Differentiation of human mesenchymal stem cell spheroids under microgravity conditions.
To develop and characterize a novel cell culture method for the generation of undifferentiated and differentiated human mesenchymal stem cell 3D structures, we utilized the RWV system with a gelatin-based scaffold. 3 × 10(6) cells generated homogeneous spheroids and maximum spheroid loading was accomplished after 3 days of culture. Spheroids cultured in undifferentiated spheroids of 3 and 10 days retained expression of CD44, without expression of differentiation markers. Spheroids cultured in adipogenic and osteogenic differentiation media exhibited oil red O staining and von Kossa staining, respectively. Further characterization of osteogenic lineage, showed that 10 day spheroids exhibited stronger calcification than any other experimental group corresponding with significant expression of vitamin D receptor, alkaline phosphatase, and ERp60 . In conclusion this study describes a novel RWV culture method that allowed efficacious engineering of undifferentiated human mesenchymal stem cell spheroids and rapid osteogenic differentiation. The use of gelatin scaffolds holds promise to design implantable stem cell tissue of various sizes and shapes for future regenerative treatment.


[Etiology, diagnosis and course of infectious diarrhea in the Liestal canton hospital (5-year retrospective study)].
Between 1987 and 1991 219 patients (1.3% of all hospitalized patients) with acute infectious diarrhea were investigated retrospectively. 52% of the patients were hospitalized and 48% were outpatients. In 55% the inducing diarrhea microorganism could be identified. The most frequently detected pathogens were endemic Salmonella sp. and Campylobacter jejuni (65%). Imported diarrheas (Shigella sp. and parasites) were rare, as only 15% of the patients had a history of travel. All Clostridium difficile infections were associated with antibiotic treatment. The stool examinations for bacteria were positive in 92/160 patients (57%). Stool examinations for occult blood or fecal leukocytes were highly useful in detecting the infectious agent. In 70% of the patients with positive occult blood test or 81% of the patients with fecal leukocytes, an infectious agent in the stool was found. All patients recovered with few complications. 31% of the patients were treated by antibiotics because of septic disease or pathogenic parasites.


A titanium and visible light-polymerized resin obturator.
Obturator prostheses are typically large, and their weight and size are often important design factors. This article describes the fabrication of an obturator prosthesis with a titanium framework and visible light-polymerized denture base resin. It is speculated that these low-density materials may produce prostheses lighter than similar ones made with conventional materials. An added advantage is that visible light-polymerizing resins facilitate relining.


[Strategies of diagnosis and treatment for peritoneal metastasis of gastric cancer].
Peritoneal metastasis of gastric cancer is the main cause of death in gastric cancer patients. Peritoneal metastasis of gastric cancer is difficult to diagnose in its early stage due to lack of obvious clinical signs and symptoms, and poor treatment outcomes and prognosis are often associated with late stage peritoneal metastasis. Therefore, it is crucial to utilize effective early diagnostic tools and to improve the long-term outcomes and the prognosis of patients with advanced gastric cancer. Recently, systemic chemotherapy and intraperitoneal chemotherapy are the first line therapy, and cytoreductive operation plus abdominal cavity thermochemotherapy may be the best method in the treatment of peritoneal metastasis. However, conversion therapy has been gradually incorporated into the treatment of peritoneal metastasis of gastric cancer because of the better efficacy and the higher survival.


Plasma Metabolomic Profiling after Feeding Dried Distiller's Grains with Solubles in Different Cattle Breeds.
Dried distiller's grains with solubles (DDGS) are rich in nutrients and can enhance animals' growth and immunity. However, there are few reports on the effects of a diet of DDGS on plasma metabolism and the related action pathways in domestic animals. In this study, groups of Guanling yellow cattle (GY) and Guanling crossbred cattle (GC) having a basal diet served as the control groups (GY-CG and GC-CG), and DDGS replacing 25% of the diet of GY and GC served as the replacement groups (GY-RG and GC-RG), with three cattle in each group. Plasma samples were prepared for metabolomic analysis. Based on multivariate statistical and univariate analyses, differential metabolites and metabolic pathways were explored. Twenty-nine significantly different metabolites (p < 0.05) were screened in GY-RG compared with those in GY-CG and were found to be enriched in the metabolic pathways, including choline metabolism in cancer, linolenic acid metabolism, and amino acid metabolism. Nine metabolites showed significant differences (p < 0.05) between GC-RG and GC-CG and were mainly distributed in the metabolic pathways of choline metabolism in cancer, glycerophospholipid metabolism, prostate cancer metabolism, and gonadotropin-releasing hormone (GnRH) secretion. These results suggest that a DDGS diet may promote healthy growth and development of experimental cattle by modulating these metabolic pathways. Our findings not only shed light on the nutritional effects of the DDGS diet and its underlying mechanisms related to metabolism but also provide scientific reference for the feed utilization of DDGS.


Association between TNF-alpha, TGF-beta1, IL-10, IL-6 and IFN-gamma gene polymorphisms and generalized aggressive periodontitis.
The aim of this study was to investigate links among cytokine genetic variants and generalized aggressive periodontitis (GAgP). Thirty-five patients with generalized aggressive periodontitis and 85 healthy controls without periodontitis were included in the study. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as clinical parameters. Polymorphisms of IL-6, IL-10, IFN-gamma, TGF-ss1 and TNF-alpha gene were analysed using the polymerase chain reaction sequence-specific primer method (PCR-SSP). No significant differences were observed for IL-6, IL-10, IFN-gamma, and TGF-ss1 cytokine polymorphisms, from the genotype distribution and allele frequency, between GAgP and healthy control groups. In contrast, significant differences were observed in the TNF-alpha gene polymorphism between GAgP and healthy control groups (P = 0.002). Our data suggest that TNF-alpha (-308) may be associated with the development of generalized aggressive periodontitis. These results should be replicated in a larger and more diverse population of patients diagnosed with generalized aggressive periodontitis to determine of these findings are generalizable.


Neuropsychological function following mild exposure to pentaborane.
Neuropsychological tests and self-report personality inventories were administered to 14 workers and rescue squad personnel approximately 2 months following mild exposure to pentaborane, a highly toxic volatile liquid boron hydride. Performance decrements were evident on 5 of 11 neuropsychological tests, including Block Design and measures of sustained attention and recent memory. Neuropsychological deficits were not related to emotional changes reported on the Hopkins Symptom Checklist nor to the presence of CT scan abnormality. These results indicate mild residual brain dysfunction following pentaborane intoxication, including possible dysfunction in subcortical regions mediating memory processes and in cortical areas mediating visuo-spatial abilities.


No effect of beta-carotene supplementation on plasma lipoproteins in healthy smokers.
A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene intake may exert a protective effect through an impact on lipoprotein metabolism, we conducted a randomized, double-blind trial in healthy, male cigarette smokers. Total cholesterol, high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I (apo) A-I, apo B-100, and lipoprotein(a) were measured before and after 14 wk of treatment with beta-carotene (20 mg/d, n = 25) or placebo (n = 25). The beta-carotene and placebo groups were comparable with respect to all initial characteristics, but initial apo B-100 was significantly higher in the beta-carotene group (1.23 vs 1.44 g/L). During the intervention, plasma concentrations of beta-carotene increased 15-fold in the treatment group. Mean concentrations of total and HDL cholesterol, lipoprotein(a), apo A-I, and apo B-100 did not change significantly in either group. We conclude that a 20 mg beta-carotene supplement/d does not influence plasma lipoproteins in healthy male smokers.


Decisional Balance and Contemplation Ladder to Support Interventions for HIV Pre-Exposure Prophylaxis Uptake and Persistence.
Fewer than 60,000 males-inclusive of all sexual identities-were prescribed HIV pre-exposure prophylaxis (PrEP) by mid-2017 in the United States. Efforts to increase PrEP uptake among gay, bisexual, and other men who have sex with men (GBM), in particular, are ongoing in research and practice settings, but few tools exist to support interventions. We aimed to develop and validate tools to support motivational interviewing interventions for PrEP. In 2017, a national sample of HIV-negative GBM of relatively high socioeconomic status (n = 786) was asked about sexual behaviors that encompass Centers for Disease Control and Prevention guidelines for PrEP use, a 35-item decisional-balance scale (i.e., PrEP-DB) assessing benefits and consequences of PrEP use, and questions assessing location on the motivational PrEP cascade and derivative-the PrEP contemplation ladder. Principal axis factoring with oblique promax rotation was used for PrEP-DB construct identification and item reduction. The final 20-item PrEP-DB performed well; eigenvalues indicating a 4-factor solution provided an adequate fit to the data. Factors included the following: health benefits (α = 0.91), health consequences (α = 0.82), social benefits (α = 0.72), and social consequences (α = 0.86). Ladder scores increased across the cascade (ρ = 0.89, p < 0.001), and health benefits (β = 0.50, p < 0.001) and health consequences (β = -0.37, p < 0.001) were more strongly associated with ladder location than social benefits (β = 0.05, p > 0.05) and social consequences (β = -0.05, p > 0.05) in the fully adjusted regression model. The PrEP-DB demonstrated good reliability and predictive validity, and the ladder had strong construct validity with the motivational PrEP cascade. PrEP uptake and persistence interventions and additional empirical work could benefit from the utility of these measures.


Amazonian deforestation and soil biodiversity.
Clearance and perturbation of Amazonian forests are one of the greatest threats to tropical biodiversity conservation of our times. A better understanding of how soil communities respond to Amazonian deforestation is crucially needed to inform policy interventions that effectively protect biodiversity and the essential ecosystem services it provides. We assessed the impact of deforestation and ecosystem conversion to arable land on Amazonian soil biodiversity through a meta-analysis. We analyzed 274 pairwise comparisons of soil biodiversity in Amazonian primary forests and sites under different stages of deforestation and land-use conversion: disturbed (wildfire and selective logging) and slash-and-burnt forests, pastures, and cropping systems. Overall, 60% and 51% of responses of soil macrofauna and microbial community attributes (i.e., abundance, biomass, richness, and diversity indexes) to deforestation were negative, respectively. We found few studies on mesofauna (e.g., microarthropods) and microfauna (e.g., protozoa and nematodes), so those groups could not be analyzed. Macrofauna abundance and biomass were more vulnerable to the displacement of forests by pastures than by agricultural fields, whereas microbes showed the opposite pattern. Effects of Amazonian deforestation on macrofauna were more detrimental at sites with mean annual precipitation >1900 mm, and higher losses of microbes occurred in highly acidic soils (pH < 4.5). Limited geographic coverage, omission of meso- and microfauna, and low taxonomic resolution were main factors impairing generalizations from the data set. Few studies assessed the impacts of within-forest disturbance (wildfires and selective logging) on soil species in Amazonia, where logging operations rapidly expand across public lands and more frequent severe dry seasons are increasing the prevalence of wildfires.


Towards a full reference library of MS(n) spectra. Testing of a library containing 3126 MS2 spectra of 1743 compounds.
A library consisting of 3766 MS(n) spectra of 1743 compounds, including 3126 MS2 spectra acquired mainly using ion trap (IT) and triple-quadrupole (QqQ) instruments, was composed of numerous collections/sources. Ionization techniques were mainly electrospray ionization and also atmospheric pressure chemical ionization and chemical ionization. The library was tested for the performance in identification of unknowns, and in this context this work is believed to be the largest of all known tests of product-ion mass spectral libraries. The MS2 spectra of the same compounds from different collections were in turn divided into spectra of 'unknown' and reference compounds. For each particular compound, library searches were performed resulting in selection by taking into account the best matches for each spectral collection/source. Within each collection/source, replicate MS2 spectra differed in the collision energy used. Overall, there were up to 950 search results giving the best match factors and their ranks in corresponding hit lists. In general, the correct answers were obtained as the 1st rank in up to 60% of the search results when retrieved with (on average) 2.2 'unknown' and 6.2 reference replicates per compound. With two or more replicates of both 'unknown' and reference spectra (the average numbers of replicates were 4.0 and 7.8, respectively), the fraction of correct answers in the 1st rank increased to 77%. This value is close to the performance of established electron ionization mass spectra libraries (up to 79%) found by other workers. The hypothesis that MS2 spectra better match reference spectra acquired using the same type of tandem mass spectrometer (IT or QqQ) was neither strongly proved nor rejected here. The present work shows that MS2 spectral libraries containing sufficiently numerous different entries for each compound are sufficiently efficient for identification of unknowns and suitable for use with different tandem mass spectrometers.


The Tax Exclusion for Employer-Sponsored Insurance Is Not Regressive-But What Is It?
Conventional wisdom says that the tax exclusion for employer-sponsored health insurance (ESI) is "regressive and therefore unfair." Yet, by the standard definition of regressive tax policy, the conventional view is almost certainly false. It confuses the absolute size of the tax exclusion with its proportional effect on income. The error results from paying attention only to the marginal tax rate applied to ESI benefits as a portion of income and ignoring the fact that benefits are normally a much larger share of income for people with lower wages. This article explains the difference and then considers other distributional effects of ESI. It suggests that ESI-for those who receive it-further redistributes toward those with lesser means or greater need. The most evident effect is by need, favoring employees with families over those without. Yet there is good reason to believe there is also a redistribution by income, with the package of wages plus benefits being less unequal than wages alone would be. Therefore reformers should be much more careful before criticizing either ESI or its subsidy through the tax code as "unfair," especially as the likelihood of enacting something better in the United States seems quite low.


NUT Midline Carcinoma of the Sublingual Gland: Clinical Presentation and Review.
NUT midline carcinoma (NMC) is a rare and aggressive disease encountered in the midline of the head and neck or mediastinum. Due to its sparse incidence and subtle pathologic features, we aim to increase knowledge and awareness for this pathologic entity. We present an exemplary case of a young, healthy male presenting with oral cavity pain and cervical lymphadenopathy. This patient was initially diagnosed with an unspecified, highly aggressive sublingual gland malignancy and underwent locoregional resection with free flap reconstruction however suffered a rapid local recurrence and widely extensive metastasis within just 1 month. After rigorous analysis, final pathologic diagnosis revealed a poorly differentiated carcinoma with evidence of squamous differentiation that eventually, post-mortem tested positive for NMC. Only one prior case of sublingual gland NMC has been previously reported as we discuss the literature regarding all sublingual gland malignancies as well as the pathologic features and treatment options for NMC. We recommend consideration of testing for the NUT proto-oncogene at the time of biopsy in the clinical setting of a poorly differentiated midline carcinoma, especially with squamous differentiation, of the head or neck in order to identify patients for clinical trial enrollment and appropriately counsel on the poor clinical prognosis. Improving clinician awareness is critical to increase diagnostic accuracy and need to study prospective treatment outcomes as the first step toward improving management of this difficult disease.


USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors.
USP9X, is highly expressed in neural progenitors and, essential for neural development in mice. In humans, mutations in USP9X are associated with neurodevelopmental disorders. To understand USP9X's role in neural progenitors, we studied the effects of altering its expression in both the human neural progenitor cell line, ReNcell VM, as well as neural stem and progenitor cells derived from Nestin-cre conditionally deleted Usp9x mice. Decreasing USP9X resulted in ReNcell VM cells arresting in G0 cell cycle phase, with a concomitant decrease in mTORC1 signalling, a major regulator of G0/G1 cell cycle progression. Decreased mTORC1 signalling was also observed in Usp9x-null neurospheres and embryonic mouse brains. Further analyses revealed, (i) the canonical mTORC1 protein, RAPTOR, physically associates with Usp9x in embryonic brains, (ii) RAPTOR protein level is directly proportional to USP9X, in both loss- and gain-of-function experiments in cultured cells and, (iii) USP9X deubiquitlyating activity opposes the proteasomal degradation of RAPTOR. EdU incorporation assays confirmed Usp9x maintains the proliferation of neural progenitors similar to Raptor-null and rapamycin-treated neurospheres. Interestingly, loss of Usp9x increased the number of sphere-forming cells consistent with enhanced neural stem cell self-renewal. To our knowledge, USP9X is the first deubiquitylating enzyme shown to stabilize RAPTOR.


Evaluation of a Spotted Fever Group Rickettsia Public Health Surveillance System in Tennessee.
Spotted fever group (SFG) rickettsioses are endemic in Tennessee, with ∼2,500 cases reported during 2000-2012. Because of this substantial burden of disease, we performed a three-part evaluation of Tennessee's routine surveillance for SFG rickettsioses cases and deaths to assess the system's effectiveness. Tennessee Department of Health (TDH) SFG rickettsioses surveillance records were matched to three patient series: 1) patients with positive serologic specimens from a commercial reference laboratory during 2010-2011, 2) tertiary medical center patients with positive serologic tests during 2007-2013, and 3) patients identified from death certificates issued during 1995-2014 with SFG rickettsiosis-related causes of death. Chart reviews were performed and patients were classified according to the Council of State and Territorial Epidemiologists' case definition. Of 254 SFG Rickettsia-positive serologic specimens from the reference laboratory, 129 (51%) met the case definition for confirmed or probable cases of rickettsial disease after chart review. The sensitivity of the TDH surveillance system to detect cases was 45%. Of the 98 confirmed or probable cases identified from the medical center, the sensitivity of the TDH surveillance system to detect cases was 34%. Of 27 patients identified by death certificates, 12 (44%) were classified as confirmed or probable cases; four (33%) were reported to TDH, but none were correctly identified as deceased. Cases of SFG rickettsioses were underreported and fatalities not correctly identified. Efforts are needed to improve SFG rickettsiosis surveillance in Tennessee.


Novel mechanisms of brequinar sodium immunosuppression on T cell activation.
Brequinar sodium (BQR) is a novel immunosuppressive agent that acts by inhibiting the activity of dihydroorotate dehydrogenase, the fourth enzyme in the de novo pyrimidine biosynthetic pathway. The activity of BQR as an immunosuppressive agent is believed to be inhibition of antigen-induced lymphocyte proliferation through inhibition of DNA and RNA synthesis. BQR, therefore, has a different mechanism of action than cyclosporine and may potentiate the immunosuppressive effects of cyclosporine. In this study, we determined the effect of BQR on peripheral blood mononuclear cell (PBMC) activation in a series of in vitro culture systems. In these studies, BQR inhibited PHA-stimulated activation in a dose-dependent fashion beginning at 10(-6) M. The immunosuppressive effect of BQR was similar in magnitude to cyclosporine. Proliferation assays suggested an additive immunosuppression by the combination of BQR and cyclosporine. Similar inhibition of CD2-stimulated or CD3-stimulated activation of PBMC was found. The mechanisms of action of BQR were complex. BQR inhibited interleukin 2 protein production in response to mitogen stimulation. Cell surface interleukin 2 receptor expression was inhibited by BQR. BQR inhibited cell cycle progression, preventing progression from G0/G1 into S and G2 + M phases. BQR had no effect on induction of transcripts for the interleukin 2 receptor, but markedly inhibited the production of transcripts for interleukin 2. Thus, our studies indicate that BQR exerts a potent immunosuppression on mitogen-induced PBMC activation through multiple mechanisms. Consequently, BQR may be an effective agent for immunosuppression in organ transplantation or inflammatory diseases.


Highly contorted superhelicene hits near-infrared circularly polarized luminescence.
Herein we describe a novel superhelicene structure consisting of three hexa-peri-hexabenzocoronene (HBC) units arranged in a helical geometry and creating two carbo[5]helicenes and a carbo[7]helicene. The central HBC bears a tropone moiety, which induces a saddle-helix hybrid geometry into the 3D structure of the prepared nanographene. The introduction of multiple helicenes and the position of the tropone unit trigger near-infrared circularly polarized luminescence (NIR-CPL, up to 850 nm, |g lum| = 3.0 × 10-3) combined with good photoluminescence quantum yields (ϕ F = 0.43) and upconverted emission based on two-photon absorption (TPA). Compared to previously reported superhelicenes of similar size, higher quantum yields, CPL brightness, and red-shifted absorption and emission spectra are achieved. Besides, chiroptical properties of enantiopure thin films were evaluated. These findings place this novel superhelicene as the first NIR-CPL superhelicene ever reported and make it a promising candidate for use as a chiral luminescent material in optoelectronic devices.


Prosthodontic treatment of a patient with hemimandibular elongation: a clinical report.
This clinical report describes prosthodontic treatment of a patient with hemimandibular elongation that resulted in significant dentofacial asymmetry. A maxillary metal-ceramic fixed dental prosthesis and crowns were fabricated. To eliminate the negative horizontal overlap, 3 mandibular teeth were reduced to the gingival level. The mandibular prosthetic restoration was completed with metal and composite resin using an electroforming technique.


CT Findings of Risk Factors for Persistent Type II Endoleak from Inferior Mesenteric Artery to Determine Indicators of Preoperative IMA Embolization.
To identify the computed tomography (CT) findings of persistent type II endoleak from the inferior mesenteric artery (IMA) which indicate the need for preoperative IMA embolization. Included were 120 patients (96 males, 49-93 years old, mean: 77.7) who underwent endovascular aortic aneurysm repair (EVAR) between June 2007 and October 2010. The relationship between persistent type II endoleak and CT findings of IMA orifice was examined. CT showed no type II endoleak from IMA in 106 patients (89%; Group N), and transient type II endoleak from IMA in 10 patients (8.3%; Group T). CT showed persistent type II endoleak from IMA in 4 patients (3.3%; Group P) and three of them underwent reintervention. Univariate Cox-Mantel test analysis indicated that stenosis (p = 0.0003) and thrombus (p = 0.043) in IMA orifice were significant factors for persistent type II endoleak. The ratios of patients with proximal IMA more than 2.5 mm diameter in Groups N, Y, and P were 26/106 (24%), 5/10 (50%) and 4/4 (100%), respectively. Indicators for embolization of IMA prior to EVAR for the prevention of type II endoleak appear to be: (1) more than 2.5 mm in diameter and (2) no stenosis due to calcification or mural thrombus in IMA orifice.


[Analysis of the results of bronchoalveolar lavage (BALF) in patients with pulmonary sarcoidosis].
Bronchoalveolar lavage is a relatively new method in pulmonology. Treatment of broncho-alveolar fluid-washing/BALF/obtained after the procedure of broncho-alveolar lavage/BAL/enables obtaining of samples for investigation of inflammatory and immune cells, so-called alveolar, which, treated by different laboratory procedures, represent the source for different informations at many lung diseases. Analysis of BALF is significant in the differential diagnosis of interstitial lung changes, in the estimate of process activity as well in analysis of therapy with glucocorticosteroids, as well as in the estimate of immune cells state, particularly T abd B lymphocyte subpopulations. We have analysed BALF in 161 patients with lung sarcoidosis with the purpose of analysing the process activity and according to activity of lymphocyte alveolitis in relation to total lymphocyte number in BALF cytogram and by identification of T and B lymphocytes and their subpopulations/CD4, CD8, CD11/as well as by the index CD4/CD8. We have determined the CD4, CD8, CD11 values as well as B lymphocytes by monoclonal antibodies, manufactured by ORTHO-mune/USA/, signed by the manufacturer as OKT4, OKT8, OKT11, OKT22, conjugated by gost antimice IgG antibodies. The working procedure we have done according to instructions of the manufacturer by immunofluorescent technic.


The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue.
Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'. Because BAT is a specialized metabolic tissue that takes up and burns lipids and is linked to systemic metabolic homeostasis, we hypothesized that there might be thermogenic lipokines that activate BAT in response to cold. Here we show that the lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a stimulator of BAT activity, and that its levels are negatively correlated with body-mass index and insulin sensitivity. Using a global lipidomic analysis, we found that 12,13-diHOME was increased in the circulation of humans and mice exposed to cold. Furthermore, we found that the enzymes that produce 12,13-diHOME were uniquely induced in BAT by cold stimulation. The injection of 12,13-diHOME acutely activated BAT fuel uptake and enhanced cold tolerance, which resulted in decreased levels of serum triglycerides. Mechanistically, 12,13-diHOME increased fatty acid (FA) uptake into brown adipocytes by promoting the translocation of the FA transporters FATP1 and CD36 to the cell membrane. These data suggest that 12,13-diHOME, or a functional analog, could be developed as a treatment for metabolic disorders.


[Management of a pregnant woman with Streptococcus group B].
The relative rarity (1 to 5 cases for 1,000 births) of neonatal infections secondary to B Streptococcus, the epidemiological characteristics of this germ, especially the unstable vaginal carriage, make it difficult to select a therapeutic approach. Systematic screening of B Streptococcus and the treatment of all carriers or only of high-risk patients, present several practical problems, are complex to implement but the cost/benefit ratio seems however acceptable. Prophylactic intrapartum antibiotic treatment of known carriers of B Streptococcus does not seem debatable any longer, at least the treatment of those presenting other risk factors: premature delivery, premature rupture of the membranes, fever occurring during delivery. Today, the best prophylaxis of neonatal infections seems to be the intrapartum antibiotic treatment (ampicillin) resulting in a spectacular decrease of the frequency of neonatal contamination.


Luminescent lanthanide ions hosted in a fluorescent polylysin dendrimer. Antenna-like sensitization of visible and near-infrared emission.
We have investigated the complexation of the luminescent Nd(3+), Eu(3+), Gd(3+), Tb(3+), Er(3+), and Yb(3+) ions by a polylysin dendrimer containing 21 amide groups in the interior and, in the periphery, 24 chromophoric dansyl units which show an intense fluorescence band in the visible region. Most of the experiments were performed in 5:1 acetonitrile/dichloromethane solution at 298 K. On addition of the lanthanide ions to dendrimer solutions, the fluorescence of the dansyl units is quenched; in Nd(3+), Er(3+), and Yb(3+), a sensitized near-infrared emission of the lanthanide ion is observed. At low metal ion concentrations, each dendrimer hosts only one metal ion and when the hosted metal ion is Nd(3+) or Eu(3+), the fluorescence of all the 24 dansyl units of the dendrimer is quenched with unitary efficiency. Quantitative measurements were performed in a variety of experimental conditions, including protonation of the dansyl units and measurements in rigid matrix at 77 K where a sensitized Eu(3+) emission could also be observed. The results obtained have been interpreted on the basis of the energy levels and redox potentials of dendrimer and metal ions.


HLA Genotyping in Patients with End-Stage Renal Disease Waiting For Cadaveric Renal Transplantation in Federation of Bosnia and Herzegovina.
The research was conducted by genotyping two Human Leukocyte Antigen (HLA) gene classes. The main objective of this research was to investigate distribution and frequency of the allelic groups, genotypes and haplotypes in the gene loci of HLA class I (HLA-A*, -B*, -C*) and HLA class II (HLA-DRB1*, -DQB1*) in patients included in the program of cadaveric renal transplantation. Our study covered 186 blood samples of patients who are registered on the list for cadaveric renal transplantation in Federation of Bosnia and Herzegovina and included 59 control, healthy unrelated individuals. For the HLA typing, we have used three different methods: micro lymphocyte cytotoxicity test (MLCT), Polymerase Chain Reaction (PCR) - Sequence Specific Primers (SSP) and PCR - Sequence-Specific Oligonucleotides (SSO) or Luminex technology. All patients and cadaveric donors were tested using the three methods because the system is polymorphic. Analysis of the results of genotyping HLA class I gene loci identified dominant HLA-A*02, HLA-B*35, HLA-C*07 allelic groups. Analysis of the HLA class II gene loci genotyping showed that HLA-DRB1*11 and HLA-DQB1*03 loci had the highest incidence in HLA class II. Based on our results and previous research, there were no observed differences between allelic frequencies and genotypes of healthy people and people with ESRD. Differences between allelic groups occurred, but they were not statistically significant, except HLA-C*01 (p = 0.020).


Structural symmetry in evolutionary games.
In evolutionary game theory, an important measure of a mutant trait (strategy) is its ability to invade and take over an otherwise-monomorphic population. Typically, one quantifies the success of a mutant strategy via the probability that a randomly occurring mutant will fixate in the population. However, in a structured population, this fixation probability may depend on where the mutant arises. Moreover, the fixation probability is just one quantity by which one can measure the success of a mutant; fixation time, for instance, is another. We define a notion of homogeneity for evolutionary games that captures what it means for two single-mutant states, i.e. two configurations of a single mutant in an otherwise-monomorphic population, to be 'evolutionarily equivalent' in the sense that all measures of evolutionary success are the same for both configurations. Using asymmetric games, we argue that the term 'homogeneous' should apply to the evolutionary process as a whole rather than to just the population structure. For evolutionary matrix games in graph-structured populations, we give precise conditions under which the resulting process is homogeneous. Finally, we show that asymmetric matrix games can be reduced to symmetric games if the population structure possesses a sufficient degree of symmetry.


[The clinical characteristics and prognosis of acute myocardial infarction complicated by cardiogenic shock].
To observe the effect of reperfusion therapy on the prognosis of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) in reperfusion era. 89 cases of AMI with CS were included with 57 male and 32 female. 50 cases received conservative therapy and 39 cases reperfusion therapy. 28 of the 39 cases had successful reperfusion and 11 cases failed. 18 patients had intra-aortic balloon pump (IABP) within 1 hour of CS, they constituted an early group; 35 patients treated with IABP 1 hour after CS were of a late group. A group of 36 cases were not treated with IABP (no IABP group). The mortality of the early group with IABP was significantly lower than that of the late and no IABP group (33.3% vs. 74.2% vs. 86.1%, P < 0.01). The mortality of the group with successful reperfusion was significantly lower than that of unsuccessful reperfusion and conservative no IABP group (42.8% vs. 81.8% vs. 84.0% , P < 0.01). logistic regression analysis showed that successful reperfusion therapy (OR 4.232, 95% CI 1. 07 - 12.730, P = 0.01) and THE TIME of using IABP (OR 0.22, 95% CI 0.063 - 0.764, P =0.017) were independent risk factors for death. Early successful reperfusion and early institution of IABP were the most important therapeutic measures for reducing mortality of AMI complicated by CS.


CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum.
The voltage-gated Ca(2+) (CaV) channel acts as a key player in β cell physiology and pathophysiology. β cell CaV channels undergo hyperactivation subsequent to exposure to type 1 diabetic (T1D) serum resulting in increased cytosolic free Ca(2+) concentration and thereby Ca(2+)-triggered β cell apoptosis. The present study was aimed at revealing the subtypes of CaV1 channels hyperactivated by T1D serum as well as the biophysical mechanisms responsible for T1D serum-induced hyperactivation of β cell CaV1 channels. Patch-clamp recordings and single-cell RT-PCR analysis were performed in pancreatic β cells from CaV1 channel knockout and corresponding control mice. We now show that functional CaV1.3 channels are expressed in a subgroup of islet β cells from CaV1.2 knockout mice (CaV1.2(-/-)). T1D serum enhanced whole-cell CaV currents in islet β cells from CaV1.3 knockout mice (CaV1.3(-/-)). T1D serum increased the open probability and number of functional unitary CaV1 channels in CaV1.2(-/-) and CaV1.3(-/-) β cells. These data demonstrate that T1D serum hyperactivates both CaV1.2 and CaV1.3 channels by increasing their conductivity and number. These findings suggest CaV1.2 and CaV1.3 channels as potential targets for anti-diabetes therapy.


Boronic acid-modified alginate enables direct formation of injectable, self-healing and multistimuli-responsive hydrogels.
One-step functionalization of alginate with boronic acid groups allowed spontaneous formation of biocompatible hydrogels under basic conditions without additional complementary molecules or crosslinking agents. The dynamic nature of boronate ester bonds formed with vicinal diols present on alginate pyranose rings provided remarkable self-healing, injectable and multi-stimuli responsive properties to the material.


The Fanconi anemia pathway: repairing the link between DNA damage and squamous cell carcinoma.
Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components. In response to DNA damage, nuclear FA proteins associate into high molecular weight complexes through a cascade of post-translational modifications and physical interactions, followed by the repair of damaged DNA. Hematopoietic cells are particularly sensitive to the loss of these interactions, and bone marrow failure occurs almost universally in FA patients. FA as a disease is further characterized by cancer susceptibility, which highlights the importance of the FA pathway in tumor suppression, and will be the focus of this review. Acute myeloid leukemia is the most common cancer type, often subsequent to bone marrow failure. However, FA patients are also at an extreme risk of squamous cell carcinoma (SCC) of the head and neck and gynecological tract, with an even greater incidence in those individuals who have received a bone marrow transplant and recovered from hematopoietic disease. FA tumor suppression in hematopoietic versus epithelial compartments could be mechanistically similar or distinct. Definition of compartment specific FA activities is now critical to assess the effects of today's bone marrow failure treatments on tomorrow's solid tumor development. It is our hope that current therapies can then be optimized to decrease the risk of malignant transformation in both hematopoietic and epithelial cells. Here we review our current understanding of the mechanisms of action of the Fanconi anemia pathway as it contributes to stress responses, DNA repair and squamous cell carcinoma susceptibility.


Use of combined microscopic and spectroscopic techniques to reveal interactions between uranium and Microbacterium sp. A9, a strain isolated from the Chernobyl exclusion zone.
Although uranium (U) is naturally found in the environment, soil remediation programs will become increasingly important in light of certain human activities. This work aimed to identify U(VI) detoxification mechanisms employed by a bacteria strain isolated from a Chernobyl soil sample, and to distinguish its active from passive mechanisms of interaction. The ability of the Microbacterium sp. A9 strain to remove U(VI) from aqueous solutions at 4 °C and 25 °C was evaluated, as well as its survival capacity upon U(VI) exposure. The subcellular localisation of U was determined by TEM/EDX microscopy, while functional groups involved in the interaction with U were further evaluated by FTIR; finally, the speciation of U was analysed by TRLFS. We have revealed, for the first time, an active mechanism promoting metal efflux from the cells, during the early steps following U(VI) exposure at 25 °C. The Microbacterium sp. A9 strain also stores U intracellularly, as needle-like structures that have been identified as an autunite group mineral. Taken together, our results demonstrate that this strain exhibits a high U(VI) tolerance based on multiple detoxification mechanisms. These findings support the potential role of the genus Microbacterium in the remediation of aqueous environments contaminated with U(VI) under aerobic conditions.


The perception of spatial structure with oblique viewing: an explanation for Byzantine perspective?
Earlier work has confirmed that (i) observers can judge divergent receding lines, placed directly in front of them, to be parallel, and (ii) converging lines which are displaced laterally, so that they are viewed obliquely, can also be judged to be parallel. The former observation is in accord with traditional views of perspective while the latter, which is in accord with the depictions of objects found in Byzantine painting, is not in accord with perspective but is predicted by the relative magnitude of the visual angles subtended by the near and far ends of the pair of lines. To investigate whether these effects occurred when the stimulus was clearly three-dimensional, experiments were conducted with a novel apparatus, consisting of a framework of computer-controlled motor-driven luminous rods. This could be remotely adjusted so that all visible sides appeared to be parallel, ie to resemble a cube. Results showed that observers set the sides of this trapezohedron framework as diverging when it was viewed immediately in front of them, a result which is concordant with linear perspective, ie they see the normal projection of a cube as having converging edges. When the framework was displaced from the median plane so that it was viewed obliquely, the sides were set as converging and the magnitude of this effect was significantly related to angle of view, ie observers see the normal projection of a cube as having diverging sides.(ABSTRACT TRUNCATED AT 250 WORDS)


Randomized, comparative study of the effectiveness of three different techniques of interscalene brachial plexus block using 0.5% ropivacaine for shoulder arthroscopy.
Interscalene brachial plexus block is an effective regional anesthesia technique for shoulder surgeries. The superiority of the popular ultrasound-guided blocks over peripheral nerve stimulator-confirmed blocks remains unclear. In this study the efficacy of these different block techniques was compared. This prospective, randomized, clinical study included 109 patients (ASA grades I-III) who receive 20 mL 0.5% ropivacaine with ultrasound-guided blocks (U group), peripheral nerve stimulator-confirmed blocks (N group), or ultrasound-guided and peripheral nerve stimulator-confirmed blocks (dual guidance; NU group) for elective shoulder arthroscopy. Block onset time, duration, and effectiveness on the Lovett rating scale were assessed. There was no statistically significant intergroup difference in duration of block performance, irrespective of the technique (P = 0.232). Onset time of complete warmth sensation loss (P < 0.001) and muscle strength abolition (P < 0.001) was significantly longer and mean Lovett rating scale score distribution was significantly higher in the N group than in the other groups (P < 0.001). These findings show a statistically significant correlation between the performance of the used block technique and the necessity of conversion to general anesthesia because of insufficient block in the N group (58.54%) than in the U (24.44%) and NU (19.57%) groups. Peripheral nerve stimulator-confirmed needle placement is not necessary to ensure effectiveness of ultrasound-guided blocks, which is expressed as a lack of necessity of conversion to general anesthesia. Nevertheless, the dual guidance technique is recommended to reduce the risk of complications and might be considered the regional anesthesia of choice for shoulder surgery.


Point-of-care documentation.
A custom-made software application can make electronic charting of patient goals and outcomes simple and quick for the nurse, as well as making it easier for decision-makers to identify problem areas.


Integrative modelling of reported case numbers and seroprevalence reveals time-dependent test efficiency and infectious contacts.
Mathematical models have been widely used during the ongoing SARS-CoV-2 pandemic for data interpretation, forecasting, and policy making. However, most models are based on officially reported case numbers, which depend on test availability and test strategies. The time dependence of these factors renders interpretation difficult and might even result in estimation biases. Here, we present a computational modelling framework that allows for the integration of reported case numbers with seroprevalence estimates obtained from representative population cohorts. To account for the time dependence of infection and testing rates, we embed flexible splines in an epidemiological model. The parameters of these splines are estimated, along with the other parameters, from the available data using a Bayesian approach. The application of this approach to the official case numbers reported for Munich (Germany) and the seroprevalence reported by the prospective COVID-19 Cohort Munich (KoCo19) provides first estimates for the time dependence of the under-reporting factor. Furthermore, we estimate how the effectiveness of non-pharmaceutical interventions and of the testing strategy evolves over time. Overall, our results show that the integration of temporally highly resolved and representative data is beneficial for accurate epidemiological analyses.


Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms.
Mitofilin, also known as heart muscle protein, is a recently identified mitochondrial protein. We have isolated two human cDNAs that encode different isoforms of mitofilin. Using reverse PCR, we provide evidence that both isoforms are derived by alternative splicing and encode two proteins of 88 and 90 kDa that are detected in immunoblot analyses with mitofilin-specific antibodies. Immunofluorescence microscopy, fractionating of human osteosarcoma cells, and protease protection experiments with isolated mitochondria and mitoplasts indicate that mitofilin is an integral membrane protein of the inner mitochondrial membrane. 35S-labeled mitofilin is transported into isolated yeast mitochondria in a reaction that depends on the membrane potential across the inner mitochondrial membrane (delta psi). During mitochondrial in vitro import, mitofilin is proteolytically processed to the mature protein that is also detected in cellular fractions, indicating that the amino-terminal leader sequence is removed. Sequence analysis and our results suggest that mitofilin is anchored in the inner mitochondrial membrane with an amino-terminal transmembrane domain, while the majority of the protein is extruding into the intermembrane space.


Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix.
It has been known for decades that the tumor extracellular matrix (ECM) is dysfunctional leading to loss of tissue architecture and promotion of tumor growth. The altered ECM and tumor fibrogenesis leads to tissue stiffness that act as a physical barrier to immune cell infiltration into the tumor microenvironment (TME). It is becoming increasingly clear that the ECM plays important roles in tumor immune responses. A growing body of data now indicates that ECM components also play a more active role in immune regulation when dysregulated ECM components act as ligands to interact with receptors on immune cells to inhibit immune cell subpopulations in the TME. In addition, immunotherapies such as checkpoint inhibitors that are approved to treat cancer are often hindered by ECM changes. In this review we highlight the ways by which ECM alterations affect and regulate immunity in cancer. More specifically, how collagens and major ECM components, suppress immunity in the complex TME. Finally, we will review how our increased understanding of immune and immunotherapy regulation by the ECM is leading towards novel disruptive strategies to overcome immune suppression.


Symptoms of Anxiety and Depression in Young Athletes Using the Hospital Anxiety and Depression Scale.
Elite young athletes have to cope with multiple psychological demands such as training volume, mental and physical fatigue, spatial separation of family and friends or time management problems may lead to reduced mental and physical recovery. While normative data regarding symptoms of anxiety and depression for the general population is available (Hinz and Brähler, 2011), hardly any information exists for adolescents in general and young athletes in particular. Therefore, the aim of this study was to assess overall symptoms of anxiety and depression in young athletes as well as possible sex differences. The survey was carried out within the scope of the study "Resistance Training in Young Athletes" (KINGS-Study). Between August 2015 and September 2016, 326 young athletes aged (mean ± SD) 14.3 ± 1.6 years completed the Hospital Anxiety and Depression Scale (HAD Scale). Regarding the analysis of age on the anxiety and depression subscales, age groups were classified as follows: late childhood (12-14 years) and late adolescence (15-18 years). The participating young athletes were recruited from Olympic weight lifting, handball, judo, track and field athletics, boxing, soccer, gymnastics, ice speed skating, volleyball, and rowing. Anxiety and depression scores were (mean ± SD) 4.3 ± 3.0 and 2.8 ± 2.9, respectively. In the subscale anxiety, 22 cases (6.7%) showed subclinical scores and 11 cases (3.4%) showed clinical relevant score values. When analyzing the depression subscale, 31 cases (9.5%) showed subclinical score values and 12 cases (3.7%) showed clinically important values. No significant differences were found between male and female athletes (p ≥ 0.05). No statistically significant differences in the HADS scores were found between male athletes of late childhood and late adolescents (p ≥ 0.05). To the best of our knowledge, this is the first report describing questionnaire based indicators of symptoms of anxiety and depression in young athletes. Our data implies the need for sports medical as well as sports psychiatric support for young athletes. In addition, our results demonstrated that the chronological classification concerning age did not influence HAD Scale outcomes. Future research should focus on sports medical and sports psychiatric interventional approaches with the goal to prevent anxiety and depression as well as teaching coping strategies to young athletes.


Value of lung diffusing capacity for nitric oxide in systemic sclerosis.
A decreased lung diffusing capacity for carbon monoxide (DLCO ) in systemic sclerosis (SSc) is considered to reflect losses of alveolar membrane diffusive conductance for CO (DMCO ), due to interstitial lung disease, and/or pulmonary capillary blood volume (VC ), due to vasculopathy. However, standard DLCO does not allow separate DMCO from VC . Lung diffusing capacity for nitric oxide (DLNO ) is considered to be more sensitive to decrement of alveolar membrane diffusive conductance than DLCO . Standard DLCO and DLNO were compared in 96 SSc subjects with or without lung restriction. Data showed that DLNO was reduced in 22% of subjects with normal lung volumes and DLCO , whereas DLCO was normal in 30% of those with decreased DLNO . In 30 subjects with available computed tomography of the chest, both DLCO and DLNO were negatively correlated with the extent of pulmonary fibrosis. However, DLNO but not DLCO was always reduced in subjects with ≥ 5% fibrosis, and also decreased in some subjects with < 5% fibrosis. DMCO and VC partitioning and Doppler ultrasound-determined systolic pulmonary artery pressure could not explain individual differences in DLCO and DLNO . DLNO may be of clinical value in SSc because it is more sensitive to DMCO loss than standard DLCO , even in nonrestricted subjects without fibrosis, whereas DLCO partitioning into its subcomponents does not provide information on whether diffusion limitation is primarily due to vascular or interstitial lung disease in individual subjects. Moreover, decreased DLCO in the absence of lung restriction does not allow to suspect pulmonary arterial hypertension without fibrosis.


Photoperiod-dependent response to androgen in the medial amygdala of the Siberian hamster, Phodopus sungorus.
The medial nucleus of the amygdala (MeA) is a steroid-sensitive region that has been implicated in the expression of behaviors such as mating and aggression. The male Siberian hamster (Phodopus sungorus) uses light cues to regulate its reproductive neuroendocrine system, reducing androgen synthesis in the autumn and increasing it in the spring. There is also evidence that short photoperiods reduce the sensitivity of the brain to the behavioral effects of androgen. The authors tested the hypothesis that MeA neurons are less responsive to androgen in short photoperiods by comparing the regional volume and average soma size of the four MeA subnuclei (anterodorsal [MeAD], anteroventral [MeAV], posterodorsal [MePD], and posteroventral) in adult male hamsters that had been castrated and then implanted with capsules containing either testosterone (T) or nothing. Animals from each group were housed in either long or short photoperiods for 15 weeks. MeAD and MeAV somata displayed photoperiod-dependent responses to androgen, increasing in size after T treatment only in long days. In contrast, the average soma size and the regional volume of the MePD subnucleus were significantly larger in T-treated males regardless of photoperiod. The authors conclude that photoperiod influences the sensitivity of the MeA to androgen.


A MODEL OF A HYBRID ZONE BETWEEN TWO CHROMOSOMAL RACES OF THE COMMON SHREW (SOREX ARANEUS).
The common shrew (Sorex araneus) is subdivided into several karyotypic races in Britain. Two of these races meet near Oxford o form the "Oxford-Hermitage" hybrid zone. We present a model which describes this system a; a "tension zone," i.e., a set of clines maintained by a balance between dispersal and selection against chromosomal heterozygotes. The Oxford and Hermitage races differ by Robertsonian fusions with monobrachial homology (kq, no versus ko), and so Fl hybrids between them would have low fertility. However, the acrocentric karyotype is found at high frequency within the hybrid zone, so that complex Robertsonian heterozygotes (kg no/q ko n) are replaced by more fertile combinations, such as (kg no/k q n o). This suggests that the hybrid zone has been modified so as to increase hybrid fitness. Mathematical analysis and simulation show that, if selection against complex heterozygotes is sufficiently strong relative to selection against simple heterozygotes, acrocentrics increase, and displace the clines for kg and no from the cline for ko. Superimposed on this separation is a tendency for the hybrid zone to move in favor of the Oxford (kg no) race. We compare the model with estimates of linkage disequilibrium and cline shape made from field data.


Role of uL3 in Multidrug Resistance in p53-Mutated Lung Cancer Cells.
Cancer is one of the most common causes of death among adults. Chemotherapy is crucial in determining patient survival and quality of life. However, the development of multidrug resistance (MDR) continues to pose a significant challenge in the management of cancer. In this study, we analyzed the role of human ribosomal protein uL3 (formerly rpL3) in multidrug resistance. Our studies revealed that uL3 is a key determinant of multidrug resistance in p53-mutated lung cancer cells by controlling the cell redox status. We established and characterized a multidrug resistant Calu-6 cell line. We found that uL3 down-regulation correlates positively with multidrug resistance. Restoration of the uL3 protein level re-sensitized the resistant cells to the drug by regulating the reactive oxygen species (ROS) levels, glutathione content, glutamate release, and cystine uptake. Chromatin immunoprecipitation experiments and luciferase assays demonstrated that uL3 coordinated the expression of stress-response genes acting as transcriptional repressors of solute carrier family 7 member 11 (xCT) and glutathione S-transferase α1 (GST-α1), independently of Nuclear factor erythroid 2-related factor 2 (Nrf2). Altogether our results describe a new function of uL3 as a regulator of oxidative stress response genes and advance our understanding of the molecular mechanisms underlying multidrug resistance in cancers.


Radiographic image subtraction in gas ionography.
The feasibility of radiographic image subtraction based on electrostatic imaging techniques is demonstrated. Ionographic latent images are essentially foil electrets with surface charge densities modulated by x-ray transmission through the object. Latent image charging at one polarity corresponding to the production of the primary image, and latent image discharging with the opposite polarity, are used to create the final latent image representing the region of interest. The technique is simple and could be in its present form applied to industrial radiography. Using high-pressure xenon ionographic chambers, the technique could be developed into a clinical tool as an inexpensive alternative to conventional digital radiography.


Genetic epidemiological analysis of esophageal cancer in high-incidence areas of China.
Genetic epidemiological studies have shown that genetic susceptibility to esophageal cancer (EC) is an important cause of its high incidence within families in some areas of China. The purpose of this study was to obtain evidence of a genetic basis of EC in Xin-an and Xin-xiang counties in China. Familial aggregation and complex segregation analyses were performed of 79 EC families in these counties. The heritability of EC was examined using Falconer's method and complex segregation analysis was conducted with the SEGREG program in Statistical Analysis for Genetic Epidemiology (SAGE version 5.3.1). The results showed that the distribution of EC in families did not fit well into a binomial distribution. The heritability of EC among first-degree and second- degree relatives was 67.0±7.31% and 43.1%±9.80%, respectively, and the summing up powered heritability was 53.2±6.74%. The segregation ratio was 0.045. Complex segregation analysis showed that the genetic model of EC was additive. The current results provide evidence for an inherited propensity to EC in certain high-risk groups in China, and support efforts to identify the genes that confer susceptibility to this disease.


Hepatic graft versus host disease: a study of the predictive value of liver biopsy in diagnosis.
Ninety-six liver biopsies [32 bone marrow transplant (BMT), 7 pre-BMT, and 57 non-BMT] are reviewed for histological evidence of graft versus host disease (GVHD), based on bile duct atypia and related inflammatory changes. In addition, the presence of cholestasis, piecemeal necrosis, and attachment of lymphocytes to vascular endothelium (endothelialitis) are evaluated. The 57 non-BMT biopsies include examples of viral hepatitis (acute and chronic), nonviral chronic hepatitis, extrahepatic biliary obstruction, cytomegalovirus hepatitis, primary biliary cirrhosis, and orthotopic liver transplant rejection. Although the sensitivity of bile duct damage as an indicator of GVHD appears high (only one probable false negative was noted), there is considerable overlap between the changes of GVHD and occasional cases of acute and chronic hepatitis and extrahepatic biliary obstruction. Nine of the 57 non-BMT biopsies (15%) were felt to be consistent with GVHD and represent "false positives". Despite this relative lack of specificity, analysis of several features in combination provided clues to improve accuracy of diagnosis. The findings of extensive bile duct damage with minimal inflammatory changes is characteristic of GVHD. Possibly more predictive is the presence of endothelialitis of portal or central veins, which was seen in only three non-BMT biopsies, being present in eight cases of GVHD.


Lithographic fabrication of diffractive optical elements in hybrid sol-gel glass on 3-D curved surfaces.
We demonstrate the lithographic fabrication of diffractive optical elements (DOEs) in hybrid SiO2/TiO2 sol-gel glass on 3-D curved surfaces. The concentric circular gratings with periods of 20 μm, 10 μm and 5 μm have been fabricated in sol-gel glass on concave lens by laser direct writing successfully. Continuous 3-Dimensional surface relief with a height of 435 nm, 110 nm and 50 nm has been obtained for the period of 20 μm, 10 μm and 5 μm respectively. The optical test results of the fabricated DOE shows only a little bit deviation from the theoretical calculated results which can be explained by 3-D curved surface effect. We believe this technology can be an effective method to fabricate DOEs with even more complex surface profile on 3-D curved surfaces in terms of its simplicity and cost-effectiveness.


Neither eosinophils nor neutrophils require ATG5-dependent autophagy for extracellular DNA trap formation.
The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin, which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation. We decided to investigate this apparent dependence on autophagy for ET release and generated genetically modified mice that lack, specifically in eosinophils or neutrophils, autophagy-related 5 (Atg5), a gene encoding a protein essential for autophagosome formation. Interestingly, neither eosinophils nor neutrophils from Atg5-deficient mice exhibited abnormalities in ET formation upon physiological activation or exposure to low concentrations of PMA, although we could confirm that human and mouse eosinophils and neutrophils, after pre-treatment with inhibitors of class III PI3K, show a block both in reactive oxygen species (ROS) production and in ET formation. The so-called late autophagy inhibitors bafilomycin A1 and chloroquine, on the other hand, were without effect. These data indicate that ET formation occurs independently of autophagy and that the inhibition of ROS production and ET formation in the presence of 3-MA and wortmannin is probably owing to their additional ability to block the class I PI3Ks, which are involved in signalling cascades initiated by triggers of ET formation.


Sunscreens: the impervious path from theory to practice.
The preparation of commercial products able to protect the skin against damage from solar radiation requires safe and photo-stable stable UV-absorbing molecules with high extinction coefficients, prepared with solvents of the appropriate polarities and polarizabilities in formulas which allow the uniform spreading of the UV-absorbing substances. The products should also maintain the ingredients on the top of the skin and provide efficient scavenging activities against singlet oxygen and other directly or indirectly generated reactive oxygen species. Because of the high doses of UV used to test high SPF, simple and reproducible methods are needed to estimate the protection afforded by the product before risking the induction of severe burns to the volunteers, as can occur when the value of the product's SPF is smaller than the expected one. This paper describes several aspects of the preparation of commercial sunscreens. It also points out several of the hidden hypotheses which, when not tested, might lead to the overestimation of the protection factor of a product.


Is urologist burnout different on the other side of the pond? A European perspective.
The rate of burnout among physicians appears to be on the rise and urologist are no exception. In fact, urology appears to be one of the specialties most affected, with European urologists reporting burnout rates of up to 54% and those working in the United States up to 68%.Herein, we review the relatively few studies looking at burnout in European urologists to estimate its prevalence and discuss what could be done to reverse the trend. A total of seven studies were identified assessing burnout in urologists in Europe and Turkey. While the rates vary (9.3-68%), they indicate that burnout is prevalent within urology, with data from other studies suggesting there is a rising trend. Although the topic has been studied for many years, with an increased focus in the last decade, little seems to have been done to improve the situation.


Risk Factors for the Development of Cataract in Children with Uveitis.
To determine the risk factors for the development of cataract in children with uveitis of any etiology. Cohort study. Two hundred forty-seven eyes of 140 children with uveitis were evaluated for the development of vision-affecting cataract. Demographic, clinical, and treatment data were collected between the time of presentation and the first instance cataract was recorded or findings at final follow-up. Main outcome measures included the prevalence of cataract and distribution by type of uveitis, incidence of new onset cataract time to cataract development, and risk factors for the development of cataract. The prevalence of cataract in our cohort was 44.2% and was highest among eyes with panuveitis (77.1%), chronic anterior uveitis (48.3%), and intermediate uveitis (48.0%). The overall incidence of newly diagnosed cataract was 0.09 per eye-year, with an estimated 69% to develop uveitis-related cataract with time. The main factors related with cataract development were the number of uveitis flares per year (hazard ratio [HR] = 3.06 [95% confidence interval {CI}, 2.15-4.35], P < .001), cystoid macular edema (HR = 2.87 [95% CI, 1.41-5.82], P = .004), posterior synechia at presentation (HR = 2.85 [95% CI, 1.53-5.30], P = .001), and use of local injections of corticosteroids (HR = 2.37 [95% CI, 1.18-4.75], P = .02). Treatments with systemic and topical corticosteroids were not significant risk factors. In this study, we found that development of cataract is common among pediatric eyes with uveitis and is most strongly related to the extent of inflammation recurrences and ocular complications. We suggest that controlling the inflammation, even using higher doses of systemic and topical corticosteroids, is of importance in preventing ocular complications, such as cataract.


The relationship between clinical and echocardiographic findings in mitral valve prolapse.
Incorporating prognostically related auscultatory, M-mode, 2DE and recent Doppler echocardiographic features, the following strict criteria for establishing the diagnosis of mitral valve prolapse (MVP) have been advanced: 1. auscultatory; mid-to-late systolic clicks and a late systolic murmur at the apex or mid-to-late systolic clicks at the apex which move appropriately with maneuvers that alter LV volume or late systolic murmur at the apex in young patients (coinciding that a similar murmur in elderly population is non-specific for MVP); 2. two-dimensionally "targeted" M-mode criterion: marked (greater than 3 mm) late systolic buckling posterior to C-D line (moderate 2 mm late systolic buckling or 3 mm holosystolic displacement "arouse suspicion" but do not establish MVP); 3. two-dimensional echocardiographic criteria: severe bowing of leaflet(s) on the parasternal long axis and four-chamber view (mild to moderate bowing alone are unacceptable) or left atrial coaptation point; 4. Doppler echocardiographic criteria: moderate or severe Doppler mitral regurgitation with any degree of leaflet bowing or mild Doppler mitral regurgitation with at least moderate bowing of one leaflet (mild leaflet bowing and mild mitral regurgitation can be regarded as "probable MVP"). The concept of mitral valve prolapse syndrome encompasses that which was earlier described in patients with a high prevalence of symptoms. In controlled studies, however, it has become apparent that cardiac and psychiatric symptoms can be found as frequently in normal subjects as in those with MVP. These results indicate that clinicians may have erroneously diagnosed patients with MVP because of premature acceptance that MVP is the cause of a distinctive syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)


Aminoterminal propeptides of type III procollagen in human cerebrospinal fluid.
The concentrations of aminoterminal propeptides of procollagen type III were determined by radioimmunoassay in the cerebrospinal fluids of 64 patients with various neurological disorders, including 4 infant patients (less than 1 year). In cerebrospinal fluids of adult patients with normal composition (protein, glucose, cell count), adult patients with pathologic composition, and infant patients the peptide levels (mean value +/- S.D.) were 4.07 +/- 1.26 micrograms/l, 8.15 +/- 6.78 micrograms/l, and 56.9 +/- 31.0 micrograms/l, respectively. The concentrations ranged from 1.96 to 265 micrograms/l and were independent of the respective serum propeptide levels. No statistic correlation with other parameters was found. Gel chromatography revealed a high degree of molecular weight heterogeneity, a substantial portion of immunoreactive material was eluted even with the void volume of Sephacryl S 300. Different slopes of radioimmunoinhibition curves indicate heterogenous antigenicity among the propeptides from various patients. Interaction of the propeptides with fibronectin and/or heparin is probably not responsible for the heterogeneity. The diagnostic potential of cerebrospinal fluid propeptide levels for local connective tissue (collagen) turnover remains to be elucidated.


An accurate mass tag strategy for quantitative and high-throughput proteome measurements.
We describe and demonstrate a global strategy that extends the sensitivity, dynamic range, comprehensiveness, and throughput of proteomic measurements based upon the use of peptide "accurate mass tags" (AMTs) produced by global protein enzymatic digestion. The two-stage strategy exploits Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry to validate peptide AMTs for a specific organism, tissue or cell type from "potential mass tags" identified using conventional tandem mass spectrometry (MS/MS) methods, providing greater confidence in identifications as well as the basis for subsequent measurements without the need for MS/MS, and thus with greater sensitivity and increased throughput. A single high resolution capillary liquid chromatography separation combined with high sensitivity, high resolution and accurate FT-ICR measurements has been shown capable of characterizing peptide mixtures of significantly more than 10(5) components with mass accuracies of < 1 ppm, sufficient for broad protein identification using AMTs. Other attractions of the approach include the broad and relatively unbiased proteome coverage, the capability for exploiting stable isotope labeling methods to realize high precision for relative protein abundance measurements, and the projected potential for study of mammalian proteomes when combined with additional sample fractionation. Using this strategy, in our first application we have been able to identify AMTs for >60% of the potentially expressed proteins in the organism Deinococcus radiodurans.


Investigating the role of ASCC1 in the causation of bone fragility.
Bi-allelic variants in ASCC1 cause the ultrarare bone fragility disorder "spinal muscular atrophy with congenital bone fractures-2" (SMABF2). However, the mechanism by which ASCC1 dysfunction leads to this musculoskeletal condition and the nature of the associated bone defect are poorly understood. By exome sequencing, we identified a novel homozygous deletion in ASCC1 in a female infant. She was born with severe muscular hypotonia, inability to breathe and swallow, and virtual absence of spontaneous movements; showed progressive brain atrophy, gracile long bones, very slender ribs, and a femur fracture; and died from respiratory failure aged 3 months. A transiliac bone sample taken postmortem revealed a distinct microstructural bone phenotype with low trabecular bone volume, low bone remodeling, disordered collagen organization, and an abnormally high bone marrow adiposity. Proteomics, RNA sequencing, and qPCR in patient-derived skin fibroblasts confirmed that ASCC1 was hardly expressed on protein and RNA levels compared with healthy controls. Furthermore, we demonstrate that mutated ASCC1 is associated with a downregulation of RUNX2, the master regulator of osteoblastogenesis, and SERPINF1, which is involved in osteoblast and adipocyte differentiation. It also exerts an inhibitory effect on TGF-β/SMAD signaling, which is important for bone development. Additionally, knockdown of ASCC1 in human mesenchymal stromal cells (hMSCs) suppressed their differentiation capacity into osteoblasts while increasing their differentiation into adipocytes. This resulted in reduced mineralization and elevated formation of lipid droplets. These findings shed light onto the pathophysiologic mechanisms underlying SMABF2 and assign a new biological role to ASCC1 acting as an important pro-osteoblastogenic and anti-adipogenic regulator.


The psychological health and well-being experiences of female military veterans: a systematic review of the qualitative literature.
Women in the military are a minority group who, in addition to facing exposure to traumatic events due to the nature of the work, face additional stressors while deployed. It is argued that these exposures and experiences place individuals at a significantly higher risk of finding it difficult adjusting post deployment. This paper focuses on the psychological health and well-being of female veterans post-deployment. A systematic review of the literature related to female veterans' experiences upon returning home from deployment was conducted. Eight in-depth qualitative studies met the inclusion criteria for the study and were analysed using thematic analysis. Five key themes were identified in the papers: (1) bringing the war home, (2) post-deployment adjustment, (3) loss, (4) failed belongingness and (5) post-traumatic growth. These studies provide a useful insight into the different psychological health and well-being experiences that female veterans encounter. Additionally, the associated effects upon the individual and their families and communities are considered.


Dietary myo-inositol deficiency decreased intestinal immune function related to NF-κB and TOR signaling in the intestine of young grass carp (Ctenopharyngodon idella).
In this study, we investigated the effects of dietary myo-inositol on the intestinal immune barrier function and related signaling pathway in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.33 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila. The results indicated that compared with the optimal dietary myo-inositol level, myo-inositol deficiency (27.0 mg/kg diet): (1) decreased lysozyme (LZ) and acid phosphatase (ACP) activities, as well as complement 3 (C3), C4 and immunoglobulin M (IgM) contents in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (P < 0.05). (2) down-regulated the mRNA levels of anti-microbial substance: liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, hepcidin, β-defensin-1 and mucin2 in the PI, MI and DI of young grass carp (P < 0.05). (3) up-regulated pro-inflammatory cytokines [IL-1β (not in DI), TNF-α and IL-8], nuclear factor kappa B P65 (not NF-κB P52), c-Rel, IκB kinaseα (IKKα), IKKβ and IKKγ mRNA levels in the PI, MI and DI of young grass carp (P < 0.05); and down-regulated pro-inflammatory cytokines IL-15 (not in DI) and inhibitor of κBα (IκBα) mRNA levels (P < 0.05). (4) down-regulated the mRNA levels of anti-inflammatory cytokines [IL-10 (not in DI), IL-11, IL-4/13B (not IL-4/13A), TGF-β1 and TGF-β2], target of rapamycin (TOR), eIF4E-binding proteins 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6k1) in the PI, MI and DI of young grass carp (P < 0.05). All data indicated that myo-inositol deficiency could decrease fish intestine immunity and cause inflammation under infection of A. hydrophila. Finally, the optimal dietary myo-inositol levels for the ACP and LZ activities in the DI were estimated to be 415.1 and 296.9 mg/kg diet, respectively.


Complementary and Alternative Medicine Use in a Pregnant Population, Northwest Ethiopia.
Complementary and alternative medicine (CAM) appears to be the source of healthcare particularly in the majority of pregnant communities of Africa due to its intrinsic qualities as well as its accessibility and affordability. Despite acknowledged benefits of CAM use in pregnancy, majority of users are unaware of its safety and effects on fetal development. The present study was aimed at examining CAM use among pregnant women in Northwest Ethiopia to provide an opportunity for future investigations on the effectiveness of CAM modalities in the management of pregnancy-related complications across the country. This was an institution-based cross-sectional study which was conducted at Poly Clinic Health Center in the Northwest part of Ethiopia between March and May 2018. Two hundred and eighty two Ethiopian women were conveniently recruited to take part in the study. Structured questioners were used for the survey. Descriptive statistics of sociodemographic and CAM use characteristics were expressed in frequencies and proportions. Chi-square test was performed to determine the difference between CAM user and nonuser. Besides, binary logistic regression analyses were performed to examine predictors of CAM use in the study population. The result was considered statistically significant if P value ≤ 0.05. The prevalence rate of CAM use in pregnant women was 89.36% with the commonest practice of spiritual healing (65.2%) and herbal supplement (51.8%) CAM therapies. Use of CAM positively associated with marital status and previous number of children. The odds of using CAM among single/not married women were 3.22 times higher (COR: 3.22, CI: 1.07-9.64) as compared to married women. Pregnant women with no children were 3.30 times more likely (COR: 3.30, CI: 0.92-11.84) to use CAM than those women having ≥3 children. Lower odds of using CAM significantly associated with educational level (COR: 0.20, CI: 0.046-0.93) and antenatal care (COR: 0.45, CI: 0.18-1.13) in a binary logistic regression model. A considerable number of pregnant women were utilizing CAM including herbal products as part of their maternity care. This finding provides a reference on the use of CAM for policy-makers, health professionals, and parents. Further studies are needed to investigate the effectiveness and safety of specific CAM modalities with particular focus on herbal medicinal products.


Protocatechuic Acid Enhances Osteogenesis, but Inhibits Adipogenesis in C3H10T1/2 and 3T3-L1 Cells.
Abnormal activation of adipogenesis in mesenchymal stem cells (MSCs) and preadipocyte cells is associated with human metabolic disorders, such as osteoporosis and obesity. This study investigated the biological effects of protocatechuic acid (PCA) on the modulation of osteogenesis and adipogenesis in cultured cells. PCA stimulation of MSCs significantly increased intracellular mineralization during osteogenesis, but reduced lipid accumulation in both MSCs and 3T3-L1 preadipocyte cells during adipogenesis. Reverse transcription-polymerase chain reaction and immunoblotting analyses showed a dose-dependent upregulation of proosteogenic runt-related transcription factor 2 due to induction of β-catenin. PCA reduced the expression of proadipogenic transcription factor, peroxisome proliferator-activated receptor-γ, and suppressed its promotor activity. These results suggest PCA exerts stimulatory effects on the osteogenesis of MSCs and inhibitory effects on the adipogenesis of MSCs and 3T3-L1 cells. PCA may contribute to maintain a coordinated metabolic balance between adipogenesis and osteogenesis, and thus may be useful for the prevention and alleviation of osteoporosis and obesity.


Molecular interactions of bisphenols and analogs with glucocorticoid biosynthetic pathway enzymes: an in silico approach.
Glucocorticoids are known to have vital effects on metabolism, behavior and immunity. Any sort of impairment in their synthesis may lead to the generation of numerous ill health effects. Different environmental toxicants, including bisphenols and their analogs pose deleterious effect on the biosynthesis of glucocorticoids, thereby leading to endocrine disruption. In order to assess the effect of these environmental toxicants on gluocorticoid biosynthetic pathway, an in silico study was performed. This involved molecular docking studies of 18 ligands with the selected participating enzymes of the pathway. These enzymes were CYP11A1, CYP11B2, CYP19A1, CYP17A1, 3α/20β-HSD, 3β/17β-HSD and CYP21A2. Comparison of their binding affinity was made with the known inhibitors of these enzymes. In case of CYP11A1, Bisphenol M (BP M) had the lowest docking score (D score) of -8.699 kCal/mol, and was better than that of the standard, Metyrapone. Bisphenol PH (BP PH) was found to have significant affinity with CYP11B2. In case CYP19A1, results were found to be comparable with the standards, Exemestane and Letrozole. BP PH elicited better results than the standard Abiraterone acetate against CYP17A1. BP M had a D score of -7.759 against 3α/20β-HSD, again better results than the standard, Trilostane. Upon molecular docking of BP PH against CYP21A2, it was seen that amongst all the analogs, it had maximum interactions along with the lowest D score. From all the above instances mentioned, it is quite evident that certain BPA analogs have more potential to modulate the enzymes involved in comparison to the known inhibitors.


High mortality rate after extubation failure after pediatric cardiac surgery.
The objective of this study was to evaluate the different causes of extubation failure and the consequent mortality rates in a pediatric population after cardiac surgery. We studied 184 consecutive patients with a median age of 9 months (range, 0-165). In 158 patients, extubation was successful (group A). Nine patients were reintubated for upper airway obstruction and finally extubated successfully (group B). Seventeen patients were reintubated for cardiorespiratory failure, finally leading to death in 11 of 17 patients (65%) (group C). Group B patients were younger and had a longer intubation period compared to group A patients. Group C patients had more reoperations (30% vs 4% in group A patients, p < 0.001), a lower PaO2 on admission at the intensive care unit as well as just prior to extubation, a lower base deficit before extubation, and needed more inotropic support during their stay in the intensive care unit. We conclude that extubation failure after pediatric cardiac surgery due to cardiorespiratory failure is a bad prognostic sign. Patients with high inotropic support and a low PaO2 prior to extubation are especially at risk and probably need careful evaluation before final extubation.


Cloning and sequence analysis of the cDNA for the pituitary glycoprotein hormone alpha-subunit of the European eel.
A cDNA library constructed using mRNAs isolated from pituitary glands of estradiol-treated eels was screened with a cDNA fragment for the rat glycoprotein hormone alpha-subunit. Three out of 10,000 cDNA clones were revealed and subcloned in pUC13 for characterization and sequencing. All three had the same nucleotide sequence except for a single, silent change in the coding sequence for one of them, and for the location of the poly(A) tail. Analysis of the deduced amino acid sequence strongly suggests that these cDNA clones encode the precursor for the eel common glycoprotein hormone alpha-subunit. This precursor would therefore consist of a 93 amino acid apoprotein preceded by a 24 amino acid long signal peptide. Alignment with glycoprotein hormone alpha-subunits from fish and mammals reveals high homology, ranging from 60 to 90%. Particularly, the ten cysteines and the two putative N-linked glycosylation sites were at the same position. Comparison between fish and mammals shows also that two regions are highly conserved, comprising about half of the protein length. This high conservation rate through evolution argues for the importance of these regions in the conservation of biological properties of the alpha-subunits. In contrast, other regions are highly variable and could be responsible for the immunological specificity. Northern blot analysis of pituitary RNA from control and estradiol-treated eels showed that estradiol treatment strongly increases the pituitary content of mRNA encoding the glycoprotein hormone alpha-subunit.


POPULATION STRUCTURE AND KINSHIP IN POLISTES (HYMENOPTERA, VESPIDAE): AN ANALYSIS USING RIBOSOMAL DNA AND PROTEIN ELECTROPHORESIS.
Six variable protein loci and one variable ribosomal DNA restriction site were used for an analysis of population structure in five species of Polistes from Texas. A sample-reuse algorithm was developed that estimated FST , FIS , and ø (the coefficient of kinship) from probabilities of identity. Of the four species analyzed in detail only one, Polistes exclamans, had statistically significant values of FST . These values may reflect natural constraints on successful nesting for migrants of this species. Three of the four species had significant values of FIS and three of the four species had significant values of ø. In many cases ø also differed from the expected value under haplodiploidy and random mating. Values of ø did not differ from expectations under haplodiploidy and local inbreeding. These results emphasize that theories of social behavior and evolution based on coefficients of kinship should include some explicit consideration of population structure.


Release of histamine from hamster mast cells by concanavalin A and phytohemagglutinin.
Concanavalin A (Con A) and phytohemagglutinin (PHA) released histamine from hamster mast cells incubated in a serum-free medium. Concentrations of Con A and PHA approximating those optimal for transforming lymphocytes also released maximal amounts of histamine without apparent cytotoxicity. Higher concentrations of mitogen inhibited both lymphocyte transformation and histamine release. Incubation at 37 C for 15 min released histamine, although longer times were more effective. Supernatants from cultured hamster splenocytes stimulated with Con A also released histamine from added mast cells. However, the effect could be inhibited by the addition of 0.1 M methyl alpha-D-mannoside or by passing the spleen cell culture supernatants through Sephadex G-75 to remove Con A. This mitogen-induced release of mast cell histamine is therefore not mediated by a lymphokine but probably results from a direct interaction of mitogens with receptors on mast cells.


Electrospun CuS/PVP Nanowires and Superior Near-Infrared Filtration Efficiency for Thermal Shielding Applications.
Selective filtration of near-infrared (NIR) regions is of primary importance to energy saving via thermal shielding. However, uniform coating of highly effective nanomaterials on flexible substrates remains very challenging. Here, we introduce new material processing and fabrication methodologies that manufacture electrospun copper sulfide/polyvinylpyrrolidone (CuS/PVP) nanowires for enhanced thermal shielding efficiency. Electrospinning offers well-dispersed CuS nanoparticles in a thermal shielding film, which is not achievable in typical solution coating processes. Directly deposited CuS/PVP nanowires on a flexible polymer membrane are enabled by a fluorination treatment that decreases the interfacial electrostatic repulsion. Monitoring of in situ temperature change of a box-shielded, CuS/PVP nanowire film demonstrates excellent NIR shielding efficiency (87.15%). Direct integration of the film with a model car and exposure to direct sunlight demonstrates about twice-higher shielding efficiency than commercial tungsten oxide films. Overall, the comprehensive study of nanomaterial preparation, surface treatment, and integration techniques allows the fabrication of highly flexible and reliable thermal shielding films.


[Local application of interferon beta to skin lesions of malignant melanoma and malignant lymphoma--clinical and histopathological analysis].
Interferon (IFN) beta was applied locally to skin lesions of malignant melanoma (MM: 3 cases in stage IV and 1 case in stage II) and malignant lymphoma (ML: 3 cases of mycosis fungoides in stages II-III and 1 case of primary cutaneous lymphoma in stage III). It was found that IFN beta was remarkably effective for ML (3 in CR and 1 in PR), but far less effective for MM (3 in PD and 1 in NC). Biopsy specimens of clinically regressed areas revealed histopathology entirely different from each other, skin lesion of MM being infiltrated by numerous inflammatory cells such as lymphocytes and macrophages, whereas that of ML infiltrated Least. Local application of IFN beta appears to provide a new modality for treatment of cutaneous ML, which has the primary lesions on skin and has been hardly controlled by systemic chemoimmunotherapy.


The decline in family care for the aged in nineteenth-century Ontario: fact or fiction.
Two myths exist concerning the care of the aged in the past. The first purports that the aged were cared for by their families and that public assistance for the aged destroyed familial responsibility towards the elderly. In response to this contention, a second myth, which argues that the aged were not cared for by relatives, highlights the sufferings of abandoned and destitute aged people in institutions. In nineteenth-century Ontario, while the aged were not always cared for by kin, they were rarely willingly abandoned by their families. Evidence from diaries, letters, and institutional records indicates that families regularly provided whatever amount of care their resources would allow. However, financial restrictions, or the illness or senility of an aged person, often made it impossible for a family to cope with the demands this care entailed. When this occurred, many families institutionalized their aged in a House of Industry or an Asylum. While families have been blamed for subjecting the aged to the harsh conditions of these institutions, in most instances, they did so out of necessity and not by choice. It was the lack of public assistance and adequate facilities for the care of the aged, and not the irresponsibility of families, which caused the suffering which was so common among the aged poor during the last century.


Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity.
Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most of the effect, and the Moraxella mutant lacking UspA2 was more sensitive to the lytic effect of human serum compared with the wild type. Interestingly, among the large number of bacteria analyzed, only M. catarrhalis has this unique ability to interfere with the innate immune system of complement by binding C3.


High transverse momentum triggered correlations over a large pseudorapidity acceptance in Au + Au collisions at square root(s(NN)) = 200 GeV.
A measurement of two-particle correlations with a high transverse momentum trigger particle (p(T)(trig) > 2.5 GeV/c) is presented for Au+Au collisions at square root(s(NN)) = 200 GeV over the uniquely broad longitudinal acceptance of the PHOBOS detector (-4 < Delta eta < 2). A broadening of the away-side azimuthal correlation compared to elementary collisions is observed at all Delta eta. As in p+p collisions, the near side is characterized by a peak of correlated partners at small angle relative to the trigger particle. However, in central Au+Au collisions an additional correlation extended in Delta eta and known as the "ridge" is found to reach at least |Delta eta| approximately = 4. The ridge yield is largely independent of Delta eta over the measured range, and it decreases towards more peripheral collisions. For the chosen (p(T)(trig) cut, the ridge yield is consistent with zero for events with less than roughly 100 participating nucleons.


Pathological Complete Response after Immune-Checkpoint Inhibitor Followed by Salvage Surgery for Clinical Stage IV Pulmonary Adenocarcinoma with Continuous Low Neutrophil-to-Lymphocyte Ratio: A Case Report.
Immune-checkpoint inhibitors (ICIs) play a crucial role in the treatment of advanced nonsmall cell lung cancer (NSCLC); however, most patients fail this treatment after a limited period. We here report a patient with a pathological complete response after treatment with ICI for stage IV pulmonary adenocarcinoma. A 73-year-old man was referred to our hospital because of hoarseness. A roentgenogram and chest CT scan revealed a huge (78-mm diameter) pulmonary tumor in the right upper lobe and a tumor with cavitation in the left lower lobe. A CT scan also showed enlarged upper mediastinal lymph nodes (LNs). Transbronchial lung biopsy of the tumors showed adenocarcinomas in both. The tumor in the right upper lobe was considered to be the primary with mediastinal LNs metastasis and that in the left lower lobe a pulmonary metastasis. The disease was determined to be cT4N2M1a stage IVA. He was treated with first-line chemotherapy comprising cisplatin, pemetrexed, and bevacizumab for 6 cycles. However, 6 months after initial treatment, the primary and metastatic tumors enlarged, and he was treated with second-line anti-programed death 1 therapy for 7 months with a partial response. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed weak accumulation of FDG in the primary tumor only with no accumulation in the left pulmonary metastasis or mediastinal lymph node (LNs), despite the LNs still being enlarged. He was diagnosed as having ycT1bN0M0 stage IA2 disease and underwent right upper lobectomy. Postoperative pathological findings revealed that cancer tissues had been replaced by scar tissue and that CD4-positive T cells, rather than CD8-positive T cells, were predominant. It was also noted that he had a lower neutrophil-to-lymphocyte ratio (NLR) during immunotherapy than before immunotherapy and after surgery. He was diagnosed to be ypT0N0M0 stage 0 (Ef.3). His postoperative course was uneventful, and he remained well for 12 months after surgery with no further treatment. Neoadjuvant chemotherapy with ICIs for advanced NSCLC may be a promising modality, even for clinical stage IV disease, in the near future. Furthermore, NLR during immunotherapy may be a promising biomarker of ICIs treatment.


Feeding mastitis milk to organic dairy calves: effect on health and performance during suckling and on udder health at first calving.
Infection pathways of S. aureus udder infections in heifers are still not well understood. One hypothesis is that calves become infected with S. aureus via feeding mastitis milk. Especially on small-scale farms, pasteurisers are not economic. The purpose of this randomised comparative study was to investigate the influence of feeding milk containing S. aureus genotype B (SAGTB) on the health and development of calves and udder health of the respective heifers. Additionally, a method reducing the bacterial load to obtain safer feeding milk was tested. Thirty-four calves were fed mastitis milk from cows with subclinical SAGTB mastitis. One group was fed untreated milk (UMG). For the other group, milk was thermised at 61°C for one minute (heat treated milk group = HMG). After weaning, calves were followed up until first calving. A milk sample of these heifers was taken at first milking to compare udder health of both groups. Thermisation of milk led to an effective reduction of S. aureus in the feeding milk. 78% of the analysed pools were free of S. aureus, a reduction of at least one log was obtained in the other pools. Under the conditions of this study, no effects of feeding milk containing SAGTB on udder health after first calving were observed. But a power analysis indicated that the sample size in the current setup is insufficient to allow for assessment on mastitis risk after SAGTB exposition, as a minimal number of 4 calves infected (vs. 0 in the HMG) would have shown significant effects. High bacterial load, however, was associated with an increased incidence rate of diarrhoea. Thus, thermisation as a minimal preventive measure before feeding mastitis milk to calves might be beneficial for maintaining calf health.