Tongue palate contact patterns of velar stops in normal adult English speakers.
This paper provides a more detailed description of normal tongue palate contact patterns for the occlusion phase of velar stops than currently exists. The study used electropalatography (EPG) to record seven normally speaking adults' contact patterns of voiceless velar stops in nine VkV contexts. A variety of EPG indices measured: per cent complete closures across the palate; place of articulation; articulatory distance between /k/ and /t/; and amount of contact. Complete EPG closure occurred in the majority (81%) of tokens. Some speakers almost always had complete closures regardless of context, whereas other speakers produced them only with high front vowels. As expected, place of articulation and amount of contact were heavily influenced by vowel context. The most fronted and most contact occurred in /i/ contexts and the most retracted and least contact in /a/ contexts. There was considerable interspeaker variability on all measures, particularly in the precise location of velar placement and articulatory distance between alveolar and velar placement. The implications for diagnosing and treating abnormal velar articulations are discussed.


Differential response patterns in the si barrel and septal compartments during mechanical whisker stimulation.
A growing body of evidence suggests that the barrel and septal regions in layer IV of rat primary somatosensory (SI) cortex may represent separate processing channels. To assess this view, pairs of barrel and septal neurons were recorded simultaneously in the anesthetized rat while a 4x4 array of 16 whiskers was mechanically stimulated at 4, 8, 12, and 16 Hz. Compared with barrel neurons, regular-spiking septal neurons displayed greater increases in response latencies as the frequency of whisker stimulation increased. Cross-correlation analysis indicated that the incidence and strength of neuronal coordination varied with the relative spatial configuration (within vs. across rows) and compartmental location (barrel vs. septa) of the recorded neurons. Barrel and septal neurons were strongly coordinated if both neurons were in close proximity and resided in the same row. Some barrel neurons were weakly coordinated, but only if they resided in the same row. By contrast, the strength of coordination among pairs of septal neurons did not vary with their spatial proximity or their spatial configuration within the arcs and rows of the barrel field. These differential responses provide further support for the view that the barrel and septal regions represent the cortical gateway for processing streams that encode specific aspects of the sensorimotor information associated with whisking behavior.


Gene variants and the response to childhood obesity interventions: A systematic review and meta-analysis.
Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177.


Impact of universal gowning and gloving on health care worker clothing contamination.
To determine whether gowning and gloving for all patient care reduces contamination of healthcare worker (HCW) clothing, compared to usual practice. Cross-sectional surveys. Five study sites were recruited from intensive care units (ICUs) randomized to the intervention arm of the Benefits of Universal Gown and Glove (BUGG) study. All HCWs performing direct patient care in the study ICUs were eligible to participate. Surveys were performed first during the BUGG intervention study period (July-September 2012) with universal gowning/gloving and again after BUGG study conclusion (October-December 2012), with resumption of usual care. During each phase, HCW clothing was sampled at the beginning and near the end of each shift. Cultures were performed using broth enrichment followed by selective media. Acquisition was defined as having a negative clothing culture for samples taken at the beginning of a shift and positive clothing culture at for samples taken at the end of the shift. A total of 348 HCWs participated (21-92 per site), including 179 (51%) during the universal gowning/gloving phase. Overall, 51 (15%) HCWs acquired commonly pathogenic bacteria on their clothing: 13 (7.1%) HCWs acquired bacteria during universal gowning/gloving, and 38 (23%) HCWs acquired bacteria during usual care (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2-0.6). Pathogens identified included S. aureus (25 species, including 7 methicillin-resistant S. aureus [MRSA]), Enterococcus spp. (25, including 1 vancomycin-resistant Enterococcus [VRE]), Pseudomonas spp. (4), Acinetobacter spp. (4), and Klebsiella (2). Nearly 25% of HCWs practicing usual care (gowning and gloving only for patients with known resistant bacteria) contaminate their clothing during their shift. This contamination was reduced by 70% by gowning and gloving for all patient interactions.


Dietary Patterns and Their Association with Anxiety Symptoms among Older Adults: The ATTICA Study.
Abstract: By 2050, the global population aged 60 years and over is expected to reach nearly 2.1 billion and affective disorders might be also expected to increase. Although nutrition has been related with affective disorders, there is a lack of studies assessing the relation between dietary habits and anxiety among European and Mediterranean older populations. In the present study, we aimed to evaluate the association between dietary habits, energy intake, and anxiety symptoms using data from 1128 Greek older adults (>50 years) without pre-existing cardiovascular disease (CVD) or any other chronic disease who participated in the ATTICA study. Various socio demographic lifestyle, bio-clinical (e.g., blood pressure), and psychological (e.g., depression) characteristics were used, and dietary habits as well as energy intake were calculated using standard procedures. Older people with anxiety were more likely to be sedentary, to be smokers, and to show symptoms of depression. The saturated fat and added sugars (SFAS) dietary pattern was associated with higher anxiety levels (non-standardized b (95% CI): 5.82 (0.03 to 11.61)). No association between energy intake tertiles and anxiety levels pictured in the later regression model. Moreover, female gender, family status, and depression were positively related to anxiety. Therefore, promoting healthy dietary habits could reduce anxiety symptoms of the older adults.


A randomized controlled trial of a behavioral economic intervention for alcohol and marijuana use.
A recent study demonstrated that a single 50-min supplemental session that targeted the behavioral economic mechanisms of substance-free reinforcement and delayed reward discounting (Substance-Free Activity Session: SFAS) enhanced the efficacy of a standard alcohol brief motivational intervention (BMI) for college drinkers. The purpose of the current study was to conduct a randomized controlled trial intended to replicate and extend the aforementioned study by focusing on both drug and alcohol misuse and reducing session length in order to enhance dissemination potential. Participants were 97 college students (58.8% women; 59.8% White/Caucasian, and 30.9% African American; M age = 20.01, SD = 2.23) who reported at least 1 heavy drinking episode in the past month (M = 4.01 episodes). Most participants (62%) reported recent marijuana use (M = 12.22 days of past-month use). After completing a baseline assessment and an individual 30-min alcohol-focused BMI, participants were randomized to either the 30-min SFAS session or an education control session. A series of mixed model intent-to-treat analyses revealed that both groups reported drinking reductions and that participants in the BMI + SFAS group reported fewer days using marijuana at the 6-month follow-up. These results do not support the incremental efficacy of the briefer SFAS for reducing drinking but suggest that it may improve marijuana outcomes. Future research is needed to identify the ideal length and timing of the SFAS supplement to BMIs.


Small size yet big action: a simple sulfate anion templated a discrete 78-nuclearity silver sulfur nanocluster with a multishell structure.
A discrete 78-nucleus silver-sulfur nanocluster with a sulfate-centered multishell structure was isolated and characterized. Its crystal structure revealed 18 and 60 Ag atoms in the inner and outer shell, respectively. The inner shell of 18-nuclearity Ag atoms is a very rare convex polyhedron featuring an elongated triangular orthobicupola. The incorporation of a sulfate anion and multishell arrangement in the nanocluster led to a dramatic decrease in the band gap (Eg = 1.40 eV). Our study showed that simple anions can also induce the formation of high-nuclearity silver clusters with excellent optical properties.


[Reabilitation patients with intraarticular fractures of the tibial proximal end].
The works is devoted to guestions of optimization results of surgical treatment of patients with intraarticular fractures of the tibial proximal end. Active and passive mobilization of knee joint was carried out from the first days after operation. As of the result use of improved and developt systems for diagnosis and surgical treatment of 136 patients with intra-articulare fractures of the proximal tibia end the specific weight positive immediate results has come up to 93%, that of long-term results--to 89%.


A Decaheme Cytochrome as a Molecular Electron Conduit in Dye-Sensitized Photoanodes.
In nature, charge recombination in light-harvesting reaction centers is minimized by efficient charge separation. Here, it is aimed to mimic this by coupling dye-sensitized TiO2 nanocrystals to a decaheme protein, MtrC from Shewanella oneidensis MR-1, where the 10 hemes of MtrC form a ≈7-nm-long molecular wire between the TiO2 and the underlying electrode. The system is assembled by forming a densely packed MtrC film on an ultra-flat gold electrode, followed by the adsorption of approximately 7 nm TiO2 nanocrystals that are modified with a phosphonated bipyridine Ru(II) dye (RuP). The step-by-step construction of the MtrC/TiO2 system is monitored with (photo)electrochemistry, quartz-crystal microbalance with dissipation (QCM-D), and atomic force microscopy (AFM). Photocurrents are dependent on the redox state of the MtrC, confirming that electrons are transferred from the TiO2 nanocrystals to the surface via the MtrC conduit. In other words, in these TiO2/MtrC hybrid photodiodes, MtrC traps the conduction-band electrons from TiO2 before transferring them to the electrode, creating a photobioelectrochemical system in which a redox protein is used to mimic the efficient charge separation found in biological photosystems.


Perception of texture by vision and touch: multidimensionality and intersensory integration.
A series of six experiments offers converging evidence that there is no fixed dominance hierarchy for the perception of textured patterns, and in doing so, highlights the importance of recognizing the multidimensionality of texture perception. The relative bias between vision and touch was reversed or considerably altered using both discrepancy and nondiscrepancy paradigms. This shift was achieved merely by directing observers to judge different dimensions of the same textured surface. Experiments 1, 4, and 5 showed relatively strong emphasis on visual as opposed to tactual cues regarding the spatial density of raised dot patterns. In contrast, Experiments 2, 3, and 6 demonstrated considerably greater emphasis on the tactual as opposed to visual cues when observers were instructed to judge the roughness of the same surfaces. The results of the experiments were discussed in terms of a modality appropriateness interpretation of intersensory bias. A weighted averaging model appeared to describe the nature of the intersensory integration process for both spatial density and roughness perception.


Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths.
A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants. The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens.


Barriers Influencing Linkage to Hypertension Care in Kenya: Qualitative Analysis from the LARK Hypertension Study.
Hypertension, the leading global risk factor for mortality, is characterized by low treatment and control rates in low- and middle-income countries. Poor linkage to hypertension care contributes to poor outcomes for patients. However, specific factors influencing linkage to hypertension care are not well known. To evaluate factors influencing linkage to hypertension care in rural western Kenya. Qualitative research study using a modified Health Belief Model that incorporates the impact of emotional and environmental factors on behavior. Mabaraza (traditional community assembly) participants (n = 242) responded to an open invitation to residents in their respective communities. Focus groups, formed by purposive sampling, consisted of hypertensive individuals, at-large community members, and community health workers (n = 169). We performed content analysis of the transcripts with NVivo 10 software, using both deductive and inductive codes. We used a two-round Delphi method to rank the barriers identified in the content analysis. We selected factors using triangulation of frequency of codes and themes from the transcripts, in addition to the results of the Delphi exercise. Sociodemographic characteristics of participants were summarized using descriptive statistics. We identified 27 barriers to linkage to hypertension care, grouped into individual (cognitive and emotional) and environmental factors. Cognitive factors included the asymptomatic nature of hypertension and limited information. Emotional factors included fear of being a burden to the family and fear of being screened for stigmatized diseases such as HIV. Environmental factors were divided into physical (e.g. distance), socioeconomic (e.g. poverty), and health system factors (e.g. popularity of alternative therapies). The Delphi results were generally consistent with the findings from the content analysis. Individual and environmental factors are barriers to linkage to hypertension care in rural western Kenya. Our analysis provides new insights and methodological approaches that may be relevant to other low-resource settings worldwide.


Chronic pulmonary aspergillosis: prevalence, favouring pulmonary diseases and prognosis.
Chronic pulmonary aspergillosis (CPA) is an emerging disease in patients with common chronic pulmonary diseases (CPDs). While its prevalence is linked to tuberculosis (TB) in endemic countries, epidemiological and prognostic data are lacking in low TB incidence countries. The aim of this study was to describe these features in CPA patients hospitalised in France between 2009 and 2018.We estimated the prevalence and mortality of hospitalised CPA patients using the French nationwide administrative hospital database. We also assessed the association with CPD, thoracic interventions and malnutrition.From 2009 to 2018, 17 290 patients were hospitalised in France for CPA, with an increasing prevalence during this period. Most patients were male (63.5%) with a median age of 65 years at CPA diagnosis, living in farming regions and large cities. The proportion of underlying chronic obstructive pulmonary disease (COPD) and emphysema during the previous 5 years was 44% and 22%, respectively, whereas it was only 3% for both TB and non-TB mycobacterial (NTM) infections. The mortality rates during the first hospitalisation, at 1 year and at 5 years were 17%, 32% and 45%, respectively. In multivariate analysis, mortality rates were increased in patients aged >65 years, male patients and patients with malnutrition, diabetes or lung cancer history. The risk of mortality in patients with COPD or emphysema was higher than in those with previous mycobacterial lung infection.In France, CPA is an emerging infection commonly associated with non-mycobacterial CPD. This shift in the distribution profile of underlying CPD will likely worsen CPA mortality.


ADP-ribosylation of cyclophilin A by Pseudomonas aeruginosa exoenzyme S.
The virulence of the opportunistic pathogen Pseudomonas aeruginosa (Pa) is in part mediated by the type III secretion (TTS) of bacterial proteins into eukaryotic hosts. Exoenzyme S (ExoS) is a bifunctional Pa TTS effector protein, with GTPase-activating (GAP) and ADP-ribosyltransferase (ADPRT) activities. Known cellular substrates of TTS-translocated ExoS (TTS-ExoS) ADPRT activity include proteins in the Ras superfamily and ERM family proteins. This study describes the ADP-ribosylation of a non-G-protein substrate of TTS-ExoS, cyclophilin A (CpA), a peptidyl-prolyl isomerase (PPIase). Four novel 17 kDa proteins (pI 6.5-6.8) were recognized in a proteomic screen of lysates of human epithelial cells that had been exposed to ExoS-producing Pa, but not an isogenic non-ExoS producing strain. The proteins were identified as isoforms of CpA using MALDI-TOF mass spectrometry and confirmed by Western blotting. Mutagenesis analysis identified arginine 55 and 69 of CpA as sites of ExoS ADP-ribosylation. Examination of the effect of ExoS ADP-ribosylation on CpA function found a moderate (19%) decrease in prolyl isomerization of a Xaa-Pro containing peptides. In comparison, GST-CpA co-immunoprecipitation studies found ExoS ADP-ribosylation of CpA to efficiently inhibit CpA binding to calcineurin/PP2B phosphatase. Our results support that ExoS ADP-ribosylates and affects the function of the cytosolic protein, CpA, with the predominant functional effect relating to interference of CpA-cellular protein interactions.


SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism.
Tumors frequently develop resistance to cisplatin, a platinum drug used as a cornerstone of present-day chemotherapy regimens, significantly decreasing its usefulness in the clinic. Although it is known that cisplatin-resistant (CP-r) cancer cells commonly grow more slowly and exhibit reduced uptake of various compounds, including nutrients, the effect of tumor metabolism on cisplatin resistance is unclear. It was found that in CP-r cells, uptake of 2-deoxyglucose was reduced due to dysfunction and altered morphology of mitochondria compared with cisplatin-sensitive parental cancer cells. The CP-r cells overexpressed SIRT1, a histone deacetylase that plays a central role in DNA damage response and transcriptional silencing. Incubation of drug-sensitive cells in low glucose medium induced the expression of SIRT1 and increased cellular resistance to cisplatin. Reduced SIRT1 expression by a SIRT1 SMART small interfering RNA duplex sensitized the >20-fold resistant CP-r cells to cisplatin treatment 1.5- to 2-fold, and SIRT1 overexpression by SIRT1 cDNA transfection increased cisplatin resistance in cisplatin-sensitive cells by 2- to 3-fold. Our findings therefore suggest that reduced glucose use and altered mitochondrial metabolism mediated by SIRT1 is one of several alterations that contribute to cellular resistance to cisplatin.


A review of the epidemiological methods used to investigate the health impacts of air pollution around major industrial areas.
We performed a literature review to investigate how epidemiological studies have been used to assess the health consequences of living in the vicinity of industries. 77 papers on the chronic effects of air pollution around major industrial areas were reviewed. Major health themes were cancers (27 studies), morbidity (25 studies), mortality (7 studies), and birth outcome (7 studies). Only 3 studies investigated mental health. While studies were available from many different countries, a majority of papers came from the United Kingdom, Italy, and Spain. Several studies were motivated by concerns from the population or by previous observations of an overincidence of cases. Geographical ecological designs were largely used for studying cancer and mortality, including statistical designs to quantify a relationship between health indicators and exposure. Morbidity was frequently investigated through cross-sectional surveys on the respiratory health of children. Few multicenter studies were performed. In a majority of papers, exposed areas were defined based on the distance to the industry and were located from <2 km to >20 km from the plants. Improving the exposure assessment would be an asset to future studies. Criteria to include industries in multicenter studies should be defined.


Aggressive behaviour among drug-using women from Cape Town, South Africa: ethnicity, heavy alcohol use, methamphetamine and intimate partner violence.
Women have generally been found to be the victims of violence, but scant attention has been paid to the characteristics of women who perpetrate aggression and violence. In South Africa, violence is a prevalent societal issue, especially in the Western Cape. This study aimed at identifying factors that were associated with aggression among a sample of 720 substance-using women. We conducted multivariate logistic regression to identify factors that are significantly associated with these behaviours. Ethnicity (Wald Χ2 = 17.07(2), p < 0.01) and heavy drinking (Wald Χ2 = 6.60 (2), p = 0.01) were significantly related to verbal aggression, methamphetamine use was significantly related to physical (Wald Χ2 = 2.73 (2), p = 0.01) and weapon aggression (Wald Χ2 = 7.94 (2), p < 0.01) and intimate partner violence was significantly related to verbal (Wald Χ2 = 12.43 (2), p < 0.01) and physical aggression (Wald Χ2 = 25.92 (2), p < 0.01). The findings show high levels of aggression among this sample, and highlight the need for interventions that address methamphetamine, heavy drinking and intimate partner violence among vulnerable substance-using women.


Effects of thoracic kinesio taping on pulmonary functions, respiratory muscle strength and functional capacity in patients with chronic obstructive pulmonary disease: A randomized controlled trial.
Respiratory and peripheral muscle dysfunctions seen in Chronic Obstructive Pulmonary Disease (COPD) cause ventilatory limitation, dyspnea and inactivity, which then result in a reduction in functional capacity. Kinesio Taping (KT) is a rehabilitative technique performed by the cutaneous application of a special elastic tape, thus increasing muscle activation and blood circulation. To investigate the effects of KT application that was applied on respiratory muscles to improve pulmonary function, respiratory muscle strength and functional capacity in patients with COPD. In total, 27 COPD patients (16 in KT group, 11 in control group) were included. Thoracic KT was applied to facilitate the respiratory muscles along the subcostal area for KT group. Deep breathing exercises were applied to both groups. Interventions were done 2 days a week, through 6 weeks. Pulmonary function and maximal respiratory mouth pressures were measured with a spirometer. Severity of dyspnea and fatigue were assessed with Modified Medical Research Council dyspnea scale and Modified Borg Scale, respectively. Functional capacity was evaluated using six-minute walk test. Percentage predicted of forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF) value, percentage predicted of peak expiratory flow (PEF%) and walking distance were significantly increased in KT group (p = 0.038, p = 0.011, p = 0.013, p = 0.004, respectively). The severity of dyspnea and fatigue were reduced in KT group (p < 0.05). There was no significant change for other variables in-group and between-group analyses (p > 0.05). Thoracic KT may be beneficial for improving pulmonary function and functional capacity in patients with COPD.


Crystal structure of beta-luffin, a ribosome-inactivating protein, at 2.0 A resolution.
The crystal structure of beta-luffin at 2.0 A resolution was solved by the molecular-replacement method using polyalanyl trichosanthin as the search model. The structure was refined with CNS1.1, giving R(work) = 0.162 and R(free) = 0.204. The r.m.s.d.s of the bond lengths and bond angles are 0.008 A and 1.3 degrees, respectively. The overall structure is similar to those of other type I RIPs. Three N-acetylglucosamine (Nag) molecules are linked to residues Asn2, Asn78 and Asn85 of the protein.


Endothelin antagonists for hypertension and renal disease.
The endothelin system has been implicated in the pathogenesis of arterial hypertension and renal disorders. Endothelin-1, the predominant isoform of the endothelin peptide family, regulates vasoconstriction and cell proliferation in tissues both within and outside the cardiovascular system through activation of Gi-protein-coupled ET(A) and ET(B) receptors. Endothelin synthesis is regulated through autocrine mechanisms by endothelin converting enzymes, chymases, and non-endothelin converting enzyme metalloproteases. In-vitro experiments have demonstrated that endothelin-1 stimulates growth in vascular smooth muscle and in the kidney. Recent studies indicate that endothelin mRNA and protein are also increased in vivo in the kidney and vasculature in hypertension and renal disease. Studies using molecular or pharmacological inhibition of the endothelin system demonstrate that endothelin-1 contributes to the functional and structural changes associated with arterial hypertension and glomerulosclerosis, and that these effects are only in part dependent on blood pressure. These experimental studies and first clinical trials suggest that endothelin antagonists may offer therapeutic potential to reduce end-organ damage in diseases associated with vascular remodeling and renal injury.


The reliability of evidence about psychiatric diagnosis after serious crime: part II. Agreement between experts and treating practitioners.
In this second part of our study, we examined the extent of agreement between treating practitioners and expert witnesses on psychiatric diagnoses in evidence presented in criminal proceedings. We found good agreement on diagnoses of acquired brain injury, schizophrenia-spectrum psychoses, depressive disorders, intellectual disability, substance abuse, and personality disorders; fair agreement on substance-induced psychotic disorder; and poor agreement on the presence of anxiety disorders. A proportion of defendants with diagnosis by experts of substance-induced psychotic disorder also had a diagnosis of schizophrenia-spectrum psychosis by treating practitioners. Treating practitioners and experts engaged by the prosecution rarely made the diagnosis of post-traumatic stress disorder. Overall, there was moderate agreement between experts and treating practitioners on the principal Axis I disorder, and the evidence for psychiatric diagnoses presented by treating practitioners in criminal cases was found to be generally reliable.


Downregulation of mitogen-activated protein kinases in human colon cancers.
Activation of the mitogen-activated protein kinases (MAPKs) appears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not been clearly defined. The purpose of our study was to determine whether MAPK activity and protein levels were increased in colorectal cancers. Colorectal cancers and adjacent normal mucosa from 21 patients were extracted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase assays, respectively. In addition, changes in myelin basic protein (MBP) kinase activity and autophosphorylation were determined by in-gel kinase assays. The activities of ERK1/2, JNK1 and p38 were downregulated in the majority of cancers; ERK3 kinase activity was increased in 10 of 21 cancers. The presence of proteins displaying increased MBP phosphorylation and autophosphorylation was identified specifically in the cancers by in-gel kinase assays. Our findings demonstrate that the constitutive activation of ERK1/2, JNK1 and p38 is not a feature of colorectal cancers. Moreover, our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.


Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.
We have previously shown that the human 70-kilodalton heat shock protein gene (hsp70) is induced by the adenovirus E1A gene product and during the S-G2 phase of the cell cycle. In this study, we investigated the effect of E1A on the expression of other human hsp genes. A gene encoding one form of the hsp89 protein (hsp89 alpha) was activated during an adenovirus infection with kinetics similar to those of activation of hsp70. The induction required a functional E1A gene. However, the hsp89 transcript was not cell cycle regulated. Genes encoding another form of hsp89 and the hsp27 protein were not induced by E1A or during the cell cycle. Further examination of hsp70 expression revealed a greater complexity than previously seen. S1 nuclease analysis using an hsp70 cDNA as well as a distinct hsp70 genomic clone demonstrated three related hsp70 transcripts; two were induced by E1A, and one was not. Both of the E1A-inducible genes were regulated during the cell cycle. All three were induced by heat shock. These results suggest common aspects of control among certain members of this family of cellular genes distinct from heat shock control. Finally, using viruses that express the individual E1A proteins, we found that the hsp70 gene is induced by the 12S and the 13S E1A products. The efficiency of induction by the 12S product was somewhat less than that by the 13S product but only by a factor of less than 2. This is in contrast to the induction of early viral genes, for which the 13S product is considerably more efficient than the 12S product.


Development of the Dementia Quality of Life questionnaire (D-QOL): UK version.
The importance of using quality of life measures for clinical practice and research in dementia is well established. Quality of life being people's perception of their position in life in context of their culture, hence the need for developing culturally sensitive quality of life measures. This study aimed at producing the UK version of the US Dementia-Quality of Life (D-QOL), a validated instrument for measuring quality of life in people with mild to moderate dementia. The study was conducted in three stages--adaptation, piloting and validation. In the adaptation stage, the US D-QOL was translated by a panel comprising lay people and researchers. In the piloting stage the draft was tested by administering it to fifteen patients with dementia and their feedback on acceptability, relevance and clarity. In the validation stage, 36 patients with mild to moderate dementia were administered UK D-QOL on two occasions with an interval of two weeks. The results showed that the UK version of D-QOL has comparable psychometric properties to the US version. We conclude that the UK version of D-QOL is a reliable and valid measure of quality of life in UK population with mild to moderate dementia.


Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins on Human Energy Expenditure.
Skeletal muscle endocannabinoids and sphingolipids (particularly sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP) in humans. The endocannabinoid system may increase sphingolipid synthesis via cannabinoid receptor-1. To investigate in human skeletal muscle whether endocannabinoids are responsible for the effect of sphingomyelins on SLEEP. Muscle endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)], endocannabinoid congeners [oleoylethanolamide (OEA), palmitoylethanolamide (PEA)], and sphingomyelin content were measured with liquid chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect calorimeter. Mediation analyses tested whether the inverse associations between sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related OEA and PEA. Inpatient study. Fifty-three Native Americans who are overweight. SLEEP. AEA (r = 0.45, P = 0.001), 2-AG (r = 0.47, P = 0.0004), OEA (r = 0.27, P = 0.05), and PEA (r = 0.53, P < 0.0001) concentrations were associated with the total sphingomyelin content. AEA, OEA, and PEA correlated with specific sphingomyelins (SM18:1/23:0, SM18:1/23:1, and SM18:1/26:1) previously reported to be determinants of SLEEP in Native Americans (all r > 0.31, all P < 0.03). Up to half of the negative effect of these specific sphingomyelins on SLEEP was accounted for by AEA (all P < 0.04), rendering the direct effect by sphingomyelins per se on SLEEP negligible (P > 0.05). In skeletal muscle, AEA is responsible for the sphingomyelin effect on SLEEP, indicating that endocannabinoids and sphingomyelins may jointly reduce human whole-body energy metabolism.


CC Chemokine Receptor 2-Targeting Copper Nanoparticles for Positron Emission Tomography-Guided Delivery of Gemcitabine for Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with dire prognosis due to aggressive biology, lack of effective tools for diagnosis at an early stage, and limited treatment options. Detection of PDAC using conventional radiographic imaging is limited by the dense, hypovascular stromal component and relatively scarce neoplastic cells within the tumor microenvironment (TME). The CC motif chemokine 2 (CCL2) and its cognate receptor CCR2 (CCL2/CCR2) axis are critical in fostering and maintaining this kind of TME by recruiting immunosuppressive myeloid cells such as the tumor-associated macrophages, thereby presenting an opportunity to exploit this axis for both diagnostic and therapeutic purposes. We engineered CCR2-targeting ultrasmall copper nanoparticles (Cu@CuOx) as nanovehicles not only for targeted positron emission tomography imaging by intrinsic radiolabeling with 64Cu but also for loading and delivery of the chemotherapy drug gemcitabine to PDAC. This 64Cu-radiolabeled nanovehicle allowed sensitive and accurate detection of PDAC malignancy in autochthonous genetically engineered mouse models. The ultrasmall Cu@CuOx showed efficient renal clearance, favorable pharmacokinetics, and minimal in vivo toxicity. Systemic administration of gemcitabine-loaded Cu@CuOx effectively suppressed the progression of PDAC tumors in a syngeneic xenograft mouse model and prolonged survival. These CCR2-targeted ultrasmall nanoparticles offer a promising image-guided therapeutic agent and show great potential for translation.


Procalcitonin Clearance, CD64, and HLA-DR as Predictors of Outcome in Febrile Neutropenic Children With Lymphoreticular Malignancies.
Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy. There has been a lot of improvement in supportive care in FN that has drastically reduced the infection-related mortality in these patients. The focus now is on reducing infection-related morbidity, healthcare costs and optimizing the quality of life of the child as well as their family during these episodes. In this study, biomarkers were studied as predictors of outcome so that outcome can be predicted earlier, and treatment modified accordingly. To measure procalcitonin levels (at baseline and day 3), procalcitonin clearance, neutrophil CD64 expression levels (at baseline) and monocyte HLA-DR expression levels (at baseline), and their correlation with outcome. Tertiary care hospital. Cross-sectional observational study. Sixty-five episodes of FN in children below 12 years with lymphoreticular malignancies. Children receiving antibacterial and/or antifungal treatment within the last 7 days were excluded from the study. The subjects recruited into the study had undergone complete clinical and laboratory evaluation as per hospital protocol. Procalcitonin (day 0 and 3), neutrophil CD64 expression, and monocytic HLA-DR expression levels were measured in these patients. Sixty-five episodes of FN were studied in children with lymphoreticular malignancy. It was found that procalcitonin and HLA-DR are very good markers of outcome, whereas CD64 although a good marker, was inferior to procalcitonin and HLA-DR in predicting outcome. Procalcitonin clearance was found to be superior to single value of procalcitonin. Furthermore, procalcitonin on day 3 was found to be a better predictor of outcome compared with its baseline value. Also, it was found that procalcitonin and HLA-DR had a significant correlation with baseline C-reactive protein levels. On the basis of the findings of the study we suggest that serial monitoring of procalcitonin levels be used in febrile neutropenic children with cancer. Procalcitonin levels on day 3 alone can be offered in resource poor setting. The role of HLA-DR and CD64 also seems promising and needs to be further explored in larger multicentric studies.


Mindfulness-based stress reduction as a novel treatment for interstitial cystitis/bladder pain syndrome: a randomized controlled trial.
Mindfulness-based stress reduction (MBSR) is a standardized meditation program that may be an effective therapy for interstitial cystitis/bladder pain syndrome (IC/BPS), a condition exacerbated by stress. The aims of this study were to explore whether MBSR improved IC/BPS symptoms and the feasibility/acceptability of MSBR among women with IC/BPS. This randomized controlled trial included women with IC/BPS undergoing first- or second-line therapies. Women were randomized to continuation of usual care (UC) or an 8-week MBSR class + usual care (MBSR). Participants completed baseline and 8-week post-treatment questionnaires, including the O'Leary-Sant Symptom Problem Index (OSPI), the visual analog pain scale (VAS), the Short Form Health Survey (SF-12), the Female Sexual Function Index (FSFI), and the Pain Self-Efficacy Questionnaire (PSEQ). The Global Response Assessment (GRA) was completed post-treatment. Analyses were performed using Student's t test, Chi-squared, and MANOVA where appropriate. Eleven women were randomized to UC and 9 to MBSR, without differences in group characteristics. More MBSR participants' symptoms were improved on the GRA (7 out of 8 [87.5 %] vs 4 out of 11 [36.4 %], p = 0.03). The MBSR group showed greater improvement in the OSPI total (p = 0.0498) and problem scores (p = 0.036); the OSPI symptom score change did not differ. PSEQ scores improved in MBSR compared with UC (p = 0.035). VAS, SF-12, and FSFI change did not differ between groups. Eighty-six percent of MBSR participants felt more empowered to control symptoms, and all participants planned to continue MBSR. This trial provides initial evidence that MBSR is a promising adjunctive therapy for IC/BPS. Its benefit may arise from patients' empowerment and ability to cope with symptoms.


Effects of diet on the development of Schistosoma mansoni in Biomphalaria glabrata and on the neutral lipid content of the digestive gland-gonad complex of the snail.
In a previous study, when the snail Biomphalaria glabrata was infected with Schistosoma mansoni and maintained on a diet of hen's egg yolk, it produced fully developed cercariae in about one-half the time taken by snails fed Romaine lettuce. Increased lipids were also noted in the snails fed the yolk diet. The purpose of the present study was to further investigate nutritional effects of a high-lipid diet on larval schistosome development and to reexamine the time to cercarial patency in infected snails maintained on either the yolk or lettuce diet and to use high-performance thin-layer chromatography (HPTLC) to analyze the neutral lipids in the digestive gland-gonad complex (DGG) of snails maintained on both diets. Infected snails maintained at 26 C and fed either diet produced fully developed cercariae by 4 wk postinfection (PI). Likewise, infected snails maintained at 23 C and fed either diet produced fully developed cercariae by 6 wk PI. The contention that the yolk diet enhanced the time to cercarial patency was not confirmed. The HPTLC analysis of neutral lipids showed that the DGG of infected snails fed the yolk diet contained significantly greater amounts of free sterols and cholesteryl esters but not triacylglycerols than that of the infected snails fed the lettuce diet.


Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study.
The use of proactive genetic screening for disease prevention and early detection is not yet widespread. Professional practice guidelines from the American College of Medical Genetics and Genomics (ACMG) have encouraged reporting pathogenic variants that confer personal risk for actionable monogenic hereditary disorders, but only as secondary findings from exome or genome sequencing. The Centers for Disease Control and Prevention (CDC) recognizes the potential public health impact of three Tier 1 actionable disorders. Here, we report results of a large multi-center cohort study to determine the yield and potential value of screening healthy individuals for variants associated with a broad range of actionable monogenic disorders, outside the context of secondary findings. Eligible adults were offered a proactive genetic screening test by health care providers in a variety of clinical settings. The screening panel based on next-generation sequencing contained up to 147 genes associated with monogenic disorders within cancer, cardiovascular, and other important clinical areas. Sequence and intragenic copy number variants classified as pathogenic, likely pathogenic, pathogenic (low penetrance), or increased risk allele were considered clinically significant and reported. Results were analyzed by clinical area and severity/burden of disease using chi-square tests without Yates' correction. Among 10,478 unrelated adults screened, 1619 (15.5%) had results indicating personal risk for an actionable monogenic disorder. In contrast, only 3.1 to 5.2% had clinically reportable variants in genes suggested by the ACMG version 2 secondary findings list to be examined during exome or genome sequencing, and 2% had reportable variants related to CDC Tier 1 conditions. Among patients, 649 (6.2%) were positive for a genotype associated with a disease of high severity/burden, including hereditary cancer syndromes, cardiovascular disorders, or malignant hyperthermia susceptibility. This is one of the first real-world examples of specialists and primary care providers using genetic screening with a multi-gene panel to identify health risks in their patients. Nearly one in six individuals screened for variants associated with actionable monogenic disorders had clinically significant results. These findings provide a foundation for further studies to assess the role of genetic screening as part of regular medical care.


Tumor Necrosis Factor-α Suppresses Activation of Sustained Potassium Currents in Rat Small Diameter Sensory Neurons.
Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, produces pain and hyperalgesia by activating and/or sensitizing nociceptive sensory neurons. In the present study, using whole-cell patch clamp techniques, the regulation of potassium currents by TNF-α was examined in acutely dissociated small dorsal root ganglion neurons. We found that acute application of TNF-α inhibited, in a dose-dependent manner, the non-inactivating sustained potassium current without changing the rapidly inactivating transient current or the kinetics of steady-state inactivation. The effects of TNF-α on potassium currents were similar to that of prostaglandin E2 as reported previously and also demonstrated in the current study. Furthermore, indomethacin, a potent inhibitor for both cyclo-oxygenase (COX) -1 and COX-2, completely blocked the effect of TNF-α on potassium currents. These results suggest that TNF-α may sensitize or activate sensory neurons by suppressing the sustained potassium current in nociceptive DRG neurons, possibly via stimulating the synthesis/release of endogenous prostaglandins.


The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study.
Recent studies have demonstrated the potential of microRNAs (miRNA) as biomarkers in various cardiovascular disorders. The aim of the present study was to quantitatively evaluate the expression levels of miRNAs in patients with chronic congestive heart failure (CHF) in order to identify differential expression profiles as biomarkers with prognostic values. The study included 20 clinically stable [New York Heart Association (NYHA) II] and 22 decompensated (NYHA III and IV) CHF patients and 15 healthy controls. miRNA profiling was performed using a microarray method. Dysregulated miRNAs were evaluated for their biomarker potential. Microarray profiling revealed an increase in the expression of miR-21, miR-650, miR-744, miR-516-5p, miR-1292, miR-182, miR-1228, miR-595, miR-663b, miR-1296, miR-1825, miR-299-3p, miR-662 miR-122, miR-3148 and miR-518e and a decrease in the expression of miR-129-3p, miR-3155, miR-3175, miR-583, miR-568, miR-30d, miR-200a-star, miR-1979, miR-371-3p, miR-155-star and miR-502-5p in sera of CHF patients. The prognostic value of miR-182 [area under the curve (AUC) 0.695] was found to be superior to pro-brain type natriuretic peptide (NT-proBNP; AUC 0.350) and high-sensitivity C-reactive protein (hs-CRP) (AUC 0.475) by receiver operator characteristic (ROC) analysis. Cox regression analysis showed that miR-182 could predict cardiovascular mortality (P = 0.032). We demonstrated the increased expression levels of circulating miRNAs in CHF as compared with controls. Moreover, miR-182 was found to be a potential prognostic marker in CHF.


Deletion analysis of the Clostridium perfringens enterotoxin.
To further our knowledge of the structure-function relationship and mechanism of action of the Clostridium perfringens enterotoxin (CPE), a series of recombinant CPE (rCPE) species containing N- and C-terminal CPE deletion fragments was constructed by recombinant DNA approaches. Each rCPE species was characterized for its ability to complete the first four early steps in the action of CPE, putatively ordered as specific binding, a postbinding physical change to bound CPE, large-complex formation, and induction of alterations in small-molecule membrane permeability. These studies demonstrated that (i) at least 44 amino acids can be removed from the N terminus of CPE without loss of cytotoxicity, (ii) removal of the first 53 amino acids from the N terminus of CPE produces a fragment that appears to be noncytotoxic because it cannot undergo the post-binding physical change step in CPE action, (iii) removal of as few as five amino acids from the C terminus of CPE produces a noncytotoxic fragment lacking receptor binding activity, and (iv) a fragment lacking the first 44 N-terminal amino acids of native CPE formed twice as much large complex and was twice as cytotoxic as native CPE. From these structure-function results, it appears that the minimum-size cytotoxic CPE fragment comprises approximately residues 45 to 319 of native CPE. Results from these deletion fragment studies have also contributed to our understanding of CPE action by (i) independently supporting previous suggestions that binding, the postbinding physical change step, and large-complex formation represent important steps in CPE cytotoxicity and (ii) providing independent evidence confirming the putative sequential order of these early events in CPE action.


Enantioselective Tandem Cyclization of Alkyne-Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis.
Reported is the enantioselective synthesis of tetracyclic indolines using silver(I)/chiral phosphoric acid catalysis. A variety of alkyne-tethered indoles are suitable for this process. Mechanistic studies suggest that the in situ generated silver(I) chiral phosphate activates both the alkyne and the indole nucleophile in the initial cyclization step through an intermolecular hydrogen bond and the phosphate anion promotes proton transfer. In addition, further modifications of the cyclization products enabled stereochemistry-function studies of a series of bioactive indolines.


Mucociliary function of the eustachian tube: assessment by saccharin test in patients with dry perforations of the tympanic membrane.
The mucociliary function of the Eustachian tube was assess in 44 patients with dry perforations of the lympanic membrane by means of the saccharin test. A saccharin crystal was placed on the mucous membrane of the middle ear as close to the orifice of the Eustachian tube as possible, and the time taken for the patient to taste the saccharin was measured. The function of the Eustachian tube was also assessed by means of the aspiration test and by the Valsalva maneuver. No relationship was found between the results of the saccharin test, aspiration test, and the Valsalva maneuver. However, a correlation seems to exist between the hearing improvement obtained as determined by the postoperative air-bone gap, the positive or negative results of the saccharin test, and (in cases with positive saccharin test) the saccharin perception time.


Real-time synthesis of bleeding for virtual hysteroscopy.
In this paper we present a method for simulating bleeding in a virtual reality hysteroscopic simulator for surgical training. The simulated bleeding is required to be visually appealing while at the same time instantaneously responsive to any feedback that the surgeon may be conducing to the virtual environment. In order to meet these real-time requirements, we have based the simulation on graphical fluid solvers. These solvers primarily work best over a 2D domain. For correct visualization in the hysteroscopic simulator, it is, however, necessary to perform the simulation fully in 3D. Therefore in this paper we also present the design modifications for 3D graphical fluid solving and show how to use parallelization to maintain real-time behavior. We also discuss how the incorporation of massless particles into the simulation can improve the visual quality of the results by limiting numerical dissipation effects.


Experimental verification of a mathematical model for pelleted growth of Streptomyces coelicolor A3(2) in submerged batch culture.
A published mathematical model for growth of pellets of filamentous microorganisms has been tested by comparison of model predictions with experimental data on growth of Streptomyces coelicolor in liquid batch culture. The original model considered the classification of pellets into a range of size classes. Growth resulted in movement of pellets to classes of increasing size, while shear forces produced mycelial fragments which entered the smallest size class, from which they grew to form further pellets. This model did not correctly describe changes in pellet size distributions during growth and was therefore modified in two ways. In the first, new pellets were assumed to be formed by the break-up, by shear forces, of existing pellets into two pellets of equal size, rather than removal of small hyphal fragments from the pellet surface. The second modification assumed that the outer shell of active mycelial biomass had a density less than 1 g cm-3 and that hyphal density within this shell decreased with distance from the pellet centre. The modified model generated predictions which agreed closely with experimental data on biomass concentration, pellet size distribution, pellet number and pellet radius during batch growth, thereby supporting the assumptions on which the model was based. The model did not accurately describe final biomass concentration, through lack of consideration of autolysis of mycelia at the centre of larger pellets in which growth was limited by diffusion of nutrients. Attempts to incorporate autolysis into the model improved prediction of biomass concentration but were not based on sound biological assumptions and increased the complexity of the model. Further experimental work is required for accurate description of the effects of autolysis on pellet growth.


A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling.
As in mammals, the Drosophila EGF receptor controls many aspects of growth and development. The rate limiting component of Drosophila Egfr signaling is Rhomboid, a seven transmembrane domain protein, whose expression prefigures Egfr signaling. Little is known about the molecular mechanism of Rhomboid function but genetic evidence suggests that it controls the activation of the ligand Spitz, a TGFalpha-like factor. Spitz/Egfr signaling regulates cell determination in the eye but here there is no apparent function for Rhomboid, an observation that casts doubt on this prevailing model of Rhomboid function. We describe our identification of six new rhomboid-like genes in Drosophila, and a large family of related genes present in organisms as diverse as bacteria and mammals; a human rhomboid homolog has also recently been described. Drosophila rhomboid-3 corresponds to the roughoid mutation; it cooperates with rhomboid-1 to control Egfr signaling in the eye, thereby solving the puzzle of the apparent lack of Rhomboid-1 function there. Rhomboid-1 and Roughoid/Rhomboid-3 act in the signal-emitting not signal-receiving cell, supporting the idea that Spitz activation is regulated by Rhomboid-like molecules.


Comparison of extracted teeth and simulated resin blocks on apical canal transportation.
We aimed to compare apical canal transportation of extracted teeth and two types of simulated resin blocks. Mesiobuccal root of extracted maxillary molars, high hardness simulated resin blocks (Knoop hardness=40) and low hardness simulated resin blocks (Knoop hardness=22) were prepared with K-files using step-back technique (n=15 canals in each group). Double exposure radiographic technique was used for extracted teeth. Simulated resin blocks were stabilized and scanned before and after preparation. Pre and post-preparation pictures were superimposed and apical transportation was measured. The data were analyzed statistically using ANOVA and Tukey HSD tests. There was no significant difference in apical canal transportation between extracted teeth and high hardness resin blocks (P>0.05). Low hardness resin blocks showed more apical transportation than the other groups (P<0.05). Under the conditions of this study, apical canal transportation for extracted teeth and high hardness simulated resin blocks were similar.


Family Caregivers' Anticipatory Grief: A Conceptual Framework for Understanding Its Multiple Challenges.
The end-of-life trajectory of cancer patients in palliative care (PC) elicits an anticipatory grief (AG) process in family caregivers (FCs). Although widely recognized, AG lacks conceptual clarification. This study aims to qualitatively explore the experience of FCs of patients with terminal cancer to identify the core characteristics and the specific adaptive challenges related to AG in the context of end-of-life caregiving. Data were collected through in-depth semi-structured interviews conducted in a clinical sample of 26 FCs of cancer patients in PC. Findings from thematic analysis suggest that the AG experience is characterized by traumatic distress from being exposed to life-threatening conditions and the separation distress induced by loss anticipation and current relational losses, challenging the FCs to long-term emotional regulation effort demands. These results contribute to the conceptualization of AG and may inform intervention programs for the main challenges the FCs face when adjusting to loss during end-of-life caregiving.


Epidural anesthesia in low-risk obstetrical patients.
The use of epidural anesthesia in obstetrics has increased markedly in the last decade, and some authorities are now stating that epidural block may be the anesthetic method of choice for most women. In spite of this growth in popularity, no studies have been reported that deal with the outcomes of epidural anesthesia in low-risk obstetrical patients, that group of women for whom family physicians are most likely to provide care. A retrospective cohort study of factors associated with epidural anesthesia in a low-risk obstetrical population was performed. Epidural anesthesia was administered by obstetrical anesthesiologists, and patients were monitored by nurses experienced with epidural anesthesia. Although retrospective studies cannot establish cause-and-effect relationships, it was found, when compared with deliveries without epidural anesthesia, that epidural anesthesia deliveries were associated with changes in several parameters of labor and delivery. Although epidural anesthesia was observed to be a very safe procedure, three of the variables (higher use of low forceps, increased use of oxytocin, and greater total costs) may be of some clinical importance and should be considered by both the delivering physician and the patients when choosing obstetrical anesthesia.


Selective prefrontal cortex responses to joint attention in early infancy.
The process by which two people share attention towards the same object or event is called joint attention. Joint attention and the underlying triadic representations between self, other person and object are thought to be unique to humans, supporting teaching, cooperation and language learning. Despite the progress that has been made in understanding the behavioural importance of joint attention during early social development, almost nothing is known about the brain substrate that supports joint attention in the developing infant. We examined responses in five-month-old infants' prefrontal cortex during triadic social interactions using near-infrared spectroscopy. The results demonstrate that, even by the age of five months, infants are sensitive to triadic interactions and, like adults, they recruit a specific brain region localized in left dorsal prefrontal cortex when engaged in joint attention with another person. This suggests that the human infant is neurobiologically prepared for sharing attention with other humans, which may provide the basis for a wide variety of uniquely human social and cultural learning processes.


Disconnected and Hyperactive: A Replication of Sensorimotor Cortex Abnormalities in Patients With Schizophrenia During Proactive Response Inhibition.
Inhibitory failure represents a core dysfunction in patients with schizophrenia (SP), which has predominantly been tested in the literature using reactive (ie, altering behavior after a stimulus) rather than proactive (ie, purposefully changing behavior before a stimulus) response inhibition tasks. The current study replicates/extends our previous findings of SP exhibiting sensorimotor cortex (SMC) hyperactivity and connectivity abnormalities in independent samples of patients and controls. Specifically, 49 clinically well-characterized SP and 54 matched healthy controls (HC) performed a proactive response inhibition task while undergoing functional magnetic resonance imaging and resting-state data collection. Results indicated that the majority of SP (84%) and HC (88%) successfully inhibited all overt motor responses following a cue, eliminating behavioral confounds frequently present in this population. Observations of left SMC hyperactivity during proactive response inhibition, reduced cortical connectivity with left SMC, and increased connectivity between left SMC and ventrolateral thalamus were replicated for SP relative to HC in the current study. Similarly, negative symptoms (eg, motor retardation) were again associated with SMC functional and connectivity abnormalities. In contrast, findings of a negative blood oxygenation level-dependent response in the SMC of HC did not replicate. Collectively, current and previous findings suggest that SMC connectivity abnormalities may be more robust relative to evoked hemodynamic signals during proactive response inhibition. In addition, there is strong support that these SMC abnormalities are a key component of SP pathology, along with dysfunction within other sensory cortices, and may be associated with certain clinical deficits such as negative symptoms.


Mitral valve surgery for ischemic papillary muscle rupture: outcomes from the Japan cardiovascular surgery database.
Ischemic papillary muscle rupture (PMR) is a catastrophic complication following acute myocardial infarction (AMI). We evaluated early outcomes of PMR by using data from the Japan Cardiovascular Surgery Database, a nationwide Japanese registry. We retrospectively analyzed data from 196 patients diagnosed with PMR following AMI in Japan between January 2014 and December 2017. Risk factors for operative mortality and severe complications following mitral valve surgery were analyzed. The 30-day and hospital mortality rates were 20% and 26%, respectively. Chronic hemodialysis, abrupt rupture after AMI, resuscitation before surgery, and preoperative venoarterial extracorporeal membrane oxygenation were associated with mortality. Mitral valve replacement was chosen mainly (90%) for surgical correction of mitral regurgitation in these patients. There was no significant difference in short-term outcomes between mitral valve replacement versus mitral valve repair, despite non-matched characteristics in background between the treatment groups. Concomitant coronary artery bypass grafting had no impact on short-term outcomes. Information derived from the nationwide database of patients with AMI-associated PMR show that PMR is a rare condition in the modern era. However, PMR is a severe disease with a mortality rate as high as 26%. The severity of the condition is associated with the risk for poor outcomes.


Developing a Mental Health Measurement Strategy to Capture Psychological Problems among Lower Caste Adolescent Girls in Rural, South India.
Adolescent girls vulnerable to early marriage and school dropout in rural India may be at elevated risk of psychosocial problems. However, few screening instruments have been culturally adapted and validated to measure this risk. This paper describes the process by which the Primary Health Questionnaire PHQ-9, a screening instrument for depression, was tested for cultural validity as part of the Samata evaluation - an intervention to support low caste adolescent girls in rural south India to attend and complete secondary school and to delay marriage until adulthood. Three focus groups discussions (FGDs) were held with 20 adolescent girls and six outreach workers of the Samata programme in rural north Karnataka, south India. The FGDs were used to explore local expressions of psychosocial problems and to understand the acceptability and appropriateness of PHQ-9 items. A thematic content analysis was conducted on the transcripts of the FGDs. Descriptions of local expressions of psychosocial problems generally matched the items on the PHQ-9. However, not all representations of psychological symptoms were captured by this tool. Persistent worry, loneliness and isolation, and externalised behaviours were also described by participants as common expressions of psychosocial distress. Based on the limitations of translation methods, local stakeholders must be involved in evaluating the cultural appropriateness of mental health screening tools. The current research demonstrates a strategy by which to assess the cultural validity of Western psychiatric instruments with key stakeholders in low- and middle-income settings.


Clinical Scoring Systems in Predicting the Outcomes of Small Bowel Bleeding.
The aim was to assess the clinical Glasgow-Blatchford score (GBS), Rockall score (CRS), and AIMS65 score in predicting outcomes (rebleeding, need for intervention, and length of stay) among patients with small bowel hemorrhage. We conducted a retrospective study of patients with small bowel bleeding (SBB). Rebleeding, need for intervention, and length of stay was investigated by 3 scoring systems. The area under the receiver operator characteristic curve was used to analyze the performance of 3 scoring systems. Among 162 included patients, the scores of rebleeding, intervention, and length of stay ≥10 days groups were higher than no rebleeding, non-intervention, and length of stay <10 days groups, respectively (P < .05). The CRS, GBS, and AIMS65 scoring systems demonstrated statistically significant difference in predicting rebleeding (AUROC 0.693 vs. 0.790 vs. 0.740; all P < .01), intervention (AUROC: 0.726 vs. 0.825 vs. 0.773; all P < .01) and length of stay (AUROC 0.651 vs. 0.631 vs. 0.635; all P < .05). Higher cut-off scores achieved better sensitivity/specificity [rebleeding (CRS > 2, GBS > 7, AIMS65 > 0); need for intervention (CRS > 2, GBS > 7, AIMS65 > 0); length of stay (CRS > 0, GBS > 7, AIMS65 > 1)] in the risk stratification. The GBS system is reliable to be recommended for routine use in predicting rebleeding and the need for intervention for early decision making in patients with SBB. The 3 scoring systems are poorly useful in predicting length of stay.


Clinicopathological Characteristics and Prognostic Factors of Patients with Gastric Cancer Accompanying Neuroendocrine Differentiation (NEDGC).
Gastric carcinoma with neuroendocrine differentiation (NEDGC) is a relatively rare pathologic diagnosis in clinical practice, which has no specific guidelines or treatment recommendations yet. In this study, we aim to investigate the clinicopathological characteristics and prognostic factors of this disease. We retrospectively analyzed clinicopathological data from a series of 82 NEDGC patients who underwent surgery for gastrectomy at Huashan Hospital Fudan University between January 2007 and December 2018. Furthermore, a series of 50 cases were used to analyze 3-year overall survival (OS). Ages of the patients ranged from 26 to 83 years (M:F, 4.8:1). The majority of patients suffered from some symptoms (97.6%), as the most common one was abdominal pain (48.8%). Most of the tumors were ≥5 cm (53.7%), in the lower part of the stomach (47.5%), and with advanced T (87.8% ≥T3) and N (67.1% ≥N1) stage. As to the neuroendocrine markers, Syn showed a slight advantage on sensitivity than CgA (79.3 and 75.6%, respectively). The 3-year OS was 54%. Advanced T stage (≥T3) of the primary tumor, positive lymphovascular invasion (LVI), large tumor size (5.5cm), high neutrophil-to-lymphocyte ratio (NLR, 2.51), and low prealbumin level (173.87 mg/L) were associated with inferior OS based on the univariate analysis. Low preoperative hemoglobin level (113.87g/L), laparoscopic-assisted gastrectomy, and advanced N stage (N3) were three independent risk factors for 3-year OS of NEDGC patients in both univariate and multivariate analysis. The TN staging system for gastric adenocarcinoma also has a prognostic value for NEDGC patients, while N3 stage works as an independent predictor of patients' survival. Since most of the NEDGC patients were in advanced stage, proper indications to perform operative laparoscopy should be selected.


Multifractal Downscaling of Rainfall Using Normalized Difference Vegetation Index (NDVI) in the Andes Plateau.
In this paper, a multifractal downscaling technique is applied to adequately transformed and lag corrected normalized difference vegetation index (NDVI) in order to obtain daily estimates of rainfall in an area of the Peruvian Andean high plateau. This downscaling procedure is temporal in nature since the original NDVI information is provided at an irregular temporal sampling period between 8 and 11 days, and the desired final scale is 1 day. The spatial resolution of approximately 1 km remains the same throughout the downscaling process. The results were validated against on-site measurements of meteorological stations distributed in the area under study.


ActivinA Induced SMAD1/5 Signaling in an iPSC Derived EC Model of Fibrodysplasia Ossificans Progressiva (FOP) Can Be Rescued by the Drug Candidate Saracatinib.
Balanced signal transduction is crucial in tissue patterning, particularly in the vasculature. Heterotopic ossification (HO) is tightly linked to vascularization with increased vessel number in hereditary forms of HO, such as Fibrodysplasia ossificans progressiva (FOP). FOP is caused by mutations in the BMP type I receptor ACVR1 leading to aberrant SMAD1/5 signaling in response to ActivinA. Whether observed vascular phenotype in human FOP lesions is connected to aberrant ActivinA signaling is unknown. Blocking of ActivinA prevents HO in FOP mice indicating a central role of the ligand in FOP. Here, we established a new FOP endothelial cell model generated from induced pluripotent stem cells (iECs) to study ActivinA signaling. FOP iECs recapitulate pathogenic ActivinA/SMAD1/5 signaling. Whole transcriptome analysis identified ActivinA mediated activation of the BMP/NOTCH pathway exclusively in FOP iECs, which was rescued to WT transcriptional levels by the drug candidate Saracatinib. We propose that ActivinA causes transcriptional pre-patterning of the FOP endothelium, which might contribute to differential vascularity in FOP lesions compared to non-hereditary HO.


Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt.


Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review.
Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.


A probabilistic arsenic exposure assessment for children who contact chromated copper arsenate (CCA)-treated playsets and decks, Part 2: Sensitivity and uncertainty analyses.
A probabilistic model (SHEDS-Wood) was developed to examine children's exposure and dose to chromated copper arsenate (CCA)-treated wood, as described in Part 1 of this two-part article. This Part 2 article discusses sensitivity and uncertainty analyses conducted to assess the key model inputs and areas of needed research for children's exposure to CCA-treated playsets and decks. The following types of analyses were conducted: (1) sensitivity analyses using a percentile scaling approach and multiple stepwise regression; and (2) uncertainty analyses using the bootstrap and two-stage Monte Carlo techniques. The five most important variables, based on both sensitivity and uncertainty analyses, were: wood surface residue-to-skin transfer efficiency; wood surface residue levels; fraction of hand surface area mouthed per mouthing event; average fraction of nonresidential outdoor time a child plays on/around CCA-treated public playsets; and frequency of hand washing. In general, there was a factor of 8 for the 5th and 95th percentiles and a factor of 4 for the 50th percentile in the uncertainty of predicted population dose estimates due to parameter uncertainty. Data were available for most of the key model inputs identified with sensitivity and uncertainty analyses; however, there were few or no data for some key inputs. To evaluate and improve the accuracy of model results, future measurement studies should obtain longitudinal time-activity diary information on children, spatial and temporal measurements of residue and soil concentrations on or near CCA-treated playsets and decks, and key exposure factors. Future studies should also address other sources of uncertainty in addition to parameter uncertainty, such as scenario and model uncertainty.


Preventive care use by school-aged children: differences by socioeconomic status.
Use of ambulatory care services by children from low-income families has increased substantially since the early 1960s. However, in few studies have attempts been made to disaggregate physician visits according to type (eg, preventive upsilon diagnosis and treatment). In this study, receipt of preventive care (including physical, vision, and dental examinations), based on a sample of 16,838 children aged 5 to 16 years from the 1982 National Health Interview Survey, was examined. The results indicate that children in families with incomes below the poverty level, especially those without Medicaid insurance, are much less likely to receive routine preventive care on a timely basis. Poor school-aged children with Medicaid are much more likely to receive timely preventive care than their counterparts without Medicaid coverage. The effectiveness of preventive care for children is discussed and suggestions for improving access to routine preventive care are presented.


Sequential injection analysis for automation of the Winkler methodology, with real-time SIMPLEX optimization and shipboard application.
A multipurpose analyzer system based on sequential injection analysis (SIA) for the determination of dissolved oxygen (DO) in seawater is presented. Three operation modes were established and successfully applied onboard during a research cruise in the Southern ocean: 1st, in-line execution of the entire Winkler method including precipitation of manganese (II) hydroxide, fixation of DO, precipitate dissolution by confluent acidification, and spectrophotometric quantification of the generated iodine/tri-iodide (I(2)/I(3)(-)), 2nd, spectrophotometric quantification of I(2)/I(3)(-) in samples prepared according the classical Winkler protocol, and 3rd, accurate batch-wise titration of I(2)/I(3)(-) with thiosulfate using one syringe pump of the analyzer as automatic burette. In the first mode, the zone stacking principle was applied to achieve high dispersion of the reagent solutions in the sample zone. Spectrophotometric detection was done at the isobestic wavelength 466 nm of I(2)/I(3)(-). Highly reduced consumption of reagents and sample compared to the classical Winkler protocol, linear response up to 16 mg L(-1) DO, and an injection frequency of 30 per hour were achieved. It is noteworthy that for the offline protocol, sample metering and quantification with a potentiometric titrator lasts in general over 5 min without counting sample fixation, incubation, and glassware cleaning. The modified SIMPLEX methodology was used for the simultaneous optimization of four volumetric and two chemical variables. Vertex calculation and consequent application including in-line preparation of one reagent was carried out in real-time using the software AutoAnalysis. The analytical system featured high signal stability, robustness, and a repeatability of 3% RSD (1st mode) and 0.8% (2nd mode) during shipboard application.


Hypo- and hyperosmolal saline and raffinose on kidney cortical cell volume at 37 degrees C.
Cell water content was measured in respiring rat renal cortical slices incubated in hypo- and hyperosmolal saline with and without raffinose and ouabain for 60 min at 37 degrees C. At 60 min, hyposmolal saline (228 mosmol/kg H2O) caused a 16% swelling of cells, whereas addition of 73 mM raffinose (299 mosmol/kg H2O) caused a 33% shrinkage. Physiological saline plus raffinose (364 mosmol/kg H2O) caused a 28% cell shrinkage, whereas addition of saline (385 mosmol/kg H2O) produced only a 10% decrease in cell volume. The effects of raffinose were reversible. At physiological Na concentrations, osmole for osmole raffinose was 4 times as effective in shrinking cells as saline, but only 2 times as effective at Na of 112 mM. Osmotic effectiveness of saline changed, that of raffinose did not. Ouabain caused no changes in cell volume and did not prevent the effect of raffinose. In conclusion, there is no volume regulation to nonelectrolyte solutes and only partial volume regulation to saline, and this is due to differential osmotic effects of these solutes, that of saline decreasing from low to high Na.


The real action in health care.
It's not taking place in the White House or Congress. The show to watch is the boisterous, free-market affair, precipitated by employers fed up with rising medical costs, and carried on by insurers and HMOs scrapping for turf.


A concentration-dependent biphasic positive inotropic action of ouabain on isolated heart of rat and guinea-pig.
Log dose-response curves of ouabain on rat and guinea-pig heart revealed the existence of a concentration-dependent, biphasic inotropic effect of ouabain. With rat as with guinea pig heart the "first" effect observed at the lowest concentrations of ouabain, was relatively small (rat: 115% of control, at 10(-6) M ouabain; guinea-pig: 110% of control, at 6.25.10(-10) M ouabain) but statistically highly significant (p less than or equal to 0.001). The shape of the concentration-effect relationship for this first action differed between species. With rat heart it was sigmoid in character and had a flat slope, with guinea-pig on the contrary it was almost bell-shaped (i.e. the effect disappeared with increasing ouabain concentration). The shape of the concentration-effect relationship for the "second" action was sigmoid in shape for both species used (rat: between 10(-6) - 10(-4) M; guinea-pig: between 10(-8) - 10(-6) M ouabain). From the results is was concluded that the dual positive inotropic effect of ouabain supports the existence of at least two different mechanisms of action of this drug. Furthermore, it was suggested that a species-dependent binding of calcium to the cardiac sarcolemma may be responsible for the different shapes of the "first" positive inotropic effect of ouabain.


The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE.
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet. The EUROMENE network of European researchers and clinicians aims to promote cooperation and advance research on ME/CFS. To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review. Further we suggest strategies to improve biomarker development and encourage researchers to take these into consideration for designing and reporting biomarker studies.


Enhancing risk prediction capabilities in patients with carotid artery disease using a 2-level computational approach.
One of the main causes of death worldwide is carotid artery disease, which causes increasing arterial stenosis and may induce a stroke. To address this problem, the scientific community aims to improve our understanding of the underlying atherosclerotic mechanisms, as well as to make it possible to forecast the progression of atherosclerosis. Additionally, over the past several years, developments in the field of cardiovascular modeling have made it possible to create precise three-dimensional models of patient-specific main carotid arteries. The aforementioned 3D models are then implemented by computational models to forecast either the progression of atherosclerotic plaque or several flow-related metrics which are correlated to risk evaluation. A precise representation of both the blood flow and the fundamental atherosclerotic process within the arterial wall is made possible by computational models, therefore, allowing for the prediction of future lumen stenoses, plaque areas and risk prediction. This work presents an attempt to integrate the outcomes of a novel plaque growth model with advanced blood flow dynamics where the deformed luminal shape derived from the plaque growth model is compared to the actual patient-specific luminal model in terms of several hemodynamic metrics, to identify the prediction accuracy of the aforementioned model. Pressure drop ratios had a mean difference of <3%, whereas OSI-derived metrics were identical in 2/3 cases.Clinical Relevance-This establishes the accuracy of our plaque growth model in predicting the arterial geometry after the desired timeline.


Monocyte ferritin in idiopathic haemochromatosis, thalassaemia and liver disease.
Monocyte ferritin (MF) content was measured in normal subjects and patients with a variety of disorders of iron storage. MF was above the normal range in 4 patients with idiopathic haemochromatosis (IHC). However, in 4 patients with transfusion siderosis (TS), secondary to aplastic anaemia, who had similar elevations in serum ferritin, MF was highly elevated. 10 patients with thalassaemia intermedia and thalassaemia major with no previous history of transfusions, but with elevated serum ferritin, also had significantly elevated MF. Disproportionately low MF in IHC could reflect defective ferritin metabolism in reticuloendothelial cells in this disorder. Finally, in 3 patients with acute rises in serum ferritin caused by acute hepatitis, MF was not increased. This suggests that MF is not directly affected by high circulating levels of serum ferritin raised acutely, but rather reflects iron storage status in conditions not associated with primary disorders of iron metabolism.


[Clinicoelectroneuromyographic characteristics of neuralgic amyotrophy].
Clinical and genealogical examinations of 155 patients with neural amyotrophies were carried out. Use was made of general and local electromyography, determinations of the speed of impulse transmission along the efferent fibres of the peripheral nerves, and examinations of the H-reflex. The examinations revealed a great diversity of the clinical forms of the neural amyotrophies, each forms having a definite clinical picture, type of hereditary transmission, and characteristic electrophysiological changes. The electroneuromyographic examinations showed that in cases of Charcot-Marie-Tooth's classical neural amyotrophy neuritic changes were prevailing in rapidly-progressing autosomo-dominant neural amyotrophies and autosomo-recessive infantile neural amyotrophy the peripheral efferent neuron was affected over its entire length. A complex examination of Roussy-Levy's syndrome revealed a pronounced dissociation between the relatively unimpaired motor function and the considerable delay of the impulse transmission along the efferent fibres of the peripheral nerves. In heterozygotic carries signs of mononeuron dysfunction were determined.


Development and validation of a new non-disease-specific survey tool to assess self-reported adherence to medication.
Background: Patients' non-adherence to medication affects both patients themselves and healthcare systems. Consequences include higher mortality, worsening of disease, patient injuries, and increased healthcare costs. Many existing survey tools for assessing adherence are linked to specific diseases and assessing medication-taking behavior or identifying barriers or beliefs. This study aimed to develop and validate a new non-disease-specific survey tool to assess self-reported medication-taking behavior, barriers, and beliefs in order to quantify the causes of non-adherence and measure adherence. Methods: The survey tool was developed after literature searches and pilot testing. Validation was conducted by assessing the psychometric properties of content, construct, reliability, and feasibility. Content validity was assessed by subject matter experts and construct validity by performing exploratory factor analysis. Reliability assessment was performed by calculating internal consistency, Cronbach's alpha and test/retest reliability, intraclass correlation coefficient (ICC), and standard error of measurement (SEm). A receiver operating characteristic (ROC) curve and the Lui method were used to calculate the statistical cut-off score for good versus poor adherence. Survey responses from Norwegian medication users over 18 years recruited via social media were used for the factor analysis and Cronbach's alpha. Results: The final survey tool contains 37 causes of non-adherence connected to medication-taking behavior and barriers to adherence and beliefs associated with adherence. The overall result for all 37 items demonstrated reliable internal consistency, Cronbach's alpha = 0.91. The factor analysis identified ten latent variables for 29 items, explaining 61.7% of the variance. Seven of the latent variables showed reliable internal consistency: medication fear and lack of effect, conditional practical issues, pregnancy/breastfeeding, information issues, needlessness, lifestyle, and avoiding stigmatization (Cronbach's alpha = 0.72-0.86). Shortage showed low internal consistency (Cronbach's alpha = 0.59). Impact issues and personal practical issues showed poor internal consistency (Cronbach's alpha = 0.51 and 0.48, respectively). The test/retest reliability ICC = 0.89 and SEm = 1.11, indicating good reliability. The statistical cut-off score for good versus poor adherence was 10, but the clinical cut-off score was found to be 2. Conclusion: This survey tool, OMAS-37 (OsloMet Adherence to medication Survey tool, 37 items), demonstrated to be a valid and reliable instrument for assessing adherence. Further studies will examine the ability of the tool for measuring adherence enhancing effect following interventions.


Effect of paclitaxel elution from reservoirs with bioabsorbable polymer compared to a bare metal stent for the elective percutaneous treatment of de novo coronary stenosis: the EUROSTAR-II randomised clinical trial.
To compare the angiographic and clinical performance of a paclitaxel-eluting stent using reservoirs technology and a bioabsorbable polymer, without surface coating (CoStar), vs. an equivalent bare metal stent (BMS) using an identical metallic platform. Three hundred and three (303) patients (335 lesions) with de novo coronary artery stenosis suitable for elective percutaneous treatment were randomised in an international multicentre single-blind trial to receive the CoStar stent (n=152) or the equivalent BMS (n=151). At eight months, the primary endpoint of in-segment binary restenosis was significantly lower in the CoStar than in the BMS group (17.6 vs. 30.3%, p=0.029). In-stent late loss (0.41 vs. 0.81 mm; p<0.0001) and all the other angiographic secondary endpoints also favoured CoStar. The composite of cardiac death, myocardial infarction related to the target vessel and target lesion revascularisation was significantly lower at eight months in the CoStar arm (19.7 vs. 29.1%; hazard ratio 0.54, 95% CI: 0.34-0.87; p=0.010), mainly due to lower incidence of target lesion revascularisation (15.1 vs. 26.5%; 95% CI: hazard ratio 0.45, 95% CI: 0.27-0.76; p=0.002). As compared with a bare metal stent of identical design, the paclitaxel elution from reservoirs results in significantly less binary restenosis, less late loss and lower revascularisation rates at eight months. Therefore, based on these data, the CoStar paclitaxel-eluting stent was found to be effective and safe.


Calcium currents, charge movement and dihydropyridine binding in fast- and slow-twitch muscles of rat and rabbit.
1. The Vaseline-gap technique was used to record slow calcium currents and asymmetric charge movement in single fibres of fast-twitch muscles (extensor digitorum longus (e.d.l.) and sternomastoid) and slow-twitch muscles (soleus) from rat and rabbit, at a holding potential of -90 mV. 2. The slow calcium current in soleus fibres was about one-third of the size of the current in e.d.l. fibres, but was very similar otherwise. In both e.d.l. and soleus fibres, the dihydropyridine (DHP), nifedipine, suppressed the calcium current entirely. 3. In these normally polarized fibres, nifedipine suppressed only part (qns) of the asymmetric charge movement. The proportion of qns suppressed by various concentrations of nifedipine was linearly related to the associated reduction of the calcium current. Half-maximal suppression of both parameters was obtained with about 0.5 microM-nifedipine. The calcium current and the qns component of the charge movement also were suppressed over the same time course by nifedipine. Another DHP calcium antagonist, (+)PN200/110, was indistinguishable from nifedipine in its effects of suppressing calcium currents and qns. 4. In all muscle types, the total amount of qns in each fibre was linearly related to the size of the calcium current (in the absence of DHP). On average, qns was 3.3 times larger in e.d.l. fibres than in soleus fibres. 5. In contrast to the other dihydropyridines, (-)bay K8644, a calcium channel agonist, did not suppress any asymmetric charge movement. 6. The potential dependence of the slow calcium current implied a minimum gating charge of about five or six electronic charges. The movement of qns occurred over a more negative potential range than the change in calcium conductance. 7. Experiments on the binding of (+)PN200/110 indicated that e.d.l. muscles had between about 2 and 3 times more specific DHP binding sites than did soleus muscle. 8. These results point to a close relationship between slow calcium channels, the qns component of the charge movement and DHP binding sites, in both fast- and slow-twitch mammalian muscle. qns appears to be part of the gating current of the T-system calcium channels.


[Neurobiological basis of drug addiction].
INTRODUCTION. Drugs of abuse cause addiction, characterized by compulsive and out of control drug use. Several neurochemical and molecular changes take place in the brain during the first phase of drug use which lead to dependence, addiction and drug abuse. DEVELOPMENT. Every drug of abuse acts through similar neurophysiological mechanisms, mostly based on the abnormal activation of the mesolimbic dopamine system. Although the addicted brain tries to adapted to the drug action, there are permanent neural changes at the cellular and molecular levels which seem to underlie the addictive process and the emergence of abstinence symptoms after drug taking stops. Furthermore, these neural changes appear to subserve the emergence of cravings once the abstinent syndrome has been overcome. Cravings are the main factor leading to relapse, and they are often initiated by exposure to drug related cues.