O6-alkylguanine-DNA alkyltransferase activity in normal human tissues and cells.
Normal adult human tissues and cultured bronchial epithelial cells and fibroblasts exhibit O6-alkylguanine-DNA alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkylation lesion O6-methylguanine from DNA. The amount repaired by extracts of liver, peripheral lung, and colon extracts was proportional to the amount of extract protein. Repair of O6-methylguanine led to stoichiometric regeneration of guanine in the DNA and stoichiometric formation of S-methylcysteine in protein. Alkyltransferase activity varies in the different human tissues tested in the decreasing order of liver greater than colon greater than esophagus greater than peripheral lung greater than brain. Extracts of lung tissues, cultured human bronchial epithelial cells, and fibroblasts had similar alkyltransferase activities. Various human tissues exhibit 2- to 10-fold higher alkyltransferase activity than corresponding rat tissues. Whereas the interindividual variation of the activity was 4- to 5-fold in ten or more human lung and colon specimens, the interindividual variation in the inbred rat was less than 20%. The present results show that different human tissues and cells have a several-fold higher capacity to repair O6-methylguanine in DNA than do rat tissues and that the repair process occurs via a mechanism similar to that shown previously in other mammalian cells and Escherichia coli.


Knowledge, attitudes, and practices of violence in hospitals: the case of users of the reception and emergency service of the Ebolowa Regional Hospital.
The phenomena of incivility and violence are increasingly recurrent within health facilities in Cameroon. This study examines the knowledge, attitudes, and practices of violence by users in the reception and emergency departments of the Ebolowa Regional Hospital (ERH). This was a qualitative study of a non-random sample of users encountered in the reception and emergency department at the ERH in southern Cameroon. The principle of saturation was used to determine the sample size. An interview guide was used to collect the data. Demographic data were analyzed by EPI Info 7 and qualitative data by thematic analysis. Acts of violence in hospitals are perceived as the use of intense and brutal force that affects the physical and/or moral integrity of others. The forms of violence cited include physical, moral, verbal, and psychological violence. The most frequently cited reasons for the violence were: negligence, the insolence of the nurse, abandonment of the patient without care or information, care not explained and not mentioned in the care booklet, lack of speed in care, insufficient communication about the illness of a relative and ineffective care despite the patient's fatigue. According to the participants, the circumstances that could lead individuals to do violence to nursing staff on duty include theft of medicines, contempt, rudeness, negligence in care, late care, abandonment of patients and poor hospital hygiene, refusal to answer questions, deception or professional incompetence, lack of welcome, attempts to extort or overcharge for prescriptions, and swindling and adultery. The consequences of violence mentioned in the responses mainly included: fighting, injuries, as well as staff reluctance, low hospital attendance, self-medication, and loss of life. Most respondents did not know or had no idea about legal sanctions after an act of violence, but one response mentioned the existence of sanctions such as police custody and blame. Violence in hospitals is a major problem that can have serious consequences for patients, health care staff, and the health care system. The reasons given for the violence highlight the importance of clear and effective communication between patients and healthcare staff, as well as prompt and quality medical care.


On indexing in the Web of Science and predicting journal impact factor.
We discuss what document types account for the calculation of the journal impact factor (JIF) as published in the Journal Citation Reports (JCR). Based on a brief review of articles discussing how to predict JIFs and taking data differences between the Web of Science (WoS) and the JCR into account, we make our own predictions. Using data by cited-reference searching for Thomson Scientific's WoS, we predict 2007 impact factors (IFs) for several journals, such as Nature, Science, Learned Publishing and some Library and Information Sciences journals. Based on our colleagues' experiences we expect our predictions to be lower bounds for the official journal impact factors. We explain why it is useful to derive one's own journal impact factor.


CLINICAL outcomes and loss to follow-up among people living with HIV participating in the NAMWEZA intervention in Dar es Salaam, Tanzania: a prospective cohort study.
Psychosocial factors have been linked with loss to follow-up (LTFU) and clinical outcomes among people living with HIV (PLH), however little is known about the effect of psychosocial support on LTFU among PLH in treatment and care. The purpose of this study was to explore the effect of NAMWEZA ("Yes, together we can") friends' psychosocial support intervention on clinical outcomes and LTFU among PLH. NAMWEZA is based on a novel program using "appreciative inquiry", positive psychology approaches to empower, promote positive attitudes and foster hope. PLH participating in the NAMWEZA intervention in HIV care clinics in Dar es Salaam Tanzania were compared with non-exposed PLH obtained from facilities that routinely collect clinical information and both followed longitudinally for 24 months. Baseline sociodemographic, clinical measures (CD4 cell count, hemoglobin (HGB), weight), and LTFU measures were collected. Chi square, Fisher's exact tests, and t-tests were used to compare the frequencies for categorical variables and the means of continuous variables from the intervention and the comparison groups to identify variables that were significantly different across the two groups. Random effects models were performed to examine the bivariate associations between the intervention status and clinical outcomes. At the end of 24 months of follow-up mean CD4 count and HGB levels increased significantly in both intervention and comparison groups (p = 0.009 and p < 0.0001, respectively). Weight increased significantly only in the intervention group (p = 0.003). Cumulative LTFU was three times higher in the comparison compared to the intervention (p < 0.001) group. Having a low CD4 count, extremes of weight, low HGB, younger age, and male gender were significantly associated with LTFU among the unexposed group, while being on ART for duration of 12 months or more was protective against LTFU in those intervened. Among PLH on ART, exposed or not exposed to NAMWEZA intervention, clinical care outcomes improved over time. LTFU was much higher in the comparison group with factors commonly known to predict LTFU only apparent in the comparison group. NAMWEZA could be a promising peer-facilitated model to reduce LTFU among PLH in care that can be integrated in ART services; however, more research is needed to evaluate its longer term effects.


The Role of Parietal Epithelial Cells in the Pathogenesis of Podocytopathy.
Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role in various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and lupus podocytopathy. In this review, we attempt to dissect the diverse role of PECs in the pathogenesis of podocytopathy based on currently available information.


Lactic acid chemical peels as a new therapeutic modality in melasma in comparison to Jessner's solution chemical peels.
Many chemicals have been used in the skin peeling for melasma such as Jessner's solution and glycolic acid. Lactic acid is an alpha-hydroxy acid that has not been used before in chemical peeling of melasma. The purpose of the present work was to evaluate the efficacy and safety of lactic acid in chemical peeling of melasma in comparison to Jessner's solution chemical peels. This study was conducted at the Department of Dermatology and Venereology, Baghdad Hospital, in the period between April 2001 and August 2002. Thirty patients with melasma were included in this study. They were mostly of skin type IV according to Fitzpatrick's classification, 26 (86.67%) were women, and 4 (13.33%) were men, with an age range from 18 and 50 years (mean+/-SD, 33.53+/-6.96 years). Full clinical examination was done to all patients including Wood's light. The severity of melasma was assessed by MASI (Melasma Area Severity Index). Pure lactic acid full strength (92%, pH 3.5) was used as a new peeling agent on the left side of the face while Jessner's solution was applied to the right side of the face. The chemical peeling sessions were done every 3 weeks until the desired response was achieved. Follow-up was carried out for 6 months after the last session. Six patients were defaulted from the study after the first session for unknown reasons. Twenty-four patients completed the study. Twenty (83.33%) were women and four were men (16.67%). Wood's light examination showed increased contrast in all patients of mostly epidermal melasma. The number of sessions ranged from 2 to 5. All patients showed marked improvement as calculated by MASI score before and after treatment, and the response was highly statistically significant. No side effect was recorded in all treated patients. Lactic acid was found to be an effective and safe peeling agent in the treatment of melasma, and it was as effective as Jessner's solution.


Beyond the metaphor of the pendulum: electroconvulsive therapy, psychoanalysis, and the styles of American psychiatry.
It is common to represent the history of American psychiatry by comparing it to a pendulum. In this metaphorical rendering, psychiatry has swung back and forth between extremes of emphasis on psyche (life events and inner conflict ruling etiological thinking, talk therapy dominating treatment) and soma (biochemical sources dominating etiological thinking, somatic treatments dominating treatment). This article argues that, while this metaphor is suited to capturing certain aspects of American psychiatric history, it distorts others by, for example, exaggerating the extent of dogmatism on either side and obscuring continuities in psychiatry's history. The article looks specifically at the reception by psychoanalysts to the introduction of electroconvulsive therapy. It shows that psychoanalytic views of ECT were diverse and more receptive to ECT than the pendulum metaphor might lead us to believe.


Toward Fine-Grained Talking Face Generation.
Talking face generation is the process of synthesizing a lip-synchronized video when given a reference portrait and an audio clip. However, generating a fine-grained talking video is nontrivial due to several challenges: 1) capturing vivid facial expressions, such as muscle movements; 2) ensuring smooth transitions between consecutive frames; and 3) preserving the details of the reference portrait. Existing efforts have only focused on modeling rigid lip movements, resulting in low-fidelity videos with jerky facial muscle deformations. To address these challenges, we propose a novel Fine-gRained mOtioN moDel (FROND), consisting of three components. In the first component, we adopt a two-stream encoder to capture local facial movement keypoints and embed their overall motion context as the global code. In the second component, we design a motion estimation module to predict audio-driven movements. This enables the learning of local key point motion in the continuous trajectory space to achieve smooth temporal facial movements. Additionally, the local and global motions are fused to estimate a continuous dense motion field, resulting in spatially smooth movements. In the third component, we devise a novel implicit image decoder based on an implicit neural network. This decoder recovers high-frequency information from the input image, resulting in a high-fidelity talking face. In summary, the FROND refines the motion trajectories of facial keypoints into a continuous dense motion field, which is followed by a decoder that fully exploits the inherent smoothness of the motion. We conduct quantitative and qualitative model evaluations on benchmark datasets. The experimental results show that our proposed FROND significantly outperforms several state-of-the-art baselines.


Coulomb drag by small momentum transfer between quantum wires.
We demonstrate that in a wide range of temperatures Coulomb drag between two weakly coupled quantum wires is dominated by processes with a small interwire momentum transfer. Such processes, not accounted for in the conventional Luttinger liquid theory, cause drag only because the electron dispersion relation is not linear. The corresponding contribution to the drag resistance scales with temperature as T2 if the wires are identical, and as T5 if the wires are different.


Poly[μ-aqua-aqua-(μ-benzene-1,2,4,5-tetra-carboxyl-ato)gadolinate(III)potassium(I)].
In the title compound, [KGd(C(10)H(2)O(8))(H(2)O)(2)](n), the Gd(3+) ion is nine-coordinated by eight O atoms from five individual benzene-1,2,4,5-tetra-carboxyl-ate (btec) ligands and one water mol-ecule, and the K(+) ion is eight-coordinated by six O atoms from five individual btec ligands and two water mol-ecules. In the crystal, the btec half-mol-ecules are completed by crystallographic inversion symmetry. GdO(9) and KO(8) polyhedra are connected, forming layers in the ab plane, which are further inter-connected by μ(8)- or μ(12)-bridging btec ligands, forming a three-dimensional structure.


Ultrastructural insights into the replication cycle of salmon pancreas disease virus (SPDV) using salmon cardiac primary cultures (SCPCs).
Salmon pancreas disease virus (SPDV) has been affecting the salmon farming industry for over 30 years, but despite the substantial amount of studies, there are still a number of recognized knowledge gaps, for example in the transmission of the virus. In this work, an ultrastructural morphological approach was used to describe observations after infection by SPDV of an ex vivo cardiac model generated from Atlantic salmon embryos. The observations in this study and those available on previous ultrastructural work on SPDV are compared and contrasted with the current knowledge on terrestrial mammalian and insect alphaviral replication cycles, which is deeper than that of SPDV both morphologically and mechanistically. Despite their limitations, morphological descriptions remain an excellent way to generate novel hypotheses, and this has been the aim of this work. This study has used a target host, ex vivo model and resulted in some previously undescribed features, including filopodial membrane projections, cytoplasmic stress granules or putative intracytoplasmic budding. The latter suggests a new hypothesis that warrants further mechanistic research: SPDV in salmon may have retained the capacity for non-cytolytic (persistent) infections by intracellular budding, similar to that noted in arthropod vectors of other alphaviruses. In the notable absence of a known intermediate host for SPDV, the presence of this pattern suggests that both cytopathic and persistent infections may coexist in the same host. It is our hope that the ultrastructural comparison presented here stimulates new research that brings the knowledge on SPDV replication cycle up to a similar level to that of terrestrial alphaviruses.


Pregnant Women's Knowledge and Beliefs about the Safety and Outcomes of Delivery at Various Gestational Ages.
Objectives Despite the morbidity associated with late preterm and early-term births, there is limited data on pregnant women's perception of neonatal risk based on gestational age (GA). Therefore, our objective was to determine pregnant women's perception of neonatal risks at varying GAs. Method Through an anonymous 24-question survey, pregnant women were asked to designate the GA at delivery that is desirable, safe, and defined as full term. Responses were compared based on race, history of preterm birth, and medical comorbidities. Results Among the 233 survey respondents, the majority (62.9%) desired delivery at 36 to 39 weeks' gestation. Black women were more likely to desire delivery at 28 to 35 weeks compared with other racial/ethnic groups ( p = 0.005). Women with a history of preterm birth or medical complications were less likely to desire delivery at 40 weeks. More than 40% of respondents thought delivery at 8 months of pregnancy was safe and 40.3% responded that 37 weeks' gestation is considered term. Conclusion Misconceptions surrounding the definition of a term pregnancy are pervasive and vary by race, obstetric history, and medical comorbidities. Our findings highlight the need for patient education about appropriate gestational length, especially in minority and high-risk populations.


Signal Detection of Potentially Drug-Induced Liver Injury in Children Using Electronic Health Records.
Background: This study proposes a quantitative 2-stage procedure to detect potential drug-induced liver injury (DILI) signals in pediatric inpatients using an data warehouse of electronic health records (EHRs). Methods: Eight years of medical data from a constructed database were used. A two-stage procedure was adopted: (i) stage 1: the drugs suspected of inducing DILI were selected and (ii) stage 2: the associations between the drugs and DILI were identified in a retrospective cohort study. Results: 1,196 drugs were filtered initially and 12 drugs were further potentially identified as suspect drugs inducing DILI. Eleven drugs (fluconazole, omeprazole, sulfamethoxazole, vancomycin, granulocyte colony-stimulating factor (G-CSF), acetaminophen, nifedipine, fusidine, oseltamivir, nystatin and meropenem) were showed to be associated with DILI. Of these, two drugs, nystatin [odds ratio[OR]=1.39, 95%CI:1.10-1.75] and G-CSF (OR = 1.91, 95%CI:1.55-2.35), were found to be new potential signals in adults and children. Three drugs [nifedipine [OR = 1.77, 95%CI:1.26-2.46], fusidine [OR = 1.43, 95%CI:1.08-1.86], and oseltamivi r [OR = 1.64, 95%CI:1.23-2.18]] were demonstrated to be new signals in pediatrics. The other drug-DILI associations had been confirmed in previous studies. Conclusions: A quantitative algorithm to detect potential signals of DILI has been described. Our work promotes the application of EHR data in pharmacovigilance and provides candidate drugs for further causality assessment studies.


Role of cell surface O-linked oligosaccharides in adhesion of HL60 cells to fibronectin: regulation of integrin-dependent cell adhesion by O-linked oligosaccharide elongation.
The adhesion of the myelogenous leukemia cell line, HL60, to fibronectin and its fragments, heparin binding fragment (40 kDa) and cell attachment fragment (120 kDa), was enhanced by culturing with benzyl-alpha-GalNAc (BZ alpha GalNAc). Enhancement of cell adhesion to fibronectin was also observed on treatment of HL60 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA). However, an additive effect of BZ alpha GalNAc and TPA treatments was not observed. The expression of VLA4 and VLA5 did not change during treatment with BZ alpha GalNAc or TPA. Cell adhesion to fibronectin before and after treatment with BZ alpha GalNAc or TPA was inhibited by anti-VLA4 and anti-VLA5 monoclonal antibodies. Staining of the cells with Helix pomatia lectin demonstrated that culturing of the cells with BZ alpha GalNAc blocked elongation of O-linked oligosaccharides on the cell surface and led to accumulation of GalNAc-O-Ser/Thr. Labeling of cell surface carbohydrates with [3H]-glucosamine followed by treatment with TPA revealed that O-glycosylated glycoproteins including CD43 were released from the cell surface during this treatment. These findings indicate that integrin-dependent cell adhesion, particularly VLA4- or VLA5-dependent cell adhesion, of HL60 cells is prevented with the extension of O-linked oligosaccharides and recovers with the disappearance of O-linked oligosaccharides from the cell surface.


Nutrition practices in hospitalized adults receiving noninvasive forms of respiratory support: A scoping review.
The use of noninvasive respiratory support is increasing, with noninvasive ventilation (NIV) and high-flow nasal cannula providing unique barriers to nutrition support. Limited data related to nutrition management for these patients in the intensive care unit (ICU) exist; however, the literature in non-critically ill patients is not well described, and its improvement may help to inform practice within the ICU. Therefore, a scoping review was conducted of MEDLINE, EmCare, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases on August 18, 2022, to identify original publications that included adult patients receiving noninvasive respiratory support in a hospital setting with data related to nutrition management. Data were extracted on study design, population, details of respiratory support, and concepts relating to nutrition management (grouped into nutrition screening, assessment, delivery route, intake, and anthropometry). Eleven studies were included, most of which were small (<100 patients), single-center, observational trials in patients receiving NIV only. Five studies reported results related to route of nutrition and nutrition assessment, two on anthropometry, and one each on quantifying intake and nutrition screening; some studies reported multiple parameters. There was a lack of consensus regarding the ideal method for nutrition assessment and route of nutrition. Oral nutrition was the route most frequently reported, yet calorie and protein delivery via this route were inadequate, and barriers to intake included poor appetite, fatigue, and patient cognition. Future research should address barriers pertinent to this population and the impact of nutrition on outcomes.


Any link of gout disease control among hypertensive patients and onset of end-stage renal disease? Results from a population-based study.
To determine the impact of allopurinol non-adherence as a proxy for uncontrolled disease on primary prevention of end-stage renal disease (ESRD). A cohort of 2752 patients with gout diagnosis was reconstructed using the Québec Régie de l'assurance maladie du Québec and MedEcho administrative databases. Eligible patients were new users of allopurinol, aged 45-85, with a diagnosis of hypertension, and treated with an antihypertensive drug between 1997 and 2007. Major risk factor for ESRD onset was chronic kidney disease at stages 1 to 3 [rate ratio (RR) = 8.00; 95% confidence interval (CI): 3.16-22.3 and the severity of hypertension (≥ 3 vs < 3 antihypertensives)] was a trending risk factor as a crude estimate (RR = 1.94; 95%CI: 0.68-5.51). Of 341 patients, cases (n = 22) and controls (n = 319), high adherence level (≥ 80%) to allopurinol therapy, compared with lower adherence level (< 80%), was associated with a lower rate of ESRD onset (RR = 0.35; 95%CI: 0.13-0.91). Gout control seem to be associated with a significant decreased risk of ESRD onset in hypertensive populations, further research should be conducted confirming this potential associated risk.


Joint effect of triclosan and copper nanoparticles on wastewater biological nutrient removal.
Triclosan (TCS) is widely used in household and personal care products, and its release into wastewater might have impact on wastewater biological treatment for its antibacterial property. Besides, emerging pollutant such as copper nanoparticles (CuNPs) will also release from nanoparticle-containing products, showing a joint effect with TCS on biological nutrient removal. The TCS of 1 and 10 mg/L inhibited the nitrosification and nitrification stage, and the first step of denitrification was suppressed as well, causing a decline in final TN removal efficiency. Additionally, the phosphorus uptake was inhibited seriously, leading to a remarkable decrease in phosphorus removal efficiency. When they were co-existed, the TCS concentration decreased due to the absorption by CuNPs, and the released Cu2+ from CuNPs increased. Further investigation revealed that when 5 mg/L CuNPs and 1 mg/L TCS were immediately added to the activated sludge, the final joint toxicity was similar to the individual effect of 1 mg/L TCS, while 10 mg/L CuNPs contributed to the final stronger toxicity. When TCS was sufficiently reacted with CuNPs in wastewater, their final toxicity to activated sludge was enhanced because the extent of toxicity relief caused by decrease in TCS concentration was less than the degree of deteriorating effect due to the promotion of Cu2+ release from CuNPs.


Coping with acne vulgaris. Evaluation of the chronic skin disorder questionnaire in patients with acne.
The present study investigated how patients with acne vulgaris cope with their disease. By means of questionnaires, relations and interactions between acne and psyche were evaluated. In addition to the evaluation of a specific questionnaire for patients with chronic skin disorders (CSD), assessing psychosocial impairment by the disease, depression and social anxiety were investigated in patients with acne. The study included 50 patients with acne. The CSD showed significant correlations with Beck's depression inventory, the interaction-anxiety questionnaire and the health locus of control scale. The CSD revealed significant differences compared to a control group of 33 patients with healthy skin. Furthermore the patients' attitudes towards triggering factors and disease-related limitations in everyday life are presented. The results of the study demonstrate that patients with acne suffer from emotional distress and psychosocial problems caused by their disease; however, impairment is not correlated with the objective severity of acne.


Modulation of the unfolded protein response is the core of microRNA-122-involved sensitivity to chemotherapy in hepatocellular carcinoma.
The loss of microRNA-122 (miR-122) expression correlates to many characteristic properties of hepatocellular carcinoma (HCC) cells, including clonogenic survival, anchorage-independent growth, migration, invasion, epithelial-mesenchymal transition, and tumorigenesis. However, all of these findings do not sufficiently explain the oncogenic potential of miR-122. In the current study, we used two-dimensional differential in-gel electrophoresis to measure changes in the expression of thousands of proteins in response to the inhibition of miR-122 in human hepatoma cells. Several proteins that were upregulated on miR-122 inhibition were involved in the unfolded protein response (UPR) pathway. The overexpression of miR-122 resulted in the repression of UPR pathway activation. Therefore, miR-122 may act as an inhibitor of the chaperone gene expression and negatively regulate the UPR pathway in HCC. We further showed that the miR-122 inhibitor enhanced the stability of the 26S proteasome non-ATPase regulatory subunit 10 (PSMD10) through the up-regulation of its target gene cyclin-dependent kinase 4 (CDK4). This process may activate the UPR pathway to prevent chemotherapy-mediated tumor cell apoptosis. The current study suggests that miR-122 negatively regulates the UPR through the CDK4-PSMD10 pathway. The down-regulation of miR-122 activated the CDK4-PSMD10-UPR pathway to decrease tumor cell anticancer drug-mediated apoptosis. We identified a new HCC therapeutic target and proclaimed the potential risk of the therapeutic use of miR-122 silencing.


[Magnetic resonance imaging of dilated cardiomyopathy].
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy with a prevalence of 1 out of 2,500 in adults. Due to mild clinical symptoms in the early phase of the disease, the true prevalence is probably even much higher. Patients present with variable clinical symptoms ranging from mild systolic impairment of left ventricular function to congestive heart failure. Even sudden cardiac death may be the first clinical symptom of DCM. The severity of the disease is defined by the degree of impairment of global left ventricular function. Arrhythmias, such as ventricular or supraventricular tachycardia, atrioventricular (AV) block, ventricular extrasystole and atrial fibrillation are common cardiac manifestations of DCM. Magnetic resonance imaging (MRI) plays an important role in the exact quantification of functional impairment of both ventricles and in the evaluation of regional wall motion abnormalities. With its excellent ability for the assessment of myocardial structure, it is becoming increasingly more important for risk stratification and therapy guidance.


Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study.
This case-control study evaluated reproductive and other factors in relation to epithelial ovarian cancer (EOC) risk. Between 1993 and 1995, the authors recruited 655 EOC cases and 3,899 population controls aged 50-74 years who were born in and residents of Sweden. Data were collected through mailed questionnaires. Odds ratios were estimated by unconditional logistic regression. Parity reduced EOC risk (odds ratio = 0.61, 95% confidence interval (CI): 0.46, 0.81) for uniparous compared with nulliparous women. The risk of EOC decreased with incomplete pregnancies, early menopausal age, late age at first birth, and unilateral oophorectomy; increased with family history of ovarian cancer; and was not associated with menarcheal age, lactation, irregular menses, and menopausal symptoms. Histology-specific odds ratios of EOC for ever compared with never users of oral contraceptives were: serous, 0.56 (95% CI: 0.42, 0.74); mucinous, 1.96 (95% CI: 1.04, 3.68); endometrioid, 0.71 (95% CI: 0.49, 1.03); clear cell, 0.66 (95% CI: 0.31, 1.43); and all EOCs, 0.73 (95% CI: 0.59, 0.90). Prolonged oral contraceptive use reduced EOC risk, with persistent protection up to 25 years after the last use. Ever use of hormone replacement therapy increased EOC risk (odds ratio = 1.41, 95% CI: 1.15, 1.72). Among etiologic hypotheses, the retrograde transportation hypothesis accommodates most epidemiologic findings concerning EOC risk.


Chemical conjugate TMV-peptide bivalent fusion vaccines improve cellular immunity and tumor protection.
Chemical conjugation of CTL peptides to tobacco mosaic virus (TMV) has shown promise as a molecular adjuvant scaffold for augmentation of cellular immune responses to peptide vaccines. This study demonstrates the ease of generating complex multipeptide vaccine formulations using chemical conjugation to TMV for improved vaccine efficacy. We have tested a model foreign antigen target-the chicken ovalbumin-derived CTL peptide (Ova peptide), as well as mouse melanoma-associated CTL epitopes p15e and tyrosinase-related protein 2 (Trp2) peptides that are self-antigen targets. Ova peptide fusions to TMV, as bivalent formulations with peptides encoding additional T-help or cellular uptake via the integrin-receptor binding RGD peptide, showed improved vaccine potency evidenced by significantly enhanced numbers of antigen-reactive T cells measured by in vitro IFNgamma cellular analysis. We measured the biologically relevant outcome of vaccination in protection of mice from EG.7-Ova tumor challenge, which was achieved with only two doses of vaccine ( approximately 600 ng peptide) given without adjuvant. The p15e peptide alone or Trp2 peptide alone, or as a bivalent formulation with T-help or RGD uptake epitopes, was unable to stimulate effective tumor protection. However, a vaccine with both CTL peptides fused together onto TMV generated significantly improved survival. Interestingly, different bivalent vaccine formulations were required to improve vaccine efficacy for Ova or melanoma tumor model systems.


Classification of Isolates from the Pseudomonas fluorescens Complex into Phylogenomic Groups Based in Group-Specific Markers.
The Pseudomonas fluorescens complex of species includes plant-associated bacteria with potential biotechnological applications in agriculture and environmental protection. Many of these bacteria can promote plant growth by different means, including modification of plant hormonal balance and biocontrol. The P. fluorescens group is currently divided into eight major subgroups in which these properties and many other ecophysiological traits are phylogenetically distributed. Therefore, a rapid phylogroup assignment for a particular isolate could be useful to simplify the screening of putative inoculants. By using comparative genomics on 71 P. fluorescens genomes, we have identified nine markers which allow classification of any isolate into these eight subgroups, by a presence/absence PCR test. Nine primer pairs were developed for the amplification of these markers. The specificity and sensitivity of these primer pairs were assessed on 28 field isolates, environmental samples from soil and rhizosphere and tested by in silico PCR on 421 genomes. Phylogenomic analysis validated the results: the PCR-based system for classification of P. fluorescens isolates has a 98.34% of accuracy and it could be used as a rapid and simple assay to evaluate the potential of any P. fluorescens complex strain.


[Current pharmacotherapy of epilepsy in adults].
The availability of new antiepileptic drugs (AEDs) has expanded the spectrum of medical treatment options in epilepsy. However, the development of ten new compounds (vigabatrin, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin) has not changed the basic principles of epilepsy treatment. The choice of an AED depends upon seizure type or seizure syndrome, efficacy, safety, tolerability, patient age and gender, concomitant medication, and comorbid conditions. In general, most of the newer AEDs are not necessarily more effective but usually better tolerated than the traditional agents mainly because of their favorable pharmacokinetic profiles and fewer drug interactions. Because treatment options have been widened with the introduction of these new compounds, drug therapy can now be tailored to the requirements of the individual patient. Nevertheless, significant safety and efficacy issues continue to exist and there is a strong need for the development of even better agents. This clinical review focuses on current aspects of drug therapy in epilepsy.


Oral glucose tolerance test should be performed after stroke and transient ischemic attack.
Diabetes mellitus predicts an increased risk of stroke, and acute hyperglycemia during acute stroke predicts the presence of undiagnosed diabetes mellitus. Based on recent investigations, 28% of previously nondiabetic stroke or transient ischemic attack patients have undetected diabetes mellitus, and 29% have impaired glucose tolerance, while only 43% have normal glycemic control. Oral glucose tolerance test is a far more sensitive and reliable test of diabetes mellitus than fasting blood glucose or HbA1c, and is recommended in the World Health Organization criteria for diagnosing diabetes mellitus and impaired glucose tolerance. Secondary prevention of stroke is different in patients with diabetes mellitus and the detection of impaired glucose tolerance would ring alarm bells of impending diabetes mellitus and promote lifestyle changes. As screening with inexpensive oral glucose tolerance test would have a hit rate of one in three patients in revealing undetected diabetes mellitus and another one in three in revealing impaired glucose tolerance, it should be implemented in guidelines as an inexpensive test for monitoring stroke and transient ischemic attack patients.


In vitro characterization of native mammalian smooth-muscle protein synaptopodin 2.
An analysis of the primary structure of the actin-binding protein fesselin revealed it to be the avian homologue of mammalian synaptopodin 2 [Schroeter, Beall, Heid, and Chalovich (2008) Biochem. Biophys. Res. Commun. 371, 582-586]. We isolated two synaptopodin 2 isoforms from rabbit stomach that corresponded to known types of human synaptopodin 2. The purification scheme used was that developed for avian fesselin. These synaptopodin 2 forms shared several key functions with fesselin. Both avian fesselin and mammalian synaptopodin 2 bound to Ca(2+)-calmodulin, alpha-actinin and smooth-muscle myosin. In addition, both proteins stimulated the polymerization of actin in a Ca(2+)-calmodulin-dependent manner. Synaptopodin 2 has never before been shown to polymerize actin in the absence of alpha-actinin, to polymerize actin in a Ca(2+)-calmodulin-dependent manner, or to bind to Ca(2+)-calmodulin or myosin. These properties are consistent with the proposed function of synaptopodin 2 in organizing the cytoskeleton.


Prevalence and correlates of child maltreatment among mothers in the Kurdistan province, Western Iran.
Parental child maltreatment is a serious public health issue worldwide. As mothers take on a significant proportion of parenting duties in two-parent families, knowledge of maternal risk factors for child maltreatment is essential. In this cross-sectional study, 135 mothers with their last child under 18 years in Kurdistan province were enrolled. A validated Persian version of the ISPCAN Child Abuse Screening Tool-Parent version, Beck Anxiety Inventory, and Beck Depression Inventory were administered. The prevalence of severe and moderate physical punishment was 78.5% and 71.9%, respectively. Psychological punishment was reported by 99.3% of respondents, and 48.9% reported neglect. A relationship was found between child physical and emotional abuse and low maternal education (p < 0.01), domestic violence (p = 0.02), maternal exposure to maltreatment during childhood (p = 0.03), maternal depression (p < 0.01), and maternal anxiety (p < 0.01). A relationship was also found between child neglect and residence in rural areas (p < 0.01), domestic violence, and low maternal education (p = 0.02). Maternal child maltreatment in Iran is increased in mothers with psychological disorders and those with certain demographic characteristics. Clinicians should be alert to these potential risk factors.


Two cases of hyperparathyroidism initially diagnosed as aneurysmal cyst.
The authors present two cases of primary hyper-parathyroidism initially diagnosed as aneurysmal cyst. The aspects of differential diagnosis are discussed, and the importance of evaluating all of the diagnostic elements in order to formulate a correct diagnosis is emphasized.


A cross-sectional survey of pain in palliative care in Portugal.
The purpose of this work is to study the prevalence, intensity, and treatment of pain in Portuguese palliative care teams. Twenty-one palliative care teams were invited to participate in a cross-sectional survey. Ten of these accepted and were included in the study. Data of all patients observed on the 18th week of 2011 were collected. The data collected concerning pain were: demographic data, pain intensity, drugs prescribed, and invasive techniques. The intensity of pain was rated using a five-point verbal rating scale from none to maximum. The Pain Management Index (PMI) was used to calculate the adequacy of the analgesia. A total of 164 patients were included in this study. One hundred fifty-one (92 %) had cancer. The median age was 71 years (16 to 95). Eighty-four (51 %) were females. Pain was directly assessed in 136 (83 %) of the patients, whereas 27 patients could not report pain because of cognitive failure. Of those directly assessed, 77 (57 %) had pain when they were assessed: 42 (55 %) mild, 25 (32 %) moderate, 9 (12 %) severe, and 1 (1 %) maximum. Non-opioid analgesics were used: paracetamol in 61 (37 %) and NSAID in 20 (12 %). Tramadol was the only opioid for mild to moderate pain used in 25 (15 %) patients. The opioids most used for moderate to intense pain were: morphine 74 (45 %), transdermal (TD) fentanyl 32 (20 %), and buprenorphine TD 28 (17 %). The adjuvants most used were: corticosteroids 38 (23 %), gabapentin 37 (23 %), and amitriptyline 15 (9 %). Only five (4 %) patients had a negative PMI, meaning an inadequate analgesia. The general prevalence of pain is similar to that reported by other. The prevalence of moderate to severe pain is also similar to that reported in other studies, although severe pain is somewhat lower than indicated in most reports. According to the PMI, pain control was acceptable to good.


Respiratory epithelial cyst of the cerebellopontine angle.
A case of a 29-year-old woman with a cystic lesion in the right cerebellopontine angle, who had three bouts of chemical meningitis in 1 year, is reported. The lesion proved to be a delicate, thin-walled cyst, in part with a squamous lining and in part with a respiratory epithelial (tall, columnar, ciliated, mucus-secreting) lining. Various possibilities to explain this unusual epithelium are explored.


Milk folate secretion is not impaired during iron deficiency in humans.
The purpose of this study was to examine whether maternal iron and/or folate status influences human milk folate secretion and is responsible for growth faltering of Otomi infants in Capulhuac, Mexico. Breast-feeding mothers (n = 71) were randomized at 22 +/- 13 d (baseline) postpartum to receive a daily multivitamin supplement containing folic acid (400 microg) with and without iron (18 mg). Mothers provided blood and milk samples at baseline, and at 82 +/- 15 and 138 +/- 18 d postpartum. Iron supplementation significantly improved hematocrit and transferrin receptor concentrations but had no influence on maternal folate status or milk folate or iron concentrations. Forty-three percent of mothers (29/68) had low blood folate concentrations at baseline, whereas only 6% (4/66) had low blood folate concentrations at approximately 138 d postpartum. Milk folate concentrations did not differ between Fe-deficient and Fe-sufficient women and provided adequate levels of dietary folate by approximately 82 d postpartum. While milk iron concentrations were unrelated to maternal iron status, they decreased during lactation, and, by approximately 138 d, they provided only 55% of the current recommendation. In conclusion, milk folate concentrations appear to be well preserved during maternal iron deficiency; hence, faltering growth among infants in Capulhuac, Mexico is unlikely the result of reduced milk folate concentration secondary to maternal Fe deficiency. However, milk Fe concentrations showed a temporal decline. Whether the disjuncture between recommended and actual Fe intakes among infants born with low Fe reserves and weaned to foods low in bioavailable Fe has functional consequences is worthy of further investigation.


Forestomach lesions induced by butylated hydroxyanisole and ethylene dibromide: a scientific and regulatory perspective.
Selected pathology lesions from 9 studies, 5 with butylated hydroxyanisole (BHA) and 4 with ethylene dibromide (EDB) are reviewed and their relative importance in regulatory evaluation is discussed. When Fischer 344 (F344) rats were fed BHA at 0.5% and 2.0% of the diet for 2 years, an increased number of rats of both sexes had epithelial hyperplasia of the forestomach at both treatment levels, compared to controls. At the 2.0% level, an increased number of rats had forestomach papilloma or forestomach squamous cell carcinoma. In a second study, in which F344 rats were fed BHA at 1.0% and 2.0% of the diet for 2 years, increased numbers of rats in both treatment groups were reported to have hyperplasia or papilloma of the forestomach. At the 2.0% level, increased numbers of rats developed squamous cell carcinoma of the forestomach. More Syrian golden hamsters fed BHA at 1.0% and 2.0% of the diet for 2 years reportedly had hyperplasia, papilloma or squamous cell carcinoma of the forestomach than did nontreated animals. Ingestion of BHA at 0.5% and 1.0% of the diet by B6C3F1 mice for 2 years was reported to produce an increase of animals with hyperplasia or papilloma of the forestomach at both dosage levels, compared to nontreated mice. When beagle dogs were fed BHA at 1.0% and 1.3% of the diet for 180 days, no lesions/tumors of the distal esophagus or stomach were identified at gross necropsy or by light or electron microscopy. When EDB was administered by gavage to Osborne-Mendel rats and B6C3F1 mice under conditions of the National Toxicology Bioassay Program, more rats and mice, both male and female, developed squamous cell carcinoma of the forestomach than did nontreated groups. EDB administered via inhalation to F344 rats and B6C3F1 mice did not cause squamous cell carcinoma of the forestomach; however, other neoplasms occurred which were considered to be treatment-related. Information gleaned from the BHA and EDB studies with multiple animal species facilitated regulatory decision-making regarding the potential toxicity/carcinogenicity of these compounds to man.


FMR1 enhancer is regulated by cAMP through a cAMP-responsive element.
FMR1 (Fra X Mental Retardation 1), a gene of unknown function, is responsible for an important hereditary mental retardation, the fragile X syndrome. In this study, a 22-bp enhancer (methylation sensitive element, MSE) in the FMR1 promoter was defined by DNase I footprinting assay, and the binding of this element by nuclear factor was prevented by DNA CpG methylation. A cAMP-responsive element (CRE)-like sequence and a myc-binding sequence in MSE were identified. In the transfection assay, MSE demonstrated a strong, methylation-sensitive enhancer activity. MSE could be bound by recombinant CRE-binding protein (CREB), and its activity was stimulated by CREB in a co-transfection assay. In PC12 cells, forskolin elevated MSE activity several fold, and this induction was abolished in CRE mutants. The involvement of cAMP in the expression of FMR1 should be a clue to both the function of FMR1 and the pathogenesis of fragile X syndrome.


Assessing personality disorders using a systematic clinical interview: evaluation of an alternative to structured interviews.
The aim of this study was to assess interrater reliability and provide initial data bearing on the validity of a method of assessing personality disorders (PDs) that does not presume that patients can accurately self-report personality pathology. In a sample of 24 outpatients, two clinician-judges independently applied the Shedler-Westen Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 2000), a 200-item Q-sort procedure for assessing personality pathology, to data from the Clinical Diagnostic Interview (Westen, 2002), a systematic clinical interview that mirrors and standardizes methods used by experienced clinicians to diagnose personality. In 16 of the 24 cases, the treating clinician also independently described the patient using the SWAP-200 Q-sort, based on longitudinal knowledge of the patient over the course of treatment, blind to the interview data. Interrater reliability was uniformly high, with median correlations between interviewers at r > .80. Interviewer-treating clinician correlations were also high, with median convergent validity coefficients at r > .80. Diagnostic overlap (discriminant validity) was moderate for dimensional DSM-IV diagnoses, reflecting extensive comorbidity among disorders, but minimal for empirically derived diagnoses identified in prior research. Treating clinicians' dimensional PD diagnoses using this method also strongly predicted interviewer-rated measures of adaptive functioning. The findings provide preliminary support for the reliability and validity of an alternative to structured interviews for diagnosing personality pathology, and suggest that the way to improve validity of personality diagnosis may not be to minimize clinical inference but to quantify it using psychometric instruments.


Measuring impact: a cross-sectional multi-stage cluster survey to assess the attainment of durable solutions in post-tsunami Aceh, Indonesia.
There exists little agreement on the choice of indicators to be used to assess the impact of humanitarian assistance. The 2004 Indian Ocean tsunami led to significant mortality and displacement in Aceh Province, Indonesia, as well as a nearly unprecedented humanitarian response. Six years after the disaster we conducted an impact assessment of humanitarian services rendered in Aceh using a comprehensive set of rights-based indicators and sought to determine modifiable predictors of improved outcomes in disaster-affected households. A sample of 597 returned and non-returned households in Banda Aceh and Meulaboh was selected using a multistage stratified cluster survey design. We employed principle components analysis and the Framework on Durable Solutions for Internally Displaced Persons to develop a comprehensive and rights-based approach to humanitarian impact measurement using multivariate regression models. The attainment of durable solutions was equivalent in both returned households 100.1 [CI] 97.63-102.5) and households that integrated elsewhere (99.37 [CI] 95.43-103.3, P = 0.781). Standard of living as well as education and health facility satisfaction increased significantly whereas monthly income decreased after the tsunami, from 2585241 IDR ([CI] 2357202-2813279 IDR) to 2038963 ([CI] 1786627-2291298 IDR, P < 0.001). Shelter (P = 0.007) and legal assistance (P < 0.001) were both significantly associated with positive durable solutions outcomes, whereas prolonged displacement duration was significantly associated with poorer outcomes (P < 0.001). Livelihood assistance received after one year was associated with higher odds of increasing or maintaining pre-tsunami income levels (OR = 3.02, P = 0.008), whereas livelihood assistance received within one year was associated with lower odds of attaining pre-tsunami income (OR = 0.52, P = 0.010). We find that after adjusting for pre-tsunami conditions and tsunami-related damages, the impact of sectoral responses can be assessed. The duration of displacement was the strongest negative predictive factor for the attainment of durable solutions, suggesting that measures to reduce displacement time may be effective in mitigating the long-term effects of disaster on households. The durable solutions framework is a novel and effective impact measurement tool and can be used to identify factors amenable to intervention and inform future disaster recovery efforts.


Comparison of temporal artery thermometer to standard temperature measurements in pediatric intensive care unit patients.
To determine the accuracy of noninvasive infrared temporal artery thermometry compared with rectal, axillary, and pulmonary artery catheter measurements in pediatric intensive care patients, and to determine whether temporal artery temperatures are affected by circulatory shock or by vasopressor use. We hypothesized that temporal artery temperatures do not differ from axillary and rectal temperatures in critically ill children, but temporal artery accuracy is decreased by shock or vasopressor use. Observational study, unblinded. Pediatric intensive care unit of a quarternary referral children's hospital. Seventy-five temperature comparison pairs were obtained in 44 pediatric intensive care unit patients. Temperature measurements were made using a temporal artery thermometer with simultaneously obtained rectal, axillary, and, when available, pulmonary artery catheter measurements. Mean bias was calculated between comparison pairs using each temperature method. Bland-Altman analysis demonstrated wide variability between methods. No significant differences in mean bias were seen between method pairs for all temperatures, but bias was significantly less in pulmonary artery catheter-rectal pairs compared with other method pairs. In febrile (> 38 degrees C) patients, bias in rectal-temporal artery and rectal-axillary was significantly greater than in temporal artery-axillary pairs (p < .001). Mean bias in pulmonary artery catheter-rectal pairs was also significantly smaller than in other pairs for all patients (p = .008) and febrile patients (p = .049). Presence of shock or vasopressor use did not significantly increase bias in any comparison pair. Sensitivity and specificity of both temporal artery and axillary for diagnosing fever were similar and improved with fever definition at temperatures > 38.5 degrees C. Temporal artery and axillary temperature measurements showed variability to rectal temperatures but had marked variability in febrile children. Neither was sufficiently accurate to recommend replacing rectal or other invasive methods. As temporal artery and axillary provide similar accuracy, temporal artery thermometers may serve as a suitable alternative for patients in whom invasive thermometry is contraindicated.


Fully Automated Online Dynamic In-Tube Extraction for Continuous Sampling of Volatile Organic Compounds in Air.
Comprehensive and time-dependent information (e.g., chemical composition, concentration) of volatile organic compounds (VOCs) in atmospheric, indoor, and breath air is essential to understand the fundamental science of the atmosphere, air quality, and diseases diagnostic. Here, we introduced a fully automated online dynamic in-tube extraction (ITEX)-gas chromatography/mass spectrometry (GC/MS) method for continuous and quantitative monitoring of VOCs in air. In this approach, modified Cycle Composer software and a PAL autosampler controlled and operated the ITEX preconditioning, internal standard (ISTD) addition, air sampling, and ITEX desorption sequentially to enable full automation. Air flow passed through the ITEX with the help of an external pump, instead of plunger up-down strokes, to allow larger sampling volumes, exhaustive extraction, and consequently lower detection limits. Further, in order to evaluate the ITEX system stability and to develop the corresponding quantitative ITEX method, two laboratory-made permeation systems (for standard VOCs and ISTD) were constructed. The stability and suitability of the developed system was validated with a consecutive 19 day atmospheric air campaign under automation. By using an electrospun polyacrylonitrile nanofibers packed ITEX, selective extraction of some VOCs and durability of over 1500 extraction and desorption cycles were achieved. Especially, the latter step is critically important for on-site long-term application at remote regions. This ITEX method provided 2-3 magnitudes lower quantitation limits than the headspace dynamic ITEX method and other needle trap methods. Our results proved the excellence of the fully automated online dynamic ITEX-GC/MS system for tracking VOCs in the atmospheric air.


Higher free testosterone level is associated with faster visual processing and more flanker interference in older men.
The aim of this study was to investigate the relation between free testosterone (FT) level and basic cognitive functions in older men. Three cognitive computer tasks were aimed to measure visual-processing speed, ability to suppress inappropriate responses, and visuospatial cognition, respectively. The tasks employed were a visual backward masking task, the Eriksen flanker task, and a mental rotation task. Participants were 72 older men (mean age=67.2 years, range 57-79). The influence of FT, age, alcohol consumption, and education on task performances was examined by means of multiple linear regression analysis. FT level was positively associated with accuracy on the short intervals (33 and 50ms) of the backward masking task and negatively with response latency on congruent flanker-task trials. These results indicate faster visual-processing speed in older men with higher FT levels. FT level was positively associated with interference elicited by irrelevant incongruent flankers, which implies that older men with higher levels of free testosterone exert less inhibitory control. Consistent with previous research, higher FT levels were associated with faster 'same-different' responses for unrotated mental rotation stimuli, but not with the slopes of the response time rotation functions. Older age was associated with lower backward masking accuracy at 33ms and with lower overall mental rotation accuracy. Higher education level was associated with faster processing speed for congruent flankers and with higher overall mental rotation accuracy. Alcohol consumption did not affect the task performances. Our results suggest that higher FT levels in older men may promote sustained visual-processing speed and visuospatial ability, probably at the expense of some inhibitory functioning.


A Vascular Complications Risk (VASCOR) score for patients undergoing invasive cardiac procedures in the catheterization laboratory setting: A prospective cohort study.
Vascular complications are still common in the catheterization laboratory setting. However, no risk scores for their prediction have been described. With a view to bridging this gap, the present study sought to develop and validate a score for prediction of vascular complications associated with arterial access in patients undergoing interventional cardiology procedures. This prospective multicenter cohort study included adult patients who underwent cardiac catheterization via the femoral or radial route. The outcomes of interest were: access site hematoma; major and minor bleeding; and retroperitoneal hemorrhage, pseudoaneurysm, or arteriovenous fistula requiring surgical repair. Past medical history as well as pre-procedural, intra-procedural, and post-procedural variables were collected. Patients were randomly allocated to the derivation or validation cohorts at a 2:1 ratio. The following equation constituted the score: (>6F introducer sheath×4.0)+(percutaneous coronary intervention×2.5)+(history of vascular complication after prior interventional cardiology procedure×2.0)+(prior use of warfarin or phenprocoumon×2.0)+(female sex×1.5)+(age⩾60 years×1.5). The maximum score is 13.5 points. A score dichotomized at ⩾3 (best cutoff for balancing sensitivity and specificity) was moderately accurate (sensitivity=0.66 (95% confidence interval: 0.59-0.73); specificity=0.59 (95% confidence interval: 0.56-0.61)). Patients with a score ⩾3 were at increased risk of complications (odds ratio: 2.95; 95% confidence interval: 2.22-3.91). This study yielded a score that is capable of predicting vascular complications and easily applied in daily practice by providers working in the catheterization laboratory setting.


Case report: Type 2 diabetes mellitus with plantar malignant melanoma: Report of two cases.
Malignant melanoma is a highly malignant tumor that originates from melanocytes. It has a poor prognosis and rarely occurs on the foot. Diabetic foot ulcer is one of the most serious chronic complications of diabetes. This paper reports two cases of type 2 diabetes patients with malignant melanoma on the foot. Clinicians should improve their understanding of patients with diabetes with acral malignant melanoma. When diabetic foot ulcers occur repeatedly and continue not to heal, the clinical features of the cutaneous lesions are similar to malignant melanoma, and a pathological biopsy of the lesions should be performed promptly to obtain a clear diagnosis, avoid a missed diagnosis and improve the survival rate.


Prevalence and antibiotic resistance profile of mercury-resistant oral bacteria from children with and without mercury amalgam fillings.
Genes encoding resistance to mercury and to antibiotics are often carried on the same mobile genetic element and so it is possible that mercury-containing dental materials may select for bacteria resistant to mercury and to antibiotics. The main aim of this study was to determine whether the prevalence of Hg-resistant oral bacteria was greater in children with mercury amalgam fillings than in those without. A secondary aim was to determine whether the Hg-resistant isolates were also antibiotic resistant. Bacteria in dental plaque and saliva from 41 children with amalgam fillings and 42 children without such fillings were screened for mercury resistance by cultivation on a HgCl(2)-containing medium. Surviving organisms were identified and their susceptibility to mercury and to several antibiotics was determined. Seventy-eight per cent and 74% of children in the amalgam group and amalgam-free group, respectively, harboured Hg-resistant bacteria; this difference was not statistically significant. Nor was there any significant difference between the groups in terms of the proportions of Hg-resistant bacteria in the oral microflora of the children. Of Hg-resistant bacteria, 88% and 92% from the amalgam group and the amalgam-free group, respectively, were streptococci; 41% and 33% were resistant to at least one antibiotic, most frequently tetracycline. The results of this study show that there was no significant difference between children with amalgam fillings and those without such fillings with regard to the prevalence, or the proportion, of Hg-resistant bacteria in their oral microflora. The study also found that Hg-resistant bacteria were common in children regardless of whether or not they had amalgam fillings and that many of these organisms were also resistant to antibiotics.


Isolated cleft of the ala nasi: A report of seven cases.
Craniofacial clefts other than cleft lip & palate are reported to be 1.4 to 4.9 per 100,000 live births. Of these, clefts of nose are usually associated with other clefts. Isolated cleft of Ala is rare, 0.7% of all clefts reported by Monasterio. In an analysis of photographic records of 3,500 consecutive patients with craniofacial clefts including cleft lip & palate registered with us between 1985- 2012 which were accessed through our data base, 13 patients with nasal clefts were identified, seven out of which had Isolated cleft of the Ala. All were treated by a rotation flap of the Ala with good results with the longest follow up of 14Yrs. The authors have emphasised the rarity of the condition and presented a simple surgical procedure for correction. In the opinion of the authors this very simple procedure which can be performed by the junior surgeon gives a good long term result in the management of cleft Ala.


Amygdala reactivity predicts automatic negative evaluations for facial emotions.
The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. In the present study, the role of the amygdala in automatic, involuntary appraisal processes, which are believed to be a crucial component of emotion processing, was investigated in 23 healthy subjects. Amygdala activity was recorded in response to masked displays of angry, sad, and happy facial expressions using functional magnetic resonance imaging (fMRI). In a subsequent experiment, the subjects performed a masked affective priming task that characterizes automatic emotion processing by investigating the biasing effect of subliminally presented emotional faces on evaluative ratings to subsequently presented neutral stimuli. In the affective priming task, significant valence-congruent evaluation manipulation was observed. Subjects rated neutral targets more positively if they were primed by happy faces. Significant correlations were found between amygdala responses to masked negative facial expressions and negative evaluation shifts elicited by the corresponding emotion quality in the affective priming task. Spontaneous amygdala reactivity to facial emotions appears to be a determinant of automatic negative evaluative response tendencies. This finding might shed some light on how amygdala hyperresponsivity contributes to negative cognitive biases commonly observed in affective disorders.


Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits.
The aim of this study was to explore the effects of dabigatran and rivaroxaban on the activities of various coagulation factors. To achieve that, 60 rabbits were randomly divided into experimental groups that received different doses of dabigatran or rivaroxaban. The effects of dabigatran and rivaroxaban on the activities of FII, FV, FVIII, FX, and activated protein C (APC) were analyzed. In the dabigatran groups, activated partial thromboplastin time and thromboplastin time (TT) were prolonged after drug administration, and the activities of FII, FV, FVIII, and FX were inhibited as the drug concentration increased. Low doses of dabigatran inhibited APC activity. In the rivaroxaban groups, APTT and TT were not significantly prolonged after drug administration. In contrast, the high-dose rivaroxaban group exhibited prolonged PT, and the degree of inhibition of the activities of FII, FV, FVIII, and FX increased as the drug concentration increased. Rivaroxaban had no significant effect on APC activity regardless of dosage. As the drug concentration increased, both NOACs had more significant inhibitory effects on the activities of FII, FV, FVIII, and FX. Low concentrations of dabigatran generated an inhibitory effect on APC activity, while high concentrations of dabigatran had no significant effect. Rivaroxaban had no significant effect on APC activity.


Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in humans and rabbits.
Large doses of oral aspirin inhibit platelet aggregation and vascular synthesis of the antiaggregatory vasodilator prostaglandin I2 (PGI2) by irreversibly acetylating the cyclooxygenase enzyme. In order to determine if one can achieve selective inactivation of platelet cyclooxygenase using oral doses of aspirin, we studied human and rabbit platelet aggregation and rabbit aortic synthesis of PGI2 before and 3 hr after various doses of aspirin. In rabbits, lower doses of aspirin produced a major inhibition of platelet aggregation and a minor inhibition of PGI2 synthesis, while higher doses of aspirin inhibited both platelet aggregation and vascular PGI2 synthesis. In humans, we found that a dose equivalent to approximately 1/4 of one 300 mg aspirin tablet consistently produced a major inhibition of cyclooxygenase-dependent platelet aggregation in a pattern similar to the inhibition of rabbit platelet aggregation where the majority of rabbit PGI2 synthetic capacity was not inhibited. In another rabbit study, we found that it takes the vasculature over 24 hr to return to control PGI2 synthetic capacity following a single, high dose of oral aspirin. In conclusion, we speculate that approximately 1/4 of an aspirin tablet, which inhibits a major portion of cyclooxygenase-dependent human platelet aggregation, may not inhibit a major portion of vascular cyclooxygenase-dependent PGI2 synthesis and may be more efficacious as an antithrombotic agent in man than are higher doses of aspirin.


Reducing the number of rigid bronchoscopies performed in suspected foreign body aspiration cases via the use of chest computed tomography: is it safe? A literature review.
Foreign body aspiration is common and potentially life threatening. Although rigid bronchoscopy has the potential for serious complications, it is the 'gold standard' of diagnosis. It is used frequently in light of the inaccuracy of clinical examination and chest radiography. Computed tomography is proposed as a non-invasive alternative to rigid bronchoscopy. This study aimed to evaluate the accuracy and safety of computed tomography used in the diagnosis of suspected foreign body aspiration, and compare this with the current gold standard, in order to examine the possibility of using computed tomography to reduce the number of diagnostic rigid bronchoscopies performed. The study comprised a review of literature published from 1970 to 2013, using the PubMed, Scopus, Web of Knowledge, Embase and Medline electronic databases. The sensitivity for computed tomography ranged between 90 and 100 per cent, with four studies demonstrating 100 per cent sensitivity. Specificity was between 75 and 100 per cent. Radiation exposure doses averaged 2.16 mSv. Computed tomography is a sensitive and specific modality in the diagnosis of foreign body aspiration, and its future use will reduce the number of unnecessary rigid bronchoscopies.


Homocysteine in angiographically proven coronary disease.
The research included 200 subjects, of which 150 had angiographically proven coronary disease with the coronary artery stenosis of 50% or more, and 50 subjects who did not have angiographically proven coronary disease. Patients were chosen randomly out of approximately 1000 patients who underwent angiography. All the subjects were treated at the Clinical Center of University of Tuzla--at the Clinic for Cardiovascular Diseases. The average value of homocysteine concentration in plasma of patients with angiographically proven coronary disease was 13.86 micromol/L, and 10.65 micromol/L in the controls, which is statistically significant difference (P < 0.0001). Lowered values of ejective fraction of the left ventricle of 50% and over was found in 25 patients (or 16.66%) with angiographically proven coronary disease, while the control group had only 4 subjects (or 8%). Student's t-test have proven that the average values of ejective fraction of the left ventricle of subject with angiographically proven coronary disease were statistically significantly different in comparison with the values of ejective fraction of the subjects in the control group (t = 5.87, df = 197, P < 0.0001). In all the groups the negative values of coefficients of correlation (R) shows that with the increase of plasma homocysteine concentrations the ejective fractions of the left ventricle dropped. Using logistical regressive analysis it was established that the following factors contribute the most to the development of coronary disease: increased concentration of plasma LDL-cholesterol, increased concentration of plasma homocysteine, diabetes mellitus and hereditary factors. In all the different forms of angiographically proven coronary disease (coronary disease in a one-vessel or in multiple-vessels), the increased concentration of plasma homocysteine was the significant risk factor for the development of coronary disease.


Waterlogging affects plant morphology and the expression of key genes in tef (Eragrostis tef).
Tef [Eragrostis tef (Zucc.) Trotter], an allotetraploid cereal that is a staple food to over 60 million people in the Horn of Africa, has a high nutritional content and is resistant to many biotic and abiotic stresses such as waterlogging and drought. Three tef genotypes, Alba, Tsedey, and Quncho, were subjected to waterlogging conditions and their growth, physiology, and change in transcript expression were measured with the goal of identifying targets for breeding cultivars with improved waterlogging tolerance. Root and shoot growth and dry weight were observed over 22 days. Stomatal conductance and chlorophyll and carotenoid contents were quantified. Microscopy was used to monitor changes in the stem cross sections. Illumina RNA sequencing was used to obtain the expression profiles of tef under flooding and control conditions and was verified using qPCR. Results indicated differences in growth between the three genotypes. Waterlogged Tsedey plants grew higher and had more root biomass than normally watered Tsedey plants. Quncho and Alba genotypes were more susceptible to the excess moisture stress. The effects of these changes were observed on the plant physiology. Among the three tested tef genotypes, Tsedey formed more aerenchyma than Alba and had accelerated growth under waterlogging. Tsedey and Quncho had constitutive aerenchyma. Genes affecting carbohydrate metabolism, cell growth, response to reactive oxygen species, transport, signaling, and stress responses were found to change under excess moisture stress. In general, these results show the presence of substantial anatomical and physiological differences among tef genotypes when waterlogged during the early growth stage.


[Application of p16/Ki-67 immunocytochemistry in triage of patients with atypical squamous cells of undetermined significance].
Objective: To investigate the clinical value of p16/Ki-67 immunocytochemistry in patients with atypical squamous cells of undetermined significance(ASC-US). Methods: One hundred and seventy-one cases of thin-prep cytology test (TCT) diagnosed as ASC-US underwent p16/Ki-67 immunocytochemistry. All patients had colposcopy and biopsy from March 2015 to January 2016. Ninety of the 171 cases underwent high-risk HPV test at the same time. Results: p16/Ki-67 immunocytochemistry was positive in 43.9% (75/171) of the 171 cytology samples; the sensitivity and specificity of p16/Ki-67 immunocytochemistry were 77.6%(52/67) and 77.9%(81/104) in detecting CIN2+ , and the positive and negative predictive value were 69.3%(52/75) and 84.4%(81/96), respectively. The sensitivity and specificity in diagnosing CIN2+ were 100.0%(34/34) and 10.7%(6/56) for HPV test, and the positive and negative predictive value were 40.5%(34/84) and 6/6. p16/Ki-67 immunocytochemistry showed lower sensitivity but obviously higher specificity than high-risk HPV detection. Conclusion: p16/Ki-67 immunocytochemistry is a good triage test for identifying CIN2+ in ASC-US specimens.


A metabolomic investigation into the temperature-dependent virulence of Pseudomonas plecoglossicida from large yellow croaker (Pseudosciaena crocea).
Pseudomonas plecoglossicida is associated with multiple fish diseases, and temperature is one of the most important environmental factors related to its outbreak. To elucidate the influence of temperature variation on the pathogen, the global metabolomics of P. plecoglossicida (NZBD9) were analysed at the virulent (18°C) and avirulent (12°C and 28°C) temperatures. The result showed that the levels of Phosphoric acid, Tyrosine, Spermidine and Sucrose were significantly reduced,while Itaconic acid, Glucaric acid and Isomaltose were increased in P. plecoglossicida at 18°C. These metabolic adjustments assist P. plecoglossicida to survive in adverse environments, proliferate in the host, colonize and resist host immune clearance during the initial steps of infection. The results suggested that L321_03626 and L321_18122 genes played a key role in the regulation of these metabolic adaptions and thus regulated P. plecoglossicida virulence at virulent temperature, which was proved by further gene silencing and artificial infection. The present study, for the first time, determines the P. plecoglossicida metabolomic responses to temperature variation, which is helpful to explore its pathogenic mechanism and provides reference for disease control.


Curating Clinically Relevant Transcripts for the Interpretation of Sequence Variants.
Variant interpretation depends on accurate annotations using biologically relevant transcripts. We have developed a systematic strategy for designating primary transcripts and have applied it to 109 hearing loss-associated genes that were divided into three categories. Category 1 genes (n = 38) had a single transcript; category 2 genes (n = 33) had multiple transcripts, but a single transcript was sufficient to represent all exons; and category 3 genes (n = 38) had multiple transcripts with unique exons. Transcripts were curated with respect to gene expression reported in the literature and the Genotype-Tissue Expression Project. In addition, high-frequency loss-of-function variants in the Genome Aggregation Database and disease-causing variants in ClinVar and the Human Gene Mutation Database across the 109 genes were queried. These data were used to classify exons as clinically significant, insignificant, or of uncertain significance. Interestingly, 6% of all exons, containing 124 reportedly disease-causing variants, were of uncertain significance. Finally, we used exon-level next-generation sequencing quality metrics generated at two clinical laboratories and identified a total of 43 technically challenging exons in 20 different genes that had inadequate coverage and/or homology issues that might lead to false-variant calls. We have demonstrated that transcript analysis plays a critical role in accurate clinical variant interpretation.


Potential use of shared antigens for immunization against gram-negative bacillary infections.
The demonstration of common antigens shared by all Enterobacteriaceae has led to evaluation of the effects of immunization of animals and man with these antigens in protecting against bacterial infections and challenge with LPS. Both active and passive immunization with the Re mutant of S. minnesota and the J5 mutant of E. coli afforded significant protection to mice and rabbits against lethal challenge with viable bacteria and heterologous LPS. KDO appears to be the antigenic determinant responsible for induction of protective antibody after immunization with the Re mutant but the antigenic determinant of the J5 mutant has yet to be identified. Studies in volunteers indicate that human immunization with R mutants can be accomplished without excess adverse reactions and that such immunization may protect against Gram-negative bacillary infections.


Fluorescence response of a 4-trifluoroacetylaminophthalimide to iodide ions upon 254 nm irradiation in MeCN.
The title trifluoroacetylaminophthalimide derivative produced a violet fluorescence (lambdaFLmax 392 nm) in MeCN, and it displayed a green emission (lambdaFLmax 506 nm) after irradiation at 254 nm in the presence of iodide ions. The corresponding amidate ion of the trifluoroacetamide was identified as the green fluorescence emitter. The deprotonation reaction may be caused by proton-abstracting solvated electrons generated by a photochemical charge--transfer-to-solvent process from I(-) to MeCN.


The nursing shortage, patient care, and ethics.
Although nursing shortages are not new, many nurses consider the present shortage to be different from those in the past. Nurses are again questioning whether patients are receiving the quality of care they deserve. Overwhelmed by this nursing shortage, nurses are trying to reconcile how to fulfill their duties to advocate for good patient care and to warn patients about conditions that are possibly detrimental to their welfare. This article discusses two ethical issues that nurses, in the midst of a nursing shortage, face in their clinical practice: lack of control over their practice and potential for harm to patients and themselves. There is also a description of strategies that nurses can use to promote and maintain an environment within the organization that supports providing good patient care.


THE CYTONUCLEOPROTEINS OF AMEBAE. I. SOME CHEMICAL PROPERTIES AND INTRACELLULAR DISTRIBUTION.
Autoradiographs of whole Amoeba proteus host cells fixed after the implantation of single nuclei from A. proteus donors labeled with any one of 8 different radioactive amino acids showed that the label had become highly concentrated in the host cell nucleus as well as in the donor nucleus and that the cytoplasmic activity was relatively low. When these amebae were sectioned, the radioactivity was found to be homogeneously distributed throughout the nuclei. The effect of unlabeled amino acid "chaser," the solubility of the labeled material, and the long-term behavior of the labeled material gave evidence that the radioactivity was in protein. At equilibrium, the host cell nucleus contained approximately 30 per cent of the radioactivity distributed between the two nuclei. This unequal nuclear distribution is attributed to the presence of two classes of nuclear proteins: a non-migratory one that does not leave the nucleus during interphase, and a migratory one, called cytonucleoprotein, that shuttles between nucleus and cytoplasm in a non-random manner. It is estimated that between 12 per cent and 44 per cent of the cytonucleoproteins are present in the cytoplasm of a binucleate cell at any one moment. Nuclei of Chaos chaos host cells also concentrated label acquired from implanted radioactive A. proteus nuclei.


A combined approach using transporter-flux assays and mass spectrometry to examine psychostimulant street drugs of unknown content.
The illicit consumption of psychoactive compounds may cause short and long-term health problems and addiction. This is also true for amphetamines and cocaine, which target monoamine transporters. In the recent past, an increasing number of new compounds with amphetamine-like structure such as mephedrone or 3,4-methylenedioxypyrovalerone (MDPV) entered the market of illicit drugs. Subtle structural changes circumvent legal restrictions placed on the parent compound. These novel drugs are effectively marketed "designer drugs" (also called "research chemicals") without any knowledge of the underlying pharmacology, the potential harm or a registration of the manufacturing process. Accordingly new entrants and their byproducts are identified postmarketing by chemical analysis and their pharmacological properties inferred by comparison to compounds of known structure. However, such a heuristic approach fails, if the structures diverge substantially from a known derivative. In addition, the understanding of structure-activity relations is too rudimentary to predict detailed pharmacological activity. Here, we tested a combined approach by examining the composition of street drugs using mass spectrometry and by assessing the functional activity of their constituents at the neuronal transporters for dopamine, serotonin, and norepinephrine. We show that this approach is superior to mere chemical analysis in recognizing novel and potentially harmful street drugs.


Popliteal artery entrapment syndrome: non-invasive diagnosis by MDCT and MRI.
We present a case of a 19-year-old male patient complaining of right leg pain, which appeared after exercise and abated with rest. Computed tomography (CT) and magnetic resonance angiography (MRA) showed occlusion of right popliteal artery. Volume rendering CT image showed not only occlusion of right popliteal artery but also abnormal course of the medial head of the gastrocnemius muscle (MHG). CT and MR images of right popliteal fossa showed the abnormal anatomy that MHG coursed between popliteal artery with thrombus and popliteal vein. Popliteal artery entrapment syndrome was diagnosed non-invasively by multidetector CT and MRI. Sectional radiological and three-dimensional images are useful for not only depiction of the arterial changes but also identification of the abnormal anatomic structures responsible for the entrapment.


First description of a fatal equine infection with Halicephalobus gingivalis in Portugal. Relevance for public health.
Halicephalobus gingivalis is a small saprophytic rhabditid nematode, represented only by females with a typical rhabditoid oesophagus and one egg in the uterus, capable of infecting vertebrates. This opportunistic parasite present in the soil, manure and decaying humus, is thought to penetrate through previous injuries to the mouth, eyes and skin of horses and migrate to various organs. The brain is one such organ, where the females lay their eggs, leading to malacia and causing a sudden onset of neurological signs, such as anorexia, ataxia, urinary incontinence, blindness, decreased menace and tonal reflexes, tremors and aggressiveness. The disease is invariably fatal whenever brain lesions are present, and the diagnosis usually achieved only post-mortem. The present work aims to describe the first case of infection by H. gingivalis ever reported in Portugal. An 8-year old warmblood horse presented with an 8-day history of progressive blindness involving the left eye, initially with normal pupillary reflexes, advancing to bilateral blindness and increasing deterioration in clinical condition. After euthanasia, the animal was submitted for necropsy. Organ samples were collected and fixed in 10% neutral buffered formalin for routine histopathology. A large mass was found in the left kidney corresponding to fibrous tissue heavily infiltrated with inflammatory cells and numerous nematodes. In the brain, multiple, bilateral and asymmetrical foci of malacia containing several rhabditoid nematodes, larvae and zygotes, and high numbers of inflammatory cells were found. The nematodes were identified as H. gingivalis. The clinical history, necropsy and histological findings presented constitute a typical case of H. gingivalis infection in a horse, never previously described in Portugal to the authors' best knowledge. Humans can be infected by contact with contaminated manure, which makes this nematode a public health concern, especially for people living and/or working in close proximity to horses.


TNP-Ficoll response in Xenopus laevis: substitution and reconstitution in thymectomized animals.
The capacity to respond to haptenated Ficoll, though thymus-independent in mammals, is lost in Xenopus laevis following thymectomy at any stage of development. This capacity can be restored to thymectomized Xenopus by whole allogeneic thymus implants, by thymus implants from animals treated with N-methyl-N-nitrosourea (which have an active thymus medulla but no cortex, and which lack certain thymus-dependent immunological functions), and Concanavalin A. These results are discussed in terms of the cell populations and/or factors which may be involved.


Development rate rather than social environment influences cognitive performance in Australian black field crickets, Teleogryllus commodus.
Cognitive functioning is vital for enabling animals of all taxa to optimise their chances of survival and reproductive success. Learning and memory in particular are drivers of many evolutionary processes. In this study, we examine how developmental plasticity can affect cognitive ability by exploring the role the early social environment has on problem solving ability and learning of female black field crickets, Teleogryllus commodus. We used two learning paradigms, an analog of the Morris water maze and a novel linear maze, to examine cognitive differences between individuals reared in two acoustic treatments: silence or calling. Although there was no evidence of learning or memory, individuals that took longer to mature solved the Morris water maze more quickly. Our results suggest that increased investment into cognitive development is likely associated with increased development time during immature stages. Inconsistent individual performance and motivation during the novel linear maze task highlights the difficulties of designing ecologically relevant learning tasks within a lab setting. The role of experimental design in understanding cognitive ability and learning in more natural circumstances is discussed.


Comparison of the toxicological potential of two JUUL ENDS products to reference cigarette 3R4F and filtered air in a 90-day nose-only inhalation toxicity study.
Electronic nicotine delivery systems (ENDS) are generally recognized as less harmful alternatives for those who would otherwise continue to smoke cigarettes. The potential toxicity of aerosols generated from JUUL Device and Virginia Tobacco (VT3) or Menthol (ME3) JUULpods at 3.0% nicotine concentration was assessed in rats exposed at target aerosol concentrations of 1400 μg/L for up to 6 h/day on a 5 day/week basis for at least 90 days (general accordance with OECD 413). 3R4F reference cigarette smoke (250 μg/L) and Filtered Air were used as comparators. JUUL ENDS product aerosol exposures at >5x the 3R4F cigarette smoke level resulted in greater plasma nicotine and cotinine levels (up to 2x). Notable cigarette smoke related effects included pronounced body weight reductions in male rats, pulmonary inflammation evidenced by elevated lactate dehydrogenase, pro-inflammatory cytokines and neutrophils in bronchoalveolar lavage fluid, increased heart and lung weights, and minimal to marked respiratory tract histopathology. In contrast, ENDS aerosol exposed animals had minimal body weight changes, no measurable inflammatory changes and minimal to mild laryngeal squamous metaplasia. Despite the higher exposure levels, VT3 and ME3 did not result in significant toxicity or appreciable respiratory histopathology relative to 3R4F cigarette smoke following 90 days administration.


Effects of probiotics on Toll‑like receptor expression in ulcerative colitis rats induced by 2,4,6‑trinitro‑benzene sulfonic acid.
The present study aimed to investigate the regulatory effect of probiotics on the expression of Toll‑like receptors (TLRs) in an ulcerative colitis (UC) rat model, and to determine the role of probiotics in the underlying mechanisms through which UC develops and progresses in rat models. Rats were randomly allocated to one of the four following groups: i) The healthy control, ii) the model, iii) the Golden bifid treatment group, and iv) the TLR4 monoclonal antibody (TLR4mAb) intervention group. The UC rat model was established using 2,4,6‑trinitro‑benzene sulfonic acid. The general status and histological changes of rats were scored using the disease activity index and the histopathological scoring method, respectively. In these rats, the expression of TLR4 and TLR2 was measured using reverse transcription‑quantitative polymerase chain reaction. The expression of TLR4 and TLR2 in the model group was significantly higher than that in the healthy control group. However, when compared with the model rats, those that received either Golden bifid treatment or TLR4mAb intervention exhibited significantly decreased mRNA expression levels of TLR4 and TLR2 (P<0.05). The development of UC is characterized by an abnormal immune response in the intestines. Probiotics alleviated inflammatory reactions in rats with UC. The underlying mechanism of UC may be associated with the expression of TLRs and the subsequent release of inflammatory cytokines.


Enteric-coated pellets: theoretical analysis of effect of dispersion in the stomach on blood level profiles.
The advantages of encapsulated enteric-coated pellets as dosage forms are discussed theoretically and compared to enteric-coated tablets. An enteric-coated tablet may take from approximately 0.5 to more than 8 hr to pass from the stomach to the duodenum. On the other hand, enteric-coated pellets are subjected to dispersion in the stomach, but they pass through the pyloric sphincter after a mean residence time in the stomach that would not be different from that exhibited by a suspension dosage form. The dispersion effect causes a theoretical reduction in peak blood level over that of an enteric-coated tablet of equivalent potency while maintaining bioavailability. It is hypothesized that enteric-coated pellets will reduce intestinal side effects that may occur with enteric-coated tablet preparations.


Occupation and suicide: Colorado, 2004-2006.
Occupation has been identified as a risk factor for suicide. Changes in work environments over time suggest occupations at high risk of suicide may also change. Therefore, periodic examination of suicide by occupation is warranted. The purpose of this article is to describe suicide rates by occupation, sex, and means used in Colorado for the period 2004-2006. To provide information useful in designing suicide prevention programs, the methods used in suicide across occupational groups also are examined. Data from the Colorado Violent Death Reporting System (COVDRS) were obtained for suicides that occurred between 2004 and 2006. Denominators to calculate rates by age, sex, and race used are from the 2000 US Census of the Population data. Men had higher suicide rates than women in all occupation categories except computers and mathematics. Among men, those in farming, fishing, and forestry (475.6 per 100,000) had the highest age-adjusted suicide rates. Among women, workers with the highest suicide rates were in construction and extraction (134.3 per 100,000). The examination of lethal means showed that workers in farming, fishing, and forestry had higher rates of suicide by firearms (50.18 per 100,000) compared with other workers. Healthcare practitioners and technicians had the highest rate of suicide by poisoning (14.25 per 100,000). Workers involved in construction and extraction (26.43 per 100,000) had higher rates of suicide by hanging, suffocation, or strangling. Significant differences in means of suicide were seen by occupation, which could guide future suicide prevention interventions that may decrease work-related suicide risks.


Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease.
RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs. Analysing brain tissue from males of the Huntington's disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.


Association of Ambient Air Pollution with Blood Pressure in Adolescence: A Systematic-review and Meta-analysis.
We systematically reviewed the association of ambient air pollution with blood pressure (BP) as a primary outcome in adolescents (10-19 years). Five databases (Ovid Medline, Ovid Embase, Web of Science, The Cochrane Library, and LILACS) were searched for relevant articles published up to August 2022. Meta-analyses were conducted using STATA v17 (Protocol - OSF Registries https://doi.org/10.17605/OSF.IO/96G5Q). Eight studies (5 cohort, 3 cross-sectional) with approximately 15,000 adolescents were included. Data from 6 studies were suitable for inclusion in the meta-analyses. In sub-group analyses, non-significant positive associations were observed for cohort studies assessing long-term exposure to PM10, PM2.5, and NO2 on systolic and diastolic BP. At age 12 years old (3702 adolescents), we found significant positive associations for long-term exposure to PM2.5(β=5.33 (1.56, 9.09) mmHg) and PM10 (β=2.47 (0.10, 4.85) mmHg) on diastolic BP. Significant positive associations were observed (3,592 adolescents) for long-term exposure to PM10(β=0.34 (0.19, 0.50) mmHg) and NO2 on diastolic BP (β=0.40 (0.09, 0.71) mmHg), and PM10 on systolic BP (β=0.48 (0.19, 0.77) mmHg). The overall quality of evidence analysed was graded as "low/very low." Insufficient data for short-term exposures to PM2.5, PM10, NO2, CO on BP led to their exclusion from the meta-analysis. Inconsistent associations were reported for gender-stratified results. The evidence, though of low-quality and limited, indicated that ambient air pollution was positively associated with adolescent BP. Future studies need improved measures of air pollutant exposures, consideration of gender and socio-economic circumstances on the observed pollution effects, as well as adjustment for other potential confounding factors.


Spinal cord injury medicine and rehabilitation.
The rehabilitation of spinal cord injury (SCI) is a complicated process, but one in which new research is developing novel and increasingly promising methods of restorative neurology. Spinal cord injury medicine addresses not only the neurologic injury, but all the secondary complications in other organ systems whose regulation is disrupted after SCI. To some degree, the rehabilitation of SCI is focused on return to the community and functional goals are paramount, regardless of whether they can be achieved through some mechanism of compensation or due to a growing effort at engendering neurologic plasticity and recovery. The authors present a typical case of cervical incomplete SCI and discuss the medical complications and considerations for care during acute rehabilitation. They also review current methods of planning and executing rehabilitation, along with emerging methods that are leading to, in varying degrees, greater neurologic recovery. Finally, new approaches in SCI rehabilitation, namely neuromodulation, are discussed as efforts are made to further augment neural plasticity and recovery in SCI.


Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis.
To assess the anti-cancer effect of lobaplatin on human gastric cancer cells, and to explore the underlying molecular mechanisms. The human gastric cancer cell lines MKN-28, AGS and MKN-45 were used. The cytotoxicity of lobaplatin was detected using an MTS cell proliferation assay. Flow cytometry was used to detect cell apoptosis using Annexin V-FITC Apoptosis Detection Kit. The expression of apoptosis-regulated genes was examined at the protein level using Western blot. Lobaplatin inhibited the proliferation of human gastric cancer cells and induced apoptosis, which may be associated with the up-regulation of Bax expression, poly(ADP-ribose) polymerase (PARP) cleavage, p53 expression and the reduction of Bcl-2 expression. The cytotoxicity of lobaplatin may be due to its ability of inducing apoptosis of gastric cancer cells, which would support the potential use of lobaplatin for the therapy of gastric cancer.