Polymorphism in jasmonate signaling partially accounts for the variety of volatiles produced by Nicotiana attenuata plants in a native population.
Herbivore- and jasmonate-induced volatile organic compounds (VOCs), which mediate indirect defense, must provide reliable information for predators that frequently learn to associate their release with feeding herbivores. Yet little is known about variation of these cues within populations of native plants, on a scale encountered by predators. We examined variation in herbivore-elicited VOC emissions and patterns of herbivore-induced jasmonate signaling from accessions of Nicotiana attenuata co-occurring in a native population. VOC emissions elicited by herbivore oral secretions (OS) and by methyl jasmonate (MJ) were characterized using gas chromatography-mass spectrometry (GC-MS), high-resolution two-dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-ToF-MS) and micro-hydrolysis and micro-hydrogenation reactions. Accessions varied in emissions of abundant (trans-alpha-bergamotene, alpha-duprezianene, trans-beta-ocimene, and cis-3-hexenol) and total detectable VOCs, as well as the accumulation of jasmonates, the jasmonate antagonist salicylic acid (SA), abscisic acid (ABA) and jasmonate signaling-related transcripts after OS elicitation. Yet MJ treatment exacerbated differences in VOC emission, suggesting that much variation in VOC emission is caused by processes downstream of jasmonate signaling. Co-occurring N. attenuata plants emit different VOCs following simulated herbivore elicitation as a result in part of differences in jasmonate production and responsiveness, which could reduce the effectiveness of induced indirect defense.


Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development.
Temporal lobe epilepsy often manifests months or even years after an initial epileptogenic insult (e.g., stroke, trauma, status epilepticus) and, therefore, may be preventable. However, no such preventive treatment is currently available. Aim of this study was to test an antioxidant agent, 7,8-dihydroxyflavone (7,8-DHF), that is well tolerated and effective in preclinical models of many neurological disorders, as an anti-epileptogenic drug. However, 7,8-DHF also acts as a TrkB receptor agonist and, based on the literature, this effect may imply an anti- or a pro-epileptogenic effect. We found that low- (5 mg/kg), but not high-dose 7,8-DHF (10 mg/kg) can exert strong anti-epileptogenic effects in the lithium-pilocarpine model (i.e., highly significant reduction in the frequency of spontaneous seizures and in the time to first seizure after status epilepticus). The mechanism of these different dose-related effects remains to be elucidated. Nonetheless, considering its excellent safety profile and antioxidant properties, as well as its putative effects on TrkB receptors, 7,8-DHF represents an interesting template for the development of effective and well-tolerated anti-epileptogenic drugs.


Overview of systematic reviews on strategies to improve treatment initiation, adherence to antiretroviral therapy and retention in care for people living with HIV: part 1.
We sought to map the evidence and identify interventions that increase initiation of antiretroviral therapy, adherence to antiretroviral therapy and retention in care for people living with HIV at high risk for poor engagement in care. We conducted an overview of systematic reviews and sought for evidence on vulnerable populations (men who have sex with men (MSM), African, Caribbean and Black (ACB) people, sex workers (SWs), people who inject drugs (PWID) and indigenous people). We searched PubMed, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science and the Cochrane Library in November 2018. We screened, extracted data and assessed methodological quality in duplicate and present a narrative synthesis. We identified 2420 records of which only 98 systematic reviews were eligible. Overall, 65/98 (66.3%) were at low risk of bias. Systematic reviews focused on ACB (66/98; 67.3%), MSM (32/98; 32.7%), PWID (6/98; 6.1%), SWs and prisoners (both 4/98; 4.1%). Interventions were: mixed (37/98; 37.8%), digital (22/98; 22.4%), behavioural or educational (9/98; 9.2%), peer or community based (8/98; 8.2%), health system (7/98; 7.1%), medication modification (6/98; 6.1%), economic (4/98; 4.1%), pharmacy based (3/98; 3.1%) or task-shifting (2/98; 2.0%). Most of the reviews concluded that the interventions effective (69/98; 70.4%), 17.3% (17/98) were neutral or were indeterminate 12.2% (12/98). Knowledge gaps were the types of participants included in primary studies (vulnerable populations not included), poor research quality of primary studies and poorly tailored interventions (not designed for vulnerable populations). Digital, mixed and peer/community-based interventions were reported to be effective across the continuum of care. Interventions along the care cascade are mostly focused on adherence and do not sufficiently address all vulnerable populations.


Development of a new platform for neglected tropical disease surveillance.
An expanded global focus on the control and elimination of neglected tropical diseases (NTDs) has called attention to the need to develop and validate surveillance strategies that are cost effective and can be integrated across diseases. Here, we describe a multiplex tool for the sensitive detection of antibody responses to NTDs as well as vaccine preventable diseases, malaria, and waterborne and zoonotic infections. The assay platform is robust, can be performed with either serum or dried blood spots and can be adapted to local epidemiological conditions and public health priorities. Multiplex assays open the door to conducting routine serosurveillance for NTDs through demographic health surveillance or malaria indicator surveys.


Ethanol production by thermophilic bacteria: metabolic control of end product formation in Thermoanaerobium brockii.
Specific changes in the chemical and microbial composition of Thermoanaerobium brockii fermentations were compared and related to alterations of process rates, end product yields, and growth parameters. Fermentation of starch as compared with glucose was associated with significant decreases in growth rate and intracellular fructose-1,6-bisphosphate concentration and with a dramatic increase in the ethanol/lactate product ratio. Glucose or pyruvate fermentation in the presence of acetone was correlated with increased substrate consumption, growth (both rate and yield), acetate yield, and quantitative reduction of acetone to isopropanol in lieu of normal reduced fermentation products (i.e., H2, ethanol, lactate). Acetone altered pyruvate phosphoroclastic activity of cell extracts in that H2, lactate, and ethanol levels decreased, whereas the acetate concentration increased. Glucose fermentation in the presence of exogenous hydrogen was associated with inhibition of endogenous H2 production and either increased ethanol/acetate product ratios and decreased growth at less than 0.5 atm (51 kPa) of H2 or total growth inhibition at 1.0 atm (102 kPA). The effects of exogenous hydrogen on glucose fermentation were totally reversed by the addition of acetone. Glucose fermentation in coculture with Methanobacterium thermoautotrophicum correlated with increased growth (both rate and yield), acetate yield, and the formation of methane in lieu of monoculture reduced products. In coculture, but not monoculture, T. brockii grew on ethanol as the energy source, and acetate and methane were the end products as a direct consequence of hydrogen consumption by the methanogen.


Concentrations of glycosylated prolactin in the pituitary gland and plasma of lean and obese barrows.
We measured glycosylated PRL (G-PRL) in the pituitary gland and plasma of lean and obese barrows (castrated male pigs) by immunoblotting. We found that G-PRL constituted 40% or more of total monomeric PRL in the pituitary gland of these animals. Furthermore, pituitary G-PRL concentrations in obese barrows averaged 58% higher than in those of lean controls. The non-glycosylated PRL concentrations were also higher in the pituitaries of obese barrows in comparison to lean controls, but the magnitude of the difference was smaller (42%). Plasma concentrations of the two forms, or total immunoreactive PRL measurable by radioimmunoassay, did not differ significantly between the two groups. The pituitary data suggest that the state of PRL secretion is altered in obese barrows, and that the alteration is more pronounced for G-PRL than for the non-glycosylated counterpart.


Factors influencing R wave amplitude in patients with ischaemic heart disease.
R wave amplitude changes during exercise have been ascribed to alteration in left ventricular volume and their measurement advocated for the improved diagnosis of coronary disease. The reproducibility of exercise QRS changes and their relation to ST segment depression, respiratory pattern, and left ventricular volume during ischaemia were studied in 10 patients with angina and coronary disease. QRS amplitude was measured in a 16 lead precordial map during three identical exercise tests in each patient and left ventricular volume assessed continuously using gated blood pool imaging with a single scintillation probe during manoeuvres to provoke ischaemia. During exercise, QRS amplitude increased or remained unchanged in four patients and fell in six patients in a consistent manner for each patient. R wave amplitude was not affected by changes in respiratory pattern. R wave amplitude did not alter in 33 of 39 episodes of left ventricular volume increase (mean 32%) or decrease (mean 36%) in end-diastolic counts. These findings suggest that precordial R wave changes during ischaemia are not determined primarily by alteration in left ventricular volume or the respiratory pattern. Though reproducible in each patient and following a definite relation to ST segment depression, the variable directional response during exercise suggest that R wave amplitude changes have little diagnostic value.


CD4+ and CD8+ T-cell skewness in classic Kaposi sarcoma.
It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providing some further insights into the complex role of the immune system in CKS pathogenesis, we performed an extensive analysis of the TCR BV repertoire in both CD4(+) and CD8(+) T cells in 30 human herpesvirus 8-positive Sardinian patients with CKS and an equal number of age-matched healthy controls. We used a panel of monoclonal antibodies covering approximately 70% of human BV subfamilies and third complementarity determining region (CDR3) spectratyping. Patients with CKS showed an increased frequency of BV expansions in both CD4(+) and CD8(+) lymphocytes, with no prevalent clones. On spectratyping analysis, most of the 720 BV CDR3 profiles obtained from both CD4(+) and CD8(+) T cells in patients with CKS were skewed. In particular, the surprising increase of BV skewing observed in CD4(+) lymphocytes mimics the pattern of progressive TCR BV narrowing described in responses to persistent viral antigen stimulations. Our findings support the hypothesis that CKS evolution is associated with inadequate activation rather than impairment of the immune system.


The glucocorticoid receptor: cause of or cure for obesity?
Glucocorticoid hormones (GCs) are important regulators of lipid metabolism, promoting lipolysis with acute treatment but lipogenesis with chronic exposure. Conventional wisdom posits that these disparate outcomes are mediated by the classical glucocorticoid receptor GRα. There is insufficient knowledge of the GC receptors (GRα and GRβ) in metabolic conditions such as obesity and diabetes. We present acute models of GC exposure that induce lipolysis, such as exercise, as well as chronic-excess models that cause obesity and lipid accumulation in the liver, such as hepatic steatosis. Alternative mechanisms are then proposed for the lipogenic actions of GCs, including induction of GC resistance by the GRβ isoform, and promotion of lipogenesis by GC activation of the mineralocorticoid receptor (MR). Finally, the potential involvement of chaperone proteins in the regulation of adipogenesis is considered. This reevaluation may prove useful to future studies on the steroidal basis of adipogenesis and obesity.


Photochemical conversion of solar energy.
Energy is the most important issue of the 21st century. About 85% of our energy comes from fossil fuels, a finite resource unevenly distributed beneath the Earth's surface. Reserves of fossil fuels are progressively decreasing, and their continued use produces harmful effects such as pollution that threatens human health and greenhouse gases associated with global warming. Prompt global action to solve the energy crisis is therefore needed. To pursue such an action, we are urged to save energy and to use energy in more efficient ways, but we are also forced to find alternative energy sources, the most convenient of which is solar energy for several reasons. The sun continuously provides the Earth with a huge amount of energy, fairly distributed all over the world. Its enormous potential as a clean, abundant, and economical energy source, however, cannot be exploited unless it is converted into useful forms of energy. This Review starts with a brief description of the mechanism at the basis of the natural photosynthesis and, then, reports the results obtained so far in the field of photochemical conversion of solar energy. The "grand challenge" for chemists is to find a convenient means for artificial conversion of solar energy into fuels. If chemists succeed to create an artificial photosynthetic process, "... life and civilization will continue as long as the sun shines!", as the Italian scientist Giacomo Ciamician forecast almost one hundred years ago.


Memory formation in the absence of experience.
Memory is coded by patterns of neural activity in distinct circuits. Therefore, it should be possible to reverse engineer a memory by artificially creating these patterns of activity in the absence of a sensory experience. In olfactory conditioning, an odor conditioned stimulus (CS) is paired with an unconditioned stimulus (US; for example, a footshock), and the resulting CS-US association guides future behavior. Here we replaced the odor CS with optogenetic stimulation of a specific olfactory glomerulus and the US with optogenetic stimulation of distinct inputs into the ventral tegmental area that mediate either aversion or reward. In doing so, we created a fully artificial memory in mice. Similarly to a natural memory, this artificial memory depended on CS-US contingency during training, and the conditioned response was specific to the CS and reflected the US valence. Moreover, both real and implanted memories engaged overlapping brain circuits and depended on basolateral amygdala activity for expression.


Arrhythmogenic right ventricular cardiomyopathy: a focused update on diagnosis and risk stratification.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterised by fibrofatty replacement of predominantly the right ventricle and high risk of ventricular arrhythmias and sudden cardiac death (SCD). Early diagnosis and accurate risk assessment are challenging yet essential for SCD prevention. This manuscript summarises the current state of the art on ARVC diagnosis and risk stratification. Improving the 2010 diagnostic criteria is an ongoing discussion. Several studies suggest that early diagnosis may be facilitated by including deformation imaging ('strain') for objective assessment of wall motion abnormalities, which was shown to have high sensitivity for preclinical disease. Adding fibrofatty replacement detected by late gadolinium enhancement or T1 mapping in cardiac MRI as criterion for diagnosis is increasingly suggested but requires more supporting evidence from consecutive patient cohorts. In addition to the traditional right-dominant ARVC, standard criteria for arrhythmogenic cardiomyopathy (ACM) and arrhythmogenic left ventricular cardiomyopathy (ALVC) are on the horizon. After diagnosis confirmation, the primary management goal is SCD prevention, for which an implantable cardioverter-defibrillator is the only proven therapy. Prior studies determined that younger age, male sex, previous (non-) sustained ventricular tachycardia, syncope, extent of T-wave inversion, frequent premature ectopic beats and lower biventricular ejection fraction are risk factors for subsequent events. Previous implantable cardioverter-defibrillator indication guidelines were however limited to three expert-opinion flow charts stratifying patients in risk groups. Now, two multivariable risk prediction models (arvcrisk.com) combine the abovementioned risk factors to estimate individual risks. Of note, both the flow charts and prediction models require clinical validation studies to determine which should be recommended.


Distinct abnormalities in the innate immune system of children with Down syndrome.
To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS). Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41). Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01). Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.


[Effects of Apheresis Platelet Transfusion on PLT, MPV, PDW and PCT].
To investigate the changes of platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) before and after apheresis platelet transfusion, the correlation between the parameters and their clinical significance. A total of 38 patients who received apheresis platelet transfusion were selected, their results of blood routine test closest to the time point of apheresis platelet transfusion were consulted from hospital information system and the changes of PLT, PCT, MPV and PDW were compared before and after transfusion. The correlation between above parameters was analyzed. The correlation of body mass index (BMI) with the increased multiple and increased value after platelet infusion was also analyzed. Compared with pre-infusion, PLT and PCT significantly increased (both P <0.001) while MPV and PDW showed no significant difference after apheresis platelet transfusion (P >0.05). The difference of PLT and PCT before and after apheresis platelet transfusion had no correlation with PLT and PCT before transfusion (r =0.002, r =0.001), while the difference of MPV and PDW was negatively correlated with MPV and PDW before transfusion (r =-0.462, r =-0.610). The PLT growth rate was positively correlated with PCT growth rate before and after apheresis platelet transfusion (r =0.819). BMI was positively correlated with the increased multiple of PLT after infusion (r =0.721), but not with the increased value of PLT after infusion (r =0.374). Apheresis platelet transfusion can cause platelet parameters change and shows different characteristics. Characteristic changes of platelet parameters and their correlation can be used as reference indices to evaluate the efficacy of apheresis platelet transfusion.


MUC1-Mediated Metabolic Alterations Regulate Response to Radiotherapy in Pancreatic Cancer.
Purpose:MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models.Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations. We also investigated whether inhibition of glycolysis could revert MUC1-mediated metabolic alterations and radiation resistance by using in vitro and in vivo models.Results: MUC1 expression diminished radiation-induced cytotoxicity and DNA damage in pancreatic cancer cells by enhancing glycolysis, pentose phosphate pathway, and nucleotide biosynthesis. Such metabolic reprogramming resulted in high nucleotide pools and radiation resistance in in vitro models. Pretreatment with the glycolysis inhibitor 3-bromopyruvate abrogated MUC1-mediated radiation resistance both in vitro and in vivo, by reducing glucose flux into nucleotide biosynthetic pathways and enhancing DNA damage, which could again be reversed by pretreatment with nucleoside pools.Conclusions: MUC1-mediated nucleotide metabolism plays a key role in facilitating radiation resistance in pancreatic cancer and targeted effectively through glycolytic inhibition. Clin Cancer Res; 23(19); 5881-91. ©2017 AACR.


The role of 19-hydroxy-delta4-androstene-3,17-dione in the conversion of circulating delta4-androstene-3, 17-dione to estrone.
A mixture of 4-14C-delta4-androstene-3, 17-dione and 6,7-3 H-19-hydroxy-delta4-androstene-3, 17-dione was intravenously injected into three women, and the 3H/14C ratios in urinary 19-hydroxyandrostenedione and urinary estrogens were determined. The ratios of 3H/14C in the estrogens were similar to those of the dose, while the ratios in urinary 19-hydroxyandrostenedione were mcuh higher than those of the dose. The fractional conversions of androstenedione to estrone and of 19-hydroxyandrostenedione to estrone are therefore similar. However, little, if any, 19-hydroxyandrostenedione produced during aromatization enters the circulation and mixes with injected 19-hydroxyandrostenedione.


[Complications and morbidity and mortality rates in a postanesthetic intensive care unit].
To describe the complications leading to admission of obstetric patients to intensive care or intensive postanesthetic care units. To describe the morbidity and mortality rates in such patients. We carried out a descriptive study based on patient records of 23,246 births at the Hospital Materno Infantil belonging to the University Hospitals Virgen del Rocio in Sevilla, Spain, over a 3-year period (2001-2003). In the 23,246 births reviewed, 746 women (3%) required admission to the obstetric postoperative intensive care unit. The most common reasons were pre-eclampsia in 146 cases (19%), ectopic pregnancy in 97 cases (13%), and postpartum bleeding in 75 cases (10%). Among the 146 cases of preeclampsia treated in the unit, there were 8 cases of eclampsia and 7 of acute pulmonary edema. Two deaths (0.3%) occurred, due to eclampsia in 1 case and to pulmonary thromboembolism in the other. Obstetric patients are at risk of serious complications that require admission to intensive care or intensive postanesthetic care units, and we therefore emphasize the need to create such units at tertiary care hospitals.


A national survey of human Mycobacterium bovis infection in France. Network of Microbiology Laboratories in France.
To evaluate the role of Mycobacterium bovis in the epidemiology of human tuberculosis in France. A national survey in France in 1995 using a questionnaire mailed to all French microbiological laboratories performing mycobacteria cultures. M. bovis was isolated in 38 out of 7075 cases of bacteriologically confirmed tuberculosis (0.5%) notified to the National Reference Centre (CNR) in 1995, resulting in an incidence of 0.07 per 100,000 population. Incidence rates increased with age, and were the highest among patients of 75 years or more (range 0.02-0.33/100,000). Two cases of tuberculosis due to M. bovis were reported in foreign-born children who had come to France for treatment of their disease. No cases were reported among French-born children. The site of tuberculosis was pulmonary in 17 cases, extra-pulmonary in 14, both pulmonary and extra-pulmonary in one, and unknown in six. Extra-pulmonary sites were more frequent in older patients, and pulmonary sites more frequent in younger patients. Two patients were coinfected with the human immunodeficiency virus. Occupational exposure was identified in 13 cases and ingestion of non pasteurised milk in three. In addition, 11 patients had a possible risk of exposure related to their country of birth, family contact or occupation. In France, the 0.5% proportion of human tuberculosis due to M. bovis is similar to that of other developed countries. The higher incidence of the disease among older people is likely to reflect the efficacy of the control measures for tuberculosis in cattle.


Identification of African Elephant Polyomavirus in wild elephants and the creation of a vector expressing its viral tumor antigens to transform elephant primary cells.
Wild elephant populations are declining rapidly due to rampant killing for ivory and body parts, range fragmentation, and human-elephant conflict. Wild and captive elephants are further impacted by viruses, including highly pathogenic elephant endotheliotropic herpesviruses. Moreover, while the rich genetic diversity of the ancient elephant lineage is disappearing, elephants, with their low incidence of cancer, have emerged as a surprising resource in human cancer research for understanding the intrinsic cellular response to DNA damage. However, studies on cellular resistance to transformation and herpesvirus reproduction have been severely limited, in part due to the lack of established elephant cell lines to enable in vitro experiments. This report describes creation of a recombinant plasmid, pAelPyV-1-Tag, derived from a wild isolate of African Elephant Polyomavirus (AelPyV-1), that can be used to create immortalized lines of elephant cells. This isolate was extracted from a trunk nodule biopsy isolated from a wild African elephant, Loxodonta africana, in Botswana. The AelPyV-1 genome contains open-reading frames encoding the canonical large (LTag) and small (STag) tumor antigens. We cloned the entire early region spanning the LTag and overlapping STag genes from this isolate into a high-copy vector to construct a recombinant plasmid, pAelPyV-1-Tag, which effectively transformed primary elephant endothelial cells. We expect that the potential of this reagent to transform elephant primary cells will, at a minimum, facilitate study of elephant-specific herpesviruses.


A new glossiphoniid leech from Catemaco Lake, Veracruz, México.
Haementeria acuecueyetzin n. sp. from Catemaco Lake, Veracruz, Mexico, is described based on the examination of 6 specimens. This new hematophagous leech species resembles other members of the genus in the number and position of the eyespots, number of compact salivary glands, and in the presence of 2 pairs of spheroidal mycetomes, but it is distinguished from the other species by having 6 rows of longitudinal smooth white papillae in the dorsal surface and numerous tubercles in dorsal and ventral surfaces. This new species represents the third species of Haementeria in the Northern Hemisphere of the Americas.


Prediabetes and Type 2 Diabetes are Independent Risk Factors for Computed Tomography-Estimated Nonalcoholic Fatty Pancreas Disease.
Nonalcoholic fatty pancreas disease (NAFPD) is characterized by excessive fat deposition in the pancreas in the absence of alcohol consumption. In this study, we aimed to detect a possible relationship between adipose tissue accumulation, prediabetes and diabetes. This cross-sectional and retrospective study included 110 patients. Three groups were classified as controls, patients with prediabetes and patients with type 2 diabetes. The abdominal computed tomography (CT) attenuation measurement results of the pancreas were evaluated independently by two experienced radiologists. CT measurements and biochemical parameters were compared between study groups. The relationship between continuous variables was assessed by using one-way ANOVA. To determine the changes in the dependent variable for the effects on study groups, the independent variable was adjusted using ANCOVA. A p-value less than 0.05 was considered statistically significant. The presence of prediabetes and type 2 diabetes was correlated with a decrease in the mean Hounsfield Unit (HU) value of the pancreas (p=0.002). Age was determined to be an independent risk factor and was correlated with NAFPD (p=0.0001). When compared to the controls (p=0.041), 71% of patients with prediabetes and 67% of patients with type 2 diabetes were observed to have an increased incidence of NAFPD. Decreased serum amylase was found to be correlated with the mean HU value of the pancreas (p=0.043). NAFPD was independently correlated with both prediabetes and type 2 diabetes adjusted for age (p=0.0001) in this study. Additionally, age was determined to be an independent risk factor and was correlated with NAFPD.


An exoskeletal robot for human elbow motion support-sensor fusion, adaptation, and control.
In order to help everyday life of physically weak people, we are developing exoskeletal robots for human (especially for physically weak people) motion support. In this paper, we propose a one degree-of-freedom (1 DOF) exoskeletal robot and its control system to support the human elbow motion. The proposed controller controls the angular position and impedance of the exoskeletal robot system based on biological signals that reflect the human subject's intention. The skin surface electromyogram (EMG) signals and the generated wrist force by the human subject during the elbow motion have been fused and used as input information of the controller. In order to make the robot flexible enough to deal with vague biological signal such as EMG, fuzzy neuro control has been applied to the controller. The experimental results show the effectiveness of the proposed exoskeletal robot system.


Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.
Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure-response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure-response functions spanning the global range of exposure. Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000-422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction. Bill & Melinda Gates Foundation and Health Effects Institute.


A longitudinal description of incompetent to stand trial admissions to a state hospital.
Evidence is clear that the nation is experiencing an increasing number of incompetent to stand trial (IST) admissions to state hospitals. As a result, defendants in need of treatment can wait in jail for weeks for admission for restoration. This study was conducted to better understand this growing population and to inform hospital administration about the characteristics of IST admissions. The study was conducted at the Department of State Hospitals (DSH) facility in Napa (DSH-Napa), a 1200-bed primarily forensic inpatient psychiatric facility located in northern California. The records of patients found IST and admitted to DSH-Napa for restoration of competence between the dates of 1/1/2009 and 12/31/2016 were eligible for inclusion in the study. There were a total of 3158 unduplicated IST admissions available during the specified time period. Our data indicate that the number of admissions with more than 15 prior arrests increased significantly, from 17.7% in 2009 to 46.4% in 2016. In contrast, the percent of patients reporting prior inpatient psychiatric hospitalization evidenced a consistent decrease over time from over 76% in 2009 to less than 50% in 2016. Our data add to the body of literature on the potential causes of the nationwide increase in competency referrals. The literature is clear that jails and prisons are now the primary provider of the nation's mental health care. Our data suggest that another system has assumed this role: state hospitals and other providers charged with restoring individuals to competence.


Dorsal Anterior Cingulate Cortex Encodes the Integrated Incentive Motivational Value of Cognitive Task Performance.
Humans can seamlessly combine value signals from diverse motivational incentives, yet it is not well understood how these signals are "bundled" in the brain to modulate cognitive control. The dorsal ACC (dACC) is theorized to integrate motivational value dimensions in the service of goal-directed action, although this hypothesis has yet to receive rigorous confirmation. In the present study, we examined the role of human dACC in motivational incentive integration. Healthy young adult men and women were scanned with fMRI while engaged in an experimental paradigm that quantifies the combined effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on cognitive task performance. Monetary incentives modulated trial-by-trial dACC activation, whereas block-related effects of liquid incentives on dACC activity were observed. When bundled together, incentive-related dACC modulation predicted fluctuations in both cognitive performance and self-report motivation ratings. Statistical mediation analyses suggest that dACC encoded the incentives in terms of their integrated subjective motivational value, and that this value signal was most proximally associated with task performance. Finally, we confirmed that these incentive integration effects were selectively present in dACC. Together, the results support an account in which dACC integrates motivational signals to compute the expected value of goal-directed cognitive control.SIGNIFICANCE STATEMENT How are primary and secondary incentives integrated in the brain to influence goal-directed behavior? Using an innovative experimental fMRI paradigm that combines motivational incentives that have historically been studied independently between species (e.g., monetary rewards for humans, food rewards for animals), we examine the relationship between incentive motivational value and cognitive control allocation. We find evidence that the integrated incentive motivational value of combined incentives is encoded in human dorsal ACC. Further, self-reported motivational shifts mediated the effects of incentive-modulated dorsal ACC activity on task performance, revealing convergence in how self-reported and experimentally induced motivation are encoded in the human brain. Our findings may inform future translational studies examining affective/motivational and cognitive impairments in psychopathology (e.g., anxiety, depression, addiction).


Bone-added osteotome sinus floor elevation with simultaneous placement of non-submerged sand blasted with large grit and acid etched implants: a 5-year radiographic evaluation.
Implant survival rates using a bone-added osteotome sinus floor elevation (BAOSFE) procedure with simultaneous placement of a non-submerged sand blasted with large grit and acid etched (SLA) implant are well documented at sites where native bone height is less than 5 mm. This study evaluated the clinical results of non-submerged SLA Straumann implants placed at the time of the BAOSFE procedure at sites where native bone height was less than 4 mm. Changes in graft height after the BAOSFE procedure were also assessed using radiographs for 5 years after the implant procedure. The BAOSFE procedure was performed on 4 patients with atrophic posterior maxillas with simultaneous placement of 7 non-submerged SLA implants. At least 7 standardized radiographs were obtained from each patient as follows: before surgery, immediately after implant placement, 6 months after surgery, every year for the next 3 years, and after more than 5 years had passed. Clinical and radiographic examinations were performed at every visit. Radiographic changes in graft height were calculated with respect to the implant's known length and the original sinus height. All implants were stable functionally, as well as clinically and radiographically, during the follow-up. Most of the radiographic reduction in the grafted bone height occurred in the first 2 years; reduction after 2 years was slight. The simultaneous placement of non-submerged SLA implants using the BAOSFE procedure is a feasible treatment option for patients with severe atrophic posterior maxillas. However, the grafted bone height is reduced during the healing period, and patients must be selected with care.


Spinal cord lesions in patients with multiple sclerosis: comparison of MR pulse sequences.
To compare T2-weighted conventional spin-echo (CSE), fast spin-echo (FSE), shorttau inversion recovery (STIR) FSE, and fluid-attenuated inversion recovery (FLAIR) FSE sequences in the assessment of cervical multiple sclerosis plaques. Twenty patients with clinically confirmed multiple sclerosis and signs of cervical cord involvement were examined on a 1.5-T MR system. Sagittal images of T2-weighted and proton density-weighted CSE sequences, T2-weighted FSE sequences with two different sets of sequence parameters, STIR-FSE sequences, and FLAIR-FSE sequences were compared by two independent observers. In addition, contrast-to-noise measurements were obtained. Spinal multiple sclerosis plaques were seen best on STIR-FSE images, which yielded the highest lesion contrast. Among the T2-weighted sequences, the FSE technique provided better image quality than did the CSE technique, but lesion visibility was improved only with a repetition time/echo time of 2500/90; parameters of 3000/150 provided poor lesion contrast but the best myelographic effect and overall image quality. CSE images were degraded by prominent image noise; FLAIR-FSE images showed poor lesion contrast and strong cerebrospinal fluid pulsation artifacts. The STIR-FSE sequence is the best choice for assessment of spinal multiple sclerosis plaques. For T2-weighted FSE sequences, shorter echo times are advantageous for spinal cord imaging, long echo times are superior for extramedullary and extradural disease. FLAIR-FSE sequences do not contribute much to spinal imaging for multiple sclerosis detection.


Experience of Adversity during a First Lactation Modifies Prefrontal Cortex Morphology in Primiparous Female Rats: Lack of Long Term Effects on a Subsequent Lactation.
Reproductive experience is associated with morphological and functional plasticity in brain areas important for cognitive and emotional responses, including the infralimbic (IL) medial prefrontal cortex (mPFC). Here we examined whether suboptimal conditions during a first lactation could modify lactation-induced morphological IL mPFC changes, leading to alterations in stress responses and attention and whether any observed effects would persist into a second lactation. Reduced availability of bedding and nesting material (LB) was used to induce unfavorable conditions in primiparous (P) mothers. In normal bedding (NB) conditions, P mothers exhibited high spine number and density on postpartum day (PPD)10, which greatly decreased 2 weeks after weaning of their pups. In contrast, P-LB mothers had a lower spine number and density on PPD10, which markedly increased after weaning. LB exposure did not modify stress responsiveness to a ferret odor on PPD5 in primiparous or in multiparous (M) females. Number of errors and trials to criterion in the attention set shifting task were not modified by a history of adversity in multiparous females, although this group tended to exhibit higher attentional abilities than M-NB females. These results suggest that adversity acutely reduces morphological plasticity in the maternal mPFC during lactation, an effect that is not associated with significant changes in stress responses and/or glucocorticoid production. Medial PFC morphological changes induced by LB subside during a subsequent lactation as does the effect of maternity itself.


Chemoenzymatic dynamic kinetic resolution: a powerful tool for the preparation of enantiomerically pure alcohols and amines.
Chemoenzymatic dynamic kinetic resolution (DKR) constitutes a convenient and efficient method to access enantiomerically pure alcohol and amine derivatives. This Perspective highlights the work carried out within this field during the past two decades and pinpoints important avenues for future research. First, the Perspective will summarize the more developed area of alcohol DKR, by delineating the way from the earliest proof-of-concept protocols to the current state-of-the-art systems that allows for the highly efficient and selective preparation of a wide range of enantiomerically pure alcohol derivatives. Thereafter, the Perspective will focus on the more challenging DKR of amines, by presenting the currently available homogeneous and heterogeneous methods and their respective limitations. In these two parts, significant attention will be dedicated to the design of efficient racemization methods as an important means of developing milder DKR protocols. In the final part of the Perspective, a brief overview of the research that has been devoted toward improving enzymes as biocatalysts is presented.


[Morphological manifestation of the action of the complement-antibody system on the surface structures of S. typhimurium].
An electron-microscopic study of the negatively-stained S. typhimurium cells from the culture subjected to the action of a specific hyperimmune antiserum in the presence of a complement (the "complement-antibody" system) pointed to increase in the population of morphological signs of cell destruction--an increase in the number of small bacterial fragments. Many cells which retained the configuration of bacterial cells also had signs of specific affection. The determining sign of specificity of the process was the presence on the surface of the great majority of the mentioned morphological types of accumulations of bacterial fragments of the stain in the form of dark stains surrounded by a lighter ring. The stains were as a rule round with the diameter of the dark zone of about 80 A. The light framing of about 30 A in width consisted of 12 subunits. A conclusion was drawn that further experimental analysis was necessary for detalization of this process and reproduction of a complete picture of bacteriolysis.


Elevated levels of CCR6+ T helper 22 cells correlate with skin and renal impairment in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of pathological features. Our study investigated the potential role of CCR6+ T cells in organ impairment of SLE patients. We analyzed CCR6+/- T cell subset populations and compared the concentrations of IL-22, IFN-γ, TNF-α, and IL-17A cytokines in 67 patients with newly diagnosed SLE and 26 healthy controls. We found that SLE patients had elevated percentages of CCR6+ T, CCR6+ Th22, Th17, Th17.1, and CCR6- Th2 cell subsets, along with increased concentrations of IL-22, IFN-γ, TNF-α, and IL-17 cytokines. Higher levels of CCR6+ T and CCR6+ Th22 cells, along with plasma IL-22 were observed in SLE patients with sole skin and/or renal impairment. The percentage of Th22 cells also correlated with Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) and IgG levels, and inversely correlated with C3 levels in SLE patients with sole skin impairment. SLE patients with sole renal impairment showed a correlation between the percentage of Th22 cells and ESR levels. Our data indicated that CCR6+ Th22 cells may contribute to the pathogenesis of new onset SLE patients with skin or renal impairment, and CCR6 may, thus, be a possible therapeutic target for SLE treatment.


Anger state during acute insulin-induced hypoglycaemia.
This study sought to examine the effects of insulin-induced hypoglycaemia on anger state, and to describe the associations between change in the anger state and measures of anger trait and anger expression (assessed using the State-Trait Anger Expression Inventory). A hyperinsulinaemic glucose clamp was used to achieve controlled euglycaemia (5.0 mmol/L) and hypoglycaemia (2.6 mmol/L) in 18 nondiabetic subjects and 30 people with insulin-dependent diabetes mellitus (IDDM). Subjects underwent both hypoglycaemic and euglycaemic conditions, separated by 2 weeks, in a counterbalanced order. During each study condition subjects were asked to complete a questionnaire on anger state. Results at euglycaemia and hypoglycaemia were compared, and differences between the conditions were correlated with measures of anger trait and anger expression. Hypoglycaemia caused both nondiabetic and IDDM subjects to report a significant increase in feelings of anger, despite being in a nonconfrontational setting. However, there were no clear associations between an individual's change in reported anger and measures of anger trait and anger expression. No association was found between the change in anger state and the intensity of an individual's symptomatic response to hypoglycaemia.


Factors affecting endoscopic third ventriculostomy success in adults.
Endoscopic third ventriculostomy (ETV) is a standard treatment in hydrocephalus of certain aetiologies. The most widely used predictive model is the ETV success score. This is frequently used to predict outcomes following ETV in adult patients; however, this was a model developed in paediatric patients with often distinct aetiologies of hydrocephalus. The aim of this study was to assess the predictive value of the model and to identify factors that influence ETV outcomes in adults. A retrospective study design was used to analyse consecutive patients who underwent ETV at a tertiary neurosurgical centre between 2012 and 2020. Observed ETV outcomes at 6 months were compared to pre-operative predicted ETV success scores. A multivariable Bayesian logistic regression analysis was used to determine the factors that best predicted ETV success and those factors that were redundant. A total of 136 patients were analysed during the 9-year study. Thirty-one patients underwent further cerebrospinal fluid diversion within 6 months. The overall ETV success rate was 77%. Observed ETV outcomes corresponded well with predicted outcomes using the ETV success score for the higher scores, but less well for lower scores. Location of obstruction at the aqueduct irrespective of aetiology was the best predictor of success with odds of 1.65 of success. Elective procedures were also associated with higher success compared to urgent ones, whereas age under 70, nature and location of obstructive lesion (other than aqueductal) did not influence ETV success. ETV was successful in three-quarters of adult patient with hydrocephalus within 6 months. Obstruction at the level of the aqueduct of any aetiology was a good predictor of ETV success. Clinicians should bear in mind that adult hydrocephalus responds differently to ETV compared to paediatric hydrocephalus, and more research is required to develop and validate an adult-specific predictive tool.


Modular femoral head dissociation after dislocation and entrapment in reconstruction ring: a case report.
Dissociation of modular components is an infrequent potential complication characteristically unique to modularity. We present a patient in whom dissociation of the modular femoral head occurred at attempted closed reduction after dislocation, with the intraoperative findings including entrapment of the head between the rim of a reconstruction ring and the acetabular bone. In the case a dislocation in a patient that was previously reconstructed with a reinforcement ring and a modular femoral stem occurs, dissociation of the modular head should be considered as an extremely uncommon complication that does not outweigh the advantages given by modularity.


Isolation of highly active monoclonal antibodies against multiresistant gram-positive bacteria.
Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics. Staphylococci and enterococci are the predominant Gram-positive species associated with hospital-acquired infections. These infections often lead to extended hospital stay and excess mortality. In this study, a panel of fully human monoclonal antibodies was isolated from a healthy individual by selection of B-cells producing antibodies with high opsonic killing against E. faecalis 12030. Variable domains (VH and VL) of these immunoglobulin genes were amplified by PCR and cloned into an eukaryotic expression vector containing the constant domains of a human IgG1 molecule and the human lambda constant domain. These constructs were transfected into CHO cells and culture supernatants were collected and tested by opsonophagocytic assay against E. faecalis and S. aureus strains (including MRSA). At concentrations of 600 pg/ml, opsonic killing was between 40% and 70% against all strains tested. Monoclonal antibodies were also evaluated in a mouse sepsis model (using S. aureus LAC and E. faecium), a mouse peritonitis model (using S. aureus Newman and LAC) and a rat endocarditis model (using E. faecalis 12030) and were shown to provide protection in all models at a concentration of 4 μg/kg per animal. Here we present a method to produce fully human IgG1 monoclonal antibodies that are opsonic in vitro and protective in vivo against several multiresistant Gram-positive bacteria. The monoclonal antibodies presented in this study are significantly more effective compared to another monoclonal antibody currently in clinical trials.


A diagnostic formulation for anosognosia in Alzheimer's disease.
To determine the earliest symptoms of anosognosia in people with Alzheimer's disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. A consecutive series of 750 patients with very mild or probable Alzheimer's disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer's disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer's disease. Anosognosia in those with Alzheimer's disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer's disease was shown, which may contribute to the early identification of this condition.


[The social representations of workers regarding the Family Health Program].
The scope of this study is to analyze the social representations of workers regarding the Family Healthcare Program (FHP) to check its potential and limitations in order to change the healthcare model. Data were obtained through semi-structured interviews with eighteen health workers and by observing the working process of the teams of the Healthy Family Program (HFP) of five Regional Administrations in the Federal District. The data obtained from the interviews were analyzed using ALCESTE software, which generated two main trends. The first is related to social representations of the FHP, composed of several classes: the first class deals with FHP as a strategy to change the healthcare model; the second class refers to the difficulties of infrastructure, and the fifth class deals with family interaction based on medical practice. The second trend deals with daily practices of the HFP, composed of a third class, namely the actions developed by the HFP, and a fourth class that demonstrates the forms of organization and division of labor.


Assessment of estrogen receptors and apoptotic factors in cryopreserved human ovarian cortex.
The aims of this study were: (i) to examine frozen-thawed ovarian tissues for features of follicular health and atresia by histology; (ii) to assess the expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) by real-time PCR; (iii) to evaluate the Bax/Bcl-2 ratio, as an apoptotic index, in the ovarian tissues before and after cryopreservation. Ovarian cortical biopsies were obtained from 11 patients. The fragments were subdivided into two groups, fresh (control tissues) and cryopreserved tissues obtained by direct plunging into liquid nitrogen. Both tissue groups were subjected to a histological evaluation of the healthy and atretic follicles, immunohistochemical localization of the ER, and a real-time PCR (qPCR) to evaluate the expression of ER, Bax, Bcl-2 as well as beta-actin, as control gene. Damage was observed in 31% of primordial, 45% of primary, and 75% of secondary follicles in the cryopreserved tissue group. The qPCR analysis showed that the level of ERbeta was greater in fresh than cryopreserved tissues, whereas the ERalpha expression and Bax/Bcl-2 ratio were similar in both tissue groups. A significant inverse association was observed between ERalpha mRNA levels in the fresh tissue group and subjects' ages. The results show that cryopreservation and thawing of human ovarian tissue does not affect the morphology of primordial or primary follicles and that cryopreservation does not affect apoptosis. However, cryopreservation seems to have an inhibitory effect on the level of ERbeta. Additional studies are needed to evaluate the differential effects of freezing follicles at different stages of follicular development and ovarian steroidogenesis.


Altered retinoid metabolism in female Long-Evans and Han/Wistar rats following long-term 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treatment.
This study investigated the effects of long-term low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on retinoid, thyroid hormone, and vitamin D homeostasis in Long-Evans and Han/Wistar rats using a tumor promotion exposure protocol. Female rats (ten/group) were partially hepatectomized, initiated with nitrosodiethylamine (NDEA), and given TCDD once per week by sc injection for 20 weeks at calculated daily doses of 0, 1, 10, 100, or 1000 ng/kg bw/day. Groups of nonhepatectomized/uninitiated rats (five/group) were identically maintained. After 20 weeks, the rats were killed, and apolar retinoid levels were determined in the liver and kidneys. No consistent differences were seen between partially hepatectomized/initiated and nonhepatectomized/uninitiated animals with respect to apolar retinoid levels or hepatic TCDD concentration. Further analyses of polar and apolar retinoid levels in liver, plasma, and kidney, as well as free thyroxine (FT4) and vitamin D (25-OH-D(3)) concentrations were carried out in partially hepatectomized/inititated animals. In Long-Evans rats, TCDD exposure dose-dependently decreased hepatic retinyl ester concentrations at doses of 1-100 ng/kg bw/day. Likewise, hepatic all-trans-retinoic acid (all-trans-RA) concentration was decreased 39 and 54% at 10 and 100 ng/kg bw/day respectively, whereas 9-cis-4-oxo-13,14-dihydro-retinoic acid (9-cis-4-oxo-13,14-dihydro-RA), a recently discovered retinoic acid metabolite, was decreased approximately 60% in the liver at 1 ng/kg bw/day. TCDD dose-dependently increased plasma retinol and kidney retinol concentrations, whereas all-trans-RA concentration was also increased in the plasma and kidney at 10 and 100 ng/kg bw/day. Plasma 9-cis-4-oxo-13,14-dihydro-RA was decreased to below detection limits from doses of 1 ng/kg bw/day TCDD. A qualitatively similar pattern of retinoid disruption was observed in the Han/Wistar rat strain following TCDD exposure. FT4 was decreased to a similar extent in both strains, whereas 25-OH-D(3) was decreased only at 100 ng/kg bw/day in Long-Evans rats. Together these results show that TCDD disrupts both retinoid storage and metabolism of retinoic acid and retinoic acid metabolites in liver, kidney, and plasma from doses as low as 1 ng/kg bw/day. Furthermore, 9-cis-4-oxo-13,14-dihydro-RA was identified as a novel and sensitive indicator of TCDD exposure, in a resistant and sensitive rat strain, thereby extending the database of low-dose TCDD effects.


Elevated dissolved phosphorus in riparian groundwater along gaining urban streams.
Findings of low concentrations of dissolved phosphorus in groundwater in large surveys [e.g., United States Geological Survey's National Water-Quality Assessment (NAWQA) Program ( Dubrovsky, N. M.; et al. The Quality of Our Nation's Water: Nutrients in the Nation's Streams and Groundwater, 1992-2004 . U.S. Geological Survey Circular 1350; USGS : Reston, VA , 2010 . ); >5000 wells] support the common perception that groundwater is generally of little importance for transporting phosphorus. Here, we address whether this applies to urban riparian settings, where discharging groundwater may potentially contribute to urban stream syndrome and downstream eutrophication problems. This survey study includes 665 samples of groundwater collected along gaining stream reaches at six urban sites. Considering the combined sample set, 27% had soluble reactive phosphorus (SRP) concentrations >0.1 mg L(-1), which is more than double that determined in the NAWQA Program (12%), while for individual sites the range was 12-52%, excluding one site with consistently low SRP (0%). None of the sites showed significant correlation between SRP and the artificial sweetener acesulfame, a promising wastewater indicator, including two with known wastewater contamination (but the lowest SRP). Rather, high SRP concentrations were associated with geochemically reducing conditions. This could mean that natural aquifer or stream sediment materials were a primary contributor of the elevated SRP observed in this study.


Volumetric assessment of extracranial carotid artery aneurysms.
The extracranial carotid artery aneurysm (ECAA) is a rare pathology for which clinical treatment guidelines are lacking. In general, symptoms or growth of the aneurysm sac are thought to indicate intervention. ECAAs may present in a large variety of shapes and sizes, and conventional diameter measurements fail to indicate geometrical differences. Therefore, we propose a protocol to measure ECAA size by 3D volumetric assessment. The volumes of 40 ECAAs in computed tomography angiography (CTA) images were measured through manual segmentation, by two independent operators. Volumes of the entire internal carotid artery (ICA) and the ECAA were measured separately. Excellent inter- and intraoperator reliability was found for both ICA and ECAA volumes, with all intraclass correlation coefficients above 0.94. Bland-Altman analysis revealed normal differences for both inter- and intraoperator agreement. For all volumes, similarity of the segmentations was excellent. Outliers were explained by presence of intraluminal ECAA thrombus, which hampered identification of the aneurysm outer wall. These results implicate robustness of our protocol, which is designed as a step-up towards (semi)automatic volumetric measurements to monitor patients with ECAA. Future (semi)automatic volumetric assessments are recommended and such techniques can be developed and validated using the proposed protocol and manual reference segmentations.


Environmental accounting for Arctic shipping - a framework building on ship tracking data from satellites.
Arctic shipping is on the rise, leading to increased concern over the potential environmental impacts. To better understand the magnitude of influence to the Arctic environment, detailed modelling of emissions and environmental risks are essential. This paper describes a framework for environmental accounting. A cornerstone in the framework is the use of Automatic Identification System (AIS) ship tracking data from satellites. When merged with ship registers and other data sources, it enables unprecedented accuracy in modelling and geographical allocation of emissions and discharges. This paper presents results using two of the models in the framework; emissions of black carbon (BC) in the Arctic, which is of particular concern for climate change, and; bunker fuels and wet bulk carriage in the Arctic, of particular concern for oil spill to the environment. Using the framework, a detailed footprint from Arctic shipping with regards to operational emissions and potential discharges is established.


Evidence for the coidentification of GAP-43, a growth-associated protein, and F1, a plasticity-associated protein.
GAP-43 is a fast-axonally transported protein whose expression correlates with periods of axon growth both during development and during regeneration. Similarities in molecular weight (43-47 kDa), pI (4.3-4.5), and aberrant behavior in acrylamide gels suggested that GAP-43 might be related or identical to protein F1, a protein kinase C substrate that has been shown to undergo a change in phosphorylation state during long-term potentiation in the hippocampus. Here we show that GAP-43 and protein F1 comigrate by two-dimensional PAGE and that antiserum raised against GAP-43 specifically immunoprecipitates protein F1. More direct evidence that GAP-43 and protein F1 are identical proteins was obtained by performing S. aureus V8 protease digests of a mixture of purified 32P-labeled protein F1 and purified GAP-43. Under these conditions, 2 phosphorylated peptide fragments of protein F1 corresponded exactly to 2 Coomassie-stainable bands from purified GAP-43. We conclude on the basis of these data that GAP-43 and protein F1 are identical proteins. Using light-microscopic immunocytochemistry, we also show that GAP-43/protein F1 immunoreactivity is localized to neuropil areas of the hippocampus consistent with its roles as a protein kinase C substrate in vivo and in long-term potentiation. These findings suggest that nerve growth during development and regeneration, and synaptic plasticity in the adult mammalian brain, may be mediated by a common mechanism involving the phosphorylation of GAP-43/protein F1.


Balloon tibioplasty: a useful tool for reduction of tibial plateau depression fractures.
Reduction of the articular surface in displaced tibial plateau fractures is still challenging and may result in joint incongruence, leading to posttraumatic arthrosis. Conventional techniques use bone tamps and similar instruments, which can increase the surgical trauma due to their size. "Balloon tibioplasty" is a novel minimally invasive technique for the reduction of depressed tibial plateau fractures. We successfully applied an inflatable balloon, commercially available from kyphoplasty, to elevate the depressed articular fragments. This technique allowed for reduction of the depressed tibial plateau fragment without classic fenestration of the tibia, thereby minimizing surgical trauma. Furthermore, under fluoroscopic control, optimal centering of the expanding tibioplasty balloon allows a widespread and continuously increasing reduction force to the fracture area. After fluoroscopy or arthroscopic confirmation of reduction of the articular surface, the cavity resulting from tibioplasty was filled with ceramic bone cement through small incisions and fractures were fixed with a small fragment locking T-plate (3.5 mm). Balloon tibioplasty was applied in 5 patients with displaced tibial plateau fractures (OTA type B2/3). No intra- or postoperative complications were observed. This new technique may be a useful tool to facilitate the reduction of select depressed tibial fractures in the future.


Prevalence and correlates of pregnancy self-testing among pregnant women attending antenatal care in western Kenya.
In sub-Saharan Africa little is known about how often women use pregnancy self-tests or characteristics of these women despite evidence that pregnancy self-testing is associated with early antenatal care (ANC) initiation. Understanding the characteristics of women who use pregnancy self-tests can facilitate more targeted efforts to improve pregnancy testing experiences and entry into the ANC pathway. We conducted a cross-sectional survey among pregnant women enrolling in a pre-exposure prophylaxis (PrEP) implementation study to determine the prevalence and factors associated with pregnancy self-testing among women in western Kenya. Overall, in our study population, 17% of women obtained a pregnancy self-test from a pharmacy. Pregnancy test use was higher among employed women, women with secondary and college-level educated partners, and women who spent 30 minutes or less traveling to the maternal and child health (MCH) clinic. The most reported reasons for non-use of pregnancy self-tests included not thinking it was necessary, lack of knowledge, and money to pay for the test. Future research should focus on understanding the knowledge and attitudes of women toward pregnancy self-testing as well as developing community-based models to improve access to pregnancy testing and ANC.


Initial angiographic appearance of intracranial vascular occlusions in acute stroke as a predictor of outcome of thrombolysis: initial experience.
To determine whether the initial angiographic morphology and location of intracranial arterial occlusions in acute stroke are reliable predictors of success of thrombolysis. Thirty-three intracranial occlusions were studied in 32 patients who underwent intraarterial thrombolysis with urokinase within 6 hours from clinical onset of stroke symptoms. The initial angiographic appearance of each occlusion was categorized as cutoff, tapered, meniscus, tram-track, or tandem. Following thrombolysis, outcomes were classified as complete, partial, or no recanalization. Complete recanalization was accomplished in 17 of the 33 lesions, partial recanalization in nine, and no effect in seven. Tram-track (n = 3) and tapered (n = 7) lesions demonstrated the highest rates of at least partial recanalization (100% and 86%, respectively), whereas cutoff lesions (n = 13) demonstrated the lowest rate (69%). Intracranial hemorrhage was associated with higher doses of urokinase. Complete recanalization success rates were 60% for M1 lesions (n = 10), 43% for M2 or A2 lesions (n = 14), and 33% for M3 lesions (n = 3). Vertebrobasilar lesion (n = 5) success rates for complete and at least partial recanalization were 80% and 100%, respectively. Relationships were found to exist between the success rate of recanalization and initial angiographic lesion location and morphology, which represent important trends; however, further studies with a larger sample size are needed.


Bioengineering in the oral cavity: insights from articular cartilage tissue engineering.
Cartilage failure in diarthrodial joints results in pain and a reduction in quality of life. The goal of cartilage tissue engineering is to replace or regenerate these mechanically loaded tissues to restore function to the joint. Recent advances in the authors' laboratory have resulted in the production of cartilage and fibrocartilage with clinically relevant properties. A review of salient results will constitute the bulk of this manuscript. After providing a brief background of the clinical problem, this review will highlight several specific tissue engineering tools. The approaches used to produce mechanically functional cartilage through tissue engineering have several parallels to the problems faced in osseointegration, eg, the need for mechanically appropriate tissues at the implantation site. The discussion that follows will focus on how approaches developed in identifying alternative cell sources and various exogenous stimuli for producing new cartilage may be applicable to osseointegration.


Multiple imputation and direct estimation for qPCR data with non-detects.
Quantitative real-time PCR (qPCR) is one of the most widely used methods to measure gene expression. An important aspect of qPCR data that has been largely ignored is the presence of non-detects: reactions failing to exceed the quantification threshold and therefore lacking a measurement of expression. While most current software replaces these non-detects with a value representing the limit of detection, this introduces substantial bias in the estimation of both absolute and differential expression. Single imputation procedures, while an improvement on previously used methods, underestimate residual variance, which can lead to anti-conservative inference. We propose to treat non-detects as non-random missing data, model the missing data mechanism, and use this model to impute missing values or obtain direct estimates of model parameters. To account for the uncertainty inherent in the imputation, we propose a multiple imputation procedure, which provides a set of plausible values for each non-detect. We assess the proposed methods via simulation studies and demonstrate the applicability of these methods to three experimental data sets. We compare our methods to mean imputation, single imputation, and a penalized EM algorithm incorporating non-random missingness (PEMM). The developed methods are implemented in the R/Bioconductor package nondetects. The statistical methods introduced here reduce discrepancies in gene expression values derived from qPCR experiments in the presence of non-detects, providing increased confidence in downstream analyses.


A low-cost, high-fidelity simulator for transabdominal chorionic villus sampling.
Chorionic villus sampling (CVS) remains essential for first trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use. We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily-available materials costing less than $10 and can be refrigerated and re-used to train maternal fetal medicine (MFM) fellows in CVS. All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for three months and dozens of simulated procedures each without any apparent qualitative degradation in performance. We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS.


raf oncogenes in carcinogenesis.
There are three active raf genes in man and at least two in Xenopus and Drosophila. The mammalian c- and A-raf genes have 16 coding exons, which span 40 and 20 kb, respectively. B-raf is larger and extends over greater than 46 kb. Human c-raf-1 maps to chromosome 3p25 and A-raf-1 to Xp21. c-raf-1 RNA is present in many tissues, while A-raf and B-raf expression is restricted. A- and c-raf encode cytoplasmic ser/thr protein kinases of 68 and 74 kDa, which contain three conserved regions (CR). CR1 and 2 are in the amino terminal half, CR1 comprises the presumed ligand binding site, and CR3 represents the carboxy terminal kinase domain. All three genes can be artificially activated by deletions, provided CR3 is preserved. However, only c-raf-1 occurs naturally in truncated versions, such as v-raf and v-mil in the acutely transforming retroviruses 3611-MSV and MH2. raf transformation can also be affected by point mutation, suggesting that this mechanism may activate c-raf-1 as an oncogene in carcinogenesis.


Treating ulcerative colitis by Adacolumn therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan.
The Adacolumn selectively depletes granulocytes and monocytes/macrophages, which are thought to be part of the immunopathogenesis of ulcerative colitis. This work aims at evaluating the safety and clinical efficacy of the Adacolumn in patients with ulcerative colitis in large population-based data sets. The Adacolumn post marketing surveillance in Japan was undertaken on 697 patients in 53 medical institutions over 7 years from 29 October 1999 to 28 October 2006. Clinical efficacy and safety data were provided by patients' physicians in the participating institutes. Safety was evaluated in all the 697 patients and efficacy in 656 patients. At entry, 92% of the patients were on salicylates, 74% on prednisolone and only 9% on immunomodulators. Approximately 40% of patients had severe ulcerative colitis and over 70% had ulcerative colitis that was refractory to conventional medications. There was no serious adverse events; mild to moderate adverse events were seen in 7.7% of the patients. The overall response (remission or significantly improved) was 77.3%; the remission rate based on clinical activity index was 71.1%, while 17.1% remained unchanged and 5.6% worsened. Patients were subgrouped into severe, moderate and mild ulcerative colitis based on clinical activity index (n=578), the response rates were 63.2%, 65.7% and 80.4%, respectively (P<0.001). Endoscopic assessment of efficacy showed very significant mucosal healing, Matts' endoscopic index improved from 3.2+/-0.04 to 2.1+/-0.7 (n=219, P<0.001); reduction in prednisolone dose (P<0.0001); leucocyte count (n=358, P<0.0001) and C-reactive protein (n=314, P<0.0001). Patients who received > or =6 Adacolumn sessions (n=319) did better than patients who received < or =5 sessions (n=188, P=0.004) and multivariate logistic regression analysis revealed that baseline granulocyte count was the strongest predictor of clinical response to Adacolumn (P=0.0191, odds ratio 1.151). This post marketing surveillance provides the largest ever efficacy and safety data on the Adacolumn therapeutic leucocytapheresis in patients with ulcerative colitis. As a non-pharmacologic treatment for patients with active ulcerative colitis most of whom were refractory to conventional drug therapy, the observed efficacy was very significant. Baseline granulocyte count was convincingly an independent predictor of clinical response.


[Cervical myelopathy as complication of manual therapy in a patient with a narrow cervical canal].
A 31-year-old man had manipulative therapy because of pain in the neck, the left shoulder and the left arm. Immediately after cervical traction he developed neurological symptoms. Clinical investigation led to the diagnosis of cervical myelopathy. The patient had a rather narrow cervical canal. Six weeks after treatment with external fixation and corticosteroids the situation had improved markedly, with remaining hypesthesia in both hands and the right leg.


VE-cadherin: adhesion at arm's length.
VE-cadherin was first identified in the early 1990s and quickly emerged as an important endothelial cell adhesion molecule. The past decade of research has revealed key roles for VE-cadherin in vascular permeability and in the morphogenic events associated with vascular remodeling. The details of how VE-cadherin functions in adhesion became apparent with structure-function analysis of the cadherin extracellular domain and with the identification of the catenins, a series of cytoplasmic proteins that bind to the cadherin tail and mediate interactions between cadherins and the cytoskeleton. Whereas early work focused on the armadillo family proteins beta-catenin and plakoglobin, more recent investigations have identified p120-catenin (p120(ctn)) and a related group of armadillo family members as key binding partners for the cadherin tail. Furthermore, a series of new studies indicate a key role for p120(ctn) in regulating cadherin membrane trafficking in mammalian cells. These recent studies place p120(ctn) at the hub of a cadherin-catenin regulatory mechanism that controls cadherin plasma membrane levels in cells of both epithelial and endothelial origin.


Graves' ophthalmopathy--a clinical review.
Graves' ophthalmopathy occurs in 2% to 7% of patients with Graves' disease with the major manifestations being proptosis, ophthalmoplegia, optic neuropathy and/or eyelid retraction. Although autoimmune in nature, the precise pathophysiology is unknown. The course of the ophthalmopathy is not influenced by the mode of treatment of the hyperthyroidism. In addition to restoration of the euthyroid state, the aims of treatment include relief of eye pain, correction of extraocular muscle dysfunction, protection of visual acuity and improvement of appearance. Specific therapy depends on the severity of the ophthalmopathy and varies from lubricating eye drops in mild disease to high-dose steroids and radiotherapy or decompressive surgery in severe cases.


Personality functioning in patients with avoidant personality disorder and social phobia.
Avoidant personality disorder (APD) and social phobia (SP) are closely related, such that they are suggested to represent different severity levels of one social anxiety disorder. This cross-sectional study aimed to compare patients with APD to patients with SP, with particular focus on personality dysfunction. Ninety-one adult patients were examined by diagnostic interviews and self-report measures, including the Index of Self-Esteem and the Severity Indices of Personality Problems. Patients were categorized in three groups; SP without APD (n = 20), APD without SP (n = 15), and APD with SP (n = 56). Compared to patients with SP without APD, patients with APD reported more symptom disorders, psychosocial problems, criteria of personality disorders, and personality dysfunction regarding self-esteem, identity and relational problems. These results indicate that APD involves more severe and broader areas of personality dysfunction than SP, supporting the conceptualization of APD as a personality disorder as proposed for DSM-5.


Hydrated Eutectic Electrolyte Induced Bilayer Interphase for High-Performance Aqueous Zn-Ion Batteries with 100°C Wide-Temperature Range.
The practical implementation of aqueous zinc-ion batteries (AZIBs) encounters challenges such as dendrite growth, parasitic reactions, and severe decay in battery performance under harsh environments. Here, we introduce a novel hydrated eutectic electrolyte (HEE) composed of Zn(ClO4 )2 ·6H2 O, ethylene glycol, and InCl3 solution to effectively extend the lifespan of AZIBs over a wide temperature range from -50 to 50°C. Molecular dynamics simulations and spectroscopy analysis demonstrated that the H2 O molecules are confined within the liquid eutectic network through dual-interaction, involving coordination with Zn2+ and hydrogen bonding with EG, thus weakening the activity of free water and extending the electrochemical window. Importantly, cryo-transmission electron microscopy and spectroscopy techniques revealed that HEE in-situ forms a zincophobic/zincophilic bilayer interphase by the dissociation-reduction of eutectic molecules. Specifically, the zincophilic interphase reduces the energy barrier for Zn nucleation, promoting uniform Zn deposition, while the zincophobic interphase prevents active water from contacting the Zn surface, thus inhibiting the side reactions. Furthermore, the relationships between the structural evolution of the liquid eutectic network and interfacial chemistry at electrode/electrolyte interphase were further discussed in this work. The scalability of this design strategy can bring benefits to AZIBs operating over a wide temperature range. This article is protected by copyright. All rights reserved.


Importance of Tenon's capsule in squint surgery.
A procedure for dealing with Tenon's capsule in squint surgery on the horizontal muscles, which preserves intact the relations of the various expansions of Tenon's capsule, distorts and damages them as little as possible and replaces Tenon's capsule as an intact layer over the muscle at the end of surgery is outlined. It depends on adequate fixation and the avoidance of damage to and distortion of Tenon's capsule by the use of muscle hooks to 'fish' for the muscle. It is claimed that this method produces less fibrosis around the muscle post-operatively and allows a better final result.


The power and limits of personal change: When a bad past does (and does not) inspire in the present.
Observing other people improve their lives can be a powerful source of inspiration. Eight experiments explore the power, limits, and reasons for this power of personal change to inspire. We find that people who have improved from undesirable pasts (e.g., people who used to abuse extreme drugs but no longer do) are more inspiring than people who maintain consistently desirable standings (e.g., people who have never used extreme drugs to begin with), because change is perceived as more effortful than stability (Experiments 1a and 1b). The inspirational power of personal change is rooted in people's lack of access to the internal struggles and hard work that many others may endure to successfully remain 'always-good.' Accordingly, giving observers access into the effort underlying others' success in maintaining consistently positive standings restores the inspiring power of being 'always-good' (Experiments 2-4). Finally, change is more inspiring than stability across many domains but one: people who used to harm others but have since reformed (e.g., ex-bullies or ex-cheaters) do not inspire, and in many cases are indeed less inspiring than people who have never harmed others to begin with (Experiments 5-7). Together, these studies reveal how, why, and when one's past influences one's present in the eyes of others: having some "bad" in your past can be surprisingly positive, at least partly because observers assume that becoming "good" is harder than being "good" all along. (PsycINFO Database Record


Premenstrual symptoms are relieved by massage therapy.
Twenty-four women meeting Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for premenstrual dysphoric disorder (PDD) were randomly assigned to a massage therapy or a relaxation therapy group. The massage group showed decreases in anxiety, depressed mood and pain immediately after the first and last massage sessions. The longer term (5 week) effects of massage therapy included a reduction in pain and water retention and overall menstrual distress. However, no long-term changes were observed in the massaged group's activity level or mood. Future studies might examine the effects of a longer massage therapy program on these symptoms. Overall, the findings from this study suggest that massage therapy may be an effective adjunct therapy for treating severe premenstrual symptoms.


Pharmacological screen for activities of 12-hydroxyibogamine: a primary metabolite of the indole alkaloid ibogaine.
The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. Ibogaine undergoes first pass metabolism and is O-demethylated to 12-hydroxyibogamine (12-OH ibogamine). Radioligand binding assays were conducted to identify the potency and selectivity profiles for ibogaine and 12-OH ibogamine. A comparison of 12-OH ibogamine to the primary molecular targets identified previously for ibogaine demonstrates that the metabolite has a binding profile that is similar, but not identical to the parent drug. Both ibogaine and 12-OH ibogamine demonstrated the highest potency values at the cocaine recognition site on the 5-HT transporter. The same rank order (12-OH ibogamine > ibogaine), but lower potencies were observed for the [3H]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH ibogamine were equipotent at vesicular monoamine and dopamine transporters. The metabolite demonstrated higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor complex compared to the parent drug. Quantitation of the regional brain levels of ibogaine and 12-OH ibogamine demonstrated micromolar concentrations of both the parent drug and metabolite in rat brain. Drug dependence results from distinct, but inter-related neurochemical adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine's ability to alter drug-seeking behavior may be due to combined actions of the parent drug and metabolite at key pharmacological targets that modulate the activity of drug reward circuits.


A comparative study of the clinicopathological significance of E-cadherin and catenins (alpha, beta, gamma) expression in the surgical management of oral tongue carcinoma.
E-cadherin and catenins are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin-catenin adhesion is an important step in the progression of many epithelial cancers. E-cadherin and catenins expression in carcinoma of the tongue were evaluated in relation to their clinicopathological features and prognostic values. Immunohistochemical staining was carried out with E-cadherin and (alpha, beta, gamma)-catenin monoclonal antibodies for 85 surgical specimens of oral tongue carcinoma, nine matched metastatic lymph nodes, and seven locally recurrent tumours. There was under-expression in 85% of E-cadherin, 94% of alpha-catenin, 89% of beta-catenin, and 83% of gamma-catenin in the primary tumours. There was no correlation of E-cadherin/catenin expression with sex, age, cancer stage, and differentiation. Nodal metastasis was found in 68% of patients with weak expression of gamma-catenin compared with 9% with strong expression in primary tumours (chi-square, P = 0.02). E-cadherin was a significant prognostic factor for survival and recurrence; patients with weak E-cadherin expression had 53% 5-year survival compared with 85% with strong expression (Wilcoxon, P = 0.0159). Both E-cadherin and catenins were highly under-expressed in oral tongue carcinoma, metastatic lymph node, and recurrent tumour. gamma-catenin had predictive value for nodal metastasis. E-cadherin was, however, a more important prognostic factor for recurrence and survival.


From neural stem cells to glioblastoma: A natural history of GBM recapitulated in vitro.
Due to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that have complicated the development of effective therapeutic strategies. This complex pathogenesis makes necessary the development of experimental models that could be used to further understand the disease, and also to provide a more realistic testing ground for potential therapies. In this report, we describe the process of transformation of primary mouse embryo astrocytes into immortalized cultures with neural stem cell characteristics, that are able to generate GBM when injected into the brain of C57BL/6 mice, or heterotopic tumours when injected IV. Overall, our results show that oncogenic transformation is the fate of NSC if cultured for long periods in vitro. In addition, as no additional hit is necessary to induce the oncogenic transformation, our model may be used to investigate the pathogenesis of gliomagenesis and to test the effectiveness of different drugs throughout the natural history of GBM.


Re-treatment profiles during long-term maintenance therapy in a periodontal practice in Norway.
Periodontal therapy coupled with active maintenance has been shown to be effective in maintaining periodontal health, however, the question of re-treatment is rarely alluded to in the literature. To quantify the type and extent of re-treatment in a group of patients who had completed a definitive course of periodontal treatment in a Norwegian specialist periodontal practice. The study also investigated factors associated with the provision of periodontal surgery as a re-treatment modality. A consecutive group of patients who had comprehensive periodontal treatment, which included periodontal surgery, and were subsequently maintained for between 10 and 17 years were studied. One hundred and one patients with an average age at reassessment of 59.4 (standard deviation (SD) 9.0) years were studied. The average length of the review period was 13.1 (SD 1.9) years. In addition to routine maintenance, 50 patients had further re-treatment and 40 of those who were re-treated had periodontal surgery in the study period. Logistic regression showed that independent predictors of surgical re-treatment, with the effects adjusted for other variables in the model, were uncertain or poor prognosis at baseline, erratic or poor post baseline compliance and a family history of periodontal disease. Considerable amounts of re-treatment, including in many cases extensive non-surgical treatment or periodontal surgery, were provided for patients who had surgical periodontal treatment and were subsequently maintained for least 10 years in a specialist periodontal practice.


A multicopy suppressor of a cell cycle defect in S. pombe encodes a heat shock-inducible 40 kDa cyclophilin-like protein.
Cyclophilins are peptidyl-prolyl cis-trans isomerases (PPIases) which have been implicated in intracellular protein folding, transport and assembly. Cyclophilins are also known as the intracellular receptors for the immunosuppressive drug cyclosporin A (CsA). The most common type of cyclophilins are the 18 kDa cytosolic proteins containing only the highly conserved core domain for PPIase and CsA binding activities. The wis2+ gene of the fission yeast Schizosaccharomyces pombe was isolated as a multicopy suppressor of wee1-50 cdc25-22 win1-1, a triple mutant strain which exhibits a cell cycle defect phenotype. Sequence analysis of wis2+ reveals that it encodes a 40 kDa cyclophilin-like protein, homologous to the mammalian cyclophilin 40. The 18 kDa cyclophilin domain (CyP-18) of wis2 is followed by a C-terminal region of 188 amino acids. The C-terminal region of wis2 is essential for suppression of the triple mutant defect. Furthermore this region of the protein is able to confer suppression activity on the 18 kDa S.pombe cyclophilin, cyp1, since a hybrid protein consisting of an 18 kDa S.pombe cyclophilin (cyp1) fused to the C-terminus of wis2 shows suppression activity. We also demonstrate that the level of wis2+ mRNA increases 10- to 20-fold upon heat shock of S.pombe cells suggesting a role for wis2+ in the heat-shock response.


[Survey and analysis on digital construction of primary hospitals in Guizhou Province].
To investigate the utilization status and awareness of digital hospital construction among medical staff in critical care department of primary hospitals, so as to promote the process of digital medical health. One to two doctors and nurses (in the department on that day) from public hospitals in 88 counties and urban areas in 9 cities of Guizhou Province were enrolled of field investigation. The questionnaires form were filled in on-site and sorted out and analyzed by special personnel. A total of 297 medical staff from the department of critical care medicine of 146 hospitals were included. All the questionnaires were filled in with their real names, including 152 doctors and 145 nurses. There were 24 class III Grade A hospitals and 122 class II and all the hospitals had implemented digital information management. The awareness of hospital digital information management system was generally low among the surveyed medical staff, and the awareness of hospital information system (HIS) was the highest (86.5%), followed by laboratory information management system (LIS, 41.4%) and image archiving and communication system (PACS, 40.7%). The awareness of hospital management system (HERP) was the lowest (7.7%). The total number of remote consultations conducted by hospitals using big data Internet was 25 428 times in 2020, with a median of 24.5 (88.0, 240.0) times in each hospital. From 2018 to 2020, the total number of patients admitted to the intensive care unit of the hospital was 50 473, 57 565 and 57 907, respectively, of which the number of patients over 65 years old accounted for 37.47%, 41.26% and 43.31%, respectively (all P > 0.05). There were 4 242 cases of remote consultation using big data Internet in the department every year, with a median of 257.50 (96.50, 958.25) cases. 12.12% of the departments had independent critical monitoring systems, and 8.75% of them could capture data automatically to form tables. 96.30% of the medical staff participated in systematic and professional training on basic knowledge, basic theory and basic medical care skills through the Internet platform, and the number of meetings, studies and training in the provinces and prefectures were 282 and 357 times per year, respectively. More than 90% of the departments initiated remote consultation, arranged referral or admitted patients who had improved status after treatment in superior hospitals through the Internet platform. Most of the patients (69.02%) were from the lower level of the hospital. The total number of out-patient consultations was 2 959 times per year, with a median of 296 (185 473) times. 54.79% of the departments had fixed service villages, and 28.08% of the departments had fixed service population. The median furthest visit distance was 52.5 (30.0, 80.0) kilometers, and the median average visit distance was 30.0 (20.0, 50.0) kilometers. 54.88% of medical staff believed that the biggest difficulties encountered during house visits were insufficient energy and too large service groups or regions. More than 90% of medical staff had been exposed to cloud learning and cloud training, and most of the surveyed medical staff believed that cloud learning and cloud training greatly improved medical service capacity and service efficiency of medical institutions (71.04% and 67.01%, respectively). Meanwhile, they believe that "Internet+health big data" projects from various aspects brought advantage to medical institutions, but there are also low utilization rate of Internet medical equipment by village doctors, low acceptance for telemedicine and mobile hospitals by farmers. Guizhou public hospitals have implementation of digital information management at the grass-roots level, the surveyed health care workers have a relatively low awareness of the digital information management system, hospital use big data Internet for remote consultation is uneven, intensive care medicine is a clinical discipline used in most remote consultation information system, and can complete two-way referrals. In the past three years, the discipline operation showed an upward trend year by year. Medical staff use artificial intelligence devices such as cloud learning and training to improve medical service capacity and efficiency. The digital transformation of primary hospitals is being continuously improved.