Transcriptomic signatures of peroxisome proliferator-activated receptor α (PPARα) in different mouse liver models identify novel aspects of its biology.
The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that regulates lipid catabolism and inflammation and is hepatocarcinogenic in rodents. It is presumed that the functions of PPARα in liver depend on cross-talk between parenchymal (hepatocytes) and non-parenchymal (Kupffer and endothelial cells) fractions as well as inter-organ interactions. In order to determine how cellular composition and inter-organ interactions influence gene expression upon pharmacological activation of PPARα, we performed a meta-analysis of transcriptomics data obtained from mouse hepatocytes (containing only the parenchymal fraction), mouse liver slices (containing both fractions), and mouse livers exposed to a PPARα agonist. The aim was to obtain a comprehensive view of common and model-specific PPARα-dependent genes and biological processes to understand the impact of cross-talk between parenchymal and non-parenchymal fractions as well as the effect of inter-organ interactions on the hepatic PPARα transcriptome.To this end we analyzed microarray data of experiments performed in mouse primary hepatocytes treated with the PPARα agonist Wy14643 for 6 or 24 h (in vitro), mouse precision cut liver slices treated with Wy14643 for 24 h (ex vivo), and livers of wild type and Ppara knockout mice treated with Wy14643 for 6 h or 5 days (in vivo). In all models, activation of PPARα significantly altered processes related to various aspects of lipid metabolism. In ex vivo and in vivo models, PPARα activation significantly regulated processes involved in inflammation; these processes were unaffected in hepatocytes. Only in vivo models showed significant regulation of genes involved in coagulation, carcinogenesis, as well as vesicular trafficking and extracellular matrix. PPARα-dependent regulation of genes/processes involved in lipid metabolism is mostly independent of the presence of non-parenchymal cells or systemic factors, as it was observed in all liver models. PPARα-dependent regulation of inflammatory genes requires the presence of non-parenchymal cells, as it was observed only ex vivo and in vivo. However, the full spectrum of PPARα biology at the level of lipid metabolism, immunity, carcinogenesis, as well as novel aspects of PPARα signaling such as coagulation, vesicular trafficking and the extracellular matrix, seems to require systemic factors, as it was observed exclusively in vivo.


The incidence, benefits and variables associated with breastfeeding: implications for practice.
The health, nutritional and psychological benefits of breastfeeding are widely acknowledged. Breastfeeding is the recommended infant-feeding method for the first four to six months of life. Despite the well-documented benefits of breastfeeding, researchers in the United States have noted a decline in its incidence and duration over the last several years. In order to address this decline, clinicians need to be familiar with what is currently known about breastfeeding trends and benefits, as well as variables associated with infant-feeding choices and reasons for premature weaning. Current breastfeeding research and implications for nursing practice are the focus of this article. Specifically, health practitioners are encouraged to develop a prolactation protocol for their practice. This involves development and/or utilization of educational and support services that span the prenatal period and continue until the child is weaned.


Heptamethine cyanine dyes with a robust C-C bond at the central position of the chromophore.
Novel, highly fluorescent, monofunctional, water-soluble heptamethine cyanine dyes containing a robust C-C bond at the central position of the near-infrared fluorophore system were prepared by the Suzuki-Miyaura method. The reaction proceeded efficiently to replace the meso-chlorine atom with a carboxy-functionalized aryl moiety and afforded the desired compounds in high yields. This methodology is particularly attractive due to its versatility and the utilization of environmentally friendly water as solvent. The new compounds possess excellent spectral properties and readily label bioactive molecules on solid support. The results demonstrate the potential of using the new compounds as fluorescent antennae for molecular imaging, spectroscopy, microscopy, and chemical or biological molecular recognition studies.


Long-term follow-up of a patient with Kawasaki disease and coronary aneurysm associated with asymptomatic thrombosis: a case report.
A 20-year-old male was first diagnosed with Kawasaki disease at age 2 years 9 months. Coronary angiography in the acute phase revealed coronary aneurysms, so chronic antiplatelet therapy was initiated with aspirin and ticlopidine. The patient was asymptomatic and was followed up. Stress myocardial imaging showed asymptomatic myocardial ischemia at age 20 years. Coronary angiography was performed, and revealed 99% occlusion of the right coronary artery and collateral circulation from the left coronary artery. Occlusion was attributed to coronary aneurysm thrombosis. Much remains unknown about the long-term prognosis in patients with coronary aneurysm associated with Kawasaki disease. Asymptomatic children who are followed up sometimes develop ischemic heart disease as young adults. This case highlights the need for long-term follow-up in patients with Kawasaki disease and coronary aneurysms.


Chirped-pulse amplification of laser pulses with dispersive mirrors.
We report a novel implementation of chirped-pulse amplification (CPA) by dominantly using dispersive multilayer mirrors for chirp control. Our prototyp dispersive-mirror (DMC) compressor has been designed for a kHz Ti:sapphire amplifier and yielded--in a proof-of-concept study--millijoule-energy, sub-20-fs, 790-nm laser pulses with an overall throughput of approximately 90% and unprecedented spatio-temporal quality. Dispersive-mirror-based CPA permits a dramatic simplification of high-power lasers and affords promise for their advancement to shorter pulse durations, higher peak powers, and higher average powers with user-friendly systems.


L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans.
A sensitive RIA for human GH-releasing hormone-(1-44)-NH2 [hGHRH-(1-44)-NH2] was developed which allows its measurement in human plasma extracts. The assay did not detect hGHRH-(1-37)-OH or hGHRH-(1-40)-OH. A method to extract hGHRH from plasma was developed using silicic acid and acid-acetone, by which recovery of synthetic hGHRH-(1-44)-NH2 from plasma averaged 74.3%. Serial dilutions of plasma extracts gave an inhibition curve parallel with that of synthetic hGHRH-(1-44)-NH2 in the RIA system. On Sephadex G-50 columns, hGHRH-like immunoreactivity (hGHRH-LI) in plasma extracts eluted as a single peak corresponding to hGHRH-(1-44)-NH2. This hGHRH-LI peak, when subjected to reverse phase HPLC, emerged at the position where hGHRH-(1-44)-NH2 was eluted. hGHRH-LI was detectable in the peripherally circulating plasma of all subjects tested. The mean basal level of plasma hGHRH-LI in normal subjects was 9.4 +/- 0.7 (+/- SE) pg/ml (n = 22; range, 2.8-18.1 pg/ml), comparable to the basal plasma hGHRH-LI concentration in patients with hypothalamic lesions (11.3 +/- 1.1 pg/ml; n = 7). Oral administration of L-dopa (0.5 g) caused a significant increase in both plasma hGHRH-LI and GH levels in normal subjects, and the plasma hGHRH-LI peak slightly preceded or coincided with that of plasma GH in individual subjects. There was also a significant correlation between plasma hGHRH-LI and the GH rises after L-dopa administration when their net increments were compared. All of the patients with hypothalamic lesions had significant increases in plasma GH after hGHRH-(1-44)-NH2 injection (1 microgram/kg BW, iv), indicating the presence of functioning somatotrophs in their pituitaries. When L-dopa was orally administered to these patients, neither plasma hGHRH-LI nor GH concentration changed throughout a 120-min observation period. These findings suggest that 1) hGHRH, immunologically and chromatographically indistinguishable from synthetic hGHRH-(1-44)-NH2, is detectable in peripheral plasma in humans; 2) L-dopa stimulates the release of hypothalamic hGHRH, alterations of which are reflected in changes in peripheral levels; and 3) the source of circulating hGHRH is not restricted to the hypothalamus, since hGHRH-LI is present in the peripheral plasma of patients with hypothalamic lesions in amounts similar to those found in normal subjects.


[Assessment of respiratory health status in the population of middle school students].
The aim of the study was to assess the prevalence of asthma and to identify the basic host and environmental risk factors for asthma and symptoms suggestive of asthma in Polish adolescents aged 15 years. The study was performed as a cross-sectional questionnaire survey comprising population of 854 - 68.3% of all eligible students, attending schools located in Jaworzno. Parents or guardians filled the questionnaire, which contained questions on the occurrence of respiratory and allergic symptoms and diseases, family history of these pathologies, data on exposure to indoor factors and socioeconomic status of the family. Statistical analyses involved calculation of the prevalence of asthma and symptoms suggestive of asthma and identification of risk factors on the basis of multivariate logistic regression. Wheezing in the last year preceding the survey was reported in 44 (5.1%) adolescents, attacks of dyspnea with wheezing in 22 (2.6%), and asthma in 46 (5.4%) adolescents. The results of multivariate logistic regression revealed that the presence of atopy was the most important risk factor for asthma (odds ratio: OR - 7.8; p = 0.0001). Other statistically significant risk factors for asthma and symptoms suggestive of asthma were positive history of allergy in mothers (OR - 8.3; p = 0.04) and positive history of severe respiratory disease in early childhood (OR - 4.7; p = 0.007). The results of our study justify the need for activities aimed at proper job orientation in future for adolescents with the presence of atopy.


Up-regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury.
Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro-inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT-III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.


Magnesium and molecular crowding of the cosolutes stabilize the i-motif structure at physiological pH.
Most of the important genomic regions, especially the G,C rich gene promoters, consist of sequences with potential to form G,C-tetraplexes on both the DNA strands. In this study, we used three C-rich oligonucleotides (11Py, 21Py, and HTPy), of which 11Py and 21Py are located at various transcriptional regulatory elements of the human genome while HTPy sequence is a C-rich strand of human telomere sequence. These C-rich oligonucleotides formed i-motif structures, verified by Circular Dichroism (CD), UV absorption melting experiments, and native gel electrophoresis. The CD spectra revealed that 11Py and 21Py form i-motif structures at acidic pH values of 4.5 and 5.7 in the presence of 100 mM NaCl but remain unstructured at pH 7.0. However, 21Py can form stable i-motif structure even at neutral pH in presence of 1 mM MgCl2 . UV-thermal melting studies showed stabilization of 21Py i-motif at pH 5.7 in the presence of Na+ or K+ with increasing concentration of MgCl2 or CaCl2 from 1 to 10 mM. Significant shift in the CD peak of HTPy sequence was observed as the positive peak from 286 nm shifted to 276 nm while the negative peak from 265 to 254 nm. Further, inevitable necessity of 1 mM Mg2+ to form i-motif structure at neutral pH was observed. Under similar ionic conditions and neutral pH, all the three C-rich sequences were able to form stable i-motif structures (11Py, 21Py) or altered i-motif/homoduplex structures (HTPy) in the presence of MgCl2 and cell mimicking molecular crowding conditions of 40 wt% PEG 200. It is concluded that presence of Mg2+ ions and molecular crowding agents induce and stabilize i-motif structures at physiological solution environment.


Prognostic Assessment of Stress-Related Factors in Healthcare Workers During the COVID-19 Pandemic.
The COVID-19 pandemic is an extraordinary challenge for all countries and affects the psychological wellbeing of healthcare professionals working with people suffering from COVID-19 and puts them at a high risk of mental health problems. The aim of the study was to identify stress-related factors that affect the mental health of healthcare workers during the COVID-19 pandemic in Ukraine. A total of 1098 Ukrainian healthcare workers were surveyed using an online questionnaire consisting of questions relating to a) socio-demographic characteristics; b) perceptions of the COVID-19 related situation; and c) stress and protective factors. Respondents were divided into two groups, depending on whether they provided care to the patients with COVID-19 or not. Of the 1087 healthcare workers, 863 (79.4%) were found to have anxiety / fear caused by the COVID-19. No significant difference was detected between professionals who did and did not provide personal assistance to patients with COVID-19 concerning anxiety / fear related to COVID-19 (p=0.0776). Based on logistic regression model (χ2(6)=263.70, p=0.000) the most significant predictive factors for anxiety / fear caused by the COVID-19 were factors related to safety and risk perception (the risk of getting infected, dying, infecting loved ones, perception of the threat of the epidemic spread), information factors (constant news about COVID-19), as well as factors related to the organisation of care (lack of staff in health care facilities). Negative risk perception, high consumption of COVID-19 news, and shortage of staff in health care facilities were significant predictors of anxiety / fear caused by the COVID-19.


Inhibition of proteinase-like peptidase activities in serum and tissue from breast cancer patients.
The inhibitory profiles of several proteinase-like peptidases active on synthetic peptide (MCA) substrates, present in sera and 100,000g supernatants of malignant tissue from patients with breast cancer, have been studied using a series of known inhibitors including epoxysuccinyl peptides (E-64, Ep-475), Z-Phe-Phe-diazomethane, PMSF, iodoacetamide, 1-10-O-phenanthroline, leupeptin, aprotinin, elastatinal and alpha 2-macroglobulin. While in general the inhibition profiles confirmed reported substrate specificities some anomalies were observed. In particular, the serum activities on two cathepsin B substrates were unaffected by specific cysteine proteinase inhibitors and in breast tissue only 20-37% of activity towards these two substrates was apparently due to the presence of endopeptidases. However, the potent inhibition of other proteinase-like activities by the epoxysuccinyl peptides and leupeptin, or similar inhibitors, may be useful agents in the study of methods of combating tumour spread.


Helical screw sense bias in chiral polyfluorene stimulated by solvent.
Conjugated homopolymer poly(9,9-bis(3-((S)-2-methylbutylpropanoate))fluorene) (PSF) with chiral pendants was synthesized and characterized. Dissolution experiments show that PSF is well dissolved in racemic limonene at high temperature and begins aggregating upon sequential cooling treatment. The corresponding assemblies were transferred to quartz plate by the spin-coating method. Comparably, film casting from chloroform solution was also prepared. Upon annealing thermal treatments, these PSF films exhibited perfect mirror circular dichroism (CD) Cotton effects and dissymmetry ratios. Optical absorption spectroscopy (UV-vis), CD, and fluorescence spectroscopy results reveal that chiral side chains successfully induced M- and P-helical structures in aggregates and films, and this significant difference was ascribed to their differential supramolecular conformations.


Screening for ovarian cancer in women with breast cancer with transvaginal sonography and color flow imaging.
The aim of the present study was to determine the efficacy of transvaginal color flow imaging as a screening tool for ovarian cancer. Six hundred patients with previous breast carcinoma were screened for ovarian cancer. Screening was performed using transvaginal sonography with color flow imaging. Serum CA 125 levels were measured in patients with abnormal sonographic findings. Eighty-three percent of the ovaries were detected in the premenopausal patients by ultrasonographic scanning and only 26% of the ovaries were detected in the postmenopausal patients. Intraovarian blood vessels were detected in 11% of the premenopausal women. The PI was less than 1 in 80% of these ovaries, but, on repeated examinations, the values of PI increased in all the blood vessels to greater than 1. Intraovarian blood vessels were detected in 1.8% of the normal ovaries observed in the postmenopausal women, but PI was always greater than 1. Eleven women with complex ovarian cysts (not simple) and one woman with enlarged ovaries underwent explorative laparotomy. In three women, primary malignant ovarian tumors were diagnosed and in one woman metastatic ovarian cancer was diagnosed. The specificity of sonography in detecting malignant ovarian tumors was 97.5% and the positive predictive value was 25%. The specificity of color flow imaging in detecting primary malignant ovarian tumors was 99.8% and the positive predictive value was 60%. In selected groups of women, screening for ovarian cancer with transvaginal color flow imaging may be justified.


Using data about accepted and rejected articles in the Journal of Dental Education to increase authors' chances of article acceptance.
The purpose of our study was to identify trends and compare keywords from titles and methods among articles accepted and rejected for publication in the Journal of Dental Education (JDE). The titles and abstracts of JDE articles submitted between 2010 and 2020 were extracted. We studied the frequencies of keywords in the title and abstracts and used simple descriptive data to present the information. Additionally, keywords from the methods section from JDE articles reviewed between 2015 and 2020 were analyzed by acceptance versus rejection. University of Michigan Medical School's committee on human subject studies provided an exemption (HUM00196884). Articles with the terms "knowledge," "skills," and "attitudes" appear, separately or together, in the titles of submissions to JDE 510 times during the study period-190 in accepted articles and 320 in rejected articles (an acceptance rate of 37.3%). The term "clinical" is in the title of 337 articles submitted to JDE-195 accepted and 142 rejected (an acceptance rate of 57.9%). However, the term "pre-clinical" is associated with only 56 articles in the last 10 years-36 accepts and 20 rejects (64.3%). Studies with cross-sectional study design were accepted at a rate of 72.0% and manuscripts with cohort study designs were accepted at 53.3%. Systematic reviews were accepted at 44.4%, surveys were accepted at 36.7%, meta analyses were accepted at 28%. Questionnaires were accepted at 14%. Higher quality study designs were more likely to be accepted for publication. Studies including a randomizing process and studies that were longitudinal in nature were more likely to be accepted for publication.


The role of endothelin in connective tissue diseases.
Vascular dysregulation is centrally involved in the pathogenesis of diverse rheumatological diseases. The resulting pulmonary arterial hypertension as well as Raynaud's phenomenon may be accompanied by distinct tissue fibrosis. The pleiotropic cytokine endothelin may represent a link between these vascular and fibrotic processes, which are most evidently seen in systemic sclerosis. Among three closely related isoforms, endothelin-1 (ET-1) is the most common in humans, and is often referred to as ET in the literature. ET-1 is involved in physiological processes of vascular tone and mitogenesis, whereas under pathological conditions fibrosis, vascular hypertension and inflammation are induced. Its expression is dependent on tissue and cell type as well as on the underlying disease entity and its stage. Elevated plasma and tissue levels have been demonstrated in idiopathic pulmonary hypertension, systemic sclerosis as well as in other connective tissue diseases and correlate to haemodynamic parameters and disease outcome. The biological effects are mediated by two membrane receptors (ET-1-receptor A and B) belonging to the G-protein-coupled serpentine family. Both receptors are differentially expressed by different cell types as well as in different diseases entities. Antagonizing these receptors therapeutically has already been successful. However, the differential action of ET is counterbalanced by other mediators, prominently nitric oxide. Consequently, the suspected direct relation of vascular and fibrotic processes through ET still needs to be further evaluated.


Immune response to a molecularly defined internal image idiotope.
A monoclonal anti-idiotope termed 87.92.6 mimics the neutralization/cell-attachment site of the reovirus type 3 hemagglutinin (HA3). The second complementarity determining regions of the VH and VL of 87.92.6 share sequence similarity with a determinant on the HA3. We have used synthetic peptides (termed VH, VL, and Reo peptides, respectively) to probe the immunologic significance of this sequence similarity. Antibodies specific for Reo peptide or VL peptide neutralized reovirus type 3 infectivity. Although Reo peptide was an effective immunogen by itself, free VL peptide or VH peptide were unable to elicit antibodies unless they were linked to each other (VH-VL peptide). Immunization with reo peptide, 87.92.6, or the HA3 elicited a specific lymphocyte proliferative response to VH peptide, indicating that VH peptide may bear an important TH determinant. As found previously for 87.92.6, VL peptide elicited a delayed-type hypersensitivity response specific for reovirus type 3. Reovirus type 3 specific cytolytic lymphocytes specifically lysed targets coated with VH-VL peptide, but not VH or VL peptide alone. These results suggest that immune cross-reactivity between an external Ag and an internal image antibody can be understood at the primary structural level. These observations may have important implications for understanding the development of autoantibodies, network interactions, and the regulation of immune responses.


Neuroimaging and renal ultrasound manifestations of Oculocerebrorenal syndrome of Lowe.
Oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, hypotonia, and cognitive developmental delay with renal complications developing in the first few months of life. Clinical and laboratory findings of Lowe syndrome are well documented. Though a small number of case reports describe the neuroimaging features and the renal ultrasound manifestations of this disease, a comprehensive review of all the imaging manifestations has not been reported. The authors present a case of OCRL and review the neuroimaging and renal ultrasound manifestations of this multisystem disease.


Self-reported sleep and health among Norwegian hospital nurses in intensive care units.
Shift work, and especially night work, is associated with poor health. Nurses, work a variety of work schedules including night work. So far, few studies have specifically investigated sleep and health among intensive care nurses. We investigated sleep, sleepiness, fatigue, subjective health complaints, anxiety and depression in 150 intensive care nurses (convenience sample representing a response rate of 56·2%). The nurses worked at two major University hospitals in Norway and answered a questionnaire survey. The intensive care nurses reported poorer sleep, more sleepiness, more fatigue, more anxiety and more depression compared to normative data. Poor sleep was reported by 70% and excessive sleepiness by 25% of the nurses; however, the design of the study did not allow us to determine the causes underlying these findings. Multiple linear regression analyses showed that age was positively associated with sleep problems, fatigue, subjective health complaints and anxiety and depression. In contrast, shift work experience was negatively associated with sleep problems, suggesting better coping with shift work over time. Nurses working in intensive care units reported poorer sleep, more sleepiness, more fatigue, more anxiety and more depression compared to Norwegian norm groups. Age was positively related to these complaints, whereas shift work experience was negatively related to poor sleep. More studies are needed on strategies to improve sleep and health in nurses.


[Promotion of wound healing with fibroblast growth factor in combined burn radiation injury].
Rats were subjected to 15% burn and severe radiation injury. Recombinant bFGF and simple support treatment were used to treat local wound and total body injury. The results indicated that wound healing was improved by 28.5%, and the time required for 50% area of healing was 9 days earlier in the treated group than control group 60 days after injury. Pathological observation showed that bFGF stimulated proliferation of fibroblast and collagen synthesis. It improved regeneration of capillary and formation of granulation tissue. In the early phase, bFGF enhanced reactive inflammation in the wound and phagocytosis of leucocytes in the body, and enhanced recovery of natural killing activity of spleen cells. These reactions would be beneficial to local wound healing.


Correction: Mesoporous titania thin films as efficient enzyme carriers for paraoxon determination/detoxification: effects of enzyme binding and pore hierarchy on the biocatalyst activity and reusability.
Correction for 'Mesoporous titania thin films as efficient enzyme carriers for paraoxon determination/detoxification: effects of enzyme binding and pore hierarchy on the biocatalyst activity and reusability' by N. Frančičet al., Analyst, 2014, 139, 3127-3136.


[Incidental thyroid microcarcinoma in benign thyroid disease. Incidence in a total of 100 consecutive thyroidectomies].
Over the past few years, incidental thyroid microcarcinoma has become a frequent disease and its incidence in some reports is considerable. Discovering new cases depends on the extended indications for total thyroidectomy for benign disease, on progress in the field of diagnostic instruments (ultrasound, scintigram, fine needle biopsy for cytology, CT scan, MRI), and on the pathology examination of very thin slices of specimens. In spite of the high incidence reported in some autopsy series, suggesting that this tumour may have a good prognosis, some Authors report an overall incidence of up to 11% of local recurrence, metastasis or mortality. For all these reasons the surgical treatment of incidental thyroid microcarcinoma is still controversial. The aim of this study was to estimate the incidence and examine the clinical-pathological findings of incidental thyroid microcarcinoma in a series of 100 consecutive thyroidectomies and to evaluate whether complete removal of the gland should be adopted in all cases. In the present series the incidence of incidental thyroid microcarcinoma was 21.6% (19/88). Total thyroidectomy was considered the treatment of choice for diffuse benign disease and appeared to be necessary for both the diagnosis and treatment of incidental thyroid microcarcinoma.


Obesity reduces mammary epithelial cell TGFβ1 activity through macrophage-mediated extracellular matrix remodeling.
Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta-1 (TGFβ1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high-fat diet model of obesity in mice and breast tissue from women, we observed that TGFβ1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFβ1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese mice with either IgG control or anti-F4/80 antibodies to deplete macrophages. Mice treated with anti-F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFβ1 activity within mammary epithelial cells. Given the role of TGFβ1 as a tumor suppressor, reduced epithelial TGFβ1 activity and enhanced TGFβ1 within the ECM of obese mammary tissue may enhance breast cancer risk.


Gap between the Expectations and Perceptions of Students regarding the Educational Services Offered in a School of Nursing and Midwifery.
Awareness of students' opinions about the various aspects of training provided is an essential factor to evaluate the quality of education. The aim of this study was to determine the gap between the students' expectations and perceptions from the educational services provided to them in the School of Nursing and Midwifery in Shahrekord University of Medical Sciences. In this cross-sectional study, 320 students were selected by stratified random sampling method and data were collected by SERVQUAL questionnaire to examine the areas of assurance, responsiveness, empathy, tangibles and confidence. Data analysis was conducted by descriptive (frequency, percentage, mean±SD) and analytical (paired t-test, independent t-test and One-Way ANOVA) statistics in SPSS 20. The mean scores of the students' expectations and perceptions of the educational services delivered to them were 4.34±0.63 and 3.56±0.68, respectively, with a significant, negative gap (-0.77±0.77, p<0.001). The lowest gap of quality was derived for assurance (-0.65) followed by reliability (-0.69), accountability (-0.74), and empathy (-0.81), and the greatest gap observed in tangibles (-0.96). A negative gap was observed between the students' expectations and perceptions of the quality of educational services delivered to them. This means that the quality of services delivered to students was less than what they expected. The highest gap was related to the tangibles. In order to improve the educational services, paying attention to different areas of quality of educational services, especially, the tangibles, is necessary.


Ventilator-associated pneumonia.
Ventilator-associated pneumonia is the most common nosocomial infection. Mortality rates, morbidity, and costs are all increased in the patient with VAP, and every measure should thus be taken to prevent its development. There are several clearly defined risk factors for VAP, and awareness of these can facilitate early diagnosis and hence treatment. In this article, we discuss the risk factors, strategies for prevention, approaches to diagnosis and management plan for the patient with VAP.


Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.
There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS.


Certain characteristics of Corynebacterium pyogenes infection.
Isolation, characterisation and antibiotic sensitivity of 18 strains of Corynebacterium pyogenes from different animals have been reported. All the C pyogenes isolates uniformly differed from the typical strains of this species by the utilisation of trehalose and their failure to acidify maltose. The majority of the strains failed to grow in the presence of 0.1 per cent potassium tellurite. Tuberculosis-like lung lesion in a seven-day-old calf yielded one of the strains of C pyogenes. Histopathological changes in the calf lung have also been described.


Phosphopeptide modification and enrichment by oxidation-reduction condensation.
Many cellular processes are regulated by the reversible phosphorylation of proteins. Despite the importance of monitoring protein phosphorylation, available methods to modify and enrich phosphopeptides from complex mixtures for subsequent mass spectrometric analysis are challenging. Here the oxidation-reduction condensation was shown for the first time to directly modify the phosphate of phosphopeptides and phosphoproteins. By coupling with a solid-phase resin, the oxidation-reduction condensation was validated for capture and recovery of phosphoserine-, phosphothreonine-, and phosphotyrosine-containing peptides from a peptide mixture. In addition, full-length phosphoproteins or phosphopeptides from a protein digestion were captured and recovered using the oxidation-reduction condensation, demonstrating its compatibility with protein mixtures. The strategy modifies all phosphopeptides, maintains high chemical selectivity, requires only two steps, and relies on commercially available reagents, suggesting that the oxidation-reduction condensation has the potential to enhance phosphopeptide enrichment methods and encourage development of efficient biochemical and proteomics tools targeting phosphorylation.


Photodynamic inactivation of biofilm: taking a lightly colored approach to stubborn infection.
Microbial biofilms are responsible for a variety of microbial infections in different parts of the body, such as urinary tract infections, catheter infections, middle-ear infections, gingivitis, caries, periodontitis, orthopedic implants, and so on. The microbial biofilm cells have properties and gene expression patterns distinct from planktonic cells, including phenotypic variations in enzymic activity, cell wall composition and surface structure, which increase the resistance to antibiotics and other antimicrobial treatments. There is consequently an urgent need for new approaches to attack biofilm-associated microorganisms, and antimicrobial photodynamic therapy (aPDT) may be a promising candidate. aPDT involves the combination of a nontoxic dye and low-intensity visible light which, in the presence of oxygen, produces cytotoxic reactive oxygen species. It has been demonstrated that many biofilms are susceptible to aPDT, particularly in dental disease. This review will focus on aspects of aPDT that are designed to increase efficiency against biofilms modalities to enhance penetration of photosensitizer into biofilm, and a combination of aPDT with biofilm-disrupting agents.


Building a search tool for compositely annotated entities using Transformer-based approach: Case study in Biosimulation Model Search Engine (BMSE).
The Transformer-based approaches to solving natural language processing (NLP) tasks such as BERT and GPT are gaining popularity due to their ability to achieve high performance. These approaches benefit from using enormous data sizes to create pre-trained models and the ability to understand the context of words in a sentence. Their use in the information retrieval domain is thought to increase effectiveness and efficiency. This paper demonstrates a BERT-based method (CASBERT) implementation to build a search tool over data annotated compositely using ontologies. The data was a collection of biosimulation models written using the CellML standard in the Physiome Model Repository (PMR). A biosimulation model structurally consists of basic entities of constants and variables that construct higher-level entities such as components, reactions, and the model. Finding these entities specific to their level is beneficial for various purposes regarding variable reuse, experiment setup, and model audit. Initially, we created embeddings representing compositely-annotated entities for constant and variable search (lowest level entity). Then, these low-level entity embeddings were vertically and efficiently combined to create higher-level entity embeddings to search components, models, images, and simulation setups. Our approach was general, so it can be used to create search tools with other data semantically annotated with ontologies - biosimulation models encoded in the SBML format, for example. Our tool is named Biosimulation Model Search Engine (BMSE).


Core/Shell Face-Centered Tetragonal FePd/Pd Nanoparticles as an Efficient Non-Pt Catalyst for the Oxygen Reduction Reaction.
We report the synthesis of core/shell face-centered tetragonal (fct)-FePd/Pd nanoparticles (NPs) via reductive annealing of core/shell Pd/Fe3O4 NPs followed by temperature-controlled Fe etching in acetic acid. Among three different kinds of core/shell FePd/Pd NPs studied (FePd core at ∼8 nm and Pd shell at 0.27, 0.65, or 0.81 nm), the fct-FePd/Pd-0.65 NPs are the most efficient catalyst for the oxygen reduction reaction (ORR) in 0.1 M HClO4 with Pt-like activity and durability. This enhanced ORR catalysis arises from the desired Pd lattice compression in the 0.65 nm Pd shell induced by the fct-FePd core. Our study offers a general approach to enhance Pd catalysis in acid for ORR.


Marijuana-produced changes in pain tolerance. Experienced and non-experienced subjects.
The effect of marijuana and placebo on pain tolerance was compared in cannabis-experienced and naive subjects. A statistically significant increase in tolerance was observed after smoking marijuana. Although there was no statistically significant interaction between the drug effect and having had previous cannabis experience, there was a definite trend towards a greater increase for the experienced (16%) compared to the naive group(8%).


Explosive Growth in British Physician Associate Education Since 2008.
Physician associate (PA) education in the United Kingdom has grown substantially since the establishment of 4 PA education programs in the late 2000s. From those 4 programs in 2008, the number of universities educating PAs fell to a nadir of 2 programs in 2012 and then rose to 29 by the end of 2017. Due to program closures, the number of students enrolled in the early years fluctuated substantially. In 2008, 43 students entered PA education; in 2010, only 17 students started PA training, but in 2017, the number of students enrolled in PA programs soared to 853. Early in the course of PA education, programs were only offered in the greater London and West Midlands areas of England. As of 2017, PAs were being educated in all 4 countries of the United Kingdom, although the explosive growth in the number of programs is expected to slow as 2020 nears.


JAAD Grand Rounds quiz: A subcutaneous nodule on the right shoulder.
At the conclusion of this learning activity, physician participants should be able to assess their own diagnostic and patient management skills and use the results of this exercise to help determine personal learning needs. Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.


Esophageal perforation in eosinophilic esophagitis: five cases in children.
Background and study aims Eosinophilic esophagitis (EoE) is a chronic immune disease with increasing incidence. It is clinically defined by symptoms of esophageal dysfunction and histologically by eosinophilic polynuclear cell infiltration of the esophageal mucosa. Symptoms are not specific and include gastroesophageal reflux disease (GERD), dysphagia, vomiting or dietary blockages. Chronic inflammation of the mucosa may lead to narrowing of the esophageal lumen responsible for impactions. Extraction procedures can be complicated by dissection and perforation. Rare spontaneous ruptures of the esophagus known as Boerhaave syndrome are also possible. We report five cases of esophageal perforation in children with EoE, three with spontaneous rupture and two after an endoscopic procedure. The evolution was favorable under medical treatment.


Total diet, individual meals, and their association with gastroesophageal reflux disease.
Background: To identify the association of total diet and individual meals with gastroesophageal reflux disease (GERD). Methods: This age- and sex-matched case-control study was carried out among 217 subjects (106 cases and 111 controls). Data were collected using a demographic questionnaire and a GERD checklist and a 3-day food record. Results: Cases consumed more fat (median: 26.3 [3.2-71.5] g vs. 21.8 [4.3-58.1] g; P=0.04)and more energy percent form carbohydrates (median: 72.5 [0-100] vs. 69.0 [0-100]; P=0.02)at lunch, and less energy (median: 129.5 kcal [0-617.6] vs. 170.5 kcal [0-615.7]; P=0.01) and protein (2.4 [0-19.4] g vs. 3.1 [0-21.8] g; P=0.01) at evening snack, compared to controls.The volume of food was significantly different between the two group only at lunch (median:516 [161-1292] g vs. 468 [198-1060] g; P=0.02). The percentage of energy from total dietary protein showed a significant association with GERD after adjusting for confounders (odds ratio[OR]=0.89; 95% CI: 0.81-0.98). Regarding the individual meals, amount of fat consumed at lunch (OR=1.02; 95% CI: 1.00-1.05), and amount of protein intake at evening snack (OR=0.92;95% CI: 0.85-1.00) were significantly associated with GERD. Meanwhile, caloric density and meal frequency did not differ significantly between the two groups. Conclusion: Amount of fat consumed at lunch is positively associated with GERD, whereas the percentage of energy from total protein and amount of protein intake at evening snack are more likely to be inversely associated with GERD.


Nonequilibrium thermodynamics and boundary conditions for reaction and transport in heterogeneous media.
Nonequilibrium interfacial thermodynamics is formulated in the presence of surface reactions for the study of diffusiophoresis in isothermal systems. As a consequence of microreversibility and Onsager-Casimir reciprocal relations, diffusiophoresis, i.e., the coupling of the tangential components of the pressure tensor to the concentration gradients of solute species, has a reciprocal effect where the interfacial currents of solutes are coupled to the slip velocity. The presence of surface reactions is shown to modify the diffusiophoretic and reciprocal effects at the fluid-solid interface. The thin-layer approximation is used to describe the solution flowing near a reactive solid interface. Analytic formulas describing the diffusiophoretic and reciprocal effects are deduced in the thin-layer approximation and tested numerically for the Poiseuille flow of a solution between catalytic planar surfaces.


[Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs].
To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs; while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.


[Iris heterochromia in acquired Horner's syndrome].
Horner's syndrome (HS) is related to an interruption of the oculosympathetic nerve pathway. The classic clinical findings associated with this condition are ptosis, miosis, and enophthalmos. Heterochromia is typically described in congenital HS, but it is an uncommon finding in acquired HS. We report a case of post-traumatic HS associated with heterochromia. A literature review indicates that this type of heterochromia may be related to a reduction in the number of iris melanocytes. This mechanism may be the same in the physiological iris color modifications in adulthood.


[Ventricular cardiac resynchronization--initial surgical experience].
Cardiac resynchronization therapy (CRT) is a recent method for patients with myocardial failure resulting from systolic malfunction. CTR is achieved by simultaneous stimulation of both ventricles which resynchronizes the time of depolarization of the left ventricle and improves myocardial contractility, diminishing mitral regurgitation. Usually the TCR is applied percutaneously/transvenously but in some cases it is impossible to use such techniques due to several reasons. The authors of this article suggest the minithoracotomy as an alternative approach of the left ventricle for implantation of the epicardic electrode. This technique has proven to be simple and safe, allowing short implantation times in comparison with the traditional technique, as well as a better choice of the site of electrode implantation.


Circular RNA expression profile in peripheral blood mononuclear cells from Crohn disease patients.
Crohn disease (CD) is a multifactorial autoimmune disease which is characterized by chronic and recurrent gastrointestinal tract inflammatory disorder. However, the molecular mechanisms of CD remain unclear. Increasing evidences have demonstrated that circular RNAs (circRNAs) participate in the pathogenesis of a variety of disease and were considered as ideal biomarkers in human disease. This study aimed to investigate circRNA expression profiles and detect new biomarkers in inflammatory bowel disease (IBD). Differentially expression of circRNAs between CD and HCs (health controls) were screened by microarray analysis. Peripheral blood mononuclear cells (PBMCs) from 5 CD patients and 5 HCs were included in the microarray analysis. Then, the differences were validated by quantitative polymerase chain reaction (qPCR) following reverse transcription polymerase chain reaction (RT-PCR) in the patients of CD and sex- and age-matched HCs. The most differential expressed circRNA was further validated in ulcerative colitis (UC) patients. Statistical significance between CD, UC, and HCs was analyzed by Student t test for unpaired samples or one-way analysis of variance (ANOVA). Diagnostic value of each circRNA was assessed by receiver operating characteristic (ROC) curve. We identified 155 up-regulated circRNAs and 229 down-regulated ones by microarray analysis in PBMCs from CD patients compared with HCs. Besides, 4 circRNAs (092520, 102610, 004662, and 103124) were significantly up-regulated validated by RT-PCR and qPCR between CD and HCs. ROC curve analysis suggested important values of circRNAs (092520, 102610, 004662, and 103124) in CD diagnosis, with area under the curve (AUC) as 0.66, 0.78, 0.85, and 0.74, respectively. Then, we further identified that the relative expression levels of circRNA_004662 was upregulated significantly in CD patients compared with UC patients. Herein, the upregulation of the 4 circRNAs (092520, 102610, 004662, or 103124) in PBMCs can be served as potential diagnostic biomarkers of CD, and circRNA_004662 might be a novel candidate for differentiating CD from UC. Moreover, a circRNA-microRNA-mRNA network predicted that circRNA_004662 appeared to be correlated with mammalian target of rapamycin (mTOR) pathway.


Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt.
Ischemic preconditioning (IPC) is thought to protect by activating survival kinases during reperfusion. We tested whether binding of adenosine receptors is also required during reperfusion and, if so, how long these receptors must be populated. Isolated rabbit hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. IPC reduced infarct size from 32.1 +/- 4.6% of the risk zone in control hearts to 7.3 +/- 3.6%. IPC protection was blocked by a 20-min pulse of the nonselective adenosine receptor blocker 8-(p-sulfophenyl)-theophylline when started either 5 min before or 10 min after the onset of reperfusion but not when started after 30 min of reperfusion. Protection was also blocked by either 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1-selective receptor antagonist, or MRS1754, an A2B-selective antagonist, but not by 8-(3-chlorostyryl)caffeine, an A2A-selective antagonist. Blockade of phosphatidylinositol 3-OH kinase (PI3K) with a 20-min pulse of wortmannin also aborted protection when started either 5 min before or 10 or 30 min after the onset of reperfusion but failed when started after 60 min of reflow. U-0126, an antagonist of MEK1/2 and therefore of ERK1/2, blocked protection when started 5 min before reperfusion but not when started after only 10 min of reperfusion. These studies reveal that A1 and/or A2B receptors initiate the protective signal transduction cascade during reperfusion. Although PI3K activity must continue long into the reperfusion phase, adenosine receptor occupancy is no longer needed by 30 min of reperfusion, and ERK activity is only required in the first few minutes of reperfusion.


Improving the life-course development of socially disadvantaged mothers: a randomized trial of nurse home visitation.
We evaluated a comprehensive program of prenatal and postpartum nurse home visitation for socially disadvantaged women bearing first children. Eighty-five per cent of the participating women were either teenagers (less than 19 years at registration), unmarried, or of low socioeconomic status. Women were randomly assigned to either nurse home visitation or comparison services (free transportation for prenatal and well-child care and/or sensory and developmental screening for the child). During the first four years after delivery of their first child, in contrast to their counterparts in the comparison group, nurse-visited White women who had not graduated from high school when they registered in the study returned to school more rapidly; nurse-visited, poor, unmarried White women showed an 82 per cent increase in the number of months they were employed, had 43 per cent fewer subsequent pregnancies, and postponed the birth of second children an average of 12 months longer.


Achieving dynamic behaviour and thermal expansion in the organic solid state via co-crystallization.
Thermal expansion involves a response of a material to an external stimulus that typically involves an increase in a crystallographic axis (positive thermal expansion (PTE)), although shrinking with applied heat (negative thermal expansion (NTE)) is known in rarer cases. Here, we demonstrate a means to achieve dynamic molecular motion and thermal expansions in organic solids via co-crystallizations. One co-crystal component is known to exhibit dynamic behaviour in the solid state while the second, when varied systematically, affords co-crystals with linear thermal expansion coefficients that range from colossal to nearly zero. Two co-crystals exhibit rare NTE. We expect the approach to guide the design of molecular solids that enable predesigned motion related to thermal expansion processes.


The feasibility and safety of training patients in opioid treatment to serve as peer recovery support service interventionists.
Background: The use of peer interventionists may be helpful in addressing problems associated with substance use disorders. However, implementation issues such as training, supervision, and the impact of delivering the intervention on the interventionists themselves require additional examination. This report describes the training methods and peer interventionist outcomes in a pilot study of a single-session Peer Recovery Support Services (PRSS) telephone intervention to facilitate enrollment in medication for opioid use disorder (MOUD) treatment. Methods: This was a secondary analysis of a pilot study testing a PRSS intervention in adults using illicit opioids who reported a recent non-fatal opioid overdose (N = 80, with 40 PRSS participants). Candidates recruited from MOUD treatment programs were trained to deliver the PRSS intervention. Assessments of adverse events, global health, and peer satisfaction were used to evaluate the effects of serving as an interventionist. Fidelity and proportion of cases enrolling in MOUD were calculated for each interventionist. Results: Four consented candidates were trained to deliver the PRSS intervention to thirty-six study participants (90% PRSS arm). All interventionists successfully maintained fidelity to the PRSS intervention and reported no negative effects. Interventionists experienced differential success in encouraging treatment enrollment ranging from 16%-60% of their cases. Conclusions: This pilot study demonstrates promise in utilizing peer interventionists to deliver a brief PRSS intervention with limited training and no reported negative effects on the interventionists themselves. Factors contributing to the differential success of the interventionists are unclear. Future research on the variable efficacy of peer interventionists is warranted to identify, quantify, and evaluate specific interactional elements associated with peer efficacy. Additionally, further evaluation of training, supervision practices, and the effects of serving as a PRSS interventionist, is needed. Trial Registration: Clinical Trials.gov http://www.clinicaltrials.gov; Identifier: NCT02922959.


Benchmarking total knee replacement constructs using noninferiority analysis: the New Zealand joint registry study.
The aim of this study was to compare the relative performance of total knee replacement constructs and discern if there is variability in performance in currently commonly used prostheses in the New Zealand Joint Registry (NZJR) using a noninferiority analysis. All patients who underwent a primary total knee replacement (TKR) registered in the NZJR between 1st January 1999 to June 2020 were identified. Using a noninferiority analysis, the performance of total knee replacement prostheses were compared with the best performing contemporary construct. Construct all-cause revision rate was estimated using the 1-Kaplan Meier survival function method to estimate net failure. The difference in all-cause revision rates between the contemporary benchmark and all other constructs was tested. In total 110 183 TKR were recorded and 25 constructs (102 717 procedures) had > 500 procedures at risk at 3 years post-primary of which 5 were inferior by at least 20 % relative risk of which, one was inferior by at least 100 % relative risk. 14 constructs were identified with > 500 procedures at risk at 10 years with 5 inferior by at least 20 %, of which 2 were inferior by > 100 % relative risk. We discerned that there is great variability in construct performance and at all time points, greater than 25 % of constructs are inferior to the best performing construct by at least 20 %. These results can help inform patients, clinicians and health care funders when considering TKR surgery.


Neuroprogression in Schizophrenia and Psychotic Disorders: The Possible Role of Inflammation.
Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e.g., increased levels of cytokines such as interleukin-6 (IL-6). Moreover, the tryptophan/kynurenine metabolism is regulated via pro- and anti-inflammatory cytokines and is closely related to the glutamatergic neurotransmission. Certain molecules of this metabolism, such as quinolinic acid or 3OH-kynurenine, have neurotoxic effects and seem to play a role in chronification. Studies with immune/anti-inflammatory-based therapeutic approaches show that acuity or chronicity of the inflammation influence the outcome of therapeutic interventions.


Fabry disease and sleep disorders: a systematic review.
Fabry disease (FD) is an X-chromosome-linked disorder characterized by a reduced or complete absence of the enzyme α-galactosidase, resulting in the accumulation of lysosomal globotriaosylceramide. Despite the presence of these deposits in multiple organs, the problem of sleep disorders within this population has very rarely been documented. This study aimed to investigate the types and prevalence of sleep disorders among patients with FD. Screening of the following medical databases using key terms was performed on 10 February 2023: PubMed, Scopus, and Embase. A total of 136 records were identified. The quality assessment of the studies was conducted by using tools from the National Institutes of Health (NIH) and critical appraisal tools from the Joanna Briggs Institute (JBI). The study included nine studies on sleep disorders in patients with FD. The overall quality of the majority of these studies was assessed as either poor or fair. Among 330 patients, there was a slightly higher representation of female patients (56%). Sleep problems manifested 4-5 years after the onset of FD and sometimes even after 10-11 years. Genotypes of disease associated with sleep problems were rarely described. Within the FD population, the most commonly reported conditions were excessive daytime sleepiness (EDS) as well as obstructive and central sleep apnea (OSA, CSA). However, EDS occurred more frequently in FD patients, while the prevalence of OSA and CSA was within the ranges observed in the general population. The studies included indicated a lack of association between organ impairment by primary disease and EDS and OSA. The effectiveness of enzyme replacement therapy (ERT) in treating sleep disorders was not demonstrated. The findings of this report revealed the presence of many sleep-related disorders within the FD population. However, very few studies on this subject are available, and their limited results make it difficult to truly assess the real extent of the prevalence of sleep disturbances among these individuals. There is a need to conduct further studies on this topic, involving a larger group of patients. It is important to note that there are no guidelines available for the treatment of sleep disorders in patients with FD.


Musical Agency during Physical Exercise Decreases Pain.
Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful.


Acute Aortic Occlusion and Its Sequelae: Metabolic, Pathologic Etiology, and Management.
Acute occlusion of the abdominal aorta is a catastrophic occurrence that results in high risk of limb loss and death. The etiology has historically been either acute embolism obstructing the aortic bifurcation in 8% to 75% of patients, or thrombosis of existing aorta-iliac occlusive disease in 35% to 84% of patients. Other etiologies include thrombosis of either a previously placed endograft or aortic graft or acute dissection. The most common symptoms are severe pain in almost 100% of patients or lower extremity paralysis/paresis in up to 80% of patients. Evaluation in the past was by angiography, but presently, computed tomography angiography is the preferred imaging study. Treatment is dependent on the etiology and includes embolectomy, aorta femoral bypass, axillary femoral bypass, and endovascular techniques. The aim of intervention is to restore flow in the shortest time period. Mortality rates vary widely from 17% to 52%, amputation occurs in up to 30% of patients. Paraplegia can occur in 40% of patients, renal insufficiency in 40% to 70%, and visceral ischemia in 6% to 14%. Both mortality and morbidity are affected by the duration of ischemia and the local and systemic complications of reperfusion injury. Complications of acute aortic occlusion can be reduced by a more prompt diagnosis, rapid intervention, and a more rapid and complete reestablishment of perfusion.


Yearling proportion correlates with habitat structure in a boreal forest landbird community.
Landbird vital rates, such as productivity and adult survivorship, can be estimated by modeling mist-netting capture data. The proportion in which an adult breeding bird is 1 year of age (a "yearling"), however, has been studied only minimally in a few landbird species. Here we relate yearling proportion to habitat-structure covariates, including reclamation age, in a boreal forest landbird community. Data were collected at 35 constant-effort mist-netting stations over a 6-year period, and consisted of 12,714 captures of adults, of 29 landbird species, including 4,943 captures of yearlings. Accuracy of age determination (yearling or older) was assessed based on recapture data and error rates were estimated at a mean of 8.1% (range 0.0-19.4%) among the 29 species, with 20 species showing age-error rates <10%. The estimated mean yearling proportion was 0.407, ranging from 0.178 to 0.613 among species. Remote-sensed Enhanced Vegetation Index (EVI), a measure of habitat greenness, was positively correlated with age since reclamation up to 20 years, at which time it became comparable to that of natural stations. The probability of capturing a yearling for species associated with mature forest was lower at stations with higher EVI and the opposite was the case for species favoring successional habitats. These results suggest that yearling birds are being excluded from preferred breeding habitats by older birds through despotism and/or that yearlings are simply selecting poorer habitat due to lack of breeding experience or other factors. This dynamic appears to be operating in multiple species within this forest landbird community. Captured yearlings may also be "floaters", or non-breeding individuals not holding territories. However, presuming that yearlings show lower reproductive success whether floating or not, our results suggest that stations with high yearling proportions could be located within sink as opposed to source habitats. Overall, we infer that yearling proportion may become an important vital-rate measure of habitat quality and reclamation efforts, when combined with indices of population size, productivity, reproductive condition and survivorship.


Ultrasound Breast Elastographic Evaluation of Mass-Forming Ductal Carcinoma-in-situ with Histological Correlation - New Findings for a Toothpaste Sign.
It is unclear as to whether the size ratio elastographic technique is useful for assessing ultrasound- detected ductal carcinoma-in-situ (DCIS) masses since they commonly lack a significant desmoplastic reaction. The objectives of this study were to determine the accuracy of this elastographic technique in DCIS and examine if there was any histopathological correlation with the grey-scale strain patterns. Female patients referred to the radiology department for image-guided breast biopsy were prospectively evaluated by ultrasound elastography prior to biopsy. Histological diagnosis was the gold standard. An elastographic size ratio of more than 1.1 was considered malignant. Elastographic strain patterns were assessed for correlation with the DCIS histological architectural patterns and nuclear grade. There were 30 DCIS cases. Elastographic sensitivity for detection of malignancy was 86.7% (26/30). 10/30 (33.3%) DCIS masses demonstrated predominantly white elastographic strain patterns while 20/30 (66.7%) were predominantly black. There were 3 (10.0%) DCIS masses that showed had a co-existent bull's-eye sign and 7 (23.3%) other masses had a co-existent toothpaste sign, a strain pattern that has never been reported in the literature. Four out of 4/5 comedo DCIS showed a predominantly white strain pattern (p=0.031) while 6/7 cases with the toothpaste sign were papillary DCIS (p=0.031). There was no relationship between the strain pattern and the DCIS nuclear grade. The size ratio elastographic technique was found to be very sensitive for ultrasound-detected DCIS masses. While the elastographic grey-scale strain pattern should not be used for diagnostic purposes, it correlated well with the DCIS architecture.


Balanced-detection interferometric cavity-assisted photothermal spectroscopy employing an all-fiber-coupled probe laser configuration.
The interferometric cavity-assisted photothermal spectroscopy (ICAPS) method has been proven highly suitable for sensitive and compact gas detection by application of an optical cavity as transducer for photothermal spectroscopy. This work reports on the implementation of an overall fiber-coupled probe laser configuration detecting the reflectance of the individual interferometers in a balanced-detection ICAPS system. The layout greatly improves the overall sensor system robustness. Two identical 1 mm path length cavities were used for balanced detection, enabling sensor operation close to the fundamental limit of shot noise by efficiently cancelling excess noise. A quantum cascade laser served as a mid-infrared excitation source to induce refractive index changes in the sample, and a near-infrared fiber laser served as probe source to monitor the photo-induced refractive index variations. The metrological figures of merit for the sensor were investigated by SO2 detection. For the targeted absorption band centered at 1380.93 cm-1, a 3 ppbv minimum detection limit was achieved with a 1 s integration time, corresponding to a normalized noise equivalent absorption of 4.5 × 10-9 cm-1 W Hz-1/2.


Acrylamide-derived cytotoxic, anti-proliferative, and apoptotic effects on A549 cells.
Acrylamide is a very common compound even reaching up to our daily foods. It has been studied in a wealth of cell lines on which it proved to have various toxic effects. Among these cell lines, human lung adenocarcinoma cell line (A549) is one of that on which acrylamide's toxicity has not been studied well yet. We intended to determine the half maximal inhibitory concentration (IC50) dose of acrylamide and to investigate its cytotoxic, anti-proliferative and apoptotic effects on A549 cells. We determined the IC50 dose by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Then, the mode of cell death was evaluated by flow cytometry using Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Next, we performed transmission electron microscopy (TEM) and confocal microscopy analyses for morphological alterations and apoptotic indices. According to the MTT assay results, A549 cell viability decreases proportionally with increasing acrylamide concentrations and IC50 for A549 was 4.6 mM for 24 h. Annexin-V FITC/PI assay results indicated that acrylamide induces apoptosis in 64% of the A549 cells. TEM and confocal microscopy analyses showed nuclear condensations, fragmentations, cytoskeleton laceration, and membrane blebbing, which are morphological characteristics of apoptosis. Our research suggests that acrylamide causes cytotoxic, anti-proliferative, and apoptotic effects on A549 cells at 4.6 mM IC50 dose in 24 h.


Optimizing transport efficiency on scale-free networks through assortative or dissortative topology.
We find that transport on scale-free random networks depends strongly on degree-correlated network topologies whereas transport on Erdös-Rényi networks is insensitive to the degree correlation. An approach for the tuning of scale-free network transport efficiency through assortative or dissortative topology is proposed. We elucidate that the unique transport behavior for scale-free networks results from the heterogeneous distribution of degrees.


Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies.
Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with antimycobacterial activity currently used to treat leprosy. Fixed and random effects meta-analysis of cohort studies and systematic review. Electronic and manual searches were combined. Observational studies on treatment of multidrug-resistant and extremely drug-resistant tuberculosis with Cfz or a Cfz-containing regimen, and published guidance and documents relating to cost and availability were eligible. 5 observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI (0.0 to 0.6%)), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered. While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for patients with MDR-TB.


Amniotic fluid embolism: a case study.
A case study involving a young woman delivering twins illustrates the dangers of this rare occurrence, the precise cause of which is still unknown. A rare complication of pregnancy.


The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis.
This study was undertaken to investigate how fibroblasts respond to stimulation with particulate wear debris and/or conditioned media obtained from pathologic tissue, and whether these activated fibroblasts express compounds that are involved in bone resorption. Conditioned media from explant cultures of synovial tissue, periprosthetic soft tissue (interface membranes), titanium particles, and proinflammatory cytokines were used to stimulate fibroblasts. RNase protection assay was used to measure altered gene expression, and enzyme-linked immunosorbent assay, Western blot hybridization, and flow cytometry were used to determine fibroblast protein expression. Tartrate-resistant acid phosphatase staining was used to identify multinucleated osteoclast-like cells. The most dominant compounds measured in the conditioned media from interface membranes were tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), interleukin-1beta (IL-1beta), IL-6, IL-8, and vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear debris and responded to cytokine/chemokine stimulation. The most prominent up-regulated genes and proteins secreted by fibroblasts in response to stimulation were matrix metalloproteinase 1, MCP-1, IL-1beta, IL-6, IL-8, cyclooxygenase 1 (COX-1), COX-2, leukemia inhibitory factor 1, transforming growth factor beta1 (TGFbeta1), and TGFbeta receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNFalpha, or IL-1beta. Stimulated fibroblasts cocultured with bone marrow cells in the presence of macrophage colony-stimulating factor induced osteoclastogenesis. Interface membrane fibroblasts respond directly to particulate wear debris, possibly via phagocytosis, expressing proinflammatory cytokines and RANKL. Thus, these cells may be actively involved in osteoclastogenesis and pathologic (periprosthetic) bone resorption.


Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women.
In eumenorrheic women with endometriosis and in oligo-amenorrheic women with polycystic ovarian disease (PCO), chronic administration of a long-acting GnRH agonist (GnRH-a) reduced the circulating concentrations of estrogens and androgens to levels similar to those of castrated women. The concommittant elevation of LH in both groups suggested that the measured immunoreactive LH had reduced bioactivity. In seven women with endometriosis, bioactive LH (BA LH) measured as the in-vitro secretion of testosterone by dispersed Leydig cells, was significantly (p less than 0.001) reduced from 10.8 +/- 1.2 (SEM) to 4.4 +/- 0.2 mIU/ml at the end of 28 days of GnRH-a therapy. In five women with PCO, BA LH decreased from 44.2 +/- 15.5 to 5.7 +/- 0.6 mIU/ml (p = 0.06). These changes of BA LH appeared to be responsible for the suppression of ovarian androgen secretion during GnRH-a treatment and in turn may have contributed to the profound decreases of estrogen production by reducing the amount of precursor androgen available for aromatization. Free alpha subunit levels increased simultaneously with the decrease of BA LH at the end of therapy, suggesting a post-receptor effect of GnRH-a. Beta subunit levels became undetectable. Cross-reaction of alpha subunit in the RIA for LH was sufficient to only partially account for the LH levels measured. On sephadex G-100 chromatography the excess immunoreactive material was detected at and immediately following the alpha subunit tracer. Further studies will be necessary to elucidate the chemical nature of the immunoreactive LH secreted during GnRH-a therapy.


Big data, small explanatory and predictive power: Lessons from random forest modeling of on-farm yield variability and implications for data-driven agronomy.
Collection and analysis of large volumes of on-farm production data are widely seen as key to understanding yield variability among farmers and improving resource-use efficiency. The aim of this study was to assess the performance of statistical and machine learning methods to explain and predict crop yield across thousands of farmers' fields in contrasting farming systems worldwide. A large database of 10,940 field-year combinations from three countries in different stages of agricultural intensification was analyzed. Random effects models were used to partition crop yield variability and random forest models were used to explain and predict crop yield within a cross-validation scheme with data re-sampling over space and time. Yield variability in relative terms was smallest for wheat and barley in the Netherlands and for wheat in Ethiopia, intermediate for rice in the Philippines, and greatest for maize in Ethiopia. Random forest models comprising a total of 87 variables explained a maximum of 65 % of cereal yield variability in the Netherlands and less than 45 % of cereal yield variability in Ethiopia and in the Philippines. Crop management related variables were important to explain and predict cereal yields in Ethiopia, while predictive (i.e., known before the growing season) climatic variables and explanatory (i.e., known during or after the growing season) climatic variables were most important to explain and predict cereal yield variability in the Philippines and in the Netherlands, respectively. Finally, model cross-validation for regions or years not seen during model training reduced the R2 considerably for most crop x country combinations, while for wheat in the Netherlands this was model dependent. Big data from farmers' fields is useful to explain on-farm yield variability to some extent, but not to predict it across time and space. The results call for moderate expectations towards big data and machine learning in agronomic studies, particularly for smallholder farms in the tropics where model performance was poorest independently of the variables considered and the cross-validation scheme used.


Effect of Mitral Valve Surgery in Patients With Dilated Cardiomyopathy and Severe Functional Mitral Regurgitation.
Surgical treatment of functional mitral regurgitation (FMR) improves ventricular remodeling in patients with dilated cardiomyopathy (DCM). However, it is unclear whether surgical treatment improves long-term outcomes. We investigated the effects of mitral valve (MV) surgery in patients with DCM and FMR.Methods and Results:Of 525 patients with DCM hospitalized due to heart failure between January 1996 and September 2014, 70 who had severe FMR despite receiving optimal medical therapy were enrolled in the study. Of these patients, 16 underwent surgery for FMR (surgery group; repair=14, replacement=2); the remaining 54 who refused or decided not to undergo surgery were classified as the medication group. There were no differences in age, sex, medication, or echocardiographic parameters between the 2 groups (P>0.05). During the mean follow-up period of 53.6±43.6 months, the occurrence of clinical outcomes (i.e., all-cause death or left ventricular assist device implantation) was 54.3%; the occurrence of clinical outcomes was lower in the surgery group (P=0.008, log-rank test). Multivariate Cox regression analysis using clinical data revealed that MV surgery (hazard ratio [HR] 0.257, 95% confidence interval [CI] 0.103-0.640; P=0.004) and diabetes mellitus (HR 2.924, 95% CI 1.243-6.876; P=0.014) were independent predictors of clinical outcomes after adjusting for age and sex. Surgery for severe FMR provides better long-term outcomes in patients with DCM.


The use of a real-time luciferase assay to quantify gene expression dynamics in the living yeast cell.
A destabilized version of firefly luciferase was used in living yeast cells as a real-time reporter for gene expression. This highly sensitive and non-invasive system can be simultaneously used upon many different experimental conditions in small culture aliquots. This allows the dose-response behaviour of gene expression driven by any yeast promoter to be reported and can be used to quantify important parameters, such as the threshold, sensitivity, response time, maximal activity and synthesis rate for a given stimulus. We applied the luciferase assay to the nutrient-regulated GAL1 promoter and the stress-responsive GRE2 promoter. We find that luciferase expression driven by the GAL1 promoter responds dynamically to growing galactose concentrations, with increasing synthesis rates determined by the light increment in the initial linear phase of activation. In the case of the GRE2 promoter, we demonstrate that the very short-lived version of luciferase used here is an excellent tool to quantitatively describe transient transcriptional activation. The luciferase expression controlled by the GRE2 promoter responds dynamically to a gradual increase of osmotic or oxidative stress stimuli, which is mainly based on the progressive increase of the time the promoter remains active. Finally, we determined the dose-response behaviour of a single transcription factor binding site in a synthetic promoter context, using the stress response element (STRE) as an example. Taken together, the luciferase assay described here is an attractive tool to rapidly and precisely determine and compare kinetic parameters of gene expression.


A Novel Prognostic Ferroptosis-Related lncRNA Signature Associated with Immune Landscape in Invasive Breast Cancer.
Breast cancer (BC) represents the most common form of malignant tumors in women. However, the effectiveness of BC immunotherapy remains very low. Ferroptosis is a recently described form of programmed cell death which has unique characteristics, and associated long-chain noncoding RNAs (lncRNA) are thought to influence the occurrence and development of a variety of tumors. We identified 1,636 lncRNAs associated with ferroptosis in BC patients. 299 differentially expressed ferroptosis-related lncRNAs were subjected to univariate, LASSO regression, and multivariate Cox regression analyses to construct a ten ferroptosis-related lncRNA signature. This ten ferroptosis-related lncRNA signature performed very well in predicting survival of BC patients, and the risk score of the mRNA signature was identified as an independent prognostic factor in this cancer entity. In addition, the signature could be used to predict the immune landscape of BC patients. Low-risk patients had enriched immune-related pathways and more infiltration of most types of immune cells. The signature was also associated with the tumor mutation burden in BC. The results have allowed us to assess the potential for immunotherapy targets exposed by this model. The ferroptosis-related lncRNA risk model reported in the current study has clinical utility in BC prognosis and predicted immunotherapy response.


Advantages of table-top radiography in pediatric IVPs.
Evidence is presented to support the use of a nongrid table-top procedure for pediatric IVPs. The patient dose and image quality is compared in grid and nongrid techniques using identical film-screen systems. All projections are KUBs of children with abdominal thicknesses less than 13 cm who are involved in IVP examinations. Image quality is shown to be affected adversely beyond 13 cm. The use of the table-top method is helpful to the radiologist and technologist and beneficial to the patient.


When infection isn't infection.
Following open reduction and internal fixation for a proximal humerus fracture a 71-year-old man re-presented with wound changes consistent with infection and elevated inflammatory markers. No significant improvement was seen with concomitant intravenous antibiotics and multiple debridement procedures. This case was further complicated by soft tissue breakdown at the site of a left thigh haematoma also requiring debridement. Surgical site infections represent the most common cause of morbidity postoperatively. This case highlights the importance of considering a number of differential diagnoses. A diagnosis of pyoderma gangrenosum prompted systemic corticosteroid therapy giving rapid clinical improvement.


[Molecular epidemiology and antibiotic resistance of Pseudomonas aeruginosa isolated from blood in a hospital in Shandong Province from 2014 to 2021].
Objective: To identify the antibiotic resistance, virulence genes, and sequence types of Pseudomonas aeruginosa (P. aeruginosa) strains isolated from blood. Methods: From November 2014 to December 2021, a total of 94 nonrepetitive P. aeruginosa isolates were obtained from blood samples of patients at the First Affiliated Hospital of Shandong First Medical University in Shandong Province, China. The bacteria were identified using matrix-assisted laser desorption ionization time of flight mass spectrometry. Antibiotic resistance of the P. aeruginosa isolates was detected using Vitek 2 Compact system. Polymerase chain reaction (PCR) was conducted for the 18 virulence genes, and multi locus sequence typing (MLST) was performed to identify the sequence types of the P. aeruginosa strains. The resistance rates and distributions of virulence genes between carbapenem resistant pseudomonas aeruginosa (CRPA) and carbapenem susceptible pseudomonas aeruginosa (CSPA) isolates were compared using the Chi-square test. Results: Among 94 P. aeruginosa isolates, 19 (20.2%) isolates were found to be multidrug resistant (MDR) bacteria, of which 17 were CRPA isolates and 2 were CSPA isolates. All strains contained more than 10 virulence genes. Except for exoU gene, the detection rate of other genes was above 83%. MLST analysis revealed a total of 66 different STs, including 59 existing STs and 7 novel STs. Among them, ST244 (n=11, 11.7%) and ST270 (n=7, 7.4%) were the dominant STs. Although these two types of isolates harbored the same virulence genes, the resistance rates to carbapenem were different. 54.5% (6/11) ST244 isolates were CRPA but all 7 ST270 isolates were CSPA. Conclusion: Although the resistance rates of P. aeruginosa strains isolated from blood were at a low level, some MDR and CRPA isolates were detected. As the high virulence gene detection rates and genetic diversity were found for P. aeruginosa strains isolated from blood, close attention should be paid to avoid transmission and outbreaks.


Evoked potentials: modifications by classical conditioning.
Visual evoked potentials to a positive discriminative stimulus change systematically during sensory conditioning and extinction. Changes due to conditioning are manifested in the increased amplitude of the late component of the evoked response. This effect is attenuated during extinction and reappears after reconditioning.


Surgery for mitral regurgitation.
Mitral regurgitation is a valvular heart lesion that is difficult to diagnose accurately; thus, it is difficult to determine the appropriate timing for surgical correction. With increasing use of reparative techniques, including local resection of valve pathology and placement of an annuloplasty ring, and the realization that chronic atrial fibrillation leads to decreased long-term survival, the timing of surgery has changed. In addition, serial noninvasive studies have indicated that despite the absence of symptoms, patients may progress to a myopathic condition if the regurgitation progresses over a long period and surgery is not performed when signs of left ventricular dysfunction are evident. Preservation of the papillary muscle is also extremely important for late postoperative function in patients with mitral regurgitation, and reparative surgery that preserves both anterior and posterior papillary muscle complexes and continuity with the anulus appears to satisfy this assumption. Worldwide experience is reviewed and I present conclusions related to the appropriate indications for mitral valve repair or replacement in patients with mitral regurgitation.


The Glucocorticoid Receptor in Cardiovascular Health and Disease.
The glucocorticoid receptor is a member of the nuclear receptor family that controls many distinct gene networks, governing various aspects of development, metabolism, inflammation, and the stress response, as well as other key biological processes in the cardiovascular system. Recently, research in both animal models and humans has begun to unravel the profound complexity of glucocorticoid signaling and convincingly demonstrates that the glucocorticoid receptor has direct effects on the heart and vessels in vivo and in vitro. This research has contributed directly to improving therapeutic strategies in human disease. The glucocorticoid receptor is activated either by the endogenous steroid hormone cortisol or by exogenous glucocorticoids and acts within the cardiovascular system via both genomic and non-genomic pathways. Polymorphisms of the glucocorticoid receptor are also reported to influence the progress and prognosis of cardiovascular disease. In this review, we provide an update on glucocorticoid signaling and highlight the critical role of this signaling in both physiological and pathological conditions of the cardiovascular system. With increasing in-depth understanding of glucocorticoid signaling, the future is promising for the development of targeted glucocorticoid treatments and improved clinical outcomes.


Assessment of aortocoronary bypass graft patency by intra-arterial digital subtraction angiography compared to selective graft angiography.
The value of digital subtraction angiography (DSA), in assessing aortocoronary bypass graft patency, was evaluated by studying 22 consecutive patients with 54 aortocoronary saphenous vein bypass grafts, who had postoperative angina pectoris. Each patient underwent selective graft angiography and non-gated DSA. The DSA consisted of a run of 15 to 20 frames, taken at 2.3 frames per second during injection of diluted contrast in the ascending aorta, performed after a test exposure was made. Thirty-two of the 54 grafts (59%) were patent. Thirty of the 32 grafts were seen to be patent by both selective graft angiography and DSA. In addition, a further two grafts were found to be patent on DSA, but were not able to be selectively catheterised and were not seen on the conventional aortogram. Selective graft angiography revealed four tight proximal graft stenoses, of which one only was seen on DSA; and poor distal run-off in five grafts, two of which showed up as late filling grafts on DSA. In summary, the accuracy of intra-arterial DSA in assessment of bypass graft patency was excellent. All grafts seen to be patent on selective graft angiography were also seen by DSA alone and in addition two grafts which could not be selectively catheterised were found to be patent. However, in patients with postoperative chest pain, selective graft angiography is probably required as non-gated intra-arterial DSA does not provide sufficient information to assess graft stenoses, distal flow and the native coronary vessels.


Anterior chamber cytokine production and postoperative macular edema in diabetic patients undergoing femtosecond laser-assisted cataract surgery.
To evaluate the impact of femtosecond laser-assisted cataract surgery (FLACS) and manual cataract surgery (MCS) on pro-inflammatory cytokine expression in diabetic versus non-diabetic patients. Outpatient surgical center in Vaughan, Ontario, Canada. Prospective cohort study. Diabetic and non-diabetic patients undergoing non-complicated MCS or FLACS were assigned into four cohorts: MCS non-diabetic (n=30), FLACS non-diabetic (n=42), MCS diabetic (n=40), and FLACS diabetic (n=40). Aqueous humor inflammatory mediator concentrations were evaluated at MCS onset and following femtosecond laser treatment. Presence of cystoid macular edema, anterior chamber inflammation, central retinal thickness, macular volume, and retinal microvascular changes (through optical coherence tomography angiography), were evaluated preoperatively and on postoperative day 1, week 1, month 1 (POM1), and month 3 (POM3). Diabetic patients receiving FLACS had a higher concentration of interleukin (IL)-7, IL-13, and interferon-induced protein-10 than MCS diabetic patients; they also demonstrated higher levels of vascular endothelial growth factor, and lower levels of interferon (IFN)-γ, granulocyte colony stimulating factor, and IFN-α2 compared to MCS non-diabetic patients. Macular volume appeared to be significantly higher in MCS diabetic vs. MCS non-diabetic patients at POM1, and between FLACS diabetic vs. FLACS non-diabetic patients at POM3. There were no other significant differences between the cohorts for any parameter. FLACS use in diabetic patients demonstrated some differences in anterior chamber cytokine expression compared to non-diabetic FLACS or diabetic MCS patients; however, there was no increase in clinical inflammatory biomarkers. FLACS appears to be a safe technique to use in diabetic patients.


[Subcapsular hepatic hematoma due to vessel injury from the rigid portion of a guidewire during endoscopic retrograde cholangiopancreatography].
A 58-year-old male receiving two types of antithrombotic medication developed acute obstructive suppressive cholangitis due to choledocholithiasis. During the first endoscopic retrograde cholangiopancreatography (ERCP) procedure, we performed biliary plastic stenting. Seven days after this procedure and with continued antithrombotic treatment, we performed ERCP with endoscopic sphincterotomy and stone extraction. Twelve hours after this procedure, the patient suffered transient unconsciousness and progression of anemia. Sixty hours after the procedure, he experienced right hypochondralgia and hiccups. Ultrasonography and computed tomography revealed a subcapsular hepatic hematoma. Bleeding was successfully arrested with selective arterial embolization. We suspected that the cause of these problems was vessel injury from the rigid portion of the guidewire during the ERCP procedure.


Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex.
To separate the direct pharmacological effects of cocaine from those associated with active drug self-administration we employed a yoked control-operant paradigm and investigated the expression of well established markers of the rapid action of cocaine, i.e. the inducible early genes Arc and Zif268 and trophic factors, i.e. brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF-2), in rats after a single intravenous (i.v.) cocaine self-administration session. Animals self-administering cocaine (SA, 0.25 mg/0.1 ml saline per infusion, 2-h session) did more active lever-presses than yoked-cocaine (YC) and yoked-vehicle (YV) animals. This goal-oriented behaviour was accompanied by a selective increase in Arc mRNA levels in the medial prefrontal cortex (mPFC). There were no changes in the expression of the other genes in this brain region. mRNA levels of Arc and Zif268 in striatum and Zif268 in the nucleus accumbens markedly increased both in SA and YC animals; but there was no change in the expression of FGF-2 and BDNF. No changes were observed in hippocampus, hypothalamus, frontal cortex, and midbrain in SA and YC animals compared to YV animals in any of the genes. These findings demonstrate that a single session of cocaine i.v. self-administration is sufficient to shape rat behaviour towards goal-directed behaviours and selectively up-regulate Arc expression in mPFC (of SA animals), providing the first evidence that the mPFC's function is already profoundly influenced by the first voluntary cocaine exposure.