Increased serum concentrations and surface expression on peripheral white blood cells of decay-accelerating factor (CD55) in patients with active ulcerative colitis.
Inflammatory stimuli induce expression and release of decay-accelerating factor (DAF), a complement-regulatory protein present on peripheral-blood cells. Therefore, in ulcerative colitis (UC), an inflammatory colonic disease in which activated leukocytes are involved, DAF may be released from leukocytes into the circulation. In this study we compared serum DAF concentrations and surface DAF expression on peripheral-blood cells in patients with UC with disease activity. Peripheral-blood samples were obtained from 60 patients with UC (30 with active and 30 with inactive disease) and 19 healthy volunteers. Serum DAF concentrations were determined by means of immunoassay, and surface DAF expression on blood cells was examined with the use of flow cytometry. Serum DAF concentrations in patients with active disease (mean 48.6 ng/mL) were significantly higher than those in patients whose disease was in remission (33.3 ng/mL; P =.0003) and those in healthy controls (32.3 ng/mL; P =.0007). Surface DAF expression on neutrophils, CD14+ monocytes, and subsets of lymphocytes in patients with active UC was significantly increased compared with that in patients with UC in remission and in healthy controls. The increased serum DAF concentrations and surface DAF expression on leukocyte fractions in patients with active disease fell to significantly lower levels when the disease had gone into remission after medical therapy. Serum DAF concentrations are increased in UC patients in relation to disease activity. The likely source of increased DAF concentrations is peripheral-blood leukocytes that have been activated as part of the UC disease process.


The impact of a continuing training program on the perceived improvement in quality of health care delivered by health care professionals.
There is abundant scientific literature concerning factors that affect patients' perceptions of the quality of health care. However, there are few published works that consider the opinions of health care professionals. This article aims to conjointly analyse two organisational strategies that determine professional health care practice: continuous training and quality of care. The objective is to examine the opinions of physicians and nurses on the improvement of the quality of care after a 'learning by doing' program. An evaluation method was designed that integrates the main variables that intervene in quality of care. An online questionnaire was utilised for collecting opinions on the effects of the training program. A total of 184 nurses and 180 other medical professionals participated in the program and all of them were asked to complete the questionnaire. A descriptive, and inferential statistical analysis was undertaken and results showed that there is a direct relationship between perceptions about: satisfaction, professional competence, training modality, optimisation of health resources and quality of care.


Building Community and Transforming Knowledge: Histories of Women's Health Practitioners and Community-Based Health Services in 20th-Century Alberta, Canada.
As new government health policy was created and implemented in the late 1910s and the late 1960s, women patients and health practitioners recognized gaps in the new health services and worked together to create better programs. This article brings the histories of the district nursing program (1919-43) and local birth control centres (1970-79) together to recognize women's health provision (as trained nurses or lay practitioners) as community-based and collaborative endeavours in the province of Alberta. The district nursing and birth control centre programs operated under different health policies, were influenced by different feminisms, and were situated in different Indigenous-settler relations. But the two programs, occurring half a century apart, provided space for health workers and their patients to implement change at a community level. Health practitioners in the early and late twentieth century took women's experiential knowledge seriously, and, therefore, these communities formed a new field of women's health expertise.


Project EX-India: A classroom-based tobacco use prevention and cessation intervention program.
Tobacco use experimentation is most frequent between the ages of 15–24 in India. Therefore, programming to counteract tobacco use among adolescents is needed. There is a lack of evidence-based teen tobacco use prevention and cessation programs. The current study provides an outcome evaluation of the Project EX tobacco use prevention and cessation program among Indian adolescents (16–18 years). An eight-session classroom-based curriculum was adapted to the Indian context and translated from English to Hindi (local language). Next, it was tested using a quasi-experimental design with 624 Indian students at baseline, involving two program and two control schools, with a three-month post-program follow-up. Project EX involves motivation enhancement (e.g., talk shows and games) and coping skills (e.g., complementary and alternative medicine) components. Program participants rated complementary and alternative medicine (CAM) activities like meditation, yoga and healthy breathing higher than talk shows and games. Compared to the standard care control condition, the program condition revealed a prevention effect, but not a cessation effect. Implications for prevention/cessation programming among Indian teens are discussed. This study was approved by the Independent Ethics Committee, Mumbai.


Acute cholecystits leading to ischemic ECG changes in a patient with no underlying cardiac disease.
Although chest pain with ST-segment elevation is often indicative of cardiac ischemia, it has also been described with surgical conditions such as acute cholecystitis. We report the case of a 34-year-old Caucasian female who was referred with symptoms consistent with acute cholecystitis. An electrocardiogram (ECG) showed unexpected changes with inferolateral ST-segment elevation indicative of an inferolateral myocardial infarct. Further investigations and analysis of the results along with the clinical picture meant an acute cardiac event was excluded. Gallstones were seen on ultrasound and an inflamed gallbladder, consistent with acute cholecystitis, was confirmed at laparoscopic cholecystectomy. This led to the resolution of her symptoms and a return to the isoelectric baseline of the ST segments on the ECG. Five previous cases of cholecystitis induced ECG changes have been described in the literature. This case describes the youngest patient with no previous cardiac disease. We review the literature and suggest the pathophysiological mechanism to explain these findings. When the initial diagnostic interventions for chest pain with ST-segment elevation do not yield the expected results, an alternative diagnosis such as cholecystitis should be considered.


Lack of impact of age on acute side effects and tolerance of curative radiation therapy.
The aim of this study was to determine the impact of age on the occurrence, severity, and timing of acute side effects related to radiotherapy. We analysed the data of 423 patients. Of the patients, 295 (70%) were under the age of 65 (group 1) and 128 (30%) were over the age of 65 (group 2). The frequencies of radiotherapy-induced side effects were 89% in group 1 and 87% in group 2 (p=0.286). The mean times to occurrence were 2.5±0.1 weeks in group 1 and 2.2±0.1 weeks in group 2 (p=0.013). Treatment was ended in 2% of patients in group 1 and 6% of those in group 2 (p=0.062). Treatment interruption was identified in 18% of patients in group 1 and 23% in group 2 (p=0.142). Changes in performance status were greater in older patients (p=0.013). There were no significant differences according to the frequency or severity of side effects, except skin and genitourinary complications, between the groups. Early normal tissue reactions were not higher in older versus younger patients, though there was a tendency towards an earlier appearance.


A Whole Genome Sequencing-Based Genome-Wide Association Study Reveals the Potential Associations of Teat Number in Qingping Pigs.
Teat number plays an important role in the reproductive performance of sows and the growth of piglets. However, the quantitative trait loci (QTLs) and candidate genes for the teat number-related traits in Qingping pigs remain unknown. In this study, we performed GWAS based on whole-genome single-nucleotide polymorphisms (SNPs) and insertions/deletions (Indels) for the total number of teats and five other related traits in 100 Qingping pigs. SNPs and Indels of all 100 pigs were genotyped using 10× whole genome resequencing. GWAS using General Linear Models (GLM) detected a total of 28 SNPs and 45 Indels as peak markers for these six traits. We also performed GWAS for the absolute difference between left and right teat number (ADIFF) using Fixed and random model Circulating Probability Unification (FarmCPU). The most strongly associated SNP and Indel with a distance of 562,788 bp were significantly associated with ADIFF in both GLM and FarmCPU models. In the 1-Mb regions of the most strongly associated SNP and Indel, there were five annotated genes, including TRIML1, TRIML2, ZFP42, FAT1 and MTNR1A. We also highlighted TBX3 as an interesting candidate gene for SSC14. Enrichment analysis of candidate genes suggested the Wnt signaling pathway may contribute to teat number-related traits. This study expanded significant marker-trait associations for teat number and provided useful molecular markers and candidate genes for teat number improvement in the breeding of sows.


Brominated flame retardants in three terrestrial passerine birds from South China: geographical pattern and implication for potential sources.
Polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), polybrominated biphenyls (PBBs) and pentabromotoluene (PBT) were investigated in light-vented bulbul (LVB), long-tailed shrike (LTS) and oriental magpie-robin (OMR) collected from seven sampling sites in South China. ∑PBDEs, DBDPE, PBB 153, and PBT levels ranged from 35 to 15,000, no detected (nd)-130, nd-6800, and nd-6.8 ng/g lipid weight, respectively. Positive correlations were found between δ(15)N values and brominated flame retardant (BFR) concentrations. The BFR geographic pattern indicated that PBDEs were linked to e-waste recycling and local industry activities as well as urbanization; PBB 153 was derived from e-waste; DBDPE was mainly come from local industry activities; and no specific source was observed for PBT. PBDE congener profiles were found to be depended on bird species and sampling sites with relatively high abundances of lower brominated congeners in e-waste site and significantly higher abundance of BDE153 in LTS and OMR than in LVB.


Production and characterization of pharmacologically active recombinant human phosphodiesterase 4B in Dictyostelium discoideum.
Phosphodiesterase 4B (PDE4B) is an important therapeutic target for asthma and chronic obstructive pulmonary disease. To identify PDE4 subtype-specific compounds using high-throughput assays, full-length recombinant PDE4 proteins are needed in bulk quantity. In the present study, full-length human PDE4B2 was expressed in the cellular slime mould Dictyostelium discoideum (Dd). A cell density of 2 x 10(7) cells/mL was obtained and up to 1 mg/L recombinant PDE4B2 was purified through Ni-NTA affinity chromatography. The expressed protein was soluble and its activity was comparable to PDE4B2 protein expressed in mammalian cells (K(m)=1.7 microM). The functional significance of the Dd expression system is supported by the demonstration that, in concert with proteins expressed in mammalian systems, there are no major changes in the affinity for PDE4B2 inhibitors and substrates. These findings thus provide the first evidence that Dd can be utilized for the expression and purification of functionally active full-length human PDE4B2 in large amounts required for high-throughput screening of pharmacologically active compounds against this therapeutic target.


Corrigendum: Strategies for Efficient Gene Editing in Protoplasts of Solanum tuberosum Theme: Determining gRNA Efficiency Design by Utilizing Protoplast (Research).
[This corrects the article DOI: 10.3389/fgeed.2021.795644.].


Mystery and intrigue: the attraction of feline medicine.
When it comes to vet care, cats are often perceived as trickier patients than dogs. But, says Ellie Mardell, with time and patience, cats offer vets the chance to practise some interesting medicine.


Serum myostatin levels are associated with physical function and hospitalization in peritoneal dialysis patients.
Myostatin functions as a negative regulator of skeletal muscle growth. The association of myostatin with muscle parameters in dialysis patients is inconsistent, and there are no studies associating myostatin with physical function and outcomes in peritoneal dialysis (PD) patients. Therefore, we assessed the association of serum myostatin with lean mass, physical function, and hospitalization in a prospective cohort of PD patients. Lean mass, physical function, and serum myostatin were assessed at baseline. Patients were followed up for at least 24 months and hospitalization was recorded. Serum myostatin levels were positively correlated with handgrip strength and Appendicular Lean Mass Index among male patients. Binary logistic regression models were performed including myostatin levels and physical function parameters as independent variables. Serum myostatin, handgrip strength, gait speed, and Short Physical Performance Battery were associated with hospitalization. Lower serum myostatin and physical function were associated with hospitalization in PD patients.


A method of quantify confounding in regression analyses applied to data on diet and CHD incidence.
We present a method to display the results of linear regression when the independent variables are highly correlated. In this method the sum of squares of regression (SSR) for pairs of variables are partitioned into orthogonal and shared components. A shared component is the reduction in the SSR of one of the variables when the other variable is added to the regression equation. This method shows how the SSR for one variable depends on the other variables present in the regression equation and explains apparent inconsistencies between forward and backward stepwise regression. To demonstrate the potential usefulness of this method we reanalyzed previously reported data on the relationship between coronary heart disease (CHD) and diet. The analysis suggested that carbohydrate and alcohol intake are negatively associated with CHD because they are associated with greater caloric intake. Protein and fat intake are also associated with greater caloric intake, but in addition they are associated with factors that increase the risk of CHD.


[Image-guided ablation of bone tumors: review of current techniques].
Multiple interventional radiology techniques are available for percutaneous ablation of bone tumors: alcohol, laser, radiofrequency, microwave, ultrasound, and cryogenic ablation. Several indications have already been validated, including radiofrequency ablation of osteoid osteoma and bone metastases, with results superior to conventional treatment. More indications should be added over the coming years. The purpose of this article is to review the principles of the different ablation techniques, summarize their respective indications and results and discuss their implementation and the eventual combination with cementoplasty techniques.


Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome.
Arthralgia is an adverse class effect of aromatase inhibitors (AIs). To date, its exact mechanism remains unclear. The purpose of this study was to investigate the changes in clinical rheumatologic features and magnetic resonance imaging (MRI) of hands and wrists in AI and tamoxifen users. This is a prospective single-center study including 17 consecutive postmenopausal patients with early breast cancer receiving either tamoxifen (n = 5) or an AI (n = 12). At baseline and after 6 months, patients filled in a rheumatologic history questionnaire and a rheumatologic examination including a grip strength test was done. At the same time points, MRI of both hands and wrists was performed. The primary end point was tenosynovial changes from baseline on MRI. Secondary end points were changes from baseline for morning stiffness, grip strength, and intra-articular fluid on MRI. Wilcoxon signed ranks was used to test changes from baseline and the Spearman correlation coefficient to assess the association between rheumatologic and MRI changes from baseline. At 6 months, patients on AI had a decrease in grip strength (P = .0049) and an increase in tenosynovial changes (P = .0010). The decrease in grip strength correlated well with the tenosynovial changes on MRI (P = .0074). Only minor changes were seen in patients on tamoxifen. AI users reported worsening of morning stiffness and showed an increase in intra-articular fluid on MRI. The functional impairment of hands in the AI-associated arthralgia syndrome is characterized by tenosynovial changes on MRI correlating with a significant decrease in hand grip strength.


1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine β-synthase.
High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY owing to its negative impact on collagen maturation. HCY is cleared by cystathionine β-synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3-E1 murine preosteoblasts treated with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)(2) D(3) . Quantitative real-time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH)(2) D(3) treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine, and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH)(2) D(3) -treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knockout osteoblasts, in which upregulation of cbs in response to 1,25(OH)(2) D(3) was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs. To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY levels. In conclusion, this study showed that cbs is a primary 1,25(OH)(2) D(3) target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3).


Combination of the Ilizarov Method and Intramedullary Fixation for the Treatment of Congenital Pseudarthrosis of the Tibia in Children: A Retrospective Observational Study.
Congenital pseudoarthrosis of the tibia (CPT) is a rare disease in children, and its treatment remains a challenge for orthopedic surgeons. The purpose of this study was to evaluate treatment outcomes of patients with CPT treated by using the Ilizarov method combined with intramedullary fixation. Eighteen patients evaluated retrospectively from January 2009 to January 2020 were treated using the Ilizarov method combined with intramedullary fixation. Demographic data, clinical characteristics, and complications were all recorded and investigated during the period of follow-up. Ankle function was evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at the last follow-up. The average follow-up was 39.2 months (25-85 months) for all 18 patients. The mean age was 6.2 years (3.5-11.2 years). Fourteen (77.8%) patients had a primary bone union at the site of pseudarthrosis, while four obtained union after secondary surgical intervention. The mean duration of the Ilizarov method was 8.1 months (4.2-13.5 months). Eight (44.4%) patients had a pin-tract infection during treatment. Four (22.2%) patients had proximal tibial valgus with a mean angle of 12.1° (5-25°), while seven (38.9%) patients had ankle valgus deformities with a mean of 10.3° (5-20°). Eleven (61.1%) patients had an average 1.4 cm of limb length discrepancy (LLD) (0.6-3.1 cm) postoperatively. Five (27.8%) patients had refracture and recovered after a secondary surgery. At the last follow-up, the average postoperative AOFAS score was 72 (55-84). The Ilizarov method combined with intramedullary fixation is an effective method for the treatment of CPT, which can facilitate bony union and help to prevent refracture. Management of fibular pseudarthrosis is associated with functional outcomes. It is necessary to follow up until skeletal maturity and evaluate long-term clinical outcomes.


[Cancer Genome Atlas Pan-cancer Analysis Project].
Cancer can exhibit different forms depending on the site of origin, cell types, the different forms of genetic mutations which also affect cancer therapeutic effect. Although many genes have been demonstrated to change a direct result of the change in phenotype, however, many cancers lineage complex molecular mechanisms are still not fully elucidated. Therefore, The Cancer Genome Atlas (TCGA) Research Network analyzed a large human tumors, in order to find the molecular changes in DNA, RNA, protein and epigenetic level, The results contain a wealth of data provides us with an opportunity for common, personality and new ideas throughout the cancer lineages form a whole description. Pan-cancer genome program first compares the 12 kinds of cancer types. Analysis of different tumor molecular changes and their functions, will tell us how effective treatment method is applied to a similar phenotype of the tumor.


A simple method for insertion of a left atrial catheter in congenital heart disease.
A relatively simple and safe method is described for the insertion of a left atrial pressure line in patients undergoing operation for repair of congenital heart defects. This method has been utilized successfully in 12 patients undergoing repair of a ventricular septal defect and tetralogy of Fallot.


A Timely Oral Option: Single-Agent Vinorelbine in Desmoid Tumors.
Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine. A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed. A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%). Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.


Endoscopic electromyography of the sphincter of Oddi.
Endoscopic electromyography of the human sphincter of ODDI has provided useful information for the patho-physiological studies on the choledocho-duodenal junction. The pattern and rhythm of the electromyogram observed on the spincter of ODDI were different from those of the duodenum recorded simultaneously in basal tracings of our initial four cases. In the half of other ten cases with consecutive tracings, the different pattern and rhythm of electromyograms between the sphincter of ODDI and the duodenum were also confirmed. It was possible, from our results, to speculate that the functional independence of the sphincter of ODDI from the duodenal wall muscles was in existence.


Relationship between mental health and climacteric adjustment in middle aged women: a confirmatory analysis.
Climacteric changes in women are associated with an increased probability of psychological symptoms. Identifying the relationship between adjustment to this period and mental health helps to plan for middle-aged women's health improvement. Therefore, the present study aimed to investigate the relationship between climacteric adjustment (CA) and mental health in middle aged women. This cross-sectional study was conducted on 190 women aged 40 to 53 years. Mental health symptoms (including hypochondriasis, anxiety, depression, and social impairment) and CA were assessed using 28-item general health questionnaire and the CA questionnaire, respectively, as a self-report. Data were analyzed using linear and stepwise regression methods, and the fitting of the resulting conceptual model was assessed using AMOS software. The results showed that hypochondriasis score and social impairment, anxiety level and CA in the perfection dimension, and social impairment score and CA in perfection, decline in beauty, and sexual silence dimensions had an inverse relationship. Moreover, the relationship between anxiety score and CA in the reaction to end of menstruation and the relationship between social impairment and decline of femininity were positive and significant. Factor analysis of the conceptual model obtained from the study results demonstrated a good model fit (CMIN /DF = 0.807, P = .671). The results showed a relationship between CA and psychological symptoms in middle-aged women. In other words, the level of hypochondriasis, anxiety, and social impairment symptoms decreased with increasing CA in sexual silence, perfection, and decline in beauty.


Post-operative retransfusion of unwashed filtered shed blood reduces allogenic blood demand in hip hemiarthroplasty in traumatic femoral neck fractures-a prospective randomized trial.
Patients who undergo hip hemiarthroplasty (HHA) due to traumatic femoral neck fracture frequently require red blood cell (RBC) transfusion. Although post-operative autologous blood transfusion (ABT) is well established in elective arthroplasty, its role in trauma patients remains unclear. Two hundred twenty-nine patients with a traumatic femoral neck fracture that underwent HHA at our level-I trauma centre between 2005 and 2009 were prospectively randomized to a high-vacuum drainage or an ABT device. In this single-institution analysis, the number of RBC units as well as the amount of retransfused shed blood were recorded and compared according to study groups. Additionally, the significance of confounding factors for allogenic blood demand such as age, gender, pre-operative Hb level, surgical approach, type of prosthesis and amount of intra-operative RBC units were evaluated using multivariate analysis. One hundred thirty-five patients were randomized in the high-vacuum group while 94 patients received an ABT device. Intention to treat analysis revealed no significant difference in post-operative RBC demand (ABT: 0.87 RBC, high-vacuum drainage: 1.01 RBC; P = 0.374). However, patients that actually received retransfusion (N = 35) had a reduced post-operative RBC demand (0.49 RBC units, P = 0.014). While only one third of trauma patients treated with an ABT device during HHA actually receive retransfusion, retransfused patients seem to significantly benefit from this treatment as reflected by a reduced pos-toperative RBC demand.


Development of a minimally invasive, injectable, shape memory suture and delivery system.
Suturing in space-confined surgical settings encountered during microsurgical procedures can be technically complex and time intensive. This paper presents the development of a new injector and new shape-memory alloy clip that can replace conventional suture. Engineering and surgical assessments of the injector and clips were performed. A prototype of the delivery system was tested in simulated surgical settings and compared to conventional suturing techniques for surgical time and wound strength. In various micro-surgical scenarios, the new injectable system proved to be 5 to 20-times more efficient and to have wound strengths over three-times that of conventional suturing. Further, the wounds closed by the shape-memory alloy clips could be forced to open and then recover to a watertight state, unlike conventional sutures which break upon failure. This new injector and shape-memory alloy clips proved to be quicker, stronger, and technically easier than conventional suturing. Future work is underway to test the injectable delivery system and the shape-memory alloy clips using a real-time, in vivo porcine model.


Adverse outcomes after non-hepatic surgeries in patients with alcoholic liver diseases: a propensity-score matched study.
The influence of alcoholic liver disease (ALD) on the postoperative outcomes is not completely understood. Our purpose is to evaluate the complications and mortality after nonhepatic surgeries in patients with ALD. We conducted a retrospective cohort study included adults aged 20 years and older who underwent nonhepatic elective surgeries using data of Taiwan's National Health Insurance, 2008-2013. Using a propensity-score matching procedure, we selected surgical patients with ALD (n = 26,802); or surgical patients without ALD (n = 26,802) for comparison. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of postoperative complications and in-hospital mortality associated with ALD. Patients with ALD had higher risks of acute renal failure (OR 2.74, 95% CI 2.28-3.28), postoperative bleeding (OR 1.64, 95% CI 1.34-2.01), stroke (OR 1.51, 95% CI 1.34-1.70) septicemia (OR 1.47, 95% CI 1.36-1.58), pneumonia (OR 1.43, 95% CI 1.29-1.58), and in-hospital mortality (OR 2.64, 95% CI 2.24-3.11) than non-ALD patients. Patients with ALD also had longer hospital stays and higher medical expenditures after nonhepatic surgical procedures than the non-ALD patients. Compared with patients without ALD, patients with ALD who had jaundice (OR 4.82, 95% CI 3.68-6.32), ascites (OR 4.57, 95% CI 3.64-5.74), hepatic coma (OR 4.41, 95% CI 3.44-5.67), gastrointestinal hemorrhage (OR 3.84, 95% CI 3.09-4.79), and alcohol dependence syndrome (OR 3.07, 95% CI 2.39-3.94) were more likely to have increased postoperative mortality. Surgical patients with ALD had more adverse events and a risk of in-hospital mortality after nonhepatic surgeries that was approximately 2.6-fold higher than that for non-ALD patients. These findings suggest the urgent need to revise the protocols for peri-operative care for this population.


Medical students' perceptions of peer feedback on an anatomy student-selected study module.
The study aimed to determine student views of peer feedback on their student-selected study (SSS) module. A questionnaire was developed to study perceptions of three groups of medical students (N = 42) towards feedback received from peers about their anatomy SSS presentation. Most students felt comfortable receiving and giving feedback. They also felt that received feedback was fair, adequate and helpful, and that receiving feedback made them reflect. Slightly more students reported inadequate feedback from their peers about the presentations' content, compared to other aspects, due to their peers' relative lack of knowledge about their 'specialized' subject. Students would be reluctant to give feedback if anonymity was removed. The attitudes of medical students towards peer feedback were largely positive. We advocate further studies to evaluate quality of feedback, and the role of anonymity in peer feedback, and its effect on group dynamics and cohesion.


High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase.
Nonalcoholic steatohepatitis is a clinicopathologic condition that may progress to liver fibrosis. Hyperglycemia is supposed to be one of the factors inducing hepatic fibrogenesis, but the mechanism has not been fully clarified. Oxidative stress is increasingly found in patients with diabetes/hyperglycemia in which conditions reactive oxygen species (ROS) are produced. We performed experiments using hepatic stellate cells (HSCs) in culture in order to confirm the effect of high glucose concentrations on cell proliferation, type I collagen production, ROS production and activation of mitogen-activated protein (MAP) kinase pathway. High glucose stimulated cell growth of HSCs and up-regulated the levels of activated/phosphorylated extracellular signal-regulated kinase 1/2 and free radical production in HSCs. The MAP kinase phosphorylation and cell proliferation were suppressed by diphenylene iodonium chloride, an NADPH oxidase inhibitor, and by calphostin C, a protein kinase C (PKC)-specific inhibitor. Increased type I collagen mRNA and protein levels were also observed in HSCs at high glucose concentrations. Our findings indicate that high glucose concentrations may stimulate ROS production through PKC-dependent activation of NADPH oxidase, and induce MAP kinase phosphorylation subsequent to proliferation and type I collagen production by HSCs.


Advances in hyphenated analytical techniques for shotgun proteome and peptidome analysis--a review.
Proteomics is defined as the analysis of part or all of the protein components of a complex biological system (a cell, organ or tissue) at a given moment. Due to the huge number of proteins encoded by the genome, novel analytical techniques must be developed to meet the need of large scale analysis. This has led to the hyphenation of multiple techniques to achieve this object. Here current status of the hyphenated analytical techniques of one-dimensional and multidimensional liquid chromatography-mass spectrometry for shotgun proteomic analysis is reviewed, and on-line techniques for automated sample preparation and injection are also covered. In addition, the hyphenated techniques for peptidome analysis are also covered.


Quantitative analysis of renal medullary anatomy in rats and rabbits.
The mean renal tubular diameters, number of tubules per unit of cross-sectional area, and fraction of the total volume occupied by each medullary structure were determined at various levels of the renal medulla of the rat and rabbit. Statistical estimates of anatomic variables were made using spatial sampling techniques on histologic sections. Osmotic diuresis and renal venous occlusion were used to allow fixation of renal tubules and blood vessels in an open state. The distribution of volume fractions of medullary structures are similar in rats and rabbits. Diameters of outer medullary tubular segments and inner medullary thin limbs of Henle are also similar in rats and rabbits. Marked differences between rats and rabbits, however, are seen in the size and number of collecting ducts in the inner medulla. Rabbit inner medullary collecting ducts increase in diameter and decrease in number in the papillary direction relatively closer to the cortex than do those of the rat. Luminal diameters of papillary collecting ducts are more than twice as great in the rabbit as in the rat. An additional finding was that short loops of Henle in the rabbit have their bends relatively closer to the cortex than those of the rat. The quantitative anatomic data derived in this study, when combined through mathematical modeling with knowledge of transport properties of renal tubular membranes, should lead to a clearer understanding of renal function.


"Am I too emotional for this job?" An exploration of student midwives' experiences of coping with traumatic events in the labour ward.
midwifery is emotionally challenging work, and learning to be a midwife brings its own particular challenges. For the student midwife, clinical placement in a hospital labour ward is especially demanding. In the context of organisational tensions and pressures the experience of supporting women through the unpredictable intensity of the labour process can be a significant source of stress for student midwives. Although increasing attention is now being paid to midwives' traumatic experiences and wellbeing few researchers have examined the traumatic experiences of student midwives. Such research is necessary to support the women in their care as well as to protect and retain future midwives. this paper develops themes from a research study by Davies and Coldridge (2015) which explored student midwives' sense of what was traumatic for them during their undergraduate midwifery education and how they were supported with such events. It examines the psychological tensions and anxieties that students face from a psychotherapeutic perspective. a qualitative descriptive study using semi-structured interviews. a midwifery undergraduate programme in one university in the North West of England. 11second and third year students. interviews were analysed using interpretative phenomenological analysis. the study found five themes related to what the students found traumatic. The first theme Wearing the Blues referred to their enculturation within the profession and experiences within practice environments. A second theme No Man's Land explored students' role in the existential space between the woman and the qualified midwives. Three further themes described the experiences of engaging with emergency or unforeseen events in practice and how they coped with them ("Get the Red Box!", The Aftermath and Learning to Cope).This paper re-examines aspects of the themes from a psychotherapeutic perspective. researchers have suggested that midwives' empathic relationships with women may leave them particularly vulnerable to secondary traumatic stress. For student midwives in the study the close relationships they formed with women, coupled with their diminished control as learners may have amplified their personal vulnerability. The profession as a whole is seen by them as struggling to help them to safely and creatively articulate the emotional freight of the role. for midwifery educators, a focus on the psychological complexities in the midwifery role could assist in giving voice to and normalising the inevitable anxieties and difficulties inherent in the role. Further research could explore whether assisting students to have a psychological language with which to reflect upon this emotionally challenging work may promote safety, resilience and self-care.


Diffuse contralateral pulmonary metastases in malignant mesothelioma. An unusual radiographic presentation.
We describe a patient with malignant pleural mesothelioma involving the lung parenchyma bilaterally in a diffuse nodular fashion. This pattern of metastasis is seldom reported for this tumor.


Prevalence, awareness, and treatment of osteoporosis among Korean women: The Fourth Korea National Health and Nutrition Examination Survey.
This study aimed to assess the factors associated with the prevalence, awareness, and treatment of osteoporosis in a representative sample of Korean women. Data were obtained from dual energy X-ray absorptiometry measurement of the lumbar vertebrae and femoral neck, and from a standardized questionnaire in 2870 Korean women aged 50years and older who participated in the Fourth Korea National Health and Nutrition Examination Survey 2008-2009. Osteoporosis was defined by World Health Organization T-score criteria, and awareness and treatment were defined by self-report of an osteoporosis diagnosis and self-report of current anti-osteoporotic medication use, respectively. We assessed the relationship between multiple risk factors and prevalence, awareness, and treatment. Osteoporosis was reported in 39.1% of Korean women. Among those with osteoporosis, only 37.5% were aware of their diagnosis and 23.5% received pharmacological treatment. Despite higher prevalence among respondents who were older, of lower body weight, calcium intake, physical activity, and education levels, the awareness and treatment rates of these groups were similar or lower than that of the low-risk controls in multivariate logistic regression models. Moreover, easily identifiable risk factors (e.g., history of fracture, falls, height loss, familial osteoporosis) were not associated with awareness and treatment. Participants who had undergone health screening in the previous 2years exhibited increased awareness and treatment rates independently of other demographic factors. Osteoporosis was highly prevalent in this Korean study but was underdiagnosed and undertreated. Routine health screenings could be an effective strategy to increase osteoporosis awareness and treatment.


Unilateral lacrimal fistula in a patient with uterus didelphys and renal agenesis.
A 30-year-old female patient presented to our clinic because of lacrimation from an orifice close to the left lower eyelid. Ocular examinations and analyses revealed uterus didelphys and unilateral renal agenesis associated with a left lacrimal fistula. The patient underwent fistulectomy and external dacryocystorhinostomy. We decided to report on this patient owing to the unusual concurrent systemic abnormalities.


Estrogen-dependent abdominal hyperalgesia induced by ovariectomy in adult mice: a model of functional abdominal pain.
Some abdominal pain syndromes are characterized by persistent pain without demonstrable pathology. Many of them are prevalent in women and it is known that sex hormones are associated with differences in pain perception between males and females. To model a process of functional abdominal pain in females we studied the time course and estrogen dependency of a hyperalgesic state induced by ovariectomy in adult mice. Three groups of C57/BL6 mice were used: virgin mice, proven breeders (2 or 3 successful pregnancies) and retired breeders (more than three successful pregnancies). Within each group, a third of the mice were ovariectomized (OVX), a third received sham surgery and a third were controls. OVX mice, but not sham or controls, developed a robust mechanical hyperalgesia and allodynia in the abdomen, hindlimbs and proximal tail, but not in the forelimbs, that was established 4 weeks after OVX and lasted for the 7 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX mice. Thermal pain thresholds (hot plate) remained unchanged. The reproductive history of the animals had no influence on the hyperalgesia. In another series of experiments a slow release pellet containing 17beta-estradiol was implanted in half of the OVX mice and a similar pellet without the hormone in the other half. Hormone replacement prevented the development of hyperalgesia in OVX animals but did not stop the involution of the internal reproductive organs. We conclude that OVX in mice provides a useful model for a hormonally dependent hyperalgesic state resembling functional pain.


Complex spiking neural networks with synaptic time-delay based on anti-interference function.
The research on a brain-like model with bio-interpretability is conductive to promoting its information processing ability in the field of artificial intelligence. Biological results show that the synaptic time-delay can improve the information processing abilities of the nervous system, which are an important factor related to the formation of brain cognitive functions. However, the synaptic plasticity with time-delay of a brain-like model still lacks bio-interpretability. In this study, combining excitatory and inhibitory synapses, we construct the complex spiking neural networks (CSNNs) with synaptic time-delay that more conforms biological characteristics, in which the topology has scale-free property and small-world property, and the nodes are represented by an Izhikevich neuron model. Then, the information processing abilities of CSNNs with different types of synaptic time-delay are comparatively evaluated based on the anti-interference function, and the mechanism of this function is discussed. Using two indicators of the anti-interference function and three kinds of noise, our simulation results consistently verify that: (i) From the perspective of anti-interference function, an CSNN with synaptic random time-delay outperforms an CSNN with synaptic fixed time-delay, which in turn outperforms an CSNN with synaptic none time-delay. The results imply that brain-like networks with more bio-interpretable synaptic time-delay have stronger information processing abilities. (ii) The synaptic plasticity is the intrinsic factor of the anti-interference function of CSNNs with different types of synaptic time-delay. (iii) The synaptic random time-delay makes an CSNN present better topological characteristics, which can improve the information processing ability of a brain-like network. It implies that synaptic time-delay is a factor that affects the anti-interference function at the level of performance.


Near-haploid clones in a malignant fibrous histiocytoma.
Near-haploid solid tumors are very rare. In a storiform-pleomorphic malignant fibrous histiocytoma (MFH) of bone, we found three cell populations: one with a near-haploid, a second with a near-diploid, and a third with a near-tetraploid chromosome number. The near-haploid cells had few structural rearrangements: i(12p) and t(13q21q) in one clone, and these two and an additional t(19;?)(p11;?) in another clone. One structurally normal copy of all chromosomes was also present, except that the only chromosome 13 was involved in the t(13q21q). There were also two near-diploid clones, one without the t(19;?) and one with a single copy of this derivative chromosome. This is the first tumor with i(12p) among bone and soft tissue tumors.


MK-801, an N-methyl-D-aspartate receptor antagonist, blocks quinolinic acid-induced lipid peroxidation in rat corpus striatum.
In this study, we evaluate the possible participation of lipid peroxidation (LP) in the neurotoxic events that follow after quinolinic acid (QUIN) microinjection into the rat corpus striatum. Two hours after QUIN (240 nmol/microliters) intrastriatal administration, lipid peroxidation was found increased by 32% vs. control as measured by thiobarbituric acid-reactive substances (TBARS). At the same time tested, the enhancement in LP was of 55% vs. control as measured by lipid fluorescent products (LFP) formation (a second index of lipid peroxidation employed). The increase of QUIN-induced lipid peroxidation was completely abolished by pretreatment of rats with an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (10 mg/kg, i.p.), 60 min before QUIN microinjection. Results suggest an NMDA receptor involvement in the QUIN-induced oxidative processes.


Potassium-stimulated release of [3H]taurine from cultured GABAergic and glutamatergic neurons.
The effect of depolarizing concentrations of potassium (56 mM) on the release of [3H]taurine was examined in two types of cultured neurons from mouse brain: cerebral cortex neurons, which are largely GABAergic, and cerebellar neurons, which after treatment with kainate consist almost entirely of glutamatergic granule cells. The release of [3H]taurine was compared to that of gamma-[3H]aminobutyric acid [( 3H]GABA) in cortical neurons and to that of D-[3H]aspartate in granule cells. Cortical neurons responded to potassium stimulation (1 min or continuously) by an immediate increase in [3H]GABA efflux of more than six times over the basal efflux, followed by a sharp decline despite the persistence of the stimulatory agent. The potassium-induced release of [3H]GABA was largely calcium-dependent. The release of [3H]taurine was considerably less in magnitude, only doubling after the stimulus, with a time course delayed in both onset and decline. The release of [3H]taurine was partially calcium-dependent and was also decreased in low-chloride solutions. In cerebellar granule cells, exposure to potassium resulted in a large (sixfold) and prompt release of D-[3H]aspartate, largely calcium-dependent. A totally different pattern was observed for the release of [3H]taurine. A stimulatory effect occurred only when cells were exposed continuously to potassium. Taurine efflux was very delayed, with a broad stimulus plateau reached after 15-20 min of stimulation. Taurine release was unaffected by omission of calcium, but it was abolished in a low-chloride medium. These results suggest that taurine is released from cells handling other neuroactive amino acids as neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnostic accuracy of MRI parameters in pure akinesia with gait freezing.
To determine the usefulness of MRI measurements in patients with pure akinesia with gait freezing (PAGF), Richardson's syndrome, and Parkinson's disease for diagnosis. We obtained MRI measurements for patients with PAGF, Richardson's syndrome, or Parkinson's disease: 9 patients with PAGF, 26 with Richardson's syndrome, and 93 with Parkinson's disease. We measured the area of the pons and midbrain on midsagittal MRIs and the midbrain width on axial MRIs. We also calculated the mean values of the superior cerebellar peduncle, middle cerebellar peduncle, and cerebral crus width; the pons area-to-midbrain area ratio; the middle cerebellar peduncle width-to-superior cerebellar peduncle width ratio; and the magnetic resonance (MR) Parkinsonism index. The Richardson's syndrome group had the highest pons area-to-midbrain area ratio and MR Parkinsonism index; the Parkinson's disease group had the lowest values. The Parkinson's disease group also had the highest midbrain width and cerebral crus width, with the lowest values being seen in the Richardson's syndrome group. The PAGF group had the intermediate values of the pons area-to-midbrain area ratio and MR Parkinsonism index between the Richardson's syndrome group and the Parkinson's disease group, whereas significant differences were found only in the pons area-to-midbrain area ratio. Results from receiver operating characteristic curve analyses showed that the pons area-to-midbrain area ratio has a higher sensitivity, specificity, and accuracy than the MR Parkinsonism index. The pons area-to-midbrain area ratio is more useful to distinguish PAGF from Richardson's syndrome and Parkinson's disease than the MR Parkinsonism index.


Streamlined approach to mapping the magnetic induction of skyrmionic materials.
Recently, Lorentz transmission electron microscopy (LTEM) has helped researchers advance the emerging field of magnetic skyrmions. These magnetic quasi-particles, composed of topologically non-trivial magnetization textures, have a large potential for application as information carriers in low-power memory and logic devices. LTEM is one of a very few techniques for direct, real-space imaging of magnetic features at the nanoscale. For Fresnel-contrast LTEM, the transport of intensity equation (TIE) is the tool of choice for quantitative reconstruction of the local magnetic induction through the sample thickness. Typically, this analysis requires collection of at least three images. Here, we show that for uniform, thin, magnetic films, which includes many skyrmionic samples, the magnetic induction can be quantitatively determined from a single defocused image using a simplified TIE approach.


Improved synthesis of antibacterial 3-substituted 6-anilinouracils.
3-Substituted 6-anilinouracils, presently the most promising class of inhibitors of the bacterial DNA polymerase in Gram-positive bacteria, have been prepared by a general and straightforward three-step procedure starting from a readily available 1-benzyloxymethyl-protected derivative of 6-chlorouracil.


Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos).
Confocal laser endomicroscopy enables real-time in vivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were enrolled. The colonic mucosa was examined with high-definition colonoscopy, histopathology, and CLE at 4 colonic sites. Subsequently, patients requiring medical treatment escalation were referred for repeat endoscopy with CLE after 6 to 8 weeks. The baseline frequency of fluorescein leakage (P < .001), microerosions (P < .001), tortuosity of the crypts (P = .001), distortion of the crypts openings (P = .001), presence of inflammatory infiltrates (P < .001), and decreased crypt density (P < .001) were significantly higher in active ulcerative colitis compared with inactive ulcerative colitis and control subjects. A decrease in histopathologic score after medical treatment escalation was correlated with improvement in crypt tortuosity (rs = .35, P = .016), distortion of crypt openings (rs = .30, P = .045), and decreased crypt density (rs = .33, P = .026) but not in other features. CLE is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( NCT01684514.).


In vitro percutaneous penetration through hairless rat skin: influence of temperature, vehicle and penetration enhancers.
Theoretically, a positive relation is expected between skin temperature and the percutaneous penetration of topically applied substances. The aim of the present study was to evaluate the influence of the temperature on the in vitro percutaneous penetration of dihydrotestosterone. Hairless rat skin was mounted in static diffusion cells placed in a water bath at different temperatures (28.6, 35.1 and 38.2 degrees C, respectively). Different vehicles were tested as well as the addition of penetration promoting molecules such as oleic acid and limonene. A saline buffer was used as the receptor phase. Penetration through the skin was evaluated by means of scintillation counting of the radiolabelled dihydrotestosterone. Experiments were followed for a period of 29 h. The total amount of penetrant, dihydrotestosterone, as well as the flux, were calculated from these kinetics. Our results demonstrate a temperature effect with the highest penetration at 38.2 degrees C. The vehicle was also found to influence the penetration of dihydrotestosterone in a significant way. Furthermore, limonene presented better penetration promoting properties compared with oleic acid.


SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma.
The 20S proteasome is a multicatalytic enzyme complex responsible for intracellular protein degradation in mammalian cells. Its antigen level or enzymatic activity in blood plasma are potentially useful markers for various malignant and nonmalignant diseases. We have developed a method for highly selective determination of the 20S proteasome using a Surface Plasmon Resonance Imaging (SPRI) technique. It is based on the highly selective interaction between the proteasome's catalytic β5 subunit and immobilized inhibitors (the synthetic peptide PSI and epoxomicin). Inhibitor concentration and pH were optimized. Analytical responses, linear ranges, accuracy, precision and interferences were investigated. Biosensors based on either PSI and epoxomicin were found to be suitable for quantitative determination of the proteasome, with a precision of ±10% for each, and recoveries of 102% and 113%, respectively, and with little interference by albumin, trypsin, chymotrypsin, cathepsin B and papain. The proteasome also was determined in plasma of healthy subjects and of patients suffering from acute leukemia. Both biosensors gave comparable results (2860 ng·mL-1 on average for control, and 42300 ng·mL-1 on average for leukemia patients).FigureThe synthetic peptide aldehyde Z-Ile-Glu(OBut)-Ala-Leu-H (PSI) and a microbial α',β' epoxyketone peptide epoxomicin was used to develop SPRI biosensor for the highly selective determination of the 20S proteasome concentration, and to evaluate the sensor applicability for the determination of 20S proteasome in human blood plasma.


Melanoma, thyroid, cervical, and colon cancer risk after use of fertility drugs.
This study was undertaken to evaluate melanoma, thyroid, colon, and cervical cancer risks after clomiphene or gonadotropins. Retrospective cohort of 8422 women (155,527 women-years) evaluated for infertility (1965-1988). Through 1999, cancers were ascertained by questionnaire, cancer and death registries. Poisson regression estimated adjusted rate ratios (RRs). Clomiphene use did not significantly increase risk of melanoma (RR=1.66; 95% CI, 0.9-3.1), thyroid (RR=1.42; 95% CI, 0.5-3.7), cervical (RR=1.61; 95% CI, 0.5-4.7), or colon cancer (RR=0.83; 95% CI, 0.4-1.9). We found no relationship between clomiphene dose or cycles of use and cancer risk at any site. Clomiphene use may impart stronger effects on risks of melanoma (RR=2.00; 95% CI, 0.9-4.6) and thyroid cancer among women who remained nulliparous (RR=4.23; 95% CI, 1.0-17.1). Gonadotropins did not increase cancer risk for these sites. Fertility drugs do not appear to have strong effects on these cancers. Nonetheless, follow-up should be pursued to assess long-term risks and to monitor effects among women who remain nulliparous.


Multilayer neural networks for solving a class of partial differential equations.
In this paper, training the derivative of a feedforward neural network with the extended backpropagation algorithm is presented. The method is used to solve a class of first-order partial differential equations for input-to-state linearizable or approximate linearizable systems. The solution of the differential equation, together with the Lie derivatives, yields a change of coordinates. A feedback control law is then designed to keep the system in a desired behavior. The examination of the proposed method, through simulations, exhibits the advantages of it. They include easily and quickly finding approximate solutions for complicated first-order partial differential equations. Therefore, the work presented here can benefit the design of the class of nonlinear control systems, where the nontrivial solutions of the partial differential equations are difficult to find.


Posterior mandibular widening secondary to advancement sagittal split osteotomy: A retrospective study.
Patients sometimes spontaneously report a modification of the width of their lower face after an advancement bilateral sagittal split osteotomy (ABSSO). The main goal of our study was to assess the variation of the bigonial distance (BGD) before and after ABSSO in a group of patients. The second goal was to look for a possible relation between the variation of BGD and the amount of mandibular advancement. We conducted a retrospective radiological study on patients who underwent an isolated ABSSO (Obwegeser-Dal Pont II type osteotomy) for a class II malocclusion in our department over a 26 months period. The measures were made on standardized frontal and lateral teleradiographies taken before, one day and one year postoperatively. Fifty patients (36 females, 14 males; mean age: 24) could be included. BGD was significantly increased one day (+9.8mm, P<10(-3)) and one year after surgery (+4mm, P<10(-3)). There was no relation between the amount of mandibular advancement and the increase of BGD. Our results suggest that ABSSO is responsible for posterior mandibular enlargement which must be taken into account during the aesthetic preoperative assessment. Further studies are mandatory to identify the risk factors for this phenomenon.


At least three alternatively spliced mRNAs encoding two alpha subunits of the Go GTP-binding protein can be expressed in a single tissue.
Hybridization blot (Northern) analysis of mRNA coding for alpha subunits of the Go signal-transducing protein detects three bands at 5.7, 4.2, and 3.2 kilobases (kb). We showed previously that the largest is a splice variant coding for the type 2 form of the polypeptide (alpha o2) and the two smaller RNAs react with a probe specific for the seventh of the eight exons that code for the type 1 form (alpha o1). In the present work we demonstrate that the 3.2- and 4.2-kb mRNAs also result from alternative splicing, the splice site being located 31 nucleotides downstream from the termination codon of the open reading frame, and that therefore the alpha o mRNA is made up of at least nine exons. All three alpha o mRNAs are expressed in both heart and brain, more in the latter than the former, as well as in the hamster insulin-secreting tumor (HIT) cell from which the cDNAs encoding the splice variants had been cloned. In contrast, in lung and testis we found only the 5.7-kb alpha o2 mRNA. The same analysis was unable to detect alpha o-specific sequences in either kidney, pancreas (whole), spleen, or liver, while at the same time detecting strong bands for alpha s mRNA. A comparison of the nucleotide sequences of the 5'- and 3'-untranslated regions of the hamster cDNAs cloned here indicated that previously cloned alpha o cDNAs all belong to the same alpha o1A slice subclass derived from 3.2-kb mRNA. The comparison also revealed that the sequences of the untranslated regions are highly conserved among three species (rat, hamster, and brain). Their 3' tails are 99.1% (HIT versus bovine, 200 known bases) and 99.7% (HIT versus rat, 229 bases) identical, and their 5' leader sequences are 92.7% (HIT versus bovine, 165 known bases) and 90.7% (HIT versus rat, 670 bases) identical. This indicates that untranslated regions of mRNAs need not exhibit high degrees of species variation.


[Therapeutic adherence of patients with cardiovascular risk in primary care. REAAP project].
To describe the perceptions and daily experiences of primary care (PC) physicians in dealing with the lack of therapeutic adherence in patients with cardiovascular risk, as well as their expectations and possible areas for improvement. A qualitative study (within the framework of the REAAP project: Network of Experts in Adherence in Primary Care) carried out in several autonomous communities in Spain using an open-ended questionnaire completed by PC physicians and analyzed using the framework analysis method to guide the coding of the topics. Eighteen physicians participated, and three main themes were identified from their responses: an approach to adherence during clinical practice, barriers that hinder the appropriate adherence, and interventions to improve it. The strategies most frequently mentioned to facilitate patients' therapeutic adherence were improving physician-patient communication and continuity of care, involving community pharmacies, and simplifying treatment by prescribing drugs in fixed combinations. There is no single ideal strategy to facilitate therapeutic adherence, and it is necessary to combine several interventions to optimize it. The first step is to understand the problems and the tools available. Initiatives such as the REAAP project are an important means to improve patient adherence, and for healthcare personnel to recognize the importance that this issue deserves.


Human hepatoma cells synthesize and secrete insulin-like growth factor Ia prohormone under growth hormone control.
Nucleotide sequencing of cDNAs encoding human insulin-like growth factor I (IGF-I) predicts the existence of two different prohormone forms of IGF-I. The E peptide regions extend the carboxy-terminus of the 70 amino acid core IGF-I molecule (BCAD domains) by either an additional 35 (IGF-Ia) or 77 (IGF-Ib) amino acids. Employing antiserum directed against a peptide sequence unique to the E peptide region of IGF-Ia prohormone, we have identified EIa immunoreactive material (IR-EIa) in the conditioned medium of a human hepatoma cell line, HepG2. Human growth hormone (GH) had dose-dependent stimulatory effects on IR-EIa secretion; incubation of HepG2 cells with GH at maximal concentrations (1-5 micrograms/ml) increased specific IR-EIa in 24 h conditioned medium 3-fold. The addition of human placental lactogen, insulin, IGF-I, dexamethasone, beta-estradiol, or progesterone had no significant effect. Acid chromatography of HepG2 cell conditioned medium revealed a single elution peak of IR-EIa corresponding to M(r) = 12,000-20,000. There was no immunologically detectable 7500 M(r) IGF-I peptide in acid-chromatographed conditioned medium under either basal or stimulated conditions. Biosynthetic labelling of HepG2 cell products with [35S]Trans label and immunoprecipitation with antisera specific to the E or to the AD regions of the IGF-Ia molecule indicated a single species of approx. 14,000 M(r). These data indicate that the E peptide region of IGF-Ia is translated and released as part of the larger molecule in cultured HepG2 cells, and that the levels of this prohormone are regulated by GH.


[Balancing Family and Career in Medicine: Greatly Desired but Given Little Consideration Results of the Study Arm VI of the KARiMED Study].
Family life and professional practice are both highly important for young physicians. Accordingly, a good balancing of both areas of life is necessary. Despite political framework conditions and legal requirements that have been in place for years, implementation of measures to achieve this seems to be difficult, especially in medicine, and is associated with great reservations and problems on the part of those involved. By means of an online survey, the medical mid-level staff from university and peripheral hospitals was questioned on topics related to family, children and professional biographical as well as career-relevant topics and subsequently analyzed on a gender-specific basis. Of the study participants, 65.1% were married and already had children or expressed a desire to have children (86.0%). Most were employed full-time (80.8%). The majority of part-time employees were female (87.4%). For 34.6%, there was a career break of 18.5±21.3 months, 87.8% of which were taken due to pregnancy or children. Female physicians generally took significantly more parental leave than male physicians (6-12 months: females 62.2%; males 22.4%; 12 months or more: females 25.2%; males 6.6%). Family planning received little support from superiors (21.2% much to very much support) and 45.6% reported having experienced problems with their return to work or career advancement. Almost 60% of the participants did not have any specific working time models in their own hospital for employees with children who need to be cared for. In order to implement a work-life balance for physicians, changes are first and foremost necessary on the part of the institutions. In addition, the respective superiors must rethink in order to enable a parallelization of these two areas of their employees' lives. However, young physicians must also rethink their view of this issue. Demanding changes in labor law while continuing traditional family constellations at home does not seem to do address this issue adequately.


Effect of a waste management intervention program on knowledge, attitude, and practice (KAP) of nurses and housekeepers: a quasi-experimental study, Egypt.
Improper healthcare waste management practice is alarming in developing countries because resources are inadequate and waste management is often delegated to poorly educated and untrained laborers. This study aimed to compare the pre-KAP versus post-KAP towards the waste management program for nurses and housekeepers. In addition, it aimed to explore possible factors affecting the pre- and post-KAP in Mansoura Emergency University Hospital, Egypt. One hundred thirty-three newly employed nurses, housekeepers, and those who need refreshment training as nominated by head nurses and link occupational health and safety nurses in the hospital were recruited for the study. The study's intervention included multiple training sessions using a PowerPoint presentation in Arabic with appropriate illustrations followed by an open discussion. An Arabic self-administered questionnaire containing demographic and occupational history, knowledge (27 questions), attitude (10 questions), and practice (9 questions) was used pre- and post-intervention. The overall KAP scores among the studied healthcare workers were significantly higher after the intervention. The pre- and post-knowledge scores were significantly different with respect to education, job description, and duration of employment (p < 0.05). The post-attitude scores were significantly different with respect to education and job description only (p < 0.05). The total pre-practice scores were significantly different with respect to education and job description (p < 0.05). However, the post-practice scores were significantly different with respect to sex, age, education, and job description (p < 0.05). There was a significant improvement in the KAP scores post-intervention. The post-knowledge and attitude scores were significantly better in nurses and participants with a higher education. The post-practice score was significantly better for females, participants with an age ≥ 30 years, higher education, and nursing jobs. The combination of training and supervision was crucial for the success of waste management programs. Higher education levels are required for housekeepers to be capable of gaining better knowledge, follow rules, and be ready for any challenges in the future.


EMGLAB: an interactive EMG decomposition program.
This paper describes an interactive computer program for decomposing EMG signals into their component motor-unit potential (MUP) trains and for averaging MUP waveforms. The program is able to handle single- or multi-channel signals recorded by needle or fine-wire electrodes during low and moderate levels of muscular contraction. It includes advanced algorithms for template matching, resolving superimpositions, and waveform averaging, as well as a convenient user interface for manually editing and verifying the results. The program also provides the ability to inspect the discharges of individual motor units more closely by subtracting out interfering activity from other MUP trains. Decomposition accuracy was assessed by cross-checking pairs of signals recorded by nearby electrodes during the same contraction. The results show that 100% accuracy can be achieved for MUPs with peak-to-peak amplitudes greater than 2.5 times the rms signal amplitude. Examples are presented to show how decomposition can be used to investigate motor-unit recruitment and discharge behavior, to study motor-unit architecture, and to detect action potential blocking in doubly innervated muscle fibers.


Posthypoxic disturbances in glutamatergic signal transduction in rat brain neurons: correction effect of preconditioning.
Severe 3-h hypobaric hypoxia was followed by impairment of Ca(2+)-mediated glutamatergic signal transduction in the posthypoxic period (no less than 72 h). This impairment manifested in changes in the calcium response to glutamate application in slices of rat brain cortex. Moderate hypoxic preconditioning prevented these disturbances developed over the first day after sever hypoxia.


Carbonic anhydrase inhibition and calcium transients in soleus fibers.
We simultaneously measured cytoplasmic Ca2+ transients using Fura-2 and isometric force in rat soleus fiber bundles. In the presence of the carbonic anhydrase inhibitor, chlorzolamide, we observed a decreased amplitude and retarded decay of the Ca2+ signal. This corresponded with a decreased isometric force and a retarded muscle relaxation. We conclude that muscle carbonic anhydrase participates in excitation-contraction coupling, possibly by rapidly providing protons that are exchanged for Ca2+ across the sarcoplasmic reticulum membrane.


Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation.
Interaction with integrin and focal adhesion kinase (FAK) regulates the cancer cell adhesion and invasion into extracellular matrix (ECM). In addition, phosphorylation of FAK correlates with the increase of cell motility and invasion. Adhesion and spreading of cancer cells on a variety of ECM proteins, including collagen type IV (Coll IV), leads to an increase in tyrosine phosphorylation and activation of FAK. In this study, we investigated the mechanism of activation of FAK and its downstream extracellular signal-regulated kinase (ERK)-1/2 signaling following stimulation by interleukin (IL)-1alpha and adhesion to ECM with subsequent enhancement of pancreatic cancer cell adhesion and invasion. In immunoblotting analysis, all three pancreatic cancer cell lines (AsPC-1, BxPC-3, and Capan-2) expressed the protein of FAK and beta1 integrin. Enhancement of FAK protein association with beta1 integrin when cells were plated on Coll IV was more increased by stimulation with IL-1alpha. Preincubation with anti-beta1 integrin antibody and FAK siRNA transfection inhibited the association of FAK with beta1 integrin of pancreatic cancer cells. FAK phosphorylation was observed by adhesion to Coll IV, furthermore, stronger FAK phosphorylation was observed by stimulation with IL-1alpha of pancreatic cancer cells adhered to Coll IV in time-dependent manner. Genistein, a tyrosine kinase inhibitor, markedly inhibited the FAK phosphorylation. IL-1alpha stimulation and Coll IV adhesion enhanced the activation of Ras, as evidenced by the increased Ras-GTP levels in pancreatic cancer cells. Activation of Ras correlated with the phosphorylation of ERK. While not statistical affecting the apoptosis of pancreatic cancer cells, IL-1alpha-induced adhesion and invasion on Coll IV were inhibited with FAK gene silencing by siRNA, beta1 integrin blocking, and inhibition of FAK phosphorylation. PD98059, a MEK inhibitor, also inhibited IL-1alpha-induced enhancement of adhesion and invasion in pancreatic cancer cells. Our results demonstrated that activation of FAK is involved with the aggressive capability in pancreatic cancer through Ras/ERK signaling pathway. Based on our results, we suggest that the modification of IL-1, FAK, and integrins functions might be a novel therapeutic approach to aggressive spread of pancreatic cancer.


Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors.
The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chemical, plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.


Correlation between apparent diffusion coefficient of magnetic resonance imaging and tumor-infiltrating lymphocytes in breast cancer.
To evaluate a possible correlation between apparent diffusion coefficient (ADC) value and tumor-infiltrating lymphocytes (TILs) level in breast cancer (BC). A second objective was to assess whether there were other histopathologic features that could affect mean ADC value. In this 4-year retrospective study were included 125 patients who underwent radical or modified mastectomy for monofocal BC. All subjects had performed preoperative MRI with the same 1.5-T machine and protocol, which consisted of STIR, DWI and DCE sequences. Based on TIL score, BCs were stratified into two groups: absent-low TIL (≤ 10%) and medium-high TIL (> 10%). The t test was used to correlate mean ADC value with TIL groups. Receiver operating characteristic curve and Youden index were used in order to identify ADC value threshold to distinguish the two TIL groups. BC patients with absent-low TIL level and medium-high TIL one were, respectively, 66 (52.8%) and 59 (47.2%). Mean ADC value was 1.05 ± 0.19 * 10-3 mm2 s-1. Absent-low TIL group showed a lower mean ADC value than medium-high TIL one (0.96 ± 0.18 * 10-3 mm2 s-1 vs 1.14 ± 0.16 * 10-3 mm2 s-1; p < 0.0001). ADC value threshold in order to distinguish the two TIL groups with maximum sensitivity (67.8%) and specificity (80.3%) was 1.03 * 10-3 mm2 s-1. ADC value was shown to be significantly related to TILs level (p < 0.0001) and cancer histotype (p = 0.0006), with a lower mean ADC value correlated to absent-low TIL level and ductal histotype. BCs with absent-low TIL showed a statistically significant lower mean ADC value than those with medium-high TIL. ADC value threshold in order to distinguish these two groups was 1.03 * 10-3 mm2 s-1.


Lack of blockade of central dopaminergic receptors by narcotics: comparison with chlorpromazine.
d-Amphetamine and saline were used as discriminative stimuli in rats. After 0.6 mg/kg d-amphetamine administration, food reinforcement was contingent upon pressin 1 lever in 2-lever operant chamber. Responding on the other lever was reinforced only after saline injection of equal volume. The animals learned to discriminate between d-amphetamine and saline to a criterion of 85% correct. Administration of 2.5, 5.0 and 7.5 mg/kg morphine, and 0.02 and 0.04 mg/kg fentanyl produced saline-appropriate responses. Pretreatment with morphine and fentanyl had no significant effect on the d-amphetamine induced discriminative stimulus. In contrast, 1.25 and 2.5 mg/kg chlorpromazine antagonized d-amphetamine discrimination. These results indicate that despite their similar effect on brain dopamine turnover, morphine and fentanyl do not act on the same receptor site(s) as the neuroleptics, that is, they probably do not block brain dopamine receptors.


The psychology of team interaction.
This paper aims to review psychological research results and methods which might be relevant to the issue of team interaction in the medical domain. The complex research on team performance is coherently organized into a proposed framework focussing in detail on task and social orientations of interacting team members.


Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer's disease.
Resolving glial contributions to Alzheimer's disease (AD) is necessary because changes in neuronal function, such as reduced synaptic density, altered electrophysiological properties, and degeneration, are not entirely cell autonomous. To improve understanding of transcriptomic heterogeneity in glia during AD, we used single-nuclei RNA sequencing (snRNA-seq) to characterize astrocytes and oligodendrocytes from apolipoprotein (APOE) Ɛ2/3 human AD and age- and genotype-matched non-symptomatic (NS) brains. We enriched astrocytes before sequencing and characterized pathology from the same location as the sequenced material. We characterized baseline heterogeneity in both astrocytes and oligodendrocytes and identified global and subtype-specific transcriptomic changes between AD and NS astrocytes and oligodendrocytes. We also took advantage of recent human and mouse spatial transcriptomics resources to localize heterogeneous astrocyte subtypes to specific regions in the healthy and inflamed brain. Finally, we integrated our data with published AD snRNA-seq datasets, highlighting the power of combining datasets to resolve previously unidentifiable astrocyte subpopulations.


Sustainable Polyvinyl Chloride-Derived Soft Carbon Anodes for Potassium-Ion Storage: Electrochemical Behaviors and Mechanism.
Soft carbon is a promising anode material for potassium-ion batteries due to its favorable properties such as low cost, high conductivity, stable capacity, and low potential platform. Polyvinyl chloride, as a white pollutant, is a soft carbon precursor that can be carbonized at varying temperatures to produce soft carbons with controllable defect and crystal structures. This work investigates the effect of carbonization temperature on the crystalline structures of the obtained soft carbons. In situ Raman spectroscopy was used to elucidate the adsorption-intercalation charge storage mechanism of potassium ions in soft carbons. Soft carbons prepared at the temperature of 800 °C have a defect-rich, short-range ordered structure, which provides optimal intercalation and adsorption sites for potassium ions, resulting in a satisfactory capacity of 302 mAh g-1 . This work presents new possibilities for designing soft carbon materials from recycling plastics for potassium-ion batteries.


Separation of fosetyl and phosphonic acid in food matrices with mixed-mode HPLC column coupled with tandem mass spectrometric detection and method application to other highly polar pesticides.
The aluminum salt of fosetyl (tris(ethyl phosphonate)) is an antifungal agrochemical. This paper presents a novel high performance liquid chromatography (HPLC) method for the simultaneous determination of fosetyl and the phosphonic acid, its main metabolite, in food samples. The method is based on an ion-displacement separation performed on the recently released Luna Omega PS C18 mixed-mode HPLC column. Baseline separation of fosetyl and phosphonic acid was feasible. This was achieved by optimizing the mobile phase composition and by introducing ethylenediaminetetraacetate for all matrices in the generally used extraction medium for polar pesticides and the injection solution. The binary mobile phase consisted of 10% (v/v) methanol in water and aqueous formate buffer (pH = 3.5) in gradient elution mode. The main advantages of the method over previous method include the stable retention time and peak resolution without the need for long column priming, conditioning or regeneration. Moreover, the approach was tested with other polar pesticides including glyphosate, glufosinate, and perchlorate and showed fit-for-purpose separation. The method was validated for spinach, cherry, and wheat flour samples, and was successfully applied on oat flour and arugula quality control samples. The results obtained for the five analytes met the requirements set by EU. The limit of quantifications was much lower than the maximum residue limits and ranged from 0.02 to 0.20 mg/kg.


Phase II Study of Recombinant Antitumor and Antivirus Protein Injection Compared With Placebo in Metastatic Colorectal Cancer After Failure of Standard Treatment.
Novaferon showed moderate efficacy and was well-tolerated in patients with metastatic colorectal cancer (mCRC), especially with the 20 μg injected 3 times a week strategy.Although Novaferon did not provide a survival benefit for mCRC patients who have failed standard treatment, it may play a role in improvement of immune function. To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens. We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 μg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 μg Novaferon injected 3 times per week, (c) 40 μg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival. There was no significant difference in overall survival among the four cohorts. The 20-μg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in the placebo group remained the same. Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-μg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients.


Risk factors for multidrug-resistant tuberculosis among tuberculosis patients in Serbia: a case-control study.
Multidrug resistant (MDR) tuberculosis (TB) represents TB which is simultaneous resistant to at least rifampicin (R) and isoniazid (H). Identifying inadequate therapy as the main cause of this form of the disease and explaining the factors leading to its occurrence, numerous social determinants that affect the risk of developing resistance are highlighted. The objectives of the study was to identify independent factors of MDR-TB among tuberculosis patients. Case-control study was conducted from 1st September 2009 to 1st June 2014 in 31 healthcare institutions in Serbia where MDR-TB and TB patients were treated. TB patients infected with MDR- M. tuberculosis and non MDR- M. tuberculosis strain were considered as cases and controls, respectively. Cases and controls were matched by the date of hospitalization. The data was collected using structured questionnaire with face to face interview. Bivariate and multivariable logistic regression analysis (MLRA) were used to identify determinants associated with MDR-TB. A total of 124 respondents, 31 cases and 93 controls were participated in the study. MLRA identified six significant independent risk factors for the occurrence of MDR-TB as follows: monthly income of the family (Odds ratio (OR) = 3.71; 95% Confidence Interval (CI) = 1.22-11.28), defaulting from treatment (OR = 3.33; 95% CI = 1.14-9.09), stigma associated with TB (OR = 2.97; 95% CI = 1.18-7.45), subjective feeling of sadness (OR = 4.05; 95% CI = 1.69-9.70), use of sedatives (OR = 2.79; 95% CI = 1.02-7.65) and chronic obstructive pulmonary disease (OR = 4.51; 95% CI = 1.07-18.96). In order to reduce burden of drug resistance, strategies of controlling MDR-TB in Serbia should emphasize multi-sectorial actions, addressing health care and social needs of TB patients.


Antibiotic Regimen Changes during Cystic Fibrosis Pediatric Pulmonary Exacerbation Treatment.
Rationale/Objectives: Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized. Methods: This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics. Results: In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV1) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (P = 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV1 were less for PEx with antibiotic changes than for those without changes (odds ratio [OR], 0.89 [95% confidence interval (CI), 0.80-0.98]). The odds of returning to ⩾100% of baseline ppFEV1 did not differ between PEx with versus without antibiotic changes (OR, 0.94 [95% CI, 0.86-1.03]). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 [95% CI, 1.12-1.22]). Conclusions: In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.


[Development of a system of quality indicators for primary care prescriptions].
To identify and validate indicators to improve the assessment of prescribing by primary care paediatricians, incorporating the values and views of the professionals involved. Nominal group technique, validated through a Delphi survey. Paediatricians and primary care pharmacists. A nominal group was formed with thirteen specialists. The question raised at the meeting was: "What indicators focusing on the drug and what indicators linked to diagnosis and treatment do you find most helpful in assessing the quality of prescription in paediatrics?", each panellist proposed indicators that were discussed and weighted on a scale from 1 to 9. The highest scored indicators were included in a two round Delphi survey, intended for all paediatricians and primary care pharmacists. Validity of the indicator; Indicators with a median score equal to or greater than 7 were considered valid. Degree of consensus; it was considered that there was consensus if the interquartile range was not more than 3 points. We generated 29 indicators focusing on the drug and 27 incorporating the diagnosis. Nineteen focusing on the drug and 13 incorporating the diagnosis were included in the survey. There was a high degree of agreement between the group and survey results. A set of quality indicators for paediatric prescribing has been generated using this tecnique, with consensus of a representative group of stakeholders and validated by all of them.


The sensitivity and specificity of the WHO's ICOPE screening tool, and the prevalence of loss of intrinsic capacity in older adults: A scoping review.
The World Health Organization has developed the Integrated Care for Older People (ICOPE) program, a public health strategy to maintain older adults' functional abilities and promote healthier aging. The approach comprises a 5-step pathway. Step 1 is the screening for impairment in functions, and Step 2 is an in-depth evaluation to confirm the presence and severity of functional impairment. These initial two steps are crucial to determine the subsequent plan of care (Step 3) and follow-up (Step 4). The fifth step encompasses actions to support families and caregivers and to engage communities. This review gathers data from the literature on the prevalence of positive screenings regarding intrinsic capacity detected by the program's first-step screening tool, and on currently available results regarding the instrument's sensitivity and specificity. Electronic searches were conducted in the PubMed, Cochrane, Embase, and SciElo databases, the medRxiv platform, and recent human aging scientific events, looking for research analyzing the ICOPE screening instrument. Studies reporting data on the prevalence of positive screenings for loss of intrinsic capacity using the proposed screening tool and/or findings on the instrument's sensitivity and specificity were included. A total of 7 publications with participants aged 50 years or more were selected. The prevalence of at least one impairment in intrinsic capacity detected by the instrument varied among the studies from 17.1 % to 94.3 %. Sensitivity ranged from 26.4 % to 100 % and specificity from 22 % to 96 %, depending on the setting and the assessed domain. Currently available data are heterogeneous, and different results were found among the studies due to diverse settings and methodologies. The evidence on the ICOPE screening tool's performance in different populations is still scarce and reinforces the need for further research worldwide.


EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma.
In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients. The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides. Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells. EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients.


Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.
Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.