Identification of breast cancer prognostic modules based on weighted protein-protein interaction networks.
Breast cancer is one of the leading causes of mortality in females. A number of prognostic markers have been identified, including single genes, multi-gene signatures and network modules; however, the robustness of these prognostic markers is insufficient. Thus, the present study proposed a more robust method to identify breast cancer prognostic modules based on weighted protein-protein interaction networks, by integrating four sets of disease-associated expression profiles. Three identified prognostic modules were closely associated with prognosis-associated functions and survival time, as determined by Cox regression and Kaplan-Meier survival analyses. The robustness of these modules was verified with an independent profile from another platform. Genes from these modules may be useful as breast cancer prognostic markers. The prognostic modules could be used to determine the prognoses of patients with breast cancer and characterize patient recovery.


Behavioral Investments in the Short Term Fail to Produce a Sunk Cost Effect.
A cognitive bias known as the sunk cost effect has been found across a number of contexts. This bias drives the continued investment of time, effort, or money into an endeavor on the basis of prior investments into it. In Studies 1 and 2, we attempted to observe whether this effect occurs for short-term behavioral investments. In both studies, a reverse, or no sunk cost effect was found. In Study 3, we attempted to find an effect using hypothetical scenarios that were analagous to the behavioral investments presented in Study 1. This also failed to reveal an effect. Finally, Study 4 was an attempt to replicate a previously used hypothetical investment scenario; with results this time revealing the effect. A number of explanations for this pattern of results, such as participation and salient physical exertion, are discussed, with the possibility that some short-term behavioral investments are not subject to the sunk cost effect.


Mathematical models of parasite responses to host immune defences.
We examine the evolution of microparasites in response to the immune system of vertebrate hosts. We first describe a simple model for an acute infection. This model suggests that the within-host dynamics of the microparasite will be a 'race' between parasite multiplication and a clonally expanding response by the host immune system, resulting either in immune-mediated clearance or host death. In this very simple model, in which there is only a single parasite and host genotype, maximum transmission is obtained by parasites with intermediate rates of growth (and virulence). We examine how these predictions depend on key assumptions about the parasite and the host, and consider how this model may be expanded to incorporate the effect of additional complexities such as host-parasite co-evolution, host polymorphism, and multiple infections.


Distribution of pathogens and antimicrobial resistance in ICU-bloodstream infections during hospitalization: a nationwide surveillance study.
Changing microorganism distributions and decreasing antibiotic susceptibility over the duration of hospitalization have been described for the colonization or infection of selected organ systems. Few data are available on bacteremias in the intensive care unit (ICU) setting. We conducted a nationwide study on bloodstream infection (BSI) using data from the Swiss Centre for Antibiotic Resistance (ANRESIS). We analyzed data on BSI detected in the ICU from hospitals that sent information on a regular basis during the entire study period (2008-2017). We described specific trends of pathogen distribution and resistance during hospitalization duration. We included 6505 ICU- BSI isolates from 35 Swiss hospitals. We observed 2587 possible skin contaminants, 3788 bacteremias and 130 fungemias. The most common microorganism was Escherichia coli (23.2%, 910), followed by Staphylococcus aureus (18.7%, 734) and enterococci (13.1%, 515). Enterococcus spp (p < 0.0001) and Candida spp (p < 0.0001) increased in proportion, whereas E. coli (p < 0.0001) and S. aureus (p < 0.0001) proportions decreased during hospitalization. Resistances against first- and second-line antibiotics increased linearly during hospitalization. Pathogen distribution and antimicrobial resistance in ICU-BSI depends on the duration of the hospitalization. The proportion of enterococcal BSI, candidemia and resistant microorganisms against first- and second-line antibiotics increased during hospitalization.


Initial Decomposition Pathways of Aqueous Hydroxylamine Solutions.
This work examined the reaction pathways involved in the initial decomposition of aqueous hydroxylamine solutions via the overall reaction, 2NH2OH → NH3 + HNO + H2O, using quantum chemistry calculations incorporating solvent effects. Several possible decomposition mechanisms were identified and investigated: three neutral-neutral bimolecular, two water-catalyzed, one neutral trimolecular, two ion-neutral bimolecular, and one cation-catalyzed. Optimized structures for the reactants, products, and transition states were obtained at the ωB97XD/6-311++G(d,p)/SCRF = (solvent = water) level of theory, and the total electron energies of such structures were calculated at the CBS-QB3 level of theory. The cation-catalyzed reaction 2NH2OH + NH3OH+ → NH4+ + HNO + H2O + NH2OH (maximum energy barrier (ΔE0‡) = 53.6 kJ/mol) and the anion-neutral bimolecular reaction NH2OH + NH2O- → NH3 + 1NO- + H2O (ΔE0‡ = 79.0 kJ/mol) were both found to be plausible candidates for the dominant step in the initial decomposition. The results of this study indicate that both acidic and basic conditions can affect the thermal stability of hydroxylamine in water.


The Family APGAR Index: study on relationship between family function, social support, global stress and mental health perception in women.
The aim of the study was to evaluate how far women are satisfied with their family function to compare the obtained results with the perception of a global stress (S. Cohen PSS) by the women under study and their mental health (D. Goldberg GHQ-28). The study was aided by the Family APGAR Index (designed by G. Smilkstein) used for the first time in Poland. A group of women (n = 98; mean age = 38) with different levels of education and subdivided into four occupational categories was selected for the study. About 75% of women were married and 80% of them had children. The results obtained differ significantly as far as general assessment and individual indicators are concerned. In 16% of women, the results suggest a serious dysfunction of their families. There are distinct differences between individual occupational groups. The general assessment of family function was significantly correlated with the estimate of the global stress (-31), with the total estimate (-26), as well as with the individual indicators of mental health--especially anxiety and sleeplessness (-33) and depression (-29). Women's satisfaction from the function of their families has, therefore, proved to be a significant factor contributing to lower level of the global stress and constituting a barrier against the occurrence of mental health disturbances.


Factors affecting enamel and ceramic wear: a literature review.
Enamel wear by ceramics may adversely affect maintenance of the vertical dimension of occlusion and can increase the potential for thermal sensitivity. In this article, factors related to the abrasion of enamel by dental ceramics are critically reviewed. Concepts of physical, microstructural, chemical, and surface characteristics of dental ceramics on wear are presented based on research published since 1950. A PubMed search for key words (wear of enamel and ceramic) was supplemented with a hand search to identify relevant peer-reviewed articles published in English. Based on the literature, it can be concluded that material factors, their proper handling, and control of the patient's intrinsic risk factors related to wear are critically important to the reduction of enamel wear by dental ceramics.


Chiral exceptional point in transformation cavity.
Unlike the ideal circular whispering gallery cavities, those without mirror symmetry intrinsically support resonant modes exhibiting chirality which indicates an imbalance between clockwise and counterclockwise wave components. In extreme cases, nearly degenerate pairs of copropagating modes can be found around the chiral exceptional points (EPs) in parameter spaces. The chiral EPs have been studied in various schemes; however, most attention has been focused on the cases with piecewise constant or periodic refractive index profiles. In this Letter, we report the formation of a chiral EP in a gradient-index cavity designed by conformal transformation optics. Here, the mirror symmetry of the cavity is broken solely by its gradient index profile, and the parameter space is constructed with coordinate transformation parameters. We unveil the chirality, nonorthogonality, and complex-square-root topology near the chiral EP, which can be explained by the non-Hermitian model Hamiltonian.


[Isoprinosine treatment of herpes zoster. Résults of a control study in 36 subjects (author's transl)].
A double-blind trial comparing isoprinosine with a placebo was conducted in 36 subjects. Improvement of skin lesions was significantly better in the treatment group (p less than or equal to 0.01). Before entering the trial, patients in the treatment group had significantly more severe pain than those in the placebo group (p less than or equal to 0.01), the difference disappeared after treatment. Healing of skin lesions was more rapid in patients treated before the 5th day of the disease (p less than or equal to 0.03). None of the subjects developed post-zoster neuralgia. The clinical effects of the drugs were accompanied by a decrease in serum rosette activity. We consider isoprinosine as an innocuous and effective treatment of herpes zoster.


Trilateral retinoblastoma in a patient with Peutz-Jeghers syndrome.
Germline loss of function mutations in tumor suppressor genes RB1 and LKB1/STK11 are associated with the autosomal dominant cancer predisposing syndromes familial retinoblastoma and Peutz-Jeghers syndrome (PJS), respectively. We present a rare case of a young woman with trilateral retinoblastoma diagnosed as an infant who survived and was then diagnosed with PJS as a teenager. There was no family history of either disorder. Analysis of the LKB1/STK11 gene sequence identified a germline frameshift mutation (c.107del) leading to a nonsense mutation near the N-terminus of the protein, confirming a clinical diagnosis of Peutz-Jeghers syndrome. Extensive RB1 gene analysis failed to detect germline mutations or deletions, and immunohistochemical analysis of her ocular tumors demonstrated nuclear staining of immunoreactive pRB. This result suggests that the RB1 gene is intact. We estimate the chance of trilateral retinoblastoma and PJS occurring in the same individual at approximately 1 in 134 billion live births, and we discuss the possibility that this case could be explained by a putative modifier of pRB action that is associated with the LKB1/STK11 pathway.


Label free quantitative proteomics analysis on the cisplatin resistance in ovarian cancer cells.
Quantitative proteomics has been made great progress in recent years. Label free quantitative proteomics analysis based on the mass spectrometry is widely used. Using this technique, we determined the differentially expressed proteins in the cisplatin-sensitive ovarian cancer cells COC1 and cisplatin-resistant cells COC1/DDP before and after the application of cisplatin. Using the GO analysis, we classified those proteins into different subgroups bases on their cellular component, biological process, and molecular function. We also used KEGG pathway analysis to determine the key signal pathways that those proteins were involved in. There are 710 differential proteins between COC1 and COC1/DDP cells, 783 between COC1 and COC1/DDP cells treated with cisplatin, 917 between the COC1/DDP cells and COC1/DDP cells treated with LaCl3, 775 between COC1/DDP cells treated with cisplatin and COC1/DDP cells treated with cisplatin and LaCl3. Among the same 411 differentially expressed proteins in cisplatin-sensitive COC1 cells and cisplain-resistant COC1/DDP cells before and after cisplatin treatment, 14% of them were localized on the cell membrane. According to the KEGG results, differentially expressed proteins were classified into 21 groups. The most abundant proteins were involved in spliceosome. This study lays a foundation for deciphering the mechanism for drug resistance in ovarian tumor.


Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.
The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = -0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.


Experimental probing of dynamic self-organized columnar assemblies in colloidal liquid crystals.
Self-organized supramolecular assemblies are widespread in nature and technology in the form of liquid crystals, colloids, and gels. The reversible nature of non-covalent bonding leads to dynamic functions such as stimuli-responsive switching and self-healing, which are unachievable from an isolated molecule. However, multiple intermolecular interactions generate diverse conformational and configurational molecular motions over various time scales in their self-assembled states, and their specific dynamics remains unclear. In the present study, we have experimentally unveiled the static structures and dynamical behaviors in columnar colloidal liquid crystals by a coherent X-ray scattering technique using refined model samples. We have found that controlling the size distribution of the colloidal nanoplates dramatically changed their static and dynamic properties. Furthermore, the resulting dynamical behaviors obtained by X-ray photon correlation spectroscopy have been successfully decomposed into multiple distinct modes, allowing us to explore the dynamical origin in the colloidal liquid-crystalline state. The present approaches using a columnar liquid crystal may contribute to a better understanding of the dynamic nature of molecular assemblies and dense colloidal systems and bring valuable insights into rational design of functional properties of self-assembled materials such as stimuli-responsive liquid crystals, self-healing gels, and colloidal crystals. For these materials, the motion of constituent particles and molecules in the self-assembled state is a key factor for structural formation and dynamically responsive performance.


The effect of raw and fermented rapeseed cake on growth performance, carcass traits, and breast meat quality in turkey.
The objective of this study was to determine the effect of including 15% of raw or fermented rapeseed cake (RRC or FRC) in turkey diets on growth performance, carcass traits, and breast meat characteristics. A total of 1,350 day-old female Hybrid Converter turkeys were allocated to 3 dietary treatments (9 replicates per treatment and 50 birds each) and fed complete isocaloric and isonitrogenous diets. In the control group, soybean meal was the main source of dietary protein, whereas the experimental groups were fed diets containing 15% of RRC or FRC. The fermentation of rapeseed cake reduced the content of glucosinolates and phytate-phosphorus. In comparison with RRC, turkeys receiving FRC achieved significantly higher final BW, comparable with that noted in the control group. The experimental factor had no effect on carcass dressing percentage or carcass fat content, whereas turkeys fed diets containing rapeseed cake were characterized by lower relative weight of breast muscles and higher relative gizzard weight. The muscles of birds from groups RRC and FRC had also significantly lower cholesterol concentration. In comparison with control diet, diets RRC and FRC contributed to a significant decrease in the levels of saturated fatty acids and an increase in the share of n-6 polyunsaturated fatty acids in the total fatty acid pool in breast meat. The highest concentrations of n-3 polyunsaturated fatty acids and the most desirable n-6/n-3 polyunsaturated fatty acid ratio were noted in the breast muscles of RRC group turkeys. Both RRC and FRC reduced catalase and superoxide dismutase activity, and decreased the malondialdehyde content of muscle tissue. In conclusion, the replacement of RRC with FRC in diets led to an increase in the final BW of turkeys, but it had no influence on carcass quality and the majority of meat quality traits. The inclusion of rapeseed products in turkey diets positively affected meat quality, improving the fatty acid profile and antioxidant status, but it also decreased the yield of breast muscles.


Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.
Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.


Reconstructing past changes in locus-specific recombination rates.
Recombination rates vary at the level of the species, population and individual. Now recognized as a transient feature of the genome, recombination rates at a given locus can change markedly over time. Existing inferential methods, predominantly based on linkage disequilibrium patterns, return a long-term average estimate of past recombination rates. Such estimates can be misleading, but no analytical framework to infer recombination rates that have changed over time is currently available. We apply coalescent modeling in conjunction with a suite of summary statistics to show that the recombination history of a locus can be reconstructed from a time series of genetic samples. More usefully, we describe a new method, based on n-tuple dataset subsampling, to infer past changes in recombination rate from DNA sequences taken at a single time point. This subsampling strategy can correctly assign simulated loci to constant, increasing and decreasing recombination models with an accuracy of 84%. While providing an important stepping-stone to determining past recombination rates, n-tuple subsampling still exhibits a moderate error rate. Theoretical limitations indicated by coalescent theory suggest that highly accurate inference of past recombination rates will remain challenging. Nevertheless, we show for the first time that reconstructing historic recombination rates is possible in principle.


Prognosis and sequelae of meth(acrylate) sensitization in beauticians and consumers of manicure materials.
Allergic contact dermatitis from (meth)acrylic monomers (ACDMA) in manicure products is increasing. To evaluate the prognosis, work performance impairment and sequelae of a cohort of beauticians and manicure consumers with ACDMA sensitized from the exposure to manicure products. We conducted a telephone survey with patients diagnosed with ACDMA. One hundred and six patients were evaluated, including 75 (70.8%) beauticians and 31 (29.2%) consumers. All were women with a mean age of 39 (19-62). Thirty-seven of 75 beauticians (49.3%) continued to work. Twenty-seven of 106 (25.5%) patients continued to use manicure products with (meth)acrylates regularly. Seventeen of 51 (33.3%) patients who discontinued the exposure described ongoing nail/periungual changes. Nine of 58 (15.5%) patients who required dental restoration, orthodontic or occlusal splint materials recalled reactions from them; and, 25 of 96 (26%) who used sanitary napkins recalled intolerance to them starting after the diagnosis of ACDMA. Fifteen of 25 (60%) discontinued the use of sanitary napkins. 49.3% beauticians continued to work; most patients stopped wearing acrylic manicure materials; reactions from dental materials were not uncommon, however, removal of dental materials was never required; and, reactions to sanitary napkins developing after the diagnosis of ACDMA were common most leading to discontinuation of use.


Australian Dental Research Fund Trebitsch Scholarship. Immunohistological analysis of an in vivo Porphyromonas gingivalis-induced lesion in mice.
Animal models have been used to study the pathogenic ability of putative periodontopathic bacteria. Injection of mice with live Porphyromonas gingivalis extracts has been shown to induce primary lesions which develop at the site of injection within one day and secondary lesions which develop at a distant site some 3-5 days later. These lesions are primarily polymorphonuclear cell (PMN) infiltrates. Recently, extensive data have shown that PMN activity may in part be controlled by T cells. Hence the aim of this report was to use the mouse model to determine the presence of T cells and macrophages in primary lesions in order to describe a baseline to be used for comparison in future studies.


Conceptualizing antiretroviral adherence in Beijing, China.
International health experts agree that China is on the verge of an AIDS crisis. In response, the Chinese government initiated the "Four Frees and One Care" policy in 2003 to decrease economic barriers and increase access to antiretroviral therapies for people with HIV. However, long-term treatment success requires not only access, but high rates of medication adherence. This qualitative interview study with 29 persons receiving HIV care at Beijing's Ditan Hospital identified barriers to and facilitators of medication adherence. The interviews were guided by an a priori conceptual model of adherence with four components: access, knowledge about medications, motivation, and proximal cues to action. Barriers to adherence were related to stigma and fear of discrimination; the medications themselves (including side-effects and complicated dosing regimens); and other economic issues (i.e. costs of transportation, lab tests and hospitalizations). Facilitators included participants' strong will to live, use of electronic reminders and family support. These results support the conceptual model and suggest that successful interventions must minimize stigma as it negatively affects all components of the model for adherence.


Structure and expression of the genes encoding the alpha and beta subunits of yeast phenylalanyl-tRNA synthetase.
The two genes FRS1 and FRS2 encoding, respectively, the large (alpha) and small (beta) subunits of cytoplasmic phenylalanyl-tRNA synthetase from bakers' yeast have been cloned and sequenced. The derived protein primary structures are confirmed by peptide sequences evenly distributed along the reading frames. These predict a subunit Mr of 67,347 for alpha and 57,433 for beta, in good agreement with earlier determinations carried out on the purified protein. These subunit sequences have been compared to those of Escherichia coli phenylalanyl-tRNA synthetase as well as to the small beta subunit of the corresponding yeast mitochondrial enzyme; limited but significant homology was found between the two alpha subunits on the one hand and between the three beta subunits on the other hand. The results suggest that these three enzymes, from E. coli, yeast cytoplasm, and yeast mitochondria, have strongly diverged from one another. The initiation sites of transcription have been determined for both yeast genes. Their 5'-upstream regions show no sequence similarities that would have indicated a coordinate control of gene expression at the transcriptional level. Measurements of steady-state levels of FRS-mRNAs in overproducing strains indicate that there is no restriction in mRNA synthesis. Therefore the control of gene expression, leading to a balanced synthesis of alpha and beta subunits, is likely to occur at the translational level.


Welcoming teleretinography into diabetes integrated care.
Integrated Care (IC) is a perfect fit for people with diabetes. Fundus examination (FE) is a disease marker for diabetologists and identifies potentially blinding complications (Diabetic Retinopathy, DR). In our Diabetes Clinic (DC) in Pescara, Italy, FE is possibly provided with telemedicine in same day as other exams, avoiding it to be a standalone clinical one; images taken with a retinal digital camera are graded by a remote ophthalmologist within a shared Electronic Health Record (EHR), immediately readable by other stakeholders; a dedicated care path to the Eye Clinic, University of Chieti-Pescara is provided for urgent cases. Personnel's worktime shortening allows gaining time for ophthalmologists' eye examinations in outpatient settings and other stakeholders' work in the DC. The need for a DR digital screening system is growing worldwide: our experience confirms the ease of implementation, and the advantage of sharing clinical data with all stakeholders when working within an EHR, aiming to optimize an IC effective system.


Sequential renal and bone marrow transplants in a child with Fanconi anemia.
FA is an autosomal recessive disorder characterized by small stature and renal abnormalities. FA can lead to progressive bone marrow failure, myelodysplastic syndrome, or acute leukemia. Using a multidisciplinary team approach, we managed a 3-yr-old boy with FA who simultaneously developed renal and hematopoietic failure. Because renal function was insufficient to support the conditioning regimen for HCT, we performed a deceased donor renal transplant in December 2012 prior to HCT with the known risk of graft-versus-graft rejection of the donor kidney. Seven months later he underwent allogeneic HCT. He obtained myeloid engraftment on day +11 and peripheral blood chimerism demonstrated all donor by day +21. He developed asymptomatic CMV reactivation and despite antirejection medications, mild skin graft-versus-host disease. He has maintained excellent renal function and remains transfusion independent with full hematopoietic recovery. He has not experienced any renal rejection episodes nor developed donor-specific antibodies toward his renal donor. Peripheral blood chimerism remains completely HCT donor. He is clinically well, now greater than two and a half yr after renal transplant and two yr after HCT. The continuing close collaboration between the Pediatric Nephrology and Bone Marrow Transplant teams is a major factor in this successful outcome.


Decisional balance and stage of change in relation to weight loss, exercise and dietary fat reduction among Pacific Islands people.
It has been postulated that changes in lifestyle follow five 'stages of change', which reflect a 'decisional balance' between the advantages and disadvantages of making such a change. We have assessed this model among Pacific Islands people in New Zealand. We questioned 105 Pacific Islands volunteers to identify their decisional balance for their reduction in dietary fat intake (DFI), weight control (WC) and the adoption of regular exercise habits (REH). Answers were used to develop a closed questionnaire, which was completed by a second group of 195 Pacific Islands volunteers. The major reported advantages were good health (45%) and increased physical attractiveness (41%) for WC; disease prevention (70%) for DFI; and increased fitness (71%) for REH. The major reported disadvantages were losing too much weight (40%) for WC; eating fatty foods was enjoyable (50%) for DFI; and the time required (47%) for REH. Major differences in responses were found by age, sex, Islands group and educational status. The derived decisional balance questions related to the stage of change with advantages outweighing disadvantages for those in the maintenance/action phases and the converse for those in the precontemplative phase. The use of this model will be helpful in evaluating long-term programs aimed at the primary prevention of non-insulin-dependent diabetes through lifestyle change.


The therapeutic dental challenge of xeroderma pigmentosum patients: case report.
Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a hypersensitivity to ultraviolet (UV) radiation leading to defective deoxyribonucleic acid (DNA) repair and predisposing to skin tumorigenesis. This paper reports the safe approaches used for the dental treatment of XP patients, controlling the ultraviolet (UV) sources at the dental office. An XP 29-year-old woman was referred for oral pain and sensitivity at the service of periodontology, UV rays were checked with a UV-meter. During the examination, the patient kept her sunglasses while the practitioner was dressed in dark colors using an anti-UV filter over the surgical light. Facial dark brown pigmentations, limited mouth opening, tumor resection scar on the tongue, moderate periodontitis, and dental caries were noticed. Moderate periodontitis and dental caries were diagnosed. Treatment was planned in collaboration with the dermatologist. Soft scaling and root planning were performed in short sessions and self-curing material was used for coronary fillings after caries removal. In taking care of XP patients, particular attention should be given by dental professionals to: i) the office management for a UV-safe environment; ii) the adoption of suitable dental care and safe biomaterials with short sessions and regular controls; and iii) the adoption of personal protections by patients and practitioners.


Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis.
To evaluate serum creatine kinase (CK) levels of amyotrophic lateral sclerosis (ALS) patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients. We analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI), serum creatinine (Cr), and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan-Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS. Baseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20-2,574 U/L), and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169) versus 117 (111) U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001). CK levels were also correlated with serum Cr (p = 0.011) and the spontaneous potential score of electromyography (EMG) (p = 0.037) but not correlated with age (p = 0.883), disease duration (p = 0.116), or BMI (p = 0.481). Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221-0.947, p = 0.035) after adjusting for age, sex, site of onset, serum Cr, and BMI. Serum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients.


Prolongation of murine skin allograft survival by immunologic manipulation with anti-interleukin 2 receptor antibody.
Administration of a rat monoclonal antibody (M7/20) directed against the murine interleukin 2 (IL 2) receptor in combination with sublethal x-irradiation of the recipient significantly enhanced the survival of skin allografts, both when the grafts were MHC disparate from the hosts and when only minor histocompatibility differences were present compared with untreated controls. No prolongation in graft survival was seen with either treatment alone at the dose employed. M7/20 and x-ray-treated allograft recipients also displayed significantly decreased alloantigen-specific reactivity against donor-strain spleen cells in both delayed-type hypersensitivity and cytotoxicity assays. Thus, such combination treatment reduces expression of host immune reactivity against graft determinants by several criteria. This work provides additional evidence that monoclonal antibodies directed against the IL 2 receptor may be useful in clinical transplantation.


Bioprospecting marine actinomycetes for antileishmanial drugs: current perspectives and future prospects.
Revived analysis interests in natural products in the hope of discovering new and novel antileishmanial drug leads have been driven partially by the increasing incidence of drug resistance. However, the search for novel chemotherapeutics to combat drug resistance had previously concentrated on the terrestrial environment. As a result, the marine environment was often overlooked. For example, actinomycetes are an immensely important group of bacteria for antibiotic production, producing two-thirds of the known antibiotics. However, these bacteria have been isolated primarily from terrestrial sources. Consequently, there have been revived efforts to discover new compounds from uncharted or uncommon environments like the marine ecosystem. Isolation, purification and structure elucidation of target compounds from complex metabolic extract are major challenges in natural products chemistry. As a result, marine-derived natural products from actinomycetes that have antileishmanial bioactivity potentials have been understudied. This review highlights metagenomic and bioassay approaches which could help streamline the drug discovery process thereby greatly reducing time and cost of dereplication to identify suitable antileishmanial drug candidates.


[Assessment of the cost of the curative treatment of myocardial infarction in the Abidjan Cardiology Institute].
We carried out an economical study on a period of four years from august 2001 to june 2005 in 100 patients with acute myocardial infarction admitted in the intensive care unit and in the medicine department of the Abidjan Cardiology institute. The aim of this study was to evaluate the total cost of an hospitalisation for myocardial infarction in a sub-saharan country. The average estimated cost was 944 481 F CFA (1439.7 euros) (range: 105,4237.7 euros) This cost was mainly explained by medical treatment with 324,996 F CFA, being 34.4% of the mean total cost followed by the cost of bedroom (300,200 F CFA (31.8%) and explorations costs (31.8%). 55% of our patients spent more than one million for the treatment. Neither the siege nor the appearance of left ventricular insufficiency had any incidence on the cost.


In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis.
In this work, we assess antituberculosis activity of OTB-658 in vitro and in vivo. In vitro, OTB-658 showed bacteriostatic effectiveness with a lower MIC than linezolid against Mycobacterium tuberculosis. The minimal bactericidal concentrations and time-kill curves for OTB-658 indicated inhibition activity similar to that of linezolid. OTB-658 entered macrophages to inhibit M. tuberculosis growth. OTB-658 had a low mutation frequency (10-8), which would prevent drug-resistant mutations from emerging in combination regimens. In vivo, OTB-658 reduced CFU counts in the lungs and slightly inhibited bacterial growth in the spleen in the early stage and steady state in acute and chronic murine TB models. These results support the preclinical evaluation of OTB-658 and further clinical trials in China.


Early adolescent Depo-Provera exposure increases stillbirths in adult sooty mangabeys.
The 3-month injectable contraceptive medroxyprogesterone acetate (MPA; Depo-Provera) is a synthetic progestin that protects against pregnancy by suppressing ovulation. Studies have focused on the resumption of ovulation after MPA-treatment cessation but neglected potential long-term effects of MPA exposure on future successful reproduction. MPA is frequently administered to adolescent girls; however, long-term fertility effects of adolescent MPA exposure have not been explored. We investigated fertility after extended MPA exposure in a species of old world primate, the sooty mangabey (Cercocebus atys). Female sooty mangabeys (n=31) received chronic MPA-treatment for 4-8 years. At MPA-treatment onset, subjects were either parous adults (n=14) or nulliparous adolescents (n=17), with adolescent-treated subjects being further divided into those who had reached first ovulation (n=10) and those who had not (n=7). After MPA-treatment cessation, adolescent-treated females had a significantly higher incidence of stillbirth than did age-matched and parity-matched controls, whereas adult-treated females did not differ from their matched controls. Females placed on MPA-treatment prior to first ovulation had a significantly higher incidence of stillbirth post-treatment than did females placed on MPA-treatment after first ovulation. Diabetic females had an increased incidence of stillbirth as compared to nondiabetic females; however, when controlling for diabetes, MPA exposure prior to first ovulation was still a significant positive predictor of stillbirth. These findings suggest that the post-treatment fertility effects of chronic MPA exposure vary with the developmental timing of treatment onset and raise concern about the use of MPA as a contraceptive for adolescent girls.


Pharmacodynamics and differential activity of nitrofurantoin against ESBL-positive pathogens involved in urinary tract infections.
Although nitrofurantoin has been used for >60 years for the treatment of uncomplicated urinary tract infections, its pharmacodynamic properties are not fully explored. Use is increasing because of increasing resistance to other antimicrobials due to ESBLs. We tested nine ESBL+ and two ESBL- strains in time-kill assays. Bactericidal activity and regrowth were assessed for all species and concentrations. Early-phase pharmacodynamics was analysed with a sigmoidal Emax model and the maximal killing rate, slope and EC50/MIC ratio were determined for each species. A bactericidal effect was found at ≥2× MIC for Enterobacter cloacae after 4-8 h, for Klebsiella pneumoniae after 8-10 h and for Escherichia coli after 12-16 h. Overall, no killing was observed at low sub-MIC concentrations, whereas regrowth was found at 0.5-1× MIC after a short decline in cfu. The lowest maximal killing rates were observed for E. coli (0.21 ± 0.05 h(-1)), followed by K. pneumoniae (0.37 ± 0.09 h(-1)) and E. cloacae (0.87 ± 0.01 h(-1)). Surprisingly, the Hill slopes for these three species were significantly different (10.45 ± 9.37, 2.68 ± 0.64 and 1.01 ± 0.06, respectively), indicating a strong concentration-dependent early-phase antibacterial activity against E. cloacae. EC50/MIC ratios were significantly lower for E. coli (0.24 ± 0.08 mg/L) and K. pneumoniae (0.27 ± 0.03 mg/L) as compared with E. cloacae (0.77 ± 0.18 mg/L). Nitrofurantoin was bactericidal against all species, demonstrating an unusual differential pattern of activity with concentration-dependent-type killing behaviour against E. cloacae and time-dependent killing behaviour against E. coli, which may have significant consequences on species-dependent dosing regimens. The results also demonstrate that the pharmacodynamic properties of some drugs cannot be generalized within a family, here the Enterobacteriaceae.


F90927: a new member in the class of cardioactive steroids.
F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca2+ channel by shifting its voltage-dependent activation toward more negative potentials. This leads to an increased influx of Ca2+ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca2+ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca2+ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the alpha1 subunit. F90927 exhibits no use dependence and interacts with Ca2+ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca2+ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca2+ channel.


Ewing's sarcoma of scapula: a rare entity.
Ewing's sarcoma is the second most common malignant bone tumour of childhood and adolescence. It may affect any bone, but it is frequent in the femur, ilium and the tibia. Here the authors are reporting a case of Ewing's sarcoma involving scapula in a 14-year-old boy presenting with pain and swelling around the shoulder. Swelling was removed which on histopathological examination showed solid sheets closely packed, poorly differentiated small cells that have a high nuclear-cytoplasmic ratio, fine chromatin and small nucleoli. A tentative diagnosis of Ewing's sarcoma was made which was confirmed by immunohistochemistry.


Overuse Injuries in the IDF's Combat Training Units: Rates, Types, and Mechanisms of Injury.
Overuse injuries are responsible for most lost training days and attrition from combat training in the Israeli Defense Forces (IDF) as in armies around the world. The purpose of this study is to understand the rates, types, and mechanism of occurrence of overuse injuries in the IDF in order to provide the IDF's commanders a detailed updated situation report in order to enable commanders decision-making, prevention policy, and further research of this highly significant military public health issue. A cross-sectional study including 20,000 soldiers recruited to combat units during the year of 2013 was performed. Most of the data were collected from the IDF's computerized medical consultation records package. Descriptive statistics (percent, mean, standard deviation, and median) were used in order to express results. The study was approved by the IDF's institutional review board. The overall injury rate was 24.5%. The total number of injuries was 6,393 with an average of 1.32 ± 0.22 injuries per injured soldier. The injury rate was 18.4% in the infantry units and 36.1% in non-infantry units. Of all injuries, 87% occurred in the lower back and lower limb regions. The most frequent injury sites were the calf and ankle (34%), the knee region (22%), and the lower back (19%). Of all injuries, 74% occurred during running (45%) or long-distance walking (29%). The average lost training days due to injuries was 9 d per soldier and 6.5 d per injury. The total number of stress fractures was 494-2.5% of all soldiers (four fractures per 100 person years). The calf and ankle region was the most frequent site of stress fractures and accounted for 84% of all stress fractures, the vast majority of them (95%) were fractures of the distal tibia. The average number of lost training days due to stress fractures was 16 ± 6.1 per fracture. As in other armies around the world, overuse injuries in the IDF are a major public health problem and poses a significant challenge to the IDF's commanders and the medical corps policy leaders. Further studies should be performed in order to identify the risk factors for these injuries especially in the lower back and the lower limb regions as part of the effort to try and reduce the rates of these injuries as much as possible. This study emphasizes the need for a continuous surveillance and monitoring system for overuse injuries as a significant and integral component of any intervention plan in the domain of overuse injuries.


Existence Arbuscula Mycorrhiza and Its Application Effect to Several Variety of Corn Plant (<I>Zeal mays </I> L.) in Marginal Dry Land.
Arbuscula mycorrhiza (AM) have a very large function in symbiosis with plant roots, it's very important to be studied further because AM utilization is an alternative solution to improve the yield of corn plant in poor land. Until now the productivity of corn plant, especially in Southeast Sulawesi, Indonesia is lower than it's genetic potential, one of the causes is the cultivation of many plant done in sub optimal land with low technology applications especially the use of organic and biological fertilizer very low. This study aimed to observe the presence of AM and evaluate the growth and productivity of corn plant that AM inoculated. The study consisted two series of experiments, namely (1) Existence arbuscula mycorrhiza in rhizosphere of dominant weed (bladygrass) in dry land in Kendari, Southeast Sulawesi, Indonesia, was observed descriptively, (2) Effect of arbuscula mycorrhiza to several variety of corn plant (Zea mays L.) in Marginal dry land. The experiment was arranged based Randomized Block Design (RBD) consisted of eight treatments corn variety. The results showed that spore populations were found in rhizosphere of dominant weed was 792-901 spores 100 g-1 soil, 70-90% roots infection. Some genera found are Glomus, Gigasphora, Acaulospora, Entrophospora, Scutellospora. Symbiosis effect of arbuscula mycorrhiza with plant growth indicates that Phosphorus uptake was highest in Batu Putih variety. However the highest in yield was show in Dana variety. Compared with the lowest production, the production difference was higher in Dana 47.70%. Existence of arbuscula mycorrhiza in dominant weed rhizosphere in dry land is very high. The response of various varieties of maize plants to arbuscula mycorrhiza indicates that local varieties have a higher adaptability compared with introduction varieties.


[Crescentic glomerulonephritis].
Concerning crescentic glomerulonephritis (CrGN) to present clinically rapidly progressive glomerulonephritis (RPGN), we reviewed mainly the clinical features, the immunopathogenesis, the therapy and its outcome in the analysis of our cases. In our 46 patients, we found 20 patients of 'idiopathic' CrGN but felt it difficult to differ whether they were pauci-immune type or immune-complex type. Recently antineutrophil cytoplasmic autoantibody (ANCA) has been generally recognized to have a high positive predictive value in the patients having 'idiopathic' RPGN of pauci-immune type, and its serum concentration is likely to correlate with the activity of the disease. Thus we feel that the check of ANCA will be necessary to resolve our question. 'Idiopathic' RPGN of pauci-immune type may also nowadays be renal-limited systemic necrotizing glomerulonephritis caused by the same mechanism of other systemic vasculitides, but the further clinical and pathogenetical study as well as revealing the significance of ANCA will be necessary in order to elucidate whether 'idiopathic' CrGN is a single homogeneous entity caused only throughout ANCA-related unknown mechanisms. Finally we referred about the infectious complications due to immunosuppressive therapy for RPGN, because we had experienced death of 22% patients due to infection.


Fertility preservation for patients with breast cancer: The Korean Society for Fertility Preservation clinical guidelines.
With advances in the methods of cancer treatment used in modern medicine, the number of breast cancer survivors has been consistently rising. As the number of women who wish to become pregnant after being diagnosed with breast cancer increases, it is necessary to consider fertility preservation in these patients. However, medical doctors may be unaware of the importance of fertility preservation among cancer patients because most patients do not share their concerns about fertility with their doctors. Considering the time spent choosing and undergoing treatment, an early referral to a reproductive specialist is the best way to prevent a delay in cancer treatment. Since it is not easy to make decisions on matters related to cancer diagnosis and fertility, patients should be provided with enough time for decision-making, and to allow for this, an early referral will provide patients with sufficient time to choose an appropriate method of fertility preservation. The currently available options of fertility preservation for patients with breast cancer include cryopreservation of embryos, oocytes, and ovarian tissue and gonadotropin-releasing hormone agonist treatment before and during chemotherapy. An appropriate method of fertility preservation must be selected through consultations between individual patients and health professionals and analyses of the pros and cons of different options.


A Population-Based Registry Study of Extended Bisphosphonate Use: Minimal Shift After Landmark Publications About Shorter Treatment Duration.
Optimal duration of bisphosphonate therapy was unknown until the FLEX study was published in 2006 showing a 5-year course to be adequate for most women. In 2008, a link between long-term bisphosphonate and atypical femoral fractures was reported and confirmed in later studies. We hypothesized these landmark observations should have led to a decrease in use of bisphosphonates for >5 or 10 years, from 2010 onward. The Manitoba Bone Mineral Density (BMD) Registry with linkage to provincial pharmacy data was used to determine the percentage of long- and very long-term bisphosphonate users from therapy start. The cohort comprised women aged >50 years with BMD between 1995 and 2018 with oral bisphosphonate first prescribed for >90 days with adherence >75% in the first year. For each calendar year of continued therapy, the percentage of patients and medication possession rate was tabulated. The percentage of users beyond 5 years was compared among patients who started therapy in 1998-2004 (those taking 5 years of therapy still finish before 2010) versus 2005-2012 (all new therapy starts overlap 2010 in those taking ≥5 years of treatment). The cohort included 2991 women with mean follow-up 8.8 (1.3) years, 64.9% of whom took continuous oral bisphosphonate for >5 years and 41.9% for >10 years. In the earlier versus later era, there were 74.4% versus 70.2% who completed 5 years. With respect to longer treatment, there were 68.0% and 60.5% of patients treated for 6 or more years (p < 0.0001) and 46.6% versus 33.5% treated for >10 years (p = 0.08). Medication possession rate was >79% in every year of therapy. Landmark studies leading to more limited bisphosphonate courses may have slightly reduced longer-term treatment, but up to one-third of adherent patients in the modern era still receive continuous bisphosphonate therapy for >10 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Adsorption-Inhibition of Clathrate Hydrates by Self-Assembled Nanostructures.
The mechanism by which safranine O (SFO), an ice growth inhibitor, halts the growth of single crystal tetrahydrofuran (THF) clathrate hydrates was explored using microfluidics coupled with cold stages and fluorescence microscopy. THF hydrates grown in SFO solutions exhibited morphology changes and were shaped as truncated octahedrons or hexagons. Fluorescence microscopy and microfluidics demonstrated that SFO binds to the surface of THF hydrates on specific crystal planes. Cryo-TEM experiments of aqueous solutions containing millimolar concentrations of SFO exhibited the formation of bilayered lamellae with an average thickness of 4.2±0.2 nm covering several μm2 . Altogether, these results indicate that SFO forms supramolecular lamellae in solution, which might bind to the surface of the hydrate and inhibit further growth. As an ice and hydrate inhibitor, SFO may bind to the surface of these crystals via ordered water molecules near its amine and methyl groups, similar to some antifreeze proteins.


Effect of Schizosaccharomyces pombe on aromatic compounds in dry sherry wines containing high levels of gluconic acid.
Volatile compounds have been determined in control dry sherry wines and those supplemented with gluconic acid, which were inoculated with the Schizosaccharomyces pombe 1379 (ATCC 26760) yeast strain. These compounds were grouped, according to volatiles exhibiting the identical odor quality, into nine groups of the same odor character (aromatic series) as a way of establishing the aroma profile for the studied wines. Control and supplemented wines showed changes in the balsamic, spicy, roasty, and fruity aromatic series, and tasters judged the aroma as typical of wines subjected to biological aging. This fission yeast may be used as a treatment to reduce gluconic acid contents in wines obtained from rotten grapes, making feasible the incorporation of these wines into the biological aging process. In addition, this procedure may also help to accelerate the traditional biological aging in sherry winemaking due to the contribution of some specific compounds by S. pombe to the wine.


Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility.
Angiopoietin-like protein 1 (ANGPTL1) is a potent regulator of angiogenesis. Growing evidence suggests that ANGPTL family proteins not only target endothelial cells but also affect tumor cell behavior. In a screen of 102 patients with lung cancer, we found that ANGPTL1 expression was inversely correlated with invasion, lymph node metastasis, and poor clinical outcomes. ANGPTL1 suppressed the migratory, invasive, and metastatic capabilities of lung and breast cancer cell lines in vitro and reduced metastasis in mice injected with cancer cell lines overexpressing ANGPTL1. Ectopic expression of ANGPTL1 suppressed the epithelial-to-mesenchymal transition (EMT) by reducing the expression of the zinc-finger protein SLUG. A microRNA screen revealed that ANGPTL1 suppressed SLUG by inducing expression of miR-630 in an integrin α(1)β(1)/FAK/ERK/SP1 pathway-dependent manner. These results demonstrate that ANGPTL1 represses lung cancer cell motility by abrogating the expression of the EMT mediator SLUG.


Comparative Effectiveness of Prostate Cancer Treatment Options: Limitations of Retrospective Analysis of Cancer Registry Data.
Retrospective analyses of cancer registry and institutional data have consistently found better survival after radical prostatectomy versus radiation therapy, which contrasts with findings from a randomized trial. This is likely because of the inability of retrospective studies to fully account for comorbidity differences across treatment groups because of the lack of detailed data in the registries. We use a unique population-based data set with detailed data regarding comorbidities and functional limitations to assess whether this can provide valid comparisons of survival across prostate cancer treatment groups. The Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data set results from a linkage between the SEER database and the MHOS database, which includes detailed information regarding patient-reported comorbidity and functional limitations. We analyzed 3102 patients with prostate cancer in SEER-MHOS and used latent class analysis to identify the healthiest group with minimal comorbidity burden and functional limitations. Among the healthiest group, we examined overall survival across treatments using the Kaplan-Meier method. Three distinct health groups were identified using latent class analysis; the healthiest group comprised 57% of the cohort and had a 10-year overall survival of 67%. Other health groups had higher rates of comorbidities or functional limitations. Among the healthiest group, 10-year overall survival differed across treatment groups: no local treatment (55%), external beam radiation therapy (69%), brachytherapy (76%), and radical prostatectomy (85%). Survival curves for the 3 treated groups separated at 4 years of follow-up. Despite the detailed health status information available in SEER-MHOS, our retrospective analysis could not fully account for patient selection biases across prostate cancer treatment groups. These findings highlight an important limitation of retrospective studies using population-based data sets and serve as a reminder to interpret results with caution.


Reach of Palliative Care for Parkinson Disease: Results From a Large National Survey of Patients and Care Partners.
People with Parkinson disease (PWP) and their care partners have high palliative care needs resulting from disabling motor and nonmotor symptoms. There is growing support for palliative care (PC) approaches to Parkinson disease. However, little is known regarding the extent to which the palliative needs of PWP and care partners are currently being met. This study's primary objective is to describe PWP's and care partners' perceptions of the extent to which their PC needs are being met. Secondary objectives are to describe their perceptions of the quality of clinical communication and their knowledge of PC. PWPs and care partners (n = 12,995) who had consented to receiving surveys from the Parkinson's Foundation were emailed an electronic survey. PC was operationalized as comprising 5 key components: systematic assessment and management of (1) nonmotor symptoms, (2) PWPs' emotional and spiritual needs, (3) care partners' needs, (4) the completion of annual advance care planning, and (5) timely referrals to specialist palliative care and hospice when appropriate. A total 1,882 individuals (1,266 PWP and 616 care partners) responded to the survey (response rate 14.5%). Few PWP (22%) reported that their neurologists never asked regarding bothersome nonmotor symptoms or did so or only if they brought it up. Fifty percent of PWP reported that pain as a specific nonmotor symptom was never managed or managed only if they brought it up. Similarly, PWPs' emotional and spiritual needs (55%), care partners' well-being (57%), and completion of advance care planning documentation (79%) were never addressed or only addressed if PWP brought it up. The quality of clinical communication was generally rated as open and honest (64% PWP). Fewer PWP (30%) reported that doctors helped them deal with the uncertainties of Parkinson disease. Most PWP (85%) reported being knowledgeable regarding PC, and 68% reported that the goal of PC was to help friends and family cope with the illness. Although some elements of PC are currently being addressed in routine care for PWP, there are many gaps and opportunities for improvement. These data may facilitate focused attention and development of resources to improve the quality and availability of PC for Parkinson disease.


Prognostic Role of Body Mass Index in Advanced Small Bowel Adenocarcinoma Patients Receiving Palliative Chemotherapy.
As small bowel adenocarcinoma (SBA) is a rare cancer worldwide, prognostic factors have not been clearly defined. The purpose of this study is to assess the prognostic role of clinicopathologic features, including body mass index (BMI), in patients with advanced SBA. A total of 28 consecutive patients with advanced SBA treated with palliative chemotherapy were retrospectively enrolled and analyzed. Clinicopathologic features, progression-free survival (PFS), and overall survival (OS) were compared according to BMI level. Eighteen patients had BMI < 25 kg/m(2) (overweight/normal/underweight in Asian) and ten patients had BMI ≥ 25 kg/m(2) (obese in Asian). Baseline characteristics were similar regardless of patient's BMI. Compared to patients with BMI < 25 kg/m(2), patients with BMI ≥ 25 kg/m(2) had higher response rate to chemotherapy (40.0% vs. 0%, P = 0.010), longer OS (11.2 vs. 7.0 months, P = 0.018) and a tendency toward prolonged PFS (2.1 vs. 1.9 months, P = 0.085). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) is an independent positive prognostic factor of OS (adjusted hazard ratio 0.35, P = 0.024). In conclusion, baseline BMI ≥ 25 kg/m(2) has a positive prognostic role in patients with advanced SBA.


NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests.
Swiss mice are among the most commonly used outbred strains in biomedical research. Because prior knowledge of the baseline phenotypes of mouse strains will allow informed selection of strains for particular experiments, we sought to characterize the behavior of two previously untested outbred Swiss strains--NIH Swiss and Black Swiss--in the two most widely used paradigms for evaluating the cognitive abilities of mice. Unlike the C57BL/6J and C57BL/6J-Tyr(c-2J) controls, animals of both outbred Swiss strains were unable to demonstrate learning in the Morris water maze and contextual fear conditioning paradigms. A polymerase chain reaction assay revealed that all of the NIH Swiss and Black Swiss mice tested were homozygous for the recessive retinal degeneration 1 mutation of the Pde6b gene. Histological examination of NIH Swiss and Black Swiss mouse eyes confirmed the presence of retinal degeneration, which causes visual image blindness. These findings indicate that NIH Swiss and Black Swiss mice are visually im paired and thus may be unsuitable for use in some experiments.


Integration of Bacterial Small RNAs in Regulatory Networks.
Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.


The acidic activation domain of the baculovirus transactivator IE1 contains a virus-specific domain essential for DNA replication.
IE1 is a potent transcriptional transactivator of the baculovirus Orgyia pseudotsugata multiple nucleopolyhedrovirus (OpMNPV) and has been shown to be essential for viral DNA replication. IE1 contains an acidic activation domain (AAD) at the N terminus that is essential for transcriptional transactivation, but its role in viral DNA replication is unknown. In this study the role of the IE1 AAD in DNA replication is investigated. We have determined that deletion of the AAD eliminates the ability of IE1 to support DNA replication, showing that the AAD is essential for DNA replication as well as transcriptional transactivation. Replacement of the AAD with the archetype domain from herpesvirus VP16 and the evolutionarily related domain from Autographa californica MNPV (AcMNPV) IE1 produces chimeric proteins that are potent transactivators. Surprisingly, however, these chimeric proteins were unable to support DNA replication, indicating that there is a host- or virus-specific replication subdomain in the AAD that was not functionally replaced by the VP16 or AcMNPV AAD. Using N- and C-terminal deletion mutants, the region of the AAD that was essential for DNA replication was mapped to amino acids 1 to 65. AAD deletion mutants also showed that an IE1 that is functional for transcriptional transactivation is not required for viral DNA replication. The IE1 AAD therefore contains an essential replication domain that is separable from the transcriptional activation domains. Our results suggest that IE1 specifically interacts with a component of the viral replication complex, supporting the view that it acts as a nucleating factor by binding to the viral replication origins.


GABA and fermented litchi juice enriched with GABA promote the beneficial effects in ameliorating obesity by regulating the gut microbiota in HFD-induced mice.
Gamma-aminobutyric acid (GABA) dietary intervention is considered to have therapeutic potential against obesity. Microbial enrichment is an effective strategy to naturally and safely enhance GABA production in food. As litchi is "the king of GABA" in fruits, the retention or enrichment of its content during processing has been a key issue in the litchi industry. This study aimed to investigate the potential of GABA and fermented litchi juice enriched with GABA (FLJ) to protect against obesity in a high-fat diet (HFD) mouse model. Supplementation of GABA and FLJ displayed an anti-obesogenic effect by attenuating body weight gain, fat accumulation, and oxidative damage, and improving the serum lipid profile and hepatic function. Sequencing (16S rRNA) of fecal samples indicated that GABA and FLJ intervention displayed different regulatory effects on HFD-induced gut microbiota dysbiosis at different taxonomic levels. The microbial diversity, the relative abundance of Firmicutes and Bacteroidetes as well as the F/B ratio of GABA and FLJ groups were reversed compared to those of the HFD-induced mice. Our finding broadens the potential mechanisms by which GABA regulates gut flora in the amelioration of obesity and provides guidance for developing FLJ as a functional food to prevent obesity.


Synthesis and expression in Escherichia coli of DNA encoding the murine lambda 1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen.
A 658 bp DNA sequence corresponding to the murine lambda 1 chain of a monoclonal antibody, Se155-4, specific for the Salmonella serotype B O-antigen, was designed using Escherichia coli preferred codons and chemically synthesized by ligation of synthetic fragments into a linearized plasmid followed by transformation into E. coli. A synthetic signal peptide (ompA) was fused to express the L chain as a free polypeptide into the periplasm of E. coli cells. After isolation and purification, heterologous recombination of the E. coli L chain with mouse H chain gave an active antigen-binding protein. The activity was 15-20% when compared to protein created by an equivalent association of isolated natural mouse L and H chains as measured by a direct EIA assay. In inhibition experiments with the polysaccharide antigen, the two proteins showed identical titration curves and 50% inhibition points, indicating comparable KA values.


[Thymectomy in myasthenia gravis (author's transl)].
10 myasthenia patients were treated surgically during a four year period, 1970 TO 1973. Thymectomy was only resorted to in the most severe cases of the disease. A sternum splitting incision was preferred. Postoperative diffculties were usually avoided by routine use of a volume-controlled respirator. Oro-tracheal intubation was preferred to tracheostomy in order to avoid infection. In 9 patients it was possible to reduce the daily dose of medicine. Clinical improvement, sometimes delayed, occurred in 8 patients. All the patients had been incapacitated preoperatively but in 6 cases they were able to return to work. The mortality rate was nil. There was one case of postoperative pneumonia and one delayed sternal union.


Quantifying the value of biomarkers for predicting mortality.
In light of widespread interest in the prognostic value of biomarkers, we apply three discrimination measures to evaluate the incremental value of biomarkers--beyond self-reported measures--for predicting all-cause mortality. We assess whether all three measures--area under the receiver-operating characteristic curve, continuous net reclassification improvement, and integrated discrimination improvement--lead to the same conclusions. We use longitudinal data from a nationally representative sample of older Taiwanese (n = 639, aged 54 or older in 2000, examined in 2000 and 2006, with mortality follow-up through 2011). We estimate age-specific mortality using a Gompertz hazard model. The broad conclusions are consistent across the three discrimination measures and support the inclusion of biomarkers, particularly inflammatory markers, in household surveys. Although the rank ordering of individual biomarkers varies across discrimination measures, the following is true for all three: interleukin-6 is the strongest predictor, the other three inflammatory markers make the top 10, and homocysteine ranks second or third. The consistency of most of our findings across metrics should provide comfort to researchers using discrimination measures to evaluate the prognostic value of biomarkers. However, because the degree of consistency varies with the level of detail inherent in the research question, we recommend that researchers confirm results with multiple discrimination measures.


Dynamics of Torque Teno virus viremia could predict risk of complications after allogeneic hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for several hematological diseases. However, the first year post-transplantation is often complicated by infections and graft-versus-host disease (GVHD). Improvements in immunological monitoring could reduce such post-transplant complications. Torque Teno virus (TTV), a chronically persisting DNA virus, is reported to be a marker for immune function in immunocompromised patients. In the present study, the TTV kinetics were analyzed to investigate the potential role of TTV viremia as immune-competence read-out after allo-HSCT. Twenty-three monocentric allo-HSCT recipients were retrospectively tested for TTV-DNA in whole blood at given day post-transplant. Dynamics of TTV viremia was analyzed with respect to episodes of non-TTV viral reactivations (CMV, EBV, and BKPyV), acute GVHD, and recovery of immune cells. Recipients affected by persisting viral infections and/or GVHD during the first 100 days after allo-HSCT showed a significantly higher median TTV load at day +30 than patients with a less complicated clinical course (p = 0.005). This was also associated with a total lymphocyte count <5.5E+08 cells/L in this high-risk group (p = 0.039). These findings suggest that TTV could represent an additional parameter to identify patients at higher risk for complications in the first 100 days following allo-HSCT. Prospective studies, including the monitoring of lymphocyte subsets, are required to define the potential use of TTV in immunological monitoring after allo-HSCT.


Prediction of metabolizable energy of broiler diets from chemical analysis.
Eighty-six broiler diets were studied to develop prediction equations for true metabolizable energy (TME) with nitrogen correction (TMEn) and calculated apparent metabolizable energy (AMEn) from chemical composition. Analyses were selected according to their capacity to represent the terms used in energy calculations, namely, dietary gross energy and energy excreted relative to diet consumed. Dietary gross energy was found to be highly correlated with ether extract alone. Prediction of excreta loss improved substantially with inclusion of two terms: a measurement of fiber [either crude fiber (CF), acid detergent fiber (ADF), or neutral detergent fiber (NDF)] and ash. A composite variable based on starch plus crude protein in place of fiber and ash yielded similar predictions. Accuracy of prediction of TMEn approached that of the biological analysis, but prediction of TME was somewhat less successful. Neutral detergent fiber was less satisfactory as a predictor than ADF or CF. Calculated AMEn was also highly predictable from ether extract or diet gross energy and a measurement of fiber alone; ash apparently was less helpful for AMEn. Previously published equations based on ether extract, ash, and an estimate of fiber gave results similar to the derived equations.


Rhinovirus infections in Tecumseh, Michigan: frequency of illness and number of serotypes.
We studied rhinovirus-associated illnesses from 1976 to 1981 among residents of the community of Tecumseh, Michigan, in a continuation of similar studies done in 1966-1971. Rhinoviruses were the most frequently isolated respiratory pathogen in all age groups, including young children. The pattern of age-specific isolation rates was similar to that for total respiratory illness. Rhinovirus-associated illnesses were generally mild but of relatively long duration; restriction of daily activity was frequent, especially in certain age groups. Typing of all isolates has been completed; with high-quality antisera nearly all isolates could be typed. Thus, new serotypes are probably not evolving, and most have already been identified. Differences in frequency of occurrences of different serotypes were evident, but ranking in order of importance was difficult based on existing data.


A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment.
This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence. Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD. Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability. Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.


Diosgenin stimulates rat TM4 cell proliferation through activating plasma membrane translocation and transcriptional activity of estrogen receptors.
Sertoli cells (SCs) function as "nurse cells," which play crucial roles in supporting spermatogenesis through establishing a unique and essential environment in the male reproductive tract. Given the important roles of SCs in male fertility, this study was designed to evaluate the effect of diosgenin, an aglycone of the steroidal saponin, on TM4 cell proliferation and to elucidate the possible mechanisms. We showed that diosgenin increased the proliferation of TM4 cell and primary SCs in a time- and concentration-dependent manner. Diosgenin increased cyclins D1 and E as well as CDK4/6 and CDK2 expression but inhibited P27 expression, with no significant alterations of cyclin B and cdc2 (cell division cycle 2), resulting in cell-cycle G1/S transition. Diosgenin significantly inhibited apoptosis, as reflected by decreased percentage of TUNEL-positive cells; decreased expression of Bax (Bcl-2-associated X protein), AIF (apoptosis-inducing factor), and cleaved caspases 3 and 9; and increased expression of Bcl-2 (B-cell lymphoma 2). Diosgenin induced an immediate and transient plasma membrane translocation of ESR1 and ESR2 from the nucleus, which was inhibited by the antiestrogen ICI 182 780 and PP2, an inhibitor of SRC. Moreover, ICI 182 780 and PP2 significantly inhibited diosgenin-induced cell-cycle transition and inhibition of apoptosis. Activation of extracellular regulated protein kinase (ERK)/Akt signaling was also involved in diosgenin-induced TM4 cell proliferation, which was SRC- and ESR-dependent. Furthermore, diosgenin induced late activation of nuclear ESR transcriptional activity, which in turn directly regulated cell cycle and apoptosis-related factors, such as cyclin D and Bcl-2. Taken together, the results show that diosgenin activated SRC-ESR translocation-ERK/Akt-ESR transcriptional activity, leading to cell-cycle transition and inhibition of apoptosis and thus final cell proliferation. These findings may better our understanding of the pharmacological actions of diosgenin and advance therapeutic approaches to male infertility.


Fabrication and Imaging Monatomic Ni Kagome Lattice on Superconducting Pb(111).
Artificial fabrication of a monolayer Kagome material can offer a promising opportunity to explore exceptional quantum states and phenomena in low dimensionality. Here, we have systematically studied a monatomic Ni Kagome lattice grown on Pb(111) by scanning tunneling microscopy/spectroscopy (STM/STS) and density functional theory (DFT). Sawtooth edge structures with distinct heights due to subsurface Ni atoms have been revealed, leading to asymmetric edge scattering of surface electrons on Pb(111). In addition, a local maximum at about -0.2 eV in tunneling spectra represents a manifestation of characteristic phase-destructive flat bands. Although charge transfer from underlying Pb(111) substrate results in a vanishing magnetic moment of Ni atoms, the proximity-induced superconducting gap is slightly enhanced on the Ni Kagome lattice. In light of single-atomic-layer Ni Kagome lattice on superconducting Pb(111) substrate, it could serve as an ideal platform to investigate the interplay between Kagome physics and superconductivity down to the two-dimensional limit.


Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update.
Cystic fibrosis transmembrane conductance receptor (CFTR) modulators are a new class of drugs that treat the underlying cause of cystic fibrosis. To date, there are four approved medications, which are mutation-specific. Although the number of mutations that respond to these agents is expanding, effective CFTR modulators are not available to all cystic fibrosis patients. The purpose of this article is to review the approved CFTR modulators and discuss the mutations that can be treated with these agents, as well as, review the long-term benefits of modulator therapy. More people with cystic fibrosis can be effectively treated with CFTR modulators. The new, highly effective triple therapy, elexacaftor/tezacaftor/ivacaftor is indicated for more than 90% of patients with cystic fibrosis and ivacaftor is now approved for children as young as 6 months of age with 1 of 30 CFTR mutations. Long-term use of modulator therapy is associated with fewer pulmonary exacerbations, maintenance of lung function, improved weight gain, and quality of life. CFTR modulators are the first therapies developed to treat the underlying defect in cystic fibrosis. Their use is associated with preserved lung function and improved health in patients with cystic fibrosis.


[Assessment of host status in patients treated with mFOLFOX6 adjuvant chemotherapy after colorectal cancer surgery].
We examined the association of the physical, nutritional, and immune status with adverse events in patients treated with mFOLFOX6 adjuvant chemotherapy after colorectal cancer surgery. This study included 17 patients, 7 male and 10 female. The median age was 62( range, 32-75) years. The median number of treatment cycles was 12 (range, 4-12). Age, performance status( PS), body mass index( BMI),serum albumin level( Alb),Onodera's prognostic nutritional index( PNI), controlling nutritional status( CONUT),Glasgow prognostic score( GPS),the granulocyte/lymphocyte ratio( G/L),neutrophil count, and the total lymphocyte count( TLC) were evaluated with regard to the nutrition and immunity status of the host before chemotherapy. The incidents of toxicity of greater than Grade 2 severity, excluding gastrointestinal events or gastrointestinal toxicities, were analyzed to determine the correlation with host status. Any toxicities and toxicities without digestive symptoms were observed in 11 patients( 64.7%),and the number of incidents was significantly increased in patients with a PNI of <45. Gastrointestinal toxicities were observed in 4 patients (23.5%), but there were no significant correlations with any of the factors investigated. Toxicities are observed to a greater extent in patients with a PNI of <45 during adjuvant chemotherapy. These findings suggest that nutritional support may be required to safely administer mFOLFOX6 adjuvant chemotherapy.


Modified Nissen fundoplication in the treatment of gastroesophageal reflux disease.
Twenty-five consecutive patients underwent a primary modified Nissen fundoplication for gastroesophageal reflux disease. According to this procedure, an increase of the diameter of the gastric wrap to a comfortable passage of the surgeon's index finger between oesophagus and gastric wrap was obtained, while the length of the gastric wrap was 1.0 cm. The fixation of the wrap on the anterior wall of the oesophagus was done at the level of the mucosal cardia 1.0 cm above the gastroesophageal junction strengthened by four mesh pledgets. Two more stitches between the seromuscular layer of the gastric fundus and the oesophageal musculature were placed to prevent reduction of created oesophagogastric intussusception. The results of this modified Nissen procedure are excellent during the early postoperative follow-up period, ranging from 10 to 45 months and averaging 26 months.


Comparative RNAseq Analysis of the Insect-Pathogenic Fungus Metarhizium anisopliae Reveals Specific Transcriptome Signatures of Filamentous and Yeast-Like Development.
The fungus Metarhizium anisopliae is a facultative insect pathogen used as biological control agent of several agricultural pests worldwide. It is a dimorphic fungus that is able to display two growth morphologies, a filamentous phase with formation of hyphae and a yeast-like phase with formation of single-celled blastospores. Blastospores play an important role for M. anisopliae pathogenicity during disease development. They are formed solely in the hemolymph of infected insects as a fungal strategy to quickly multiply and colonize the insect's body. Here, we use comparative genome-wide transcriptome analyses to determine changes in gene expression between the filamentous and blastospore growth phases in vitro to characterize physiological changes and metabolic signatures associated with M. anisopliae dimorphism. Our results show a clear molecular distinction between the blastospore and mycelial phases. In total 6.4% (n = 696) out of 10,981 predicted genes in M. anisopliae were differentially expressed between the two phases with a fold-change > 4. The main physiological processes associated with up-regulated gene content in the single-celled yeast-like blastospores during liquid fermentation were oxidative stress, amino acid metabolism (catabolism and anabolism), respiration processes, transmembrane transport and production of secondary metabolites. In contrast, the up-regulated gene content in hyphae were associated with increased growth, metabolism and cell wall re-organization, which underlines the specific functions and altered growth morphology of M. anisopliae blastospores and hyphae, respectively. Our study revealed significant transcriptomic differences between the metabolism of blastospores and hyphae. These findings illustrate important aspects of fungal morphogenesis in M. anisopliae and highlight the main metabolic activities of each propagule under in vitro growth conditions.


Further observations on carcinoma in situ of the urinary bladder: silent but extensive intraprostatic involvement.
Of seven patients with carcinoma in situ of the urinary bladder in the absence of an associated papillary carcinoma, five were found to have silent but extensive intraductal prostatic involvement. In three of these the carcinoma in situ was associated with microinvasion. The mean age at the time of diagnosis was 68 years. All had symptoms characteristic of carcinoma in situ, including hematuria, dysuria, and urgency. In three patients the prostatic involvement was diagnosed on transurethral resection. In two it was discovered only after radical cystectomy. The prostatic involvement was neither suspected clinically nor has it been previously emphasized. Although three patients are alive, apparently free of disease up to 15 months postcystectomy, two have died, one of disease. The importance of prostatic assessment in the evaluation of the patient with carcinoma in situ of the urinary bladder is emphasized.


Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma.
The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.


Surface-coordinated metal-organic framework thin films (SURMOFs) for electrocatalytic applications.
The design and development of highly efficient electrocatalysts are very important in energy storage and conversion. As a kind of inorganic organic hybrid material, metal-organic frameworks (MOFs) have been used as electrocatalysts in electrocatalytic reactions due to their structural diversities and fascinating functionalities. Particularly, MOF thin films are coordinated on substrate surfaces by a liquid phase epitaxial (LPE) layer by layer (LBL) growth method (called surface-coordinated MOF thin films, SURMOFs), and recently have been studied in various applications due to their precisely controlled thickness, preferred growth orientation and homogeneous surface. In this review, we will summarize the preparation and electrocatalysis of SURMOFs and their derived thin films (SURMOF-D). The SURMOF based thin films possess diverse topological structures and flexible properties, providing abundant catalytically active sites and fast charge transfer for efficient electrocatalytic performance in the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), carbon dioxide reduction reaction (CRR), supercapacitors, tandem electrocatalysis and so on. The research challenges and problems of SURMOFs for electrocatalytic applications are also discussed at the end of the review.


[Synthetic RGD-containing peptide K16GRGDSPC affected the adhesion, proliferation and osteogenic differentiation of rabbit bone marrow stromal cells on PLGA-[ASP-PEG] scaffold materials].
To explore the effects of synthetic RGD-containing peptide K16GRGDSPC covalent bonding with PLGA-[ASP-PEG] scaffold materials on the adhesion, proliferation and osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs). The peptide was synthesized by solid-phase synthesis method and characterized by mass spectrometry and high pressure liquid chromatography. PLGA-[ASP-PEG] scaffold materials were modified with the peptide by cross linker Sulfo-LC-SPDP and detected by XPS. The BMSCs obtained from rabbit were cultured on PLGA-[ASP-PEG] modified with the peptide and those cultured on unmodified PLGA-[ASP-PEG] were also observed as control group. The adhesion and proliferation behaviors of the cells were analyzed by conventional precipitation method, micropipette aspiration technique, MTT assay and Coomassie Brilliant Blue dyes. The osteogenic differentiation of the cells was showed by the activity of alkaline phosphatase (ALP) assayed by ALP Assay Kit and the mRNA levels of ALP, osteocalcin (OCN), osteopontin (OPN) and collagen I assessed by real-time PCR (RT-PCR). Immunofluorescence stain was also used to detect the expression of core binding factor a1 (Cfba1) which was an osteogenic maker as well. The peptide was successfully manufactured and linked to the surface of the PLGA-[ASP-PEG] by the cross-linker. The abilities of adhesion and proliferation and the expressions of osteogenic makers of the cells were significantly higher than those of control group (P < 0.05). RGD-containing peptide K16GRGDSPC could promote the adhesion, proliferation and osteogenic differentiation of BMSCs on the biomimetic bone-matrix materials.


Transmission dynamics of the M184V drug resistance mutation in primary HIV infection.
M184V in HIV-1 reverse transcriptase is among the most common mutations in patients failing antiretroviral therapy but is found only rarely in cases of transmitted drug resistance. To investigate this apparent paradox, we developed an allele-specific real-time PCR (AS-PCR) assay to determine the transmission of M184V in newly infected individuals. M184V transmission may occur to a greater extent than previously thought. Persistence of M184V may commonly involve linkage to other drug resistance mutations. The presence of M184V as a single substitution in newly infected individuals was shown to wane over time, as a likely consequence of reversion and overgrowth by more fit wild-type viruses. The M184V mutation can be documented in newly infected individuals, and the alternative hypothesis that this substitution might impact on the ability of HIV to be transmitted is unfounded.


Mapping gender and sexual minority representation in cancer research: a scoping review protocol.
Addressing the risk of people from gender and sexual minority (GSM) groups experiencing inequities throughout the cancer continuum requires a robust evidence base. In this scoping review, we aim to map the literature on cancer outcomes among adults from GSM groups and the factors that influence them along the cancer continuum. This mixed-methods scoping review will follow the approach outlined by JBI. We will systematically search electronic databases for literature in collaboration with a health sciences librarian. Two reviewers will screen titles and abstracts to determine eligibility based on inclusion criteria, and then retrieve full text articles for data extraction. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Quantitative data will be qualitized through a narrative interpretation and pooled with qualitative data. We will use meta-aggregation to synthesize findings. This protocol was developed in collaboration with GSM patient and public advisors. We will engage people from GSM groups, community organizations and knowledge users in disseminating results. This review will direct future research efforts by expanding the wider body of research examining cancer disparities across the cancer continuum that GSM groups experience, identifying literature gaps and limitations, and highlighting relevant social determinants of health that influence cancer outcomes for adults from GSM groups.


Biodegradable Cable-Tie Rapamycin-eluting Stents.
"Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.


[Chances of abortion prophylaxis in early pregnancy (author's transl)].
7870 pregnancies during the years 1964-1970 observed in a cooperative clinical study give the data basis of an exploratory statistical analysis. Here the associations of drugs taken during the first three months of pregnancy with the incidence of early spontaneous abortions before the fifth month are demonstrated. The rates are corrected for time of enrollment. Women having taken antiemetic drugs or preparations containing vitamins or minerals have less abortions than women without intake of these drugs. This is found especially in the presence of early nausea or vomiting and of bleedings in the first trimenon. It is important that these drugs have not been used for the treatment of bleedings. Therefore the takers and the non-takers are comparable. A success of the then usual treatment with female sexual hormones could not be found. The high abortion rates of women treated with tranquilizers cannot be interpreted as a failure of this treatment because of the epidemiological non-experimental character of the study.


Implementing the standards of best practice for simulation.
The Standards of Best Practice: Simulation are a resource for quality and consistency of simulation, evaluation of outcomes, and improvement of simulation programs. The Standards provide guidelines for practice and a vital framework for strategic planning, research, and faculty development. This article discusses challenges and shares approaches to enhance implementation of the Standards into practice to improve education, increase patient safety, and reduce variability in simulation experiences.