Patient and public involvement in cancer research: A scoping review.
Patient and public involvement (PPI) in research emphasizes the importance of doing research with, rather than for people with lived health/illness experience(s). The purpose of this scoping review is to investigate the breadth and depth of scientific literature on PPI in cancer research and to identify how is PPI applied and reported in cancer research. We searched MEDLINE, Embase, CINAHL, and PsycInfo up to March 2022. All titles/abstracts and full-text results were screened by two reviewers. Data were analyzed and are presented in both narrative and tabular format. We screened 22,009 titles/abstract, reviewed 375 full-text articles, of which 101 studies were included in this review. 66 papers applied PPI; 35 used co-design methodologies. PPI in cancer research in published research has increased steadily since 2015 and often includes those with a past diagnosis of cancer or relatives/informal caregivers. The most common applied methods were workshops or interviews. PPI was generally used at the level of consultation/advisor and occurred mainly in early stages of research. Costs related to PPI were mentioned in 25 papers and four papers described training provided for PPI. Results of our review demonstrate the nature and extent of PPI expansion in cancer research. Researchers and research organizations entering the fray of PPI should consider planning and reporting elements such as the stage, level, and role type of PPI, as well as methods and strategies put in place to assure diversity. Furthermore, a thorough evaluation of whether all these elements meet the stated PPI purpose will help to grasp its impact on research outcomes. Two patients participated in the stakeholder consultation as part of the scoping review methodology, contributed to the discussion on refining the results, and critically reviewed the manuscript. Both are co-authors of this manuscript.


Delayed removal of maxillary third molar displaced into the maxillary sinus.
The present article reports the late removal of a wisdom tooth displaced into the maxillary sinus associated with the curettage of the adjacent infection tissue, under general anesthesia. A male patient, 42 years-old, was forwarded to remove a right wisdom tooth which was displaced into the right maxillary sinus for 10 months. The patient reported that the tooth was tried to be removed using odontosection in two moments without any success. Since then, the patient has been having (applicants) episodes of sinusitis. It had been planned to remove the tooth and the cleaning of the right maxillary sinus. The surgical procedure was done through the Caldwell-Luc access, followed by the removal of the dental fragments which were into the maxillary sinus and curettage of the cavity in order to remove the granulation tissue, associated to copious irrigation. The surgical removal of the tooth displaced into the maxillary sinus associated with the sinus curettage was successfully achieved, solving the patient complaints.


Low Rates of Chest Wall Toxicity When Individualizing the Planning Target Volume Margin in Patients With Early Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy.
Chest wall (CW) toxicity is a potentially debilitating complication of stereotactic body radiation therapy for non-small cell lung cancer, occurring in 10% to 40% of patients. Smaller tumor-to-CW distance has been identified as a risk factor for CW toxicity. We report our experience with individualizing the planning target volume (PTV) along the CW in an effort to reduce the volume of this organ at risk receiving 30 Gy to 50 Gy. We performed an institutional review board-approved retrospective analysis of patients with stage I (T1-2aN0M0) non-small cell lung cancer who received stereotactic body radiation therapy between June 2009 and July 2016. Four-dimensional computed tomography was used for treatment planning. A uniform 5-mm expansion of the internal target volume was generated for the PTV. Areas of overlap with the CW were removed from the PTV. Treatment was delivered with cone beam computed tomography guidance. CW toxicity was assessed per the Common Terminology Criteria for Adverse Events, version 5. Descriptive statistics were used to analyze outcomes. The median follow-up time was 36.8 months. A total of 260 tumors were treated in 225 patients. 225 tumors in 203 patients were peripheral. The internal target volumes for 143 tumors (63.6%) were located within 5 mm of the CW. The median total dose was 48 Gy (range, 42-60 Gy) in 4 fractions (range, 3-5 fractions). The overall rate of grade 1 to 2 CW toxicity was 2.2%, and 2.8% for tumors located within 5 mm of the CW. There were no grade 3/4 cases and no increase in local recurrences with the use of a truncated PTV with a 3-year local control of 92.1% (95% confidence interval, 87.4%-96.8%). Truncation of the PTV margin along the CW resulted in a marked reduction of CW toxicity for tumors in close proximity to the CW, with only a 2.8% rate of grade 1 to 2 CW toxicity. Despite PTV reduction, there was no appreciable increase in local failures. A multi-institutional validation of this technique is needed before general incorporation into clinical practice.


Does bright-light therapy influence autonomic heart-rate parameters?
30 inpatients suffering from major depression (DSM-III-R), who did not fulfill the criteria of seasonal affective disorder (SAD), were treated with either doxepin or amitripytyline as monotherapy and supportively with bright light for 14 days. From days 15 to 19, bright light was replaced by dim light. 18 drug-free control subjects underwent an analogous sequence of bright- and dim-light applications. Phototherapy was applied between 06:00 and 07:30. Heart-rate (HR) analysis was performed in the patients and control subjects before and after the 5th session of bright and dim lights, respectively. 12 patients (40%) experienced improvement of mood during bright-light therapy (group I) while 18 (60%) did not (group II). Patients of group I, who reached significantly higher scores in the seasonal pattern assessment questionnaire than patients of group II, showed an increase of the coefficient of HR variation (HRV) during deep breathing as well as an increment of the high-frequency (HF) peak of spectral analysis exclusively after the bright-light sessions. Patients of group II did not show a significant alteration of these parameters, neither under the conditions of bright-light treatment nor under dim light. The control subjects experienced an increment of the HF power exclusively after bright light. The results suggest that a distinct subgroup of patients with non-SAD major depression shows a more pronounced light-associated increment of parasympathetically controlled cardiac functions than the other depressed patients and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemical self-assembly strategies for designing molecular electronic circuits.
Design principles are demonstrated for fabricating molecular electronic circuits using the inherently self-limiting growth of molecular wires between gold nanoparticles from the oligomerization of 1,4-phenylene diisocyanide.


Conserved HA-peptides expressed along with flagellin in Trichoplusia ni larvae protects chicken against intranasal H7N1 HPAIV challenge.
The immunization of poultry where H5 and H7 influenza viruses (IVs) are endemic is one of the strategies to prevent unexpected zoonoses. Our group has been focused on conserved HA-epitopes as potential vaccine candidates to obtain multivalent immune responses against distinct IV subtypes. In this study, two conserved epitopes (NG-34 and CS-17) fused to flagellin were produced in a Baculovirus platform based on Trichoplusia ni larvae as living biofactories. Soluble extracts obtained from larvae expressing "flagellin-NG34/CS17 antigen" were used to immunize chickens and the efficacy of the vaccine was evaluated against a heterologous H7N1 HPAIV challenge in chickens. The flagellin-NG34/CS17 vaccine protected the vaccinated chickens and blocked viral shedding orally and cloacally. Furthermore, no apparent clinical signs were monitored in 10/12 vaccinated individuals. The mechanism of protection conferred is under investigation.


Obstetric and neonatal risk of pregnancies after assisted reproductive technology: a matched control study.
The aim of the study was to evaluate the obstetric and neonatal outcome of pregnancies after assisted reproduction technology (ART) in comparison with matched controls from spontaneous pregnancies. A total of 12 920 deliveries at the Department of Obstetrics and Gynecology, University of Szeged, from 1 January 1995 to 31 December 2001 were subjected to retrospective analysis. Two hundred and eighty-four singleton, 75 twin and 17 triplet pregnancies after ovulation induction (n = 114; 30.3%), intrauterine insemination (n = 33; 8.8%) and in vitro fertilization (n = 229; 60.9%) were evaluated. The pregnancy outcome of the singleton and twin pregnancies was compared with that for controls matched with regard to age, gravidity and parity and previous obstetric outcome after spontaneous pregnancies. Twenty-four percent of the assisted reproductive pregnancies were multiple pregnancies. The incidences of singleton intrauterine growth retardation (IUGR) and preterm birth were reasonably similar to those among the controls (IUGR: 6.3% vs. 4.2%; preterm births: 13.0% vs. 9.9%, for the cases and the controls, respectively). As compared with the controls, there was an increased incidence of cesarean section among the singleton (41.2% vs. 34.5%, p = 0.12; OR 1.33; 95% CI 0.95-1.87) and twin assisted reproduction pregnancies (66.7% vs. 60.0%), but without significant differences. Increased obstetric risk could be observed concerning threatened preterm delivery and cesarean section rate in the study group. The perinatal outcome of singleton and twin pregnancies following assisted reproductive techniques is comparable with that of spontaneously conceived, matched pregnancies.


[Giant insulinoma].
Islet-cell tumors are the most common neuroendocrine tumors that arise from the endocrine pancreas. They are typically benign and sporadic. Diagnosis is generally established late because clinical signs lack specificity. The insulinoma is difficult to localize since it is very small in size, often not exceeding 2cm. We report an exceptional case of giant insulinoma initially revealed by a pseudo-polycythemia in an 80-year-old man. He had been treated for hypertension for a few months. Routine biological investigations showed elevated hematocrit and haemoglobin, suggesting Vaquez disease. History taking revealed recent episodes of nocturnal agitation. On admission, he had reddish skin with a suspected enlarged spleen, but total blood volume was normal. Imaging studies showed a voluminous tumor located between the pancreas and the spleen. The presence of an insulinoma was confirmed on the basis of an elevated level of proinsulin at the time of an asymptomatic episode of hypoglycemia. Spleno-pancreatectomy was performed. Histopathological examination revealed a malignant, well-differentiated neuroendocrine malignant tumor.


[Positron emission tomography for volume delineation of pelvic nodal involvement].
Radiotherapy planification has recently known important developments, with the rise of new technologies, such as conformational radiation therapy, intensity-modulated radiation therapy (IMRT) or stereotaxic radiation therapy. Delineation of target volumes has become primordial. Hybrid imaging by positron emission tomography associated to computed tomography scanner (PET-CT) gives an access to functional and morphological information. Radiotherapist and nuclear physicians working closely have the potential to allow a more optimal delineation, and a better preservation of organs at risk. During the past few years, this has been explored by many articles, and we propose a literature review organized by localization, about the use of PET-CT for pelvic nodes delineation.


Clinical and Prognostic Value of Depressive Symptoms and N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Eisenmenger Syndrome.
Eisenmenger syndrome (ES) is commonly associated with depressive symptoms and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). We investigated the predictive value of depressive symptoms and NTproBNP levels for long-term outcomes in patients with ES. Blood was drawn to measure NT-proBNP, and depressive symptoms were measured using the Korean version of the Beck Depression Inventory (BDI) in an outpatient clinic sample of 64 patients with ES (67% female; median age = 41.5 years [range, 21.0-74.8 years]). Cardiac events (hospitalization, emergency department visits, and cardiac death) were monitored during 3 years of follow-up. During the follow-up period, 15 (23.4%) patients experienced a cardiac event. The combination of depressive symptoms and NT-proBNP levels better predicted future cardiac events than either variable alone. Patients with NT-proBNP > 510 pg/ml and a total BDI score > 10 had a 9.6 times higher risk for cardiac events than did patients with NT-proBNP ≤ 510 pg/ml or total BDI score ≤ 10 (p < .001). Depressive symptoms and NT-proBNP levels are both associated with adverse clinical outcomes in ES.


ERK and p38 MAPK signaling pathways are involved in ochratoxin A-induced G2 phase arrest in human gastric epithelium cells.
Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic, and immunotoxic effects. Recent work from our laboratory found that OTA evoked G2 phase arrest in GES-1 cells in vitro by modulating the key factors Cdc25C, Cdc2 and cyclinB1, which were critical to the G2/M phase transmission, suggested that OTA-induced G2 arrest mediate at least in part OTA toxicity effect. However, the molecular mechanism of this effect is currently unclear. In the present study, we showed that treatment of GES-1 cells with OTA could induce the activation of MAPK family members ERK and p38. ERK inhibitor PD98059 and p38 inhibitor SB203580 significantly reversed the depression of Cdc25C/p-Cdc25C, Cdc2/p-Cdc2, cyclinB1 as well as the cyclinB1-Cdc2 complex, thereby, abolished the delay in G2 phase. In addition, silencing ERK and p38 expression with siRNA significantly inhibited OTA-induced G2 arrest in GES-1 cells as well. Collectively, these data suggest that the ERK and p38 MAPK signaling pathways play important roles in the regulation of OTA-induced G2 arrest in GES-1 cells.


Effects of graduating during economic downturns on mental health.
This study examined the effects of economic downturns at the time of graduation on short-term and long-term mental health of graduates. Using a large longitudinal dataset whose respondents graduated from their highest level of education between 2001 and 2018 in Australia, the study investigated the effects of initial labor market conditions on psychological distress measures, quality-of-life mental health scales, and diagnoses of depression or anxiety since graduation. Evidence suggests the presence of a scarring effect of graduating during a recession on the mental health of young adults, particularly significant and persistent for men. Higher unemployment rates at graduation were associated with increased risks of high psychological distress and diagnoses of depression or anxiety, and lower levels of social functioning and mental well-being among men lasting over a decade. The psychological effect was largely driven by young adults with vocational or secondary qualifications or receiving no government allowance at graduation. Policies should consider the psychological effect of graduating during recessions and focus particularly on vulnerable groups who are susceptible to adverse labor market conditions, such as graduates who are in cyclically sensitive occupations and have less or no work benefits and social protection.


A lightweight, partially absorbable mesh (Ultrapro) for endoscopic hernia repair: experimental biocompatibility results obtained with a porcine model.
A meticulous surgical technique, a mesh of adequate dimensions, and use of a mesh with good biocompatibility properties are decisively important for minimizing the development of recurrences after endoscopic hernia repair surgery. Mesh "shrinkage" is a function of the mesh's biocompatibility, that is, the properties of the mesh. Large-pore, lightweight polypropylene meshes possess the best biocompatibility, and the newly developed meshes meet these requirements. Using a totally extraperitoneal technique in an experimental animal model, 10 domestic pigs were implanted with a lightweight, large-pore polypropylene mesh containing an absorbable component consisting of poliglecaprone (Ultrapro). After a period of 91 days, diagnostic laparoscopy followed by explantation of the specimens for macroscopic, histologic, and immunohistochemical evaluation was performed. The mean mesh shrinkage was a mere 1.9%. The partial volume of the inflammatory cells was a low 15.8%. The markers of cell turnover, namely Ki67 and the apoptosis index, were, at 5.8 and 2.1, respectively, also very low. The extracellular matrix showed a low value of transforming growth factor-beta (TGF-beta) (50.8). The mean value of collagen 1 was 136.9. As a result of its good biocompatibility and elastic properties, the lightweight, large-pore Ultrapo mesh showed only a very slight tendency to "shrink." This renders it extremely well suited for clinical use in hernia repair surgery, and its minimal shrinkage characteristic should help in achieving low complication and recurrence rates.


Ankle pulse pressure to diastole ratio as a novel non-invasive costless screening tool for subclinical atherosclerosis.
Atherosclerosis develops gradually as a subclinical condition and eventually becomes clinically apparent as heart disease or stroke. The degree of decreased arterial compliance affects both pulse pressure (PP) and diastolic blood pressure (DBP). These relations would be clear in the distal periphery. We propose that the ankle PP/ankle DBP ratio (APPD) can uncover the ongoing subclinical vascular risk. Based on the elastic chamber theory, APPD = (Cs-Cd)/(Cd-C0) in which Cs, Cd, and C0 represent arterial compliance at systolic pressure, diastolic pressure, and zero-pressure. For a given ventricular ejection, the value of Cs-Cd (i.e. PP) positively differs in the same person from brachium to ankle based on the distance from the heart, degree of arterial stiffness, and the local arterial function. On the other hand, the decreased arterial compliance increases the speed of reflected pulse waves to the heart resulting in earlier ventricular ejection by which the value of Cd-C0 (i.e. DBP) decreases over the arterial tree. In the same person, studies of ankle-brachial blood pressure (BP) differences revealed that PP greatly differed from brachium to ankle while DBPs were of minimal change or almost equivalent. However, DBP would be lower in those with arterial stiffness compared to others of the same age. Accordingly, APPD increases as arterial compliance decreases. Moreover, decreased APPD after a certain limit would reflect either local arterial stenosis or a compromised left ventricular function. When we divided ankle PP by ankle DBP, we could control the diversity of ankle PP as being not related to the BP level and possibly fluctuates in the same person. Additionally, APPD will indicate the extra rapid reflected pulse wave given in decreased DBP. Since increased common carotid artery intima-media thickness (CIMT) is a well-established marker of atherosclerosis, we initially studied 115 subjects apparently free form vascular diseases and had not taken a drug that can affect BP on the day of the study, aged 40-60 years, without a history of stroke, coronary heart disease or peripheral vascular disease to evaluate the relation between APPD and CIMT. The association was statistically significant even after adjusting for age, sex and important covariates and the area under the receiver operating characteristic curve was 0.902 ± 0.031. Therefore, the potential applicability of APPD as a tool for subclinical atherosclerosis was greatly proven.


Ferroptosis assassinates tumor.
In 2020, nearly 20 million peoples got cancer and nearly 10 million peoples died of cancer, indicating the cancer remains a great threat to human health and life. New therapies are still in urgent demand. We here develop a novel cancer therapy named Ferroptosis ASsassinates Tumor (FAST) by combining iron oxide nanoparticles with cancer-selective knockdown of seven key ferroptosis-resistant genes (FPN, LCN2, FTH1, FSP1, GPX4, SLC7A11, NRF2). We found that FAST had notable anti-tumor activity in a variety of cancer cells but little effect on normal cells. Especially, FAST eradicated three different types of tumors (leukemia, colon cancer, and lung metastatic melanoma) from over 50% of cancer mice, making the mice survive up to 250 days without tumor relapse. FAST also significantly inhibited and prevented the growth of spontaneous breast cancer and improved survival in mice. FAST showed high pan anti-tumor efficacy, high cancer specificity, and in vivo safety. FAST defines a new form of advanced nanomaterials, advanced combinatorial nanomaterials, by combining two kinds of nanomaterials, a chemical nanomaterial (iron oxide nanoparticles) and a biochemical nanomaterial (adeno-associated virus), which successfully turns a general iron nanomaterial into an unprecedented assassin to cancer.


Accurate prediction of RNA-binding protein residues with two discriminative structural descriptors.
RNA-binding proteins participate in many important biological processes concerning RNA-mediated gene regulation, and several computational methods have been recently developed to predict the protein-RNA interactions of RNA-binding proteins. Newly developed discriminative descriptors will help to improve the prediction accuracy of these prediction methods and provide further meaningful information for researchers. In this work, we designed two structural features (residue electrostatic surface potential and triplet interface propensity) and according to the statistical and structural analysis of protein-RNA complexes, the two features were powerful for identifying RNA-binding protein residues. Using these two features and other excellent structure- and sequence-based features, a random forest classifier was constructed to predict RNA-binding residues. The area under the receiver operating characteristic curve (AUC) of five-fold cross-validation for our method on training set RBP195 was 0.900, and when applied to the test set RBP68, the prediction accuracy (ACC) was 0.868, and the F-score was 0.631. The good prediction performance of our method revealed that the two newly designed descriptors could be discriminative for inferring protein residues interacting with RNAs. To facilitate the use of our method, a web-server called RNAProSite, which implements the proposed method, was constructed and is freely available at http://lilab.ecust.edu.cn/NABind .


Controlled sleep restriction for rhythmic movement disorder.
Rhythmic movement disorder is a parasomnia that is difficult to treat. In our study, 3 weeks of controlled sleep restriction with hypnotic administration in the first week resulted in almost complete resolution of the movements in 6 children. This therapeutic success suggests that rhythmic movement disorder results from a voluntary self-soothing behavior.


Scavenger Receptor B1 oxidative post-translational modifications are responsible for its loss in Rett syndrome.
The modulation of the HDL receptor scavenger receptor B1 (SRB1) was evaluated in skin fibroblasts isolated from Rett syndrome (RTT) patients, a rare neurodevelopmental disorder affecting almost exclusively females associated in up to 95% of cases to de novo loss-of-function mutations in the X-chromosome-linked gene encoding the methyl-CpG-binding protein 2 (MeCP2). Patients showed an altered plasma lipid profile, while their skin fibroblasts showed a dramatic reduction in SRB1 (immunogold, Western blot and immunohistochemistry). The decreased SRB1 levels were demonstrated to be the consequence of its binding with 4-hydroxy-2-nonenal (4HNE), a product of lipid peroxidation, and its increased ubiquitination. Therefore the loss of SRB1 in RTT cells is a consequence of the chronic oxidative stress status present in RTT. In addition RTT fibroblast presented high intracellular levels of H2O2 and 4HNE protein adducts. This finding was correlated with the constitutive activation of NADPH oxidase (NOX) and was reverted by DPI (NOX inhibitor) or Desferal (Iron chelator) pre-treatment. To confirm the alteration of status redox in RTT cells, the activity of several enzymes involved in protecting the cell from OS was also evaluated. Glutathione peroxidase (GPx), Supeoxide dismutase and Glucose-6-phosphate dehydrogenase (G6PDH) activity were decreased respect to control. These data paralleled with a constitutive activation of NRF2 and elevated gene expression of Heme oxigenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO-1). Of note, when NRF2 pathway was stimulated via exogenous oxidants, RTT fibroblast did not respond as the control cells.


Effect of cyclosporin A on proteinuria in the course of glomerulopathy associated with WT1 mutations.
Denys-Drash syndrome (DDS) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis (DMS), genitourinary defects, and a higher risk of developing Wilms' tumor. It is commonly assumed that the DMS is unresponsive to any medications. In this report, we present a patient with Denys-Drash syndrome, in whom the cyclosporine A (CsA) was found to induce total remission. This observation and observations of other authors confirm that in genetic forms of nephrotic syndrome, the proteinuric effect of CsA may be due to a non-immunologic mechanism. We confirm the beneficial effect of CsA treatment in DDS; however, the potential nephrotoxicity of this drug will probably not allow long-term use.


Distinct mechanisms of site-specific oxidative DNA damage by doxorubicin in the presence of copper(II) and NADPH-cytochrome P450 reductase.
The anticancer mechanism of doxorubicin (DOX), an anthracycline antibiotic, is believed to involve DNA damage through topoisomerase II inhibition and free radical generation. The free radical generation may also participate in genotoxicity, as well as cardiotoxicity, in normal human cells. The present study showed that DOX generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), an indicator of oxidative DNA damage, in HL-60 cells, but not in H(2)O(2)-resistant HP100 cells, suggesting the involvement of H(2)O(2) in cellular DNA damage. Since DOX has both p-quinone and p-hydroquinone residues, free radical generation can be initiated by either reduction or oxidation of DOX. To clarify whether the oxidized or reduced form is more important for DOX-induced H(2)O(2) generation, we investigated the site-specific DNA damage induced by DOX in the presence of Cu(II), in comparison with that in the presence of cytochrome P450 reductase, using (32)P-labeled DNA fragments. DOX caused DNA damage in the presence of Cu(II) or cytochrome P450 reductase. The degree of Cu(II)-mediated DNA damage, including 8-oxodG formation, was much greater than that of cytochrome P450 reductase-mediated DNA damage. DOX plus Cu(II) caused DNA damage specifically at guanine, thymine and cytosine residues, particularly at 5'-GG-3', 5'-GT-3' and 5'-TG-3' sequences. Scavenger experiments suggested the involvement of reactive species generated from H(2)O(2) and Cu(I). When cytochrome P450 reductase and NADPH were used instead of Cu(II), every nucleotide was uniformly damaged, suggesting the participation of.OH. We conclude that DOX may induce carcinostatic and genotoxic effects through oxidation of its p-hydroquinone moiety by metal ion rather than through p-quinone reduction by cytochrome P450 reductase.


Lack of association between CLEC5A gene single-nucleotide polymorphisms and Kawasaki disease in Taiwanese children.
Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.


Feasibility and acceptability of patient partnership to improve access to primary care for the physical health of patients with severe mental illnesses: an interactive guide.
Even in countries with universal healthcare systems, excess mortality rates due to physical chronic diseases in patients also suffering from serious mental illness like schizophrenia is such that their life expectancy could be lessened by up to 20 years. The possible explanations for this disparity include: unhealthy habits (i.e. smoking; lack of exercise); side-effects of psychotropic medication; delays in the detection or initial presentation leading to a more advanced disease at diagnosis; and inequity of access to services. The main objective of this paper is to explore the feasibility and acceptability of patient partnership for developing an interactive guide to improve access to primary care providers for chronic diseases management and health promotion among patients with severe mental illnesses. A participatory action research design was used to engage patients with mental illness as full research partners for a strategy for patient-oriented research in primary care for persons with schizophrenia who also have chronic physical illnesses. This strategy was also developed in partnership with a health and social services centre responsible for the health of the population of a territory with about 100,000 inhabitants in East-end Montreal, Canada. A new interactive guide was developed by patient research partners and used by 146 participating patients with serious mental illness who live on this territory, for them to be better prepared for their medical appointment with a General Practitioner by becoming more aware of their own physical condition. Patient research partners produced a series of 33 short videos depicting signs and symptoms of common chronic diseases and risk factors for the leading causes of mortality and study participants were able to complete the corresponding 33-item questionnaire on an electronic touch screen tablet. What proved to be most relevant in terms of interactivity was the dynamic that has developed among the study participants during the small group learning sessions, a training technique designed for healthcare professionals that was adapted for this project for, and with patient partners. This research has shown the feasibility and acceptability of patient partnership and patient-oriented research approaches to the R&D process of a new medical tool and intervention for patients with serious mental illness, and its acceptability for addressing inequity of this disadvantaged population in terms of access to primary care providers.


Effective Expression of the Serratia marcescens Phospholipase A1 Gene in Escherichia coli BL21(DE3), Enzyme Characterization, and Crude Rapeseed Oil Degumming via a Free Enzyme Approach.
Crude oil degumming by phospholipid removal is crucial to guarantee oil quality. Phospholipase degumming could produce green vegetable oil by reducing energy consumption and protecting the environment. To develop a novel phospholipase for oil degumming, we cloned the Serratia marcescens outer membrane phospholipase A gene (OM-PLA1) and expressed its 33 KDa protein in engineered Escherichia coli BL21(DE3). OM-PLA1 activity reached 18.9 U mL-1 with the induction of 0.6 mM isopropyl β-D-1-thiogalactopyranoside for 4 h. The optimum temperature and pH were 50°C and 7.5, respectively. Mg2+, Ca2+, Co2+, and Mn2+ at 0.1 mM L-1 significantly increased OM-PLA1 activity. The kinetic equations of OM-PLA1 and Lecitase Ultra were y = 13.7x+0.74 (Km = 18.53 mM, Vmax = 1.35 mM min-1) and y = 24.42x+0.58 (Km = 42.1 mM, Vmax = 1.72 mM min-1), respectively. The phosphorus content decreased from 22.6 to 9.3 mg kg-1 with the addition of 15 units of free recombinant OM-PLA1 into 150 g of crude rapeseed oil. OM-PLA1 has the close degumming efficiency with Lecitase Ultra. The S. marcescens outer membrane phospholipase gene (OM-PLA1) possessed higher substrate affinity and catalytic efficiency than Lecitase Ultra. This study provides an alternative approach to achieve crude vegetable oil degumming with enzymatic technology.


Milk and egg phospholipids act as protective surfactants against luminal acid in Necturus gastric mucosa.
Our previous studies indicate that milk phospholipids have anti-ulcer properties in rats and humans, possibly by forming a hydrophobic surfactant layer at the epithelial surface. In the present study we measured intracellular pH and parameters of membrane resistances in gastric epithelium exposed to luminal acid using a microelectrode technique. Chambered isolated Necturus maculosus antral mucosa was exposed to pH 2.3, with or without 20-25 min pre-treatment with milk or egg phospholipids. The pH in surface epithelial cells was measured with double-barrelled liquid sensor pH/PD-microelectrodes. Pre-treatment with phospholipids (2500-5000 micrograms P/mL) significantly (P < 0.01, n = 14) opposed intracellular acidification. Phospholipids significantly (P < 0.05, n = 14) increased the ratio of apical and basal membrane resistances, suggesting that they primarily affect the apical cell membrane. In contrast, there was no significant change in transmucosal resistance suggesting lack of effect on paracellular shunts in the 'leaky' epithelium. Exogenous phospholipids of dietary origin may be used to form a protective layer in the gastric mucosa against irritants.


Use of the minor hemoglobin ratio for the determination of gestational age.
Maternal and cord blood hemoglobin A1c were quantitated at the time of delivery by radioimmunoassay. Other cord blood hemoglobins were quantitated by column chromatography using Bio-Rex 70. The minor hemoglobin ratio : formula: (see text),showed an excellent linear correlation (r2 = 0.88) with gestational age. Therefore, the ratio of : formula: (see text), could be a useful test to determine gestational age in the third trimester.


[Lung volume reduction surgery for emphysema and bullous pulmonary emphysema].
The improvement of respiratory symptoms for emphysematous patients by surgery is a concept that has evolved over time. Initially used for giant bullae, this surgery was then applied to patients with diffuse microbullous emphysema. The physiological and pathological concepts underlying these surgical procedures are the same in both cases: improve respiratory performance by reducing the high intrapleural pressure. The functional benefit of lung volume reduction surgery (LVRS) in the severe diffuse emphysema has been validated by the National Emphysema Treatment Trial (NETT) and the later studies which allowed to identify prognostic factors. The quality of the clinical, morphological and functional data made it possible to develop recommendations now widely used in current practice. Surgery for giant bullae occurring on little or moderately emphysematous lung is often a simpler approach but also requires specialised support to optimize its results.


The diagnostic effect of α-defensin, D-dimer, and IL-6 in periprosthetic joint infection: A systematic review and diagnostic meta-analysis.
Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of α-defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice. Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration. A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing α-defensin, D-dimer, and IL-6. The sensitivity and specificity of α-defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than α-defensin. The detection of α-defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.


On testing temporal niche differentiation in carabid beetles.
It is first shown that den Boer's (1985) claims that competition should be rejected as a factor explaining community structure are not warranted by his tests on temporal niche differentiation in carabid beetles. The power of these tests is so low that they are unlikely to detect even the most extreme pattern of niche differentiation. A major factor that affects their power is the procedure of building up an artificial species pool from the local communities to which the test is to be applied. Alternative tests are then presented, and applied to data on annual activity cycles of carabids in three forest biotopes in Belgium. Three factors are shown to strongly affect their outcome: the unit into which the time scale is divided, the criteria used to incorporate constraints, and the set of species selected. Nevertheless, they provide some evidence that there is a growing niche differentiation from the successional to the climax forest, as predicted by competition theory. Other hypotheses, however, could explain the observed pattern.


Transport of uranium(VI) in red soil in South China: influence of initial pH and carbonate concentration.
Uranium-contaminated wastewater associated with uranium (U) mining and processing inevitably releases into soil environment. In order to assess the risk of U wastewater contamination to groundwater through percolation, U adsorption and transport behavior in a typical red soil in South China was investigated through batch adsorption and column experiments, and initial pH and carbonate concentration were considered of the high-sulfate background electrolyte solution. Results demonstrated that U adsorption isotherms followed the Freundlich model. The adsorption of U to red soil significantly decreased with the decrease of the initial pH from 7 to 3 in the absence of carbonate, protonation-deprotonation reactions controlled the adsorption capacity, and lnCs had a linear relationship with the equilibrium pH (pHeq). In the presence of carbonate, the adsorption was much greater than that in the absence of carbonate owing to the pHeq values buffered by carbonate, but the adsorption decreased with the increase of the carbonate concentration from 3.5 to 6.5 mM. Additionally, the breakthrough curves (BTCs) obtained by column experiments showed that large numbers of H+ and CO32- competed with the U species for adsorption sites, which resulted in BTC overshoot (C/C0 > 1). Numerical simulation results indicated that the BTCs at initial pH 4 and 5 could be well simulated by two-site chemical non-equilibrium model (CNEM), whereas the BTCs of varying initial carbonate concentrations were suitable for one-site CNEM. The fractions of equilibrium adsorption sites (f) seemed to correlate with the fractions of positively charged complexes of U species in solution. The values of partition coefficients (kd') were lower than those measured in batch adsorption experiments, but they had the same variation trend. The values of first-order rate coefficient (ω) for all BTCs were low, representing a relatively slow equilibrium between U in the liquid and solid phases. In conclusion, the mobility of U in the red soil increased with the decrease of the initial pH and with the increase of the initial carbonate concentrations.


The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia.
Dopamine (DA) is a major monoamine neurotransmitter in the brain and has essential roles in higher functions of the brain. Malfunctions of dopaminergic signaling have been implicated in various mental disorders such as addiction, attention deficit/hyperactivity disorder, Huntington's disease, Parkinson's disease (PD), and schizophrenia. The pathogenesis of PD and schizophrenia involves the interplay of mitochondrial defect and DA metabolism abnormalities. This article focuses on this issue in schizophrenia. It started with the introduction of metabolism, behavioral action, and physiology of DA, followed by reviewing evidence for malfunctions of dopaminergic signaling in patients with schizophrenia. Then it provided an overview of multiple facets of mitochondrial physiology before summarizing mitochondrial defects reported in clinical studies with schizophrenia patients. Finally, it discussed the interplay between DA metabolism abnormalities and mitochondrial defects and outlined some clinical studies showing effects of combination therapy of antipsychotics and antioxidants in treating patients with schizophrenia. The update and integration of these lines of information may advance our understanding of the etiology, pathogenesis, phenomenology, and treatment of schizophrenia.


Topical timolol therapy in pregnancy: is it safe for the fetus?
At 21 weeks of gestation, a 37-year-old woman was referred to our hospital. The fetus showed bradycardia and arrhythmia. Because of glaucoma the woman had previously been treated with timolol eye drops. In this paper a possible association between the timolol eye drops and the fetal cardiac arrhythmia is discussed.


The importance of CD54 and CD86 costimulation in T cells stimulated with Candida albicans and Dermatophagoides farinae antigens in patients with atopic dermatitis.
A number of studies have demonstrated an increased frequency of allergen-specific T cells producing increased amounts of interleukin-4 (IL-4) and IL-5, but little interferon-y in both the peripheral blood and skin lesions of patients with atopic dermatitis (AD). In this study, to further clarify the characteristics of T cells obtained from AD patients, we examined the dependency of the antigen-specific proliferation of peripheral blood mononuclear cells (PBMC) from AD patients on costimulatory molecules. The antigens used were Candida albicans and Dermatophagoides farinae, for which AD patients show increased levels of IgE antibodies. PBMC from control healthy donors stimulated with these antigens incorporated [3H]-thymidine much more than PBMC from AD patients. The addition of anti-CD54, -CD40, -CD80 and -CD86 monoclonal antibodies to the cultures showed that the PBMC required only CD54 and CD86 for stimulation with C. albicans, but required CD54, CD80 and CD86 for stimulation with D. farinae. Among these monoclonal antibodies, the anti-CD54 antibody suppressed the proliferative responses of most PBMC, most effectively followed by the anti-CD86 antibody. However, there were no significant differences in the requirement for costimulatory molecules of PBMC proliferation stimulated with C. albicans or D. farinae between AD patients and healthy donors. Since many studies have suggested that T-helper type 1 and T-helper type 2 immune responses are different in their dependency on CD80 or CD86 costimulation, our present results suggest that the allergen-specific T cells of AD patients are not completely shifted to a T-helper type 2 subset.


Direct admission versus interhospital transfer for revascularisation in non-ST-segment elevation myocardial infarction.
The differences in outcomes and process parameters for NSTEMI patients who are directly admitted to an intervention centre and patients who are first admitted to a general centre are largely unknown. There are differences in process indicators, but not for clinical outcomes, for NSTEMI who are directly admitted to an intervention centre and patients who are first admitted to a general centre. We aim to compare process indicators, costs and clinical outcomes of non-ST-segment elevation myocardial infarction (NSTEMI) patients stratified by center of first presentation and revascularisation strategy. Hospital claim data from patients admitted with a NSTEMI between 2017 and 2019 were used for this study. Included patients were stratified by center of admission (intervention vs. general center) and subdivided by revascularisation strategy (PCI, CABG, or no revascularisation [noRevasc]). The primary outcome was length of hospital stay. Secondary outcomes included: duration between admission and diagnostic angiography and revascularisation, number of intracoronary procedures, clinical outcomes at 30 days (MACE: all-cause mortality, recurrent myocardial infarction and cardiac readmission) and total costs (accumulation of costs for hospital claims and interhospital ambulance rides). A total of 9641 NSTEMI events (9167 unique patients) were analyzed of which 5399 patients (56%) were admitted at an intervention center and 4242 patients to a general center. Duration of hospitalization was significantly shorter at direct presentation at an intervention centre for all study groups (5 days [2-11] vs. 7 days [4-12], p < 0.001). For PCI, direct presentation at an intervention center yielded shorter time to diagnostic angiography (1 day [0-2] vs. 1 day [1-2], p < 0.01) and revascularisation (1 day [0-3] vs. 4 days [1-7], p < 0.001) and less intracoronary procedures per patient (2 [1-2] vs. 2 [2-2], p < 0.001). For CABG, time to revascularisation was shorter (8 days [5-12] vs. 10 days [7-14], p < 0.001). Total costs were significantly lower in case of direct presentation in an intervention center for all treatment groups €10.211 (8750-18.192) versus €13.741 (11.588-19.381), p < 0.001) while MACE was similar 11.8% versus 12.4%, p = 0.344). NSTEMI patients who were directly presented to an intervention center account for shorter duration of hospitalization, less time to revascularisation, less interhospital transfers, less intracoronary procedures and lower costs compared to patients who present at a general center.


beta-Amino acid transport in pig small intestine in vitro by a high-affinity, chloride-dependent carrier.
This study describes unidirectional influx of amino acids and D-glucose across the small intestinal brush-border membrane of fully weaned eight week old pigs. Influx is minimal in the duodenum and maximal in the distal and/or mid small intestine. Influx of beta-alanine, taurine and N-methyl-aminoisobutyric acid is chloride-dependent. The activation stoichiometry for taurine influx is 1.0 +/- 0.2 chloride/2.4 +/- 0.3 sodium/1 taurine. Influx of D-glucose, lysine, glycine and glutamate is chloride-independent. An ABC test demonstrates a common beta-amino acid carrier: (a) the apparent affinity constant K1/2Taurine is 44 +/- 13 microM (means +/- S.D.) and the inhibitory constant (KiTaurine) against beta-alanine influx is 41 +/- 5 microM (means +/- S.E.). (b) K1/2beta-alanine is 97 +/- 23 microM and Kibeta-alanine against taurine influx is 160 +/- 22 microM. (c) KiHypotaurine against taurine and beta-alanine influx is 43 +/- 4 (n = 7) and 22 +/- 5 microM (n = 7), respectively. In conclusion, a high affinity, low capacity, sodium- and chloride-dependent carrier of beta-amino acids is present in pig small intestine.


Antiextensor effects of 3,3-diphenyl-n-propylamine in the mouse.
Diphenylpropylamine has antiextensor activity in the MES test and worsens clonic seizures produced by pentylenetetrazol. The drug also prevents tonic hindlimb extension produced by large doses of pentylenetetrazol. Diphenylpropylamine appears, therefore, to be a phenytoin-like compound. However, unlike most antiextensor agents, diphenylpropylamine has neuroexcitatory effects and antagonizes barbital-induced loss of the righting reflex.


A novel variant in FN1 in a family with fibronectin glomerulopathy.
Glomerulopathy with fibronectin deposits (GFND) is a rare glomerular disorder. We report a 28-year-old male diagnosed with GFND by mass spectrometry on kidney biopsy tissue. Whole-exome sequencing (WES) identified that a previously undescribed FN1 gene mutation (c.3051G > T, p.W1017C) was likely responsible for this patient's fibronectin glomerulopathy. We discuss the implications of this novel variant of FN1 and the importance of WES to identify a mutation in a gene of interest.


Exposure assessment to ochratoxin A through the intake of three cereal derivatives from the Moroccan market.
Previous studies reported the contamination of cereals products with OTA in Morocco. Given bread, pasta and semolina are staple consumed food in the country, this study aims to assess the OTA exposure levels for the adult consumers in the country through cereal derivatives intake, by using a deterministic model based on the crossover of consumption and contamination data of 457 cereals products samples. The study also set out to determine under what conditions the OTA contributions from these 3 cereal derivatives alone were enough to cause a real public health problem in the country. The Estimated Weekly Intake EWI (ng/kg b.w./week) was used as an indicator of exposure for each cereal derivative. The global exposure (Total EWI) was determined by the summation of the EWI obtained for each cereal derivative for different consumers groups and at different OTA levels and nine scenarios were elaborated. Results showed that the total average OTA intake from the three cereal derivatives was estimated at 13.5 ng/kg b.w./week. Despite its low contamination levels, bread has been shown to be the main vector of exposure to OTA because of the high consumption levels by Moroccan adults. Its contribution to the total OTA intake was between 81 and 84% depending on the scenario. The contribution of the other investigated cereal products to total OTA intake seems to be modest and does not exceed 10% and 7% for semolina and pasta, respectively. The predominance of cereal derivatives in Moroccan food thus constitutes a potential risk factor for OTA exposure. Indeed, the risk of occurrence of potential adverse effects of OTA is real in three scenarios discussed in the study since the PTWI established by JECFA (100 ng/kg b.w./week) was exceeded. Moreover, the Maximum limit (3 ng/g) set by Moroccan regulations in 2016, seems to be less protective for the Moroccan consumers compared to other countries due to the high consumption level of cereal products. This situation is likely to cause a public health problem by the occurrence of specific pathologies at highly OTA exposed adults, especially high bread consumers.


Trust, social support and patient type--associations between patients perceived trust, supportive communication and patients preferences in regard to paternalism, clarification and participation of severely injured patients.
Trust is an important aspect of physician-patient-interaction, both in terms of compliance and patient- and physician-reported outcomes. Trust-building communication is especially important in terms of severely injured patients because of severity of their injuries and frequently associated physical and psychological consequences. Patients preferences concerning medical treatment (patient type) is also regarded to be important in terms of trust. The objective of this study was to investigate the relationships between patients perceived trust, supportive communication of physicians and patient type of severely injured patients. Seventy-one severely injured patients, who were predominantly injured in the workplace or in traffic accidents and were treated in one of four hospitals in Northrhine-Westfalia between 2001 and 2005, completed a self-administered questionnaire. "Trust in physicians_short form" (TRIP_sf) describes different aspects, such as general trust, competence of doctors and the feeling to be in good hands. "Informational support" and "emotional support" comprise verbal and non-verbal aspects, such as clear and understandable information or devotion and empathic manner. "Patient type" measures patients preferences in regard to paternalism of physician, clarification of medical facts and participation in treatment. Trust is strongly correlated with informational (.628**) and emotional support (.542**) and is less correlated with patients preferences of "paternalism" (.250*)", "clarification" (.438**) and participation" (.378**). Informational and emotional support are in general not significantly correlated with type of patient, all correlations were adjusted for age, gender, marital and socioeconomic status, length of hospital stay, and severity of injury. Trust is significantly related to patient type but more related to doctor support: the results confirm the importance of supportive communication in terms of emotional and informational support. Medical education should integrate sound knowledge about the psychosocial aspects of physician patient interaction to enable doctors to provide effective social support and to identify and consider patients preferences.


The endogenous inhibitor of NCX1 does not resemble the properties of digitalis compound.
In our previous study, we ware successful in isolation and purification of an endogenous inhibitor of the Na/Ca exchanger (NCX1) from the calf ventricle extracts. The purified factor has characterized to have strong positive inotropic effect on isometric contractions of isolated ventricle strips of guinea pig. A possibility is that besides the NCX1 the endogenous factor may also interact with other ion-transport systems (e.g., Na,K-ATPase) involved in modulation of muscle contractility-relaxation. Therefore, a primary goal of the present study was to detect a possible effect of newly found NCX1 inhibitor on Na,K-ATPase and Ca-ATPase activities. The preparations of isolated sarcolemma vesicles were used for this goal. Although the crude extracts of calf ventricles can inhibit both the Na/Ca exchange and Na,K-ATPase, these two inhibitory activities can be separated on the Sephadex G-10 column, meaning that different molecular entities might be responsible for inhibition of Na/Ca exchange and Na,K-ATPase. Addition of 100 U of purified endogenous factor to the assay medium results in nearly complete inhibition of forward (Na(i)-dependent Ca-uptake) and reverse (Na(o)-dependent Ca-efflux) modes of Na/Ca exchange. On the other hand, no effect was detected on activities of Na,K-ATPase and Ca-ATPase even in the presence of 500 U of purified factor in the assay medium. In light of the present data, it is concluded that the endogenous inhibitor of NCX1 does not resemble the targeting properties of digitalis like compound. Obviously, more systematic studies are required in the future for resolving a possible interaction of the endogenous inhibitor of NCX1 with other ion-transport systems involved in calcium homeostasis and action potential.


Intercalative interaction of asymmetric copper(II) complex with DNA: experimental, molecular docking, molecular dynamics and TDDFT studies.
The intercalative interactions of small molecules with DNA are important in a variety of biological processes including mutagenesis, carcinogenesis, and chemotherapy. A comprehensive research protocol including experiments and calculations was employed to investigate the intercalative interaction between metallointercalator copper(II) complex and DNA. The intercalative binding mode has been validated by UV spectra, fluorescence spectra, CD spectra and viscosity measurements. The classical molecular dynamics simulation was carried out to investigate the intercalative interaction between asymmetric copper(II) complex and DNA. An analytical method was proposed to simulate the dynamically changing absorption spectra of intercalator/DNA system. According to the established model, the changing process of the electronic absorption spectra for intercalator/DNA system can be predicted accurately. A rational explanation for the change law of absorption spectra has been proposed. Moreover, the analyses of the frontier orbital reveal that the red shift of the absorption spectra is due to the increase of π orbital energy caused by the coupling of the π orbital of the intercalated ligand with the π orbital of DNA. This cause of red shift of spectra is completely different from the previous inference. All these insights are of crucial importance for correctly analyzing the absorption spectra of intercalative interaction, as well as for explaining the macroscopic phenomena observed in experiments at the molecular level.


Heat waves, ambient temperature, and risk of myocardial infarction: an ecological study in the Community of Madrid.
Episodes of extreme heat are associated with increased morbidity and mortality in chronically-ill patients but there is a need to clearly establish the relationship between extreme heat and myocardial infarction. The aim of this study was to analyze the relationship between the incidence of ST-segment elevation myocardial infarction (STEMI) and maximum temperature, in particular during heat wave alert periods (HWAP). The population studied consisted of confirmed STEMI cases registered in the Infarction Code of the Community of Madrid between June 2013 and June 2017. Incidence rate ratios (IRR) adjusted for trend and seasonality and 95%CI were estimated using time series regression models. A total of 6465 cases of STEMI were included; 212 cases occurred during the 66-day period of HWAP and 1816 cases during the nonalert summer period (IRR, 1.14; 95%CI, 0.96-1.35). The minimum incidence rate was observed at the maximum temperature of 18°C. Warmer temperatures were not associated with a higher incidence (IRR,1.03; 95%CI, 0.76-1.41), whereas colder temperatures were significantly associated with an increased risk (IRR, 1.25; 95%CI, 1.02-1.54). No effect modification was observed by age or sex. We did not find an increased risk of STEMI during the 66 days of HWAP in the Community of Madrid between June 2013 and June 2017. However, an increased risk was found during colder temperatures. No extra health resources for STEMI management are required during periods of extreme heat, but should be considered during periods of cold weather.


Risk factors for faecal sand excretion in Icelandic horses.
Sandy soil is often mentioned as a risk factor in the development of sand-related gastrointestinal disease (SGID) in the horse. There are other variables, but few studies confirm any of these. To investigate soil type, pasture quality, feeding practice in the paddock, age, sex and body condition score as risk factors for sand intake in the horse. Faeces were collected from 211 Icelandic horses on 19 different studs in Denmark together with soil samples and other potential risk factors. Sand content in faeces determined by a sand sedimentation test was interpreted as evidence of sand intake. Soil types were identified by soil analysis and significance of the data was tested using logistic analysis. Of horses included in the study, 56.4% showed sand in the faeces and 5.7% had more than 5 mm sand as quantified by the rectal sleeve sedimentation test. Soil type had no significant effect when tested as main effect, but there was interaction between soil type and pasture quality. Significant interactions were also found between paddock feeding practice and pasture quality. To evaluate the risk of sand intake it is important to consider 3 variables: soil type, pasture quality and feeding practice. Pasture quality was identified as a risk factor of both short and long grass in combination with sandy soil, while clay soil had the lowest risk in these combinations. Feeding practice in the paddock revealed feeding directly on the ground to be a risk factor when there was short (1-5 cm) or no grass. Also, no feeding outdoors increased the risk on pastures with short grass, while this had no effect in paddocks with no grass. More than 50% of all horses investigated in this study had sand in the faeces. The identification of risk factors is an important step towards prevention of SGID. Further research is necessary to determine why some horses exhibit more than 5 mm sand in the sedimentation test and whether this is correlated with geophagic behaviour.


Cerium oxide nanoclusters: commensurate with concepts of polyoxometalate chemistry?
The mixed-valent cerium(III/IV) oxide clusters {Ce(10)} and {Ce(22)}, derived from condensation reactions of cerium carboxylate coordination polymers, exhibit molecular growth tendencies similar to those of 'classical' group V and VI polyoxometalates, but with increasing nuclearity approach the structure of the parental oxide, CeO(2).


Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial.
In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids. The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10-30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21-24, and rescue medication use (puffs/day) over Weeks 1-24. Analyses were conducted across the full range of reversibility (-850-896 mL); however, results are presented for the range -100-400 mL because there were few participants with values outside this range. The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range. FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.


Posterior nasal nerve neurectomy for the treatment of chronic rhinosinusitis with nasal polyposis: a randomized controlled trial.
Managing Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is always challenging due to the chronicity of the disease and its intractable course. Posterior nasal neurectomy (PNN) can be effective in alleviating symptoms of CRSwNP. The study was conducted in a tertiary care referral hospital from August 2019 to April 2022. A total of 46 patients of CRSwNP were included (23 patients in the study and 23 in the control group). Patients in the study group underwent endoscopic sinus surgery (ESS) and PNN and patients in the control group with ESS. The symptoms and quality-of-life improvement were assessed at 1, 4, 12, and 24 weeks after the surgery. On intragroup analysis between the preoperative and postoperative scores (SNOT-22, RSDI and LK Score), we found a significant difference for each (p < 0.05). When the improvement of outcome scores was compared between the two groups, a significant difference was obtained for SNOT-22 and RSDI scores at 1 week and 4 weeks (p < 0.05). There was no significant difference found for the duration of surgery/complications between the two groups (p = 1.00). The PNN can be an effective add-on procedure in patients with CRSwNP in alleviating short-term control of the symptoms and the quality of life. A larger sample size with long-term follow-up may be required for a better understanding of the efficacy of the PNN in patients with CRSwNP.


Discrete membrane surface charge distributions. Effect of fluctuations near individual channels.
Each gating mechanism controlling permeability in a membrane may be influenced by only a few charge binding sites on the membrane surface, so that fluctuations in the occupancy of these sites are important. Tow extreme cases arise. (a) The time scale of these fluctuations is much shorter than the gating time constant. Then the gating mechanisms are subject to a rapidly varying electric field. If the gating in the absence of these fluctuations obeys exponential kinetics, so does the gating in the presence of the fluctuations. Changes in surface charge do not simply shift the gating variable curves on the voltage axis, but also change their shape. Such effects are seen experimentally and cannot be explained in terms of conventional surface charge theory. If the activation curve in the absence of any surface charge binding is symmetric about the half-activation point, when some of the surface charge sites are occupied the activation curve is in general asymmetric. (b) The fluctuations occur much more slowly than the gating reaction. There are several pools of channels present with different time constant and activation curves. Again the activation curve is asymmetric about the half-activation point, and its shape is changed by alterations in the surface charge. The kinetics of gating of the whole population of channels are multiexponential.


Presence of growth hormone receptor (GH-R) mRNA and protein in goat ovarian follicles and improvement of in vitro preantral follicle survival and development with GH.
This study aimed to demonstrate the expression of growth hormone receptor (GH-R) mRNA and protein in goat ovarian follicles in order to investigate the effects of GH on the survival and development of preantral follicles. The ovaries were processed for the isolation of follicles to study GH-R mRNA expression or to localization of GH-R by immunohistochemical analysis. Pieces of ovarian cortex were cultured for 7 days in minimum essential medium(+) (MEM(+)) in the presence or absence of GH at different concentrations (1, 10, 50, 100, and 200 ng/mL). High expression levels of GH-R mRNA were observed in granulosa/theca cells from large antral follicles. However, preantral follicles do not express mRNA for GH-R. Immunohistochemistry demonstrated that the GH-R protein was expressed in the oocytes/granulosa cells of antral follicles, but any protein expression was observed in preantral follicles. The highest (P < 0.05) rate of normal follicles and intermediate follicles was observed after 7 days in MEM(+) plus 10 ng/mL GH (70%). In conclusion, GH-R mRNA and protein are expressed in caprine antral follicles, but not in preantral follicles. Moreover, GH maintains the survival of goat preantral follicles and promotes the development of primordial follicles.


Re-Evaluating the Role of PTHrP in Breast Cancer.
Parathyroid-hormone-related protein (PTHrP) is a protein with a long history of association with bone metastatic cancers. The paracrine signaling of PTHrP through the parathyroid hormone receptor (PTHR1) facilitates tumor-induced bone destruction, and PTHrP is known as the primary driver of humoral hypercalcemia of malignancy. In addition to paracrine signaling, PTHrP is capable of intracrine signaling independent of PTHR1 binding, which is essential for cytokine-like functions in normal physiological conditions in a variety of tissue types. Pre-clinical and clinical studies evaluating the role of PTHrP in breast cancer have yielded contradictory conclusions, in some cases indicating the protein is tumor suppressive, and in other studies, pro-growth. This review discusses the possible molecular basis for the disharmonious prognostic indications of these studies and highlights the implications of the paracrine, intracrine, and nuclear functions of the protein. This review also examines the current understanding of the functional domains of PTHrP and re-evaluates their role in the unique context of the breast cancer environment. This review will expand on the current understanding of PTHrP by attempting to reconcile the functional domains of the protein with its intracrine signaling in cancer.


Gait acquisition and analysis system for osteoarthritis based on hybrid prediction model.
Osteoarthritis (OA) is the most common type of joint-related diseases, which affects millions of people worldwide. Expensive and time-consuming medical imaging can provide precise structural description of knee joints, but lacks the functional descriptions. Gait analysis can provide functional descriptions of knee joints. However, orthopedic surgeons always observe the patient's gait qualitatively and perform subjective assessments through rating scales at present due to the lack of a quantitative gait analysis system. To solve these problems, a gait acquisition and analysis system is developed to provide a cheap, easy-to-use solution for quantitative recording and functional description of OA patients. Firstly, an automatic gait acquisition platform is designed for the clinical setting based on the RGB-D camera and the developed software of gait data recording. In addition, the effective working space of gait acquisition platform is evaluated for clinical applications by comparing with the ground-truth from infrared optical trackers. Secondly, the acquired gait data is analyzed with a novel hybrid prediction model to assess the gait anomalies quantitatively and objectively. In the hybrid model, the extracted features of gait data contain the manually-extracted features and the automatically-extracted features from Long Short-Term Memory network. Experimental results on real patients demonstrate that the proposed gait analysis system can quantitatively predict gait anomalies with a high accuracy of 98.77 %. Therefore, this gait acquisition and analysis system achieves quantitative recording and objective assessment of gait anomalies for clinical OA treatments.


Age and gender differences of basic electrocardiographic values and abnormalities in the general adult population; Tehran Cohort Study.
Although several studies are available regarding baseline Electrocardiographic (ECG) parameters and major and minor ECG abnormalities, there is considerable controversy regarding their age and gender differences in the literature. Data from 7630 adults aged ≥ 35 from the Tehran Cohort Study registered between March 2016 and March 2019 were collected. Basic ECG parameters values and abnormalities related to arrhythmia, defined according to the American Heart Association definitions, were analyzed and compared between genders and four distinct age groups. The odds ratio of having any major ECG abnormality between men and women, stratified by age, was calculated. The average age was 53.6 (± 12.66), and women made up 54.2% (n = 4132) of subjects. The average heart rate (HR) was higher among women(p < 0.0001), while the average values of QRS duration, P wave duration, and RR intervals were higher among men(p < 0.0001). Major ECG abnormalities were observed in 2.9% of the study population (right bundle branch block, left bundle branch block, and Atrial Fibrillation were the most common) and were more prevalent among men compared to women but without statistical significance (3.1% vs. 2.7% p = 0.188). Moreover, minor abnormalities were observed in 25.9% of the study population and again were more prevalent among men (36.4% vs. 17% p < 0.001). The prevalence of major ECG abnormalities was significantly higher in participants older than 65. Major and minor ECG abnormalities were roughly more prevalent in male subjects. In both genders, the odds of having major ECG abnormalities surge with an increase in age.


Atrial natriuretic factor in high-altitude pulmonary hypertension: the influence of acute hypoxia on plasma atrial natriuretic factor, renin, and aldosterone concentrations in highlanders with initially normal or elevated pulmonary artery pressure and without evidence of right ventricular hypertrophy.
Since the renin-angiotensin-aldosterone system and atrial natriuretic factor are directly involved in the regulation of hemodynamics and structural alterations in the circulatory system, the interest of investigators in the observed changes in this system during exogenous hypoxia and the resultant development of high-altitude pulmonary hypertension is quite understandable. The authors measured the plasma levels of hormones from the major vasoconstrictor neurohumoral system and from one vasodilatory system and correlated them with hemodynamic variables in native highlanders of Tien-Shan.


High-density rafts preferentially host the complement activator measles virus F glycoprotein but not the regulators of complement activation.
The fusion (F) protein of measles virus (MeV) activates the alternative pathway of human complement in the presence of both CD46 and CD55 which regulate the complement activation [Devaux, P., Christiansen, D., Plumet, S., Gerlier, D., 2004. Cell surface activation of the alternative complement pathway by the fusion protein of measles virus. J. Gen. Virol. 85, 1665-1673]. The original observation of cold detergent-resistant membranes sedimenting at a higher density than the membrane rafts lead us to analyse the respective distribution of F, CD46 and C55 molecules in what we call heavy rafts (HRs) and in the classical low-density membrane rafts (Rs). Membrane rafts were isolated after cold TX100 solubilization and flotation on a sucrose gradient. The denser fractions collected from the lower part of the gradient could be further separated into a translucent pellet (HR) and a soluble supernatant (S). HR and R were both sensitive to TX100 solubilization after cholesterol depletion and solubilized by octyl-d-glucoside but differed in their lipid and protein composition. A proteomic analysis revealed that the HR fraction was derived from heterogeneous cellular membranes including plasma membrane, early endosomes and rough endoplasmic reticulum. Interestingly, CD55 and CD46 almost exclusively associated with R and S fractions, respectively, while after MeV infection or transient expression, MeV-F distributed almost equally between R, HR and S fractions. However more immature MeV-F(0) than mature MeV-F(1) proteins was associated with the HR fraction whereas this ratio was reverse in R and S fractions. After activation of the alternative pathway of human complement by F expressing cells, both C3b and F protein associated with R, HR and S fractions. When four or five of the five cysteines located in the transmembrane and cytoplasmic tail of F protein were substituted with serine residues, the mutated F distributed almost exclusively in HR fractions and was still efficient in activating the complement. We propose that the partitioning of F, CD46 and CD55 molecules in different membrane microdomains could account for the ability of F to escape complement regulation by the CD55 and CD46 regulators.


Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP.
Using biochemical assays, it has been demonstrated that expression of Ebola virus VP40 alone in mammalian cells induced production of particles with a density similar to that of virions. To determine the morphological properties of these particles, cells expressing VP40 and the particles released from the cells were examined by electron microscopy. VP40 induced budding from the plasma membrane of filamentous particles, which differed in length but had uniform diameters of approximately 65 nm. When the Ebola virus glycoprotein (GP) responsible for receptor binding and membrane fusion was expressed in cells, we found pleomorphic particles budding from the plasma membrane. By contrast, when GP was coexpressed with VP40, GP was found on the filamentous particles induced by VP40. These results demonstrated the central role of VP40 in formation of the filamentous structure of Ebola virions and may suggest an interaction between VP40 and GP in morphogenesis.


Crystal structure of a tethered dimer of HIV-1 proteinase complexed with an inhibitor.
HIV-1 proteinase (HIV PR) is a dimeric enzyme composed of two identical polypeptide chains that associate with twofold symmetry. We have determined to 1.8 A the crystal structure of a covalently tethered dimer of HIV PR. The tethered dimer:inhibitor complex is identical in nearly every respect to the complex of the same inhibitor with the wild type dimeric molecule, except for the linker region. Our results suggest that the tethered dimer may be a useful surrogate enzyme for studying the effects of single site mutations on substrate and inhibitor binding as well as on enzyme asymmetry, and for simulating independent mutational drift of the two domains which has been proposed to have led to the evolution of modern day, single-chain aspartic proteinases.


Which factors do provoke binge-eating? An exploratory study in female students.
To study the different factors (external, emotional, cognitive, and physiological) which may trigger binge-eating in young females. A total of 110 female students (between 14 and 25 years of age) filled out the Eating Disorder Inventory (EDI) and the Binge Eating Trigger Checklist (BETCH), a new screening device to evaluate the type of situations (and their experienced discomfort) which subjects identify as antecedents of a binge-eating episode. Approximately 41% of the female students reported binge-eating and 15% admitted they have daily binges. The binge-eating triggers most frequently reported and at the same time having the highest level of discomfort were emotional triggers (feeling bored, depressed, anxious, tense, and sad) and physiological triggers (being hungry and feeling an urge to eat sweets). Fewer food-related cues have been reported whereas dysfunctional cognitions were rarely mentioned as antecedents of binge-eating. Binge-eating, as perceived and reported by female students, seems to be provoked by a combination of different antecedents, both emotional and physiological.


Geographic association between mammography use and mortality reduction in the US.
Breast cancer mortality rates in women have been declining at the same time as breast cancer incidence rates, mammography rates and use of effective adjuvant therapy have been increasing. The objective of this study was to examine population data on breast cancer screening and breast cancer mortality to see if there is any geographic association between mammographic screening and breast cancer mortality reduction in the US, after adjusting for therapy use. Regression analysis of the estimated annual percent reduction of breast cancer mortality was performed on mammography use from the Behavioral Risk Factors Surveillance System (BRFSS) at state level. A secondary regression analysis on the SEER-11 region, at an aggregated Health Services Area (HSA) level, was carried out to adjust for use of adjuvant therapy. The annual percent change in the incidence of early stage cancer, calculated from SEER cancer data was used as a surrogate for mammography use. Adjuvant therapy use was estimated from SEER data and adjusted using the Patterns of Care data. All the analyses showed a small but significant negative correlation between mammography usage and mortality reduction (correlation of -0.285, p-value 0.045) in breast cancer (state level) and change in "early" stage breast cancer and mortality reduction (at HSA level) unadjusted (correlation of -0.307, p-value 0.065) and adjusted (partial correlation of -0.337, p-value 0.044) for adjuvant therapy use. The results of the two analyses appear to show a moderate effect of mammography usage on decreasing breast cancer mortality in the US, which seems to support the conclusions of randomized mammographic screening trials. While randomized controlled trials are certainly the gold standard in appraising the efficacy of new screening or treatment modalities, such trials are conducted under standardized conditions and do not always reflect the effect of these interventions at population level. This paper attempts to examine population level effects through ecologic analyses. Results, however, need to be interpreted cautiously owing to the limitations and biases inherent in such analyses.


Splenic flexure volvulus in a child with chronic idiopathic intestinal pseudo-obstruction syndrome.
Splenic flexure volvulus in a child with chronic idiopathic intestinal pseudo-obstruction syndrome is extremely rare. Here we present a case report of this unusual condition in a 7-year-old girl. The splenic flexure volvulus was managed by pressure reduction from the cecal antegrade continence enema, after which elective resection of the splenic flexure and primary anastomosis were performed because she had similar attacks during 4 months after the first detorsion. Postoperatively she made an uneventful recovery. Possible factors of pathogenesis and therapeutic measures are discussed.


Are nonconscious processes sufficient to produce false memories?
Seamon, Luo, and Gallo (1998) reported evidence that nonconscious processes could produce false recognition in a converging-associates task, whereby subjects falsely remember a nonstudied lure (e.g., sleep) after studying a list of related words (bed, rest, awake...). Zeelenberg, Plomp, and Raaijmakers (2003) failed to observe this false recognition effect when list word recognition was at chance. We critically evaluate the evidence for nonsconscious processing and report the results of a new experiment designed to overcome previous methodological limitations. Consistent with Seamon et al., we found that conscious activation of a related lure during study was not necessary for its subsequent recognition; consistent with Zeelenberg et al., we found no evidence for recognition of related lures under conditions where there was no memory for studied words. It is currently unknown whether conscious recollection of the studied items is necessary for false recognition or if nonconscious activation of the lure is sufficient.


Mitotic gene conversion of large DNA heterologies in Saccharomyces cerevisiae.
Gene conversion of large DNA heterologous fragments has been shown to take place efficiently in Saccharomyces cerevisiae. It has been found that a 2.6 kb LEU2 DNA fragment in a multicopy plasmid was replaced by a 3.1 kb PGI1 chromosomal DNA fragment, when both fragments were flanked by homologous DNA regions. Gene conversion was asymmetric in a total of 481 recombinants analyzed. In contrast, truncated PGI1 or LEU2 genes in multicopy plasmids, gave no recombinants that restored a complete plasmid copy of these genes in a total of 242 recombinants studied, confirming that a conversion tract is disrupted by a heterologous region. The asymmetry of the events detected suggest that gene conversion of large DNA heterologies involves a process whereby a gap first covers one heterologous fragment and then this is followed by new DNA synthesis using the other heterologous fragment as a template. Therefore, it is likely that large DNA heterologies are converted by a double-strand gap repair mechanism.


Impact of clinical pharmacist-based parenteral nutrition service for bone marrow transplantation patients: a randomized clinical trial.
Parenteral nutrition (PN) is a well-documented supportive care which maintains the nutritional status of patients. Clinical pharmacists are often involved in providing PN services; however, few studies have investigated the effect of a clinical pharmacy-based PN service in resource-limited settings. We designed a randomized clinical trial to compare the clinical pharmacist-based PN service (intervention group) with the conventional method (control group) for adult patients undergoing hematopoietic stem cell transplantation in Shariati Hospital, Tehran, Iran (2011-2012). In the intervention group, the clinical pharmacists implemented standard guidelines of nutrition support. The conventional method was a routine nutrition support protocol which was pursued for all patients in the bone marrow transplantation wards. Main study outcomes included nutritional status (weight, albumin, total protein, pre-albumin, and nitrogen balance), length of hospital stay, time to engraftment, rate of graft versus host disease, and mortality rate. Patients were followed for 3 months. Fifty-nine patients were randomly allocated to a study group. The overall intake (oral and parenteral) in the control group was significantly lower than standard daily needed calories (P < 0.01). Patients in the intervention group received fewer days of PN (10.7 ± 4.2 vs. 18.4 ± 5.5 days, P < 0.01). All nutritional outcomes were either preserved or improved in the intervention group while the nutritional status in the control group was deteriorated (P values < 0.01). Length of hospital stay was significantly shorter in the intervention group (P < 0.01). Regarding PN complications, hyperglycemia was observed more frequently in the intervention group (34.5 %, P = 0.01). Two patients in the control group expired due to graft versus host disease at the 3-month follow-up. A clinical pharmacist-based nutrition support service significantly improved nutritional status and clinical outcomes in comparison with the suboptimal conventional method. Future studies should assess the cost effectiveness of clinical pharmacists' PN services.


Suppression of the Antioxidant System and PI3K/Akt/mTOR Signaling Pathway in Cisplatin-Resistant Cancer Cells by Quercetin.
We studied the effect of quercetin on ovarian adenocarcinoma SKOV-3 cell line and isogenic subline SKOV-3/CDDP resistant to the anticancer drug cisplatin. It was found that in resistant cells, quercetin in a concentration of 100 μM that causes a decrease in the cell viability suppressed the expression of genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1), transcription factor Nrf2, and kinases of the PI3K/Akt/mTOR signaling pathway. In parental cells, quercetin, on the contrary, increased the expression of these genes. The results confirm the redox-dependent regulation induced by quercetin and its opposite nature in cisplatin-sensitive and cisplatin-resistant cancer cells.


Metastatic oncocytic adrenocortical carcinoma of mandible: an extraordinarily rare occurrence.
Adrenocortical carcinoma (ACC) is an uncommon primary cancer in the adrenal gland. Its incidence of showing metastasis in the head and neck region is very rare. Herein, we present a case of a 46-year-old man who presented with complaints of pain and numbness on the left side of the lower face for 4 months. Radiographic examination revealed an osteolytic lesion with an ill-defined border in the left body region of the mandible. Histopathologic examination revealed a tumor composed of sheets of oval to polygon-shaped tumor cells predominantly displaying abundant eosinophilic granular cytoplasm. These tumor cells showed features of a high degree of anaplasia. On immunohistochemical examination, tumor cells were focally positive for synaptophysin, inhibin, vimentin, pancytokeratin (pan-CK), cytokeratin (CK)5/6, CD68, and CK8/18 and immunonegative for CK7, chromogranin, melan-A, S100, SMA, and SATB2. The Ki-67 proliferation index was approximately 20%. To the best of our knowledge, this is the first case of metastatic oncocytic ACC to the oral cavity region.


Tyrosine phosphorylation and translocation of LAT in platelets.
Platelet aggregation is accompanied by the tyrosine phosphorylation of several proteins including syk. However, some of these proteins are not identified. Recent studies showed that LAT is a syk substrate and is tyrosine phosphorylated during T cell stimulation. In this study, we demonstrated that LAT is present in platelets and is tyrosine phosphorylated in response to ADP- and thrombin-stimulated aggregation. Moreover, LAT, like syk and beta3, translocates to the cytoskeleton during the late stage of thrombin-stimulated irreversible aggregation and not during ADP-stimulated reversible aggregation.


Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats.
The present study determined the effect of maternal nicotine exposure during the early developmental period on AT(1)R and AT(2)R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg/kg/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine treatment. Nicotine significantly increased brain AT(1)R in fetuses at gestation 15 and 21 days and decreased central AT(2)R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT(1)R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT(2)R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT(1)R mRNA abundance did not change during postnatal development, AT(2)R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT(1)R mRNA in the female offspring. In contrast, it decreased AT(2)R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT(1)R/AT(2)R mRNA ratio in the brain of adult animals, which was significantly up-regulated in nicotine-treated animals with females being more prominent than males. The results demonstrate that perinatal nicotine exposure alters AT(1)R and AT(2)R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.


The benefits of liposomes for chilling canine sperm for 4 days at 4°C.
This study comprises 3 experiments exploring the possible benefits and mechanism of action of liposomes for chilling (4°C) canine sperm over a period of 4 days. In the first experiment, 20 ejaculates collected from 5 Beagle dogs were chilled in an extender containing 6% low density lipoproteins (LDL) (Control), or one of 7 extenders containing different concentrations (2, 4, 6, 8, 10, 15, 20%) of liposomes (LIPO). These ejaculates were chilled over 4 days and motility was assessed daily using a Hamilton Thorne analyzer (HTM-IVOS, 14.0). The 2% LIPO obtained the best results (p=0.038) after four days (72.55% motile spermatozoa and 31.4% progressive spermatozoa). In experiment 2, 10 ejaculates were collected from same 5 dogs and chilled in 6% LDL or 2% LIPO-based extenders. Sperm integrity characteristics were assessed prior to refrigeration and every 48h for four days (D0, D2, and D4). Acrosome integrity was assessed using the FITC-PSA test (Fluorescein IsoThiocyanate-Pisum Sativum Agglutinin), plasma membrane (PM) integrity using both the hypo-osmotic swelling test (HOSt) and SYBR14/Propidium Iodide test (SYBR14/PI), and DNA integrity using the Acridine-Orange test (AO). The 2% LIPO extender provided equivalent preservation of sperm integrity parameters to the reference extender (6% LDL). In experiment 3, a Langmuir-Blodgett trough was used to evaluate the mechanistic interactions between LDL, LIPO, prostatic fluid, and the canine spermatozoal membrane during chilling. Results indicate that LDL and LIPO interact differently with the biomimetic membrane. The most likely conclusion of these findings is that LDL and liposomes employ different protective mechanisms during the chilling (4°C) of canine spermatozoa.


Autoimmune thyroiditis during leuprolide acetate treatment.
Autoimmune thyroiditis developed in a 9-year-old girl with precocious puberty approximately 8 months after initiation of Leuprolide acetate therapy. In addition, gonadotropin concentrations as measured by radioimmunoassay appeared high. Treatment with levothyroxine, in addition to continued Leuprolide acetate treatment, resolved gonadotropin elevation and hypothyroidism.


Simulated root canals preparation time, comparing ProTaper Next and WaveOne Gold systems, performed by an undergraduate student.
The aim of this study was to compare the WaveOne Gold and ProTaper Next systems regarding the time spent preparing simulated canals performed by an inexperienced student. 0 simulated L-shaped canals were randomly divided into two groups (n = 40) and numbered in order of instrumentation. Canals were instrumented with WaveOne Gold (group 1) and ProTaper Next (group 2) systems. The effective instrumentation time and the number of instrumentation cycles were recorded. All procedures were performed by the same operator. Statistical analysis was obtained by the Mann - Whitney, Kruskal - Wallis test with significance of p<0.05. There were no statistically significant differences regarding the mean instrumentation time between the two instrumentation systems. The instrumentation time decreased over the experimental period, regardless of the technique used. Through a short learning curve, an inexperienced operator can prepare simulated canals in a very predictable time. Time spent was similar in a multi-file instrument system (ProTaper Next) and a single-file system (WaveOne Gold). Key words:Dental education, endodontics, preclinical, root canal preparation, undergraduate.


Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth.
Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.


Insight into the mechanism of myosin-fibrin gelation induced by non-disulfide covalent cross-linking.
To explore the mechanism of non-disulfide covalent cross-linking between myosin and fibrin, the gel strength, texture parameters, rheological properties, protein conformation and microstructure and possible cross-linking sites were investigated during the gelling of myosin-fibrin gels. Higher ε-(γ-glutamyl)-lysine level in myosin-fibrin gels with transglutaminase significantly enhanced the textural properties, rheology properties and water holding capacity of myosin-fibrin gels, compared with pure myosin gel and myosin-fibrin gels with ehylenediaminetetraacetic acid; Fourier infrared spectra (FTIR) and circular dichroism (CD) spectra demonstrated that the structural transition from α-helix to β-sheet significantly was improved in myosin-fibrin gels with the addition of transglutaminase than other groups. Scanning electron microscopy revealed that high level of ε-(γ-glutamyl)-lysine cross-linking contributed to the formation of myosin-fibrin gels with a dense gel network structure with thick walls and low porosity. Myosin heavy chain was mainly involved in the cross-linking with α/β/γ-chains of fibrinogen; liquid chromatography-tandem mass spectrometry further demonstrated that Lys1085 of myosin heavy chain was non-disulfide covalently bound to Gln195 of fibrinogen to form "K-Q" isopeptide during the cross-linking of myosin-fibrin.