for Chemical Shifts and Scalar Coupling Constants: The 2D Real-Time J-Upscaled PSYCHE-DIAG.
The facile determination of chemical shift and scalar coupling constants in NMR spectra is often prevented by spectral overlap and limited resolution. Here, we present a high-resolution NMR experiment for the simultaneous detection of both resonance frequencies and coupling patterns even with small J-values. A PSYCHE-decoupled DIAG (Pure Shift Yielded by Chirp Excitation- DIAGonal) experiment, which resolves chemical shift in the indirect dimension of a 2D experiment is combined with real-time J-upscaling in order to visualize small coupling constants that would otherwise be hidden in the linewidth of a regular proton or DIAG spectrum.


Metabolic engineering of Escherichia coli for the production of polylactic acid and its copolymers.
Polylactic acid (PLA) is a promising biomass-derived polymer, but is currently synthesized by a two-step process: fermentative production of lactic acid followed by chemical polymerization. Here we report production of PLA homopolymer and its copolymer, poly(3-hydroxybutyrate-co-lactate), P(3HB-co-LA), by direct fermentation of metabolically engineered Escherichia coli. As shown in an accompanying paper, introduction of the heterologous metabolic pathways involving engineered propionate CoA-transferase and polyhydroxyalkanoate (PHA) synthase for the efficient generation of lactyl-CoA and incorporation of lactyl-CoA into the polymer, respectively, allowed synthesis of PLA and P(3HB-co-LA) in E. coli, but at relatively low efficiency. In this study, the metabolic pathways of E. coli were further engineered by knocking out the ackA, ppc, and adhE genes and by replacing the promoters of the ldhA and acs genes with the trc promoter based on in silico genome-scale metabolic flux analysis in addition to rational approach. Using this engineered strain, PLA homopolymer could be produced up to 11 wt% from glucose. Also, P(3HB-co-LA) copolymers containing 55-86 mol% lactate could be produced up to 56 wt% from glucose and 3HB. P(3HB-co-LA) copolymers containing up to 70 mol% lactate could be produced to 46 wt% from glucose alone by introducing the Cupriavidus necator beta-ketothiolase and acetoacetyl-CoA reductase genes. Thus, the strategy of combined metabolic engineering and enzyme engineering allowed efficient bio-based one-step production of PLA and its copolymers. This strategy should be generally useful for developing other engineered organisms capable of producing various unnatural polymers by direct fermentation from renewable resources.


Multidipole analysis of simulated epileptic spikes with real background activity.
This simulated magnetoencephalographic study was designed to determine the variability in source parameters with real subject background activity when applying multidipole spatial-temporal dipole analyses, for which the correct model was compared with undermodeled and overmodeled cases. The simulated sources were created from patches of the cortical surface of each subject's MRI. One- and two-source frontal lobe spikes were generated in two cortical regions seen commonly in frontal lobe epilepsy patients tested at our site (orbital frontal and premotor cortex). In general, the modeling results were adequate for the correct model order and the correct model order plus one. In addition, if the localization error was less than 10 mm from the simulated source, the peak latency of the spike and orientation were very reliable, but the peak amplitude was not. The additional source in the overmodeled condition, on the other hand, was not localized reliably across the different epochs within subjects. The results suggest that consistency of the spike localization and inconsistency of other sources will allow one to determine reliably the appropriate model order in real data, and therefore determine single and multifocal spike generators.


Ultrastructural observations of previtellogenic ovarian follicles of dove.
Dove ovarian follicle is a complex structure composed of oocyte surrounded by a somatic compartment consisting of theca externa, theca interna and granulosa. The structure of ovarian follicle (1 and 2 mm) of dove was studied by electron microscopy. The granulosa was pseudostratified in the 1-mm-diameter follicles and stratified with two or three irregular rows of cells in the 2-mm-diameter follicles. In the larger follicle indentations between oocyte and granulosa cells become more numerous and the microvilli of granulosa cell elongated to form a zona radiata with similarly elongated oocyte microvilli. Lining bodies were present at the tips of granulosa microvilli and in the cortical region of the oocyte. In the oocyte cortex were observed coated pits, coated vesicles, dense tubules, multivesicular bodies and primordial yolk spheres. Primordial yolk spheres may contain lining bodies and were observed fused with dense tubules and multivesicular bodies or associated with smooth cisternae.


Similar Efficacy Observed for First-Line Immunotherapy in Racial/Ethnic Minority Patients With Metastatic NSCLC.
Limited data exist on the impact of immunotherapy use in ethnic minority patients with non-small cell lung cancer (NSCLC), because they have been underrepresented in immunotherapy trials. This study aims to evaluate race/ethnicity and other demographic, socioeconomic, and clinical factors of patients with metastatic NSCLC treated with first-line immunotherapy. A retrospective cohort study of 5,920 patients diagnosed with lung cancer treated at Montefiore Einstein Cancer Center from January 1, 2013, to June 1, 2022, was used to identify patients with metastatic NSCLC without EGFR, ALK, or ROS1 alterations who underwent first-line immunotherapy (n=248). The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of immunotherapy. Among the 248 patients, median follow-up time was 12.0 months, median age at start of treatment was 66 years, and 39.1% were non-Hispanic Black, 30.2% were Hispanic, and 30.7% were non-Hispanic White. OS (P=.39), PFS (P=.29), and TTD (P=.98) were similar among racial/ethnic groups. Patients with an ECOG performance status (PS) of <2 at the start of immunotherapy had longer OS compared with those with ECOG PS of ≥2 (P<.0001). PD-L1 expression (<50% vs ≥50%; P=.03) and body mass index (BMI) (P=.01) were also found to be associated with PFS, and ECOG PS (P<.0001) and BMI (P=.02) were associated with TTD. In a multivariate analysis of OS and PFS, ECOG PS was the only variable found to be significant. Our study observed similar benefits of immunotherapy in patients with metastatic NSCLC in different racial and ethnic groups. Furthermore, ECOG PS was associated with OS, and PD-L1 expression and BMI were associated with PFS and TTD. These findings help identify potential factors associated with outcomes and care while patients are undergoing immunotherapy.


[Meibomian gland disfunction in computer vision syndrome].
This article reviews ethiology and pathogenesis of dry eye syndrome due to meibomian gland disfunction (MDG). It is showed that blink rate influences meibomian gland functioning and computer vision syndrome development. Current diagnosis and treatment options of MDG are presented.


Urban land-use and respiratory symptoms in infants.
Children's respiratory health has been linked to many factors, including air pollution. The impacts of urban land-use on health are not fully understood, although these relationships are of key importance given the growing populations living in urban environments. We investigated whether the degree of urban land-use near a family's residence is associated with severity of respiratory symptoms like wheeze among infants. Wheeze occurrence was recorded for the first year of life for 680 infants in Connecticut for 1996-1998 from a cohort at risk for asthma development. Land-use categories were obtained from the National Land Cover Database. The fraction of urban land-use near each subject's home was related to severity of wheeze symptoms using ordered logistic regression, adjusting for individual-level data including smoking in the household, race, gender, and socio-economic status. Nitrogen dioxide (NO(2)) exposure was estimated using integrated traffic exposure modeling. Different levels of urban land-use intensity were included in separate models to explore intensity-response relationships. A buffer distance was selected based on the log-likelihood value of models with buffers of 100-2000 m by 10 m increments. A 10% increase in urban land-use within the selected 1540 m buffer of each infant's residence was associated with 1.09-fold increased risk of wheeze severity (95% confidence interval, 1.02-1.16). Results were robust to alternate buffer sizes. When NO(2), representing traffic pollution, was added to the model, results for urban land-use were no longer statistically significant, but had similar central estimates. Higher urban intensity showed higher risk of prevalence and severity of wheeze symptoms. Urban land-use was associated with severity of wheeze symptoms in infants. Findings indicate that health effect estimates for urbanicity incorporate some effects of traffic-related emissions, but also involve other factors. These may include differences in housing characteristics or baseline healthcare status.


High-dimensional multiplexed immunohistochemical characterization of immune contexture in human cancers.
Biomarker assessments of tumor specimens is widely used in cancer research to audit tumor cell intrinsic as well as tumor cell extrinsic features including the diversity of immune, stromal, and mesenchymal cells. To comprehensively and quantitatively audit the tumor-immune microenvironment (TiME), we developed a novel multiplex immunohistochemistry (mIHC) platform and computational image processing workflow using a single formalin-fixed paraffin-embedded (FFPE) tissue section. Herein, we validated this platform using nine matched primary newly diagnosed and recurrent head and neck squamous cell carcinoma (HNSCC) sections sequentially subjected to immunodetection with a panel of 29 antibodies identifying malignant tumor cells, and 17 distinct leukocyte lineages and their functional states. Image cytometric analysis was applied to interpret chromogenic signals from digitally scanned and coregistered light microscopy-based images enabling identification and quantification of individual tumor cells, structural features, immune cell phenotypes and their functional state. In agreement with our previous study via a 12-plex imaging mIHC platform, myeloid-inflamed status in newly diagnosed primary tumors associated with significantly short progression free survival, independent of lymphoid-inflamed status. Spatial distribution of tumor and immune cell lineages in TiME was also examined and revealed statistically significant CD8+ T cell exclusion from tumor nests, whereas regulatory T cells and myeloid cells, when present in close proximity to tumor cells, highly associated with rapid cancer recurrence. These findings indicate presence of differential immune-spatial profiles in newly diagnosed and recurrent HNSCC, and establish the robustness of the 29-plex mIHC platform and associated analytics for quantitative analysis of single tissue sections revealing longitudinal TiME changes.


[Structural remodeling of the renal vascular bed in experimental stenosis of the pulmonary trunk].
A hemodynamic model of the pulmonary trunk stenosis was created in the experiment that involved twenty two pups to reveal the regularities of the structural changes in the different areas of the renal vascular bed. The animals were monitored from the six months up to two years of age. Specimens obtained from different parts of their kidneys were investigated histologically, histochemically, morphometrically and stereometrically. The material taken from ten dogs of the corresponding age was used for control. It was found that the establishment of pulmonary trunk stenosis and the impairment of the blood outflow from the kidneys was followed by a structural remodeling of all the regions of renal vascular bed. This process included the hyperplasia and hypertrophy of the smooth myocytes in the media of the vascular wall as well as migration of these cells into the intima with the formation of specialized structures, regulating the hemodynamics, as well as the accumulation of the extracellular matrix in the walls of renal arteries and veins.


Risk of partial school closure for COVID-19 by socio-economic level in the period 2020-22.
The objective was to analyse the risk of partial school closure by economic level in Barcelona city. In this ecological study, the risk of partial school closure for the academic years 2020-21 and 2021-22 was estimated by dividing the total number of days that each child was in quarantine or isolation by the total number of days that each child was at risk to be in quarantine or isolation in the academic year. The association between partial school closure risk and mean income by district was estimated with the Spearman rho. The lower the mean income, the higher the risk of partial closure (Spearman rho = 0.83; P-value = 0.003) during the academic year 2020-21. Specifically, the children from the district with the lowest income had a six times greater risk of partial school closure compared with those from the highest-income district. This risk did not show a significant socioeconomic gradient in the academic year 2021-22. The risk of partial school closure presented an inverse socioeconomic gradient in the city of Barcelona according to average income by district in the academic year 2020-21. This distribution was not observed in the academic year 2021-22.


Lightness dependence of achromatic loci in color-appearance coordinates.
Shifts in the appearance of color under different illuminant chromaticity are known to be incomplete, and fit nicely with a simple linear transformation of cone responses that aligns the achromatic points under two illuminants. Most chromaticity-transfer functions with von-Kries-like transformations use only one set of values to fit the color shifts from one illuminant to another. However, an achromatic point shifts its chromaticity depending on the lightness of the test stimulus. This lightness dependence of the achromatic-point locus is qualitatively similar to a phenomenon known as the Helson-Judd effect. The present study suggests that the lightness dependency of achromatic points appears to be a general trend, which is supported by the results from deriving the optimal von-Kries coefficients for different lightness levels that best fit the color shifts under a different illuminant chromaticity. Further, we report that such a lightness dependence of the achromatic-point loci can be represented simply as a straight line in coordinates defined using color-appearance models such as CIECAM when normalized for daylight.


Psychological distress and quality of life after orthopedic trauma: an observational study.
Little is known about the clinical consequences of psychological morbidity associated with orthopedic trauma. The objective of our study was to investigate the extent of psychological symptoms that patients experience following orthopedic trauma and whether these are associated with quality of life. All patients attending 10 orthopedic fracture clinics at 3 university-affiliated hospitals between January and October 2003 were screened for study eligibility. Eligible patients were aged 16 years or older, were English-speaking, were being followed actively for a fracture(s), were cognitively able to complete the questionnaires and provided informed consent. All consenting patients completed a baseline assessment form, the Symptom Checklist-90-Revised and a health-related quality of life questionnaire (the Medical Outcomes Study 36-item Short Form [SF-36]). We conducted regression analyses to determine predictors of quality of life among study patients. Of the patients, 250 were eligible, and 215 agreed to participate; 59% were men; the patients' mean age was 44.5 (standard deviation [SD] 18.8) years. Over one-half (54%) of the patients had lower extremity fractures. Patient Physical Component summary scores were associated with older age (ss = -0.28, p 0.001), ongoing litigation (ss = -0.18, p = 0.02), fracture location (ss = -0.18, p = 0.01) and Positive Symptom Distress Index (i.e., the intensity of psychological symptoms; ss = -0.08, p = 0.003). This model predicted 21% of the variance in patients' Physical Component summary scores. Somatization was an important psychological symptom negatively associated with Physical Component summary scores. Reduced Mental Component summary scores were associated with ongoing litigation (ss = -0.18, p = 0.03) and Global Severity Index of psychological symptoms (ss = -0.50, p 0.001). This model explained 31% of the variability in patients' Mental Component summary scores. In a prospective study of 215 patients, 1 in 5 met the threshold for psychological distress. Only ongoing litigation and psychological symptoms were significantly associated with both SF-36 Physical Component and Mental Component summary scores. Future research is necessary to determine whether orthopedic trauma patients would benefit from early screening and intervention to address comorbid psychopathology.


Patient Outcomes Related to In-Hospital Delays in Appendicectomy for Appendicitis: A Retrospective Study.
Background and objective In many hospitals, the availability of operating theatres and access to senior surgical and anaesthetic support diminish during night hours. Therefore, urgent surgery is sometimes postponed until the following morning rather than performed overnight, if it is judged to be safe. In this study, we aimed to determine if a delay in laparoscopic appendicectomy in cases of acute appendicitis of over 12 hours, analogous to an overnight delay, correlated with worse patient outcomes. Our primary outcome was delayed discharge from the hospital. Our secondary outcomes were appendicitis severity, conversions, and postoperative complications. Methods We undertook a retrospective review of the medical records of patients who underwent laparoscopic appendicectomy for appendicitis at a UK district general hospital between 01/01/2018 and 30/08/2019. For each patient, clinical and demographic information, and time of hospital admission, surgery, and discharge were collected. Delayed discharge was defined as "time to discharge" >24 hours after surgery. Results A total of 446 patients were included in the study. In 137 patients (30.7%), "time to surgery" was under 12 hours; in 309 patients (69.3%) "time to surgery" was over 12 hours. Of note, 319 patients (71.5%) had a delayed discharge; 303 patients (67.9%) had complicated appendicitis, and 143 patients had severe appendicitis (32.1%). No statistically significant association between "time to surgery" and delayed discharge, appendicitis severity, conversion, or 30-day re-presentations was observed. Conclusion Time from admission to the start of appendicectomy did not affect patient outcomes. Short in-hospital delays in appendicectomy, such as an overnight delay, may be safe in certain patients and should be determined based on clinical judgement.


Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses.
The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.


The clinical aspects of the acute facet syndrome: results from a structured discussion among European chiropractors.
The term 'acute facet syndrome' is widely used and accepted amongst chiropractors, but poorly described in the literature, as most of the present literature relates to chronic facet joint pain. Therefore, research into the degree of consensus on the subject amongst a large group of chiropractic practitioners was seen to be a useful contribution. During the annual congress of The European Chiropractors Union (ECU) in 2008, the authors conducted a workshop involving volunteer chiropractors. Topics were decided upon in advance, and the participants were asked to form into groups of four or five. The groups were asked to reach consensus on several topics relating to a basic case of a forty-year old man, where an assumption was made that his pain originated from the facet joints. First, the participants were asked to agree on a maximum of three keywords on each of four topics relating to the presentation of pain: 1. location, 2. severity, 3. aggravating factors, and 4. relieving factors. Second, the groups were asked to agree on three orthopaedic and three chiropractic tests that would aid in diagnosing pain from the facet joints. Finally, they were asked to agree on the number, frequency and duration of chiropractic treatment. Thirty-four chiropractors from nine European countries participated. They described the characteristics of an acute, uncomplicated facet syndrome as follows: local, ipsilateral pain, occasionally extending into the thigh with pain and decreased range of motion in extension and rotation both standing and sitting. They thought that the pain could be relieved by walking, lying with knees bent, using ice packs and taking non-steroidal anti-inflammatory drugs, and aggravated by prolonged standing or resting. They also stated that there would be no signs of neurologic involvement or antalgic posture and no aggravation of pain from sitting, flexion or coughing/sneezing. The chiropractors attending the workshop described the characteristics of an acute, uncomplicated lumbar facet syndrome in much the same way as chronic pain from the facet joints has been described in the literature. Furthermore, the acute, uncomplicated facet syndrome was considered to have an uncomplicated clinical course, responding quickly to spinal manipulative therapy.


Microwave spectra and nuclear quadrupole structure of the NH3-N2 van der Waals complex and its deuterated isotopologues.
The microwave spectrum of the NH3-N2 van der Waals complex has been observed in a supersonic molecular jet expansion via broadband (2-8 GHz) chirped-pulse Fourier-transform microwave spectroscopy. Two pure rotational R(0) transitions (J = 1 - 0) with different hyperfine structure patterns were detected. One transition belongs to the (ortho)-NH3-(ortho)-N2 nuclear spin isomer in the ground K = 0 state reported earlier [G. T. Fraser et al., J. Chem. Phys. 84, 2472 (1986)], while another one is assigned to the (para)-NH3-(para)-N2 spin isomer in the K = 0 state not reported before (K is the projection of the total angular momentum J on the intermolecular axis). The complicated hyperfine structure arising from three quadrupole 14N nuclei of NH3-N2 was resolved for both transitions, and the quadrupole coupling constants associated with the NH3 and N2 subunits were precisely determined for the first time. These constants provided the dynamical information about the angular orientation of ammonia and nitrogen indicating that the average angle between the C 3 axis of NH3 and the N2 axis is about 66°. The average van der Waals bond lengths are slightly different for (ortho)-NH3-(ortho)-N2 and (para)-NH3-(para)-N2 and amount to 3.678 Å and 3.732 Å, respectively. Similar results for the deuterated isotopologues, ND3-N2, NHD2-N2, and NH2D-N2, and their nuclear spin isomers were also obtained thus confirming and extending the analysis for the parent NH3-N2 complex.


A recombinant O-polysaccharide-protein conjugate approach to develop highly specific monoclonal antibodies to Shiga toxin-producing Escherichia coli O157 and O145 serogroups.
Shiga toxin-producing Escherichia coli (STEC) is the major etiologic agent of hemolytic-uremic syndrome (HUS). The high rate of HUS emphasizes the urgency for the implementation of primary prevention strategies to reduce its public health impact. Argentina shows the highest rate of HUS worldwide, being E. coli O157 the predominant STEC-associated HUS serogroup (>70%), followed by E. coli O145 (>9%). To specifically detect these serogroups we aimed at developing highly specific monoclonal antibodies (mAbs) against the O-polysaccharide (O-PS) section of the lipopolysaccharide (LPS) of the dominant STEC-associated HUS serogroups in Argentina. The development of hybridomas secreting mAbs against O157 or O145 was carried out through a combined immunization strategy, involving adjuvated-bacterial immunizations followed by immunizations with recombinant O-PS-protein conjugates. We selected hybridoma clones that specifically recognized the engineered O-PS-protein conjugates of O157 or O145 serogroups. Indirect ELISA of heat-killed bacteria showed specific binding to O157 or O145 serogroups, respectively, while no cross-reactivity with other epidemiological important STEC strains, Brucella abortus, Salmonella group N or Yersinia enterocolitica O9 was observed. Western blot analysis showed specific recognition of the sought O-PS section of the LPS by all mAbs. Finally, the ability of the developed mAbs to bind the surface of whole bacteria cells was confirmed by flow cytometry, confocal microscopy and agglutination assays, indicating that these mAbs present an exceptional degree of specificity and relative affinity in the detection and identification of E. coli O157 and O145 serogroups. These mAbs may be of significant value for clinical diagnosis and food quality control applications. Thus, engineered O-PS specific moieties contained in the recombinant glycoconjugates used for combined immunization and hybridoma selection are an invaluable resource for the development of highly specific mAbs.


Symptoms and signs of temporomandibular disorders and oral parafunctions among Saudi children.
This study aimed to record the prevalence of signs and symptoms of temporomandibular disorders (TMD) and oral parafunctions among Saudi children. A questionnaire and a clinical examination of signs and symptoms of TMD were performed on 1940 stratified randomly selected schoolchildren. The sample was divided into three groups, 505 with primary, 737 with mixed and 734 with permanent dentition. The prevalence of TMD signs was found to be 20.7% and the most common sign of TMD was joint sounds (11.8%). The second most common sign was restricted mouth opening (5.3%). Muscle and temporomandibular joint (TMJ) pain as well as deviation upon jaw opening appeared infrequently. TMJ sounds were significantly increasing with age (P < 0.05). TMD symptoms as reported by the parents were evident in 24.2% of the returned questionnaires (1113). The most common symptoms were headache (13.6%) and pain on chewing (11.1%). The incidence of headache was found to be significantly increasing from primary to permanent dentition (P < 0.01). No sex difference in the prevalence of any symptom was reported. Nail biting was the most common oral parafunction (27.7%) while bruxism was the least common (8.4%). All parafunctions except bruxism were significantly related to age. Cheek biting and thumb sucking were reported more in females than in males. The importance of a screening examination for symptoms and signs of TMD should not be overlooked in the clinical assessment of the pediatric patient.


Disagreement and aggression in the operating theatre.
This paper is a report of a study to determine the national spread of incidents of disagreement within and between professional groups in operating departments and the frequency of perceived aggressive behaviour demonstrated by operating department personnel. There is both anecdotal and empirical evidence supporting the idea of the operating team as the ultimate example of teamworking in health care. At the same time, international concern is expressed over the level of interprofessional conflict and aggression reported in operating departments. Such reports do not sit well with notions of excellence in teamwork as conceptualized by theorists. A questionnaire survey was designed, and sent to a random sample of National Health Service operating departments in England (n = 62) in 2002. Usable survey questionnaires were returned from 37 departments (response rate 59.6) and yielded 391 individual responses. Respondents included nurses (58%, n = 227), surgeons (9.7%, n = 38), anaesthetists (14.32%, n = 56) and operating department practitioners (17.9%, n = 70) of all grades. Half of the respondents reported experiencing aggressive behaviour from consultant surgeons (53.4%, n = 209). Daily disagreements between nurses and consultants about list management were reported. Perceptions of lack of understanding of roles and shared goals for patient care between the professional groups were also reported. Similar reports were received from all geographical locations in the sample. Further research is needed to conceptualize the complex nature of interprofessional working in operating theatres before steps can be taken to develop a less stressful and more efficient working environment.


Identifying Stages of Kidney Renal Cell Carcinoma by Combining Gene Expression and DNA Methylation Data.
In this study, in order to take advantage of complementary information from different types of data for better disease status diagnosis, we combined gene expression with DNA methylation data and generated a fused network, based on which the stages of Kidney Renal Cell Carcinoma (KIRC) can be better identified. It is well recognized that a network is important for investigating the connectivity of disease groups. We exploited the potential of the network's features to identify the KIRC stage. We first constructed a patient network from each type of data. We then built a fused network based on network fusion method. Based on the link weights of patients, we used a generalized linear model to predict the group of KIRC subjects. Finally, the group prediction method was applied to test the power of network-based features. The performance (e.g., the accuracy of identifying cancer stages) when using the fused network from two types of data is shown to be superior to that when using two patient networks from only one data type. The work provides a good example for using network based features from multiple data types for a more comprehensive diagnosis.


pilS loci in Neisseria gonorrhoeae are transcriptionally active.
Piliation is an important virulence determinant for Neisseria gonorrhoeae. PilE polypeptide is the major protein subunit in the pilus organelle and engages in extensive antigenic variation due to recombination between pilE and a pilS locus. pilS were so-named as they are believed to be transcriptionally silent, in contrast to the pilE locus. In this study, we demonstrate the presence of a small, pil-specific RNA species. Through using a series of pilE deletion mutants, we show by Northern blotting and quantitative reverse transcriptase PCR analysis (qRT-PCR), that these smaller RNA species are not derived from the primary pilE transcript following some processing events, but rather, arose through transcription of the pilS loci. Small transcriptome analysis, in conjunction with analysis of pilS recombinants, identified both sense and anti-sense RNAs originating from most, but not all, of the pilS gene copies. Focusing on the MS11 pilS6 locus, we identified by site-directed mutagenesis a sense promoter located immediately upstream of pilS6 copy 2, as well as an anti-sense promoter immediately downstream of pilS6 copy 1. Whole transcriptome analysis also revealed the presence of pil-specific sRNA in both gonococci and meningococci. Overall, this study reveals an added layer of complexity to the pilE/pilS recombination scheme by demonstrating pil-specific transcription within genes that were previously thought to be transcriptionally silent.


Investigating the efficiency of silica materials with wall-embedded nitroxide radicals for dynamic nuclear polarisation NMR.
Dynamic nuclear polarisation (DNP) can significantly enhance the sensitivity of solid-state nuclear magnetic resonance (SSNMR) experiments by transferring the electron spin polarisation of paramagnetic species to nuclei through microwave irradiation of the sample at cryogenic temperatures. Paramagnetic species required for DNP can be provided in the form of mesoporous silica materials containing nitroxide radicals either located on the porous surface or embedded in the pore walls. The present study focuses specifically on porous materials with wall-embedded radicals that were synthesised using conventional molecular imprinting protocols. More remarkably, by changing the molecular structure of the TEMPO precursor, the theoretical distance between the oxygen atoms in a pair of wall-embedded face-to-face TEMPO radicals was increased stepwise (0.7, 0.9, 1.1, 1.3 and 1.5 nm). The thermal activation of these five series of materials led to 37 TEMPO-functionalised silica materials with different radical concentrations. Their efficiency as DNP polarising agents was subsequently investigated at 9.4 T and ∼110 K under magic-angle spinning conditions (10 kHz) after impregnating them at room temperature with an aqueous solution of isotopically enriched proline. Our results show that the highest DNP efficiency was obtained for the silica materials that exhibited the shortest theoretical oxygen-oxygen distance between the TEMPO rings, suggesting that the design rules accepted for soluble DNP polarising agents may not be transposed to these materials with wall-embedded pairs of nitroxides.


Serum albumin decreases transendothelial permeability to macromolecules.
We examined the effects of serum albumin and other serum proteins on the fluxes of tracer 125I-albumin (MW 69 kDa) and 125I-haptoglobin (MW 100 kDa) across the pulmonary artery endothelial monolayer in vitro to test the role of serum proteins in modulating the endothelial barrier function. Replacement of control complete culture medium (20% fetal calf serum in DMEM) with DMEM alone increased the transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability) by 83% of the control value. Repletion with 50% calf serum or with 2.0 g% albumin (i.e., the albumin concentration in 50% serum) decreased 125I-albumin permeability to the control value. This effect of serum or albumin was concentration-dependent since neither 12.5% serum nor 0.5 g% albumin (i.e., albumin concentration in 12.5% serum) altered 125I-albumin permeability from control values. The ammonium sulfate-precipitated serum protein fraction rich in albumin decreased 125I-albumin permeability from the control DMEM value, whereas serum fractions containing predominantly gamma-globulin or depleted of protein did not significantly alter 125I-albumin permeability. Other serum proteins that have been proposed to reduce endothelial permeability, alpha 1-acid glycoprotein (0.035-0.14 g/100 ml) and fibronectin (5 mg/100 ml), did not decrease 125I-albumin permeability from DMEM values. The endothelial permeability of 125I-haptoglobin of 4.63 +/- 0.53 x 10(-6) cm/sec in the presence of DMEM was 30% of the 125I-albumin permeability value. The addition of 2.0 g% albumin or 50% serum decreased 125I-haptoglobin permeability to 57 and 31%, respectively, of the DMEM value. These results indicate the critical role of serum albumin in regulating the restrictiveness of the endothelial barrier to macromolecules.


Detection of human papillomavirus in cervical smears. A comparison of in situ hybridization, immunocytochemistry and cytopathology.
A comparison of different methods for the detection of cervical human papillomavirus (HPV) infection was made on patients attending the cervical dysplasia clinic. Cytomorphology, immunocytochemistry and in situ hybridization were compared for their ability to detect HPV. Separate cervicovaginal smears from 50 patients were tested for HPV types 6/11, 16 and 18 by in situ hybridization using 35S-labeled DNA probes. Duplicate smears from the same patients were Papanicolaou stained and evaluated for evidence of condylomatous and dysplastic changes. Twenty-five matching cervical biopsies were immunostained for HPV capsid antigen and tested by in situ hybridization for HPV DNA. The cytologic smears of 20 patients (40%) were positive for HPV DNA. Six patients had HPV 6/11, ten had HPV 16, three had HPV 18, and one had both HPV 6/11 and HPV 16. There was a high correlation between condylomatous cytopathology and antigen and DNA detection. One-third of the specimens with condylomatous changes were DNA negative by the tested probes, suggesting the presence of other HPV types in the genital tract.


Change in lung function over time in male metropolitan firefighters and general population controls: a 3-year follow-up study.
Previous studies in firefighters have been contradictory regarding their course of lung function over time. The aim of this ongoing study is to investigate how changes in lung function over time in male metropolitan firefighters compare with those in population controls, and to explore associations between firefighters' use of personal respiratory protection devices during occupational exposures and their risk of accelerated lung function decline. A prospective comparison of FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) was performed between 281 firefighters and 933 population controls. Logistic regression models were used to compare changes from baseline of FEV1 and FVC after 3 years and risk of accelerated decline between the cohorts. Within the firefighter cohort, risk of accelerated decline was compared between subgroups based on use of respiratory protection devices. Controls showed similar mean annual declines for FEV1 and FVC across age categories, whereas firefighters aged <45 years showed increasing values over time (p=0.040). Firefighters had a lower odds of accelerated FEV1 decline compared with controls (OR=0.60, 95%CI 110.44; 0.83), but firefighters who never or rarely used respiratory protection during fire knockdown had a higher odds of accelerated FEV1 decline compared with those who used it often or frequently (OR=2.20, 95%CI 1.02; 4.74). Younger generations of firefighters showed an increase in lung function relative to older colleagues, while population controls consistently showed decline of lung function across all ages. Firefighters who reported to be incompliant in using respiratory protection showed an increased risk of accelerated FEV1 decline.


Atriopeptins decrease resting and hormone-elevated cytosolic Ca in cultured mesangial cells.
The purpose of this work was to investigate the effects of atrial peptides on the cytosolic Ca levels of cultured, adherent, mesangial cells. Resting Ca levels, measured by the use of fura-2, were dose-dependently decreased by up to 30%, by atriopeptin 23. The half-maximal effect was elicited by approximately 30 pM atriopeptin-23. Atriopeptin 21 also decreased resting Ca levels by up to 30%, but this peptide was approximately 30-fold less potent than atriopeptin 23. Atriopeptin 23 (100 nM) inhibited both the Ca transient and the peak Ca value elicited by 1 nM vasopressin, but the atrial peptide had no significant effect on the Ca transient elicited by higher vasopressin concentrations. At concentrations lower than 100 nM, atriopeptin 23 had no effect on the vasopressin-induced Ca transient. Atriopeptin 23 also decreased the Ca transient and the peak Ca value elicited by 100 nM angiotensin II. Similar to vasopressin, the angiotensin II-induced Ca transient was inhibited by 100 nM but not lower concentrations of atriopeptin 23. In contrast to the effect of atriopeptin 23, atriopeptin 21 (100 nM) had no effect on the Ca transient elicited by vasopressin. These results demonstrate that atriopeptins function as modulators of resting and, under certain conditions, of hormone-increased Ca levels in cultured mesangial cells.


Medicare Advantage control of postacute costs: perspectives from stakeholders.
Medicare Advantage (MA) plans have strong incentives to control costs, including postacute spending; however, to our knowledge, no research has examined the methods that MA plans use to control or reduce postacute costs. This study aimed to understand such MA plan efforts and the possible unintended consequences. A multiple case study method was used. We conducted 154 interviews with administrative and clinical staff working in 10 MA plans, 16 hospitals, and 25 skilled nursing facilities (SNFs) in 8 geographically diverse markets across the United States. Participants discussed how MA plans attempted to reduce postacute care spending by controlling the SNF to which patients are discharged and SNF length of stay (LOS). Plans typically influenced SNF selection by providing patients with a list of facilities in which their care would be covered. To influence LOS, MA plans most commonly authorized patient stays in SNFs for a certain number of days and required that SNFs adhere to this limitation, but they did not provide guidance or assistance in ensuring that the LOS goals were met. Hospital and SNF responses to the largely authorization-based system were frequently negative, and participants expressed concerns about potential unintended consequences. In their interactions with hospitals and SNFs, MA plans attempted to influence the choice of SNF and LOS to control postacute spending. However, exerting too much influence over hospitals and SNFs, as these results seem to indicate, may have the negative consequences of delayed hospital discharge and SNFs' avoidance of burdensome plans.


Cancer risk in patients with diabetic nephropathy: A retrospective cohort study in Hong Kong.
Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease nowadays. Certain cancers are more common in patients with diabetes mellitus. However, there are no data concerning the cancer pattern in patients with DN. The aim of this study is to investigate the site-specific cancer risk and mortality in these patients.A retrospective cohort study of 5643 DN patients between 2000 and 2015 was conducted in 2 large hospitals in Hong Kong. Incidence and mortality of various cancers were compared with those of general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively.With 24,726 person-years follow-up, 250 cancers were diagnosed. Overall cancer incidence was similar between DN patients and the general population (SIR 1.05, 95% confidence interval [CI] 0.92-1.19). However, certain site-specific cancers are increased in DN patients: the highest risk was observed for laryngeal cancer (SIR 3.03, 95% CI 1.11-6.60), followed by cancers of liver (SIR 1.96, 95% CI 1.35-2.76) and colorectum (SIR 1.92, 95% CI 1.53-2.37), but the risk of prostate cancer was lower (SIR 0.48, 95% CI 0.21-0.95) in the males with DN. The SMR of all cancers was 1.17 (95% CI 1.01-1.37). For individual specific site, only colorectal cancer carried a significant higher mortality risk (SMR 2.45, 95% CI 1.82-3.23).Our data suggested that DN is associated with increased incidence of cancers of colorectum, liver, and larynx but decreased incidence of prostate cancer. Moreover, there is increased mortality of colorectal cancer in patients with DN.


Establishment of an Integrated Nontarget and Suspect Screening Workflow for Organophosphate Diesters (Di-OPEs) and Identification of Seven Previously Unknown Di-OPEs in Food Contact Plastics.
In this study, an innovative, integrated nontarget and suspect screening workflow was developed for identifying organophosphate diesters (di-OPEs) using high-resolution mass spectrometry. The workflow featured the utilization of 0.02% acetic acid as a mobile-phase additive, differentiated screening methods for alkyl and aryl di-OPEs, and a combination of electrospray negative ionization and positive ionization. Using this workflow, 18 di-OPEs were identified in the extracts of 75 food contact plastic (FCP) samples sourced from South China. Among these, six alkyl and one aryl di-OPEs were previously unknown (one unequivocal identification and six probable structures based on diagnostic evidence). (Semi)quantification revealed that bis(2,4-di-tert-butylphenyl) phosphate was the major di-OPE in FCPs, with a median concentration of 1079 ng/g (range: 23.4-158,414 ng/g). The migration efficiencies of di-OPEs from an FCP sample to four kinds of food simulants were between 2.58 and 54.3%. This study offered a useful workflow for the comprehensive profiling of di-OPEs in FCPs.


Personal involvement is related to increased search motivation and associated with activity in left BA44-a pilot study.
Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product.


Molecular insights into substrate binding mechanism of undecaprenyl pyrophosphate with membrane integrated phosphatidyl glycerophosphate phosphatase B (PgpB) using molecular dynamics simulation approach.
Undecaprenyl phosphate (C55-P) acts as carrier lipid in the synthesis of peptidoglycan, which is de novo synthesized from dephosphorylation of undecaprenyl pyrophosphate (C55-PP). The phosphatidylglycerol phosphate phosphatase B (PgpB) catalyzes the dephosphorylation of C55-PP and forms C55-P. As no structural study has been made regarding the binding of C55-PP to PgpB, in the current study, in silico molecular docking, followed by 150 ns molecular dynamics simulation of the putative binding complex in membrane/solvent environment has been performed to understand conformational dynamics. Results are compared with simulated apo form and PE inhibitor-bound form. Analysis of correlated residual fluctuation network in apo form, C55-PP bound and PE inhibitor-bound form suggests that difference in dynamic coupling between TM domain and α2 and α3 helix of periplasmic domain provides ligand binding to facilitate catalysis or to show inhibitory activity. Distance distribution in catalytic residual pair, H207-R104; H207-R201 and H207-D211 which stabilizes phosphate-enzyme intermediate shows a narrow peak in 2.4-3.6 Å in substrate-bound compared to apo form. Binding interactions and binding free energy analyses complement the partial inhibition of PE where PE has less binding free energy compared to the C55-PP substrate as well as the difference in binding interaction with catalytic pocket. Thus, the present study provides how substrate binding couples the movement in TM domain and periplasmic domain which might help in the understanding of active site communication in PgpB. C55-PP phosphatase interactions with a catalytic pocket of PgpB provide new insight for designing drugs against bacterial infection.


[Effect of ozone therapy on hemostatic changes in patients with vascular atherosclerosis].
Hemostatic changed induced by ozone therapy were studied in 81 patients with atherosclerosis of different vessels in 81 patients. It was found that use of ozone-oxygen mixtures leads to hypocoagulatory changes (diminution of platelet aggregation, lowering of fibrinogen concentration, prolongation of activated partial thromboplastin time, enhanced fibrinolytic activity) which contribute to clinical response.


Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia.
We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling.


Various physical stress factors on rat sperm motility, integrity of acrosome, and plasma membrane.
The objective of this study was to determine the effects of various physical interventions such as centrifugation regimes, Percoll gradient separation, and repeated pipetting on various viability parameters of epididymal sperm of Fischer 344 (F-344) and Sprague-Dawley (SD) rat strains. Three experiments were conducted. In experiment 1, sperm motility and acrosomal and membrane integrity were compared after exposing sperm samples to 200, 400, 600, and 800 x g centrifugal forces for 5, 10, or 15 minutes. In experiment 2, sperm motility and acrosomal and membrane integrity were compared after passing them through a Percoll separation using centrifugal forces of 600, 800, 1000, and 1200 x g for either 15 or 30 minutes. In experiment 3, the effect of repeated pipetting (2, 4, 6, 8, and 10 times) on motility and membrane integrity of rat sperm was compared with that on mouse, ram, bull, and boar sperm. The results revealed that both F-344 and SD rat sperm motility and membrane integrity were significantly affected by centrifugation (P < .05). The acrosomal integrity of SD rat sperm was affected after using 800 x g centrifugation force for 10 or 15 minutes (P < .05), whereas F-344 rat sperm acrosomal integrity was not affected by any centrifugation regimes (P > .05). Sperm from SD rats also had higher motility and membrane integrity loss than did sperm from F-344 rats after centrifugation and pipetting (P < .05). Percoll gradient separation did not cause significant motility loss or acrosomal damage to either F-344 or SD sperm (P > .05). Repeated pipetting had a dramatic adverse effect on both rat and mouse sperm motility (P < .05) as compared with sperm from bull, boar, and ram, which were not affected at all (P > .05). These data suggest that rat sperm have unique properties that need to be considered during centrifugation, Percoll gradient separation, and pipetting procedures.


Confirmation of brain death using brain radionuclide perfusion imaging technique.
To determine the reliability of radionuclide cerebral blood perfusion imaging in confirming brain death irrespective of continued heartbeat. Twenty-eight patients (19 male and 9 female, aged 17-63 years) with severe brain injury and fully supported until the final cardiac asystole were included in the study. Two sets of clinical tests aimed at ascertaining brain death in each subject were performed separately for each case within an interval of 24 h. Dynamic, planar and single photon emission computed tomographic (SPECT) brain scintigraphy were also performed after intravenous administration of 550 MBq (15 mCi) technetium-99m hexamethyl propyleneamine oxime. Following the clinical diagnosis of brain death, none of the patients was withdrawn from cardiopulmonary support or had any organ harvested. Dynamic, planar and SPECT imaging performed thereafter did not reveal any intracranial cerebral perfusion in any of the subjects, except in 1 patient where the initial scan showed posterior fossa activity that ceased, in a subsequent scan obtained after 24 h. All of the patients were declared dead only after the emergence of cardiac asystole. The findings indicate that radionuclide brain perfusion imaging is reliable, reproducible, noninvasive and simple to perform for the confirmation of brain death and as such we recommend it as an alternative to exhaustive neurophysiological tests and invasive catheter angiography.


Pyrazolate-Based Porphyrinic Metal-Organic Framework with Extraordinary Base-Resistance.
Guided by a top-down topological analysis, a metal-organic framework (MOF) constructed by pyrazolate-based porphyrinic ligand, namely, PCN-601, has been rationally designed and synthesized, and it exhibits excellent stability in alkali solutions. It is, to the best of our knowledge, the first identified MOF that can retain its crystallinity and porosity in saturated sodium hydroxide solution (∼ 20 mol/L) at room temperature and 100 °C. This almost pushes base-resistance of porphyrinic MOFs (even if MOFs) to the limit in aqueous media and greatly extends the range of their potential applications. In this work, we also tried to interpret the stability of PCN-601 from both thermodynamic and kinetic perspectives.


Intestinal obstruction after lung transplantation in children with cystic fibrosis.
Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.


Contact focusing multimodal microprobes for ultraprecise laser tissue surgery.
Focusing of multimodal beams by chains of dielectric microspheres assembled directly inside the cores of hollow waveguides is studied by using numerical ray tracing. The device designs are optimized for laser surgery in contact mode with strongly absorbing tissue. By analyzing a broad range of parameters it is demonstrated that chains formed by three or five spheres with a refractive index of 1.65-1.75 provide a two-fold improvement in spatial resolution over single spheres at the cost of 0.2-0.4 attenuation in peak intensity of the central focused beam. Potential applications include ultra precise laser ablation or coagulation in the eye and brain, cellular surgery, and the coupling of light into photonic nanostructures.


Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure.
Ketamine is widely used for procedural sedation, but there is limited knowledge on whether ketamine use is associated with elevated intraocular pressure (IOP). The aim of this study was to examine whether there are clinically important elevations of IOP associated with ketamine use during pediatric procedural sedation. We prospectively enrolled children without ocular abnormalities undergoing procedural sedation that included ketamine for nonperiorbital injuries. We measured IOP for each eye before and at 1, 3, 5, 15, and 30 minutes after initial intravenous ketamine administration. We performed Bland-Altman plots to determine if IOP measurements in both eyes were in agreement. Linear regression was used to model the mean IOP of both eyes as a function of time, dose, and age, with a robust sandwich estimator to account for repeated measures. Among 25 participants, median (interquartile range) age was 11 (9-12) years, and 18 (72%) were male. Median ketamine dose was 1.88 mg/kg (interquartile range, 1.43-2.03 mg/kg; range 0.96-4 mg/kg). Bland-Altman plots demonstrated a mean difference of IOP between eyes near zero at all time points. The largest predicted difference from baseline IOP occurred at 15 minutes, with an estimated change of 1.09 mm Hg (95% confidence interval, -0.37 to 2.55). The association between ketamine dose and mean IOP was not statistically significant or clinically meaningful (P = .90; estimated slope, 0.119 [95% confidence interval, -1.71 to 1.95]). There were no clinically meaningful levels of increased measured average IOP reached at any time point. At dosages of 4 mg/kg or less, there are not clinically meaningful associations of ketamine with elevation of IOP.


Characterization and functional properties of sub-fractions of soluble soybean polysaccharides.
Soluble soybean polysaccharide (SSPS) was fractionated into two sub-fractions, a high-molecular-weight fraction (HMF) and a low-molecular-weight fraction (LMF) by the ethanol-extraction method. Characterization of the sub-fractions, that is, analysis of chemical composition, gel filtration, and SDS-PAGE, revealed that the main component of HMF was a large polysaccharide molecule with covalently-attached peptides, possibly corresponding to the intact SSPS molecule. LMF consisted of free peptides and saccharides of small size, which might have occurred as by-products during the production process of SSPS. HMF exhibited high ability to emulsify oil droplets and stabilize alpha-casein dispersions in an acidic pH region, but this ability of LMF was inferior to HMF. On the other hand, LMF had higher activity to prevent the oxidation of emulsified lipids than HMF. These results suggest that HMF and LMF had different characteristics and functional properties, and that the combination of the two sub-fractions generates the multi-functions of commercial SSPS.


Extracellular vesicles: eat glutamine and spit acidic bubbles.
Extracellular vesicles mediate transfer of diverse molecular content to target cells in order to induce phenotypic changes, which has put them under the spotlight as likely major players in cell-to-cell communication. However, extracellular vesicle heterogeneity in terms of intracellular origin has only recently been recognized as a potential determinant of their activity. Recent work by Fan et al (2020) illustrates how lack of external resources that affect cellular homeostasis and signaling can also modulate EV biogenesis, by inducing the production of a novel subpopulation of exosomes enriched in Rab11a with context-dependent roles in Drosophila gland physiology and cancer cell aggressiveness.


Pudendal Neuralgia Due to Pudendal Nerve Entrapment: Warning Signs Observed in Two Cases and Review of the Literature.
Pudendal neuralgia is a chronic neuropathic pelvic pain that is often misdiagnosed and inappropriately treated. The Nantes criteria provide a basis for the diagnosis of pudendal neuralgia due to pudendal nerve entrapment. The 5 essential diagnostic criteria are pain situated in the anatomical territory of the pudendal nerve, worsened by sitting, the patient is not woken at night by the pain, and no objective sensory loss is detected on clinical examination. The fifth criterion is a positive pudendal nerve block. We have also clarified a number of complementary diagnostic criteria and several exclusion criteria that make the diagnosis unlikely. When pudendal neuralgia due to pudendal nerve entrapment is diagnosed according to the Nantes criteria, no further investigation is required and medical or surgical treatment can be proposed. Nevertheless, a number of warning signs suggesting other possible causes of pudendal neuralgia must not be overlooked. These warning signs (red flags) are waking up at night, excessively neuropathic nature of the pain (for example, associated with hypoesthesia), specifically pinpointed pain, which can suggest neuroma and pain associated with neurological deficit. In these atypical presentations, the diagnosis of pain due to pudendal nerve entrapment should be reconsidered and a radiological examination should be performed. The 2 cases described in this report (tumor compression of the pudendal nerve) illustrate the need to recognize atypical pudendal neuralgia and clarify the role of pelvic magnetic resonance imaging (MRI), as MRI provides very valuable information for the evaluation of diseases involving the ischiorectal fossa. The presence of red flags must be investigated in all cases of pudendal neuralgia to avoid missing pudendal neuralgia secondary to a mechanism other than nerve entrapment.


Integrated genomic analysis to identify druggable targets for pancreatic cancer.
According to the National Comprehensive Cancer Network and the American Society of Clinical Oncology, the standard treatment for pancreatic cancer (PC) is gemcitabine and fluorouracil. Other chemotherapeutic agents have been widely combined. However, drug resistance remains a huge challenge, leading to the ineffectiveness of cancer therapy. Therefore, we are trying to discover new treatments for PC by utilizing genomic information to identify PC-associated genes as well as drug target genes for drug repurposing. Genomic information from a public database, the cBio Cancer Genomics Portal, was employed to retrieve the somatic mutation genes of PC. Five functional annotations were applied to prioritize the PC risk genes: Kyoto Encyclopedia of Genes and Genomes; biological process; knockout mouse; Gene List Automatically Derived For You; and Gene Expression Omnibus Dataset. DrugBank database was utilized to extract PC drug targets. To narrow down the most promising drugs for PC, CMap Touchstone analysis was applied. Finally, ClinicalTrials.gov and a literature review were used to screen the potential drugs under clinical and preclinical investigation. Here, we extracted 895 PC-associated genes according to the cBioPortal database and prioritized them by using five functional annotations; 318 genes were assigned as biological PC risk genes. Further, 216 genes were druggable according to the DrugBank database. CMap Touchstone analysis indicated 13 candidate drugs for PC. Among those 13 drugs, 8 drugs are in the clinical trials, 2 drugs were supported by the preclinical studies, and 3 drugs are with no evidence status for PC. Importantly, we found that midostaurin (targeted PRKA) and fulvestrant (targeted ESR1) are promising candidate drugs for PC treatment based on the genomic-driven drug repurposing pipelines. In short, integrated analysis using a genomic information database demonstrated the viability for drug repurposing. We proposed two drugs (midostaurin and fulvestrant) as promising drugs for PC.


Distinct Brain Mechanisms for Conflict Adaptation within and across Conflict Types.
Cognitive conflict, like other cognitive processes, shows the characteristic of adaptation, that is, conflict effects are attenuated when immediately following a conflicting event, a phenomenon known as the conflict adaptation effect (CAE). One important aspect of CAE is its sensitivity to the intertrial coherence of conflict type, that is, behavioral CAE occurs only if consecutive trials are of the same conflict type. Although reliably observed behaviorally, the neural mechanisms underlying such a phenomenon remains elusive. With a paradigm combining the classic Simon task and Stroop task, this fMRI study examined neural correlates of conflict adaptation both within and across conflict types. The results revealed that when the conflict type repeated (but not when it alternated), the CAE-like neural activations were observed in dorsal ACC, inferior frontal gyrus (IFG), superior parietal lobe, and so forth (i.e., regions within typical task-positive networks). In contrast, when the conflict type alternated (but not when it repeated), we found CAE-like neural deactivations in the left superior frontal gyri (i.e., a region within the typical task-negative network). Network analyses suggested that the regions of ACC, IFG, superior parietal lobe, and superior frontal gyrus can be clustered into two antagonistic networks, and the ACC-IFG connection was associated with the within-type CAE. This evidence suggests that our adaptation to cognitive conflicts within a conflict type and across different types may rely on these two distinct neural mechanisms.


Diagnostic value of procalcitonin for bacterial infection in elderly patients - a systemic review and meta-analysis.
To summarise evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying systemic bacterial infections in elderly patients. Major databases, including MEDLINE, EMBASE and the Cochrane Library, were searched for studies published from 1975 to March 2013 that evaluated PCT as a marker for diagnosing systemic bacterial infections in elderly patients and that provided sufficient data to construct two-by-two tables. Four studies were available for quantitative meta-analysis. The area under a summary receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.92). The overall sensitivity and specificity estimates for PCT tests were 0.83 (95% CI: 0.38-0.98) and 0.83 (95% CI: 0.60-0.94), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0.24 to 0.96. The positive likelihood ratio for PCT (LR+ = 4.77; 95% CI: 2.49-9.13) was not sufficiently high for its use as a rule-in diagnostic tool, while its negative likelihood ratio was acceptably low for its use as a rule-out diagnostic tool (LR- = 0.20; 95% CI: 0.04-0.97). Existing data suggest that PCT tests may add to the diagnosis of sepsis in elderly patients. We did not observe the performance of the PCT test in elderly patients inferior to adult patients. Given the imperfect accuracy, we do not recommend that the PCT test be used in isolation; instead, we suggest that it be interpreted in the context of clinical findings.


Trihalomethanes in Lisbon indoor swimming pools: occurrence, determining factors, and health risk classification.
Characterization of water quality from indoor swimming pools, using chorine-based disinfection techniques, was performed during a 6-mo period to study the occurrence, distribution, and concentration factors of trihalomethanes (THM). Several parameters such as levels of water THM, water and air chloroform, water bromodichloromethane (BDCM), water dibromochloromethane (DBCM), water bromoform (BF), free residual chlorine (FrCl), pH, water and air temperature, and permanganate water oxidizability (PWO) were determined in each pool during that period. Chloroform (CF(W)) was the THM detected at higher concentrations in all pools, followed by BDCM, DBCM, and BF detected at 99, 34, and 6% of the samples, respectively. Water THM concentrations ranged from 10.1 to 155 μg/L, with 6.5% of the samples presenting values above 100 μg/L (parametric value established in Portuguese law DL 306/2007). In this study, air chloroform (CF(Air)) concentrations ranged from 45 to 373 μg/m³ with 24% of the samples presenting values above 136 μg/m³ (considered high exposure value). Several significant correlations were observed between total THM and other parameters, namely, CF(W), CF(Air), FrCl, water temperature (T(W)), and PWO. These correlations indicate that FrCl, T(W) and PWO are parameters that influence THM formation. The exposure criterion established for water THM enabled the inclusion of 67% of Lisbon pools in the high exposure group, which reinforces the need for an improvement in pool water quality.


Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care.
Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P < 0.0001). AEs most frequently observed during NSAID treatment were those related to the gastrointestinal tract (3.5% of subjects, 84% of all AEs), followed by AEs related to the nervous system (0.4%) and skin (0.1%). Most of the reported AEs (91.3%) were of mild to moderate intensity (303 of 332) and only 3.3% of them were considered severe (11 of 332). Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications.


Identification of a minimal binding element within the T7 RNA polymerase promoter.
The T7 RNA polymerase promoter has been proposed to contain two domains: the binding region upstream of position -5 is recognized through apparently traditional duplex contacts, while the catalytic domain downstream of position -5 is bound in a melted configuration. This model is tested by following polymerase binding to a series of synthetic oligonucleotides representing truncations of the consensus promoter sequence. The increase in the fluorescence anisotropy of a rhodamine dye linked to the upstream end of the promoter provides a very sensitive measure of enzyme binding in simple thermodynamic titrations, and allows the determination of both increases and decreases in the dissociation constant. The best fit value of Kd=4.0 nM for the native promoter is in good agreement with previous fluorescence and steady state measurements. Deletion of the downstream DNA up to position -1 or to position -5 leads to a fivefold increase in binding, while further sequential single-base deletions upstream result in 20 and 500-fold decreases in binding. These results indicate that the (duplex) region of the promoter upstream of and including position -5 is both necessary and sufficient for tight binding, and represents the core binding element of the promoter. We propose a model in which part of the upstream binding energy is used by T7 RNA polymerase to melt the downstream initiation region of the promoter. We also show that the presence of magnesium is necessary for optimal binding, but not for specific enzyme-promoter complex formation, and we propose that magnesium is not required for melting of the promoter.


Association of platelet-derived growth factor-D gene polymorphism with ischemic stroke in a Chinese case-control study.
Stroke is a multiple genetic disease. Platelet-derived growth factor-D has been found to be involved in the pathogenesis of atherosclerosis, suggesting possible association between platelet-derived growth factor-D and the development of ischemic stroke. However, little information on the relationship between platelet-derived growth factor-D and stroke is currently available. The aim of this study was to investigate the association between platelet-derived growth factor-D genetic variation and the risk of ischemic stroke in a Chinese population. We conducted a case-control study with 309 ischemic stroke patients and 309 sex and age (<5 years)-matched controls. DNA was extracted from the whole blood of each participant. Platelet-derived growth factor-D C/G polymorphism at position +3166 (rs7950273) was detected by TaqMan SNP genotyping assay. Overall, the combined rates of platelet-derived growth factor- D CG and GG are 51% in patients in contrast with 46% in controls. There were no significant differences in the genotype frequencies of platelet-derived growth factor-D +3166 polymorphisms between the patients and controls with history or family history of hypertension or diabetes (P = 0.770). However, among people without history or family history of hypertension or diabetes, platelet-derived growth factor-D CG/GG is significantly more frequently expressed in patients (60%) than in controls (43%) (odds ratio 1.97; 95% confidence interval 1.19-3.26). This significant association holds after adjustment for age, sex, smoking and alcohol intaking (odds ratio 1.86; 95% confidence interval 1.11-3.10) (P = 0.018). Our study found that the G allele of rs7950273 of the platelet-derived growth factor-D gene is associated with higher risk of ischemic stroke in a Chinese population without history or family history of hypertension or diabetes. Future studies with larger and ethnically diverse populations are needed to further evaluate the platelet-derived growth factor-D polymorphism and stroke association, as well as its pathophysiological mechanisms.


Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.
There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery. Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models. A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) -0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) -0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) -0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) -0.307(0.09) mm/year, P = 0.00078). The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.


Optical trapping of microrods: variation with size and refractive index.
Optical traps can be characterized in terms of two simple parameters: the stiffness, given by the gradient of the force at mechanical equilibrium, and the strength, as expressed by the maximum restoring force available for displacement in a given direction. We present numerical calculations of these quantities for dielectric microrods of varying radius and refractive index held horizontally in pairs of holographically generated Gaussian beams. The resulting variations are seen to be influenced by optical resonances, as well as by the relative sizes of the beam waist and rod diameter. In addition, it is shown that trapping in these systems is sensitive to the polarization state of the incident field; i.e., for certain rods, trapping will occur for beams polarized perpendicular to the long axis of the rod, but not for beams polarized parallel to the long axis. Finally, friction coefficients are evaluated and used to estimate the maximum rates at which the rods may be dragged through the ambient medium.


Hyaluronan and Collagen Are Prominent Extracellular Matrix Components in Bovine and Porcine Ovaries.
The extracellular matrix (ECM) is a major component of the ovarian stroma. Collagen and hyaluronan (HA) are critical ovarian stromal ECM molecules that undergo age-dependent changes in the mouse and human. How these matrix components are regulated and organized in other mammalian species with reproductive characteristics similar to women such as cows and pigs, has not been systematically investigated. Therefore, we performed histological, molecular, and biochemical analyses to characterize collagen and HA in these animals. Bovine ovaries had more collagen than porcine ovaries when assessed biochemically, and this was associated with species-specific differences in collagen gene transcripts: Col3a1 was predominant in cow ovaries while Col1a1 was predominant in pig ovaries. We also observed more HA in the porcine vs. bovine ovary. HA was distributed across three molecular weight ranges (<100 kDa, 100-300 kDa, and >300 kDa) in ovarian tissue and follicular fluid, with tissue having more >300 kDa HA than the other two ranges. Transcripts for HA synthesis and degradation enzymes, Has3 and Hyal2, respectively, were predominant in cow ovaries, whereas Has2, Kiaa1199, and Tmem2 tended to be predominant in pig ovaries. Together, our findings have implications for the composition, organization, and regulation of the ovarian ECM in large mammalian species, including humans.


Pregnancy-associated plasma protein-E (PAPP-E).
A full-length cDNA encoding a novel human protein was cloned from placenta cDNA. The corresponding 1542 amino acid protein sequence was termed 'pregnancy-associated plasma protein-E' (PAPP-E) as it shows a 62% homology to the human pregnancy-associated plasma protein-A (PAPP-A) that is a diagnostic marker for trisomies, especially Down syndrome. The conserved domain structure contains five motifs related to the short consensus repeats of complement proteins and selectins, three motifs related to the lin-notch motifs of proteins regulating early tissue differentiation, and a putative zinc-binding motif and active site of the metzincin-superfamily of metalloproteases. The PAPP-E gene was localized to chromosome 1q23-25. Northern blot analysis showed that PAPP-E is predominantly expressed in placenta.


Interaction takes two: Typical adults exhibit mind-blindness towards those with autism spectrum disorder.
Recent work suggests that we are better at interpreting the movements of others who move like us, and that individuals with Autism Spectrum Disorder (ASD) move in a quantifiably different way from typical individuals. Therefore, "social impairments" exhibited by individuals with ASD may, at least in part, represent a failure by typical individuals to infer the correct mental states from the movements of those with ASD. To examine this possibility, individuals with ASD and typical adults manually directed 2 triangles to generate animations depicting mental state interactions. Kinematic analysis of the generated animations demonstrated that the participants with ASD moved atypically, specifically with increased jerk compared to the typical participants. In confirmation of our primary hypothesis, typical individuals were better able to identify the mental state portrayed in the animations produced by typical, relative to autistic, individuals. The participants with ASD did not show this "same group" advantage, demonstrating comparable performance for the 2 sets of animations. These findings have significant implications for clinical assessment and intervention in ASD, and potentially other populations with atypical movement. (PsycINFO Database Record