Isolation and characterization of an alkaline phosphatase from pea thylakoids.
Endogenous dephosphorylation of the light-harvesting chlorophyll-protein complex of photosystem II in pea (Pisum sativum, L. cv Progress 9) thylakoids drives the state 2 to state 1 transition; the responsible enzyme is a thylakoid-bound, fluoride-sensitive phosphatase with a pH optimum of 8.0 (Bennett J [1980] Eur J Biochem 104: 85-89). An enzyme with these characteristics was isolated from well-washed thylakoids. Its molecular mass was estimated at 51.5 kD, and this monomer was catalytically active, although the activity was labile. The active site could be labeled with orthophosphate at pH 5.0. High levels of alkaline phosphatase activity were obtained with the assay substrate, 4-methylumbelliferyl phosphate (350 micromoles per minute per milligram purified enzyme). The isolated enzyme functioned as a phosphoprotein phosphatase toward phosphorylated histone III-S and phosphorylated, photosystem II-enriched particles from pea, with typical activities in the range of 200 to 600 picomoles per minute per milligram enzyme. These activities all had a pH optimum of 8.0 and were fluoride sensitive. The enzyme required magnesium ion for maximal activity but was not dependent on this ion. Evidence supporting a putative function for this phosphatase in dephosphorylation of thylakoid proteins came from the inhibition of this process by a polyclonal antibody preparation raised against the partially purified enzyme.


Analysis of human T-cell receptor V beta gene usage following immunization to tetanus toxoid in vivo.
The human T-cell antigen receptor (TcR) V beta repertoire was investigated following in vivo reimmunization with tetanus toxoid (TT). Four healthy subjects were immunized subcutaneously with TT, and 24 samples of peripheral blood T cells were taken at intervals over several weeks and used to generate TcR-C beta chain-specific first-strand cDNA. A semi-quantitative assay utilizing the polymerase chain reaction (PCR) was used to measure the amount of 22 different TcR-V beta gene transcripts in the cDNA. A peak increase in the amount of V beta 2, 4, 6, 13.1 and 14 occurred 14 days post-immunization, with each V beta increased in at least two of the four subjects. No obvious changes in the other 17 V beta genes were found. A secondary antibody response to TT occurred in all subjects by day 14. These results show that it is now possible to characterize the in vivo kinetics of the human TcR repertoire following stimulation with a conventional antigen.


Immunological aspects of B-cell derived tumors in humans and rodents.
Translocation of the c-myc protooncogene to an immunoglobulin locus is a rate-limiting step in the genesis of three B-cell derived tumors: Burkitt lymphoma (BL) in humans, mouse plasmocytoma (MPC) and rat immunocytoma (RIC). Its consequences have been best analysed in BL. They involve a non-immunological and an immunological component. The former acts by preventing the B-cell from leaving the cycling compartment and entering the resting stage when programmed to do so. The latter acts by the down-regulation of certain HLA class I polymorphic specificities, leukocyte adhesion molecules and Epstein-Barr virus (EBV) encoded proteins. Together, they contribute to the escape of the BL cell from the host immune response.--We have also described a non-clonogenic, non-tumorigenic "revertant" subline among five EBV-convertants of an originally highly tumorigenic, EBV-negative BL line. The other four convertants have remained highly tumorigenic. Suppression of the tumorigenicity is associated with a switch to a lymphoblastoid cell line (LCL)-like phenotype, accompanied by the appearance of several activation markers. It is suggested that the LCL-type immunoblast comes under the influence of host feed-back controls that normally contribute to the constancy of the B-cell pool.


The parasitoids of the asparagus miner (Diptera: Agromyzidae): field parasitism and the influence of food resources on life history.
The goals of this study were to identify pupal parasitoids of the asparagus miner, Ophiomyia simplex Loew (Diptera: Agromyzidae), and examine the effect of different diets and floral resources on the lifespan of adult asparagus miners and their parasitoids. We also measured the effect of parasitism on stem damage caused by the asparagus miner. The identity and abundance of the parasitoids of the asparagus miner were determined in asparagus fields in Michigan from weekly asparagus miner pupal collections during the 2010-2013 seasons. Twelve species of hymenopterous parasitoids were reared from asparagus miner pupae, including Chorebus rondanii (Giard) (Ichneumonoidea: Braconidae), 10 species in three families of Chalcidoidea, and one species of Bethylidae (Chrysidoidea), that represent new host records for the asparagus miner. C. rondanii and Thinodytes cephalon (Walker) (Pteromalidae) were the most common parasitoids. The effects of different diets and flowers on the lifespan of the pest and parasitoid adults were also evaluated. Buckwheat resulted in the shortest life span for the asparagus miner, whereas Riddell's goldenrod significantly increased its lifespan relative to the control. Parasitoid lifespan was doubled when individuals were fed sugar-rich diets. In the field, parasitoids preferred stems that contained more pupae and damage. The two most commonly reared parasitoids should be considered as targets for future conservation biological control efforts of the asparagus miner.


[Otorhinolaryngological consultation material in PDA: SEORL-PDA].
Occasionally, the Otolaryngologist needs to accede quickly to medical information in order to retrieve data or to solve doubts. In this way, it seems to be of interest to design a clinical guide that could be consulted as a PDA program (Pocket PC and Palm versions), in a personal computer or Internet. Clinical contents of protocols, guides, and articles, preferably based on the evidence and the clinical experience of 102 authors. Implementation of a program that allows the guide to be used in a PDA, to update it or to add notes using tools that could be downloaded from a web page. A clinical practice guide SEORL-PDA version 1.1, with thirteen ENT's topics, calculation algorithms, internal links and possibility of update the content and to add notes. SEORL-PDA is a clinical guide in PDA format, with enough information and possibilities. Its downloading and installation is easily done following the instructions of the web created with these purposes.


[Refixation of osteochondral fragments using absorbable plastic pins].
The authors report on the fixation of cartilage-bone fragments via an (absorbable) PDS rod. The study was conducted with 18 rabbit knee joints. Good healing of the fragments was seen over a period of 10 weeks. In vitro examinations of the rod showed satisfactory tearing and bending strength with only slow deterioration of strength due to hydrolysis. On the basis of these studies the authors believe that the rods are suitable for fixing small fragments in accident surgery. Other fields of application are possible and require to be investigated.


Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study.
The Gustave Roussy Immune score (GRIm-Score) emerges as a novel prognostic scoring system for patient selection in phase I trials testing targeted immunotherapy for advanced-stage cancer. We tried to assess potential prognostic roles of preoperative GRIm-Score in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC) by propensity score-matching (PSM) analysis. This PSM-based analysis was performed on our single-center prospectively-maintained database between January 2014 and October 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative GRIm-Score. Multivariable Cox-proportional hazards regression analysis and PSM analysis were both carried out to determine the final independent prognostic parameters. There were 405 patients with surgically resectable stage I-II NSCLC included. Both OS and DFS were significantly shortened along with each number increase in the GRIm-Score group, showing a step-wise fashion. Such strong correlations between preoperative GRIm-Score estimated by a modified 3-category risk scale and survival outcomes still remained validated after PSM analysis. In addition, this GRIm-Score held the superior discriminatory power for predicting both OS and DFS to the other peripheral blood biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that GRIm-Score based on a 3-category risk assessment scale could be independently predictive of both OS and DFS. The GRIm-Score tool can also serve as an effective and noninvasive marker to optimize prognostic prediction for surgically resectable stage I-II NSCLC.


Biodiversity maintenance mechanisms differ between native and novel exotic-dominated communities.
In many systems, native communities are being replaced by novel exotic-dominated ones. We experimentally compared species diversity decline between nine-species grassland communities under field conditions to test whether diversity maintenance mechanisms differed between communities containing all exotic or all native species using a pool of 40 species. Aboveground biomass was greater in exotic than native plots, and this difference was larger in mixtures than in monocultures. Species diversity declined more in exotic than native communities and declines were explained by different mechanisms. In exotic communities, overyielding species had high biomass in monoculture and diversity declined linearly as this selection effect increased. In native communities, however, overyielding species had low biomass in monoculture and there was no relationship between the selection effect and diversity decline. This suggests that, for this system, yielding behaviour is fundamentally different between presumably co-evolved natives and coevolutionarily naive exotic species, and that native-exotic status is important to consider.


Identification of women's breast cancer prevention behaviors and the associated factors: The case of the southeastern Anatolia Region.
In this study, the researchers investigated the factors that affect women's breast cancer prevention behaviors. The sample of this cross-sectional and descriptive study consisted of 406 participants aged 20 and older. The study was conducted in February-March 2021 within the administrative borders of a province located in the Southeastern Anatolia Region of Turkey. The data were collected via an online platform using Personal Information Form and the Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors. The mean Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors score of the participants was moderate as 107.20 ± 17.86. The frequency of breast cancer prevention behaviors was found to be lower in the participants with low literacy, those who were unemployed, those with low income, those living in villages and those who did not perform breast self-examination (p < 0.05). It is recommended to plan educational studies on breast cancer screening behaviors by considering regional differences.


Cross-national survey of winter and summer patterns of mood seasonality: a comparison between Italy and India.
The aim of this study was to compare winter and summer patterns of mood seasonality in university students living at different latitudes: Bologna, 44° N (Italy), and Kalyani, 22° N (India). To assess the mood seasonality, the Seasonal Pattern Assessment Questionnaire was administered to 1370 university students (808 females, 562 males; 862 Italians, 508 Indians), ranging in age between 18 and 28 years. A significantly higher Global Seasonality Score was observed in females than males as well as in Italians than Indians. The estimated rates of summer seasonal affective disorder (SAD) and summer subsyndromal SAD were higher in Indians, whereas Italians reported higher percentage of winter SAD and winter subsyndromal SAD. The present findings are discussed in relation to the different environmental features between the 2 countries: high summer temperature in India and short winter photoperiod along with its great excursion over the year in Italy.


De Novo Sequencing of Complex Mixtures of Heparan Sulfate Oligosaccharides.
Here, we describe the first sequencing method of a complex mixture of heparan sulfate tetrasaccharides by LC-MS/MS. Heparin and heparan sulfate (HS) are linear polysaccharides that are modified in a complex manner by N- and O-sulfation, N-acetylation, and epimerization of the uronic acid. Heparin and HS are involved in various essential cellular communication processes. The structural analysis of these glycosaminoglycans is challenging due to the lability of their sulfate groups, the high heterogeneity of modifications, and the epimerization of the uronic acids. While advances in liquid chromatography (LC) and mass spectrometry (MS) have enabled compositional profiling of HS oligosaccharide mixtures, online separation and detailed structural analysis of isomeric and epimeric HS mixtures has not been achieved. Here, we report the development and evaluation of a chemical derivatization and tandem mass spectrometry method that can separate and identify isomeric and epimeric structures from complex mixtures. A series of well-defined synthetic HS tetrasaccharides varying in sulfation patterns and uronic acid epimerization were analyzed by chemical derivatization and LC-MS/MS. These synthetic compounds made it possible to establish relationships between HS structure, chromatographic behavior and MS/MS fragmentation characteristics. Using the analytical characteristics determined through the analysis of the synthetic HS tetrasaccharide standards, an HS tetrasacharide mixture derived from natural sources was successfully sequenced. This method represents the first sequencing of complex mixtures of HS oligosaccharides, an essential milestone in the analysis of structure-function relationships of these carbohydrates.


Drugs and the liver: advances in metabolism, toxicity, and therapeutics.
Biotransformation of drugs is one of the major functions of liver. Hepatic drug metabolism develops early in organogenesis and continues in postnatal life through puberty. Genetic and developmental studies on hepatic drug metabolism show that immaturity, polymorphisms, and altered balance of different hepatic enzymatic activities affect pharmacologic inactivation and alter the risk of toxic effects of drugs on the hepatic parenchyma. Although drug-induced liver disease is less common in children, several reports of hepatotoxicity are published every year. Furthermore, the increasing use of nonregulated remedies (eg, herbal preparations or recreational drugs) increases the risk of unpredictable and potentially severe reactions. Many significant advances in the treatment of hepatic diseases have been achieved recently. However, differences in clinical features, natural history, and response to treatment between children and adults require evaluation of new therapeutic options in focused pediatric clinical trials.


A randomized, controlled trial of the efficacy of a communication course for first time hearing aid users.
Many centres include a communication course as part of their auditory rehabilitation. These usually take the form of a small group and include discussion of the effects of hearing loss, use of the hearing aid, hearing tactics and lip reading. To investigate the efficacy of such a rehabilitation programme a randomized, controlled trial of a communication course was undertaken. All subjects were first time hearing aid users; handicap was measured using the Quantified Denver Scale of Communication Function (QDS) at the time of hearing aid fitting, and then 13 weeks later. All subjects had a hearing aid follow-up appointment, but the treatment group (n = 22) also underwent a four-week communication course, while the control group (n = 25) had no further rehabilitation. The reduction in handicap measured by the change in QDS was significantly greater for the treatment group than for the control group (Mann Whitney U test, tied p value = 0.014). This indicates that such a communication course is efficacious in reducing handicap. Further research is required to identify the populations that will benefit most from such a course.


Lung-Derived Selectins Enhance Metastatic Behavior of Triple Negative Breast Cancer Cells.
The lung is one of the deadliest sites of breast cancer metastasis, particularly for triple negative breast cancer (TNBC). We have previously shown that the lung produces several soluble factors that may enhance the metastatic behavior of TNBC, including E-, L-, and P-selectin. In this paper, we hypothesize that lung-derived selectins promote TNBC metastatic behavior and may serve as a potential therapeutic target. Lungs were isolated from mice and used to generate lung-conditioned media (CM). Lung-derived selectins were immunodepleted and TNBC migration and proliferation were assessed in response to native or selectin-depleted lung-CM. A 3D ex vivo pulmonary metastasis assay (PuMA) was used to assess the metastatic progression of TNBC in the lungs of wild-type versus triple-selectin (ELP-/-) knockout mice. We observed that individual lung-derived selectins enhance in vitro migration (p ≤ 0.05), but not the proliferation of TNBC cells, and that ex vivo metastatic progression is reduced in the lungs of ELP-/- mice compared to wild-type mice (p ≤ 0.05). Treatment with the pan-selectin inhibitor bimosiamose reduced in vitro lung-specific TNBC migration and proliferation (p ≤ 0.05). Taken together, these results suggest that lung-derived selectins may present a potential therapeutic target against TNBC metastasis. Future studies are aimed at elucidating the pro-metastatic mechanisms of lung-derived selectins and developing a lung-directed therapeutic approach.


[Isolated and asymptomatic Brugada syndrome. A case report].
The case report of a 32-year-old man with a Brugada syndrome is presented. He was asymptomatic and without familial history of sudden death or syncope. Diagnosis criteria for Brugada syndrome were 1--a pattern of right bundle branch block and ST-segment elevation in leads V1 and V2 on the ECG, 2--no cardiac structural anomalies. Symptomatic patients with this electrical anomaly are at high risk of sudden death and need an automatic implantable defibrillator. The outcome and the treatment of asymptomatic patients are a matter of debate and are discussed in this report.


Use of isoxsuprine hydrochloride as a tocolytic agent in the treatment of preterm labour: a systematic review of previous literature.
The aim of this systematic review was to evaluate the efficacy of isoxsuprine (1-(4-hydroxyphenyl)-2-(1-methyl-2-phe-noxyethylamino)-1-propanol, CAS 395-28-8), a tocolytic agent used in both preterm labour and risk of abortion. Two analyses were conducted on data reporting the use of isoxsuprine in the prevention of preterm delivery. The first analysis examined two double-blind studies to determine the effect of isoxsuprine compared to placebo. The second analysis reviewed data from 25 publications containing individual and general patient data. Main outcome measures included delay of pregnancy and patient outcome. Analysis of double-blind studies demonstrated a positive outcome with isoxsuprine in 92% of cases compared to placebo control (44.4%, p < 0.001). This beneficial effect was maintained when either risk of abortion (92.5% in isoxsuprine treated compared to 46.4% in placebo, p < 0.001) or risk of premature delivery (89.5% in isoxsuprine treated compared to 29.4% in placebo, p < 0.001) was examined. Secondary analysis of individual patient data also revealed a beneficial effect of isoxsuprine in prolonging pregnancy in 54.5% of women at risk of abortion and in 82.3% of women at risk of premature delivery. Combination of individual and general data revealed a beneficial effect of isoxsuprine in 77.3% of cases at risk of abortion and 89% for risk of premature delivery. These findings provide preliminary evidence in favour of the effectiveness of isoxsuprine in prolonging pregnancy in women at risk of abortion or premature delivery.


Clinical significance of GCF sIL-6R and calprotectin to evaluate the periodontal inflammation.
Background Periodontitis is an inflammatory disease. The aim of this study was to investigate whether the soluble form of interleukin-6 receptor (sIL-6R) and calprotectin concentrations in gingival crevicular fluid are useful biomarkers in the evaluation of periodontitis. Methods First, a cross-sectional study was performed. A total of 34 periodontitis patients were enrolled and the gingival crevicular fluid samples were collected from the healthy and inflamed sites of periodontal pockets in each patient. The relationship between periodontal condition and gingival crevicular fluid sIL-6R and calprotectin concentrations was analysed statistically. The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontitis were determined using a receiver operating characteristic curve. Next, by using enzyme-linked immunosorbent assay, it was examined whether calprotectin induces sIL-6R production in THP-1 macrophages. Results Both gingival crevicular fluid sIL-6R and calprotectin concentrations were significantly higher in the inflamed sites than in the healthy sites ( P < 0.0001). The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontal inflammation were as follows: sIL-6R: 43.5 pg/site; calprotectin: 134.3 ng/site. In the in vitro study, calprotectin significantly induced sIL-6R production in THP-1 macrophages ( P < 0.01). Conclusions Both gingival crevicular fluid sIL-6R and calprotectin concentrations are significant biomarkers in the evaluation of periodontal inflammation.


Giant coronary artery aneurysms associated with Kawasaki disease detected on whole-heart magnetic resonance coronary angiographic screening.
Kawasaki disease (KD) is one of the most important causes of coronary artery aneurysms in children and young adults. However, the natural course of the disease and the patient prognosis remain obscure. A 72-year-old asymptomatic man with undiagnosed KD underwent whole-heart magnetic resonance coronary angiography during a health checkup. The imaging disclosed giant aneurysms in the proximal portion of the right coronary artery and the left anterior descending artery. The patient was successfully treated with coronary artery bypass grafting. The present case suggests that there may be a substantial number of patients who have attained middle to old age with undiagnosed KD.


Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation.
The aim of the present study was to evaluate the influence of the degree of modification and the polymer chain length on the mucoadhesive properties and the swelling behavior of thiolated chitosan derivatives obtained via a simple one-step reaction between the polymer and 2-iminothiolane. The conjugates differing in molecular mass of the polymer backbone and in the amount of immobilized thiol groups were compressed into tablets. They were investigated for their mucoadhesive properties on freshly excised porcine mucosa via tensile studies and the rotating cylinder method. Moreover, the swelling behavior of these tablets in aqueous solutions was studied by a simple gravimetric method. The obtained results demonstrated that the total work of adhesion of chitosan-TBA (=4-thio-butyl-amidine) conjugates can be improved by an increasing number of covalently attached thiol groups; a 100-fold increase compared to unmodified chitosan was observed for a medium molecular mass chitosan-TBA conjugate exhibiting 264 microM thiol groups per gram polymer. Also, the polymer chain length had an influence on the mucoadhesive properties of the polymer. The medium molecular mass polymer displayed a fourfold improved adhesion on the rotating cylinder compared to the derivative of low molecular mass. These results contribute to the development of new delivery systems exhibiting improved mucoadhesive properties.


Hematopoietic cell proliferation and differentiation.
Most hematopoietic stem cells are quiescent in the G0 stage of the cell cycle. Certain combinations of hematopoietic growth factors can bind to their cognate receptors on the stem cell surface, shorten the G0 stage of the cell cycle, and stimulate cell division. Hematopoietic growth factors also act on committed progenitors to increase their survival and to amplify maturing populations by stimulating proliferation. Although differentiation is probably determined largely by an intrinsic program, there is evidence that certain receptors expressed on more mature cells can also direct differentiation. This view is still controversial, as is the view that hematopoietic growth factors act merely to prevent apoptosis. Different members of the hematopoietic growth factor family of receptors recruit overlapping sets of tyrosine kinases and share common signal transduction pathways such as Ras. They also directly activate a cytoplasmic class of transcription factors that then translocate to the nucleus. The development of committed hematopoietic progenitor cells into mature effector cells is regulated by "master" transcription factors that recognize motifs in the promoters of many genes that encode lineage-specific proteins.


Condylar and temporomandibular joint disc positions after mandibular osteotomy for prognathism.
The purpose of this study was to compare the changes in temporomandibular joint (TMJ) morphology and clinical symptoms after sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) with and without a Le Fort I osteotomy. Of 43 patients with a diagnosed jaw deformity, 20 underwent IVRO without internal fixation and 23 underwent SSRO with rigid internal fixation. Some operations were performed in combination with a Le Fort I osteotomy. The TMJ symptoms and joint morphology, including the disc position, were assessed preoperatively and postoperatively using magnetic resonance imaging (MRI) and axial cephalography. A significant difference in the direction of condylar rotation was seen in horizontal axial cephalography images (P <.01). Fewer or no TMJ symptoms were reported postoperatively by 88% of the patients who underwent IVRO with or without a Le Fort I osteotomy and by 66.7% of patients who underwent SSRO with or without a Le Fort I osteotomy. In sagittal images, no change was seen in anterior disc displacement after SSRO; however, improvement was seen in 44.4% of patients with anterior disc displacement who underwent IVRO with or without a Le Fort I osteotomy. These results suggest that SSRO does not improve anterior disc displacement; IVRO improves anterior disc displacement in the initial postsurgical period, and both procedures may improve TMJ symptoms.


Impacts of Nursing Work Environment on Turnover Intentions: The Mediating Role of Burnout in Ghana.
The nursing practice environment supports excellence and decent work and has the influence to entice and retain the quality nursing workforce. Appreciating the dynamics that affect the turnover intention of RNs offer reasonable solutions to the challenges of the nursing shortage, which directly influence the quality of nursing care. There is a paucity of information on the impacts of these concepts among RNs in Sub-Saharan African. The study therefore aimed at determining the impacts of work environment and burnout on turnover intentions among RNs in Ghana. A descriptive cross-sectional design using a simple random and proportionate stratified sampling with a sample of 232 RNs from Municipal and Regional Hospitals, Sunyani, West-Central part of Ghana completed validated instruments measuring work environment, burnout, and turnover intentions. Descriptive analysis was done to find out RNs' perceptions of their work environment and turnover intentions. Mediation analysis by Baron and Kenny's approach was used to determine the mediating effect of burnout on the relationship between the domains of PPE and the turnover intention of RNs. STROBE checklist was used as the reporting tool. While most RNs had a positive perception about their work environment, greater number of them had turnover intentions. There were significant associations between some nursing work environment facets and turnover intention. The results also showed a statistically significant relationship between nurse-physician relation (β = .353, t = 5.476, p ≤ .001), nurse manager leadership (β = -0.485, t = -8.192, p ≤ .001), nursing foundation for quality care (β = .400, t = 7.059, p ≤ .001), staffing and resource adequacy on (β = 0.485, t = 8.183, p ≤ .001), and turnover intention as mediated by burnout. Burnout resulting from an unsafe work environment impact RNs' turnover intention. This phenomenon can potentially affect the human resource management and quality of nursing care. Policy strategies aimed at ensuring a professional practice environment and decreased burnout can therefore improve retention of RNs at their workplace.


Occupational health services gain favor for good reason.
Occupational health programs offer hospitals an opportunity to improve their bottom line with little financial investment. Hospitals that will be the most successful in capturing the business of employers are those that take the time to assess their markets carefully, tailor their programs to individual employer's needs, incorporate a strong sales component and consistently communicate with participating employers. Beyond capturing revenue from employers, the major benefit of occupational health programs lies in the relationships they allow hospitals to build with employees in their markets--40% of whom do not have a primary-care physician. Once introduced to the hospital, these patients and their families are likely to return to the hospital for future medical needs. The ability to establish relationships that can generate business for the hospital and its physicians for years to come makes occupational health one of the wisest and most profitable diversification strategies of the decade.


In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor.
MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system in KrasG12D/Trp53L/L (KP) mouse model. Using this in vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b in KP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted the Hus1 gene and knockout of Hus1 in KP model dramatically suppressed lung tumorigenesis. Collectively, our study developed an in vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.


Characteristics and the Model of Thermal Evolution and Gas Generation of Late Paleozoic Coal in the Qinshui Basin, Based on Hydrous Pyrolysis.
The Qinshui basin is an important coal-accumulating basin in China, and its Late Paleozoic coal is an important source rock of coalbed methane in the basin. Its thermal evolution and gas generation characteristics determined the grade of coalbed methane resources, especially the coal measure free gas resources in the basin. Late Paleozoic coal samples were collected for organic geochemical analysis, a high-volatile bituminous coal was used for hydrous pyrolysis, to propose the thermal evolution characteristics, gas generation characteristics, thermal evolution, and free gas accumulation model, and the Ordos Basin is compared. The results show that the variation trends of various geochemical parameters are different with the increase in R o. Hydrous pyrolysis shows that the gas production potential of coal is excellent. The gases produced consist mainly of CH4, C2-, CO2, and H2. C2- is produced only before the simulated temperature of 550 °C, and oil is produced only before the temperature of 500 °C. The thermal evolution stages can be divided into the immature stage, symbiosis stage, wet gas stage, and dry gas stage, and the symbiosis stage can be divided into the preliminary stage and mainly gas stage. R o, T max, (2+3)MP/(1+9)MP, saturated+arene, V daf, and H/C can be used as indicators of the thermal evolution stages. On the plane, the distribution of thermal evolution stages of the Shanxi Formation and the Taiyuan Formation is very alike. The gas generating strength of the Taiyuan Formation is higher than that of the Shanxi Formation. The gas generating strength in the north of the Taiyuan Formation is higher, while that in the south of the Shanxi Formation is higher. The second gas generation stage has a good spatio-temporal configuration relationship with accumulation factors, and the gas production is large, which is beneficial to the enrichment of the coal measure free gas resources. Relatively, the Ordos Basin has better prospects for exploration and development.


Orthotopic urethral substitution in female patients using the mitrofanoff principle.
We present our experience with orthotopic urethral substitution in female patients using the Mitrofanoff principle. We performed orthotopic urethral substitution using the Mitrofanoff principle in 18 female patients 1 to 29 years old (mean age 10). The conduit was constructed with appendix in 13 cases, tapered ileum in 4 and fallopian tube in 1. The etiology of incontinence included exstrophy in 8 patients, neurogenic bladder in 3, urogenital sinus in 3, and bilateral ectopic ureter, ectopic ureterocele, the prune-belly syndrome and post-cystectomy undiversion in 1 each. Mean followup was 29 months (range 9 to 72). A total of 16 patients achieved continence following a program of clean intermittent catheterization. There were 2 unsuccessful operations. In 1 case the appendix become ischemic and in 1 a vesicoperineal fistula developed. One patient catheterizes every 2 hours to avoid leakage. Catheterization was temporarily difficult in 5 patients, of whom 2 had an appendiceal and 3 had a tapered ileal conduit. Two patients with an ileal conduit have had chronic difficult catheterization. Orthotopic replacement of the urethra using the Mitrofanoff principle is suitable in highly select female patients who need continent diversion or a catheterizable conduit but who will not accept an abdominal stoma. It is particularly suited to patients in whom exstrophy reconstruction has failed.


Characterization of Triazine-Resistant and -Susceptible Isolines of Canola (Brassica napus L.).
Morphometric, electrophoretic, and immunological procedures were used to probe the structural and physiological differences between triazine-resistant (R) and susceptible (S) isolines of canola (Brassica napus L.). The R biotype exhibited increased grana stacking and decreased amounts of starch compared to the S biotype. Likewise, characters associated with an increase in grana stacking (lower chlorophyll a/b ratio, increased chlorophyll a/b light-harvesting complex, and relatively lower amounts of the P700 chlorophyll a protein and chloroplast coupling factor) were all observed in the R isoline of canola. Proteins which occur with approximately equal frequency in grana and stroma lamellae (plastocyanin, cutochrome f) or present only in the stroma (ribulose 1,5-bisphosphate carboxylase/oxygenase) were not quantitatively different in the two biotypes. Gross anatomical parameters (volume of epidermis, palisade mesophyll, spongy mesophyll, and air space) were similar in the two isolines. Thus, the triazine-resistance mutation does not confer a shade-type anatomy despite the chloroplast changes that are characteristic of shade biotypes or shade adaptions. These data indicate that the differences in chloroplast structure noted previously in comparisons of nonisonuclear R and S weed biotypes reflect differences in the triazineresistance factor rather than characters unrelated to triazine resistance.


The platelet release reaction: just when you thought platelet secretion was simple.
In response to agonists produced at vascular lesions, platelets release a host of components from their three granules: dense core, alpha, and lysosome. This releasate activates other platelets, promotes wound repair, and initiates inflammatory responses. Although widely accepted, the specific mechanisms underlying platelet secretion are only now coming to light. This review focuses on the core machinery required for platelet secretion. Proteomic analyses have provided a catalog of the components released from activated platelets. Experiments using a combination of in-vitro secretion assays and knockout mice have led to assignments of both vesicle-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (v-SNARE) and target membrane SNARE to each of the three secretion events. SNARE knockout mice are also proving to be useful models for probing the role of platelet exocytosis in vivo. Other studies are beginning to identify SNARE regulators, which control when and where SNAREs interact during platelet activation. A complex set of protein-protein interactions control the membrane fusion events required for the platelet release reaction. SNARE proteins are the core elements but the proteins that control SNARE interactions represent key points at which platelet signaling cascades could affect secretion and thrombosis.


Immunoprotection of recombinant Eg.myophilin against Echinococcus granulosus infection in sheep.
The aims of the present study were to investigate the immunoprotection of recombinant Echinococcus granulosus myophilin (rEg.myophilin) against the establishment of a challenge oral infection with E. granulosus eggs, as well as to determine the mechanisms underlying this protection. Sheep were subcutaneously immunized two times with rEg.myophilin, followed by the challenge with E. granulosus eggs orally. The animals were sacrificed 44 weeks after infection and the immunoglobulin (Ig) and cytokine levels were analyzed using ELISA. The results identified significant changes in several indexes of animal immune response subsequent to immunization with rEg.myophilin. These changes included reduced number of formed cysts, as well as elevated levels of IgG, IgA and cytokines. The present data suggest that immunization with rEg.myophilin in sheep can successfully reduce the formation of cysts caused by challenge E. granulosus infection and stimulate immune response, suggesting that rEg.myophilin a has potential value as a candidate vaccine against E. granulosus.


Quantitative digital subtraction radiography in the assessment of external apical root resorption induced by orthodontic therapy: a retrospective study.
The objective of this study was to evaluate density changes around the apices of teeth during orthodontic treatment by using digital subtraction radiography to measure the densities around six teeth (maxilla central incisors, lateral incisors, and canines) before and after orthodontic treatment in 36 patients and also assess treatment variables and their coorelation with root resorption. A total of 36 consecutive patient files were selected initially. The selected patients presented with a class I or II relationship and were treated with or without premolar extractions and fixed appliances. Some class II patients were treated additionally with extraoral forces or functional appliances. External apical root resorption (EARR) per tooth in millimeters was calculated and was also expressed as a percentage of the original root length. Image reconstruction and subtraction were performed using the software Regeemy Image Registration and Mosaicing (version 0.2.43-RCB, DPI-INPE, Sao Jose dos Campos, Sao Paulo, Brazil) by a single operator. A region of interest (ROI) was defined in the apical third of the root and density calibration was made in Image J® using enamel (gray value = 255) as reference in the same image. The mean gray values in the ROIs were reflective of the change in the density values between the two images. The root resorption of the tooth and the factors of malocclusion were analyzed with a one-way ANOVA. An independent t-test was performed to compare the mean amount of resorption between male and female, between extraction and nonextraction cases. The density changes after orthodontic treatment were analyzed using the Wilcoxon signedrank test. In addition, the density changes in different teeth were analyzed using the Kruskal-Wallis test. The cut-off for statistical significance was a p-value of 0.05. All the statistical analyses were carried out using SPSS (version 13.0 for Windows, Chicago, IL, USA). Gender, the age at which treatment was started and Angle's classification was not statistically related with observed root resorption. The mean percentage density reduction as assessed by DSR was greatest in both central incisor: by 27.2 and 25.2% in the upper-right and upper-left central incisors, respectively, followed by the upper-right and upper-left canine teeth (23.5 and 21.0%) and then the upper-right and upper-left lateral incisors (19.1 and 17.4%). Tooth extraction prior to treatment initiation and the duration of orthodontic treatment was positively correlated with the amount of root resorption. DSR is useful for evaluating density changes around teeth during orthodontic treatment. The density around the apices of teeth reduced significantly after the application of orthodontic forces during treatment. Assessment of density changes on treatment radiographs of patients undergoing orthodontic therapy may help in the monitoring of external apical root resorption during course of treatment.


TGF beta1 expression and angiogenesis in colorectal cancer tissue.
Transforming growth factor TGF beta1 is involved in a variety of important cellular functions,including cell growth and differentiation, angiogenesis, immune function and extracellular matrix formation. However, the role of TGF beta(1) as an angiogenic factor in colorectal cancer is still unclear. We investigate the relationship between transforming growth factor beta(1) and angiogenesis by analyzing the expression of transforming growth factor TGF beta(1) in colorectal cancer, as well as its association with VEGF and MVD. The expression of TGF beta(1),VEGF, as well as MVD were detected in 98 colorectal cancer by immunohistochemical staining. The relationship between the TGF beta(1) expression and VEGF expression,MVD was evaluated. To evaluate the effect of TGF beta(1) on the angiogenesis of colorectal cancers. Among 98 cases of colorectal cancer,37 were positive for TGF beta(1) 37.8% 36 for VEGF 36.7% respectively. The microvessel counts ranged from 19 to 139.8, with a mean of 48.7(standard deviation,21.8). The expression of TGF beta(1) was correlated significantly with the depth of invasion, stage of disease, lymph node metastasis, VEGF expression and MVD. Patients in T3-T4, stage III-IV and with lymph node metastasis had much higher expression of TGF beta(1) than patients in T1-T2, stage I-II and without lymph node metastasis (P<0.05). The positive expression rate of VEGF(58.3%) in the TGF-beta(1) positive group is higher than that in the TGF-beta(1) negative group(41.7%, P<0.05). Also, the microvessel count (54+/-18) in TGF-beta(1) positive group is significantly higher than that in TGF-beta(1) negative group(46+/-15, P<0.05). The microvessel count in tumors with both TGF-beta(1) and VEGF positive were the highest (58+/-20 36-140, P<0.05). Whereas that in tumors with both TGF-beta(1) and VEGF negative were the lowest (38+/-16, 19-60, P<0.05). TGF beta(1) might be associated with tumor progression by modulating the angiogenesis in colorectal cancer and TGF beta(1) may be used as a possible biomarker.


Effectiveness of Telehealth in Rural and Remote Emergency Departments: Systematic Review.
Emergency telehealth has been used to improve access of patients residing in rural and remote areas to specialist care in the hope of mitigating the significant health disparities that they experience. Patient disposition decisions in rural and remote emergency departments (EDs) can be complex and largely dependent on the expertise and experience available at local (receiving-end) hospitals. Although there has been some synthesis of evidence of the effectiveness of emergency telehealth in clinical practice in rural and remote EDs for nonacute presentations, there has been limited evaluation of the influence of contextual factors such as clinical area and acuity of presentation on these findings. The aims of this systematic review are to examine the outcome measures used in studying the effectiveness of telehealth in rural and remote EDs and to analyze the clinical context in which these outcome measures were used and interpreted. The search strategy used Medical Subject Headings and equivalent lists of subject descriptors to find articles covering 4 key domains: telehealth or telemedicine, EDs, effectiveness, and rural and remote. Studies were selected using the Population, Intervention, Comparator, Outcomes of Interest, and Study Design framework. This search strategy was applied to MEDLINE (Ovid), Cochrane Library, Scopus, CINAHL, ProQuest, and EconLit, as well as the Centre for Reviews and Dissemination databases (eg, National Health Service Economic Evaluation Database) for the search period from January 1, 1990, to May 23, 2020. Qualitative synthesis was performed on the outcome measures used in the included studies, in particular the clinical contexts within which they were interpreted. A total of 21 full-text articles were included for qualitative analysis. Telehealth use in rural and remote EDs demonstrated effectiveness in achieving improved or equivalent clinical effectiveness, appropriate care processes, and-depending on the context-improvement in speed of care, as well as favorable service use patterns. The definition of effectiveness varied across the clinical areas and contexts of the studies, and different measures have been used to affirm the safety and clinical effectiveness of telehealth in rural and remote EDs. The acuity of patient presentation emerged as a dominant consideration in the interpretation of interlinking time-sensitive clinical effectiveness and patient disposition measures such as transfer and discharge rates, local hospital admission, length of stay, and ED length of stay. These, together with clinical area and acuity of presentation, are the outcome determination criteria that emerged from this review. Emergency telehealth studies typically use multiple outcome measures to determine the effectiveness of the services. The outcome determination criteria that emerged from this analysis are useful when defining the favorable direction for each outcome measure of interest. The findings of this review have implications for emergency telehealth service design and policies. PROSPERO CRD42019145903; https://tinyurl.com/ndmkr8ry.


Facing Morbid Obesity: How to Approach It.
Obesity is a major public health problem, with a prevalence of 10% to 20% in Western Europe. Morbid obesity, characterized by body mass index >40 kg/m(2), showed an increased prevalence in the last 30 years. Obesity is associated with reduced economic and social opportunities, reduced quality of life, and is a determinant of several "intermediate risk factors," leading to an increased mortality and a loss in life expectancy. The rising prevalence of morbid obesity increased the demand for bariatric surgery, also called "metabolic surgery": after these interventions, there is a decrease in metabolic comorbidities, cardiovascular (CV) risk, and total mortality. In this review, we update the evaluation of morbid obese patients from the physical examination to the metabolic, CV and respiratory assessments in order to correctly stratify the CV risk and provide the best treatment. To obtain these achievements, multidisciplinary work has to be carried out with a team involving several experts with different skills.


Illustrated and online catalog of the type specimens of birds (Class: Aves) in the Ornithological Collection at the Instituto de Investigación de Recursos Biológicos Alexander von Humboldt (IAvH-A), Colombia.
The catalog of type specimens of birds deposited in the Bird Collection of Instituto de Investigación de Recursos Biológicos Alexander von Humboldt (IAvH-A) is presented. The list includes 10 specimens representing two holotypes and eight paratypes of three nominal species and five nominal subspecies. Three specimens also have tissues deposited in the Tissue Collection of the Instituto Humboldt (IAvH-CT). Corrections, additions, and updated information of the original descriptions and geographic locations are included as individual remarks for each catalog number and a gallery of photographs of each specimen is provided. An online version of the catalog is available at: http://colecciones.humboldt.org.co/catalogos/tiposaves.


Reliable Peak Power Assessment During Concentric and Flexion-Extension-Cycle Based Rowing Strokes using a Non-Modified Rowing Ergometer.
Accurate assessment of peak rowing power is crucial for rowing-specific performance testing. Therefore, within and between day reliability of a non-modified rowing ergometer was examined. 52 trained male rowers (21.0 ± 2.9 years; 1.89 ± 0.05 m; 83.2 ± 8.2 kg; 2,000-m ergometer Time Trial mean power: 369 ± 57 W) performed (two times 4) isolated concentric rowing strokes (DRIVE) and single flexion-extension cycle (FEC-type) rowing strokes (SLIDE-DRIVE) on two separate days (1 week apart). Good to excellent intraclass correlation coefficients (0.94 ≤ ICC ≤ 1.00), low standard error of measurement (≤ 2.7%), low coefficient of variation (≤ 4.9%), and suitable level of agreements (≤ 30W) for DRIVE and SLIDE-DRIVE indicated a high level of (within and between day) reliability. In addition, SLIDE-DRIVE (423 ± 157 W) revealed remarkably higher rowing power (p ≤ 0.001; ηp2 = 0.601; SMD = 0.34) compared to DRIVE (370 ± 154 W). The non-modified rowing ergometer is considered to be a reliable tool for the peak power assessment during isolated concentric contraction and FEC-type rowing strokes. Notably higher power outputs (compared to an isolated concentric contraction) during FEC rowing may refer to an underlying stretch shortening cycle.


UHF EPR spectrometer operating at frequencies between 400 MHz and 1 GHz.
A spectrometer was designed and constructed to facilitate measurements of T1, T2, spin echo signal-to-noise, and resonator quality factor, Q, between about 400 and 1000 MHz. Pulse patterns are generated at 250 MHz and mixed with the output from a second source to perform excitation and detection. A cross-loop resonator was constructed in which the same sample could be measured in the same resonator over the full range of frequencies. An air-core, 4-coil, water-cooled electromagnet with a large experimental volume was built.


Atrial natriuretic peptide attracts human spermatozoa in vitro.
Here we report that atrial natriuretic peptide (ANP), a known activator of particulate guanylate cyclase, induces attraction and swimming speed enhancement of human spermatozoa in vitro. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of ANP, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that spermatozoa followed the gradient of ANP and accumulated in it. Speed enhancement was detected in the presence of ANP without a gradient. These observations suggest either that an ANP-like substance is the physiological attractant for human spermatozoa, or, more likely, that ANP directly affects guanylate cyclase in a manner similar to that caused by the physiological attractant.


Do you see what I see? Infants' reasoning about others' incomplete perceptions.
Twelve-month-olds realize that when an agent cannot see an object, her incomplete perceptions still guide her goal-directed actions. What would happen if the agent had incomplete perceptions because she could see only one part of the object, for example one side of a screen? In the present research, 16-month-olds were first shown an agent who always pointed to a red object, as opposed to a black or a yellow object, suggesting that she preferred red over the other colours. Next, two screens were introduced while the agent was absent. The screens were (1) red or green on both sides; (2) red on the front (infants' side) but green on the back (the agent's side) or vice versa; or (3) only coloured red or green on the front. During test, the agent, who could see only the back of the screens, pointed to one of the two screens. The results revealed that while infants expected the agent to continue acting on her colour preference and point to the red rather than the green screen during test, they did so in accord with the agent's perception of the screens, rather than their own perceptions: they expected the agent to point to the red screen in (1), but to the green-front screen in (2), and they had no prediction of which screen the agent should point to in (3). The implications of the present findings for early psychological reasoning research are discussed.


Comparative analysis of preemptive analgesic effect of dexamethasone and diclofenac following third molar surgery.
The objective of the study was to compare the analgesic effectiveness of dexamethasone and diclofenac sodium administered preemptively after surgical removal of third molars. Forty-four ASA (American Society of Anesthesiologists) I patients (19 men, 35 women; 16-28 years old) randomly and double-blindly received diclofenac sodium (50 mg) or dexamethasone (8 mg) or placebo 1 h before surgery. Intensity of pain, measured with a visual analog scale (VAS), was the variable studied at different postoperative times (1 h, 2 h, 3 h, 6 h, 8 h, 12 h, 48 h, 4 d and 7 d). The total amount of rescue medication (TARM) ingested (paracetamol) was another variable of the study. The Kruskal-Wallis statistical test was used. A p value of < .05 was adopted to reject the null hypothesis. The dexamethasone group showed lower pain intensity (p < .05) than the diclofenac sodium and placebo groups (p < .05). No difference in TARM was observed among the groups (p < .05). Preemptively administered, dexamethasone was effective in controlling postoperative pain.


[The cognitive potential in normal adults].
The objective of this study was to evaluate the results of the auditory cognitive potential in a group of normal adults. The evoked response was obtained at Cz and Fz. The data collected were statistically analysed. The mean latencies of N1, P2, P2AP, N2, P3 and amplitude of P3, as well the standard deviation of these variables were presented. We briefly comment on some pitfalls related to interpretation of the results as well as the limitations of the technique as a diagnostic tool.


The positive role of professionalism and ethics training in medical education: a comparison of medical student and resident perspectives.
To assess the perspectives and preferences of medical students and residents regarding professionalism and ethics education. A new written survey with 124 items (scale: "strongly disagree" = 1, "strongly agree" = 9) was sent to all medical students (n=308) and PGY 1-3 residents (n=233) at one academic center. Of the 336 participants (200 students, 65% response; 136 residents 58% response), only 18% found current professionalism and ethics preparation sufficient. Respondents endorsed professionalism (means=7.48 to 8.11) and ethics topics (means=6.56 to 6.87), women more so than men (p<0.05). Respondents preferred clinically- and expert-oriented learning over formal, nontraditional, or independent approaches (p<0.0001). They preferred clinically-oriented assessment methods (p<0.0001), residents more so than medical students (p<0.0001). On several items, psychiatry residents expressed greater receptiveness to professionalism and ethics preparation. Medical students and residents indicate support for professionalism and ethics educational initiatives, including diverse curricular topics and clinically-attuned assessments.


Glomerular filtration rate in Nigerian children with homozygous sickle cell disease.
The study proposed to assess glomerular filtration rate as determined by endogenous creatinine clearance in steady state Nigeria children with homozygous sickle cell disease and normal controls. Twenty-four hours urinary creatinine clearance was estimated over a 6-month period in 54 steady-state homozygous sickle cell disease and 57 normal control children aged 5 to 13 years. Each child was admitted and a 24-hour urine sample (8.00 am to 8.00 am) was collected both for volume measurement and creatinine concentration determination. Blood was also collected from each child 30 minutes to end of urine collection for plasma creatinine concentration determination, haematocrit and reticulocyte counts. The results were compared between the two groups of children using student's t-test and the chi (X2) square test where necessary. The mean glomerular filtration rates +/- SD (ml/min/1.73 M2) for homozygous sickle cell disease children and normal controls were not significantly different (p > 0.05). Glomerular filtration rate did not differ significantly between the age groups in both patients and normal controls; haematocrits correlated weakly with glomerular filtration rates in the patients (r = +0.213; p < 0.001). Nigerian children with homozygous sickle cell disease who are in steady states have normal glomerular filtration rate that is hardly influenced by increasing age and low haematocrit level.


Deletion of CD163 Exon 7 Confers Resistance to Highly Pathogenic Porcine Reproductive and Respiratory Viruses on Pigs.
Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is a severe infectious disease in the swine industry. PRRSV infection is mediated by porcine CD163 (pCD163). Scavenger receptor cysteine-rich domain 5 coded by exon 7 of pCD163 is essential for PRRSV infection. In this study, we generated CD163 exon 7 deleted (CD163E7D) pigs using CRISPR/Cas9 mediated homologous recombination and somatic cell nuclear transfer (SCNT). The deletion of exon 7 had no adverse effects on CD163-associated functions. Pigs were further challenged with a highly pathogenic PRRSV (HP-PRRSV) strain. The CD163E7D pigs exhibited mild clinical symptoms and had decreased viral loads in blood. All CD163E7D pigs survived the viral challenge, while all the WT pigs displayed severe symptoms, and 2 out of 6 WT pigs died during the challenge. Our results demonstrated that CD163 exon 7 deletion confers resistance to HP-PRRSV infection without impairing the biological functions of CD163.


Objects of safety and imprisonment: Breathless patients' use of medical objects in a palliative setting.
In this article, the authors consider breathless adults with advanced non-malignant lung disease and their relationship with health objects. This issue is especially relevant now during the Covid-19 pandemic, where the experiences of breathlessness and dependence on related medical objects have sudden and global relevance. These objects include ambulatory oxygen, oxygen concentrators and inhalers, and non-pharmacological objects such as self-monitoring devices and self-management technologies. The authors consider this relationship between things and people using an interdisciplinary approach employing psychoanalytic theory (in particular Winnicott's theory of object relations and object use), Science and Technology Studies (STS) and phenomenology. This collaborative approach allows them to relate patient use of health objects to ways of thinking about the body, dependency, autonomy, safety and sense-making within the context of palliative care. The authors illustrate the theoretical discussion with three reflective vignettes from therapeutic practice and conclude by suggesting further interdisciplinary research to develop the conceptual and practice-based links between psychoanalytic theory, STS and phenomenology to better understand individual embodied experiences of breathlessness. They call for palliative care-infused, psychoanalytically informed interventions that acknowledge breathless patients' dependence on things and people, concomitant with the need for autonomy in being-towards-dying.


Abnormal recombination products result from aberrant DNA rearrangement of the human T-cell antigen receptor beta-chain gene.
Two unusual rearrangements of the T-cell antigen receptor beta-chain gene have occurred in the human T-cell tumor line CEM. The beta chain of the T-cell antigen receptor is encoded in germ-line DNA by immunoglobulin-like gene segments that rearrange during the somatic development of T cells to form active genes. Structural analysis of rearranged immunoglobulin genes has already revealed a great deal about the mechanisms by which these genes rearrange. To further characterize the mechanism by which beta-chain genes rearrange, we have determined the organization of the rearranged beta-chain gene segments in the human T-cell tumor line CEM. Three rearranged joining (J) or diversity (D) segments of the beta-chain gene are found in CEM. One of these segments rearranged during the formation of a normal rearranged beta-chain gene that comprises a variable (V beta), D beta, and J beta gene segment associated with a constant region gene segment. Two abnormal recombination products are found at the other rearranged beta-chain locus. One product has the structure, J beta-D beta-J beta, with the J beta gene segments joined in a head-to-head fashion, while the other one consists of a V beta-D beta recombined segment not associated with a J beta gene segment. We propose that the J beta-D beta-J beta structure was formed by an inversion of 6 kilobases of DNA and subsequently, a V beta-D beta rearrangement occurred. The presence of these products in CEM has important implications for our understanding of the mechanism by which somatic rearrangements of beta-chain gene segments occur.


Current issues in the diagnosis of painful bladder syndrome/interstitial cystitis.
PBS/IC, which was traditionally thought to be a rare condition, is increasingly thought to be a frequent cause of CPP. Failure to consider the bladder as a component of this pain is common, primarily because of the similarity in symptoms to other urogynecologic conditions. The diagnosis of PBS/IC has been one of exclusion; as a result, PBS/IC is frequently misdiagnosed as urogenital infection, OAB or endometriosis, among other conditions with similar symptomatology. Such misdiagnosis results in unnecessary and ineffective pharmacologic or even surgical interventions. Diagnosis of PBS/IC and appropriate management early in the disease process afford women a better outcome and a better quality of life. Making PBS/IC a diagnosis of inclusion is necessary to attain this goal. Two additions to the diagnostic armamentarium, the PUF Patient Symptom Scale and the PST, can help to identify women whose presenting complaints of CPP might have a bladder component. The high correlation between these 2 tools allows clinicians to administer the noninvasive PUF questionnaire as an initial screening device to identify women suspected of having IC. If PBS/IC is diagnosed early in the disease process, it can be treated successfully in most patients.


Remarriage of war and terror widows: a triadic relationship.
The article focuses on the intimate relationships of remarried Israeli national widows. An analysis of interviews with 15 widows and 12 of their husbands demonstrated the widows' continuing connection to the deceased husband and thus gives further corroboration to the theory of "'continuing bonds'"; husbands also express their relationship as triadic, with the fallen husband assigned a unique position in the family constellation, albeit not threatening to the new husband. The article concludes with specific guidelines for planning therapeutic programs, e.g., recommending clients to use some symbolic objects, either abstract or concrete, to help widows rebuild their self-identity.


Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect.
Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18-40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.


Osteomyelitis of the base of the skull.
Infection in the marrow of the temporal, occipital, and sphenoid bones is an uncommon, but increasing occurrence. It is usually secondary to infections beginning in the external auditory canal and is caused almost uniformly by the gram negative Pseudomonas aeruginosa bacteria. Technetium and gallium scintigraphy help in the early detection of such infections while CT scans demonstrate dissolution of bone in well-developed cases. Headache is the predominant symptom. Dysphagia, hoarseness, and aspiration herald the inevitable march of cranial nerves. We have diagnosed and treated 17 cases of osteomyelitis of the skull base. Although the total mortality rate is 53%, it is now a curable disease. Six of our last 8 patients remain alive, although 1 is still under treatment. Treatment is medical and requires the long-term concomitant intravenous administration of an aminoglycoside and a broad spectrum semisynthetic penicillin effective against the causative organism.


Quercetin induces structural chromosomal aberrations and uncommon rearrangements in bovine cells transformed by the E7 protein of bovine papillomavirus type 4.
Bovine papillomavirus type 4 (BPV-4) and bracken fern are cofactors in the carcinogenesis of the upper gastrointestinal (GI) tract of cattle. An experimental in vitro model system has been developed to analyse the co-operation between the viral transforming protein E7, the cellular ras oncogene and quercetin, one of the mutagens of bracken fern, during neoplastic progression of primary bovine cells. We now report cytogenetic studies of these cells at different stages of malignant transformation: parental primary non-transformed PalF cells; E7R cells transformed by BPV-4 E7 and activated ras but not tumorigenic, and tumorigenic E7Q cells derived from E7R cells after treatment with quercetin. All cell lines presented increased numbers of aneuploid cells. The rate of structural chromosomal aberrations observed was increased in transformed cells. In addition, E7Q cells showed chromosomes with peculiar rearrangements, which resulted in metacentric and submetacentric marker chromosomes, with an increase in the mean chromosome arm number. These markers were the products of possible centric fusions. These aberrations and rearrangements were distributed throughout the karyotype, no specific chromosome was involved and the heterochromatic centromeric regions appeared to be preserved.


Turkish female academician self-esteem and health beliefs for breast cancer screening.
This study aimed to analyse female academician health beliefs for breast cancer screening and levels of self-esteem. This cross-sectional study was conducted between October 2010 and March 2011, covering female academicians working in all faculties and vocational schools at Ondokuz Mayis University, except for the ones in the field of health (n=141). Data was collected using a questionnaire developed by researchers in the light of the related literature, the Champion's Health Belief Model Scale for Breast Cancer, and the Coopersmith Self-Esteem Inventory. Descriptive statistics, the t-test, Mann-Whitney U and correlation analysis were used to analyze the data with the SPSS 13.0 statistical package. 53.8% of the participants were single, 58.6% did not have children, 80.7% had regular menstrual cycles, 28.3% was taking birth control pills, 17.9% were undergoing hormone therapy, 11% suffered breast problems, 8.3% had relatives with breast cancer, 78,6% knew about breast self-examination (BSE), 68.3% was performing BSE, 16.2% were performing BSE monthly, 17.9% had had mammograms, and 30.3% had undergone breast examinations conductedby physicians. The women who had breast physical examinations done by physicians had higher susceptibility, self-efficacy and health motivation, and fewer barriers to mammography than those who did not have breast physical examinations. There was a relationship between the female academician self-esteem and their perceived seriousness of breast cancer, perceived barriers to BSE and health motivation. Our Turksih female academicians had medium levels of self-esteem.


Phenotypic Variation Between Stromal Cells Differentially Impacts Engineered Cardiac Tissue Function.
Understanding the relationship between parenchymal and supporting cell populations is paramount to recapitulate the multicellular complexity of native tissues. Incorporation of stromal cells is widely recognized to be necessary for the stable formation of stem cell-derived cardiac tissues; yet, the types of stromal cells used have varied widely. This study systematically characterized several stromal populations and found that stromal phenotype and morphology was highly variable depending on cell source and exerted differential impacts on cardiac tissue function and induced pluripotent stem cell-cardiomyocyte phenotype. Therefore, the choice of supporting stromal population can differentially impact the phenotypic or functional performance of engineered cardiac tissues.


The changing healthcare market: outlook for the future of cardiovascular disease treatment--Part 2.
This paper, the second in a series of 2, reviews major developments and trends in the current healthcare arena that will affect cardiovascular disease (CVD) treatment over the next 10 years. The paper also discusses the implications and future outlook for cardiovascular services in a managed care environment.


Citizen-science detects the arrival and establishment of Branchiomma luctuosum (Grube, 1870) (Annelida: Polychaeta: Sabellidae) in Albania.
The invasive fan worm Branchiomma luctuosum (Grube, 1870), originally described from the Red Sea, is first reported here from the Albanian coasts, based on records held in Vlora Bay, a locality near to Valona harbour and Narta Lagoon. Possible pathways of arrival in the area are uncertain. However, species' larval ecology and life-history traits suggest a secondary spreading through shipping. Social media data mining allowed the confirmation of its establishment in the area, with specimens showing high densities in shallow waters on artificial hard substrates and to backdate its arrival in the area since at least November 2016. Citizen science continues supporting marine biology in the Mediterranean area, especially in countries where proper field studies and research projects are still limited.


Children's verbal working memory: role of processing complexity in predicting spoken sentence comprehension.
This study investigated the role of processing complexity of verbal working memory tasks in predicting spoken sentence comprehension in typically developing children. Of interest was whether simple and more complex working memory tasks have similar or different power in predicting sentence comprehension. Sixty-five children (6- to 12-year-olds) completed a verbal working memory (listening) span task that varied in syntactic processing difficulty (simple sentences representing a "simple working memory task," complex sentences representing a "complex working memory task") and a standardized sentence comprehension test. Word recall on the simple and complex working memory tasks correlated with each other. Both memory tasks also correlated with children's sentence comprehension. Regression analyses showed that the simple working memory task remained a significant predictor of comprehension even after accounting for variance associated with age and performance on the complex working memory task. Results were interpreted to suggest that relative to more complex verbal working memory tasks, simple tasks are more robust predictors of children's sentence comprehension because they represent a basic yet robust index of working memory that sufficiently captures controlled attentional focus.


Typing Y chromosome STR haplotypes using redesigned primers.
A panel of Y-specific STR loci, including DYS19, DYS389, DYS390, DYS391, DYS392, and DYS393 was analyzed using horizontal nondenaturing polyacrylamide gel electrophoresis with a discontinuous buffer system (horizontal disk-PAGE). In order to obtain correct results for the larger DYS389 and DYS392 alleles, it was necessary to design new primers that bind closer to the repeat region and lead to a significant reduction of the amplified fragment size. Using the modified primer sets the horizontal disk-PAGE results were consistent with a nondenaturing approach using fluorescent primers and a 377 automated sequencer. The modified procedure also amplifies the second repeat stretch at the duplicated DYS389 locus as a single fragment, which results in an immediate allele identification. The results indicate that horizontal disk-PAGE with silverstaining is a simple approach to type the recommended Y-specific STR markers.


Evidence-based practice strategy: increasing timely nutrition in mechanically ventilated trauma surgical patients.
Malnutrition is common in the intensive care unit (ICU) and is related to higher incidence of morbidity and mortality among seriously ill patients. Achieving a quality nutritional care plan is a challenge to critical care practitioners and dietitians worldwide. The multifaceted and advanced therapies in the ICU historically take priority over nutritional assessments and interventions and may cause delay in achieving quality nutritional care. The initiation of nutrition in mechanically ventilated adult trauma patients is inconsistent in some hospitals. The implementation plan in this early nutrition project involved an algorithm, physicians order set, and nurse advocacy plan. Early nutritional support will likely be associated with improved clinical outcomes.


Diagnostic value of multiple biomarker panel for prediction of significant fibrosis in chronic hepatitis C.
Whether new biomarkers contribute significantly to the existing, simple noninvasive test (comprising of routine laboratory parameters such as the AST to platelet ratio index (APRI)) for predicting liver fibrosis remains unknown. We measured 7 biomarkers in 91 patients with chronic hepatitis C (CHC): haptoglobin, apolipoprotein A1, α2-macroglobulin, hyaluronic acid, type III procollagenic peptide, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1. The "multibiomarker" score (based on regression coefficients of significant biomarkers) is an independent predictive factor for significant fibrosis [APRI-adjusted odds ratio, 2.41 (95% CI, 1.28 to 4.55)]. However, the incorporation of the multibiomarker score into the APRI resulted in only a small diagnostic improvement [0.83 (95% CI, 0.74 to 0.92) vs. 0.79 (0.69 to 0.89); p=0.19]. For assessing significant fibrosis in individual CHC patients, the 7 contemporary biomarkers that we studied add only modestly to the readily available, simple noninvasive index.


Disrupted Circadian Rest-Activity Cycles in Inflammatory Bowel Disease Are Associated With Aggressive Disease Phenotype, Subclinical Inflammation, and Dysbiosis.
Patients with inflammatory bowel disease (IBD)-Crohn's disease (CD), and ulcerative colitis (UC), have poor sleep quality. Sleep and multiple immunologic and gastrointestinal processes in the body are orchestrated by the circadian clock, and we recently reported that a later category or chronotype of the circadian clock was associated with worse IBD specific outcomes. The goal of this study was to determine if circadian misalignment by rest-activity cycles is associated with markers of aggressive disease, subclinical inflammation, and dysbiosis in IBD. A total of 42 patients with inactive but biopsy-proven CD or UC and 10 healthy controls participated in this prospective cohort study. Subjects were defined as having an aggressive IBD disease history (steroid dependence, use of biologic or immunomodulator, and/or surgery) or non-aggressive history. All participants did two weeks of wrist actigraphy, followed by measurement of intestinal permeability and stool microbiota. Wrist actigraphy was used to calculate circadian markers of rest-activity- interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). Aggressive IBD history was associated with decrease rest-activity stability (IS) and increased fragmentation compared to non-aggressive IBD and health controls at 0.39 ±.15 vs. 0.51 ± 0.10 vs. 0.55 ± 0.09 (P < 0.05) and 0.83 ± 0.20 vs. 0.72 ± 0.14 (P < 0.05) but not HC at 0.72 ± 0.14 (P = 0.08); respectively. There was not a significant difference in RA by IBD disease history. Increased intestinal permeability and increased TNF-α levels correlated with an increased rest activity fragmentation (IV) at R = 0.35, P < 0.05 and R = 0.37, P < 0.05, respectively; and decreased rest-activity amplitude (RA) was associated with increased stool calprotectin at R = 0.40, P < 0.05. Analysis of intestinal microbiota showed a significant decrease in commensal butyrate producing taxa and increased pro-inflammatory bacteria with disrupted rest-activity cycles. In this study, different components of circadian misalignment by rest-activity cycles were associated with a more aggressive IBD disease history, increased intestinal permeability, stool calprotectin, increased pro-inflammatory cytokines, and dysbiosis. Wrist activity allows for an easy non-invasive assessment of circadian activity which may be an important biomarker of inflammation in IB.


On the chalcogenophilicity of mercury: evidence for a strong Hg-Se bond in [Tm(Bu(t))]HgSePh and its relevance to the toxicity of mercury.
One of the reasons for the toxic effects of mercury has been attributed to its influence on the biochemical roles of selenium. For this reason, it is important to understand details pertaining to the nature of Hg-Se interactions and this has been achieved by comparison of a series of mercury chalcogenolate complexes that are supported by tris(2-mercapto-1-t-butyl-imidazolyl)hydroborato ligation, namely [Tm(Bu(t))]HgEPh (E = S, Se, Te). In particular, X-ray diffraction studies on [Tm(Bu(t))]HgEPh demonstrate that although the Hg-S bonds involving the [Tm(Bu(t))] ligand are longer than the corresponding Cd-S bonds of [Tm(Bu(t))]CdEPh, the Hg-EPh bonds are actually shorter than the corresponding Cd-EPh bonds, an observation which indicates that the apparent covalent radii of the metals in these compounds are dependent on the nature of the bonds. Furthermore, the difference in Hg-EPh and Cd-EPh bond lengths is a function of the chalcogen and increases in the sequence S (0.010 A) < Se (0.035 A) < Te (0.057 A). This trend indicates that the chalcogenophilicity of mercury increases in the sequence S < Se < Te. Thus, while mercury is often described as being thiophilic, it is evident that it actually has a greater selenophilicity, a notion that is supported by the observation of facile selenolate transfer from zinc to mercury upon treatment of [Tm(Bu(t))]HgSCH(2)C(O)N(H)Ph with [Tm(Bu(t))]ZnSePh. The significant selenophilicity of mercury is in accord with the aforementioned proposal that one reason for the toxicity of mercury is associated with it reducing the bioavailability of selenium.


Hydrogen peroxide mediates pro-inflammatory cell-to-cell signaling: a new therapeutic target for inflammation?
Nitric oxide is now universally recognized as an extracellular signaling molecule. Nitric oxide, produced in one cell, diffuses across the extracellular space and acts with targets in an adjoining cell. In this study, we present proof that hydrogen peroxide - like nitric oxide - acts as a true first (intercellular) messenger for a multitude of pro-inflammatory ligands. RAW 264.7 macrophages were activated with three different ligands, lipopolysaccharide, interferon-gamma or advanced glycation end products in the presence of increasing concentrations of (hydrogen peroxide scavenging) catalase. As inflammatory readouts, nitric oxide and tumor necrosis factor were determined. We hypothesize that hydrogen peroxide travels between cells propagating the signal, then a certain percentage of the readout should be inhibited by catalase in a concentration-dependent manner. The experiment showed concentration-dependent inhibition of nitric oxide and tumor necrosis factor-α production in response to all three ligands/ligand combinations (interferon-gamma, lipopolysaccharide, and chicken egg albumin-derived advanced glycation end product) in the presence of increasing concentration of catalase. For example, catalase inhibited 100% of nitric oxide and 40% of tumor necrosis factor-α production at its highest concentration. Our results suggest that hydrogen peroxide travels through cell membranes into the extracellular space and enters and activates adjacent cells. Like nitric oxide, we suggest that it is a ubiquitous first messenger, able to transmit cell-to-cell pro-inflammatory signals such as nitric oxide and tumor necrosis factor-α. In a therapeutic setting, our data suggest that compounds acting as hydrogen peroxide scavengers might not even need to enter the cell to act as anti-inflammatory drugs.


G protein--mediated signaling: same receptor, multiple effectors.
The superfamily of G protein coupled receptors (GPCRs) comprises the largest group of cell surface receptors expressed by the human genome. Accordingly, these receptors are the target of a substantial portion of current pharmaceuticals. Over the past few decades there have been many substantial discoveries regarding GPCRs structure and function that have led to the current understanding of the complexity of the signal transduction which these receptors initiate. What was once generally believed to be a simple linear pathway, has become one with manifold bifurcations and multiple regulatory and feedback mechanisms. In the following we review the fundamental ground work upon which this field of research was established and the work that has more recently begun to uncover the complexity of GPCR signaling. The emerging signaling paradigm includes (i) the capacity of one receptor to couple to and initiate pathways through multiple G proteins, (ii) the capability of one G protein to activate many effectors, as well as (iii) the ability of a GPCR to transduce signals through G protein independent pathways. We also briefly touch upon some implications of GPCR oligomerization and discuss signaling cascades of two serotonin receptors, 5-HT(4) and 5-HT(7), whose pathways exemplify the richness and complexity of GPCR signaling mechanisms.


Erratum.
Alghadir, A., Zafar, H., Iqbal, Z. A., Al-Eisa, E. (2017). Work-related low back pain among physical therapists in Riyadh, Saudi Arabia. Workplace Health & Safety, 65(8), 337-345. (Original DOI: 10.1177/2165079916670167). The following acknowledgment should have been included in this article. The text is included below. Acknowledgment The authors are grateful to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs.


The expression of activins, their type II receptors and follistatin in human Fallopian tube during the menstrual cycle and in pseudo-pregnancy.
The Fallopian tube (FT) is the site of fertilization and early embryonic development. We have previously reported the expression of activins, their receptors and follistatin by the FT. Here, our aim was to study the expression of tubal activins, their type II receptors and follistatin during the menstrual cycle and following exposure to hCG in vivo. A set of 30 FTs were collected from cycling women (n = 12) at different stages of the cycle (n = 4 in each stage) and pseudo-pregnant women (n = 3) at the time of hysterectomy for benign disease. The pseudo-pregnant women were injected with hCG in the days leading up to hysterectomy, and pseudo-pregnancy was confirmed by the persistence of amenorrhea, the presence of corpus luteum and decidualization of the endometrium. FT specimens were examined using immunohistochemistry and quantitative RT-PCR. The expression of activin βA- and βB-subunits, activin type IIA and IIB receptors, and follistatin varied throughout the menstrual cycle, being lowest in the follicular phase and highest in the luteal phase. These results were demonstrated at the mRNA and protein level by quantitative RT-PCR and immunohistochemistry (P< 0.05). HCG injection rescued the expression of the candidate molecules from falling to the follicular stage levels but the expression remained lower than in the luteal phase. We suggest that activins play a role in tubal physiology and early embryonic development. Additionally, exposure of the tubal epithelium to hCG modulates the expression of tubal activins.


Localization and distribution of wolframin in human tissues.
Wolframin is a transmembrane glycoprotein of 890 aminoacids, encoded by WFS1 gene. WFS1 mutations are responsible for Wolfram syndrome, an autosomal recessive disorder. In the present paper, we first characterized the polyclonal wolframin antibody by dot blot. Secondly, we verified antibody specificity by western blotting using different human cell lines. Thirdly, we studied wolframin localization in human foetal (14-35 weeks) and adult tissues by immunohistochemistry. Wolframin expression was distributed in many organs, with different tissue and cell localization and expression levels. In foetal systems, wolframin expression was faint at 14-16 weeks and increased when development proceeded. In adult human tissues a variable positive staining was observed in both simple and stratified epithelia. A moderate wolframin expression was observed in liver and in the endocrine portion of the pancreas. In conclusion, our data suggest that this protein may have important roles in a number of different tissues, including many that are not known to be affected by WFS1-linked diseases. The immunopositivity in adult human tissues suggests that it may function maintaining physiological cellular homeostasis.


Exploring the membrane topology of prohormone convertase 1 in AtT20 Cells: in situ analysis by immunofluorescence microscopy.
Prohormone convertase 1 (PC1) was previously characterized as a partially transmembrane protein in purified chromaffin granules of bovine adrenal medulla1. This was challenged with experiments on transfected PC1 in COS1 cells, a non-endocrine cell line2. To address this issue, we undertook to analyze its extraction properties in vitro and its immunocytochemical localization in situ in AtT20 cells, an endocrine cell line that expresses PC1. Most of the 87 kDa form of PC1 was resistant to carbonate extraction suggesting that it had properties of a transmembrane protein. Under semi-permeabilized conditions whereby only the plasma membrane was permeabilized, the carboxy-terminus of PC1 was specifically immunostained whereas the amino-terminus was not. These results indicate that the amino-terminus of PC1 was within the lumen of the Golgi and granules, and some of the C-terminus was exposed to the cytosol. Thus, endogenous PC1 can assume a transmembrane orientation in situ in AtT20 cells.


Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.


Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate.
Variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy. Extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products. Cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose. The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.


Ovarian androgens but not estrogens correlate with the degree of systemic inflammation observed during controlled ovarian hyperstimulation.
To investigate the behavior and association of serum androgen and serum C-reactive protein (CRP) in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Prospective, observational study.Setting. An IVF unit of an academic medical center. Blood was drawn three times during the COH cycle from 15 patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CRP were compared among the three time points. There was a significant increase in serum ovarian androgen levels during gonadotropin treatment. After hCG administration, there was a significant increase in the levels of both serum CRP and ovarian androgens (testosterone, androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone). Significant correlations were observed between CRP and ovarian androgen levels but not with dehydroepiandrosterone sulfate or estradiol levels. In patients undergoing COH for IVF, ovarian androgen levels increase in correlation with the degree of inflammation, as reflected by CRP levels. Further studies are necessary to elucidate whether androgens play a role in or are predictive of the systemic inflammatory response in COH.


Induction of interferon-gamma by cord blood mononuclear cells is calcium dependent.
Human cord blood mononuclear cells (MNCs) are deficient in their ability to produce interferon-gamma (IFN-gamma). Previous studies have shown that phytohemagglutinin (PHA)-stimulated neonatal MNCs produced significantly less IFN-gamma than adult PHA-stimulated MNCs. The deficient IFN-gamma production is partly due to the absence of a macrophage-derived soluble mediator. Supernatants from PHA-stimulated adult macrophages and phorbol myristate acetate (PMA)-stimulated U937 cells (which were dialyzed prior to culture to remove PMA) increased IFN-gamma production in neonatal PHA-stimulated MNC (14 to 217 units/ml and 14 to 293 units/ml, respectively). The requirement for a soluble macrophage mediator was replaced by the addition of exogenous calcium chloride (CaCl2) to PHA-stimulated cord blood MNCs. The increase in IFN-gamma production by exogenous CaCl2 was blocked by the addition of the calcium channel blocker, manganese chloride (MnCl2). Furthermore, the increased IFN-gamma production by PHA-stimulated cord blood MNC in the presence of PHA-stimulated adult macrophage supernatant or PMA-stimulated U937 supernatant was abrogated by the addition of MnCl2, chlorpromazine, and verapamil. These data suggested that the soluble factor produced by PHA-stimulated adult macrophage supernatant and PHA-stimulated U937 supernatant induced IFN-gamma production in PHA-stimulated cord blood MNC by inducing calcium-dependent signals at more than one site.


Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling.
The accumulation of glomerular extracellular matrix proteins, especially fibronectin (FN), is a critical pathological characteristic of diabetic renal fibrosis. Inflammation mediated by nuclear factor-κB (NF-κB) plays a critical role in the pathogenesis of diabetic nephropathy (DN). RhoA/ROCK signaling is responsible for FN accumulation and NF-κB activation. Berberine (BBR) treatment significantly inhibited renal inflammation and thus improved renal damage in diabetes. Here, we study whether BBR inhibits FN accumulation and NF-κB activation by inhibiting RhoA/ROCK signaling and the underlying mechanisms involved. Results showed that BBR effectively inhibited RhoA/ROCK signaling activation in diabetic rat kidneys and high glucose-induced glomerular mesangial cells (GMCs) and simultaneously down-regulated NF-κB activity, which was accompanied by reduced intercellular adhesionmolecule-1, transforming growth factor-beta 1 and FN overproduction. Furthermore, we observed that BBR abrogated high glucose-mediated reactive oxygen species generation in GMCs. BBR and N-acetylcysteine inhibited RhoA/ROCK signaling activation in high glucose-exposed GMCs. Collectively, our data suggest that the renoprotective effect of BBR on DN partly depends on RhoA/ROCK inhibition. The anti-oxidative stress effect of BBR is responsible for RhoA/ROCK inhibition in DN.


A possible case of Werner syndrome presenting with multiple cancers.
The treatment of a man with six metachronous primary cancers is described. The primary lesions were in the soft palate, both edges of the tongue, the hard palate, the esophagus, and the right ureter. Pathologically, all of the first five tumors in the head and neck and esophagus were proven to be squamous cell carcinoma with various grades of differentiation, and the last one was transitional cell carcinoma. The cancers were found in the early clinical stage, and were completely controlled one by one except for the ureteral tumor under treatment. His characteristic medical history and physical findings, i.e. bilateral cataracts, short stature, baldness, diabetes mellitus, high-pitched voice, and multiple malignancies, met the clinical criteria for possible Werner syndrome, a genetic premature aging disorder, though the possibility of phenocopy of this syndrome has not been ruled out. We have followed him carefully because he might be vulnerable to malignant tumor formation.