Glucocorticoid receptors are required effectors of TGFβ1-induced p38 MAPK signaling to advanced cancer phenotypes in triple-negative breast cancer.
Altered signaling pathways typify breast cancer and serve as direct inputs to steroid hormone receptor sensors. We previously reported that phospho-Ser134-GR (pS134-GR) species are elevated in triple-negative breast cancer (TNBC) and cooperate with hypoxia-inducible factors, providing a novel avenue for activation of GR in response to local or cellular stress. We probed GR regulation by factors (cytokines, growth factors) that are rich within the tumor microenvironment (TME). TNBC cells harboring endogenous wild-type (wt) or S134A-GR species were created by CRISPR/Cas knock-in and subjected to transwell migration, invasion, soft-agar colony formation, and tumorsphere assays. RNA-seq was employed to identify pS134-GR target genes that are regulated both basally (intrinsic) or by TGFβ1 in the absence of exogenously added GR ligands. Regulation of selected basal and TGFβ1-induced pS134-GR target genes was validated by qRT-PCR and chromatin immunoprecipitation assays. Bioinformatics tools were used to probe public data sets for expression of pS134-GR 24-gene signatures. In the absence of GR ligands, GR is transcriptionally activated via p38-dependent phosphorylation of Ser134 as a mechanism of homeostatic stress-sensing and regulated upon exposure of TNBC cells to TME-derived agents. The ligand-independent pS134-GR transcriptome encompasses TGFβ1 and MAPK signaling gene sets associated with TNBC cell survival and migration/invasion. Accordingly, pS134-GR was essential for TNBC cell anchorage-independent growth in soft-agar, migration, invasion, and tumorsphere formation, an in vitro readout of cancer stemness properties. Both pS134-GR and expression of the MAPK-scaffolding molecule 14-3-3ζ were essential for a functionally intact p38 MAPK signaling pathway downstream of MAP3K5/ASK1, indicative of a feedforward signaling loop wherein self-perpetuated GR phosphorylation enables cancer cell autonomy. A 24-gene pS134-GR-dependent signature induced by TGFβ1 predicts shortened overall survival in breast cancer patients. Phospho-S134-GR is a critical downstream effector of p38 MAPK signaling and TNBC migration/invasion, survival, and stemness properties. Our studies define a ligand-independent role for GR as a homeostatic "sensor" of intrinsic stimuli as well as extrinsic factors rich within the TME (TGFβ1) that enable potent activation of the p38 MAPK stress-sensing pathway and nominate pS134-GR as a therapeutic target in aggressive TNBC.


Impact of a new hospital with close to 100% single-occupancy rooms on environmental contamination and incidence of vancomycin-resistant Enterococcus faecium colonization or infection: a genomic surveillance study.
Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of nosocomial infection, driven by its ability to spread between patients and persist in the hospital environment. To investigate the impact of a long-established cardiothoracic hospital moving to new premises with close to 100% single-occupancy rooms on the rates of environmental contamination and infection or colonization by VRE. Prospective environmental surveillance for VRE was conducted at five time-points between April and November 2019, once in the original building, and four times in the new building. Incidence rate ratios (IRRs) of VRE infection/colonization were determined for the one-year period before and after the hospital move, and compared to a nearby hospital. In the original location, the first environmental screen found 29% VRE positivity. The following four screens in the new location showed a significant reduction in positivity (1-6%; P<0.0001). The VRE infection/colonization rates were halved in the new location (IRR: 0.56; 95% confidence interval: 0.38-0.84), compared to the original location, contrasting with an increase in a nearby hospital (1.62; 1.17-2.27) over the same time-period. Genomic analysis of the environmental isolates was consistent with reduced transmission in the new hospital. The use of single-occupancy rooms was associated with reduced environmental contamination with VRE, and lower transmission and isolation of VRE from clinical samples. The cost-effectiveness of single-occupancy room hospitals in reducing healthcare-associated infections should be reassessed in the context of operational costs of emerging pandemic and increasing antimicrobial resistance threats.


Identification of DNA gyrase A mutations in ciprofloxacin-resistant isolates of Salmonella typhimurium from men and cattle in Germany.
Six multiply resistant isolates of Salmonella typhimurium var. copenhagen with high-level resistance to fluoroquinolones (e.g., MIC of ciprofloxacin: 32 micrograms/ml) were isolated from human patients (n = 3) and from cattle (n = 3). The isolates were examined by complementation tests using a set of broad-host-range plasmids, which carry either the gyrA+ or the gyrB+ genes or a combination of both from Escherichia coli K-12. The results indicated a combination of gyrA and gyrB mutations in all isolates. Subsequent direct sequencing of PCR-generated internal DNA fragments of gyrA revealed an identical double mutation in all six isolates (Ser-83-->Ala and Asp-87-->Asn). In addition, the results of phenotypic (i.e., phagetype, biotype, serotype) and genotypic characterization [i.e., ribotyping and polymerase chain reaction fingerprinting (PCR-fingerprinting)] were identical for all six isolates and were distinguishable from a quinolone-susceptible strain of the same serovar and an unrelated isolate of S. typhimurium. These data indicate the clonal identity of the fluoroquinolone-resistant strains of S. typhimurium isolated from men and cattle in Germany.


The expression and environmental regulation of P450 enzymes in human placenta.
The human placenta oxidizes several xenobiotics, although the spectrum of substrates and metabolic activities when compared with the liver appears somewhat restricted. Maternal cigarette smoking or PCB exposure increases the expression of CYP1A1. This induced activity is able to catalyze the activation of benzo(a)pyrene (B(a)P) into DNA-bound products, both in vitro and in vivo. Studies on adult human liver bolster the concept that CYP1A1 and -1A2 are differentially expressed in hepatic and extrahepatic tissues. Studies with cDNA probe or enzyme specific antibodies and substrates for CYP2A, -2B, -2C, -2D, and -2E gene products have yielded negative results. There are only minimal activities that can be found in substantial quantities in placentas without maternal smoking; one example is 7-ethoxycoumarin O-deethylase (ECOD). Aromatase and cholesterol side-chain cleaving P450 mRNAs, proteins, and activities are measurable in human placentas and do not seem to be affected by maternal cigarette smoking.


Dysfunctional T regulatory cells in multiple myeloma.
Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (T(reg)) cells play an important role in suppressing normal immune responses, we evaluated the potential role of T(reg) cells in immune dysfunction in MM. We observed a significant increase in CD4+ CD25+ T cells in patients with monoclonal gammopathy of undetermined significance (MGUS) and in patients with MM compared with healthy donors (25% and 26%, respectively, vs 14%); however, T(reg) cells as measured by FOXP3 expression are significantly decreased in patients with MGUS and MM compared with healthy donors. Moreover, even when they are added in higher proportions, T(reg) cells in patients with MM and MGUS are unable to suppress anti-CD3-mediated T-cell proliferation. This decreased number and function of T(reg) cells in MGUS and in MM may account, at least in part, for the nonspecific increase in CD4+ CD25+ T cells, thereby contributing to dysfunctional T-cell responses.


A physiotherapy triage service for orthopaedic surgery: an effective strategy for reducing wait times.
To investigate the effectiveness of a physiotherapy triage service for orthopaedic surgery referrals from primary-care physicians. A prospective, observational design was used with patients referred to an orthopaedic surgeon based out of two small urban centres in British Columbia. The level of agreement between the physiotherapist and surgeon was determined using a weighted kappa statistic (κw) with 95% CI. A patient satisfaction questionnaire was administered, and the surgical conversion rate (SCR) was calculated to assess the level of appropriate referrals. The analysis found substantial agreement (κw=0.77; 95% CI, 0.60-0.94) between surgeon and physiotherapist for surgical management decisions. All patients reported being "satisfied" or "very satisfied" with the overall care they received from the physiotherapist. The SCR of patients referred by the physiotherapist to the surgeon was 91%, versus 22% among patients referred by a general practitioner or emergency physician. More than three-fourths of patients referred by primary-care physicians did not need to see a surgeon and were able to be managed by an experienced orthopaedic physiotherapist. This triage model could have considerable impact on orthopaedic wait times in Canada by minimizing unnecessary referrals; the model could also promote timely and conservative management of non-surgical conditions by physiotherapists.


The role of non-hematopoietic stromal cells in the persistence of inflammation.
Inflammation results from the complex interaction between hematopoietic and stromal cells and growing evidence supports a key role for the stroma in driving the switch from acute resolving to persistence in chronic inflammatory diseases. Stromal cells have also been shown to play a critical role in cancer biology, being involved in cancer growth, dissemination, and inhibition of the autologous immune response, ultimately favoring persistence and metastatic spread. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis during physiological inflammation but also lead to discorded leukocyte and tumor cell accumulation in pathological inflammation and cancer. This review aims to summarize the role that pathogenic stroma plays in the pathogenesis of diseases such as cancer and chronic inflammation.


[Impact of overweight on the outcome of ovarian stimulation].
Overweight and obesity have a negative impact on the efficacy of agents used to induce ovulation, and especially on the dose of clomiphene citrate or gonadotrophins required to achieve ovulation. BMI is a major predictor of the ovarian response. In IVF-ICSI cycles, overweight is associated with a decrease in the number of oocytes. While the pregnancy rate is not dependent on weight, the risk of early miscarriage is increased in obese women. Therefore, overweight should be managed before ovarian stimulation begins. The efficacy of insulin-sensitizing agents such as metformin is not fully clear, but their combination with clomiphene citrate or FSH seems promising.


Maternal race and intergenerational preterm birth recurrence.
Preterm birth is a complex disorder with a heritable genetic component. Studies of primarily White women born preterm show that they have an increased risk of subsequently delivering preterm. This risk of intergenerational preterm birth is poorly defined among Black women. Our objective was to evaluate and compare intergenerational preterm birth risk among non-Hispanic Black and non-Hispanic White mothers. This was a population-based retrospective cohort study, using the Virginia Intergenerational Linked Birth File. All non-Hispanic Black and non-Hispanic White mothers born in Virginia 1960 through 1996 who delivered their first live-born, nonanomalous, singleton infant ≥20 weeks from 2005 through 2009 were included. We assessed the overall gestational age distribution between non-Hispanic Black and White mothers born term and preterm (<37 weeks) and their infants born term and preterm (<37 weeks) using Cox regression and Kaplan-Meier survivor functions. Mothers were grouped by maternal gestational age at delivery (term, ≥37 completed weeks; late preterm birth, 34-36 weeks; and early preterm birth, <34 weeks). The primary outcomes were: (1) preterm birth among all eligible births; and (2) suspected spontaneous preterm birth among births to women with medical complications (eg, diabetes, hypertension, preeclampsia and thus higher risk for a medically indicated preterm birth). Multivariable logistic regression was used to estimate odds of preterm birth and spontaneous preterm birth by maternal race and maternal gestational age after adjusting for confounders including maternal education, maternal age, smoking, drug/alcohol use, and infant gender. Of 173,822 deliveries captured in the intergenerational birth cohort, 71,676 (41.2%) women met inclusion criteria for this study. Of the entire cohort, 30.0% (n = 21,467) were non-Hispanic Black and 70.0% were non-Hispanic White mothers. Compared to non-Hispanic White mothers, non-Hispanic Black mothers were more likely to have been born late preterm (6.8% vs 3.7%) or early preterm (2.8 vs 1.0%), P < .001. Non-Hispanic White mothers who were born (early or late) preterm were not at an increased risk of early or late preterm delivery compared to non-Hispanic White mothers born term. The risk of early preterm birth was most pronounced for Black mothers who were born early preterm (adjusted odds ratio, 3.26; 95% confidence interval, 1.77-6.02) compared to non-Hispanic White mothers. We found an intergenerational effect of preterm birth among non-Hispanic Black mothers but not non-Hispanic White mothers. Black mothers born <34 weeks carry the highest risk of delivering their first child very preterm. Future studies should elucidate the underlying pathways leading to this racial disparity.


Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation.
This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25-3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up.


Emerging Therapies and Therapeutic Targets for Composite Liver Disease: NASH.
Liver diseases continue to destroy the lives of people, one of which is known as Non-alcoholic Steatohepatitis (NASH) that becomes a serious liver disease all around the world over the last few years. Non-alcoholic Steatohepatitis (NASH) is a progressive form of Nonalcoholic Fatty Liver Disease (NAFLD) and is characterized by liver steatosis, inflammation, different degrees of fibrosis, and hepatocellular injury. The inflammatory mediators play a vital role in the transition of Non-alcoholic Fatty Liver (NAFL) to Non-alcoholic Steatohepatitis (NASH), which further leads to Hepatocellular Carcinoma (HCC) and becomes a cause of liver transplantation. Considering the severity and complexity of the disease, we aim to summarize the works of various research groups that are working in the area of NASH to find a sophisticated treatment. The present review focused on various factors that are responsible for the development and progression of this prevalent disease, emerging pharmacotherapies as well as therapeutic targets that have been utilized for the treatment of NASH. We also have conducted the structural analysis of available targets, which will be helpful for the enhancement of drug discovery through the implementation of in silico methods. Efforts have been made to provide an update on research in the area of NASH, including the pharmacological agents that are currently undergoing clinical trials for the treatment of NASH. Besides the massive research, still, gaps and challenges are there in the drug development for NASH that also have been discussed.


Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes.
Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-alpha, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography. The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.


A Neurologic Examination for Anesthesiologists: Assessing Arousal Level during Induction, Maintenance, and Emergence.
Anesthetics have profound effects on the brain and central nervous system. Vital signs, along with the electroencephalogram and electroencephalogram-based indices, are commonly used to assess the brain states of patients receiving general anesthesia and sedation. Important information about the patient's arousal state during general anesthesia can also be obtained through use of the neurologic examination. This article reviews the main components of the neurologic examination focusing primarily on the brainstem examination. It details the components of the brainstem examination that are most relevant for patient management during induction, maintenance, and emergence from general anesthesia. The examination is easy to apply and provides important complementary information about the patient's arousal level that cannot be discerned from vital signs and electroencephalogram measures.


New Insights into the Nature of Co-components and Their Impact on Pd Structure: X-ray Absorption Studies on Toluene Acetoxylation Catalysts.
Co-components are a powerful tool to tune the performance of catalysts, but their nature and their impact on the catalysts is often controversially discussed. In this study X-ray absorption spectroscopy (XAS) was employed to elucidate the nature of co-components and their impact on the catalytic reaction. In anatase-supported Pd-based catalysts for the gas-phase acetoxylation of toluene, less noble co-components (e.g., Mn, Co, and Sb) spread over the support in their oxidic form and changed their valence state on stream. Incorporated atoms such as C or a small part of the Sb affect the electronic structure of Pd. For the noble Au, only a weak interaction with the support and Pd was observed during time on stream. Only XAS at the K-edges together with investigations of the Pd L-edge for a better understanding of the electronic structure, supplemented by STEM for elemental mapping, allow such detailed insights.


Dynamics of lipids and metabolites during the cell cycle of Chlamydomonas reinhardtii.
Metabolites and lipids are the final products of enzymatic processes, distinguishing the different cellular functions and activities of single cells or whole tissues. Understanding these cellular functions within a well-established model system requires a systemic collection of molecular and physiological information. In the current report, the green alga Chlamydomonas reinhardtii was selected to establish a comprehensive workflow for the detailed multi-omics analysis of a synchronously growing cell culture system. After implementation and benchmarking of the synchronous cell culture, a two-phase extraction method was adopted for the analysis of proteins, lipids, metabolites and starch from a single sample aliquot of as little as 10-15 million Chlamydomonas cells. In a proof of concept study, primary metabolites and lipids were sampled throughout the diurnal cell cycle. The results of these time-resolved measurements showed that single compounds were not only coordinated with each other in different pathways, but that these complex metabolic signatures have the potential to be used as biomarkers of various cellular processes. Taken together, the developed workflow, including the synchronized growth of the photoautotrophic cell culture, in combination with comprehensive extraction methods and detailed metabolic phenotyping has the potential for use in in-depth analysis of complex cellular processes, providing essential information for the understanding of complex biological systems.


Factors that distinguish continent from incontinent older adults with detrusor overactivity.
In older adults detrusor overactivity (DO) is almost as common in continent individuals as in those with urge incontinence (UUI). Thus, UUI likely reflects the contribution of additional factors. We postulated that of functionally independent individuals in whom transient causes were excluded those in whom DO was accompanied by UUI would be more likely to have smaller functional bladder capacity, less warning and less ability to avert urine loss in the face of DO. While blinded to continence status, we reviewed the records of all 52 cognitively intact and nonobstructed volunteers older than 65 years who had DO associated with urgency during urodynamic testing and had been asked to try to prevent leakage for 2 minutes. Of these individuals 31 were continent at home. In patients with UI mean functional bladder capacity +/- SD was smaller (313 +/- 153 vs 390 +/- 178 ml, p = 0.06) and warning was briefer (87 +/- 81 vs 120 +/- 116 ml), although the association with warning was less impressive (p = 0.14). The ability to forestall leakage for at least 2 minutes correlated strongly with being continent at home (p < 0.002). For continence detrusor suppression at the onset of DO was more important than sphincter contraction. Urge incontinence in older adults involves more than simply the presence of DO. Physical function, cognitive function and medications are already known to be important for continence. Our data suggest that functional bladder capacity and the ability to suppress involuntary contraction (and possibly warning) are also potentially important covariates. These factors may represent additional potential targets for behavioral and pharmacological therapy.


Disulfiram-induced epileptic seizures.
Disulfiram has been widely used for over six decades in the treatment of alcohol dependence, as an aversive therapeutic agent. Despite having very few side effects when taken without concurrent alcohol consumption, some of these may underlie serious clinical complications. Epileptic seizure induction is a rare adverse effect of disulfiram and its aetiological mechanism is unknown. We present a hospitalised 47-year-old male patient with two episodes of generalised tonic-clonic seizures during treatment with disulfiram while abstinent from alcohol.


Treatment of facial angiofibroma of tuberous sclerosis using cultured epithelial autografts.
Treatment of facial angiofibroma of tuberous sclerosis is problematic, because the skin lesions involve entire dermis. Five patients aged from 14 to 33 (mean: 23.6) years old with angiofibroma of tuberous sclerosis were treated with cultured epithelial autografts between 1995 and 2004. The entire area of the facial lesions was excised using a razor to remove large nodules, and then the remaining lesions were further abraded to a rather deep layer of the dermis to smooth the skin and remove small nodules. Then a cultured autologous epithelium was grafted onto the wound. In all patients, epithelization was complete within 10 (mean: 9) days after the surgery. All patients were followed up for more than 6 months and showed neither depigmentation due to scar formation nor hypertrophic scars. In some patients, some pebbly regrowth had occurred at 5 years postoperatively, but the appearance was quite acceptable.


[Analysis of utilization of information in the journal Medicina Clinica].
Scientific communication knowledge is specifically based in the analysis of the bibliographic references inside the publications. Pattern and laws determining the information consumption in the items of the journal Medicina Clinica are investigated in the present study as its own aim. An analysis was performed on the 13,286 references downloaded from 618 papers published by the journal in 1990. With dBASE IV was generated a database for the management of the information; data was distributed in several tables through criteria of age, documentary types, countries, journals and Bradford zones. The analysed references belong to 1,241 different journals, 110 from Spain. Being two thirds of the total sum, the publications from United States and United Kingdom have received more citations than those from Spain. The publications from european countries, like France, Germany and Italy, are scarcely present. Bradford core is constituted by the journals Medicina Clinica and The Lancet. The analysis of the bibliographic references available from the articles in this journal is able to produce knowledge on the information consumption by the practitioners; its usefulness as a complementary utility to the Indice de Citas e Indicadores Bibliométricos de Revistas Españolas de Medicina Interna y sus especialidades 1990 must be considered.


The picture complexity effect: another list composition paradox.
List composition effects refer to the findings in which a given memory phenomenon shows discrepant patterns across different list designs (i.e., mixed or pure lists). These effects have typically been reported with verbal materials (e.g., word lists, paired associates, sentences); much less research has examined whether these effects generalize to pictorial materials. In 3 experiments, we investigated whether list composition effects extend to the picture complexity effect, the finding that complex pictures are sometimes better recalled than simple pictures. Our results consistently indicated superior recall for complex pictures relative to simple pictures in mixed but not pure lists. We also examined 3 prominent theoretical accounts that have been proposed to explain list composition effects with verbal materials: (a) the item-order framework (Experiment 1), (b) the retrieval distinctiveness hypothesis (Experiment 2), and (c) the attention-borrowing theory (Experiment 3). Our findings indicated that the attention-borrowing theory is a viable candidate explanation for list composition effects with pictorial materials.


RNAi knock-down mice: an emerging technology for post-genomic functional genetics.
RNA interference (RNAi) has been extensively used for sequence-specific silencing of gene function in mammalian cells. The latest major breakthrough in the application of RNAi technology came from experiments demonstrating RNAi-mediated gene repression in mice and rats. After more than two decades of functional mouse research aimed at developing and continuously improving transgenic and knock-out technology, the advent of RNAi knock-down mice represents a valuable new alternative for studying gene function in vivo. In this review we provide some basic insight as to how RNAi can induce gene silencing to then focus on recent findings concerning the applicability of RNAi for regulating gene function in the mouse. Reviewed topics will include delivery methods for RNAi-mediating molecules, a comparison between traditional knock-out and innovative transgenic RNAi technology and the generation of graded RNAi knock-down phenotypes. Apart from the exciting possibilities RNAi provides for studying gene function in mice, we discuss several caveats and limitations to be considered. Finally, we present prospective strategies as to how RNAi technology might be applied for generating conditional and tissue-restricted knock-down mice.


Correlation between percentage of fat mass and level of disease activity in rheumatoid arthritis.
Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation. To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis. This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28). The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson's correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76). The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.


Survival of Aeromonas hydrophila in Fresh Tomatoes ( Lycopersicum esculentum Mili) Stored at Different Temperatures and Treated with Chlorine.
This study examines the survival of two Aeromonas hydrophila strains ( A. hydrophila ATCC 7965 [strain A] and A. hydrophila isolated from food [strain B]) on the surface and core tissue of fresh tomatoes stored at different temperatures and the efficacy of chlorine treatment on their survival. Counts of A. hydrophila on the surface of tomatoes stored at 25 and 35 °C were significantly higher between days 1 and 4 for both strains as compared to results obtained at 6°C. Core tissue counts of A. hydrophila cells on tomatoes dipped in a cellular suspension at 25°C and stored at 25°C were significantly higher (P < 0.05) than counts obtained with dip suspensions at 6 or 35°C. In chopped tomatoes stored at 25 and 35°C, populations of aerobic mesophiles showed significant increases after 96 and 70 h, respectively. The populations of both A. hydrophila strains in chopped tomatoes stored at 6°C increased significantly after 96 h, while at 25 and 35°C the counts increased in the first hours of incubation. Viable counts of A. hydrophila on the surface and central tissue of tomatoes significantly decreased (P < 0.05) when the samples were dipped for 2 min in chlorine at a concentration of 50 ppm (50 μg/ml). The results suggest that tomatoes should be kept at low temperatures during storage, shipping, and retail stocking and that chlorine at a concentration of 50 ppm should be used to reduce the levels of A. hydrophila .


Transient Neuropathic Pain Following Mechanically Assisted Manipulation of the Spine: A Clinical Case Study.
We describe the case of a patient developing acute neuropathic pain in the sciatic nerve distribution following spinal manipulation. Manipulative treatment with an Activator Adjusting Instrument (AAI) was recommended and performed. Within 24 hours, the patient developed severe 10/10 pain originating from the left gluteal area at the site of one of the activator deployments with radiation all the way down his left leg to the foot. He was able to maintain distal left leg strength and sensation. Relief was achieved with subsequent physical therapy techniques to relax his deep gluteal muscles, raising the hypothesis of temporary injury to the deep gluteal muscles, with painful contractions resulting in gluteal region pain as well as sciatic nerve inflammation as the nerve passed through that region. This clinical case illustrates some of the perils and risks of spinal manipulation, particularly in the elderly, and the need for careful patient selection.


Concurrent autoimmune hepatitis in multiple sclerosis.
Autoimmune hepatitis (AIH) is a rare and chronic inflammatory disorder associated with extrahepatic autoimmune diseases, including, infrequently, multiple sclerosis (MS). Short Reports: We report five cases of MS and AIH association. One patient developed AIH while under interferon beta-1b and the remaining while off disease-modifying therapy, although after methylprednisolone bolus in three. All presented a liver biopsy compatible with AIH. Hepatitis resolution was achieved with immunosuppressive treatment, but one patient died after a fulminant hepatitis requiring liver transplant. A thorough review of published cases supports this clear, although rare, association and a liver biopsy should be considered in AIH suspected cases.


Transfer-printing and host-guest properties of 3D supramolecular particle structures.
Mechanically robust and crystalline supramolecular particle structures have been constructed by decoupling nanoparticle assembly and supramolecular glue infiltration into a sequential process. First, beta-cyclodextrin (CD)-functionalized polystyrene particles (d approximately 500 nm) were assembled on a CD-functionalized surface via convective assembly to form highly ordered, but mechanically unstable, particle crystals. Subsequently, the crystals were infiltrated by a solution of adamantyl-functionalized dendrimers, functioning as a supramolecular glue to bind neighboring particles together and to couple the entire particle crystal to the CD surface, both in a noncovalent manner. The supramolecular particle crystals are highly robust, as witnessed by their ability to withstand agitation by ultrasonication. When assembled on a poly(dimethylsiloxane) (PDMS) stamp, the dendrimer-infiltrated particle crystals could be transfer-printed onto a CD-functionalized target surface. By variation of the geometry and size of the PDMS stamps, single particle lines, interconnected particle rings, and V-shaped particle assemblies were obtained. The particle structures served as 3D receptors for the binding of (multiple) complementary guest molecules, indicating that the supramolecular host functionalities of the particle crystals were retained throughout the fabrication process.


Fluorinative Rearrangements of Substituted Phenylallenes Mediated by (Difluoroiodo)toluene: Synthesis of α-(Difluoromethyl)styrenes.
Phenylallenes undergo fluorinative rearrangement upon the action of (difluoroiodo)toluene in the presence of 20 mol % BF3 ⋅OEt2 to yield α-difluoromethyl styrenes. This unprecedented reaction was entirely chemoselective for the internal allene π bond, and showed remarkable regioselectivity during the fluorination event. Substituted phenylallenes, phenylallenes possessing both phenyl- and α-allenyl substituents, and diphenylallenes were investigated, and good functional-group compatibility was observed throughout. The ease with which allenes can be prepared on a large scale, and the operational simplicity of this reaction allowed us to rapidly access fluorine-containing building blocks that have not been accessed by conventional deoxyfluorination strategies.


Surgical treatment for distal tubal occlusion. A review of 167 cases.
Surgery was performed on 167 patients for distal tubal occlusion. In 143 cases a terminal microsurgical salpingostomy was performed and in 24, a cuff neostomy. The overall intrauterine pregnancy rate was 20.4%, and 16.8% of the patients had live births. The ectopic gestation rate was 1.8%. None of the patients with a cuff neostomy became pregnant.


Critical review of type specimens deposited in the Malacological collection of the biological institute/Ufrj, Rio de Janeiro, Brazil.
The Malacological Collection of the Biological Institute of Federal University of Rio de Janeiro figures as an important repository of specimens, containing c.a. 21,000 lots, most of them collected at deep sea of southeast Brazil. A critical review of literature and types deposited in this collection revealed the existence of 191 lots containing type specimens (23 holotypes and 168 paratypes), corresponding to 129 nominal species divided in three classes: Gastropoda (109 names, subdivided in 62 Caenogastropoda; 32 Heterobranchia and 15 Vetigastropoda), Bivalvia (17 names subdivided in 10 Protobranchia; 6 Heterodonta and 1 Pteriomorphia), and Scaphopoda (3 names). For each species, an updated list of data is provided, including the collecting location (revised or corrected, when necessary), number of specimens actually present (i.e., physically found in the collection), nomenclatural acts (if needed) and any other specific issue concerning particular species. It is beyond the scope of this study to discuss classifications or promote subjective judgment on taxonomy at any level for names treated here.


[Sexual violence against women in Tunisia].
Sexual violence exists everywhere in the world. It depends mainly on the cultural and religious norms conveyed in the various societies. This is a neglected area of research. Available data are insufficient, especially in Arab-Muslim context. In this paper, we comprehensively review the scientific literature in order to clarify the cultural, religious and legal aspects of the concept of sexual violence against women in Tunisia, and ask the question of the urgent need to put in place strategies to counter this problem. The National Office for Family and Population published in 2011 the results of the national survey on violence against women in Tunisia, including data on sexual violence and its impact on women's health and well-being. According to this survey, 14.2% of women reported having been sexually abused by an intimate partner during their lifetime and 9.0% reported having experienced it during the last 12 months. One out of every six Tunisian women has been the victim of a sexual violence in a conjugal setting. More men than women legitimized violence against women in contexts where family control, especially conjugal control, is exercised over them. In a study examining the impact of culture and religion on experiences and sexual practice of women in Tunisian society, the majority of respondents thought that sexuality in women was a religious duty and that they do not have the right to refuse their husbands or to rebel. Thus, women would be doubly sanctioned having neither the right to express their desire nor not to respond to their husband's desire. A survey of a representative sample of Tunisian women found that 56.9% of the participants reported being victims of domestic violence, particularly sexual violence (10.7%) consisting mainly of rape and sodomy, at least once in their lifetime. This survey showed that those victims expressed dissatisfaction with overall quality of life. Moreover, contrary to Western literature, sexual violence was the least reported form of violence by teenage girls in Tunisian schools. Indeed, cultural values of modesty, virginity and honor are socially much more demanded for girls, in Arab countries in general, reinforcing staggering silence and inaction around violence experienced by school-aged adolescents. In Tunisian society, the cultural "solution" to rape wants the woman to marry her rapist which safeguards her family's integrity by legitimizing the union. Sexual violence has detrimental effects on female victims' physical and mental health. Even if the information on this form of violence is not easy to obtain in our environment, and that rates of subjects reporting sexual violence in their lifetimes are not important, the problem of sexual violence must be considered as a public health problem requiring urgent interventions and a greater institutional will.


Phenotate: crowdsourcing phenotype annotations as exercises in undergraduate classes.
Computational documentation of genetic disorders is highly reliant on structured data for differential diagnosis, pathogenic variant identification, and patient matchmaking. However, most information on rare diseases (RDs) exists in freeform text, such as academic literature. To increase availability of structured RD data, we developed a crowdsourcing approach for collecting phenotype information using student assignments. We developed Phenotate, a web application for crowdsourcing disease phenotype annotations through assignments for undergraduate genetics students. Using student-collected data, we generated composite annotations for each disease through a machine learning approach. These annotations were compared with those from clinical practitioners and gold standard curated data. Deploying Phenotate in five undergraduate genetics courses, we collected annotations for 22 diseases. Student-sourced annotations showed strong similarity to gold standards, with F-measures ranging from 0.584 to 0.868. Furthermore, clinicians used Phenotate annotations to identify diseases with comparable accuracy to other annotation sources and gold standards. For six disorders, no gold standards were available, allowing us to create some of the first structured annotations for them, while students demonstrated ability to research RDs. Phenotate enables crowdsourcing RD phenotypic annotations through educational assignments. Presented as an intuitive web-based tool, it offers pedagogical benefits and augments the computable RD knowledgebase.


Hemoglobin oxidation at functional amino acid residues during routine storage of red blood cells.
Routine storage of red blood cells (RBCs) results in the progressive accumulation of storage lesions. While the clinical relevance of these lesions is still a matter of debate, alterations to RBC morphology and biochemistry, especially in terms of energy and redox homeostasis, are likely to affect RBC physiology and functionality at a minimum. Identification of oxidative modifications that accumulate on key RBC proteins will help bridge the gap between storage induced alterations and post-transfusion RBC viability. Five AS-3 units were analyzed during routine storage via one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis-nano-high-performance liquid chromatography coupled online with tandem mass spectrometry and advanced database searches. We identified oxidative modifications to functional residues of hemoglobin (Hb) beta chain, including proximal histidine, cysteine beta 94 (counting initiator methionine in the sequence), and histidine 144. Semiquantitative analysis indicates that up to approximately 20% of total Hb could be targeted by these oxidative modifications that are overlooked by standard proteomics approaches using routine database search conditions. Progressive accumulation of oxidized residues in stored RBCs and selective accumulation in vesicles was observed, further substantiating the hypothesis that vesiculation represents a self-protective mechanism in ageing RBCs. Several of the oxidized residues identified play well-established roles in heme iron coordination, 2,3-diphosphoglycerate binding, and nitric oxide homeostasis. Further functional and structural studies are necessary to determine possible associations between these modifications and impaired gas transport homeostasis in RBCs from old units.


Resistance of Sclerotinia homoeocarpa Field Isolates to Succinate Dehydrogenase Inhibitor Fungicides.
Sclerotinia homoeocarpa isolates were collected from golf courses in Japan and the United States (2016-2017). Japan isolates were collected during a monitoring study and the U.S. isolates were collected due to field failure. Five succinate dehydrogenase inhibitor (SDHI) active ingredients (boscalid, fluopyram, fluxapyroxad, isofetamid, and penthiopyrad) were examined using in vitro sensitivity assays to determine cross-resistance. Sequence analysis revealed a point mutation leading to an amino acid substitution (H267Y) and a silent mutation (CTT to CTC) at codon 181 in the SdhB subunit gene. Isolates with the B-H267Y (n = 10) mutation were resistant to boscalid and penthiopyrad and had increased sensitivity to fluopyram. SdhB silent mutation 181C>T isolates (n = 2) were resistant to boscalid, isofetamid, and penthiopyrad. Sequence analysis revealed 3 mutations leading to an amino acid substitution (G91R, n = 5; G150R, n = 1; G159W, n = 1) in the SdhC subunit gene. Isolates harboring the SdhC (G91R or G150R) mutations were resistant to boscalid, fluxapyroxad, isofetamid, and penthiopyrad. A genetic transformation system was used to generate mutants from a SDHI sensitive isolate to confirm the B-H267Y and C-G91R mutations were direct determinants of SDHI resistance and associated with in vitro sensitivity assay results.


[Synthetic peptide antigens for medical cell biology].
The research in cell biology and medical sciences have been advanced through the use of antibodies specifically reactive with cellular proteins. In addition to conventional polyclonal and monoclonal antibodies, a third type of antibodies has come wide spread use within the past five years. Synthetic peptide antigens have been shown to elicit antibodies that can react with full length protein containing that peptide. Such antibodies are directed against a specific region of the protein chosen in advance by the investigator and so have a predetermined specificity. In basic research, these antibodies are usefull in identifying the protein product to particular cells or subcellular organelles and purifying the protein by immunoaffinity chromatography techniques. In medicine, such antibodies may provide reagents for passive vaccination, antitoxin therapy and targetted immunotherapy of neoplasia.


Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis.
The identification of factors which increase the risk of acute pancreatitis, the most common and most severe complication of endoscopic retrograde cholangiopancreatography (ERCP), is of considerable importance. However, in four large prospective studies, the reported incidence of identified risk factors for post-ERCP pancreatitis was found to be variable. The aim of this study was to identify the most important risk factors for post-ERCP pancreatitis. We performed a meta-analysis of 15 prospective clinical studies, selected out of 52 reviewed articles, in which risk factors for pancreatitis were identified. Of the 14 risk factors identified, five were patient characteristics and nine were related to the endoscopic technique. When patient-related risk factors were analysed, the relative risk for suspected sphincter of Oddi dysfunction was 4.09 (95 % CI 3.37 to 4.96; P < 0.001); for female gender, 2.23 (95 % CI 1.75 to 2.84, P < 0.001); and for previous pancreatitis, 2.46 (95 % CI 1.93 to 3.12, P < 0.001). Two endoscopy-related factors were confirmed: for precut sphincterotomy the relative risk was 2.71 (95 % CI 2.02 to 3.63, P < 0.001); for pancreatic injection the relative risk was 2.2 (95 % CI 1.6 to 3.01, P < 0.001). This meta-analysis provides a clear basis for planning pharmacological studies or studies of new endoscopic techniques in patients at high risk of developing post-ERCP pancreatitis. Knowing which patients are most at risk may also make it easier to decide who should be considered unsuitable for same-day discharge.


Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.
Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.


Increased Bioavailable Berberine Protects Against Myocardial Ischemia Reperfusion Injury Through Attenuation of NFκB and JNK Signaling Pathways.
Activation of Janus kinase (JNK) is involved in the pathogenesis of cardiac ischemia reperfusion injury. We previously demonstrated that oral treatment of rats with high doses of berberine (BBR) improved cardiac function in ischemia reperfusion injury. It is unknown if BBR modulates JNK activation. We developed a new formula, solid dispersion of BBR with sodium caprate (HGSD), which increases its bioavailability and membrane permeability. The present study examined if HGSD-mediated inhibition of JNK protects the heart from ischemia reperfusion injury.The cardioprotective effect of HGSD was examined in rat hearts subjected to global 45 minutes ischemia followed by 30 minutes reperfusion. Hemodynamic parameters and troponin levels in the perfusate, and TNF-α, IL-6, JNK, and NFκB levels in the heart were determined. To further explore the cardioprotective mechanism of HGSD, H9c2 cells subjected to hypoxia/reoxygenation were incubated with serum containing HGSD in the absence or presence of an activator or inhibitor of JNK.Pretreatment of rats with HGSD for 7 days significantly improved recovery of heart function in animals subjected to ischemia reperfusion injury compared to untreated controls. In addition, HGSD pretreatment inhibited cardiac production of TNF-α and IL-6, and attenuated ischemia reperfusion induced cardiac JNK activation and nuclear translocation of NFκB compared to untreated controls. In H9c2 cells subjected to hypoxia/reoxygenation, the presence of JNK activator diminished the release of TNF-α and IL-6 and the nuclear translocation of NFκB.HGSD treatment protects the heart from ischemia reperfusion injury through attenuation of NFκB and JNK signaling pathways.


[Antioxidant activities of green and black teas determined by the cumene hydroperoxide/hemoglobin.methylene blue method].
Antioxidant activity in tea was measured by the new cumene hydroperoxide/hemoglobin.methylene blue(CHP/Hb.MB) method developed in our laboratory. Using the CHP/Hb.MB method, we investigated the activities of polyphenols(11 varieties) in order to determine their reactivity on CHP. According to the CHP/Hb.MB method, an increase in the number of hydroxyl groups in polyphenols induced high antioxidant activity. We found that this method was capable of measuring the antioxidant activity of polyphenols. Consequently, we were able to measure the antioxidant activities of heated, green, powdered and black teas by this method. The average of antioxidant activities of heated green tea was 207 nmol/ml, while that of green tea was 280 nmol/ml, powdered green tea was 481 nmol/ml and black tea was 215 nmol/ml respectively.


Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated.
Glycoprotein (GP) IIb/IIIa antagonists are effective therapeutic agents, but elicit thrombocytopenia with a frequency that approaches 2%. Here, we provide evidence that thrombocytopenia in humans treated with the GP IIb/IIIa antagonist roxifiban is immune mediated. Two patients underwent conversion to a highly positive drug-dependent antibody (DDAB) status temporally associated with thrombocytopenia. Despite the continued presence of DDABs, the fall in platelet count was reversed by discontinuation of drug treatment, pointing to the exquisite drug dependency of the immune response. DDABs appear to bind to neoepitopes in GP IIb/IIIa elicited on antagonist binding. This information was used to develop an enzyme-linked immunosorbent assay (ELISA) for DDAB using solid-phase GP IIb/IIIa. A high level of specificity is indicated by the observation that DDAB binding is dependent on the chemical structure of the GP IIb/IIIa antagonist and that only 2% to 5% of human blood donors and 5% of chimpanzees present with pre-existing DDABs. Furthermore, none of 108 nonthrombocytopenic patients from the phase II roxifiban study showed an increase in antibody titer. Absorption of thrombocytopenia plasma with platelets reduced the DDAB ELISA signal, indicating that the test detects physiologically relevant antibodies. Screening patients for pre-existing or increasing DDAB titer during treatment with GP IIb/IIIa antagonists may reduce the incidence of drug-induced thrombocytopenia.


[The role of color doppler ultrasonography, thyroid function and auto antibody for the screening of Graves' disease in pregnancy].
To determine whether color doppler ultrasonography (CDU), thyroid function or thyroid autoimmune antibodies could identify Graves' disease in pregnancy(GDP) in pregnant patients with newly diagnosed thyrotoxicosis. It is an observational study. Sixty-eight pregnant patients with newly diagnosed thyrotoxicosis including gestational hyperthyroidism(GHT) subjects (GHT group, n=33) and GDP subjects (GDP group, n=35), and 62 age-and sex-matched healthy subjects (C1 group: pregnant, n=32, C2 group: non-pregnant, n=30) were recruited. Thyroid function, human chorionic gonadotropin(HCG), thyroid autoimmune antibodies were detected. Peak systolic velocity of the superior thyroid artery (STA-PSV) and diastole inner diameter(STA-D) of the superior thyroid artery were measured by CDU. A ROC curve was used to evaluate STA-PSV, STA-D, thyroid function and thyroid autoimmune antibodies for identification of GDP. The area under the ROC curve of STA-PSV, STA-D and thyroid stimulating hormone (TSH), free T4 (FT4) for GDP were 0.905, 0.887, 0.803 and 0.786, respectively. The optimal cut-off points of STA-PSV, STA-D, TSH and FT4 for GDP were 40 cm/s, 2.0mm, 0.03 mIU/L and 30 pmol/L with the sensitivity of 82.9%, 72.1%, 81.8%, 76.2% and specificity of 81.8%, 87.9%, 75.2%, 80.3%, respectively. Detection of STA-PSV and STA-D by CDU, as well as thyroid function, is useful in screening GDP in pregnant patients with thyrotoxicosis.


Open-ended rectangular waveguides as antennas for medical diagnostics.
Open-ended rectangular waveguides, potentially useful as microwave antennas for medical diagnostics are described. Reflection coefficients have been measured for the waveguides fitted with standard flanges in contact with water and skin. Antenna matching to the tissue is discussed. Near-field radiation patterns in phantom solutions were measured to obtain operature and depth distribution patterns.


Novel peptide-based copper(II) complexes for total hydrolytic cleavage of DNA.
Stable Cu(II) complexes with histamine- and histidine-containing dipeptides histidylserine and histidylphenylalanine have been developed. Their interaction in solution has been investigated, and the stability of their complexes was determined. The nature of binding in these complexes has been explained with the help of potentiometric pH titrations and 1H-NMR spectroscopy. The geometry of these complexes has been established by electronic spectra. The DNA-binding and -cleavage abilities of these Cu(II) complexes have been probed by the absorption, thermal denaturation, fluorescence, and electrophoresis experiments. The results suggest that these peptide-based Cu(II) complexes effectively bind and efficiently cleave DNA under mild biological conditions. Since Cu(II) complexes are known to play an important role in phosphodiester bond cleavages, these results assume importance.


HMG CoA reductase inhibitors.
Beta-hydroxy-beta-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (HMG CoA RIs) are now being prescribed in many different countries, and the number of patients treated with these compounds is estimated to be over 1.5 million. The spectrum of indications for these drugs is enlarging. Thus, not only patients with primary hypercholesterolemia are suitable candidates for therapy with HMG CoA RIs, but also patients with other forms of familial and non-familial (secondary) dyslipidemias. The safety and tolerance profile is remarkably good and adverse effects tend to be mild and rare. Currently, several primary and secondary intervention trials are ongoing or in preparation to investigate the influence of HMG CoA RIs on cardiovascular morbidity and mortality.


Limits to neural stimulation in echo-planar imaging.
Simple electrical circuits are used to model neural stimulation. The stimulation current is evaluated for a variety of magnetically induced waveforms and for sinusoidal stimulation as a function of frequency. Experimental results obtained using a small scale magnetic stimulator show that the transient response rather than the steady-state behavior determines the stimulation characteristics thus suggesting a nonlinear model. We show that a nonlinear circuit changes a steady-state current solution into a repeated transient solution and thereby better explains our experimental results. Our model also shows that for very short times and high frequencies, contrary to the current widely held view, neural stimulation is independent of the magnetic field switching rate dB/dt, but depends on the final magnetic field value, Bm. At lower frequencies and rise-times, there may be a small advantage in using square wave over sine wave gradient modulation for whole body echo-planar imaging (EPI). It is found that the peak stimulation fields Bm, for both sinusoidal and trapezoidal waveforms are equal for equal risetimes. This means that for a given image array size and imaging time, trapezoidal modulation EPI ultimately can be made to operate below the neural triggering threshold while the equivalent sine modulation EPI version transcends the threshold.


Ischemic Stroke in the Elderly: Septuagenarians Versus Octogenarians.
Stroke prevalence is known to increase with age. Approximately 50% of acute ischemic stroke patients are aged between 70 and 89 years. In this study, records of 770 ischemic stroke patients who were 70-89 years old were retrospectively examined (407 septuagenarians and 363 octogenarians). The demographics, comorbid conditions, ischemic stroke type, and stroke outcome for the two age groups were analyzed. Comorbid hypertension, diabetes mellitus, and HbA1c levels of ≥6.5% more frequently occurred in septuagenarians than in octogenarians (80.6% versus 70.8%, p=0.002; 32.2% versus 21.8%, p=0.001; and 35% versus 23.2%, p=0.003, respectively), whereas atrial fibrillation was significantly higher in octogenarians (49.3% versus 41.5%, p=0.03). Hypercholesterolemia, previous stroke history, and antiaggregant and/or anticoagulant use were not significantly different between the two age groups. Based on the Oxfordshire Community Stroke Project classification, the most common stroke subtype in the septuagenarian group was a lacunar infarction and in the octogenarian group, it was a partial anterior circulation infarct. According to the Modified Ranking Score, the number of patients living independently was higher for septuagenarians (42.8% versus 27.8%, p<0.001). The present findings indicate that the clinical characteristics of ischemic stroke differed between septuagenarians and octogenarians. Therefore, elderly stroke patients cannot be accepted as a homogeneous group. Because this is a hospital-based study, our findings need to be tested via additional epidemiological studies.


Results of 90 consecutive hepatectomies for hepatocellular carcinoma: a multivariate analysis of survival.
The surgical results and postoperative management of 90 patients with hepatocellular carcinoma (HCC) who underwent hepatectomy were reviewed, and clinical factors relating to HCC were analyzed to determine what type of HCC responds best to hepatectomy. The patients consisted of 69 men and 21 women. Serum anti-hepatitis C virus was positive in 76.9% of patients and hepatitis B surface antigen was positive in 18.9%. The operative procedures consisted of right lobectomy in six patients, left lobectomy in seven, right hepatic segmentectomy in eight, left lateral segmentectomy in 13, two adjoining subsegmentectomy in 17, subsegmentectomy in 29, and partial hepatectomy in 10. Liver cirrhosis was confirmed histopathologically in 63 patients. There were two operative deaths and two other in-hospital deaths. During the follow-up period, HCC recurred in 64 of the remaining 86 patients at the following sites: liver in 56 patients (87.5%), bones in four (6.3%), lymph nodes in three (4.7%), and lung in one (1.6%). Transcatheter arterial chemoembolization was performed in 22 of the patients with recurrence, transcatheter arterial chemoembolization in combination with percutaneous ethanol injection was performed in 14, hepatectomy was performed in six, and irradiation with Linac x-rays was performed in eight. The cumulative 3- and 5-year survival rates were 63.8% and 37.8%, respectively. Univariate and multivariate analyses of factors influencing survival disclosed that having a single HCC nodule of up to a maximal diameter of 4.0 cm, an absence of intrahepatic metastasis, and a functional liver reserve estimated as clinical stage I contributed significantly and independently to increasing the survival rate.


Intimate relationships in young adults with perinatally acquired HIV: a qualitative study of strategies used to manage HIV disclosure.
An increasing number of children born with perinatally acquired HIV (PAH) are surviving into late adolescence and early adulthood. At this developmental stage, forming and sustaining intimate relationships is important. Young adults with PAH face both normative challenges and additional, HIV-related, relationship stressors. One key issue is the decision about whether and how to share their HIV status with others. Being able to disclose one's HIV status to sexual partners may reduce the risk of onward HIV transmission but is associated with the fear of rejection. There has been little research on how young people with PAH manage such disclosure-related stressors in intimate relationships. This study examined how disclosure challenges are managed by young adults with PAH in the UK within their intimate relationships. Seven participants (five females and two males) currently or previously in an intimate relationship, aged 18-23 years, were recruited from a UK hospital clinic. The majority of participants were of sub-Saharan African origins. They took part in in-depth interviews, with data analysed according to the principles of interpretative phenomenological analysis. Four themes were elicited: (1) decisions about starting, continuing or resuming relationships shaped by disclosure, (2) disclosing early to avoid the pain of future rejection, (3) using condoms to avoid disclosure and (4) testing likely partner reactions to disclosure. The study revealed the significant extent to which HIV disclosure affected the experience of relationships in this population. Interventions to support adolescents and young adults with PAH to disclose to their partners should be developed alongside guidance for professionals. Future research should include older samples of adults with PAH and studies in sub-Saharan African settings.


The Impact of Primary Tumor and Locoregional Metastatic Lymph Node SUVmax on Predicting Survival in Patients with Rectal Cancer.
The aim of this study was to evaluate the impact of maximum standard uptake value (SUVmax) of the primary tumor and locoregional metastatic lymph node in predicting survival in patients with the preoperative rectal adenocarcinoma. One hundred and fifteen patients [mean age ± standard deviation (SD): 58.7±11.4 years] with biopsy-proven rectal adenocarcinoma underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging were included in this study. All patients were followed-up for a minimum of 12 months (mean ± SD: 29.7±13.5 months). Tumor-node-metastasis 2017 clinical staging, SUVmax of the primary rectal tumor and locoregional lymph nodes on the PET/CT studies were evaluated. All patients had increased FDG activity of the primary tumor. The mean ± SD SUVmax of the primary tumor and locoregional metastatic lymph node were 21.0±9.1 and 4.6±2.8, respectively. Primary tumor SUVmax did not have an effect on predicting survival (p=0.525) however locoregional metastatic lymph node SUVmax had an effect (p<0.05) on predicting survival. Clinical stage of the disease was a factor predicting survival (p<0.001). 18F-FDG PET/CT is an effective imaging modality for detecting primary tumors and metastases in rectal adenocarcinoma and clinical stage assessment with PET/CT had an effect on predicting survival. Furthermore, in our study locoregional lymph node SUVmax was defined as a factor in predicting survival.


Pulmonary hemorrhage after cryoballoon ablation for pulmonary vein isolation in the treatment of atrial fibrillation.
Pulmonary vein isolation has evolved over the past years as an alternative for the treatment of symptomatic recurrences of atrial fibrillation refractory to antiarrhythmic drug treatment. Both radiofrequency energy and cryoballoon ablation have proven useful in this setting. We present the case of a 55-year-old male patient undergoing cryoballoon ablation complicated with pulmonary hemorrhage. The cause of this rare complication may be found in the damage of vascular venous structures near the ablation zone or, alternatively, in hemorrhagic damage of the pulmonary vein surrounding tissue (or less probably to direct injury of the lingular bronchus). The extremely low temperatures achieved in this case (which are often associated with deep balloon position inside the veins) are alarming and should alert the physician about the possibility of an excessively intrapulmonary vein deployment of the cryoablation balloon.


Catalytic Asymmetric Benzylation of Azomethine Ylides Enabled by Synergistic Lewis Acid/Palladium Catalysis.
The synergistic chiral Lewis acid/achiral Pd catalyst system was successfully applied in the enantioselective benzylation of various imine esters, giving a range of α-benzyl-substituted α-amino acid derivatives in satisfactory yield with excellent enantioselectivity. It is worth noting that this strategy exhibits good tolerance for bicyclic and monocyclic benzylic electrophiles. Furthermore, the utility of this synthetic protocol was demonstrated by the expedient preparation of enantioenriched antihypertensive drug α-methyl-l-dopa.


Acute myeloid leukemia during pregnancy: a systematic review and meta-analysis.
Data regarding clinical characteristics, therapy, maternal and fetal outcomes of pregnancy-associated acute myeloid leukemia (PA-AML) are limited. This study (including 138 cases published between 1955 and 2013) provides comprehensive assessment of these clinical parameters and may serve as a platform for developing management recommendations. Most patients (58%) received anthracycline-cytarabine-based regimens (ACBRs), which were associated with significantly increased complete remission (CR: 91%). Yet, the maternal overall survival (OS: ∼30%) was relatively low, probably reflecting reduced application of risk-adapted consolidation and allogeneic stem cell transplantation (allo-SCT). Fetal exposure to ACBRs resulted in a live birth rate of 87%, with complications (16%) diagnosed only in chemotherapy-subjected neonates. This study demonstrates safety and efficacy of ACBRs during pregnancy. Therapy and delivery schedule should allow early referral of high-risk patients to allo-SCT. Generation of a pool of high-quality data on PA-AML could contribute to providing evidence-based therapy and lead to improved maternal and fetal survival.


[Diagnosis, treatment, and prognosis of primary appendiceal tumors: analysis of 37 cases].
To investigate the pathology, diagnosis,treatment, and prognosis of primary appendiceal tumors. The clinical data of 37 patients with primary tumors of the appendix, 16 males and 21 females, aged 56 +/- 13 (35-87) hospitalized Jan. 1977 to Feb. 2007 were analyzed retrospectively. Appendicitis and abdominal mass were the major clinical manifestations. All 37 cases received surgical operation with the diagnosis confirmed by pathology. The pathological types included carcinoid tumor (n=12), mucinous tumor (n=17), and adenocarcinoma (n=8). Only 4 cases were diagnosed pathologically by biopsy before operation, 28 cases were diagnosed by intra-operative frozen section, and 5 cases were diagnosed after operation. Single appendectomy were performed in 17 cases, ileocecalectomy in 9 cases, right hemicolectomy in 8 cases, and other operation patterns in 3 cases. The 1, 3, and 5-year survival rates of the primary appendix carcinoid tumor, mucinous tumor, and adenocarcinoma were 100.0%, 100.0%, and 91.7%, 100.0%, 86.7%, and 71.5%, and 75.0%, 50.0%, and 50.0% respectively. A rare disease, appendiceal tumors lack specific clinical features. Intra-operative exploration and frozen section are very important for diagnosis and operation choice. The prognosis of primary appendix carcinoid tumors is better.


Evidence of Altered Mitochondrial Protein Expression After Chronic Ethanol Consumption in the Aged Estrogen-Deficient Female Rat Heart.
Estrogen loss has been implicated to increase the risk of alcoholic cardiomyopathy in postmenopausal women. The purpose of this study was to identify novel mitochondrial protein targets for the treatment of alcoholic cardiomyopathy in aged women using a state-of-the-art proteomic approach. We hypothesized that chronic ethanol (EtOH) ingestion exacerbates maladaptive mitochondrial protein expression in the aged female heart. Adult (3 months) and aged (18 months) F344 ovary-intact or ovariectomized (OVX) rats were randomly assigned an EtOH or control Lieber-DeCarli "all-liquid" diet for 20 weeks. Proteomic analyses were conducted in mitochondria isolated from left ventricles using isobaric tags for relative and absolute quantification (iTRAQ) 8plex labeling and mass spectrometry (n = 3 to 5/group). After EtOH, significant differences (false discovery rate <5%) were observed in electron transport chain components (NADH dehydrogenase [ubiquinone] flavoprotein 2) as well as proteins involved in lipid metabolism (2,4 dienoyl-CoA reductase) and cellular defense (catalase), suggesting a possible link to congestive heart failure. Directional changes in protein levels were confirmed by Western blotting. Additionally, EtOH significantly reduced state 3 mitochondrial respiration in all groups, yet only reduced respiratory control index in the aged OVX rat heart (p < 0.05). Collectively, the data reveal that EtOH-induced changes in the mitochondrial proteome exacerbate cardiac dysfunction in aged and estrogen-deficient hearts, but not in adult. In conclusion, iTRAQ is a powerful tool for investigating new mitochondrial targets of alcoholic cardiomyopathy.


Clinical Analysis of 77 Patients with Allergic Bronchopulmonary Aspergillosis in Peking Union Medical College Hospital.
Objective To summarize the clinical features of allergic bronchopulmonary aspergillosis(ABPA)to facilitate its early diagnosis and treatment. Methods We retrospectively analyzed the clinical data of 77 patients who had been admitted to Peking Union Medical College Hospital from January 1996 to July 2015 with ABPA. Results The average age of these 77 patients(38 men and 39 women)was(41.8±18.3)years. The co-morbidities included bronchial asthma(n=74,96%)and pulmonary cystic fibrosis(n=3,4%). The main symptoms and signs of ABPA were chronic cough(100%),sputum production(97%),wheeze(86%),sputum plugs(25%),blood-stained sputum(18%),hemoptysis(9%),chest pain(9%),fever(47%),weight loss(30%),and night sweat(12%). Laboratory tests revealed elevated levels of blood eosinophils absolute count(87%),anti-aspergillus antigen-specific IgE(89%)and specific IgG(57%)as well as a positive result of Aspergillus antigen skin test(88%). Pulmonary function testing showed that the incidences of obstructive ventilation and diffusion dysfunction were 66% and 65%,respectively;in addition,bronchodilatation test showed positive result in 60% of the patients. The most common CT findings were central bronchiectasis(81%),patchy infiltrations(79%),pleural thickening(49%),mediastinal adenopathy(35%),nodular opacities(25%),mucoid impaction(21%),and fleeting infiltrations(35%). In addition,44 cases(58%)were misdiagnosed as tuberculosis,pneumonia,lung abscess,and/or lung cancer autoimmune diseases. Conclusions ABPA can be easily misdiagnosed. ABPA should be carefully considered in patients with asthma or pulmonary cystic fibrosis who also suffer from wheeze,sputum plugs,elevated eosinophils central bronchiectasis,and fleeting infiltrations.


Effects of early and recent adverse experiences on adrenal response to psychosocial stress in depressed adolescents.
As observed in depressed adults, there is considerable variability in the degree and direction of hypothalamic-pituitary-adrenal (HPA) dysfunction in depressed adolescents. The variability in HPA findings may be attributed to experiential factors. A modified version of a standard psychosocial stressor used in adults, the Trier Social Stress Test (TSST), was administered to 30 adolescents with major depressive disorder and 25 healthy adolescent volunteers. Cortisol concentrations were measured in saliva samples collected before and after the stressor. Information was also gathered on early and recent adverse experiences with standard interviews. Participants from both groups had increased cortisol secretion in response to TSST. Compared with control subjects, depressed subjects showed more elevated and prolonged cortisol secretion in response to TSST. The combination of early-life adversity and high levels of chronic stress during adolescence was the most powerful predictor of enhanced adrenal response to the TSST. These results support previous findings on the role of experiential factors on HPA response to stress and in the development of mood disorders. Dissection of the heterogeneous pathophysiology of adolescent depression will assist in developing more specific interventions for different subgroups of patients.


Effects of growing conditions on purple corncob (Zea mays L.) anthocyanins.
Purple corn ( Zea mays L.) has been used for centuries as a natural food colorant in South America and, more recently, in Asia and Europe. However, limited information is available on the factors affecting their anthocyanin concentration and profiles. In this study, 18 purple corn samples grown under different conditions in Peru were evaluated for quantitative and qualitative anthocyanin composition as well as total phenolics. High variability was observed on monomeric anthocyanin and phenolic contents with yields ranging from 290 to 1333 mg/100 g dry weight (DW) and from 950 to 3516 mg/100 g DW, respectively, while 30.5-47.1% of the total phenolics were anthocyanins. The major anthocyanins present were cyanidin-3-glucoside, pelargonidin-3-glucoside, peonidin-3-glucoside, cyanidin-3-maloylglucoside, pelargonidin-3-maloylglucoside, and peonidin-3-maloylglucoside, and 35.6-54.0% of the anthocyanins were acylated. Potassium sources/concentrations on the soil and seedling density did not significantly affect anthocyanin composition. The growing location affected anthocyanin levels and the percentage of anthocyanins to total phenolics ( p < 0.01) and should be taken into account when choosing a material for color production.


Improving the management of disruptive behavior and reducing antipsychotic medications in nursing facility residents.
The objective of this work is to improve the management of disruptive behavior in the nursing facility setting through an interdisciplinary team (IDT) approach to reduce the use of antipsychotic medications in accordance with the Centers for Medicare & Medicaid Services initiative. The process began with a search and review of more than 100 peer-reviewed articles, government, and association resources that focused on the management of disruptive behavior in older adults. While data were limited to the past 10 years, the vast majority of data reviewed were within the past 5 years. This information was reviewed and discussed by all of the coauthors who meet in person at the American Society of Consultant Pharmacists as a work group. This group was tasked with identifying strategies through an IDT to improve the management of disruptive behavior and reduce the use of antipsychotic medications in nursing facility residents. In addition, significant follow-up work was accomplished following the live working session. Through an IDT, strategies can be implemented for long-term care residents to prevent and better manage disruptive behavior. These strategies can result in the reduction of the use of antipsychotic medications. The field of long-term care would benefit from further research to identify additional nonpharmacologic and pharmacologic treatments for managing disruptive behavior.


Does HPA-Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?
The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic-pituitary-adrenal (HPA)-axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool-age children (N = 306, 36-39 months) and their mothers, recruited to over-represent low-income families, we explored the associations among diurnal cortisol levels and effortful control, and we tested a model in which diurnal cortisol and effortful control account for the effects of family income on child adjustment. Continuous indicators of morning cortisol level and diurnal slope, as well as dichotomous indicators reflecting low morning levels and flat diurnal slope, were examined as predictors of rank-order changes in two dimensions of effortful control, executive control and delay ability. Low income was related to a flat diurnal cortisol slope, and above the effects of family income, a flat diurnal cortisol slope predicted lower social competence. Low morning cortisol level predicted smaller gains in executive control and higher total adjustment problems. Further, delay ability predicted lower adjustment problems above the effects of income and diurnal cortisol levels. The results suggest that HPA-axis dysregulation and effortful control contribute additively to children's adjustment.


Stereocomplexity and stereoselective synthesis of triamine molecules bearing four chiral carbon centers: Stereodifferentiated preparation of all 10 stereoisomers of 2,6-bis[1-(1-phenylethylamino)ethyl]pyridines.
Compounds (S,S)-2,6-bis(1-hydroxyethyl)pyridine, (R,R)-2,6-bis(1-acetoxyethyl)pyridine, and (1R,1'S)-2-(1-acetoxyethyl)-6-(1'-hydroxyethyl)pyridine were obtained by lipase-catalyzed kinetic acetylation of 2,6-bis(1-hydroxyethyl)pyridine as enantiomerically pure forms. The stereospecific replacement of hydroxy groups with (R)-phenylethylamine or (S)-phenylethylamine via its methanesulfonate or toluenesulfonate simultaneously or stepwise afforded all the stereoisomers of 1. Stereospecific preparation of all the 10 possible stereoisomers of 2,6-bis[1-(1-phenylethylamino)ethyl]pyridines 1a-f was achieved. Triamine 1b reacted with ZnCl2 to form Zn-triamine complex 16, the structure of which was determined by X-ray crystallographic analysis.


Comparative gene expression profiling of normal and human colorectal adenomatous tissues.
Adenomatous colorectal polyps are the precursors of the majority of colorectal cancers. Investigation into the gene expression changes in the progression of colorectal adenoma may offer potential targets for the development of novel diagnostic strategies. Previous gene expression studies have generally been based on a limited number of cases or only focused on a single or a few genes. The present study aimed to identify molecular characteristics of colorectal adenoma through analysis of pathways and gene ontology. The study identified 808 upregulated and 857 downregulated genes. Among the 40 pathways enriched with differentially-expressed genes, the Staphylococcus aureus infection pathway and the intestinal immune network for immunoglobulin A production pathway were identified as the most statistically noteworthy pathways at the early stage for colorectal tumorigenesis (P<0.05). These results provide new understanding of colorectal adenoma pathogenesis, with the hope of offering theoretical support for future therapeutic studies.


ADAPTIVE SEX ALLOCATION IN A SIMULTANEOUS HERMAPHRODITE.
When applied to hermaphrodite organisms, the local mate competition hypothesis predicts an increase of the ratio of sperm to ova produced as the number of mates increases. Here we test this prediction using a hermaphroditic platyhelminth parasite (trematode), Echinostoma caproni. This worm inhabits the small intestine of vertebrates, inevitably inducing the formation of highly subdivided populations, a condition known to promote local mate competition. Moreover this echinostome exhibits an unrestricted mating pattern involving both selfing and outcrossing as well as multiple fertilizations. We quantified the investment in reproductive organs by estimations of testes, cirrus sac, ovary, and egg size and fecundity when echinostomes were isolated alone, in pairs, or in groups of 20 worms. Adult body size was also recorded as a covariate. When mating group size increases (singles, pairs, or groups) we observed a significant increase in resource allocation to male function in addition to a significant decrease in ovary size. Smaller ovaries do not seem to affect egg size, but do result in a reduction in fecundity. Finally, our results are in accordance with the expected theoretical relationship between male allocation and the number of potential mates given local mate competition.


Analysis of sera from ovarian cancer patients for immune complexes.
In contrast to other malignancies, circulating immune complexes (CICS) are usually not detected by conventional assays in the sera of ovarian cancer patients. However, a polyethylene glycol (PEG) precipitation assay has been reported to detect putative CICS in ovarian cancer. To determine if CICS were indeed present, we analyzed sera from 12 women with ovarian cancer. All were negative for CICS by the Raji cell assay; 5 (42%) were positive by the PEG assay. However, the PEG precipitate did not possess characteristics of immune complexes. IgG in sera or in the precipitate sedimented in sucrose gradients solely at the same rate as 7S monomeric IgG. In addition, the precipitates were not able to activate the complement system and the four IgG subclasses were present in the same relative concentration as that found in normal serum. The results suggest that it is probably a misnomer to label the material detected in ovarian cancer sera by the PEG precipitation assay as CICS. Instead a non-immune interaction of IgG with other components, possibly membrane fragments, is probably being measured.


Cystathionine gamma-synthase is essential for methionine biosynthesis in Fusarium graminearum.
Methionine (Met) plays an important role in various cellular processes in both eukaryotes and prokaryotes. Cystathionine gamma-synthase encoded by STR2 gene is a key enzyme in Met biosynthesis in Saccharomyces cerevisiae. In this study, we identified FgMETB, a homologue of S. cerevisiae STR2, from Fusarium graminearum using the Protein Basic Local Alignment Search Tool (BLASTP) program. The FgMETB deletion mutants were unable to grow on fructose gelatin agar (FGA) medium containing SO(4)(2-) as sole sulphur source. In addition, more than 90 % conidia of the mutants were not able to germinate in 2 % sucrose solution within 6 or 12 h of incubation. Supplementation of 1 mM Met or 0.5 mg ml(-1) homocysteine, but not 1 mM cysteine or 0.5 mg ml(-1) glutathione, rescued the defect of mycelial growth and spore germination of FgMETB deletion mutants. These results indicated that the enzyme encoded by FgMETB is involved in conversion of cysteine into homocysteine. Inoculation tests showed that the FgMETB deletion mutant exhibited decreased virulence significantly on wheat heads, which is consistent with a low level of deoxynivalenol (DON) production of the mutant in wheat kernels. Fungicide sensitivity assays revealed FgMETB deletion mutants showed increased sensitivity to the sterol demethylation inhibitor tebuconazole, but did not change their sensitivities to other fungicides. Taken together, results of this study indicated that FgMETB plays a critical role in the regulation of various cellular processes in F. graminearum.


RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.
Loss of function in epigenetic acting genes together with driver alterations in the PIK3CA pathway have been shown significantly associated with poor outcome in cervical squamous cell cancer. More recently, a CoxBoost analysis identified 16 gene alterations and 30 high level activated proteins to be of high interest, due to their association with either good or bad outcome, in the context of treatment received by chemoradiation. The objectives here were to review and confirm the significance of these molecular alterations as suggested by literature reports and to pinpoint alternate treatments options for poor-responders to chemoradiation.


[Intracoronary radiotherapy].
Intervenient cardiology is significantly more represented in attempts to solve problems of heart coronary artery disease in comparison to aortocoronary bypass procedures. Resthenoses of coronary artery blood vessel after PTCA, or PTCA and stent placement are frequent. The main causes are: neointimal hyperplasia, late contraction, and remodelling. The application of brachitherapy offers the possibility to prevent resthenosis especially stent resthenosis. Our report encompasses eight patients diseased from coronary artery occlusionn. Half of there patients had a stent resthenosis. The average degree of blood vessel occlusionn before the intervenient manipulation was 78%, and after treatment 25%-30%. Early results after recanalisation of coronary blood vessel are thus fat satisfactory, but results are to be followed carefully.


Suicide victim of paraquat poisoning make suitable corneal donor.
This report addresses the possibility of expanding transplant corneal donor pool by inclusion of more patients who have suffered poisoning with paraquat pre-mortem. A 27-year-old depressed man committed suicide by ingesting 50 mL of 24% paraquat (Gramoxone, Syngenta, Taiwan). He was treated aggressively with gastric lavage, with large amounts of normal saline, followed by infusion of activated charcoal and magnesium citrate. Blood paraquat level was 1.90 μg/mL. Charcoal hemoperfusion was performed for 8 hours using a charcoal-containing dialysis machine. Furthermore, pulse therapies of cyclophosphamide (15 mg/kg/day for 2 days) and methylprednisolone (1 g/day for 3 days) were administered, followed by dexamethasone (20 mg/day for 14 days). Methylprednisolone pulse therapy was repeated since PaO(2) on the 15th day of poisoning was <60 mm Hg. Chest radiography demonstrated diffuse ground glass opacities of both lungs, with thickening of the intralobular interstitium, compatible with interstitial pneumonitis. Arterial blood gas found persistent hypoxemia and large alveolar-arterial oxygen tension differences. Respiratory failure developed on the 21st day and he was intubated for mechanical ventilatory support. As the patient expressed his wish for organ donation, the corneas were harvested after expiration on the 22nd day. His corneas were transplanted in two recipients and visual acuities of the recipients were doing well at 6 months after transplantation.


Severe myocarditis following high-dose interleukin-2 administration.
We observed a patient who developed unusually severe myocardial dysfunction during therapy for renal cell carcinoma with high-dose interleukin-2 (IL-2). Although cardiac isoenzymes became markedly elevated shortly after the completion of 14 doses of IL-2 (100,000 U/kg of IL-2 every eight hours), serial electrocardiograms revealed only nonspecific changes. Echocardiography documented diffuse myocardial dysfunction, with akinesis of the anteroseptal region, suggestive of myocardial infarction. This anteroseptal hypokinesis persisted over a five-day period. The patient died unexpectedly and postmortem evaluation of the heart revealed a severe, diffuse lymphocytic, and eosinophilic myocarditis with myocyte necrosis, especially prominent in the anteroseptal region. This is the first histologically confirmed case of myocarditis reported, to our knowledge, in association with IL-2 therapy for cancer.


FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial.
Acne vulgaris has increased in women over the past 10 years; it currently affects 20-30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone's efficacy in order to establish it as an alternative to cyclines. Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months. The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage. ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.


Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium.
Shroom family proteins have been implicated in the control of the actin cytoskeleton, but so far only a single family member has been studied in the context of developing embryos. Here, we show that the Shroom-family protein, Shroom2 (previously known as APXL) is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. In Xenopus embryos that lack Shroom2 function, we observed defects in pigmentation of the eye that stem from failure of melanosomes to mature and to associate with the apical cell surface. Ectopic expression of Shroom2 in naïve epithelial cells facilitates apical pigment accumulation, and this activity specifically requires the Rab27a GTPase. Most interestingly, we find that Shroom2, like Shroom3 (previously called Shroom), is sufficient to induce a dramatic apical accumulation of the microtubule-nucleating protein gamma-tubulin at the apical surfaces of naïve epithelial cells. Together, our data identify Shroom2 as a central regulator of RPE pigmentation, and suggest that, despite their diverse biological roles, Shroom family proteins share a common activity. Finally, because the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2 mutations may be a contributing factor in these human visual system disorders.


Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up.
Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC. The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl. At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as "successful ablation", a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up.


A multi-country comparison of jurisdictions with and without mandatory nutrition labelling policies in restaurants: analysis of behaviours associated with menu labelling in the 2019 International Food Policy Study.
To examine differences in noticing and use of nutrition information comparing jurisdictions with and without mandatory menu labelling policies and examine differences among sociodemographic groups. Cross-sectional data from the International Food Policy Study (IFPS) online survey. IFPS participants from Australia, Canada, Mexico, United Kingdom and USA in 2019. Adults aged 18-99; n 19 393. Participants in jurisdictions with mandatory policies were significantly more likely to notice and use nutrition information, order something different, eat less of their order and change restaurants compared to jurisdictions without policies. For noticed nutrition information, the differences between policy groups were greatest comparing older to younger age groups and comparing high education (difference of 10·7 %, 95 % CI 8·9, 12·6) to low education (difference of 4·1 %, 95 % CI 1·8, 6·3). For used nutrition information, differences were greatest comparing high education (difference of 4·9 %, 95 % CI 3·5, 6·4) to low education (difference of 1·8 %, 95 % CI 0·2, 3·5). Mandatory labelling was associated with an increase in ordering something different among the majority ethnicity group and a decrease among the minority ethnicity group. For changed restaurant visited, differences were greater for medium and high education compared to low education, and differences were greater for higher compared to lower income adequacy. Participants living in jurisdictions with mandatory nutrition information in restaurants were more likely to report noticing and using nutrition information, as well as greater efforts to modify their consumption. However, the magnitudes of these differences were relatively small.