Comparing sense of coherence, depressive symptoms and anxiety, and their relationships with health in a population-based study.
The strong negative correlations observed between the sense of coherence (SOC) scale and measures of depression and anxiety raise the question of whether the SOC scale inversely measures the other constructs. The main aim of the present study was to examine the discriminant validity of the three measures by comparing their associations with health indicators and behaviours. The participants were 25 to 74-year-old Finnish men (n=2351) and women (n=2291) from the National Cardiovascular Risk Factor Survey conducted in 1997. The SOC scale had high inverse correlations with both depression (r=-0.62 among both men and women) and anxiety measures (r=-0.57 among the men and r=-0.54 among the women). Although confirmatory factor analyses suggested that it was possible to differentiate between SOC, cognitive depressive symptoms and anxiety, the estimated correlations were even higher than those mentioned above. Education was related only to SOC, but the associations of SOC, cognitive depressive symptoms and anxiety with self-reported and clinically measured health indicators (body mass index, blood pressure, cholesterol) and health behaviours were almost identical. The variation in the lowest SOC tertile was more strongly associated with health variables than in the highest tertile. To conclude, the size of the overlap between the SOC and depression scales was the same as between depression and anxiety measures. This indicates that future studies should examine the discriminant validity of different psychosocial scales more closely, and should compare them in health research in order to bring parallel concepts into the same scientific discussion.


Predictors for Depression, Anxiety and psychotic symptoms in a very elderly population: data from a 3-year follow-up study.
This study examined the predictors for Depression, Anxiety and psychotic symptoms in a population of very elderly persons. A total of 894 persons with a mean age of 84.5 years were examined twice using a 3-year interval. Physicians performed a structured psychiatric interview and persons with a current disorder or symptom were excluded. Persons who had a history of psychosis, were affected with Dementia and had an insufficient social network had an increased frequency of psychotic symptoms. A history of Depression/Anxiety increased the frequency of having Anxiety and Depression. An insufficient social network was associated with Anxiety. In this study Anxiety, Depression and psychotic symptoms in the very elderly seem to be linked to a lifetime psychological vulnerability, since all were related to a previous psychiatric history. Additionally, psychotic symptoms seemed to emerge due to structural brain damage, as seen in Dementia.


A CNT-PDMS wearable device for simultaneous measurement of wrist pulse pressure and cardiac electrical activity.
Simultaneous measurement of multi-physiological signals can provide effective diagnosis and therapeutic assessment of diseases. This paper reports a carbon nanotube (CNT) - Polydimethylsiloxane (PDMS) - based wearable device with piezo-resistive and voltage-sensing capabilities for simultaneously capturing wrist pulse pressure and cardiac electrical signal. The layout design of sensing elements in the device was guided by analyzing strain distribution and electric field distribution for minimizing the interference between wrist pulse and cardiac electric activity during measurement. Each device was preconditioned under the strain of 20% until the resistance change of the device reached equilibrium. After preconditioning, the relationship between the resistance change and the pressure was calibrated, which determined the device sensitivity to be 0.01 Pa-1 and the linear pressure range of the device to be 0.4 kPa to 14.0 kPa. Mechanisms of CNT-PDMS for sensing strain signal and electrical pulse signal were explored by scanning electron microscopy (SEM) imaging and equivalent circuit modeling. The device was applied to monitor the wrist pulse and ECG signals of volunteers during the recovering process after physical exercises.


Extension of the two-dimensional mass channel cluster plot method to fast separations utilizing low thermal mass gas chromatography with time-of-flight mass spectrometry.
Implementation of a data reduction and visualization method for use with high-speed gas chromatography and time-of-flight mass spectrometry (GC-TOFMS) is reported. The method, called the "2D m/z cluster method" facilitates analyte detection, deconvolution, and identification, by accurately measuring peak widths and retention times using a fast TOFMS sampling frequency (500 Hz). Characteristics and requirements for high speed GC are taken into consideration: fast separations with narrow peak widths and high peak capacity, rapid data collection rate, and effective peak deconvolution. Transitioning from standard GC (10-60+ minute separations) to fast GC (1-10 min separations) required consideration of how to properly analyze the data. This report validates use of the 2D m/z cluster method with newly developed GC technology that produces ultra-fast separations (∼1 min) with narrow analyte peak widths. Low thermal mass gas chromatography (LTM-GC) operated at a heating rate of 250 °C/min coupled to a LECO Pegasus III TOFMS analyzed a 115 component test mixture in 120 s with peak widths-at-base, wb (4σ), of 350 ms (average) to produce a separation with a high peak capacity, nc ∼ 340 (at unit resolution Rs = 1). The 2D m/z cluster method is shown to separate overlapped analytes to a limiting Rs ∼ 0.03, so the effective peak capacity was increased nearly 30-fold to nc ∼10,000 in the 120 s separation. The method, when coupled with LTM-GC-TOFMS, is demonstrated to provide unambiguous peak rank (i.e. the number of analytes per overlapped peak in the total ion current (TIC)), by visualizing locations of pure and chromatographically overlapped m/z. Hence, peak deconvolution and identification using MCR-ALS (multivariate curve resolution - alternating least squares) is demonstrated.


Concurrent Gabapentin and Opioid Use and Risk of Mortality in Medicare Recipients with Non-Cancer Pain.
Gabapentin is prescribed for pain and is perceived as safe generally. However, gabapentin can cause respiratory depression, exacerbated by concomitant central nervous system depressants (e.g., opioids), a concern for vulnerable populations. We compared mortality rates among new users of either gabapentin or duloxetine with or without concurrent opioids in the 20% Medicare sample. We conducted a new-user design retrospective cohort study, in Medicare enrollees ages 65-89 years with noncancer chronic pain and no severe illness who filled prescriptions between 2015 and 2018 for gabapentin (n = 233,060) or duloxetine (n = 34,009). Daily opioid doses, estimated in morphine milligram equivalents (MMEs), were classified into none, low (0 < MME < 50), and high (≥ 50 MME), based on Centers for Disease Control and Prevention (CDC) recommendations. The outcomes were all-cause mortality (primary) and out-of-hospital mortality (secondary). We used inverse probability of treatment weighting to adjust for differences between gabapentin and duloxetine users. During 116,707 person-years of follow-up, 1,379 patients died. All-cause mortality rate in gabapentin users was 12.16 per 1,000 person-years vs. 9.94 per 1,000 in duloxetine users. Risks were similar for users with no concurrent opioids (adjusted hazard ratio (aHR) = 1.03, 95% confidence interval (CI): 0.80-1.31) or low-dose daily opioids (aHR = 1.06, 95% CI: 0.63-1.76). However, gabapentin users receiving concurrent high-dose daily opioids had an increased rate of all-cause mortality compared with duloxetine users on high-dose opioids (aHR = 2.03, 95% CI: 1.19-3.46). Out-of-hospital mortality yielded similar results. In this retrospective cohort study of Medicare beneficiaries, concurrent use of high-dose opioids and gabapentin was associated with a higher all-cause mortality risk than that for concurrent use of high-dose opioids and duloxetine.


Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells.
Toll-like receptors (TLRs) recognize distinct microbial components and induce innate immune responses. TLR5 is triggered by bacterial flagellin. Here we generated Tlr5-/- mice and assessed TLR5 function in vivo. Unlike other TLRs, TLR5 was not expressed on conventional dendritic cells or macrophages. In contrast, TLR5 was expressed mainly on intestinal CD11c+ lamina propria cells (LPCs). CD11c+ LPCs detected pathogenic bacteria and secreted proinflammatory cytokines in a TLR5-dependent way. However, CD11c+ LPCs do not express TLR4 and did not secrete proinflammatory cytokines after exposure to a commensal bacterium. Notably, transport of pathogenic Salmonella typhimurium from the intestinal tract to mesenteric lymph nodes was impaired in Tlr5-/- mice. These data suggest that CD11c+ LPCs, via TLR5, detect and are used by pathogenic bacteria in the intestinal lumen.


Successful pregnancy in a treated patient with biotinidase deficiency.
We report a patient with biotinidase deficiency treated with biotin during pregnancy with favourable outcome.


Diversity and development of local inhibitory and excitatory neurons associated with dopaminergic nuclei.
For regulation of voluntary movement and motivation the midbrain dopaminergic system receives input from a variety of brain regions. Often this input is mediated by local non-dopaminergic neurons within or closely associated with the dopaminergic nuclei. In addition to the dopaminergic neurons, some of these non-dopaminergic neurons also send functionally important output from the ventral midbrain to forebrain targets. The aim of this review is to introduce subtypes of GABAergic and glutamatergic neurons, which are located in the dopaminergic nuclei or the adjacent brainstem and are important for the regulation of the dopaminergic pathways. In addition, we discuss recent studies beginning to reveal mechanisms for their development, which may hold the key to understanding the diversity of these neurons.


Analysis of quality of life after randomized controlled trial of alpha-1 adrenoceptor antagonist alone and in combination with cyclooxygenase-2 inhibitor in patients who underwent low-dose-rate brachytherapy for prostate cancer.
The goal of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibitors on quality of life (QoL) of patients undergoing low-dose-rate (LDR) brachytherapy. A total of 310 patients with prostate cancer who had undergone LDR brachytherapy were enrolled. The patients were randomized (1 : 1) to the monotherapy group (tamsulosin alone: 0.2 mg/day, n = 156) and the combination group (tamsulosin: 0.2 mg/day plus celecoxib: 200 mg/day, n = 154) without placebo. Using the expanded prostate cancer index composite (EPIC) and medical outcomes study 8-item short form health survey (SF-8) questionnaire, QoL was evaluated at baseline and at 1, 3, 6, and 12 months after seed implantation. The mean changes in scores from baseline to 1 and 3 months after seed implantation for the urinary (1M: -10.5, 3M: -10.9) and bowel (1M: -2.4, 3M: -4.2) domains of EPIC in the combination group were not significantly different from those (urinary 1M: -11.0, 3M: -11.4, bowel 1M: -2.3, 3M: -4.6) in the monotherapy group. The mean changes in scores from baseline to 1 and 3 months after seed implantation for the physical component summary (1M: 0.009, 3M: -0.32) and mental component summary (1M: 0.41, 3M: 0.36) of SF-8 in the combination group were not significantly different from those (physical component 1M: -0.89, 3M: -0.22, mental component 1M: 1.3, 3M: 1.1) in the monotherapy group. Combination treatment with celecoxib and tamsulosin during the peri-operative period is not warranted for improving QoL in patients undergoing LDR brachytherapy.


[Arthrolysis of the knee joint].
The surgical treatment of the extensor rigidity of the knee joint described by Payr was performed in fourteen cases at the Orthopedic University Hospital of Giessen. A flexion of more than 90 degrees was achieved in all patients. In case of correct indication, this method has still its value in orthopedia even regarding the changed patient categories.


Differential sensitivity of peripheral blood lymphocytes of untreated leprosy patients to mitomycin C.
The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 microgram/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant (p less than 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 +/- 1.19 in controls, 19.97 +/- 3.51 in PB, and 29.66 +/- 5.92 in MB patients. The differences in the frequency of MMC-induced SCEs between the 3 groups were found to be highly significant (p less than 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease.


Nuclear co-repressor (NCoR) is required to maintain insulin sensitivity in C2 C12 myotubes.
Nuclear co-repressor (NCoR) regulates peripheral insulin sensitivity; however, its role in modulating insulin sensitivity in skeletal muscle remains elusive. Present study investigated protein expression and effect of NCoR on insulin sensitivity in murine skeletal muscle cell line C2 C12 . Myotubes as compared to myoblasts of C2 C12 cells were found to be more sensitive in response to insulin as increase in insulin-stimulated phosphorylation of AKT at serine 473 residue (pAKTS473 ) was significantly higher in myotubes. Incidentally, reduced protein level of NCoR coincided with differentiation of myoblasts into myotubes of C2 C12 cells. However, insulin stimulation per se failed to affect protein level of NCoR either in myoblasts or myotubes of C2 C12 cells. To assess the role of NCoR on insulin sensitivity, NCoR was transiently knocked down using siRNA in myotubes of C2 C12 . In fact, transient silencing of NCoR led to significant reduction in insulin-stimulated pAKTS473 and impaired glucose uptake. This observation is in contrast to published studies where NCoR has been reported to negatively regulate insulin signaling cascade. Furthermore, transient silencing of NCoR failed to improve insulin sensitivity in chronic hyperinsulinemia-induced insulin-resistant model of C2 C12 cells. Importantly, inhibition of lysosomal protein degradation pathway using ammonium chloride restored protein level of NCoR but failed to increase glucose uptake in serum-starved C2 C12 myotubes. Collectively, data from present study show differential protein level of NCoR under different cell state (myoblast and myotubes) of C2 C12 cells and NCoR proves to be vital for maintaining insulin sensitivity in C2 C12 myotubes.


Prenatal smoking exposure and asymmetric fetal growth restriction.
Prenatal smoking exposure causes intrauterine fetal growth restriction (IUGR), although its effects on fetal proportionality are less clearly defined. The present study assessed fetal proportionality in babies with IUGR using maternal salivary cotinine to indicate maternal smoking exposure. A case-control study at the Liverpool Women's Hospital, UK of babies with asymmetric and symmetric IUGR and non-growth restricted babies was carried out. 270 white women including 90 IUGR cases and 180 controls were enrolled. Asymmetry presented in 52.2% of IUGR cases. Geometric mean maternal cotinine concentration was higher with asymmetric (p=0.002) than symmetric IUGR (p=0.07), when compared to controls. Maternal smoking exposure was independently associated with asymmetric IUGR (OR 2.4, 95% CI, 1.5-4.4, p</=0.001). Maternal anaemia was more frequent in babies with symmetric IUGR (OR 1.9, 1.3-3.4, p=0.002), but not in asymmetric babies. Rohrer's index ranged between 1.64 and 2.25 for asymmetric infants and significantly decreased with increasing maternal cotinine concentration in IUGR babies. Increased cotinine was not associated with shortened gestational age in IUGR babies. Asymmetric IUGR occurred more frequently in heavy smokers. Stopping smoking even late in pregnancy may be beneficial for improved fetal outcomes. Symmetric IUGR was associated with maternal anaemia, highlighting the importance of prenatal nutritional status.


Cost-effectiveness of MR-mammography vs. conventional mammography in screening patients at intermediate risk of breast cancer - A model-based economic evaluation.
The aim of this study was to analyze the cost-effectiveness of screening patients of intermediate risk of breast cancer with MR-Mammography (MRM) versus conventional mammography (XM). A decision model for both diagnostic modalities and a subsequent markov model for the simulation of follow-up costs and outcomes was developed. Input parameters were acquired from published literature for this markov modelling study. The expected cumulative costs and outcomes were calculated for both modalities in a 30-year timeframe in US-dollar ($) and quality-adjusted life years (QALYs). A deterministic sensitivity analysis and a probabilistic sensitivity analysis incorporating 30,000 Monte Carlo iterations were performed to investigate the model stability. In total, XM with its consecutive treatments resulted in total costs of $ 5,492.68 and an average cumulative quality of life of 18.87 QALYs, compared to MRM with costs of $ 5,878.66 and 18.92 QALYs. The corresponding incremental cost-effectiveness ratio (ICER) for MRM was $ 8,797.60 per QALY - distinctly below international willingness-to-pay thresholds for cost-effectiveness. The results were confirmed within the limits of the sensitivity analyses. In patients with intermediate risk for breast cancer due to their dense breast tissue, two-yearly screening with MRM may be considered as cost-effective.


Lymphatic malformations of the head and neck-current concepts in management.
Lymphatic malformations of the head and neck, also known as lymphangiomas or cystic hygromas, are a diverse group of lesions. They can be small and superficial or large and extensive, and management can be a challenge. Surgically they can be difficult to remove completely because of their poorly defined borders and the potential for damaging neighbouring structures. We review the dilemmas posed in diagnosis and treatment, and discuss the contemporary management of these interesting entities including sclerotherapy, which is gaining popularity.


Evolution of erect growth forms in domesticated wheats: possible effects of grazing.
Wild wheats tend to have a prostrate growthform during the early part of their vegetative growth phase. However, at a later stage the leaves and spike-bearing stalks change the pattern of growth and develop in an erect position. Domesticated wheats develop differently, with an erect growth form dominating the entire growth phase.It is suggested that heavy grazing, especially during early winter months might have played a role in the eradication of spontaneously appearing erect mutants of wild wheat. Such mutants increased in frequency only under domestication.


Targeted in vivo mutagenesis of a sensor histidine kinase playing an essential role in ABA signaling of the moss Physcomitrium patens.
Land plants exhibit various adaptation responses to unfavorable water environments, such as drought and flooding. The phytohormone abscisic acid (ABA) and ethylene play essential roles in plant adaptation to drought and flooding, respectively. It remains largely unknown how plants integrate environmental information for water availability. In the moss Physcomitrium patens, we recently reported that not only ethylene/flooding signaling but also ABA/osmostress signaling are mediated by ethylene receptor-related sensor histidine kinases (ETR-HKs). Subfamily I ETR-HKs of this moss were found to interact with a RAF kinase (ARK) and were required for ABA-dependent activation of SNF1-related protein kinase 2 (SnRK2) via ARK activation. To elucidate the mechanisms of ARK regulation by ETR-HKs, here we employed targeted in vivo mutagenesis of PpHK5, a member of subfamily I ETR-HKs. Analyses of ABA-insensitive Pphk5 mutants indicated that PpHK5 mutations affecting the interaction with ARK resulted in loss of PpHK5 function to activate ABA signaling. We also identified a PpHK5 mutation that does not affect ARK interaction but resulted in loss of PpHK5 function. These results suggest that physical interaction between ETR-HK and ARK is essential but not sufficient for the regulation of ARK activity, and the C-terminal response regulator domain is involved in regulating ARK activation.


The effect of an intrauterine device on mast cell numbers and distribution in the hamster uterus.
The effect of an IUD on mast cell numbers and distribution in the uterus was studied in castrated, castrated hormone-treated and cycling hamsters. The device had a stimulatory effect on total mast cell numbers in those animals that received no treatment, peanut oil, or estrogen therapy and in all cycling animals. The device also apparently causes mast cells to be redistributed in the different areas of the uterus. The results indicate that the IUD alters the uterine mast cell response to exogenous hormones and cycle times.


Molecular analyses of the functional microbial community in composting by PCR-DGGE targeting the genes of the β-glucosidase.
The study investigated the β-glucosidase-producing microbial communities and the enzymatic dynamics of CMCase and β-glucosidase during the process of cattle manure-rice straw composting. In order to analyze the succession of functional community by PCR-denaturing gradient gel electrophoresis (DGGEs), three sets of PCR primers were designed to amplify the family 1 and 3 β-glucosidase genes from both bacteria and fungi. The results showed in general that the stable functional community composition as well as for the high level enzymatic activities of both cellulase and β-glucosidase occurred during the last phase (days 14-31) of composting. In the process of composting, that functional groups were determined by the stable bands (GH1-F, GH1-H, GH1-G, GH3E-D and GH3E-E) may significantly contribute to the increase of β-glucosidase activities in the later phase. Especially, the bands from the family 1 β-glucosidase genes were appeared before that from the family 3 β-glucosidase genes from fungi, then the former was substituted for the latter gradually in the cooling phase. We found significant correlations between the β-glucosidase activity and the communities of the functional bacteria and fungi. The results indicated that different β-glucosidase-producing microbe release different amounts or activities of β-glucosidase, and that the composition of microbial communities may play a major role in determining overall β-glucosidase activity during the composting process.


The Pandemic Stressor Scale: factorial validity and reliability of a measure of stressors during a pandemic.
This study aimed to assess the factorial validity and reliability of the Pandemic Stressor Scale (PaSS), a new measure to assess the severity of distress for different stressors relevant during a pandemic or epidemic. The PaSS was administered in N = 2760 German participants. Exploratory factor analysis was used to extract factors. The factor structure obtained in the German sample was examined in N = 1021 Austrian participants using confirmatory factor analysis. χ2, RMSEA, SRMR, CFI, TLI were assessed as global goodness of fit indices for two models (Model 1: nine-factor model; Model 2: nine-factor model combined with a second-order general factor). We additionally assessed factor loadings, communalities, factor reliability, discriminant validity as local fit indices. Internal consistency, item discrimination, and item difficulty were assessed as additional test quality criteria. The results of the exploratory factor analysis suggested a nine-factor solution with factor loadings accounting for 50.4% of the total variance (Factor 1 'Problems with Childcare', Factor 2 'Work-related Problems', Factor 3 'Restricted Face-to-Face Contact', Factor 4 'Burden of Infection ', Factor 5 'Crisis Management and Communication', Factor 6 'Difficult Housing Condition', Factor 7 'Fear of Infection', Factor 8 'Restricted Access to Resources', Factor 9 'Restricted Activity'). The confirmatory factor analysis showed a sufficient global fit for both tested models (Model 1: χ2 (369, N = 1021) = 1443.28, p < .001, RMSEA = .053, SRMR = .055, CFI = .919, TLI = .904; Model 2: χ2 (396, N = 1021) = 1948.51, p < .001, RMSEA = .062, SRMR = .074, CFI = .883, TLI = .871). The results of the chi-square difference test indicated a significantly better model-fit of Model 1 compared to Model 2 (∆χ2 (27, N = 1021) = 505.23, p < .001). Local goodness of fit indices were comparable for both tested models. We found good factor reliabilities for all factors and moderate to large factor loadings of the items as indicators. In Model 2, four first-order factors showed small factor loadings on the second-order general factor. The Pandemic Stressor Scale showed sufficient factorial validity for the nine measured domains of stressors during the current COVID-19 pandemic.


[Neutropenia and sepsis].
The clinical management of neutropenic infections represents a great diagnostic and therapeutic challenge. Established sepsis criteria only partially reflect the neutropenic setting. Diagnostic procedures are frequently impaired by thrombocytopenia and progressive respiratory insufficiency. Increased tendency to bleed, engraftment, and fulminant progression represent major therapeutic challenges. Thus, crucial for the diagnosis and therapy of neutropenic sepsis are clear and well-communicated algorithms, rapid action, and close collaboration between oncologists and intensivists.


Exclusive breastfeeding among Saudi mothers: Exposing the substantial gap between knowledge and practice.
Rates of exclusive breastfeeding are exceedingly low in the Arabic world. This study aims to estimate the local prevalence of, and knowledge about, exclusive breastfeeding in Saudi Arabia. This is a cross-sectional survey of mothers of infants aged 6-12 months who attended Taif-based "well-baby clinic." A structured questionnaire was developed to explore predictors of, and participants' knowledge about, exclusive breastfeeding. Participants in the study were 202 mothers. The rate for initiation of breastfeeding in the first hour after childbirth was 13.9%. The prevalence of exclusive breastfeeding was 16.3%. Knowledge level was great among participating mothers as 65.3% of mothers scored over 75% of the total knowledge score and 95% got more than half of the questions right. Only having 3-6 children (P = 0.023) and 1-year interpregnancy interval (P = 0.005) were associated with the positive likelihood of exclusive breastfeeding. Baby age (P = 0.0218), birth in a private facility (P = 0.00843), and university education (P = 0.0131) were associated with better knowledge. Rates of exclusive breastfeeding practice are low in Saudi Arabia despite adequate knowledge about its benefits and necessity.


Differential androgen response to adrenocorticotropic hormone stimulation in polycystic ovarian syndrome: relationship with insulin secretion.
To investigate the relationship between insulin and adrenal androgens in patients with polycystic ovarian disease (PCOD). Patients with PCOD and a group of volunteers who attended the department during a period of 6 months were studied. Department of Gynaecology and Obstetrics, Università Cattolica del Sacro Cuore, Roma, Italy. Healthy women with ovulatory cycles (hospital personnel, n = 8) and women affected by PCOD (n = 32) were studied on day 5 to 6 of their follicular phase. All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 to 6 of the cycle. Then plasma samples were collected at 7.00 A.M.; at 11.00 P.M., 2 mg of dexamethasone (DEX) were orally administered with blood samples collected the day after at 7.00 A.M. (effect of DEX). Then adenocorticotropic hormone (ACTH, Synacten; Ciba-Geigy, Varese, Italy) 250 micrograms was injected intravenously (IV) and samples collected 60 minutes later (effect of ACTH). Plasma glucose and insulin concentration were assayed on OGTT samples collected at time 0, 30, 60, 90, 120, 180, and 240 minutes after glucose ingestion. Data are expressed as area under the curve. Cortisol, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T), androstenedione (A), and dehydroepiandrosterone sulphate (DHEAS) plasma levels were evaluated on the samples collected before and after DEX or ACTH administration. Data are expressed as absolute concentrations and percent increase in respect to values before the treatment. According to the OGTT response, 21 patients were classified as hyperinsulinemic and 11 as normoinsulinemic. The ideal body weight was greater in hyperinsulinemic patients. No differences in baseline hormone levels were found between the two groups. Only sex hormone binding globulin levels were significantly greater in normoinsulinemic patients (P less than 0.05). Also, the plasma concentration of all steroids after DEX were similar in both groups. Intravenous injection of ACTH significantly increased plasma androgens levels. Cortisol, DHEAS, and T enhancement did not differ in normoinsulinemic and hyperinsulinemic patients, whereas significantly greater A (P less than 0.01) and 17-OHP (P less than 0.05) plasma concentrations were observed after ACTH injection in hyperinsulinemic when compared with normoinsulinemic PCOD subjects. Control group after IV ACTH showed an increase of A and 17-OHP similar to those found in normoinsulinemic PCOD group. These data suggest that insulin could be involved in the androgen production by adrenal gland and it could influence the responsiveness of adrenal to its trophic hormones.


Extending the Debate Between Spearman and Wilson 1929: When do Single Variables Optimally Reproduce the Common Part of the Observed Covariances?
The covariances of observed variables reproduced from conventional factor score predictors are generally not the same as the covariances reproduced from the common factors. We sought to find a factor score predictor that optimally reproduces the common part of the observed covariances. It was found algebraically that-under some conditions-the single observed variable with highest loading on a factor reproduces the non-diagonal elements of the observed covariance matrix more exactly than the conventional factor score predictors. This finding is linked to Spearman's and Wilson's 1929 debate on the use of single variables as factor score predictors. A population-based and a sample-based simulation study confirmed the algebraic result that taking a single variable can outperform conventional factor score predictors in reproducing the non-diagonal covariances when the nonzero loading size and the number of nonzero loadings per factor are small. The results indicated that a weighted aggregation of variables does not necessarily lead to an improvement of the score over the variable with the highest loading.


Chewing pattern and muscular activation in open bite patients.
Different studies have indicated, in open bite patients, that masticatory muscles tend to generate a small maximum bite force and to show a reduced cross-sectional area with a lower EMG activity. The aim of this study was to evaluate the kinematics parameters of the chewing cycles and the activation of masseters and anterior temporalis muscles of patients with anterior dental open bite malocclusion. There have been no previous reports evaluating both kinematic values and EMG activity of patients with anterior open bite during chewing. Fifty-two young patients (23 boys and 29 girls; mean age±SD 11.5±1.2 and 10.2±1.6years, respectively) with anterior open bite malocclusion and 21 subjects with normal occlusion were selected for the study. Kinematics parameters and surface electromyography (EMG) were simultaneously recorded during chewing a hard bolus with a kinesiograph K7-I Myotronics-Usa. The results showed a statistically significant difference between the open bite patients and the control group for a narrower chewing pattern, a shorter total and closing duration of the chewing pattern, a lower peak of both the anterior temporalis and the masseter of the bolus side. In this study, it has been observed that open bite patients, lacking the inputs from the anterior guidance, that are considered important information for establishing the motor scheme of the chewing pattern, show narrower chewing pattern, shorter lasting chewing cycles and lower muscular activation with respect to the control group.


Cellular programming of plant gene imprinting.
Gene imprinting, the differential expression of maternal and paternal alleles, independently evolved in mammals and in flowering plants. A unique feature of flowering plants is a double-fertilization event in which the sperm fertilize not only the egg, which forms the embryo, but also the central cell, which develops into the endosperm (an embryo-supporting tissue). The distinctive mechanisms of gene imprinting in the endosperm, which involve DNA demethylation and histone methylation, begin in the central cell and sperm prior to fertilization. Flowering plants might have coevolved double fertilization and imprinting to prevent parthenogenetic development of the endosperm.


Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy.
The macrophage is known to be a multifunctional antigen presenting cells and playing a central role in inflammation. Macrophages infiltrate into malignant tumor tissues in high numbers (the so-called tumor-associated macrophages [TAMs]) and many studies over the past decade have demonstrated that macrophages have protumor functions and are closely related to tumor progression. It has been shown that protumor macrophages that have differentiated through interaction with tumor cells are involved in stem cell niches, immunosuppression, invasion, and metastasis. Consistent with these functions, studies using human tumor samples have demonstrated that a higher density of macrophages, especially macrophages with the M2 phenotype, is closely associated with worse clinical prognosis in many kinds of malignant tumors. Infiltrating TAMs themselves or polarization pathway of TAMs are considered as new therapeutic targets for the therapy of malignant tumors.


Synthesis and cytotoxic activity of novel 10-alkylated docetaxel analogs.
An alkylation method of docetaxel at the C-10 position has been established by a radical coupling reaction using a 10-xanthate derivative of 7-O-TES-10-deacetylbaccatin III and appropriate alkenes. In addition the cytotoxic activity of 10-alkylated docetaxel analogs was evaluated. Among these analogs, a derivative having a methoxycarbonyl group at the end of the alkyl moiety exhibited more potent cytotoxic activity than docetaxel.


Using machine learning to find genes associated with sudden death.
To search for significant biomarkers associated with sudden death (SD). Differential genes were screened by comparing the whole blood samples from 15 cases of accidental death (AD) and 88 cases of SD. The protein-protein interaction (PPI) network selects core genes that interact most frequently. Machine learning is applied to find characteristic genes related to SD. The CIBERSORT method was used to explore the immune-microenvironment changes. A total of 10 core genes (MYL1, TNNC2, TNNT3, TCAP, TNNC1, TPM2, MYL2, TNNI1, ACTA1, CKM) were obtained and they were mainly related to myocarditis, hypertrophic myocarditis and dilated cardiomyopathy (DCM). Characteristic genes of MYL2 and TNNT3 associated with SD were established by machine learning. There was no significant change in the immune-microenvironment before and after SD. Detecting characteristic genes is helpful to identify patients at high risk of SD and speculate the cause of death.


Taurolin for the prevention of parenteral nutrition related infection: antimicrobial activity and long-term use.
A case is described in which bis (1, 1 dioxoperhydro-1, 2, 4-thiadiazinyl-4-) methane (Taurolin) has saferly been administered on a long term basis to prevent recurrent sepsis in a patient receiving parenteral nutrition. A 26-year-old male with Crohn's disease receiving parenteral nutrition suffered repeated episodes of sepsis and developed an infected intra-atrial thrombus despite repeated courses of antimicrobial chemotherapy and surgical intervention. Continued parenteral nutrition was essential du5e to intestinal failure. Taurolin was administered in the parenteral feed, as a 0.3% solution, to prevent recrudescent and recurrent infection. This concentration was shown, in vitro, to be bactericidal to a variety of pathogenic organisms. No recurrence of sepsis, nor any evidence of side effects was observed throughout the 12 month period of Taurolin administration. After 12 months the taurolin was discontinued and within 2 weeks the patient was re-admitted with recurrent septicaemia. Following re-introduction of Taurolin the infection was controlled and the patient remains well. In our experience the addition of taurolin to the nutritive feeds of a patient at risk of sepsis is a safe and effective method of preventing recurrent sepsis.


Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. We present our 10-year experience (October 2012 to October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose-busulfan (BU), fludarabine (FLU), and melphalan (MEL). Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years) with acute myeloid leukemia (AML, n = 17), myelodysplastic syndrome (MDS, n = 4), or chronic myeloid leukemia (CML, n = 2) underwent allo-HCT post-BU-FLU-MEL. Four patients had treatment-related AML/MDS. Donor/stem cell source was matched sibling donor (MSD) PBSC (n = 7), matched unrelated donor (MUD) PBSC (n = 2), umbilical cord blood (UCB) (n = 3), or haploidentical-BMT (n = 11). Risk stratification was low (n = 2), intermediate (n = 15), high (n = 3), and very high risk (n = 1). The two patients with CML had failed tyrosine kinase inhibitor therapies. With a median follow-up of 41.6 months, the relapse rate is only 4.5% with an overall survival (OS) 100%, progression-free survival (PFS) 95.5%, and graft-versus-host-free-relapse-free survival (GRFS) 67.8%. The donor source and the acute graft-versus-host disease (GvHD) prophylaxis regimen significantly impacted grade II-IV aGvHD 66.7% versus 19.2% (p = .039) and chronic graft-versus-host-disease (cGvHD) 66.7% versus 0% (p = .002) in the patients receiving MSD or MUD PBSC compared to haplo-BMT, respectively, resulting in improved GRFS in haplo-BMT, 83.3% compared to 40% matched donor peripheral blood stem cell transplant (PBSCT) (p = .025). Our results demonstrate that BU-FLU-MEL is efficacious conditioning for disease control in young patients with myeloid malignancies undergoing MSD or alternative donor allo-HCT, but in the setting of PBSC grafts with cyclosporine A-methotrexate (CSA-MTX) GvHD prophylaxis, it results in an unacceptably high incidence of GvHD.


Implications and characteristics of high bleeding risk in East Asian patients undergoing percutaneous coronary intervention: Start with what is right rather than what is acceptable.
Recent advances in percutaneous coronary intervention (PCI) technology and medication have changed the main focus of PCI from preventing ischemic to preventing bleeding events. Bleeding risk assessment is essential for preventing bleeding. Several types of assessment tools have been established, but they are heterogeneous, making interpretation, generalization, and comparison between trials difficult. In 2019, the Academic Research Consortium (ARC) introduced a new consensus document with 20 criteria to define high bleeding risk (HBR). The applicability of the ARCHBR criteria were subsequently investigated, and 4 studies have already demonstrated wide applicability worldwide, including in Japan. Nevertheless, it hase been suggested that bleeding risk is higher in people from East Asian countries than in people from Western countries. Patients with HBR have a 3-fold higher risk of major bleeding, and in Japan approximately 50% of patients undergoing PCI have HBR. In addition, patients with overlapping factors, such as older age, renal disease, and anemia, are at increased risk of bleeding, and each additional factor further increases the risk. In Japanese patients undergoing PCI, in addition to the ARC-HBR criteria, low body weight, heart failure, and peripheral arterial disease are high-risk subsets for bleeding. The addition of these factors to the ARCHBR criteria increases the prevalence of HBR in Japanese patients to 58% and improves the sensitivity of diagnostic evaluations. The additional factors are clinically important because they are often encountered in everyday practice, and Japan's newly updated guideline has adopted them as criteria for HBR. Studies found a temporal trend over the past 20 years of a gradual and consistent increase of bleeding risk. This finding contrasts with improved outcomes in people at risk of ischemic and thrombotic events. Therefore, further research is needed to eliminate the risk of bleeding while maintaining the efficacy of antithrombotic therapy after PCI.


The epidemiology of the first described carbapenem-resistant Klebsiella pneumoniae outbreak in a tertiary care hospital in Saudi Arabia: how far do we go?
The purpose of this investigation was to describe the first documented carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in a tertiary care facility in Saudi Arabia. We initiated a prospective study to follow all cases of CRKP as well as the active surveillance of patients in areas where cases were identified. We also conducted a retrospective review of the microbiology database for any missed cases of CRKP. Pulsed field gel electrophoresis (PFGE) was conducted for the available CRKP isolates. During March 2010, a cluster of eight CRKPs was detected primarily in the adult intensive care unit (ICU). Patients with CRKPs were put under strict contact isolation, along with appropriate infection control measures. A retrospective review of K. pneumoniae isolates over the previous 6 months revealed two more CRKPs. The PFGE results during the outbreak period showed that the majority of strains were genetically indistinguishable or closely related. The majority of patients had prolonged hospital stay (91%), indwelling devices (81%), surgical procedures (74%), carbapenem use (62%), and colonization/infection with other multiple drug-resistant organisms (MDROs) (57%). Two-fifths of patients with CRKP had clinical infection and 38% died during the current hospitalization. Contact isolation, hand hygiene, environmental cleaning, and staff education may control CRKP outbreak in the acute care setting, but did not prevent endemicity.


Further in vitro exploration fails to support the allosteric three-site model.
Ongoing debate in the ribosome field has focused on the role of bound E-site tRNA and the Shine-Dalgarno-anti-Shine-Dalgarno (SD-aSD) interaction on A-site tRNA interactions and the fidelity of tRNA selection. Here we use an in vitro reconstituted Escherichia coli translation system to explore the reported effects of E-site-bound tRNA and SD-aSD interactions on tRNA selection events and find no evidence for allosteric coupling. A large set of experiments exploring the role of the E-site tRNA in miscoding failed to recapitulate the observations of earlier studies (Di Giacco, V., Márquez, V., Qin, Y., Pech, M., Triana-Alonso, F. J., Wilson, D. N., and Nierhaus, K. H. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 10715-10720 and Geigenmüller, U., and Nierhaus, K. H. (1990) EMBO J. 9, 4527-4533); the frequency of miscoding was unaffected by the presence of E-site-bound cognate tRNA. Moreover, our data provide clear evidence that the reported effects of the SD-aSD interaction on fidelity can be attributed to the binding of ribosomes to an unanticipated site on the mRNA (in the absence of the SD sequence) that provides a cognate pairing codon leading naturally to incorporation of the purported "noncognate" amino acid.


The socio-cultural significance of the diagnostic label "neurasthenia" in Japan's mental health care system.
This paper is an attempt to explore the socio-cultural significance of deliberately disguising schizophrenia as neurasthenia, neurosis or malfunction of autonomic nervous system. To understand its significance, the socio-cultural background of Japanese attitudes toward mental illness and Japan's mental health care system is also examined from a non-Western standpoint.


A system for rapidly converting quadriceps contraction to a digital signal for use in microcomputer-oriented muscle therapy and stroke patient assessment schedules.
A system for testing quadriceps performance is described involving a microcomputer, quadriceps switch, analogue-to-digital converter, electromyograph, and an interface unit that rapidly converts quadriceps contraction to a digital signal to be read by a microcomputer. A computer program, developed in response to a need for new patient assessment schedules in active rehabilitive therapy for strokes, tests the patient's control over function of the quadriceps muscle in the affected leg. The software is written in BBC BASIC and designed to run on an Acorn BBC Model 'B' microcomputer. Speed of interpretation of inputs is a few milliseconds.


The validity of subjective measures of body image disturbance.
We examined weight dissatisfaction (actual weight minus self-stated ideal weight) and weight goal (normative weight minus self-stated ideal weight) subjective indices in a large clinical sample to determine how the indices discriminate between diagnostic categories and relate to other measures of body image disturbance. Approximately 200 anorexic, bulimic, and eating disorder not otherwise specified (NOS) participants reported their self-stated ideal weight and completed the Mizes Anorectic Cognitions (MAC) Questionnaire, Eating Disorders Inventory (EDI), and Restraint Scale-Revised. Compared with bulimic and NOS participants, anorexics reported less weight dissatisfaction but had an ideal weight that is farthest from normative weight. The weight dissatisfaction measure correlates well with other measures of body image disturbance, and both measures show evidence of discriminant validity. These two measures highlight the substantial differences in the nature of body image disturbance between the eating disorder diagnostic groups. Theoretical, clinical, and practical implications are discussed.


Multiple Objective Measures of Skill (MOMS): a new approach to the assessment of technical ability in surgical trainees.
The assessment of surgical technical skills has become an important topic in recent years. This study presents the validation of a 6-task skills examination for junior surgical trainees (at the level of the Membership of the Royal College of Surgeons). Six tasks were evaluated in a project that also examined the feasibility of this method of assessment. The tasks were knowledge of sutures and instruments; knowledge of surgical devices; knot formation; skin-pad suturing, closure of an enterotomy; excision of a skin lesion; and laparoscopic manipulation. Comparisons were made between a group of junior trainees (n = 13), and a group of seniors (n = 8). Each of the 6 tasks was able to be used to discriminate between the 2 groups. In all, there were 19 primary analyses across the 6 tasks, and 17 of these showed significant differences between the groups (P values ranging from 0.037 to < 0.001). There was generally a strong correlation between the analyses, and when a mean rank was calculated, the difference between groups was significant (P = 0.005 on Mann-Whitney U test; mean ranks 13.9 and 6.3 [of 21], for juniors and seniors respectively). Reliability of the 6-task assessment was very good at 0.70 (Cronbach's Alpha). A skills examination is a feasible and effective method of assessing the technical ability of basic surgical trainees.


Development of the IgA system in the mammary gland.
1) Lymphoblasts in gut-associated lymphoid tissue, committed to the production of IgA, can home to the mammary glands of syngeneic mice and differentiate there into IgA-containing plasmablasts. The phenomenon is limited to near term and lactating recipients. 2) The ability of lymphocytes originating in gut-associated lymphoid tissue and sensitized to intestinal antigens to migrate to the mammary gland can account for the specificity of milk IgA toward intestinal microorganisms and the consequent passive protection offered to suckling infants. 3) The secretory immune system of the mammary gland is apparently under hormonal control since mammotropic hormones given to virgin females can induce morphological and functional characteristics seen naturally only during pregnancy and lactation. Examples are increased numbers of IgA plasma cells and the ability to trap their circulating precursors taken from mesenteric lymph nodes.


Early ligature of renal artery during radical laparoscopic transperitoneal nephrectomy: description of standard technique and direct access.
We compared two techniques of early ligature of the renal artery during transperitoneal laparoscopic radical nephrectomy: a standard technique and a direct approach to the artery. Of 100 patients undergoing transperitoneal laparoscopic radical nephrectomy at our institution, in the last 70, we used early renal-artery ligature. Of these, the standard technique after exposure of the vascular pedicle was used in 45 patients (group A), and ligature with a direct access to the renal artery was attempted in 25 patients (group B). No statistical differences were noted between the two groups in terms of age, lesion size, operative time, estimated blood loss, or intraoperative and postoperative complications. There were no recurrences of disease by CT evaluation in either group during follow-up (range 1-46 months). Transperitoneal laparoscopic radical nephrectomy with direct access to renal artery for early ligature is technically difficult but feasible and safe.


Perampanel attenuates epileptiform phenotype in C6 glioma.
Epileptic seizures are frequent in patients with glioma, and anticonvulsive treatment is often indicated. Glioma cells release glutamate via the Xc- antiporter system, which appears to be a major pathomechanism of glioma-associated seizures and excitotoxicity. In addition, the proliferation and survival of the tumor cells are promoted. Therefore, anticonvulsants that attenuate glutamate-mediated receptor activation could be especially effective. In this study, we investigated the effects of AMPA receptor antagonist perampanel in rat C6 glioma model. In first pilot experiments, perampanel reduced glucose uptake but had no impact of extracellular glutamate level in vitro. To analyze the effects of perampanel in vivo, we injected C6 cells orthotopically into the neocortex of Wistar rats in order to establish a model of glioma-associated epilepsy. Spontaneous recurrent discharges in brain slices were abolished upon perfusion with the AMPA receptor blocker perampanel, supporting the major role of glutamatergic excitation. With respect to the tumor progression, no effect of perampanel on survival of the animals or on glioma size was determined. Our data demonstrate that perampanel inhibit epileptiform discharges in organotypic brain slices of glioma, but failed to attenuate tumor growth or promote animal survival.


A calculation strategy for the structure determination of symmetric dimers by 1H NMR.
The structure determination of symmetric dimers by NMR is impeded by the ambiguity of inter- and intramonomer NOE crosspeaks. In this paper, a calculation strategy is presented that allows the calculation of dimer structures without resolving the ambiguity by additional experiments (like asymmetric labeling). The strategy employs a molecular dynamics-based simulated annealing approach to minimize a target function. The experimental part of the target function contains distance restraints that correctly describe the ambiguity of the NOE peaks, and a novel term that restrains the symmetry of the dimer without requiring the knowledge of the symmetry axis. The use of the method is illustrated by three examples, using experimentally obtained data and model data derived from a known structure. For the purpose of testing the method, it is assumed that every NOE crosspeak is ambiguous in all three cases. It is shown that the method is useful both in situations where the structure of a homologous protein is known and in ab initio structure determination. The method can be extended to higher order symmetric multimers.


Hydrogen ion titration of lysozyme in alcohol-water solutions.
H+ titration curves of hen egg-white lysozyme were obtained at 0.15 I in the presence of small amounts (less than 15%) of methanol, ethanol and n-propanol. The acidity constants of two groups (whose pK values in water are, respectively, 42 and 3.5) are increased in water-alcohol mixtures in comparison to water. From the evaluation of these constants as a function of alcohol concentration and hydrocarbon chain length, it is suggested that these alcohols interact specifically with lysozyme. As pK values of 4.2 and 3.5 in water are generally assigned to Asp-101 and Asp-52 respectively, it seems that interaction occurs within the active site of the enzyme.


Breed predilections and prognosis for subungual squamous cell carcinoma in dogs.
To better document the prevalence, breed predilections, and clinical behavior of subungual squamous cell carcinomas in dogs. Retrospective analysis of records from 278 812 canine biopsy submissions including 1518 subungual squamous cell carcinomas from dogs in Canada between the years 2003 and 2021. In agreement with previous studies, giant schnauzers [odds ratio (OR): 56.7], standard schnauzers (OR: 20.3), Gordon setters (OR: 18.3), black standard poodles (OR: 11.1), Kerry blue terriers (OR: 9.4), Rottweilers (OR: 7.0), and several other breeds of large black dogs had a strong predilection for development of subungual squamous cell carcinomas. In giant schnauzers and standard poodles specifically, the risk of developing additional tumors on additional digits was 56%. There were no local postoperative recurrences, and the risk of detecting metastatic disease within 5 y after initial diagnosis was very low at 4%. Moderately large black, or black and tan, dogs have a marked increase in the prevalence of subungual squamous cell carcinomas. At least in giant schnauzers and black standard poodles, the risk of developing additional similar tumors on additional digits is high, but the metastatic risk is very low. Veterinarians receiving a histologic diagnosis of subungual squamous cell carcinoma in a large black (or predominantly black) dog should advise the owners of a substantial risk that the dog will develop similar tumors on other digits in 2 or 3 y following initial diagnosis, but that the risk of local recurrence or metastatic spread is extremely low.


Effects of activity on ascending aortic velocity in children with valvar aortic stenosis.
The peak velocity of aortic blood flow was measured in 12 normal children and 20 children with valvar aortic stenosis (AS) by continuous-wave Doppler ultrasound (CWD). Measurements were made at rest, after 2 forms of exercise and, in the 11 children who underwent cardiac catheterization, while under sedation. The exercise was both formal cycle ergometry and a 200-meter jog. The peak velocity in normal children was 1.5 +/- 0.2 m/s at rest, increasing to 2.1 +/- 0.4 m/s (p less than 0.01) after running and to 1.9 +/- 0.4 m/s (p less than 0.01) after cycling. Peak velocity in children with AS was 3.5 +/- 0.8 m/s at rest, increasing to 4.4 +/- 0.8 m/s (p less than 0.01) after running and to 4.5 +/- 0.5 m/s (p less than 0.01) after cycling. The increase in peak velocity was greater in children with AS than in normal children. Measurements of left ventricular (LV) aortic pressure differences by cardiac catheterization were compared to those made by CWD, using the modified Bernoulli equation. The best correlation of the CWD prediction of LV aortic pressure differences was achieved when the children were sedated. The peak velocity of blood flow in the ascending aorta varied with level of activity, and this variability must be considered when using the Bernoulli equation to predict LV aortic pressure differences. CWD prediction of the LV aortic pressure difference was best when the child was sedated (r = 0.98). It is therefore prudent to consider the velocity measurement proximal to the AS to calculate LV aortic pressure differences more accurately unless the child is sedated.(ABSTRACT TRUNCATED AT 250 WORDS)


Income-related inequality in obesity and its determinants in Spain: What happens beyond the obesity threshold?
This paper computes and decomposes income-related inequalities in three metrics of obesity, namely, status, depth and severity, for Spain, a European country characterized by a universal health care system with very high and rising obesity prevalence rates. Furthermore, this paper investigates the main determinants of the reduction in obesity inequalities observed over time among the female Spanish population. To compute these inequality indexes, we use cross-sectional and individual-level data gathered from the Spanish National Health Survey. We document income-related inequalities in obesity, that are more pronounced in depth and severity and are to the detriment of poor women in Spain. University education is the most important determinant for all three inequality indexes. We further report that inequalities in obesity tend to decline over time for women, which is explained mainly by a substantial decrease in the degree of inequality in secondary education and a large decrease in the income elasticity of obesity.


Expression of functionally relevant cell surface markers in dibutyltin-exposed human natural killer cells.
Butyltin (BT) compounds are known for their worldwide contamination. Dibutyltin (DBT) is used as a stabilizer in plastic products, and as a deworming agent in poultry. Poultry products have been shown to contain measurable levels of DBT. Drinking water has also been reported to contain BTs due to leaching from PVC pipes. We, and others, have found measurable levels of DBT in human blood. BTs appear to increase the risk of cancer and other viral infections in exposed individuals. In previous studies we have shown that the tumor killing function of natural killer (NK) lymphocytes was greatly diminished after as little as a 1 h exposure to DBT and the inhibition continued even after removal of the compound. We also showed that there was a significant decrease in NK cell lysis of K562 target cells after an exposure to 1.5 microM DBT for 24 h. This 24 h exposure also decreased the ability of NK cells to bind to tumor cells. Loss of binding function was not seen when NK cells were exposed to 5-10 microM DBT for 1 h. However, NK cells exposed to 5 microM DBT for 1 h and then incubated in DBT-free media for 24, 48, or 96 h, showed a significant loss of tumor-binding function within 24 h. The effects of DBT exposure on seven cell surface molecules that are involved in NK-cell interactions with target cells were investigated. The results indicated that the exposure of NK cells to 1.5 microM DBT for 24 h decreased the expression of CD2, CD11a, CD16, CD11c. There was no decrease in expression of any of the markers studied when NK cells were exposed to 5 microM DBT for 1 h, consistent with the fact that a 1-h exposure had no effect on the ability of NK cells to bind tumor cells. However, when NK cells were exposed to 5 microM DBT for 1 h followed by 24, 48 or 96 h incubations in DBT-free media there was decreased expression of several of the cells surface molecules with the most dramatic decreases being in CD16 and CD56.


Delayed hydrocephalus after resection of supratentorial malignant gliomas.
To report our experience with 12 patients who developed delayed hydrocephalus after resection of supratentorial malignant gliomas. The charts of all affected patients were analysed retrospectively for clinical presentation, time interval between initial operation and occurrence of hydrocephalus, neuroradiological findings, constituents of cerebrospinal fluid (CSF), surgical treatment, and outcome. After initial good recovery following tumour resection all patients deteriorated secondarily due to development of hydrocephalus which was not encountered in the first postoperative CT-scans. Incidence is 3.4% overall and is 8.3% if exclusively calculated for frontal gliomas but increases to 15.2% if specified for patients with ventricular entry during tumour resection. Development of hydrocephalus is suggested to be due to proteinic precipitation since analysis of CSF revealed marked elevation of proteins in all patients. Whereas shunting of mere hydrocephalus yields satisfactory results outcome in cases of multiloculated hydrocephalus necessitating placement of multiple catheters is questionable. Development of hydrocephalus after resection of malignant gliomas is not rare. It should be considered in patients with delayed deterioration after initial improvement. Outcome in relation to hydrocephalus is favourable in cases of mere communicating hydrocephalus, occurrence of multiloculated hydrocephalus, however, heralds a poor prognosis.


Toxicity of an overproduced foreign gene product in Escherichia coli and its use in plasmid vectors for the selection of transcription terminators.
A rat insulin gene which was fused to Escherichia coli signals for the initiation of translation could not be retained when expressed from the strong rrnB ribosomal RNA promoters or an induced trp/lac (= tac) hybrid promoter. When the latter promoter was repressed by transformation into a lac-repressor-overproducing strain, the insulin gene fragment could be retained. Upon induction of the promoter with isopropyl-beta-D-galactosidase the growth rate of the cells was reduced, and in most cases the cells subsequently lysed. Deletion of the translational initiation signals, changing the reading frame, or insertion of an efficient transcription terminator between the promoter and the rat insulin gene each permitted retention of the fragment. The first two observations indicate that overproduction of the specific polypeptide, and not of the RNA, is detrimental to the cell. The third finding has been exploited for the testing and selection of transcription terminators. The rpoC terminator, which is located distal to the rplJL /rpoBC operon, has been shown to terminate transcripts from the rrnB promoters. It was also shown that the putative rrnB terminators, T1 and T2, each function separately in vivo.


Mutation analysis of the receptor for colicins E1-E7. A pilot study.
Thirty eight mutant clones of the colicin indicator strain Escherichia coli K 12 ROW, selected by their insensitivity to any of the colicins E1-E7, were isolated. Comparison of their sensitivity-resistance patterns to colicins E1-E7 enabled us to draw a rough preliminary map of the receptor for E colicins. In this receptor, the highly specific binding site for colicin E1 partially overlaps with the domain shared by all colicins E2 through E7. A specific binding site of this domain appears to be common for colicins E3 and E6; a part of the E3 and E6 binding site is also common for colicins E4 and E5 and a small, least specific, part also for colicins E2 and E7. Using colicin assay experiments, the binding capacity of colicin E receptor mutants could be estimated. A decreased, but not completely lost ability of certain mutants to bind colicins E, correlated to their lowered sensitivity to them, was found. Thus the phenomenon of partial colicin resistance was established, showing that colicin sensitivity--resistance is not a qualitative but a quantitative marker.


Simultaneous analysis of endosulfan, chlorpyrifos, and their metabolites in natural soil and water samples using gas chromatography-tandem mass spectrometry.
Analysis of endosulfan, chlorpyrifos, and their nonpolar metabolites in extracts from environmental aqueous and soil samples was performed using a gas chromatography-tandem mass spectrometry (GC-MS/MS) technique. Full-scan GC-MS analysis showed poor sensitivity for some of the metabolites (endodiol and endosulfan ether). A multisegment MS/MS method was developed and MS/MS parameter isolation time, excitation time, excitation voltage, and maximum excitation energy were optimized for chosen precursor ions to enhance selectivity and sensitivity of the analysis. The use of MS/MS with optimized parameters quantified analytes with significantly higher accuracy, and detection limits were lowered to ~1/6th compared with the full-scan method. Co-eluting compounds, chlorpyrifos and chlorpyrifos oxon, were also analyzed successfully in the MS/MS mode by choosing exclusive precursor ions. Analysis of soil and water phase samples from contaminated soil slurry bioreactors showed that the MS/MS method could provide more reliable estimates of these pesticide and metabolites (especially those present in low concentrations) by annulling interferences from soil organic matter.


Impact of the COVID-19 lockdown on psychological health and nutritional habits in Italy: results from the #PRESTOinsieme study.
The present work aims to present the results of the 'PRESTOinsieme' (which is 'we will be together soon' in English). The web-based survey (www.prestoinsieme.com) describes changes in lifestyle habits and symptoms of psychological discomfort in the Italian population during the COVID-19 lockdown. Cross-sectional online survey disseminated by messaging apps (ie, WhatsApp and Telegram) and social networks (ie, Instagram, Facebook and LinkedIn). Italy. Italian population older than 16 years of age. COVID-19 lockdown. Survey respondents filled out a set of validated questionnaires aimed at assessing lifestyle habits and psychological health, that is, the General Health Questionnaire (GHQ-12) to screen for psychological distress, the Impact of Event Scale-Revised (IES-R) to screen for post-traumatic stress and the Center for Epidemiologic Studies Depression Scale (CES-D). Survey respondents totalled 5008. Moderate or severe psychological distress was reported in 25.5% and 22% of survey respondents, respectively. Lower age, female gender, being unemployed (OR 1.57, 95% CI 1.22 to 2.02) or being a student (OR 1.73, 95% CI 1.31 to 2.28) were predictors of more severe depressive symptoms. The present study is one of the largest population-based surveys conducted in Italy during the first COVID-19 lockdown, providing valuable data about the Italian population's psychological health. Further studies should be conducted to understand whether psychological distress persists after the end of the lockdown.


[Our experience in the surgical treatment of cysts and fistulas of the thyroglossal duct].
A clinical series of cysts and fistulas of the thyroglossal tract has been examined. Clinical aspects of this pathology and the results obtained with surgical treatment are compared with reported data.


The topography of nerve cell loss from the locus caeruleus in elderly persons.
A topographical analysis of nerve cell loss from the locus caeruleus in "mentally normal" old people shows cell loss to be uniformly diffuse throughout the whole nucleus with no preferential involvement of any one particular area. Such findings contrast with those of ours on Alzheimer's disease and suggest differing mechanisms underlying the cell loss of old age and Alzheimer's disease. Cell loss in Alzheimer's disease is thought to relate to primary pathogenetic events in terminal fields of cerebral cortex. In "normal" old age, cell loss may be determined by changes occurring at perikaryal level possibly in respect of the cytotoxic effects of noradrenaline degradation and neuromelanin accumulation.


Toll-like Receptor 9 Can be Activated by Endogenous Mitochondrial DNA to Induce Podocyte Apoptosis.
Toll-like receptor 9 (TLR9) senses bacterial DNA characteristic of unmethylated CpG motifs to induce innate immune response. TLR9 is de novo expressed in podocytes of some patients with glomerular diseases, but its role in podocyte injury remains undetermined. Since TLR9 activates p38 MAPK and NFkB that are known to mediate podocyte apoptosis, we hypothesized that TLR9 induces podocyte apoptosis in glomerular diseases. We treated immortalized podocytes with puromycin aminonucleosides (PAN) and observed podocyte apoptosis, accompanied by TLR9 upregulation. Prevention of TLR9 upregulation by siRNA significantly attenuated NFκB p65 or p38 activity and apoptosis, demonstrating that TLR9 mediates podocyte apoptosis. We next showed that endogenous mitochondrial DNA (mtDNA), whose CpG motifs are also unmethylated, is the ligand for TLR9, because PAN induced mtDNA accumulation in endolysosomes where TLR9 is localized, overexpression of endolysosomal DNase 2 attenuated PAN-induced p38 or p65 activity and podocyte apoptosis, and DNase 2 silencing was sufficient to activate p38 or p65 and induce apoptosis. In PAN-treated rats, TLR9 was upregulated in the podocytes, accompanied by increase of apoptosis markers. Thus, de novo expressed TLR9 may utilize endogenous mtDNA as the ligand to facilitate podocyte apoptosis, a novel mechanism underlying podocyte injury in glomerular diseases.


Characterization of a copper responsive promoter and its mediated overexpression of the xylanase regulator 1 results in an induction-independent production of cellulases in Trichoderma reesei.
Trichoderma reesei represents an important workhorse for industrial production of cellulases as well as other proteins. The large-scale production is usually performed in a substrate-inducing manner achieved by a fine-tuned cooperation of a suite of transcription factors. Their production and subsequent analysis are, however, often either difficult to manipulate or complicated by the concomitant production of other inducible proteins. Alternatives to control gene expression independent of the nutritional state are thus preferred in some cases to facilitate not only biochemical studies of proteins but also genetic engineering of the producer. We identified a copper transporter encoding gene tcu1 (jgi:Trire2:52315) in T. reesei, the transcription of which was highly responsive to copper availability. Whereas excess copper repressed the expression of tcu1 from T. reesei, eliminating copper addition in the medium resulted in a high-level transcription of tcu1. The usefulness of the system was further illustrated by the high-level expression of specific cellulases driven by the tcu1 promoter in T. reesei when cultivated on D-glucose or glycerol as the sole carbon source. A recombinant T. reesei strain, which overexpressed the main transcription activator of hydrolases (xylanase regulator 1) under the control of tcu1 promoter, was found to be relieved from the carbon catabolite repression and thus displayed a constitutive cellulase expression. Moreover, the amount and activities of cellulases produced by this strain on glycerol or glucose fully recapitulated those of the parental strain produced on Avicel. Expression of T. reesei tcu1 gene was tightly controlled by copper availability, and a homologous protein expression system was developed based on this promoter. Deregulation of XYR1 (xylanase regulator 1) mediated by the tcu1 promoter not only overcame the carbon catabolite repression of cellulases but also resulted in their full expression even on the non-inducing carbon sources.


Increased biventricular hemodynamic forces in precapillary pulmonary hypertension.
Precapillary pulmonary hypertension (PHprecap) is a condition with elevated pulmonary vascular pressure and resistance. Patients have a poor prognosis and understanding the underlying pathophysiological mechanisms is crucial to guide and improve treatment. Ventricular hemodynamic forces (HDF) are a potential early marker of cardiac dysfunction, which may improve evaluation of treatment effect. Therefore, we aimed to investigate if HDF differ in patients with PHprecap compared to healthy controls. Patients with PHprecap (n = 20) and age- and sex-matched healthy controls (n = 12) underwent cardiac magnetic resonance imaging including 4D flow. Biventricular HDF were computed in three spatial directions throughout the cardiac cycle using the Navier-Stokes equations. Biventricular HDF (N) indexed to stroke volume (l) were larger in patients than controls in all three directions. Data is presented as median N/l for patients vs controls. In the RV, systolic HDF diaphragm-outflow tract were 2.1 vs 1.4 (p = 0.003), and septum-free wall 0.64 vs 0.42 (p = 0.007). Diastolic RV HDF apex-base were 1.4 vs 0.87 (p < 0.0001), diaphragm-outflow tract 0.80 vs 0.47 (p = 0.005), and septum-free wall 0.60 vs 0.38 (p = 0.003). In the LV, systolic HDF apex-base were 2.1 vs 1.5 (p = 0.005), and lateral wall-septum 1.5 vs 1.2 (p = 0.02). Diastolic LV HDF apex-base were 1.6 vs 1.2 (p = 0.008), and inferior-anterior 0.46 vs 0.24 (p = 0.02). Hemodynamic force analysis conveys information of pathological cardiac pumping mechanisms complementary to more established volumetric and functional parameters in precapillary pulmonary hypertension. The right ventricle compensates for the increased afterload in part by augmenting transverse forces, and left ventricular hemodynamic abnormalities are mainly a result of underfilling rather than intrinsic ventricular dysfunction.


[The history of the weekly revue Die medicinische Reform (1848/49) and exchange of letters between Rudolf Virchows and his publisher George Reimer].
The medical journal Medicinische Reform. Eine Wochenschrift edited by Rudolf Virchow and Rudolf Leubuscher in Berlin from July 1848 to June 1849 was in spite of its short life-time one of the most important and influential periodicals during the time of German revolution and medical reforms in the middle of the 19th century. The paper gives a view of the history of edition of this ephemeral but outstanding journal as an essential source for our knowledge of the development of social medicine in Germany. Moreover it can be seen as an example for a new kind of modern scientific journals. Printing the Medicinische Reform through the years of revolution in 1848/49 was on the merits of the publishing house of Georg Reimer. In 1849 Virchow himself stopped editing the paper. Several reprints show the importance of the periodical for the history of siences (1879 Berlin, partial by Virchow; 1975 Hildesheim; 1983 Berlin). The article ends with a first complete publication of the correspondence between Virchow and Reimer about the weekly Medicinische Reform.


Assessment of reference values for polychlorinated biphenyl concentration in human blood.
A chemical factory which produced polychlorinated biphenyls (PCBs) operated in Brescia, North Italy, (about 200000 inhabitants) from the 1930s to the 1980s. High levels of PCBs were recently found in soil, food and people living in an area close to the factory. We performed a survey among the general population living in non-polluted areas of the town in order to define the reference values (RVs) of the non-exposed population. A random sample of subjects aged 20-79 years (50% males) was selected. Participants underwent PCB determination and were interviewed on their residential and occupational history and current diet. For RV determination, subjects who had resided in the polluted area or consumed any food produced in the area in their lifetime were excluded. Eight hundred and ninety-two subjects were contacted, 579 (65%) of whom agreed to participate; 311 of them were considered for RV determination (53% male, mean age=48.7 years). Total PCB serum levels, computed as the sum of the 24 congeners determined, were: mean=5.15ng/ml (SD=8.83), median=4.11ng/ml, range=0.4-34.12ng/ml, 95th centile=14.38ng/ml. Lipid-adjusted mean and median were 897 and 705ng/g lipid, respectively. PCB values showed positive correlations with age (Spearman's r=0.76) and with serum concentration of total cholesterol (r=0.40) and triglycerides (r=0.36). No association was found with gender, cigarette smoking, alcohol or diet. Seven PCB congeners, (PCB 180, 153, 138, 170, 194, 118, and 156), including those at higher chlorination, were present in more than 30% of the subjects and contributed 99% of the total PCB levels, with a modest role of dioxin-like congeners.


Incidence of and Risk Factors for Free Bowel Perforation in Patients with Crohn's Disease.
Incidence of and risk factors for intestinal free perforation (FP) in patients with Crohn's disease (CD) are not established. To establish rate of and risk factors for FP in a large cohort of CD patients. Medical records of CD patients who visited Asan Medical Center from June 1989 to December 2012 were reviewed. After matching the FP patients to controls (1:4) by gender, year, and age at CD diagnosis, and disease location, their clinical characteristics were compared using conditional logistic regression analysis. Among 2043 patients who were included in our study cohort, 44 patients (2.15%) developed FP over a median follow-up period of 79.8 months (interquartile range 37.3-124.6), with an incidence of 3.18 per 1000 person-years [95% confidence interval (CI) 2.37-4.28]. All 44 patients underwent emergency surgery, and eight patients underwent reoperation within 12 months (8/44, 18.2%). Multivariable-adjusted analysis revealed that anti-TNF therapy [odds ratio (OR), 3.73; 95% CI 1.19-11.69; p = 0.024] was associated with an increased risk of FP. The incidence of FP in a large cohort of Korean CD patients was 2.15%, which was similar to that in Western reports. Anti-TNF therapy could be risk factors for FP.


Differentiation of the pulmonary surfactant system. Disaturated phosphatidylcholine accumulation in fetal rat lung in vivo and in vitro.
Fetal rat lung was placed in organ culture at 15 days gestation (22 days total gestation period), before biochemical and morphological development of the pulmonary surfactant system. At the fifth day of culture numerous Type II cells containing lamellar bodies were present as determined by electron micrography. Phospholipid accumulation in the cultures increased abruptly beginning at 6 days in culture. The phospholipid which accumulated between the sixth and twelfth culture days was composed of 21--27% disaturated phosphatidylcholines. Both the percent of disaturated phosphatidylcholines in the phospholipid fraction and the qualitative pattern of accumulation as a function of time were similar to observations for fetal rat lung developing in vivo. The data presented provide evidence for development of the pulmonary surfactant system in organ culture in vitro.


The impact of health plan report cards on managed care enrollment.
How does the release of health plan performance ratings influence employee health plan choice? A natural experiment at General Motors (GM) Corporation provides valuable evidence on this question. During the 1997 open enrollment period, GM disseminated a health plan report card for the first time. By comparing 1996 and 1997 enrollment patterns, our analysis estimates the impact of the report card information while accounting for fixed, unobserved plan traits. Results indicate that employees are less likely to enroll in plans requiring relatively high out-of-pocket contributions. Results with respect to report card ratings suggest that individuals avoid health plans with many below average ratings.


Anti-inflammatory activities of two new deoxygenated N-acetyl glucosamines in lipopolysaccharide-activated mouse macrophage RAW264.7 cells.
Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements. We investigated the anti-inflammatory properties of two synthesized derivatives of N-acetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1β, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively. Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF α and IL-1β expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.


Dysphagia rehabilitation in Japan.
This article describes the features of Japanese dysphagia rehabilitation, particularly where it differs from that in the United States. Many kinds of professionals participate in dysphagia rehabilitation; nurses and dental associates take important roles, and the Japanese insurance system covers that. Videofluorography and videoendoscopy are common and are sometimes done by dentists. Intermittent catheterization is applied to nutrition control in some cases. The balloon expansion method is applied to reduce pharyngeal residue after swallowing. If long-term rehabilitation does not work effectively in dysphagia due to brainstem disorder, the authors consider reconstructive surgery to improve function.


Critical role of bone marrow angiotensin II type 1 receptor in the pathogenesis of atherosclerosis in apolipoprotein E deficient mice.
It is suggested that the angiotensin II (Ang II)-Ang II type 1 receptor (AT1R) pathway plays a pivotal role in the pathogenesis of atherosclerosis. Recently, bone marrow (BM) cells were reported to express AT1R. Here, we investigated the role of AT1R in BM in the pathogenesis of atherosclerosis. Genetic ablation or pharmacological blockade of AT1R led to a significant reduction and stabilization of atherosclerotic lesions in ApoE-/- mice. To elucidate the role of AT1R in BM, we generated several BM chimeric mice. Ang II promoted atherosclerosis progression in the BM chimeric mice that had AT1aR in BM, regardless of the absence of AT1aR in the recipient vasculature (P<0.05). BM chimeric mice whose BM AT1aR was disrupted showed significantly less atherosclerotic lesions in aorta (P<0.05) and more stable plaque with reduced accumulation of BM-derived cells compared with BM chimeric mice that had AT1aR-positive BM. Most of the BM-derived cells in atheroma were positive for a macrophage marker and expressed matrix metalloproteinase (MMP)-9 and monocyte chemoattractant protein-1. Our findings suggest that AT1R in BM plays an important role in the pathogenesis of atherosclerosis.


Nucleation and growth of apatite on chemically treated titanium alloy: an electrochemical impedance spectroscopy study.
Bone-like apatite formed on the surface of Ti6Al4V pretreated with NaOH solution after having been immersed in simulated body fluid (SBF), while no apatite formed on the surface of untreated Ti6Al4V. In the present study, electrochemical impedance spectroscopy (EIS) measurement was used to investigate the nucleation and growth of apatite on chemically treated Ti6Al4V immersed in the SBF solution, and the difference between the behaviors of treated and untreated Ti6Al4V. Appropriate equivalent circuit models were constructed to describe the nucleation and growth of apatite, and thin oxide film formed on the surface of untreated Ti6Al4V. It was found that EIS is a useful method for investigating the nucleation and growth of bone-like apatite on Ti6Al4V pretreated with NaOH solution.


The structure of memorized knowledge in students and clinicians: an explanation for diagnostic expertise.
This paper provides for the first time evidence of a consistent difference in the memory structures of novice and expert clinicians. The diagnostic performance of first- and third-year clinical medical students, senior house officers, registrars and consultants on four clinical problems in general medicine was studied. Comparisons were made of all diagnostic interpretations offered and the forceful features (personally important pieces of information which act as a key to particular memory structures which in turn give rise to the clinical interpretation) from which these were derived. Results demonstrate that the numbers of interpretations made and the numbers of forceful features identified did not differ significantly between groups (P greater than 0.05). However, the actual interpretations made in three out of four cases, and the actual forceful features identified in all cases, did differ significantly between groups (P less than 0.05). The numbers of interpretations made by all groups were large and demonstrated enormous variability. Highly individualized multiple responses to clinical information are associated with easy diagnoses. We conclude that there is no difference between groups of differing clinical experience in the breadth of thought but that there are marked differences in the precise content and structure of thought. This allows coherent explanation of variation in diagnostic expertise with clinical experience. The significance of the findings is discussed.


Relationship of circulatory BDNF with cognitive deficits in people with Parkinson's disease.
Brain-derived neurotrophic factor (BDNF) and cognitive function are diminished in people with Parkinson's disease (PD). The relationship of cognitive function and serum level of BDNF, however is yet to be examined. The aim of this study was to examine serum BDNF levels in PD. Subsequently, the relationship of cognitive function to the serum levels of BDNF was evaluated. Serum BDNF levels were measured in 29 idiopathic PD subjects and 30 healthy-matched controls using ELISA technique. Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA) scale. Serum BDNF levels and MOCA total score were significantly lower (P<0.001) in PD patients versus healthy controls. MOCA total score correlated with serum BDNF (r=0.44; P=0.012) but not with age, years of education, duration of disease and severity of symptoms. The regression analysis showed that serum BDNF accounted (P=0.019) for 19% of MOCA total score variance. The data confirm lowered serum BDNF in PD. Additionally; it suggests that BDNF may play a role in the cognitive deficit of PD. Further studies are required to identify association of BDNF in cognitive decline with PD.


Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease.
Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024). Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications.


Synthesis and anticancer profile of novel sphingoid base-like compounds with a quaternary stereocentre.
The synthesis of novel sphingoid base-like compounds with a quaternary stereocentre was achieved in a sequence featuring [3,3]-sigmatropic rearrangements and olefin cross-metathesis transformation as the key reaction steps, which were accompanied by the rational selection of suitable functional group transformations. The stereochemistry of the desired tetra-substituted carbon bearing nitrogen functionality was determined via NOESY experiments of the advanced oxazolidine-2-thiones. Cell viability experiments revealed significant antiproliferative/cytotoxic activity of the target compounds 7, ent-7 and 29 against the Jurkat cell line, with the IC50 values of 6.6 μM, 5.6 μM and 6.1 μM, respectively.


Foreword.
Delivering multifaceted, quality care to women living with metastatic breast cancer (MBC) demands professional competence and an advanced level of practice. The breast cancer nursing community is evolving to meet this need as more nurses are appointed specifically for the advanced disease setting, while nurses who previously worked only in early stage disease are now delivering care across the disease trajectory, fulfilling a 'diagnosis to death' nursing model. The MBC nursing community, linked by UK charity Breast Cancer Care and the Roche Nursing Matters programme, offers forums for learning, and provides ongoing support to this group of nurses. This supplement has been commissioned by Roche Products Ltd to continue supporting nurses who treat patients with MBC by sharing learning and best practice, with a view to encouraging innovation in service delivery.


Antibodies to granulocytes detected by an indirect immunofluorescence method not requiring chemical modification of cells.
IgG antibodies to neutrophil polymorphonuclear cells (PMNs) were detected by a simple indirect immunofluorescence method that did not require chemical or enzymatic modification of the cells. Based on recent information about the human PMN Fc gamma-receptor, nonspecific binding of IgG to PMNs was virtually completely prevented by incubating cells at 37 degrees C with human serum diluted 1 to 3 in the presence of a high concentration of rabbit IgG. This also facilitated distinction of sera with weak anti-PMN activity from normal sera. On the other hand, nonspecific staining remained on a fraction (10-25%) of mononuclear leukocytes. Following first-time transfusion of 0.5 to 5 units of whole blood or red cell concentrate, 4 of 27 patients (15%) developed anti-leukocyte antibodies. Anti-leukocyte antibodies were detected in 51 percent of 47 patients with reported febrile transfusion reactions; the IgG antibodies bound to PMNs in 38 percent of these 47 patients. Since only about one in three patients with febrile transfusion reactions had detectable IgG anti-PMN antibodies, fever may be caused by lysis of leukocytes other than PMNs.


Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral white matter at 1.5 T.
Several studies have investigated the T1 and T2 relaxation time of choline, creatine and N-acetyl aspartate in cerebral white matter in normal human subjects. However, these studies demonstrate a large variation in T1 and T2 values. In the present study, relaxation times of choline, creatine and N-acetyl aspartate were determined in cerebral white matter in 15 control subjects (age 21 +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively.


Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin.
Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum.


Synthesis of functionalized 2-aryl-5-nitro-1H-indoles and their activity as bacterial NorA efflux pump inhibitors.
In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Staphylococcus aureus. The NorA protein from the major facilitator superfamily of efflux pumps confers resistance to a variety of structurally dissimilar antimicrobials such as norfloxacin, ethidium bromide, berberine and acriflavin. The compound [4-benzyloxy-2-(5-nitro-1H-2-yl)-phenyl]-methanol was the most potent pump inhibitor.


Epithelial markers to detect occult microinvasion in serous ovarian tumors.
Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis "serous borderline tumors with stromal microinvasion" seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of "eosinophilic metaplastic" cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that "eosinophilic metaplastic" cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of microinvasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)