Standard versus bony increased-offset reverse shoulder arthroplasty: a retrospective comparative cohort study.
To date, only a few comparative studies with small sample sizes have compared a traditional reverse shoulder arthroplasty (tRSA) to a bony increased-offset RSA (BIO-RSA). We hypothesized that the BIO-RSA would lead to lower notching rates and improved range of motion (ROM) compared with a tRSA. A retrospective review was performed of 69 tRSAs and 61 BIO-RSAs performed by a single surgeon. At 2 years postoperative, ROM and Constant scores were compared. Radiographs were examined for scapular notching, scapular spurring or ossification, and graft healing. At the 2-year follow-up, the BIO-RSA group demonstrated improved anterior forward flexion compared with the tRSA group (145° ± 20° vs. 138° ± 20°, respectively; P = .017). There was no difference in external or internal rotation between the 2 groups. The BIO-RSA group had a higher Constant score than the tRSA group (69 ± 9 vs. 61 ± 13; P < .001). The radiographs showed no difference between the 2 groups, including scapular notching (P = .150). At the 2-year follow-up, BIO-RSA does not lead to a clinically significantly improvement in ROM, Constant scores, or change in scapular notching compared with a tRSA.


Reevaluation of taurine levels and distribution of cysteic acid decarboxylase in developing human fetal brain regions.
The possibilities of interference by glycerophosphoryl ethanolamine (GPE) in the estimation of taurine levels in cerebral cortex, midbrain, cerebellum, medullapons, and spinal cord of developing human fetal brain regions were eliminated by hydrolyzing tissue extracts with 6 M HCl. Cysteic acid thus produced was separated from taurine by ion-exchange chromatography using Biorad-AG resin. Fluorescamine was used as fluorogen. Data reveal that the estimation of taurine in human fetal brain regions is affected if GPE is present as a contaminant in the assay system. Cysteic acid decarboxylase activity was measured using cysteic acid as the substrate. Higher enzymic activity was recorded with increased fetal body weight, but the reverse was true for taurine level.


Extrathoracic airways changes during plethysmographic measurements of lung volume.
In six healthy subjects cineradiographic studies during panting against a closed shutter showed widening and narrowing of the whole extrathoracic airways. At the epiglottic level, the mean lateral maximum diameter was 121% of the minimum diameter for an applied pressure of 11.4 cm H2O and 152% for 28.4 cm H2O, while posteroanterior diameter changes were 148% for 12.3 cm H2O and 182% for 28.2 cm H2O, respectively. There was a significant correlation between anteroposterior diameter changes and mouth pressure (Pm) swings (P less than 0.05). In 6 cadavers, the compliance of extrathoracic airways (isolated from the lower respiratory tract by an inflated balloon in the upper trachea) was 1.5 ml X cm H2O-1 after adding 30 ml of air, and 1 ml X cm H2O-1 after removing 30 ml of air. Flow rate in and out the extrathoracic airways averaged 0.089 and 0.163 L X sec-1 for swings in Pm of 9.5 and 18.5 cm H2O, respectively. There was a significant correlation (P less than 0.05) between flow rate and delta Pm. For a given delta Pm, flow was higher in those cadavers with more compliant extrathoracic airways. We conclude that extrathoracic airways change their volume during panting, and that these volume changes, as well as the internal flow rate thus created, depend on the Pm swings.


HPrK regulates succinate-mediated catabolite repression in the gram-negative symbiont Sinorhizobium meliloti.
The HPrK kinase/phosphatase is a common component of the phosphotransferase system (PTS) of gram-positive bacteria and regulates catabolite repression through phosphorylation/dephosphorylation of its substrate, the PTS protein HPr, at a conserved serine residue. Phosphorylation of HPr by HPrK also affects additional phosphorylation of HPr by the PTS enzyme EI at a conserved histidine residue. Sinorhizobium meliloti can live as symbionts inside legume root nodules or as free-living organisms and is one of the relatively rare gram-negative bacteria known to have a gene encoding HPrK. We have constructed S. meliloti mutants that lack HPrK or that lack key amino acids in HPr that are likely phosphorylated by HPrK and EI. Deletion of hprK in S. meliloti enhanced catabolite repression caused by succinate, as did an S53A substitution in HPr. Introduction of an H22A substitution into HPr alleviated the strong catabolite repression phenotypes of strains carrying Delta hprK or hpr(S53A) mutations, demonstrating that HPr-His22-P is needed for strong catabolite repression. Furthermore, strains with a hpr(H22A) allele exhibited relaxed catabolite repression. These results suggest that HPrK phosphorylates HPr at the serine-53 residue, that HPr-Ser53-P inhibits phosphorylation at the histidine-22 residue, and that HPr-His22-P enhances catabolite repression in the presence of succinate. Additional experiments show that Delta hprK mutants overproduce exopolysaccharides and form nodules that do not fix nitrogen.


Transitions between versions of the International Classification of Diseases and chronic disease prevalence estimates from administrative health data: a population-based study.
Diagnosis codes in administrative health data are routinely used to monitor trends in disease prevalence and incidence. The International Classification of Diseases (ICD), which is used to record these diagnoses, have been updated multiple times to reflect advances in health and medical research. Our objective was to examine the impact of transitions between ICD versions on the prevalence of chronic health conditions estimated from administrative health data. Study data (i.e., physician billing claims, hospital records) were from the province of Manitoba, Canada, which has a universal healthcare system. ICDA-8 (with adaptations), ICD-9-CM (clinical modification), and ICD-10-CA (Canadian adaptation; hospital records only) codes are captured in the data. Annual study cohorts included all individuals 18 + years of age for 45 years from 1974 to 2018. Negative binomial regression was used to estimate annual age- and sex-adjusted prevalence and model parameters (i.e., slopes and intercepts) for 16 chronic health conditions. Statistical control charts were used to assess the impact of changes in ICD version on model parameter estimates. Hotelling's T2 statistic was used to combine the parameter estimates and provide an out-of-control signal when its value was above a pre-specified control limit. The annual cohort sizes ranged from 360,341 to 824,816. Hypertension and skin cancer were among the most and least diagnosed health conditions, respectively; their prevalence per 1,000 population increased from 40.5 to 223.6 and from 0.3 to 2.1, respectively, within the study period. The average annual rate of change in prevalence ranged from -1.6% (95% confidence interval [CI]: -1.8, -1.4) for acute myocardial infarction to 14.6% (95% CI: 13.9, 15.2) for hypertension. The control chart indicated out-of-control observations when transitioning from ICDA-8 to ICD-9-CM for 75% of the investigated chronic health conditions but no out-of-control observations when transitioning from ICD-9-CM to ICD-10-CA. The prevalence of most of the investigated chronic health conditions changed significantly in the transition from ICDA-8 to ICD-9-CM. These results point to the importance of considering changes in ICD coding as a factor that may influence the interpretation of trend estimates for chronic health conditions derived from administrative health data.


Conducting routine fatigue assessments for use in clinical oncology practice: patient and provider perspectives.
Fatigue is the most common symptom associated with cancer and its treatment. The present study measured patient and provider perceptions of the feasibility and acceptability of conducting computerized fatigue assessments during routine follow-up outpatient clinic visits. A subset of 64 patients from a larger study, testing items for inclusion in a fatigue item bank, completed two computerized fatigue assessments at 2- to 3-month intervals. After the second assessment, patients completed a questionnaire about the usefulness of the assessments and the understandability of graphic reports depicting the fatigue scores. They were also asked about the optimal frequency for conducting fatigue assessments. Providers were asked similar feasibility questions. Providers thought displays of fatigue scores would be more useful than patients did. Patients and providers also differed on the frequency with which fatigue assessments should be conducted. Interestingly, of the 37% of patients who reported that assessments should be conducted at a different frequency than the choices that were offered, 50% reported that the assessments should be conducted according to their treatment schedule. The majority of providers thought fatigue assessments should be administered at each MD visit. Patients and providers differed about the perceived usefulness of displaying fatigue scores and the frequency with which routine assessments should be conducted. However, both patients and providers appeared to endorse the notion that routine assessments would be beneficial. Integration of routine assessments of commonly experienced symptoms such as fatigue may have important implications for improving symptom management in the future, ultimately resulting in better overall patient care.


Reversibility of the transformed and neoplastic phenotype. IV. Effects of long-term interferon treatment of C3H/10T1/2 cells transformed by methylcholanthrene and SV40 virus.
The effects of long-term treatment with mouse interferon on the phenotype of untransformed C3H/10T1/2 cells and cloned derivatives transformed by methylcholanthrene (MCA) and Simian virus 40 (SV40) were investigated. Continuous presence of interferon induced morphologic reversion, with the development of thick, submembranous filaments in MCA-transformed cells, whereas no morphological effects were detected in SV40-transformed cells. Interferon inhibited the proliferation of all three cell lines and maintained low saturation densities. However, prolonged treatment of MCA-transformed cells with interferon rendered them tolerant toward the anti-proliferative and antiviral activities of interferon although 2-A synthetase activity was induced. Interferon treatment reduced the capacity of both MCA and SV40-transformed cells to form colonies in agar and decreased the tumorigenicity of MCA-transformed but not SV40-transformed cells in mice. These results indicate that the same cell type transformed by different means has different sensitivities to a number of interferon-induced changes in the cell phenotype.


[Retracted] Morphine‑induced delayed pre‑conditioning against anoxia/reoxygenation injury in pulmonary artery endothelial cells: The role of mitochondrial KATP channels.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the flow cytometric plots featured in Fig. 2A on p. 1050 contained repeating patterns of dots, both vertically and horizontally, in addition to a variety of other apparent anomalies. The authors were asked to provide an explanation to account for the apparent anomalies in this figure, but they did not respond to the request posed by the Editorial Office. Therefore, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 1047‑1053, 2016; DOI: 10.3892/mmr.2015.4629].


Surgery and chemotherapy. A new method of treatment for squamous cell bronchial carcinoma.
Between April, 1981, and December, 1982, 32 patients with squamous cell bronchial carcinoma were treated with a chemotherapy regimen followed by operation. The preoperative chemotherapeutic agents used were cisplatin, bleomycin, and mitomycin C. A thoracotomy was performed 3 to 4 weeks after the last day of the last treatment. Of the 29 undergoing resection, three (10.3%) had no tumor cells in the resected specimen and four (12.5%) had only a few neoplastic microcenters in tissue necrosis or fibrosis. We suggest that the use of this new chemotherapy combination with surgical resection provides excellent palliation, increases resectability, and has a potential for increasing the cure rate in squamous cell carcinoma of the lung.


[What can structured doctoral programs contribute to ensure quality of medical dissertations and scientific careers/junior promotion? An evaluation using the "Experimental Medicine" program initiative of Ulm University as an example].
Structured doctoral programs in medicine are intended to contribute to the quality of medical dissertations/doctoral theses by providing scientific skills and also inspire doctoral candidates to pursue a career in research. Here we present the potential contributions of the doctoral program "Experimental Medicine" of Ulm University with regard to the increase of individual quality indicators, e. g., the duration and evaluation of the doctoral theses as well as the study participants' scientific career intentions and current field of activity. All previous participants of the doctoral program (N = 144) were contacted as well as medical graduates with an experimental doctorate as individual doctorate (control group) (N = 559) who had submitted a doctoral thesis in the same period. The response rate was 55.4 % (N = 72) among program participants versus 21.7 % (N = 116) in the control group. Information on the doctoral thesis process, scientific and professional careers and quality indicators were collected in an online survey and compared statistically using U-tests or Chi-square tests. The participants' evaluation of the program and their confidence in scientific competences, rated on a 5-point rating scale, were outlined descriptively. Program participants were satisfied with the supervision of their work (M 2.17; SD 0.84). According to the participants' evaluation, particular support was given to increase competence in scientific presentations (M 1.9; SD 0.83), in literature research (M 2.21; SD 0.96) and in the critical appraisal of scientific publications (M 2.28; SD 0.91). However, they felt comparatively less competent regarding the selection of research methods (M 3.21; SD 1.11) and the application of statistical methods (M 3.53; SD 1.13). Program participants needed less time to complete their doctoral theses than the control group (median 4 years versus 5 years) and received the overall grade of "summa cum laude" (excellent) more frequently (22.9 % versus 2.7 %). In comparison, their doctoral theses were more often part of third-party funded projects (59 % versus 36.1 %). In addition, the participants more frequently wished to pursue a habilitation (29.2 % versus 13.3 %) or aspire to an academic career (13.9 % versus 1.7 %). Despite methodological limitations, the results support the structured doctoral program, particularly with regard to the duration and evaluation of the doctorate. The program should be further optimized, though, with respect to specific aspects, particularly in terms of "career paths in research".


Catalytic generation and selective heterocoupling of two electron-rich alkenes.
Complex heterocyclic products were synthesized from simple alkynamine and alkynol derivatives in a double cycloisomerization/heterodimerization cascade reaction. The reaction includes the heterocoupling reaction of two different electron-rich alkenes and leads to the formation of four new bonds and three stereocenters (two of them quaternary).


The sites of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossal nuclei in the rat.
The sites of origin of serotoninergic afferents in the trigeminal motor (Vm), facial (VII), and hypoglossal nuclei (XII) were studied in the rat by fluorescent retrograde labeling with Fluoro-Gold, in combination with immunofluorescence histochemistry for serotonin (5-HT). The results indicated: (1) The nucleus raphe magnus, nucleus raphe pallidus, and nucleus raphe obscurus contained 5-HT neurons projecting to the Vm, VII or XII. (2) The nucleus raphe dorsalis sends 5-HT fibres to the Vm and VII, but not to the XII. (3) The gigantocellular reticular nucleus pars alpha contained 5-HT neurons projecting to the VII.


Calyx to parenchyma ratio in pelvi-ureteric junction obstruction.
To review the ultrasonography of patients who had undergone pyeloplasty for pelvi-ureteric junction (PUJ) obstruction, and document the changes in calyceal distension and parenchymal thickness after pyeloplasty, to attempt to establish an additional prognostic indicator. Fifty-eight patients who underwent pyeloplasty for PUJ obstruction were assessed retrospectively. Pre- and postoperative ultrasonograms were analysed for both pyelocaliectasis, graded according to the Society for Fetal Urology criteria, and the ratio of the depth of calyces to the thickness of the parenchyma (C/P ratio). Patients underwent nuclear medicine renography before and 3 months after pyeloplasty. The results were analysed using the paired t-test, Kruskal-Wallis test, Spearman's correlation coefficient by rank test and the Mann-Whitney U-test. There was no significant difference in hydronephrosis grade before and after surgery (P < 0.05) but there was a significant difference in the C/P ratios (P < 0.01). There was no correlation between C/P ratios and the results of diuresis renography. Hydronephrosis as measured by an estimate of pelvic volume is an insensitive marker of improvement after pyeloplasty. Reduced calyceal distension correlates well with other favourable prognostic indicators. Therefore, the C/P ratio may be an additional indicator of the appropriateness of surgical intervention, and should be the subject of further study.


Re-evaluating pathogenicity of variants associated with the long QT syndrome.
Genetic testing for congenital long QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies (AF) in the general population. This study aims to evaluate the presence of LQTS-associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants. Variants associated with LQTS from the Human Gene Mutation Database were extracted and matched to the gnomAD to evaluate population-based AF. We used MetaSVM to predict the function of LQTS variants. Allele distribution by protein topology in KCNQ1, KCNH2, and SCN5A was compared between gnomAD (n = 123,136) and a cohort of LQTS patients aggregated from eight published studies (n = 2,683). Among the 1,415 LQTS-associated single nucleotide variants in 30 genes, 347 (25%) are present in gnomAD; 24% of the 347 variants were predicted as functionally tolerated compared with 4% of variants not present in gnomAD (P < 0.001). Of the 347 pathogenic variants in gnomAD, seven (2%) had an AF of ≥ 0.001 and 65 (19%) variants had an AF of ≥ 0.0001. In KCNQ1, KCNH2, and SCN5A, allele distribution by protein functional region was significantly different with gnomAD alleles appearing less frequently in highly pathogenic domains than case alleles. A significant number of LQTS variants have insufficient evidence for pathogenicity and relatively common AF in the general population. Caution should be used when ascribing pathogenicity to these variants.


A TMS investigation on the role of the cerebellum in pitch and timbre discrimination.
Growing neuroimaging and clinical evidence suggests that the cerebellum plays a critical role in perception. In the auditory domain, the cerebellum seems to be important in different aspects of music and sound processing. Here we investigated the possible causal role of the cerebellum in two auditory tasks, a pitch discrimination and a timbre discrimination task. Specifically, participants performed a pitch and a timbre discrimination task prior and after receiving offline low frequency transcranical magnetic stimulation (TMS) over their (right) cerebellum. Suppressing activity in the right cerebellum by means of inhibitory 1 Hz TMS affected participants' ability to discriminate pitch but not timbre. These findings point to a causal role of the cerebellum in at least certain aspects of sound processing and are important in a clinical perspective helping understanding the impact of cerebellar lesions on sensory functions.


Comparison of separations of fatty acids from fish products using a 30-m Supelcowax-10 and a 100-m SP-2560 column.
Commercial fish oils and foods containing fish may contain trans and/or isomerized fatty acids (FA) produced during processing or as part of prepared foods. The current American Oil Chemists' Society (AOCS) official method for marine oils (method Ce 1i-07) is based on separation by use of poly(ethylene glycol) (PEG) columns, for example Supelcowax-10 or equivalent, which do not resolve most unsaturated FA geometric isomers. Highly polar 100-m cyanopropyl siloxane (CPS) columns, for example SP-2560 and CP Sil 88 are recommended for separation of geometric FA isomers. Complementary separations were achieved by use of two different elution temperature programs with the same CPS column. This study is the first direct comparison of the separations achieved by use of 30-m Supelcowax-10 and 100-m SP-2560 columns for fatty acid methyl esters (FAME) prepared from the same fish oil and fish muscle sample. To simplify the identification of the FA in these fish samples, FA were fractionated on the basis of the number and type of double bonds by silver-ion solid-phase extraction (Ag⁺-SPE) before GC analysis. The results showed that a combination of the three GC separations was necessary to resolve and identify most of the unsaturated FA, FA isomers, and other components of fish products, for example phytanic and phytenic acids. Equivalent chain length (ECL) values of most FAME in fish were calculated from the separations achieved by use of both GC columns; the values obtained were shown to be consistent with previously reported values for the Supelcowax-10 column. ECL values were also calculated for the FA separated on the SP-2560 column. The calculated ECL values were equally valid under isothermal and temperature-programmed elution GC conditions, and were valuable for confirmation of the identity of several unsaturated FAME in the fish samples. When analyzing commercially prepared fish foods, deodorized marine oils, or foods fortified with marine oils it is strongly recommended that quantitative data acquired by use of PEG columns is complemented with data obtained from separations using highly polar CPS columns.


Shear bond strength and enamel fracture behavior of ceramic brackets Fascination® and Fascination®2.
The purpose of this study was to compare the shear bond strength and incidence of enamel fractures of the ceramic brackets Fascination® and Fascination®2. A total of 360 teeth (180 first upper bicuspids and 180 lower incisors) were stored in 96% ethanol, while 360 other teeth (180 first upper bicuspids and 180 lower incisors) were stored in 0.1% thymol. All 720 teeth were bonded one-half each with Fascination® and Fascination®2 brackets using three different adhesives and three different light curing units. The teeth were debonded with a debonding-device according to DIN EN ISO 10477 using a universal testing machine with a crosshead speed of 1 mm per minute. The enamel surface was then examined stereomicroscopically (10x and 40x magnification). The non-parametric Mann-Whitney U test was used, since the data were not normally distributed. The Fascination®2 brackets provided significantly lower shear bond strength than Fascination® brackets (p = 0.003). Fascination® brackets demonstrated significantly fewer, smaller enamel fractures than Fascination®2 brackets (p = 0.012). The lower shear bond strength of the Fascination®2 brackets is clinically acceptable, but our study's experimental design did not enable us to prove whether this is clinically associated with a lower risk of enamel fracture.


The functional and structural connectomes of telomere length and their association with cognition in mild cognitive impairment.
Previous findings on the relationship between telomere length and cognition have inconclusive, despite the relatively consistent telomere-shortening associated atrophy in the subcortical regions. Perhaps, there could be other more important telomere-associated factors in the brain, such as functional connectivity (FC) and structural connectivity (SC) that modulate cognition. The current study examined the relationship between telomere length, connectivity, and cognition. Telomere length measurements, neurocognitive scores, diffusion tensor and resting-state functional magnetic resonance imaging scans were collected from 82 older adults with mild cognitive impairment. SC and FC matrices were derived from these scans and, in various combinations, entered into connectome-based predictive models to predict telomere length. The telomere-associated features were then used to predict memory and executive functions. Leave-one-out cross-validation was performed. Predictive accuracy was assessed via the correlation between predicted and observed scores (rpredicted-observed). Correlation analyses were carried out between cognition and telomere length. Telomere length was significantly and negatively correlated with executive functions (EF), after controlling for demographical confounds. Telomere length was best predicted by negative SC and positive FC features (rpredicted-observed = .57; p < .001). The telomere-associated negative SC features significantly predicted EF scores (rpredicted-observed = -.26; p = .015). Telomere-shortening was associated with better EF and alterations in both FC and SC. This enhanced EF can be partly attributed to the telomere-associated changes in SC. Given that telomere is known to be a nonspecific marker of health, our findings illustrated a potential clinical use of telomere length to predict individualized health-related information from FC and SC features.


Postpartum spontaneous coronary, vertebral, and mesenteric artery dissections: a case report.
Spontaneous coronary artery dissection is a rare cause of myocardial infarction that must always be considered on a clinician's differential diagnosis, particularly in patients <50-years old with a paucity of typical vascular risk factors. We describe a case of a 33-year-old white woman, 3 weeks postpartum, presenting with retrosternal chest and back pain, neck pain and stiffness, and intermittent headaches. Subsequent workup revealed concurrent spontaneous dissections in three separate medium-sized arterial beds. She was successfully managed in a conservative fashion, highlighting that percutaneous or surgical revascularization can often be foregone in favor of conservative medical therapy.


The double-edged sword of H19 lncRNA: Insights into cancer therapy.
H19 long non-coding RNA (lncRNA) has many functions in cancer. Some studies have reported that H19 acts as an oncogene and is involved in cancer progression by activating epithelial-mesenchymal transition (EMT), the cell cycle and angiogenesis via mechanisms like microRNA (miRNA) sponging - the binding to and inhibition of miRNA activity. This makes H19 lncRNA a potential target for cancer therapeutics. However, several conflicting studies have also found that H19 suppresses tumour development. In this review, we shed light on the possible reasons for these conflicting findings. We also summarise the current literature on the applications of H19 lncRNA in cancer therapy in many cancers and explore new avenues for future research. This includes the use of H19 in recombinant vectors, chemoresistance, epigenetic regulation, tumour microenvironment alteration and cancer immunotherapy. The relationship between H19 and the master tumour suppressor gene p53 is also explored. In most studies, H19 knockdown via RNA interference (RNAi) or epigenetic silencing inhibits cancer development. Thus, H19 lncRNA could be a promising target for the development of cancer therapeutics. This warrants further investigations into its translational research to improve cancer therapy outcomes.


Full-field hard X-ray nano-tomography at SSRF.
An in-house designed transmission X-ray microscopy (TXM) instrument has been developed and commissioned at beamline BL18B of the Shanghai Synchrotron Radiation Facility (SSRF). BL18B is a hard (5-14 keV) X-ray bending-magnet beamline recently built with sub-20 nm spatial resolution in TXM. There are two kinds of resolution mode: one based on using a high-resolution-based scintillator-lens-coupled camera, and the other on using a medium-resolution-based X-ray sCMOS camera. Here, a demonstration of full-field hard X-ray nano-tomography for high-Z material samples (e.g. Au particles, battery particles) and low-Z material samples (e.g. SiO2 powders) is presented for both resolution modes. Sub-50 nm to 100 nm resolution in three dimensions (3D) has been achieved. These results represent the ability of 3D non-destructive characterization with nano-scale spatial resolution for scientific applications in many research fields.


Sequence deduced physical properties in the D-loop region common to five vertebrate mitochondrial DNAs.
Some sequence-induced physical properties of the region of the replication origin in human, mouse, rat, ox and xenopus mitochondrial DNA have been studied: characteristic profiles of stability can be observed, a consensus pattern of hydrogen bond donor/acceptor associated to a symmetrical distribution of base roll angles variation is found upstream of the 5' ends of the D-loop strand. In spite of diversity, evolution has conserved the collective physical properties in parts of the origin of replication region suggesting specific functions for these non-coding sequences.


A specific ultrastructural marker for disseminated lipogranulomatosis (Faber).
An ultrastructural investigation of two cutaneous lesions in a two-year-old Turkish boy with disseminated lipogranulomatosis (Farber) revealed curvilinear bodies in fibroblasts, histiocytes, and endothelial cells; "elongated membranes" in fibroblasts and endothelial cells; "zebra bodies" in endothelial cells; and spindle-shaped bodies in Schwann cells. In peripheral lymphocytes only alterations of mitochondria (swelling and ruptured cristae) but no inclusion bodies were found. Curvilinear bodies were numerous and easily identifiable; they appear to be characteristic of Farber's disease, and naming them "Farber bodies" is proposed. The diagnosis of this ceramide storage disease, in which the histological examination is relatively unspecific, can therefore be confirmed ultrastructurally.


Plant Oxidative Stress: Biology, Physiology and Mitigation.
Due to climate change plants are frequently exposed to abiotic and biotic stresses, and these stresses pose serious threats to plant growth and productivity [...].


Physical activity levels six months after a randomised controlled physical activity intervention for Pakistani immigrant men living in Norway.
To our knowledge, no studies have aimed at improving the PA level in south Asian immigrant men residing in Western countries, and few studies have considered the relevance of SCT constructs to the PA behaviour of this group in the long term. The observed low physical activity (PA) level among south Asian immigrants in Western countries may partly explain the high prevalence of cardiovascular diseases (CVD) and type 2 diabetes (T2D) in this group. We have shown previously in a randomised controlled trial, the Physical Activity and Minority Health study (PAMH) that a social cognitive based intervention can beneficially influence PA level and subsequently reduce waist circumference and insulin resistance in the short-term. In an extended follow-up of the PAMH study: we aimed 1) to determine if the intervention produced long-term positive effects on PA level six months after intervention (follow-up 2 (FU2)), and 2) to identify the social cognitive mediators of any intervention effects. Physically inactive Pakistani immigrant men (n = 150) who were free of CVD and T2D were randomly assigned to a five months PA intervention or a control group. Six months after the intervention ended, we telephoned all those who attended FU1 and invited them for a second follow-up test (FU2) (n = 133). PA was measured using ActiGraph accelerometers. Statistical differences between groups were determined by use of ANCOVA. Significant differences (baseline to FU2) between the groups were found for all PA variables (e.g., total PA level, sedentary time, PA intensity). Support from family and outcome expectancies increased more in the intervention group compared with the control group. Self-efficacy did not differ significantly between groups. Our results show that a multi component PA programme can increase PA over the short and long term in a group of immigrant Pakistani men. However, we could not identify the factors that mediated these changes in PA. PROTOCOL ID: 07112001326, NCT ID: NCT00539903.


Pleural effusion secondary to endometriosis: A systematic review.
Endometriosis-associated pleural effusion is a rare occurrence with poorly defined clinical characteristics. A systematic review was performed to examine all articles on endometriosis-associated pleural effusion extracted from 4 databases (PubMed, Embase, Web of Science and Scopus) from inception until November 2022. A total of 142 articles (isolated cases and small retrospective series) involving 176 patients (median age 33 years) with endometriosis-associated pleural effusion were included. The most frequent symptoms were dyspnea (67%), chest pain (55%) and abdominal pain (40%). Pleural effusion was predominantly unilateral (89%), right-sided (88.5%) and massive (56%). Ascites was evident in 42% of the cases. Pleural fluid had a bloody appearance in 99% of cases and always met the exudate criteria. Pleural fluid cytology identified only 9% of the patients, with pleural biopsy being the most common diagnostic procedure (74%). Most patients were treated with hormones (76%), thoracic surgery (60%) and abdominal surgery (27%). Effusion recurrence was observed in 26% of cases after a median follow-up of 1 year. The presence of right-sided hemorrhagic pleural effusion in a young woman warrants an assessment for the possibility of endometriosis. Despite conventional treatment, effusion recurs in approximately a quarter of patients.


Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction.
Individuals living or working in moldy buildings complain of a variety of health problems including pain, fatigue, increased anxiety, depression, and cognitive deficits. The ability of mold to cause such symptoms is controversial since no published research has examined the effects of controlled mold exposure on brain function or proposed a plausible mechanism of action. Patient symptoms following mold exposure are indistinguishable from those caused by innate immune activation following bacterial or viral exposure. We tested the hypothesis that repeated, quantified doses of both toxic and nontoxic mold stimuli would cause innate immune activation with concomitant neural effects and cognitive, emotional, and behavioral symptoms. We intranasally administered either 1) intact, toxic Stachybotrys spores; 2) extracted, nontoxic Stachybotrys spores; or 3) saline vehicle to mice. As predicted, intact spores increased interleukin-1β immunoreactivity in the hippocampus. Both spore types decreased neurogenesis and caused striking contextual memory deficits in young mice, while decreasing pain thresholds and enhancing auditory-cued memory in older mice. Nontoxic spores also increased anxiety-like behavior. Levels of hippocampal immune activation correlated with decreased neurogenesis, contextual memory deficits, and/or enhanced auditory-cued fear memory. Innate-immune activation may explain how both toxic mold and nontoxic mold skeletal elements caused cognitive and emotional dysfunction.


Acid-free extraction of valuable metal elements from spent lithium-ion batteries using waste copperas.
A large amount of hazardous spent lithium-ion batteries (LIBs) is produced every year. Recovery of valuable metals from spent LIBs is significant to achieve environmental protection and alleviate resource shortages. In this study, a green and facile process for recovery of valuable metals from spent LIBs by waste copperas was proposed. The effects of heat treatment parameters on recovery efficiency of valuable metals and the redox mechanism were studied systematically through phase transformation behavior and valence transition. At low temperature (≤460 °C), copperas reacted with lithium on the outer layer of LIBs preferentially, but the reduction of transition metals was limited. As the temperature rose to 460-700 °C, the extraction efficiency of valuable metals was greatly enhanced due to the generation of SO2, and the gas-solid reaction proceeded much fast than the solid-solid reaction. In the final stage (≥700 °C), the main reactions were the thermal decomposition of soluble sulfates and the combination of decomposed oxides with Fe2O3 to form insoluble spinel. Under the optimum roasting conditions, i.e., at a copperas/LIBs mass ratio of 4.5, and a roasting temperature of 650 °C and roasting time of 120 min, the leaching efficiencies of Li, Ni, Co and Mn were 99.94%, 99.2%, 99.5% and 99.65%, respectively. The results showed that valuable metals can be selectively and efficiently extracted from the complex cathode materials by water leaching. This study used waste copperas as an aid to recover metals and provided an alternative technical route for green recycling of spent LIBs.


Retraction: Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasion via regulation of the NF-κB signaling pathway in osteosarcoma cells.
[This retracts the article DOI: 10.1039/C8RA08973F.].


Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents.
To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.


Usefulness of Semi-cylindrical Beam Spoiler in Treatment of Early Glottic Cancer Using 6 MV Photon Beam.
To assess the dosimetric influence of a semi-cylindrical beam spoiler (sCBS) for the treatment of early glottic cancer using a 6 MV photon beam. The 2D dose distributions were also calculated and measured with and without the sCBS and with a 0.5 cm thick bolus. A retrospective study of 8 patients treated between 2012 and 2018 was performed. The 2D dose distributions obtained from the treatment planning system (TPS) and film measurements were in good agreement. In the planning study, the V95%, V100%, conformal index (CI), and homogeneity index (HI) of all pPTVs for the sCBS plans were better than those for the open field plans (p<0.01). Especially, sCBS plans had better skin sparing effect than bolus plans (p<0.05). The sCBS of the 6 MV photon beam could be a useful tool for the treatment of early glottic cancers.


Pulmonary chemoreflex and phrenic sympathetic efferents.
The pulmonary chemoreflex components such as reactions of phrenic sympathetic neuron (PhSN) activity, phrenic nerve activity, heart rate and blood pressure were tested in chloralose-anesthetized, paralyzed cats. 10 micrograms to 160 micrograms phenylbiguanide (PBG) in 0.9% NaCl was injected into the pulmonary circulation. PBG injected into the right atrium (in 11 of 19 experiments) and into the pulmonary artery (in 5 of 8 experiments), evoked short-latency (1-1.4 sec) dose-dependent increase in PhSN activity accompanied by increase in blood pressure, and followed by decrease in these two variables. In all experiments, activity of the phrenic nerve was depressed, and bradycardia occurred after PBG injection. All responses to PBG injections into the pulmonary artery were abolished following bilateral vagotomy. In the same procedure related to the right atrium after vagotomy, the increases in PhSN activity and blood pressure were also abolished, although a decrease in heart rate, PhSN activity and in the amplitude of phrenic nerve discharges together with an increase in their frequency persisted. Our results suggest that short-latency increase in PhSN activity is a component of pulmonary chemoreflex.


Compliance with Specialist Referral for Increased Cancer Risk in Low-Resource Settings: In-Person vs. Telehealth Options.
Efforts are underway to improve the accuracy of non-specialist screening for oral cancer (OC) risk, yet better screening will only translate into improved outcomes if at-risk individuals comply with specialist referral. Most individuals from low-resource, minority, and underserved (LRMU) populations fail to complete a specialist referral for OC risk. The goal was to evaluate the impact of a novel approach on specialist referral compliance in individuals with a positive OC risk screening outcome. A total of 60 LRMU subjects who had screened positive for increased OC risk were recruited and given the choice of referral for an in-person (20 subjects) or a telehealth (40 subjects) specialist visit. Referral compliance was tracked weekly over 6 months. Compliance was 30% in the in-person group, and 83% in the telehealth group. Approximately 83-85% of subjects from both groups who had complied with the first specialist referral complied with a second follow-up in-person specialist visit. Overall, 72.5% of subjects who had chosen a remote first specialist visit had entered into the continuum of care by the study end, vs. 25% of individuals in the in-person specialist group. A two-step approach that uses telehealth to overcome barriers may improve specialist referral compliance in LRMU individuals with increased OC risk.


A combined deformable model and medical transformer algorithm for medical image segmentation.
Deep learning-based segmentation models usually require substantial data, and the model usually suffers from poor generalization due to the lack of training data and inefficient network structure. We proposed to combine the deformable model and medical transformer neural network on the image segmentation task to alleviate the aforementioned problems. The proposed method first employs a statistical shape model to generate simulated contours of the target object, and then the thin plate spline is applied to create a realistic texture. Finally, a medical transformer network was constructed to segment three types of medical images, including prostate MR image, heart US image, and tongue color images. The segmentation accuracy of the three tasks achieved 89.97%, 91.90%, and 94.25%, respectively. The experimental results show that the proposed method improves medical image segmentation performance.


Anodic oxidation of o-nitrophenol on BDD electrode: variable effects and mechanisms of degradation.
The electrochemical oxidation of pesticide, o-nitrophenol (ONP) as one kind of pesticide that is potentially dangerous and biorefractory, was studied by galvanostatic electrolysis using boron-doped diamond (BDD) as anode. The influence of several operating parameters, such as applied current density, supporting electrolyte, and initial pH value, was investigated. The best degradation occurred in the presence of Na2SO4 (0.05 M) as conductive electrolyte. After 8h, nearly complete degradation of o-nitrophenol was achieved (92%) using BDD electrodes at pH 3 and at current density equals 60 mA cm(-2). The decay kinetics of o-nitrophenol follows a pseudo-first-order reaction. Aromatic intermediates such as catechol, resorcinol, 1,2,4-trihydroxybenzene, hydroquinone and benzoquinone and carboxylic acids such as maleic glycolic, malonic, glyoxilic and oxalic, have been identified and followed during the ONP treatment by chromatographic techniques. From these anodic oxidation by-products, a plausible reaction sequence for ONP mineralization on BDD anodes is proposed.


The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat.
1. The effects of levodopa alone (50 mg kg-1) and levodopa (10 mg kg-1) plus benserazide (50 mg kg-1) were tested on the levels of dopa, dopamine, 3-methoxytyrosine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), measured by h.p.l.c. with electrochemical detection, in samples of plasma, CSF, urine, striatum and hypothalamus of rats taken 30 min after injection. Levodopa plus benserazide produced significantly higher levels of dopa in plasma and brain than levodopa alone and reduced the peripheral synthesis and metabolism of dopamine. 2. When given chronically over 6 weeks the advantages of adding benserazide (50 mg kg-1 day-1) to levodopa (40 mg kg-1 day-1) were less marked and although more dopamine was present in the striatum than with levodopa given alone (200 mg kg-1 day-1) there was no evidence of any increase in its metabolites (HVA and DOPAC) and therefore of its turnover and utilisation. 3. The most striking effect of chronic treatment with levodopa plus benserazide was the appearance of large quantities of 3-MT in plasma, CSF and brain. 4. When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide. 5. It is concluded that this difference in levodopa distribution may depend on the persistence in benserazide-treated animals of 3-MT, which has a long half-life and may compete with dopa for transport into the blood and brain. 6. The implication of these findings to the treatment of Parkinsonism is discussed.


CT-based radiomics can identify physiological modifications of bone structure related to subjects' age and sex.
Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.


Identification and characterization of a type III polyketide synthase involved in quinolone alkaloid biosynthesis from Aegle marmelos Correa.
Quinolone alkaloids, found abundantly in the roots of bael (Aegle marmelos), possess various biological activities and have recently gained attention as potential lead molecules for novel drug designing. Here, we report the characterization of a novel Type III polyketide synthase, quinolone synthase (QNS), from A. marmelos that is involved in the biosynthesis of quinolone alkaloid. Using homology-based structural modeling, we identify two crucial amino acid residues (Ser-132 and Ala-133) at the putative QNS active site. Substitution of Ser-132 to Thr and Ala-133 to Ser apparently constricted the active site cavity resulting in production of naringenin chalcone from p-coumaroyl-CoA. Measurement of steady-state kinetic parameters demonstrates that the catalytic efficiency of QNS was severalfold higher for larger acyl-coenzymeA substrates as compared with smaller precursors. Our mutagenic studies suggest that this protein might have evolved from an evolutionarily related member of chalcone synthase superfamily by mere substitution of two active site residues. The identification and characterization of QNS offers a promising target for gene manipulation studies toward the production of novel alkaloid scaffolds.


[Correlation between the prevalence of schizophrenia and the sociodemographic status in different areas of Copenhagen].
The results of a statistical study of the prevalence of schizophrenia are presented. The study was designed to determine whether the prevalence of schizophrenic patients admitted to Copenhagen Community Hospital (KH) in 1994 was higher in the low sociodemographic areas of Copenhagen and lower in the high sociodemographic areas. The Jarman's underprivileged area score (UPA score) was used as the sociodemographic index. The study was a retrospective case-referent study. One hundred and eighty-seven patients admitted to KH on the diagnosis of schizophrenia and who were living in one of the four communities connected to KH comprised the study group. A high correlation was found between the prevalence of schizophrenia and the UPA score in the four communities (r = 0.87), but the result was not significant (t:p = 0.15). The high correlation shows that there is a tendency for schizophrenic people to live in the low sociodemographic areas of Copenhagen, but the statistical material is too small to rule out the possibility that this is a statistical fluctuation. To show a statistically significant correlation, a larger study is needed.


Coat protein sequence analysis reveals occurrence of new strains of Sweet potato feathery mottle virus in Uganda and Tanzania.
The 3'-proximal part (1.8 kb) of the Sweet potato feathery mottle virus (SPFMV) genome was studied in four SPFMV isolates collected from farmers' fields in western Uganda (SPFMV-Bny), eastern Uganda (SPFMV-Sor) and Bagamoyo district, Tanzania (SPFMV-TZ1 and SPFMV-TZ2). Unlike the other three SPFMV isolates, SPFMV-Sor was not detected with the polyclonal antisera to SPFMV. It showed moderately high coat protein (CP) nucleotide (93.3-96.7%) and amino acid (93.6-96.8%) sequence identity to the isolates of the SPFMV strain group C. In contrast, identities (78.1-80.1%, and 79.9-83.1%) to isolates of the SPFMV strain groups O, RC, and the East African (EA) strain group were low. Similar to some isolates (SPFMV-CH2 and SPFMV-6) of strain group C, but different from other SPFMV isolates, SPFMV-Sor contained a deletion of 6 nucleotides in the CP-encoding region (CP amino acid positions 62-63). Phylogenetic analysis of the CP sequences indicated that SPFMV-Sor belongs to the SPFMV strain group C that has not been reported from Africa. Sequence data were obtained for the first time from Tanzanian SPFMV isolates in this study, and phylogenetic analysis indicated that they belong to the strain group EA, which is unique to East Africa.


Risk factors for renal-cell carcinoma in Denmark. III. Role of weight, physical activity and reproductive factors.
A population-based case-control study of risk factors for renal-cell carcinoma was conducted in Denmark from 1989 to 1992. A total of 368 histologically verified cases and 396 controls were included. Information on weight, height, physical activity and reproductive factors were collected in a structured interview, along with information on other suspected risk factors. A significant increase in risk was seen for obese women but not obese men. Although there was no clear gradient, the risk was highest among women with a relative weight in the upper 5% (OR 6.1; 95% CI, 2.3 to 16.1). The increased risk was most evident for high relative weight in ages 30 to 50. No association was observed for height or physical activity. Use of amphetamines was associated with increased risk but, because of the close link with obesity, we were unable to provide evidence that amphetamines are an independent risk factor. We found some evidence for an association with reproductive variables, including decreased risk for women with late menarche and first pregnancy and birth. We observed no association with number of pregnancies or age at menopause, or use of estrogen-containing medication.


[Relationship between hospital volumes and health outcomes: epidemiological evidence supporting the revision process of the Ministry of Health Decree no. 70 of 2 April 2015.]
Since its enactment on 2 April 2015, the Decree of the Ministry of Health no.70 has provided a key framework for the reorganization of services to enhance the quality and safety of care. This decree presents the volume thresholds for a series of nosological areas and diagnostic-therapeutic procedures, aiming to improve healthcare outcomes. These thresholds are expected to be periodically updated based on the most recent scientific developments. In this perspective, this work intends to establish whether statistical correlations exist between volumes of activity and outcomes of hospital care. The scope is limited to several clinical conditions and therapeutic procedures for which specific indicators are provided by the National Healthcare Outcomes Programme (Programma Nazionale Esiti - PNE). For each condition or procedure, the analysis shows the volume-outcome relationship by hospital centre by means of the Levenberg-Marquardt algorithm (software: XLSTAT). The existence of breakpoints is assessed through the use of segmented models (software: "segmented" R-Package). The results show a statistical correlation for the following: acute myocardial infarction (breakpoint: 91 hospitalizations per year; 95% CI: 81-101; p<0.0001); repair of an unruptured abdominal aortic aneurysm (breakpoint: 69 procedures per year; 95% CI: 52-86; p=0.146); lung cancer (breakpoint: 96 procedures per year; 95% CI: 60-132; p<0.01); knee arthroplasty (breakpoint: 91 procedures per year; 95% CI: 51-131; p=0.484). Conversely, the statistical analysis did not allow to accurately highlight a breakpoint for the isolated aorto-coronary bypass, percutaneous transluminal coronary angioplasty and hip arthroplasty. These results represent a useful knowledge contribution to support the revision process of the above-mentioned Decree. As regards the procedures that may not be currently assessed through this statistical analysis method, literature data is referred to that confirm that the current regulatory thresholds are in the safe range.


Pathological responses after angiogenesis or EGFR inhibitors in metastatic colorectal cancer depend on the chemotherapy backbone.
Optimal preoperative treatment before colorectal cancer metastases (CRCM) resection remains unclear. This study evaluated pathological responses (pR) in CRCM resected after chemotherapy alone or combined with angiogenesis or epidermal growth factor receptor (EGFR) inhibitors. Pathological response was retrospectively evaluated on 264 resected metastases from 99 patients. The proportion of responding metastases after different preoperative treatments was reported and compared. Patient's progression-free survival (PFS) and overall survival (OS) were compared based on pR. The combination of anti-angiogenics with oxaliplatin-based chemotherapy resulted in more pR than when they were combined with irinotecan-based chemotherapy (80% vs 50%; P<0.001). Inversely, the combination of EGFR inhibitors with oxaliplatin-based chemotherapy seemed to induce fewer pR than when they were combined with irinotecan-based treatment (53% vs 72%; P=0.049). Overall survival at 5 years was improved for patients with a pR in all resected metastases compared with those who did not achieve a pR (68.5% vs 32.6%; P=0.023) and this response was the only factor predicting OS in a multivariate analysis. The chemotherapy partner combined with angiogenesis or EGFR inhibitors influenced pR in resected CRCM. In our exploratory analysis anti-angiogenic/oxaliplatin-based regimens and anti-EGFR/irinotecan-based regimens were associated with the highest pR. Prospective randomised trials should be performed to validate these observations.


Development of Open-source Software and Gaze Data Repositories for Performance Evaluation of Eye Tracking Systems.
In this paper, a range of open-source tools, datasets, and software that have been developed for quantitative and in-depth evaluation of eye gaze data quality are presented. Eye tracking systems in contemporary vision research and applications face major challenges due to variable operating conditions such as user distance, head pose, and movements of the eye tracker platform. However, there is a lack of open-source tools and datasets that could be used for quantitatively evaluating an eye tracker's data quality, comparing performance of multiple trackers, or studying the impact of various operating conditions on a tracker's accuracy. To address these issues, an open-source code repository named GazeVisual-Lib is developed that contains a number of algorithms, visualizations, and software tools for detailed and quantitative analysis of an eye tracker's performance and data quality. In addition, a new labelled eye gaze dataset that is collected from multiple user platforms and operating conditions is presented in an open data repository for benchmark comparison of gaze data from different eye tracking systems. The paper presents the concept, development, and organization of these two repositories that are envisioned to improve the performance analysis and reliability of eye tracking systems.


New type of [Bi6O6(OH)3](NO3)3·1.5H2O sheets photocatalyst with high photocatalytic activity on degradation of phenol.
A new type of [Bi6O6(OH)3](NO3)3·1.5H2O sheets photocatalyst was synthesized via a hydrothermal route. The photocatalytic properties were characterized by SEM, TEM, XRD and UV spectroscopy. It exhibited slightly better photocatalytic activity on phenol degradation than that of classic TiO2 P25 under UV illumination. Hydroquinone, catechol, resorcinol, and benzoquinone were identified as photodegradation intermediates. It has the advantages of high effective photodegradation efficiency and easy separation properties.


Screening with the FMR1 protein test among mentally retarded males.
The fragile X syndrome is characterized by X-linked mental retardation with additional features such as a long face with large protruding ears, macroorchidism, and eye-gaze avoidance. The disorder is caused by an abnormally expanded CGG repeat within the first exon of the fragile X mental retardation (FMR1) gene that is associated with shutdown of transcription and absence of the fragile X mental retardation protein (FMRP). Detection of patients and carriers of the fragile X syndrome is done by DNA analysis of the CGG repeat, whereas the FMRP antibody test allows rapid detection of male patients using bloodsmears. In a screening program for the fragile X syndrome in the southwest of the Netherlands, 412 males with mental retardation of unknown cause were subjected to the protein test. The patients were scored for fragile X features and their DNA tested for the FMR1 mutation, as reported previously. The FMRP test detected two fragile X patients with a repeat expansion in FMR1, whereas normal protein expression was observed in all the retarded male patients with a normal repeat. The FMRP test was found to be suitable for screening among a large population of retarded males. The results also suggest that mutations other than the CGG repeat leading to absence of detectable FMRP are apparently rare among mentally retarded males.


Muscularity and the gay ideal: body dissatisfaction and disordered eating in homosexual men.
The present study investigated body concerns in a community sample of 52 homosexual men, as well as two comparison groups comprising 51 heterosexual men and 55 heterosexual women. Gay men were found to score significantly more highly than heterosexual men on all measures of disordered eating, and did not differ significantly from women on Drive for Thinness or Bulimia. They also scored significantly more highly than heterosexual men and women on Drive for Muscularity (a scale developed for this study), suggesting that the gay 'ideal' involves not only being thin, but also being muscular. Interestingly, however, gay men did not differ significantly from heterosexual men on body esteem, with both groups scoring higher than the women. While body esteem was found to be related to self-esteem for all of the groups, for gay men only self-esteem was negatively related to the importance to others of appearance, weight, and muscularity, perhaps reflecting increased pressure within the gay community to attain the ideal body shape.


Covalent binding of benzene and its metabolites to DNA in rabbit bone marrow mitochondria in vitro.
Rabbit bone marrow mitochondria, stripped of their outer membrane (mitoplasts), have been shown to carry out the NADPH-dependent bioactivation of radiolabelled benzene in vitro to metabolites capable of covalently binding to mtDNA, thereby inhibiting transcription. The metabolites of benzene produced in bone marrow cells by the microsomal cytochrome P-450 are thought to be phenol, catechol, hydroquinone and p-benzoquinone (Andrews et al., Life Sci., 25 (1979) 567; Irons et al., Chem.-Biol. Interact., 30 (1980) 241). Incubation of mitoplasts from rabbit bone marrow cells in vitro with varying concentrations of the putative microsomal metabolites showed a concentration-dependent inhibition of RNA synthesis. The 50% inhibitory molar concentration (IC50) for each metabolite was determined to be: 1,2,4- benzenetriol , 6.3 X 10(-7); p-benzo-quinone, 2 X 10(-6); phenol, 2.5 X 10(-5); hydroquinone, 5 X 10(-5); catechol, 2 X 10(-3); benzene, 1.6 X 10(-2). DNA, isolated from rabbit bone marrow cell or rat liver mitoplasts prelabelled in DNA with [3H]dGTP and exposed to [14C]benzene in vitro, was enzymatically hydrolyzed to nucleosides which were chromatographed on a Sephadex LH-20 column to separate free nucleosides from nucleoside-adducts. The elution profiles indicated that rat liver mtDNA contained six guanine nucleoside-adducts and rabbit bone marrow cell mtDNA contained seven guanine nucleoside-adducts. Incubation of bone marrow mitoplasts in vitro in the presence of benzene and the hydroxyl radical scavenger, mannitol, resulted in the inhibition of formation of four of the guanosine-adducts. When [3H]dATP was substituted as the prelabelled precursor nucleotide, the LH-20 column profile indicated that two adenine nucleoside-adducts were also formed from benzene in vitro. Furthermore, a comparison of the Sephadex LH-20 column profiles of purine adducts derived from [14C]benzene- and [3H]dGMP-labelled mtDNA with profiles generated by individually incubating each of the putative unlabelled metabolites with bone marrow mitoplasts in vitro has indicated that p-benzoquinone, phenol, hydroquinone and 1,2,4- benzenetriol form adducts with guanine. One of the two adenosine-adducts may arise from hydroquinone; the compound forming the other adduct is unknown at the present time. Exposure of mitoplasts to catechol in vitro resulted in the formation of a guanine nucleoside-adduct that was present in rat liver mtDNA but absent from the DNA isolated from rabbit bone marrow cell mitoplasts exposed to [14C]benzene in vitro. This suggests that catechol is probably not a major metabolite of benzene formed in bone marrow cell mitochondria.


New Zealand sea lion (Phocarctos hookeri) epidemic 2002 (abstract).
The New Zealand sea lion is a threatened species and two unusual events contributed to a decrease in recruitment in 2002. The first was a marked reduction (20%) in the number of pups born at the principal Auckland Island rookeries. Secondly, the mortality rate for pups was significantly elevated and was 33% by the end of February, almost three times the mean for that time of the year. Counts of females at rookeries indicated that the lowered fecundity was possibly due to a scarcity of food resources, supported by the fact that male pups (n=50) in 2002 grew poorly with the lightest recorded liveweights for the previous 8 years. Lowered fecundity may also have resulted from infection leading to foetal death, seen in an adult by-catch female, or abortion. Necropsies were conducted on 126/133 pups that died at Sandy Bay and for many the cause of death was multifactorial and included stillbirth, trauma, malnutrition, and severe anaemia caused by hookworm (Uncinaria spp) infection. An unusual disease presentation seen for the first time in 2002 was characterised by systemic bacterial infection that caused suppurative polyarthritis, severe necrotising fasciitis, myositis and osteomyelitis, suppurative peritonitis, pleuritis, or meningitis. For 41 pups, this syndrome was the primary cause of death and for an additional 16 it was a contributing factor along with hookworm infection or trauma. A consistent isolate has been Klebsiella pneumoniae with frequent isolations of Salmonella spp.


Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas.
We have compared proviral integrations near (putative) proto-oncogenes in Moloney murine leukemia virus-induced primary and transplanted T cell lymphomas. We previously found proviruses integrated near c-myc, pim-1, and N-myc in primary tumors (Selten et al., 1984; Van Lohuizen et al., 1989a; Van Lohuizen et al., 1989b). We have now identified an additional common proviral integration site, called pim-2, that carries somatically acquired proviruses in the majority of transplanted tumors. In primary tumors integration near pim-2 is usually undetectable or present in only a minor fraction of the tumor cells. This subpopulation selectively grows out upon transplantation. Insertion near pim-2 is a relatively late event in tumorigenesis and is often preceded by proviral insertions in other common insertion sites, yielding tumor clones which carry proviruses in up to three different common insertion sites within the same cell (c-myc, pim-1 and pim-2). The data suggest that pim-2 plays an important role in tumor progression.


Measuring intestinal permeability in celiac disease ex vivo, using Ussing chambers.
Multicellular organisms need epithelial barriers to remain compartmentalized and protected from external influences. Although much progress has been made in understanding barrier integrity disruption in Celiac disease (CD), the regulatory and genetic mechanisms underlying the increased intestinal epithelial flux are still unknown. As we learn more about the regulation of permeability in homeostasis and pathogenesis, we will be able to develop strategies to strengthen the epithelial barrier function in intestinal disorders, including CD. For this purpose, Ussing chambers are increasingly used in native tissue, such as gut mucosa or cell monolayers, to assess the integrity of the barrier. In particular, the Ussing chambers allow the measurement of paracellular and transcellular parameters of CD small intestinal biopsies under physiologically specific conditions. In diverse types of diseases, this method is commonly used to determine epithelial barrier defects, but its application to CD has not yet been widely expanded. To provide a great model of barrier ex vivo studies in CD, we facilitate a standard protocol to measure paracellular and transcellular permeability using the Ussing chamber.


Heterogeneity of estrogen binding sites in breast cancer: morphologic demonstration and relationship to endocrine response.
Breast cancer specimens from 184 patients were analyzed for estrogen binding by two different histochemical techniques using conjugates of estradiol, bovine serum albumin, and fluorescein. In one conjugate estradiol was bound at position 6, in the other at position 17. Results were in agreement in 64% (p less than .001), but obvious differences in ligand distribution were noted. Results were also correlated with estrogen receptor (ER) analysis by dextran-coated charcoal assay (DCC) and were in accord in 65% and 67% of specimens respectively (p less than .001). In 114 cases, the tissue samples were also studied with the estrogen receptor immunocytochemical assay (ERICA) of Greene and his colleagues, which employs monoclonal antibodies to ER protein. Results were in accord with DCC in 86% (p less than .001). The pattern of staining with ERICA differed from that of either histochemical method. In 43 cases assay results were correlated with clinical endocrine response. Overall, the best statistical prognostic parameters were obtained with ERICA. Analysis of combined assay results revealed that patients with assays positive by all techniques were the most likely to respond to hormonal treatment (p less than .001), whereas if one or more assays were negative the chances for a good response were significantly less favorable. These data suggest that DCC and ERICA are both a measure of the same estrogen binding site (type I) while the histochemical methods apparently identify two other separate and distinct sites (putative type II sites). A degree of positive interaction may exist between these multiple estrogen binding sites.


Water permeability of elastomers.
In a previous study it has been shown that the free moisture content in freeze-dried BCG vaccine dispensed in vials sealed with rubber stoppers increased during storage. The search for the source of this increase led us to explore the possibility that this additional moisture could originate from the rubber stoppers themselves. Therefore, the water permeability of various rubber stoppers has been studied, and the water content of grey butyl stoppers during some operations (autoclaving, oven-drying, freeze-drying, storage) used in the manufacturing of BCG vaccine has been determined. Our experiments showed: rapid water uptake during steam-autoclaving and rapid water release during subsequent oven-drying of the stoppers; a slow water uptake of the stoppers during freeze-drying and a slow water permeation through the stoppers when vials containing Indicating Drierite were stored in a water-saturated atmosphere. Among 12 types of rubber stoppers tested, the grey butyl stoppers and the silicone stoppers showed the lowest water uptake. Moisture-resistant wrappings decreased significantly the moisture uptake of Drierite. To delay moisture from reaching the vaccine it is recommended that the stoppers employed be as dry as possible.


Effect of tetramethyl lead on freshwater green algae.
The toxicity of tetramethyl lead (Me4Pb) towards freshwater algae was studied by bubbling biologically generated Me4Pb from one flask containing 5 mg of Pb 1-1 as Me3PbOAc into the culture medium in another flask where a test alga Scenedesmus quadricauda was grown. As Me4Pb is not soluble in water and is volatile, the exposure of an alga to this lead compound was only momentary. It was estimated that less than 0.5 mg of Pb(Me4Pb) had passed through the culture medium. The primary productivity and cell growth (determined by dry weight), however, decreased by 85% and 32% respectively, as compared with the controls without exposure to Me4Pb. Furthermore, cells exposed to Me4Pb tended to clump together and striking alterations in cell fine-structure were observed. An electron microscopic analysis by an energy dispersive spectrometer revealed that Pb ions had penetrated the cell and were deposited within concretion bodies. Similar results were obtained with the green algae Ankistrodesmus falcatus and Chlorella pyrenoidosa.


Worming pathways to and from DAF-16/FOXO.
In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.


Impact of freestanding emergency centers on hospital emergency department use.
This study was conducted to determine whether hospital emergency department (ED) use has been affected by the presence of freestanding emergency centers (FECs) in hospitals' service areas. A sample of FECs was drawn and hospitals in their service areas identified. ED visits to those hospitals from 1970 to 1980 were compared with those of a comparison group of hospitals not studied. The presence of FECs did not lead to a decline in ED visits to hospitals in their service areas. The study documented that FECs are located near hospitals that are larger than average and that have busier EDs. Because of the relative newness of FEC development, future studies of this type should be conducted. This study could not answer the question of whether FECs caused the growth of hospital ED visits to slow. It did not attempt to measure the impact FECs have on private medical practices or determine whether FECs attract currently underserved patient groups.


A preliminary study of chemotherapeutic treatment for bladder tumors.
Our objective was to develop new methods of chemotherapeutic treatment for bladder tumors. Once or twice a week under cystoscopy 10 to 20 mg, doxorubicin hydrochloride were administered directly into the tumors. This procedure was repeated until the size of the tumors was reduced or had disappeared completely under cystoscopic study. A new type of flexible needle was fabricated for this purpose. In 9 patients studied the total success rate was 78%. No significant side effects were seen in any of the patients.


Rumen In Vitro Fermentation and In Situ Degradation Kinetics of Winter Forage Brassicas Crops.
The aim of the present study was to evaluate the nutritional value, the rumen in vitro fermentation, and the in situ degradation of Brassica oleracea (L.) ssp. acephala (kales) and Brassica napus (L.) ssp. napobrassica (swedes) for winter use. Five varieties of each brassica were used in three field replicates and were randomized in a complete block nested design. All forage varieties were harvested at 210 days post-sowing to analyze the chemical composition, in vitro gas production, volatile fatty acid (VFA) production and in situ dry matter (DM) and crude protein (CP) degradability. Kales presented higher DM and neutral detergent fiber (NDF) content (p < 0.01), whereas swedes showed higher CP, metabolizable energy (ME), glucose, fructose, total sugars, NFC, and nonstructural carbohydrate (NSC) content (p < 0.01). The kale and swede varieties differed in their CP and sugar concentrations, whereas the kale varieties differed in their DM and raffinose content. The rates of gas production were higher for swedes than for kales (p < 0.01). No differences between the brassica species (p > 0.05) were observed in the total VFA production, whereas kales had a higher proportion of acetate and swedes had higher proportions of butyrate (p < 0.05). Only the swede varieties showed differences in VFA production (p < 0.05). The soluble fraction "a", potential and effective in situ DM degradability were higher in swedes (p < 0.01), but kales presented greater DM and CP degradation rates. Differences were observed between brassica species in the chemical composition, degradation kinetics, and ruminal fermentation products, whereas differences among varieties within species were less frequent but need to be considered.


Miswak and oral health: An evidence-based review.
Poor oral health has been associated with several chronic and systemic disease. Currently, the most common method of teeth cleaning is the use of a toothbrush together with dentifrices. However, natural chewing stick such as S. persica miswak is still used in many developing countries due to their low cost and availability. The present review aims to summarize the evidences on effectiveness of miswak in promoting oral health. The search was performed using Medline via Ebscohost, Scopus and Google Scholar database to obtain relevant articles published between 2010 to May 2020 using the following set of keywords 1) Miswak OR Salvadora OR persica AND 2) dental OR caries OR plaque OR oral OR orthodontics. Isolated microbial inhibition studies were excluded from the review due to its well-established wealth of literature. Miswak was administered as ten different forms, namely mouthwash, toothpaste, chewing stick, essential oil, aqueous extract, ethanol extract, probiotic spray, dental varnish, dental cement or chewing gum. All studies reported a positive effect of miswak as an anti-plaque, anti-gingivitis, anti-cariogenic, promotion of gingival wound healing, whitening properties, orthodontic chain preservation, and biocompatibility with oral cells. Miswak in its different forms demonstrated positive effect towards oral health maintenance and management.


Uteroplacental production of eicosanoids in ovine pregnancy.
Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systemic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF1 alpha) in nonpregnant (n = 4) and pregnant (n = 8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE2, PGF2 alpha, PGFM, 6-keto-PGF1 alpha, and TxB2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p less than 0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316 +/- 19 and 245 +/- 38 pg/ml), while levels of PGFM and PGI2 metabolite 6-keto-PGF1 alpha were elevated 23-fold (31 +/- 14 to 708 +/- 244 pg/ml) and 14-fold (12 +/- 4 to 163 +/- 78 pg/ml), respectively (p less than 0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE2 (397 +/- 36 and 293 +/- 22 pg/ml) and 6-keto-PGF1 alpha (269 +/- 32 and 204 +/- 32 pg/ml), p less than 0.05, but not PGF2 alpha or TxB2. Although PGFM concentrations appeared to be greater in uterine venous (1197 +/- 225 pg/ml) as compared to uterine arterial (738 +/- 150 pg/ml) plasma, this did not reach significance (0.05 less than p less than 0.1). In normal ovine pregnancy arterial levels of PGI2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE2 and metabolize PGF2 alpha.


I Know What to Do; I Can Do It; It Will Work: The Brief Parental Self Efficacy Scale (BPSES) for Parenting Interventions.
Parental self-efficacy predicts outcomes for parenting interventions for child behaviour problems, but there is a need for a brief measure that can be repeated over treatment and applies to a wide age range. The present study describes the development of such a measure, the Brief Parental Self-Efficacy Scale (BPSES). The psychometrics of the BPSES is presented across a wide age range from preschool to late adolescent in a sample comprised of four different intervention contexts. Evidence for structural validity, internal consistency, content validity, configural measurement invariance (equivalent factor structure) and test-retest reliability is presented alongside convergent validity against measures of parental self-efficacy, child behaviour problems, as well as self-report and observed parenting styles. Finally, lower levels of BPSES at baseline predicted increased disengagement from an intensive, individualised family therapy intervention for antisocial youth, while higher baseline levels predicted increased response to a group parenting programme for primary school aged children. The BPSES shows promise as a measure that can be used across a wide age-range, for a variety of parenting interventions for disruptive behaviour problems and which is sufficiently brief to be used as a routine outcome measurement during treatment.


Identifying pneumococci in parapneumonic pleural effusion: Is there a role for culture-independent methods?
To evaluate culture-independent procedures (immunochromatography and quantitative polymerase chain reaction [qPCR]) in the detection and susceptibility of Streptococcus pneumoniae directly from culture-negative pleural fluid (PF) in children. Detection of S. pneumoniae in PF of children with parapneumonic effusion and/or empyema by using two culture-independent methods: an immunochromatographic membrane test (IMT) which identifies the pneumococcal C antigen, and a real-time PCR test to detect pneumococcal genes lytA and pbp2b, a marker of susceptibility of β-lactam agents, in PF samples. We tested 36 PF specimens and recorded the previous use of antimicrobials. In the final analysis, 34 samples were included. IMT and qPCR presented positive results in 23 (67.6%) and 24 (70.6%) of the samples, respectively, showing a moderate agreement (k = 0.518) between the two methods. From the 36 children included, 34 (94.4%) had antibiotic data available by the time when PFs were collected. Thirty-four (100%) children had been given treatment before PF sampling, with 33 (97%) receiving β-lactam antibiotics administered empirically. Of the 24 lytA real-time positive samples, 21 (87.5%) were also positive for pbp2b, a marker of β-lactam susceptibility. The reduced sensitivity of culture for pneumococcal detection can be improved through the addition of IMT and qPCR analysis. The utility of qPCR combining detection of lytA and a marker of β-lactam susceptibility should be explored further.


A review on the role of PTENP1 in human disorders with an especial focus on tumor suppressor role of this lncRNA.
PTENP1 is a long non-coding RNA which has been regarded as a pseudogene of the PTEN tumor suppressor gene. However, it has been shown to be a biologically active transcript that can function as a competing endogenous RNA and enhance expression of PTEN protein. This lncRNA has two transcripts, namely PTENP1-202 and PTENP1-202 with sizes of 3996 and 1215 bps, respectively. PTENP1 acts as a sponge for some PETN-targeting miRNAs, such as miR-17, miR-20a, miR-19b, miR-106b, miR-200c, miR-193a-3p, miR-499-5p and miR-214. Besides, it can affect miR-20a/PDCD4, miR-27a-3p/EGR1, miR-17-5p/SOCS6 and miR-19b/TSC1 axes. This long non-coding RNA participates in the pathoetiology of several types of cancers as well as non-malignant conditions such as alcohol-induced osteopenia, insulin resistance, osteoporosis, sepsis-associated cardiac dysfunction and spinal cord injury. In the current review, we elucidate the role of PTENP1 in human disorders, particularly malignant conditions based on evidence acquired from cell line assays, animal studies and investigations on human samples.


Optimal EPR detection of weak nitroxide spin adduct and ascorbyl free radical signals.
We have investigated the optimal nominal power settings for the electron paramagnetic resonance detection of typical nitroxides, nitroxide spin adducts, and the ascorbyl free radical. In room temperature aqueous solution, we find that, for all the nitroxides examined, saturation effects begin at approx. 25 mW nominal power with maximum signal intensity achieved at approx. 100 mW power when using a TM110 cavity. For the ascorbyl free radical, we find that saturation effects begin at approx. 16 mW nominal power and that maximum peak-to-peak signal amplitude is obtained at approx. 40 mW microwave power. For the ascorbyl free radical, we find that a modulation amplitude of approx. 0.65 G yields the maximum signal height for the doublet signal. This information will help researchers maximize the EPR signal height of minimally detectable free radicals such as encountered in biological systems.


Molecular docking and optical sensor studies based on 2,4-diamino pyrimidine-5-carbonitriles for detection of Hg2.
An organic chemical sensor based on pyrimidine was successfully produced through the green reaction between aromatic aldehyde, malononitrile, and guanidine carbonate using SBA-Pr-SO3H. This fluorescence intensity of chemosensor (2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile) decreases by the addition of Hg2+ and its detection limit is about 14.89 × 10-5 M, in fact, through the green synthesis, the ligand was yielded to detect Hg2+ and the importance of ligand was considered in docking studies. The molecular docking of 2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile compound has been done with the protein selective estrogen receptor 5ACC complexed with (Azd9496), Human Anaplastic Lymphoma Kinase Pdb; 2xp2 complex with crizotinib (PF-02341066) and human wee1 kinase Pdb; 5vc3 complexed with bosutinib. The ligands 2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile generate very good docking results with the protein Pdb; 2xp2, which is responsible for effective tumor growth inhibition.


A Double-Blinded Randomized Clinical Study on the Therapeutic Effect of Gastrografin in Prolonged Postoperative Ileus After Elective Colorectal Surgery.
Postoperative ileus is a common problem with significant clinical and economic consequences. We hypothesized that Gastrografin may have therapeutic utility by accelerating the recovery of postoperative ileus after colorectal surgery. The aim of this trial was to study the impact of oral Gastrografin administration on postoperative prolonged ileus (PPI) after elective colorectal surgery. The main endpoint of this randomized, double-blinded, controlled trial was time of resolution of PPI. The secondary endpoints were overall hospital length of stay, time to start oral intake, time to first passage of flatus or stools, time of need of nasogastric tube, and need of parenteral nutrition. Included criteria were patients older than 18 years, operated for colonic neoplasia, inflammatory bowel disease, or diverticular disease. There were two treatments: Gastrografin administration and placebo. The sample size was calculated taking into account the average length of postoperative ileus after colorectal resection until tolerance to oral intake. Statistical analysis showed that 29 subjects in each group were needed. Twenty-nine patients per group were randomized. Groups were comparable for age, gender, ASA Physical Status Classification System, stoma construction, and surgical technique. No statistical differences were observed in mean time to resolution between the two groups, 9.1 days (CI 95%, 6.51-11.68) in Gastrografin group versus 10.3 days (CI 6.96-10.29) in Placebo group (P = 0.878). Even if not statistically significant, time of resolution of PPI, overall length of stay, time of need of nasogastric tube, and time to tolerance of oral intake were shorter in the G group. Gastrografin does not accelerate significantly the recovery of prolonged postoperative ileus after elective colorectal resection when compared with placebo. However, it seems to clinically improve all the analyzed variables.


[Assessment of blood pressure and endothelin-1 plasma concentration in young, hypertensive patients after treatment with angiotensin converting enzyme inhibitor].
Endothelin (ET) is the strongest endogenic substance causing vasoconstriction. The aim of this study was to assess the influence of ACEI therapy on serum concentration of ET-1 plasma activity in young patients with essential mild-to-moderate hypertension. 19 persons with essential mild-to-moderate hypertension were enrolled into study (14 male and 5 female). The average age of this group was 17.6+/-1.4 years. The patients were untreated or there was a 7 day wash out period. The blood pressure and serum concentration of ET-1 plasma were measured before enrolling and after 6 weeks of trandolapril (2 mg per day) therapy. The concentration of endothelin-1 was measured using RIA methods. In analyzed group there was a significant both SBP and DBP lowering after the ACEI therapy. SBP was reduced from 142.6+/-9.7 to 129.3+/-8.4 mmHg (p<0.003), DBP from 85.7+/-6.9 to 79.8+/-8.6 mmHg (p<0.01). The average serum concentration of endothelin-1 was: before treatment 9.33+/-1.9 fmol/ml and after therapy 8.96+/-2.2 fmol/ml. The treatment with ACEI drug (trandolapil) induced the significant decrease of SBP and DBP in young hypertensives. 6-weeks trandolapril therapy was associated with the reduction of serum concentration of ET-1, but not statistically significant.


PREEMACS: Pipeline for preprocessing and extraction of the macaque brain surface.
Accurate extraction of the cortical brain surface is critical for cortical thickness estimation and a key element to perform multimodal imaging analysis, where different metrics are integrated and compared in a common space. While brain surface extraction has become widespread practice in human studies, several challenges unique to neuroimaging of non-human primates (NHP) have hindered its adoption for the study of macaques. Although, some of these difficulties can be addressed at the acquisition stage, several common artifacts can be minimized through image preprocessing. Likewise, there are several image analysis pipelines for human MRIs, but very few automated methods for extraction of cortical surfaces have been reported for NHPs and none have been tested on data from diverse sources. We present PREEMACS, a pipeline that standardizes the preprocessing of structural MRI images (T1- and T2-weighted) and carries out an automatic surface extraction of the macaque brain. Building upon and extending pre-existing tools, the first module performs volume orientation, image cropping, intensity non-uniformity correction, and volume averaging, before skull-stripping through a convolutional neural network. The second module performs quality control using an adaptation of MRIqc method to extract objective quality metrics that are then used to determine the likelihood of accurate brain surface estimation. The third and final module estimates the white matter (wm) and pial surfaces from the T1-weighted volume (T1w) using an NHP customized version of FreeSurfer aided by the T2-weighted volumes (T2w). To evaluate the generalizability of PREEMACS, we tested the pipeline using 57 T1w/T2w NHP volumes acquired at 11 different sites from the PRIME-DE public dataset. Results showed an accurate and robust automatic brain surface extraction from images that passed the quality control segment of our pipeline. This work offers a robust, efficient and generalizable pipeline for the automatic standardization of MRI surface analysis on NHP.


Plasma esterase activities in rats fed magnesium-deficient diets.
In a study with rats it was determined whether dietary magnesium concentration affects plasma esterase activities. The feeding of a diet with 0.01% (w/w) instead of 0.04% magnesium reduced plasma magnesium concentration by 50%. Plasma total esterase, arylesterase and butyrylcholinesterase activities were significantly decreased in the magnesium-deficient rats. In rats fed a diet containing 0.02% magnesium, plasma magnesium concentration was lowered by 30%, and group mean plasma total esterase activity was decreased, but not the activities of arylesterase and butyrylcholinesterase.


Ribavirin treatment of the acquired immunodeficiency syndrome (AIDS) and the acquired-immunodeficiency-syndrome-related complex (ARC). A phase 1 study shows transient clinical improvement associated with suppression of the human immunodeficiency virus and enhanced lymphocyte proliferation.
To assess safety, tolerance, and the clinical and laboratory effects of oral ribavirin in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. Three uncontrolled phase I trials of increasing duration: 14 days, 8 weeks, and 12 months. Outpatient clinic of a university-referral hospital. All patients were antibody-positive for the human immunodeficiency virus (HIV) by radioimmunoprecipitation assay, all had recovered from Pneumocystis carinii pneumonia, and none had Kaposi sarcoma at entry. Nine of ten patients with AIDS had less than 100 CD4+ lymphocytes/mm3 at entry and all patients with the AIDS-related complex had fewer than 200 CD4+ lymphocytes/mm3. Five patients with AIDS and five with the AIDS-related complex entered the 14-day trial. All but two patients with AIDS went on to the 8-week trial, along with seven additional patients with AIDS. Five surviving patients with AIDS and 3 patients with the AIDS-related complex went on to the 1-year study. Oral ribavirin, 1200 mg twice daily for 3 days was given, followed by 300 mg twice daily for 11 days. During an 8-week trial, a loading dose of oral ribavirin was administered for 3 days, followed by a dose of 300 mg twice daily for 8 weeks. Prolonged regimen of a 3-day loading dose was given, followed by a dose of 300 mg twice daily for 1 year. Ribavirin treatment was well tolerated, with anemia requiring transfusion in one of the ten patients with AIDS receiving the drug for 8 weeks; no other significant toxicity occurred. Six of nine patients initially positive for HIV-1 in blood became negative during ribavirin treatment. Six of nine patients with AIDS had a twofold improvement in lymphoproliferative response to at least one lectin with ribavirin treatment. Mean survival from first episode of P. carinii pneumonia was 17.3 months in patients with AIDS receiving 8 weeks of ribavirin and 21.2 months in patients with AIDS receiving prolonged treatment. Oral ribavirin, 600 mg daily, was well tolerated and safe in the patients with severe AIDS and the AIDS-related complex. Ribavirin therapy merits extensive evaluation in a multicenter controlled trial to assess its efficacy.


Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers.
To improve the drug permeation into and/or across the skin, essential oils extracted from Alpinia oxyphylla (AO) were evaluated using in vitro and in vivo permeation techniques with Wistar rats as the animal model. Hydrocarbons and oxygenated sesquiterpenes were the major components in the lower-polarity fraction (AO-1) and higher-polarity fraction (AO-2), respectively. Permeation of indomethacin was significantly enhanced after treatment with AO-1 and AO-2 in the in vitro and in vivo studies. AO-2 generally showed a higher ability to promote drug permeation compared to AO-1. The increment of skin/vehicle partitioning may be the predominant mechanism for this enhancing activity. Both transepidermal water loss (TEWL) and colorimetric evaluation showed limited irritation to skin by AO essential oils at the macroscopic level. Human skin fibroblasts were used to investigate the in vitro screening of skin toxicity. AO-1 slightly increased prostaglandin E(2) (PGE(2)) formation from skin fibroblasts. A striking result was observed with AO-2, which greatly inhibited the release of PGE(2). Moreover, both AO essential oils had no statistically significant effect on PGE(2) release by human lung epithelial cells. The results of this study indicate that skin disruption and inflammation do not necessary correspond to the enhancing efficiency of the enhancers tested.