Clinical Outcomes After Intensifying Antihypertensive Medication Regimens Among Older Adults at Hospital Discharge.
Transient elevations of blood pressure (BP) are common in hospitalized older adults and frequently lead practitioners to prescribe more intensive antihypertensive regimens at hospital discharge than the patients were using before hospitalization. To investigate the association between intensification of antihypertensive regimens at hospital discharge and clinical outcomes after discharge. In this retrospective cohort study, patients 65 years and older with hypertension who were hospitalized in Veterans Health Administration national health system facilities from January 1, 2011, to December 31, 2013, for common noncardiac conditions were studied. Data analysis was performed from October 1, 2018, to March 10, 2019. Discharge with antihypertensive intensification, defined as receiving a prescription at hospital discharge for a new or higher-dose antihypertensive than was being used before hospitalization. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not receive antihypertensive intensifications at hospital discharge. The primary outcomes of hospital readmission, serious adverse events, and cardiovascular events were assessed by competing risk analysis. The secondary outcome was the change in systolic BP within 1 year of hospital discharge. The propensity-matched cohort included 4056 hospitalized older adults with hypertension (mean [SD] age, 77 [8] years; 3961 men [97.7%]), equally split between those who did vs did not receive antihypertensive intensifications at hospital discharge. Groups were well matched on all baseline covariates (all standardized mean differences <0.1). Within 30 days, patients receiving intensifications had a higher risk of readmission (hazard ratio [HR], 1.23; 95% CI, 1.07-1.42; number needed to harm [NNH], 27; 95% CI, 16-76) and serious adverse events (HR, 1.41; 95% CI, 1.06-1.88; NNH, 63; 95% CI, 34-370). At 1 year, no differences were found in cardiovascular events (HR, 1.18; 95% CI, 0.99-1.40) or change in systolic BP among those who did vs did not receive intensifications (mean BP, 134.7 vs 134.4; difference-in-differences estimate, 0.6 mm Hg; 95% CI, -2.4 to 3.7 mm Hg). Among older adults hospitalized for noncardiac conditions, prescription of intensified antihypertensives at discharge was not associated with reduced cardiac events or improved BP control within 1 year but was associated with an increased risk of readmission and serious adverse events within 30 days.


The effect of by-product inclusion and concentrate feeding rate on milk production and composition, pasture dry matter intake, and nitrogen excretion of mid-late lactation spring-calving cows grazing a perennial ryegrass-based pasture.
Interest is growing in the use of by-products as economical sources of nutrients that complement grazed grass, particularly at times when grass supply is insufficient to meet the nutritional demands of lactating dairy cattle. The objective of this research was to assess the effect of the amount of by-product inclusion and concentrate feeding rate on pasture dry matter intake, milk production and composition, and N excretion from spring-calving cows grazing summer pasture during mid-late lactation. Forty-eight Holstein Friesian dairy cows were randomly assigned to 1 of 4 dietary treatments in a 2 × 2 factorial design. Cows were grazed in one group on a perennial ryegrass-based sward, with pelleted concentrates offered twice daily during milking over a 63-d experimental period. The dietary treatments were 3 kg of concentrate containing 35% by-products; 6 kg of concentrate containing 35% by-products; 3 kg of concentrate containing 95% by-products; and 6 kg of concentrate containing 95% by-products on a fresh matter basis. The by-products used were soybean hulls, palm kernel expeller, and maize dried distillers grains with solubles, included in equal proportions on a dry matter basis. Pasture dry matter intake (14.5 kg/d) was not affected by the amount of by-product inclusion or feeding rate. By-product inclusion had no effect on milk yield (27.1 kg/d) or milk solids (MS) yield (2.0 kg/d). Cows offered 6 kg of concentrate had a greater milk (+1.6 kg/d) and MS (+0.13 kg/d) yield, consumed more N (+0.08 kg/d), and excreted a lower proportion of N in the milk (0.25 vs. 0.27) and feces (0.39 vs. 0.41) and a higher proportion in the urine (0.39 vs. 0.32) compared with cows offered 3 kg of by-product-based concentrate. In conclusion, by-products can be included at up to 95% of the concentrate fed to cows grazing pasture without affecting pasture dry matter intake, milk production or composition, or N excretion. Cows offered 6 kg of concentrates produced more milk and MS than cows offered 3 kg but had higher urinary N excretion. Economics of this yield response will depend on milk and concentrate prices.


The T cell repertoire to a multideterminant antigen. Clonal heterogeneity of the T cell response, variation between syngeneic individuals, and in vitro selection of T cell specificities.
The specificity of lysozyme-induced T cell proliferative responses by individual B10.A mice was compared by using a panel of three peptides. A surprising degree of variation in the focus of the responses was observed among individual animals, both in the newly isolated lymph node cell populations and in long term T cell lines. The responses to each determinant after hen egg-white lysozyme immunization were not equal and in examining the mice as a group some determinants tended to be dominant. However, despite each animal favoring a restricted number of determinants, the responding T cell populations were still highly heterogeneous. The data suggest that many determinants are involved in the response to the whole Ag. The role of one or more dominant determinants can be overestimated because the degree of heterogeneity in long term T cell lines appears to be less than in freshly obtained lymph node cells, indicating that a process of in vitro selection occurs. We observed that the T cells responsive to one peptide, 46-61, appeared to have a selective advantage in vitro culture.


Urban structure and dengue fever in Puntarenas, Costa Rica.
Dengue is currently the most important arboviral disease globally and is usually associated with built environments in tropical areas. Remotely sensed information can facilitate the study of urban mosquito-borne diseases by providing multiple temporal and spatial resolutions appropriate to investigate urban structure and ecological characteristics associated with infectious disease. In this study, coarse, medium and fine resolution satellite imagery (Moderate Resolution Imaging Spectrometer, Advanced Spaceborne Thermal Emission and Reflection Radiometer and QuickBird respectively) and ground-based data were analyzed for the Greater Puntarenas area, Costa Rica for the years 2002-04. The results showed that the mean normalized difference vegetation index (NDVI) was generally higher in the localities with lower incidence of dengue fever during 2002, although the correlation was statistically significant only in the dry season (r=-0.40; p=0.03). Dengue incidence was inversely correlated to built area and directly correlated with tree cover (r=0.75, p=0.01). Overall, the significant correlations between dengue incidence and urban structural variables (tree cover and building density) suggest that properties of urban structure may be associated with dengue incidence in tropical urban settings.


Two-year use of flash glucose monitoring is associated with sustained improvement of glycemic control and quality of life (FLARE-NL-6).
The FreeStyle Libre (FSL) is a flash glucose monitoring (FGM) system. The Flash Monitor Register in the Netherlands (FLARE-NL-4) study previously demonstrated the positive effects of FSL-FGM use during 1 year on glycemic control, quality of life and disease burden among persons with diabetes mellitus (DM). The present follow-up study assesses the effects of FSL-FGM after 2 years. Patients included in the FLARE-NL-4 study who continued FSL-FGM during the 1-year study period were invited to participate (n=687). Data were collected using questionnaires (the 12-Item Short Form Health Survey version 2 (SF-12v2) and the EuroQol 5-Dimension 3-Level (EQ-5D-3L) for quality of life), including self-reported hemoglobin A1c (HbA1c). A total of 342 patients agreed to participate: mean age 48.0 (±15.6) years, 52% men and 79.5% with type 1 DM. HbA1c decreased from 60.7 (95% CI 59.1 to 62.3) mmol/mol before use of FSL-FGM to 57.3 (95% CI 55.8 to 58.8) mmol/mol after 1 year and 57.8 (95% CI 56.0 to 59.5) mmol/mol after 2 years. At the end of the 2-year follow-up period, 260 (76%) persons were still using the FSL-FGM and 82 (24%) had stopped. The main reason for stopping FSL-FGM was financial constraints (55%). Concerning the whole 2-year period, there was a significant decrease in HbA1c among persons who continued use of FSL-FGM (-3.5 mmol/mol, 95% CI -6.4 to -0.7), while HbA1c was unaltered compared with baseline among persons who stopped FSL-FGM (-2.4 mmol/mol, 95% CI -7.5 to 2.7): difference between groups 2.2 (95% CI -1.3 to 5.8) mmol/mol. After 2 years, persons who continued use of FSL-FGM had higher SF-12 mental component score and higher EQ-5D Dutch tariff score and felt less often anxious or depressed compared with persons who discontinued FSL-FGM. Although the considerable number of non-responders limits generalizability, this study suggests that persons who continue to use FSL-FGM for 2 years may experience sustained improvement in glycemic control and quality of life.


Analysis of the Tropism of SARS-CoV-2 Based on the Host Interactome of the Spike Protein.
The β-coronavirus SARS-CoV-2 causes severe acute respiratory syndrome (COVID-19) in humans. It enters and infects epithelial airway cells upon binding of the receptor binding domain (RBD) of the virus entry protein spike to the host receptor protein Angiotensin Converting Enzyme 2 (ACE2). Here, we used coimmunoprecipitation coupled with bottom-up mass spectrometry to identify host proteins that engaged with the spike protein in human bronchial epithelial cells (16HBEo-). We found that the spike protein bound to extracellular laminin and thrombospondin and endoplasmatic reticulum (ER)-resident DJB11 and FBX2 proteins. The ER-resident proteins UGGT1, CALX, HSP7A, and GRP78/BiP bound preferentially to the original Wuhan D614 over the mutated G614 spike protein in the more rapidly spreading Alpha SARS-CoV-2 strain. The increase in protein binding to the D614 spike might be explained by higher accessibility of cryptic sites in "RDB open" and "S2 only" D614 spike protein conformations and may enable SARS-CoV-2 to infect additional, ACE2-negative cell types. Moreover, a novel proteome-based cell type set enrichment analysis (pCtSEA) found that host factors like laminin might render additional cell types such as macrophages and epithelial cells in the nephron permissive to SARS-CoV-2 infection.


The crystal structure of the Y66L variant of green fluorescent protein supports a cyclization-oxidation-dehydration mechanism for chromophore maturation.
The crystal structure of a colorless variant of green fluorescent protein (GFP) containing the Y66L substitution has been determined to 1.5 A. Crystallographic evidence is presented for the formation of a trapped intermediate on the pathway of chromophore maturation, where the peptide backbone of residues 65-67 has condensed to form a five-membered heterocyclic ring. The hydroxyl leaving group remains attached to the ring as confirmed by high-resolution electrospray mass spectrometry. The alpha-carbon of residue 66 exhibits trigonal planar geometry, consistent with ring oxidation by molecular oxygen. Side chain positions of surrounding residues are not perturbed, in contrast to structural results obtained for the GFPsol-S65G/Y66G variant [Barondeau, D. P., Putnam, C. D., Kassmann, C. J., Tainer, J. A., and Getzoff, E. D. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 12111-12116]. The data are in accord with a reaction pathway in which dehydration is the last of three chemical steps in GFP chromophore formation. A novel mechanism for chromophore biosynthesis is proposed: when the protein folds, the backbone condenses to form a cyclopentyl tetrahedral intermediate. In the second step, the ring is oxidized by molecular oxygen. In the third and final step, elimination of the hydroxyl leaving group as water is coupled to a proton transfer reaction that may proceed via hydrogen-bonded solvent molecules. Replacement of the aromatic Tyr66 with an aliphatic residue appears to have a profound effect on the efficiency of ring dehydration. The proposed mechanism has important implications for understanding the factors that limit the maturation rate of GFP.


The Value of Population Screening in Advancing Personalized Medicine in the Field of Lung Cancer.
During the past decade, progress has been made in the field of lung cancer molecular biology and onco-immunology, leading to prolonged survival of patients. The combination of increased fundamental knowledge and the pharmaceutical pipeline has allowed the development of various tyrosine kinase inhibitors, targeting numerous molecular alterations. These drugs are now available in daily practice and have transformed survival outcomes for patients harboring EGFR, ALK or ROS1 alterations. Multiple clinical trials are now ongoing in order to increase the number of approved drugs, thus overcoming the issues of rare mutations and tyrosine kinase inhibitors resistance. Immune checkpoint inhibitors development has also changed lung cancer outcomes, but underwhelming response rates highlight the need for immune biomarkers. While PD-L1 expression was the first approved immune biomarker, it has shown several limitations and new biomarkers have to be identified to predict response or resistance to immune checkpoint inhibitors. Testing methods, molecular results and targeted therapeutic schedules will be harmonized in the coming years, with the help of dedicated molecular multidisciplinary boards.


Magnetic resonance evaluation of breast implants and soft-tissue silicone.
After several years of research in many disciplines, concern for the safety of silicone gel-filled breast implants continues. Although systemic effects of silicone are debated, there is growing consensus that implant rupture and other local breast complications from implants are very real concerns. This paper reviews the history of breast augmentation with an emphasis on the great variety of implants manufactured during the last generation. A classification scheme consisting of 14 breast implant categories is described, and the MR appearance of many is illustrated. The MR signs of implant rupture and pitfalls associated with those signs are reviewed. Indications and contraindications for MR imaging of implants and soft tissue silicone are presented. The author's breast implant and soft-tissue silicone MR imaging experience with follow-up surgical experience over the last 6 years is summarized and discussed. For 1,626 single lumen silicone gel-filled implants imaged, the sensitivity for rupture was 74% and the specificity was 98%. For those implants, 64.9% showed no evidence rupture on MR, 7.9% were indeterminate, and 27.2% were definitely ruptured. Of those that were ruptured, 26.2% had silicone outside as well as within the fibrous capsule. Of the 442 implants that were shown to be ruptured, 54.8% were in a state of uncollapsed rupture, 12.9% minimally collapsed rupture, 4.1% partially collapsed rupture, and 28.3% fully collapsed rupture.


Antitumor effects of epidermal growth factor receptor antisense oligonucleotides in combination with docetaxel in squamous cell carcinoma of the head and neck.
Antisense approaches targeting the epidermal growth factor receptor (EGFR) have been demonstrated to inhibit the growth of squamous cell carcinoma of the head and neck (SCCHN). Docetaxel is an effective chemotherapeutic agent in the treatment of SCCHN. The present study was undertaken to evaluate the antitumor mechanisms of EGFR antisense (AS) oligonucleotides administered in combination with docetaxel in preclinical models of SCCHN. SCCHN cells lines and xenografts were treated with an EGFR AS oligonucleotide targeting region 760-779 of EGFR mRNA (GenBank accession XM_004738) alone and in combination with docetaxel. Proliferation in vitro and tumor growth in vivo were examined in addition to determinations of EGFR expression and signaling pathways to evaluate antitumor mechanisms. A combination of docetaxel with EGFR AS resulted in increased cytotoxicity compared with treatment with docetaxel plus EGFR sense oligonucleotides or docetaxel alone after 24 h. Tumor volumes were significantly reduced in the mice treated with a combination of intratumoral EGFR AS and systemic docetaxel compared with mice receiving monotherapy. The combination of docetaxel plus EGFR AS resulted in decreased expression levels of EGFR, phosphotyrosine signal transducers and activators of transcription 3, vascular endothelial growth factor, and pAKT compared with expression levels after either treatment alone. A combination of EGFR AS and docetaxel may be effective in the treatment of SCCHN with a reduced toxicity profile compared with standard chemotherapy regimens.


Delayed cervical spine metastasis from intracranial solitary fibrous tumor.
Cervical spine metastasis from primary intracranial solitary fibrous tumors (SFTs) is an extremely rare clinical entity. This report focuses on its metastatic tendency, radiological imaging, management plan, and follow-up strategies in view of its long latency period for metastasis. A 35-year-old female presented with right-side cervical radiculopathy. Magnetic resonance imaging spine showed C7 vertebral body collapse with retropulsion and neural compression. Two years ago, the patient had surgical resection of intracranial SFT (World Health Organization grade 3) with no evidence of recurrence on follow-up imaging. Cervical C7 metastasis has been decompressed and fused by the anterior cervical approach. Histopathology confirmed SFT metastasis to the spine, and the patient received adjuvant radiotherapy. Cervical metastasis from well-controlled primary intracranial SFT poses a significant challenge for its diagnostic and management planning. Serial pre-emptive surveillance is warranted with regular imaging and appropriate patient counseling.


Emerging molecular methods for male infertility investigation.
Male factors account for approximately 50% of reproductive pathology. Different disorders, including urogenital and endocrine system development abnormalities, lead to testicular and gametogenesis defects. Parallely, studies have reported that somatic and germ cell genome decay are a major cause of male infertility. It has been shown that in somatic karyotype, there is a higher incidence of chromosomal aberrations in infertile men than neonatal population and significant chromosome Y microdeletion or specific gene alterations in affected spermatogenesis. Karyotyping and FISH application at somatic and germ cell levels are no longer sufficient to investigate the potential contribution of genome disorders on male infertility. A wide range of molecular methods are required for better understanding of male infertility causes. Molecular omes and omics techniques have become a great tool to investigate male infertility from chromosome to protein. This review reports different molecular tests and methods that can be offered for male infertility investigation.


Dispersal and genetic structure in a tropical small mammal, the Bornean tree shrew (Tupaia longipes), in a fragmented landscape along the Kinabatangan River, Sabah, Malaysia.
Constraints in migratory capabilities, such as the disruption of gene flow and genetic connectivity caused by habitat fragmentation, are known to affect genetic diversity and the long-term persistence of populations. Although negative population trends due to ongoing forest loss are widespread, the consequence of habitat fragmentation on genetic diversity, gene flow and genetic structure has rarely been investigated in Bornean small mammals. To fill this gap in knowledge, we used nuclear and mitochondrial DNA markers to assess genetic diversity, gene flow and the genetic structure in the Bornean tree shrew, Tupaia longipes, that inhabits forest fragments of the Lower Kinabatangan Wildlife Sanctuary, Sabah. Furthermore, we used these markers to assess dispersal regimes in male and female T. longipes. In addition to the Kinabatangan River, a known barrier for dispersal in tree shrews, the heterogeneous landscape along the riverbanks affected the genetic structure in this species. Specifically, while in larger connected forest fragments along the northern riverbank genetic connectivity was relatively undisturbed, patterns of genetic differentiation and the distribution of mitochondrial haplotypes in a local scale indicated reduced migration on the strongly fragmented southern riverside. Especially, oil palm plantations seem to negatively affect dispersal in T. longipes. Clear sex-biased dispersal was not detected based on relatedness, assignment tests, and haplotype diversity. This study revealed the importance of landscape connectivity to maintain migration and gene flow between fragmented populations, and to ensure the long-term persistence of species in anthropogenically disturbed landscapes.


Trends in Pediatric Candidemia: Epidemiology, Anti-Fungal Susceptibility, and Patient Characteristics in a Children's Hospital.
Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. The awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. CBSIs occurring from 2006-2016 among patients in a large children's hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI, and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to the anti-fungal agent use. The overall incidence rate of CBSI among this complex patient population was 1.97/1000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in neonatal intensive care unit (NICU) patients. Anti-fungal resistance was minimal: 96.7% of isolates were fluconazole, 99% were micafungin, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed anti-fungal agent included for NICU patients. Overall, CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Pediatric CBSI characteristics differ substantially from those in adults. The improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI, while continuing to maintain low resistance rates among Candida isolates.


A comparative study of the collision induced dissociation and the electron capture dissociation of model peptides using ESI-FTMS.
Tandem mass spectra of several model peptides, including KG3WG3K, NG3WG3N, RG7R, RG3WG3R, RG3DG3R, RG3EG3R, RG3FG3R and RG5WG5R were studied using both SORI-CID and ECD methods. By cross comparing the fragmentation pattern of these peptides using the same dissociation method and the same peptide using different dissociation methods, interesting spectral features that are related to the mechanisms of dissociation under SORI-CID and ECD conditions were extracted. Both dissociation methods were believed to be charge-directed. Due presumably to the stepwise ion activation, peptide ion dissociation under SORI-CID conditions was influenced mainly by "localized" hydrogen bonds. Consistent with previous literature findings, mobility proton model could be used to account for the spectral features observed. Substantial changes in the fragmentation patterns of these peptides were observed by using ECD methods. By postulating that the initial tertiary structures of the peptide ions were retained prior to electron capture process, the changes in fragmentation pattern could be attributed to the directing effect of the "global" hydrogen-bonding network. From the present results, no special preference was observed for cleavage at the backbone linkages adjacent to tryptophan residue over other inter-residual linkages. The previous reported nine-times cleavage preference at the C-terminal side of the tryptophan residue should therefore be attributed to some sequence specific phenomena.


A meta-analysis of variables that predict significant intracranial injury in minor head trauma.
Previous studies have presented conflicting results regarding the predictive effect of various clinical symptoms, signs, and plain imaging for intracranial pathology in children with minor head injury. To perform a meta-analysis of the literature in order to assess the significance of these factors and intracranial haemorrhage (ICH) in the paediatric population. The literature was searched using Medline, Embase, Experts, and the grey literature. Reference lists of major guidelines were crosschecked. Control or nested case-control studies of children with head injury who had skull radiography, recording of common symptoms and signs, and head computed tomography (CT) were selected. CT presence or absence of ICH. Sixteen papers were identified as satisfying criteria for inclusion in the meta-analysis, although not every paper contained data on every correlate. Available evidence gave pooled patient numbers from 1136 to 22 420. Skull fracture gave a relative risk ratio of 6.13 (95% CI 3.35 to 11.2), headache 1.02 (95% CI 0.62 to 1.69), vomiting 0.88 (95% CI 0.67 to 1.15), focal neurology 9.43 (2.89 to 30.8), seizures 2.82 (95% CI 0.89 to 9.00), LOC 2.23 (95% CI 1.20 to 4.16), and Glasgow Coma Scale (GCS) <15 of 5.51 (95% CI 1.59 to 19.0). There was a statistically significant correlation between intracranial haemorrhage and skull fracture, focal neurology, loss of consciousness, and GCS abnormality. Headache and vomiting were not found to be predictive and there was great variability in the predictive ability of seizures. More information is required about the current predictor variables so that more refined guidelines can be developed. Further research is currently underway by three large study groups.


CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.
Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids.


Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.
Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.


Phytohaemagglutinin and transfer factor in the leucocyte migration inhibition test in patients with sarcoidosis.
A new system of phytohaemagglutinin stimulation in vitro using the leucocyte migration inhibition test has been applied to patients with active and inactive sarcoidosis and subjects with a persistently negative response to tuberculin. Patients with active sarcoidosis and the tuberculin-negative subjects have a depressed response to the mitogen. This response is improved by the addition of transfer factor to the cultures.


Quality of mango nectar processed by high-pressure homogenization with optimized heat treatment.
This work aimed to evaluate the effect of high-pressure homogenization (HPH) with heat shock on Aspergillus niger, vitamin C, and color of mango nectar. The nectar was processed at 200 MPa followed by heat shock, which was optimized by response surface methodology by using mango nectar ratio (45 to 70), heat time (10 to 20), and temperature (60 to 85 °C) as variables. The color of mango nectar and vitamin C retention were evaluated at the optimized treatments, that is, 200 MPa + 61.5 °C/20 min or 73.5 °C/10 min. The mathematical model indicates that heat shock time and temperature showed a positive effect in the mould inactivation, whereas increasing ratio resulted in a protective effect on A. niger. The optimized treatments did not increase the retention of vitamin C, but had positive effect for the nectar color, in particular for samples treated at 200 MPa + 61.5 °C/20 min. The results obtained in this study show that the conidia can be inactivated by applying HPH with heat shock, particularly to apply HPH as an option to pasteurize fruit nectar for industries.


Effective Weight Loss for Children: A Meta-analysis of Intervention Studies 2002-2015.
Investigators have implemented a variety of strategies for managing and treating childhood overweight and obesity over the past decade, yet the high prevalence of childhood overweight or obesity remains. The aim of this meta-analysis was to examine the effectiveness of childhood overweight or obesity interventions addressing weight loss from 2002-September 2015. The population focused on in this review were children who were overweight. The treatment group interventions focused on weight loss for overweight children, and included dietary, physical activity, life style changes, or a combination of treatments. Control groups received no treatment other than what they would usually receive in their normal daily lives including standard healthcare assessments. Outcomes for the studies were focused on whether the overweight children in the treatment groups lost weight. The criteria for the meta-analysis were met by 16 intervention studies, with a total of 19 outcomes reported within those studies. Two thousand, three hundred and seventeen participants ranged from 6 to 15 years of age with a mean age of 12 years or less. The majority of the 16 studies were conducted outside the United States (n = 13), with half reporting data on the cost of running the programming (n = 8) and were overwhelmingly conducted by interdisciplinary teams without nurses as members of the team (n = 13). The M effect was g = .732, p < .001 with a 95% confidence interval of 0.351 to 1.113, with quality scores ranging from 20 to 29 out of a possible 41. The heterogeneity analyses overall Q score was 378, an I-squared of 95, with a fail-safe N of 415. Diverse interventions included in this meta-analysis had a significant positive effect on weight loss in overweight children. Future research needs to focus on the role of the nurse in ensuring development and translation of the effective interventions in real world settings, at a scale that would move beyond small segments of the affected populations of overweight children.


Consent and assessment of capacity to decide or refuse treatment.
Consent protects the right of patients to decide what happens to them. Before any medical intervention, adults must give valid consent, which must be voluntary, informed and given free of undue influence. When consent is being obtained, patients must be informed about the intervention, why it is being done and its risks; information they are given must be recorded. Every effort should be made to explain the issues in terms that the patient can understand and by providing support and aids to communicate. Consent can be expressed, where patients say they consent or put it in writing, or implied, where a healthcare professional infers from their behaviour that they consent. While different types of consent are valid, some are evidence of stronger proof in court that valid consent has been given. Competent adults have the right to refuse treatment, regardless of the reasons they give for refusal and even if the refusal will result in death; clinicians must respect their decision. In some circumstances-such as when an unconscious person is admitted as an emergency-healthcare professionals can make decisions on behalf of patients, and must do so in patients' best interests.


Λ-Invariant and Topological Pathways to Influence the Strength of Submicron Crystals.
In small volumes, sample dimensions are known to strongly influence mechanical behavior: especially strength and crystal plasticity. This correlation fades away at the so-called "mesoscale," loosely defined at several micrometers in both experiments and simulations. However, this picture depends on the "entanglement" of the initial defect configuration. In this Letter, we study the effect of dislocation topology through the use of a novel observable for dislocation ensembles (the Λ invariant) that depends only on mutual dislocation linking: It is built on the natural vortex character of dislocations, and it has a continuum-discrete correspondence that may assist multiscale modeling descriptions. We investigate arbitrarily complex initial dislocation microstructures in sub-micron-sized pillars using three-dimensional discrete dislocation dynamics simulations for finite volumes. We demonstrate how to engineer nanoscale dislocation ensembles that are independent from sample dimensions, either by biased-random dislocation loop deposition or by sequential mechanical loads of compression and torsion.


Current State and Problems of Radiation Risk Communication: Based on the Results of a 2012 Whole Village Survey.
The entire village of Iitate was contaminated by radioactive material from the Fukushima Daiichi Nuclear Power Plant; even today, the residents remain evacuated. For the villagers, risk communication is an important element of recovery and maintaining health. This analysis focuses on the problem of radiation, presents results from a questionnaire of villagers, and examines methods for future risk communication activities. In May 2012, anonymous surveys were sent to 2914 heads of households whose addresses were registered in Iitate. Their understanding of radiation and information needs were extracted from the answers. There were 1755 valid responses (61.4%). In relation to understanding, the most frequent answer was "There are numerous opinions and I do not know which one is true" (72.2%), followed by "I definitely want opportunities to learn more about how radiation is created" (41.6%). Residents felt that they could not determine which of the available information was reliable. The 60s+ age group responded more than younger age groups that "I do not have much information and do not know much about it," "I do not know much about it, so I want to learn more," and "I definitely want opportunities to learn more about how radiation is created." Among information needs, "publications" (50.2%) and "community associations" (45.9%) received many responses; residents want study groups to be held at places and through media that give them regular opportunities to connect with each other. Residents in their 20s and 30s preferred "publications," while those in their 40s, 50s, and 60s+ were more likely to request "community associations" and "resident meetings." In addition, we found gender differences in both understanding and information needs. These results indicate that radiation and health risk communication should be addressed in a way that aligns with residents' needs by age and gender.


Globin expression in Rous sarcoma virus-transformed quail myoblasts.
Viral transformation affects certain developmental processes by blocking the differentiation of cells such as primitive muscle cells (myoblasts) or primitive red blood cells (erythroblasts). Embryonic quail myoblasts, transformed with a temperature-sensitive (ts) mutant of Rous sarcoma virus (RSV) are blocked in differentiation at the viral permissive temperature of 35 degrees C, but fuse to form myotubes at the nonpermissive temperature of 41 degrees C. We have shown that viral transformation of quail myoblasts also causes transcription of non-muscle-specific genes, ie, globins at 35 degrees C that are not observed in uninfected myoblasts or myotubes. Transformed myoblasts shifted to 41 degrees C for 5 days still contain these globin transcripts. Both alpha-like and beta-like globins are expressed.


[Prevention of disorders of myocardial contractile function under stress by the preliminary adaptation of animals to physical load].
Rats adapted to exercise (daily swimming for one hour over 30 days) and control animals were subjected to emotional-painful stress (EPS) according to the pattern of anxiety neurosis. It has been established that EPS decreases the amplitude as well as the rate of contractions and relaxations of the isolated papillary muscles of animals by 2-3 times and also reduces the resistance of the contractile function of the myocardium to the excess of Na+ and H+ ions, ousting Ca2+ from the sites of its binding in the sarcolemma. Adaptation to exercise exerts an opposite effect. The preliminary adaptation of animals prior to EPS prevents or limits the stress-related depression of the contractility of the myocardium and the diminution of its resistance to the factors replacing Ca2+. The preliminary adaptation to exercise may be used for preventing stress-related disorders of cardiac contractility.


Pasteurella haemolytica leukotoxin: comparison of 51chromium-release, trypan blue dye exclusion, and luminol-dependent chemiluminescence-inhibition assays for sensitivity in detecting leukotoxin activity.
Dilutions of concentrated, dialyzed Pasteurella haemolytica culture supernatant were caused to react with bovine neutrophil (PMN) suspensions, and then the trypan blue dye exclusion (TBDE), 51chromium (51Cr)-release, and luminol-dependent chemiluminescence-inhibition (LDCLI) assays were done to compare their relative sensitivities in detecting biological activity of P haemolytica leukotoxin (cytotoxin). The culture supernatant was concentrated approximately 200:1, and when caused to react as an undiluted preparation with bovine PMN, it was cytotoxic for 38.6% and 80.4% of PMN as determined by TBDE and 51Cr-release assays, respectively. This undiluted leukotoxin preparation caused 100% inhibition of the luminol-dependent chemiluminescence responses of bovine PMN. The LDCLI assay was the most sensitive of the 3 in vitro assays for P haemolytica leukotoxin activity--being approximately 17 times and 2,480 times more sensitive than the 51Cr-release and TBDE assays, respectively. The relative advantages and disadvantages of the 3 assays as in vitro systems for detecting and titrating leukotoxin activity and investigating the role of leukotoxin in disease pathogenesis and immunity are discussed. Because of its sensitivity, specificity, economy, technical ease, and potential for adaptation to automation, the LDCLI assay would seem to be the in vitro assay of choice for quantitating P haemolytica leukotoxin activity. To aid standardization of studies of leukotoxin between different laboratories, it is suggested that P haemolytica leukotoxin be quantitated and expressed as chemiluminescence inhibitory units.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of affinity aqueous two-phase systems for the fractionation of CD133(+) stem cells from human umbilical cord blood.
In a further attempt to establish a novel stem cell primary recovery strategy, the use of aqueous two-phase systems (ATPS) complemented with the use of antibodies (known as immunoaffinity ATPS) is explored in this work. This type of liquid-liquid extraction systems exploits antigen-antibody affinity and represents a novel and selective approach for the purification of stem cells. The proposed bioengineering strategies include the implementation of traditional [polyethylene glycol (PEG), dextran (DEX) and ficoll] and novel (Ucon) immunoaffinity ATPS to prove the viability of cluster of differentiation 133 (CD133(+) ) stem cells from human umbilical cord blood. Furthermore, the addition of the antibody is implemented to identify conditions under which contaminants and stem cells of interest concentrate in opposite phases. The objective of this work is to establish the initial basis for the development of a novel and scalable purification bioprocess for the selective recovery of CD133(+) stem cells employing immunoaffinity ATPS. The reported methodology allows a partitioning of 62% CD133(+) stem cells to the top phase of the ficoll 400,000-DEX 70,000 immunoaffinity ATPS. In PEG 8,000-DEX 500,000 and Ucon-DEX 75,000 systems, no difference was observed when compared with the conventional ATPS (without antibody addition), as the CD133 antibody does not have preference for the desired clean top phase. In all experiments, cell viability was at least 98% after ATPS recovery. This research highlights the challenges that must be addressed to allow the potential establishment of a separation process using immunoaffinity ATPS for the recovery and purification of stem cells.


The time course of responding to aversiveness in females with a history of non-suicidal self-injury.
Non-suicidal self-injury is a risk factor for suicidal behavior, particularly in females. Two prominent theories of suicide suggest that habituation to the psychophysiological aversiveness of NSSI is a mechanism by which NSSI exposure may lead to increased risk for suicide. Several laboratory studies examining the relationship between physiological habituation and suicide attempt history have yielded mixed results, potentially due to their use of broad measures of physiological arousal and/or focus on specific psychopathologies. However, no studies have examined the association between the time course (e.g., habituation, initial reactivity) of responding to aversiveness and NSSI, which may help to elucidate psychophysiological mechanisms of NSSI. Therefore, we examined habituation and initial reactivity to aversiveness (indexed by the time course of acoustic startle reflex, a well-validated measure of defensive responding) in three groups of young adult females - those with a history of NSSI, psychiatric controls matched on potential confounds (e.g., psychopathology, trauma history, demographics), and healthy controls. Results indicated that individuals with a history of NSSI exhibited blunted initial reactivity and marginally slower habituation to aversiveness relative to the two control groups. The NSSI group's insensitivity to aversiveness may reflect prior psychophysiological habituation, and may be a mechanism through which prior NSSI exposure leads to increased risk for suicidal behavior.


Stroke incidence is decreasing in whites but not in blacks: a population-based estimate of temporal trends in stroke incidence from the Greater Cincinnati/Northern Kentucky Stroke Study.
Although other studies (in largely white populations) have found that stroke incidence declined during the 1990s, we previously reported that stroke incidence in our population (18% of which was black) did not change during that decade and that incidence rates in blacks were significantly higher than in whites. We sought to update temporal trends in stroke incidence by adding new data obtained from our large, biracial population in 2005. The objective of this study was to examine temporal trends in stroke incidence and case-fatality within a large biracial population over time by comparing stroke incidence rates from 1993 to 1994, 1999, and 2005. Within the Greater Cincinnati/Northern Kentucky population of 1.3 million, all strokes among area residents were ascertained at all local hospitals during July 1993 to June 19/94 and calendar years 1999 and 2005. A sampling scheme was used to ascertain cases in the out-of-hospital setting. Only first-ever strokes were included in this analysis. Race-specific incidence rates, standardized to the 2000 US Census population, and case-fatality rates were calculated. The number of physician-confirmed first-ever strokes in patients >or=20 years of age was 1942 in 1993 to 1994, 2041 in 1999, and 1921 in 2005. In all study periods, blacks had higher stroke incidence than whites, and case-fatality rates were similar between races. In contrast to previous study periods, we found a significant decrease in overall stroke incidence in 2005. When stratified by race and stroke subtype, this change was driven by a decrease in ischemic stroke incidence among whites, whereas ischemic stroke incidence in blacks was unchanged. Hemorrhagic stroke incidence was unchanged in both races. For the first time, we report a significant decrease in stroke incidence within our population, which is consistent with other reports in the literature. This decrease was found only among whites, which suggests a worsening of the racial disparity in stroke incidence.


Kinetics of lysozyme activity recovered from conventional and silicone hydrogel contact lens materials.
We determined the activity of lysozyme recovered from various conventional and silicone hydrogel (SH) contact lens materials as a function of time, using an in vitro model. Polymacon, omafilcon, etafilcon, vifilcon, lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A and senofilcon A contact lenses (n = 5) were incubated in lysozyme solution for time periods ranging from 1 h to 28 days. Following the specified incubation period, the lysozyme deposited on the lenses was extracted and the sample extracts were assessed for lysozyme activity and total lysozyme. We found no significant difference (NSD) between omafilcon and polymacon lens materials for the initial 3 days (P > 0.05); however, there was a significant difference between the two lenses from 5 to 28 days (P < 0.05). There was NSD (P > 0.05) between etafilcon and vifilcon lens materials at all time-points and significant differences were seen between various SH lens materials at different time points. After 28 days, lysozyme deposited on etafilcon (90 +/- 3%) and vifilcon (91.4 +/- 3%) exhibited the greatest activity. Lysozyme deposited on polymacon (17.8 +/- 4%), lotrafilcon A (23.4 +/- 4%) and lotrafilcon B (24 +/- 5%) exhibited the lowest activity. Lysozyme deposited on omafilcon, galyfilcon, senofilcon and balafilcon exhibited 38 +/- 3%, 62.3 +/- 8%, 47 +/- 6% and 61 +/- 7% of activity, respectively. The reduction in activity of lysozyme deposited on contact lens materials is time-dependent and the rate of reduction varies between lens materials. This variation in activity recovered from lenses could be due to the differences in surface/bulk material properties or the location of lysozyme on these lenses.


Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case.
A 15-month-old girl with severe hemolytic anemia and progressive respiratory failure is presented. She was well until the age of six months when she developed a pulmonary infection. During the next six months, she had frequent respiratory infections and her paleness became evident. At the age of 12 months, she was observed to have easy fatigability and muscle weakness, and she received her first blood transfusion. She was referred to our hospital at the age of 15 months. The physical examination revealed a malnourished girl with hypotonia, nystagmus, generalized muscle weakness and severe breathing difficulty requiring ventilatory support The hemoglobin (Hb) was 9.7 g/dl; hematocrit (Hct) 29%, mean corpuscular volume (MCV) 101 fl and reticulocyte count 15%. Peripheral blood smear revealed macrocytosis and stomatocytosis (30% of the red cells) and polychromasia. Sweat chloride test was 90 and 94 mEq/L on two separate occasions. The serum vitamin E level was 0.26 mg/dl (N: 0.44-0.68). She was found to be heterozygous for factor V Leiden mutation. Although malnutrition, low serum vitamin E and elevated sweat chloride test were suggestive of cystic fibrosis, this diagnosis failed to account for all the findings in the patient. A search for a red cell enzyme deficiency revealed that the red cell triosephosphate isomerase (TPI) activity was low. DNA analysis showed the 315 G-C (105 Glu-Asp) TPI mutation, thus confirming the diagnosis of TPI deficiency.


Enflurane as a primary anesthetic agent for patients with chronic obstructive pulmonary disease.
For years, halothane has been the anesthetic agent of choice for patients with chronic obstructive pulmonary disease (COPD) and reversible airway disease (asthma). Enflurane was compared with halothane in 100 patients with COPD substantiated by spirometry and history. Intraoperative and postoperative complications in each relatively homogenous 50-patient group were assessed. Spirometry, blood gases, chest x-rays, incidence of complications involving secretions, coughing, wheezing, and cardiovascular problems were similar in both groups. Enflurane appears to be equivalent to halothane as an anesthetic in such patients.


High risk of misinterpreting liver and spleen stiffness using 2D shear-wave and transient elastography after a moderate or high calorie meal.
Food intake increases liver stiffness, but it is believed that liver stiffness returns to baseline two hours after a meal. The aim of this study was to investigate the impact of different sized meals on liver stiffness. Liver and spleen stiffness was measured with transient elastography (TE) and real-time 2-dimensional shear wave elastography (2D-SWE). Patients ingested a 625 kcal and a 1250 kcal liquid meal on two consecutive days. We measured liver and spleen elasticity, Controlled attenuation parameter (CAP) and portal flow at baseline and after 20, 40, 60, 120 and 180 minutes. Sixty patients participated, 83% with alcoholic liver disease. Twenty-eight patients had METAVIR fibrosis score F0-3 and 32 patients had cirrhosis. Liver stiffness, spleen stiffness and CAP increased after both meals for all stages of fibrosis. False positive 2D-SWE liver stiffness measurements caused 36% and 52% of patients with F0-3 fibrosis to be misclassified with higher stages of fibrosis after the moderate and high caloric meal. Likewise, 10% and 13% of compensated cirrhosis patients were misclassified with clinically significant portal hypertension after the two meals. We observed similar misclassification rates with TE. After three hours, liver stiffness remained elevated more than 20% from baseline in up to 50% of patients. Liver stiffness, spleen stiffness and CAP increase after a meal across all stages of fibrosis and across elastography techniques. Up to half of patients may be misclassified with higher stages of fibrosis, if they are assessed after less than three hours fasting period.


Management of Late Twin-to-Twin Transfusion Syndrome beyond 26 Weeks: Comparison between Fetoscopic Laser Therapy versus Traditional Management.
A proportion of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) can present after 26 weeks of gestation. The aim of this study was to compare perinatal outcomes of late TTTS treated by fetoscopic laser coagulation versus traditional management with amniodrainage and/or emergency preterm cesarean delivery (CD). Retrospective cohort from January 2012 to January 2023 of consecutive MCDA twin pregnancies complicated by TTTS after 26 weeks and evaluated in our referring centers. We analyzed perinatal outcomes of cases treated with fetoscopic laser surgery at our national referral fetal surgery center in Queretaro, Mexico, and compared them with those managed with traditional management (amniodrainage and/or emergency preterm CD). The primary outcome was survival at discharge and the secondary outcome was gestational age (GA) at birth. Among the study population, 46 TTTS cases were treated by fetoscopy at 27+6 (26+0-31+0) weeks+days and were compared with a group of 39 cases who underwent emergency preterm CD. In comparison to the group who underwent traditional management, the group treated by laser fetoscopy showed a significantly higher GA at birth (32+3 vs. 29+1 weeks+days, p < 0.001), lower frequency of preterm delivery below 37 weeks (91.3% vs. 100%, p = 0.06), 34 weeks (63.0% vs. 100%, p < 0.001), 32 weeks (50% vs. 74.4%, p = 0.02), or 30 weeks (28.3% vs. 53.8%, p = 0.01), and significantly higher perinatal survival (89.1% vs. 71.8%, p < 0.05 of at least one twin; and 65.2% vs. 38.5%, p = 0.01 of both twins, respectively). MCDA twins complicated with TTTS can be treated with fetoscopic laser surgery between 26 and 31 weeks of gestation, which is a feasible and safe option, and such cases are associated with a higher GA at birth and better perinatal survival than those managed with amniodrainage and/or emergency preterm CD.


Evidence for mediation of two releaser pheromones in the aggregation behavior of the gregarious desert locust,Schistocerca gregaria (forskal) (Orthoptera: Acrididae).
The response of nymphal and adult gregarious phase desert locust,Schistocerca gregaria, to a choice of two columns of air, one permeated with airborne volatiles emanating from nymphs or adults and the other untreated, was investigated in a single-chamber bioassay arena. The nymphs, whether released individually or in groups, preferred to be within the precinct of the air column treated with airborne volatiles of the nymphs but were indifferent to volatiles of the adults. Conversely, older adults responded only to their own volatiles but not to those of the nymphs or young adults. The young adults were responsive only to volatiles of the older adults. Charcoal-trapped volatiles from the nymphs and the adults reproduced the effect of living locusts. These results indicate that there are two different aggregation pheromones inS. gregaria: a juvenile pheromone produced by nymphs and an adult pheromone specific to adults.


Effects of seepage and weak interlayer on the failure modes of surrounding rock: model tests and numerical analysis.
The presence of weak interlayers and groundwater are common adverse geological conditions in tunnels. To investigate the modes of failure of rock masses surrounding tunnels owing to weak interlayers and groundwater, model tests and numerical simulations were conducted in this study based on two cases, and a model that considers only the weak interlayer was conducted for comparison. Based on the tests, differences between two models in terms of rock pressure, displacement, cracks and strain were analysed. The results reveal that the presence of groundwater has a significant effect on the space-time distribution of stress, displacement and cracks in the surrounding rock. Furthermore, based on the numerical model, the seepage field was analysed in terms of pore water pressure, permeability and the seepage process to understand the joint action of groundwater and weak interlayer on the failure mechanism of tunnels. The results show that the groundwater and interlayer complement each other to induce the failure mode of the surrounding rock. The water accelerates slip in the interlayer and the development of cracks. Conversely, low strength, muddy weak interlayers serve as the channels of water flow, resulting in deformations and cracks at different locations and different failure modes.


Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.
Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk. We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.


Ulipristal Acetate before Hysteroscopic and Laparoscopic Surgery for Uterine Myomas: Help or Hindrance?
Ulipristal acetate ([UPA], Esmya®) is an orally active selective progesterone-receptor modulator that has been approved as preoperative treatment for uterine myomas. This systematic review aims to summarize the available data on surgical outcomes of patients undergoing myomectomy by hysteroscopy or by laparoscopy after preoperative treatment with UPA. this review was performed following PRISMA guidelines and was registered in PROSPERO (CRD42018092201). PubMed, EMBASE, and Medline databases were systematically searched electronically until March 2018 for keywords concerning this topic. There were included only peer-reviewed, English language journal articles. two prospective studies and 4 retrospective studies were included. The effect of UPA on the endometrium does not increase the technical difficulty during hysteroscopic myomectomy, but it increases the chance of complete primary resection in complex hysteroscopic myomectomies. Moreover, UPA does not increase the overall technical difficulty of laparoscopic myomectomy. Contradictory results have been reported on the impact of UPA on the separation of the myoma from the myometrium and on the consistency of the myomas. current results support the use of UPA prior to both surgical procedures. Further studies should confirm these preliminary findings and to assess the long-term outcomes of myomectomies following UPA treatment.


The association between insomnia symptoms and risk of cardio-cerebral vascular events: A meta-analysis of prospective cohort studies.
Background Insomnia symptoms have been suggested to be associated with the risk of cardio-cerebral events. However, the results of previous studies have been inconsistent. Therefore, we conducted a meta-analysis to examine whether there were associations between cardio-cerebral vascular events and insomnia symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening or non-restorative sleep. Design A meta-analysis of prospective cohort studies. Methods PubMed, Web of science and the Cochrane Library were searched without language restriction. Prospective cohort studies of adults with at least a 2-year follow-up duration were included. Random effect models were used in order to pool the results for each insomnia symptom. Subgroup and sensitivity analyses were conducted in order to assess potential heterogeneity, and funnel plots and Egger's tests were used in order to assess publication bias. Results Fifteen studies (23 cohorts) were included. Positive associations were observed between difficulty initiating sleep, difficulty maintaining sleep and non-restorative sleep with risk of cardio-cerebral vascular events. The pooled relative risks and 95% confidence intervals were 1.27 (1.15-1.40), 1.11 (1.04-1.19) and 1.18 (1.05-1.33), respectively. However, less evidence existed to support the conclusions about the association between early-morning awakening and cardio-cerebral vascular events. Conclusion Our meta-analysis demonstrated that insomnia symptoms of difficulty initiating sleep, difficulty maintaining sleep and non-restorative sleep were associated with an increased risk of future cardio-cerebral vascular events.


Mechanosignaling-related angiocrine factors drive osteoblastic phenotype in response to zirconia.
The growing use of zirconia as a ceramic material in dentistry is attributed to its biocompatibility, mechanical properties, esthetic appearance, and reduced bacterial adhesion. These favorable properties make ceramic materials a viable alternative to commonly used titanium alloys. Mimicking the physiological properties of blood flow, particularly the mechanosignaling in endothelial cells (ECs), is crucial for enhancing our understanding of their role in the response to zirconia exposure. In this study, EC cultures were subjected to shear stress while being exposed to zirconia for up to 3 days. The conditioned medium obtained from these cultures was then used to expose osteoblasts for a duration of 7 days. To investigate the effects of zirconia on osteoblasts, we examined the expression of genes associated with osteoblast differentiation, including Runx2, Osterix, bone sialoprotein, and osteocalcin genes. Additionally, we assessed the impact of mechanosignaling-related angiocrine factors on extracellular matrix (ECM) remodeling by measuring the activities of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) during the acquisition of the osteogenic phenotype, which precedes mineralization. Our data revealed that mechanosignaling-related angiocrine factors play a crucial role in promoting an osteoblastic phenotype in response to zirconia exposure. Specifically, exposed osteoblasts exhibited significantly higher expression levels of genes associated with osteoblast differentiation, such as Runx2, Osterix, bone sialoprotein, and osteocalcin genes. Furthermore, the activities of MMP2 and MMP9, which are involved in ECM remodeling, were modulated by mechanosignaling-related angiocrine factors. This modulation is likely an initial event preceding the mineralization phase. Based on our findings, we propose that mechanosignaling drives the release of angiocrine factors capable of modulating the osteogenic phenotype at the biointerface with zirconia. This process creates a microenvironment that promotes wound healing and osseointegration. Moreover, these results highlight the importance of considering the mechanosignaling of endothelial cells in the modulation of bone healing and osseointegration in the context of blood vessel effects. Our data provide new insights and open avenues for further investigation into the influence of mechanosignaling on bone healing and the osseointegration of dental devices.


[Nursing ethics and new challenges].
The nursing profession has always placed great importance on the ethical requirements linked to its activities. However, the understanding and content to these activities has evolved over the course of history. Two approaches have been developed as the principal issues of nursing ethics: the ethics of virtue and the ethics of principles. The first approach enquires into the attitudes that must be held by a person in order to act as a good nurse. The second follows an inverse course and considers the actions and principles that must be respected in order to be a good professional. An approach that harmonises both perspectives must pose the following questions: What do we understand by nursing care? On what ethical principles is this form of understanding care based? What moral attitudes are related to caring correctly? In a modern professional model, the definition and exercise of care necessarily include consideration of team work. Similarly, carrying out a good caring function, that is to say quality nursing, requires apprenticeship on the one hand, and, on the other, the assimilation of the attitudes that are required in a person involved in caring. Both elements improve the capacity of the professionals to prevent and resolve ethical conflicts in the practice of care.


Family Income and Material Deprivation: Do They Matter for Sleep Quality and Quantity in Early Life? Evidence From a Longitudinal Study.
The aim of this article is to investigate the determinants of sleeping patterns in children up to age 9 on a large and geographically homogeneous sample of British children and parents, focusing in particular on the role of economic and social factors, specifically on income. The data of this study come from the Avon Longitudinal Study of Parents and Children, a long-term health research project that recruited over 14000 pregnant women who were due to give birth between April 1991 and December 1992 in Bristol and its surrounding areas, including some of Somerset and Gloucestershire. Logistic regression models for the sleep problem dummies and log-linear models for the sleep quantity. One additional item in the material deprivation index is associated to an increase of around 10-20% in the odds of having at least 1 sleep problem. Similarly, children from the richest families are less likely to have any sleep problem up to 115 months (around 20% reduction in the odds). Mother's characteristics (i.e., education and mental health in the pregnancy period) are also significant predictors. Sleep quantity does not vary much and is not sensitive to socioeconomic factors. Exposure to income-related inequalities affects child sleep. Further research is needed to understand if sleep in early life influences future health and economic trajectories.


Valuation and handling of dialogue in leadership: a grounded theory study in Swedish hospitals.
Leadership can positively affect the work environment and health. Communication and dialogue are an important part in leadership. Studies of how dialogue is valued and handled in first-line leadership have not so far been found. The aim of this study is to develop a theoretical understanding of how first-line leaders at hospitals in western Sweden value and handle dialogue in the organisation. The study design was explorative and based on grounded theory. Data collection consisted of interviews and observations. A total of 11 first-line leaders at two hospitals in western Sweden were chosen as informants, and for four of them observation was also used. One core category emerged in the analysis: leaders' communicative actions, which could be strategically or understanding-oriented, and experienced as equal or unequal and performed equitably or inequitably, within a power relationship. Four different types of communicativeactions emerged: collaborative, nurturing, controlling, and confrontational. Leaders had strategies for creating arenas and relationships for dialogue, but dialogue could be constrained by external circumstances or ignorance of the frameworks needed to conduct and accomplish dialogue. First-line leaders should be offered guidance in understanding the consequences of consciously choosing and strengthening the communication component in leadership. The positive valuation of dialogue was not always manifest in practical action. One significant consequence of not using dialogue was that information with impact on organisational efficiency and finances was communicated upwards in the management system.


Cloning and sequencing of the pertussis toxin genes: operon structure and gene duplication.
Pertussis toxin, a protein composed of five different subunits (S1, S2, S3, S4, and S5), is the major virulence factor of Bordetella pertussis. We have cloned and sequenced a DNA fragment of 4.7 kilobases that contains the genes coding for the five subunits. The genes are clustered within 3.2 kilobases in the following order: S1, S2, S4, S5, and S3. A sequence closely resembling Escherichia coli promoters is found only before the S1 gene, and a possible termination signal is present at the end of the S3 gene, which suggests that the pertussis toxin genes are organized in a single operon. A possible Shine-Dalgarno sequence is present before the S1 gene but not before the other four genes that 8-12 nucleotides upstream from the ATG codon show a new consensus sequence, 5'TCC(T)GG3', possibly involved in the regulation of translation. We have also found sequence homology between the S2 and S3 genes and their protein products indicating that gene duplication played a major role in the evolution of pertussis toxin.


Environmental chemicals in pregnant women in the United States: NHANES 2003-2004.
Exposure to chemicals during fetal development can increase the risk of adverse health effects, and while biomonitoring studies suggest pregnant women are exposed to chemicals, little is known about the extent of multiple chemicals exposures among pregnant women in the United States. We analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. We analyzed data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003-2004, a nationally representative sample of the U.S. population. For each chemical analyte, we calculated descriptive statistics. We calculated the number of chemicals detected within the following chemical classes: polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), organochlorine pesticides, and phthalates and across multiple chemical classes. We compared chemical analyte concentrations for pregnant and nonpregnant women using least-squares geometric means, adjusting for demographic and physiological covariates. The percentage of pregnant women with detectable levels of an individual chemical ranged from 0 to 100%. Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons, and perchlorate were detected in 99-100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes. We found, generally, that levels in pregnant women were similar to or lower than levels in nonpregnant women; adjustment for covariates tended to increase levels in pregnant women compared with nonpregnant women. Pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy making.


Association of hematological parameters with metabolic syndrome in Beijing adult population: a longitudinal study.
The purposes of the study were to estimate the incidence of metabolic syndrome (MetS) and to systematically evaluate the relationship between hematological parameters and MetS in a 5-year follow-up of Beijing adult population. The longitudinal study included 3,180 adults, aged 20-65 years, who attended health check-ups in Beijing Tongren Hospital in 2007 and 2012. Multivariate logistic regression was conducted to explore the associations between hematological parameters and MetS. The 5-year cumulative incidence of MetS in this sample was 10.82 % (14.22 % for males and 7.59 % for females). Among all the hematological parameters, white blood cell count (WBC) was positively associated with MetS for 20-35-year-old (male OR 1.482, 95 % CI 1.169-2.974; female OR 1.398, 95 % CI 1.145-3.011), and 36-50-year-old (male OR 2.012, 95 % CI 1.290-4.010; female OR 3.400, 95 % CI 1.818-4.528) male and female subjects. Alanine aminotransferase (ALT) was significantly associated with the incidence of MetS for males (20-35-year-old OR 2.080, 95 % CI 1.371-3.159; 36-50-year-old OR 2.421, 95 % CI 1.335-3.412; 51-65-year-old OR 4.267, 95 % CI 1.161-6.781). Low-density lipoprotein cholesterol (LDL-C) was positively associated with MetS for 51-65-year-old (male OR 3.078, 95 % CI 2.468-5.131; female OR 2.140, 95 % CI 1.524-4.359) for male and female subjects. WBC is positively associated with MetS for young adults, while LDL-C is positively associated with MetS for elderly people. ALT is positively associated with MetS for males. Our findings provide further evidence in support of using hematological markers for early detection of individuals at risk for MetS.


Effects of dextran sulfates on the acute infection and growth stages of Toxoplasma gondii.
Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005-4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.


Soy- and rice-based formula and infant allergic to cow's milk.
Soy milk formula has limited medical indications for infants feeding, although in several parts of the world it has been used as a source of nutrition in a large number of children. It used to be the main alternative feeding for infants allergic to cow's milk who did not breastfeed before the introduction of extensively hydrolyzed formulas. Although there is a debate, the fact that some children are allergic to soy or some children with cow's milk allergy can present with concomitant soy allergy, restricted the use of soy formulas for treatment of infants allergic to cow's milk. Other grain-based formulas like the rice-based ones are promising in infants with cow's milk allergy. Grain-based formulas could be an alternative and cheaper way of nutrition for infants allergic to cow's milk than extensively hydrolyzed formulas. Further large scale longitudinal clinical studies are required to clarify the safety of soy and other grain-based formulas for treatment of cow's milk allergy.


Comparison of ornithine transcarbamylase from rat liver and intestine. Evidence for differential regulation of enzyme levels.
Ornithine transcarbamylase (OTCase) was purified from the small intestine of rat and the properties of the gut enzyme were compared with those of the enzyme from liver. The enzymes from both sources bound to the transition-state analog inhibitor, delta-N-(phosphonoacetyl)-L-ornithine, immobilized on Sepharose and eluted with carbamyl phosphate as a homogeneous preparation. The specific activities of the pure enzymes were 966 mumol min-1 mg-1 and 928 mumol min-1 mg-1 from liver and gut respectively, and the molecular mass, based on electrophoretic mobility, was 38 000 Da. The isoelectric point of the enzymes from both sources was 7.3. The enzymes from both sources cross-react to the same extent with antibodies against the liver enzyme on Western transfers and the size of the mRNA was identical on Northern transfers probed with a cDNA for the liver enzyme. Although OTCase is apparently the same gene product in both liver and gut, the enzyme levels respond differently to alterations in the protein content of the diet. OTCase in liver increased from 0.76 mumol min-1 microgram-1 DNA on 15% casein to 1.3 mumol min-1 microgram-1 DNA on 60% casein (P less than 0.01) whereas in small intestine the level decreased from 8.8 nmol min-1 microgram DNA on 15% casein to 5.7 nmol min-1 microgram-1 DNA on 60% casein (P less than 0.05). When expressed on a fresh-weight basis, the enzyme activity in liver shows the characteristic increase with increasing protein, whereas the activity in gut does not. The connection between these differences in gene expression and the different physiological roles of OTCase in liver and gut is discussed.


Pulse Intake Improves Nutrient Density among US Adult Consumers.
The objective was to examine trends in pulse (dry beans, dry peas, chickpeas and lentils) intake over a 10-year period and to compare nutrient intakes of pulse consumers and non-consumers to better understand the impact of pulse consumption on diet quality in the US population. NHANES 2003-2014 data for respondents (≥19 years) with 2 days of intake was used to evaluate trends in pulse intake. Pulse consumers were identified as those NHANES respondents who consumed pulses on one or both days. Differences in energy adjusted nutrient intakes between non-consumers and consumers were assessed. There were no significant trends in pulse intakes for the total population or for pulse consumers over the 10-year period. In 2013-2014, approximately 27% of adults consumed pulses with an intake of 70.9 ± 2.5 g/day over 2 days, just slightly <0.5 cup equivalents/day. At all levels of consumption, consumers had higher (p < 0.01) energy adjusted intakes of fiber, folate, magnesium. Higher energy adjusted intakes for potassium, zinc, iron and choline and lower intakes of fat were observed for consumers than for non-consumers at intakes ≥69.4 ± 1.01 g/day. These data suggest that pulse consumption in the US population may result in better diet quality with diets that are more nutrient dense than those without pulses.


Efficient study design for next generation sequencing.
Next Generation Sequencing represents a powerful tool for detecting genetic variation associated with human disease. Because of the high cost of this technology, it is critical that we develop efficient study designs that consider the trade-off between the number of subjects (n) and the coverage depth (µ). How we divide our resources between the two can greatly impact study success, particularly in pilot studies. We propose a strategy for selecting the optimal combination of n and µ for studies aimed at detecting rare variants and for studies aimed at detecting associations between rare or uncommon variants and disease. For detecting rare variants, we find the optimal coverage depth to be between 2 and 8 reads when using the likelihood ratio test. For association studies, we find the strategy of sequencing all available subjects to be preferable. In deriving these combinations, we provide a detailed analysis describing the distribution of depth across a genome and the depth needed to identify a minor allele in an individual. The optimal coverage depth depends on the aims of the study, and the chosen depth can have a large impact on study success.


Prevalence and risk factors of varicose veins among female hairdressers: a cross sectional study in north-east of Iran.
Venous diseases including varicose veins and chronic venous insufficiency are one of the most important pathogenic factors worldwide. High prevalence of varicose veins and its complications is an emerging problem in the twenty-first century. This study aimed to determine the prevalence and associated risk factors of varicose veins in female hairdressers in Shahroud, north of Iran in 2012. In this cross-sectional study, 197 employed hairdressers, licensed by the Health Department of Shahroud University of Medical Sciences, Iran, were studied. Standard physical examination was used to check the condition of varicose veins of the lower extremities of participants. Data were collected by demographic information form. Proportional odds model for ordinal logistic regression was used to assess the relationship between risk factors and status of varicose disease in subjects. Prevalence of varicose veins was 47.7%. Varicose veins were significantly associated with age (OR=1.08; 95% CI: 1.03, 1.13); family history of varicose disease (OR=1.99; 95% CI: 1.03, 3.82), blood pressure (OR=4.41; 95% CI: 1.63, 11.90); and duration of standing (OR=2.34; 95% CI: 1.05, 5.22). Varicose veins in the legs of female hairdressers had a high prevalence, and it was associated with increasing age, family history of varicose disease, high blood Pressure, and prolonged standing.


Efficacy and Safety of Sitagliptin in Hispanic/Latino Patients with Type 2 Diabetes: A Pooled Analysis from Ten Randomized, Placebo-Controlled Phase 3 Clinical Trials.
To assess the efficacy and safety profile of the dipeptidyl-peptidase-4 inhibitor sitagliptin in a population of self-identified Hispanic/Latino patients with type 2 diabetes. Data were pooled from ten randomized, double-blind studies in which subjects were treated with sitagliptin 100 mg/day (as mono- or combination therapy) or placebo, and used to evaluate the glycemic efficacy, safety, and tolerability of sitagliptin compared with placebo after 24 weeks of treatment. A total of 804 Hispanic/Latino patients were included in the analysis. Baseline characteristics in the treatment groups were similar (mean baseline HbA1c of approximately 8.5%). The LS mean HbA1c changes from baseline were - 0.94% with sitagliptin and - 0.32% with placebo, and the between-group difference was - 0.62%, p < 0.001. After 24 weeks of treatment, 35% and 18% of subjects were at the HbA1c goal of < 7% in the sitagliptin and placebo groups, respectively. Body weight increased slightly in both treatment groups. Incidences of adverse events of hypoglycemia were similar and low (1.9% and 1.4% for sitagliptin and placebo, respectively) in both groups in studies in which insulin or sulfonylurea were not used and were similar (9% and 11% for sitagliptin and placebo, respectively) when all studies were included. Overall safety and tolerability of treatment with sitagliptin and placebo were similar. No clinically meaningful differences between the safety profile of sitagliptin in the Hispanic/Latino population analyzed here and broader populations previously evaluated were observed. In this pooled analysis of sitagliptin therapy vs placebo in Hispanic/Latino patients, sitagliptin provided significant improvement in glycemic control and was generally well tolerated. Merck & Co., Inc., Kenilworth, NJ, USA.


Insights into charge carrier dynamics in organo-metal halide perovskites: from neat films to solar cells.
Organo-metal halide perovskites have recently obtained world-wide attention as promising solar cell materials. They have broad and strong light absorption along with excellent carrier transport properties which partially explain their record power conversion efficiencies above 22%. However, the basic understanding of the underlying physical mechanisms is still limited and there remain large discrepancies among reported transport characteristics of perovskite materials. Notably, the carrier mobility of perovskite samples either in thin films or within solar cells obtained using different techniques can vary by up to 7-8 orders of magnitude. This tutorial review aims to offer insights into the scope, advantages, limitations and latest developments of the techniques that have been applied for studying charge carrier dynamics in perovskites. We summarize a comprehensive set of measurements including (1) time-resolved laser spectroscopies (transient absorption, time-resolved photoluminescence, terahertz spectroscopy and microwave conductivity); (2) electrical transient techniques (charge extraction by linearly increasing voltage and time-of-flight); and (3) steady-state methods (field-effect transistor, Hall effect and space charge limited current). Firstly, the basics of the above measurements are described. We then comparatively summarize the charge carrier characteristics of perovskite-based neat films, bilayer films and solar cells. Finally, we compare the different approaches in evaluating the key parameters of transport dynamics and unravel the reasons for the large discrepancies among these methods. We anticipate that this tutorial review will serve as the entry point for understanding the experimental results from the above techniques and provide insights into charge carrier dynamics in perovskite materials and devices.


Arthroscopic Simulation-Based Training of Orthopaedic Surgery Residents: Past, Present, and Future.
Simulation-based training is required by many medical specialties. Barriers, however, have prevented widespread implementation of simulators for arthroscopic training. The advantages of arthroscopic simulator-based training of residents include decreased errors, decreased cost of training, and improved patient care. Before an educational program can focus on the type of simulator, it is essential to have a validated curriculum and framework for how to use those simulators. One of the most validated systems is called proficiency-based progression training. Proficiency-based progression is essentially a paradigm in which basic skills must be mastered and demonstrated via objective evaluation, before moving on to more advanced skills. There are a variety of different validation methods and tools that have been described, with the Arthroscopic Surgical Skill Evaluation Tool being the most widely used tool. It is essential that any simulator has evidence and validation that it will ultimately improve surgical skills in the operating room. In the future, emerging technologies such as virtual reality, augmented reality, and three-dimensional printing will likely play a major role in the creation of newer simulators and may improve access to residents throughout the world.


Substrate-affected lattice structural evolution in compressed monolayer ReS2.
At ambient conditions, the lattice structure of supported ultrathin transition metal dichalcogenides (TMDs) can be effectively modified by a substrate. When compressed, the effect of substrate is far from settled. In this study, the effects of an Si substrate on the lattice structures of compressed monolayer and multilayer ReS2 were investigated by performing high-pressure Raman measurements and first-principle calculations. Our results revealed substrate-affected strain in compressed monolayer ReS2, which resulted in a distorted unit with S atoms sliding within a single layer. This was evidenced by the split of the Ag-5 mode above 1.7 GPa. However, unlike that of the monolayer ReS2, the Ag-5 mode of multilayer ReS2 remained symmetric up to 4.2 GPa, which can be due to weaker substrate-affected strain in compressed multilayer ReS2 when compared with that in the monolayer ReS2. The noticeably different high-pressure responses between multilayer ReS2 and monolayer ReS2 can be due to the effect of interlayer interactions, and the split of the Ag-5 mode provides a clear indication of the prominent strain in compressed supported ReS2.


Integration of Mental and Behavioral Health in Pediatric Health Care Clinics.
Integrating behavioral health services into primary and pediatric health care settings is important to increase availability and access to quality mental and behavioral health care for children and adolescents. The Mental and Behavioral Health Capacity Project implemented models of pediatric integrated health care at Federally Qualified Health Clinics covering largely rural communities in Louisiana and impacted communities on the Florida Panhandle. The objectives of this article are to describe the programs and demonstrate sustainability and effectiveness of services provided. A subsample from the Louisiana clinics collected data at intake and follow-up at 1, 3, and 6-month intervals. The hypotheses were that child behavior problems and parenting stress would significantly decrease over the course of treatment. This study was conducted at 2 Federally Qualified Health Clinics in rural southeast Louisiana that provide pediatric primary health care. Sample parameters were child patients younger than 18 years presenting at primary health care clinics in Southeast Louisiana (N = 177); the mean age was 9.8 years (standard deviation = 4.3 years). Brief behavioral health services included parental education, medication management, stress management, empowerment, and psychodynamic interventions. The main outcome measures were the Pediatric Symptom Checklist and the Parenting Stress Index. Statistically significant decreases in child behavior problems and parenting stress were revealed, with 87% reporting satisfaction with services. Utilizing community-based and culturally sensitive approaches, mental and behavioral health integrated into pediatric health care clinics can be sustainable and effective at improving child behavior problems, parenting stress, and overall family functioning.


Bile acid synthesis precursors in familial combined hyperlipidemia: the oxysterols 24S-hydroxycholesterol and 27-hydroxycholesterol.
Familial combined hyperlipidemia (FCHL), the most common inherited disorder of lipid metabolism is characterized by increasing cholesterol synthesis precursors due to hepatic overproduction of cholesterol. The bile acids synthesis pathway has not been previously studied in FCHL. The aim of this work was to study the oxysterol levels which are involved in the bile acids synthesis from cholesterol in FCHL. Clinical parameters and subclinical atherosclerosis were studied in a total of 107 FCHL patients and 126 normolipidemic controls. Non cholesterol sterols (desmosterol and lanosterol) and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) were measured by high performance liquid chromatography tandem mass spectrometry. Desmosterol and lanosterol, markers of cholesterol synthesis, had a positive correlation with BMI and apo B. However, no correlation was found for 24S-hydroxycholesterol and 27-hydroxycholesterol, precursors of bile acids, with these clinical parameters. Only 27-hydroxycholesterol had a positive correlation with apo B, ρ=0.204 (P=0.037). All oxysterol levels were higher in FHCL as compared to normal controls. A total of 59 FCHL subjects (59%) presented values of 24S-hydroxycholesterol above the 95th percentile of this oxysterol in the control population. All oxysterols showed no association with fat mass in contrast with non-cholesterol sterols. FCHL subjects with oxysterol overproduction had less carotid intima media thickness (cIMT), which suggests less atherosclerosis in these subjects. In summary, our data indicate that high oxysterol levels might be good markers of FCHL, unrelated to fat mass, and may exert a protective mechanism for cholesterol accumulation.


Induction of deoxycytidine kinase by 5-azacytidine in an HL-60 cell line resistant to arabinosylcytosine.
Induction of 2'-deoxycytidine kinase (dCK) by 5-azacytidine (5-Aza-C) in a dCK-deficient HL-60 cell line resistant to 1-beta-D-arabinofuranosylcytosine (Ara-C) (HL-60/Ara-C) was examined by measurement of the incorporation of [3H]deoxycytidine ([3H] dCyd) into cellular DNA, the kinetic properties of purified dCK, the cytotoxic potency (IC50 values), and the DNA methylation patterns of 5-Aza-C-treated and untreated cells. Following a 72-hr exposure to 1 microM 5-Aza-C, the incorporation of [3H]dCyd into DNA was increased 6-fold and the total dCK activity was increased 12-fold, with a peak for both on day 6. The onset of dCK induction was dependent on the length of exposure time. The IC50 values for cell growth inhibition by Ara-C on day 3 were 0.08 microM for HL-60 cells, 12.5 microM for HL-60/Ara-C cells, and 0.55 microM for HL-60/Ara-C cells pretreated with 5-Aza-C for 40 hr. The Km and Vmax of dCyd for HL-60 dCK were similar to those for 5-Aza-C-induced HL-60/Ara-C dCK. The restriction enzymes Hpall, which cleaves CCGG sequences but cannot cleave at sites methylated at the internal cytosines (5'-CMeCGG), and Mspl, which cleaves sequences with internal methylated cytosine but cannot cleave at sites methylated at external cytosines (5'-MeCCGG), were used for DNA methylation pattern determination. The newly synthesized DNA of HL-60 wild-type cells was cleaved by Mspl to a greater extent than that of HL-60/Ara-C cells. After exposure to 1 microM 5-Aza-C for 40 hr, methylation patterns of newly synthesized DNA reverted in HL-60/Ara-C cells to a clevage pattern similar to that in HL-60 wild-type cells. When compared with untreated control, DNAs from 5-Aza-C-treated resistant cells were cleaved to a greater extent by Mspl than by Hpall, suggesting that internal cytosine-residue methylation was relatively uninhibited.(ABSTRACT TRUNCATED AT 250 WORDS)


Prosopis juliflora pollen allergen induced hypersensitivity and anaphylaxis studies in guinea pigs.
In vivo and in vitro allergenic activities of Prosopis juliflora pollen allergens were measured in guinea pigs. Intracutaneous skin test showed an early wheal flare response and a late erythema-redness, sensitized with various concentrations (100, 50, 25, 5 and 1.5 micrograms/ml) of Prosopis juliflora pollen extract after administration of a challenging dose. A 50 micrograms/ml sensitizing dose of Prosopis juliflora pollen allergen gave optimum skin response as both early and late effects. The nature of immunochemical reactivity between pollen allergens and reaginic antibodies were further characterized by histamine release test, gel diffusion test, radioallergosorbent test and passive cutaneous anaphylaxis test. These tests confirm allergenicity caused by Prosopis juliflora pollen allergens and showed the binding of allergens with reaginic antibody and its regulation in guinea pigs.


Psychological distress and smoking behavior: the nature of the relation differs by race/ethnicity.
We explored how the relation between psychological distress and smoking behavior differed as a function of race/ethnicity of respondents to a representative national survey. Data from the 2007 Health Information National Trends Survey were analyzed. Participants reported experiences of psychological distress in the past 30 days, race/ethnicity, current smoking status (smoker/nonsmoker), and number of cigarettes smoked per day. Logistic regression and linear regression analyses were used to examine the influence of race, distress, and their interaction on smoking behavior using survey weighting techniques to account for sampling strategy and nonresponse. For current smoking status, there was a significant interaction between race and psychological distress. Follow-up analyses indicated that psychological distress was related to smoking status for White but not for Black or Hispanic respondents. Similar results were found for number of cigarettes smoked per day among current smokers. The results suggest that the often-reported association between psychological distress and smoking is relatively specific to White individuals. The relation does not appear to characterize either Black or Hispanic individuals.