Association of obesity with incident atrial fibrillation in Korea and the United Kingdom.
Obesity has been linked to atrial fibrillation (AF) burden and severity, and epidemiological studies suggest that AF is more prevalent in whites than Asian. We aimed to investigate whether obesity mediates associations with AF in Europe and Asia using patient-level data comparisons of two cohort studies. Using Korean National Health Insurance Service's Health Screening (NHIS-HealS) and U.K. Biobank data, we included 401,206 Korean and 477,926 British aged 40-70 years without previous AF who received check-ups. The incidence and risk of AF were evaluated regarding different body mass index (BMI) values. The obese proportion (BMI ≥ 30.0 kg/m2, 2.8% vs. 24.3%, P < 0.001) was higher in the U.K. than the Korean. In the Korean and U.K. cohort, the age- and sex-adjusted incidence rates of AF were 4.97 and 6.54 per 1000 person-years among obese individuals. Compared to Koreans, the risk of AF was higher in the British population, with adjusted hazard ratios of 1.41 (Korea, 95% CI 1.26-1.58) and 1.68 (UK, 95% CI 1.54-1.82) in obese participants (P for interaction < 0.05). Obesity was associated with AF in both populations. British subjects had a greater incidence of AF related to the high proportion of obese individuals, especially participants in the obesity category, the risk of AF also increased.


Belovsky's model of optimal moose size.
Belovsky's (1978) model for optimal size in moose is applied to red deer. Criticisms are levelled at Belovsky's model. In particular, the equation he derives relating net energy intake to body weight is shown to be fundamentally invalid. Modifications are suggested using existing published information and an analysis of previously unpublished data on red deer stomach size as a function of body weight. I conclude that quantitative predictions of optimal body size are likely to be very difficult as slight changes in the relevant parameters lead to huge changes in predicted optimal weights.


Effects of sensory nerve blockade on cutaneous microvascular responses to ischemia-reperfusion injury.
Examine the effects of sensory nerve blockade on cutaneous post-occlusive reactive hyperemia (PORH) and local thermal hyperemia (LTH) following prolonged upper limb ischemia. In nine males [28 years (standard deviation:6)], volar forearm skin blood flux normalized to maximum vasodilation (%SkBFmax) was assessed at control (CTRL) and sensory nerve blockade (EMLA) treated sites during the PORH response following 20-min of complete arm ischemia and during rapid LTH (33-42 °C, 1 °C·20 s-1, held for ~30-min + 20-min at 44 °C) before and after ischemia-reperfusion (IR) injury. EMLA increased mean [95 % confidence-interval] PORH amplitude by 21%SkBFmax ([9,33]; p = 0.003), delayed time to peak by 111 s ([40,182]; p = 0.007) and increased area under the curve by 19,462%SkBFmax·s ([11,346,27,579]; p < 0.001) compared to CTRL. For LTH, EMLA delayed onset time by 76 s ([46,106]; p < 0.001) Pre-IR and by 46 s ([27,65]; p < 0.001) Post-IR compared to CTRL. Post-IR onset time was delayed for CTRL by 26 s ([8,43]; p = 0.007), but was not different for EMLA (p > 0.050) compared to Pre-IR. EMLA delayed time to initial peak by 24 s ([4,43]; p = 0.022, Main time effect) and it attenuated the initial peak by 27%SkBFmax ([12,43]; p = 0.002) Pre-IR and by 16%SkBFmax ([3,29]; p = 0.020) post-IR compared to CTRL. Post-IR, the initial peak was not different for CTRL (p > 0.050), but it was increased by 16%SkBFmax ([5,26]; p = 0.005) for EMLA compared to Pre-IR. Neither EMLA nor IR altered the steady-state heating plateau (all p > 0.050). For the current model of IR injury, sensory nerves appear to have a negligible influence on the LTH response in non-glabrous forearm skin once vasodilation has been initiated.


Determination of film-coated tablet parameters by near-infrared spectroscopy.
Near-infrared (near-IR) spectroscopy was used in the determination of three parameters of theophylline tablets film-coated with ethylcellulose. Spectra of individual intact tablets were collected on two near-IR spectrometers: a grating-based spectrometer, and an acousto-optic tunable filter spectrometer. Calibrations were developed for the prediction of the time to 50% dissolution (t50%) of theophylline for tablets of varying coat thickness, for the determination of the thickness of the ethylcellulose coat applied, and for the prediction of the hardness of coated tablets. Principal component analysis was performed on the spectra prior to calibration development. The standard errors of calibration (SEC) and prediction (SEP) for determination of dissolution rates were 2.8 and 6.6 min, respectively. The SEC for the coating thickness calibration was 0.0002 inches, with an SEP of 0.00024 inches, and the SEC and SEP for the determination of tablet hardness were 0.54 and 0.62 kilopons, respectively.


Development and external validation of a non-invasive molecular status predictor of chromosome 1p/19q co-deletion based on MRI radiomics analysis of Low Grade Glioma patients.
The 1p/19q co-deletion status has been demonstrated to be a prognostic biomarker in lower grade glioma (LGG). The objective of this study was to build a magnetic resonance (MRI)-derived radiomics model to predict the 1p/19q co-deletion status. 209 pathology-confirmed LGG patients from 2 different datasets from The Cancer Imaging Archive were retrospectively reviewed; one dataset with 159 patients as the training and discovery dataset and the other one with 50 patients as validation dataset. Radiomics features were extracted from T2- and T1-weighted post-contrast MRI resampled data using linear and cubic interpolation methods. For each of the voxel resampling methods a three-step approach was used for feature selection and a random forest (RF) classifier was trained on the training dataset. Model performance was evaluated on training and validation datasets and clinical utility indexes (CUIs) were computed. The distributions and intercorrelation for selected features were analyzed. Seven radiomics features were selected from the cubic interpolated features and five from the linear interpolated features on the training dataset. The RF classifier showed similar performance for cubic and linear interpolation methods in the training dataset with accuracies of 0.81 (0.75-0.86) and 0.76 (0.71-0.82) respectively; in the validation dataset the accuracy dropped to 0.72 (0.6-0.82) using cubic interpolation and 0.72 (0.6-0.84) using linear resampling. CUIs showed the model achieved satisfactory negative values (0.605 using cubic interpolation and 0.569 for linear interpolation). MRI has the potential for predicting the 1p/19q status in LGGs. Both cubic and linear interpolation methods showed similar performance in external validation.


Maturational changes of amino acid concentration in cerebrospinal fluid of the rat.
The cisternal spinal fluid (CF), plasma, and brain stem concentrations of 6 amino acids were measured in suckling rats between birth and one months of age. Each of the amino acids studied had its distinctive maturational pattern of CF concentration. Presumably these amino acids have separate mechanisms of transport from CF, which mature at different times.


Expression and functional analyses of microRNA417 in Arabidopsis thaliana under stress conditions.
MicroRNAs (miRNAs) are 20-25 nucleotides-long RNA transcripts that are capable of suppressing target gene expression by either mRNA cleavage or translational repression. Although many recent reports propose that miRNAs play diverse roles in growth, development, morphogenesis, and stress responses of plants, the biological roles of many miRNAs remain to be verified. Here, we investigated stress-responsive expression patterns and functional roles of miRNA417 in seed germination and seedling growth of Arabidopsis thaliana under various abiotic stress conditions. miRNA417 was expressed constantly throughout the entire growth stages and ubiquitously in all organs including stems, roots, leaves, and flowers. The expression of miRNA417 was regulated by salt stress, dehydration stress, or abscisic acid treatment. To examine the biological roles of miRNA417 in stress responses, the transgenic Arabidopsis plants that constitutively overexpress miRNA417 under the control of cauliflower mosaic virus 35S promoter were generated, and their phenotypes were analyzed under stress conditions. Results showed that seed germination of the transgenic plants was retarded compared with the wild-type plants in the presence of high salt or abscisic acid. These results imply that miRNA417 plays a role as a negative regulator of seed germination in Arabidopsis plants under salt stress conditions.


Clinical and tomographic comparison of dental implants placed by guided virtual surgery versus conventional technique: A split-mouth randomized clinical trial.
Our objective was to compare guided virtual surgery to conventional surgery in terms of angular deviation of single dental implants placed in the posterior mandible. Patients with bilateral homologous single teeth missing in the posterior mandible were eligible for this split-mouth randomized clinical trial. Cone beam computed tomography (CBCT) was performed for virtual planning of implant position and manufacturing of the stereolithographic guides. One week after the surgery, a second CBCT scan was superimposed to the initial planning. Primary endpoint was the angular deviation between virtual and clinical implant position. Secondary endpoints were linear deviations and patient-reported outcomes collected with a questionnaire. Data from 12 patients were available for analysis. Angular deviation was significantly lower using stereolithographic guides as compared to conventional guides (2.2 ± 1.1° vs. 3.5 ± 1.6°, p = .042). Linear deviations were similar for both techniques in the coronal (2.34 ± 1.01 vs. 1.93 ± 0.95 mm) and apical (2.53 ± 1.11 vs. 2.19 ± 1.00 mm) dimensions (p ˃ .05). The selection of the surgical technique had no significant impact on the patient-reported outcomes. Our data suggest that the angular discrepancy between the virtual and the clinical implant position is slightly lower when using stereolithographic guides as compared to conventional guides.


Use of CT and artificial intelligence in suspected or COVID-19 positive patients: statement of the Italian Society of Medical and Interventional Radiology.
The COVID-19 pandemic started in Italy in February 2020 with an exponential growth that has exceeded the number of cases reported in China. Italian radiology departments found themselves at the forefront in the management of suspected and positive COVID cases, both in diagnosis, in estimating the severity of the disease and in follow-up. In this context SIRM recommends chest X-ray as first-line imaging tool, CT as additional tool that shows typical features of COVID pneumonia, and ultrasound of the lungs as monitoring tool. SIRM recommends, as high priority, to ensure appropriate sanitation procedures on the scan equipment after detecting any suspected or positive COVID-19 patients. In this emergency situation, several expectations have been raised by the scientific community about the role that artificial intelligence can have in improving the diagnosis and treatment of coronavirus infection, and SIRM wishes to deliver clear statements to the radiological community, on the usefulness of artificial intelligence as a radiological decision support system in COVID-19 positive patients. (1) SIRM supports the research on the use of artificial intelligence as a predictive and prognostic decision support system, especially in hospitalized patients and those admitted to intensive care, and welcomes single center of multicenter studies for a clinical validation of the test. (2) SIRM does not support the use of CT with artificial intelligence for screening or as first-line test to diagnose COVID-19. (3) Chest CT with artificial intelligence cannot replace molecular diagnosis tests with nose-pharyngeal swab (rRT-PCR) in suspected for COVID-19 patients.


MiR-337-3p confers protective effect on facet joint osteoarthritis by targeting SKP2 to inhibit DUSP1 ubiquitination and inactivate MAPK pathway.
To probe the performance of miR-337-3p on the facet joint osteoarthritis (FJOA) and its underlying mechanism. qRT-PCR and Western blot were utilized to analyze the levels of miR-337-3p and DUSP1 in the synovial tissues from 36 FJOA patients and 10 healthy controls. The human synovial fibroblasts of FJOA were isolated and cultured followed by cell transfection. Then, cells were exposed to 10 ng/mL of IL-1β to induce inflammatory response of synovial fibroblasts. The alternation on cell biological function in cell models was determined. The binding of miR-337-3p and SKP2 was predicted by StarBase, TargetScan, DIANA-microT and miRmap, and further verified by RIP assay and dual-luciferase reporter assay. Co-IP experiment and ubiquitination assay were used to display the binding of SKP2 and DUSP1 as well as the ubiquitination and degradation of DUSP1. After that, the FJOA rat model was established and miR-337-3p mimic or negative control was given to rats by tail vein injection. The pathological changes of synovial tissues, synovitis score, and inflammation level in rats were assessed. The low expressions of miR-337-3p and DUSP1 were noticed in the synovial tissues of FJOA patients and in IL-1β-induced synovial fibroblasts, and highly expressed p-p38 MAPK was noticed. Upregulation of miR-337-3p/DUSP1 or downregulation of SKP2 inhibited IL-1β-induced proliferation and inflammatory response of synovial fibroblasts. SKP2 was the target gene of miR-337-3p, and SKP2 induced the ubiquitination and degradation of DUSP1. MiR-337-3p exerted a protective effect on FJOA rats by alleviating damage of rat synovial tissues, promoting cell apoptosis and repressing inflammatory response. MiR-337-3p plays a protective role in FJOA by negatively targeting SKP2 to suppress DUSP1 ubiquitination and inactivate the p38 MAPK pathway.


Assessment of serum calcium and phosphorus in pulmonary tuberculosis patients before, during and after chemotherapy.
Our study was aimed to assess the levels of serum calcium and phosphorus in pulmonary tuberculosis patients. Blood samples were collected from 40 patients with pulmonary tuberculosis before treatment (PTB-0), at the end of 2 months of intensive phase of treatment (PTB-2) and after 6 months of treatment (PTB-6). Age and weight matched normal healthy volunteers (n = 37) served as normal controls. Serum was analyzed for calcium and phosphorus. Serum calcium significantly decreased to hypocalcemic levels and serum phosphorus significantly decreased but was within normophosphatemic limits in pulmonary tuberculosis. Chemotherapy for tuberculosis managed to raise serum levels of both the ions, with hypocalcemia still persisting in majority of patients during treatment but getting resolved in a significant percentage of patients at the end of 6 months of treatment. Results indicate the need for calcium and phosphorus supplements in tuberculosis patients during chemotherapy. This study also warrants the need for regular monitoring of serum calcium and phosphorus in patients undergoing anti-tuberculosis treatment.


Morphological methods for evaluation of myocardial protection.
A review is presented of histological, histochemical, and electron microscopical methods considered useful in the morphological evaluation of intraoperative myocardial protection. Transmural samples of myocardium should be studied since the response of the ventricular walls to ischemic injury is not homogeneous. Collection of samples should be continued until the injury reaches a stable end-point. Emphasis is placed on the fact that ischemic injury is modified considerably by reflow phenomena. Ultrastructural studies are indispensable and histological methods are of limited value in the morphological evaluation of early myocardial injury.


Quality and human health risk assessment of uranium and other heavy metals in drinking water from Kwale County, Kenya.
Heavy metal contamination in drinking water is a global health concern. Anthropogenic and geogenic activities exacerbate the concentrations of these metals in surface and groundwater. In this study, we sampled drinking water sourced from surface and groundwater resources at the environs of Mrima Hill and the Kwale heavy minerals sand deposit, Kwale County, Kenya. The concentrations of Cr, Ni, Cu, As, Cd, Pb, and U were measured using the inductively coupled plasma mass spectrometer. The water quality indices were evaluated using the weighted arithmetic index method, while the human health risks due to exposure to these heavy metals through the ingestion pathway were assessed using deterministic and probabilistic techniques. The concentrations of Cr and Cd in samples from both study areas exceeded the national and international maximum contaminant levels in drinking water. The concentration levels of Ni, Cu, As, and U in all samples from both study areas were within the recommended values in drinking water. Therefore, the quality of water from both study areas was unsuitable for human consumption due to Cd and Cr contamination. The non-carcinogenic risk assessment also showed that the hazard indices (HI) evaluated for both children and adults at the study areas were higher than unity. In addition, the estimated carcinogenic risks of both population groups were more than the recommended value of 10-4. This study shows that the residents near Mrima Hill and the Kwale heavy minerals sand deposit remain susceptible to carcinogenic and non-carcinogenic health risks emanating from exposure to these heavy metals in drinking water.


Development of a Recombinase-aided Amplification Combined With Lateral Flow Dipstick Assay for the Rapid Detection of the African Swine Fever Virus.
To establish a sensitive, simple and rapid detection method for African swine fever virus (ASFV) B646L gene. A recombinase-aided amplification-lateral flow dipstick (RAA-LFD) assay was developed in this study. Recombinase-aided amplification (RAA) is used to amplify template DNA, and lateral flow dipstick (LFD) is used to interpret the results after the amplification is completed. The lower limits of detection and specificity of the RAA assay were verified using recombinant plasmid and pathogenic nucleic acid. In addition, 30 clinical samples were tested to evaluate the performance of the RAA assay. The RAA-LFD assay was completed within 15 min at 37 °C, including 10 min for nucleic acid amplification and 5 minutes for LFD reading results. The detection limit of this assay was found to be 200 copies per reaction. And there was no cross-reactivity with other swine viruses. A highly sensitive, specific, and simple RAA-LFD method was developed for the rapid detection of the ASFV.


Quantum-enhanced sensing of displacements and electric fields with two-dimensional trapped-ion crystals.
Fully controllable ultracold atomic systems are creating opportunities for quantum sensing, yet demonstrating a quantum advantage in useful applications by harnessing entanglement remains a challenging task. Here, we realize a many-body quantum-enhanced sensor to detect displacements and electric fields using a crystal of ~150 trapped ions. The center-of-mass vibrational mode of the crystal serves as a high-Q mechanical oscillator, and the collective electronic spin serves as the measurement device. By entangling the oscillator and collective spin and controlling the coherent dynamics via a many-body echo, a displacement is mapped into a spin rotation while avoiding quantum back-action and thermal noise. We achieve a sensitivity to displacements of 8.8 ± 0.4 decibels below the standard quantum limit and a sensitivity for measuring electric fields of 240 ± 10 nanovolts per meter in 1 second. Feasible improvements should enable the use of trapped ions in searches for dark matter.


Predictors and moderators of treatment outcome in patients receiving multi-element psychosocial intervention for early psychosis: results from the GET UP pragmatic cluster randomised controlled trial.
BackgroundThe GET UP multi-element psychosocial intervention proved to be superior to treatment as usual in improving outcomes in patients with first-episode psychosis (FEP). However, to guide treatment decisions, information on which patients may benefit more from the intervention is warranted.AimsTo identify patients' characteristics associated with (a) a better treatment response regardless of treatment type (non-specific predictors), and (b) a better response to the specific treatment provided (moderators).MethodSome demographic and clinical variables were selected a priori as potential predictors/moderators of outcomes at 9 months. Outcomes were analysed in mixed-effects random regression models. (Trial registration: ClinicalTrials.gov, NCT01436331)ResultsAnalyses were performed on 444 patients. Education, duration of untreated psychosis, premorbid adjustment and insight predicted outcomes regardless of treatment. Only age at first contact with the services proved to be a moderator of treatment outcome (patients aged ⩾35 years had greater improvement in psychopathology), thus suggesting that the intervention is beneficial to a broad array of patients with FEP.ConclusionsExcept for patients aged over 35 years, no specific subgroups benefit more from the multi-element psychosocial intervention, suggesting that this intervention should be recommended to all those with FEP seeking treatment in mental health services.


Investigating the impacts of some meteorological parameters on air pollution in Balikesir, Turkey.
Air pollution is one of the most important environmental problems in Balikesir, situated in the western part of Turkey, during the winter periods. The unfavorable climate as well as the city's topography, and inappropriate fuel usage cause serious air pollution problems. The air pollutant concentrations in the city have a close relationship with meteorological parameters. In the present study, the relationship between daily average total suspended particulate (TSP) and sulphur dioxide (SO2) concentrations measured between 1999--2005 winter seasons were correlated with meteorological factors, such as wind speed, temperature, relative humidity and pressure. This statistical analysis was achieved using the stepwise multiple linear regression method. According to the results obtained through the analysis, higher TSP and SO2 concentrations are strongly related to colder temperatures, lower wind speed, higher atmospheric pressure and higher relative humidity. The statistical models of SO2 and TSP gave correlation coefficient values (R2) of 0.735 and 0.656, respectively.


Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol.
Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine. In the rest of the hemispheres the apomorphine-induced decrease in dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol. The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine. Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect. In general, the tyrosine concentration tended to be higher on the lesioned than on the intact side in all brain structures investigated. The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow.


Women's trust in and use of information sources in the treatment of menopausal symptoms.
Frequent shifts in expert opinion over whether or not women should use hormone therapy (HT) or another menopausal treatment have left women in a difficult position; they must determine where they can obtain trustworthy menopause information. In this study, conducted 10-12 months after the Women's Health Initiative study first published results, we identified sources women use for information about menopause treatments, identified how trust-related dimensions (trustworthiness, knowledge, helpfulness, bias, and vested interest) influenced use of these sources, and determined how these trust dimensions varied with women's HT use status. A total of 765 women >45 and <61 years of age from a Midwestern managed care organization responded to a survey. Trust dimensions regarding family, friends, physicians, pharmacists, other health care providers (HCP), and various media as sources of menopause information, and use of these sources for menopause information were examined. Women ranked physicians significantly higher than pharmacists and other HCP for trustworthiness, helpfulness, and knowledgeability. Perceived bias, knowledgeability, and helpfulness showed the strongest influence on trust in physician as well as nonpharmacist HCP. Menopause stage, HT use status, and helpfulness influenced use of physician for information. Helpfulness and knowledgeability influenced trust in the pharmacist, whereas actual use was predicated on having used HT, trust, and helpfulness. Women who had never used HT trusted HCP less. HCP have important roles in providing menopause information to perimenopausal women. HCP may need to reach out and initiate these important discussions with their patients.


Application of PAT Probes in Aluminum Phosphate Adjuvant Manufacturing.
This study is focused on monitoring process parameters and quality attributes of aluminum phosphate (AlPO4) using multiple in-line probes incorporated into an industrial-scale adjuvant suspension manufacturing unit. The manufacturing of aluminum adjuvant suspension was monitored at manufacturing scale using conductivity, turbidity, infrared, and particle sizing and count probes to follow the continuous evolution of particle formation and size distribution, and the reaction kinetics during the synthesis of AlPO4. The data showed that AlPO4 forms large particles at the early stages of mixing, followed by a decrease in size and then stabilization towards the later stages of mixing and pH adjustment. The results provided a complementary view of process events and assisted in optimizing several parameters, e.g., flow rate of reactants AlCl3 and Na3PO4 solutions, mixing rate, pH, and conductivity of AlPO4, as well as adjuvant quality attribute such as particle size, thus streamlining and shortening the process development stage. The results of this study showed the usefulness of the in-line probes to automate continuous assessment of AlPO4 batch-to-batch consistency during in-house adjuvant production at the industrial scale.


Diet, obesity, and metabolic control in girls with insulin dependent diabetes mellitus.
To investigate whether girls with insulin dependent diabetes mellitus (IDDM) were more overweight than nondiabetic girls, and how diet, insulin treatment, metabolic control, age, and pubertal status were related to body weight and fat content. Case-control study. 48 IDDM girls aged 10-19 years and controls matched for age and social class participated in the study. Overweight was assessed by body mass index (BMI), relative weight, and body fat from skinfold thicknesses. Food consumption data were collected by a 48 hour recall method. The girls with IDDM were more overweight than control girls according to all measures of obesity (for example, mean BMI 20.3 v 18.9 kg/m2). The daily insulin dose/body weight correlated positively with BMI and per cent body fat. Girls with IDDM are more overweight than their peers, which indicates that a more effective prevention of obesity is needed in the treatment of diabetes.


Adopting Safe-by-Design in Science and Engineering Academia: The Soil May Need Tilling.
In recent years, Safe-by-Design (SbD) has been launched as a concept that supports science and engineering such that a broad conception of safety is embraced and structurally embedded. The present study explores the extent to which academics in a distinctively relevant subset of science and engineering disciplines are receptive towards the work and teaching practices SbD would arguably imply. Through 29 interviews with researchers in nanotechnology, biotechnology and chemical engineering differences in perceptions of safety, life-cycle thinking and responsibility for safety were explored. Results indicate that although safety is perceived as a paramount topic in scientific practice, its meaning is rigorously demarcated, marking out safety within the work environment. In effect, this creates a limited perceived role responsibility vis-à-vis safety in the production of knowledge and in teaching, with negligible critical consideration of research's downstream impacts. This is at odds with the adoption of a broader conception of, and responsibility for, safety. The considerations supporting the perceived boundaries demarcating scientific practice are scrutinized. This study suggests that implementing SbD in academia requires systemic changes, the development of new methods, and attention for researchers' and innovators' elementary views on the meaning of and responsibility for safety throughout the innovation chain.


Impact of central venous catheter repair in pediatric intestinal failure.
Patients with intestinal failure (IF) require long-term parenteral nutrition through central venous catheters (CVCs). When damaged, catheter replacement or repair is considered. Limited literature exists on repair outcomes in this population. We aimed to assess the impact of repair on durability of exiting CVCs and infection rates. This was a retrospective cohort study of pediatric IF patients with tunneled silicone CVCs over 10 years. Outcomes were evaluated by assessing CVC longevity, repair success, replacement, and postrepair infection rates. One hundred thirty-eight repairs and 45 replacements were conducted in 37 patients with repair and replacement rates of 4.7 and 1.5 per 1000 catheter days, respectively. Twenty patients (54%) required ≥1 repair. For CVCs requiring repair, median CVC durability without and with repairs were at 123 and 391 days, respectively (P < .0001). Overall repair success rate was 96% with significantly lower success in the emergency department at 81% (P = .007). The 7-day postrepair infection rate was 2.2% without specific risk factors identified. Most repairs (76%) were performed by the Pediatric Gastroenterology division. Variability in practice was noted among services, including frequency of periprocedural antibiotic use and performance of temporary repairs before permanent repairs. A gradual increase in CVC repair rate was noted over time. Our study showed that CVC repair is effective in prolonging CVC durability in pediatric IF patients without increasing infection rates. Incorporating a temporary repair as a step before permanent repair may offer a route to address potential intraluminal thrombosis before permanent repair.


Urinary cytology: the subjective diagnostic clues and their evaluation by computer.
Subjective diagnostic clues of cells contained in the urinary sediment are summarized and correlated with the clinical data. The rationale, techniques and strategy of the automation process for cells in the urinary sediment are discussed. The encouraging preliminary results of the application of a high-resolution approach to automation by the TICAS system are briefly presented.


Simulation-based medical error disclosure training for pediatric healthcare professionals.
Ethical and regulatory guidelines recommend disclosure of medical errors to patients and families. Yet few studies examine how to effectively train healthcare professionals to deliver communications about adverse events to family members of affected pediatric patients. This pilot study uses a preintervention-postintervention study design to investigate the effects of medical error disclosure training in a simulated setting for pediatric oncology nurses (N=16). The results of a paired t test showed statistically significant increases in nurses' communication self-efficacy to carry out medical disclosure (t = 6.68, p < .001). Ratings of setting "realism" and simulation effectiveness were high (21 out of 25 composite score). Findings provide preliminary support for further research on simulation-based disclosure training for healthcare professionals.


Effects of Bacillus subtilis on Production Performance, Bone Physiological Property, and Hematology Indexes in Laying Hens.
This study was to investigate the effects of Bacillus subtilis on production performance and bone pathophysiological characteristics of layers. Twenty-four 48-week-old Lohmann Pink-shell laying hens were randomly divided into two groups: a basic diet (control) and the basic diet mixed with Bacillus subtilis (0.5 g/kg) for a 60-day trial. Statistically, independent-sample t-test was used to assess the treatment differences. The results showed that Bacillus subtilis supplementation improved the percent of marketable eggs (p < 0.05) with reduced numbers of broken and soft-shelled eggs but had no effects on egg weight, height of albumen, yolk color, and Haugh unit (p > 0.05). Bacillus subtilis supplement also elevated maximum load (p = 0.06), maximum stress (p = 0.01), stiffness (p < 0.01), and Young's modulus (p < 0.01) but suppressed maximum strain (p = 0.06) in the femur. In addition, compared with control birds, phosphorous concentration (p < 0.01) was reduced in serum at day 61 but increased in the femur (p < 0.05) in Bacillus subtilis fed birds. Bacillus subtilis fed birds also had lower magnesium concentrations in both femur (p = 0.04) and feces (p = 0.09). Furthermore, Bacillus subtilis increased plasma estrogen concentration (p = 0.01) and femur TNF receptor superfamily member 11b (OPG) expression (p < 0.05) but reduced plasma IL-1 (p < 0.01) and TNF-α (p < 0.01) concentrations. These results indicate that Bacillus subtilis could be used as a health promotor to reduce overproduction-induced inflammation and associated bone damage and to increase marketable egg production. The data provide evidence for developing a management strategy to use Bacillus subtilis as a feed additive to improve marketable egg production and health and welfare status of laying hens.


Molecularly targeted agents: their promise as cancer chemopreventive interventions.
Molecular medicine has fully entered in to the oncology arena. The development of targeted therapies is one of the major ongoing efforts in cancer treatment. Targeted therapy refers to treatment strategies directed against molecular targets considered to be involved in neoplastic transformation. Such molecularly targeted agents (MTA) are currently under study in all treatment settings including that of chemoprevention, defined as the use of natural or synthetic agents to interrupt the carcinogenic process, to nip tumours in the bud. This review article aims to provide a general overview of the potential use of some of these MTA in the chemoprevention setting.


Taste receptor function.
This chapter summarizes the available data about taste receptor functions and their role in perception of food with emphasis on the human system. In addition we illuminate the widespread presence of these receptors throughout the body and discuss some of their extraoral functions. Finally, we describe clinical aspects where taste receptor signaling could be relevant.


Association of diabetes with frequency and cost of hospital admissions: a retrospective cohort study.
Acute inpatient hospital admissions account for more than half of all health care costs related to diabetes. We sought to identify the most common and costly conditions leading to hospital admission among patients with diabetes compared with patients without diabetes. We used data from the General Internal Medicine Inpatient Initiative (GEMINI) study, a retrospective cohort study, of all patients admitted to a general internal medicine service at 7 Toronto hospitals between 2010 and 2015. The Canadian Institute for Health Information (CIHI) Most Responsible Diagnosis code was used to identify the 10 most frequent reasons for admission in patients with diabetes. Cost of hospital admission was estimated using the CIHI Resource Intensity Weight. Comparisons were made between patients with or without diabetes using the Pearson χ2 test for frequency and distribution-free confidence intervals (CIs) for median cost. Among the 150 499 hospital admissions in our study, 41 934 (27.8%) involved patients with diabetes. Compared with patients without diabetes, hospital admissions because of soft tissue and bone infections were most frequent (2.5% v. 1.9%; prevalence ratio [PR] 1.28, 95% CI 1.19-1.37) and costly (Can$8794 v. Can$5845; cost ratio [CR] 1.50, 95% CI 1.37-1.65) among patients with diabetes. This was followed by urinary tract infections (PR 1.16, 95% CI 1.11-1.22; CR 1.23, 95% CI 1.17-1.29), stroke (PR 1.13, 95% CI 1.07-1.19; CR 1.19, 95% CI 1.14-1.25) and electrolyte disorders (PR 1.11, 95% CI 1.03-1.20; CR 1.20, 95% CI 1.08-1.34). Soft tissue and bone infections, urinary tract infections, stroke and electrolyte disorders are associated with a greater frequency and cost of hospital admissions in patients with diabetes than in those without diabetes. Preventive strategies focused on reducing hospital admissions secondary to these disorders may be beneficial in patients with diabetes.


Annexin V is directly involved in cystic fibrosis transmembrane conductance regulator's chloride channel function.
The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-activated chloride channel, which is regulated by protein-protein interactions. The extent to which CFTR is regulated by these interactions remains unknown. Annexin V is overexpressed in cystic fibrosis (CF), and given the functional properties of annexin V and CFTR we considered whether they are associated and if so whether this has implications for CFTR function. Using co-immunoprecipitation and overlay experiments, we show that annexin V is associated with nucleotide-binding domain 1 (NBD1) of CFTR. Surface plasmon resonance (SPR) indicated different KD values in the absence and presence of both calcium and ATP, suggesting that this interaction is calcium- and ATP-dependent. Using an siRNA approach and overexpression, we showed that CFTR chloride channel function and its localization in the cell membranes were dependent on annexin V expression. We concluded that annexin V is necessary for normal CFTR chloride channel activity. Furthermore, we show that CFTR and annexin V are partially co-distributed in normal epithelial cells in human bronchi. In conclusion, we show for the first time that annexin V is associated with CFTR and is involved in its function.


Influences of feedstock sources and pyrolysis temperature on the properties of biochar and functionality as adsorbents: A meta-analysis.
Biochar is a porous, amorphous, stable, and low-density carbon material derived from the carbonization of various biological residues. Biochars have multifunctional properties that make them promising adsorbents for the remediation of organic and inorganic contaminants from soil and water. High temperature treatment (HTT) and the properties of feedstocks are key factors influencing the properties of biochars. Feedstocks have distinctive physicochemical properties due to variations in elemental and structural composition, and they respond heterogeneously to specific pyrolysis conditions. The criteria for the selection of feedstocks and pyrolysis conditions for designing biochars for specific sorption properties are inadequately understood. We evaluated the influence of pyrolysis temperature on a wide range of feedstocks to investigate their effects on biochar properties. With increasing HTT, biochar pH, surface area, pore size, ash content, hydrophobicity and O/C vs. H/C (ratios that denote stability) increased, whereas, hydrophilicity, yield of biochar, O/C, and H/C decreased. Discriminant analysis of data from 533 published datasets revealed that biochar derived from hardwood (HBC) and softwood generally have greater surface area and carbon content, but lower content of oxygen and mineral constituents, than manure- (MBC) and grass-derived biochars (GBC). GBC and MBC have abundant oxygen-containing functional groups than SBC and HBC. The sequence of stability and aromaticity of feedstocks was MBC < GBC < SBC < HBC. Therefore, SBC and HBC are suitable for sorption of hydrophobic molecules. Biochars produced from low HTT are suitable for removal of ionic contaminants, whereas those produced at high HTT are suitable for removal of organic contaminants. The influences of biochar properties on sorption performance of heavy metals and organic contaminants are critically reviewed.


In vitro regulation of cholesterol metabolism by low density lipoproteins in skin fibroblasts from hypo-and hyperresponding squirrel monkeys.
When squirrel monkeys (Saimiri sciureus) are fed diets containing cholesterol, some individuals (hyperresponders) become hypercholesterolemic, while others (hyporesponders) are able to maintain nearly normal plasma cholesterol concentrations. Skin fibroblasts were grown from three hyperresponder and threehyporesponder squirrel monkeys, previously characterized on the basis of their plasma cholesterol response to two cholesterol-containing diets and the pheno-type of their parents. The rates of cholesterol synthesis and esterification were determined in the cultured fibroblasts incubated with low density lipoproteins isolated from normocholesterolemic squirrel monkeys or hypercholesterolemic rhesus monkeys. Both lipoprotein preparations influenced the metabolic parameters measured in a similar manner in cells from both hypo- and hyperresponder animals. Exposure of skin fibroblasts to low density lipoproteins resultd in a stimulation of cholesterol esterification and a suppression of cholesterol synthesis in cells from both hypo- and hyperresponder animals. When incubated with increasing concentrations of low density lipoprotein cholesterol, up to 50 microgram/ml, fibroblasts from both hypo-and hyperresponding animals responded with a similar maximum percentage suppression of sterol synthesis. Thus, hyperresponsiveness to dietary cholesterol in squirrel monkeys, although a heritable characteristic, is not associated with an inability of low density lipoprotein to suppress cholesterol synthesis or stimulate cholesterol esterification as occurs in familial hypercholesterolemia in man.


Risk Factors For Necrotizing Fasciitis And Its Outcome At A Tertiary Care Centre.
Necrotizing fasciitis (NF) is a serious and potentially fatal condition where there is rapid progression of inflammation of skin, subcutaneous tissue, and superficial fascia and can be mono-microbial or poly-microbial. The disease is rapidly progressive in nature and if not promptly treated leads to significant morbidity or even mortality. This study was designed to explore the various risk factors commonly present and study the outcome of the disease. This was a cross sectional study done in tertiary centre over period of one year from April 2014 to March 2015. Patient admitted with soft tissue infection were presumptively made diagnosis of NF based on clinical features and final diagnosis was made after pre-operative surgical findings. Forty two (40.38%) patients had final diagnosis of NF out of 102 soft tissue infections. Twentynine (69%) of 42 patients with NF fully recovered with surgical and medical management. Eleven (26.2%) of these patients succumbed to their illness and two (4.8%) needed amputation of limb to control the infection. The most common co-morbid condition was alcoholism, followed by diabetes mellitus. The incidence of necrotizing fasciitis in patients admitted with soft tissue infection was 40.38%. Mortality and morbidity due to this condition was found to be high.


Retinal slip compensation of pitch-constrained blue bottle flies flying in a flight mill.
In the presence of wind or background image motion, flies are able to maintain a constant retinal slip velocity by regulating flight speed to the extent permitted by their locomotor capacity. Here we investigated the retinal slip compensation of tethered blue bottle flies (Calliphora vomitoria) flying semi-freely along an annular corridor in a magnetically levitated flight mill enclosed by two motorized cylindrical walls. We perturbed the flies' retinal slip by spinning the cylindrical walls, generating bilaterally averaged retinal slip perturbations from -0.3 to 0.3 m s-1 (or -116.4 to 116.4 deg s-1). When the perturbation was less than ∼0.1 m s-1 (38.4 deg s-1), the flies successfully compensated the perturbations and maintained a retinal slip velocity by adjusting their airspeed up to 20%. However, with greater retinal slip perturbation, the flies' compensation became saturated as their airspeed plateaued, indicating that they were unable to further maintain a constant retinal slip velocity. The compensation gain, i.e. the ratio of airspeed compensation and retinal slip perturbation, depended on the spatial frequency of the grating patterns, being the largest at 12 m-1 (0.04 deg-1).


PHLDA3 Is an Important Downstream Mediator of p53 in Squamous Cell Carcinogenesis.
Squamous cell carcinomas (SCCs) are one of the most frequent solid cancer types in humans and are derived from stratified epithelial cells found in various organs. SCCs derived from various organs share common important properties, including genomic abnormalities in the tumor suppressor gene p53. There is a carcinogen-induced mouse model of SCC that produces benign papilloma, some of which progress to advanced carcinoma and metastatic SCCs. These SCCs undergo key genetic alterations that are conserved between humans and mice, including alterations in the genomic p53 sequence, and are therefore an ideal system to study the mechanisms of SCC tumorigenesis. Using this SCC model, we show that the PHLDA3 gene, a p53-target gene encoding a protein kinase B repressor, is involved in the suppression of benign and metastatic tumor development. Loss of PHLDA3 induces an epithelial‒mesenchymal transition and can complement p53 loss in the formation of metastatic tumors. We also show that in human patients with SCC, low PHLDA3 expression is associated with a poorer prognosis. Collectively, this study identifies PHLDA3 as an important downstream molecule of p53 involved in SCC development and progression.


Nuclear localization of estrogen receptor-immunoreactivity in the preoptic area of female rats and its reduction by intraventricular colchicine treatment.
The subcellular localization of estrogen receptor (ER) was investigated in the preoptic area of ovariectomized female rats by electron microscopic immunohistochemistry, using a monoclonal antibody to ER. ER-immunoreactivity was localized in the nuclei of neurons of the periventricular preoptic nucleus (Pe) and the medial preoptic area (MPA). ER-immunoreactivity had a speckled pattern in the nucleus, but was not observed in the nucleolus or cytoplasm. After intraventricular colchicine treatment, ER-immunoreactivity within the nucleus was reduced drastically in neurons of the Pe and the MPA. The possible mechanism by which colchicine alters ER-immunoreactivity is mentioned.


Healing of oral lichenoid lesions after replacing amalgam restorations: a systematic review.
We sought to systematically review the literature related to oral lichenoid lesions (OLLs) and amalgam restorations. Cohort and case-controlled studies (no randomized controlled trials or controlled clinical trials available) were reviewed with respect to inclusion criteria and data on patients with OLLs, treatment interventions, and the measurement of outcomes. Fourteen cohort and 5 case-controlled trials met the criteria. The study population consisted of 1158 patients (27% male and 73% female; age range, 23-79 years). From 16% to 91% of patients had positive patch test results for at least 1 mercury compound. Of 1158 patients, 636 had to have their restorations replaced. The follow-up period ranged from 2 months to 9 1/2 years. Complete healing ranged from 37.5% to 100%. The greatest improvements were seen in lesions in close contact with amalgam. Protocols must be standardized to obtain valid results. The replacement of amalgam restorations can result in the resolution or improvement of OLLs. Patch testing seems to be of limited value. The topographic relationship between an OLL and an amalgam restoration is a useful--but not conclusive--marker.


Protein synthesis in cells infected by chilo iridescent virus (iridovirus, type 6).
Synthesis of the polypeptides induced in CIV-infected cells was studied using radiolabelled methionine in a permissive cell line of Choristoneura fumiferana. Analysis of labelled cell extracts by high resolution polyacrylamide gel electrophoresis (PAGE) revealed the sequential appearance of at least 28 structural and non-structural polypeptides in permissive conditions. This was confirmed by analysis of protein synthesis in non-permissive cell lines of Lymantria dispar, Aedes albopictus or by the use of protein, RNA and DNA synthesis inhibitors in the permissive cell line.


Detection and discrimination of B pertussis and B holmesii by real-time PCR targeting IS481 using a beacon probe and probe-target melting analysis.
A beacon probe was designed to detect one of the two documented single nucleotide changes in IS481 target allele of Bordetella holmesii genome as compared to Bordetella pertussis. PCR amplified product targeting a region of IS481 in presence of the probe was subjected to a post-PCR hybridization and melting cycle. Hybrid of the probe with B. pertussis specific target had a different thermal stability than that with allele having the single nucleotide change in B. holmesii. The melting of B. pertussis-probe hybrid occurred in a single phase; while that of B. holmesii-probe hybrid was biphasic-one for allele identical to that in B. pertussis and the other for that with a single nucleotide change in B. holmesii genome, with a difference in melting temperature (T(m)) of 6.5 degrees C. The characteristic melting profile and T(m) analysis was the basis for discriminatory detection of B. pertussis from B. holmesii. The method was applied in a representative set of clinical isolates of B. pertussis and B. holmesii and the result was in agreement with conventional culture method.


Early detection in lung cancer. Case finding and screening.
There is general agreement that the most effective approach to lung cancer is primary prevention--stop smoking. Richards has proposed the MVROCST--the Monosyllabic Verbal Response Office Cancer Screening Test: "Do you smoke?" If "yes," intervene. If "no," move on. Ample evidence exists that a clear message from a physician to a patient about the importance of stopping smoking makes a difference. In contrast to the maze of arguments and data on early detection, this is something that each physician clearly can and should do. A reduced risk for lung cancer may begin as early as 5 years after cessation of cigarette use. Huuskonen has proposed conceptualizing screening as a coordinated intervention with the goal of identifying populations at risk and working to modify that risk. Primary prevention should be central to any efforts to reduce mortality from lung cancer, and attention to this area needs to increase despite the difficulties and frustration. Despite declining percentages of smokers in the population as a whole, it is estimated that more than 3000 teenagers become regular smokers each day in the United States. In this environment, the question of whether to recommend a CXR or sputum for early detection is not going to disappear in the near future. The NCI has recognized the persistent and important nature of this debate and is currently funding the Prostate, Lung, Colon and Ovary Cancer Screening Trial. This is a large and powerful randomized study of men and women aged 60 to 74. The lung cancer arm is designed to look at the usefulness of a yearly CXR intervention in reducing cancer-specific mortality. The overall power of the study (based on national mortality data) is 0.99 for a 15% reduction in lung cancer mortality and 0.89 for a 10% reduction, with differentially better sensitivity in men than women. The study is currently in progress at multiple sites and will be completed over the next 12 to 14 years. In the meantime, what is the right approach? It is useful in considering this question to return to the concepts of early detection, screening, and case finding. 1. Early detection in lung cancer remains a concept of uncertain applicability because of the unknowns and variability in the natural history of the disease. The available, accessible, and acceptable detection tools appear to be inadequate by current evidence. This is not a static field, however, and new work in the area of biomarkers carries promise for significantly more sensitive and specific techniques. Tockman and colleagues conclude that early detection is conceptually sound, although not currently practical, and further research may expand the role of intervention. In the end, a judgement on early detection in lung cancer must be linked to the proposed setting--screening or case finding. 2. Screening, defined as the application of a test to the general population to define disease risk further with the implied benefit of improved treatment and outcome, cannot be recommended for lung cancer. This is the perspective of the major organizations cited previously, and it is based on admittedly imperfect but nonetheless convincing data. 3. Case finding, the situation of the patient who seeks care and is available for informed discussion and negotiation on possible testing, is a potentially different situation.(ABSTRACT TRUNCATED)


Effect on liver function of acetonaemia and the fat cow syndrome in cattle.
The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis.


Prospective associations between parental substance use and youth highly processed food intake in the Fragile Families and Child Wellbeing Study.
Given growing evidence of overlap in characteristics of addictive substances and highly processed foods (e.g., ice cream), transdiagnostic approaches may be appropriate. Prior work indicates youth with parents who use addictive substances are at risk for greater substance use. The current study tested hypotheses that parental substance use behaviors would prospectively predict greater youth highly processed food intake [but not minimally processed food intake (e.g., fruit)]. The Fragile Families and Child Wellbeing Study was a longitudinal birth cohort study of youth (N = 4,898) born in large U.S. cities in 1998-2000. The current study was an archival data analysis using parental substance use data collected at youth birth and when youth were age 3, and youth diet data collected when youth were ages 5, 9, and 15. Over and above the influence of covariates including family income, prenatal maternal illicit drug use significantly predicted 0.34, 0.23, and 1.32 servings increase in youth sugary food/beverage intake at ages 5, 9, and 15, respectively, and 0.25 servings increase in youth snack foods or chips intake at age 9. Prenatal maternal illicit drug use did not significantly predict youth fruit and vegetable intake at any age. Less consistent and weaker significant prospective associations emerged between postnatal maternal substance use and youth diet, and between paternal substance use and youth diet. Prenatal exposure to illicit drugs may present transdiagnostic risk for greater youth highly processed food intake and substance use. Future causal and mechanistic research is warranted.


Assessment of treatment success and short-term effectiveness using C-arm CT immediately after hepatic chemoembolization of HCC.
To investigate semiquantitative analyses based on amount and morphology of iodized oil uptake about non-enhanced C-arm cone-beam CT(C-arm CT) immediately following hepatic chemoembolization of HCC. We retrospectively reviewed 40 C-arm CT images taken immediately following chemoembolization in 29 consecutive patients who underwent hepatic chemoembolization for HCC lesions(n=97). Two radiologists scored iodized oil uptake in the index tumours from Grade 0(complete) to 4(invisible). To describe the morphologic characteristics of uptake, the lesions scored as Grade 1 to 3 were subclassified as 'defective' and 'not-defective' with respect to uptake. To evaluate the performance of this modality, we performed a receiver operating characteristic curve analysis. All treated lesions were classified into 'complete treatment'(n=50) and 'viable HCC'(n=47). Thirty-one lesions were evaluated as Grade 0, two as Grade 4, and the rest (n=64) as between Grades 1 and 3, and the lesions of Grade 3 or 4 were all viable. Of the defective uptake lesions(n=35), 28 lesions were also viable. The areas under the curves of the lesions were 0.827 to 0.860. The analysis of C-arm CT based on the amount and morphologic characteristics of iodized oil uptake may be useful to predict the effectiveness of the hepatic chemoembolization of HCC.


Analysis of the vasodilator nerve function by nicotine in isolated dog skin artery.
Mechanisms underlying the relaxation induced by nicotine were analyzed in cutaneous arterial strips isolated from dogs and with the endothelium removed. In the strips treated with prazosin and precontracted with prostaglandin F2 alpha, nicotine produced relaxations which were not influenced by atropine but abolished by hexamethonium. Relaxations induced by nicotine were partially inhibited by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the remaining relaxations were abolished by desensitization to calcitonin gene-related peptide (CGRP) or treatment with CGRP-(8-37), a CGRP receptor antagonist, or with capsaicin. Desensitization to vasoactive intestinal polypeptide (VIP) or a VIP receptor antagonist did not influence the nicotine-induced relaxation. In the strips densensitized to CGRP, the nicotine-induced relaxation was abolished by L-NA; the inhibitory effect was reversed by L-arginine. Perivascular nerves containing NADPH diaphorase and CGRP immunoreactivity were histochemically identified in the cutaneous artery. CGRP immunoreactivity was abolished by treatment with capsaicin. It is concluded that nicotine produces relaxation in dog cutaneous arterial strips, possibly mediated by NO and CGRP liberated from vasodilator nerves.


Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling.
C. elegans cdf-1 was identified in a genetic screen for regulators of Ras-mediated signaling. CDF-1 is a cation diffusion facilitator protein that is structurally and functionally similar to vertebrate ZnT-1. These proteins have an evolutionarily conserved function as positive regulators of the Ras pathway, and the Ras pathway has an evolutionarily conserved ability to respond to CDF proteins. CDF proteins regulate Ras-mediated signaling by promoting Zn(2+) efflux and reducing the concentration of cytosolic Zn(2+), and cytosolic Zn(2+) negatively regulates Ras-mediated signaling. Physiological concentrations of Zn(2+) cause a significant inhibition of Ras-mediated signaling. These findings suggest that Zn(2+) negatively regulates a conserved element of the signaling pathway and that Zn(2+) regulation is important for maintaining the inactive state of the Ras pathway.


Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor.
The angiotensin II type 1 receptor (AT1) is a 7-transmembrane domain GPCR that when activated by its ligand angiotensin II, generates signaling events promoting vascular dysfunction and the development of cardiovascular disease. Here, we show that the single-transmembrane oxidized LDL (oxLDL) receptor (LOX-1) resides in proximity to AT1 on cell-surface membranes and that binding of oxLDL to LOX-1 can allosterically activate AT1-dependent signaling events. oxLDL-induced signaling events in human vascular endothelial cells were abolished by knockdown of AT1 and inhibited by AT1 blockade (ARB). oxLDL increased cytosolic G protein by 350% in Chinese hamster ovary (CHO) cells with genetically induced expression of AT1 and LOX-1, whereas little increase was observed in CHO cells expressing only LOX-1. Immunoprecipitation and in situ proximity ligation assay (PLA) assays in CHO cells revealed the presence of cell-surface complexes involving LOX-1 and AT1. Chimeric analysis showed that oxLDL-induced AT1 signaling events are mediated via interactions between the intracellular domain of LOX-1 and AT1 that activate AT1. oxLDL-induced impairment of endothelium-dependent vascular relaxation of vascular ring from mouse thoracic aorta was abolished by ARB or genetic deletion of AT1. These findings reveal a novel pathway for AT1 activation and suggest a new mechanism whereby oxLDL may be promoting risk for cardiovascular disease.


Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis.
Homozygous loss in the genomic sequence, a mechanism for inactivating tumor-suppressor genes (TSGs) in cancer, has been used as a tag for the identification of novel TSGs, and array-based comparative genomic hybridization (array-CGH) has a great potential for high-throughput identification of this change. We identified a homozygous loss of the very-low-density lipoprotein receptor (VLDLR) gene (9p24.2) from genome-wide screening for copy-number alterations in 32 gastric cancer (GC) cell lines using array-CGH. Although previous reports demonstrated mRNA or protein expression of VLDLR in various cancers including GC, the association between genomic losses or epigenetic silencing of this gene and carcinogenesis has never been reported before. Homozygous deletion of VLDLR was also seen in primary GCs, albeit infrequently, and about half of GC cell lines showed lost or reduced VLDLR expression. The VLDLR expression was restored in gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. According to methylation analyses, hypermethylation of the VLDLR promoter region, which all of GC lines without its expression showed, occurred in some primary GCs. Restoration of VLDLR type I expression in GC cells reduced colony formation. These results suggest that not only the expression of VLDLR but also genetic or epigenetic silencing of this gene may contribute to tumor formation and be involved in gastric carcinogenesis.


[Glycosylation modifications improve secretion and activity of intein spliced coagulation factor VIII].
to investigate the effect of glycosylation modification on secretion of intein spliced B-domain-deleted FVIII (BDD-FVIII). a total of 226 amino acid residues of FVIII B domain with six potential asparagines-linked glycosylation sites (N6) were incorporated into heavy chain of BDD-FVIII. By dual-vector co-transfer of heavy and light chain genes with fused intein (N6HCIntN and IntCLC) into cultured 293 cells, the amounts of spliced BDD-FVIII protein and coagulation activity in culture supernatant were observed by ELISA and Coatest method respectively. the amounts of spliced BDD-FVIII protein and activity were up to (123 ± 18) ng/ml and (0.94 ± 0.11) U/ml in supernatant from cells co-transfected with N6HCIntN and IntCLC genes. And they were higher than those of cells co-transfected with intein-fused heavy (HCIntN) and light chain (IntCLC) genes [(86 ± 12) ng/ml and (0.65 ± 0.07) U/ml, both P < 0.05]. Spliced BDD-FVIII protein and activity could also be detected in the supernatant from mixed cells individually transfected with N6HCIntN and IntCLC genes [(18 ± 6) ng/ml and (0.15 ± 0.05) U/ml]. it demonstrated that the glycosylation modified heavy chain can improve the secretion of intein spliced BDD-FVIII and the protein splicing can occur independent of cellular mechanism.


Adrenal cortical hormones in the spermatic vein of 95 patients with left varicocele.
Adrenocortical hormones were measured in the peripheral and spermatic venous blood samples, taken simultaneously at the time of a high vasoligation for left varicocele in 95 patients. Our results do not confirm the hypothesis of MacLeod that the deleterious effects of a varicocele on male fertility are caused by an higher local concentration of adrenocortical hormones, due to venous reflux through incompetent valves. If this is the case it occurs only in a minority of patients.


[Cell density of the corneal endothelium after penetrating keratoplasty. A retrospective study by specular microscopy].
Endothelial cell density of 70 penetrating grafts and 11 lamellar keratoplasties was studied by specular microscopy. In perforating transplants, mean cell density was 1150 cells/mm2. No correlation could be established between cell counts and diagnosis or associated surgical procedures. Minimal cell density for a clear transplant appears to be of the order of 450 cells/mm2. In lamellar keratoplasties cell loss is reduced, and this may be one way to increase the proportion of clear grafts when endothelium is healthy.


Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke.
The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.


Decreased adherence to the substrate in Rous sarcoma virus-transformed chicken embryo fibroblasts.
Cell-substrate adherence in cultures of chicken embryo fibroblasts was examined by determining the number of cells which could be detached from the culture dish by a stream of medium. Transformed cells were significantly less adherent than their normal counterparts. In cultures infected with a mutant of Rous sarcoma virus which is temperature-conditional for transformation, adherence changed promptly following a temperature shift. This change did not require progression through the cell cycle. The transformation-specific decrease in adherence required new protein synthesis, but the restoration of adherence which occurred following a shift to the restrictive temperature could occur in the absence of new protein synthesis. Inhibitor experiments suggested the importance of microfilaments and perhaps microtubules in the changes in detachability. In addition, there was a positive correlation between levels of surface LETS protein and cell substrate adherence following a temperature shift, although it seems probable that the bulk of the surface LETS is neither necessary nor sufficient for maintenance of normal cell substrate adherence.


Analysis of cytodiagnostic urinalysis findings in 77 patients with concurrent renal biopsies.
We investigated the value of cytodiagnostic urinalysis in detecting and scoring the severity of the four types of renal lesions (glomerular, interstitial, tubular, and vascular). Both cytodiagnostic urinalysis and concurrent renal biopsy were performed in 77 patients (47 from native kidneys and 30 from transplants) and the scoring and findings assessed in a double-blinded fashion. Evaluation of the reproducibility for the counting of renal cells showed a low intraobserver and interobserver variation. Cytodiagnostic urinalysis correlated with the renal biopsy with respect to primary lesions in 42 (89%) of the native kidney cases, and in 23 (77%) of the transplant kidney cases. The accuracy of diagnosis of glomerular lesions in both native and transplanted kidneys was 0.91, and for acute rejection in transplanted kidneys, the accuracy of diagnosis was 0.73. Severity scores showed good correlation between cytodiagnostic urinalysis and renal biopsy in both transplanted and in native kidneys and cytodiagnostic urinalysis correlated well with the increase in creatinine levels. The most important components of cytodiagnostic urinalysis for the diagnosis of glomerular lesions were dysmorphic erythrocytes and proteinuria. The specificity and sensitivity of dysmorphic erythrocytes for a glomerular lesion were 0.89 and 0.88, respectively. In cases with biopsy-proven glomerular lesions, more severe changes were found by cytodiagnostic urinalysis when the biopsy showed proliferative lesions in the glomeruli than when normal glomeruli were found by light microscopy. Cytodiagnostic urinalysis has the advantage over renal biopsy that it can be repeated as often as necessary and thus allows observation of the development or regression of the renal lesion over time. We conclude that cytodiagnostic urinalysis is well correlated with the renal biopsy and that it provides valuable and quantitative information regarding the disease process in the kidney.


Microbial metabolites and immune regulation: New targets for major depressive disorder.
Treatments for depression and mood disorders have been singularly targeted at the brain without consideration for the context of the rest of the body. As evidence mounts for a role of autoimmunity and inflammation as risk factors and contributors to mood disorders, attention has shifted to one of the primary immunoregulatory organs in the body--the gut. Gut-brain interactions have been established and correlative links between the microbiome and mood have been examined, but with novel tools and a base of understanding, focus shifts to the mechanisms of these communications. In this review, we examine how the small molecules produced by metabolic processes of bacteria in the gut influence the host immune system. The gaps in knowledge discussed here include the under characterized diversity of small molecules crossing the gut walls, as well as the need to close the logical loop connecting the microbiome to the immune system, and the immune system to behavior and mood. As we move past the dawn of this field, more precise understanding using novel tools and techniques will help move toward a more informed and systematic process for clinically evaluating the efficacy of probiotics and bacterially derived compounds as antidepressants and mood regulators.


Impact of non-menthol flavours in e-cigarettes on perceptions and use: an updated systematic review.
Given the exponential increase in the use of e-cigarettes among younger age groups and in the growth in research on e-cigarette flavours, we conducted a systematic review examining the impact of non-menthol flavoured e-cigarettes on e-cigarette perceptions and use among youth and adults. PubMed, Embase, PyscINFO and CINAHL were systematically searched for studies published and indexed through March 2018. Quantitative observational and experimental studies that assessed the effect of non-menthol flavours in e-cigarettes on perceptions and use behaviours were included. Specific outcome measures assessed are appeal, reasons for use, risk perceptions, susceptibility, intention to try, initiation, preference, current use, quit intentions and cessation. Three authors independently extracted data related to the impact of flavours in tobacco products. Data from a previous review were then combined with those from the updated review for final analysis. Results were then grouped and analysed by outcome measure. The review included 51 articles for synthesis, including 17 published up to 2016 and an additional 34 published between 2016 and 2018. Results indicate that non-menthol flavours in e-cigarettes decrease harm perceptions (five studies) and increase willingness to try and initiation of e-cigarettes (six studies). Among adults, e-cigarette flavours increase product appeal (seven studies) and are a primary reason many adults use the product (five studies). The role of flavoured e-cigarettes on smoking cessation remains unclear (six studies). This review provides summary data on the role of non-menthol flavours in e-cigarette perceptions and use. Consistent evidence shows that flavours attract both youth and adults to use e-cigarettes. Given the clear findings that such flavours increase product appeal, willingness to try and initiation among youth, banning non-menthol flavours in e-cigarettes may reduce youth e-cigarette use. Longitudinal research is needed to examine any role flavours may play in quit behaviours among adults.


Patient dose in angiographic interventional procedures: A multicentre study in Italy.
The Council Directive 2013/59/EURATOM considers interventional radiology to be a special practice involving high doses of radiation and requiring strict monitoring to ensure the best quality assurance programs. This work reports the early experience of managing dose data from patients undergoing angiography in a multicentre study. The study was based on a survey of about 15,200 sample procedures performed in 21 Italian hospitals centres involved on a voluntary basis. The survey concerned the collection of data related to different interventional radiology procedures: interventional cardiology, radiology, neuroradiology, vascular surgery, urology, endoscopy and pain therapy from a C-Arm and fixed units. The analysis included 11 types of procedures and for each procedure, air-kerma, kerma-area product and fluoroscopy time were collected. The duration and dose values of fluoroscopic exposure for each procedure is strongly dependent on individual clinical circumstances including the complexity of the procedure; the observed distribution of patient doses was very wide, even for a specified protocol. The median values of the parameters were compared with the diagnostic reference levels (DRL) proposed for some procedures in Italy (ISTISAN) or internationally. This work proposes local DRL values for three procedures. This first data collection serves to take stock of the situation on patient's dosimetry in several sectors and is the starting point for obtaining and updating DRL recalling that these levels are dependent on experience and technology available.


Dynamics comparison of two myoglobins with a distinct heme active site.
Sperm whale myoglobin (swMb) is a well-studied heme protein, both experimentally and theoretically. Comparatively, little attention has been paid to another member of Mb family, Aplysia limacina myoglobin (apMb). swMb and apMb have the same overall structure and perform the same biological function, i.e., O(2) carrier, while using a distinct heme active site. To provide insights into the structure-function relationship for these two Mbs, we herein made a comparison in terms of their dynamics properties using molecular dynamics simulation. We analyzed the overall structure and protein motions, as well as the intramolecular contacts, namely salt-bridges and hydrogen bonds, especially the interactions between the heme propionate groups and the polypeptide chain. The internal cavities in apMb were also compared to the well-known xenon and other cavities in swMb. Based on current simulations, we propose a unique "arginine gate" for apMb, which has a similar function to the histidine gate observed for swMb in previous studies. This study provides valuable information for understanding the homology of heme proteins, and also aids in rational design of structural and functional heme proteins by alternating the heme active site.


Prevention of mother to child transmission of HIV: evaluation of a pilot programme in a district hospital in rural Zimbabwe.
Zimbabwe has one of the highest rates of HIV seroprevalence in the world. In 2001 only 4% of women and children in need of services for prevention of mother to child transmission of HIV were receiving them. Pilot implementation of the first programme for prevention of mother to child transmission of HIV in rural Zimbabwe. 120 bed district hospital in Buhera district (285,000 inhabitants), Manicaland, Zimbabwe. Programme uptake indicators monitored for 18 months; impact of policy evaluated by assessing up-scaling of programme. Voluntary counselling and testing services for HIV were provided in the hospital antenatal clinic. Women identified as HIV positive and informed of their serostatus and their newborn were offered a single dose antiretroviral treatment of nevirapine; mother-child pairs were followed up through routine health services. Nursing staff and social workers were trained, and community mobilisation was conducted. No services for prevention of mother to child transmission of HIV were available at baseline. Within 18 months, 2298 pregnant women had received pretest counselling, and the acceptance of HIV testing reached 93.0%. Of all 2137 women who had an HIV test, 1588 (74.3%) returned to collect their result; 326 of the 437 HIV positive women diagnosed had post-test counselling, and 104 (24%) mother-child pairs received nevirapine prophylaxis. Minimum staffing, an enhanced training programme, and involvement of district health authorities are needed for the implementation and successful integration of services for prevention of mother to child transmission of HIV. Voluntary counselling and testing services are important entry points for HIV prevention and care and for referral to community networks and medical HIV care services. A district approach is critical to extend programmes for prevention of mother to child transmission of HIV in rural settings. The lessons learnt from this pilot programme have contributed to the design of the national expansion strategy for prevention of mother to child transmission of HIV in Zimbabwe.


Developmental progress in urban Aboriginal infants: a cohort study.
To measure, describe and investigate potential predictors of early developmental progress in urban Aboriginal infants. The Gudaga study is a longitudinal birth cohort study of urban Aboriginal infants. At 12 months 134 infants were assessed using the Griffiths Mental Development Scales (GMDS). The infants' developmental progress was compared with standardised norms. Total scores for the Aboriginal infants for the GMDS were significantly lower than the standards (mean difference (MD) =-4.7, P < 0.001; 95% confidence interval (CI): -6.37, -2.96). The difference was small and not clinically significant. Infant performance on the locomotor scale was equivalent to the standards; however, their performance was significantly lower on all other subscales. Reported problem alcohol use at home was the only factor found to be negatively correlated with developmental progress (MD =-7.8, P= 0.01; 95% CI: -13.9, -1.8). The presence of three or more risk factors was also found to be associated with lower developmental scores (MD =-5.4, P= 0.01; 95% CI: -9.6, -1.3). This study shows that urban Aboriginal infants are mostly developing within the normal range at 12 months. The lower scores overall compared with standards indicate that differences in development appear early in Aboriginal children and this supports the case for early intervention. The association with exposure to problem drinking and the effect of cumulative family stress may be useful in designing screening tools and interventions.


Upregulation of KDM6B contributes to lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in mice.
Histone H3K27me3 demethylase KDM6B (also known as Jumonji domain-containing protein D3, JMJD3) plays vital roles in the etiology of inflammatory responses; however, little is known about the role of KDM6B in neuroinflammation-induced anxiety-like behavior. The present study aimed to investigate the potential role of KDM6B in lipopolysaccharide (LPS)-induced anxiety-like behavior and to evaluate whether it is associated with the modulation of vestigial-like family member 4 (VGLL4). The elevated plus maze, light-dark box, and open-field test were performed to test the anxiety-like behavior induced by LPS in C57BL/6 J male mice. Levels of relative protein expression in the hippocampus were quantified by western blotting. KDM6B inhibitor GSK-J4 and microglia inhibitor minocycline as well as adeno-associated virus of Vgll4 shRNA were used to explore the underlying mechanisms. We found that KDM6B, VGLL4, interleukin-1β (IL-1β), and ionized calcium-binding adaptor molecule-1 (Iba-1, microglia marker) protein levels were increased in LPS-dose dependent manner in the hippocampus but not in prefrontal cortex. GSK-J4 treatment attenuated LPS-induced VGLL4, the signal transducer and activator of transcription 3 (STAT3), IL-1β and Iba-1 upregulation and anxiety-like behavior. Knockdown VGLL4 with Vgll4 shRNA prevented the increase of anxiety-like behavior and levels of STAT3, IL-1β, and Iba-1 expression in the hippocampus of LPS-treated mice. Moreover, minocycline, an inhibitor of microglia treatment blunted LPS-induced anxiety-like behavior. Collectively, these results demonstrate that the induction of neuroinflammation by LPS promotes KDM6B activation in the hippocampus, and LPS-induced anxiety-like behavior is associated with upregulation of VGLL4 by KDM6B in the hippocampus.


Thyroid Disorders and Peripheral Arterial Disease.
Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.


Involvement of calcitonin and its receptor in the control of calcium-regulating genes and calcium homeostasis in zebrafish (Danio rerio).
Calcitonin (CT) is one of the hormones involved in vertebrate calcium regulation. It has been proposed to act as a hypocalcemic factor, but the regulatory pathways remain to be clarified. We investigated the CT/calcitonin gene-related peptide (CGRP) family in zebrafish and its potential involvement in calcium homeostasis. We identified the presence of four receptors: CTR, CRLR1, CRLR2, and CRLR3. From the phylogenetic analysis, together with the effect observed after CT and CGRP overexpression, we concluded that CTR appears to be a CT receptor and CRLR1 a CGRP receptor. The distribution of these two receptors shows a major presence in the central nervous system and in tissues involved in ionoregulation. Zebrafish embryos kept in high-Ca(2+)-concentration medium showed upregulation of CT and CTR expression and downregulation of the epithelial calcium channel (ECaC). Embryos injected with CT morpholino (CALC MO) incubated in high-Ca(2+) medium, showed downregulation of CTR together with upregulation on ECaC mRNA expression. In contrast, overexpression of CT cRNA induced the downregulation of ECaC mRNA synthesis, concomitant with the downregulation in the calcium content after 30 hours postfertilization. At 4 days postfertilization, CT cRNA injection induced upregulation of hypercalcemic factors, with subsequent increase in the calcium content. These results suggest that CT acts as a hypocalcemic factor in calcium regulation, probably through inhibition of ECaC synthesis.


Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study.
Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy. Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data. Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective. In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.


Deriving surface-energy anisotropy for phenomenological phase-field models of solidification.
The free energy of classical density functional theory of an inhomogeneous fluid at coexistence with its solid is used to describe solidification in two-dimensional hexagonal crystals. A coarse-graining formalism from the microscopic density functional level to the macroscopic single order parameter level is provided. An analytic expression for the surface energy and the angular dependence of its anisotropy is derived and its coefficients related to the two-point direct correlation function of the liquid phase at coexistence.


Correction: Role of microglia in the dissemination of Zika virus from mother to fetal brain.
[This corrects the article DOI: 10.1371/journal.pntd.0008413.].


Intercalated architecture of MA2Z4 family layered van der Waals materials with emerging topological, magnetic and superconducting properties.
The search for new two-dimensional monolayers with diverse electronic properties has attracted growing interest in recent years. Here, we present an approach to construct MA2Z4 monolayers with a septuple-atomic-layer structure, that is, intercalating a MoS2-type monolayer MZ2 into an InSe-type monolayer A2Z2. We illustrate this unique strategy by means of first-principles calculations, which not only reproduce the structures of MoSi2N4 and MnBi2Te4 that were already experimentally synthesized, but also predict 72 compounds that are thermodynamically and dynamically stable. Such an intercalated architecture significantly reconstructs the band structures of the constituents MZ2 and A2Z2, leading to diverse electronic properties for MA2Z4, which can be classified according to the total number of valence electrons. The systems with 32 and 34 valence electrons are mostly semiconductors. Whereas, those with 33 valence electrons can be nonmagnetic metals or ferromagnetic semiconductors. In particular, we find that, among the predicted compounds, (Ca,Sr)Ga2Te4 are topologically nontrivial by both the standard density functional theory and hybrid functional calculations. While VSi2P4 is a ferromagnetic semiconductor and TaSi2N4 is a type-I Ising superconductor. Moreover, WSi2P4 is a direct gap semiconductor with peculiar spin-valley properties, which are robust against interlayer interactions. Our study thus provides an effective way of designing septuple-atomic-layer MA2Z4 with unusual electronic properties to draw immediate experimental interest.


HSP47 levels determine the degree of body adiposity.
Adiposity varies among individuals with the influence of diverse physiological, pathological, environmental, hormonal, and genetic factors, but a unified molecular basis remains elusive. Here, we identify HSP47, a collagen-specific chaperone, as a key determinant of body adiposity. HSP47 expression is abundant in adipose tissue; increased with feeding, overeating, and obesity; decreased with fasting, exercise, calorie restriction, bariatric surgery, and cachexia; and correlated with fat mass, BMI, waist, and hip circumferences. Insulin and glucocorticoids, respectively, up- and down-regulate HSP47 expression. In humans, the increase of HSP47 gene expression by its intron or synonymous variants is associated with higher body adiposity traits. In mice, the adipose-specific knockout or pharmacological inhibition of HSP47 leads to lower body adiposity compared to the control. Mechanistically, HSP47 promotes collagen dynamics in the folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPARγ protein from proteasomal degradation, partly related to MDM2. The study highlights the significance of HSP47 in determining the amount of body fat individually and under various circumstances.


Glutaraldehyde and human T cell rosettes.
Blood mononuclear cells from ten healthy donors and cells from fifty cultured human lymphoblastoid lines were tested for the capacity to form rosettes with sheep erythrocytes. The effect of adding glutaralhehyde before scoring rosettes and the effect of substituting glutaraldehyde-fixed for fresh sheep cells were both examined. The results suggest that glutaraldehyde increases the apparent proportion of rosette-forming cells by altering the sheep erythrocytes in such a way that they will adhere to some B lymphocytes. Although a small number of cells carry both surface immunoglobulins and receptors for fresh sheep erythrocytes, the rosette test with fresh sheep cells identifies T lymphocytes more accurately in the absence of glutaraldehyde than in its presence.


Penile prosthesis implantation: surgical implants in the era of oral medication.
In patients who are not satisfied with the results of oral agents (phosphodiesterase-5 inhibitors) or in whom oral agents or other medical treatment fails to produce an adequate response, penile prosthesis implantation is an excellent treatment modality for restoring erectile function. Patient/partner acceptance, use, and satisfaction rates of penile pros-theses are better than for many other alternatives including pharmacologic injections. In-flatable penile prostheses are most frequently used and have the highest satisfaction rates. Complications of these multipiece prostheses continue to decline, and patient satisfaction rates, tolerability, and longevity continue to increase.


Ovine gammaherpesvirus-2 infection associated with chronic interstitial pneumonia in a sheep.
Sheep Associated-Malignant Catarrhal Fever (SA-MCF) is severe, frequently lethal, lymphoproliferative disease predominantly of ruminants, that is caused by ovine gammaherpesvirus-2 (OvHV-2), a member of the MCF virus (MCFV) complex. However, SA-MCF in sheep is a rare entity with few demonstrations of natural diseases worldwide. This report documents the clinical, radiographical, pathological, immunohistochemical, and molecular findings of SA-MCF in a sheep. A 4-year-old, female, mixed-breed sheep with progressive emaciation for at least one month was humanely euthanized due to poor prognosis. Clinically, the animal had tachypnea, ruminal hypomotility, productive coughing with bilateral muffling sounds during pulmonary auscultation. Radiographical evaluation revealed alveolar opacity of the cranioventral pulmonary region. Grossly, there were distinct rib impressions on the pleural surface of the lungs, suggestive of interstitial pneumonia. Histopathologic evaluation of the lungs revealed several disease patterns including 1) chronic interstitial pneumonia with vasculitis and proliferating vascular lesions, and thrombosis; 2) pulmonary abscesses associated with embolic dissemination of Corynebacterium pseudotuberculosis from superficial lymph node due to caseous lymphadenitis, CLA; 3) granulomatous pneumonia associated with pulmonary nematodes; and 4) chronic pleuritis, probably due to caseous lymphadenitis. Additional significant histologic findings included widespread lymphocytic vasculitis and proliferating vascular lesions in multiple tissues, atrophic enteritis, segmental degeneration of myocardial fibers with lymphocytic pericarditis, lymphocytic interstitial nephritis, and non-suppurative encephalitis. An immunohistochemistry (IHC) assay, based on the monoclonal antibody 15A (MAb-15A), that is specific to all MCFV known to cause MCF, revealed positive, intracytoplasmic, intralesional immunoreactivity, predominantly within bronchial and bronchiolar epithelial cells of the lungs and cryptal epithelial cells of the small intestine, followed by the renal tubular epithelium, cardiomyocytes, and with patchy immunolabelling within neurons of the cerebral cortex. Molecular testing done to detect a wide range of bacterial and viral agents of ruminant diseases, only amplified OvHV-2 DNA from fresh tissue fragments of the lungs, kidney, liver, spleen, and cerebrum. Direct sequencing confirmed that the PCR amplicon derived from the pulmonary fragments had 99.2-99.7% nucleotide sequence identity with OvHV-2 reference strains and strains of OvHV-2 from Brazil. The clinical, radiographical, gross, histopathologic, IHC, and molecular findings in the lungs are consistent with chronic interstitial pneumonia associated with infection by OvHV-2. Furthermore, the non-detection of other viral agents associated with pulmonary diseases in ruminants suggest that OvHV-2 was directly associated with the development of chronic pneumonia in this sheep. Additionally, the dental alterations, CLA, and the pulmonary nematode may have contributed towards the reduced immunological statue of the animal and facilitated the occurrence of SA-MCF. These findings may indicate that OvHV-2 may be a major participant in the pathogenesis of pulmonary disease of sheep under special conditions. Moreover, the proliferating vascular lesions identified in multiple tissues are additional evidence of chronic manifestations of OvHV-2 infections as described in chronic SA-MCF of cattle, while the widespread vasculitis is consistent with SA-MCF. Additionally, the IHC findings using the MAb-15A confirmed that this diagnostic approach is efficient to identify intralesional antigens of OvHV-2.