Ultrasonographic thyroid nodular findings in Japanese children.
The Fukushima Health Management Survey conducted after the accident at the Fukushima Nuclear Power Plant included thyroid ultrasound examinations for children aged ≤18 years at the time of the accident. The purpose of this study was to investigate the frequency of thyroid nodular lesions detected using high-quality ultrasonography in a general population of Japanese children, in whom such data have not been previously characterized. The current study investigated 4,365 free-living children aged between 3 and 18 years in three Japanese prefectures (Aomori, Yamanashi and Nagasaki). The same ultrasonography equipment as that used in the Fukushima Survey was employed to observe thyroid nodular lesions. The following categories of findings were used-'A', further examinations are not necessary; 'B', the presence of thyroid nodules with a diameter of ≥5.1 mm or thyroid cysts with a diameter of ≥20.1 mm; and 'C', immediate further examinations are required. As a sub-category of 'A', 'A1' was defined as the absence of nodules or cysts, and 'A2' was defined as the presence of thyroid nodules with a diameter of ≤5.0 mm or thyroid cysts with a diameter of ≤20.0 mm. Overall, 4,321 (99 %) of the total participants were classified with a status of 'A' and 44 (1 %) were classified with a status of 'B'. No participants were classified with a status of 'C'. A total of 56.5 % of the total participants was classified with a status of 'A2'. Thyroid nodules were identified in 1.6 % of the total participants and thyroid cysts were identified in 56.9 % of the participants. The current study provides data regarding the actual frequency of ultrasonographically detected thyroid nodular lesions among the Japanese children. These results would be useful for evaluating thyroid findings in Japanese children, although careful interpretation is required.


The Adolescent and Adult Psychoeducational Profile: assessment of adolescents and adults with severe developmental handicaps.
The purpose of this study was to determine the reliability and validity of the Adolescent and Adult Psychoeducational Profile (AAPEP), an assessment instrument designed for adolescents and adults with severe developmental handicaps. Subjects were 60 adolescents and adults, 30 with autism and 30 with mental retardation but without autism. The groups were matched on age and IQ. Results suggested high interrater reliability on all function areas of the AAPEP (Vocational Skills, Independent Functioning, Leisure Skills, Vocational Behavior, Functional Communication, Interpersonal Behavior) and on all three scales (Direct Observation, Home, School/Work). Validity measures suggested that the recommendations generated from the AAPEP were viewed by blind experts as more helpful than those already generated for the individual clients and contained in their Individual Education Programs (IEPs) or Individual Habilitation Plans (IHPs). Informal measures indicated that parents and/or group home staff also found AAPEP recommendations helpful. Finally, reliability and validity measures were also encouraging for moderately and severely handicapped adolescents and adults without autism. The AAPEP appears to be an effective new instrument for those working with older handicapped clients.


The Inter-Rater Consistency of Clinician Ratings of Posttraumatic Stress Disorder (PTSD) Therapy Content.
Effective communication between clinicians is essential for the success of mental health interventions in multidisciplinary contexts. This relies on a shared understanding of concepts, diagnoses and treatments. A major assumption of clinicians when discussing psychological treatments with each other is that both parties have a shared understanding of the theory, rationale and application of the respective technique. We aimed to determine to what extent there is inter-rater agreement between clinicians in describing the content of group therapy sessions. Pairs of clinicians, drawn from a large multidisciplinary team (13), were asked to provide ratings of the therapeutic content and emphasis of N = 154 group therapy sessions conducted during an intensive residential treatment program for post-traumatic stress disorder (PTSD). In most therapeutic content domains there was a moderate level of agreement between clinicians regarding session content (Cohen's Kappa 0.4 to 0.6), suggesting that clinicians have a broad shared understanding of therapeutic content, but that there are also frequent discordant understandings. The implications of these findings on multidisciplinary team communication, patient care and clinical handovers are discussed and directions for further research are outlined.


Association of in vitro fertilization outcome with circulating insulin-like growth factor components prior to cycle initiation.
Components of the insulin-like growth factor (IGF) system enhance in vitro embryo quality and implantation rates in both animal models and human in vitro fertilization (IVF). We evaluated whether differences in serum levels of these components in women prior to initiation of an IVF cycle would be predictive of subsequent outcome. In this retrospective study sera from women obtained at day 2 of their IVF cycle (at baseline before stimulation) were assayed for IGF-I, IGF-II, and IGF binding protein (BP)-1 by enzyme-linked immunosorbent assay. Samples from 54 women with a live birth, 38 with a transient biochemical pregnancy, 45 with a spontaneous abortion, 54 who did not become pregnant, and 35 who had an ectopic pregnancy were available for analysis. Associations between the assays and outcome were evaluated by the Kruskal-Wallis test and receiver operating characteristic analysis. There were no differences in the number of oocytes retrieved, oocyte quality, fertilization rates, or embryo grade between groups. Median concentrations of IGF-I were elevated in women with a live birth (29.1 ng/mL) as compared to women with a biochemical pregnancy (25.6 ng/mL), with spontaneous abortion (21.2 ng/mL), who were not pregnant (18.7 pg/mL), or who had an ectopic pregnancy (4.2 pg/mL) (P < .001). Conversely, median levels of IGF-II were reduced in women with a live birth (294.5 ng/mL) as opposed to 357.5, 393.6, 407.2, and 426.9 ng/mL in women with a biochemical pregnancy, with ectopic pregnancy, with spontaneous abortion, or who were not pregnant, respectively (P < .001). Median IGFBP-1 concentrations were markedly elevated in women with a live birth (23.6 ng/mL) compared to 18.3, 14.1, 13.8, and 9.5 ng/mL in women with a biochemical pregnancy, with spontaneous abortion, who were not pregnant, or with an ectopic pregnancy (P < .001). The combination of IGF-I and IGFBP-1 best predicted the occurrence of a live birth with an area under the curve of 0.892. Maternal serum levels of IGF-I, IGF-II, and IGFBP-1 prior to initiation of an IVF cycle are correlated with the likelihood of a live birth. Alterations in maternal IGF system components may influence oocyte quality or the success of early postfertilization events and embryo implantation.


Case Report of Idiopathic Intracranial Hypertension in Pregnancy.
Idiopathic intracranial hypertension (IIH) is a disease of increased intracranial pressure with an unknown cause that is seen most often in women during their childbearing years. Women can be under care for IIH when they become pregnant, or it may occur during pregnancy. In the past, women with IIH who became pregnant were often counseled to terminate their pregnancies, to give birth early, and even to be sterilized to prevent future pregnancies. Today, multiple therapeutic options are available. In this case report, I describe the case of a woman with IIH who was treated with a cerebral spinal fluid shunt and gave birth to two sets of twins. This case report adds new information to the limited nursing literature currently available on this disease.


Conservative treatment for thoracic outlet syndrome.
Conservative treatment of thoracic outlet syndrome consists initially of pain control and medicinal and physical measures. Therapy then addresses tight muscles, with strengthening of weakened neck and shoulder girdle muscles. Range of motion and nerve gliding exercises are instituted simultaneously, and the patient is educated in proper posture and ergonomics at home and in the work setting.


Phosphorylated and dephosphorylated myosin light chains of Drosophila fly and larva.
1. The present study confirmed that light chains of Drosophila adult fibrillar (flight) muscle myosin consist of Lf1, Lf2, Lf2' and Lf3, and tubular muscle myosin light chains contain Lt1, Lt2, Lt2' and Lt3, as revealed by two-dimensional (isoelectric focusing and SDS-gel electrophoresis) gel electrophoresis. 2. Larva myosin light chains were of all the tubular type. However, it was found that Lt1 and Lt2' are produced by phosphorylation of Lt2, and Lf1 is produced by phosphorylation of Lf2'. 3. Injection of radioactive phosphate into Drosophila fly resulted in phosphorylations of Lf1 and Lt1. When larva or late pupa myosin was incubated with myosin light chain kinase from chicken gizzard or adult flies, phosphorylation of Lt1, Lf2' and Lt2' occurred. Drosophila myosin light chain kinase phosphorylated Lf1 in addition to Lt1 and L2' (Lf2' + Lt2') of adult myosin. 4. Dephosphorylation of adult myosin by potato acid and calf intestine alkaline phosphatases led to the shift of Lf1 (34,000), Lt1 (31,000) and L2' (Lf2' + Lt2') (30,000) to L2 (Lf2 + Lt2) positions (30,000). 5. Peptide mapping analyses revealed that larva Lt1, Lt2', Lt2 and adult Lt1 were all the same; therefore, it is thought that a single species of Lt2 specific to the tubular type of myosin and its phosphorylated isoforms (Lt1, Lt2') exist. 6. The peptide map of Lf1 was slightly different from that of Lt1, but very similar to that of L2' in adult myosin. L2 and L2' of adult myosin showed very similar peptide maps, but there were several different peptide fragments.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxidative stress induces axonal beading in cultured human brain tissue.
Oxidative stress has been implicated in the pathogenesis of a number of human neurodegenerative disorders of the central nervous system (CNS), including Alzheimer's disease (AD). To better understand the pathological effects of oxidative stress on CNS neurons we used a primary human brain cell culture model of hydrogen peroxide-induced oxidative stress. Neuronal and astrocytic morphology was visualised by immunofluorescence with antibodies to the neuron-specific microtubule component beta-tubulin III and against glial fibrillary acidic protein (GFAP), respectively. After exposure to 40 mM H(2)O(2) for 60-90 min, axonal swelling was observed, which developed into axonal beading after 48 h. No beading was observed in GFAP-positive astrocytes. Despite the concentration of H(2)O(2) used, neurons remained attached to the substratum and showed no signs of apoptosis. This was attributed to the neuroprotective effect of the B-27 medium supplement, which contained antioxidants. The axonal swelling and beading was consistent with a disruption of microtubules by oxidative stress and subsequent hold-up of axonal transport.


Cerium oxide nanoparticles (nCeO2) exert minimal adverse effects on microbial communities in soils with and without biosolids amendment.
Increased use of nano-cerium oxide (nCeO2) in an array of industrial applications has raised environmental concerns due to potential increased loadings to the soil environment. This research investigated the potential adverse effects of nCeO2 (10-30 nm) on the soil microbial community in two exposure scenarios: direct application to soil, and indirect application to soil through chemical spiking of biosolids, followed by mixing into soil. Total Ce in test soils without, and with biosolids amendment, ranged from 44 to 770, and 73 to 664 mg Ce kg-1 soil, respectively. In order to help distinguish whether observed effects were elicited by the solid-phase colloids or the activity of dissolved Ce, a soluble Ce salt (Ce (NO3)3) treatment was included in select assays. A suite of tests was used to investigate effects on critical processes: microbial growth (heterotrophic plate count), microbial activity (organic matter (OM) decomposition, enzyme activity and, nitrification) and diversity (structural and functional). Although results showed significant inhibition on microbial growth in soil without biosolids amendment at ≥ 156 mg Ce kg-1 soil by week 5, these results were inconsistent and non-significant thereafter. In general, nCeO2 showed no evidence of consistent adverse effects on OM decomposition, nitrification, soil enzyme activities and functional diversity. Leucine aminopeptidase showed significant (p< 0.05) stimulatory effects over time at ≥ 44 mg Ce kg-1 in soils without biosolids, which was not observed in soils with biosolids amendment. The lack of inhibitory effects of nCeO2 may be attributed to its low solubility; Ce in soil extracts (0.01 M CaCl2) were all below detection (< 0.003 mg kg-1) in the nCeO2-spiked soils, but detectable in the Ce (NO3)3 samples. In contrast, soluble Ce at 359 mg Ce kg-1 showed a significant reduction in OM decomposition and effects on microbial genomic diversity based on the 16S rDNA data in soils with and without biosolids amendment (359 and 690 mg Ce kg-1). The nCeO2 behaviour and effects information described herein are expected to help fulfill data gaps for the characterization of this priority nanomaterial.


Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations.
Functional precision medicine is a strategy whereby live tumor cells from affected individuals are directly perturbed with drugs to provide immediately translatable, personalized information to guide therapy. The heterogeneity of human cancer has led to the realization that personalized approaches are needed to improve treatment outcomes. Precision oncology has traditionally used static features of the tumor to dictate which therapies should be used. Static features can include expression of key targets or genomic analysis of mutations to identify therapeutically targetable "drivers." Although a surprisingly small proportion of individuals derive clinical benefit from the static approach, functional precision medicine can provide additional information regarding tumor vulnerabilities. We discuss emerging technologies for functional precision medicine as well as limitations and challenges in using these assays in the clinical trials that will be necessary to determine whether functional precision medicine can improve outcomes and eventually become a standard tool in clinical oncology.


Associations of low handgrip strength with cancer mortality: a multicentre observational study.
Handgrip strength (HGS) is associated with poor clinical outcomes, including all-cause, non-cardiovascular, and cardiovascular mortalities. The published cut-off points for HGS are mostly based on community populations from Western countries, lacking information on cancer patients from China. The objective of this study was to establish sex-specific cut-off points for Chinese cancer patients and investigate the effect of low HGS on cancer mortality. We did a retrospective cohort study of patients who were diagnosed with malignant cancer from June 2012 to December 2018. HGS was measured using a hand dynamometer in 8257 cancer patients. Optimal stratification was used to solve threshold points. The hazard ratio (HR) of all cancer mortality and cancer-specific mortality was calculated using Cox proportional hazard regression models. Among all participants, there were 3902 (47.3%) women and 4355 (52.7%) men. The median age was 58 years old. The cut-off points of HGS to best classify patients with respect to time to mortality were <16.1 kg for women and <22 kg for men. Low HGS was associated with overall cancer mortality in both women and men [HR = 1.339, 95% confidence interval (CI) = 1.170-1.531, P < 0.001; HR = 1.346, 95% CI = 1.176-1.540, P < 0.001, respectively]. For specific cancer types, low HGS was associated with breast cancer (HR = 1.593, 95% CI = 1.230-2.063, P < 0.001) in women, and lung cancer (HR = 1.369, 95% CI = 1.005-1.866, P = 0.047) and colorectal cancer (HR = 1.399, 95% CI = 1.007-1.944, P = 0.045) in men. On the basis of our sex-specific cut-off points, low HGS was strongly associated with cancer mortalities. These results indicate the usefulness of HGS measurement in routine clinical practice for improving patient assessments, cancer prognosis, and intervention.


Plastic cylindrical cement mold in the treatment of long bone metastatic fractures.
Presented here is a simple and practical surgical technique for creating a cement spacer in the cement-metal composite fixation of pathological fractures. This technique has been effectively used in several of our patients for fixation of pathological fractures due to metastatic disease of long bones.


Possible role of endogenous catecholamines in the contractions induced in rabbit aorta by ouabain, sodium depletion and potassium depletion.
Effects of ouabain, Na+ depletion and K+ depletion on the tension development of rabbit aorta were studied. Contraction in the strips was induced by ouabain and Na+-free solution substituted with Li+, tris or sucrose. The contractions were rarely seen under alpha-adrenergic blockade, in reserpinized aorta and mechanically denervated aorta. Contractions induced by norepinephrine were potentiated by Na+ depletion, K+ depletion and ouabain. Contractions induced by high K+ solution were also potentiated by Na+ depletion and ouabain. The potentiation in Li+ solution, K+-free solution and with ouabain was not seen under alpha-adrenergic blockade, in reserpinized aorta and denervated aorta although the potentiation by tris and sucrose solutions was still observed. These data suggest that Na+ depletion, K+ depletion and ouabain release endogenous catecholamines which affect the contraction of the vascular smooth muscle of rabbit aorta.


Inhibition of the recovery from potentially lethal damage by lonidamine.
Lonidamine [1-(2,4-dichlorobenzyl)-1-H-indazol-3-carboxylic acid] is shown to inhibit recovery from potentially lethal damage after exposure of cells to X-rays, methyl methane sulfonate, or bleomycin and heat (43 degrees C, 1h). Inhibition is most effective when the drug is present before and after exposure of 10 to 25 mg l-1, a concentration readily achievable in vivo.


Association of Olfactory Impairment With All-Cause Mortality: A Systematic Review and Meta-analysis.
Olfactory impairment is highly prevalent and associated with multiple comorbidities, including neurodegenerative, cardiovascular, nutritional, and immune disorders. However, epidemiologic associations between olfactory impairment and mortality are discordant. To systematically clarify the epidemiologic associations between olfactory impairment and mortality. The PubMed, Embase, and Cochrane Library databases were searched from inception to August 13, 2021. Two blinded reviewers selected observational studies published as full-length, English-language articles in peer-reviewed journals that reported the presence or severity of chronic olfactory impairment, whether objectively measured or self-reported, in association with any mortality estimate, among adults aged 18 years or older. Two reviewers independently extracted data, evaluated study bias using the Newcastle-Ottawa Scale, and appraised the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, heterogeneity was measured using I2 statistics, sources of heterogeneity were investigated using meta-regression and subgroup meta-analyses, and publication bias was qualitatively and quantitatively assessed. Hazard ratios for all-cause mortality. One retrospective cohort study and 10 prospective cohort studies (with a total of 21 601 participants) from 1088 nonduplicated records were included. Ten studies had a low risk of bias, whereas 1 study had a moderate risk; exclusion of the latter did not alter conclusions. Nine studies were included in the meta-analysis. Olfactory loss was associated with a significantly higher pooled hazard of all-cause mortality (hazard ratio, 1.52; 95% CI, 1.28-1.80; I2 = 82%). Meta-regression sufficiently explained heterogeneity, with longer mean follow-up duration weakening the pooled association, accounting for 91.3% of heterogeneity. Self-reported and objective effect sizes were similar. Associations were robust to trim-and-fill adjustment and the Egger test for publication bias. The overall quality of evidence was moderate. The findings of this systematic review and meta-analysis suggest that olfactory impairment is associated with all-cause mortality and may be a marker of general health and biological aging. Further research is required to establish the underlying mechanisms and the scope for interventions.


Fluorescent magnetic nanohybrids as multimodal imaging agents for human epithelial cancer detection.
Cetuximab conjugated fluorescent magnetic nanohybrids (CET-FMNHs) were synthesized for detection of human epithelial cancer via magnetic resonance (MR) and optical imaging. Spherical FMNHs consist of MnFe(2)O(4) magnetic nanocrystals encapsulated in pyrene-labeled PCL-b-PMAA as a surfactant prepared by a nano-emulsion method. FMNHs demonstrated excellent colloidal stability and biocompatibility for biomedical application. Antibody conjugated fluorescent magnetic nanohybrids (CET-FMNHs) served as effective agents for both magnetic resonance (MR) and fluorescence optical imaging of cancer cell lines.


Cardiac arrhythmias and In-hospital mortality amongst patients with takotsubo cardiomyopathy: A retrospective study in an Italian population.
Takotsubo cardiomyopathy (TTC) is an acute non-ischemic cardiomyopathy classically associated with an intense emotional or physiologic trigger. Data on the relationship between arrhythmias and mortality in TTC have been limited by small sample sizes. The aim of this study is to assess the impact of ventricular and atrial arrhythmias and advanced atrioventricular block on in-hospital mortality in a large inpatient population with TTC. Data was obtained from the Italian National Healthcare System Databank from 2009 to 2016. Patients with TTC were identified using diagnosis codes and clinical characteristics were collected, with a primary outcome of mortality. Univariate and multivariate logistic regression analyses were used to identify significant predictors for mortality, and patients with TTC were further analyzed according to sex and age. There were 10,861 patients with TTC; 91.7% were women (9959) and the mean age was 70.7 +/- 11.9 years. The mortality rate was 2.2%; while 1.2% of patients had ventricular arrhythmias, 10.0% had atrial arrhythmias, and 1.3% had advanced atrioventricular block. Male sex, increased age and ventricular arrhythmias were predictors of mortality. In a sex-stratified analysis, ventricular arrhythmias and advanced age remained independent predictors for mortality in women. In this large retrospective analysis, male sex and the presence of ventricular arrhythmias are strong predictors of mortality in patients hospitalized with TTC.


In vitro evolution predicts that the IMP-1 metallo-beta-lactamase does not have the potential to evolve increased activity against imipenem.
In vitro evolution was used to predict whether the IMP-1 metallo-beta-lactamase has the potential to evolve an increased ability to confer resistance to imipenem. Screening of eight libraries containing 9.8 x 10(6) +/- 1.4 x 10(6) (mean +/- standard error) variants per library, with an average of 1.2 mutations per variant, detected no increased resistance to imipenem. The results predict, with >99.9% confidence, that even under intense selection the IMP-1 beta-lactamase will not evolve to confer increased resistance to imipenem.


Studies on biomarkers of oxidative stress and associated genotoxicity and histopathology in Channa punctatus from heavy metal polluted canal.
Some investigations were made on the Satha canal water and health of dwelling fish Channa punctatus at Satha village, district Aligarh (U.P). Metal bioaccumulation and induction of biomarkers such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH), DNA damage and histopathology are potential indicators of stress in C. punctatus exposed to effluents. In canal water Cr, Mn, Fe and Ni concentrations were exceeding the permissible limits set by both Bureau of Indian standards (BIS) and WHO. Fe (74%) was highly bioavailable and accumulated in all organs (gill, liver, kidney, muscle and integument). The highest metal pollution index (MPI) value of 53 was observed in gills and the lowest 6 in liver tissue. SOD and LPO were significantly higher in all tissues, whereas CAT, GST and GSH levels declined significantly compared to fish from the reference site. Concomitant damage to DNA was observed with significantly higher mean tail length in the exposed fish gill cells (19 μm) and in liver (12.7 μm) compared to reference fish (5 and 4 μm respectively). Histopathology in gill and liver also show significant damage. Therefore, it can be concluded that the sugar mill effluent has the potential to cause oxidative stress, DNA damage and histopathology in C. punctatus. This canal is a prime source of water and fish food to the local residents of the area. Therefore, the consumers may suffer adverse health effects like that in indicator organism.


Characterization, leachability and valorization through combustion of residual chars from gasification of coals with pine.
This paper presents the study of the combustion of char residues produced during co-gasification of coal with pine with the aim of characterizing them for their potential use for energy. These residues are generally rich in carbon with the presence of other elements, with particular concern for heavy metals and pollutant precursors, depending on the original fuel used. The evaluation of environmental toxicity of the char residues was performed through application of different leaching tests (EN12457-2, US EPA-1311 TCLP and EA NEN 7371:2004). The results showed that the residues present quite low toxicity for some of pollutants. However, depending on the fuel used, possible presence of other pollutants may bring environmental risks. The utilization of these char residues for energy was in this study evaluated, by burning them as a first step pre-treatment prior to landfilling. The thermo-gravimetric analysis and ash fusibility studies revealed an adequate thermochemical behavior, without presenting any major operational risks. Fluidized bed combustion was applied to char residues. Above 700°C, very high carbon conversion ratios were obtained and it seemed that the thermal oxidation of char residues was easier than that of the coals. It was found that the char tendency for releasing SO(2) during its oxidation was lower than for the parent coal, while for NO(X) emissions, the trend was observed to increase NO(X) formation. However, for both pollutants the same control techniques might be applied during char combustion, as for coal. Furthermore, the leachability of ashes resulting from the combustion of char residues appeared to be lower than those produced from direct coal combustion.


[Inhibition of the reactions of DNA hydrolysis and RNA synthesis by the alkaloid sanguinarine].
The increase of the contour length of the low molecular linear duplex DNA in the complex with an alkaloid sanguinarine has been evidenced by the viscometric method. The enzymatic hydrolysis of modified DNA by pancreatic deoxyribonuclease I and RNA synthesis of DNA by rat liver nuclear RNA polymerase were studied. Sanguinarine has been shown to inhibit the first stages of DNA hydrolysis. This alkaloid is a weaker inhibitor than ethidium bromide, a more potent inhibitor than actinomycin D and exerts an inhibiting effect similar to that of distamycin A. Sanguinarine also decreases the rate of the labelled precursor incorporation into the acid-insoluble fractions by nuclear RNA polymerase from rat liver. A 50% inhibition by sanguinarine was observed at the same alkaloid concentration as that of ethidium bromide.


Many scenarios exist for selective inclusion and reporting of results in randomized trials and systematic reviews.
To collate and categorize the ways in which selective inclusion and reporting can occur in randomized controlled trials (RCTs) and systematic reviews. Searches of the Cochrane Methodology Register, PubMed, and PsycInfo were conducted in April 2011. Methodological reports describing empirically investigated or hypothetical examples of selective inclusion or reporting were eligible for inclusion. Examples were extracted from the reports by one author and categorized by three authors independently. Discrepancies in categorization were resolved via discussion. Two hundred ninety reports were included. The majority were empirical method studies (45.5%) or commentaries (29.3%). Eight categories (30 examples) of selective reporting in RCTs, eight categories (27 examples) of selective inclusion in systematic reviews, and eight categories (33 examples) of selective reporting in systematic reviews were collated. Broadly, these describe scenarios in which multiple outcomes or multiple data for the same outcome are available, yet only a subset is included or reported; outcome data are reported with inadequate detail; or outcome data are given different prominence through its placement across or within reports. An extensive list of examples of selective inclusion and reporting was collated. Increasing trialists' and systematic reviewers' awareness of these examples may minimize their occurrence.


Effects of anionic surfactants on ligand-promoted dissolution of iron and aluminum hydroxides.
We investigated the influence of the surfactants sodium dodecyl sulfate (SDS) and rhamnolipid (RhL) on ligand-promoted dissolution of goethite (alpha-FeOOH) and boehmite (gamma-AlOOH) at pH 6. The siderophore desferrioxamine B (DFOB), its derivate desferrioxamine D (DFOD), ethylenediaminetetraacetic acid (EDTA), and 8-hydroxyquinoline-5-sulfonic acid (HQS) were used as ligands. The rates of ligand-promoted dissolution of goethite were significantly increased in the presence of low concentrations of anionic surfactants (<80 microM SDS; <6 mg/L RhL). At higher surfactant concentrations, however, the effects of surfactants were negligible. The dissolution rates in the presence of surfactants were not correlated with adsorbed amounts of ligands. Three possible factors contributing to these observations were further investigated and discussed: (i) adsorbed surfactants may influence ligand adsorption by changes in the ligand's surface speciation, (ii) re-adsorption of Fe-DFOB or Fe-DFOD complexes may lead to an underestimation of siderophore-promoted dissolution rates at high surfactant concentrations, and (iii) co-adsorption of protons to goethite with SDS may influence the dissolution rates. However, our results show that none of these three factors can satisfactorily explain the observed effects of anionic surfactants on ligand-promoted dissolution rates of iron and aluminum hydroxides.


Overexpression of MUC1 enhances proangiogenic activity of non-small-cell lung cancer cells through activation of Akt and extracellular signal-regulated kinase pathways.
Angiogenesis is an important process required for tumor progression. Mucin 1 (MUC1) is a transmembrane glycoprotein that is aberrantly upregulated in many types of cancer, including non-small-cell lung cancer (NSCLC). However, the biological significance of MUC1 overexpression in lung cancer angiogenesis is not completely understood. We showed that enforced expression of MUC1 in two NSCLC cell lines, A549 and NCI-H460, which have a low level of endogenous MUC1, promoted their ability to induce vascular endothelial growth factor (VEGF)-dependent endothelial cell migration and tube formation. There was a significant increase in VEGF expression in MUC1-overexpressing NSCLC cells. Moreover, MUC1 overexpression resulted in a marked elevation in phosphorylated Akt and extracellular signal-regulated kinase (ERK)1/2, indicative of activation of both signaling pathways. Most importantly, inhibition of Akt or ERK signaling using specific chemical inhibitors restrained the proangiogenic activity of MUC1-overexpressing NSCLC cells. Taken together, our present data demonstrate that the aberrant upregulation of MUC1 favors tumor angiogenesis in NSCLC, likely through the activation of both Akt and ERK pathways and elevation of VEGF production. MUC1 may thus be a potential antiangiogenic target in NSCLC.


BAFF and the plasticity of peripheral B cell tolerance.
BAFF and its receptors play a crucial role in peripheral B cell selection and survival, by dictating the set point for mature primary B cell numbers and adjusting thresholds for specificity-based selection during transitional differentiation. The notion that selective stringency can be varied on the basis of homeostatic demands reveals a previously unappreciated degree of plasticity in B cell tolerance, and suggests a paradigm that unites peripheral negative and positive selection with the maintenance of mature B cell numbers. Moreover, it implies a developmentally regulated coupling of BCR and BAFF receptors at the transitional stages and beyond.


Salivary Gland Lesions: A Clinico-Pathological Correlation.
To study the usefulness of clinical features, histopathological and radiological features in diagnosis and management of salivary gland lesions. Prospective study conducted at the department of ENT of a tertiary care centre in central India. A total of 162 patients who were treated over a period of 2 years for salivary gland lesions were studied with regards to correlation between clinical diagnosis, cytological examination and radiological features with histopathological diagnosis. Mean age group was 23.94 (± 15.43) years. There was slight male preponderance. Commonest presenting complaint was swelling. The most common gland involved was minor salivary glands followed by parotid gland. Sensitivity of clinical diagnosis, USG and FNAC for neoplastic lesions was found to be 80%, 95.65% and 79.61% respectively. Specificity of clinical diagnosis, USG and FNAC for neoplastic lesions was found to be 100%, 100% and 97.23% respectively. At the end of the study we concluded that combination of thorough clinical examination, radiological and cytological examination help in proper diagnosis, but it should always be confirmed on histopathology because some surprises are expected with regards to the nature of salivary gland lesions.


Monitoring dynamic binding of chromatin proteins in vivo by single-molecule tracking.
Single-molecule fluorescence microscopy has been used for decades to quantify macromolecular dynamics occurring in specimens that are in direct contact with a coverslip. This has permitted in vitro analysis of single-molecule motion in various biochemically reconstituted systems as well as in vivo studies of single-molecule motion on cell membranes. More recently, thanks to improvements in fluorescent tags and microscopes, it has been possible to follow individual molecules inside thicker specimens such as the nucleus of living cells. This has enabled a detailed description of the live-cell binding of nuclear proteins to DNA. In this protocol we describe a method to quantify intranuclear binding using single-molecule tracking (SMT).


Repeated measures of mammographic density and texture to evaluate prediction and risk of breast cancer: a systematic review of the methods used in the literature.
It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk. The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the Quality in Prognostic Studies tool. Twenty articles were included. The Breast Imaging Reporting and Data System and Cumulus were most commonly used for classifying mammographic density and automated assessment was used on more recent digital mammograms. Time between mammograms varied from 1 year to a median of 4.1, and only nine of the studies used more than two mammograms. Several studies showed that adding change of density or mammographic features improved model performance. Variation in risk of bias of studies was highest in prognostic factor measurement and study confounding. This review provided an updated overview and revealed research gaps in assessment of the use of texture features, risk prediction, and AUC. We provide recommendations for future studies using repeated measure methods for mammogram images to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.


The latent form of macropain (high molecular weight multicatalytic protease) restores ATP-dependent proteolysis to soluble extracts of BHK fibroblasts pretreated with anti-macropain antibodies.
Specific immunoadsorption of the high molecular weight multicatalytic protease, macropain, from postmicrosomal extracts of BHK fibroblasts inhibited ATP-dependent proteolysis of exogenous protein substrates. The immunoprecipitated macropain represented the latent (L) form of the protease because it had low protease activity but was activated by methods that activate purified macropain L. Reconstitution of the antibody-treated extracts with purified macropain L, but not macropain A, from bovine heart or human erythrocytes, completely restored ATP-dependent proteolysis, even though ATP did not directly activate either purified macropain L or the immunoprecipitated protease. Reconstituted ATP-dependent proteolysis was saturable with respect to added macropain and never exceeded the level of proteolysis present in the original extract. These results indicate that macropain L plays a key role in ATP-dependent proteolysis but suggest that the protease may require interaction with or modification by another cellular component to demonstrate this effect.


An adaptive real-time beat detection method for continuous pressure signals.
A novel adaptive real-time beat detection method for pressure related signals is proposed by virtue of an enhanced mean shift (EMS) algorithm. This EMS method consists of three components: spectral estimates of the heart rate, enhanced mean shift algorithm and classification logic. The Welch power spectral density method is employed to estimate the heart rate. An enhanced mean shift algorithm is then applied to improve the morphologic features of the blood pressure signals and detect the maxima of the blood pressure signals effectively. Finally, according to estimated heart rate, the classification logic is established to detect the locations of misdetections and over detections within the accepted heart rate limits. The parameters of the algorithm are adaptively tuned for ensuring its robustness in various heart rate conditions. The performance of the EMS method is validated with expert annotations of two standard databases and a non-invasive dataset. The results from this method show that the sensitivity (Se) and positive predictivity (+P) are significantly improved (i.e., Se > 99.45 %, +P > 98.28 %, and p value 0.0474) by comparison with the existing scheme from the previously published literature.


Sovateltide (IRL-1620) affects neuronal progenitors and prevents cerebral tissue damage after ischemic stroke.
Stimulation of endothelin B receptors by its agonist IRL-1620 (INN, sovateltide) provides neuroprotection and neurological and motor function improvement following cerebral ischemia. We investigated the effect of sovateltide on stem and progenitor cells mediated neural regeneration and its effect on the cerebral tissue repair and restoration of neurological and motor function. Sovateltide (5 μg/kg) was injected intravenously in permanent middle cerebral artery occluded (MCAO) rats at 4, 6, and 8 h at days 0, 3, and 6. Neurological and motor function tests were carried out pre-MCAO and at day 7 post-MCAO. At day 7, significantly reduced expression of neuronal differentiation markers HuC/HuD and NeuroD1 was seen in MCAO + vehicle than sham rats. Sovateltide treatment upregulated HuC/HuD and NeuroD1 compared to MCAO + vehicle and their expression was similar to sham. Expression of stem cell markers Oct 4 and Sox 2 was similar in rats of all of the groups. Significantly reduced infarct volume and DNA damage with recovery of neurological and motor function was observed in sovateltide-treated MCAO rats. These results indicate that sovateltide initiates a regenerative response by promoting differentiation of neuronal progenitors and maintaining stem cells in an equilibrium following cerebral ischemic stroke.


Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase.
Small interfering RNAs (siRNA) are potent reagents for directed post-transcriptional gene silencing and a major new genetic tool for investigating mammalian cells. When synthetic siRNAs are used for gene silencing, the costs can be substantial because of variations in siRNA efficacies. An alternative to chemically synthesized siRNAs are siRNAs produced by bacteriophage T7 RNA polymerase. We found that siRNAs synthesized from the T7 RNA polymerase system can trigger a potent induction of interferon alpha and beta in a variety of cell lines. Surprisingly, we also found very potent induction of interferon alpha and beta by short single-stranded RNAs (ssRNAs) transcribed with T3, T7 and Sp6 RNA polymerases. Analyses of the potential mediators of this response revealed that the initiating 5' triphosphate is required for interferon induction. We describe here an improved method for T7 siRNA synthesis that alleviates the interferon response while maintaining full efficacy of the siRNAs.


International nursing students: a phenomenological perspective.
Colleges and universities are faced with the challenge of how to create learning environments relevant to the internationalization of society and culture. International learning experiences, the focus of this article, may be one effective tool for internationalizing nursing curricula. Baccalaureate nursing students with international education experiences who were residing in a rural USA state were invited to participate in a qualitative descriptive study informed by phenomenology. Sixteen nursing students participated in mail surveys and eleven in interviews. Participants were mainly female, Caucasian, university seniors with an average age of 31 years. Thematic statements were isolated into nine experiential structures and four essential themes. Themes were identified as preparing, adjusting, caring, and transforming and were found to be influenced by culture, values, and ethics. A descriptive diagram was created summarizing the structure of meaning. Significance of this nursing study was the identification of plausible descriptive insights that may be useful to educators who assist students with international education experiences.


Pharmacologic factors associated with gentamicin nephrotoxicity in rabbits.
Nine rabbits were given subcutaneous doses of 7.5 mg of gentamicin/kg every 24 hr, and nine were given 2.5 mg of gentamicin/kg every 8 hr for three weeks or longer. Renal function was evaluated by monitoring of the concentration of creatinine in serum and the rate of clearance of gentamicin from serum. In the animals receiving the 8-hr divided dosage, a deterioration of renal function as early as day 7 was demonstrated by the rate of clearance of gentamicin, and deterioration by day 21 was evidenced by the concentration of creatinine in serum; the renal function of the animals receiving the single daily dose was unchanged. There was no relationship between peak or trough concentrations of gentamicin in serum and the development of nephrotoxicity. The animals receiving the 8-hr dosages had a significantly longer daily duration of exposure to concentrations of greater than or equal to 0.1, greater than or equal to 1.0, greater than or equal to 2.0, and greater than or equal to 3.0 microng of gentamicin/ml in serum than did animals receiving the daily dosage.


P2X7 receptor and the NLRP3 inflammasome: Partners in crime.
Adenosine triphosphate (ATP) is a molecule that on one hand plays a central role in cellular energetics and which on the other is a ubiquitous signaling molecule when released into the extracellular media. Extracellular ATP accumulates in inflammatory environments where it acts as a damage-associated molecular pattern and activates the purinergic P2X receptor 7 (P2X7) in immune cells. P2X7 receptor activation induces the formation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome and the activation of the inflammatory caspase-1. Caspase-1 causes an inflammatory type of cell death called pyroptosis through the release of pro-inflammatory cytokines and intracellular content. Consequently, intense research efforts have been devoted to the design of novel anti-inflammatory therapies, focusing in particular on the P2X7 receptor and the NLRP3 pathway and the introduction of new blocking molecules in early phase clinical trials.


Bone marrow edema in the cervical spine of symptomatic rheumatoid arthritis patients.
To investigate the frequency and clinical significance of bone marrow edema (BME) in a series of patients with rheumatoid arthritis (RA) and symptomatic involvement of the cervical spine. We studied 19 consecutive RA patients with cervical spine magnetic resonance imaging (MRI) according to a specifically designed protocol that included short inversion time inversion recovery sequences. All cases had neck pain unresponsive to conventional treatment, neurological symptoms, or signs suggestive of cervical myelopathy, or cervical pain with evidence of atlantoaxial subluxation on radiographs. The mean age of the 19 patients (15 women and 4 men) at time of the study was 59 +/- 12 years (range, 23-82) and the median disease duration was 14 +/- 7.4 years (range, 4-30). BME was observed in 74% (14/19) of the patients: at the atlantoaxial level alone in 16% of the patients; subaxially alone in 16%; and at both levels in 42% of the patients. At the atlantoaxial level, BME was usually observed involving the odontoid process, whereas subaxially BME was limited to the vertebral plates and the interapophyseal joints. Patients with BME had higher erythrocyte sedimentation rate (ESR) values at the time of MRI examination (P = 0.014) and more severe atlantoaxial joint MRI synovitis scores (P = 0.05) compared with the remaining patients; the frequency of odontoid erosions was also greater in this group, but the difference did not reach statistical significance. Altogether, these data suggest a more severe inflammatory response in these patients. In this group a significant correlation was found between BME scores at atlantoaxial level and (1) ESR values (r = 0.854; P = 0.001) and (2) atlantoaxial joint MRI synovitis scores (r = 0.691; P = 0.001). BME is frequently observed in patients with established RA and symptomatic cervical spine involvement. Both atlantoaxial and subaxial levels are equally affected. The presence of BME seems related to the intensity of the inflammatory response and to the severity of the atlantoaxial joint synovitis.


The heart in polymyositis-dermatomyositis.
Fourteen patients with polymyositis-dermatomyositis (PM-DM) underwent prospective cardiac assessment with non-invasive techniques. One patient had electrocardiographic evidence of Long-Ganong-Levine syndrome with multiple supraventricular premature beats. Echocardiographically one patient had late systolic prolapse of the posterior mitral leaflet and another had paradoxical movements of the interventricular septum. The study suggests that cardiac involvement is infrequent in PM-DM.


Approach and management of dysnatremias in cirrhosis.
Hypervolemic (dilutional) hyponatremia is the most common dysnatremia in cirrhosis, with a prevalence close to 50% in patients with ascites, while hypovolemic hyponatremia occurs in a minority of cases. Hyponatremia carries a poor prognosis, being associated with increased mortality and reduced survival after liver transplantation. Hypernatremia is rarer and is also associated with an adverse prognosis. Increased non-osmotic secretion of arginine vasopressin and altered renal tubular sodium handling due to impaired free water generation are the mechanisms leading to hypervolemic hyponatremia, while diuretic-induced fluid loss is the main cause of hypovolemic hyponatremia. Hypernatremia usually follows hypotonic fluid losses due to osmotic diuresis (glycosuria) or lactulose-induced diarrhea. The main clinical manifestations of dysnatremias are due to their effects on the central nervous system: astroglial cell hyperhydration follows hyponatremia-an abnormality that exacerbates ammonia neurotoxicity-while the opposite abnormality occurs with hypernatremia. Asymptomatic or mildly symptomatic hypervolemic hyponatremia is mainly managed by correcting of precipitating factors and non-osmotic fluid restriction. Severe, life-threatening hyponatremia requires hypertonic saline infusion, avoiding rapid and complete correction of serum sodium concentration to prevent neurological sequelae such as osmotic demyelination. V2 receptor blockade by vaptans may be considered in patients with sustained hyponatremia waitlisted for liver transplantation. Diuretic withdrawal and plasma volume expansion are required in hypovolemic hypernatremia. Prompt recognition, removal of the precipitating factor(s) and non-osmotic fluid administration represent the mainstays of hypernatremia management. Rapid correction of long-standing hypernatremia can lead to cerebral edema and has to be avoided.


Automated assembly of high-density carbon fiber electrode arrays for single unit electrophysiological recordings.
Objective.Carbon fiber (CF) is good for chronic neural recording due to the small diameter (7µm), high Young's modulus, and low electrical resistance, but most high-density carbon fiber (HDCF) arrays are manually assembled with labor-intensive procedures and limited by the accuracy and repeatability of the operator handling. A machine to automate the assembly is desired.Approach.The HDCF array assembly machine contains: (1) a roller-based CF extruder, (2) a motion system with three linear and one rotary stages, (3) an imaging system with two digital microscope cameras, and (4) a laser cutter. The roller-based extruder automatically feeds single CF as raw material. The motion system aligns the CF with the array backend then places it. The imaging system observes the relative position between the CF and the backend. The laser cutter cuts off the CF. Two image processing algorithms are implemented to align the CF with the support shanks and circuit connection pads.Main results.The machine was capable of precisely handling 6.8μm carbon fiber electrodes (CFEs). Each electrode was placed into a 12μm wide trenches in a silicon support shank. Two HDCF arrays with 16 CFEs populated on 3 mm shanks (with 80μm pitch) were fully assembled. Impedance measurements were found to be in good agreement with manual assembled arrays. One HDCF array was implanted in the motor cortex in an anesthetized rat and was able to detect single unit activity.Significance.This machine can eliminate the manual labor-intensive handling, alignment and placement of single CF during assembly, providing a proof-of-concepts towards fully automated HDCF array assembly and batch production.


Role of the Electrocardiographic MVP Risk Score (Morphology-Voltage-P Wave Duration) in Predicting the Development of Atrial Fibrillation in Patients With Systemic Arterial Hypertension.
There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5-2% of the general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF. This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months. Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an [area under the curve, 0.69; 95% confidence intervals (CI), 0.59-0.79] and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF. The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.


Implementation and monitoring of a quality management system based on the standard UNE-EN-ISO 15189 in a urine culture unit.
To evaluate the implementation of a quality management system based on ISO-15189 in a urine culture unit. The effectiveness of improvement actions was measured by quality indicators. The errors in the pre-analytical phase and the rate of contaminated urine decreased significantly. The traceability, response time and external quality control were fulfilled. The implementation of ISO-15189 was effective in improving the management of a urine culture unit.


Correction to: Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits.
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The correlation of potassium content and moisture in bovine liver samples analyzed for trace mineral concentrations.
Beef cattle in the United States are often found to be deficient in essential trace minerals such as copper and zinc. Established reference ranges for mineral concentrations exist and usually designate a concentration as adequate, marginal, deficient, or excessive. This research investigates a new method of interpreting detected elemental concentrations in bovine liver that will add confidence to the final diagnosis. This is based on the hypothesis that a correlation exists between potassium concentration and moisture in a bovine liver sample. This relationship between potassium and moisture content enables the diagnostician to more accurately predict mineral concentrations and wet weight regardless of sample moisture loss. Correlations were found between potassium content and percentage of moisture in experimental samples, clinical biopsies, and a validation study, to a statistical significance of P < 0.001. Experimental samples had a correlation coefficient of R2 = 0.95 and the mathematical relationship y = 2513.2x(-1.0662). Clinical biopsies had a correlation of R2 = 0.83 and the mathematical relationship y = 2203.4x(-0.991). The validation study had a correlation of R2 = 0.55 and a mathematical relationship y = 2321.4x(-0.952). An exponent of -1 is predicted by conservation of potassium mass. These findings have practical significance in maintaining and improving cattle growth, health, reproduction, and food safety.


Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation.
The graft-versus-host disease (GVHD) characteristics of 150 consecutive patients undergoing reduced intensity conditioning allogeneic (allo-RIC) transplants and 88 patients undergoing myeloablative conditioning regimen were analysed. All patients received the same GVHD prophylaxis and peripheral blood stem cells from a human leucocyte antigen identical sibling. The cumulative incidence of acute GVHD (aGVHD) was 67% and 44% in the myeloablative and allo-RIC regimen groups, respectively (P < 0.001), and was 39% vs. 29%, respectively (P = 0.043), for grades 2-4 aGVHD. Only conditioning type (myeloablative versus allo-RIC) significantly influenced the incidence of aGVHD in multivariate analysis: Hazard ratio (HR) = 2.16 [95% confidence interval (CI): 1.52-3.07], P < 0.0001. The cumulative incidence of chronic GVHD (cGVHD) was 63% and 71% among myeloablative and allo-RIC patients respectively (P = 0.084). This trend was because of the higher incidence of limited cGVHD, but not extensive cGVHD among allo-RIC recipients [HR = 3.3 (95% CI: 1.42-8.08), P = 0.0017]. Moreover, among patients who developed cGVHD, the cumulative incidence of limited cGVHD was significantly lower in the myeloablative group than in the allo-RIC group (7% vs. 25%, P = 0.007). Duration of immunosuppression was shorter among allo-RIC patients (35.5% vs. 68.8% required systemic immunosuppression 36 months after transplant, P = 0.028). Although prospective controlled trials are required to further evaluate the effect of the conditioning regimen on GVHD, our results suggest that RIC modifies the incidence and characteristics of both acute and cGVHD after allogeneic transplantation, and decreases the immunosuppression requirements in long-term follow up when compared with myeloablative conditioning.


In situ hybridization histochemistry as a tool to study gene expression and its regulation in the central nervous system.
The recent application of in situ hybridization histochemistry to neuroanatomy, neuroendocrinology, and neuropharmacology has permitted explorations into the regulation of gene expression in the central nervous system (CNS) at the level of single neurons. Although cDNAs were the first probes to be used in hybridization studies, cRNAs and synthetic oligonucleotides have been recently employed because of the many advantages these single-stranded probes offer compared to the cDNAs. Using synthetic oligonucleotides, we described the distribution of the calmodulin mRNA and the regulation of proenkephalin mRNA in the rat brain. The results reported show the specificity of the hybridization and that the levels of calmodulin mRNA are more abundant in the cerebral cortex than in the striatum. Furthermore, we demonstrated that the administration of 6-hydroxydopamine in early postnatal life induces an increase in the expression of striatal proenkephalin mRNA measured at postnatal day 32.


Establishment of conditions for ovum pick up and IVM of jennies oocytes toward the setting up of efficient IVF and in vitro embryos culture procedures in donkey (Equus asinus).
Most wild and domestic donkey breeds are currently endangered or threatened. Their preservation includes the creation of a Genome Resource Bank. Embryos cryopreservation allows the preservation of genetics from both male and female and is the fastest method to restore a breed. Because embryo production in vivo is limited in equids, our objective was to establish conditions for in vitro production of embryos in donkey using ovum pick up (OPU), IVM, IVF, and in vitro culture of zygotes. Donkey cumulus-oocyte complexes (COCs) were collected by transvaginal ultrasound-guided aspirations OPU in adult cyclic jennies and in vitro matured in tissue culture medium 199 supplemented with fetal calf serum and epidermal growth factor for 24, 30, 34, or 38 hours. They were preincubated with oviductal fluid for 30 minutes, coincubated with frozen-thawed donkey semen treated with procaine for 18 hours, and cultured for 30 hours in Dulbecco's Modified Eagle Medium-F12 supplemented with NaHCO3, fetal calf serum, and gentamycin. From the five OPU sessions, we collected 92 COCs in 193 follicles (48%) with an average of 4.2 COCs per jenny. All COCs were expanded after more than 24-hour IVM. At collection, jennies oocytes contained a germinal vesicle. Metaphase 1 oocytes were observed after 30-hour IVM and 44% were in metaphase 2 after 34-hour IVM. In our conditions, IVM of donkey oocytes was slower than IVM of equine oocytes and optimal duration for donkey oocytes IVM may be 34 hours. Only 15% of jennies oocytes contained two pronuclei after coincubation with donkey spermatozoa and none of them developed further after 48 hours post-IVF. Moreover, some parthenogenetic activation occurred. Thus, the treatment of donkey sperm with procaine may not be efficient for IVF. In conclusion, we established for the first time conditions for OPU in jennies with high recovery rates. We reported that IVM of jennies oocytes can produce 44% of metaphase 2 oocytes after 34 hours in culture and we described for the first time the chronology of IVM of donkey oocytes. Further studies are in progress to establish efficient conditions for IVF and development of donkey zygotes.


Water diffusion in the human hippocampus in epilepsy.
The hippocampus plays a central role in the generation and propagation of seizures in patients with complex partial seizures. Hippocampal sclerosis (HS) is a common structural abnormality in patients with refractory epilepsy. The aim of this study was to quantify diffusion in the hippocampus in patients with epilepsy to evaluate the diffusion changes associated with HS. We scanned 20 subjects (14 patients and 6 controls) with a 1.5T magnetic resonance (MR) system using a cardiac-gated, navigated spin-echo diffusion-weighted sequence. Hippocampal ADC measurements were performed on maps of the ADC measured in three orthogonal directions labeled x, y, and z. The mean ADC (ADCav) and an anisotropy index (AI) were calculated. Hippocampi which fulfilled the MR criteria for HS had a higher ADCav (p < 0.001) and a lower AI (p=0.04) than normal appearing hippocampi in patients and hippocampi in controls. These results imply a loss of structural organization in sclerotic hippocampi and an expansion of the extracellular space. Quantitative measurements of diffusion can be used as an independent parameter for the identification and characterization of abnormal hippocampi in epilepsy.


Impact of climate change in the epidemiology of vector-borne diseases in domestic carnivores.
Vector-borne diseases are medically important in humans and animals but were long considered tropical and known to first affect production animals. This is no longer true and we can see today that they are common in domestic animals and that they are also present in temperate countries, especially in Europe. In recent years, an increase in the diagnosis of vector borne diseases among humans and animals has been observed, which may partly due to the development of diagnostic tools. Their study requires exchanges and collaborations between the many actors involved, especially since the epidemiology seems to be constantly evolving. The veterinary practitioner is the first one to notice the emergence of cases and to implement prevention measures. He also acts as a sentinel to alert epidemiologists. Many factors can explain the epidemiological changes, i.e. all human factors, such as the increase in commercial transportation, but also owners traveling with their pet during the holidays, the development of "outdoor" activities, the increase of individual housings with gardens; to these human factors must be added the ignorance of the risks, linked to animals in general and to wildlife in particular; then the environmental changes: forest fragmentation, establishment of parks; the increase of wild mammal populations (deer, carnivores, rodents, etc.); finally, climate changes. Climate change is a reality which may explain the increase of density of arthropod vectors, but also of their hosts, changes in periods of activity and variations in geographical distribution. The authors show the proof of the climate modifications and then explain how it has an impact in Europe on ticks, mosquitoes, sandflies and even fleas. They conclude on the practical consequences for veterinary practitioners, especially with the diagnosis of parasitic diseases or diseases in areas where they usually do not occur. However, not any epidemiological modification should be linked to climate change, since many other factors are involved and often even overriding.


Comparative Fourier transform infrared spectroscopy study of cold-, pressure-, and heat-induced unfolding and aggregation of myoglobin.
We studied the cold unfolding of myoglobin with Fourier transform infrared spectroscopy and compared it with pressure and heat unfolding. Because protein aggregation is a phenomenon with medical as well as biotechnological implications, we were interested in both the structural changes as well as the aggregation behavior of the respective unfolded states. The cold- and pressure-induced unfolding both yield a partially unfolded state characterized by a persistent amount of secondary structure, in which a stable core of G and H helices is preserved. In this respect the cold- and pressure-unfolded states show a resemblance with an early folding intermediate of myoglobin. In contrast, the heat unfolding results in the formation of the infrared bands typical of intermolecular antiparallel beta-sheet aggregation. This implies a transformation of alpha-helix into intermolecular beta-sheet. H/2H-exchange data suggest that the helices are first unfolded and then form intermolecular beta-sheets. The pressure and cold unfolded states do not give rise to the intermolecular aggregation bands that are typical for the infrared spectra of many heat-unfolded proteins. This suggests that the pathways of the cold and pressure unfolding are substantially different from that of the heat unfolding. After return to ambient conditions the cold- or pressure-treated proteins adopt a partially refolded conformation. This aggregates at a lower temperature (32 degrees C) than the native state (74 degrees C).


White blood cell count is associated with plasma total homocysteine in Japanese men.
White blood cell (WBC) count has been related to risk for coronary heart disease. The relationship may be due to the association between WBC count and cardiovascular risk factors. So far, it has been shown that WBC count is associated with body mass index, total cholesterol, triglyceride, glucose, blood pressure and some lifestyle factors. It is not known, however, whether WBC count is associated with other risk factors such as total homocysteine or gamma-glutamyl transferase. The association between WBC count, total homocysteine and gamma-glutamyl transferase was analyzed cross-sectionally in middle-aged Japanese men. In a univariate regression analysis WBC count was associated positively with total homocysteine (beta (standard regression coefficient) = 0.112; p<0.001) but not with gamma-glutamyl transferase (beta = 0.033; p = 0.309). In a multivariate analysis which included cigarette smoking, physical activity, ethanol consumption, vegetable intake and body mass index, the association between WBC count and total homocysteine remained significant (beta = 0.062; p = 0.026). The association may partially explain the reported association between elevated WBC count and cardiovascular disease.


Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport.
2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution.


"Iron priming" guides folding of denatured aporubredoxins.
The relationship between iron uptake by aporubredoxins (apoRds) and formation of native holorubredoxins (holoRd), including their Fe(SCys)(4) sites, was studied. In the absence of denaturants, apoRds exhibited spectroscopic features consistent with structures very similar to those of the folded holoRds. However, additions of either ferric or ferrous salts to the apoRds in the absence of denaturants gave less than 40% recovery of the native holoRd circular dichroism and UV-vis spectroscopic features. In the presence of either 6 M urea or 6 M guanidine hydrochloride, the nativelike structural features of the apoRds were absent. Nevertheless, nearly quantitative recoveries of the native holoRd spectroscopic features were achieved by addition of either ferric or ferrous salts to the denatured apoRds without diluting the denaturant. Consistent with this observation, the native spectroscopic features were unaffected by addition of the same denaturant concentrations to the as-isolated holoRds. Denaturing concentrations of urea or guanidine hydrochloride also increased the rates of holoRd recoveries from apoRds and ferrous salts. Mass spectrometry confirmed that ferric iron binding to the denatured apoRds precedes the recoveries of protein secondary structures and Fe(SCys)(4) sites. Thus, iron binding to the apoRds guides, both kinetically and thermodynamically, refolding to the native holoRd structures. Our results imply that the ferrous oxidation state would more efficiently drive formation of the native holoRd structure from the nascent apoprotein in vivo, but that the Fe(SCys)(4) site must attain the ferric state in order to achieve its native structure.


The use of flow microfluorometry for pharmaceutical testing.
The techniques and procedures of rapid flow microfluorometry (FMF) in the development and testing of pharmaceuticals can be useful in the following ways: (1) cell identification and use of more precise and accurate endpoints of cell viability in cytotoxicity screening assays; (2) faster methods for determining total cellular protein, diameter, and volume in fixed cells and lymphocytes obtained in clinical studies, and adjustment of dosing regimens may be made rapidly based on such analyses; (3) studies of cellular nucleic acid content, mitotic cell progression, and growth in drug-treated cell populations, and investigations conducted on whether a particular drug is acting on a sensitive cell population or whether its effects are consistent throughout a particular group of cells or tissues; (4) measurement of drug penetration, uptake, concentration, resistance, and cell cycle specificity in cells and tissues, and (5) automated scoring of chromosome number, ploidy, and aberrations in treated cells as additional evidence of toxic activity of pharmaceutical substances. The binding of drugs to cellular macromolecules and other structures can result in a multiplicity of effects on cell growth, metabolism, chromosome content, morphology, and neoplastic potential. The methods and results described in this review can be used individually and in combination, along with commonly used techniques. It is hoped that an integrated approach to basic cellular biology, pharmacology, physiology, genetics, and toxicology as applied to drug development and testing can be furthered through use of FMF. Caution must be exercised, however, in extrapolating results found in one study of chemotherapeutic efficacy to other circumstances of clinical practice, since interindividual differences in response are not abrogated by this new technology. The introduction of flow microfluorometry is likely to engender a significant delay in its validation by the Food and Drug Administration as a means of generating data suitable for support of approval of the pharmaceutical products and processes that it regulates. This is due to the complex theoretical considerations associated with FMF and the attendant need for instrument familiarization and training of Food and Drug Administration reviewers. As with any new technology, time must pass and further experimentation be conducted before a laboratory method can become a universally accepted, commercially useful, and viable technique.


Dependence of cat vestibulo-ocular reflex direction adaptation on animal orientation during adaptation and rotation in darkness.
Four series of experiments investigated how adaptive changes in direction of the cat's vestibulo-ocular reflex (VOR) vary with position of the animal during adaptive training and postadaptive testing. In all experiments VOR was measured electrooculographically during rotations about earth-horizontal and vertical axes in the dark before and after 2 h of adaptation in which 0.25 Hz sinusoidal whole body rotation about a horizontal/vertical axis was paired with synchronous 0.25 Hz rotation of a visual pattern about a vertical/horizontal axis, respectively. In upright sagittal (US) experiments, coupling of pitch rotation with visual pattern rotation about an earth vertical axis yielded an adaptive horizontal VOR response to pitch rotation whose gain had a local maximum at 0.25-0.5 Hz plus a sustained rise for frequencies below 0.1 Hz. When post-tests were done with the animal rolled 90 degrees onto its side and rotated about the earth vertical axis (pitch relative to the cat), the low frequency rise was eliminated and the 0.25 Hz peak was reduced. In on side sagittal (SS) experiments, where training was done in the latter (on side) position, training produced only the 0.25 Hz peak without the low frequency rise, indicating that the rise is due to coupling of otolith input to horizontal VOR. Again the 0.25 Hz peak was reduced when testing was done with the cat oriented 90 degrees from the training position (in the US position). This indicates that the cross-coupled canal-ocular reflex response is modulated or gated by the position of the animal with respect to gravity.(ABSTRACT TRUNCATED AT 250 WORDS)


Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa.
The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha-chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin-substance P- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Of the three peptides present, only VIP produced a concentration-dependent relaxation. A substance with VIP-like immunoreactivity was released during nerve-induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium-depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.


Prognostic significance of grading (MIB-1 system) in patients with myxoid liposarcoma.
To determine the relation between clinical outcome and tumour grade defined by a MIB-1 (Ki-67) score based grading system. The clinical and pathological features of 50 patients with myxoid liposarcoma were evaluated, and MIB-1 immunostaining was performed to grade these patients' tumours. Univariate and multivariate analyses were conducted to evaluate survival. Clinical follow up details were available for all patients (median, 46.5 months; range, 9-408). Univariate analysis revealed that the tumour site (p < 0.05), round cell component content (p < 0.01), necrosis (p < 0.01), mitosis (p < 0.01), MIB-1 labelling index (p < 0.001), and tumour grade (p < 0.001) had a significant impact on overall survival. Multivariate analysis showed that, of the variables evaluated, the tumour grade defined by a MIB-1 score based grading system was the most significant adverse prognostic factor. Tumour grade determined by the grading system using the MIB-1 score (MIB-1 system) is a very strong prognostic factor in patients with myxoid liposarcoma.


Full Genome of Phialocephala scopiformis DAOMC 229536, a Fungal Endophyte of Spruce Producing the Potent Anti-Insectan Compound Rugulosin.
We present the full genome of Phialocephala scopiformis DAOMC 229536 (Helotiales, Ascomycota), a foliar endophyte of white spruce from eastern Quebec. DAOMC 229536 produces the anti-insectan compound rugulosin, which inhibits a devastating forestry pest, the spruce budworm. This genome will enable fungal genotyping and host-endophyte evolutionary genomics in inoculated trees.


Modeling and optimization of poly(3hydroxybutyrate-co-3hydroxyvalerate) production from cane molasses by Azohydromonas lata MTCC 2311 in a stirred-tank reactor: effect of agitation and aeration regimes.
The effects of agitation and aeration rates on copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] production by Azohydromonas lata MTCC 2311 using cane molasses supplemented with propionic acid in a bioreactor were investigated. The experiments were conducted in a three-level factorial design by varying the impeller (150-500 rev min(-1)) and aeration (0.5-1.5 vvm) rates. Further, the data were fitted to mathematical models [quadratic polynomial equation and artificial neural network (ANN)] and process variables were optimized by genetic algorithm-coupled models. ANN and hybrid ANN-GA were found superior for modeling and optimization of process variables, respectively. The maximum copolymer concentration of 7.45 g l(-1) with 21.50 mol% of 3HV was predicted at process variables: agitation speed, 287 rev min(-1); and aeration rate, 0.85 vvm, which upon validation gave 7.20 g l(-1) of P(3HB-co-3HV) with 21 mol% of 3HV with the prediction error (%) of 3.38 and 2.32, respectively. Agitation speed established a relative high importance of 72.19% than of aeration rate (27.80%) for copolymer accumulation. The volumetric gas-liquid mass transfer coefficient (k (L) a) was strongly affected by agitation and aeration rates. The highest P(3HB-co-3HV) productivity of 0.163 g l(-1) h(-1) was achieved at 0.17 s(-1) of k (L) a value. During the early phase of copolymer production process, 3HB monomers were accumulated, which were shifted to 3HV units (9-21%) during the cultivation period of 24-42 h. The enhancement of 7.5 and 34% were reported for P(3HB-co-3HV) production and 3HV content, respectively, by hybrid ANN-GA paradigm, which revealed the significant utilization of cane molasses for improved copolymer production.


Oseltamivir-induced behavioral changes in a female Lebanese adolescent: a case report of a usual drug with unusual side effect.
Neuropsychiatric symptoms, including abnormal behavior, after oseltamivir use among influenza patients have been of concern. In recent years, many case reports of neuropsychiatric events during or after oseltamivir treatment were reported; however, literature review revealed no such cases in Lebanon. Oseltamivir is the most widely prescribed medication against influenza and is generally well tolerated, causing random gastrointestinal disturbances, including nausea, vomiting, diarrhea and abdominal pain. However, in rare instances, it has been reported to stimulate behavioral activities in adolescents. We report herein a case of an oseltamivir-related neuropsychiatric event in a female adolescent in Lebanon, which resolved 2 days after stopping the drug.


Predicting bacteriophage proteins located in host cell with feature selection technique.
A bacteriophage is a virus that can infect a bacterium. The fate of an infected bacterium is determined by the bacteriophage proteins located in the host cell. Thus, reliably identifying bacteriophage proteins located in the host cell is extremely important to understand their functions and discover potential anti-bacterial drugs. Thus, in this paper, a computational method was developed to recognize bacteriophage proteins located in host cells based only on their amino acid sequences. The analysis of variance (ANOVA) combined with incremental feature selection (IFS) was proposed to optimize the feature set. Using a jackknife cross-validation, our method can discriminate between bacteriophage proteins located in a host cell and the bacteriophage proteins not located in a host cell with a maximum overall accuracy of 84.2%, and can further classify bacteriophage proteins located in host cell cytoplasm and in host cell membranes with a maximum overall accuracy of 92.4%. To enhance the value of the practical applications of the method, we built a web server called PHPred (〈http://lin.uestc.edu.cn/server/PHPred〉). We believe that the PHPred will become a powerful tool to study bacteriophage proteins located in host cells and to guide related drug discovery.


Standalone titanium/polyetheretherketone interbody cage for anterior lumbar interbody fusion: Clinical and radiological results at 24 months.
Anterior lumbar interbody fusion (ALIF) is a common procedure for patients suffering degenerative, deformity, or posttraumatic pathologies of the lumbar spine. The aim of this study is to evaluate the clinical and radiological outcomes of a combination Titanium/Polyetheretherketone (Ti/PEEK) 3-screw fixation ALIF cage. This was a prospective multisurgeon series of 87 patients (105 implants), with a minimum 24-month follow-up. Twelve patients (12/87) were supplemented with posterior percutaneous pedicle screw fixation for additional stability for pars defect spondylolisthesis correction. Radiological follow-up with fine-cut computed tomography (CT) scan occurred at 4-6 months, and again at 18-24 months if no fusion observed on initial CT, was performed to evaluate early and final fusion rates, and integration of the Ti/PEEK cage at the end-plate junction. Clinical follow-up included the subjective measures of pain and functional status and objective wearable device monitoring. The fusion rate was 85% (97/105 implants) 6 months postoperatively, with no implant-related complications, and 95% at 24 months, based on independent radiological assessment. Patients experienced statistically significant improvement in subjective pain and functional outcomes compared to preoperative status. The objective measures revealed a daily step count with a 27% improvement, and gait velocity with a mean increase from 0.97 m/s to 1.18 m/s, at 3 months postoperatively. A Ti/PEEK cage, with allograft and bone morphogenetic protein-2 (BMP-2), achieved rapid interbody progression to fusion and is an effective implant for use in anterior lumbar surgery with high early fusion rates and no peri-endplate lucency. Supercritical CO2 allograft provided an osteoconductive scaffold and combined well with BMP-2 to facilitate fusion.


An impedimetric chemical sensor for determination of detergents residues.
A new impedimetric sensor based on an interdigitated electrode array with electrode digits located at the bottom of microcapillaries formed in silicon dioxide is presented. Microcapillaries are opened at the top, so that in contact with an electrolyte solution the ac current flows close to the surface of the capillary wall from one electrode to another and is significantly affected by changes in the surface conductance at the SiO2/electrolyte interface. Adsorption of detergents on the sensor surface affects the charge distribution in the electrical double layer and thus the surface conductance. These changes are registered by measuring impedance. Effect of surface adsorption of ionic and non-ionic surfactants on the sensor impedance is studied. The sensor is shown to be able to measure commercial detergents residues in a tap water starting from 5 ppm even in solutions with high electrolyte conductivity.


Male Sex Associated with Increased Long-term Cardiovascular Mortality after Peripheral Vascular Surgery for Atherosclerosis Despite Optimal Medical Treatment.
The cardiovascular burden and consequences of peripheral atherosclerosis appear to differ between men and women. Data regarding long-term outcomes, including the impact of medical prophylactic treatment, are insufficient. This study examined long-term outcomes according to sex following primary vascular surgery, adjusted for multiple variables as well as recommended medical prophylaxis. All Danish patients who underwent peripheral vascular surgery from January 2000 to December 2007 were stratified into five procedural groups: (a) aorto-iliac bypass or thromboendarterectomy, (b) femoro-femoral crossover, (c) thromboendarterectomy of the femoral arteries, (d) infrainguinal bypass, or (e) axillo- uni-, and bifemoral bypass. Data were analyzed according to sex for differences in myocardial infarction, stroke, and death, individually and combined, after surgery. A total of 11,234 patients were included: 6,289 males and 4,945 females. The overall adjusted hazard ratio for male patients compared with female patients for death was 1.11 (95% CI 1.06-1.17), for MI was 1.16 (95% CI 1.04-1.29), for stroke was 0.99 (95% CI 0.89-1.11), and for any major adverse cardiovascular event was 1.10 (95% CI 1.05-1.16). These findings show that, despite indication, severity, and concomitant medical treatment of peripheral artery disease, men have a higher risk of mortality and adverse cardiovascular events following surgery for peripheral arterial disease.


WNT Signaling in Cancer Immunosurveillance.
Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy.


The effects of glucose on myocardial substrate utilization in acute myocardial infarction or angina pectoris.
Infusion of glucose-insulin-potassium during acute myocardial infarction has favorable clinical and hemodynamic effects, presumably as a result of decreased myocardial utilization of free fatty acids. In 14 patients with coronary artery disease, hypertonic glucose (a bolus of 10 g followed by infusion of a 30% glucose solution at a constant rate of 10 mg/kg/min) was infused and arterial and coronary sinus levels of glucose, lactate and free fatty acids were measured before and after 15 and 30 minutes of infusion. Arterial glucose and lactate levels increased significantly after glucose infusion, whereas free fatty acid levels decreased significantly. Modest but significant correlations also existed between glucose arterial levels and the arterial-coronary sinus glucose difference (r = 0.53, p less than 0.001); arterial lactate and the arterial-coronary sinus lactate difference (r = 0.35, p less than 0.01); arterial free fatty acids; and the arterial-coronary sinus free fatty acid difference (r = 0.62, p less than 0.001). These results with a hypertonic glucose infusion are similar to those reported after infusion of glucose-insulin-potassium without the potential for harmful adverse effects from infusions of insulin or potassium. Therefore, infusion of hypertonic glucose may be beneficial in patients with coronary artery disease. Further work is necessary to study its effects in different subgroups of patients with coronary artery disease.


Endoscopic submucosal tunnel dissection vs conventional endoscopic submucosal dissection for large colorectal neoplasms: a single-centre retrospective study.
Colorectal endoscopic submucosal dissection (ESD) is still not widely used due to its technical difficulty and the risk of complications. Several techniques, such as traction techniques, pocket techniques and others, have been proposed to facilitate it. One modified pocket technique especially suitable for large lesions is endoscopic submucosal tunnel dissection (ESTD). The aim of this study was to evaluate the safety and efficacy of ESTD and compare ESTD to the conventional ESD (CESD) for treating large colorectal lesions. The charts of consecutive patients referred to the Arcispedale Santa Maria Nuova (Reggio Emilia, Italy) for colorectal ESD between January 2014 and February 2021 for colorectal neoplasms > 40 mm were retrospectively analysed. The primary outcome of the study was the en bloc resection rate. Secondary outcomes were complete and curative resection rates, procedure speed, the adverse events rate and the recurrence rate. There were 59 patients (M:F ratio 29:30, median age 70 years [range 50-93 years]). Of 59 colorectal lesions > 40 mm, 25 were removed by ESTD and 34 by CESD. The en bloc resection rate was 100% in both groups and the complete resection rate was similar (ESTD 92% vs CESD 97.1%, p = 0.569), while the curative resection rate was higher in the CESD group, but not significantly (94.1% vs 76%, p = 0.061). Procedure speed was significantly faster with ESTD (22 vs 17 mm2/min, p = 0.045), and the overall incidence of adverse events was low (6.8%). Eight patients were referred to surgery due to non-curative resection. During follow-up, no recurrence was observed in either treatment group. ESTD achieves a very high en bloc resection rate and is faster than CESD.


Analysis of head movements coupled with trunk drift in healthy subjects.
Accelerometers were used to measure sequential head tilt and trunk drift in 14 healthy young subjects while they performed three kinds of head task. First, maximum inclination angles in anterior, posterior, right and left directions were measured to estimate cervical ranges of motion for flexion-extension and lateral bending. The inclination angles measured (61.2 degrees on average for flexion, 51.7 degrees for extension, 42.7 degrees for right bending and 43.9 degrees for left bending) were consistent with previous findings. Secondly, cross-correlation analysis was applied to evaluate the degree of functional coupling between the head and trunk during flexion-extension and lateral bending. Significantly higher correlation coefficients were found between head tilt and trunk drift when these movements were in the same (iso-) directional condition than in a different (allo-) directional condition. The coupled trunk drift in flexion-extension for the iso-directional condition (10.3 degrees on average) was much larger than for the allodirectional condition (2.3 degrees). Finally, head turning was recorded as oval traces in a biaxial plane. In both clockwise and counter-clockwise head turning conditions, the maximum inclination angles of the traces were larger in the anterior-posterior direction (59.8 degrees anterior and 58.2 degrees posterior, in the clockwise condition, and 47.4 degrees and 47.4 degrees in the counter-clockwise condition) than in the right-left direction (36.3 degrees right and 39.0 degrees left, in the clockwise condition, and 40.5 degrees and 36.7 degrees in the counter-clockwise condition), and the angles in the four directions were almost equal to flexion-extension and lateral bending. The characteristics of the traces recorded and a possible application of the present recording system are discussed.


[D. Documentation and statistics. Therapy code for all surgically active disciplines].
The study group of the German Society for Medical Documentation. Information and Statistics presents a suggested code that is an extension of VESKA. Since it only extends from Head to Gynecology, the Eltze-Eichler code is recommended for Orthopedics and Extremities. A general 6-digit code classified under different facets is being developed.


Mental health knowledge and attitudes in a transition year student group: a pilot survey.
Introduction Stigma towards mental health disorders remains a significant problem in society. Numerous public awareness campaigns and, to a lesser extent, educational interventions have been carried out to date to help address this issue. A brief questionnaire was formulated and administered to two small groups of transition year students from schools throughout Ireland who participated in a week-long placement in a Psychiatric Hospital in Dublin in 2012. The input was from psychiatry and allied health professionals covering a wide range of mental health topics. It was administered before the first session and immediately after the last session. The input for each group in terms of topics was almost identical. In all, 24 students participated, and the majority had either gone to school with, had observed in passing, or had a friend of the family or a relative with a mental illness, although only 21% had had knowledge on mental illness up to the intervention. The post-intervention scores demonstrated that the week had an impact on most of these views. Their attitudes to individuals with mental illness as regards employment, treatment, assistance, and recovery were encouraging, even at baseline, and all their responses improved following the sessions. There was a view that those with mental illness were somewhat reluctant to seek professional help. Although the results of this study are very encouraging as regards attitudes towards mental health and their response to education, far more research and interventions are needed to explore and address stigma in more detail.


YAP mediates the interaction between the Hippo and PI3K/Akt pathways in mesangial cell proliferation in diabetic nephropathy.
Glomerular mesangial cell (MC) proliferation is one of the main pathological changes in diabetic nephropathy (DN), but its mechanism needs further elaboration. The Hippo and PI3K/Akt signalling pathways are involved in the regulation of MC proliferation, but their relationship in hyperglycaemia-induced MC proliferation has not been reported. We used db/db mice and high-glucose-cultured mesangial cells to generate a diabetic nephropathy model. An MST1-knockdown plasmid was used to identify whether the PI3K/Akt pathway is linked to the Hippo pathway through MST1. LY294002 and SC79 were used to verify the role of the PI3K/Akt signalling pathway in MC cells. RNA silencing and overexpression were performed by using YAP and PTEN-expression/knockdown plasmids to investigate the function of YAP and PTEN, respectively, in the Hippo and PI3K/Akt signalling pathways. By examining a potential feedback loop, we found decreased phosphorylation of MST1 and Lats1 and increased PI3K/Akt activation in db/db mice and high glucose-treated MCs, along with increased MC proliferation. The results of our gene silencing experiment proved PI3K/Akt-mediated intervention in the Hippo pathway and the regulatory effect of YAP on PI3K/Akt through PTEN. The Hippo pathway is inhibited under diabetic conditions, leading to YAP activation and promoting MC proliferation. The PI3K/Akt pathway is activated through the inhibitory effect of YAP on its repressor, PTEN. Finally, activation of the PI3K/Akt pathway inhibits the Hippo pathway, resulting in nuclear YAP accumulation and accelerating MC proliferation and DN formation.


Glucocorticoids in malignant lymphoid cells: gene regulation and the minimum receptor fragment for lysis.
We have examined clones of human malignant lymphoid cells for markers that correlate with glucocorticoid-mediated cell lysis. In glucocorticoid-sensitive clones of CEM, a human T-cell lymphoblastic leukemia line, two genes correlate with glucocorticoid-induced cell lysis. The glucocorticoid receptor (GR) itself is induced by standard glucocorticoids in sensitive clones and not in insensitive clones. The phenylpyrazolo-glucocorticoid cortivazol (CVZ) is capable of lysing several clones resistant to high concentrations of standard potent glucocorticoids. When these clones were tested for cortivazol responses, they were not only lysed by cortivazol but also showed induction of GR mRNA. Thus receptor induction appears to correlate with the lysis function of receptor in these cells. To determine what parts of the GR are required for lysis, we have mapped this function by transfecting and expressing GR and GR fragment genes in a GR-deficient CEM clone. Our results indicate that none of the known trans-activation regions of the GR are required. Removal of the steroid binding domain gives a fragment that is fully constitutive. Only one and one-half "Zn fingers" of the DNA binding region are required. We also find in CEM cells rapid suppression of the c-myc protooncogene, preceding growth arrest and cell lysis by glucocorticoids. This occurs only in clones possessing both intact receptors and lysis function. Thus the simple presence of GR alone is not sufficient to guarantee c-myc down-regulation. Introduction into the cells of c-myc driven by a promoter that does not permit suppression by glucocorticoids confers resistance to steroids. Furthermore, suppression of c-myc by antisense oligonucleotides also kills the cells. Therefore, c-myc appears to be a pivotal gene related both to ability of steroid to kill and to cell viability.