Estimating Occupancy Levels in Enclosed Spaces Using Environmental Variables: A Fitness Gym and Living Room as Evaluation Scenarios.
The understanding of occupancy patterns has been identified as a key contributor to achieve improvements in energy efficiency in buildings since occupancy information can benefit different systems, such as HVAC (Heating, Ventilation, and Air Conditioners), lighting, security, and emergency. This has meant that in the past decade, researchers have focused on improving the precision of occupancy estimation in enclosed spaces. Although several works have been done, one of the less addressed issues, regarding occupancy research, has been the availability of data for contrasting experimental results. Therefore, the main contributions of this work are: (1) the generation of two robust datasets gathered in enclosed spaces (a fitness gym and a living room) labeled with occupancy levels, and (2) the evaluation of three Machine Learning algorithms using different temporal resolutions. The results show that the prediction of 3-4 occupancy levels using the temperature, humidity, and pressure values provides an accuracy of at least 97%.


Clinical results with 131I-toluidine blue and triple radionuclide subtraction for preoperative localization of enlarged parathyroid glands.
Clinical results from the application of a triple radionuclide subtraction study for preoperative localization of enlarged parathyroid glands are presented in this paper. A scintillation camera image was recorded after i.v. injection of 131I-toluidine blue. The contributions to this image from activity in the thyroid gland and in blood were determined after recording of additional images (obtained after injection of 99mTcO4- and 113mIn, respectively) using an iterative computer algorithm that also provides an estimate for a uniform background. Subtraction of these contributions gives an image that may be interpreted as an image of the selective accumulation of 131I-toluidine blue in the parathyroids. One or more enlarged glands were correctly localized in 17 of 21 cases, but in four cases there were only false positives. In ten cases the correctly localized glands weighed 900 mg or less.


Efficacy Assessment and Analysis of Related Factors of Ultrasound-Guided Percutaneous Lauromacrogol Injection for Cystic Thyroid Nodules.
This study aimed to investigate the factors influencing the short-term and long-term efficacy of sclerotherapy for cystic thyroid nodules. Ninety-nine cystic thyroid nodules that underwent ultrasound-guided fine-needle aspiration biopsy, detection of thyroglobulin in fine needle aspirate (Tg-FNA), and ultrasound-guided percutaneous lauromacrogol injection were retrospectively enrolled from July 2018 to July 2021. All nodules were followed up at 3 and 12 months after the procedure. Factors related to lauromacrogol injection efficacy, including initial volume, vascularity, pathological types, and Tg-FNA level, were analyzed. The nodules were classified as non-effective (VRR <50%) and effective groups (VRR ≥50%) at 3 months to evaluate short-term prognosis, and non-cured (VRR <90%) and cured groups (VRR ≥90%) at 12 months to evaluate long-term prognosis. The volume of cystic thyroid nodules tended to shrink during follow-up. The resolution rate was 79.80% (79/99) at 3 months and 96.91% (94/97) at 12 months. The cure rate was 80.41% (78/97) at 12 months. Independent factors for the long-term prognosis included Tg-FNA level and vascularity (P < .05). Only Tg-FNA level was an independent factor for the short-term prognosis (P < .05). The area under the receiver operating characteristic curve for assessing the efficacy at 3 months was 0.79 (95% confidence interval [CI]: 0.65-0.89). With a cutoff value of Tg-FNA 126.92 ng/mL, the specificity was 0.70, and the sensitivity was 0.85. Ultrasound-guided percutaneous lauromacrogol injection is an effective treatment option for cystic thyroid nodules. It is less effective in viscous or vascular predominantly cystic nodules.


Knowledge mobilisation in healthcare: a critical review of health sector and generic management literature.
The health policy domain has displayed increasing interest in questions of knowledge management and knowledge mobilisation within healthcare organisations. We analyse here the findings of a critical review of generic management and health-related literatures, covering the period 2000-2008. Using 29 pre-selected journals, supplemented by a search of selected electronic databases, we map twelve substantive domains classified into four broad groups: taxonomic and philosophical (e.g. different types of knowledge); theoretical discourse (e.g. critical organisational studies); disciplinary fields (e.g. organisational learning and Information Systems/Information Technology); and organisational processes and structures (e.g. organisational form). We explore cross-overs and gaps between these traditionally separate literature streams. We found that health sector literature has absorbed some generic concepts, notably Communities of Practice, but has not yet deployed the performance-oriented perspective of the Resource Based View (RBV) of the Firm. The generic literature uses healthcare sites to develop critical analyses of power and control in knowledge management, rooted in neo-Marxist/labour process and Foucauldian approaches. The review generates three theoretically grounded statements to inform future enquiry, by: (a) importing the RBV stream; (b) developing the critical organisational studies perspective further; and (c) exploring the theoretical argument that networks and other alternative organisational forms facilitate knowledge sharing.


Combating childhood obesity: Reactions of children aged 10-11 years towards the National Child Measurement Programme.
The aim of this study was to explore the reactions of children aged 10-11 years towards being weighed and measured and subsequently told their correct weight as part of the National Child Measurement Programme (NCMP). The study was undertaken in primary schools in a Primary Care Trust (PCT) in the North East of England, UK. One-to-one semi-structured interviews were conducted post-NCMP measurement (and the feedback) with a sample of 21 children, aged 10-11 years, conveniently sampled from the primary schools in the PCT. Findings from the study indicate that the NCMP, especially the weight feedback letter caused annoyance, panic and worry among children who were indicated to have weight problems and oversensitised all children about weight issues, regardless of their weight category. The NCMP is a potentially useful 'wake-up call' to the fact that something needs to be done for children identified to be overweight or obese but needs to be delivered with a sensitivity to the impact of the news on the child.


Cardiac transplantation.
Cardiac transplantation has proven to be an effective and life-saving option for those patients with congestive heart failure who deteriorate despite maximal medical management. The recipients have been able to return to life as productive citizens with improved quality as well as quantity of life. Advances in assist-device technology will mean that more patients will survive until donor hearts become available and ultimately may supplement the organ supply by serving as an alternative to transplant in some patients.


High-throughput screening of the static friction and ideal cleavage strength of solid interfaces.
We present a comprehensive ab initio, high-throughput study of the frictional and cleavage strengths of interfaces of elemental crystals with different orientations. It is based on the detailed analysis of the adhesion energy as a function of lateral, γ(x, y), and perpendicular displacements, γ(z), with respect to the considered interface plane. We use the large amount of computed data to derive fundamental insight into the relation of the ideal strength of an interface plane with its adhesion. Moreover, the ratio between the frictional and cleavage strengths is provided as good indicator for the material failure mode - dislocation propagation versus crack nucleation. All raw and curated data are made available to be used as input parameters for continuum mechanic models, benchmarks, or further analysis.


Cumulative risk assessment of phthalates in edible vegetable oil consumed by Chinese residents.
Phthalates have been widely used as plasticizers in various industries and are widely focused on in the international community as a result of their reproductive toxicity. Exposure of Chinese residents to phthalates via edible vegetable oil occurs often. In the present study, gas chromatography-mass spectrometry was used to detect the two main phthalates bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) in four major edible vegetable oil sources: an edible oil blend, soybean oil, peanut oil and rapeseed oil (a total of 1016 samples), as collected throughout China. Furthermore, cumulative risk assessment was used to estimate the reproductive health risk to Chinese residents caused by the phthalates that come from edible vegetable oils. Both phthalates were detected in four major edible vegetable oil sources. The phthalate with the highest detection rate was DBP (13.48%), followed by DEHP (7.78%). The results of the cumulative risk assessment showed that the hazard indices of these two phthalates in edible vegetable oils were less than 1, except in soybean oil. Nevertheless, the two phthalates had the lowest detection rates in soybean oil, which were 1.94% (DEHP) and 5.16% (DBP). In China, contamination levels of phthalates in the soils where oil crops are cultivated have a great influence on the phthalate concentrations in edible vegetable oils. It is recommended that Chinese residents who are consuming soybean oil choose well-known brands and regularly change their brand of consumption. The phthalates in edible vegetable oils pose a relatively small reproductive health risk to Chinese residents. © 2019 Society of Chemical Industry.


FGF21 promotes myocardial angiogenesis and mediates the cardioprotective effects of exercise in myocardial infarction mice.
The mechanism by which aerobic exercise promotes cardiac function after myocardial infarction (MI) is still not fully understand. In this study, we investigated the role of fibroblast growth factor 21 (FGF21) in exercise protecting the cardiac function of MI mice. In vivo, MI was induced by left anterior descending coronary artery ligation in wild-type and fgf21 knockout mice on the C57BL/6 background. One week after MI, the mice underwent aerobic exercise for 4 wk. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with H2O2, recombinant human FGF21 (rhFGF21), fibroblast growth factor receptor 1 (FGFR1) inhibitor (PD166866), and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) to explore the potential mechanisms. Scratch wound healing and tubule formation analysis were used to detect the migration and tubule formation ability of HUVECs. Our results showed that aerobic exercise significantly promoted angiogenesis and cardiac function through enhancing the expression of FGF21 and activating FGFR1/PI3K/AKT/VEGF pathway. But such changes in cardiac from aerobic exercise were attenuated by fgf21 knockout mice. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) enhanced angiogenesis and cell migration through FGF21/FGFR1/PI3K/AKT/VEGF signaling pathway. Under the intervention of H2O2, rhFGF21 also played the role of promoting angiogenesis and cell migration through the same mechanism. In conclusion, our results showed that FGF21 promoted the aerobic exercise-induced angiogenesis and improved cardiac function via FGFR1/PI3K/AKT/VEGF signal in MI mice.NEW & NOTEWORTHY FGF21 activated FGFR1/PI3K/AKT/VEGF signaling pathway mediated angiogenesis in MI mice. FGF21 deficiency attenuated aerobic exercise-induced cardiac angiogenesis in MI mice. FGF21/FGFR1/PI3K/AKT/VEGF signal played an important role in aerobic exercise to promote myocardial angiogenesis and improved cardiac function.


Corneal opacities in Gaucher disease.
To describe the corneal findings in a variant of Gaucher disease. Case report. In an 18-year-old man, ophthalmic and general clinical evaluation, and enzymatic and molecular genetics studies were performed. Diffuse, well-defined, small, linear, or dotlike corneal opacities were observed through, out the posterior two thirds of the corneal stroma in both eyes. The patient had calcific valvular heart disease. Enzymatic and ultrastructural studies were consistent with Gaucher disease. Analysis of the glucocerebrosidase gene disclosed homozygosity for a D409H mutation. Corneal opacities are a distinguishing ocular feature of the variant of Gaucher disease associated with the D409H mutation and with calcific cardiac disease.


Grass production and decomposition in Southern Guinea savanna, Nigeria.
Annual grass production in ungrazed plots was 2,731 kg ha-1, litter production was 1,619 kg ha-1 and decomposition was 1,789 kg ha-1. In grazed plots the corresponding figures were 3,157 kg ha-1, 1,440 kg ha-1, and 1,475 kg ha-1 respectively; cattle consumed 1,405 kg ha-1. Litter disappearance was greatest in the dry season: 1,226 kg ha-1 (69% of the annual total) disappearing in the 4 months of December to March in the ungrazed plots, largely due to consumption (790 kg ha-1 in December to March) by fungus-growing termites (Macrotermitinae). A positive linear relationship was found between maximum grass biomass and annual rainfall in West Africa.


POU-domain sequences from the flatworm Dugesia tigrina.
Redundant primers matching well-conserved sequences within vertebrate and invertebrate POU genes were used in the PRC (polymerase chain reaction) to detect three different POU-domain-containing genes within the genome of the flatworm, Dugesia tigrina. Two of these genes appear to be close homologues of class-III POU genes previously identified in Dugesia japonica, while the third represents a new class-III POU gene. Nucleotide sequences encoding highly related POU domains within the two species of planaria exhibited a surprisingly poor degree of shared identity. Since only class-III POU genes have been observed to date in flatworms, these genes may represent ancestral versions of the multiple classes of POU genes that exist in vertebrates, and may play important roles in the development of metazoan nervous tissue.


Mothers' stories about their experiences in the neonatal intensive care unit.
The purpose of this article is to let mothers tell the stories of their neonatal intensive care unit (NICU) experiences and to determine how well these experiences fit the Preterm Parental Distress Model. Interviews were conducted with 31 mothers when their infants were six months of age corrected for prematurity and were analyzed using the conceptual model as a framework. The analysis verified the presence in the data of the six major sources of stress indicated in the Preterm Parental Distress Model: (1) pre-existing and concurrent personal and family factors, (2) prenatal and perinatal experiences, (3) infant illness, treatments, and appearance in the NICU, (4) concerns about the infant's outcomes, (5) loss of the parental role, and (6) health care providers. The study indicates that health care providers, and especially nurses, can have a major role in reducing parental distress by maintaining ongoing communication with parents and providing competent care for their infants.


Exposure to IR Rotations in Osteopathic Medical Schools: Trends in Residency Applications and Matching.
Medical student exposure to interventional radiology (IR) through dedicated rotations represents a vital component for students to consider IR as a career and to ensure a successful match into the integrated residency pathway. Students from osteopathic medical schools have historically been underrepresented in integrated IR positions. During the 2022 match, 84.1% of successfully matched applicants overall were from U.S. allopathic medical schools, whereas 15.9% were from osteopathic medical schools. This brief report aims to categorize the landscape of IR rotation exposure at osteopathic medical schools and proposes a framework to increase student access to IR.


Are radiographic indices reliable indicators for quantitative bone mineral density and vitamin D status after femoral neck fractures? A retrospective study in 112 elderly patients.
Radiographic parameters and indices obtained from hip x-rays are a potential tool to promptly estimate bone quality in elderly hip fracture patients. Preoperative decision in whether to use cemented or cement augmented implants might be supported by this information and thus improve patient safety. Subsequently, this study was conducted to evaluate radiographic parameters as a prescreening tool for bone quality. A retrospective analysis of 112 elderly patients with a femoral neck fracture after low-energy trauma was performed (81 % female, 19 % male). Three radiological indices were calculated on hip x-rays: cortical index antero-posterior CTI (ap), cortical index lateral CTI (lat) and canal to calcar ratio CCR. These indices were analyzed for correlations with DXA T-Scores and serum 25-hydroxyvitamin D (25(OH)D) using the Spearman test. Median age of patients was 80 (IQR 72-86) years. A linear correlation was found for CTI (lat) and T-Score at the total hip (p < 0.001, r = 0.589), femoral neck (p = 0.005, r = 0.405) and the lumbar spine (p = 0.002, r = 0.299). A significant correlation was also indicated between CTI (lat) and 25(OH)D (p = 0.002, r = 0.293). CTI (lat) at a cut-off level of 0.4 showed a sensitivity of 79 % and a specificity of 56 % in predicting a T-score ≤ -2.5 at the total hip. Gender specific analysis revealed a higher sensitivity (100 %) and specificity (73 %) of CTI (lat) at a cut-off level of 0.4 for men. For severe vitamin D deficiency (<10 ng/ml) sensitivity and specificity were 75 % and 65 %. Radiographic indices as the CTI (lat) exhibit a direct correlation to BMD and serum 25OH vitamin D levels. A CTI (lat) cut-off level of 0.4 is recommended for identifying patients at risk of osteoporosis expressed by T-Scores ≤ -2.5 and severe vitamin D deficiency.


Elective neck management for high-grade salivary gland carcinoma.
To determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). Between October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3-34years). Occult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. Patients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection.


Pharmacokinetics of tetrodotoxin in puffer fish Takifugu rubripes by a single administration technique.
Marine puffer fish accumulates tetrodotoxin (TTX) in the liver and ovary. In this study, we examined the pharmacokinetics of TTX in Takifugu rubripes by a single administration under general anesthesia at 20 degrees C for 300 min. The blood concentration-time profile showed multiple distinct phases after injection into hepatic portal vein. The area under the blood concentration-time curve (AUC) increased linearly at the dosage of 0.25-0.75 mg TTX/kg body weight, and the total body clearance was 2.06+/-0.17 mL/min/kg body weight. The AUCs following administration into the hepatic portal vein and hepatic vein were closely similar (147+/-33 versus 141+/-1 ng.min/microL), indicating negligible hepatic first-pass effect. Comparison of the AUCs following an administration to the hepatic vein and gastrointestinal tract (0.25 mg TTX/kg body weight) elucidated the bioavailability of TTX to be 62%. There was no significant increase in the AUCs following direct injection into the gastrointestinal tract (0.50 versus 1.0 mg TTX/kg body weight). At the dosage of 0.25 mg TTX/kg body weight into the hepatic vein, hepatic portal vein or gastrointestinal tract, TTX amount in the liver accounted for 84+/-6%, 70+/-9% or 49+/-17% of the total TTX amount applied, respectively. These results demonstrate that TTX is absorbed into the systemic circulation from the gastrointestinal tract by saturable mechanism and finally accumulated in the liver within 300 min.


Medium effects on the antioxidant activity of dipyridamole.
Very strong medium effects have been observed when testing the antioxidant activity of dipyridamole (DP) in different media such as benzene, tert-butanol, methanol solutions and egg yolk lecithin unilamellar and multilamellar vesicles. Actually, dipyridamole behaves as a very poor antioxidant in benzene while its ability to inhibit the lipid peroxidation reaction increases with increasing solvent polarity, being the highest in lipid vesicles. This behavior can not be rationalized on the basis of the classical chain breaking mechanism which operates in the case of phenolic and amine antioxidants and involving the transfer of a hydrogen atom to peroxyl radicals. An explanation is instead given in terms of an electron transfer reaction which leads to the oxidation of DP by the chain carrying peroxyl radical to give the dipyridamole cation radical, DP+*, and the peroxyl anion LOO-, and whose rate constant is expected to increase in strongly polar media. EPR and electrochemical data supporting this interpretation have been collected.


Gastroschisis and low incidence of early-onset infection: a case for antimicrobial stewardship.
Early onset infection (EOI) in gastroschisis is rare. Excess antibiotic exposure in neonates increases necrotizing enterocolitis and mortality. We evaluated antibiotic exposure and EOI in gastroschisis. Retrospective cohort analysis between 2010-2016 in the Children's Hospital Neonatal Database. Included: Infants ≥32 weeks with gastroschisis admitted <48 h. Excluded: major anomalies or surgical intervention prior to admission. EOI diagnosis (<72 h). In 2021 patients with gastroschisis, median gestational age was 36 weeks (IQR 35, 37). 93.9% patients received empiric antibiotics after delivery, with median 7 days duration (IQR 3, 9). Only 13 patients (0.64%) had early positive blood culture. The rate of late onset blood stream infection (7.08%) was higher, and higher in complex (18%) than simple gastroschisis (4.8%, p < 0.001). Despite low incidence of EOI and risks of excess antibiotic exposure, neonates with gastroschisis are exposed to long courses of empiric antibiotics. These data should stimulate interinstitution work to improve antibiotic prescribing.


Spatial variability in the nutrient composition of Populus tremuloides: clone-to-clone differences and implications for cervids.
Populus tremuloides, a clonal angiosperm, is a major food item for many temperate-region herbivores. Clonal variation in chemical composition has potentially important implications for vertebrate herbivores because a single clone may be areally large and hence, may comprise a large part of available forage. The objectives of this study were: (1) to examine spatial variability in nutrient concentrations and quality within and among 24 clones of trembling aspen, and (2) to evaluate these differences with respect to cervid nutritional requirements; notably Cervus elaphus and Odocoileus hemionus. Between-clone concentrations of all chemical components were significantly different. In terms of cervid nutrition, most clones provided adequate concentrations of Ca, Mg, Mn, and Zn. Crude protein was limiting in some clones and P in most. Additionally, P metabolism may be impaired by the high Ca:P ratios typical of some clones. Of the structural constituents, neutral detergent fiber showed the greatest intraclonal variability. Dry-matter digestibility varied sufficiently to conjecture that cervid energy balances may be affected. Overall, although clone-to-clone differences were not so substantial to conclude that selective browsing would be nutritionally cost-effective, it is proposed that cervids stand to benefit by fortuitously browsing on nutritionally superior clones owing to the multiplier effect.


How Do We Learn About Error? A Cross-Sectional Study of Urology Trainees.
This qualitative descriptive study aims to explore trainees' experiences of error disclosure (ED) during their surgical postgraduate training and the factors influencing the intention-behavior gap for ED. This study employs an interpretivist methodology and a qualitative descriptive research strategy. Data were collected using focus group interviews. Data coding was performed by the principal investigator using Braun and Clarke's reflexive thematic analysis. Themes were developed from the data in a deductive manner. Analysis was carried out using NVivo 12.6.1. All participants were at various stages of an 8-year specialist program under the auspices of the Royal College of Surgeons in Ireland. The training program involves clinical work in a teaching hospital under the supervision of senior doctors in their specialist field. Trainees attend mandatory communication skills training days throughout the program. Study participants were recruited using purposive sampling from a sampling frame of 25 urology trainees on a national training scheme. Eleven trainees participated in the study. Participants' stage of training ranged from first to final year. Seven key themes emerged from the data relating to the trainees' experiences of error disclosure and the intention-behavior gap for ED. These themes include observed positive and negative practice in the workplace, impact of stage of training, importance of interpersonal interactions, perceived blame/responsibility for multifactorial error or recognized complication, lack of formal training in ED, cultural aspects of the training environment and medicolegal issues around ED. While trainees recognize the importance of ED, personal psychological factors, negative environmental culture, and medicolegal concerns are significant barriers to the practice of ED. A training environment that focuses on role-modelling and experiential learning with adequate time for reflection and debriefing is paramount. Areas for further research include broadening the scope of this study of ED across different medical and surgical subspecialties.


Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.
Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3(+) regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, mast cell-derived AREG fully restored optimal Treg cell function. These findings reveal EGFR as a component in the regulation of local immune responses and establish a link between mast cells and Treg cells. Targeting of this immune regulatory mechanism may contribute to the therapeutic successes of EGFR-targeting treatments in cancer patients.


Linking childhood obesity to the built environment: a multi-level analysis of home and school neighbourhood factors associated with body mass index.
This study examines environmental factors associated with BMI (body mass index) levels among adolescents with the aim of identifying potential interventions for reducing childhood obesity. Students (n=1,048) aged 10-14 years at 28 schools in London, ON, completed a survey providing information on age, sex, height, weight, home address, etc., which was used to construct age-sex adjusted BMI z-scores. The presence of recreation opportunities, fast-food outlets and convenience stores was assessed using four areal units around each participant's home and school neighbourhood: "circular buffers" encompassing territory within a straight-line distance of 500 m and 1000 m; and "network buffers" of 500 m and 1000 m measured along the street network. School neighbourhoods were also assessed using school-specific "walksheds". Multilevel structural equation modeling techniques were employed to simultaneously test the effects of school-environment (Level 2) and home-environment (Level 1) predictors on BMI z-scores. Most participants (71%) had a normal BMI, 16.9% were overweight, 7.6% were obese, and 4.6% were considered underweight. Multilevel analyses indicated that built environment characteristics around children's homes and schools had a modest but significant effect on their BMI. The presence of public recreation opportunities within a 500 m network distance of home was associated with lower BMI z-scores (p<0.05), and fast-food outlets within the school walkshed was associated with higher BMI z-scores (p<0.05). Interventions and policies that improve children's access to publicly provided recreation opportunities near home and that mitigate the concentration of fast-food outlets close to schools may be key to promoting healthy lifestyles and reducing childhood obesity.


Persistent and new-onset symptoms after cholecystectomy in patients with uncomplicated symptomatic cholecystolithiasis: A post hoc analysis of 2 prospective clinical trials.
Laparoscopic cholecystectomy is the gold standard for treating biliary colic in patients with gallstones, but post-cholecystectomy abdominal pain is commonly reported. This study investigates which symptoms are likely to persist and which may develop after a cholecystectomy. Patients from 2 previous prospective trials who underwent laparoscopic cholecystectomy for symptomatic cholecystolithiasis were included. Patients completed questionnaires on pain and gastrointestinal symptoms before surgery and at 6 months follow-up. The prevalence of persistent and new-onset abdominal symptoms was evaluated. A total of 820 patients received cholecystectomy and were included, 75.4% female (n = 616/820) mean age 49.4 years (standard deviation 13.7). At baseline, 74.1% (n = 608/820) of patients met all criteria for biliary colic. Cholecystectomy successfully resolved biliary colic in 94.8% (n = 327/345) of patients, but 36.5% (n = 299/820) of patients reported persistent abdominal pain after 6 months of follow-up. The prevalence of most abdominal symptoms reduced significantly. Symptoms such as flatulence (17.8%, n = 146/820) or restricted eating (14.5%, n = 119/820) persisted most often. New-onset symptoms were frequent bowel movements (9.6%, n = 79/820), bowel urgency (8.5%, n = 70/820), and new-onset diarrhea (8.4%, 69/820). Postcholecystectomy symptoms are mainly flatulence, frequent bowel movements, and restricted eating. Newly reported symptoms are mainly frequent bowel movements, bowel urgency, and diarrhea. The present findings give clinical guidance in informing, managing, and treating patients with symptoms after cholecystectomy.


Effect of acute and chronic oral zinc administration in hyperprolactinemic patients.
The inverse relationship between zinc (Zn(++)) and prolactin (PRL) was detected in in vitro studies, whereas in vivo results are contradictory. In order to evaluate this controversial subject we studied patients with hyperprolactinemia. Basal serum Zn(++) levels and serum PRL response to acute and chronic oral Zn(++) administration were evaluated in seven patients with prolactinomas and one with idiopathic hyperprolactinemia. Serum PRL levels did not change after acute oral Zn(++) administration (37.5 mg), although Zn(++) levels increased from 1.11+/-0.15 to 2.44+/-0.39 mug/mL (P<0.05). ZnZn(++) administration (47.7 mg daily) during 60 days increased serum Zn(++) levels from 1.11 +/- 0.15 to 1.59 +/- 0.58 mug/mL (p < 0.05) but caused no change in serum PRL levels. The TRH tolerance test (200 mug) was performed before and after 60 days of Zn(++) administration, and PRL response to TRH was unchangeable and similar in both tests. We concluded that acute or chronic Zn(++) administration does not inhibit PRL secretion in basal condition or by TRH effect in hyperprolactinemic patients.


Fischoederius cobboldi: A scanning electron microscopy investigation of surface morphology of adult rumen fluke.
Adults Fischoederius cobboldi are conical-shaped, concave ventrally and convex dorsally, measures about 8-10mm in length and 4-6mm in width across the mid section. Scanning electron microscopy (SEM) of entire body showed that the tegumental surface exhibits highly corrugation and transverse folds alternating with grooves and without spines. At higher magnification, the surface of each fold is further increased with a meshwork of ridges separated by irregular-sized pits. The ventral surface has more complex corrugations and invaginations than those of the dorsal surface of the body. Both anterior and posterior suckers have thick edges covered with transverse folds and appear spineless. The genital pore is located at the anterior one-third of the body. There are two types of sensory papillae on the surface: type 1 is bulbous in shape and nipple-like tips, measuring 10-15 μm in diameter at the base, and also type 2 is a similar shape and has short cilia on tips. These sensory papillae occur in large clusters, each having between 7 and 25 units depending on the region of the body. Clusters of papillae on the ventral surface and around the anterior suckers tend to be more abundant and larger in size. The dorsal side of the body exhibit similar surface features, but papillae appear less numerous and are smaller. Corrugations and invaginations of the dorsal aspect are also less extensive than those on the ventral surface of the body.


Intravitreous hepatocyte growth factor in patients with proliferative diabetic retinopathy: a case-control study.
The aim of the present study was to evaluate the vitreous levels of hepatocyte growth factor (HGF) in patients with proliferative diabetic retinopathy (PDR) and to investigate its relationship with vascular endothelial growth factor (VEGF) and retinopathy activity. In addition, the relationship between intravitreous HGF levels and the presence of epiretinal membranes (ERM), as well as the expression of c-Met in ERM were also investigated. In this case-control study, serum and vitreous samples as well as ERM specimens were obtained during vitrectomy from 28 diabetic patients with PDR and 30 non-diabetic control subjects. HGF and VEGF were determined by ELISA and c-Met expression by immunohistochemistry. Vitreal levels of both VEGF and HGF were higher in patients with PDR in comparison with the control group (p<0.0001). However, after correcting for total vitreous protein concentration, HGF (ng/mg of proteins) was lower in diabetic patients than in non-diabetic control subjects (p=0.02). No correlation was detected between the vitreal levels of HGF and VEGF. In addition, intravitreous VEGF but not HGF was found to be related to PDR activity. Both diabetic patients and non-diabetic patients in whom ERM had been excised presented higher HGF intravitreous levels. Finally, a significant expression of c-Met in ERM membranes were observed in both diabetic patients with PDR and in non-diabetic subjects. In conclusion, both HGF and VEGF increased, but were not related, in the vitreous fluid of diabetic patients with PDR. Our findings suggest that HGF is related to pathological conditions in which fibroproliferative processes or wound healing are involved rather than with angiogenesis itself.


Tryptophan accumulation in Saccharomyces cerevisiae under the influence of an artificial yeast TRP gene cluster.
Plasmid pME559, carrying all five yeast TRP genes, was constructed. This plasmid is a yeast/Escherichia coli shuttle vector based on pBR322 and 2 micron-DNA sequences derived from plasmid pJDB207. We studied in yeast (i) the stability of the plasmid under selective and non-selective conditions, (ii) expression of all five TRP genes and (iii) tryptophan accumulation in yeast transformants. These studies were conducted in comparison with an earlier construction, pME554, which differs from plasmid pME559 in the expression of the TRP1 gene and which carries the TRP2 wild type instead of the TRP2fbr mutant allele. For stable maintenance of the plasmids in yeast a selection was necessary. Plasmid pME559 displayed normal expression of all TRP genes, and enzyme levels on average 23-fold higher than in the wild type strain were found. In comparison, the maximal tryptophan flux observed in such a plasmid-carrying strain was about ten-fold higher than the maximal flux capacity in the wild type strain.


Orthodontic approach to treat complex hypodontia using miniscrews in a growing patient.
This article reports orthodontic treatment of a case of hypodontia of five premolars in an 11-year-old female patient with a positive tooth size-arch length discrepancy in both dental arches. The patient had a straight profile with balanced facial growth. Setup manufacture revealed the possibility of achieving ideal occlusion by mesializing permanent molars up to 15 mm, in addition to keeping a primary molar in the dental arch. With the aid of absolute anchorage, the proposed mechanics was performed and the occlusion predicted in the setup was achieved, while profile and facial growth pattern were maintained. The use of miniscrews for extensive orthodontic movements was successful. Furthermore, one primary molar was extensively mesialized. The indication of gingivoplasty to correct gingival smile proved effective. This is considered a useful technique for orthodontists.


Case Report: A Rare Fungal Keratitis Caused by Plectosphaerella Cucumerina.
To report a rare case of fungal keratitis caused by Plectosphaerella cucumerina. This study retrospectively reviewed the medical records of a case of fungal keratitis. Silt-lamp biomicroscopy revealed corneal infiltration and epithelial defects. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were performed to assist in the diagnosis and evaluate corneal conditions. The isolate was identified as Plectosphaerella cucumerina by MALDI-TOF mass spectrometry. The patient was treated with topical 5% pimaricin and oral voriconazole for 1 month and recovered. Fungal keratitis caused by Plectosphaerella cucumerina is rare. AS-OCT and IVCM can help locate the lesion and diagnose fungal keratitis. Furthermore, MALDI-TOF mass spectrometry showed potential prospects in the identification of filamentous fungi. Plectosphaerella cucumerina rarely infects humans and is sensitive to antifungal agents such as pimaricin and voriconazole.


Quantification of relative mRNA expression in the rat brain using simple RT-PCR and ethidium bromide staining.
We developed a protocol for quantification of relative gene expression using reverse transcription-polymerase chain reaction (RT-PCR) without the use of radioisotopes, special equipment or extra nucleotide fragments, such as competitors. The relative gene expression of GABA(A) receptor beta(1) subunit (GABA(A)Rbeta(1)) and phospholipase C beta(4) subtype (PLCbeta(4)) in rat cerebrum and cerebellum were determined by comparing the ratio of PCR products generated by linear amplification of the target cDNA segments and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) cDNA segment as a reference. The density of PCR products was measured from digitized images of photographs of ethidium-bromide-stained agarose gels. The linear region of PCR amplification was within the linear range (from 0.3 to 12 ng DNA in a single band) of the detection system. The accuracy of the present method was <2-fold difference in gene expression in a single determination and a 1.5-fold difference was statistically significant after repeated measurements. The estimated relative expression of PLCbeta(4) was significantly higher in cerebellum than cerebrum, and that of GABA(A)Rbeta(1) was the same in these two regions. Using the present method, it is possible to quantify several different subunits and subtypes of known ion channel, neurotransmitter receptor and intracellular signaling enzyme gene families.


Impact of California's Senate Bill 27 on Antimicrobial-Resistant Escherichia coli Urinary Tract Infection in Humans: Protocol for a Study of Methods and Baseline Data.
Overuse of antibiotics contributes to antimicrobial resistance (AMR) and is a growing threat to human health worldwide. Previous work suggests a link between antimicrobial use in poultry and human AMR extraintestinal pathogenic Escherichia coli (E coli) urinary tract infections (UTIs). However, few US-based studies exist, and none have comprehensively assessed both foodborne and environmental pathways using advanced molecular and spatial epidemiologic methods in a quasi-experimental design. Recently, California enacted Senate Bill 27 (SB27), which changed previous policy to require a veterinarian's prescription for the use of antibiotic drugs, and which banned antibiotic use for disease prevention in livestock. This provided an opportunity to evaluate whether SB27 will result in a reduction in antimicrobial-resistant infections in humans. We describe in detail the methods implemented to achieve the overarching objective of this study to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTIs. A summary of the overall approach and the partnerships between Columbia University, George Washington University (GWU), Johns Hopkins Bloomberg School of Public Health, Kaiser Permanente Southern California (KPSC) Research and Evaluation, the Natural Resources Defense Council, Sanger Institute at Stanford University, Sutter Health Center for Health Systems Research, the University of Cambridge, and the University of Oxford is presented. The collection, quality control testing, and shipment of retail meat and clinical samples are described. Retail meat (chicken, beef, turkey, and pork) was purchased from stores throughout Southern California from 2017 to 2021. After processing at KPSC, it was shipped to GWU for testing. From 2016 to 2021, after clinical specimens were processed for routine clinical purposes and immediately before discarding, those with isolated colonies of E coli, Campylobacter, and Salmonella from KPSC members were collected and processed to be shipped for testing at GWU. Detailed methods of the isolation and testing as well as the whole-genome sequencing of the meat and clinical samples at GWU are described. KPSC electronic health record data were used to track UTI cases and AMR patterns among the cultured specimens. Similarly, Sutter Health electronic health record data were used to track UTI cases in its Northern California patient population. From 2017 to 2021, overall, 12,616 retail meat samples were purchased from 472 unique stores across Southern California. In addition, 31,643 positive clinical cultures were collected from KPSC members during the same study period. Here, we presented data collection methods for the study, which was conducted to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTI. To date, it is one of the largest studies of its kind to be conducted. The data collected during this study will be used as the foundation for future analyses specific to the various objectives of this large body of work. DERR1-10.2196/45109.


Review: the role of hyperthermia in treating pancreatic tumors.
There is only marginal improvement in outcome of treating pancreatic cancer in the last two decades. Time to open up and have a fresh look at complementary adjuvant treatment options. Hyperthermia may be one such option. Hyperthermic intraperitoneal chemotherapy (HIPEC) predominantly as a intrasurgical procedure has already proved its justification. Non-invasive loco regional hyperthermia as complement to either chemo or radiation has not yet reached a comparable status of evidence. However the potential to eventually grow into such evidence is already clearly observable. This review presents the various methodologies available for hyperthermia, covers the initial clinical data that has been published and gives an outlook to what can be expected in the next 2-3 years to come. Hyperthermia has the potential to significantly prolong life expectancies and this while maintaining a satisfying quality of life!


A case of tachycardia-induced cardiomyopathy due to chronic ectopic atrial tachycardia.
Only a few reports exist that chronic supraventricular tachycardia causes ventricular dilation and poor left ventricular contraction--so-called "tachycardia-induced cardiomyopathy." Clinical and electrophysiologic features of chronic supraventricular tachycardia including chronic persistent ectopic atrial tachycardia (EAT) in adults have also been described by a few investigators. We report a rare case of long follow-up of chronic EAT-induced severe cardiomyopathy and mitral regurgitation that was well controlled after medical treatment.


Operant conditioning of the short-latency cervical somatosensory evoked potential in quadriplegics.
Operant conditioning of short-latency cervical somatosensory evoked potentials (CSEP) was demonstrated in five cervical cord injury subjects. Subjects were conditioned to augment the N14 potential, thought to originate from the dorsal column nucleus. Increased N14 potential was associated with an increase in N19 and P22 potentials, and either a decrease (base) or no change (train) in the brachial plexus potential. The N19 potential was correlated with significant reductions in the sensation-twitch (S/T) ratio during conditioning sessions, indexing improved sensation to low-intensity percutaneous stimulation. Moreover, S/T ratios decreased significantly during conditioning sessions, and were reduced significantly relative to initial baseline values. The results do not appear to be associated with trivial mediating influences.


Design, synthesis, in vitro, and in silico biological evaluations of coumarin-indole hybrids as new anti-α-glucosidase agents.
A series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole. The thirteen various derivatives 4a-m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed. Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose. Compound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors.


Aggrecan and versican: two brothers close or apart.
Aggrecan (Acan) and versican (Vcan) are large chondroitin sulfate proteoglycans of the extracellular matrix. They share the same structural domains at both N- and C-termini. The N-terminal G1 domain binds hyaluronan (HA), forms an HA-rich matrix, and regulates HA-mediated signaling. The C-terminal G3 domain binds other extracellular matrix molecules and forms a supramolecular structure that stores transforming growth factor β (TGFβ) and bone morphogenetic proteins (BMPs) and regulates their signaling. EGF-like motifs in the G3 domain may directly act like an EGF ligand. Both Acan and Vcan are present in cartilage, intervertebral disc, brain, heart, and aorta. Their localizations are essentially reciprocal. This review describes their structural domains, expression patterns and functions, and regulation of their expression.


Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.
Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, imatinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFRα. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFRα/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFRβ-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFRα signaling was suggestive of protective effects against BBB dysfunction during the subacute phase of stroke. Vascular TGF-β1 expression was downregulated in both imatinib-treated and C-KO mice, along with sustained levels of MMP9. Therefore, PDGFRα effects may be mediated by TGF-β1 which exerts potent protective effects in the BBB.


Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.
The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.


'uidA-antibiotic-resistance cassettes for insertion mutagenesis, gene fusions and genetic constructions.
We have constructed a series of promoterprobe cassettes that provides powerful tools for insertion mutagenesis, transcription fusions and genetic constructions. These cassettes contain the Tn9 chloramphenicol (CmR) and the Tn903 kanamycin (KmR) resistance genes which are expressed in a large variety of microorganisms; these antibiotic-resistance markers were associated with the uidA promoterless gene. This beta-glucuronidase-encoding gene of Escherichia coli K-12 has been successfully used as reporter gene for various organisms including prokaryotes and eukaryotes. The resulting 'uidA-KmR and 'uidA-CmR cassettes (truncated at the ') can be excized with most of the commonly used restriction enzymes. Furthermore, they are borne by ApR or CmR plasmids which facilitate their utilization. These promoter-probe cassettes allow transcriptional signal localization and regulation studies.


CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review.
Despite improved understanding of the pathogenesis of neuroinflammatory disorders of the brain and development of new diagnostic markers, our biomarker repertoire to demonstrate and monitor inflammation remains limited. Using PubMed database, we reviewed 83 studies on CSF cytokines and chemokines and describe the pattern of elevation and possible role of cytokines/chemokines as biomarkers in viral and autoimmune inflammatory neurological disorders of the CNS. Despite inconsistencies and overlap of cytokines and chemokines in different neuroinflammation syndromes, there are some trends regarding the pattern of cytokines/chemokine elevation. Namely B cell markers, such as CXCL13 and BAFF are predominantly investigated and found to be elevated in autoantibody-associated disorders, whereas interferon gamma (IFN-γ) is elevated mainly in viral encephalitis. Th2 and Th17 cytokines are frequently elevated in acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO), whereas Th1 and Th17 cytokines are more commonly elevated in multiple sclerosis (MS). Cytokine/chemokine profiling might provide new insights into disease pathogenesis, and improve our ability to monitor inflammation and response to treatment.


Synthesis and anti-HBV activity of novel 3'-N-phenylsulfonyl docetaxel analogs.
Nine new 3'-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course.


The mucosal immune system of the respiratory tract.
Most viruses use host mucosal surfaces as their initial portals of infection. The respiratory tract has the body's second-largest mucosal surface area after the digestive tract. An understanding of the unique nature of the mucosal immune system of respiratory organs is therefore extremely important for the development of new-generation vaccines and novel methods of preventing and treating respiratory infectious diseases, including viral infections.


Effects of Microlectures on Nursing Students' Understanding of Key Medication Administration Concepts: A Quasi-Experimental Design.
Microlectures comprise short audio or video presentations designed to provide a concise explanation of key concepts or topics. The study aimed to develop a microlecture module for a nursing course in medication administration and test whether it could improve learning. The study had a quasi-experimental design. Four classes of sophomore nursing students were divided into the treatment (n = 109) and control groups (n = 84). Pretests, posttests, integrated examinations, and simulated experiences were employed. Analysis of covariance were used to analyze the students' pretest, posttest, and integrated examination performances. The treatment group performed better than the control group. This study provides nursing educators with a different approach to traditional teaching and sheds light on how to design a microlecture.


Indobufen versus aspirin in acute ischaemic stroke (INSURE): rationale and design of a multicentre randomised trial.
Indobufen can reversibly inhibit platelet aggregation and showed to be effective in the treatment of ischaemic heart and peripheral vascular diseases. However, it is unclear whether indobufen is an alternative antiplatelet agent for treatment of patients with ischaemic stroke. To test whether indobufen is non-inferior to aspirin in reducing the risk of new stroke at 3 months in patients with moderate to severe ischaemic stroke. The Indobufen vs Aspirin in Acute Ischaemic Stroke (INSURE) is a randomised, double-blind, double-dummy, positive drug control, non-inferior multicentre clinical trial conducted in 200 hospitals in China. Participants will be randomised at a 1:1 ratio to receive either 100 mg indofufen two times daily or 100 mg aspirin once daily within 72 hours of the onset of symptoms from day 1 to 3 months. The primary efficacy outcome is a new stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is a severe or moderate bleeding event within 3 months. The INSURE trial will evaluate whether indobufen is non-inferior to aspirin in reducing the risk of new stroke at 3 months in patients with moderate to severe ischaemic stroke. NCT03871517.


Long term effects of the anorectic agent fenfluramine alone and in combination with aminorex on pulmonary and systemic circulation in the pig.
We have investigated the effects of chronic oral administration of two anorectic substances, fenfluramine and aminorex, especially on the pulmonary circulation in young pigs with one ligated pulmonary artery. The pulmonary vascular reactivity was tested by alveolar hypoxia, alveolar hyperoxia and infusion of prostaglandin F2ALPHA. No elevation of pulmonary arterial pressures or resistances were found due to the intake of fenfluramine or aminorex over a three month period. The responses to the vasoconstrictor stimuli, hypoxia and prostaglandin F2alpha, and to the vasodilator stimulus, hyperoxia, were equal and not augmented in the drug groups. Fenfluramine or aminorex could therefore could therefore not be shown to have an adverse effect on the pulmonary circulation or on the reactivity of the pulmonary vascular bed in the pig, but fenfluramine elevated systemic arterial pressure.


Bioinformatics analyses show dysregulation of calcium-related genes in Angelman syndrome mouse model.
Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by the loss of function of the UBE3A protein in the brain. In a previous study, we showed that activity-dependent calcium dynamics in hippocampal CA1 pyramidal neurons of AS mice is compromised, and its normalization rescues the hippocampal-dependent deficits. Therefore, we expected that the expression profiles of calcium-related genes would be altered in AS mice hippocampi. We analyzed mRNA sequencing data from AS model mice and WT controls in light of the newly published CaGeDB database of calcium-related genes. We validated our results in two independent RNA sequencing datasets from two additional different AS models: first one, a human neuroblastoma cell line where UBE3A expression was knocked down by siRNA, and the second, an iPSC-derived neurons from AS patient and healthy donor control. We found signatures of dysregulated calcium-related genes in AS mouse model hippocampus. Additionally, we show that these calcium-related genes function as signatures for AS in other human cellular models of AS, thus strengthening our findings. Our findings suggest the downstream implications and significance of the compromised calcium signaling in Angelman syndrome. Moreover, since AS share similar features with other autism spectrum disorders, we believe that these findings entail meaningful data and approach for other neurodevelopmental disorders, especially those with known alterations of calcium signaling. This work was supported by the Angelman Syndrome Foundation and by the Israel Science Foundation, Grant Number 248/20.


Intraoperative stress and anxiety reduction with music therapy: a controlled randomized clinical trial of efficacy and safety.
The purpose of this study was to investigate the music therapy (MT) effect in levels of intraoperative anxiety in patients undergoing crossectomy with stripping of the great saphenous vein and to assess the efficacy, safety, and feasibility of this alternative therapy as a complement of standard intraoperative care. The study is a simple blind, controlled, parallel groups, prospective randomized clinical trial. Patients were allocated by means of randomized controlled sampling. The study was performed in the surgery room of Getafe University Hospital in Madrid. The study was carried out in 40 patients, 20 randomized to the experimental group and 20 randomized to the control group, with an age range from 27 to 70 years. The control group was given intraoperative routine attention, and the experimental group was given an MT passive intervention that consisted of audition of musical fragments during varicose veins surgery. These pieces previously showed relaxing actions on the cardiovascular system. The anxiety levels were measured by means of pre- and postsurgical questionnaires by a blinded investigator for the study arm to which the patients had been randomized. Heart rate and systolic and diastolic blood pressures were determined during the intervention, and adrenaline and noradrenaline plasma levels were determined before and after the surgical procedure. The majority of the patients in the MT group (95%) and standard care group (90%) completed the study. There were no statistical differences between the control and experimental groups in heart rate gradient or systolic and diastolic blood pressures measured after the intervention. The anxiety state and the stress feeling scale score after surgery were significantly inferior in the MT group (94.7% vs 57.9% decrease in anxiety levels, P < .05, and stress score of 1.31 vs 2.36, P < .05, respectively). The adverse events ratio was low and occurred with similar frequency in both groups. The MT intervention was easily implemented in the context of nursing care received during varicose vein surgery and was positively accepted and valued by the majority of the patients. MT is a safe procedure that is proved to reduce anxiety and stress in the study patients.


Anaerobic treatment of hydrothermally solubilised sugarcane bagasse and its kinetic modelling.
The aim of this study was the evaluation of anaerobic treatment for the soluble organics generated from a steam-explosion pre-treatment of sugarcane bagasse. The batch analysis revealed that about 50% of the organics was possible to be degraded into methane whilst the rest was biologically inert and composed of mostly lignin. Based on the experiment a kinetic model composed of 14 kinds of soluble substances and 5 kinds of anaerobic microorganisms was developed. The model was used to simulate the process performance of a continuous anaerobic bioreactor with MLSS concentration at 2500-15,000mg/L. The simulation indicated that the bioreactor could receive the influent until 0.4kg-COD/kg-MLSS/d of loading without significant deterioration of methane conversion. By addition of powdered activated carbon, the rest of unbiodegradable soluble organics and dark brown colour in the effluent were removed to 840mg-C/L and 760 unit respectively at adsorption of 190mg-C/g-PAC and 1200unit/g-PAC.


Effect of electrolyte and pH changes on the sinus node pacemaking in humans.
The importance of plasma electrolytes and pH levels in determining heart rate is not yet well grounded. Hemodynamic and biochemical data were collected during 8 purely diffusive hemodialysis, which allowed changes in extracellular fluid to be achieved without eliciting notable changes in the autonomic control of heart rate. A significant heart rate increase was obtained after potassium decrease and calcium and pH increase, with no significant variations in indices of autonomic activity. Model-based computer simulations were then used to separate the effects of each ionic species and pH on sinus node cell pacemaker activity. This analysis revealed that changes in physiological range of potassium, calcium, and pH could cause large heart rate variations from 60 to 90 bpm. Nonlinear heart rate dependence on potassium was also recognized. It was concluded that electrolyte and pH changes in physiological range have an important, complex, impact on the pacemaking rhythm independently of autonomic outflow.


Titanium dioxide nanotubes incorporated gellan gum bio-nanocomposite film for wound healing: Effect of TiO2 nanotubes concentration.
The synthesized titanium dioxide nanotubes (TiO2-NTs) were emerged as wound healing enhancer as well as exhibited significant wound healing activity on Sprague Dawley rats. In our present study, the blends of GG and TiO2-NTs bio-nanocomposite film was characterised by fourier transform infrared (FTIR), x-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis, atomic force microscopy (AFM). The morphology of TiO2-NTs was investigated using transmission electron microscopy (TEM). The mechanical properties study shows that the GG + TiO2-NTs (20 w/w %) bio-nanocomposite film possessed the highest tensile strength and young modulus which are (4.56 ± 0.15) MPa and (68 ± 1.63) MPa, respectively. GG + TiO2-NTs (20 w/w %) also displays the highest antibacterial activity with (16 ± 0.06) mm, (16 ± 0.06) mm, (14 ± 0.06) mm, and (12 ± 0.25) mm inhibition zone were recorded against Staphylococcus aureus, Streptococcus, Escherichia coli, and Pseudomonas aeruginosa. The prepared bio-nanocomposite films have good biocompatibility against 3T3 mouse fibroblast cells and caused accelerated healing of open excision type wounds on Sprague Dawley rat model. The synergistic effects of bio-nanocomposite film like good swelling and WVTR properties, excellent hydrophilic nature, biocompatibility, wound appearance and wound closure rate through in vivo test makes it a suitable candidate for wound healing applications.


Accommodation in phakic and pseudophakic eyes measured with subjective and objective methods.
To measure accommodation subjectively and objectively and assess anterior segment changes during accommodation in phakic eyes and pseudophakic eyes. Department of Ophthalmology, Medical Health and Science Centre, University of Debrecen, Debrecen, Hungary. Case series. Subjective and objective accommodation measurements and pupillometry were performed in phakic and pseudophakic patients. Refraction and pupil diameter were recorded with different accommodation stimuli. Corneal higher-order aberrations (HOAs) and anterior chamber depths (ACDs) were detected with a rotating Scheimpflug camera. The mean age of the 44 patients in the phakic group was 36.34 years ± 16.6 (SD) and of the 27 patients in the pseudophakic group, 69.3 ± 9.98 years. The mean subjective accommodation was 4.49 ± 3.48 diopters (D) in phakic eyes and showed significant correlation with age, spherical aberration, changes in pupil diameter, and ACD. The mean subjective accommodation was 0.50 ± 0.28 D in pseudophakic eyes. In phakic eyes, the mean objective accommodation was 0.46 ± 1.02 D, 1.06 ± 1.33 D, and 2.2 ± 1.9 D with 2.0 D, 3.0 D, and 5.0 D, respectively, of stimulus. In pseudophakic eyes, measurable objective accommodation was recorded. In phakic eyes, the correlations were significant between these values and age, changes in ACD, pupil size, and corneal spherical aberration. In pseudophakic eyes, the only correlation was with the spherical equivalent value. The magnitude of accommodation was greater with subjective measures than objective measures. In pseudophakic eyes, senile miosis and HOAs can be regarded as underlying factors in subjective accommodation; however, objective accommodation is not clinically significant. No author has a financial or proprietary interest in any material or method mentioned.


Genetic association of tumor necrosis factor-β, interleukin-10, and interleukin-1 gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients.
Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)β, interleukin (IL)-10, IL-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. Subjects comprised 33 kidney transplant recipients with pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these 96 kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the NcoI polymorphic site at position +252 of TNFβ gene, the RsaI polymorphic site at position -592 of IL-10 gene, and the AvaI polymorphic site at position -511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL-1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. Univariate analysis showed that recipient IL-10, IL-1β, and IL-1 RN polymorphisms were not associated with the presence of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG genotype, recipient TNFβ +252AA + AG genotype was significantly associated with susceptibility to pneumonia (P = .006). Age of 45 years or older was not significantly associated with susceptibility to develop pneumonia but had a tendency to develop it (P = .119). After adjusting for age of 45 years or older, recipient TNFβ+252 AA + AG genotype (odds ratio = 5.366, 95% confidence intervals = 1.470 - 19.589, P = .011) independently predicted the risk for pneumonia within the first year after kidney transplantation in the multivariate analysis. These results suggested that recipient TNFβ gene polymorphism may be useful in predicting pneumonia, hence identifying individuals who could benefit from preventive treatment and a less potent immunosuppression regimen.


The dynamics of the rec-system in variable environments: haploid selection in a cyclical two-state environment.
The dynamics of a 3-locus infinite population with non-overlapping generations and panmixia was studied. Loci are di-allelic: two loci affect fitness under cyclical symmetric haploid selection while the third one is a modifier of recombination (rec-modifier). Selection favors alternatively haplotypes AB and ab or Ab and aB. It has been proven that under alternating selection (when period of selection consists of two generations) a dominant suppressor of recombination is displaced and the allele for non-zero recombination becomes fixed within the population. For populations with inversion heterozygosity within the selective system (i.e. with zero recombination in heterozygote for rec-modifier and non-zero for homozygotes) fixation of one of the alleles (depending on the initial point) at the rec-modifier locus is predicted. For other values of recombination parameters, the behavior of the system was studied numerically. A full bifurcation picture of parameters was obtained. Many of the results related to the case of a two-generation period hold also in the case of longer period lengths.


Management of pneumatosis intestinalis in children over the age of 6 months: a conservative approach.
Pneumatosis intestinalis (PI) is an uncommon and poorly understood condition. Although it can be an incidental finding in asymptomatic individuals, it can also be secondary to life-threatening bowel ischaemia and sepsis. In premature infants, it is a pathognomonic sign of necrotising enterocolitis. There is no consensus regarding management and long-term outcome of children with PI. Review of our experience of PI in children beyond the early infantile period. Retrospective review of patient's records and radiological images from 2013 to 2015. Eighteen patients (three girls) had radiologically confirmed PI. The median age was 4.5 years (range 8 months-13 years). Background medical conditions (number): short bowel syndrome (one), congenital heart disease (two), sickle cell disease (one), epilepsy (three), cerebral palsy (six), myotonic dystrophy (four) and peroxisomal biogenesis defect (one).Six children (33%) presented with abdominal distension, four (22%) with abdominal pain, three (17%) with bilious vomiting, two (11%) with diarrhoea and one (6%) with rectal bleeding. Two (11%) were asymptomatic. One had air in portal vein and two had pneumoperitoneum.All patients with symptomatic PI were treated conservatively with successful outcome and complete resolution of PI. None required surgical intervention. PI in children who are not on chemotherapy or immunosuppressant appears to follow a benign course and is responsive to conservative management. In contrast to adults, portal venous gas and pneumoperitoneum do not predict the need for surgical intervention.


Nanoplastic adsorption characteristics of bisphenol A: The roles of pH, metal ions, and suspended sediments.
Nanoplastics (NPs) are widely found in the environment and can act as a vector for various toxic substances and promote their diffusion and bioenrichment, but the underlying mechanisms are largely unknown. Here, the adsorption characteristics of bisphenol A (BPA) onto NPs were explored. The results show that the adsorption of BPA on NPs was dominated by saturated single-layer adsorption and affected by both intra-particle diffusion and liquid film diffusion. Electrostatic interaction, π-π interaction, and hydrophobic effects played key roles in adsorption. In addition, the introduction of electrolytes inhibited the adsorption of BPA onto NPs. Interestingly, the introduction of suspended sediment promoted the formation of heterogeneous aggregates of NPs-SS, thereby reducing the adsorption capacity, indicating that aggregation may play an important role in the adsorption behavior of NPs. Overall, our results provide new insights into the adsorption behavior of BPA on NPs and the underlying mechanisms under different environmental conditions.


Peel oils from three Citrus species: volatile constituents, antioxidant activities and related contributions of individual components.
In the present study, peel oils were extracted through hydrodistillation and cold pressing from three Citrus species (Valencia orange, Ponkan and Eureka lemon) to investigate their volatile constituents and antioxidant activities. A total of 47 volatile components were identified by GC-MS, and then grouped by principal component analysis. The extraction methods were found to have an obvious effect on the proportion of terpenes and oxygenated compounds in the six Citrus oils, especially for Eureka lemon oils. The major fractions in the Citrus oils were found to be monoterpenes (78.65-96.57%), with limonene occupying a dominant percentage (51.22-86.65%). Furthermore, γ-terpinene and terpinolene displayed strong DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging abilities and efficient inhibition of lipid peroxidation, while oxygenated compounds of α-terpineol and terpinen-4-ol showed poor DPPH radical-scavenging abilities. Therefore, hydrodistillated Eureka lemon oil with high levels of α-terpineol (9.11%) and terpinen-4-ol (4.69%) presented low radical scavenging capability. Citral displayed a high pro-oxidant ability against thiobarbituric acid reactive species formation, which might lead to the decreased ability of the Eureka lemon oils in inhibition of lipid peroxidation, since citral was significantly high in Eureka lemon oils. This study facilitated the understanding of volatile constituents and antioxidant activities in different Citrus peel oils.


The Impact of Vitiligo on Quality of Life and Psychosocial Well-Being in a Nepalese Population.
The authors collected demographics and assessed the impact of vitiligo using Vitiligo Quality of Life (VitiQoL) and Vitiligo Impact Scale (VIS), followed by a focused survey and semistructured interviews with 22 participants in midwestern Nepal. VitiQoL and VIS scales did not indicate a large impact on quality of life; however, through interviews/focused surveys, participants expressed unhappiness/worry, problems in finding partners, securing employment, and social discrimination due to their skin lesions. These stressors are highlighted along with lack of proper physician counseling and vitiligo-related myths, which create psychosocial distress that may not be given priority in underdeveloped countries like Nepal.


The impact of city financial ecology on firm financing efficiency: Evidence from China's strategic emerging industries.
Based on the concept of bionics and the connotation of city financial ecology, this study constructs a 3-level and 27-indicator evaluation index system, including financial ecology growth, soil, and air. This study uses the entropy-TOPSIS model to weigh indicators objectively and evaluate the financial ecology of 343 China's prefecture-level cities during 2009-2016. This study uses the DEA-Tobit method to assess the financing efficiency of 4013 China's strategic emerging listed firms during 2010-2017 and runs random-effect Tobit panel regressions. Regression results suggest that a city's financial ecology overall has a positive effect on strategic emerging firms' financing efficiency. Therefore, the government should: improve the multi-tiered financial market system and encourage financial innovation; transform the economic growth model and optimize the industrial structure; establish an information-sharing mechanism and construct a social credit system.


TIM-3 Qualifies as a Potential Immunotherapeutic Target in Specific Subsets of Patients with High-Risk Soft Tissue Sarcomas (HR-STS).
(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes (p < 0.001), high TIL counts (p < 0.001), and high PD-1 (p < 0.001) and PD-L1 expression (p < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.


Positive bias in mycophenolic acid concentrations determined by the CEDIA assay compared to HPLC-UV method: is CEDIA assay suitable for therapeutic drug monitoring of mycophenolic acid?
Both immunoassays and chromatographic methods are available for therapeutic drug monitoring of mycophenolic acid (MPA), an immunosuppressant. We studied the suitability of cloned enzyme donor immunoassay (CEDIA) assay for routine monitoring of MPA by comparing values obtained by the CEDIA assay with corresponding values obtained by using a high-performance liquid chromatography combined with ultraviolet detection (HPLC-UV) method. We compared MPA concentrations obtained by a reference HPLC-UV method and CEDIA assay on Hitachi 917 analyzer (Roche Diagnostics, Indianapolis, IN) using 60 patient specimens (18 liver transplant recipient and 42 kidney transplant recipients). When MPA concentrations in all 60 transplant recipients obtained by the HPLC-UV (x-axis) method were compared with corresponding values obtained by the CEDIA method (y-axis), the following regression equation was obtained: y = 1.1558x + 0.2876 (r = 0.97). Interestingly, much lower bias was observed in 42 renal transplant recipients as revealed by the following regression equation; y = 1.1181x + 0.2745 (r = 0.98). However, more significant positive bias was observed in 18 liver transplant recipients as following regression equation as observed: y = 1.3337x + 0.1493 (r = 0.94). We conclude that MPA concentrations determined by the CEDIA assay showed significant positive bias compared to HPLC-UV method. Therefore, caution must be exercised in interpreting therapeutic drug monitoring result of MPA if CEDIA assay is used.


Real-world opioid prescription to patients with serious, non-malignant, respiratory illnesses and chronic breathlessness.
Chronic breathlessness is a disabling symptom that is often under-recognised and challenging to treat despite optimal disease-directed therapy. Low-dose, oral opioids are recommended to relieve breathlessness, but little is known regarding long-term opioid prescription in this setting. To investigate the long-term efficacy of, and side-effects from, opioids prescribed for chronic breathlessness to patients with advanced, non-malignant, respiratory diseases. A prospective cohort study of all patients managed by the advanced lung disease service, an integrated respiratory and palliative care service, at the Royal Melbourne Hospital from 1 April 2013 to 3 March 2020. One hundred and nine patients were prescribed opioids for chronic breathlessness. The median length of opioid use was 9.8 (interquartile range (IQR) = 2.8-19.8) months. The most commonly prescribed initial regimen was an immediate-release preparation (i.e. Ordine) used as required (37; 33.9%). For long-term treatment, the most frequently prescribed regimen included an extended-release preparation with an as needed immediate-release (37; 33.9%). The median dose prescribed was 12 (IQR = 8-28) mg oral morphine equivalents/day. Seventy-one (65.1%) patients reported a subjective improvement in breathlessness. There was no significant change in the mean modified Medical Research Council dyspnoea score (P = 0.807) or lung function measurements (P = 0.086-0.727). There was no association between mortality and the median duration of opioid use (P = 0.201) or dose consumed (P = 0.130). No major adverse events were reported. Within this integrated respiratory and palliative care service, patients with severe, non-malignant respiratory diseases safely used long-term, low-dose opioids for breathlessness with subjective benefits reported and no serious adverse events.


Relationship between gambling and video-game playing: a response to Johansson and Gotestam.
This paper reviews the many similarities and commonalities between video-game playing and slot machine gambling in response to Johansson and Gotestam in 2004.


Genetic background influences expression and function of the cation channel TRPM4 in the mouse heart.
Transient receptor potential melastatin 4 (TRPM4) cation channels act in cardiomyocytes as a negative modulator of the L-type Ca2+ current. Ubiquitous Trpm4 deletion in mice leads to an increased β-adrenergic inotropy in healthy mice as well as after myocardial infarction. In this study, we set out to investigate cardiac inotropy in mice with cardiomyocyte-specific Trpm4 deletion. The results guided us to investigate the relevance of TRPM4 for catecholamine-evoked Ca2+ signaling in cardiomyocytes and inotropy in vivo in TRPM4-deficient mouse models of different genetic background. Cardiac hemodynamics were investigated using pressure-volume analysis. Surprisingly, an increased β-adrenergic inotropy was observed in global TRPM4-deficient mice on a 129SvJ genetic background, but the inotropic response was unaltered in mice with global and cardiomyocyte-specific TRPM4 deletion on the C57Bl/6N background. We found that the expression of TRPM4 proteins is about 78 ± 10% higher in wild-type mice on the 129SvJ versus C57Bl/6N background. In accordance with contractility measurements, our analysis of the intracellular Ca2+ transients revealed an increase in ISO-evoked Ca2+ rise in Trpm4-deficient cardiomyocytes of the 129SvJ strain, but not of the C57Bl/6N strain. No significant differences were observed between the two mouse strains in the expression of other regulators of cardiomyocyte Ca2+ homeostasis. We conclude that the relevance of TRPM4 for cardiac contractility depends on homeostatic TRPM4 expression levels or the genetic endowment in different mouse strains as well as on the health/disease status. Therefore, the concept of inhibiting TRPM4 channels to improve cardiac contractility needs to be carefully explored in specific strains and species and prospectively in different genetically diverse populations of patients.


Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation.
Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score ('base' model). In the second model, we added to the 'base' model the 20 most common medical conditions and applied a stepwise backward selection of variables ('disease' model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia.


Abnormalities of CD4+ T lymphocyte proliferative responses from patients with recently diagnosed insulin-dependent diabetes mellitus.
To investigate the abnormalities of cell-mediated immunity in patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM), we studied the responses of the two major T lymphocyte subsets from peripheral blood lymphocytes (PBL) to mitogen stimulation. Samples for PBL were obtained from a group of IDDM patients and from a group of normal controls. CD4+ and CD8+ T cells were isolated and were subsequently stimulated with three specific lymphocyte mitogens, namely Phytohemagglutinin (PHA), Concanavalin A (Con A) and Pokeweek mitogen (PWM). The proliferative response was measured by incorporation of radioactive thymidine in lymphocyte cultures which were stimulated by the three mitogens. The responses of CD8+ T cells from IDDM patients and from controls were not significantly different. However, CD4+ T cells from IDDM patients showed significantly depressed responses to PHA and Con A and to a much lesser extent to PWM. These data provide new information regarding the CD4+ T lymphocyte abnormalities found in patients with IDDM.


Microinjection of neuropeptide Y into periaqueductal grey produces anti-nociception in rats with mononeuropathy.
The present study was carried out to investigate the effects of neuropeptide Y (NPY) in the midbrain periaqueductal grey (PAG) on the nociceptive modulation in mononeuropathic rats. NPY was microinjected into the PAG. The latency of paw withdrawal (PWL), assessed by the hot-plate (52 ) and the Randall Selitto test, was measured. Intra-PAG administration of 0.05, 0.1 and 0.2 nmol of NPY significantly increased the PWLs in a dose-dependent manner. Co-administration of 0.2 nmol of NPY(28-36) and 5.5 nmol of naloxone significantly attenuated the NPY-induced increase in PWLs. The results suggest that Y(1) receptor may mediate NPY-induced anti-nociception, and that the opioid receptors in PAG may also be involved in this process in mononeuropathic rats.


Potential effects of vildagliptin on biomarkers associated with prothrombosis in diabetes mellitus.
Diabetes mellitus (DM) is one of the risks linked with susceptibility of thrombosis. We tried to inspect the effect of a novel oral antidiabetic agent, vildagliptin, in preventing prothrombosis associated with DM. DM was produced by a dose of streptozotocin (STZ) or in albino wistar rats. Rats were treated orally with pioglitazone, standard treatment and vildagliptin alone and in combination for 3 weeks. Finally, the varied levels of coagulation biomarkers, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen and inflammatory parameters, nitric oxide (NO), C-reactive protein (CRP) and TNF-α and lipid profile were estimated along with platelet count and total leukocyte count (TLC). In vitro fibrinolytic activity of both the drugs was also determined. Vildagliptin significantly reduced cholesterol, triglycerides, TLC, CRP and TNF-α and increased aPTT and NO levels in STZ diabetic rats. However, pioglitazone was more successful in reducing fibrinogen and platelet count. Nevertheless, combination of the drugs was also effective than pioglitazone or vildagliptin alone in improvising hypercoagulation and inflammatory biomarkers. It is evident from the present study that vildagliptin has an influence on the biomarkers linked to the progression of thrombosis and may delay thrombogenesis linked to DM. Hence, vildagliptin alone and in combination might prove as an encouraging therapy for DM-linked thrombosis marked by inflammation and hypercoagulation.


Paenibacillus sp. strain HC1 xylanases responsible for degradation of rice bran hemicellulose.
Paenibacillus sp. strain HC1 is the first bacterium capable of growing on rice bran hemicellulose as a sole carbon source. Two xylanases (Xyl-I and -II) were purified from the bacterial culture fluid and enzymatically characterized. Xyl-I and -II showed monomer forms with molecular masses of 30 and 18kDa, respectively, and were most active at around pH 5.0 and 45 degrees C. Xylooligosaccharides were degraded to xylobiose and xylose by Xyl-I, but not by Xyl-II, suggesting that Xyl-I plays an important role in complete depolymerization of xylan. Both enzymes acted endolytically on rice bran hemicellulose, indicating that Xyl-I and -II contribute to the structure determination and practical use of the polysaccharide, an unutilized biomass in technology.


Do vitamin E and selenium have beneficial effects on trinitrobenzenesulfonic acid-induced experimental colitis.
The balance between oxidant and antioxidant systems may be important in the pathogenesis and/or maintenance of tissue injury in ulcerative colitis. This study was designed to evaluate the effects of vitamin E and selenium supplementations on tissue injury and oxidative stress in trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. Trinitrobenzenesulfonic acid administration severely changed the normal architecture of the colon and significantly increased the levels of malondialdehyde, protein carbonyl, and xantine oxidase (P < 0.001) in the colon homogenates of these rats. Supplementation of selenium to the trinitrobenzenesulfonic acid-treated rats neither improved the histopathological findings nor decreased the levels of malondialdehyde and protein carbonyl. Vitamin E supplementation reduced the levels of malondialdehyde and protein carbonyl but did not improve the colonic lesions. Supplementation of vitamin E + selenium significantly reduced both the severity of colonic lesions and the levels of malondialdehyde and protein carbonyl. In conclusion, we suggest that antioxidants and specific micronutrients may have beneficial effects in the treatment of ulcerative colitis.


Physiological ¹⁸F-FDG uptake by the spinal cord: is it a point of consideration for cancer patients?
It is essential to be familiar with normal patterns of (18)F FDG distribution in the whole body for accurate PET interpretation. We assessed FDG uptake by the spinal cord to evaluate its characteristics in cancer patients. For 101 cancer patients who underwent (18)F FDG PET/CT the spinal cord along its segments was visually assessed for FDG uptake, regarding MaxSUV-measurement ≥1 as cut-off point. This assessment was correlated with the patient's database variables. MRI and FDG PET-CT follow-up were included in the evaluation of positive subjects with FDG cord uptake. Forty-nine (48.5%) were positive for FDG cord uptake. The most encountered sites were the eleventh and twelfth dorsal vertebrae (36/49; 73.5%), all cervical (24/49; 49%), and the first lumbar segments (19/49; 38.7%). 38/49 (77.6%) and 11/49 (22.4%) were detected in the winter and summer, respectively (P = 0.007). MRI was available for 25 of the positive FDG cord uptake patients and showed no cord abnormalities, and in follow-up FDG PET-CT studies within 3-6 months 41/49 (83.7%) faded completely, while stationary or reduced uptake was observed for the remainder (8/49; 16.3%). FDG uptake in multiple consecutive segments of the spinal cord is not uncommon in cancer patients. This must be recognized as physiological, to avoid misdiagnosis as malignant involvement. Such physiological uptake is mostly encountered in the cervical, last two dorsal, and first lumbar levels, and quite frequently in winter.


Serotonin systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors and induce anorexia via a leptin-independent pathway in mice.
NEFA/nucleobindin2 (NUCB2), a novel satiety molecule, is associated with leptin-independent melanocortin signaling in the central nervous system. Here, we show that systemic administration of m-chlorophenylpiperazine (mCPP), a serotonin 5-HT1B/2C receptor agonist, significantly increased the expression of hypothalamic NUCB2 in wild-type mice. The increases in hypothalamic NUCB2 expression induced by mCPP were attenuated in 5-HT2C receptor mutant mice. Systemic administration of mCPP suppressed food intake in db/db mice with leptin receptor mutation as well as lean control mice. On the other hand, the expression of hypothalamic NUCB2 and proopiomelanocortin (POMC) was significantly decreased in hyperphagic and non-obese 5-HT2C receptor mutants compared with age-matched wild-type mice. Interestingly, despite increased expression of hypothalamic POMC, hypothalamic NUCB2 expression was decreased in 5-HT2C receptor mutant mice with heterozygous mutation of beta-endorphin gene. These findings suggest that 5-HT systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors, and induce anorexia via a leptin-independent pathway in mice.


Intraoperative Frozen Section in "Suspicious for Papillary Thyroid Carcinoma" after Adoption of the Bethesda System.
To evaluate the accuracy and utility of intraoperative frozen section examination (iFSE) in patients with a preoperative fine-needle aspiration (FNA) cytology of "suspicious for malignancy" (SFM)-Bethesda V, after the adoption of the Bethesda System for Reporting Thyroid Cytopathology. Case series with chart review. Tertiary medical center. All patients with SFM-Bethesda V who underwent thyroid surgery with iFSE between 2010 and 2015 were included. In cases where the iFSE was reported to be malignant, a total thyroidectomy was performed; otherwise, thyroid lobectomy (hemithyroidectomy) was performed. The current series included 47 patients diagnosed preoperatively with FNA cytology of SFM-Bethesda V. The malignancy rate was 74.5% (35 of 47). Twenty-four patients with nonmalignant iFSE results underwent lobectomy during their initial surgery: 12 were subsequently found with benign final histology and did not undergo completion thyroidectomy; the other 12 patients had malignant results on final histology, but only 4 of them underwent completion thyroidectomy. iFSE resulted in a sensitivity and specificity of 65.7% and 100%, respectively, with a positive predictive value of 100% (23 of 23) and a negative predictive value of 50% (12 of 24). Accuracy of the iFSE methodology was 74.5% (35 of 47). With no significant preoperative clinical or sonographic predictors for thyroid malignancy and given the high specificity of iFSE, our results support the use of iFSE for patients with preoperative FNA cytology of SFM-Bethesda V who are undergoing thyroid surgery, to determine the extent of required surgery.