[Laparoscopic cholecystectomy in an overnight admission].
to determine the feasibility and desirability of laparoscopic cholecystectomy (LC) in an overnight versus a several day admission. Although LC is performed in U.S.A. as outpatient surgery this has not been generally accepted in Europe. The main objections, are the risk of complications becoming apparent at home. Considering the specific local conditions and the general attitude towards early discharge we tried to assess the degree of feasibility and acceptance of a overnight admission in our patients. Two groups of forty patients each, with symptomatic gallstones, received LC either in an overnight or a several day admission. Preoperative and intraoperative data and postoperative recovery were prospectively assessed. The general and female age, the duration and frequency of the biliary pain, the duration and the degree of difficulty of the operation and the necessity of the subhepatic drainage were all significant in favour of the group with a shorter stay. No postoperative complications were recorded. Overnight LC is safe and effective in treating patients requiring LC. The option of the patient must also be considered.


Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists.
The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo.


Selenium-deficiency as contributing factor to anemia and thrombocytopenia in dialysis patients.
Se is an essential component of glutathione peroxidase and thereby protects cells against peroxidation of their membrane lipids. Dialysis patients have significantly lower plasma Se levels than healthy controls. The obvious role of Se in protection against development of certain forms of cardiomyopathy was investigated for the case of blood cells. There is evidence that decreased half-lives of erythrocytes and thrombocytes, found in dialysis patients, correlate with degree of Se deficiency.


Timing of the anesthetist's preoperative outpatient interview.
Hospitalization arouses anxiety among patients admitted for day bed surgery. The effect of the anesthetist's routine preoperative interview on the anxiety levels of 63 unpremedicated women scheduled for elective outpatient therapeutic abortions was examined using the State-Trait Anxiety Inventory. The anesthetist's preoperative interviews were performed at the following times: Group 1, in the outpatient clinic one week before surgery; group 2, in the day bed unit at the time of admission to hospital; group 3, outside the operating room immediately prior to surgery. State anxiety was measured before and after patients were seen by the anesthetists. In group 1, and in groups 1 and 2, it was readministered outside the operating room immediately before surgery. Baseline anxiety Trait and State scores were not significantly different in the 3 groups (Trait: group 1, 43.3 +/- 2.2; group 2, 36.9 +/- 2.3; group 3, 38.8 +/- 2.2. State: group 1, 50.6 +/- 3.5; group 2, 43.0 +/- 2.4; group 3, 49.0 +/- 3.0). Only in group 3 did the anesthetist's interview significantly reduce patient's anxiety (before visit 49.1 +/- 3.0; after visit 46.0 +/- 2.8; P less than 0.05). A small but statistically significant reduction in State anxiety scores is achieved when patients are seen by the anesthetist immediately prior to surgery.


Effectiveness of an Education Program on Donation and Transplant Aimed at Students of the Nursing Degree Course.
Health workers' awareness and knowledge of transplant medicine can improve people's sensitivity and reduce their degree of opposition to donations. The medical literature contains numerous examples of education programs aimed at university students. This work describes the experience of an education program for students of the second and third year of a nursing degree course. From April to September 2013, an education program was set up for 80 university students. It was divided into 3 stages: group self-learning based on prearranged topics, sharing of the results, and participation in the final seminar. The effectiveness was assessed according to a pretest/posttest design. The first questionnaire contained 19 questions, and the second contained 27. The questions were subdivided into specific areas: subjective knowledge, objective knowledge, attitude, awareness, participation in the event, evaluation of the information material handed out, and appreciation of the tools used. There was a significant increase for items relating to knowledge, whereas awareness and attitude (already high at the start of the program) showed no changes. After the program, many students discussed the question of donation with their relatives and friends, and about 70% filled in a donor card. The students expressed a highly positive opinion of the initiative and the tools used. The initiative proved its validity, improving subjective and objective knowledge to a statistically significant extent and also increasing awareness and attitude. The students' evaluation was extremely positive.


Activation of RAW264.7 macrophages by active fraction of Albizia julibrissin saponin via Ca2+-ERK1/2-CREB-lncRNA pathways.
The saponin active fraction from the stem bark of Albizia julibrissin (AJSAF) is an ideal vaccine adjuvant, but its mechanism of action remains unclear. The recent evidences indicate that long noncoding RNAs (lncRNAs) play essential roles in regulating the activation and function of macrophages. The current experiments were designed to investigate the effects of AJSAF on the activation of RAW264.7 macrophages and to explore its intracellular molecular mechanisms using a global gene expression microarray. AJSAF could significantly enhance phagocytic activity, induce reactive oxygen species (ROS), promote surface molecule expression, and up-regulate the mRNA and protein expression of cytokines and chemokines in RAW264.7 cells. AJSAF induced the differential expression of 223 mRNAs and 103 lncRNAs in RAW264.7 cells. Bioinformatics were used to predict the potential target mRNAs and function of up-regulated lncRNA A_30_P01018532 in RAW264.7 cells induced by AJSAF. The total 99 co-expressed mRNAs were classified as putative target genes of A_30_P01018532. A_30_P01018532 was associated with the inflammatory and immune response. AJSAF significantly increased the intracellular free Ca2+ levels and induced the phosphorylation of ERK1/2 and CREB in RAW264.7 cells. Moreover, Ca2+ chelator BAPTA-AM, ERK1/2 inhibitor PD98059 and CREB inhibitor KG-501 significantly inhibited the up-regulation of TNF-α, CCL2, CXCL2, CCL22, and A_30_P01018532 in RAW264.7 cells induced by AJSAF. These results suggested that AJSAF could activate RAW264.7 cells via Ca2+-ERK1/2-CREB pathways and that A_30_P01018532 might be an important regulator of mRNA expression in AJSAF-activated macrophage. This study may provide insights into the molecular mechanisms of action of AJSAF.


Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections.
Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)-a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway. PRC2 inactivation also facilitates proper regeneration after urothelial damage from UTIs, by attenuating basal cell hyperplasia and increasing urothelial differentiation. In addition, treatment with Ezh2-specific small-molecule inhibitors improves outcomes of the chronic and severe bladder infections in mice. These findings collectively suggest that the PRC2-dependent epigenetic reprograming controls the amplitude of inflammation and severity of UTIs and that Ezh2 inhibitors may be a viable non-antibiotic strategy to manage chronic and severe UTIs.


The significance of early diagnosis in the management of testicular tumour patients.
Surveying the therapeutic results of 16 testicular tumour patients treated in the recent 5 years, the authors stress, beside the generally accepted and use complex treatment, the importance of recognizing the disease in its early stage.


The Wingate anaerobic test's past and future and the compatibility of mechanically versus electro-magnetically braked cycle-ergometers.
The 30-year-old Wingate anaerobic test (WAnT) has proven a useful and a much-needed tool in the exercise physiology lab. However, the WAnT suffers from difficulties that partially stem from its original design but are mainly due to a large array of highly non-standardized procedures and the use of different testing modalities-mainly mechanically versus electro-magnetically braked ergometers. The present communication reviews and analyzes the deviations from WAnT's optimal use and proposes amendments that could make it a more valid, reliable, and a universally useful test.


Heterodimerization of apelin and opioid receptors and cardiac inotropic and lusitropic effects of apelin in 2K1C hypertension: Role of pERK1/2 and PKC.
Kappa Opioid receptors (KORs) change the impact of apelin on the phosphorylated ERK1/2 (pERK1/2). However, the role of interaction between KOR and apelin receptors (APJ) on the cardiac contractility effects of apelin and in regulation of pERK1/2 and PKC in the heart of renovascular hypertensive (2K1C) rats is unknown. Hemodynamic factors, the heterodimerization of KOR and APJ, the expression of KOR mRNA and protein and pERK1/2 in the left ventricle of 2K1C rats were measured following APJ, KOR, PKC and Gi path inhibition by F13A, nor-BNI, chelerythrine and PTX respectively. Apelin in 40 and 60μg/kg doses increased cardiac contractility, and reduced mean arterial pressure. The cardiac impacts in both doses were reduced by F13A, nor-BNI and chelerytrine and blocked by PTX. Hypertension increased the expression of KORs and heterodimerization of APJ and KOR, and reduced pERK1/2 in the left ventricle. Apelin, in both doses reduced (normalized) heterodimerization and recovered the reduction in pERK1/2. The recovery of ERK1/2 phosphorylation was accompanied by reduction of KOR and APJ heterodimerization. 2K1C hypertension increased the expression of KORs and heterodimerization of APJ and KORs. The heterodimerization was associated by reduction of ERK phosphorylation and altered the cardiac inotropic and lusitropic effects of apelin. These changes may participate in pathophysiology of cardiac dysfunction in renovascular hypertension that is associated with subnormal level of serum apelin. Apelin- induced recovery of ERK1/2 phosphorylation and KOR-APJ dimerization may nominate apelin as a therapeutic goal in treatment of this kind of hypertension.


Association of interferon-gamma inducible protein 10 polymorphism with treatment response to pegylated interferon in HBeAg-positive chronic hepatitis B.
Interferon-gamma inducible protein 10 (IP-10) plays an important role in the clinical outcome of chronic hepatitis B (CHB). This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) G-201A of the IP-10 gene and treatment response to pegylated interferon (PEG-IFN) in patients with hepatitis B e antigen (HBeAg)-positive CHB. We retrospectively analysed data of patients with HBeAg-positive CHB treated with PEG-IFN for 48 weeks. Virological response (VR) was defined as HBeAg clearance and HBV DNA <2,000 IU/ml at 24 weeks post-treatment. The SNPs G-201A, IFNL3 (rs12979860) and HLA-DPA1 (rs3077) were assessed. Among 107 patients, VR was achieved in 45 (42.1%) patients. Hepatitis B surface antigen (HBsAg) clearance and decline (<100 IU/ml) were observed in 10 (9.3%) and 22 (20.6%) patients, respectively. The distribution of GG, GA and AA genotypes of G-201A was 76.6%, 19.6% and 3.7%, respectively. Patients with GG genotype, compared to those with non-GG genotype, achieved higher VR rate (48.8% versus 19.2%; P=0.011), decreased HBsAg (25.6% versus 4.0%; P=0.019), and demonstrated a trend in HBsAg clearance (11.0% versus 4%; P=0.294). Patients with GG genotype had more rapid HBsAg decline and higher baseline serum IP-10 levels than those with non-GG genotype (432.2 ±339.0 versus 257.3 ±145.7 pg/ml; P=0.028). SNPs rs12979860 and rs3077 were not associated with VR. Logistic regression analysis suggested that SNP G-201A was an independent predictor of VR (odds ratio 3.81, 95% CI 1.31, 11.12; P=0.014). Data from this study demonstrated for the first time that IP-10 polymorphism is independently associated with treatment response to PEG-IFN in patients with HBeAg-positive CHB.


Characterization of an extracellular matrix-degrading protease derived from a highly metastatic tumor cell line.
A proteolytic activity associated with the microsomal fraction of L-5178Y/Esb tumor cells has been characterized. The enzyme has a molecular weight of 80-90 kD as determined by affinity-labelling with [3H]DFP and SDS-gel electrophoresis. It cleaves ester substrates at the carboxyl position of lysine and arginine and can activate the proenzyme plasminogen. The enzyme is found to be associated with the plasma membranes of high and low metastatic tumor cell lines and is shed in high-molecular-weight form mainly by the high metastatic variant. The pH optimum for esterase and protease activities was 7.5-8.5. Although similar to trypsin in substrate specificity, the enzyme was not inhibited by lima-bean trypsin inhibitor but was inhibited by DFP, PMSF, aprotinin and leupeptin. Partially purified preparations of the protease can alone degrade 125I-labelled endothelial cell extracellular matrix, pointing at the putative role of this enzyme in tumor invasion.


The budding yeast protein Chl1p has a role in transcriptional silencing, rDNA recombination, and aging.
We show that the budding yeast protein Chl1p, required for sister-chromatid cohesion, also modulates transcriptional silencing at HMR and telomeres. The absence of this protein results in increased silencing at HMR and, conversely, in decreased silencing at the telomere. The regulation of silencing by Chl1p at these two loci is dependent on the presence of Sir proteins. Chl1p also acts synergistically with Sir2p to suppress rDNA recombination. In the absence of this protein, yeast cells exhibit reduced life span and hypersensitivity to heat stress. These observations suggest a role of Chl1p in regulating chromatin structure.


Identifying new-onset conditions and pre-existing conditions using lookback periods in Australian health administrative datasets.
The condition onset flag (COF) variable was introduced into the hospitalization coding practice in 2008 to help distinguish between the new and pre-existing conditions. However, Australian datasets collected prior to 2008 lack the COF, potentially leading to data waste. The aim of this study was to determine if an algorithm to lookback across the previous admissions could make this distinction. All patients requiring kidney replacement therapy (KRT) identified in the Australia and New Zealand Dialysis and Transplant Registry in New South Wales, South Australia and Tasmania between July 2008 and December 2015 were linked with hospital admission datasets using probabilistic linkage. Three different lookback periods entailing either one, two or three admissions prior to the index admission were investigated. Conditions identified in an index admission but not in the lookback periods were classified as a new-onset condition. Conditions identified in both the index admission and the lookback period were deemed to be pre-existing. The degrees of agreement were determined using the kappa statistic. Conditions examined for new onset were myocardial infarction, pulmonary embolism and pneumonia. Conditions examined for prior existence were diabetes mellitus, hypertension and kidney failure. Secondary analyses evaluated whether the conditions identified as pre-existing using COF were captured consistently in the subsequent admissions. 11 140 patients on KRT with 69 403 admissions were analysed. Lookback over a single admission interval (Period 1) provided the highest rates of true positives with COF for all three new-onset conditions, ranging from 89% to 100%. The levels of agreement were almost perfect for all conditions (k = 0.94-1.00). This was consistent across the different time eras. All lookback periods identified additional new-onset conditions that were not classified by COF: Lookback Period 1 picked up a further 474 myocardial infarction, 84 pulmonary embolism and 1092 pneumonia episodes. Lookback Period 1 had the highest percentage of true positives when identifying the pre-existing conditions (64-80%). The level of agreement was moderate to strong and was similar across the time eras. Secondary analysis showed that not all pre-existing conditions identified using COF carried forward to the subsequent admission (61-82%) but increased when looking forward across >1 admission (87-95%). The described algorithm using a lookback period is a pragmatic, reliable and robust means of identifying the new-onset and pre-existing patient conditions, thereby enriching the existing datasets predating the availability of the COF. The findings also highlight the value of concatenating a series of hospital patient admissions to more comprehensively adjudicate the pre-existing conditions, rather than assessing the index admission alone.


Multiscale composite model of fiber-reinforced tissues with direct representation of sub-tissue properties.
In many fiber-reinforced tissues, collagen fibers are embedded within a glycosaminoglycan-rich extrafibrillar matrix. Knowledge of the structure-function relationship between the sub-tissue properties and bulk tissue mechanics is important for understanding tissue failure mechanics and developing biological repair strategies. Difficulties in directly measuring sub-tissue properties led to a growing interest in employing finite element modeling approaches. However, most models are homogeneous and are therefore not sufficient for investigating multiscale tissue mechanics, such as stress distributions between sub-tissue structures. To address this limitation, we developed a structure-based model informed by the native annulus fibrosus structure, where fibers and the matrix were described as distinct materials occupying separate volumes. A multiscale framework was applied such that the model was calibrated at the sub-tissue scale using single-lamellar uniaxial mechanical test data, while validated at the bulk scale by predicting tissue multiaxial mechanics for uniaxial tension, biaxial tension, and simple shear (13 cases). Structure-based model validation results were compared to experimental observations and homogeneous models. While homogeneous models only accurately predicted bulk tissue mechanics for one case, structure-based models accurately predicted bulk tissue mechanics for 12 of 13 cases, demonstrating accuracy and robustness. Additionally, six of eight structure-based model parameters were directly linked to tissue physical properties, further broadening its future applicability. In conclusion, the structure-based model provides a powerful multiscale modeling approach for simultaneously investigating the structure-function relationship at the sub-tissue and bulk tissue scale, which is important for studying multiscale tissue mechanics with degeneration, disease, or injury.


Latent alcohol use patterns and their link to depressive symptomatology in medical care patients.
To investigate latent patterns of alcohol use and bingeing by gender and their association with depressive symptom severity and individual depressive symptoms. Cross-sectional data were collected from January 2017 to March 2018 as part of a joint screening recruiting for different intervention studies. Ambulatory practices and general hospitals from three sites in Germany. A total of 5208 male and 5469 female proactively recruited alcohol users aged 18-64 years. Frequency and typical quantity of alcohol use, frequency of bingeing, alcohol-related problems (assessed by the Alcohol Use Disorder Identification Test); depressive symptom severity, individual depressive symptoms (assessed with the Patient Health Questionnaire-8); and socio-demographics and health-related variables. Latent categorical analysis identified six patterns of alcohol use, with the majority of patients engaging in 'light use plus no or occasional bingeing' (males: 41.85%; females: 64.04%), followed by 'regular use plus occasional bingeing' (males: 34.03%; females: 16.17%). Multinomial logistic regression analyses (three-step approach with correction for classification uncertainty, as implemented in the Mplus R3STEP command) controlling for socio-demographics and health-related variables revealed that severity of depressive symptoms was positively associated with 'frequent use plus frequent bingeing' when compared with 'light use plus no or occasional bingeing' [relative risk ratio (RRR)male = 1.07, 95% confidence interval (CI) = 1.03-1.11; RRRfemale = 1.09, 95% CI = 1.04-1.14]. Severity of depressive symptoms was negatively associated with 'regular use plus occasional bingeing' for males (RRRmale = 0.98, 95% CI = 0.95-1.00) and positively with 'occasional use plus occasional bingeing' for females (RRRfemale = 1.03, 95% CI = 1.01-1.05) when compared with 'light use plus no or occasional bingeing'. Individual depressive symptoms were differentially associated with alcohol use patterns, with depressed mood, poor appetite or overeating, feelings of worthlessness or guilt and psychomotor agitation or retardation, being especially pronounced in the 'frequent use plus frequent bingeing' class (RRRsmale = 1.72-2.36; RRRsfemale = 1.99-2.17). Patterns of 'frequent alcohol use plus frequent bingeing' and 'occasional alcohol use plus occasional bingeing' appear to have positive associations with depression when compared with 'light alcohol use plus no or occasional bingeing'.


Association of Single-Nucleotide Polymorphism in ANK1 with Late-Onset Alzheimer's Disease in Han Chinese.
Recently, two CpG sites in ankyrin 1 (ANK1) gene were identified to be hypermethylated and associated with Alzheimer's disease (AD)-related neuropathology in two large independent studies. Genetic variations are indicated to be involved in DNA methylation, especially when the associated single-nucleotide polymorphisms (SNPs) are located adjacent to the CpG site. Accordingly, ANK1 polymorphisms might contribute to late-onset AD (LOAD) risk. One polymorphism rs515071 was identified to be a potential risk factor for type 2 diabetes (T2D). As shared genetic background was found underlying T2D and AD, we postulate that rs515071 polymorphism may be associated with late-onset AD (LOAD) risk and assessed the association in 982 LOAD patients and 1346 sex- and age-matched healthy controls. Our results showed that minor allele A of rs515071 significantly increased LOAD risk in the APOE ε4 (+) subgroup (genotype P = 0.015, allele P = 0.020). After adjusting for age and gender, the association remained significant under the dominant model (OR = 1.809, 95 % confidence interval (CI) = 1.186-2.757, P = 0.006). In conclusion, our findings demonstrate that rs515071 in ANK1 is a novel genetic risk for LOAD susceptibility in Han Chinese.


An investigation of the effects of laser-assisted zona pellucida drilling on the preimplantation mouse embryo and the competency of embryo implantation.
To investigate the impact of laser-assisted zona pellucida (ZP) drilling on the mouse embryo, with particular emphasis on molecular mechanisms, and the efficiency of embryo attachment capability using an in vitro model of implantation. Experimental study. Academic research laboratory. C57BL/6JOlaHsd mouse embryos and B6C3F1 × B6D2F1 mouse embryos. Eight-cell stage mouse embryos were randomly assigned to a laser-assisted ZP drilling group (n = 343), ZP partial drilling group (n = 312), ZP quarter thinning group (n = 289), and control group (n = 353). Embryos were cultured in vitro from E2.5 to E4.5 for 48 hours. To investigate the capacity to implant, E4.5 embryos (laser-assisted drilling group [n = 46], ZP partial drilling group [n = 28], ZP quarter thinning group [n = 26], and control group [n = 36]) were then transferred onto an attachment model on the basis of Ishikawa cells and cultured for another 72 hours. Blastocyst formation, hatching status, and hatching morphology at E4.5. Blastocyst cell components, the extent of apoptosis in embryonic cells (DNA fragmentation, caspase-3 activation, and expression of apoptosis-related genes), the expression of heat shock protein 70, and differentially expressed genes (DEGs) generated by RNA sequencing. Fully hatched embryo rate and stable attachment rate in the in vitro attachment model. There were no significant differences between the laser-assisted ZP manipulation groups and control group with respect to the formation of blastocysts, cell number, embryonic cell apoptosis, and cellular stress. All 3 of the laser-assisted ZP manipulations significantly increased the hatching rate at E4.5 compared with the control group, especially the ZP drilling group. However, only the ZP drilling group was associated with a significantly higher proportion of "8"-shaped hatching blastocysts. Furthermore, RNA sequencing identified 48 DEGs between blastocysts from the laser-assisted drilling group and control group; the metabolic pathways were significantly enriched in these DEGs. In addition, there were no significant differences between the laser-assisted ZP manipulation groups and control group with respect to the rate of stable attachment at E7.5, although a significantly higher entrapment rate was observed in the ZP drilling group. Laser-assisted ZP manipulations did not induce cellular apoptosis or stress in mouse blastocysts. Nevertheless, for the first time, we found that laser-assisted ZP drilling could alter the embryonic transcriptome and may affect metabolic activity. Furthermore, although laser-assisted ZP manipulations can enhance the initiation of hatching, it is evident that ZP drilling comes with a potential risk of embryo entrapment.


Emerging themes in medicinal glycoscience.
The recognition of complex carbohydrates and glycoconjugates as mediators of important biological processes has stimulated investigation into their therapeutic potential. New approaches for the simplification of glycoconjugate synthesis are overcoming the limitations of existing methods and providing a diverse array of these biomolecules. As the accessibility of glycoconjugates increases, carbohydrate-based constructs are becoming available for analysis as medicinal agents in a wide range of therapies.


Wideband slow-light modes for time delay of ultrashort pulses in symmetrical metal-cladding optical waveguide.
A widebandwidth optical delay line is a useful device for various fascinating applications, such as optical buffering and processing of ultrafast signal. Here, we experimentally demonstrated effective slow light of sub-picosecond signal over 10 THz frequency range by employing the wide slow light modes in thick symmetrical metal-cladding optical waveguide (SMCOW). Ultrahigh-order guided modes travelling as slow light in waveguide together with strong confinement provided by metal-cladding makes this scheme nearly material dispersion independent and compatible with wide bandwidth operation.


Clinical profile and comparison of scoring tools for the prediction of in-hospital mortality in convulsive status epilepticus in elderly.
The present study was aimed to study the clinical profile, etiologies, and outcome of convulsive status epilepticus (CSE) in elderly patients and also to compare the predictive accuracy of the Status Epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus - etiology, age, level of consciousness (EMSE-EAL) score for in-hospital mortality. Eighty-five elderly patients (≥60 years of age) with a diagnosis of CSE were consecutively enrolled. The distinction between the score performances was determined by comparing the means area under the receiver operating characteristic curve (AUC). The mean age of respondents was 66.3 ± 7.4 years; the most common etiology of CSE was stroke (acute and remote symptomatic) in 48.2% of cases. In-hospital mortality was 16.5% in our series, and on multivariate analysis, variables significantly related with mortality were lack of response to first-line drugs (odds ratio (OR) = 43.05, 95% confidence interval (CI) = 4.7-386.8; p = .001) and higher EMSE-EAL score (OR = 0.08, 95% CI = 0.015-0.47; p = .005). On comparison, STESS with the cutoff value of ≥3 has AUC of 0.678 (95%CI = 0.54-0.81), whereas ESME-EAL with the cutoff value of ≥40 showed AUC of 0.901 (95% CI = 0.83-0.97). Most frequent cause of CSE in elderly in our series was stroke and was also associated with high mortality. For the prediction of in-hospital mortality in elderly, EMSE-EAL-40 score is superior to STESS-3, which can be easily applied in resource-poor sectors with limited diagnostic facilities especially where continuous video-electroencephalogram (EEG) monitoring is unavailable.


The relationship of pyospermia and seminal fluid bacteriology to sperm function as reflected in the sperm penetration assay.
The relationship of the parameters of seminal fluid analysis (SFA) and seminal fluid leukocyte concentration to the in vitro sperm penetration assay (SPA) was studied in 217 men from infertile couples. Significant positive correlations were found between the SPA and sperm count, sperm motility, and morphologically normal sperm. The total number of leukocytes per milliliter, the number of polymorphonuclear leukocytes per milliliter (PMN), and the number of lymphocytes per milliliter were negatively correlated with the results of the SPA. The strongest correlation with an abnormal SPA (less than 11% of eggs penetrated) was the presence of greater than or equal to 1 PMN/100 sperm (8.17 increased relative risk of an abnormal SPA). The most important predictor variables of the percent penetration of the sperm penetration assay were total numbers of leukocytes per milliliter, sperm count, and sperm motility. Microbiologic studies of semen were not correlated with SPA results or number of leukocytes in the semen.


Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats.
Diabetic retinopathy (DR) is a multifactorial disease characterized by reactive gliosis and disbalance of angiogenesis regulators, contributing to endothelial dysfunction and microvascular complications. This study was organized to elucidate whether poly(ADP-ribose) polymerase-1 (PARP-1) inhibition could attenuate diabetes-induced damage to macroglia and correct angiogenic disbalance in diabetic rat retina. After 8 weeks of streptozotocin (STZ)-induced diabetes, Wistar male rats were treated with PARP-1 inhibitors, nicotinamide (NAm) or 3-aminobenzamide (3-AB) (100 and 30 mg/kg/daily i.p., respectively), for 14 days. After the 10-weeks experiment period, retinas were undergone an immunohistochemical staining for glial fibrillary acidic protein (GFAP), while western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of PARP-1, poly(ADP-ribosyl)ated proteins (PARs), GFAP, and angiostatin isoforms. Diabetes induced significant up-regulation and activation of retinal PARP-1, reactive gliosis development, and GFAP overexpression compared to non-diabetic control. Moreover, extensive fragmentation of both PARP-1 and GFAP (hallmarks of apoptosis and macroglia reactivation, respectively) in diabetic retina was also observed. Levels of angiostatin isoforms were dramatically decreased in diabetic retina, sustaining aberrant pro-angiogenic condition. Both NAm and 3-AB markedly attenuated damage to macroglia, evidenced by down-regulation of PARP-1, PARs and total GFAP compared to diabetic non-treated group. PARP-1-inhibitory therapy prevented formation of PARP-1 and GFAP cleavage-derived products. In retinas of anti-PARP-treated diabetic animals, partial restoration of angiostatin's levels was shown. Therefore, PARP-1 inhibitors counteract diabetes-induced injuries and manifest retinoprotective effects, including attenuation of reactive gliosis and improvement of angiogenic status, thus, such agents could be considered as promising candidates for DR management.


Vascular plexus is a differentation criterion for muscularis mucosa from muscularis propria in small biopsies and transurethral resection materials of urinary bladder?
Smooth muscle fibres are found within the superficial lamina propria of urinary bladder (Muscularis Mucosa). These muscle fibres of muscularis mucosa should be distinguished from the muscularis propria in cases with urothelial carcinoma, because the depth of infiltration affects prognosis and therapy modalities. The aim of the present study was to evaluate whether the presence of vascular plexus is a criterion for muscularis mucosa and to distinguish it from muscularis propria in urinary bladder biopsies and transurethral resection specimens. Hematoxylin-Eosin and Masson-Trichrome stained slides of 54 cases with urothelial carcinoma were reviewed. In all cases (100%), thick walled vessels were observed within the lamina propria of urinary bladder. Smooth muscle layer of lamina propria was seen in 48 of 54 cases (88.8%), and these smooth muscle fibres were co-existed with thick walled vessels. In invasive urothelial carcinoma; thin smooth muscle fibres and thick walled vessels were seen within the lamina propria in 22 of 24 cases (91.7%). There were two cases (8.3%) including only vessels in small biopsies of invasive urothelial carcinoma cases. In cases with non-invasive urothelial carcinoma; muscle fibres of muscularis mucosa and vessels were found within the lamina propia in 26 of 30 cases (86.7%). In this group, muscle fibres were not detected in 4 cases (13.3%). Muscularis mucosa can be detected histologically in urinary bladder biopsies and TUR materials. We emphasize that the presence of vascular network is a useful criterion to determine muscularis mucosa of urinary bladder, even in the absence of muscle fibres.


Idiopathic massive osteolysis of skull bones: a case report.
A rare case of idiopathic massive osteolysis involving cranial bone is reported. Radiological and computed tomographic findings are discussed, along with a brief review of the literature.


Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy.
Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike protein hemagglutinin (HA), which undergoes a dynamic conformational change that is essential to the viral life cycle and is dependent on endosomal pH. Since the cells of different potential hosts exhibit different levels of pH, the virus can only cross species barriers if HA undergoes mutations that still permit the structural change to occur. This key event occurs after influenza A enters the host cell via the endocytic route, during its intracellular transport inside endosomes. The acidic pH inside these vesicles triggers a major structural transition of HA that induces fusion of the viral envelope and the endosomal membrane, and permits the release of the viral genome. HA experiences specific mutations that alter its pH stability and allow the conformational changes required for fusion in different hosts, despite the differences in the degree of acidification of their endosomes. Experimental and theoretical studies over the past few years have provided detailed insights into the structural aspects of the mutational changes that alter its susceptibility to different pH thresholds. We will illustrate how such mutations modify the protein's structure and consequently its pH stability. These changes make HA an excellent model of the way subtle structural modifications affect a protein's stability and enable it to function in diverse environments.


Simple hand fractures that aren't.
Patients expect physicians to predict the future. Recognizing injuries that behave badly improves care and modulates expectations. Your antennae should deploy when you are presented with a simple fracture that isn't.


Interferential therapy for detrusor hyperreflexia in multiple sclerosis.
Twenty patients with detrusor hyperreflexia in multiple sclerosis were treated for frequency, urgency and incontinence, or catheter bypassing by interferential currents applied on the lumbosacral spinal marrow. Although the mechanism of action is not totally understood, subjective and objective improvements were registered in most patients. Further investigations are needed to confirm these results and to explain the favorable effect of interferential therapy.


Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1.
MicroRNAs (miRNAs) are small, non-coding RNA molecules which post-transcriptionally regulate gene expression. We have previously demonstrated that within the uterus, miRNA expression is under steroidal control and that disruption of Dicer1, the enzyme which generates mature miRNAs, leads to abnormalities in the development and function of the female reproductive tract. Despite the apparent importance of miRNAs and the enzymes which lead to their generation, little to no information exists on the mechanisms which regulate the expression of this system in the female reproductive tract. The objective of the current study was to examine steroidal regulation of the miRNAs biogenesis enzymes, Drosha, Dgcr8, Exportin-5 and Dicer1 in the mouse uterus. The results of this study indicate that estrogen and progesterone significantly increased Exportin-5 mRNA expression while only progesterone increased Dicer1 expression. We conclude from these studies that the miRNA biogenesis components Drosha, Dgcr8, Exportin-5 and Dicer1 are expressed in the mouse uterus and that Exportin-5 and Dicer1 appear to be the major steroid regulated components in the miRNA biogenesis pathway. These observations suggest that in addition to steroids modulating miRNA expression at the level of transcription, they may also influence miRNA expression by regulating the expression of the miRNA biogenesis components necessary for their processing to the mature cytoplasmic form.


Hemophagocytic lymphohistiocytosis associated with an IgG Cold agglutinin.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease eventually caused or reactivated by a viral infection, which can also lead to the production of cold agglutinins (CA). The nature of these autoantibodies is usually an IgM, less frequently an IgA or IgG, they agglutinate red blood cells at low temperatures. They can interfere with hematological parameters causing interpretation difficulties. We report a case of a 4-year-old boy who developed an IgG CA during recurrent HLH reactivated by EBV infection. The purpose of this observation is to underline HLH criteria and to analyze CA interference as well as its biological and clinical characteristics.


Tolerance of Chrysantemum maximum to heavy metals: the potential for its use in the revegetation of tailings heaps.
To find if ornamental plants are applicable to the remediation of metal-polluted areas, the tolerance of chrysanthemum plants (Chysanthemum maximum) var. Shasta to different metals under hydroponic conditions was studied. Their responses as influenced by the mycorrhizal fungus Glomus mosseae (Nicol. & Gerd.) Gerdemann & Trappe BEG25 on substrates containing mine residues were also investigated. Our results showed that chrysanthemum is a metal-tolerant plant under hydroponic conditions, plants behaving as Pb-excluders, whereas Cd, Cu and Ni were accumulated in roots. Low accumulation in flowers was observed for Cd and Cu but it was concentration-dependent. Ni and Pb were not translocated to flowers. Shoot biomass was not significantly affected by the different rates of mine residue addition for both mycorrhizal and non-mycorrhizal plants. Mycorrhizal plants accumulated less Pb and Cu in both shoots and roots than non-mycorrhizal plants. Chysanthemum could be a prospective plant for revegetation of tailings and the use of inoculation may decrease plant metal accumulation in polluted soils.


Computer simulation model on ultrasonic myocardial backscatter.
Myocardial ultrasonic tissue characterization with integrated backscatter (IB) has been studied in recent years. To evaluate the dynamic characters of the myocardium, dynamic tracing of each unit volume of myocardium is a key point. Thus, a 2D CVIB imaging algorithm based on an auto-tracing method was developed in our previous work. Where, an auto-tracking method was used in CVIB-weighted images so that the POI in each frame throughout the cardiac cycle is automatically traced to reflect the real myocardial tissue movement. It is necessary to validate the auto-tracing method. However, at present there are no appropriate models to support the process. In order to validate the auto-tracing method, two myocardium models have been established to simulate the short and long axis view of echocardiography. The motions of partially ischemic myocardium have been simulated. The models have been used to validate the 2D CVIB imaging methods in the detection of myocardial ischemia. The simulation results show that the auto-tracing algorithm is effective. The model developed in this work provides a tool for studying and developing technologies in myocardial behavior.


Endecous peruassuensis n. sp. (Orthoptera: Grylloidea: Phalangopsidae) from caves of Eastern Brazil: evidence of isolation in the subterranean realm and discussion about troglomorphisms.
We describe a new species of the genus Endecous Saussure (1878), recorded at the Lapa do Cipó and Olhos d'Água caves, which are located in the Itacarambi municipality, Minas Gerais state, Eastern Brazil. Another species, E. aguassay Mews, 2008 was recordedin the surroundings of the caves. The genus Endecous corresponds to the most common cricket in Brazilian hypogean environments. In general, these crickets inhabit the areas around cave entrances up to the aphotic zones of caves. The genus Endecous is the only cave cricket to present troglobiomorphosis, i.e., an apterous condition. The distribution of the new species is limited to these two caves, which suggests an endemism in this karst system similar to the distribution of other endemic animals, such as harvestmen and amblypygid arachnids. This species is the sixth troglobitic one described for Olhos d'Água cave, which sets this cave as a spot of subterranean fauna in Brazil.


Surface-Initiated Polymerization with Poly(n-hexylisocyanate) to Covalently Functionalize Silica Nanoparticles.
New methods are needed for covalent functionalization of nanoparticles-surface with organic polymer coronas to generate polymeric nanocomposite in a controlled manner. Here we report the use of a surface-initiated polymerization approach, mediated by titanium (IV) catalysis, to grow poly(n-hexylisocyanate) chains from silica surface. Two pathways were used to generate the interfacing in these nano-hybrids. In the first one, the nanoparticles was "seeded" with SiCl4, followed by reaction with 1,6-hexanediol to form hydroxyl groups attached directly to the surface via O-Si-O bonding. In the second pathway, the nanoparticles were initially exposed to a 9:1 mixture of trimethyl silyl chloride and chlorodimethyl octenyl silane which was then followed by hydroboration of the double bonds, to afford hydroxyl groups with a spatially controlled density and surface-attachment via O-Si-C bonding. These functionalized surfaces were then activated with the titanium tetrachloride catalyst. In our approach, thus surface tethered catalyst provided the sites for n-hexyl isocyanate monomer insertion, to "build up" the surface-grown polymer layers from the "bottom-up". A final end-capping, to seal off the chain ends, was done via acetyl chloride. Compounds were characterized by FT-IR, 1H-NMR, GC-MS, GPC, and thermogravimetric analyses.


[Post-intensive care syndrome in pediatrics]
The term "Post-intensive care syndrome" describe new impairments after critical illness, that worsen physical, cognitive, or mental health, and persist after acute care hospitalization. a bibliographic search was carried out using the Medline database. The search period was from 2012 to 2020 using keywords. Emerging evidence suggests that there are significant and persistent physical, cognitive, and psychiatric morbidities among adult and pediatric survivors of critical illness. In this population it can also affect the "social health" sphere. The families of hospitalized patients often manifest psychological symptoms. For prevention and management there are various tools, the package of measures "ABCDEFGH", the conformation and organization of the health team, early mobilization and physical rehabilitation, nutritional contribution, environmental management, intensive care unit diaries and support between pairs. Each patient´s situation is unique and the challenges they face may require different interventions. These should be studied to increase the available evidence in the pediatric population. We still do not have a specific instrument to monitor the syndrome in pediatrics or information on long-term sequelae in children.


Synoviocyte neotissues towards in vitro meniscal tissue engineering.
Meniscal injuries are a common cause of pain and osteoarthritis in dogs. We describe here the production of synoviocyte-derived autologous neotissues for potential application in meniscal tissue engineering, via two different culture techniques: contracted or tensioned synthesis of synoviocyte neotissues. Synoviocytes were obtained during routine stifle arthroscopy and cultured from 14 dogs with naturally occurring osteoarthritis of the stifle. Neotissues were analyzed for meniscal-like matrix components and their gene expression, inflammatory gene expression, and cell viability. Tension improved cell viability, and, independent of cell viability, fibrochondrogenic activity by promoting expression of collagen type 1 and aggrecan genes and attenuating gene expression of IL-6. Through this mechanism tension increased collagen protein content and chondrogenic index of neotissues. Alpha smooth muscle actin was present in all neotissues and was responsible for grossly visible contractile behavior. Application of tension to synoviocytes may be a viable culture method towards in vitro meniscal tissue engineering.


Erratum. Diabetic Gastroparesis: A Review. Diabetes Spectrum 2020;33:290-297 (https://doi.org/10.2337/ds19-0062).
[This corrects the article on p. 290 in vol. 33, PMID: 32848351.].


Assessment of sex-related neuropathology and cognitive deficits in the Tg-SwDI mouse model of Alzheimer's disease.
Cerebral amyloid angiopathy or CAA is a type of vascular dementia that can cause neuroinflammation, ischemia and hemorrhage, among other complications. CAA results from the deposition of amyloid beta (Aβ) in blood vessels and is frequently observed in individuals with Alzheimer's disease (AD). One functional output of those pathological changes is measurable cognitive decline. Still not well understood, however, is the impact of gender or sex on the pathology of CAA, as well as CAA-induced cognitive decline. Here, we studied how sex impacts deposition of CAA-related pathology and the associated cognitive decline. We observed differential hippocampal pathology as far as regions of deposition, type of morphology, and total amount of pathology when assessing CAA pathology via (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB)-labeling, as well as neurodegeneration via Fluoro Jade C (FJC)-labeling, and lysosomal associated membrane protein deposition via LAMP-1 labeling. In accordance with other studies, our data suggest female TG-SwDI mice exhibit more severe pathological alterations in CAA pathology. Additionally, behavioral assessments revealed an impact of genotype that was more pronounced in TG-SwDI females. While the primary measure of learning and memory, the water maze, suggests an overall effect of genotype, effects in measures of locomotor activity and anxiety-like behavior suggest reduced habituation in females. This could be due to a lower retention for the tasks. Results of this study offer significant insight into the importance of examining effects of sex on CAA.


How Communities Are Building Power To Improve Health.
Systemic racism has imposed stark health inequities on marginalized communities. Now, some are beginning to shift the balance of power to improve their health.


[Epiretinal visual prostheses].
Epiretinal implants consist of a camera chip capturing the scene, a visual processor calculating retina-specific pulse sequences, a transponder for data and energy, and the implant itself. The implant consists of a receiver integrated into a posterior chamber lens, a microcable, and the retina stimulator. The stimulator is fixated onto the retinal surface using retinal tacks. In animal experiments it was shown that the materials being used were tolerated, the data and energy stream did not induce any adverse events, and that the fixation was feasible using retinal tacks. Stimulation of the inner retinal surface yielded a topographically correct activation of visual cortical areas. Even after a long history of blindness, tests in humans disclosed visual percepts.


Kimura disease of naso-orbito-ethmoid region and review of surgical approaches to naso-orbito-ethmoid region.
SummaryA man in 30s had complaints of glabellar and upper nasal swelling for 8 years. It was insidious in onset and gradually progressive causing epiphora and restriction of nasal visual field. Fine-needle aspiration cytology and biopsy revealed features which were suggestive of Kimura's disease (KD). CT scans showed a well-defined subcutaneous swelling in the naso-orbito-ethmoid (NOE) region. KD presents as lymphoglandular swelling; however, NOE region is an uncommon site of occurrence. A thyroid-shaped tumour was excised by H-shaped incision approach to the NOE region.


[Therapeutic patient education in diabetes management].
Late complications of type 1 and type 2 diabetes can also be effectively avoided or delayed using active intervention and available therapies. Despite these facts, the percentage of people with diabetes following the therapy proposed by health care professionals is quite low. People with diabetes or any other chronic disease have to be involved in their own treatment. Basic knowledge is very important for the patient but the reinforcement of appropriate attitudes and a continuous process of motivation is fundamental in changing habits and behaviour. We need to educate patients, giving them the tools and skills to manage their disease, allowing them to become autonomous, empowering them. In the Therapeutic Patient Education model the patient is no longer the object but instead one of the actors in the process. He becomes part of the team and part of the solution. Goals are agreed as a result of input of the patient's desires, details of his daily life, his perceptions and the HCP's biomedical objectives. The patient takes care of himself and will, step by step, become aware of the consequences of his actions, in collaboration with his health team.


Interaction of inorganic vanadate with glucose-6-phosphate dehydrogenase. Nonenzymic formation of glucose 6-vanadate.
Inorganic vanadate (Vi) activates catalysis by glucose-6-phosphate dehydrogenase of the oxidation of glucose by NADP+. As the concentration of Glu-6-P dehydrogenase is increased, the rate of the vanadate-activated glucose oxidation becomes less sensitive to increases in enzyme concentration. The rate of glucose oxidation in the absence of Vi increases linearly with Glu-6-P dehydrogenase concentration. These results are interpreted in terms of nonenzymic formation of glucose 6-vanadate. At high enzyme concentration, vanadate ester formation becomes partially rate-limiting, and extrapolation to infinite Glu-6-P dehydrogenase concentration allows determination of the second order rate constant for formation of the ester. In separate experiments designed to test the proposed mechanism, it was found that Vi, at concentrations at which it strongly activates catalysis by Glu-6-P dehydrogenase of glucose oxidation, has no effect on the rates of oxidation of glucose 6-phosphate or 6-deoxyglucose catalyzed by Glu-6-P dehydrogenase. Sulfate, which is known to activate glucose oxidation and to inhibit glucose 6-phosphate oxidation, strongly activates 6-deoxyglucose oxidation. These experiments show that the 6-hydroxyl group of glucose is essential for the observed activation by Vi and are also consistent with the formation of glucose 6-vanadate. Also, the rate of the sulfate-activated glucose oxidation increases linearly with Glu-6-P dehydrogenase concentration. These results are consistent with the proposed mechanism for sulfate activation which involves sulfate binding to the enzyme (Anderson, W. B., Horne, R. N., and Nordlie, R. C. (1968) Biochemistry 7, 3997-4004). The second order rate constant calculated for formation of glucose 6-vanadate at pH 7.0 is 2.4 M-1 s-1. The corresponding values for glucose 6-phosphate and glucose 6-arsenate formation are approximately 9 X 10(-11) M-1 s-1 and 6.3 X 10(-6) M-1 s-1 (Lagunas, R. (1980) Arch. Biochem. Biophys. 205, 67-75).


Interpreters' experiences of general practitioner-patient encounters.
To study interpreters' experiences of problems in cross-cultural communication with special regard to the general practitioner (GP)-patient encounter. A focus-group interview with authorized interpreters was carried out. A phenomenographic method was used in the analysis. Primary health care. The interpreters displayed a number of problems mainly related to the difficulty in balancing the triad relation (GP-patient-interpreter), the role of the interpreter in relation to other healthcare staff, the time aspects of the translation procedure, and the problems of diverse health beliefs and cultural inequalities. The interpreters notice a set of difficulties that need to be highlighted in order to improve consultations with cross-cultural GP-patient encounters.


Polyclonal antisera to the individual neurofilament triplet proteins: a characterization using ELISA and immunoblotting.
In this article, the preparation and characterization of polyclonal rabbit antisera against the individual polypeptides of bovine neurofilament (68, 150, and 200 kilodaltons) is described. Selected antisera against the 68- and 150-kilodalton neurofilament polypeptides were specific for the corresponding antigen in homogenates of bovine, rat, and human brain as judged by immunoblots. The antisera against the 200-kilodalton neurofilament polypeptide cross-reacted to some extent with the 150-kilodalton neurofilament polypeptide, especially with the human antigen. The most specific antisera were used to develop an enzyme-linked immunosorbent assay (ELISA), and the cross-reactivities between the antisera and the different bovine and rat neurofilament polypeptides were determined. Contrary to the results in the immunoblots, the antiserum against the 200-kilodalton neurofilament polypeptide was subunit-specific, as was the 150-kilodalton antiserum. The 68-kilodalton antiserum displayed a minute cross-reactivity against bovine 150- and 200-kilodalton neurofilaments, but it cross-reacted somewhat more with the rat 150- and 200-kilodalton antigens. Even so, the subunit specificity of the antisera is high enough to enable the development of a quantitative ELISA for determination of the individual bovine or rat neurofilament polypeptides in a mixture. This study is the necessary preparation for such an assay.


A study on the use of sorrel seed flour (Hibiscus sabdariffa) for improving functionality of wheat flour bread.
Bread presents one of the easiest opportunities as a food vehicle for delivery of nutritional and health-promoting benefits to large segments of the world population. However, its low nutritional status due to lack of balance of essential amino acids and inadequate macro- and micronutrients has necessitated recent interest in the development of high-protein hybrid breads (HPHB). Sorrel seed, an underutilized, neglected protein-rich seed holds promising nutritional and antioxidant potentials as source of good quality protein, dietary fibre and bioactive compounds. Furthermore, germination of plant seeds increases the bioavailability of these nutritional and bioactive compounds. Hence, this study has investigated the influence of germination time on nutritional, and functional properties of sorrel seed flour. Further, the amino acid profile, dietary fibre and rheological functionality of wheat-germinated defatted sorrel seed bread were assessed. The sorrel seed was germinated for 24-48 h and defatted. Thereafter, the germinated defatted sorrel seed flours were used to partially replace wheat flour using a linear replacement (w/w) of 95-80% wheat (W) and 5-20% germinated defatted sorrel seed (GS) flours to obtain W95:GS5; W90:GS10, W85:GS15 and W80:GS20. These composite flours and 100% wheat flour (control) were used to produce breads using standard recipe and methods. Results showed significant increase (P < 0.05) in crude protein, dietary fibre and mineral contents after 24 and 48 h germination of sorrel seed. While 24 h germination significantly (P < 0.05) increased WAC from 93.75% to 103.13%, further germination (48 h) caused a reduction of 26.67% (from 93.75 to 68.75%). In vitro protein digestibility of wheat flour decreased significantly (P < 0.05) as supplementation of germinated defatted sorrel seed flour increased. Supplementation of wheat flour with germinated defatted sorrel seed flour in bread production resulted in 51.84-121.42% significant (p < 0.05) increase in the protein content of wheat bread. Similarly, total essential amino acids, dietary fibre, mineral, and ash contents followed the same increasing trend. The in-vivo biological value which ranged from 82.10 to 89.40% was significantly higher (p < 0.05) than 58.30% obtained for the control (100% wheat bread) Thus, inclusion of germinated defatted sorrel seed flour in bread production may serve as a low-cost nutritional supplement for enhancing the nutritional profile and functional benefits of wheat bread.


Preparation of spiro[4.4]oxaphospholene and -azaphospholene systems from carbohydrate templates.
Introduction of a spiro-phosphorus cycle in position 3 of monosaccharidic derivatives was studied starting from cyanohydrin or aminonitrile A. A two-step procedure involving (i) phosphonylation and (ii) carbanion-mediated phosphonate intramolecular cyclization (denoted CPIC) was used. The necessity of having an electron-withdrawing group α to the phosphorus atom in order to avoid undesired reactions was demonstrated.


Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature.
To review the literature to determine the sensitivity and specificity of gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron-emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68 Ga-PSMA PET in patients with BCR after radical prostatectomy (RP). We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were '(PSMA, 68 Ga-PSMA, 68 Gallium-PSMA, Ga-68-PSMA or prostate-specific membrane antigen)' and '(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)'. Relevant abstracts were reviewed and full-text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. Nine retrospective and two prospective studies described the sensitivity and specificity of 68 Ga-PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68 Ga-PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68 Ga-PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2-0.49 ng/mL and 0.5 to <1.0 ng/mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. The review results showed that 68 Ga-PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68 Ga-PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68 Ga-PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68 Ga-PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP.


Feeding strategies for enhanced lactobionic acid production from whey by Pseudomonas taetrolens.
High-level production of lactobionic acid from whey by Pseudomonas taetrolens under fed-batch fermentation was achieved in this study. Different feeding strategies were evaluated according to the physiological status and fermentation performance of P. taetrolens. A lactobionic acid titer of 164 g/L was obtained under co-feeding conditions affording specific and volumetric productivities of 1.4 g/g h and 2.05 g/L h, respectively. Flow cytometry assessment revealed that P. taetrolens cells exhibited a robust physiological status, which makes them particularly well-suited for employing concentrated nutrient solutions to further prolong the growth and production phases. Such detailed knowledge of the physiological status has been revealed to be a key issue to further support the development of high-yield lactobionic acid production processes under feeding strategies. The present study has demonstrated the feasibility of P. taetrolens to achieve high-level bio-production of lactobionic acid from whey through fed-batch cultivation, suggesting its major potential for industrial-scale implementation.


Cost-effective post-exposure prevention of poison ivy dermatitis.
Poison ivy (toxicodendron) dermatitis is the most common allergic contact dermatitis in the USA. No studies have shown an effect of washing after a short period of time for the prevention of binding of urushiol to the skin. Objective To evaluate the efficacy of three different modes of postcontact prevention using a surfactant (Dial ultra dishwashing soap), an oil-removing compound (Goop), and chemical inactivation (a commercial product Tecnu). A consented, unsponsored, volunteer experimental study on medical students from the University of Missouri School of Medicine, Kansas City. Each subject served as his/her own control, comparing four 2.5-cm exposed squares on the inner aspect of the forearm, three of which were treated and one untreated. Comparisons between the different agents were nonsignificant with P > 0.05. Each treatment, however, was significantly improved over the untreated control. Our study showed 70%, 61.8%, and 56. 4% protection with Tecnu, Goop, and Dial, respectively, when compared to the positive control, or to the possible maximum response, with a cost per ounce (in a local drug and automotive store) of $1.25, $0.07, and $0.07, respectively, for a decrease in protection that is nonsignificant.


[Prevalence and treatment of rheumatological adverse events due to immune checkpoint inhibitor therapy].
Immune checkpoint inhibitors (ICI) have essentially improved the treatment options for various malignant diseases. They lead to an activation of the immune system and subsequent attack of tumor cells by affecting the immune system and preventing tumor cells from avoiding detection. In addition to this desired effect, immune-related adverse events (irAE) can occur in nearly all organ systems and therefore also rheumatological irAE (rh-irAE). The occurrence of rh-irAE has been described in various publications and is specifically investigated in this review. The aim is to provide an overview on the prevalence, severity, treatment options and altered tumor response in patients with rh-irAE. We conducted a literature search for studies and case reports on rh-irAE under ICI therapy in PubMed up to January 2020 using the PICO model. A total of 18 publications were included, most of which were clinical studies (n = 13) and the rest case reports (n = 5). Several rh-irAE can occur with a wide variety of manifestations of which arthralgia, arthritis and myositis were the most common. Other rheumatic diseases, such as vasculitis, connective tissue diseases and sarcoidosis were less frequently described. The published prevalence of rh-irAE varied with a prevalence between 2.3% and 6.6%. Treatment of rh-irAE depends on the severity and most patients receive nonsteroidal anti-inflammatory drugs and glucocorticosteroids. In some cases, conventional DMARDs, such as methotrexate and biological DMARDs, were administered. Patients with rh-irAE in general had a higher tumor response rate compared to patients without side effects. A close observation of patients and early detection of rh-irAE are important in order to treat these side effects in time. Further prospective studies are necessary to systematically investigate rh-irAE.


Optimal Strategy for Antiplatelet Therapy After Endovascular Revascularization for Lower Extremity Peripheral Artery Disease.
The aim of this study was to investigate the optimal strategy for antiplatelet therapy in patients with lower extremity peripheral artery disease (PAD) after endovascular revascularization. The optimal strategy for antiplatelet therapy in patients with PAD after endovascular revascularization has not been established. From March 2008 to February 2013, 693 patients with lower extremity PAD treated with different antiplatelet therapies, such as mono-antiplatelet therapy (MAPT) and dual-antiplatelet therapy (DAPT), of various durations after endovascular revascularization were analyzed. They were classified into 2 groups (DAPT <6 months or MAPT vs. DAPT ≥6 months). The primary outcomes were major adverse cardiovascular events and major adverse limb events. The safety outcome was major bleeding. During 5-year follow-up, major adverse cardiovascular events occurred less frequently in the DAPT ≥6-month group than the DAPT <6-month or MAPT group (17.3% vs. 31.3%; hazard ratio: 0.44; 95% confidence interval: 0.30 to 0.65; p < 0.001). Major adverse limb events also occurred less frequently in the DAPT ≥6-month group than the DAPT <6-month or MAPT group (21.5% vs. 43.7%; hazard ratio: 0.42; 95% CI: 0.30 to 0.58; p < 0.001). However, major bleeding events were infrequent, with no signal toward harm with DAPT ≥6 months. Results were consistent after inverse probability-weighted adjustment and propensity score matching. Following endovascular revascularization for lower extremity PAD, DAPT ≥6 months was associated with decreased 5-year major adverse cardiovascular events and major adverse limb events.


Investigation of the Relationship between the Increase in the Intercanine width and the Children's Facial Parameters; a 6-month Follow-up Study.
The present study, as a pilot study, aimed to investigate the increase in the intercanine width in different facial forms to predict the amount of future increase in the intercanine width. The results of the pilot study showed that the intercanine width increased more in the boys with wider faces while this relationship was not observed in the girls. Based on the results of this preliminary study, the girls' facial width could not be considered as a determining criterion in evaluation of the amount of increase in the intercanine width.


Acute administration of pyridostigmine and clonidine has an additive stimulatory effect on GH release in normal children.
It has been shown in humans that both alpha 2-adrenoceptor activation by clonidine (CLON) and cholinergic enhancement by pyridostigmine (PD) have a clear-cut stimulatory effect on GH release. As this effect is probably mediated by two different mechanisms, i.e. via increased endogenous GHRH for CLON and via inhibition of endogenous somatostatin for PD, in 8 normal children we studied the effect of both single and combined acute oral administration of CLON (150 micrograms/m2) and PD (60 mg). When administered alone, CLON and PD induced a similar GH increase (peak, mean +/- SE: 14.6 +/- 2.4 vs 14.2 +/- 3.1 ng/ml; area under curve, AUC: 376.9 +/- 57.6 vs 390.0 +/- 74.3 ng/ml/h). Combined administration of CLON and PD had an additive effect on GH release (peak: 27.5 +/- 4.5 ng/ml; AUC: 920.8 +/- 153.3 ng/ml/h; p less than 0.005 vs CLON and PD alone). In conclusion, presented data show that: i) CLON and PD have similar GH-releasing effect in normal children; ii) The additive stimulatory effect on GH release exerted by acute combined administration of CLON and PD agrees with the hypothesized different mechanism of action of these two drugs; iii) A therapeutic association of CLON and PD may be envisaged in the treatment of some children of short stature.


The relationship of former board members of the German Society of Pathology to National Socialism: A prosopographic study.
This cross-sectional study explores the relationship of former presidents and board members of the German Society of Pathology (DGP) to National Socialism. The intention here is to concretely clarify how many of these individuals belonged to the National Socialist German Workers Party (NSDAP) or other Nazi organizations during the Third Reich; what significance any kind of Nazi past had on the candidature of individuals for board positions in the Federal Republic of Germany; and how a relationship to National Socialism impacted the careers of these individuals during the Third Reich, as well as later on, in the Federal Republic. A total of 60 pathologists were included in this study. Each of these individuals was an elected member of the DGP board during (1) the Weimar Republic, (2) the Nazi era, or (3) in the Federal Republic, and all were adults during the Third Reich. All 60 individuals in question were male university professors. Membership in the NSDAP has been verified for almost 60% of this collective, a percentage rate that is significantly higher than the average membership rate of medical doctors during the Third Reich (ca. 45%). It could also be demonstrated that a political allegiance to National Socialism had, especially amongst younger academics, quite a positive impact. Significantly, however, not one of the 7 DGP chairmen incumbent during the Third Reich were Nazi party members at the time they took office. In contrast, two-thirds of the DGP chairmen appointed until 1986 in the Federal Republic of Germany were former NSDAP members. Clearly, any earlier political commitment to National Socialism did not play a limiting role in the election of the DGP chairman in the Federal Republic. In any case, it can be shown that almost all the former NSDAP members were able to continue or even broaden their careers in the Federal Republic. This study reaches the conclusion that the DGP executive boards and board members of the Federal Republic of Germany had much closer ties to the National Socialist Party than the DGP executive boards during the Third Reich did. It is precisely this finding that confirms the historical, political, and social relevance of this research project dedicated to reappraising this era in history.


Successful Treatment of Pregnant and Postpartum Women With Severe COVID-19 Associated Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation.
There are limited data on the use of extracorporeal membrane oxygenation (ECMO) for pregnant and peripartum women with COVID-19 associated acute respiratory distress syndrome (ARDS). Pregnant women may exhibit more severe infections with COVID-19, requiring intensive care. We supported nine pregnant or peripartum women with COVID-19 ARDS with ECMO, all surviving and suffering no major complications from ECMO. Our case series demonstrates high-maternal survival rates with ECMO support in the management of COVID-19 associated severe ARDS, highlighting that these pregnant and postpartum patients should be supported with ECMO during this pandemic.


Improving gait efficiency to increase movement and physical activity - The impact of abnormal gait patterns and strategies to correct.
Increasing daily steps is important to maintain health and prevent both initial and subsequent cardiovascular (CV) disease (CVD) events. Even 5000 steps have been associated with reduced risk of CVD, however many adults and those with CVD walk fewer than 5000 daily steps. Reduced gait speed is a precursor to decreased physical engagement and is associated with biomarker changes linked to higher risk of CVD. Gait speed is decreased in those with CVD, which may be from changes in biomechanics including reduced step length and increased gait variability. Changes in gait and daily steps are often most discernable post-stroke, which may be from limitations of the CV system in meeting the metabolic demands of walking and the nervous system in exciting motoneuron pools to generate muscle force. This leads to gait asymmetries and decreased speed. Information regarding the effects of rehabilitation interventions (e.g., physical therapy) to increase physical activity (PA) in stroke survivors is limited. Current interventions include high intensity gait training and ischemic conditioning to improve walking speed and fatigability. Given the potential benefits of increased PA and daily steps following stroke, there is a need for more research investigating optimal dosage of daily steps and interventions to improve PA.


Maintenance of normal rat mammary epithelial cells by insulin and insulin-like growth factor 1.
Normal rat mammary epithelial cells were cultured within a rat tail collagen gel matrix formed under improved conditions for controlling pH and osmolarity. Under these conditions, growth can be maintained for up to 3 weeks with a 10- to 15-fold increase in cell number. The cells grow in response to prolactin, progesterone, epidermal growth factor, and cholera toxin, in a medium of DME: Ham's F12 supplemented with BSA and insulin at 10 micrograms/ml. When the insulin concentration was reduced to more physiological levels (10 ng/ml) the cells did not grow. However, at these more physiological concentrations it could be shown that insulin had a concentration-dependent effect on the maintenance of the cells with an optimum concentration around 25 ng/ml. The cells could be maintained in hormone-supplemented medium with low levels of insulin in a quiescent state for up to 14 days. The high levels of insulin needed for optimal growth could be replaced by insulin-like growth factor 1 (IGF-1) at much lower concentrations (25-50 ng/ml). The superphysiological level of insulin required for optimum growth is probably due to its acting weakly through an IGF-1-mediated growth-promoting mechanism. Insulin's effect on cell maintenance occurs at physiological levels and may better reflect its role in mammary cell growth.


Relationship between the presence of insomnia and walking physical activity and diet quality: A cross-sectional study in a sample of Spanish adults.
Certain lifestyle habits may influence aspects of sleep quality, such as insomnia. The main objective of the present study was to analyze the relationship of the presence of insomnia, with walking physical activity and diet quality in an adult population. A cross-sectional descriptive study was performed (subanalysis of the TRIPLE A study) between January of 2014 to June of 2015. A total of 454 subjects were selected by consecutive sampling. Insomnia was evaluated with the Atenas scale, diet quality using the diet quality index (DQI) questionnaire, and physical activity using pedometers for seven days, evaluating the total number of steps, aerobic steps, and energy expended. Of all patients, 26.8% presented with insomnia (33.8% in women and 17.5% in men). In a adjusted model, the mean differences of total steps/day, aerobic steps/day, and kilocalories/day spent in performing physical activity, between no insomnia group and insomnia group were: 1022.5 (95% CI: 177.9-1867.0), 743.9 (95% CI: 68.3-1419.4) and 39.8 (95% CI: 5.7-73.9), respectively. We did not find an association between the diet quality index (DQI) and insomnia. The findings suggest that completing daily a greater total number of steps, aerobic steps, and energy expended by walking, could be correlated with less insomnia, independent of age, sex, and other confounding variables. However, no relationship was observed between diet quality and insomnia.


Evaluating the reliability of analytical results using a probability criterion: a Bayesian perspective.
Methods validation is mandatory in order to assess the fitness of purpose of the developed analytical method. Of core importance at the end of the validation is the evaluation of the reliability of the individual results that will be generated during the routine application of the method. Regulatory guidelines provide a general framework to assess the validity of a method, but none address the issue of results reliability. In this study, a Bayesian approach is proposed to address this concern. Results reliability is defined here as "the probability (π) of an analytical method to provide analytical results (X) within predefined acceptance limits (±λ) around their reference or conventional true concentration values (μ(T)) over a defined concentration range and under given environmental and operating conditions." By providing the minimum reliability probability (π(min)) needed for the subsequent routine application of the method, as well as specifications or acceptance limits (±λ), the proposed Bayesian approach provides the effective probability of obtaining reliable future analytical results over the whole concentration range investigated. This is summarised in a single graph: the reliability profile. This Bayesian reliability profile is also compared to two frequentist approaches, the first one derived from the work of Dewé et al. [W. Dewé, B. Govaerts, B. Boulanger, E. Rozet, P. Chiap, Ph. Hubert, Chemometr. Intell. Lab. Syst. 85 (2007) 262-268] and the second proposed by Govaerts et al. [B. Govaerts, W. Dewé, M. Maumy, B. Boulanger, Qual. Reliab. Eng. Int. 24 (2008) 667-680]. Furthermore, to illustrate the applicability of the Bayesian reliability profile, this approach is also applied here to a bioanalytical method dedicated to the determination of ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) in human plasma by SPE-HPLC-UV.


The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline.
Diagnostic imaging is undoubtedly important in modern medicine, and final clinical decisions are often made based on it. Fortunately, Japan has the highest numbers of diagnostic imaging instruments, such as CT and MRI devices, and boasts easy access to them as well as a high level of diagnostic accuracy. In consequence, a very large number of imaging examinations are performed, but diagnostic instruments are installed in so many medical facilities that expert management of these examinations tends to be insufficient. Particularly, in order to avoid risks, clinicians have recently become indifferent to indications of imaging modalities and tend to rely on CT or MRI resulting in increasing the number of imaging examinations in Japan. This is a serious problem from the viewpoints of avoidance of unnecessary exposure and medical economy. Under these circumstances, the Japan Radiological Society and Japanese College of Radiology jointly initiated the preparation of new guidelines for diagnostic imaging. However, the field of diagnostic imaging is extremely wide, and it is impossible to cover all diseases. Therefore, in drafting the guidelines, we selected important diseases and focused on "showing evidence and suggestions in the form of clinical questions (CQs)" concerning clinically encountered questions and "describing routine imaging techniques presently considered to be standards to guarantee the quality of imaging examinations". In so doing, we adhered to the basic principles of assuming the readers to be "radiologists specializing in diagnostic imaging", "simultaneously respecting the global standards and attending to the situation in Japan", and "making the guidelines consistent with those of other scientific societies related to imaging". As a result, the guidelines became the largest ever, consisting of 152 CQs, nine areas of imaging techniques, and seven reviews, but no other guidelines in the world summarize problems concerning diagnostic imaging in the form of CQs. In this sense, the guidelines are considered to reflect the abilities of diagnostic radiologists in Japan. The contents of the guidelines are essential knowledge for radiologists, but we believe that they are also of use to general clinicians and clinical radiological technicians. While the number and contents of CQs are still insufficient, and while chapters such as those on imaging in children and emergency imaging need to be supplemented, the guidelines will be serially improved through future revisions. Lastly, we would like to extend our sincere thanks to the 153 members of the drafting committee who authored the guidelines, 12 committee chairpersons who coordinated their efforts, six members of the secretariat, and affiliates of related scientific societies who performed external evaluation.


Gold-Catalyzed Asymmetric Transformation of Hydroxylated Propargylic Esters.
By combining tandem asymmetric gold catalysis and subsequent stereoconvergent hydrolysis of enol ester in a one-pot process, hydroxylated propargylic esters are converted into chiral β-oxygenated ketones with mostly good enantiomeric ratios and in largely good to excellent yields. The product chiral center is formed via stereoselective cyclization of a hydroxylated allenyl ester intermediate, which is enabled by asymmetric gold-ligand cooperation.


Purification of Retinal Ganglion Cells from Differentiation Through Adult via Immunopanning and Low-Pressure Flow Cytometry.
The isolation and culturing of rodent retinal ganglion cells (RGC) is a key step in studying the function and cellular response of this crucial cell type. Typical methods used for isolation of RGCs include immunopanning or magnetic bead separation with antibodies targeting RGC specific protein markers. However, in developmental research, many of the most common markers, such as Thy-1, are not expressed in early stages of development. To help study these crucial early stage RGCs, we have developed a novel method that utilizes a transgenic mouse with a GFP tag on the protein BRN3 and a low-pressure fluorescence-activated cell sorter (FACS) system.


High resolution mapping of Dense spike-ar (dsp.ar) to the genetic centromere of barley chromosome 7H.
Spike density in barley is under the control of several major genes, as documented previously by genetic analysis of a number of morphological mutants. One such class of mutants affects the rachis internode length leading to dense or compact spikes and the underlying genes were designated dense spike (dsp). We previously delimited two introgressed genomic segments on chromosome 3H (21 SNP loci, 35.5 cM) and 7H (17 SNP loci, 20.34 cM) in BW265, a BC(7)F(3) nearly isogenic line (NIL) of cv. Bowman as potentially containing the dense spike mutant locus dsp.ar, by genotyping 1,536 single nucleotide polymorphism (SNP) markers in both BW265 and its recurrent parent. Here, the gene was allocated by high-resolution bi-parental mapping to a 0.37 cM interval between markers SC57808 (Hv_SPL14)-CAPSK06413 residing on the short and long arm at the genetic centromere of chromosome 7H, respectively. This region putatively contains more than 800 genes as deduced by comparison with the collinear regions of barley, rice, sorghum and Brachypodium, Classical map-based isolation of the gene dsp.ar thus will be complicated due to the infavorable relationship of genetic to physical distances at the target locus.


Affinity of Skp to OmpC revealed by single-molecule detection.
Outer membrane proteins (OMPs) are essential to gram-negative bacteria, and molecular chaperones prevent the OMPs from aggregation in the periplasm during the OMPs biogenesis. Skp is one of the molecular chaperones for this purpose. Here, we combined single-molecule fluorescence resonance energy transfer and fluorescence correlation spectroscopy to study the affinity and stoichiometric ratio of Skp in its binding with OmpC at the single-molecule level. The half concentration of the Skp self-trimerization (C1/2) was measured to be (2.5 ± 0.7) × 102 nM. Under an Skp concentration far below the C1/2, OmpC could recruit Skp monomers to form OmpC·Skp3. The affinity to form the OmpC·Skp3 complex was determined to be (5.5 ± 0.4) × 102 pM with a Hill coefficient of 1.6 ± 0.2. Under the micromolar concentrations of Skp, the formation of OmpC·(Skp3)2 was confirmed, and the dissociation constant of OmpC·(Skp3)2 was determined to be 1.2 ± 0.4 μM. The precise information will help us to quantitatively depict the role of Skp in the biogenesis of OMPs.


The biology of tetraploid hydatidiform moles: histopathology, cytogenetics, and flow cytometry.
We identified three cases of tetraploid hydatidiform moles (HM). A complete hydatidiform mole (CM) had a 92,XXXX karyotype. The two partial hydatidiform moles (PM) had karyotypes of 69,XXY/90,XXXY,-11,-13 and 92,XXYY, respectively. Study of chromosomal heteromorphisms in the 92,XXYY PM revealed two maternal and two paternal haploid sets. Flow cytometric analysis of nuclear DNA content from fresh placental tissue from the 69,XXY/90,XXXY,-11,-13 PM demonstrated distinct peaks in the triploid and tetraploid regions and an octaploid G2/M peak. Flow cytometric analysis of paraffin-embedded, fixed tissue was diagnostic of tetraploidy in the 92,XXXX CM and consistent with tetraploidy in the 92,XXYY PM. All three patients achieved spontaneous remission of elevated gonadotropin levels. These three cases of tetraploid HM do not fit into the usual patterns of diploid CM and triploid PM. We conclude that flow cytometric analysis of nuclear DNA may be used to identify polyploidy in fresh and paraffin-embedded, fixed placental tissues. Categorization of all molar placentas on the basis of ploidy presents rare opportunities to study the biology and natural history of gestational trophoblastic disease in tetraploid HM.


The visibility of QSEN competencies in clinical assessment tools in Swedish nurse education.
Prospective nurses need specific and sufficient knowledge to be able to provide quality care. The Swedish Society of Nursing has emphasized the importance of the six quality and safety competencies (QSEN), originated in the US, in Swedish nursing education. To investigate the visibility of the QSEN competencies in the assessment tools used in clinical practice METHOD: A quantitative descriptive method was used to analyze assessment tools from 23 universities. Teamwork and collaboration was the most visible competency. Patient-centered care was visible to a large degree but was not referred to by name. Informatics was the least visible, a notable concern since all nurses should be competent in informatics to provide quality and safety in care. These results provide guidance as academic and clinical programs around the world implement assessment of how well nurses have developed these essential quality and safety competencies.


Image-guided nerve cryoablation for post-thoracotomy pain syndrome.
Chronic post-thoracotomy pain syndrome (PTPS) can cause significant patient distress and is frequently difficult to manage. Percutaneous intercostal nerve (ICN) cryoablation by palpation of surface landmarks can be risky, as inaccurate probe placement can lead to hemo- or pneumothorax. Experience with image-guided ICN cryoablation with treatment planning and device navigation is limited. A patient with intractable PTPS was treated with ICN cryoablation under cone-beam computed tomography guidance with software-assisted needle trajectory planning and ablation zone simulation. This procedure provided the patient ~8 weeks of relief. This case demonstrated that ICN cryoablation is feasible under image guidance with device navigation and ablation simulation and may result in a few months of pain relief in cases of intractable PTPS.


[Preformation and epigenesis in the works of M. Malpighi].
The article analyzes the scientific debate arosen between Marcello Malpighi and Giovan Battista Trionfetti about the possibility of 'preformation' in plants and living organisms, the existence of spontaneous generation and the meaning and usefullness of particular structures in plants, as 'folia seminalia'.


Radiological impacts in Life Cycle Assessment - Part II: Comparison of methodologies.
In a complementary article, an overarching framework was proposed to include radiological impacts in Life Cycle Impact Assessment (LCIA). Two methodologies were derived embodying the framework: the Critical Group Methodology (CGM), adapted from the approach commonly used in Human and Environmental Risk Assessment (HERA), and UCrad, based on the compartment modelling approach commonly used in LCIA. In this paper, characterisation factors obtained by the two methodologies are compared in detail to investigate the consequences of the different approaches to fate modelling and the sensitivity of the characterisation factors to the radionuclides' half-life. Characterisation factors from the CGM methodology are strongly affected by radioactive decay at low half-life and by dilution at large distances. Conversely, UCrad factors are not affected by dilution and are affected less than CGM by radioactive decay. It is concluded that UCrad is more appropriate than CGM for LCA because it is consistent with the general approach used in LCIA. However, CGM can be used alongside UCrad to make recommendations on the location and scale of specific processes emitting radionuclides.


Insight in stable schizophrenia: relations with psychopathology and cognition.
This study evaluated the relationship among insight, sociodemographic and clinical variables, symptoms and cognitive functions in a population of outpatients with stable schizophrenia, in order to identify possible contributing factors to awareness. Two-hundred and seventy-six consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. All subjects were assessed by psychiatric scales and interview, and a wide neuropsychological battery. A factor analysis was performed to identify cognitive factors and multiple regression analyses were executed to test the contribution of variables considered to insight. Our results showed that positive and negative symptoms, executive functions, verbal memory-learning were contributors of awareness of mental illness; positive and negative symptoms explained variability in awareness of the need for treatment; positive symptoms and executive functions contributed to awareness of the social consequences of disorder. These results suggested that insight was partially influenced by positive and negative symptoms and by cognitive functions. A complex system of overlapping variables may underlie impaired insight, contributing to a different extent to specific dimensions of poor insight in patients with stable schizophrenia.


Differential expression of immune system-related components in midtrimester amniotic fluid from singleton and twin pregnancies.
We investigated differences between singleton and twin gestations in immune mediators in midtrimester amniotic fluid. Amniotic fluid from 252 singleton and 46 twin gestations were tested by enzyme-linked immunosorbent assay for interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, tumor necrosis factor-alpha, nitric oxide, Clara cell protein 16, leptin, and the 70-kDa heat shock protein. A subset of amniotic fluid was also tested for leukemia inhibitory factor, angiogenin, and migration inhibitory factor-related protein 8 and migration inhibitory factor-related protein 14. Data were analyzed by the Mann-Whitney U test and Spearman rank correlation. Median concentrations of interleukin-1beta, tumor necrosis factor-alpha, interleukin-4, Clara cell protein 16, leptin, and angiogenin were increased in amniotic fluid from twins; median levels of the 70-kDa heat shock protein, leukemia inhibitory factor, migration inhibitory factor-related protein 8, and migration inhibitory factor-related protein 14 were highest in amniotic fluid from singletons (P < .001). Elevated levels of immune activators may contribute to the increased rate of preterm premature rupture of membranes and spontaneous preterm birth in twin populations.


Hexacyanochromate ion as a paramagnetic anion probe for active sites of enzymes. Application to ribonuclease A.
The 270 MHZ proton MNR spectra of an aqueous solution of ribonuclease A in the presence of hexacyanochromate ions were measured. The C2 and C4 proton signals of the His 12 and His 119 residues were selectively broadened, indicating that this ion was bound to the active site. From analyses of concentration dependences of diamagnetic shifts, one hexacyanocobaltate ion was found to bind to the active site, with the dissociation constant of 8 mM. The paramagnetic hexacyanochromate ion is useful for mapping the active sites of enzymes for anionic substrates.


Reactivity of Pd/Fe bimetallic nanotubes in dechlorination of coplanar polychlorinated biphenyls.
A new class of bimetallic materials based on palladium-decorated iron nanotubes is described that demonstrates high reactivity in dechlorination reactions. This high dechlorination efficiency was attributed to the high surface area to volume ratio of the hollow nanotubes structure. Herein, we evaluated the effect of different conditions, such as the nanotube size, and the palladium loading on the efficiency of the dechlorination of PCB 77, a model coplanar polychlorinated biphenyl (PCB), by the Pd/Fe bimetallic nanotubes system. The efficiency of the dechlorination was lowered by decreasing the tube diameter from 200 to 100 nm. In addition, the interior surface as well as the exterior surface of the as-synthesized Pd/Fe bimetallic nanotubes was found to contribute to the high efficiency of the dechlorination of PCB 77. The dechlorination of PCB 77 by Pd/Fe bimetallic nanotubes demonstrated small activation energy indicating diffusion controlled reaction. The as-prepared Pd/Fe bimetallic nanotubes showed extended lifetime activity when used in multiple dechlorination cycles.


Multiple populations of neuropeptide-containing cells in cultures of the bovine adrenal medulla.
Cell populations containing vasoactive intestinal polypeptide (VIP), enkephalins, and catecholamines were identified in bovine adrenal medullary cultures by immunofluorescence and radioimmunoassay. Addition of forskolin to the culture medium increased the cellular levels of both VIP and the enkephalins. These changes resulted from an increase in the number of VIP-positive cells and an increase in cellular enkephalin content.


The implementation of an enhanced clinical model to improve the diagnostic yield of exome sequencing for patients with a rare genetic disease: A Canadian experience.
The introduction of clinical exome sequencing (ES) has provided a unique opportunity to decrease the diagnostic odyssey for patients living with a rare genetic disease (RGD). ES has been shown to provide a diagnosis in 29%-57% of patients with a suspected RGD, with as many as 70% remaining undiagnosed. There is a need to advance the clinical model of care by more formally integrating approaches that were previously considered research into an enhanced diagnostic workflow. We developed an Exome Clinic, which set out to evaluate a workflow for improving the diagnostic yield of ES for patients with an undiagnosed RGD. Here, we report the outcomes of 47 families who underwent clinical ES in the first year of the clinic. The diagnostic yield from clinical ES was 40% (19/47). Families who remained undiagnosed after ES had the opportunity for follow-up studies that included phenotyping and candidate variant segregation in relatives, genomic matchmaking, and ES reanalysis. This enhanced diagnostic workflow increased the diagnostic yield to 55% (26/47), predominantly through the resolution of variants and genes of uncertain significance. We advocate that this approach be integrated into mainstream clinical practice and highlight the importance of a coordinated translational approach for patients with RGD.