Simulating the impact of excise taxation for disease prevention in low-income and middle-income countries: an application to South Africa.
Excise taxes are policy tools that have been applied internationally with some success to reduce consumption of products adversely impacting population health including tobacco, alcohol and increasingly junk foods and sugary beverages. As in other low-income and middle-income countries, South Africa faces a growing burden of lifestyle diseases; accordingly we simulate the impact of multiple excise tax interventions in this setting. We construct a mathematical model to simulate the health and revenue effects of increased excise taxes, which is adaptable to a variety of settings given its limited data requirements. Applying the model to South Africa, we simulate the impact of increased tax rates on tobacco and beer and of the introduction of a tax on sugar-sweetened beverages (SSB). Drawing on surveys of product usage and risk factor prevalence, the model uses a potential impact fraction to simulate the health effects of tax interventions. Adopting an excise rate of 60% on tobacco would result in a gain of 858 923 life-years (95% uncertainty interval (UI) 480 188 to 1 310 329), while adopting an excise rate of 25% on beer would result in a gain of 568 063 life-years (95% UI 412 110 to 775 560) and the adoption of a 20% tax on SSBs would result in a gain of 688 719 life-years (95% UI 321 788 to 1 079 653). More aggressive excise tax policies on tobacco, beer and SSBs in South Africa could result in meaningful improvements in population health and raised revenue.


The Correlation Between Serum Chemokines and Clinical Outcome in Patients with Advanced Biliary Tract Cancer.
Biliary tract cancers (BTCs) are known to have a dismal prognosis. A number of chemokines play important roles in the progress of BTCs. However, the serum levels of chemokines in BTCs have not yet been explored. The sera of healthy donors (n = 8) and patients with BTCs who were enrolled in second line sunitinib trials (n = 27) were collected. The concentrations of three kinds of chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay. The median concentrations of chemokines were compared between healthy donors and BTC patients and the role of chemokines as a prognostic biomarker was examined. BTC patients generally had higher serum levels of CXCL5 and CXCL12 compared to healthy donors. Patients with cholangiocarcinoma showed significantly higher levels of serum CXCL12 than patients with gallbladder cancer. In survival analysis, only CXCL12 level showed a prognostic impact on overall survival (median OS: 6.9 vs. 0.9 months in low CXCL12 vs. high CXCL12, respectively; P = .008). High CXCL5 levels were also correlated with poor survival without statistical insignificance (median OS: 6.2 vs. 2.0 months in low CXCL5 vs. high CXCL5, respectively; P = .070). There was a significant difference in OS according to the level of CXCL12, suggesting that serum CXCL12 levels may be a useful surrogate marker for clinical outcome in advanced BTCs.


Appraising the need for care in Alzheimer's disease.
Increasing incidences of dementia necessitate the improvement of supportive measures for patients suffering from this disease and their proxies. Clinicians without psychiatric backgrounds and others involved in appraising the supportive needs of dementia patients, such as those who allocate nursing insurance, base their appraisals on the ability of patients to perform basic and instrumental activities of daily living (B-ADL, iADL). Our aim was to investigate whether a reduced ability of the patient to perform ADL is sufficient to adequately assess the supportive needs of family caregivers. Cross-sectional baseline data were obtained from dementia patients and their proxies in the context of a nationwide prospective cohort study on non-pharmacological treatment of dementia. To our knowledge, the present study is the first country-wide study to assess patients and proxies in their domestic surroundings (e.g. Mini-Mental State Examination (MMSE) Behave-AD, B-ADL and iADL for patients; Quality of Life (QOL) and depression of the proxy). Logistic and linear regression analysis show that the allocation of nursing care allowance provided by German mandatory nursing insurance is associated with scores on the B-ADL- and iADL scales, but not with the severity of behavioural symptoms or the supportive time the proxies spend on caring. However, the severity of cognitive and non-cognitive symptoms of dementia patients, correlate with each other and both parameters correlate with the time the proxy spends on caring. The time spent on caring is associated with an increase in depression and a reduction in the quality of life of the proxy. Basic and instrumental activities of daily living do not sufficiently reflect the perceived burden of care experienced by the proxy who has to cope with the imposition of the dementia patients' behavioural symptoms. When allocating nursing care, patients' behavioural symptoms should also be taken into consideration, because depressive symptoms of proxies are linked to non-cognitive symptoms in dementia patients. To provide better health care, it is necessary to identify and treat psychiatric symptoms in proxies who care for dementia patients as early as possible.


A postmarketing evaluation of the frequency of use and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years.
The 2007 US approval for use of live attenuated influenza vaccine (LAIV) in children aged 24-59 months included precautions against use in (1) children <24 months and children aged 24-59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. A postmarketing commitment was initiated to monitor LAIV use and the frequency of select safety outcomes in these cohorts. Vaccination rates and the frequency of hospitalizations or emergency department visits within 42 days after LAIV and trivalent inactivated influenza vaccine (TIV) administration were estimated from 2007 to 2009 claims data from a health insurance database. Rates of LAIV use per 10,000 child-days among cohorts 1, 2, and 4 were low relative to rates among the LAIV-recommended population (2007-2008; 0.03-0.78 vs. 1.32, 2008-2009; 0.08-3.26 vs. 5.94). However, rates of LAIV use per 10,000 child-days in cohort 3 were similar to rates among the LAIV-recommended population (2007-2008; 1.55 vs. 1.32, 2008-2009; 5.01 vs. 5.94). The rate of emergency department visits/hospitalizations within 42 days of vaccination with LAIV was the same as or less than the rate within 42 days of vaccination with TIV. Less restricted LAIV use in children with past wheezing may be related to the broad definition of recurrent wheezing used in national guidelines and the current study. In the small number of nonrecommended children receiving LAIV, no safety signals were identified.


Osmotic stress alters chromatin condensation and nucleocytoplasmic transport.
Osmotic stress is a potent regulator of biological function in many cell types, but its mechanism of action is only partially understood. In this study, we examined whether changes in extracellular osmolality can alter chromatin condensation and the rate of nucleocytoplasmic transport, as potential mechanisms by which osmotic stress can act. Transport of 10 kDa dextran was measured both within and between the nucleus and the cytoplasm using two different photobleaching methods. A mathematical model was developed to describe fluorescence recovery via nucleocytoplasmic transport. As osmolality increased, the diffusion coefficient of dextran decreased in the cytoplasm, but not the nucleus. Hyper-osmotic stress decreased nuclear size and increased nuclear lacunarity, indicating that while the nucleus was getting smaller, the pores and channels interdigitating the chromatin had expanded. The rate of nucleocytoplasmic transport was increased under hyper-osmotic stress but was insensitive to hypo-osmotic stress, consistent with the nonlinear osmotic properties of the nucleus. The mechanism of this osmotic sensitivity appears to be a change in the size and geometry of the nucleus, resulting in a shorter effective diffusion distance for the nucleus. These results may explain physical mechanisms by which osmotic stress can influence intracellular signaling pathways that rely on nucleocytoplasmic transport.


Attentional sequence-based recognition: Markovian and evidential reasoning.
Biological vision systems explore their environment via allocating their visual resources to only the interesting parts of a scene. This is achieved by a selective attention mechanism that controls eye movements. The data thus generated is a sequence of subimages of different locations and thus a sequence of features extracted from those images - referred to as attentional sequence. In higher level visual processing leading to scene cognition, it is hypothesized that the information contained in attentional sequences are combined and utilized by special mechanisms - although still poorly understood. However, developing models of such mechanisms prove out to be crucial - if we are to understand and mimic this behavior in robotic systems. In this paper, we consider the recognition problem and present two approaches to using attentional sequences for recognition: Markovian and evidential reasoning. Experimental results with our mobile robot APES reveal that simple shapes can be modeled and recognized by these methods - using as few as ten fixations and very simple features. For more complex scenes, longer attentional sequences or more sophisticated features may be required for cognition.


Seroprevalence of markers for hepatitis B, C and G in male and female prisoners--NSW, 1996.
1. Establish the prevalence of markers for hepatitis B (HBV), C (HCV) and G (HGV) in a sample of male and female inmates. 2. Examine exposure to multiple viruses. 3. Compare risk factors for HGV infection with known risk factors for HBV and HCV. Cross-sectional random sample stratified by sex, age and Aboriginality. Inmates were screened for three hepatitis markers. Participants were 789 inmates (657 male, 132 female) in 27 correctional centres in New South Wales, 1996. Overall detection of each of the three screening markers was 35% for HBV, 39% for HCV and 10% for HGV. Exposure rates were higher in female prisoners than males. Increased rates of anti-HBc were observed in Aboriginal inmates compared with non-Aboriginals (54% cf. 27%); anti-HCV and HGV-RNA were comparable between the two groups (36% cf. 41% and 9% cf. 10%). Markers were significantly higher in female injecting drug users (IDU), particularly HCV (90% cf. 66%). Thirty-five per cent of inmates were unaware of their HCV status. For HBV, 72% did not self-report past or present exposure despite serological evidence to the contrary. The multivariate analysis identified Aboriginality, long-term injecting and injecting while in prison as risk factors for HBV. HCV risk factors were female sex, non-Aboriginality, institutionalisation and IDU-associated behaviours. For HGV, female sex and previous imprisonment were significant risk factors but IDU was not. Blood-borne hepatitis viruses are common in prison inmates, particularly females (HBV, HCV and HGV), Aboriginals (HBV) and IDU (HBV and HCV). Infection can be related to a number of risk factors, which appear similar for HBV and HCV, but distinct from HGV.


Human papillomavirus: detection of viral DNA sequences and evidence for molecular heterogeneity in metaplasias and dysplasias of the uterine cervix.
Colposcopic-directed biopsies of the uterine cervix from 22 patients were analyzed for the presence of human papillomavirus (HPV) DNA and structural antigens. 11 of the biopsies were classified microscopically as mild dysplasia, 3 as moderate dysplasia, 1 as severe dysplasia, and 7 as squamous metaplasia. Nonstringent hybridization with a bovine papillomavirus type 1 DNA probe and immunocytochemical analysis with an antiserum against papillomavirus genus-specific structural antigens were performed on all specimens. Of the 11 mild dysplasias, both HPV DNA and structural antigens were detected in 5, only HPV antigens in 3, only HPV DNA in 1, and neither DNA nor structural antigens in 2. Both HPV DNA and structural antigens were present in the 3 cases of moderate dysplasia. Only HPV DNA sequences were detected in the single case of severe dysplasia. HPV DNA was detected in 2 cases of squamous metaplasia. The 5 remaining cervical biopsies showing squamous metaplasia, tissue from 3 placentas, and 6 cervical carcinomas were negative for HPV DNA and structural antigens. Restriction enzyme cleavage patterns of HPV DNA in the dysplasias suggested that there are multiple virus types or subtypes associated with cervical dysplasia. Stringent hybridization with a HPV type 11 (HPV-11) probe revealed that only 1 of 10 dysplasias contained sequences with homology to the probe. Of the remaining 9 dysplasias, 5 contained HPV sequences detected under nonstringent hybridization. 2 of 4 squamous metaplasias contained viral sequences which hybridized to the HPV-11 probe as well as 1 of 6 cervical carcinomas.


Is this the end of cytotoxic chemotherapy in Merkel cell carcinoma?
Although cytotoxic chemotherapy has been used often in the management of Merkel cell carcinoma (MCC), its benefit remains uncertain. Despite being considered a chemosensitive disease, the duration of response is generally short, and the survival benefit is unclear. With the recent FDA approval of the anti-programmed cell death ligand 1 (PD-L1) antibody avelumab for patients with advanced MCC and the limited and controversial data on chemotherapy, it is important to put in perspective whether conventional chemotherapy should remain an option for these patients. Here, we review the evidence and controversies around chemotherapy in MCC as well as two recent studies on immunotherapy that changed the treatment paradigm for this disease.


Use of a minimally invasive tubular retraction system for deep-seated tumors in pediatric patients.
Microsurgical removal is the preferred treatment for most deep-seated, intraaxial tumors in the pediatric population. The feasibility of surgery as an option has improved with advances in surgical technology and technique. Tubular retractors disperse retraction forces over a greater surface area than do conventional retractors, which can lower the risk of ischemic complications. The authors describe their experience utilizing a new tubular retractor system specifically designed for cranial applications in conjunction with frameless neuronavigation. The Vycor ViewSite retractor was used in 4 pediatric patients (ages 15 months and 9, 10, and 16 years) with deep-seated intraaxial tumors. The lesions included a papillary tumor of the pineal region, a low-grade astrocytoma in the occipital lobe, a dysembryoplastic neuroepithelial tumor arising from the basal ganglia, and an intraventricular low-grade glioma. The extent of white matter damage along the surgical trajectory (based on T2 or FLAIR and diffusion restriction/apparent diffusion coefficient signals) and the extent of resection were assessed on postoperative imaging. Satisfactory resection or biopsy was achieved in all patients. A comparison of pre- and postoperative MR imaging studies revealed evidence of white matter damage along the surgical trajectory in 1 patient. None of the patients demonstrated new neurological deficits postoperatively. Obtaining surgical access to deep-seated, intraaxial tumors is challenging. In this small series of pediatric patients, the combination of the ViewSite tubular retractor and frameless neuronavigation facilitated the surgical approach. The combination of these technologies adds to the armamentarium to safely approach tumors in deep locations.


Quantitative ultrastructural analysis in cardiac membrane physiology.
Quantitative measurements on electron micrographs of heart muscle can yield information useful for cellular physiologists and at present not obtainable in other ways. These methods are subject to preparative artifact, sampling problems, and problems inherent in the mathematical description of ultrastructure. Nevertheless they provide the best available data for membrane areas of the plasmalemma and its components, as well as for membrane areas of the sarcoplasmic reticulum and mitochondria. Morphometric methods can be used to study growth of membranes. Changes in the volumes of intracellular membrane-limited subcompartments can also be measured. Quantitative analysis of freeze-fractured membrane replicas can be carried out either by a statistical approach or by optical diffraction. In this way, physiological perturbations or developmental events leading to changes in membrane permeability can be studied for correlated changes in membrane structure.


Isolation of Newcastle disease virus from birds of prey.
In the 4 year period 1971-74 11 isolations of Newcastle Disease Virus (NDV) were made from 44 birds of prey that died in captivity. Three species of Falconiformes were involved, including one red-headed falcon (Falco chicquera), 5 European kestrels (F. tinnunculus), and 2 secretary birds (Sagittarius serpentarius), also 2 species of Strigiformes, comprising 2 barn owls (Tyto alba) and one little owl (Athene noctua). All NDV isolates were of the velogenic type.


The influence of locus of control on self-rated health in context of chronic disease: a structural equation modeling approach in a cross sectional study.
Self-rated health is a robust predictor of several health outcomes, such as functional ability, health care utilization, morbidity and mortality. The purpose of this study is to investigate and explore how health locus of control and disease burden relate to self-rated health among patients at risk for cardiovascular disease. In 2009, 414 Swedish patients who were using statins completed a questionnaire about their health, diseases and their views on the three-dimensional health locus of control scale. The scale determines which category of health locus of control - internal, chance or powerful others - a patient most identifies with. The data was analyzed using logistic regression and a structural equation modeling approach. The analyses showed positive associations between internal health locus of control and self-rated health, and a negative association between health locus of control in chance and powerful others and self-rated health. High internal health locus of control was negatively associated with the cumulative burden of diseases, while health locus of control in chance and powerful others were positively associated with burden of diseases. In addition, age and education level had indirect associations with self-rated health through health locus of control. This study suggests that self-rated health is positively correlated with internal locus of control and negatively associated with high locus of control in chance and powerful others in patients at high risk for cardiovascular disease. Furthermore, disease burden seems to be negatively associated with self-rated health.


Effects and Safety of Oral Iron for Heart Failure with Iron Deficiency: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.
Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients. Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool. Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD = 1.52%, 95% CI: 0.69 to 2.36, P = 0.0003) and serum ferritin (MD = 1.64, 95% CI: 0.26 to 3.02, P = 0.02). However, there was no between-group difference in the 6-minute walk distances (6MWT), N terminal pro B type natriuretic peptide (NT-proBNP) or hemoglobin level when compared with control group. Subgroup analyses revealed that the effects of oral iron on 6 MWT and serum ferritin could not be affected by duration and frequency of oral iron uptakes. In trial sequential analysis of LVEF and serum ferritin, the Z-curves crossed the traditional boundary and trail sequential monitoring boundary but did not reach the required information size. This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.


Noninvasive detection of hepatic lipidosis in dairy cows with calibrated ultrasonographic image analysis.
The aim was to test the accuracy of calibrated digital analysis of ultrasonographic hepatic images for diagnosing fatty liver in dairy cows. Digital analysis was performed by means of a novel method, computer-aided ultrasound diagnosis (CAUS), previously published by the authors. This method implies a set of pre- and postprocessing steps to normalize and correct the transcutaneous ultrasonographic images. Transcutaneous hepatic ultrasonography was performed before surgical correction on 151 German Holstein dairy cows (mean +/- standard error of the means; body weight: 571+/-7 kg; age: 4.9+/-0.2 yr; DIM: 35+/-5) with left-sided abomasal displacement. Concentration of triacylglycerol (TAG) was biochemically determined in liver samples collected via biopsy and values were considered the gold standard to which ultrasound estimates were compared. According to histopathologic examination of biopsies, none of the cows suffered from hepatic disorders other than hepatic lipidosis. Hepatic TAG concentrations ranged from 4.6 to 292.4 mg/g of liver fresh weight (FW). High correlations were found between the hepatic TAG and mean echo level (r=0.59) and residual attenuation (ResAtt; r=0.80) obtained in ultrasonographic imaging. High correlation existed between ResAtt and mean echo level (r=0.76). The 151 studied cows were split randomly into a training set of 76 cows and a test set of 75 cows. Based on the data from the training set, ResAtt was statistically selected by means of stepwise multiple regression analysis for hepatic TAG prediction (R(2)=0.69). Then, using the predicted TAG data of the test set, receiver operating characteristic analysis was performed to summarize the accuracy and predictive potential of the differentiation between various measured hepatic TAG values, based on TAG predicted from the regression formula. The area under the curve values of the receiver operating characteristic based on the regression equation were 0.94 (<50 vs. >or=50mg of TAG/g of FW), 0.83 (<100 vs. >or=100mg of TAG/g of FW), and 0.97 (<50 vs. >or=100mg of TAG/g of FW). The CAUS methodology and software for digitally analyzing liver ultrasonographic images is considered feasible for noninvasive screening of fatty liver in dairy herd health programs. Using the single parameter linear regression equation might be ideal for practical applications.


Transcatheter heart valve failure: a systematic review.
A comprehensive description of transcatheter heart valve (THV) failure has not been performed. We undertook a systematic review to investigate the aetiology, diagnosis, management, and outcomes of THV failure. The systematic review was performed in accordance with the PRISMA guidelines using EMBASE, MEDLINE, and Scopus. Between December 2002 and March 2014, 70 publications reported 87 individual cases of transcatheter aortic valve implantation (TAVI) failure. Similar to surgical bioprosthetic heart valve failure, we observed cases of prosthetic valve endocarditis (PVE) (n = 34), structural valve failure (n = 13), and THV thrombosis (n = 15). The microbiological profile of THV PVE was similar to surgical PVE, though one-quarter had satellite mitral valve endocarditis, and surgical intervention was required in 40% (75% survival). Structural valve failure occurred most frequently due to leaflet calcification and was predominantly treated by redo-THV (60%). Transcatheter heart valve thrombosis occurred at a mean 9 ± 7 months post-implantation and was successfully treated by prolonged anticoagulation in three-quarters of cases. Two novel causes of THV failure were identified: late THV embolization (n = 18); and THV compression (n = 7) following cardiopulmonary resuscitation (CPR). These failure modes have not been reported in the surgical literature. Potential risk factors for late THV embolization include low prosthesis implantation, THV undersizing/underexpansion, bicuspid, and non-calcified anatomy. Transcatheter heart valve embolization mandated surgery in 80% of patients. Transcatheter heart valve compression was noted at post-mortem in most cases. Transcatheter heart valves are susceptible to failure modes typical to those of surgical bioprostheses and unique to their specific design. Transcatheter heart valve compression and late embolization represent complications previously unreported in the surgical literature.


Serial S100B Sampling Detects Intracranial Lesion Development in Patients on Extracorporeal Membrane Oxygenation.
Introduction: Intracranial lesion development is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality. As neurological assessment during ECMO treatment remains challenging, protein biomarkers of cerebral injury could provide an opportunity to detect intracranial lesion development at an early stage. The aim of this study was to determine if serially sampled S100B could be used to detect intracranial lesion development during ECMO treatment. Methods: We conducted an observational cohort study of all patients treated with ECMO at ECMO Center Karolinska (Karolinska University Hospital, Stockholm, Sweden) between January and August 2018, excluding patients who did not undergo a computerized tomography scan (CT) during treatment. S100B was prospectively collected at hospital admission and then once daily. The primary end-point was any type of CT verified intracranial lesion. Receiver operating characteristics (ROC) curves and Cox proportional hazards models were employed. Results: Twenty-nine patients were included, of which 15 (52%) developed an intracranial lesion and exhibited higher levels of S100B overall. S100B had a robust association with intracranial lesion development, especially during the first 200 hours following admission. The best area-under-curve (AUC) to predict intracranial lesion development was 40 and 140 hours following ECMO initiation, were a S100B level of 0.69μg/L had an AUC of 0.81 (0.628-0.997). S100B levels were markedly increased following the development of intracranial hemorrhage. Conclusions: Serial serum S100B samples in ECMO patients were both significantly elevated and had an increasing trajectory in patients developing intracranial lesions. Larger prospective trials are warranted to validate these findings and to ascertain their clinical utility.


Entropy-Based Metrics for Occupancy Detection Using Energy Demand.
Smart Meters provide detailed energy consumption data and rich contextual information that can be utilized to assist electricity providers and consumers in understanding and managing energy use. The detection of human activity in residential households is a valuable extension for applications, such as home automation, demand side management, or non-intrusive load monitoring, but it usually requires the installation of dedicated sensors. In this paper, we propose and evaluate two new metrics, namely the sliding window entropy and the interval entropy, inspired by Shannon's entropy in order to obtain information regarding human activity from smart meter readings. We emphasise on the application of the entropy and analyse the effect of input parameters, in order to lay the foundation for future work. We compare our method to other methods, including the Page-Hinkley test and geometric moving average, which have been used for occupancy detection on the same dataset by other authors. Our experimental results, using the power measurements of the publicly available ECO dataset, indicate that the accuracy and area under the curve of our method can keep up with other well-known statistical methods, stressing the practical relevance of our approach.


Purification, characterizations of a snake guard seeds lectin with antitumor activity against Ehrlich ascites carcinoma cells in vivo in mice.
A lectin was purified (designated as TCSL) from the Snake guard seeds with molecular mass of 56±2 kDa containing two subunits (34±1 and 22±1 kDa.). TCSL exhibited high agglutination activity at the temperature range 30 to 70°C and did not lose its activity between pH 3.0 to 12.0. The lectin was stable in the presence of denaturants and agglutinated mouse, goat, cow, chicken and human erythrocytes. TCSL did not show antifungal activity whereas it agglutinated six pathogenic bacteria and showed less toxicity against brine shrimp nauplii with the LC50 of 261±29 μg/ml. TCSL showed 28% and 72% inhibition against Ehrlich ascites carcinoma (EAC) cells in vivo in mice when administered 1 mg/kg/day and 2 mg/kg/day (i.p.) respectively for five days. TCSL enhanced the number of macrophages remarkably in the normal mice. The lectin reduced the tumor burden to 62% of EAC cells and significantly increased the hemoglobin and RBC. Treating the EAC bearing mice with TCSL at 2 mg/Kg/day for ten days with a monitoring of 20 days decreased the total WBC towards the normal level and it increased the life span by 39%.


Bronchoscopic Lung Volume Reduction in Patients with Severe Emphysema.
Bronchoscopic lung volume reduction (BLVR) is a minimally invasive procedure for patients with symptomatic severe emphysema who may not be candidates for surgical lung volume reduction. BLVR has been shown to improve both functional and clinical outcomes with a relatively low risk of severe complications. Any potential candidate to BLVR should be on optimal pharmacological and nonpharmacological treatment. Radiographic and pulmonary function testing provide key data to help identify potential BLVR candidates. A variety of BLVR techniques have been published with different associated benefits and risks. Current strategies include either blocking procedures such as endobronchial valves and intrabronchial valves or nonblocking procedures such as endobronchial coils and bronchoscopic thermal vapor ablation. The aim of this review is to describe current options of BLVR including their efficacy and safety based on available data.


Magnetic Field Reference Levels for Arbitrary Periodic Waveforms for Prevention of Peripheral Nerve Stimulation.
Guidelines for prevention of peripheral nerve stimulation from exposure to low frequency magnetic fields have been developed by standard-setting bodies. Exposure limits or reference levels (RLs) are typically set in terms of the maximum root-mean-square amplitude of a sinusoidal waveform; however, environmental flux densities are often periodic, non-sinusoidal waveforms. This work presents a procedure for deriving RLs for any generalized periodic waveform using the empirical nerve-stimulation threshold data obtained from human volunteer MRI experiments. For this purpose, the "Law of Electrostimulation" (LOE), which sets forth conditions of a waveform necessary to trigger the action potential required to depolarize cell membranes, is applied to various waveforms. The results of the LOE analysis are waveform-specific, amplitude thresholds of stimulation that are found in terms of the empirically-derived rheobase threshold time-rate-of-change flux density and chronaxie from trapezoidal pulse MRI experiments. The thresholds are converted to amplitude RLs in two asymptotic frequency regimes as per the usual practice in standard setting. The resulting RLs have the same frequency dependence as in existing standards (i.e., inverse-frequency below a transition frequency and flat above). It is shown that the transition frequency is dependent only on the shape of the waveform. Both sinusoidal and non-sinusoidal waveforms have identical peak-to-peak amplitude RLs above their respective transition frequencies. Below these frequencies, all peak-to-peak amplitude RLs have the same functional dependence on frequency when the frequency is normalized to the waveform-specific transition frequency. This results in simple criteria for testing the amplitude of any arbitrary periodic waveform against potential for stimulation. These criteria are compared to guidance given for non-sinusoidal waveforms in the ICNIRP 1 Hz-100 kHz exposure standard.


Dynamic downregulation of Nogo receptor expression in the rat forebrain by amphetamine.
Nogo receptors (NgRs) are a family of cell surface receptors that are broadly expressed in the mammalian brain. These receptors could serve as an inhibitory element in the regulation of activity-dependent axonal growth and spine and synaptic formation in the adult animal brain. Thus, through balancing the structural response to changing cellular and synaptic inputs, NgRs participate in constructing activity-dependent morphological plasticity. Psychostimulants have been well documented to induce morphological plasticity critical for addictive properties of stimulants, although underlying molecular mechanisms are poorly understood. In this study, we initiated a study to investigate the response of NgRs to a stimulant. We tested the effect of acute administration of amphetamine on protein expression of two principal NgR subtypes (NgR1 and NgR2) in the rat striatum, medial prefrontal cortex (mPFC) and hippocampus. We found that a single injection of amphetamine induced a rapid and time-dependent decrease in NgR1 and NgR2 expression in the striatum and mPFC. A relatively delayed and time-dependent decrease in expression of the two receptors was seen in the hippocampus. The drug-induced decrease in NgR1 and NgR2 expression in the three forebrain regions was dose-dependent. A behaviorally active dose of the drug was required to trigger a significant reduction in NgR1 and NgR2 expression. These data indicate that NgRs are subject to the regulation by the stimulant. Amphetamine exposure exerts the inhibitory modulation of basal NgR1 and NgR2 expression in the key structures of reward circuits in vivo.


ESSAYS ON SCIENCE AND SOCIETY: Selling Science to the Public.
In this essay, Highfield reflects on his personal experiences as science journalist and editor at the British broadsheet the Daily Telegraph. Highfield believes that scientists can learn from journalists' dialogue approach to science communication. Highfield believes that readers are "ignorant but smart," and are sufficiently sceptical not to believe all the hype that they read. What is most important is that a dialogue is created. For example, large-scale experiments performed by the Daily Telegraph together with the BBC allow the public to get a glimpse of the scientific method that is often ignored.


Late Diagnosis of Coarctation Despite Prenatal Ultrasound and Postnatal Pulse Oximetry.
To determine what contribution prenatal ultrasound screening and neonatal pulse oximetry screening (POS) make to the timely diagnosis of neonatal coarctation of the aorta (CoA). We identified infants and fetuses diagnosed with isolated CoA in our referral area between 2003 and 2012 who died without surgery, underwent surgical repair before 2 months of age, or were terminated after a prenatal diagnosis. Clinical data were collected from hospital charts. Only 3 of the 90 cases were diagnosed prenatally. Two of the 3 were born alive and in 1 case the couple opted for termination of pregnancy. Nineteen of the remaining 87 cases were born in units that used POS (hand and foot) and 4 of 19 screened positive. Of the remaining 83 cases, 46 were discharged undiagnosed (7 after nondiagnostic echocardiography), including 9 with a murmur and weak femoral pulses and 8 with a murmur and normal pulses. One was diagnosed postmortem after dying at home, and 22 of the remaining 45 discharged infants were in circulatory failure on readmission. Five of the patients who were not discharged died without surgery and undiagnosed CoA was the most probable cause of death in 2 of these patients. The contribution of prenatal ultrasound screening and postnatal POS to the timely diagnosis of CoA was low. Careful physical examination of all newborns therefore continues to play a fundamental role in detecting this life-threatening cardiac defect, and better screening methods need to be developed.


Antibodies to casein kinase II in sera of patients with mixed connective tissue disease: evaluation with recombinant proteins.
In this study we determined the prevalence of autoantibodies against casein kinase II (CKII) in patients positive for anti-70K marker antibodies, which is indicative of mixed connective tissue disease. An anti-CKII ELISA was established with the use of bacterially expressed recombinant CKII proteins. Eight out of 52 anti-70K-positive sera (15%) were positive for anti-CKII antibodies, which recognized preferentially the CKII alpha subunit. All control sera (n = 52) were anti-CKII negative. Thus, the occurrence of anti-CKII antibodies may be of value for differential diagnosis.


Local structure and lithium mobility in intercalated Li3Al(x)Ti(2-x)(PO4)3 NASICON type materials: a combined neutron diffraction and NMR study.
The structural features of intercalated Li3AlxTi2-x(PO4)3 compounds, with x = 0 and 0.2, have been deduced by Rietveld analysis of neutron diffraction (ND) patterns recorded between 100 and 500 K. The Li insertion decreases the symmetry from R3̄c to R3̄ in analyzed compounds. In pristine Li1+xAlxTi2-x(PO4)3 samples, Li occupies mainly six-fold M1 sites at ternary axes; but in lithiated Li3AlxTi2-x(PO4)3 samples, Li is located near M2 positions at M3/M3' four-fold coordinated sites. In both cases, Li arrangement minimizes electrostatic Li-Li repulsions. The insertion of lithium resulted in the reduction of Ti(4+) to Ti(3+) that shifts (7)Li, (27)Al and (31)P MAS-NMR resonances towards more positive chemical shifts, improving the resolution of different sites. The detection of twelve components in (7)Li MAS-NMR spectra recorded at room temperature suggests the location of Li(+) ions at three-oxygen faces that define M2 cavities. From (7)Li MAS-NMR spectra, the occupancy of sites and mobility of lithium were investigated in the temperature range 100-500 K. The correlation between structural information, deduced by neutron diffraction, and lithium mobility, deduced by NMR spectroscopy, provides new insights into structural factors that affect lithium mobility in materials with NASICON structure.


Validation of the aging hen (Gallus gallus domesticus) as an animal model for uterine leiomyomas.
Uterine leiomyomas, or fibroids, are the most frequent gynecological tumors in premenopausal women with as many as 65% of women becoming clinically symptomatic. Uterine fibroids are benign myometrial tumors that produce large quantities of extracellular matrix proteins. Despite its high morbidity, the molecular basis underlying the development of uterine leiomyomas is not well understood. Domestic hens of Gallus gallus domesticus develop oviductal leiomyomas similar to those found in humans. We investigated the natural history of chicken leiomyomas, in vivo expression of protein biomarkers, and in vitro expression of ovarian steroid receptors. Based on the analysis of 263 hens, tumor prevalence, tumor number per hen, and tumor size increased as the hens aged. Immunohistochemistry for alpha-smooth muscle actin (SMA) and desmin confirmed the smooth muscle phenotype of the chicken leiomyomas. Intense collagen expression was detected in these oviductal leiomyomas by Mason's trichrome, and the tumors also showed increased expression of TGFB3 and collagen type I mRNAs. Consistent with human leiomyomas, chicken fibroids displayed increased BCL2 and estrogen (E) and progesterone (P) receptor expression. Chicken leiomyomas were dissociated for in vitro culture. Cells from explants were positive for SMA, desmin, and E and P receptors until the fourth passage. These cells also displayed a response similar to human cells when challenged with halofuginone, an antifibrotic agent. Our findings indicate that the chicken is an excellent complementary model for studies involving the pathophysiology of human uterine leiomyomas.


The cytotoxicity of OPA-modified CdSe/ZnS core/shell quantum dots and its modulation by silibinin in human skin cells.
Quantum dots (QDs) have emerged as alternative or complementary tools to organic fluorescent dyes currently used in bioimaging. QDs hold several advantages over conventional fluorescent dyes including greater photostability and a wider range of excitation/emission wavelengths. However, recent work suggests that QDs exert deleterious effects on cellular processes which could obscure bioassay results. This study examined the toxicity of octylamine-poly(acrylic acid) (OPA) modified CdSe/ZnS quantum dots (QDs) and a pharmacological means of preventing QD-induced cell death. Cell viability and the flow cytometry were used to access the toxicity of OPA-modified CdSe/ZnS QDs to human skin cells following a 24-h exposure. It is found that concentrations leading to a 50% reduction in malignant melanoma cell viability (TC50) for two OPA-QDs (QD545 and QD605) are 102.1, 57.3 nM in A375 cells and 67.2, 55.0 nM in A375.S2 cells, respectively. Moreover, QD545 and QD605 show low cytotoxic response in HaCaT keratinocyte cells with TC50 values of 818.2 nM and 162.0 nM, respectively. Silibinin, a natural product derived from milkweed thistle, is known for its powerful antioxidant and membrane stabilizing properties. Pretreatment of cells with silibinin, significantly reduced QD-induced cell death in A375 and A375-S2 cells. These findings suggest that QD cytotoxicity is sensitive to cell types and that pretreatment with antioxidants, such as the natural product silibinin, can modulate QD-induced cytotoxicity.


Development and validation of a smartphone addiction scale (SAS).
The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the smartphone's own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated. A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M = 26.06; SD = 5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS. Based on the factor analysis results, the subscale "disturbance of reality testing" was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach's alpha = 0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS. This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid.


A revised model for the structure and function of the lactose permease. Evidence that a face on transmembrane segment 2 is important for conformational changes.
The lactose permease is an integral membrane protein that cotransports H(+) and lactose into the bacterial cytoplasm. Previous work has shown that bulky substitutions at glycine 64, which is found on the cytoplasmic edge of transmembrane segment 2 (TMS-2), cause a substantial decrease in the maximal velocity of lactose uptake without significantly affecting the K(m) values (Jessen-Marshall, A. E., Parker, N. J., and Brooker, R. J. (1997) J. Bacteriol. 179, 2616-2622). In the current study, mutagenesis was conducted along the face of TMS-2 that contains glycine-64. Single amino acid substitutions that substantially changed side-chain volume at codons 52, 57, 59, 63, and 66 had little or no effect on transport activity, whereas substitutions at codons 49, 53, 56, and 60 were markedly defective and/or had lower levels of expression. According to helical wheel plots, Phe-49, Ser-53, Ser-56, Gln-60, and Gly-64 form a continuous stripe along one face of TMS-2. Several of the TMS-2 mutants (S56Y, S56L, S56Q, Q60A, and Q60V) were used as parental strains to isolate mutants that restore transport activity. These mutations were either first-site mutations or second-site suppressors in TMS-1, TMS-2, TMS-7 or TMS-11. A kinetic analysis showed that the suppressors had a higher rate of lactose transport compared with the corresponding parental strains. Overall, the results of this study are consistent with the notion that a face on TMS-2, containing Phe-49, Ser-53, Ser-56, Gln-60, and Gly-64, plays a critical role in conformational changes associated with lactose transport. We hypothesize that TMS-2 slides across TMS-7 and TMS-11 when the lactose permease interconverts between the C1 and C2 conformations. This idea is discussed within the context of a revised model for the structure of the lactose permease.


Copulation with immature females increases male fitness in cannibalistic widow spiders.
Copulatory cannibalism of male 'widow' spiders (genus Latrodectus) is a model example of the extreme effects of sexual selection, particularly in L. hasselti and L. geometricus where males typically facilitate cannibalism by females and mate only once. We show that these males can increase their reproductive success by copulating with final-instar, immature females after piercing the female's exoskeleton to access her newly developed sperm storage organs. Females retain sperm through their final moult and have similar fecundity to adult-mated females. This is an adaptive male tactic because immature mating increases insemination success relative to adult mating (which predicts higher paternity) and moreover, rarely ends in cannibalism, so males can mate again. Although successful only during a brief period before the female's final moult, males may employ this tactic when they associate with final-instar females in nature. Consistent with this, one-third of L. hasselti females collected as immatures in nature were already mated. Immature mating alters sexual selection on these otherwise monogynous males, and may explain male traits allowing facultative polygyny in Latrodectus Since male cohabitation with immature females is common among invertebrates, immature mating may be a widespread, previously unrecognized mating tactic, particularly when unmated females are of high reproductive value.


A balance of BMP and notch activity regulates neurogenesis and olfactory nerve formation.
Although the function of the adult olfactory system has been thoroughly studied, the molecular mechanisms regulating the initial formation of the olfactory nerve, the first cranial nerve, remain poorly defined. Here, we provide evidence that both modulated Notch and bone morphogenetic protein (BMP) signaling affect the generation of neurons in the olfactory epithelium and reduce the number of migratory neurons, so called epithelioid cells. We show that this reduction of epithelial and migratory neurons is followed by a subsequent failure or complete absence of olfactory nerve formation. These data provide new insights into the early generation of neurons in the olfactory epithelium and the initial formation of the olfactory nerve tract. Our results present a novel mechanism in which BMP signals negatively affect Notch activity in a dominant manner in the olfactory epithelium, thereby regulating neurogenesis and explain why a balance of BMP and Notch activity is critical for the generation of neurons and proper development of the olfactory nerve.


Evaluating Aseptic Presentation of Different Medical Device Packaging Configurations.
The Medical Device Regulation (MDR) of the European Union (EU) places greater emphasis on the usability of medical devices, with the goal of eliminating or reducing the risk of infection to patients. As this goal also is applicable to sterile packaging, ANSI/AAMI/ISO 11607-1:2019 introduced a usability evaluation requirement for aseptic presentation of terminally sterilized medical devices. In an effort to reduce contamination risks, this requirement focuses specifically on the sterile barrier system (SBS). However, research is limited on evaluating the usability of SBSs and their performance, from an aseptic presentation standpoint, in clinical settings. To address this research gap, we assessed 14 sterile medical devices with five different SBS configurations to elucidate how SBS configuration (type, size, and number of SBS layers) and user satisfaction levels affect usability. A total of 40 experienced clinical nurses participated in 280 individual trials (20 per SBS configuration), which were conducted in a simulated operating room. Ultraviolet fluorescent powder was used to simulate the contamination process and to evaluate the success or failure of the aseptic presentation. Pouch and tray configurations exhibited the best overall performance, while vent bags performed poorly and were considered less acceptable. Double SBS configurations outperformed single SBS configurations. The study highlighted the importance of appropriate SBS symbols to identify SBS layers, which is another patient safety-related requirement of the EU MDR. The current work also includes an analysis of the powder contamination method used in conducting the usability evaluation.


Implementing population health management: an international comparative study.
The purpose of this paper is to gain insight into how population health management (PHM) strategies can successfully integrate and reorganize public health, health care, social care and community services to improve population health and quality of care while reducing costs growth, this study compared four large-scale transformation programs: Greater Manchester Devolution, Vancouver Healthy City Strategy, Gen-H Cincinnati and Gesundes Kinzigtal. Following the realist methodology, this explorative comparative case-study investigated PHM initiatives' key features and participants' experiences of developing such initiatives. A semi-structured interview guideline based on a theoretical framework for PHM guided the interviews with stakeholders (20) from different sectors. Five initial program theories important to the development of PHM were formulated: (1) create trust in a shared vision and understanding of the PHM rationale to establish stakeholders' commitment to the partnership; (2) create shared ownership for achieving the initiative's goals; (3) create shared financial interest that reduces perceived financial risks to provide financial sustainability; (4) create a learning environment to secure initiative's credibility and (5) create citizens' and professionals' awareness of the required attitudes and behaviours. The study highlights initial program theories for the implementation of PHM including different strategies and structures underpinning the initiatives. These insights provide a deeper understanding of how large-scale transformation could be developed.


DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa): A Review of its Use as Primary and Booster Vaccination.
Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged <or=6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This article reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.


Clinical disease in kittens inoculated with a pathogenic strain of Bartonella henselae.
To evaluate disease in kittens inoculated with Bartonella henselae strain LSU16. Eighteen 12-week-old specific-pathogen-free kittens. Kittens were inoculated with B henselae strain LSU16 or saline (0.9% NaCl) solution. Blood samples were collected from kittens on alternate weeks, and bacteremia, clinical signs, and antibody concentrations were monitored for 6 months after inoculation. Kittens developed raised, erythematous areas at the site of inoculation within 72 hours. Swelling peaked at 14 days and resolved by 28 days after inoculation. Fever had a biphasic pattern, with an episode of 1- to 3-days' duration beginning 6 to 7 days after inoculation followed by an episode of 3- to 8-days' duration beginning 11 to 13 days after inoculation. Kittens were bacteremic by day 14 with peak bacteremia at days 14 to 28. Strong antibody responses to B henselae were detected. Clinical disease resolved before bacteremia became undetectable, but signs of disease correlated with the highest degree of bacteremia. Regional lymphadenopathy also was evident. Clinical disease in kittens was similar to that in adult cats infected with B henselae strain LSU16, except that lethargy and anorexia were less severe in kittens, and a biphasic pattern of fever was detected in kittens. Clinical disease after inoculation with B henselae may be strain-dependent. To limit transmission of Bartonella organisms, appropriate flea prevention should be instituted. Kittens that are febrile, anorectic, lethargic, and that have lymphadenopathy should be tested for Bartonella organisms, and contact with immunocompromised owners should be discouraged.


The Young Everest Study: preliminary report of changes in sleep and cerebral blood flow velocity during slow ascent to altitude in unacclimatised children.
Cerebral blood flow velocity (CBFV) and sleep physiology in healthy children exposed to hypoxia and hypocarbia are under-researched. To investigate associations between sleep variables, daytime end-tidal carbon dioxide (EtCO2) and CBFV in children during high-altitude ascent. Vital signs, overnight cardiorespiratory sleep studies and transcranial Doppler were undertaken in nine children (aged 6-13 years) at low altitude (130 m), and then at moderate (1300 m) and high (3500 m) altitude during a 5-day ascent. Daytime (130 m: 98%; 3500 m: 90%, p=0.004) and mean (130 m: 97%, 1300 m: 94%, 3500: 87%, p=0.0005) and minimum (130 m: 92%, 1300 m: 84%, 3500 m: 79%, p=0.0005) overnight pulse oximetry oxyhaemoglobin saturation decreased, and the number of central apnoeas increased at altitude (130 m: 0.2/h, 1300 m: 1.2/h, 3500 m: 3.5/h, p=0.2), correlating inversely with EtCO2 (R(2) 130 m: 0.78; 3500 m: 0.45). Periodic breathing occurred for median (IQR) 0.0 (0; 0.3)% (130 m) and 0.2 (0; 1.2)% (3500 m) of total sleep time. At 3500 m compared with 130 m, there were increases in middle (MCA) (mean (SD) left 29.2 (42.3)%, p=0.053; right 9.9 (12)%, p=0.037) and anterior cerebral (ACA) (left 65.2 (69)%, p=0.024; right 109 (179)%; p=0.025) but not posterior or basilar CBFV. The right MCA CBFV increase at 3500 m was predicted by baseline CBFV and change in daytime SpO2 and EtCO2 at 3500 m (R(2) 0.92); these associations were not seen on the left. This preliminary report suggests that sleep physiology is disturbed in children even with slow ascent to altitude. The regional variations in CBFV and their association with hypoxia and hypocapnia require further investigation.


Redox Neutral Radical-Relay Cobalt Catalysis toward C-H Fluorination and Amination.
A redox neutral radical-relay cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides featuring the in situ formed cobalt fluorides as the latent radical fluorinating agents is reported. Moreover, the reactivity of such a cobalt catalysis could be diverted from C-H fluorination to amination by engineering substrates' conformational flexibility. Preliminary mechanistic studies (UV-vis spectroscopy, cyclic voltammetry studies and DFT calculations, etc.) support the reaction proceeding a redox neutral radical-relay mechanism.


Interleukin-6 downregulates factor XII production by human hepatoma cell line (HepG2).
Involvement of the contact system of coagulation in the pathogenesis of various inflammatory diseases is suggested by reduced plasma levels of factor XII (Hageman factor) and prekallikrein generally considered to result from activation of the contact system. However, in many of these diseases patients develop an acute-phase response and, therefore, an alternative explanation for the decreased levels of factor XII could be the downregulation of factor XII gene expression in the liver as described for negative acute-phase proteins. We report here that interleukin-6 (IL-6), the principal cytokine mediating the synthesis of most acute-phase proteins in the liver, downregulates the production of factor XII by the human hepatoma cell line HepG2 by up to 75%. The decrease in protein secretion correlated with an equivalent decrease of factor XII mRNA likely indicating a pretranslational control of factor XII gene expression by IL-6. Downregulation of factor XII production by IL-6 in vitro parallelled that of transthyretin, a known negative acute-phase protein. Moreover, we show that, in patients developing an acute-phase response after immunotherapy with IL-2, plasma levels of factor XII correlate (r = .76, P < .0001) with those of transthyretin. Taken together, these results suggest that factor XII behaves as a negative acute-phase protein.


Vinylation of aromatic halides using inexpensive organosilicon reagents. Illustration of design of experiment protocols.
The preparation of styrenes by palladium-catalyzed cross-coupling of aromatic iodides and bromides with divinyltetramethyldisiloxane (DVDS) in the presence of inexpensive silanolate activators has been developed. To facilitate the discovery of optimal reaction conditions, Design of Experiment (DoE) protocols were used. By the guided selection of reagents, stoichiometries, temperatures, and solvents, the vinylation reaction was rapidly optimized with three stages consisting of ca. 175 experiments (of a possible 1440 combinations). A variety of aromatic iodides undergo cross-coupling at room temperature in the presence of potassium trimethylsilanoate using Pd(dba)2 in DMF in good yields. Triphenylphosphine oxide is needed to extend catalyst lifetime. Application of these conditions to aryl bromides was accomplished by the development of two complementary protocols. First, the direct implementation of the successful reaction conditions using aryl iodides at elevated temperature in THF provided the corresponding styrenes in good to excellent yields. Alternatively, the use of potassium triethylsilanolate and a bulky "Buchwald-type" ligand allows for the vinylation reactions to occur at or just above room temperature. A wide range of bromides underwent coupling in good yields for each of the protocols described.


Development of novel synthetic muscle tissues for sports impact surrogates.
Impact injuries are commonplace in sport and often lead to performance detriment and debilitation. Personal Protective Equipment (PPE) is prescribed as a mandatory requirement in most sports where these impacts are likely to occur, though the methods of governance and evaluation criteria often do not accurately represent sports specific injury scenarios. One of the key shortcomings of such safety test standards is the human surrogate to which the PPE is affixed; this typically embodies unrepresentative geometries, masses, stiffness and levels of constraint when compared to humans. A key aspect of any human surrogate element is the simulant material used. Most previous sports specific surrogates tend to use off-the-shelf silicone blends to represent all the soft tissue structures within the human limb segment or organ; this approach potentially neglects important human response phenomena caused by the different tissue structures. This study presents an investigation into the use of bespoke additive cure Polydimethysiloxane (PDMS) silicone blends to match the reported mechanical properties of human relaxed and contracted skeletal muscle tissues. The silicone simulants have been tested in uniaxial compression through a range of strain rates and fit with a range of constitutive hyperelastic models (Mooney Rivlin, Ogden and Neo Hookean) and a viscoelastic Prony series.


[Early detection of hepatobiliary cancer in mass health screening].
Mass health screening (MHS) for detecting early cancer of hepatobiliary diseases is not common. However, as high risk factors for developing hepatocellular carcinoma (HCC) has been established in Japan, MHS for HCC is available, especially in high endemic areas of hepatitis C. Intrahepatic bile duct cancer often occur in patients with Thorotrastosis. Cohort study for detection of early cancer of intrahepatic bile duct has been conducting by the Japanese Government. Early detection of bile duct cancer in health screening is very rare. It will be helpful for perform MHS to clarify the high risk factors for bile duct cancers.


A comparison of rectal versus fetlock temperatures in dorsally recumbent horses during general anesthesia.
To investigate the effect of isoflurane anesthesia on thermoregulation and peripheral heat loss in dorsally recumbent horses. Prospective, clinical study. Seven adult horses (2.6 ± 1.5 years old, 455 ± 70.2 kg). Horses underwent elective surgical procedures in dorsal recumbency under general anesthesia (GA) maintained with isoflurane in oxygen. Rectal (TR), intranasal (TN) and fetlock surface temperatures (TF) were measured every 10 minutes for the first 80 minutes following induction of GA. Room temperature (TRO) was monitored during the study. Statistical analysis to determine differences between temperature measurement sites and techniques (TR, TN and TF), and differences over time were completed using a mixed-effects model with Tukey's multiple comparison or Dunnett's multiple comparison testing where appropriate. Significance was set at p < 0.05. Following induction of anesthesia, TF was significantly increased compared with baseline (0 minutes) from 40 to 80 minutes (p < 0.01). No significant differences were detected in TR and TN at any time point compared with baseline (p > 0.05). TF was significantly lower than TN (p < 0.02) at all time points and TR from times 0 to 70 minutes (p < 0.04). There were no significant differences between TR and TN at any time (p > 0.05). In horses undergoing isoflurane GA, TF increased, indicating peripheral heat loss likely because of vasodilation, whereas TR showed a clinically relevant decrease over time. These findings are suggestive of body heat redistribution during GA in horses in dorsal recumbency. Thermographic imaging of the peripheral limbs in combination with TR and TN monitoring allowed for recognition of peripheral heat redistribution in anesthetized horses. Anesthetized horses experience peripheral heat loss through their extremities as a result of vasodilation. Mitigating peripheral heat loss may improve thermoregulation and reduce hypothermic complications in anesthetized horses.


Association of Preterm Birth With Prescription of Psychotropic Drugs in Adolescence and Young Adulthood.
Individuals born preterm have increased risk of mental health impairment compared with individuals born at term. The associations between preterm birth and attention-deficit/hyperactivity disorder and autism are well established; for depression, anxiety, psychotic and bipolar disorder, studies show divergent results. To compare the prescription of psychotropic drugs in adolescence and young adulthood between those born preterm and those born at term. This cohort study used registry data to identify all Norwegians born after 23 weeks of completed gestation between 1989 and 1998. Included individuals were those without registered birth defects, alive at age 10 years, and with available maternal data. Individuals were followed up from 2004 to 2016. Psychotropic drug prescriptions received from age 10 to 23 years were compared between preterm groups and peers born at term. Individuals were compared with their siblings to control for shared family confounding. Data analyses were performed from August 2018 through February 2020. Gestational age at birth (GA) was categorized in 4 groups: extremely preterm (GA, 23 weeks and 0 days to 27 weeks and 6 days), very preterm (GA, 28 weeks and 0 days to 31 weeks and 6 days), moderately or late preterm (GA, 32 weeks and 0 days to 36 weeks and 6 days), and full term (GA, 37 weeks and 0 days to 44 weeks and 6 days). Prescriptions of psychotropic drugs (ie, prescriptions specifically of psychostimulants, antidepressants, anxiolytics, hypnotics or sedatives, or antipsychotics or prescriptions of any of these 5 drugs) among preterm groups were compared with prescriptions among peers born at term and among siblings. Among 505 030 individuals (259 545 [51.4%] males; mean [SD] birth weight, 3533 [580] g), 762 individuals (0.2%) were extremely preterm, 2907 individuals (0.6%) were very preterm, 25 988 individuals (5.1%) were moderately or late preterm, and 475 373 individuals (94.1%) were full term. Individuals born preterm had increased risk of psychotropic drug prescription, with a dose-response association between GA and prescription. The extremely preterm group had higher rates of prescription for all drug types compared with peers born at term, with odds ratios from 1.7 (95% CI, 1.4-2.1) for antidepressants to 2.7 (95% CI, 2.1-3.4) for psychostimulants. The elevated odds of prescription of all types were less pronounced in the moderately to late preterm group, including odds ratios of 1.1 (95% CI, 1.0-1.1) for antidepressants and 1.2 (95% CI, 1.1-1.2) for psychostimulants. The increases in odds were smaller in the sibling comparison, and increases were not significant for several groups. For example, the OR for any prescription in the sibling analysis was 1.8 (95% CI, 1.2-2.8) in the very preterm group and 1.0 (95% CI, 0.9-1.1) in the moderately or late preterm group. This cohort study found higher rates of prescription of psychotropic drugs throughout adolescence and young adulthood among individuals with all degrees of preterm birth compared with those born at term. These results provide further evidence for an increased risk of mental health impairment among individuals born preterm and suggest that this is not restricted to the most preterm groups.


A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD.
Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and eliminated by nonsense-mediated mRNA decay (NMD). NMD substrates can be degraded by different routes that all require phosphorylated UPF1 (P-UPF1) as a starting point. The endonuclease SMG6, which cleaves mRNA near the PTC, is one of the three known NMD factors thought to be recruited to nonsense mRNAs via an interaction with P-UPF1, leading to eventual mRNA degradation. By artificial tethering of SMG6 and mutants thereof to a reporter mRNA combined with knockdowns of various NMD factors, we demonstrate that besides its endonucleolytic activity, SMG6 also requires UPF1 and SMG1 to reduce reporter mRNA levels. Using in vivo and in vitro approaches, we further document that SMG6 and the unique stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a novel interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. Our results show that this interaction is required for NMD and for the capability of tethered SMG6 to degrade its bound RNA, suggesting that it contributes to the intricate regulation of UPF1 and SMG6 enzymatic activities.


[Norwegian and Australian physicians' attitudes to adverse events].
As "second victims", doctors may find it difficult to meet patients and relatives with an open and regretting mind after adverse incidents. In a series of six workshops 103 doctors, 46 from Australia and 57 from Norway, were included. Initially the participants completed a questionnaire about possible reactions after serious adverse events, experiences with formal complaints and legal charges, and an option to describe a personally experienced adverse event. This was followed by an interactive educational session, where prevention and management of adverse events were discussed. A descriptive analysis based on a combination of questionnaire data and notes from the discussions has been performed. The questionnaire responses showed that Australian and Norwegian doctors mainly did agree about the most appropriate ways of responding after a serious adverse event. Subsequent discussions showed that certain issues were recurrently and similarly discussed among the participants through all the workshops. Although the majority principally did agree on an open approach, an underlying sceptical attitude emerged, partially connected to experiences of being thoughtlessly blamed by colleagues in the wisdom of hindsight. The study outlines a strategy to raise doctors' understanding of the importance of openness in order to reinforce trust in relation to all involved parties--patient, relatives, colleagues and self--after adverse events.


[Abscesses caused by deciduous teeth].
Abscesses in children, caused by deciduous teeth, ar not so frequently as seen in the permanent dentition. In most cases caries or an odontogenic infection of the associated deciduous tooth have already been treated by the dentist or oral surgeon at an earlier stage, i.e. before the infection exacerbates to an abscess. At the department of Oral and Maxillofacial Surgery of the Academic Hospital Nijmegen, between April 1997 and April 1998 20 children have been treated on a total of 1,693 patients with an odontogenic infection. Of this group, nine young children had an abscess caused by a deciduous tooth. In most cases the mandibular deciduous molars were involved. In one case an osteomyelitis of the mandible was diagnosed. All abscesses and infections could be treated adequately. The use of antibiotics is of paramount importance in the treatment of these abscesses in children.


Identification of several mutations in ATP2C1 in Lebanese families: insight into the pathogenesis of Hailey-Hailey disease.
Hailey-Hailey disease (HHD) is an inherited blistering dermatosis characterized by recurrent erosions and erythematous plaques that generally manifest in intertriginous areas. Genetically, HHD is an autosomal dominant disease, resulting from heterozygous mutations in ATP2C1, which encodes a Ca2+/Mn2+ATPase. In this study, we aimed at identifying and analyzing mutations in five patients from unrelated families diagnosed with HHD and study the underlying molecular pathogenesis. To genetically study Lebanese families with HHD, and the underlying molecular pathogenesis of the disease. We performed DNA sequencing for the coding sequence and exon-intron boundaries of ATP2C1. Heat shock experiments were done on several cell types. This was followed by real-time and western blotting for ATP2C1, caspase 3, and PARP proteins to examine any possible role of apoptosis in HHD. This was followed by TUNEL staining to confirm the western blotting results. We then performed heat shock experiments on neonatal rat primary cardiomyocytes. Four mutations were detected, three of which were novel and one recurrent mutation in two families. In order for HHD to manifest, it requires both the genetic alteration and the environmental stress, therefore we performed heat shock experiments on fibroblasts (HH and normal) and HaCaT cells, mimicking the environmental factor seen in HHD. It was found that stress stimuli, represented here as temperature stress, leads to an increase in the mRNA and protein levels of ATP2C1 in heat-shocked cells as compared to non-heat shocked ones. However, the increase in ATP2C1 and heat shock protein hsp90 is significantly lower in HH fibroblasts in comparison to normal fibroblasts and HaCaT cells. We did not find a role for apoptosis in the pathogenesis of HHD. A similar approach (heat shock experiments) done on rat cardiomyocytes, led to a significant variation in ATP2C1 transcript and protein levels. This is the first genetic report of HHD from Lebanon in which we identified three novel mutations in ATP2C1 and shed light on the molecular mechanisms and pathogenesis of HHD by linking stress signals like heat shock to the observed phenotypes. This link was also found in cultured cardiomyocytes suggesting thus a yet uncharacterized cardiac phenotype in HHD patients masked by its in-expressivity in normal health conditions.


NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation.
The transcription factor NF-kappaB plays an important role in both physiological and pathological events in the central nervous system. Nevertheless, the mechanisms of NF-kappaB-mediated regulation of gene expression, and the signaling molecules participating in the NF-kappaB pathway in the central nervous system are, to date, poorly understood. To identify such molecules, we conducted a yeast two-hybrid screen of a human brain cDNA library using NIK as bait. As a result, we identified a novel NIK and IKK(beta) binding protein designated NIBP that is mainly expressed in brain, muscle, heart, and kidney. Interestingly, low levels of expression were detected in immune tissues such as spleen, thymus, and peripheral blood leukocytes, where NF-kappaB is known to modulate immune function. We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK(beta), but not IKK(alpha) or IKK(gamma). NIBP overexpression potentiates tumor necrosis factor-alpha-induced NF-kappaB activation through increased phosphorylation of the IKK complex and its downstream I(kappa)B(alpha) and p65 substrates. Finally, knockdown of NIBP expression by small interfering RNA reduces tumor necrosis factor-alpha-induced NF-kappaB activation, prevents nerve growth factor-induced neuronal differentiation, and decreases Bcl-xL gene expression in PC12 cells. Our data demonstrate that NIBP, by interacting with NIK and IKK(beta), is a new enhancer of the cytokine-induced NF-(kappa)B signaling pathway. Because of its neuronal expression, we propose that NIBP may be a potential target for modulating the NF-(kappa)B signaling cascade in neuronal pathologies dependent upon abnormal activation of this pathway.


Gait parameters, functional mobility and fall risk in individuals with early to moderate primary open angle glaucoma: a cross-sectional study.
This study investigated the influence of early to moderate primary open angle glaucoma on gait, functional mobility and fall risk. Thirty-three participants in the early and moderate stages of primary open angle glaucoma and 34 asymptomatic controls participated in the study. Spatiotemporal gait data were obtained with the GAITRite system and included: velocity, cadence, step length, base of support, swing, stance and double support times. Functional measures included the Timed Up and Go test, the Five-Repetition Sit-To-Stand test and the Dynamic Gait Index. Fall risk was measured using the Physiological Profile Assessment. The variables contrast sensitivity, proprioception and the Timed Up and Go and Dynamic Gait Index tests were significantly different between groups. In addition, the glaucoma group presented significantly higher risk of falling compared to the control group. Individuals in the early and moderate stages of primary open glaucoma presented mobility and sensory deficits that increase the risk of falling. The results of this study suggest that adding the Timed Up and Go and Dynamic Gait Index tests to routine physical therapy assessment of individuals with early glaucoma could be useful. Rehabilitation programs should focus on maintaining and/or improving mobility and balance, and prevention of falls in this population.


The role of desire thinking in the problematic use of social networking sites among adults.
The problematic use of social networking sites (SNS) is associated with several psychiatric disorders. This behavior closely resembles addiction in terms of neurological basis and behavioral patterns. Nevertheless, successful intervention strategies and the etiology of problematic SNS use are not yet thoroughly investigated. We aimed to study whether desire thinking is associated with problematic SNS use among adults when controlling for some confounders, including boredom, affect, and impulsivity. With the help of convenience sampling, we enrolled 546 Turkish adults in this study to whom we administered a sociodemographic form, the Social Media Addiction Scale (SMAS), the Leisure Boredom Scale (LBS), the Positive and Negative Affect Schedule (PANAS), the Barratt Impulsiveness Scale (BIS-11), and the Desire Thinking Questionnaire (DTQ). To explore the association between the variables, we performed Pearson correlational and hierarchical regression analyses. The results showed that higher scores on two sub-dimensions of desire thinking, namely verbal perseveration and imaginal prefiguration, were associated with higher scores on problematic SNS use after we controlled for boredom, affect, and impulsivity. This study demonstrates that desire thinking may play a role in problematic SNS use among adults. We recommend targeting desire thinking as a potential area in treatments which may help alleviate problematic SNS use.


Lewontin and Kojima meet Fisher: linkage in a symmetric model of sex determination.
The effect of linkage and epistasis on the evolution of the sex-ratio is studied in a symmetric two-locus model of autosomal sex determination closely related to the symmetric viability model of R. C. Lewontin and K. Kojima. R. A. Fisher's expectation of an even sex ratio for autosomal sex determination by a single gene governs the dynamics when the loci are tightly linked. However, recombination may preclude optimization of the sex ratio just as occurs in viability selection models. Many of the evolutionary phenomena known for the symmetric viability model also occur here. In addition, we exhibit a series of new phenomena related to the presence of surfaces of even sex ratio.


Can a partial volume edge effect reduction algorithm improve the repeatability of subject-specific finite element models of femurs obtained from CT data?
The reliability of patient-specific finite element (FE) modelling is dependent on the ability to provide repeatable analyses. Differences of inter-operator generated grids can produce variability in strain and stress readings at a desired location, which are magnified at the surface of the model as a result of the partial volume edge effects (PVEEs). In this study, a new approach is introduced based on an in-house developed algorithm which adjusts the location of the model's surface nodes to a consistent predefined threshold Hounsfield unit value. Three cadaveric human femora specimens were CT scanned, and surface models were created after a semi-automatic segmentation by three different experienced operators. A FE analysis was conducted for each model, with and without applying the surface-adjustment algorithm (a total of 18 models), implementing identical boundary conditions. Maximum principal strain and stress and spatial coordinates were probed at six equivalent surface nodes from the six generated models for each of the three specimens at locations commonly utilised for experimental strain guage measurement validation. A Wilcoxon signed-ranks test was conducted to determine inter-operator variability and the impact of the PVEE-adjustment algorithm. The average inter-operator difference in stress values was significantly reduced after applying the adjustment algorithm (before: 3.32 ± 4.35 MPa, after: 1.47 ± 1.77 MPa, p = 0.025). Strain values were found to be less sensitive to inter-operative variability (p = 0.286). In summary, the new approach as presented in this study may provide a means to improve the repeatability of subject-specific FE models of bone obtained from CT data.


The benefits of yoga for women veterans with chronic low back pain.
Chronic low back (CLBP) pain is prevalent among military veterans and often leads to functional limitations, psychologic symptoms, lower quality of life, and higher health care costs. An increasing proportion of U.S. veterans are women, and women veterans may have different health care needs than men veterans. The purpose of this study was to assess the impact of a yoga intervention on women and men with CLBP. SUBJECTS/SETTING/INTERVENTION: VA patients with CLBP were referred by primary care providers to a clinical yoga program. Research participants completed a brief battery of questionnaires before their first yoga class and again 10 weeks later in a single-group, pre-post study design. Questionnaires included measures of pain (Pain Severity Scale), depression (CESD-10), energy/fatigue, and health-related quality of life (SF-12). Yoga attendance and home practice of yoga were also measured. Repeated-measures analysis of variance was used to analyze group differences over time while controlling for baseline differences. The 53 participants who completed both assessments had a mean age of 53 years, and were well educated, 41% nonwhite, 49% married, and had varying employment status. Women participants had significantly larger decreases in depression (p=0.046) and pain "on average" (p=0.050), and larger increases in energy (p=0.034) and SF-12 Mental Health (p=0.044) than men who participated. The groups did not differ significantly on yoga attendance or home practice of yoga. These results suggest that women veterans may benefit more than men veterans from yoga interventions for chronic back pain. Conclusions are tentative because of the small sample size and quasi-experimental study design. A more rigorous study is being designed to answer these research questions more definitively.


[The child with a bleeding tendency].
In this review some basic aspects of the clinical presentation, the laboratory testing and the management of a child with a bleeding tendency are discussed. It should help the physician in making the decision whether a laboratory examination in a child with a history of bleedings is necessary or not. In addition, the most frequent mechanisms for a defective hemostasis are explained.


Dynamics and Complexity of Dark Fermentation Microbial Communities Producing Hydrogen From Sugar Beet Molasses in Continuously Operating Packed Bed Reactors.
This study describes the dynamics and complexity of microbial communities producing hydrogen-rich fermentation gas from sugar-beet molasses in five packed-bed reactors (PBRs). The bioreactors constitute a part of a system producing hydrogen from the by-products of the sugar-beet industry that has been operating continuously in one of the Polish sugar factories. PBRs with different working volumes, packing materials, construction and inocula were tested. This study focused on analysis (based on 16S rRNA profiling and shotgun metagenomics sequencing) of the microbial communities selected in the PBRs under the conditions of high (>100 cm3/g COD of molasses) and low (<50 cm3/g COD of molasses) efficiencies of hydrogen production. The stability and efficiency of the hydrogen production are determined by the composition of dark fermentation microbial communities. The most striking difference between the tested samples is the ratio of hydrogen producers to lactic acid bacteria. The highest efficiency of hydrogen production (130-160 cm3/g COD of molasses) was achieved at the ratios of HPB to LAB ≈ 4:2.5 or 2.5:1 as determined by 16S rRNA sequencing or shotgun metagenomics sequencing, respectively. The most abundant Clostridium species were C. pasteurianum and C. tyrobutyricum. A multiple predominance of LAB over HPB (3:1-4:1) or clostridia over LAB (5:1-60:1) results in decreased hydrogen production. Inhibition of hydrogen production was illustrated by overproduction of short chain fatty acids and ethanol. Furthermore, concentration of ethanol might be a relevant marker or factor promoting a metabolic shift in the DF bioreactors processing carbohydrates from hydrogen-yielding toward lactic acid fermentation or solventogenic pathways. The novelty of this study is identifying a community balance between hydrogen producers and lactic acid bacteria for stable hydrogen producing systems. The balance stems from long-term selection of hydrogen-producing microbial community, operating conditions such as bioreactor construction, packing material, hydraulic retention time and substrate concentration. This finding is confirmed by additional analysis of the proportions between HPB and LAB in dark fermentation bioreactors from other studies. The results contribute to the advance of knowledge in the area of relationships and nutritional interactions especially the cross-feeding of lactate between bacteria in dark fermentation microbial communities.


Current management of atherosclerotic renovascular disease--what have we learned from ASTRAL?
With an increasingly ageing and atherosclerotic-prone population, clinical encounters with patients with atheromatous renovascular disease (ARVD) are commonplace. ARVD is frequently associated with chronic kidney disease (CKD) and hypertension, but evidence suggests that causality only occurs in the minority and it is likely that many atherosclerotic renal artery stenosis (RAS) lesions are incidental. Its association with extensive cardiovascular co-morbidity predisposes to a high patient mortality. The availability of renal angioplasty and stenting, which are generally safe techniques for dilating RAS lesions, has led to widespread use of these endovascular therapies in ARVD, but the outcomes after treatment have been inconsistent, with no clear evidence of benefit in many patients. There has been a great need for a large and appropriately powered randomised control trial to help guide clinical practice. In this review, we present an interpretation of the results of the recently reported Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial as well as a brief review of the latest literature, so as to provide the latest guidance regarding the management of this common condition.


Non-pharmacological interventions for fatigue in older adults: a systematic review and meta-analysis.
Non-pharmacological interventions are widely used to treat fatigue in clients with specific diseases but the findings may not be applicable to older adults experiencing fatigue, which also relates to the physiological changes of ageing. Non-pharmacological interventions for fatigue alleviation in older adults have not been reviewed and meta-analysed. To evaluate the immediate and long-term effects of non-pharmacological interventions on fatigue in community-dwelling older adults. Randomised controlled trials published from 2008 to May 2018 were searched in CINAHL, Cochrane Library, Embase, Medline, PsycINFO, PubMed and Web of Science databases. The reference lists of the publications, forward citation and clinical trial registries were also reviewed. Relevant data were extracted and meta-analysis was conducted using Cochrane Review Manager 5.3. Eight studies, with a total of 1093 participants, were identified. Non-pharmacological interventions included mindfulness meditation, a behavioural lifestyle programme, muscle relaxation, pet insect-assisted therapy, yoga, Tai Chi and cognitive behavioural therapy. Non-pharmacological interventions elicited significant immediate positive effects on fatigue (SMD: -0.40, 95% CI -0.62 to -0.18), although there was no lasting effect. Both physical and cognitive/mental interventions effectively alleviated fatigue. Non-pharmacological interventions appear to be effective in alleviating fatigue at immediate post-intervention in community-dwelling older adults. More studies with robust designs and adequate sample sizes are needed in the future.


Intrauterine transmission of ovine progressive pneumonia virus.
Ovine fetuses, newborn lambs, and ovine colostrum were examined for ovine progressive pneumonia virus. The lambs and colostrum were also examined for specific antibody. Virus was isolated from 1 fetus, from 2 newborn lambs, and from most samples of colostrum. The fetus was about 100 days old and was carried by a seronegative ewe in contact with seropositive sheep. Both newborn lambs were carried by seropositive ewes. One lamb was dead at birth; the other lamb was normal and had not nursed. Antibody specific for the virus was present in the colostrum of 12 of 14 seropositive ewes and in the serum of 8 of 11 lambs that had nursed seropositive ewes, but not in the serum of lambs that had not nursed.


Mood and global-local visual processing.
Testing hypotheses derived from neuropsychological models of mood, as well as the association of mood states and personality characteristics with global-local visual processing, were examined. Fifty-nine men completed measures associated with depression and positive mood, and were administered a brief perceptual judgment task that assessed global-local visual processing biases. Additionally, 19 of these 59 subjects were administered measures of anxiety and optimism-pessimism and completed an expanded judgment task. Affective and personality variables were then correlated with judgment task performances. Consistent with predictions, positive mood and optimism were directly associated with a global bias and inversely related to a local bias. A converse pattern of findings was obtained with depression and trait anxiety. Implications for research concerning other aspects of visual processing are discussed.


Pulmonary Infarction: In the Beginning: The Natural History of Pulmonary Infarction.
Massive pulmonary emboli can cause an abrupt onset of symptoms simultaneous with large pulmonary artery occlusions. In contrast, the temporal relationship between pulmonary vascular occlusion by smaller emboli and the development of symptoms of pulmonary infarction is unknown. We describe the time interval between embolization and the onset of clinical symptoms and signs compatible with pulmonary infarction. We examined the records of 56 patients with hereditary hemorrhagic telangiectasia (HHT) who underwent therapeutic balloon embolization of pulmonary arteriovenous malformation (PAVM) in a single center after noting that some of them experienced symptoms and signs compatible with pulmonary infarction. Because both the times of embolization and the onset of clinical symptoms were documented in medical records, we were able to calculate the time interval between embolic occlusion of vessels and the onset of symptoms. The records of 56 patients who underwent therapeutic embolization for HHT were examined. Five patients experienced a single episode of pleuritic pain postembolization, and one patient experienced episodes of pleuritic pain after each of two separate embolization procedures. Four of these pleuritic pain events evolved into a complex compatible with pulmonary infarction. The time intervals between embolization and the onset of pleuritic pain in those experiencing the infarction symptoms and signs were 24 hours, 48 ± 4 hours, 65 hours, and 67 hours, respectively. The clinically silent time interval between embolization of a pulmonary artery and the onset of symptoms and signs compatible with lung infarction is 24 hours or greater.


Genetics of amyotrophic lateral sclerosis.
The genetic cause of amyotrophic lateral sclerosis (ALS) is known in a minority of cases. Mutations in SOD1, the gene encoding a superoxide dismutase on chromosome 21, are indeed found in 20% of familial ALS patients, who constitute only 5 or 10% of all ALS patients. In rare cases, a mutation in NFH, the gene encoding the heavy subunit of neurofilament, is present. Familial ALS has been linked to other loci but the genes involved remain to be identified. A genetic component is also thought to at least contribute to the pathogenesis of sporadic ALS. Their identification is now possible thanks to progress in molecular genetics.


Macrophage- and neutrophil-derived TNF-α instructs skin langerhans cells to prime antiviral immune responses.
Dendritic cells are major APCs that can efficiently prime immune responses. However, the roles of skin-resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. In this study, we demonstrate for the first time, to our knowledge, that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin Ags to skin LCs using recombinant fusion proteins of anti-Langerin Ab and Ags resulted in the induction of the viral Ag-specific responses. We further demonstrated that such Ag-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands, polyriboinosinic polyribocytidylic acid, and R848. These enhancements were not due to the direct actions of TLR ligands on LCs, but mainly dependent on TNF-α secreted from macrophages and neutrophils recruited to local tissues. Skin LC activation and migration out of the epidermis are associated with macrophage and neutrophil infiltration into the tissues. More importantly, blocking TNF-α abrogated the activation and migration of skin LCs. This study highlights that the cross-talk between innate immune cells in local tissues is an important component for the establishment of adaptive immunity. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens.


Effects of pioneer tree species hyperabundance on forest fragments in northeastern Brazil.
Despite many studies on fragmentation of tropical forests, the extent to which plant and animal communities are altered in small, isolated forest fragments remains obscure if not controversial. We examined the hypothesis that fragmentation alters the relative abundance of tree species with different vegetative and reproductive traits. In a fragmented landscape (670 km(2) ) of the Atlantic Forest of northeastern Brazil, we categorized 4056 trees of 182 species by leafing pattern, reproductive phenology, and morphology of seeds and fruit. We calculated relative abundance of traits in 50 1-ha plots in three types of forest configurations: forest edges, small forest fragments (3.4-83.6 ha), and interior of the largest forest fragment (3500 ha, old growth). Although evergreen species were the most abundant across all configurations, forest edges and small fragments had more deciduous and semideciduous species than interior forest. Edges lacked supra-annual flowering and fruiting species and had more species and stems with drupes and small seeds than small forest fragments and forest interior areas. In an ordination of species similarity and life-history traits, the three types of configurations formed clearly segregated clusters. Furthermore, the differences in the taxonomic and functional (i.e., trait-based) composition of tree assemblages we documented were driven primarily by the higher abundance of pioneer species in the forest edge and small forest fragments. Our work provides strong evidence that long-term transitions in phenology and seed and fruit morphology of tree functional groups are occurring in fragmented tropical forests. Our results also suggest that edge-induced shifts in tree assemblages of tropical forests can be larger than previously documented.