Ribonucleoparticle-independent import of proteins into mammalian microsomes involves a membrane protein which is sensitive to chemical alkylation.
Import of the small precursor protein preprocecropin A (ppcec A) into dog pancreas microsomes under post-translational conditions does not involve the ribonucleoparticles, signal recognition particle and ribosome, and their receptors on the microsomal surface, docking protein and ribosome receptor. In this study, we attempted to obtain direct evidence for the involvement of proteinaceous membrane components in this alternative import mechanism by utilizing various sulfhydryl-modifying reagents (N-ethylmaleimide (NEM), N-iodoacetylaminoethyl-5-naphthylamine-1- sulphonic acid (AEDANS) and iodoacetamide (IAA]. As a result of observing the inhibitory effect of 2 reagents (NEM and AEDANS) on the microsomes with respect to ppcec A-import, we concluded that there is at least one membrane protein with a cytoplasmically exposed sulfhydryl involved in ppcep A-import. This membrane protein(s) is (are) distinct from membrane proteins which are known to be involved in protein import, such as the signal peptidase and the so-called signal sequence receptor.


Osteoarthritis in hemodialysis patients: relationships with bone mineral density and other clinical and laboratory parameters.
The aim of this study was to determine the role that hemodialysis (HD) plays in radiologically assessed osteoarthritis (OA) of the hand, knee, and hip. Eighty patients who had been on regular HD for at least 2 years were included. Anterior-posterior radiographs of the pelvis, weight-bearing knees, and hands and wrists of each patient were examined. Bone mineral density (BMD) of spine, femur, and forearm was measured. Radiologic assessment of the 80 patients' hands showed that 41 individuals had osteopenia, 12 had midphalangeal subperiosteal resorption, 11 had cystic bone lesions, eight had bone erosion, four had osteophytic lesions, and three had subchondral sclerosis. Bone erosion in the hands was significantly associated with HD duration, forearm T score, and serum parathyroid hormone level. Radiologically, OA was demonstrated in eight knee and ten hip joints. Minimum joint space in the tibiofemoral compartment correlated with body mass index, and minimum joint space in the hip correlated with age. The mean BMD measurements at all three sites studied in the HD patients were low. Only the duration of HD significantly correlated with forearm BMD. Osteoarticular complications are common in HD patients.


Mitogen-activated protein kinases (MAPKs) mediate SIN-1/ glucose deprivation-induced death in rat primary astrocytes.
Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and superoxide and induces NO-mediated inflammation under neuropathological conditions. Previously, we reported that glucose deprivation induced ATP depletion and cell death in immunostimulated astrocytes, which was mainly due to peroxynitrite. In this study, the role of MAPKs (ERK1/2, p38MAPK, and JNK1SAPK) signal pathway in the SIN-1/glucose deprivation-induced death of astrocytes was examined. A combined treatment with glucose deprivation and 50 microM SIN-1, an endogenous peroxynitrite generator, rapidly and markedly increased the death in rat primary astrocytes. Also, SIN-1/glucose deprivation resulted in the activation of MAPKs, which was significantly blocked by the treatment with 20 microM MAPKs inhibitors (ERK1/2, PD98059; p38MAPK, SB203580; JNK/SAPK, SP600125). Interestingly, SIN-1/glucose deprivation caused the loss of intracellular ATP level, which was significantly reversed by MAPKs inhibitors. These results suggest that the activation of MAPKs plays an important role in SIN-1/glucose deprivation-induced cell death by regulating the intracellular ATP level.


Removal of dichloromethane from waste gases in one- and two-liquid-phase stirred tank bioreactors and biotrickling filters.
The removal of dichloromethane (DCM) from polluted air was studied both in biotrickling filters and in continuous stirred tank bioreactors, using either a single-liquid aqueous phase or a combination of an aqueous-organic liquid phase. The presence of the organic phase, i.e. silicone oil, at a volume ratio of 10% of the liquid phase, increased the maximum EC by about 25% in the BTF, reaching 200 gm(3)/h, and by as much as 300% in the CSTB, reaching 350 gm(3)/h. Based on data of chloride release in the aqueous phase and carbon dioxide production in the gas phase, complete dechlorination and mineralization of the pollutant could be confirmed. When applying shock loads, a more stable behaviour was observed in the presence of the organic phase. Generally, the completely mixed reactors were also more stable than the plug-flow biotrickling filters, irrespective of the presence of the organic phase. The use of molecular techniques allowed showing that the originally inoculated DCM-degrading Hyphomicrobium strains remained present, although not dominant, after long-term bioreactor operation. Different new bacterial populations did also appear in the systems, some of which were unable to degrade DCM.


Study of inhomogeneities in sources prepared for alpha-particle spectrometry using scanning probe microscopy.
For high-resolution alpha-particle spectrometry, sources of high quality must be prepared by methods giving the thinnest and most homogeneous deposit possible on a suitable support. Surface characteristics of several types of alpha-particle sources were studied using a scanning probe microscope. Major inhomogeneities were observed, which means that the materials and techniques used for thc preparation of sources must be improved.


[Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis].
Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.


[The oxygen effect in cells of E. coli K-12 with different repair genotypes during irradiation with neutrons and gamma rays].
The oxygen enhancement ratio, as estimated after the effect of 137Cs-gamma-quanta, depends on the repair genotype of E. coli K-12 cells and increases in the studied strains in the following order: recA-uvrA(-)----recA(-)----wild type----pol A-. These variations are levelled with the effect of fast neutrons of division spectrum (0.75 MeV); the oxygen enhancement ratio for the strains under study decrease, while the oxygen effect is virtually absent in recA-uvrA--mutant.


Degradation and solid-liquid distribution of antibiotics in microbial electrolysis cells treating sewage sludge: Effects of temperature and applied voltage.
The microbial electrolysis cell (MEC) is a promising technology for antibiotic removal in sewage sludge. Temperature and voltage are key operating factors, but information about their effects on antibiotic degradation in MECs is still limited. Therefore, the effects of the temperature and applied voltage on the degradation and solid-liquid distribution of antibiotics in MECs treating sewage sludge were investigated. The results showed that the thermophilic (55 °C) MEC (T-MEC) at 0.8 V achieved the highest total antibiotic removal efficiency of 58.7 % due to the increase in bioelectrochemical activity for anodes and microbial activity in suspended sludge. The solid-liquid migration of antibiotics was facilitated, which had a significant positive correlation with antibiotic removal. Biodegradation was the rate-limiting step for the removal of fluoroquinolones, which had the highest levels in sludge. Geobacter and Thermincola were dominant bacteria in the anode biofilms of mesophilic (37 °C) MECs (M-MECs) and T-MECs, respectively.


Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study.
It has been reported that pioglitazone reduces neointimal hyperplasia after balloon-induced vascular injury in an experimental model. To determine whether pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus, we studied 44 stented lesions in 44 patients with diabetes mellitus who underwent successful coronary stent implantation. Study patients were randomized into 2 groups: the pioglitazone group (23 patients with 23 lesions) and the control group (21 patients with 21 lesions). All patients underwent serial quantitative coronary angiography and serial intravascular ultrasound scanning studies. With a motorized pullback system, multiple image slices within the stent were obtained at every 1 mm. The stent area and lumen area were measured, and the neointimal area was calculated. Measurements were averaged over the number of selected image slices. The neointimal index was calculated as the averaged neointimal area divided by the averaged stent area multiplied by 100 (%). After 6 months of treatment, angiographic in-stent restenosis (17% vs 43%, respectively, P =.0994) and target lesion revascularization (13% vs 38%, respectively, P =.0835) were less frequent in the pioglitazone group than the control group; however, these differences did not reach significance. The intravascular ultrasound scanning study demonstrated that the neointimal index in the pioglitazone group was significantly smaller than that in the control group (28% +/- 9% vs 48% +/- 15%, respectively, P <.0001). A serial intravascular ultrasound scanning assessment demonstrated that pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus.


Can Automated Vehicles Be Useful to Persons Living With Dementia? The Perspectives of Care Partners of People Living With Dementia.
Driving cessation is a complex challenge with significant emotional and health implications for people with dementia, which also affects their family care partners. Automated vehicles (AVs) could potentially be used to delay driving cessation and its adverse consequences for people with dementia and their care partners. Yet, no study to date has investigated whether care partners consider AVs to be potentially useful for people with dementia. This mixed-methods study assessed the views of 20 former or current family care partners of people with dementia on AV use by people with dementia. Specifically, questionnaires and semistructured interviews were used to examine care partners' acceptance of AV use by people with dementia and their views about the potential usefulness of AVs for people with dementia. The results demonstrated that care partners identified possible benefits of AV use by people with dementia such as their anticipated higher social participation. However, care partners also voiced major concerns around AV use by people with dementia and reported significantly lower levels of trust in and perceived safety of AVs if used by the person with dementia in their care compared to themselves. Care partners' concerns about AV use by people with dementia included concerns around the driving of people with dementia that AVs are not designed to address; concerns that are specific to AVs but are not relevant to the nonautomated driving of people with dementia; and concerns that arise from existing challenges around the nonautomated driving of people with dementia but may be exacerbated by AV use. Findings from this study can inform future designs of AVs that are more accessible and useful for people with dementia.


Reviving the interest in the versatile drug nystatin: A multitude of strategies to increase its potential as an effective and safe antifungal agent.
Nystatin is an antifungal molecule with a remarkable yet squandered versatility. In this review, its mechanism of action is explored, along with its extensive action spectrum and toxicity. A multitude of methodologies to tackle the drug's physical and chemical hurdles are outlined along with some proven-effective strategies to increase its activity and/or decrease its toxicity. A separate detailed section focused on micro and nanotechnology solutions addresses new drug delivery systems made of polymeric, metallic or lipid materials. Although the topical route depicts greater representativeness amongst these formulations, the intravenous, dental, oral, vaginal and inhalation routes are also mentioned. The unsuccessful previous attempts at developing parenteral formulations of nystatin or even the withdrawal of a nystatin-loaded multilamellar liposome should not divert research away from this drug. In fact, the interest in nystatin ought to be reawakened with the ongoing clinical trials on the promising nystatin-like genetically engineered derivate BSG005.


Autonomy support and diastolic blood pressure: Long term effects and conflict navigation in romantic relationships.
Perceiving autonomy support-or encouragement to be oneself-from a romantic partner or other close relationship partners has been shown to yield a variety of psychological health benefits, but it is less clear how perceiving autonomy support from partners is linked to physical health. In two studies we examine the associations between receiving autonomy support in romantic relationships and diastolic blood pressure, an important indicator of cardiovascular health. Results of a longitudinal study found support for a model in which autonomy supportive romantic relationships are linked with lower diastolic blood pressure. Whereas Study 1 showed general longitudinal effects, Study 2 revealed the importance of receiving autonomy support from partners during times of conflict. Implications of the findings will be discussed in the context of self-determination theory.


Screening for hepatitis C in a general adult population in a low-prevalence area: the Tromsø study.
Chronic hepatitis C virus (HCV) infection can progress to cirrhosis and end-stage liver disease in a substantial proportion of patients. The infection is frequently asymptomatic, leaving many infected individuals unaware of the diagnosis until complications occur. This advocates the screening of healthy individuals. The aim of this study was to estimate the prevalence of HCV infection in the general adult population of the municipality of Tromsø, Norway, and to evaluate the efficiency of such an approach in a presumed low-prevalence area. The study was part of the seventh survey of the Tromsø Study (Tromsø 7) in 2015-2016. Sera from 20,946 individuals aged 40 years and older were analysed for antibodies to HCV (anti-HCV). A positive anti-HCV test was followed up with a new blood test for HCV RNA, and the result of any previous laboratory HCV data were recorded. Samples positive for anti-HCV and negative for HCV RNA were tested with a recombinant immunoblot assay. All HCV RNA positive individuals were offered clinical evaluation. Among 20,946 participants, HCV RNA was detected in 33 (0.2%; 95% CI: 0.1-0.3), of whom 13 (39.4%; 95% CI: 22.7-56.1) were unaware of their infection. The anti-HCV test was confirmed positive in 134 individuals (0.6%; 95% CI: 0.5-0.7) with the highest prevalence in the age group 50-59 years. Current or treatment-recovered chronic HCV-infection was found in 85 individuals (0.4%; 95% CI: 0.3-0.5) and was associated with an unfavorable psychosocial profile. In this population-based study, the prevalence of viraemic HCV infection was 0.2%. A substantial proportion (39%) of persons with viraemic disease was not aware of their infectious status, which suggests that the current screening strategy of individuals with high risk of infection may be an inadequate approach to identify chronic HCV infection hidden in the general population.


Sirtuins mediate mammalian metabolic responses to nutrient availability.
Metabolic diseases are an increasing threat in developed countries. Dysregulation of metabolic pathways, caused by imbalances in energy homeostasis, leads to obesity, diabetes and cardiovascular disease with devastating results for both individuals and societies. Sirtuins, a conserved family of NAD(+)-dependent deacetylase enzymes found in many species, regulate various metabolic pathways and have emerged as important sensors of energy status in mammals. The nuclear sirtuins, SIRT1, SIRT6 and SIRT7, regulate the activity of key transcription factors and cofactors of numerous metabolic pathways in almost all tissues by linking nutrient signals with the cellular responses to energy demands. The mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, regulate the activity of important mitochondrial enzymes and drive metabolic cycles in response to fasting and calorie restriction. Accumulating evidence indicates that sirtuins can be beneficial in the prevention of metabolic and age-related diseases and suggests that they can be pharmacologically activated to ameliorate such diseases. This Review describes the latest advances in the understanding of the function of sirtuins as regulators of mammalian metabolism and focuses on the role of these enzymes as mediators of nutrient availability.


Internet use by patients with prostate cancer undergoing radiotherapy.
To analyze the amount of Internet use, type of Internet use, and factors that predict Internet use by patients with prostate cancer. A questionnaire evaluating the use of the Internet was given to 295 patients undergoing radiotherapy for prostate cancer in three different settings: an academic center (AC), a Veterans Affairs center (VA), and a community hospital. The study included 171 AC patients (58%), 104 VA patients (35%), and 20 community hospital patients (7%). The response rate to the questionnaire was greater than 99%. Overall, 128 (43%) of 295 patients had a home computer. This differed among the institutions, with 64% of AC patients and only 5% of VA patients having a home computer (P <0.0001). Overall, 94 (32%) of 295 patients used the Internet to access cancer information, with 48% of AC patients and 8% of VA patients using the Internet (P <0.0001). Seventeen percent of black patients (n = 113) had a home computer compared with 62% of white patients (n = 175; P <0.0001). Equal access to computers did not influence Internet use because, among those patients who had access to computers, black patients used the Internet less than did white patients (32% versus 61%, P <0.0001). Men 65 years of age or younger were more likely to use the Internet (45%) than those older than 65 years (28%; P = 0.004). Patients used many sites to access different types of information. A significant number of patients with prostate cancer access the Internet to obtain cancer information. Urologists and radiation oncologists should be familiar with this important resource to help patients access appropriate material.


Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance.
Hereditary diffuse gastric cancer (HDGC) is a relatively rare disorder, with a mutated CDH1 gene as the only known cause. Carriers of a germline mutation in CDH1 have a lifetime risk of >80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting early stages of HDGC, prophylactic gastrectomy is advised for this patient group. Little is known about other types of familial gastric cancer. The Dutch working group on hereditary gastric cancer has formulated guidelines for various aspects of medical management for families and individuals at high risk of developing gastric cancer, including criteria for referral, classification, diagnostics, and periodic gastric surveillance. These guidelines are not limited to HDGC and are therefore partially complementary to the guidelines on hereditary diffuse gastric cancer of the international gastric cancer linkage consortium (IGCLC 2010). In order to optimize the care and increase the knowledge on hereditary gastric cancer it is important to centralize medical care for these patients. National and international collaboration is warranted to improve the quality of research by increasing the size of study cohorts.


Barriers to Pre-Exposure Prophylaxis Uptake Among Online Male Sex Workers in the US.
Though barriers to HIV pre-exposure prophylaxis (PrEP) uptake among gay, bisexual, and other men who have sex with men (MSM) have received substantial research attention, less is known about what factors may be affecting PrEP uptake among male sex workers (MSWs), a population at high risk of HIV. This paper presents qualitative findings regarding why a subsample of MSM engaged in exchange sex (receiving money, drugs, shelter, or other goods in exchange for sex) with partners they met on dating/hookup websites and apps had never used PrEP. Analysis revealed several barriers to PrEP uptake including lack of awareness and knowledge about PrEP, scientific and medical concerns, issues related to individual risk perception and beliefs/preferences about risk management, practical and logistical barriers, and provider-level barriers. Nuances to these barriers are discussed, particularly as they relate to the specific type of sex work participants were engaged in. Implications for interventions are also discussed.


CaMKII phosphorylates serine 10 of p27 and confers apoptosis resistance to HeLa cells.
Protein phosphatase (PP) 6 is a serine threonine phosphatase which belongs to the PP2A subfamily of protein phosphatases. PP6 has been implicated in the control of apoptosis. A dominant negative form PP6 (DN-PP6) mutant cDNA was prepared and transfected into HeLa cells to investigate the regulation of apoptosis. HeLa cells expressing DN-PP6 showed increased resistance to apoptosis induced by TNF and cycloheximide. CaMKII phosphorylation and the expression of p27 were increased in DN-PP6 transfectants. Transient expression or activation of CaMKII increased the expression of p27. Furthermore, CaMKII phosphorylated serine 10 of p27, which induces the translocation of p27 from nucleus to cytoplasm and increases the stability of p27. Overexpression of wild type but not the S10A mutant p27 cDNA increased the expression of Bcl-xL and conferred apoptosis resistance to HeLa cells. These results indicated that PP6 and CaMKII regulated apoptosis by controlling the expression level of p27.


Drug metabolizing enzyme activities versus genetic variances for drug of clinical pharmacogenomic relevance.
Enzymes are critically important in the transportation, metabolism, and clearance of most therapeutic drugs used in clinical practice today. Many of these enzymes have significant genetic polymorphisms that affect the enzyme's rate kinetics. Regarding drug metabolism, specific polymorphisms to the cytochrome (CYP) P450 enzyme family are linked to phenotypes that describe reaction rates as "ultra", "intermediate", and "poor," as referenced to "extensive" metabolizers that are assigned to wildtype individuals. Activity scores is an alternate designation that provides more genotype-to-phenotype resolution. Understanding the relative change in enzyme activities or rate of clearance of specific drugs relative to an individual's genotypes is an important component in the interpretation of pharmacogenomic data for personalized medicine. Currently, the most relevant drug metabolizing enzymes are CYP 2D6, CYP 2C9, CYP 2C19, thiopurine methyltransferase (TPMT) and UDP-glucuronosyltransferase (UGT). Each of these enzymes is reactive to a host of different drug substrates. Pharmacogenomic tests that are in routine clinical practice include CYP 2C19 for clopidogrel, TPMT for thiopurine drugs, and UDP-1A1 for irinotecan. Other tests where there is considerable data but have not been widely implemented includes CYP 2C9 for warfarin, CYP 2D6 for tamoxifen and codeine, and CYP 2C19 for the proton pump inhibitors.


Asthma in African Americans: what can we do about the higher rates of disease?
African Americans not only have a higher prevalence of asthma than whites, they also are encumbered with higher rates of asthma-associated morbidity and death. Factors such as genetics, socioeconomic status, health maintenance behaviors, air quality, and obesity likely contribute in combination to these burdens. Further work is needed to better understand these complex risk factors. To remedy these disparities, we need to ensure that patients at higher risk are given proper care and the knowledge to control their asthma.


Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.
Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.


Have You Ever Seen a Robot? An Analysis of Children's Drawings Between Technology and Science Fiction.
Technologies have become an essential part of the daily life of our children. Consequently, artifacts that imply the early adoption of abstract thinking affect the imagination of children and young people in relation to the world of technology, now much more than they did in the past. With the emerging importance of robots in many aspects of our everyday lives, the goal of this study is to investigate which mental representations children have about robots. To this end, drawings from 104 children aged between 7 and 12 years old were used as a map of representations, considering the drawings as a proxy capable of evoking learned or emerging mental frameworks. The drawings were analyzed in several steps: they were first labeled using binary descriptors and then classified using clustering methods based on Hamming distances between drawings. Finally, questionnaire items covering children's perceptions about robots were analyzed for each of the resulting cluster separately to identify differences between them. The results show that there are relationships between the way children draw robots and their perception about robots' capabilities as well as their aspirations to pursue a career in science. These findings can provide meaningful insights into how to design educational robots and learning activities for children to learn with and about robots.


Comparison between bispectral index and patient state index as measures of the electroencephalographic effects of sevoflurane.
The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (rho(2)) and prediction probabilities (P(K)). A significant (P < 0.001) correlation between BIS and PSI was found (r(2) = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (rho(2) = 0.84 +/- 0.09) and PSI (rho(2) = 0.85 +/- 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 +/- 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 +/- 12.1), and the effect site efflux constant k(e0) was significantly smaller (P = 0.001) for PSI (0.13 +/- 0.08 min(-1)) than for BIS (0.24 +/- 0.15 min(-1)). The probability of BIS (P(K) = 0.80 +/- 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (P(K) = 0.79 +/- 0.09). The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose-response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well.


Comparative effectiveness of gastric bypass and sleeve gastrectomy on predicted 10-year risk of cardiovascular disease 5 years after surgery.
Comparative evidence is needed when deciding which bariatric operation to undergo for long-term cardiovascular risk reduction. The Effectiveness of Gastric Bypass vs. Gastric Sleeve for Cardiovascular Disease (ENGAGE CVD) study compared the effectiveness of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations for reduction of the American College of Cardiology and the American Heart Association-predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk 5 years after surgery. Data for this study came from a large integrated healthcare system in the Southern California region of the United States. This is one of the most ethnically diverse (64% non-White) bariatric populations in the literature. The ENGAGE CVD cohort consisted of 22,095 patients who underwent VSG or RYGB from 2009-2016. The VSG and RYGB were compared using a local instrumental variable approach to address observed and unobserved confounding, as well as to conduct heterogeneity of treatment effects for patients of different age groups, baseline-predicted 10-year CVD risk using the ASCVD risk score, and those who had type 2 diabetes (T2D) at the time of surgery. Patients (2771 RYGB and 6256 VVSG) were primarily women (80.6%), Hispanic or non-Hispanic Black (63.7%), and 46 ± 10 years of age, with a body mass index of 43.40 ± 6.5 kg/m2. The predicted 10-year ASCVD risk at surgery was 4.1% for VSG and 5.1% for RYGB, decreasing to 2.6% for VSG and 2.8% for RYGB 1 year postoperatively. By 5 years after surgery, patients remained with relatively low risk levels (3.0% for VSG and 3.3% for RYGB) and there were no significant differences in predicted 10-year ASCVD risk between VSG and RYGB at any time. Predicted 10-year ASCVD risk was low in this population and remained low up to 5 years for those with diabetes, Black and Hispanic patients, and older adults. Literature reporting significant differences between VSG and RYGB in 10-year ASCVD risk may be a result of residual confounding.


Evaluation of classification and regression tree (CART) model in weight loss prediction following head and neck cancer radiation therapy.
We explore whether a knowledge-discovery approach building a Classification and Regression Tree (CART) prediction model for weight loss (WL) in head and neck cancer (HNC) patients treated with radiation therapy (RT) is feasible. HNC patients from 2007 to 2015 were identified from a prospectively collected database Oncospace. Two prediction models at different time points were developed to predict weight loss ≥5 kg at 3 months post-RT by CART algorithm: (1) during RT planning using patient demographic, delineated dose data, planning target volume-organs at risk shape relationships data and (2) at the end of treatment (EOT) using additional on-treatment toxicities and quality of life data. Among 391 patients identified, WL predictors during RT planning were International Classification of Diseases diagnosis; dose to masticatory and superior constrictor muscles, larynx, and parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage, nausea, pain, dose to larynx, parotid, and low-dose planning target volume-larynx distance were significant predictive factors. The area under the curve during RT and EOT was 0.773 and 0.821, respectively. We demonstrate the feasibility and potential value of an informatics infrastructure that has facilitated insight into the prediction of WL using the CART algorithm. The prediction accuracy significantly improved with the inclusion of additional treatment-related data and has the potential to be leveraged as a strategy to develop a learning health system.


Diagnosis and management of nonallergic rhinitis with eosinophilia syndrome using cystatin SN together with symptoms.
The diagnosis and treatment of nonallergic rhinitis with eosinophilia syndrome (NARES) remain controversial. The aim of this study was to evaluate whether Cystatin SN together with symptoms can be used to diagnose NARES and to measure the efficiency of medical treatment. Seventy-five patients with chronic rhinitis (CR) and 18 control subjects were enrolled. Their clinical characteristics were reviewed and laboratory parameters were evaluated. The concentration of Cystatin SN in nasal secretions was determined using the enzyme-linked immunosorbent assay. The histological assessment of Cystatin SN in the nasal mucosa was conducted by hematoxylin and eosin staining. The logistic regression and receiver operating characteristic curves were used to assess the predictive value of parameters for NARES. Nasal obstruction, sneezing, loss of smell, and total visual analogue scale (VAS) score were significantly different among the patients with CR. In particular, olfaction score was higher in patients with NARES than in those without NARES (AR, LAR, or IR). Similarly, the Cystatin SN level was significantly different between the control subjects and patients with CR. After treatment for 2 weeks, the Cystatin SN level and VAS score were significantly decreased in the NARES group. The accuracy of Cystatin SN together with local sIgE and loss of smell to diagnose NARES was up to 0.987 (sensitivity, 100%; specificity, 93.1%). Cystatin SN with local sIgE and loss of smell may serve as one of the reliable and alternative biomarkers for the diagnosis of NARES and be used to evaluate disease severity and NARES treatment efficacy.


A formal model of interpersonal inference.
We propose that active Bayesian inference-a general framework for decision-making-can equally be applied to interpersonal exchanges. Social cognition, however, entails special challenges. We address these challenges through a novel formulation of a formal model and demonstrate its psychological significance. We review relevant literature, especially with regards to interpersonal representations, formulate a mathematical model and present a simulation study. The model accommodates normative models from utility theory and places them within the broader setting of Bayesian inference. Crucially, we endow people's prior beliefs, into which utilities are absorbed, with preferences of self and others. The simulation illustrates the model's dynamics and furnishes elementary predictions of the theory. (1) Because beliefs about self and others inform both the desirability and plausibility of outcomes, in this framework interpersonal representations become beliefs that have to be actively inferred. This inference, akin to "mentalizing" in the psychological literature, is based upon the outcomes of interpersonal exchanges. (2) We show how some well-known social-psychological phenomena (e.g., self-serving biases) can be explained in terms of active interpersonal inference. (3) Mentalizing naturally entails Bayesian updating of how people value social outcomes. Crucially this includes inference about one's own qualities and preferences. We inaugurate a Bayes optimal framework for modeling intersubject variability in mentalizing during interpersonal exchanges. Here, interpersonal representations are endowed with explicit functional and affective properties. We suggest the active inference framework lends itself to the study of psychiatric conditions where mentalizing is distorted.


Handling of a sodium load by rats on a low sodium intake and frusemide.
1. Groups of rats (n = 9-10 per group) were given a medium sodium (Na) diet or a low Na diet or a low Na diet plus low or high dose frusemide in order to have their body Na in a state of surplus or deficit or neither. 2. Body Na was measured by a 22Na whole body counting method involving Na-free chow and the drinking fluid as the only source of Na (22Na-labelled NaCl). Intraperitoneal NaCl (same specific activity) loads were given and their excretion was measured by repeated measurements of body Na over the next 48 h. 3. Rats in surplus excreted more than the load; those in neither surplus nor deficit excreted more or less exactly the load (allowing for growth); those with a small deficit retained enough Na to make up most of the deficit; those with a deficit that was larger than the load retained approximately the whole load. 4. The results support the Strauss-Hollenberg concept that there is a basal body Na above which Na is excreted and below which any available Na is retained.


Hematuria: essentials of diagnosis.
Relatively common and often serious, hematuria has numerous causes requiring differing management strategies. Diagnostic guidelines are given.


Synthesis of subunits of ligandin by isolated hepatocytes.
The pulse-chase technique was employed to determine the synthesis of the subunits of ligandin (glutathione S-transferase 1-2) by isolated hepatocytes. Ligandin comprised 2.5-3% of the total proteins synthesized. A slightly higher incorporation of [35S]methionine into the 22 k than the 25 k subunit was observed. However, the ratio of [35S]methionine incorporation into the subunits remained constant throughout the chase period, suggesting that, in spite of the considerable sequence homology, the conversion of 25 k to 22 k subunit does not occur in vivo.


Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy.
Dendritic cell- (DC-) tumor fusion cells stimulate effective in vivo antitumor responses. However, therapeutic approaches are dependent upon the coadministration of exogenous 3rd signals. The purpose of this study was to determine the mechanisms for inadequate 3rd signaling by electrofused DC-tumor cell hybrids. Murine melanoma cells were fused with DCs derived from C57BL/6 mice. Quantitative real-time PCR (qPCR) was used to determine relative changes in Th (T helper) 1 and Th2 cytokine gene expression. In addition, changes in gene expression of fusion cells were determined by microarray. Last, cytokine secretion by fusion cells upon inhibition of signaling pathways was analyzed by ELISA. qPCR analyses revealed that fusion cells exhibited a downregulation of Th1 associated cytokines IL-12 and IL-15 and an upregulation of the Th2 cytokine IL-4. Microarray studies further showed that the expression of chemokines, costimulatory molecules, and matrix-metalloproteinases was deregulated in fusion cells. Lastly, inhibitor studies demonstrate that inhibition of the PI3K/Akt/mTOR signaling pathway could restore the secretion of bioactive IL-12p70 by fusion cells. Our results suggest that combining fusion cell-based vaccination with administration of inhibitors of the PI3K/Akt/mTOR signaling pathway may enhance antitumor responses in patients.


Impotence and diabetes.
The link between impotence and diabetes has been suspected since the 1700s, but it has been only within the last few decades that it has been scientifically investigated and confirmed. Of the 5 million diabetic men in the United States, 30% to 60% suffer from impotence, a complication of their disease that many of them fear more than any other, including blindness. Diabetes is the leading physiologic cause of impotence, and it occurs in both insulin-dependent and non-insulin dependent patients. In most cases, there is no relationship between the control, the duration, or the severity of diabetes and the occurrence of impotence. Treatment methods range from adjustments in nutrition to penile implants.


Effect of 5-bromodeoxyuridine substitution on sister chromatid exchange induction by chemicals.
The fluorescence-plus-Giemsa (FPG) technique for analysis of sister chromatid exchange (SCE) is widely used as an assay for mutagenic carcinogens. There is very little information, however, on whether incorporation of the bromodeoxyuridine (BrdU) necessary for visualization of SCEs affects the sensitivity of the SCE test system to different chemical agents. We have investigated the effect of BrdU incorporation on SCE induction by labeling cells with BrdU for either the first cell cycle or the first and second cell cycles. The cells were then treated with bleomycin, which produces DNA strand breakage; proflavine, which intercalates into DNA; mitomycin C, which produces monoadducts and DNA crosslinks; or aphidicolin, which inhibits DNA polymerase alpha. Chemicals were added before BrdU exposure or during the first, second, or both cell cycles. Only mitomycin C, which induces long-lived lesions, elevated the SCE frequency when cells were treated before BrdU labeling. When bleomycin, proflavine, or mitomycin C was present concurrently with BrdU, the frequency of SCEs was increased independently of the BrdU labeling protocol. Aphidicolin, on the other hand, induced more SCEs when present for the second cell cycle, when DNA replicates on a template DNA strand containing BrdU. We also examined the induction of SCEs in the first cell cycle (twins) and in the second cell cycle (singles) after continuous treatment of cells with BrdU and the test chemicals. Only aphidicolin increased SCE frequency in the second cell cycle. These results indicate that aphidicolin, but not bleomycin, proflavine, or mitomycin C, affects BrdU-substituted DNA and unsubstituted DNA differently. This type of interaction should be taken into consideration when the SCE test is used as an assay system.


Effectiveness of multi-disciplinary rehabilitation for patients with Neuromyelitis Optica.
Neuromyelitis optica (NMO), previously considered a subtype of multiple sclerosis (MS), is now known to be a unique disorder associated with autoantibodies against aquaporin-4. The rehabilitation protocols for MS have been applied to NMO, without specific measures of efficacy. The evaluation of the effectiveness of an MS type inpatient rehabilitation program for patients with NMO. Retrospective chart reviews of 15 inpatients with NMO and 32 inpatients with MS. Clinical severity was assessed by the Expanded Disability Status Scale (EDSS), functional assessments were scored using the Functional Independence Measure (FIM), the Montebello Rehabilitation Factor Score (MRFS), and the Functional Ambulation Category (FAC). There was a higher percentage of women in the NMO group (87% vs 56% P = 0.003). The MS group had significantly more cognitive and communication deficits (P = 0.003 and P = 0.00001). No significant differences were found in admission FIM, EDSS and FAC scores. Both groups benefitted, however at discharge, the NMO group showed greater improvement in FIM scores (NMO admission 79 ± 24, discharge 98 ± 21; MS admission 80 ± 28, discharge 89 ± 28); and lower EDSS score (NMO from 7.2 ± 1.4 to 6.3 ± 1.4; MS from 7.4 ± 1.4 to 7 ± 1.5). Inpatient multidisciplinary rehabilitation programs available for the patients with MS may be successfully implemented for patients with NMO.


Novel genotypes of Cryptosporidium and Enterocytozoon bieneusi detected in plateau zokors (Myospalax baileyi) from the Tibetan Plateau.
The plateau zokor (Myospalax baileyi) is a small subterranean rodent endemic to China that lives alone in sealed underground burrows at altitudes ranging from 2000 to 4200 m above sea level on the Tibetan Plateau. Due to the unique environmental factors in the Tibetan Plateau, intestinal parasites in the local population may be more likely to develop host-adapted genotypes. We therefore conducted an epidemiological survey of common intestinal parasites in plateau zokors on the Tibetan plateau to estimate their actual gastrointestinal parasite status. Two areas with high populations of plateau zokor in Xunhua County, Qinghai Province were selected as sampling sites, and a total of 98 zokors were trapped. Four parasites, Cryptosporidium spp., Enterocytozoon bieneusi, Giardia lamblia and Blastocystis hominis, were tested in the faecal samples. The results showed that a new genotype of Cryptosporidium sp. was identified by amplification and sequencing of a portion of the small subunit ribosomal RNA (SSU rRNA) gene with an infection rate of 1.0% (1/98), and new genotypes of E. bieneusi were identified by amplification and sequencing of a portion of the internal transcribed spacer (ITS) region of the ribosomal RNA gene sequences with an infection rate of 4.1% (4/98). Neither of the two intestinal parasites, G. lamblia and B. hominis, was detected.


Fat emulsions based on structured lipids (1,3-specific triglycerides): an investigation of the in vitro interaction with plasma proteins.
Structured lipids (1,3-specific triglycerides) are new chemical entities made by enzymatic transesterification of the fatty acids in the 1,3-positions of the triglyceride. The purpose of this study was to investigate the in vitro interaction of fat emulsions based on either structured lipids or vegetable oils with human plasma proteins employing two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The structured lipids are triglycerides of the SLS and MLM types, where S is short-chain fatty acids (C4), M is medium-chain fatty acids (C8-10) and L is long-chain fatty acids (C16-18). The vegetable oil-based fat emulsions were the commercially available product, Intralipid, and a soybean oil (LLL) emulsion made de novo identically as the emulsions containing structured lipids. The SLS emulsion was found to adsorb a different protein pattern than the MLM and LLL emulsions. The protein pattern of the SLS emulsion was similar to the protein pattern of Intralipid. These findings might explain the in vivo difference in elimination found in another study, where the emulsion based on structured lipids with short-chain fatty acids in the 1,3-positions was removed more slowly from the general blood circulation compared to emulsions based on lipids with long-chain fatty acids in the 1,3-positions (LLL).


Factors associated with upper limb dysfunction in breast cancer survivors.
To analyze factors associated with upper limb dysfunction in women after breast cancer treatment. A cross-sectional study with 233 women over 18 years of age diagnosed with breast cancer and undergoing at least one cancer treatment (surgery and/or adjuvant treatment). Sociodemographic, anthropometric, and cancer treatment data were collected, as well as current physical and functional complications. Changes in breast tenderness and intercostobrachial nerve pathway, winged scapula, pain, cicatricial adherence, and lymphedema were evaluated by physical examination (inspection and palpation). Upper limb dysfunction was assessed using the DASH questionnaire. Chi-square test and logistic regression were used to verify possible associations between upper limb dysfunction and other variables. The results showed that 55.4% of women had some level of upper limb dysfunction. Evaluating treatment conditions, lymphadenectomy, lymphedema, presence of pain, and intercostobrachial nerve injury were associated with some level of upper limb dysfunction in the crude analysis. The adjusted analysis showed that only upper limb dysfunction remained associated with intercostobrachial nerve injury, regardless of age and body mass index. Upper limb dysfunction is frequent after breast cancer treatment and may be associated with neuropathies due to changes in the intercostobrachial nerve pathway.


Diagnostic procedure in suspected Graves' disease.
Diagnostic procedure in suspected Graves' disease has never been studied scientifically and actual practice seems quite variable, notably between countries. Recommendations are few and weak (expert opinion). This article presents the recommendations of an expert consensus meeting organized by the French Society of Endocrinology in 2016. In case of clinically suspected thyrotoxicosis, the first-line biological assessment is of thyroid-stimulating hormone (TSH). Free T4 and possibly free T3 assays assess biological severity and are necessary for treatment efficacy monitoring. Positive diagnosis of Graves' disease after biological confirmation of thyrotoxicosis does not always require complementary etiological examinations if clinical presentation is unambiguous, notably including extra-thyroid signs. Otherwise, first-line anti-TSH-receptor (TSH-R) antibody screening is recommended for its good intrinsic performance (sensitivity and specificity) and ease of access in France. Scintigraphy is reserved to rare cases of Graves' disease with negative antibody findings or when another etiology is suspected. Thyroid ultrasound scan may be contributive, but is not recommended in first line.


Impact of training on emergency resuscitation skills: Impact on Millennium Development Goals (MDGs) 4 and 5.
Although significant progress has been made towards Millennium Development Goal (MDG) 4 and 5 targets, maternal and neonatal mortality rates remain unacceptably high in low- and middle-income countries (LMICs). The potential for improvements in maternal and neonatal health outcomes with increased facility utilization in these countries is undermined by a lack of appropriate and timely treatment. Skilful emergency resuscitation can be the difference between life and death; therefore, training in emergency resuscitation is essential for health-care practitioners at all levels, with regular refresher sessions to ensure skill retention. Whilst there is little robust evidence on the impact of resuscitation training interventions on practitioner skills or patient outcomes, such training interventions are likely to have the greatest impact if integrated into a broader approach to improve the quality of care. Accelerated investments in training must go hand in hand with ensuring the availability of quality equipment and upgrading infrastructure to reduce the gap between current MDG status and what is achieved by the end of 2015; and to accelerate reductions in mortality rates beyond 2015 towards new Countdown targets.


Aglycemia keeps mitochondrial oxidative phosphorylation under hypoxic conditions in HepG2 cells.
Cancer cell bioenergetics, maintaining mixed aerobic glycolysis (Warburg phenotype) and oxidative phosphorylation (OXPHOS), is not fully elucidated. Hypoxia-dependent OXPHOS suppression determines aerobic glycolysis. To elucidate further details, we studied hypoxic adaptation (up to 72 h at 5 % oxygen) of hepatocellular carcinoma HepG2 cells. The key regulatory component, hypoxia-inducible factor (HIF)-1α (HIF-1α) was stabilized at 5 h in 5 % oxygen for all three studied regimens, i.e. in glycolytic cells at 5 mM or 25 mM glucose, or in aglycemic (OXPHOS) cells when glucose was replaced by galactose. However, the conventional HIF-mediated suppression of respiration was prevented at aglycemia, which correlated with a high proportion of unphosphorylated pyruvate dehydrogenase (PDH) at 5 % oxygen. Such a modified HIF response in OXPHOS cells, termed as a non-canonical one, contrasted to conventional respiration suppression down to 45 % or 43 %, observed in hypoxia-adapted glycolytic cells at 5 mM or 25 mM glucose, respectively. These hypoxic glycolytic cells had normally highly phosphorylated PDH and most likely utilized pyruvate by aminotransferase reaction of glutaminolysis to feed at least suppressed respiration. Also, glycolytic cells were rather resistant towards the staurosporine-induced apoptosis, whereas aglycemic (OXPHOS) HepG2 cells exhibited much higher susceptibility. We conclude that aglycemia modulates the hypoxic HIF signaling toward a non-canonical response that is unable to carry out complete PDH phosphorylation, allowing a high pyruvate input for OXPHOS from the elevated glycolysis, which together with ongoing glutaminolysis maintain a virtually unchanged respiration. Similar OXPHOS revival may explain distinct tumor sensitivity to chemotherapy and other pharmacological interventions.


Isolation and functional analysis of denitrifiers in an aquifer with high potential for denitrification.
Aquifers are among the main freshwater sources. The Raigón aquifer is susceptible to contamination, mainly by nitrate and pesticides, such as atrazine, due to increasing agricultural activities in the area. The capacity of indigenous bacteria to attenuate nitrate contamination in different wells of this aquifer was assessed by measuring denitrification rates with either acetate plus succinate or nitrate amendments. Denitrification activity in nitrate-amended assays was significantly higher than in unamended assays, particularly in groundwater from wells where nitrate concentration was 33.5 mg L(-1) or lower. Furthermore, groundwater denitrifiers capable of using acetate or succinate as electron donors were isolated, identified by 16S rRNA gene sequencing and evaluated for functional denitrification genes (nirS, nirK and nosZ). Phylogenetic affiliation of 54 isolates showed that all members belonged to nine different genera within the Proteobacteria (Bosea, Ochrobactrum, Azospira, Zoogloea, Acidovorax, Achromobacter, Vogesella, Stenotrophomonas and Pseudomonas). In addition, isolate AR28 that clustered separately from validly described species could potentially belong to a new genus. The majority of the isolates were related to species belonging to previously reported denitrifying genera. However, the phylogeny of the nirS and nosZ genes revealed new sequences of these functional genes. To our knowledge, this is the first isolation and sequencing of the nirS gene from the genus Vogesella, as well as the nosZ gene from the genera Acidovorax and Zoogloea. The results indicated that indigenous bacteria in the Raigón aquifer had the capacity to overcome high nitrate contamination and exhibited functional gene diversity.


[Clinical and experimental study on treating bronchial asthma with xingbei granule].
To explore the effect of the Xingbei Granule (XBG) in treating bronchial asthma and its mechanism. Systematic clinical observation and animal experimental study on the XBG were carried out. The XBG not only could reduce the symptom of asthma, improve the ventilatory function effectively, but also has the effect of antagonizing the change of asthmatic inflammatory medium, alleviating the air-way's inflammatory reaction and lowering the air-way's hyperreactivity. XBG do attain the dual goal of controlling the asthmatic symptoms and reducing the asthmatic attack.


Cytological Quantification of Nodal Mast Cells in Dogs Affected by Non-Neoplastic Condition and Mast Cell Tumor Using Different Sample Preparation Techniques: An Explorative Study.
Cytological evaluation of lymph nodes (LN) in canine cutaneous mast cell tumors (MCT) has a key role in MCT staging. However, cytological discrimination between metastatic and reactive LNs is debated and diagnostic criteria inconsistent. The aim of this study was to retrospectively quantify nodal mast cells (MCs) in non-oncological (NOD) and MCT-bearing dogs (MCTBD), using different sample preparation techniques, to evaluate the significance of the MCT number. Cytological specimens from NOD-LNs (10 fine-needle aspirates-FNAs) and MCTBD-LNs (10 FNAs, 10 scrapings, 10 touch imprints) were evaluated. MCTBD-LNs were grouped in: non-metastatic, possibly-metastatic, and metastatic based on current literature criteria. MCs were counted in 4, 8, and 20 high-power-fields, and over 500, 1000, and 2000 total cells. MCs were significantly more numerous in MCTBD-LNs than in NOD-LNs and in "metastatic" samples than in "non-metastatic". There was no significant difference between "metastatic" and "possibly metastatic" samples. Sample preparation techniques did not influence these results. A negative correlation between MCs number and sample cellularity was observed. Results were confirmed regardless of the counting method applied. MCs counting per se cannot distinguish possibly metastatic and metastatic cytological samples. Sample preparation technique and the counting method applied seem to have no influence on cytological quantification of nodal MCs in MCTBDs.


Influence of inhibitors of eicosanoid metabolism on proliferation of rat hepatoma cells and on tumor-host interaction.
The influence of eicosanoids on the proliferation of hepatoma (HTC) cells was studied in culture and in tumor-bearing rats. The cells in culture demonstrated a capacity to metabolize arachidonic acid to eicosanoids including thomboxane B2 and the prostaglandins E2 and F2 alpha a. An effect of these eicosanoids on cell proliferation was suggested by the decreased cell division seen with an inhibitor of cyclooxygenase, flurbiprofen. A biphasic effect on the proliferation of HTC cells was observed with increasing concentrations of prostaglandin F2 alpha. These studies were extended to tumor-bearing rats where inhibitory effects on the early stages of tumor growth were seen with flurbiprofen. Bleeding times were decreased in tumor-bearing rats but were restored to control values by treatment with flurbiprofen and an inhibitor of thromboxane synthetase, OKY 046. These drugs and a thromboxane/endoperoxide receptor antagonist, SQ 29, 548, were not observed to have statistically significant effects on isotope-labeled water distribution but they had substantial effects on the maintenance of body weight by tumor-bearing rats. The data suggested that the cachexia of tumor-bearing animals may be mediated at least in part by the action of eicosanoids.


Cerebrospinal fluid contacting nucleus and its 5-HT: A new insight into the regulation mechanism of general intravenous anesthesia.
General anesthesia is one of the most common clinical anesthesia methods. Many studies have suggested that 5-HT plays an important role in the mechanism of general anesthesia, but its basic principle is still unclear. The cerebrospinal fluid (CSF)-contacting nucleus, which we identified 30 years ago, contains a large number of 5-HT neurons. In the brain, many of the nuclei involved in regulating the effects of general anesthesia send projections to the CSF-contacting nucleus. Does the CSF-contacting nucleus and its 5-HT neurons participate in regulating the effect of general anesthesia? This is a new and interesting scientific question. To answer this question, rats underwent general anesthesia by intravenous injection of propofol. During the maintenance of and recovery from general anesthesia, the protein expression of c-Fos in the CSF-contacting nucleus was significantly increased. "Knockout" of this nucleus significantly increased the of number of low-frequency δ waves, which are indicative of deep anesthesia, during general anesthesia maintenance; however, the number of high-frequency β waves, which indicate consciousness, was significantly decreased. During recovery from general anesthesia, the recovery of the righting reflex (RORR) time of rats with CSF-contacting nucleus ablation was significantly prolonged; activation of 5-HT neurons in the CSF-contacting nucleus promoted recovery from general anesthesia, while inhibition of 5-HT neurons in the CSF-contacting nucleus delayed recovery from general anesthesia. The above results suggest that the CSF-contacting nucleus and its 5-HT neurons play a key role in regulating the effect of intravenous anesthesia, especially during recovery from general anesthesia.


Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways.
The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.


[The use of oxymetazoline in nasal endoscopic sinus surgery].
To assess the value of oxymetazoline used in nasal endoscopic sinus surgery (ESS). The effect of oxymetazoline on 68 patients pulse, cilium mottom and rebound phenomenon during ESS were observed. Pulse and cilium motion are no significant difference after using oxymetazoline. Oxymetazoline reduces about 59% nasal mucosal blood flow and acts over 6 hours. Oxymetazoline used as nasal decongestant and anesthesia assistant is safe and effect in ESS as routine.


Ablation of ventricular arrhythmia originating from the aortic sinus of Valsalva in an adolescent with anomalous origin of the right coronary artery.
A 16-year-old patient underwent successful ablation of ventricular arrhythmia originating from the aortic sinus of Valsalva following surgical unroofing of an anomalous right coronary artery. This case illustrates the complexity of decision making in the management of patients with anomalous coronary arteries and the importance of keeping an open mind when determining ventricular arrhythmia aetiology and origin.


Site-directed mutagenesis of tyrosine 118 within the central constriction site of the LamB (Maltoporin) channel of Escherichia coli. I. Effect on ion transport.
The three-dimensional structure of the malto-oligosaccharide-specific LamB-channel of Escherichia coli (also called maltoporin) is known from x-ray crystallography. The central constriction of the channel formed by the external loop 3 is controlled by a tyrosine residue (Y118). Y118 was replaced by site-directed mutagenesis by ten other amino acids (alanine, isoleucine, asparagine, serine, cysteine, aspartic acid, arginine, histidine, phenylalanine, and tryptophane) including neutral ones, negatively and positively charged amino acids to study the effect of their size, hydrophobicity, and charge on ion transport through LamB. The mutant proteins were purified to homogeneity. They were reconstituted into lipid bilayer membranes and single-channel conductance and ion selectivity were measured to get insight into the mechanism of ion transport through LamB. The mutation of Y118 to any other nonaromatic amino acid led to a substantial increase of the single-channel conductance by more than a factor of six at maximum. The highest effect was observed for Y118D. Additionally, a nonlinear relationship between the salt concentration in the aqueous phase and the channel conductance was observed for this mutant, indicating strong discrete charge effects on ion conductance. For all other mutants, with the exception of Y118R, linear relationships were found between single-channel conductance and bulk aqueous concentration. The individual hydrophobicity indices of the amino acids introduced inside the central constriction of the LamB channel had a somewhat smaller effect on the single-channel conductance as compared with the effect of their size and charge.


[Fluorouracil implants for colorectal cancer: a systematic review and meta-analysis].
To evaluate the benefit and safety of fluorouracil implants on colorectal cancer. Based on the methods of Cochrane systematic reviews, databases including CBM(1982 to March 2011), CNKI(1911 to March 2011), EMBASE(1966 to March 2011), and Medline(1950 to March 2011) were searched to identify randomized controlled trials assessing the benefit of fluorouracil implants on colorectal cancer. The quality of the included studies was assessed using the Cochrane's tool for assessing bias. RevMan5.0 was used for meta-analysis. Sixteen studies were included(n=1223). The quality of included studies was moderate. Fluorouracil implants could reduce the 2-year mortality(RR=0.33. 95% CI:0.18-0.59), 2-year metastasis rate(RR=0.35, 95% CI: 0.19-0.66), and 2-year recurrence rate(RR=0.48, 95% CI:0.36-0.65). There were no significant differences in complications and adverse effects between fluorouracil implants and the control group. Current evidence demonstrates that fluorouracil implants may modestly improve the outcome of colorectal cancer patients without increasing its adverse events. However, the results should be interpreted with caution due to the risk of bias of included studies.


Elevated static compliance of the total respiratory system: early predictor of weaning unsuccess in severed COPD patients mechanically ventilated.
To assess in a group of COPD patients mechanically ventilated for an episode of acute respiratory failure the respiratory mechanics with a simple and non invasive method at the bedside in order to evaluate if these parameters may be predictive of weaning failure or success. A prospective study. Intensive care and intermediate intensive care units. 23 COPD patients ventilated for acute respiratory failure and studied within 24 hours from intubation. Using end-expiratory and end-inspiratory airway occlusion technique, we measured PEEPi, static compliance of the respiratory system (Crs, st) maximum respiratory resistance (Rrsmax) and minimum respiratory resistance (Rrsmin). The weaned group (A) and the not weaned group (B) were not different regarding to static PEEPi (group A 8.5 +/- 4.0 vs group B 8.9 +/- 2.6 cmH2O), TO Rrsmax (22.4 +/- 5.3 versus 22.2 +/- 9.0 cmH2O/1/s) and to Rrsmin (17.6 +/- 5.5 versus 17.9 +/- 8.0 cmH2O/1/s), while a significant difference (p < 0.001) has been found in Cst, rs (62.7 +/- 17.% versus 111.6 +/- 18.0 ml/cm H2O). The threshold value of 88.5 ml/cmH2O was identified by discriminant analysis and provided the best separation between the two groups, with a sensitivity of 0.85 and a specificity of 0.87. Cst, rs measured non invasively in the first 24 h from intubation, provided a good separation between the patients who were successfully weaned and those who failed.


[Construction of eukaryotic expression vector expressing hepatitis C virus NS5B and EGFP fusion protein and establishment of stable transfected HepG2 cell line].
To construct a eukaryotic expression vector for expressing hepatitis C virus (HCV) recombinant NS5B-EGFP fusion protein and obtain a stable transfected HepG2 cell line. The coding region of NS5B gene of HCV was amplified by PCR and was digested by Xho I/Kpn I. This fragment was inserted into pEGFPN3 with T4 ligase and transformed E. coli TG1. The positive recombinant plasmid was selected, then the recombinant plasmid was transfected into HepG2 cell by Lipofectin AMINE 2000. Cells containing stable transformants were selected by the ability of resistance to G418 and isolated with a limited dilution. The stable transfected cell line expressing high level NS5B-EGFP fusion protein was obtained. The eukaryotic expression vector named pEGFPN3-ns5b was successfully constructed and the stable transfected HepG2 cell line expressing NS5B-EGFP fusion protein was obtained. The stable transfected HepG2 cell line could express NS5B-EGFP fusion protein, could be used for anti-HCV infection with ns5b gene as the target.


Correction to 'Self-induced class stratification in competitive societies of agents: Nash stability in the presence of envy'.
[This corrects the article DOI: 10.1098/rsos.200411.].


Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.
Recent studies have identified a subset of memory T cells with stem cell-like properties (T(SCM)) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection. The increased rates of CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis of SIV infection in RM.


Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration.
This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. ACh (0.03-3 microM) induced a hyperpolarization through activations of both apamin- and charybdotoxin-sensitive Ca2+-activated K+ channels (K(Ca)) in rabbit AVECs. The intermediate-conductance K(Ca) channel (IK(Ca)) activator 1-ethyl-2-benzimidazolinone (1-EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 microM). The ACh-induced hyperpolarization was significantly weaker, although the ACh-induced [Ca2+]i increase was unchanged, in NTG-treated rabbits (versus NTG-untreated control rabbits). The hyperpolarization induced by 1-EBIO was also weaker in NTG-treated rabbits. The reduced ACh-induced hyperpolarization seen in NTG-treated rabbits was not modified by in vitro application of the superoxide scavengers Mn-TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG-treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.


Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood.
For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics. The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4). Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.


Photodegradation of nalidixic acid assisted by TiO(2) nanorods/Ag nanoparticles based catalyst.
Two different nanosized TiO2-based catalysts supported onto glass with tailored photocatalytic properties upon irradiation by UV light were successfully employed for the degradation of nalidixid acid, a widely diffused antibacterial agent of environmental relevance known to be non-biodegradable. Anatase rod-like TiO2 nanocrystals (TiO2NRs) and a semiconductor oxide-noble metal nanocomposite TiO2 NRs/Ag nanoparticles (NPs), synthesized by colloidal chemistry routes, were cast onto glass slide and employed as photocatalysts. A commercially available catalyst (TiO2 P25), also immobilized onto a glass slide, was used as a reference material. It was found that both TiO2 NRs/Ag NPs composite and TiO2 NRs demonstrated a photocatalytic efficiency significantly higher than the reference TiO2 P25. Specifically, TiO2 NRs/Ag NPs showed a photoactivity in nalidixic acid degradation 14 times higher than TiO2 P25 and 4 times higher than bare TiO2 NRs in the first 60min of reaction. Several by-products were identified by HPLC-MS along the nalidixic acid degradation, thus getting useful insight on the degradation pathway. All the identified by-products resulted completely removed after 6h of reaction.


Virtual Reality Simulator Use Stimulates Medical Students' Interest in Orthopaedic Surgery.
To investigate whether the use of a VR arthroscopic simulator can influence medical students' attitudes toward a career in orthopaedic surgery. Twenty-five medical students completed seven unsupervised sessions on a VR hip-arthroscopic simulator. All participants completed a pre-simulator and post-simulator pseudo-anonymized questionnaire consisting of 10 questions: six 10-point Likert scale questions addressing their interest in orthopaedics, surgery, and arthroscopy; and four 5-point Likert scale questions addressing their attitudes toward simulation. Prepaired and postpaired datasets were analyzed using Wilcoxon signed rank test. Interest in both orthopaedics and surgery was found to increase after simulator use (orthopaedics: 5.3 ± .3 to 8.4 ± .2, P = .0001; surgery: 5.8 ± .3 to 9.0 ± .2; P = .0001). It was also found that simulator use increased participants' interest in arthroscopy (5.4 ± .3 to 8.0 ± .3; P = .0001) and hip-arthroscopy (5.0 ± .3 to 7.6 ± .3; P = .0001). Participants reported they were more likely to attend endoscopic and arthroscopic surgical lists after simulator use (endoscopic: 6.9 ± .3 to 8.4 ± .2; P = .0003; arthroscopic: 5.9 ± .3 to 8.4 ± .2; P = .0001). After using the simulator, participants felt more strongly that VR simulation is a valuable training modality (P = .0025), that simulation should be a mandatory part of orthopaedics and surgical training (P = .0001 and P = .0001), and that access to VR simulators improves the quality of surgical training (P = .0024). These results demonstrate that exposure to VR arthroscopic simulation increased medical students' interest in orthopaedics, surgery, and arthroscopy, without the need for direct supervision. Following VR simulator use, students reported they were more likely to engage with training opportunities, including arthroscopic and endoscopic surgery. Understanding factors that stimulate interest in orthopaedic surgery may help programs attract the broadest pool of potential trainees.


Ru-Pt core-shell nanoparticles for preferential oxidation of carbon monoxide in hydrogen.
Most of the world's hydrogen supply is currently obtained by reforming hydrocarbons. 'Reformate' hydrogen contains significant quantities of CO that poison current hydrogen fuel-cell devices. Catalysts are needed to remove CO from hydrogen through selective oxidation. Here, we report first-principles-guided synthesis of a nanoparticle catalyst comprising a Ru core covered with an approximately 1-2-monolayer-thick shell of Pt atoms. The distinct catalytic properties of these well-characterized core-shell nanoparticles were demonstrated for preferential CO oxidation in hydrogen feeds and subsequent hydrogen light-off. For H2 streams containing 1,000 p.p.m. CO, H2 light-off is complete by 30 (composite function)C, which is significantly better than for traditional PtRu nano-alloys (85 (composite function)C), monometallic mixtures of nanoparticles (93 (composite function)C) and pure Pt particles (170 ( composite function)C). Density functional theory studies suggest that the enhanced catalytic activity for the core-shell nanoparticle originates from a combination of an increased availability of CO-free Pt surface sites on the Ru@Pt nanoparticles and a hydrogen-mediated low-temperature CO oxidation process that is clearly distinct from the traditional bifunctional CO oxidation mechanism.


Coronary artery stenosis controlled by distal perfusion pressure: description of the servo-system and time-dependent changes in regional myocardial blood flow.
An animal model for the induction of coronary artery stenosis is described. In this model the degree of stenosis, as induced with commercially available hydraulic occluders, can be easily controlled by keeping constant the mean perfusion pressure (pcor) distal to the site of stenosis. This pcor is the input signal for a servo-system feeding a motor-pump, which determines the degree of inflation of the cuff around the left anterior interventricular coronary artery (LAICA). In each experiment pcor did not vary more than 2 mm Hg from the preset value of about 25 mm Hg. In 60 anesthetized open-chest dogs the time course of standard hemodynamic variables and regional myocardial blood flow in the center of the underperfused area, using the radioactive microsphere technique, were determined. Within 1 min after induction of stenosis heart rate and end-diastolic left ventricular pressure (plved) increased (by 20 and 60%, respectively) and mean aortic pressure and dplv/dtmax decreased (by 10 and 25%, respectively). After the initial decrease median myocardial blood flow further decreased between 1 and 5 min of stenosis from 0.63 to 0.32 ml.min-1.g-1 in the outer layers (P less than 0.05) and from 0.26 to 0.15 ml.min-1.g-1 in the inner layers (P less than 0.05), despite constant hemodynamic conditions and pcor. Between 5 and 120 min of stenosis these values remained unchanged in the outer layers, but decreased further in the inner layers to 0.08 ml.min-1.g-1 (P less than 0.05). The accurate control of pcor, the reproducibility of the levels of residual blood flow and the ease of handling the stenosis system indicate that coronary artery stenosis controlled by perfusion pressure distal to the stenosis is a useful animal model to study events during regional myocardial ischemia. With the use of this model of low flow ischemia a biphasic increase of myocardial vascular resistance was observed, which is initiated during the first minutes of coronary artery stenosis.


Methods employed for chest radiograph interpretation education for radiographers: A systematic review of the literature.
This systematic review aimed to determine the strength of evidence available in the literature on the effect of training to develop the skills required by radiographers to interpret plain radiography chest images. Thirteen articles feature within the review. Sample size varied from one reporting radiographer to 148 radiography students/experienced radiographers. The quality of the articles achieved a mean score of 7.5/10, indicating the evidence is strong and the quality of studies in this field is high. Investigative approaches included audit of participants' performance in clinical practice post formal training, evaluation of informal training and the impact of short feedback sessions on performance. All studies demonstrated positive attributions on user performance. Using a combination of training techniques can help maximise learning and accommodate those with different preferred learning types.


Transmembrane topology and sites of N-glycosylation of inositol 1,4,5-trisphosphate receptor.
To define the transmembrane topology of the inositol 1,4,5-trisphosphate receptor (InsP3R), we determined the subcellular location of the hydrophilic segment (residues 2463-2529 of mouse type 1 InsP3R) believed to be located at the luminal side of the endoplasmic reticulum (ER) in the six-transmembrane model but at the cytoplasmic side in the eight-transmembrane model. This hydrophilic segment includes two consensus sites for N-glycosylation (Asn-2475 and Asn-2503). We prepared an anti-peptide antibody against residues 2504-2523. Electron microscope immunocytochemical studies of mouse cerebellar Purkinje cells showed that binding of this antibody frequently occurs in the intracisternal space of the ER. We constructed three mutant receptors by site-directed mutagenesis of Asn to Gln (N2475Q, N2503Q, and N2475Q/N2503Q). By concanavalin A column chromatography of these receptors, we found that both Asn-2475 and Asn-2503 are glycosylated. These results indicate that residues 2504-2523, Asn-2475, and Asn-2503 are exposed to the ER lumen. We therefore propose that InsP3R has six membrane-spanning segments. Based on the transmembrane topology and subunit organization, we suggest that InsP3R is a member of the superfamily that includes the voltage- and second messenger-gated ion channels on the plasma membrane.


A specific antiserum recognizes clonidine-displacing substance: implications for the structure of the brain's own clonidine.
A polyclonal antiserum was raised in rabbit against the clonidine analog p-aminoclonidine (PAC) coupled to hemocyanin. The antiserum (anti-PAC3) exhibited high affinity for unconjugated [3H]PAC (Kd 0.32 +/- 0.07 nM) in a rapid-filtration radioimmunoassay. Competition experiments showed that PAC, clonidine, and naphazoline cross-reacted with the anti-PAC3 antiserum, whereas a number of other structurally related compounds did not. An endogenous clonidine-displacing substance (CDS) partially purified from bovine brain also inhibited specific [3H]PAC binding to anti-PAC3 in a dose-dependent manner. Thus, (a) anti-PAC3 antiserum is specific for clonidine and closely related compounds, and (b) CDS may structurally resemble clonidine since it is recognized by this highly specific antiserum.


Hippocampal-DMN disconnectivity in MS is related to WM lesions and depression.
The hippocampus is part of the default-mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting-state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery-Asberg Depression Rating Scale. Seed-voxel hippocampal RS FC was assessed. SPM8 was used for between-group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical-subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability.


Is it time for global adoption of endoscopic retrograde appendicitis therapy of acute appendicitis?
Acute appendicitis is a common abdominal surgical emergency worldwide. Abraham Groves performed the first documented open appendectomy in 1883. Although appendectomy is still the most effective treatment in cases of acute appendicitis, it causes a range of complications and carries the risk of negative appendectomy. In the awake of covid-19, the latest guidelines recommend antibiotic therapy as an acceptable first line treatment for acute appendicitis. However, patients treated with antibiotics have a recurrence risk of up to 30% at 1 year. Endoscopic retrograde appendicitis therapy (ERAT) has emerged as promising non-invasive treatment modality for acute uncomplicated appendicitis (AUA) which involves cannulation, appedicography, appendiceal stone extraction, appendiceal lumen irrigation, and stent insertion. ERAT aims to relieve the cause of appendicitis (e.g., obstruction or stenosis of the appendiceal lumen) and thus effectively prevent the recurrence of appendicitis. In addition, it can make a definitive diagnosis of acute appendicitis during endoscopic retrograde appendicography. Studies have shown that 93.8 to 95% of AUA patients did not have a recurrence following ERAT. In this study, we aim to summarize the current body of evidence on ERAT to situate it alongside currently established therapies for acute appendicitis, in particular, AUA.


Anticoagulants and Statins As Pharmacological Agents in Free Flap Surgery: Current Rationale.
Microvascular free flaps are key components of reconstructive surgery, but despite their common use and usual reliability, flap failures still occur. Many pharmacological agents have been utilized to minimize risk of flap failure caused by thrombosis. However, the challenge of most antithrombotic therapy lies in providing patients with optimal antithrombotic prophylaxis without adverse bleeding effects. There is a limited but growing body of evidence suggesting that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival. By inhibiting mevalonic acid, the downstream effects of statins include reduction of inflammation, reduced thrombogenicity, and improved vasodilation. This review provides a summary of the pathophysiology of thrombus formation and the current evidence of anticoagulation practices with aspirin, heparin, and dextran. In addition, the potential benefits of statins in the perioperative management of free flaps are highlighted.


Dimers of the N-terminal domain of phytochrome B are functional in the nucleus.
A plant modulates its developmental processes in response to light by several informational photoreceptors such as phytochrome. Phytochrome is a dimeric chromoprotein which regulates various aspects of plant development from seed germination to flowering. Upon absorption of red light, phytochrome translocates from the cytoplasm to the nucleus, and regulates gene expression through interaction with transcription factors such as PIF3 (refs 5-7). The phytochrome polypeptide has two domains: the amino-terminal photosensory domain with a chromophore and the carboxy-terminal domain which contains signalling motifs such as a kinase domain. The latter is widely believed to transduce the signal to downstream components. Here we show that the C-terminal domain of Arabidopsis phytochrome B (phyB), which is known as the most important member of the phytochrome family, is not directly involved in signal transduction. The N-terminal domain isolated from phyB, when dimerized and localized in the nucleus, triggered full phyB responses with much higher photosensitivity than the full-length phyB. These findings indicate that the C-terminal domain attenuates the activity of phyB rather than positively transducing the signal.


Evaluation of the impact of carotid artery bifurcation angle on hemodynamics by use of computational fluid dynamics: a simulation and volunteer study.
In this study, we evaluated the hemodynamics of carotid artery bifurcation with various geometries using simulated and volunteer models based on magnetic resonance imaging (MRI). Computational fluid dynamics (CFD) was analyzed by use of OpenFOAM. The velocity distribution, streamline, and wall shear stress (WSS) were evaluated in a simulated model with known bifurcation angles (30°, 40°, 50°, 60°, derived from patients' data) and in three-dimensional (3D) healthy volunteer models. Separated flow was observed at the outer side of the bifurcation, and large bifurcation models represented upstream transfer of the point. Local WSS values at the outer bifurcation [both simulated (<30 Pa) and volunteer (<50 Pa) models] were lower than those in the inner region (>100 Pa). The bifurcation angle had a significant negative correlation with the WSS value (p<0.05). The results of this study show that the carotid artery bifurcation angle is related to the WSS value. This suggests that hemodynamic stress can be estimated based on the carotid artery geometry. The construction of a clinical database for estimation of developing atherosclerosis is warranted.


Cortisol enhancement of PTH-stimulated cyclic AMP accumulation in cultured fetal rat long bone rudiments.
Cortisol in concentrations from 10 nM to 10 microM produced a dose-related inhibition of basal and PTH1-stimulated 45Ca and [3H]-hydroxyproline release from cultured fetal rat forelimb rudiments. PTH-stimulated cyclic AMP generation however was not diminished by cortisol; in contrast, at a concentration of 1 microM cortisol produced a 57% increase in PTH-stimulated bone cyclic AMP content. The stimulatory effect of cortisol on cyclic AMP content appeared to be the result of reduced phosphodiesterase activity, since this effect was not seen in the presence of 10 mM theophylline. It is concluded that cortisol inhibition of PTH-induced resorption in long bones is not accompanied by reduced cyclic AMP generation.


[Clinical assessment of oral health between physician and dentist--a pilot study on inter-examiner reliability].
Very little is known about the ability of physicians to assess oral health of geriatric patients. The aim of this pilot study was to assess the in ter-examiner reliability in assessment of oral health for a dentist and a physician, and to evaluate the influence of training in dental findings for the physician on inter- examiner reliability. Inter-examiner reliability between a physician and a dentist was tested in a primary geriatric hospital with 126 participants 60 years old or more (mean 77 years; 32% men) using the Revised Oral Assessment Guide (ROAG) and additional items relating to caries and dentures (14 items). Calculated were kappa-coefficients, and percentage agreement between the examiners before (n = 50) and after (n = 51) training for the physician in dentistry (n = 25 for the common training session). Before the training both kappa-values and percentage agreement were not acceptable in the different categories. After the training, with the exception of the categories swallow and tongue, the reliability of all items was moderate or good. The number of occasions on which the physician underestimated the clinical finding compared to the dentist - indicating a clinical finding was overlooked - decreased for every item; for retention of denture and decayed teeth this decrease was significant. Screening for oral health performed by a physician was insufficient regarding the different clinical aspects. Training in the use of an oral health assessment tool improved the reliability of the screening. Because of the low number of examiners the results should be interpreted as a pilot investigation on this new topic.


[The diagnostic value of computed tomography during lymphangiography on the postoperative chylothorax in lung cancer].
A successfully operated case of postoperative chylothorax in a lung cancer was reported, under the diagnosis of computed tomography during lymphangiography demonstrating the disruption of the thoracic duct. The computed tomography during lymphangiography is considered to be very useful for deciding the surgical indication of postoperative chylothorax and prompt surgical treatment is recommended when the main truncus of the thoracic duct is lacerated.


Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy.
The lack of easily measurable biomarkers remains a challenge in executing clinical trials for diabetic neuropathy (DN). Plasma Neurofilament light chain (NFL) concentration is a promising biomarker in immune-mediated neuropathies. Longitudinal studies evaluating NFL in DN have not been performed. A nested case-control study was performed on participants with youth-onset type 2 diabetes enrolled in the prospective Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Plasma NFL concentrations were measured at 4-year intervals from 2008 to 2020 in 50 participants who developed DN and 50 participants with type 2 diabetes who did not develop DN. NFL concentrations were similar in the DN and no DN groups at the first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all p < .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p = .045). A doubling of the NFL value at Assessment 2 in those without DN increased the odds of ultimate DN outcome by an estimated ratio of 2.86 (95% CI: [1.30, 6.33], p = .0046). At the final study visit, positive Spearman correlations (controlled for age, sex, diabetes duration, and BMI) were observed between NFL and HbA1c (0.48, p < .0001), total cholesterol (0.25, p = .018), and low-density lipoprotein (LDL (0.30, p = .0037)). Negative correlations were observed with measures of heart rate variability (-0.42 to -0.46, p = <.0001). The findings that NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest that NFL could be a valuable biomarker for DN.


The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.
This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.


Pelvic inflammatory disease and its sequelae in adolescents.
Pelvic Inflammatory Disease (PID) is the most common serious complication of sexually transmitted diseases (STDs). Each year over one million women in the United States experience an episode of PID, with approximately 16-20% of cases occurring in teenagers. Acute PID increases a woman's risk for recurrent PID, chronic pelvic pain, infertility, and ectopic pregnancy. Recent reports indicating that PID rates are rising and are highest among adolescent females aged 15-19 underscore the need to remain current on the clinical as well as the epidemiologic aspects of PID. We present such an update in this article. Trends in incidence and key risk factors are discussed; besides adolescence itself and STD, other important categories of risk factors include sexual activity, contraceptive method, and previous episode(s) of PID. The polymicrobial nature of PID is discussed along with an analysis of the role of specific organisms, such as Chlamydia trachomatis, Neisseria gonorrhoeae, anaerobic and aerobic bacteria, and mycoplasmas in PID. Early diagnosis and the institution of appropriate treatment regimens are essential to the prevention of PID's devastating sequelae. Clinicians must maintain a high index of suspicion for the wide range of clinical presentations associated with PID and be prepared to provide effective management, including proper evaluation and prompt treatment of sexual partners.