Exploring the emerging complexity in transcriptional regulation of energy homeostasis.
Obesity and its associated diseases are expected to affect more than 1 billion people by the year 2030. These figures have sparked intensive research into the molecular control of food intake, nutrient distribution, storage and metabolism--processes that are collectively termed energy homeostasis. Recent decades have also seen dramatic developments in our understanding of gene regulation at the signalling, chromatin and post-transcriptional levels. The seemingly exponential growth in this complexity now poses a major challenge for translational researchers in need of simplified but accurate paradigms for clinical use. In this Review, we consider the current understanding of transcriptional control of energy homeostasis, including both transcriptional and epigenetic regulators, and crosstalk between pathways. We also provide insights into emerging developments and challenges in this field.


A machine learning strategy-incorporated BiFeO3/Ti3C2 MXene electrochemical platform for simple, rapid detection of Pb2+ with high sensitivity.
The electrochemical technique has been increasingly used for the detection of heavy metal ions in the water system. However, the process for determining the optimum experimental conditions was cumbersome, time-consuming, and unsynchronized, resulting in unsatisfactory detection efficiency. Herein, a new machine learning (ML) strategy combined with BiFeO3/Ti3C2 MXene (BiFeO3/MXene) was used to fabricate a simple but efficient electrochemical Pb2+ sensor. The interconnected BiFeO3/MXene composites prepared by a hydrothermal method possessed an interconnected conductive framework, abundant active sites, and a large surface area, which gave them excellent electronic conductivity and high accumulation of Pb2+. Meanwhile, ML methods such as back-propagation artificial neural network (BPANN) and genetic algorithm (GA) combined with orthogonal experimental design (OED) were used to optimize sensor parameters such as the pH of the supporting electrolyte, the BiFeO3/MXene content, deposition potential, and deposition time. Compared with OED and the one factor at a time (OFAT) methods, the OED-ML method greatly simplified the experimental procedures and improved the electrochemical detection performance. The developed sensor showed superior detection performance for Pb2+ with a detection limit of 0.0001 μg L-1 using the OED-ML method, which was much lower than that of the OED and OFAT methods (0.0003 μg L-1). In addition, the sensor showed good repeatability, reproducibility, stability, and interference capability. The feasibility of the method was verified by detecting Pb2+ in lake samples with recoveries ranging from 98.79% to 101.3%. To our knowledge, the ML strategy was introduced for the first time in an electrochemical sensor for Pb2+ detection, which proved the feasibility and practicality of ML.


Triplet state harvesting and search for forbidden transition intensity in the nitrogen molecule.
Triplet excited states of the N2 molecule play an important role in electric discharges through air or liquid nitrogen accompanied by various afterglows. In the rarefied upper atmosphere, they produce aurora borealis and participate in other energy-transfer processes connected with atmospheric photochemistry and nightglow. In this work, we present spin-orbit coupling calculations of the intensity of various forbidden transitions, including the prediction of the electric dipole transition moment of the new 1 3 Σ g - ← A 3 Σ u + band, which is strongly prohibited by the (+|-) selection rule, the new spin-induced magnetic B ' 3 Σ u - ← A 3 Σ u + transition, magnetic and electric quadrupole transitions for the B3Πg ← X 1 Σ g + Wilkinson band, and the Lyman-Birge-Hopfield a1Πg ← X1Σg transition. Also, two other far-UV singlet-singlet quadrupole transitions are calculated for the first time, namely, the Dressler-Lutz a"1Σg +-X1Σg + and the less studied z1Δg-X1Σg + weak transitions.


The endoscopic correction of reflux by polytetrafluoroethylene injection.
Endoscopic subureteral injection of polytetrafluoroethylene (Teflon) was done in 38 patients (55 ureters) to correct vesicoureteral reflux. Followup excretory urograms and nuclear cystograms were available in 28 patients (40 ureters) 2 to 11 months after injection. Nearly 50 per cent of the patients had a neurogenic bladder. Injection was done for all grades of reflux, although the majority of cases had at least grade III reflux. After injection reflux either was eliminated or decreased in 76 per cent of the patients with neurogenic disease and in 87 per cent of those with a normally innervated bladder. This outpatient procedure is simple and brief to perform, and it is associated with minimal morbidity. As with any new antireflux technique longer followup is indicated.


The 3'-terminal exon of the family of steroid and phenol sulfotransferase genes is spliced at the N-terminal glycine of the universally conserved GXXGXXK motif that forms the sulfonate donor binding site.
The guinea pig estrogen sulfotransferase gene has been cloned and compared to three other cloned steroid and phenol sulfotransferase genes (human estrogen sulfotransferase, human phenol sulfotransferase, and guinea pig 3 alpha-hydroxysteroid sulfotransferase). The four sulfotransferase genes demonstrate a common outstanding feature: the splice sites for their 3'-terminal exons are identically located. That is, the 3'-terminal exon splice sites involve a glycine that constitutes the N-terminal glycine of an invariably conserved GXXGXXK motif present in all steroid and phenol sulfotransferases for which primary structures are known. This consistency strongly suggests that all steroid and phenol sulfotransferase genes will be similarly spliced. The GXXGXXK motif forms the active binding site for the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate. Amino acid sequence alignment of 19 cloned steroid and phenol sulfotransferases starting with the GXXGXXK motif indicates that the 3'-terminal exon for each steroid and phenol sulfotransferase gene encodes a similarly sized C-terminal fragment of the protein. Interestingly, on further analysis of the alignment, three distinct amino acid sequence patterns emerge. The presence of the conserved functional GXXGXXK motif suggests that the protein domains encoded by steroid and phenol sulfotransferase 3'-terminal exons have evolved from a common ancestor. Furthermore, it is hypothesized that during the course of evolution, the 3'-terminal exon further diverged into at least three sulfotransferase subdivisions: a phenol or aryl group, an estrogen or phenolic steroid group, and a neutral steroid group.


UAV-borne LiDAR revolutionizing groundwater level mapping.
In hydrogeological research, the systematic and periodic measurement of the piezometric level is fundamental to assess aquifer storage, identify recharge and discharge areas, define flow directions and to infer the balance between inputs and withdrawals. Furthermore, knowledge of this variable and its fluctuations is essential for the efficient management and protection of groundwater resources. In this work, a novel methodology is proposed for the remote acquisition of piezometric information from traditional large-diameter wells, using drone-borne LiDAR observations. The workflow developed consists of different stages, from flight planning and parameter setting, to point cloud generation, data processing and validation and its statistical treatment to extract piezometric information. This methodology has been applied in a small coastal aquifer with numerous wells that have served as monitoring points. The UAV-LiDAR has enabled the straightforward obtention of measurements of the piezometric level with very high vertical accuracies (RMSE of 5 cm) with minimum and maximum residuals of -8.7 and 7.9 cm respectively. Likewise, the method has shown vertical accuracies 3 times better than those inferred from the official DTM of best resolution available in Spain, which is usually used in hydrogeological works. Since the technique provides absolute values of the piezometric level, it eliminates the need for laborious levelling work prior to hydrogeological campaigns. This method has proved to be an effective alternative/complementary technique to traditional measurements of the piezometric level, allowing to monitor extensive or inaccessible areas over short periods of time and to potentially reduce gaps in hydrogeological databases.


Abdominal paracentesis for the ovarian hyperstimulation syndrome with severe pulmonary compromise.
Abdominal paracentesis is a well-tolerated therapeutic alternative to relieve the severe pulmonary compromise caused by severe ascites and pleural effusion in the ovarian hyperstimulation syndrome. An improvement in renal function may be another benefit that deserves further investigation.


A facile and versatile approach to design self-assembled monolayers on glass using thiol-ene chemistry.
This work describes an integrated approach for designing on demand Self-Assembled Monolayers (SAMs) on silicon oxides and particularly glass substrates for cell biology applications. Starting from commercially available compounds, the strategy relies on thiol-ene reaction and provides high quality SAMs exhibiting adhesive and anti-adhesive patterns.


Development and validation of a predictive model for American Society of Anesthesiologists Physical Status.
The American Society of Anesthesiologists Physical Status (ASA-PS) classification system was developed to categorize the fitness of patients before surgery. Increasingly, the ASA-PS has been applied to other uses including justification of inpatient admission. Our objectives were to develop and cross-validate a statistical model for predicting ASA-PS; and 2) assess the concurrent and predictive validity of the model by assessing associations between model-derived ASA-PS, observed ASA-PS, and a diverse set of 30-day outcomes. Using the 2014 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File, we developed and internally cross-validated multinomial regression models to predict ASA-PS using preoperative NSQIP data. Accuracy was assessed with C-Statistics and calibration plots. We assessed both concurrent and predictive validity of model-derived ASA-PS relative to observed ASA-PS and 30-day outcomes. To aid further research and use of the ASA-PS model, we implemented it into an online calculator. Of the 566,797 elective procedures in the final analytic dataset, 8.9% were ASA-PS 1, 48.9% were ASA-PS 2, 39.1% were ASA-PS 3, and 3.2% were ASA-PS 4. The accuracy of the 21-variable model to predict ASA-PS was C = 0.77 +/- 0.0025. The model-derived ASA-PS had stronger association with key indicators of preoperative status including comorbidities and higher BMI (concurrent validity) compared to observed ASA-PS, but less strong associations with postoperative complications (predictive validity). The online ASA-PS calculator may be accessed at https://s-spire-clintools.shinyapps.io/ASA_PS_Estimator/ CONCLUSIONS: Model-derived ASA-PS better tracked key indicators of preoperative status compared to observed ASA-PS. The ability to have an electronically derived measure of ASA-PS can potentially be useful in research, quality measurement, and clinical applications.


Glucose transport in primary cultured neurons.
In this study, we have examined glucose uptake and its regulation by insulin in primary cultured neurons. Glucose transport was assessed by measuring the initial rate of uptake of 3H-2-deoxyglucose, a glucose analog that is transported and phosphorylated but not further metabolized. The uptake of 2-deoxyglucose was saturable; measurements of the intracellular concentration of 2-deoxyglucose and 2-deoxyglucose-6-phosphate revealed that hexokinase activity rather than membrane transport is the rate-limiting step for glucose uptake. Insulin had no effect on 2-deoxyglucose uptake at low (0.2 mM) or high (20 mM) concentrations of substrate. The order of potency of other hexoses to competitively inhibit the accumulation of 2-deoxyglucose was D-glucose (0.2 mM) = D-mannose (0.2 mM) greater than 3-0-methylglucose (9 mM) greater than D-galactose (90 mM). Cytochalasin B was a potent inhibitor of 2-deoxyglucose uptake (IC50 = 500 nM) and phloretin was more potent than ploridzin in inhibiting uptake. The structure of glucose transporters was examined by photoaffinity labeling using 3H-cytochalasin B and by immunologic detection using antibodies raised against the human erythrocyte transporter. 3H-cytochalasin B labeled two proteins of 55 kDa and 43 kDa and the antibody recognized primarily a 43 kDa protein. The subcellular distribution of glucose transporters, estimated by measuring the number of specific cytochalasin B binding sites in subfractions of neuronal homogenates, showed 3.62 pmol/mg protein in the 11,000g pellet and 1.34 pmol/mg protein in the 200,000g pellet. 1) Neuronal glucose transport is not acutely regulated by insulin. 2) The kinetics of 2-deoxyglucose uptake into neurons are determined largely by hexokinase activity rather than membrane transport. 3) The apparent molecular weight of neuronal glucose transporters is similar to transporters in other tissues. 4) The number of glucose transporters per milligram of protein is relatively low in neurons compared to other tissues.


Fracture locations influence the likelihood of rectal and lower urinary tract injuries in patients sustaining pelvic fractures.
Rectal and lower urinary tract injuries in pelvic fractures can lead to significant complications. We sought to determine whether fracture locations could serve as markers for injury. In our retrospective review of patients with blunt pelvic fractures, the association of fracture locations with injury to the rectum, bladder, and urethra was explored with Fisher's exact test and subsequently analyzed with multiple logistic regression. Of the 362 patients reviewed, 8 had rectal injury and 24 had lower urinary tract injury. The following locations were found to be significant. Rectum: symphysis pubis (relative risk [RR] = 3.3, p < 0.001) and sacroiliac (SI) joint (RR = 2.1, p = 0.014). Bladder: symphysis pubis (RR = 2.1, p < 0.001), SI joint (RR = 2.0, p < 0.001), and sacrum (RR = 1.6, p = 0.002). Urethra: symphysis pubis (RR = 2.9, p = 0.003), SI joint (RR = 1.8, p = 0.04), and inferior ramus (RR = 4.6, p = 0.008). After multivariate analysis, the primary and independent predictors for each of the injuries were as follows: rectal injury, widened symphysis; bladder injury, widened symphysis and SI joint; and urethral injury, widened symphysis and fracture of the inferior pubic ramus. Although these associations were significant, the overall prevalence of associated rectal and urologic injuries was low. Consequently, the predictive values of these radiologic findings were also low, ranging from 5% to 9% for urethral and rectal injuries to 20% for bladder injuries. Certain fracture locations are associated with increased risk for rectal, bladder, or urethral injury. Fractures involving these locations should prompt further work-up for assessment.


Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.
Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). To compare NPI and RS for estimating prognosis in ER + breast cancer. Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.


Colony behavior of Atta sexdens rubropilosa (Hymenoptera: Formicidae) in the absence of the queen under laboratory conditions.
A colony of Atta sexdens rubropilosa was studied in the presence and absence of the queen. The frequency of 23 previously defined behaviors was quantified in terms of average frequencies of act occurrence. Colony behavioral activities such as foraging, fungal care, and refuse manipulation were not directly influenced by the queen's presence up to 30 days after the queen's death. The queen, which also seems to maintain colony cohesion aside from reproduction, indirectly affected brood care.


Prostate specific antigen after external beam radiotherapy for prostatic cancer: followup.
Between 1986 and 1989, 117 patients with pretreatment and serial posttreatment prostate specific antigen values received external beam radiotherapy at our hospital. Followup ranged from 0.6 to 5.9 years (mean 2.7). No patient had hormonal manipulation before distant recurrence. Biochemical relapse, defined as an increasing prostate specific antigen level after treatment, was observed in 44 patients. To date 30 of these 44 patients (68%) have had clinical relapse. The prognostic factors of advanced local stage, high Gleason score and high elevations of pretreatment prostate specific antigen values predicted for biochemical relapse and subsequent clinical failure. The interval between biochemical and clinical relapse was 156 +/- 46 days. Biochemical relapse is an important end point that can be used to determine the effect of treatment in prostatic cancer research.


Contrast sensitivity in macular degeneration and the relation to subjective visual impairment.
Contrast sensitivity was determined with electronic and computer equipment (Cadwell CTS 5000) and with optotype test charts (LH low contrast test) in 31 patients, aged 47-89, with macular degeneration, mostly of the age-related type. Values of maximal sensitivity and mean sensitivity in different spatial frequency bands were estimated. Visual acuity at distance and the magnification factor needed for reading were also determined. Each of these measures were correlated with a score obtained in a subjective evaluation of difficulties with visual discrimination and orientation. It was found that poor visual discrimination and orientation was better correlated with low contrast sensitivity than with low visual acuity. The outcome of the LH-test was a better predictor of orientation problems than the electronic test.


Activation of fatty acid synthesis in cell-free extracts of Saccharomyces cerevisiae.
Fatty acid synthesis from acetate in extracts of Saccharomyces cerevisiae strain LK2G12 was shown to be stimulated by alpha-glycerophosphate and citrate, and by a number of compounds related to them. Magnesium was shown to stimulate fatty acid synthesis from acetyl-coenzyme A but not from malonyl-coenzyme A, thus indicating the site of stimulation of fatty acid synthesis to be the acetyl-coenzyme A step.


Open resource of clinical data from patients with pneumonia for the prediction of COVID-19 outcomes via deep learning.
Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.


The role of taurine in the regulation of brain cell volume in chronically hyponatraemic rats.
Cells in slices prepared from the superficial cerebral cortex of normonatraemic rats underwent moderate swelling when exposed to low Na+ medium (122 mmol/l) accompanied by a large increase in the rate of efflux of preloaded taurine. In contrast, cells in slices from chronically (4 day) hyponatraemic rats did not increase in volume and the rate of taurine efflux was unchanged. The anion transport inhibitor 4,4'-diisothiocyanato-stilbene-2,2'-sulphonic acid (25 micromol/l) caused marked (-44%) reduction in taurine efflux in cells from normonatraemic rats; this response was strongly attenuated (-16%) by hyponatraemia. When slices from hyponatraemic rats were acutely exposed to medium containing 142 mmol/Na+ cells exhibited marked and paradoxical swelling. This response was completely abolished by the NaCl co-transport inhibitor bumetanide (50 micromol/l) and was not observed in slices that had not been pre-loaded with taurine. Forty eight hours after the start of the remission of hyponatraemia, cells from post-hyponatraemic rats displayed normal responses (i.e., moderate swelling and greatly accelerated taurine efflux) on exposure to 122 mmol/Na+. But at 24 h there was only partial restoration of the efflux response to 122 mmol/Na+, with an enhanced cell swelling response that was not significantly affected by bumetanide. It is concluded that (i) during chronic hyponatraemia, unlike acute hyposmotic stress, cortical cells preserve their volume and that this is not associated with any increase in the rate of taurine loss; there does however, appear to be a decrease in the anionic component of cellular taurine efflux; (ii) acute re-incubation of slices in medium containing 142 mmol/l Na+ is associated with cell swelling that may reflect up-regulation of Na/Cl/taurine co-transport; (iii) following restoration of normonatraemia the pattern of normal cellular response to acute hyposmotic stress is only gradually re-established.


Bone Marrow Transplantation Dynamics: When Progenitor Expansion Prevails.
The transplantation of healthy hematopoietic stem cells (HSCs) contained in the bone marrow is a frontline treatment option for hematopoietic diseases. Detailed analysis of post-transplant HSC kinetics is crucial as the initial engraftment of HSCs influences prognosis. Dong et al. have explored the dynamic change in HSC cell fate upon bone marrow transplantation through the utilization of single-cell transcriptomic analysis.


Antigenicity of chimeric and cyclic synthetic peptides based on nonstructural proteins of GBV-C/HGV.
In this work, new putative epitopes located in nonstructural proteins of GBV-C/HGV were synthesized using solid-phase chemistry for their use in immunoassays. The antigens were obtained in linear, chimeric and cyclic forms with the main aim of improving the sensitivity of the enzyme immunoassays. Our results showed, on one hand, that the combination of different antigens seems to be necessary to ensure good sensitivity and more specificity and, on the other hand, that cyclic compounds show higher ability to recognize anti-GBV-C/HGV antibodies than its parent peptide. Furthermore, CD and FTIR have been used in conjunction to characterize the conformational changes therein with synthetic constructs that could explain their different antigenicity.


Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome.
22q11.2 deletion syndrome (22q11.2DS) is a primary immunodeficiency characterized chiefly by the hypoplasia of the thymus resulting in T cell lymphopenia, increased susceptibility to infections, and higher risk of autoimmune diseases. The irregular thymic niche of T cell development may contribute to autoimmune and atopic complications, whereas the compensatory mechanism of homeostatic T cell proliferation and continuous immune stimulation may result in T cell senescence and exhaustion, further aggravating the immune system dysregulation. We used flow cytometry to investigate T cell maturation, delineation, proliferation, activation, and expression of senescence and exhaustion-associated markers (PD1, KLRG1, CD57) in 17 pediatric and adolescent patients with 22q11.2DS and age-matched healthy donors. 22q11.2DS patients aged 0-5 years had fewer naïve but more effector memory T cells with a tendency to approach normal values with increasing age. Young patients in particular had a higher percentage of proliferating T cells and increased expression of PD1, KLRG1, and CD57, as well as cells co-expressing several exhaustion-associated molecules (PD1, KLRG1, Tbet, Eomes, Helios). Additionally, high-risk 22q11.2DS patients with very low numbers of CD4 T cells had significantly higher percentage of Th1 and Th17 T cells, driven in part by higher proportion of mature T cell forms. The low thymic output and accelerated T cell differentiation remain the principal features of 22q11.2DS patient immunity, especially in young patients of < 5 years. Later in life, homeostatic proliferation drives expression of T cell exhaustion and senescence-associated markers, suggesting functional aberrations in addition to numeric T cell deficiency.


Complete deficiency of adenine phosphoribosyl transferase: report of a new family.
We report a case of 2,8-dihydroxyadenine urinary lithiasis with complete deficiency of adenine phosphoribosyl transferase. Adenine phosphoribosyl transferase activities in the erythrocytes, lymphocytes and granulocytes of the patient's family also were determined. The propositus and her younger brother were homozygotes for adenine phosphoribosyl transferase deficiency and her parents were heterozygotes. This is the third family with this disease to be reported.


Comparison of HAS-BLED with other risk models for predicting the bleeding risk in anticoagulated patients with atrial fibrillation: A PRISMA-compliant article.
The HAS-BLED, HEMORR2HAGES, ATRIA, and ORBIT scores are used to predict bleeding risk in anticoagulated patients with atrial fibrillation (AF). Recently, these scores have been validated in various studies. Therefore, we aimed to compare the occurrence of major bleeding across different risk categories between HAS-BLED and any of HEMORR2HAGES, ATRIA, or ORBIT scores. A systemic literature search of PubMed and Embase databases was conducted to screen the relevant studies. We calculated and pooled the odds ratios (ORs) and 95% confidence intervals (CIs) for a comparative analysis of the occurrence of major bleeding. Nine studies fulfilled the inclusion criteria in this meta-analysis. Compared with HEMORR2HAGES, there were 87% and 39% reduced rates of major bleeding in the HAS-BLED "low-risk" and "moderate-risk" groups, respectively. Compared with ATRIA, there was an 89% decreased rate of major bleeding in the HAS-BLED "low-risk" group. Compared with ORBIT, there were 84% and 44% reduced rates of major bleeding in the HAS-BLED "low-risk" and "moderate-risk" groups, respectively. Patients with HAS-BLED scores ≥3 showed an approximately 3-fold greater risk of major bleeding compared with patients with scores <3 (OR=3.00, CI: 1.21-7.43). Compared with any of HEMORR2HAGES, ATRIA, or ORBIT scores, the HAS-BLED score distributed more major bleeding events into the "low" or "moderate" risk categories.


Investigation of seven Vibrio virulence genes among Vibrio alginolyticus and Vibrio parahaemolyticus strains from the coastal mariculture systems in Guangdong, China.
To investigate the distribution of the virulence of two Vibrio species among different strains obtained from the mariculture systems on the coast of Guangdong in China and the correlation between the virulence strains and the virulence genes among Vibrio alginolyticus. Besides three strains, 72 V. alginolyticus strains and seven Vibrio parahaemolyticus strains were examined by PCR or semi-nested PCR for the virulence genes (tlh, trh, tdh, toxR, toxRS, ctxA, VPI). Additionally, the virulence of 18 V. alginolyticus strains was tested. Virulence genes homologous to those in the V. parahaemolyticus and Vibrio cholerae are widely distributed among V. alginolyticus and V. parahaemolyticus in the coastal mariculture systems in Guangdong, China. Some of the V. alginolyticus strains are pathogenic to aquatic animals, and might have derived their virulence genes from V. parahaemolyticus or V. cholerae, representing a possible reservoir of these genes. However, there is no correlation between presence and absence of the virulence genes used to investigate V. alginolyticus and its virulent strains. In this report, we also show that tlh is distributed among V. alginolyticus.


[Fractures of the neck of femur in young children (author's transl)].
The problems of femoral neck fractures in young children are discussed. Results of 12 own cases are reviewed with an average age of the patients of 7.5 years at the time of accident. The average time between accident and last examination was 12 years. The operative technique, pre- and postoperative care, indications for conservative treatment and late complications are discussed. All types of fractures should be treated operatively. K-wire fixation is sufficient in most cases and does not damage the epiphyseal plate. Immobilization in POP spika is advisable for 6 weeks. With delayed operative treatment of intracapsulare fractures the intraarticular haematoma should be aspirated. Traumatic epiphyseolysis should be reduced by manipulation or operatively and stabilized by K-wires. The treatment of pseudarthrosis is by internal fixation and bone grafting. Late valgus and especially varus deformations should be corrected by intertrochanteric osteotomy.


Telomerase activity might persist in the human thymus throughout life.
Telomerase activity has been demonstrated at low levels in peripheral blood lymphocytes but at high levels in germinal centre B cells and thymocyte subpopulations. This study shows that telomerase is activated in the normal human thymus at different times of life. Telomerase activity was detected in thymic protein extracts from two newborn babies and from a 12 year old boy, as well as in extracts from two of six adult patients. The two positive cases were patients aged 54 and 66 years. These results suggest strongly that the thymus can remain functional despite involution in elderly patients.


Reconstruction of high-energy bremsstrahlung spectra by numerical analysis of depth-dose data.
The determination of the spectral distribution of a photon beam is important for exact dosimetry and for the calculation of dose distributions. Direct measurements are not possible because of physical reasons. The approximation described uses a numerical reconstruction method based upon depth-dose data measured in water. The basic idea of the method is that a measured depth-dose curve can be thought of as a weighted superposition of monoenergetic depth-dose curves. The monoenergetic data are obtained by convolution of Monte Carlo generated energy deposition kernels. They were fitted to the measured data by means of a least squares method. Several constraints were applied to the superposition coefficients. The optimization algorithm uses the Wolfe reduced gradient method. The results were compared to Monte Carlo generated thick target spectra.


Mortality and Other Outcomes in Relation to First Hour Fluid Resuscitation Rate: A Systematic Review.
To determine the effect of different regimen of first hour fluid administration rates on mortality and severe consequences of impaired circulation in 2 to 60 months old children with impaired circulation. Systematic review of randomized controlled trials. Various databases including PubMed, Cochrane Library and EMBASE were searched. We found only two relevant trials; one was excluded as there was no comparator arm. Only one study (The FEAST Trial) compared boluses with maintenance fluid alone in children with severe febrile illness and one or more signs of impaired perfusion. The 48 hour mortality was more in the bolus group (RR 1.45, 95% CI 1.13,1.86). The quality of evidence is rated as moderate. For the children who met the WHO criteria for shock (severely impaired circulation) (n=65 children), those receiving boluses had higher mortality (RR 2.40, 95% CI 0.84, 6.88); the quality of evidence was rated as very low. A single large randomized controlled trial conducted in low-resource settings indicates that administration of fluid bolus is associated with higher mortality in comparison to the maintenance fluids alone in children with severe febrile illness and one or more signs of impaired perfusion. The findings are not generalizable to contexts with different severity of and different causes of shock and in centers with better facilities. There is urgent need for research in different settings to determine the optimal rate of fluid resuscitation in the first hour in children presenting with impaired circulation, particularly with severely impaired circulation.


A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells.
We have previously determined that the HGF promoter can be transactivated by a combination of activated Src and wild-type Stat3 in the mouse breast cell lines HC11 and SP1. To determine if this pathway is of relevance for the human disease, a series of human breast and other human cells lines were examined, and the status of key proteins in these cells determined. All of the human breast cell lines exhibited strong transactivation by a combination of activated Src and Stat3. This activation was dependent on a Stat3 recognition element present at nt-95. The exception was the ErbB2 over-expressing cell line SK-BR-3 where Stat3 alone could transactivate HGF though Src augmented this effect. Increased phosphorylation of Stat3 tyrosine 705 was also observed in this line. Analysis of three ovarian cell lines revealed that Src/Stat3 expression was not able to activate the HGF promoter in two of these lines (SKOV3 and IOSE-80PC). Src/Stat3 expression did activate HGF transcription in OVCAR3 cells, but this effect was not mediated by the Stat3 site at nt-95. Stat3 phosphorylation at tyrosine 705 was observed in IOSE-80PC cells, but was insufficient to allow for activation of the HGF promoter. Human kidney (HEK293) and cervical carcinoma (HeLa) cells were also not Src/Stat3 permissive, despite high levels of Stat3 phospho-Y705. These results suggest that human breast cells are a uniquely permissive environment for HGF transactivation by Src/Stat3 which may allow for the inappropriate activation of HGF transcription during the early stages of breast transformation. This could lead to paracrine or autocrine activation of the Met receptor in breast carcinoma cells.


Stabilities, Electronic Structures, and Bonding Properties of Iron Complexes (E1E2)Fe(CO)2(CNArTripp2)2 (E1E2=BF, CO, N2, CN-, or NO+).
The coordination of 10-electron diatomic ligands (BF, CO N2) to iron complexes Fe(CO)2(CNArTripp2)2 [ArTripp2=2,6-(2,4,6-(iso-propyl)3C6H2)2C6H3] have been realized in experiments very recently (Science, 2019, 363, 1203-1205). Herein, the stability, electronic structures, and bonding properties of (E1E2)Fe-(CO)2(CNArTripp2)2 (E1E2=BF, CO, N2, CN-, NO+) were studied using density functional (DFT) calculations. The ground state of all those molecules is singlet and the calculated geometries are in excellent agreement with the experimental values. The natural bond orbital analysis revealed that Fe is negatively charged while E1 possesses positive charges. By employing the energy decomposition analysis, the bonding nature of the E2E1-Fe(CO)2(CNArTripp2)2 bond was disclosed to be the classic dative bond E2E1→Fe(CO)2(CNArTripp2)2 rather than the electron-sharing double bond. More interestingly, the bonding strength between BF and Fe(CO)2(CNArTripp2)2 is much stronger than that between CO (or N2) and Fe(CO)2(CNArTripp2)2, which is ascribed to the better σ-donation and π back-donations. However, the orbital interactions in CN-→Fe(CO)2(CNArTripp2)2 and NO+→Fe(CO)2(CNArTripp2)2 mainly come from σ-donation and π back-donation, respectively. The different contributions from σ donation and π donation for different ligands can be well explained by using the energy levels of E1E2 and Fe(CO)2(CNArTripp2)2 fragments.


Conditional reasoning with inducements and advice.
In an earlier study of conditional reasoning, Newstead et al. [Newstead, S.E., Ellis, C.E., Evans, J.St.B.T., Dennis, I., (1997). Conditional reasoning with realistic material. Thinking and Reasoning 3, 49-96] found that people drew more inferences from conditionals framed as inducements (threats and promises) than from conditionals phrased as advice (tips and warnings). The present study was designed to test the hypothesis that this difference arose from the fact that the speaker of an inducement is normally seen to have control over the consequent event whereas the giver of advice does not. In the experiment reported here, inducement and advice conditionals were constructed in brief contexts such that in either case the speaker could be seen to have high or low control. Participants drew many more conditional inferences of all kinds for high control than for low control conditionals in either context. A second finding of interest was that participants drew many more forward (antecedent to consequent) inferences than backward inferences with these kinds of realistic conditionals.


Waste to energy conversion for a sustainable future.
Air pollution, climate change, and plastic waste are three contemporary global concerns. Air pollutants affect the lungs, green gases trap heat radiation, and plastic waste contaminates the marine food chain. Two-thirds of climate change and air pollution drivers are emitted in the process of burning fossil fuels. Pollutants settle in months, green gases take centuries, and plastics take thousands of years. The most polluted regions on the planet are also the ones that are greatly affected by climate change. Air pollutants grow in most climate-change affected areas, contributing to the greenhouse effect. Smog affects local and regional transboundary countries. The biggest greenhouse gas (GHG) emitters may not be the worst-hit victims because wind and water flow distribute green gases and plastic waste worldwide. The major polluters are often rich and developed countries, and the worst affected countries are the underdeveloped poor communities. Technologically advanced countries may help the developing countries in research into removing particulate matter, green gases, and plastic waste. Intergovernmental Panel on Climate Change (IPCC) and Paris Accord have emphasized on immeasurable efforts to encourage the conversion of pollution, green gases, and plastic waste into energy. Conversion of CO2 into petrol, GHG gases into chemicals, biowaste into biofuels, plastic waste into building bricks, and concrete waste into construction materials fosters a circular economy. This work reviews existing waste to power, energy, and value-added product conversion technologies.


The role of sentinel lymph nodes in endometrial and cervical cancer.
Sentinel lymph node assessment aims to determine lymphatic spread while preventing unnecessary interventions and morbidity for those who will not benefit from lymphadenectomy. All detection methods have demonstrated reasonable sensitivity with a low false negative rate and high negative predictive value; as long as the surgeon removes all enlarged lymph nodes and a site-specific lymphadenectomy is performed if there is no mapping. The significance of micrometastases and long term outcomes are yet to be determined.


Stereoselective crystallization induced by traces of dissolved optically active impurities.
Isothermal crystallization of D,L-sodium-ammonium tartrate with traces of different impurities admixed shows that the added chiral contaminations produce a preferential crystallization of the tartrate isomer of same handedness. The critical lowest concentration of effective seeding agents is 0.1-0.5%. 1% optically active excess material induces 1.0-3.6% optical purity in the deposited crystals. An analysis of the relevant data reported so far gives similar figures in different crystallization systems. The relation of the results to the suggested lattice energy difference between enantiomers is discussed.


Severe falciparum malaria: survival without exchange transfusion.
A case of severe falciparum malaria with trophozoites in 71% of the patients' erythrocytes is described. The patient was treated with high dose quinine and made an uneventful recovery. Exchange transfusion was not performed.


Preparedness for dental practice in Australia: a qualitative study on the experiences of final-year students and new graduates.
Limited data exists regarding the perspectives of newly graduated dental practitioners (NGDPs) and final-year students (FYS) about their preparedness for dental practice. This information is crucial to inform developments in ongoing professional development for newly qualified dental practitioners and future reviews and development of accreditation standards, policies, and the professional competencies of newly qualified dental practitioners. Thus, the primary goal of this paper was to describe the perceptions of preparedness for dental practice of NGDPs and FYSs. Individual semi-structured interviews were conducted between March and July 2020. All interviews were audiotaped, transcribed, and analysed using a thematic analysis. Eighteen NGDPs and four FYS from across Australia participated in the qualitative interviews. A strong theme from the data was that respondents believed they were well prepared for common challenges in dental practice and patient care. A second prominent theme was participants' awareness of specific areas of limitation in their knowledge and specific skills including (list them). This data highlights a high level of self-awareness and potential for self-directed learning of NGDPs. It also provides specific content areas for future curriculum developers. Newly graduated dental practitioner and final-year student participants were satisfied with the theoretical and evidence-based information in their formal learning and teaching activities to begin practicing as dental practitioners. In some areas, NGDPs felt underprepared, mostly attributed to limited clinical treatment exposure, and other contextual elements of clinical practice, and thought transitional support may be required. The research reinforces the value of seeking and learning from students' and NGDPs' perspectives.


T-cell subsets in the cerebrospinal fluid and blood of patients with multiple sclerosis.
The absolute numbers and ratios of helper/inducer (T4) and cytotoxic/suppressor (T8) T-cells were determined in cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) and various other neurologic diseases (OND). In patients with MS, the T4:T8 ratio was higher in both blood and CSF, and the increase was significantly greater in CSF than in blood. These findings were due to an increased proportion of T4-lymphocytes in the CSF and to a decreased proportion of T8-cells in blood. These results indicate the need for additional studies of CSF lymphocytes in patients with MS.


Processing and Analyzing Human Microbiome Data.
The human microbiome is associated with complex disorders such as diabetes, cancer, obesity and cardiovascular disorders. Recent technological developments have allowed researchers to fully quantify the composition of the microbiome using culture-independent approaches, resulting in a large amount of microbiome data, which provide invaluable opportunities to assess the important contributions of the microbiome to human health and disease. In this chapter, we discuss and evaluate multiple statistical approaches for processing, summarizing, and analyzing microbiome data. Specifically, we provide programming scripts for processing microbiome data using QIIME and calculating alpha and beta diversities, assessing the association between diversities and outcomes of interest using R programs, as well as interpretation of results. We illustrate the methods in the context of analyzing the foregut microbiome in esophageal adenocarcinoma.


Functional topography of cortical thumb movement representations in human primary motor cortex.
Intracortical microstimulation and single cell recordings in non-human primates showed that both, muscles and movements are represented in primary motor cortex (M1). This was also suggested in humans using electrophysiological and neuroimaging techniques. Transcranial magnetic stimulation (TMS) thus far was used to study motor cortical muscle representations, but data on movement representations in man are scarce. Therefore, we used TMS of M1 to evoke directional (flexion, extension) thumb movements and generated topographic movement maps (TMS-mov-map) in fourteen healthy individuals. TMS-mov-maps were related to the individual voluntary motor output (Vol-mov, directional thumb acceleration). Conventional TMS-motor evoked potentials (TMS-MEP) were simultaneously recorded from the prime movers (flexor and extensor pollicis brevis) and also compared to the voluntary motor output. Remarkably stable topographic maps were generated with both, thumb flexion and extension being multiply represented, overlapped and interspersed. Thumb Flexion was usually more robust than extension. TMS-mov-maps rather than TMS-MEP-maps seemed to better reflect the individual voluntary motor output. The findings emphasize existing models of multiple, overlapping finger movement representations in human M1, and indicate that this model also adapts to antagonistic thumb movements. The results suggest that investigating topographic movement maps may be an interesting adjunct in studying human motor cortical topography and its relevance for motor control.


Patient Satisfaction Following Lumbar Decompression: What is the Role of Mental Health?
To determine the association between patient-reported depressive symptoms and patient satisfaction following minimally invasive lumbar decompression. Primary, single-level/multilevel minimally invasive lumbar decompression was identified. Patient-reported outcome measures (PROMs) collected preoperatively/postoperatively included visual analog scale back/leg, Oswestry Disability Index, 9-Item Patient Health Questionnaire (PHQ-9), and 12-Item Short Form Mental Composite Score (SF-12 MCS). Patients rated current satisfaction level (0-10) with back/leg pain and disability. A paired Student's t-test compared each postoperative PROM score to its preoperative baseline. At each timepoint, patients were categorized by PHQ-9 and SF-12 MCS scores. One-way analysis of variance compared patient satisfaction with back/leg pain and disability among PHQ-9 subgroups. The Student's t-test for independent samples compared patient satisfaction between SF-12 MCS subgroups. Analysis of covariance (ANCOVA) assessed differences in satisfaction between depression subgroups while controlling for preoperative/postoperative values in corresponding PROMs. 193 patients were included. All PROMs demonstrated significant postoperative improvement from 6-weeks through 2-years (P < 0.001, all), except PHQ at 9 2-years (P = 0.874). Mean satisfaction scores ranged from 6.9-7.9 (back pain), 7.3-8.0 (leg pain), and 7.6-8.0 (disability). Satisfaction with back/leg pain and disability significantly differed among PHQ-9 subgroups at all postoperative timepoints (P < 0.001, all). Accounting for baseline and current pain/disability values, ANCOVA revealed differences between PHQ-9 subgroups only in satisfaction with back pain at 2 years (P < 0.001), leg pain at 12 weeks/1 year/2 years (P ≤ 0.047, all), and disability at 6 months/2 years (P ≤ 0.049, both). Satisfaction differed between SF-12 MCS subgroups at all timepoints (P ≤ 0.047), except back pain 6 months (P = 0.263). Accounting for baseline and postoperative pain/disability, ANCOVA revealed differences in satisfaction between SF-12 MCS groups only for back/leg pain at 2 years (P ≤ 0.001, both). Independent effect of depression at long-term follow-up was significant. This highlights the importance of understanding the interaction between physical and mental health outcomes to optimize patients' perceptions of surgical outcomes.


Safety and efficacy of switching from either unfractionated heparin or enoxaparin to bivalirudin in patients with non-ST-segment elevation acute coronary syndromes managed with an invasive strategy: results from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.
The aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy. Crossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy. We compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy. Two thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p < 0.01), and improved net clinical outcomes (9.2% vs. 11.9%, p < 0.01) than those on consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy who were administered bivalirudin (n = 1,427) had similar rates of ischemia (6.2% vs. 5.5%, p = 0.47), less major bleeding (2.5% vs. 4.9%, p < 0.001), and similar net clinical outcomes (8.0% vs. 9.4%, p = 0.17) compared with naive patients administered UFH/ENOX plus a GP IIb/IIIa inhibitor (n = 1,462). Switching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor.


Using the clinical information system and self-supervision to rationalize the need for antibiotic stewardship: An interventional study in a 2000-bed university hospital.
To describe the usefulness of electronic medical records (EMRs) and a computerized physician order entry (CPOE) system to support and assess an antimicrobial stewardship programme (ASP). At the study hospital, infectious diseases specialists supervise antimicrobial prescription when solicited by physicians in charge of patients. From January to October 2015, treatment days of antibiotic prescription, supervised or unsupervised by infectious disease specialists (SAP or UAP, respectively) in all wards, except intensive care units emergency department, bone marrow transplantation units, and paediatric units, were calculated. Embedding recommendations on carbapenem indications as a checklist into the CPOE system, a self-administered ASP was implemented in 2017. EMRs were reviewed to determine global compliance with carbapenem prescription guidelines (combining introduction of therapy and 72-h assessment) before and after implementation of a self-administered ASP in departments with a low SAP rate for these antibiotics. Among 16 090 prescriptions extracted, 19.9% were SAPs. Three patterns of prescription were identified. The first pattern (amoxicillin-clavulanate, ceftriaxone) was characterized by a high UAP rate in every department, the second pattern (cloxacillin, rifampin) was characterized by a high SAP rate in every department, and the third pattern (broad-spectrum beta-lactams) was characterized by heterogeneous distribution of SAP/UAP among departments. Carbapenem prescription was reviewed in five departments with a low SAP rate for carbapenems over 6 months: 94 before and 107 after implementation of the self-administered ASP. Global compliance with guidelines increased significantly from 22% to 37% (risk difference 15%, 95% confidence interval 2.3-28.5%; P=0.02). A clinical information system may help to rationalize antibiotic stewardship in a context of scarce medical resources. Mapping of antibiotic prescriptions and self-supervision are efficient, complementary and easy-to-implement tools.


Synthesis, Optical Properties, and Applications of Luminescent Benzothiazole: Base Promoted Intramolecular C-S Bond Formation.
A novel base-catalyzed method for the synthesis of luminescent benzothiazole derivatives had been developed under metal-free conditions via C-S bond formation, which provided an efficient, convenient, and mild alternative method for constructing substituted benzothiazoles. As-prepared benzothiazole derivatives thus produced emissions in solution with quantum yield up to 85%. In addition, they still exhibited fairly strong fluorescence in the solid state. Furthermore, the compounds were used as a facile "On-Off" fluorescence probe to create handy test strips for detecting NaClO by naked eyes.


Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: novel sulfamoylcarbamates and sulfamides derived from acetophenones.
In this study, several novel sulfamides were synthesized and evaluated for their acetylcholine esterase (AChE) and human carbonic anhydrase I, and II isoenzymes (hCA I and II) inhibition profiles. Reductive amination of methoxyacetophenones was used for the synthesis of amines. Amines were converted to sulfamoylcarbamates with chlorosulfonyl isocyanate (CSI) in the presence of BnOH. Pd-C catalyzed hydrogenolysis of sulfamoylcarbamates afforded sulfamides. These novel compounds were good inhibitors of the cytosolic hCA I, and hCA II with Ki values in the range of 45.9±8.9-687.5±84.3 pM for hCA I, and 48.80±8.2-672.2±71.9pM for hCA II. The inhibitory effects of the synthesized novel compounds on AChE were also investigated. The Ki values of these compounds were in the range of 4.52±0.61-38.28±6.84pM for AChE. These results show that hCA I, II, and AChE were effectively inhibited by the novel sulfamoylcarbamates 17-21 and sulfamide derivatives 22-26. All investigated compounds were docked within the active sites of the corresponding enzymes revealing the reasons of the effective inhibitory activity.


Externalization of phosphatidylserine during apoptosis does not specifically require either isoform of phosphatidylserine synthase.
Phosphatidylserine (PtdSer) is made in mammalian cells by two PtdSer synthases, PSS1 and PSS2. In the plasma membrane PtdSer is normally localized on the inner leaflet but undergoes transbilayer movement during apoptosis and becomes exposed on the cell surface. We induced apoptosis with staurosporine in four Chinese hamster ovary (CHO) cell lines that are deficient in PSS1 and/or PSS2 to determine if PtdSer generated by either of these enzymes is required for externalization on the cell surface during apoptosis. The onset of apoptosis was confirmed by the appearance of morphological changes and DNA fragmentation while the plasma membrane remained largely intact. In all cell lines, regardless of their content of PSS1 and/or PSS2, apoptosis occurred to approximately the same extent, and within approximately the same time frame, as in parental CHO-K1 cells. The exposure of PtdSer on the cell surface was assessed by annexin V labeling and flow cytometry. Cells that were deficient in either PSS1 or PSS2, as well as cells that were deficient in both PSS1 and PSS2, externalized normal amounts of PtdSer. Our study demonstrates, that reduction of in vitro serine-exchange activity, even by 97%, does not restrict the externalization of PtdSer during apoptosis. Moreover, a normal level of expression of PSS1 and/or PSS2 is not required for generating the pool of PtdSer externalized during apoptosis.


Synchronous bilateral primary ovarian cancer with right endometroid carcinoma and left high-grade serous carcinoma: a case report and literature review.
Epithelial ovarian cancer is the most frequent gynecologic malignancy; it has a poor prognosis and often occurs bilaterally. Most cases of synchronous bilateral ovarian cancer (SBOC) are metastases from the other ovary, while bilateral primary ovarian cancer is rare. The patient was a 47-year-old Japanese woman with a complaint of abdominal pain for 1 month. Imaging results revealed bilateral ovarian tumors with suspicion of malignancy. The patient underwent a laparotomy with total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and resection of suspected dissemination in the peritoneum. Histopathological and immunohistochemical studies showed that the right ovarian tumor was an endometrioid carcinoma (G2) and had no association with endometriotic lesions. However, the left ovarian tumor was a high-grade serous carcinoma (HGSC). The final staging was stage 1 right endometrioid carcinoma and stage IIb left HGSC. Six courses of adjuvant chemotherapy with paclitaxel, docetaxel, and carboplatin were administered. The patient showed no signs of recurrence 24 months postoperatively. To the best of our knowledge, the combination of histological types in this case may be the first report of primary bilateral ovarian cancer. In SBOC, it is important to differentiate the subtypes of histology using immunostaining, in addition to morphopathology.


Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic.
The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors' recruitment and retention during 2020 with respect to the 2017-2019 period (we observe 9511 individuals), considering donors' and their municipalities of residence characteristics. Our results show an increment of new donors, with higher proportional growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented increase in the number of new donors and in their performance. Therefore, our analyses indicate that the Tuscan voluntary blood donation system was effective in dealing with the challenges posed by the COVID-19 pandemic.


The micronucleus test in piscine erythrocytes.
Cytogenetic assays on aquatic organisms are essential, as humans are exposed throughout their lifetime to several xenobiotics present in both the water and aquatic food. The micronucleus test showed to be a useful in vivo assay for genotoxicity testing. However, many aspects of its protocol need to be refined, knowledge of confounding factors should be improved and inter-species differences need further investigation. This review summarizes the protocols developed until now, provides knowledge from hematology and physiology that might be useful to researchers dealing with the micronucleus test and indicates the drawbacks of this assay.


Stem cells in the heart: what's the buzz all about?--Part 1: preclinical considerations.
New approaches for cardiac repair have been enabled by the discovery that the heart contains its own reservoir of stem cells. These cells are positive for various stem/progenitor cell markers, are self-renewing, and exhibit multilineage differentiation potential. Recently we developed a method for ex vivo expansion of cardiac-derived stem cells from human myocardial biopsies with a view to subsequent autologous transplantation for myocardial regeneration. Here we review the state of the cardiac stem cell field and our own work on cardiosphere-derived stem cells from human hearts. The first of this two-part review outlines emerging preclinical data on the application of cardiac stem cells. Part 2 continues with a discussion of other stem cell sources with clinical potential, a summary of the critical issues surrounding stem cell therapy (with an emphasis on the crucial issue of how cell transplantation may influence arrhythmias), our perception of clinical stem cell trials to date, and the issues facing the clinical application of cardiac stem cells.


Posture during the use of electronic devices in people with chronic neck pain: A 3D motion analysis project.
Non-neutral postures during computerised device use coupled with increased usage may increase the risk of neck pain. Greater knowledge of postures that individuals with neck pain adopt during computerised device use is warranted. To evaluate neck and upper limb posture while using a tablet, laptop and desktop computer (sitting and standing) in individuals with chronic neck pain. Differences in three-dimensional kinematic variables were assessed during four conditions: tablet, laptop, desktop computer (sitting and standing) in 22 individuals with chronic neck pain >3 months. Differences between kinematic variables were determined using one-way repeated measures ANOVA with Bonferroni post-hoc tests. Compared to the desktop (sitting), tablet and laptop use resulted in increased neck flexion (mean difference tablet - 14.42°, 95% CI - 19.88, -8.96, P < 0.001; laptop -7.19°, -12.08, -2.31, P = .020); upper trunk flexion (tablet -14.89°, -20.22, -9.56, P < 0.001; laptop -5.56°, -10.02, -1.09, P = .009) and tablet bilateral shoulder elevation (left 11.01 mm, 2.01, 20.04, P < .016; right 13.08 mm, 3.09, 23.11, P < .006). Tablet and laptop use resulted in greater neck flexion, bilateral shoulder elevation and upper trunk flexion compared to a standard desktop computer, suggesting individuals with chronic neck pain should be mindful of their posture when using these smaller devices. Future research should explore how differences in posture may influence neck pain.


Correction of malunited intra-articular distal radius fractures with an inside-out osteotomy technique.
To present an inside-out osteotomy technique under arthroscopic guidance to correct an intra-articular malunion. The joint is explored with a 2.7-mm arthroscope through the standard portals without infusing any water. To allow room to introduce the curettes and the osteotomes (4-mm wide), the instrumentation portals are made slightly larger than usual. Malunited fragments are cut with the osteotomes from inside the joint and advanced out. Fragments are mobilized, and granulating tissue and/or new bone is removed with curettes and synoviotomes. After disimpaction and reduction, fixation with plates or screws via the appropriate open approach is performed under arthroscopic control. No water is used throughout the procedure except at the end of the surgery to clear out debris. Steps were corrected to 0 mm in all patients. Gaps of less than 1 mm were common. This procedure allows us to define each cartilage-containing fragment and to re-create the original articular fracture line without the fear of creating new fracture lines on the articular surface. This technique can be used for patients with irregularly defined fragments that are not amenable to classic techniques. The key to the procedure is to perform the arthroscopic exploration without water infusion (dry technique).


Genetics and epigenetics of the skin meet deep sequence.
Rapid advances in next-generation sequencing technology are revolutionizing approaches to genomic and epigenomic studies of skin. Deep sequencing of cutaneous malignancies reveals heavily mutagenized genomes with large numbers of low-prevalence mutations and multiple resistance mechanisms to targeted therapies. Next-generation sequencing approaches have already paid rich dividends in identifying the genetic causes of dermatologic disease, both in heritable mutations and the somatic aberrations that underlie cutaneous mosaicism. Although epigenetic alterations clearly influence tumorigenesis, pluripotent stem cell biology, and epidermal cell lineage decisions, labor and cost-intensive approaches long delayed a genome-scale perspective. New insights into epigenomic mechanisms in skin disease should arise from the accelerating assessment of histone modification, DNA methylation, and related gene expression signatures.


Trends in the diffusion of robotic surgery in prostate, uterus, and colorectal procedures: a retrospective population-based study.
This study aimed to propose quantifiable metrics on the adoption lifecycle of robotic-assisted surgery (RAS) within and across prostate, hysterectomy, and colorectal procedures. This was a retrospective population-based cohort study of commonly performed RAS procedures in the US conducted from July 2001 to July 2015. The patients were identified from the Premier Hospital Database using International Classification of Diseases, 9th revision, Clinical Modification codes denoting prostate, uterus, and colorectal procedures. The Diffusion of Innovations theory was applied to percent RAS utilization to determine discrete eras of technology adoption. Overall and by-era patient baseline characteristics were compared between robotic and non-robotic groups. This study included a total of 2,098,440 RAS procedures comprising prostate (n = 155,342), uterus (n = 1,300,046), and colorectal (n = 643,052) procedures. Prostate (76.7%) and uterus (28.9%) procedures had the highest robotic utilization by the end of the study period and appear to be in the last adoption era (Laggard). However, robotic utilization in colorectal procedures (7.5%) was low and remained in the first era (Innovator) for a longer time (15 vs 60 vs 135 months). Whites, privately insured, patients with fewer comorbidities, and those admitted in large teaching hospitals were more likely to undergo RAS in the early study period. AS-associated patient and hospital profiles changed over time, suggesting that selected patient cohorts should be contextualized by overall adoption of a novel medical technology. The time-discretized analysis may also inform patient selection criteria and appropriate timing for clinical study stages proposed by the Idea, Development, Exploration, Assessment, Long-term study-Devices framework.


Strategies to achieve high productivity, high conversion, and high yield in yeast fermentation of algal biomass hydrolysate.
The conversion of carbohydrates in biomass via fermentation is an important component of an overall strategy to decarbonize the production of fuels and chemicals. Owing to the cost and resources required to produce biomass hydrolysates, the economic and environmental sustainability of these fermentation processes requires that they operate with high yields, sugar conversion, and productivity. Immobilized-cell technology in a continuous bioprocess can achieve significantly higher volumetric productivities than is possible from standard batch fermentation using free cells. Here, we demonstrate approaches for improvement of ethanol yield from algal hydrolysates and a mock hydrolysate medium. Saccharomyces cerevisiae was immobilized in alginate and incorporated into a two-column immobilized cell reactor system. Furthermore, the yeast quorum-sensing molecule, 2-phenylethanol, was added to improve ethanol yield by restricting growth and diverting sugar to ethanol. The bioreactor system could achieve high ethanol volumetric productivity (>20 g/Lreactor·h) and high glucose conversion (>99%) in mock hydrolysate, while the addition of 0.2% 2-phenylethanol resulted in 4.9% higher ethanol yield. With an algal hydrolysate of <10 g/L sugar, the ethanol volumetric productivity reached 9.8 g/Lreactor·h, and the addition of 0.2% 2-phenylethanol increased the ethanol yield by up to 7.4%. These results demonstrate the feasibility of novel strategies to achieve sustainability goals in biomass conversions.


Emerging role of exosome-shuttled noncoding RNAs in gastrointestinal cancers: From intercellular crosstalk to clinical utility.
Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of reliable biomarkers and the development of precise therapeutic strategies, represents imperative objectives in this field. Exosomes, small membranous vesicles released by most cells, commonly carry functional biomolecules, including noncoding RNAs (ncRNAs), which are specifically sorted and encapsulated by exosomes. Exosome-mediated communication involves the release of exosomes from tumor or stromal cells and the uptake by nearby or remote recipient cells. The bioactive cargoes contained within these exosomes exert profound effects on the recipient cells, resulting in significant modifications in the tumor microenvironment (TME) and distinct alterations in gastrointestinal tumor behaviors. Due to the feasibility of isolating exosomes from various bodily fluids, exosomal ncRNAs have shown great potential as liquid biopsy-based indicators for different gastrointestinal cancers, using blood, ascites, saliva, or bile samples. Moreover, exosomes are increasingly recognized as natural delivery vehicles for ncRNA-based therapeutic interventions. In this review, we elucidate the processes of ncRNA-enriched exosome biogenesis and uptake, examine the regulatory and functional roles of exosomal ncRNA-mediated intercellular crosstalk in gastrointestinal TME and tumor behaviors, and explore their potential clinical utility in diagnostics, prognostics, and therapeutics.


A field test of the quotient method for predicting risk to Microtus canicaudus in grasslands.
We used gray-tailed voles, Microtus canicaudus, as an experimental model species to field test a prediction of the Quotient Method (QM) for risk to small mammals of an insecticide in grasslands. In May 1997, we placed voles into 12 0.2-ha enclosures planted with a mixture of pasture grasses. In late July, we applied 1.55 kg/ha of the insecticide Guthion(R) 2S (azinphos-methyl) in three treatments: a control (all habitat sprayed with water), full spray (all of the habitat sprayed with Guthion 2S), and half-spray (one-half of the habitat sprayed with Guthion 2S and one half with water). Five replicates were used for the half-spray and control, and two replicates for the full-spray. The Guthion 2S treatment did not depress population size, growth rate, or survival of voles in half-spray or full-spray enclosures. Our results were inconsistent with the QM prediction for use of Guthion 2S in grass habitats. These results also differed from our previous studies in alfalfa habitats in which measurable responses were detected at the same application rate. The differences probably are due to the different types of vegetation between current and previous studies. The grass habitat in our enclosures was an average of 60 cm high and was very thick from ground level to about 40 cm. Much of the residue likely accumulated in the upper strata of vegetation and did not reach ground level at this application rate. Under the conditions of this study, voles were less affected in grassland habitat than they were in alfalfa habitat.


Determination of three-dimensional structures of proteins from interproton distance data by hybrid distance geometry-dynamical simulated annealing calculations.
A new hybrid distance space-real space method for determining three-dimensional structures of proteins on the basis of interproton distance restraints is presented. It involves the following steps: (i) the approximate polypeptide fold is obtained by generating a set of substructures comprising only a small subset of atoms by projection from multi-dimensional distance space into three-dimensional cartesian coordinate space using a procedure known as 'embedding'; (ii) all remaining atoms are then added by best fitting extended amino acids one residue at a time to the substructures; (iii) the resulting structures are used as the starting point for real space dynamical simulated annealing calculations. The latter involve heating the system to a high temperature followed by slow cooling in order to overcome potential barriers along the pathway towards the global minimum region. This is carried out by solving Newton's equations of motion. Unlike conventional restrained molecular dynamics, however, the non-bonded interactions are represented by a simple van der Waals repulsion term. The method is illustrated by calculations on crambin (46 residues) and the globular domain of histone H5 (79 residues). It is shown that the hybrid method is more efficient computationally and samples a larger region of conformational space consistent with the experimental data than full metric matrix distance geometry calculations alone, particularly for large systems.


Healthcare resource utilization and cost in dementia: are there differences between patients screened positive for dementia with and those without a formal diagnosis of dementia in primary care in Germany?
It is well-known that dementia is undiagnosed, resulting in the exclusion of patients without a formal diagnosis of dementia in many studies. Objectives of the present analyses were (1) to determine healthcare resource utilization and (2) costs of patients screened positive for dementia with a formal diagnosis and those without a formal diagnosis of dementia, and (3) to analyze the association between having received a formal dementia diagnosis and healthcare costs. This analysis is based on 240 primary care patients who screened positive for dementia. Within the baseline assessment, individual data about the utilization of healthcare services were assessed. Costs were assessed from the perspective of insurance, solely including direct costs. Associations between dementia diagnosis and costs were evaluated using multiple linear regression models. Patients formally diagnosed with dementia were treated significantly more often by a neurologist, but less often by all other outpatient specialists, and received anti-dementia drugs and day care more often. Diagnosed patients underwent shorter and less frequent planned in-hospital treatments. Dementia diagnosis was significantly associated with higher costs of anti-dementia drug treatment, but significantly associated with less total medical care costs, which valuated to be € 5,123 compared, to € 5,565 for undiagnosed patients. We found no association between dementia diagnosis and costs of evidence-based non-medication treatment or total healthcare cost (€ 7,346 for diagnosed vs. € 6,838 for undiagnosed patients). There are no significant differences in total healthcare cost between diagnosed and undiagnosed patients. Dementia diagnosis is beneficial for receiving cost-intensive anti-dementia drug treatments, but is currently insufficient to ensure adequate non-medication treatment for community-dwelling patients.


Recent advance in the structural analysis of HIV-1 envelope protein.
Human immunodeficiency virus type I (HIV-1), a causative agent of AIDS, is affecting today more than 35 millions of people worldwide. The advance of anti-HIV chemotherapy has made AIDS a chronic non-fatal disease in resourceful countries. Long-awaited anti-HIV-1 vaccine is still not with us yet; however, great progress in structural analyses of the envelope protein of HIV-1 in recent years starts to shed light on rational intervention targeted at the envelope protein, as will be reviewed in this article.


Neutrophil extracellular traps in bacterial infections: strategies for escaping from killing.
Neutrophils are among the first responders to virulent factors. They kill microbes by phagocytosis, oxidative burst, and as neutrophil extracellular traps (NETs). NETs production leads to unique cell death depending on, inter alia, reactive oxygen species (ROS). Recently a number of studies highlight the mechanism of bacterial escape from extracellular traps; the process that may influence the outcome of bacterial infections.


Cytoarchitecture and neurocytology of rabbit cingulate cortex.
The rabbit cingulate cortex is highly differentiated in contrast to rodents and numerous recent advances suggest the rabbit area map needs revision. Immunohistochemistry was used to assess cytoarchitecture with neuron-specific nuclear binding protein (NeuN) and neurocytology with intermediate neurofilament proteins, parvalbumin and glutamic acid decarboxylase. Key findings include: (1) Anterior cingulate cortex (ACC) area 32 has dorsal and ventral divisions. (2) Area 33 is part of ACC. (3) Midcingulate cortex (MCC) has anterior and posterior divisions and this was verified with extensive quantitative analysis and a horizontal series of sections. (4) NeuN, also known as Fox-3, is not limited to somata and formed nodules, granular clusters and striations in the apical dendrites of pyramidal neurons. (5) Area 30 forms a complex of anterior and posterior parts with further medial and lateral divisions. (6) Area 29b has two divisions and occupies substantially more volume than in rat. (7) Area 29a begins with a subsplenial component and extends relatively further caudal than in rat. As similar areal designations are often used among species, direct comparisons were made of rabbit areas with those in rat and monkey. The dichotomy of MCC is of particular interest to studies of pain as anterior MCC is most frequently activated in human acute pain studies and the rabbit can be used to study this subregion. Finally, the area 30 complex is not primarily dysgranular as in rat and is more differentiated than in any other mammal including human. The large and highly differentiated rabbit cingulate cortex provides a unique model for assessing cingulate cortex, pain processing and RNA splicing functions.


Infected aneurysms of bilateral deep femoral arteries due to Campylobacter fetus subspecies fetus.
Infected aneurysms due to Campylobacter fetus subspecies fetus have rarely been reported. Here, we describe the first case of infected aneurysm of bilateral deep femoral arteries due to C. fetus fetus. We successfully treated this case by administration of antibiotics effective for C. fetus fetus and bilateral obturator bypass with complete resection of the infected aneurysms. The aneurysmal wall culture disclosed the presence of C. fetus fetus in a microaerobic atmosphere after the operation. A distinctive culture condition was necessary to detect C. fetus fetus. In the case of infected aneurysms, we should be aware of the possibility of infection with C. fetus fetus, and an appropriate culture for this organism may be needed.


Landscape context differentially drives diet breadth for two key pollinator species.
An animal's diet contributes to its survival and reproduction. Variation in diet can alter the structure of community-level consumer-resource networks, with implications for ecological function. However, much remains unknown about the underlying drivers of diet breadth. Here we use a network approach to understand how consumer diet changes in response to local and landscape context and how these patterns compare between closely-related consumer species. We conducted field surveys to build 36 quantitative plant-pollinator networks using observation-based and pollen-based records of visitation across the gulf-coast cotton growing region of Texas, US. We focused on two key cotton pollinator species in the region: the social European honey bee, Apis mellifera, and the solitary native long-horned bee, Melissodes tepaneca. We demonstrate that diet breadth is highly context-dependent. Specifically, local factors better explain patterns of diet than regional factors for both species, but A. mellifera and M. tepaneca respond to local factors with contrasting patterns. Despite being collected directly from cotton blooms, both species exhibit significant preferences for non-cotton pollen, indicating a propensity to spend substantial effort foraging on remnant vegetation despite the rarity of these patches in the intensely managed cotton agroecosystem. Overall, our results demonstrate that diet is highly context- and species-dependent and thus an understanding of both factors is key for evaluating the conservation of important cotton pollinators.


Correction: Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study).
[This corrects the article DOI: 10.1371/journal.pone.0153096.].


Cost-utility of exercise therapy in patients with hip osteoarthritis in primary care.
To determine the cost-effectiveness (CE) of exercise therapy (intervention group) compared to 'general practitioner (GP) care' (control group) in patients with hip osteoarthritis (OA) in primary care. This cost-utility analysis was conducted with 120 GPs in the Netherlands from the societal and healthcare perspective. Data on direct medical costs, productivity costs and quality of life (QoL) was collected using standardised questionnaires which were sent to the patients at baseline and at 6, 13, 26, 39 and 52 weeks follow-up. All costs were based on Euro 2011 cost data. A total of 203 patients were included. The annual direct medical costs per patient were significantly lower for the intervention group (€ 1233) compared to the control group (€ 1331). The average annual societal costs per patient were lower in the intervention group (€ 2634 vs € 3241). Productivity costs were higher than direct medical costs. There was a very small adjusted difference in QoL of 0.006 in favour of the control group (95% CI: -0.04 to +0.02). Our study revealed that exercise therapy is probably cost saving, without the risk of noteworthy negative health effects. NTR1462.


M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium.
Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.


Changes in sleep duration and disturbances during Covid-19 lockdown and internalizing-externalizing behaviors in children with attention deficit hyperactivity disorders.
To examine how changes in sleep patterns and sleep problems occurring between the pre-pandemic and the Covid-19 lockdown period influenced mood-behavioral functioning of children with Attention Deficit Hyperactivity Disorder (ADHD). Parents of 992 children with ADHD (85.4% boys, mean age: 11.52 years, SD = 3.17), recruited from the Italian ADHD family association, completed a modified version of the Sleep Disturbance Scale for Children and filled out 11 emotional behavioral items selected from the Child Behavior Checklist (CBCL) 6-18 questionnaire. Subgroups identified based on sleep duration changes ("maintained", "increased", "reduced") and of sleep problems during lockdown ("onset", "remission", "maintained", "no sleep problem") were analyzed to evaluate the association with internalizing and externalizing scores. Sleep duration showed no or low influence on internalizing and externalizing behaviors after control for age, sex, and socioeconomic status. Patients with ADHD with "no sleep problem" showed significant lower scores in internalizing and externalizing behaviors than those who "maintained" or had "onset" of different sleep problems. The effect sizes were higher for internalizing than externalizing behaviors. Lower internalizing scores were found in those who remitted difficulty in falling asleep, daytime sleepiness, nightmares, vs. the "maintained" or "onset" groups and those who remitted hypnic jerks vs. the "onset" group. Children with ADHD who "maintained" sleep terrors reported higher internalizing and mainly externalizing scores than the other groups. Sleep problems negatively influence daytime functioning of patients with ADHD. but mood and behavioral domains show different susceptibility to the changes of sleep problems, and different vulnerability to specific sleep problems.


Effects of porcine IL-17B and IL-17E against intestinal pathogenic microorganism.
The interleukin-17 (IL-17) family plays a critical role in host defense, allergic reactions, and even tumorigenesis on different mucous membranes. IL-17 family has been cloned in human and mouse, as well IL-17A, IL-17 F in swine. So far, current knowledge on the cloning and biological functions of porcine IL-17B (poIL-17B) and porcine IL-17E (poIL-17E) is limited. In this study, poIL-17B and poIL-17E, mainly expressed in intestine, were cloned and characterized. Expression of poIL-17B and poIL-17E was upregulated after pathogenic microorganism infection. Moreover, the significant enhanced expression of antibacterial peptides PR-39 and pBD-1 was observed when poIL-17B and poIL-17E were over-expressed in the small intestinal epithelial cell line IPEC-J2. This demonstrated that poIL-17B and poIL-17E might have anti-infective capability. Pathogens infection data showed that pathogens could up-regulate poIL-17B/E expression levels. After stimulating the cells with the pathogen, continued with probiotics, the expression of poIL-17B/E was down-regulated. Meanwhile, the induced expression of poIL-17E was greater than that of poIL-17B. Invasion data indicated that poIL-17B and poIL-17E both could inhibit effectively pathogenic microorganism, while inhibitory capability of poIL-17B was stronger than that of poIL-17E. Therefore, poIL-17B and poIL-17E both could be important members against intestinal infection in the porcine IL-17 family. This study provided a theoretical basis for the prevention of intestinal diseases in pigs and thus achieved healthy farming.


Dominant mechanisms of primary resistance differ from dominant mechanisms of secondary resistance to targeted therapies.
The effectiveness of targeted therapies is currently limited, as almost all patients eventually acquire resistance within year/year and a half from therapy initiation and a small subset of a patients fail to respond at all, demonstrating intrinsic resistance. The aim of this review was to determine the potential common features and differences between the mechanisms of intrinsic and acquired resistance to targeted therapies by analyzing established resistance-generating alterations for ten FDA-approved targeted drugs. The frequency of alterations underlying intrinsic and acquired resistance shows distinctive pattern, where dominant mechanisms of intrinsic resistance include aberrations of signals downstream or upstream of the targeted protein and dominant mechanisms of acquired resistance refer to lesions in the target itself or alterations of signals at target-level that can mimic or compensate for target function. It appears that during the evolution of acquired resistance, the tumor cell is inclined to preserve the same oncogene addiction on a targeted protein it had prior to drug administration. On the other hand, intrinsic resistance develops early in tumorogenesis and is based on randomly selected mutated signals between targeted and non-targeted signaling pathways, leading to the acquisition of cancer hallmarks. In general, there is an overlap between the mechanisms of intrinsic and acquired resistance, but the occurrence frequency and distribution of alterations underlying intrinsic and acquired resistance to targeted therapies are significantly different. Focus should be placed on different group of genes in pursuing predictive markers for intrinsic and acquired resistance to targeted therapies.


Avian enteric nerve plexuses. A histochemical study.
The enteric nerve plexuses of the domestic fowl (Gallus domesticus) were investigated in sections and stretch preparations by means of the cholinesterase and glyoxylic acid fluorescence histochemical techniques. Cholinesterase-positive and varicose and non-varicose fluorescent nerve fibers were distributed at all levels of the gut in myenteric, submucosal, muscle and mucosal plexuses, and in a perivascular plexus. The density of the innervation and the detailed distribution of the nerves varied in different parts of the intestinal tract. All nerve plexuses appeared to be best developed in the rectum. Whereas the circular muscle coat contained a substantial number of nerves at all levels of the gut, the longitudinal coat was well innervated only in the rectum. The major portion of the mucosal plexus appeared to be associated with the intestinal glands. The nerve cell bodies were restricted to the myenteric and submucosal plexuses and were mainly cholinesterase-positive. Fluorescent ganglion cells were not observed. Pretreatment of stretch preparations with NADH: Nitro BT to stain ganglion cells showed that the majority of the cells were surrounded by a meshwork of fluorescent varicose fibres, although none of the fibres appeared to be associated with individual cells. The perivascular plexus was mainly associated with the arteries. The functional significance of the innervation is discussed.


Anastomotic leakage after colorectal surgery: diagnostic accuracy of CT.
To evaluate the diagnostic accuracy of CT in postoperative colorectal anastomotic leakage (AL). Two independent blinded radiologists reviewed 153 CTs performed for suspected AL within 60 days after surgery in 131 consecutive patients, with (n = 58) or without (n = 95) retrograde contrast enema (RCE). Results were compared to original interpretations. The reference standard was reoperation or consensus (a radiologist and a surgeon) regarding clinical, laboratory, radiological, and follow-up data after medical treatment. AL was confirmed in 34/131 patients. For the two reviewers and original interpretation, sensitivity of CT was 82 %, 87 %, and 71 %, respectively; specificity was 84 %, 84 %, and 92 %. RCE significantly increased the positive predictive value (from 40 % to 88 %, P = 0.0009; 41 % to 92 %, P = 0.0016; and 40 % to 100 %, P = 0.0006). Contrast extravasation was the most sensitive (reviewers, 83 % and 83 %) and specific (97 % and 97 %) sign and was significantly associated with AL by univariate analysis (P < 0.0001 and P < 0.0001). By multivariate analysis with recursive partitioning, CT with RCE was accurate to confirm or rule out AL with contrast extravasation. CT with RCE is accurate for diagnosing postoperative colorectal AL. Contrast extravasation is the most reliable sign. RCE should be performed during CT for suspected AL. • CT accurately diagnosed clinically suspected colorectal AL and showed good interobserver agreement • Contrast extravasation was the most sensitive and specific CT sign • Retrograde contrast enema during CT improved positive predictive value • Retrograde contrast enema decreased false-negative or indeterminate original CT interpretations.


Senior nursing students' reflections on deviations from guideline adherence regarding venous blood specimen collection practice: A qualitative study.
Venous blood specimen collection is a common procedure within healthcare and both diagnoses as well as treatment evaluation, are often based on results from these analyses. However, studies among both students and staff have demonstrated suboptimal adherence to venous blood specimen collection practice guidelines which in turn might jeopardize patient safety. This study aimed to describe final semester nursing students' experiences of deviations from venous blood specimen collection practice guidelines during clinical training. This study adopted a qualitative design. Twentysix final (6th) semester nursing students were recruited through purposive sampling at a Swedish university. Data were collected through semi-structured, face-to-face, focus group interviews in September 2015. The transcribed interviews were analyzed using qualitative content analysis. The students' experiences generated two categories; 1) Striving to blend in (subcategories Feeling uncomfortable and Adapting to the prevailing practice culture) and 2) Diminished confidence (subcategories Being confused due to inconsistency and Being uncertain about guideline usefulness) forming the overall theme Being a copycat. The research concludes that nursing students adapt to the prevailing practice culture encountered during clinical training, often at the expense of guidelines adherence. Since the students are being assessed during clinical training, the eagerness to belong to the team and be well-liked might be stronger than the ambition to follow guidelines. As a consequence, nursing students in clinical training might become copycats by aligning themselves with the prevailing practice culture which in turn might jeopardize adherence with VBSC guideline practice and thereby patient safety. With the ambition to support nursing students' learning in clinical training, facilitators of learning to comprise both students and supervisors need to be further addressed. Nursing students adapt to the prevailing venous blood sample collection practice culture and become copycats.