Modeling the physiological roles of the heart and kidney in heart failure with preserved ejection fraction during baroreflex activation therapy.
Heart failure (HF) is a leading cause of death and is increasing in prevalence. Unfortunately, therapies that have been efficacious in patients with HF with reduced ejection fraction (HFrEF) have not convincingly shown a reduction in cardiovascular mortality in patients with HF with preserved ejection fraction (HFpEF). It is thought that high sympathetic nerve activity (SNA) in the heart plays a role in HF progression. Clinical trials demonstrate that baroreflex activation therapy reduces left ventricular (LV) mass and blood pressure (BP) in patients with HFpEF and hypertension; however, the mechanisms are unclear. In the present study, we used HumMod, a large physiology model to simulate HFpEF and predict the time-dependent changes in systemic and cardiac hemodynamics, SNA, and cardiac stresses during baroreflex activation. The baseline HFpEF model was associated with elevations in systolic BP, diastolic dysfunction, and LV hypertrophy and stiffness similar to clinical HFpEF. Simulating 12 mo of baroreflex activation resulted in reduced systolic BP (-25 mmHg) and LV mass (-15%) similar to clinical evidence. Baroreflex activation also resulted in sustained decreases in cardiac and renal SNA (-22%) and improvement in LV β1-adrenergic function. However, the baroreflex-induced reductions in BP and improvements in cardiac stresses, mass, and function were mostly attenuated when renal SNA was clamped at baseline levels. These simulations suggest that the suppression of renal SNA could be a primary determinant of the cardioprotective effects from baroreflex activation in HFpEF.NEW & NOTEWORTHY Treatments that are efficacious in patients with HFrEF have not shown a significant impact on cardiovascular mortality in patients with HFpEF. We believe these simulations offer novel insight into the important roles of the cardiac and renal nerves in HFpEF and the potential mechanisms of how baroreflex activation alleviates HFpEF disease progression.


Computational Methods for Identifying Similar Diseases.
Although our knowledge of human diseases has increased dramatically, the molecular basis, phenotypic traits, and therapeutic targets of most diseases still remain unclear. An increasing number of studies have observed that similar diseases often are caused by similar molecules, can be diagnosed by similar markers or phenotypes, or can be cured by similar drugs. Thus, the identification of diseases similar to known ones has attracted considerable attention worldwide. To this end, the associations between diseases at the molecular, phenotypic, and taxonomic levels were used to measure the pairwise similarity in diseases. The corresponding performance assessment strategies for these methods involving the terms "category-based," "simulated-patient-based," and "benchmark-data-based" were thus further emphasized. Then, frequently used methods were evaluated using a benchmark-data-based strategy. To facilitate the assessment of disease similarity scores, researchers have designed dozens of tools that implement these methods for calculating disease similarity. Currently, disease similarity has been advantageous in predicting noncoding RNA (ncRNA) function and therapeutic drugs for diseases. In this article, we review disease similarity methods, evaluation strategies, tools, and their applications in the biomedical community. We further evaluate the performance of these methods and discuss the current limitations and future trends for calculating disease similarity.


Fast estimation of regression parameters in a broken-stick model for longitudinal data.
Estimation of change-point locations in the broken-stick model has significant applications in modeling important biological phenomena. In this article we present a computationally economical likelihood-based approach for estimating change-point(s) efficiently in both cross-sectional and longitudinal settings. Our method, based on local smoothing in a shrinking neighborhood of each change-point, is shown via simulations to be computationally more viable than existing methods that rely on search procedures, with dramatic gains in the multiple change-point case. The proposed estimates are shown to have [Formula: see text]-consistency and asymptotic normality - in particular, they are asymptotically efficient in the cross-sectional setting - allowing us to provide meaningful statistical inference. As our primary and motivating (longitudinal) application, we study the Michigan Bone Health and Metabolism Study cohort data to describe patterns of change in log estradiol levels, before and after the final menstrual period, for which a two change-point broken stick model appears to be a good fit. We also illustrate our method on a plant growth data set in the cross-sectional setting.


Plasma sex hormone binding globulin in patients with prostatic carcinoma.
The concentrations of sex hormone binding globulin (SHBG) were measured in the plasma of 56 men, who were 47 to 85 years of age, by time-resolved immunofluorometric assay with a monoclonal antibody. Twenty-five of the men had untreated carcinoma of the prostate and 17 had untreated prostatic hyperplasia. There were 14 healthy control subjects. SHBG levels were significantly higher in patients with prostatic carcinoma (37.6 +/- 8.4 nmol/l) than in those with prostatic hyperplasia (24.5 +/- 5.2 nmol/l; P less than 0.05) or control subjects (14.9 +/- 2.8 nmol/l; P less than 0.01). It is not known why SHBG levels are higher in patients with carcinoma or hyperplasia of the prostate. The contradictory results obtained in other studies may be due to heterogeneity of the binding globulin causing its values to vary in the different assays used.


Mechanisms of synergistic suppression of ALK-positive lung cancer cell growth by the combination of ALK and SHP2 inhibitors.
Lung cancer is a major cause of cancer-related deaths. Alectinib is the first line of treatment for patients with ALK-positive lung cancer, but the survival rate beyond 2-3 years is low. Co-targeting secondary oncogenic drivers such as SHP2 is a potential strategy for improving drug efficacy. This is because SHP2 is expressed ubiquitously, but ALK expression is largely restricted to cancer cells. Thus, the combination of ALK and SHP2 inhibitors may provide a way to restrict synergistic cytotoxicity to cancer cells only, by reducing the dose of SHP2 inhibitors required for anticancer action and minimising SHP2-dependent systemic toxicity. The objective of this study was to investigate whether the combination of a SHP2 inhibitor (SHP099) with alectinib would synergistically suppress the growth of ALK-positive lung cancer cells. Our results demonstrated that the drug combination significantly and synergistically decreased cell viability at relatively low concentrations in ALK-positive H3122 and H2228 cells, due to G1 cell cycle arrest and increased apoptosis because of suppressed downstream RAS/MAPK signalling. The drug combination also induced the expression of mediators of the intrinsic apoptotic pathway, Bim and cleaved caspase-3, and modulated the expression of cell cycle mediators cyclin D1, cyclin B1, and phosphorylated CDK1.


Tumor necrosis factor-alpha induces changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine.
The stress protein hsp27 is constitutively expressed in several human cells and shows a rapid phosphorylation following treatment with tumor necrosis factor-alpha (TNF-alpha). hsp27 usually displays native molecular mass ranging from 100 to 700 kDa. Here, we have analyzed the TNF-alpha-mediated changes in the phosphorylation, cellular localization, and structural organization of hsp27 in HeLa cells. We report that the TNF-alpha-mediated hsp27 phosphorylation is a long-lasting phenomenon that correlates with the cytostatic effect of this cytokine. Following TNF-alpha treatment, the rapid phosphorylation of hsp27 occurred concomitantly with complex changes in the intracellular distribution and structural organization of this protein. This resulted in the quantitative redistribution of hsp27 toward the soluble phase of the cytoplasm. In addition, during the first 2 h of TNF-alpha treatment, a transient increase in the native molecular mass of most hsp27 molecules (< or = 700 kDa) occurred. Then, by 4 h of TNF-alpha treatment, the native size of this stress protein drastically regressed (< 200 kDa). During this phenomenon, the phosphorylated isoforms of hsp27 remained concentrated in the small or medium-sized oligomers (< 300 kDa) of this protein. We also analyzed the properties of human hsp27 in transfected murine L929 cell lines that constitutively express this protein. In these cells, TNF-alpha induced modifications in the phosphorylation, intracellular distribution, and oligomerization of human hsp27 similar to those observed in HeLa cells. Moreover, the expression of hsp27 in L929 cells was found to correlate with a reduced cytotoxicity of this cytokine. Hence, the complex changes in the phosphorylation, intracellular locale and structural organization of human hsp27 may be related to the protective activity of this protein against the deleterious effects induced by TNF-alpha.


Gestational age-dependent extravillous cytotrophoblast osteopontin immunolocalization differentiates between normal and preeclamptic pregnancies.
Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion. To investigate gestational age-related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age-matched controls (n = 24). In non-preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24-30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24-40 weeks. Cytotrophoblasts from FGR placentas were OPN-positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN-positive from 24-40 weeks. The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non-preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.


A systematic review and meta-analysis of the diagnostic accuracy of MRI for suspected ACL and meniscal tears of the knee.
To determine the diagnostic accuracy of magnetic resonance imaging (MRI) and ultrasound (US) in the diagnosis of anterior cruciate ligament (ACL), medial meniscus and lateral meniscus tears in people with suspected ACL and/or meniscal tears. MEDLINE, Web of Science and the Cochrane library were searched from inception to March 2014. All prospective studies of the diagnostic accuracy of MRI or US against arthroscopy as the reference standard were included in the systematic review. Studies with a retrospective design and those with evidence of verification bias were excluded. Methodological quality of included studies was assessed using the QUADAS-2 tool. A meta-analysis of studies evaluating MRI to calculate the pooled sensitivity and specificity for each target condition was performed using a bivariate model with random effects. Sub-group and sensitivity analysis were used to examine the effect of methodological and other study variables. There were 14 studies included in the meta-analysis of the accuracy of MRI for ACL tears, 19 studies included for medial meniscal tears and 19 studies for lateral meniscal tears. The summary estimates of sensitivity and specificity of MRI were 87 % (95 % CI 77-94 %) and 93 % (95 % CI 91-96 %), respectively, for ACL tears; 89 % (95 % CI 83-94 %) and 88 % (95 % CI 82-93 %), respectively, for medial meniscal tears; and 78 % (95 % CI 66-87 %) and 95 % (95 % CI 91-97 %), respectively, for lateral meniscal tears. Magnetic field strength had no significant effect on accuracy. Most studies had a high or unclear risk of bias. There were an insufficient number of studies that evaluated US to perform a meta-analysis. This study provides a systematic review and meta-analysis of diagnostic accuracy studies of MRI and applies strict exclusion criteria in relation to the risk of verification bias. The risk of bias in most studies is high or unclear in relation to the reference standard. Concerns regarding the applicability of patient selection are also present in most studies. III.


Differences in peritumoral pseudocapsule characteristics according to clinicopathological factors in clinical T1a renal tumors.
To evaluate the status of peritumoral pseudocapsules in renal tumors and the effects of clinicopathological factors on their formation. From January 2011 to December 2012, 258 patients with solitary clinical stage T1a renal tumors who underwent partial nephrectomy were analyzed. Status of pseudocapsule was re-evaluated by a pathologist. The mean long diameter (± SD) of the tumor and the width of the safety margin were 2.17 (± 0.94) cm and 3.2 (± 2.4) mm, respectively. A complete pseudocapsule was identified in 152 (58.9%) tumors, an incomplete pseudocapsule was identified in 69 (26.7%) tumors, and no pseudocapsule was identified in 37 (14.3%) tumors. Out of 152 tumors with complete pseudocapsules, 45 (29.6%) were confirmed to directly invade the renal parenchyma. In a multivariable analysis, age (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.021-1.070, P < 0.001) and histologic subtype (chromophobe type: OR, 19.455; 95% CI, 4.233-89.471, P < 0.001; oncocytoma: OR, 11.307; 95% CI, 1.357-94.198, P = 0.025) were significant factors for an incomplete or absent pseudocapsule. Peritumoral pseudocapsules are absent or incomplete in a significant portion of renal tumors. Old age as well as chromophobe and oncocytoma histologic subtypes were significant risk factors for an incomplete or absent peritumoral pseudocapsule.


Forensic psychiatry in Kuwait - characterization of forensic psychiatry patients evaluated over year duration in the only available forensic psychiatry unit.
The offending behavior arising from a mental disorder invokes criminal responsibility doctrines or insanity defenses and calls for legislative framework ensuring availability of care and treatment for the patient and protection of the public from harm from the offender. The conviction of mentally disordered offenders varies depending upon the local legislation and its socio-cultural context, so do the principles, procedures and guidelines for forensic assessments between different countries. The criminal Act of Kuwait, which governs the work of forensic psychiatrists remain unchanged, from a psychiatric point of view, since it was enacted in the early 1960's. To shed some light on the forensic psychiatry services running in Kuwait and describe forensic psychiatry patients evaluated in the only-available forensic psychiatry unit. Retrospective chart review of all cases referred for criminal forensic psychiatric assessments during the period from January 1st, 2016 to May 31st, 2017. The demographics, types of offences, psychiatric diagnoses, and details of psychiatric evaluations were retrieved and characterized. A total of 95 case-notes were reviewed. Most of them were males (90%), Kuwaiti nationals (77%), primary or intermediate school education (74%), and were aged 20-39 (69%). Almost all (97%) of the referrals required ascertainment of 'responsibility' for the alleged offence. Eighty-six percent (N = 81) of the offenders were referred from the police or the public prosecutor office. Eighty-three percent (N = 79) of the offenders were found to have a mental disorder while 55% (N = 52) were found to be criminally responsible. The males (57%) outnumbered the females (33%) as criminally responsible. The number of mentally ill offenders referred for criminal responsibility and fitness to stand trial is very small compared to western countries. One reason behind this could be that a substantial number of the mentally disordered offenders pass undetected through the legal system. It is then incumbent that psychiatrists and forensic mental health workers might need to provide better awareness and education about mental health to legal authorities in Kuwait.


YY1 deficiency in β-cells leads to mitochondrial dysfunction and diabetes in mice.
The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic β-cells, however, the physiological functions of YY1 in β-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. We established two models of β-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, β-cell mass and β-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of β-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in β-cells. Our results showed that loss of YY1 resulted in reduction of insulin production, β-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic β-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.


Automated image quality appraisal through partial least squares discriminant analysis.
Automatic retinal fundus image quality analysis is one of the most essential preliminary stages in automatic computer-aided retinal disease diagnosis system, which allows good-quality fundus images for accurate disease prediction through localization and segmentation of retinal regions. This paper presents new feature extraction methods using full-reference and no-reference image quality metrics for image quality classification. Basic image features, reference and no-reference features are extracted from the fundus image and applied through different classification techniques to determine the image quality for further diagnosis. In this paper, human-made categorization including good and non-good-quality fundus image classification is constructed by considering major features of retinal fundus images are illumination, clarity, image intensity, contrast and region visibility. The proposed system presented fundus image quality classification by automatic extraction of features from fundus images through image processing techniques and automatic classification of image quality through different classification algorithm. This system was thoroughly investigated on 2674 retinal fundus images from publically available datasets, namely MESSIDOR, Drishti-GS1, DRIVE, HRF, DRIONS-DB, DIARETDB0, DIARETDB1, IDRiD, INSPIRE-AVR, CHASE-DB1, ONHSD, DRIMDB and e-ophtha-EX with better performance results in terms of sensitivity, accuracy, precision and F1 score of 99.36%, 96.79%, 96.29% and 97.79%, respectively. The proposed system results were compared to the existing state-of-the-art approaches and outperform existing methods for image quality assessment representing the efficiency and robustness of our system is most suitable for automatic image analysis during retinal disease diagnosis.


A comparison of antibiotics, antibiotic resistance genes, and bacterial community in broiler and layer manure following composting.
Animal manure is an important source of antibiotics and antibiotic resistance genes (ARGs) in the environment. However, the difference of antibiotic residues and ARG profiles in layer and broiler manure as well as their compost remains unexplored. In this study, we investigated the profiles of twelve antibiotics, seventeen ARGs, and class 1 integrase gene (intI1) in layer and broiler manure, and the corresponding compost at large-scale. Compared with layer manure, broiler manure exhibited approximately six times more residual tetracyclines, especially chlortetracycline. The relative abundances of qnrS and ermA genes in broiler manure were significantly higher than those in layer manure. The concentration of tetracyclines not only had a significantly positive correlation with tetracycline resistance genes (tetA and tetC) but was also positively correlated with quinolone resistance (qepA, qnrB, and qnrS) and macrolide resistance (ermA and ermT). Most ARGs in manure were reduced after composting. However, the relative abundance of sulfonamide resistance gene sul1 increased up to 2.41% after composting, which was significantly higher than that of broiler (0.41%) and layer (0.62%) manure. The associated bacterial community was characterized by high-throughput 16S rRNA gene sequencing. The relative abundances of thermophilic bacteria had significant positive correlations with the abundance of sul1 in compost. The composting has a significant impact on the ARG-associated gut microbes in poultry manure. Variation partitioning analysis indicated that the change of bacterial community compositions and antibiotics contributed partially to the shift in ARG profiles. The results indicate that at industry-scale production broiler manure had more antibiotics and ARGs than layer manure did, and composting decreased most ARG abundances in poultry manure except for sulfonamide resistance genes.


The ophthalmic wound of Philip II of Macedonia (360-336 BCE).
The aim of this report is to present the ophthalmic wound of King Philip II of Macedonia, father of Alexander the Great. From a series of ancient literary and historical sources, a number of archaeological finds, and the paleopathological remains in the supposed tomb of Philip in Vergina, it can be deduced that the king was seriously wounded in his right eye during the siege of Methoni. The renowned physician Critobulos undertook the removal of the arrow that had injured the eye and the postoperative follow-up. He was already experienced and belonged to the official medical family of Asclepiades of Cos Island. It seems that an ugly scar remained in the area of Philip's right eye, possibly causing him psychological problems.


Computer simulation of the variable agarose fiber dimensions on the basis of mobility data derived from gel electrophoresis and using the Ogston theory.
Agarose gel electrophoresis of viruses and proteins was evaluated for estimating fiber dynamics of agarose by computer simulation based on the extended Ogston theory. By introducing functions, in place of previously used constant parameters, into the equations derived from the Ogston theory it was demonstrated that the effective fiber properties are variable as a function of both gel concentration and the size of the particle passing through the gel. This variability accounts for the curvature of plots of log(mobility) vs gel concentration in agarose gel electrophoresis as well as for the apparent dichotomy between fiber properties obtained from the electrophoresis of either viruses or proteins. Specifically, computer simulation based on the electrophoretic mobility values of five viruses and seven proteins by use of an eight (gel-specific) parameter model yielded functions relating gel concentration and/or particle size with electrophoretic mobility of particles, the retardation coefficient, K'R, and effective fiber radius, length, and volume. The simulations give further insights into, as well as mathematical basis for, a number of previously made assumptions (such as variation of agarose fiber structure with gel concentration, variation of fiber volume with particle size, continuity of the K'R vs radius plot from 0 to 45 nm), thus demonstrating the continued usefulness of the Ogston model. The mathematical model provides the elements for an improved method for the determination of particle size, charge, and potentially shape by agarose gel electrophoresis, and can be regarded as the basis for future elaboration of a computer program for the routine determination of these parameters.


Tissues concentration and excretion of deslanatoside C-3H in newborn and growing rabbits.
Deslanatoside C-3H was injected (i.p. 50 microgram/kg) into rabbits of 1, 4, 10, 20 days and more than 1 year old. The rabbits were sacrificed 2 and 6 h after dosing. Levels in all tissues were higher in newborn rabbits, decreased in the older animals and then in most tissues increased in adults to different degrees, showing the highest values in kidneys. Biliary excretion and above all urinary excretion increased with age. Levels in atria, ventricles, aorta and liver in rabbits 1 and 4 days old were consistently higher at the 6th h than those at the 2nd h, these tissues showing a particularly marked avidity with Deslanatoside C; in the older animals this behaviour was reversed. These data and those of other Authors working on other glycosides (incleding Digoxin) and other species (including newborn children) lead to the conclusion that digitalis glycosides in new born species are excreted at a lower rate and incorporated in the body tissues at a higher rate than in adults. They may also in part explain the large dosages employed in human infants in comparison with adults, as the higher distribtuion volume retains a large amount of the injected glycoside.


BMI variability and incident diabetes mellitus, Tehran Lipid and Glucose Study (TLGS).
Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20-60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals' BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94-1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10-1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01-1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08-1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53-0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.


A novel gene trap method using terminator-REMI and 3' rapid amplification of cDNA ends (RACE) in Dictyostelium.
We describe a novel restriction enzyme-mediated integration (REMI) method for gene trapping in Dictyostelium based on the use of a terminator-deficient vector. The vector has a blasticidin deaminase (bsr) gene as a selectable marker but lacks a terminator containing a poly(A) addition signal (AATAAA). Thus, the vector was expected to integrate into the coding region of a gene to create a fusion transcript flanked by the 3' proximal region of the trapped gene. The trapped gene can be identified by simply amplifying the fusion transcript by 3' rapid amplification of cDNA ends (3'-RACE). In the analysis of 35 integration events into known genes, the vectors were found to be integrated 20 times in close proximity to the 3' ends of the genes and in the direction of transcription. This strictly localized insertion seemed to be mediated by negative selection via the surveillance system referred to nonsense-mediated mRNA decay. In contrast, in 15 events the vector integrated in the opposite direction to transcription and at random positions throughout the coding sequence. Analysis of the trapped 3' sequences showed that the transcription of the fusion gene terminated prematurely without the apparent use of an endogenous terminator; nevertheless the transcript did exhibit a poly(A) tail. Based on these results, we designated the method terminator-REMI. Using this method, we have generated a library of tagged Dictyostelium clones from which we have thus far isolated 242 developmental mutants.


Surgical correction of constricted ear combined with Stahl's ear.
Constricted ear combined with Stahl's ear is a rare ear deformity, which is a kind of complex congenital auricular deformity. From 1 January 2007 to 1 January 2014, 19 patients with constricted ear combined with Stahl's ear (Spock ear) were enrolled in this study, most of which were unilaterally deformed. To correct the deformity, a double Z-shaped skin incision was made on the posterior side of the auricle, with the entire layer of cartilage cut parallel to the helix traversing the third crus to form a fan-shaped cartilage flap. The superior crura of the antihelix were shaped by the folding cartilage rim. The cartilage of the abnormal third crus was made part of the new superior crura of antihelix, and the third crus was eliminated. The postoperative aesthetic assessment of the reshaped auricle was graded by both doctors and patients (or their parents). Out of the 19 patients, the number of satisfying cases of the symmetry, helix stretch, elimination of the third crus, the cranioauricular angle, and the substructure of the reshaped ears was 14 (nine excellent and five good), 16 (six excellent and 10 good), 17 (eight excellent and nine good), 15 (five excellent and 10 good), and 13 (two excellent and 11 good), respectively. With a maximum of a 90-month follow-up, no complication was observed. The results of the study suggested that this rare deformity could be corrected by appropriate surgical treatment, with a satisfied postoperative appearance.


Zero-inflated regression models for radiation-induced chromosome aberration data: A comparative study.
Within the field of cytogenetic biodosimetry, Poisson regression is the classical approach for modeling the number of chromosome aberrations as a function of radiation dose. However, it is common to find data that exhibit overdispersion. In practice, the assumption of equidispersion may be violated due to unobserved heterogeneity in the cell population, which will render the variance of observed aberration counts larger than their mean, and/or the frequency of zero counts greater than expected for the Poisson distribution. This phenomenon is observable for both full- and partial-body exposure, but more pronounced for the latter. In this work, different methodologies for analyzing cytogenetic chromosomal aberrations datasets are compared, with special focus on zero-inflated Poisson and zero-inflated negative binomial models. A score test for testing for zero inflation in Poisson regression models under the identity link is also developed.


Breastfeeding and Readmission for Hyperbilirubinemia in Late Preterm and Term Infants in Beirut, Lebanon.
To determine whether exclusive breastfeeding is associated with readmission of jaundiced newborns. We retrieved medical records of 51 consecutive neonates >35 weeks with jaundice who were readmitted to the hospital, and compared to 164 controls. Data on gender, gestational age, birth weight, mode of delivery, feeding, bilirubin levels and breastfeeding counseling were analyzed. 24% babies were readmitted for hyperbilirubinemia reaching phototherapy level. Early term infants had significantly higher risk for readmission compared to term [OR (95% CI) 2.12 (0.99-4.53); P= 0.05]. The risk of readmission was lower amongst subjects receiving mixed/formula feeding [OR (95% CI) 0.51 (0.26-0.98); P=0.046] odds of readmission decreased for those feeding >8 times per day (OR (95% CI) 0.46 (0.23-0.91); P=0.016], and those who stayed in hospital for more than 2 days after birth [OR (95% CI) 0.95(0.93-0.97); P<0.001]. Ensuring feeding at least 8 times per day and keeping newborns beyond the first 24 hours decreases the chance of readmission.


First case report on molecular detection of Trypanosoma lewisi in an urban rat in Kelantan, Malaysia: An accidental finding.
This case report highlights the first detection of Trypanosoma lewisi, a blood protozoan parasite found in an urban rat in Kota Bharu, Kelantan. Rat trapping was carried out within the Kota Bharu vicinity near a local wet market. A total of 38 rats were captured and subjected to peripheral blood smearing using Giemsa stain. Positive rats were sent for histopathological analysis for the evaluation of the organ samples. The presence of trypanosomes was found in one sample from a blood smear. This was connected to a histological lesion on kidney tissues, which revealed a high concentration of trypanosomes. Additionally, the positive sample was confirmed as T. lewisi based on molecular diagnosis via polymerase chain reaction and subsequent sequencing and phylogenetic analysis. This finding serves as a baseline for further surveillance on T. lewisi population among urban rats in Kelantan and possible zoonotic transmission to humans.


The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression.
On the basis of experiments in rats, serotonin 4 receptor (5-hydroxytryptamine 4 [5-HT4]) agonists have been proposed as a novel therapeutic strategy for the selective treatment of respiratory depression caused by opioids while leaving analgesic effects unaffected. The effects in rats have been seen with the 5-hydroxytryptamine 4a (5-HT4a) agonist BIMU8, which is currently not available for use in humans. In a proof-of-applicability study, the clinically recommended dose of 5 mg mosapride, currently the only 5-HT4 agonist available for clinical use, was given in a placebo-controlled manner 3 times daily for 5 days to 12 healthy men and women. During the actual experiments, a further 15 mg mosapride was administered. After baseline measurements of respiratory depression, by use of a carbon dioxide rebreathing method, and of pain, by use of electrical and chemical pain stimuli, 30 mg morphine per 70 kg body weight was administered intravenously within 2 hours. After assessment of respiratory depression and pain, 2 mg naloxone was intravenously administered within 20 minutes, followed by a third assessment of respiratory depression and pain. In ancillary experiments 10 rats received 100 mg/kg mosapride orally or placebo 50 minutes before intraperitoneal injection of 10 mg/kg morphine, followed 20 minutes later by injection of naloxone, and the respiratory frequency was monitored. With placebo coadministration, the slope of the relationship between expiratory volume and CO2 concentration in the inspired air was significantly reduced, from 1.11 +/- 0.46 L/mm Hg CO2 at baseline to 0.39 +/- 0.25 L/mm Hg CO2 at the end of the morphine infusion (P < .001). Coadministration of mosapride had no effect on respiratory depression induced by morphine (slope of 0.39 +/- 0.19 L/mm Hg CO2, P > .7). In contrast, naloxone significantly reversed the slope to 0.78 +/- 0.36 L/mm Hg CO2 (P = .001). Morphine produced significant effects on electrical and chemical pain stimuli, which were partially reversed by naloxone, but mosapride did not affect the analgesic effects of morphine. In rats mosapride similarly failed to prevent a slowing of the breathing frequency after morphine administration but naloxone reversed the respiratory depression. Our results show that, with mosapride, opioid-induced respiratory depression cannot be prevented, and because other 5-HT4 agonists are not currently available for clinical use, a cure for opioid-induced respiratory depression as promised by the previous successful experiments in laboratory animals is not yet available in clinical practice.


Change in economic difficulties and physical and mental functioning: Evidence from British and Finnish employee cohorts.
The main aims of this longitudinal study were to (i) examine associations between changes in economic difficulties and health functioning among middle-aged employees and (ii) assess whether the associations remained after considering conventional domains of socioeconomic position. The associations were tested in two European welfare state occupational cohorts to strengthen the evidence base and improve generalizability. Data came from two cohorts: the Finnish Helsinki Health Study (baseline 2000-2002, follow-up 2007, N = 6328) and the British Whitehall II Study (baseline 1997-1999, follow-up 2003-2004, N = 4350). Responses to the survey item "finding it hard to afford adequate food and clothes and pay bills" repeated at baseline and follow-up were used to examine persistent, increasing, and decreasing economic difficulties. Poor physical and mental health functioning were denoted as being in the lowest quartile of the Short Form 36 physical and mental component summary. Logistic regression analyses were adjusted for sex, age, childhood economic difficulties, household income at baseline and follow-up, employment status at follow-up, and baseline health functioning. We observed strong sex- and age-adjusted associations between increasing [odds ratio (OR) range 1.69-2.96] and persistent (OR range 2.54-3.21) economic difficulties and poorer physical and mental health functioning in both British and Finnish occupational cohorts. These associations remained after full adjustments. Those reporting decreasing difficulties over follow-up also had poorer functioning (OR range 1.30-1.61) compared to those who did not have difficulties at baseline, possibly reflecting residual effects of economic difficulties at baseline. Changes in economic difficulties are associated with poorer physical and mental health functioning independent of income, employment status, and baseline health functioning.


RKIP and BRAF aberrations in human nasal polyps and the adjacent turbinate mucosae.
Little is known about the implication of BRAF and RKIP expression, or about the incidence of BRAF mutations in the formation of nasal polyposis. To determine the expression levels of the genes BRAF and RKIP, and to inspect the frequency of BRAF mutations in exons 11, 14 and 15 in human nasal polyps (NP). We analyzed 24 human NP specimens and their adjacent inferior and middle turbinates (AIT and AMT), as well as 14 control subjects [bearing 14 Control Inferior Turbinates (CIT) and 14 Control Middle Turbinates (CMT), in total]. The expression pattern of BRAF and RKIP was assessed with real-time RT-PCR. A real-time allele-specific PCR method, in combination with direct sequencing, was performed in order to inspect the frequency of the V600E mutation in exon 15, and to examine mutation status within exons 11 and 14. The control mucosae presented significantly higher mRNA levels for both genes, compared to the NP and the AIT-AMT. Moreover, in NP, AIT and AMT, RKIP was found to present higher mRNA levels, in relation to the equivalent values of the BRAF gene (P=0.003 in NP; P<0.001 both in AIT and AMT). No mutation was detected in exon 14, whereas a silent mutation (A1380G, G460G) was noted for one NP sample in exon 11. Another NP sample was found to carry two mutations, one T1799A (V600E) and one A1801G (K601E). A significant co-expression of the two genes was noted in NP (P=0.012) and AIT (P=0.019). The results of the expression levels of RKIP and BRAF, reflect the strong connection between the two genes. RKIP could play an important role in the down-regulation of wild-type BRAF, serving thus as an endogenous inhibitor of the MAPK pathway in nasal polyps and their adjacent turbinate mucosa.


The clinical implications of climate change for mental health.
Climate change affects mental health through multiple pathways, including direct and indirect impacts, physical health and awareness of the climate crisis. Climate change increases the magnitude and frequency of extreme events with little or no time for recovery. This Review aims to provide an overview of the current evidence to inform the mental health field's response to climate change. While further innovation is needed, promising approaches for health professionals are identified at the levels of interventions for individuals, community and system-wide responses, and advocacy and education. Health worker training is important, so we offer guidance on mental health assessment and clinical risks from climate change. We also outline strategies to enhance individual and community psychological resilience and promising approaches to working with people experiencing emerging climate-related disorders. Beyond clinical care, mental health professionals can lead on climate action and sustainability in health care and can research and educate on the health effects of climate change.


Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status.
Cobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (<250 pg/ml). Twelve symptomatic patients with low serum Cbl status were enrolled. Clinical presentations, Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed. Dysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy. Our TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be seen in the earlier state of Cbl deficiency, when psychiatric symptoms predominate. Hypoperfusion beyond thalamus/basal ganglia and involving frontal regions appears when cognitive problems, mostly dysexecutive syndrome, are manifested. Symmetric hypofrontality of SPECT in the context of dysexcutive syndrome serves as a distinguishing feature of non-amnestic mild cognitive impairment attributed to Cbl deficiency. Concordant with TC-99 m-ECD SPECT findings, the psychiatric symptoms and dysexcutive syndrome undergird impaired limbic and dorsolateral prefrontal circuits originating from basal ganglia respectively.


Antimicrobial susceptibilities of anaerobic bacteria isolated at the Mayo Clinic during 1982 through 1987: comparison with results from 1977 through 1981.
Results of antimicrobial susceptibility testing of anaerobic bacteria isolated at the Mayo Clinic were reviewed for 1982 through 1987 and compared with a previous survey during 1977 through 1981 at this institution. Between the earlier and the later period, clindamycin resistance increased in the Bacteroides fragilis group (from 4% of isolates to 8%). We noted continuing penicillin resistance among Bacteroides species other than B. fragilis and rare penicillin resistance among Fusobacterium organisms, with four isolates during the 1982 through 1987 period being beta-lactamase producers. The high levels of resistance to some agents seen in certain Clostridium species in 1977 through 1981 were not as great in the current survey. No major changes were noted in the susceptibilities of C. perfringens, anaerobic non-spore-forming gram-positive bacilli, and anaerobic gram-positive cocci.


Critical features for face recognition.
Face recognition is a computationally challenging task that humans perform effortlessly. Nonetheless, this remarkable ability is better for familiar faces than unfamiliar faces. To account for humans' superior ability to recognize familiar faces, current theories suggest that different features are used for the representation of familiar and unfamiliar faces. In the current study, we applied a reverse engineering approach to reveal which facial features are critical for familiar face recognition. In contrast to current views, we discovered that the same subset of features that are used for matching unfamiliar faces, are also used for matching as well as recognition of familiar faces. We further show that these features are also used by a deep neural network face recognition algorithm. We therefore propose a new framework that assumes similar perceptual representation for all faces and integrates cognition and perception to account for humans' superior recognition of familiar faces.


ICSH recommendations for assessing automated high-performance liquid chromatography and capillary electrophoresis equipment for the quantitation of HbA2.
Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2 ) in blood samples order to enable screening and diagnosis of carriers of β-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.


Effects of differential rearing on the structure of perforated synapses in the granule cell layer of the rat's accessory olfactory bulb.
The effects of differential rearing on synaptic morphology in the granule cell layer of the accessory olfactory bulb (AOB) were examined in adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were killed for electron microscopy. Two types of synapses were classified: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) non-perforated synapses. The length of the synaptic contact zone as well as the area and the length of the perimeter of both the pre- and postsynaptic terminals were measured in each observed synapse. For perforated synapses, the length of the synaptic contact zone was significantly greater in the UC and the SC than in the IC. For the presynaptic terminals of perforated synapses, the area was greater in the UC and the SC than in the IC, and the length of the perimeter was greater in the UC than in the IC. In contrast, there was no difference in the area and the length of the perimeter among the three groups for postsynaptic terminals. For non-perforated synapses, there was no statistically significant difference in either the area or the length of the perimeter of pre- and postsynaptic terminals among the three experimental groups, although the length of the synaptic contact zone was greater in the SC than in the IC.(ABSTRACT TRUNCATED AT 250 WORDS)


Dataset to develop self-report measure of emotional instability and behavioral difficulties for Malaysian youths.
The article presents reliability statistics data in relation to the development of emotional instability and behavioral difficulties scale for youths in a Malaysia context. The data were obtained from youths participants in Kuala Lumpur and Klang Valley, Selangor, Malaysia. The data has four different subscales in describing emotional instability and behavioral difficulties. The data were analyzed using Cronbach's alpha, McDonald's ω, and Gutmann's λ6 to examine internal consistency test. The data showed that this new scale can be used to measure three subscales of emotional instability and one subscale of behavioral difficulties among youths in a Malaysia context.


Spontaneous tonsillar hemorrhage.
Spontaneous tonsillar hemorrhage (STH) of non-iatrogenic causes occurs most frequently from infection. Infection can lead to erosion into a major vessel, such as the carotid artery or a smaller peripheral tonsil vessel. Whereas fatal erosion into a major vessel from a deep neck abscess was relatively common in the past, it is rare since the advent of antibiotics. Spontaneous tonsillar hemorrhage, when it does occur, appears to occur most commonly in a peripheral tonsil vessel from bacterial tonsillitis. Medical records of 860 patients with conditions considered to be susceptible to STH were reviewed. Ten cases of STH were identified. All were from peripheral tonsil vessel hemorrhage; none was secondary to major vessel erosion. Bacterial tonsillitis was the most common cause of STH and occurred in 8 of 10 cases. This condition accounted for an incidence of STH in tonsillitis of 1.1%. A history of chronic tonsillitis appeared to predispose a patient to STH. Other causes of STH were infectious mononucleosis and neoplasm. Seven of the ten peripheral STHs presented with bleeding from an obvious venous source. The other three patients had significant hemorrhages which led to arteriography. Arteriograms are indicated in patients with clinical features suggesting possible major vessel erosion or in those patients where significant bleeding is not from an obvious peripheral source. A peripheral STH can be successfully managed with local intervention and tonsillectomy.


Maternal Pseudo-Bartter Syndrome Associated with Severe Perinatal Brain Injury.
Maternal electrolyte imbalance is rarely reported as causative factor of severe perinatal brain injury. This case outlines a unique maternal and neonatal pseudo-Bartter syndrome presented with metabolic alkalosis and hypochloremia due to maternal severe vomiting. Neonatal MRI brain revealed extensive brain hemorrhages with porencephalic cysts. Subsequent investigation workup points towards maternal severe metabolic alkalosis as its cause. Careful medical attention should be paid to pregnant women with excessive vomiting to ensure a healthy outcome for both the mother and the baby.


Determination of the pK values for the alpha-amino groups of human hemoglobin.
The rate of reaction between alpha-amino groups and cyanic acid was followed at 26 degrees and ionic strength 0.2 M as a function of pH of human hemoglobin Ao solutions to determine the pK and the pH-independent second order rate constant, kappa, for these groups in the alpha and beta chains. At a given point in time, the extent of the reaction was determined by employing the Beckmann Sequencer as a quantitative tool in which the yields of leucine and histidine in the second Edman degradation cycle were used to define the rates of reaction of the alpha and beta chains, respectively. From these results, the individual were evaluated (Garner, M.H., Garner, W.H., and Gurd, F. R.N. (1973) J. Biol. Chem. 248, 5451-5455). Values for pK for the alpha and beta chains were, respectively, 6.74 and 6.93 for cyanoferrihemoglobin, 6.95 and 7.05 for carboxyhemoglobin, and 7.79 and 6.84 for deoxyhemoglobin. Values for kappa, M- minus 1 S-minus 1, for the alpha and beta chains were, respectively, 12.5 and 17 for cyanoferrihemoglobin, 12 and 18 for carboxyhemoglobin, and 91 and 24 for deoxyhemoglobin. Limits of significance were estimated for both variables in each case. The pK results for valine 1alpha agree well with the value obtained by Hill and Davis (1967) J. Biol. Chem. 242, 2005-2012) for carboxyhemoglobin and with that of Kilmartin and Rossi-Bernardi ((1971) Biochem. J. 124, 31-45) for deoxyhemoglobin. Values obtained for sperm whale myoglobin were 7.77 for pK and 7.4 for kappa. The results are useful for the interpretation of the allosteric interactions of hemoglobin with hydrogen ions, with CO2, and with phosphate.


Herbivory on calcicolous lichens: different food preferences and growth rates in two co-existing land snails.
A total of 32 calcicolous lichen species, one alga and one bryophyte were recorded on a limestone wall in the grassland Great Alvar on the Baltic island of Öland, Sweden. Fourteen (41%) of these 34 species and free-living cyanobacteria showed herbivore damage, most probably due to grazing by the land snails Chondrina clienta and Balea perversa which inhabited the limestone wall. Three laboratory experiments were conducted to examine the food preferences of individuals of C. clienta and B. perversa collected at this site and to evaluate any association between their preference and the net food quality of the lichens to the snails. Chondrina clienta and B. perversa exhibited food preferences, which differed significantly between species. Within species, variation in food choice was similar among individuals. This indicates that snail populations may be composed of polyphagous individuals with similar food preferences. Different lichen species were of different net food quality to the snails as indicated by growth rate differences. In both snail species the most preferred lichen species of the choice experiment caused the largest weight increase in juveniles, viz. Caloplaca flavovirescens for C. clienta and Aspicilia calcarea for B. perversa. This suggest that the snail species studied differ in their abilities to deal with secondary compounds and physical characteristics of certain lichens or that they can utilize the energy and nutrients of these lichens to a different extent. It is suggested that differential food preferences might reduce the intensity of interspecific competition for resources (lichens) between C. clienta and B. perversa.


Double-exposure technique in computerized tomography of the spine.
The authors present a technique for recording both soft tissue and bone on the same reproduction of CT images of the spine. Enhancement around the edge of osseous structures is a valuable aspect of this technique.


Locoregional anesthesia is associated with reduced hospital stay and need for intensive care unit care of elective endovascular aneurysm repair patients in the Vascular Quality Initiative.
It has been shown local or regional anesthetic techniques are a feasible alternative to general anesthesia for endovascular aortic aneurysm repair (EVAR). However, studies to date have shown controversial findings with respect to the benefit of locoregional anesthesia (LR) in the elective setting. The objective of this study is to compare postoperative outcomes between LR and general anesthesia (GA) in the setting of elective EVAR, using a large, multicenter database. Using the Society for Vascular Surgery Vascular Quality Initiative database, we retrospectively analyzed all patients who underwent elective EVAR from August 2003 to June 2021. Patients were grouped by anesthetic type based on the level of consciousness afforded by the anesthetic: local or regional anesthesia (LR) vs GA. Primary outcomes were total postoperative hospital length-of-stay (LOS) and intensive care unit (ICU) LOS. Propensity score matching was used for risk adjustment and to analyze the primary outcomes with confirmatory analysis using logistic or linear regression, as appropriate, in single and multilevel models. Secondary outcomes were 30-day mortality, 1-year mortality, postoperative outcomes, operative time, fluoroscopy time, and reoperation rate. These were analyzed following propensity score matching as well as using logistic regression and Cox proportional hazard regression in single and multilevel models, as appropriate. A total of 50,809 patients underwent elective EVAR from 2003 to 2021. Of these, 4302 repairs used LR (8.5%) and 46,507 (91.5%) were performed under GA. After employing propensity score matching, two groups of 3027 patients were produced. These showed no significant difference in 30-day mortality (odds ratio, 1.22; P = .53), 1-year mortality (hazard ratio, 1.06; P = .62), or any postoperative outcomes. LR was found to be significantly associated with shorter hospital stays (≤2 days) (12.5% vs 14.8%; P = .01), decreased ICU utilization (19.3% vs 30.6%; P < .001), decreased operative time (110.8 vs 117.3 minutes; P < .001), decreased fluoroscopy time (21.0 vs 22.7 minutes; P < .001), and a slight reduction in reoperation rate (1.2% vs 1.9%; P = .02), which all remained significant following single-level and multilevel multivariate analyses accounting for hospital and physician random effects. These data suggest that LR anesthesia is safe and may offer advantages in reducing resource utilization for patients undergoing elective EVAR, primarily based on associations with reduced ICU care and reduced hospital stay. Given these findings, LR may prove an advantageous technique in appropriately selected patient populations.


Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.
The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.


Cutaneous pre-B leukaemia cells with a T-lymphocyte antigen (T4).
A patient with acute lymphocytic leukaemia (ALL) is described in whom the cells originated in the pre-B cell lineage but showed an aberrant expression of T4 antigen. A B-cell origin of the leukaemic cells was indicated by reactivity for several monoclonal antibodies specific for the B-cell lineage and by cytoplasmic staining with FITC-labelled anti human mu chains.


Correction: Use of pyridazinediones as extracellular cleavable linkers through reversible cysteine conjugation.
Correction for 'Use of pyridazinediones as extracellular cleavable linkers through reversible cysteine conjugation' by Calise Bahou et al., Chem. Commun., 2019, 55, 14829-14832, https://doi.org/10.1039/C9CC08362F.


Sumoylation differentially regulates Goosecoid-mediated transcriptional repression.
Goosecoid (Gsc), a paired-like homeobox gene expressed in the vertebrate organizer, functions as a transcriptional repressor either by direct DNA binding to paired TAAT homeodomain sites or through recruitment by the forkhead/winged helix transcription factor Foxh1. Here, we report that Gsc is post-translationally modified by small ubiquitin-like modifier proteins (SUMO). Members of the PIAS family of proteins enhance Gsc sumoylation and this modification occurs on at least six lysine residues. Stable expression of a SUMO-defective Gsc mutant (Gsc 6Km) in MDA-MB-231 breast cancer cells results in morphological changes giving rise to cells with increased cell area. We demonstrate that Gsc 6Km can effectively repress Foxh1-mediated induction of the Mixl1 promoter, indicating that sumoylation is not required for Gsc-mediated repression of promoters where recruitment occurs through Foxh1. In contrast, Gsc 6Km exhibits a decreased ability to repress the induction of promoters to which it is directly recruited through paired-homeodomain binding sites, including its own promoter and that of the Xenopus Brachyury gene. Taken together, our data suggests that regulation of Gsc repressive activity by SUMO modification is promoter specific and may serve to differentially regulate genes that function to control cell morphology during early development and cancer.


Tacrolimus ointment in the treatment of hormone-dependent dermatitis: A protocol of systematic review.
Long-term use of corticosteroid ointment for external using or skin management products and cosmetics containing corticosteroid will produce a hormone-dependent effect on facial skin and destroy the barrier function of the skin. It is easy to cause repeated attacks of facial skin inflammation after drug withdrawal because corticosteroid hormones can cause the expression of inflammatory factors in the body, which has a serious impact on patients. The general treatment method is to stop using hormone drugs for psychotherapy and inform patients of the basic knowledge of hormone-dependent dermatitis and daily facial care, but the effect is not good. At present, non-steroidal ointment tacrolimus (a calcineurin inhibitor) is widely used in the treatment of hormone-dependent dermatitis. Tacrolimus ointment is effective for corticosteroid-dependent dermatitis, but adverse events can also occur. We plan to searched all randomized controlled trials (RCTs) fortacrolimus ointment therapy of hormone-dependent dermatitis in: MEDLINE, PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Springer and Web of Science, China Biomedical Literature Database (CBM), China Science Journal Database (VIP database) and Wanfang Database, China National Knowledge Infrastructure (CNKI), without the limitation of publication status and language until September 1, 2020. The systematic review will also search will also search for identify publications, meeting minutes, and grey literature (including unpublished meeting articles). The systematic review mainly to access the safety and efficacy of tacrolimus ointment for hormone-dependent dermatitis (facial corticosteroid addiction dermatitis and facial steroid dermatitis). The results of our research will facilitate evidence-based management of patients with facial corticosteroid-dependent dermatitis and provide clinical advice on their treatment options. PROSPERO CRD42020171813.


Biliary stenting with a prototype expandable Teflon endoprosthesis.
A new balloon-expandable Teflon endoprosthesis was developed for endoscopic placement in the biliary tree. After deployment to its maximum diameter the stent is hardened by exposure to UV light. We present our preliminary results with a prototype 18 Fr prosthesis. Three patients with a distal common bile duct obstruction due to unresectable pancreatic head carcinoma were treated with this stent. Insertion of the stent was the only palliative procedure. Patients were followed up until stent dysfunction or death. Stent placement was successful in all patients and no procedural complications occurred. Distal migration occurred in one patient, clogging of the stent after 149 days in another. In patients with a malignant biliary stricture this newly developed expandable endoprosthesis is effective in relieving obstructive jaundice. The technique has potential advantages over placement of current expandable metal mesh stents.


Postnatal health and care following hypertensive disorders in pregnancy: a prospective cohort study (BPiPP study).
One in 10 women have hypertensive disorders in pregnancy (HDP) and are at risk of adverse short- and long-term health outcomes, yet there is limited information on their postnatal health and care needs. This study aimed to look at postnatal physical and psychological morbidity in women with HDP, compared to women without HDP, and the postnatal care received in both groups. Within a prospective cohort study, women with and without HDP were identified and recruited on the postnatal ward of 17 maternity units across England and invited to complete a short baseline questionnaire. At 3 months postpartum, women were sent a follow-up questionnaire, with reminders. The principal outcomes were the mean score at 3 months for the Edinburgh Postnatal Depression Scale (EPDS) and the EuroQol Group 5-dimension (EQ-5D) scale. One thousand eight hundred twenty-nine women agreed to participate. Of these, 1757 (96%) completed the baseline questionnaire: 769 (44%) women had HDP and 988 (56%) women did not. Despite a difference in health-related quality of life and symptoms of depression at baseline between the two groups, at 3 months postnatal, within the 653 women who completed their follow-up questionnaire (37.2% of those who completed the baseline questionnaire) there were no significant differences between the groups (median EQ-5D VAS: 85 in women with HDP, 85 in women without HDP, p = 0.99 and mean EPDS score 5.5 in women with HDP, 5.0 in women without HDP, p = 0.80). Overall levels of physical postnatal morbidity were high, with 89% reporting one or more morbidities. Approximately 9% of women were re-admitted within 3 months after birth, higher in the HDP group (13.1%) higher compared to women without HDP (5.5%; RR 2.41; 95% CI 1.44-4.05). Overall levels of physical and psychological morbidity were high in this postnatal population. Although there were increased needs of women with HDP in the immediate postnatal period (compared to other women), their health assessments were similar at 3 months. This study highlights the unmet needs of women in the postnatal period, in addition to a missed opportunity to influence future pregnancies and improve the longer-term health of women and their babies.


Identification and characterization of a novel gene Aokap1 involved in growth and kojic acid synthesis in Aspergillus oryzae.
The elucidation of the mechanism for the growth and secondary metabolites in Aspergillus oryzae is important for industrial production and utilization. Here, we found that the expression of a novel gene Aokap1 was induced during the growth of A. oryzae. Sequence analysis revealed that AoKap1 has four transmembrane regions and is conserved in Aspergillus species. Disruption of Aokap1 caused the inhibition in mycelium growth and conidia formation, corresponding with reduced expression of brlA and abaA. Furthermore, deletion of Aokap1 resulted in elevated production of kojic acid, and the expression of kojA, kojR and kojT was up-regulated in Aokap1-disrupted strain. Meanwhile, overexpression of kojR resulted in the decreased expression of Aokap1, suggesting that disruption of Aokap1 increased kojic acid production by affecting the expression of kojA, kojR and kojT. The discovery of Aokap1 provides a new target for genetic modification of the growth and kojic acid production in A. oryzae.


Supporting Parents' Services Access During the COVID-19 Pandemic Through the Infant-Toddler Court Team Program.
Infant-Toddler Court Teams (ITCTs) are a collaborative practice designed to improve timely identification and receipt of needed services for families of infants and toddlers involved in the child welfare system and their families. The goal of the study was to explore the impact of the first year of COVID compared to the previous year, in the context of ITCT support, on: (1) parents' access to services; (2) parents' services receipt and access within 30 days and within 14 days from referral; and (3) predictors of services access and receipt. Overall, 897 instances of services needs were analyzed, 411 pre-COVID and 486 during COVID. Logistic regression models were used to test for differences pre- and during COVID, controlling for covariates. A reduction in service access was found across all services during COVID (OR = 0.2, CI: 0.1-0.3, p < .0001). Nevertheless, if a service was still available, parents were able to maintain similar levels of receipt within 30 days and within 14 days as before COVID. Moreover, a higher percentage of parents in need received mental health services in 30 or fewer days and substance use disorder services in both 14 and 30 or fewer days during COVID compared to pre-COVID. This success is notable given the significant disruption to the availability of services and barriers to accessing services caused by the pandemic. ITCTs provided a robust platform for supporting the health and well-being of families with very young children in the face of a severely reduced service landscape due to COVID-19.


[Change in cell adhesiveness to glass at a constant density of their surface-bound charges].
It has been investigated whether there exists a correlation between the adhesiveness of Chinese hamster fibroblasts to glass and the density of surface-bound charges of the cells and the glass. The adhesiveness of the cells to glass was shown to vary appreciably at constant density of their surface-bound charges.


An optimized multivitamin supplement lowers the number of vitamin and mineral deficiencies three years after Roux-en-Y gastric bypass: a cohort study.
Vitamin and mineral deficiencies are common after Roux-en-Y gastric bypass (RYGB) surgery. In particular, inadequate serum concentrations of ferritin and vitamin B12 have been found in 11% and 23% (respectively) of patients using a standard multivitamin supplement (sMVS) 1 year after RYGB. To evaluate the effectiveness and safety of Weight Loss Surgery (WLS) Forte® (a pharmaceutical-grade, optimized multivitamin supplement) compared with an sMVS and a control group (nonuser) 3 years after RYGB. General hospital specialized in bariatric surgery. A follow-up cohort study of a triple-blind randomized, controlled clinical trial. At baseline 148 patients were enrolled (74 [50%] in the sMVS group and 74 [50%] in the WLS Forte group). After a mean follow-up of 36 months, 11 (7%) patients were lost to follow-up, of whom 2 were secondary to death. At the end of the study, 11 (17%) patients in the WLS Forte and 17 (24%) in the sMVS group stopped using a supplement. In addition, 64 (47%) patients were using WLS Forte and 45 (33%) patients a sMVS. Patient characteristics and follow-up length were comparable between the groups. Significantly more patients were diagnosed with anemia (16% versus 3% [P = .021]), a ferritin deficiency (14% versus 3% [P = .043]), and a zinc deficiency (8% versus 0% [P = .033]) in the sMVS group compared with WLS Forte. Five patients developed a vitamin B12 deficiency while using WLS Forte, versus 15 of sMVS users (P = .001). No adverse events occurred that were related to supplement use. At 3 years postoperative of RYGB, an optimized multivitamin supplement (WLS Forte) was more effective in reducing anemia and ferritin, vitamin B12, and zinc deficiencies compared with a standard supplement and control.


Predictors of balance in individuals with Parkinson's disease: A cross-sectional study.
Some previous studies investigated predictors of balance in individuals with Parkinson's Disease (PD). However, outcomes commonly evaluated in the rehabilitation of individuals with PD that could predict balance deficits have not yet been investigated. To determine whether the variables muscle strength, physical activity and depression are predictors of balance in individuals with PD. This is a cross-sectional study in which the investigated variables included: trunk and knee extensors' muscle strength (modified sphygmomanometer test - MST), physical activity level (Adjusted Human Activity Profile score) and depression (Patient Health Questionnaire-9 - PHQ-9). The outcome variable was balance, as assessed by the Mini-BESTest. Multiple regression analysis was used to determine which predictor variables explain the outcome variable. A total of 50 individuals with PD, mean age 67 ± 8.8 years, 68% male, 40% HY 2.5 were included. The mean value of the dominant limb extensor muscle strength was 139 ± 45 mmHg, and the mean trunk extensor muscle strength value was 81.9 ± 19 mmHg. More than half of the sample (52%, n = 26) was classified as moderately active. Most of the sample (78%) had mild depression. The average Mini-BESTest score was 21 ± 5.4. The physical activity level explained 29% of the balance variance. When depression was included in the model, the explained variance increased to 35%. The other independent variables were not included in the model. The findings of the present study showed that the physical activity level and depression were able to explain 35% of the balance variation.


Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function.
There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment. To compare the Hestia criteria with the European Society of Cardiology (ESC) criteria for selecting low-risk patients with PE for outpatient treatment. From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 treated at home and 221 treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV and LV) diameters were measured on computed tomography images. RV dysfunction was defined as an RV/LV ratio > 1.0. Patients were classified according to the ESC criteria into low, intermediate and high-risk groups, based on blood pressure and RV dysfunction. During 3 months follow-up adverse events were scored. Adverse events occurred in 22 patients (4.5%) treated in the hospital vs. none of the patients treated at home (P < 0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home. Clinical criteria, such as the Hestia criteria, could be helpful in selecting patients, including those with RV dysfunction who have a low risk of adverse clinical outcome and could be candidates for outpatient treatment.


Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial.
Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy. Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019. Durvalumab 20 mg/kg plus tremelimumab 1 mg/kg was administered intravenously every 4 weeks for four doses, followed by up to nine doses of durvalumab monotherapy every 4 weeks for up to 12 months of treatment or disease progression. Primary end points included safety and objective response rate (ORR) on the basis of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per blinded independent central review; secondary end points were ORR on the basis of RECIST v1.1 per investigator; duration of response, disease control, and progression-free survival on the basis of RECIST v1.1 per blinded independent central review and investigator; and overall survival. gov identifier: NCT02000947. PD-(L)1-refractory (n = 38) and PD-(L)1-relapsed (n = 40) patients were treated. The most common treatment-related adverse events were fatigue (26.3%, PD-(L)1-refractory patients) and diarrhea (27.5%, PD-(L)1-relapsed patients). Grade 3 to 4 treatment-related adverse events occurred in 22 patients. Median follow-up duration was 43.6 months for PD-(L)1-refractory patients and 41.2 months for PD-(L)1-relapsed patients. The ORR was 5.3% for PD-(L)1-refractory patients (one complete response, one partial response) and 0% for PD-(L)1-relapsed patients. Durvalumab plus tremelimumab had a manageable safety profile, but the combination did not have efficacy after PD-(L)1 treatment failure.


Fractures of the humerus from arm wrestling.
Two cases of humeral shaft fracture following 'arm wrestling' are described. Only one has previously been reported from Great Britain. The literature is reviewed and the mechanism of the injury discussed.


Carbon-carbon bond-forming enantioselective synthesis of chiral organosilicon compounds by rhodium/chiral diene-catalyzed asymmetric 1,4-addition reaction.
[reaction: see text] A new synthetic method for chiral organosilicon compounds through a rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to beta-silyl alpha,beta-unsaturated carbonyl compounds has been developed. By employing (R,R)-Bn-bod* as a ligand, a range of arylboronic acids can be coupled with these substrates in very high enantiomeric excess. The resulting beta-silyl 1,4-adducts can be converted to beta-hydroxy carbonyl compounds or allylsilanes while retaining their stereochemical information.


Modified Technique for Small-Incision Lenticule Extraction: Ye's Swing Technique.
This study aimed to evaluate the lenticule integrity and refractive outcomes of a new technique, Ye's swing technique, during small-incision lenticule extraction (SMILE). This prospective study enrolled patients who underwent the SMILE procedure using a modified technique for lenticule dissection. Per the standard SMILE procedure, the cap cut was opened using a hook, and an anterior dissection was performed with a counterclockwise swing, from 8 to 12 o'clock. A posterior dissection was then performed by swinging counterclockwise, leaving a thin band of the peripheral rim undissected, from 8 to 4 o'clock. The counterclockwise swing was continued to separate the edges of the rim from 4 to 12 o'clock, after which microforceps were used to extract the lenticules. The primary outcome measures were safety and lenticule integrity at the end of the surgery, and the secondary outcome measure was efficacy. Changes in the ocular parameters from the preoperative visit to 1 month postoperative, including uncorrected and corrected distance visual acuity, manifest refraction, lenticule quality, and lenticule residual, were assessed using optical coherence tomography. A total of 246 patients (490 eyes) with myopia and myopic astigmatism were included in the present study. The dissected lenticules ranged in size from 52 to 148 µm. Postoperatively, the lenticule was completely and successfully extracted in all cases. There was no incisional edge tearing during lenticule separation. Ye's swing technique is a safe and effective procedure for lenticule dissection and refractive outcomes. We have now adopted this technique as our routine method for performing the SMILE procedure.


Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.
To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.


1H-NMR heme resonance assignments by selective deuteration in low-spin complexes of ferric hemoglobin A.
The heme methyl and vinyl alpha-proton signals have been assigned in low-spin ferric cyanide and azide ligated derivatives of the intact tetramer of hemoglobin A, as well as the isolated chains, by reconstituting the proteins with selectively deuterated hemins. For the hemoglobin cyanide tetramer, assignment to individual subunits was effected by forming hybrid hemoglobins possessing isotope-labeled hemins in only one type of subunit. The heme methyl contact shift pattern has 1-methyl and 5-methyl shifts furthest downfield in both chains and the individual subunits of the intact hemoglobin in both the cyanide- and azide-ligated species, which is consistent with a dominant rhombic perturbation due to the proximal His-F8 imidazole pi bonding in the known structure for human adult hemoglobin. The individual chain and subunit assignments confirm that the detailed electronic/magnetic properties of the heme pocket are essentially unaltered upon assembling the R-state tetramer from the isolated subunits.


The lateral neck flexor endurance test: Normative values in the young adult population.
Unilateral muscular deficits have been identified in individuals with neck pain, although no unilateral clinical tests have been described in the literature. Assessment of lateral neck flexor endurance may allow identification of abnormal unilateral muscle function. The lateral neck flexor (LNF) endurance test, where an individual holds their head parallel to the ground while side-lying, may be a clinical option. We sought to (1) determine inter-rater reliability of the LNF endurance test and (2) establish normative LNF values in healthy individuals. Inter-rater reliability was assessed for four raters, working in pairs to assess a pilot sample of 20 individuals. Normative data was subsequently collected for 60 healthy adults, age 20-40. All participants completed the International Physical Activity Questionnaire to assess physical activity and the LNF endurance test was assessed once per side. The LNF endurance test demonstrated excellent inter-rater reliability: ICC(2,1) = 0.972 [0.941-0.987]. Left and right median LNF hold times were 122.0, 133.94 s for males and 97.42, 93.73 s for females, respectively. Individual median hold time ratios were 72.1% for males and 68.7% for females. There were no meaningful correlations between reported physical activity and LNF endurance. The LNF endurance test is a reliable measure. Males generally displayed greater LNF endurance than females, although variability within groups was high. Based on the observed values in this healthy population, 120 s for males and 90 s for females with a 70% side:side ratio appear to be useful normative benchmarks although further research is required including clinical populations.


Phytoremediation of CdS/Te quantum dots by Ocimum basilicum in the presence of EDTA.
The use of nanomaterials like quantum dots (QDs) with optical properties has increased in the last decade because of their electronics, medicine, and environmental applications. The lack of recycling and appropriate disposal causes these materials to be considered new emerging contaminants. In this research, the extraction and translocation (phytoextraction) of cadmium as QDs by Ocimum basilicum "basil" in the presence of EDTA (chelating agent) was studied. For edible plants are essential to know where the contaminants are located to minimize human consumption. In this work, the phytoextraction, distribution, and translocation of cadmium (under ionic solution-CdIS and CdS/Te QDs) at 25 and 50 mg/kg-soil and in the presence of 1,000 mg/kg-soil EDTA was studied in O. basilicum (a commercialized culinary herb) for three and six weeks. Basil seedlings were grown in an environmentally controlled chamber at 24-28o C and 12/12 hours periods of light and darkness. The highest cadmium concentration was found in the roots from where it is translocated to stems and leaves. CdS/Te QDs at low concentration (25 mg/kg and 3 weeks of exposure) had the highest translocation factor, indicating that cadmium's nanocrystal (QDs) forms can affect the phytoextraction mechanism. The highest bioconcentration of cadmium was reached at a high contaminant concentration. The bioconcentration factors confirm that O. basilicum phytoextracts cadmium from soils contaminated with CdS/Te QDs and CdIS. The bioconcentration factors of cadmium (under both species CdS/Te QDs and CdIS) increase in the presence of EDTA. The bioconcentration and translocation factors suggest that consuming "basil" from contaminated soils with CdS/Te QDs at low concentrations increases the exposition to this metal.


[Effects of assertive training on interpersonal relations, social behavior, and psychiatric symptoms in patients with a mental disorder].
This study was designed to examine the effects of an assertive training program on interpersonal relations, and psychiatric symptoms in patients with a mental disorder. The study employed a quasi experimental design. The subjects included 44 patients with a mental disorder, 20 in the experimental group, and 24 in the control group. Data was collected using structured questionnaires over a 3 month period. There were greater significant increases in scores of interpersonal relations and content of communication in the experimental group than the control group. Also, there was a greater significant decrease in the score of psychiatric symptoms in the experimental group than the control group. Assertive training has an effect on increasing content of communication and decreasing psychiatric symptoms.


Current status of the role of stem cells in myocardial biology and repair.
The purpose of this article is to present an analysis of current knowledge and understanding of the role of stem cells in myocardial biology and myocardial repair following injury. This rapidly evolving field has assumed relevance for the understanding, diagnosis, and treatment of heart failure.


The morphological effects of dexamethasone on the pituitary-adrenal axis of the rat--a quantitative study.
Adult Sprague-Dawley rats received a daily intraperitoneal injection of dexamethasone (100 or 200 micrograms/kg) for 2 or 6 weeks. Quantitative assessment of the anterior pituitary corticotroph population performed using the stereological measurement of volume density (Vv). An indirect assessment of corticotroph function was also made, based on adrenal weight and histology. Adrenal changes were consistent with dose-related inhibition of corticotroph function in all dexamethasone-treated animals. Immunopositive corticotrophs were easily identified and in no treatment group was corticotroph Vv significantly less than in the appropriate vehicle-injected control group. In male animals, there was a significant increase (P less than 0.05) in Vv with 100 micrograms/kg at both 2 and 6 weeks. These results suggest that it is possible to produce inhibition of corticotroph function by the administration of such doses of dexamethasone without causing a significant reduction in the anterior pituitary corticotroph population. This may be related to the mode of negative feedback of such a regime.


Peritonitis as the first presentation of systemic lupus erythematous: a case report.
Systemic lupus erythematosus is an inflammatory disease affecting several organs. Serositis is one of the systemic lupus erythematosus presentations, but peritonitis is a relatively rare presentation. Particularly, it is extremely rare to observe peritonitis as the first presentation of systemic lupus erythematosus. Here, we present a case of peritonitis without other symptoms of systemic lupus erythematosus, in a patient who was finally diagnosed with systemic lupus erythematosus. Our patient was a 27-year-old Persian/Caucasian male with fatigue, weakness, weight loss, abdominal distension, massive ascites, and normocytic hemolytic anemia. He did not mention any prior medical conditions and did not use any drugs. There were no signs of thyroid dysfunction, cardiac dysfunction, cancers, infectious diseases, hepatitis, kidney diseases, or other diseases. Low-gradient, high-protein ascites fluid, and positive antinuclear antibody and anti-double stranded DNA were in favor of systemic lupus erythematosus. Corticosteroid pulse therapy led to resolution of ascites, and the patient was discharged with prednisolone and hydroxychloroquine. Peritonitis is a rare presentation of systemic lupus erythematosus, particularly as the first presentation and in the absence of other signs and symptoms; however, systemic lupus erythematosus should be considered as one the differential diagnoses for peritonitis when other etiologies have been ruled out.


Nerve growth factor mediates its pro-invasive effect in parallel with the release of a soluble E-cadherin fragment from breast cancer MCF-7/AZ cells.
To define better the function of Nerve Growth Factor (NGF) in breast cancer progression, we investigated whether this polypeptide was able to induce breast cancer cell invasion. NGF inhibited aggregation of tumour cells through modulation of the E-cadherin/catenin complex function. In addition, NGF induced the breast cancer cells to invade into Matrigel. We focused our attention on how NGF prevents aggregation, in order to discover the signalling pathway that leads tumour cells to acquire the invasive phenotype. Moreover, studies on the identification of signalling pathways that are responsive for NGF-induced invasion will be basically described.


Confirmation of a recombinant allele B*5603 and a hypothetical reciprocal hybrid.
From its DNA sequence, B*5603 is thought to be a product of gene conversion. We present here serological evidence of such an event and further speculate on a possible reciprocal hybrid yet to be identified. In addition, we report the allelic frequency of B*5603 in the Taiwanese population and its association with A*1101, Cw*01 and DRB1*1201.


A rapid structural degeneration of a porcine mitral valve.
A 73-year-old woman underwent both mitral and aortic valve replacements with porcine heart valve prostheses because of severe mitral regurgitation and severe aortic regurgitation. Ten months after surgery, maximal flow velocity of the aortic valve reached 4.6 m/sec and moderate mitral regurgitation was detected. Repeated mitral and aortic valve replacements with mechanical heart valves were performed. The excised mitral valve showed thinning of the 3 cusps, and 2 of them were perforated. There was pannus overgrowth on the flow surface of the porcine aortic valve. Histologic examination of the excised mitral valve revealed marked inflammatory changes with macrophages.


Molecular alterations associated with improved survival in pancreatic cancer patients treated with radiation or chemotherapy.
Multiple genetic alterations, several of which may be important prognostic markers, characterize the development of cancer in pancreas. We review our findings from previously published studies with regard to molecular alterations associated with survival differences in patients treated with conventional radiation and chemotherapies used as adjuvant or palliative therapy. K-ras-negative patients with pancreas cancer show improved survival with radiation therapy compared to K-ras-positive patients with pancreas cancer. p53 expression is associated with shorter survival when compared to no p53 expression in pancreas cancer patients treated with radiation therapy or chemotherapy. Pancreas cancer patients whose tumors express p21 show significant survival advantages when treated with chemotherapy or radiation therapy. An inverse relationship is observed with respect to p21 and p53 expression and clinical stage. Although stage and surgical resectability remain the most important variables with respect to pancreas cancer survival, these findings suggest promising opportunities for gene therapies designed to enhance p21 expression or restore wild-type K-ras or p53 function in pancreatic tumors.


Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation.
Using RNA-sequencing analysis, we investigated the relationship between ovarian stimulation and endometrial transcriptome profiles during the window of implantation (WOI) to identify candidate predictive factors for the WOI and to optimize timing for embryo transfer. Twelve women with normal basal hormone levels and regular ovulation were randomly assigned into three groups based on sampling time: late-proliferate phase (P group), and receptive phase in natural cycles (LH+7, N group) and stimulated cycles (hCG+7, S group). Transcriptome profiles of mRNAs and long non-coding RNAs (lncRNAs) were then compared among the three groups. Validation was performed using real-time qPCR. Comparison of transcriptome profiles between the natural and stimulated endometrium revealed 173 differentially expressed genes (DEGs), with a > 2-fold change (FC) and p < 0.05, under the influence of supraphysiological estradiol (E2) induced by ovarian stimulation. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity were identified. Of the 39 DEGs common to the three groups, eight genes were validated using real-time PCR. ESR1, MMP10, and HPSE were previously reported to be associated with endometrial receptivity. In addition, three novel genes (IL13RA2, ZCCHC12, SRARP) and two lncRNAs (LINC01060, LINC01104) were new potential endometrial receptivity-related markers. Using mRNA and lncRNA sequencing, we found that supraphysiological E2 levels from ovarian stimulation had a marked impact upon endometrial transcriptome profiles and may result in a shift of the WOI. The precise mechanisms underlying the supraphysiological hormone-induced shift of the WOI require further research. ChiCTR180001453.


The impact of trauma and disaster on young children.
In the past few decades, the study of the impact of trauma and disaster on children has grown; however, information about the effects on very young children is still scarce in the literature. In some regards, the characteristics of stress in young children are similar to those of older children and adults; in other ways, their reactions are unique. These characteristics, as well as mediating factors and interventions with young children, are discussed. Suggestions for future research are offered.