Heterochromatin Protein 1 (HP1) inhibits stem cell proliferation induced by ectopic activation of the Jak/STAT pathway in the Drosophila testis.
Stem cells can divide asymmetrically with respect to cell fate, producing a copy of themselves (self-renewal), while giving rise to progeny that will differentiate along a specific lineage. Mechanisms that bias the balance towards self-renewal or extend the proliferative capacity of the differentiating progeny can result in tissue overgrowth and, eventually, the formation of tumors. Recent work has explored the role of heterochromatin and heterochromatin-associated proteins in the regulation of stem cell behavior under homeostatic conditions, but less is known about their possible roles in potentiating or suppressing stem cell overproliferation. Here we used ectopic activation of the Jak/STAT pathway in germline and somatic stem cells of the D. melanogaster testis as an in vivo model to probe the function of Heterochromatin Protein 1 (HP1) in stem cell overproliferation. Forced expression of HP1 in either early germ or somatic cells suppressed the overgrowth of testes in response to ectopic Jak/STAT activation. Interestingly, HP1 expression led to distinct phenotypes, depending on whether it was overexpressed in somatic or germ cells, possibly reflecting different cell-autonomous and non-autonomous effects in each cell type. Our results provide a new framework for further in vivo studies aimed at understanding the interactions between heterochromatin and uncontrolled stem cell proliferation, as well as the complex cross-regulatory interactions between the somatic and germline lineages in the Drosophila testis.


Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature.
Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a 2 and a half year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases; In addition, 27 per cent of cases were reportedly "sterile." These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated.


Stem cell toxicity of oxazaphosphorine metabolites in comparison to their antileukemic activity.
The oxazaphosphorine agent cyclophosphamide (CP) is an alkylating agent with a relative low stem cell toxicity. The aim of this study was to further evaluate the stem cell toxicity of the active metabolites of CP and its structural analogue ifosfamide (IFO) in comparison to their antileukemic efficacy. Cells of different malignant hematologic disorders (HL-60, HS-Sultan and THP-1) and CD34+ stem cells were treated with cytotoxic CP-metabolite mafosfamide (MAFO) and IFO-metabolites 4-hydroxy-IFO (4-OH-IFO) and chloroacetaldehyde. The clonogenity of the cells was investigated by using a colony-forming assay. All metabolites reduced the formation of both tumor-derived colonies and stem cell-derived CFU-GMs in a concentration-dependent manner. Our data showed a relative tumor-specific, stem cell protecting action of the substances tested with a higher toxicity against tumor cells (IC(50) against HS-Sultan: MAFO 1.1 microM; 4-OH-IFO 1.3 microM; CAA 3 microM) than against stem cells (IC(50) MAFO 14.8 microM; 4-OH-IFO 16.9 microM; CAA 14 microM). However, while the cytotoxic action of 4-OH-IFO corresponded to MAFOs activity, CAAs cytotoxic effect against the hematologic tumor cells was lower. In conclusion, the results confirm the observed cytotoxicity of CAA against solid tumors for cells of malignant hematologic disorders. Although the relative cytotoxic specificity of CAA is lower than for 4-OH-IFO and MAFO, also CAA, like 4-OH-IFO and MAFO, was found to be in part a tumoricidal, stem cell protecting substance.


Influence of coal ash on the characteristics of corn straw pyrolysis products.
To discern influence of inorganic substances in coal on the co-utilization of coal and biomass, coal ash (CA) was added to biomass for pyrolysis. TG-FTIR and fixed bed reactor were used for pyrolysis of corn straw (CS) with CA. XRF and XRD were used to detect the reactants and products components, respectively. At constant heating rate. CA slightly promoted char and gaseous products formation. In the fixed bed reactor, the effect varied with temperature and CA addition ratio. The char and gas yields were changed due to the Si, Al, and other inorganic substances in CA. CS/CA = 1 had the greatest influence on char. Gas yield were reduced at 500-700 °C, but increased at 800 °C with a small proportion of CA. When CA was 1/10 of CS at 800 °C, the gas yield increased by 9.3%, and CH4, CO, and H2 increased by 26.1%, 8.4%, and 37.7%, respectively.


Purification and immunologic reactivity of Hymenolepis diminuta surface antigens.
The outer part of Hymenolepis diminuta tegument was extracted with 3 M KCl. The antigen was adsorbed from the extract on an affinity column containing H. diminuta-infected rat immunoglobulin immobilized on Sepharose 4B and could be eluted with 2.5 M urea at pH 2.8. Analysis of polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of both the crude extract and material eluted from the column showed that the latter was markedly purified. Double diffusion and immunoelectrophoresis revealed 11 and 4 antigenic components in the crude extract and purified preparation, respectively.


The somatic marker hypothesis: a critical evaluation.
The somatic marker hypothesis (SMH; [Damasio, A. R., Tranel, D., Damasio, H., 1991. Somatic markers and the guidance of behaviour: theory and preliminary testing. In Levin, H.S., Eisenberg, H.M., Benton, A.L. (Eds.), Frontal Lobe Function and Dysfunction. Oxford University Press, New York, pp. 217-229]) proposes that emotion-based biasing signals arising from the body are integrated in higher brain regions, in particular the ventromedial prefrontal cortex (VMPFC), to regulate decision-making in situations of complexity. Evidence for the SMH is largely based on performance on the Iowa Gambling Task (IGT; [Bechara, A., Tranel, D., Damasio, H., Damasio, A.R., 1996. Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex. Cerebral Cortex 6 (2), 215-225]), linking anticipatory skin conductance responses (SCRs) to successful performance on a decision-making paradigm in healthy participants. These 'marker' signals were absent in patients with VMPFC lesions and were associated with poorer IGT performance. The current article reviews the IGT findings, arguing that their interpretation is undermined by the cognitive penetrability of the reward/punishment schedule, ambiguity surrounding interpretation of the psychophysiological data, and a shortage of causal evidence linking peripheral feedback to IGT performance. Further, there are other well-specified and parsimonious explanations that can equally well account for the IGT data. Next, lesion, neuroimaging, and psychopharmacology data evaluating the proposed neural substrate underpinning the SMH are reviewed. Finally, conceptual reservations about the novelty, parsimony and specification of the SMH are raised. It is concluded that while presenting an elegant theory of how emotion influences decision-making, the SMH requires additional empirical support to remain tenable.


Prevalence and Prognostic Value of Malnutrition Among Elderly Cancer Patients Using Three Scoring Systems.
Background: Malnutrition is common in patients with cancer and is associated with adverse outcomes, but few data exist in elderly patients. The aim of this study was to report the prevalence of malnutrition using three different scoring systems and to examine the possible clinical relationship and prognostic consequence of malnutrition in elderly patients with cancer. Methods: Nutritional status was assessed by using controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and the nutritional risk index (NRI). Quality-of-life (Qol) was assessed during admission by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Performance status (PS) was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. The relationship between nutritional status and overall survival and Qol were examined. Results: Data were available for 1,494 elderly patients with cancer (63.65% male), the mean age was 70.76 years. According to the CONUT, NRI, and PNI, 55.02, 58.70, and 11.65% patients were diagnosed with malnutrition, respectively. Worse nutritional status was related to older, lower BMI, lower hand grip strength, and more advanced tumor stage. All malnutrition indexes were correlated with each other (CONUT vs. PNI, r = -0.657; CONUT vs. NRI scores, r = -0.672; PNI vs. NRI scores, r = 0.716, all P < 0.001). During a median follow-up of 43.1 months, 692 (46.32%) patients died. For patients malnourished, the incidence rate (events-per-1,000person-years) was as follows: CONUT (254.18), PNI (429.91), and NRI (261.87). Malnutrition was associated with increased risk for all-cause mortality (adjust HR [95%CI] for CONUT: 1.09 [1.05-1.13], P < 0.001; PNI: 0.98[0.97-0.99], P < 0.001; NRI: 0.98 [0.98-0.99], P < 0.001). All malnutrition indexes improved the predictive ability of the TNM classification system for all-cause mortality. Deterioration of nutritional status was associated with deterioration in Qol parameters and immunotherapeutic response (P < 0.001). Conclusions: Malnutrition was prevalent in elderly patients with cancer, regardless of the assessment tools used, and associated with lower Qol and the immunotherapy response.


Semi-synthetic minimal cells as a tool for biochemical ICT.
Biological systems evolved with the ability to communicate with their biotic surroundings through chemical signalling. Production, perception and decoding of the information carried by signal molecules allow individuals of a community to interact, cooperate, and coordinate their activities, establishing complex social behaviours. In this paper we speculate about the opportunity to use semi synthetic minimal cells (SSMCs) as artificial entities able to communicate, by processing biochemical information, with natural systems. SSMCs are liposome-based cell-like molecular assemblies designed for displaying minimal cellular functions, like gene transcription and translation. The technological advancements in the last few years led to successful production of functional proteins in SSMCs raises the possibility to generate semi synthetic cell-like systems expressing the biochemical apparatus for signal molecules production, perception and decoding. The variety of chemical "languages" evolutionary selected by bacteria to communicate provides a broad spectrum of biochemical opportunities exploitable to reach this goal in the near future. More in general, the consequences arising from the construction of synthetic systems capable of communicating with natural living organisms would greatly impact the applications of synthetic biology and biochemical-based information and communication technologies (ICTs) in medical sciences, for example for smart programmable and drug-producing systems.


Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer.
Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromodomain-containing protein 7 (BRD7) is implicated in multiple malignancies; however, there are no selective chemical probes to study its function in disease. Using crystal structures of BRD7 and BRD9 bromodomains (BDs) bound to BRD9-selective ligands, we identified a binding pocket exclusive to BRD7. We synthesized a series of ligands designed to occupy this binding region and identified two inhibitors with increased selectivity toward BRD7, 1-78 and 2-77, which bind with submicromolar affinity to the BRD7 BD. Our binding mode analyses indicate that these ligands occupy a uniquely accessible binding cleft in BRD7 and maintain key interactions with the asparagine and tyrosine residues critical for acetylated lysine binding. Finally, we validated the utility and selectivity of the compounds in cell-based models of prostate cancer.


Reduced risk of myocardial infarct and revascularization following coronary artery bypass grafting compared with percutaneous coronary intervention in patients with chronic kidney disease.
Coronary atherosclerotic disease is highly prevalent in chronic kidney disease (CKD). Although revascularization improves outcomes, procedural risks are increased in CKD, and unbiased data comparing coronary artery bypass grafting (CABG) and percutaneous intervention (PCI) in CKD are sparse. To compare outcomes of CABG and PCI in stage 3 to 5 CKD, we identified randomized trials comparing these procedures. Investigators were contacted to obtain individual, patient-level data. Ten of 27 trials meeting inclusion criteria provided data. These trials enrolled 3993 patients encompassing 526 patients with stage 3 to 5 CKD of whom 137 were stage 3b-5 CKD. Among individuals with stage 3 to 5 CKD, mortality through 5 years was not different after CABG compared with PCI (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.67-1.46) or stage 3b-5 CKD (HR 1.29, CI 0.68-2.46). However, CKD modified the impact on survival free of myocardial infarction: it was not different between CABG and PCI for individuals with preserved kidney function (HR 0.97, CI 0.80-1.17), but was significantly lower after CABG in stage 3-5 CKD (HR 0.49, CI 0.29-0.82) and stage 3b-5 CKD (HR 0.23, CI 0.09-0.58). Repeat revascularization was reduced after CABG compared with PCI regardless, of baseline kidney function. Results were limited by unavailability of data from several trials and paucity of enrolled patients with stage 4-5 CKD. Thus, our patient-level meta-analysis of individuals with CKD randomized to CABG versus PCI suggests that CABG significantly reduces the risk of subsequent myocardial infarction and revascularization without affecting survival in these patients.


Epidural cerebrospinal fluid collection following lumbar puncture in an adult patient: A case report and literature review.
Cerebrospinal fluid (CSF) leakage into the epidural space following lumbar puncture (LP) has been documented in pediatric patients, but there have been no reported cases in adults. We report an epidural CSF leak in an adult who presented with back pain, positional headache, urinary retention, and constipation following an LP performed as a part of a research study. The patient's magnetic resonance (MR) scan showed an extensive epidural CSF collection. Following placement in a recumbent position for 72 h, the collection fully resolved along with his neurological complaints. Symptomatic epidural CSF collections rarely occur in adults following LPs. Nevertheless, the management remains the same as for pediatric patients; bed rest for 72 h results typically in full resolution of symptoms/signs and regression of the collection on MR studies.


Ayalysis of translational parameters in cultured cells.
A method is described for the measurement of protein synthesis parameters in cultured cells. Ribosome transit times, polyribosome size distribution and relative synthetic rates are measured on individual cultures of cells. This method is applied to an analysis of cycloheximide (1 micrometer) inhibition of protein synthesis in cultured mouse hepatoma cells.


Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.
Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity. 17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner. The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM. Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2. Overall, the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue.


D2 dopamine receptor gene expression by cholinergic neurons in the rat striatum.
In situ hybridization with D2 receptor probe and immunohistochemistry with choline acetyltransferase (ChAT) antibody performed on adjacent sections demonstrate dopamine D2 receptor gene expression in cholinergic neurons of the rat caudate-putamen and nucleus accumbens. Eighty per cent of cholinergic neurons in the striatum contain detectable D2 receptor mRNA. The other neurons without detectable D2 mRNA do not display specific localization or aspect in the caudate-putamen and nucleus accumbens as compared to the other cholinergic neurons. The absence of detectable D2 mRNA in certain cholinergic neurons can be due to the limited sensitivity of the procedure that would not detect low mRNA levels, or alternatively can reflect the existence of two cholinergic cell populations in the striatum, one of which would not express the D2 receptor gene. The other forebrain cholinergic neurons do not contain D2 mRNA.


Orbital hydrocephalus: a proven cause for optic atrophy.
A 4-year-old boy with bilateral optic sheath enlargement and progressive optic atrophy and blindness is presented. Computed tomography demonstrated hydrocephalus and enlargement of the optic nerve sheath complex. The child died during an attempted repair of hypoplastic atrioventricular valves. Autopsy demonstrated a patulous perioptic subarachnoid space and optic atrophy. This condition has been described in the literature but has not had radiologic-pathologic correlation. With the availability of magnetic resonance imaging, this diagnosis may be made prospectively, thus, it is important for the radiologist to be aware of this entity because optic atrophy and blindness may be prevented by early diagnosis and surgery.


Urinary Tract Infection.
Urinary tract infections (UTIs) are common in both inpatient and outpatient settings. This article provides an evidence-based, clinically relevant overview of management of UTIs, including screening, diagnosis, treatment, and prevention. Conditions covered include acute cystitis (both uncomplicated and complicated), catheter-associated UTI, and asymptomatic bacteriuria in both women and men.


Glutamine protects intestinal barrier function of colon epithelial cells from ethanol by modulating Hsp70 expression.
In this study, we investigated the protective effect of glutamine on barrier dysfunction induced by ethanol, by using human epithelial colorectal adenocarcinoma cells (Caco-2). Our results show that addition of glutamine to culture medium significantly improved the disruption of integrity caused by ethanol, which was associated with increased expression of heat shock protein 70 (Hsp70). Ethanol exposure moderately activates heat shock factor 1 (HSF1), which was characterized by increased DNA-binding activity and phosphorylation status of HSF1. Remarkably, glutamine treatment enhanced ethanol-mediated expression of Hsp70 and activation of HSF1. Up-regulation of Hsp70 by pretreatment with heat stress also promoted recovery from the ethanol-induced barrier dysfunction. Taken together, these observations indicate that glutamine protects the intestinal barrier function in Caco-2 cells, in part by modulating HSF1-mediated Hsp70 expression.


[Developmental outcome of 5-year-old children born to opiate-dependent mothers: effects of a multidisciplinary intervention during pregnancy].
Studies on infant outcomes of opiate-dependent pregnant women find a high rate of premature mother-child separation and to a lesser extent developmental delay. The specific role of in utero heroin exposure in the determination of the developmental outcome seems to be less important than the home environment. Describe the health and development of 5-year-old children whose drug-addict mothers allowed an early multidisciplinary intervention (medical and psychological) in the maternity hospital and neonatology. Thirty-seven children (62% of the initial cohort) were seen in consultation with their parents. Growth and development was compared with a control group of 374 children of the same age. Comparisons were made between the children's and parents' state (social, medical, drug addiction, etc.) upon discharge from the maternity hospital and 5 years later. A study was conducted on those lost to follow-up. The rate of placement in 5 years was very low (13%). Seven children showed a developmental delay, 21 no disorder, and nine some problems. Anxiety (37%) and overweight (48%) were the only disorders differentiating them from the control group. Compliance with the care provided in the maternity hospital was the only item significantly related to the development of the 5-year-old children (P=0.05). The hypothesis of an attachment disorder in those with the greatest need is raised. The likely relations between the quality of the care in the maternity hospital, mother-child relations, and the attrition of the cohort are also discussed. Management of the symptoms as well as social and psychological care during pregnancy and neonatal hospitalization for opiate-dependent pregnant women facilitates a long-lasting relation with childhood professionals, avoids court-ordered placements, and reduces the appearance of developmental disorders in these children.


Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE).
Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted. In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers. Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood. We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children. The trial was registered at clinicaltrials.gov, identifier ( NCT01634464 ).


Molecular Profiles of Advanced Urological Cancers in the PERMED-01 Precision Medicine Clinical Trial.
The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio ≥ 1.3 versus 5% in the "non-matched therapy group" (n = 25). The objective response and disease control rates were higher in the "matched therapy group" (33% and 58%, respectively) than in the "non-matched therapy group" (13% and 22%), as was the 6-month OS (75% vs. 42%). the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to "matched therapy" in 19%, and provided clinical benefit in 8%.


Excitation relaxation dynamics and energy transfer in pigment-protein complexes of a dinoflagellate, revealed by ultrafast fluorescence spectroscopy.
Photosynthetic light-harvesting complexes, found in aquatic photosynthetic organisms, contain a variety of carotenoids and chlorophylls. Most of the photosynthetic dinoflagellates possess two types of light-harvesting antenna complexes: peridinin (Peri)-chlorophyll (Chl) a/c-protein, as an intrinsic thylakoid membrane complex protein (iPCP), and water-soluble Peri-Chl a-protein, as an extrinsic membrane protein (sPCP) on the inner surface of the thylakoid. Peri is a unique carotenoid that has eight C=C bonds and one C=O bond, which results in a characteristic absorption band in the green wavelength region. In the present study, excitation relaxation dynamics of Peri in solution and excitation energy transfer processes of sPCP and the thylakoid membranes, prepared from the photosynthetic dinoflagellate, Symbiodinium sp., are investigated by ultrafast time-resolved fluorescence spectroscopy. We found that Peri-to-Chl a energy transfer occurs via the Peri S1 state with a time constant of 1.5 ps or 400 fs in sPCP or iPCP, respectively, and that Chl c-to-Chl a energy transfer occurs in the time regions of 350-400 fs and 1.8-2.6 ps.


[Exercise-induced myocardial ischemia in patients with coronary artery ectasia without significant coronary stenosis].
To investigate whether exercise would induce myocardial ischemia in patients with coronary artery ectasia without significant coronary stenosis. A total of 41 patients (male 29, female 12) with coronary artery ectasia without significant coronary stenosis, confirmed by selective coronary angiography, were enrolled in the study group. Forty-one patients with normal coronary arteries were in the control group. All the patients received a clinical examination and treadmill exercise before selective coronary angiography. Eighteen patients (43.9%) had typical angina in the study group with respect to two patients in the control group (chi(2)=10.498, P=0.001). In the study group, 32 cases had positive treadmill test with respect to five cases in the control group (chi(2)=35.903, P<0.0001). Patients with coronary artery ectasia without significant coronary stenosis could get typical angina. Exercise could induce myocardial ischemia which should be paid attention to.


Glucose levels and insulin secretion in surgery-induced hyperglycemia in normoglycemic obese patients.
Transient hyperglycemia is commonly observed in non-diabetic subjects during surgery. We undertook this study to investigate (1) insulin secretion pattern and glucose levels during elective surgery, and (2) the role of pre-operative fasting in the development of surgery-induced hyperglycemia. We examined 21 severely obese normal glucose tolerant patients, who underwent bariatric surgery. From the 21 operated subjects, 14 remained fasted while seven patients received 75 g glucose the preoperative night. They sampled at baseline and from the onset of operation frequently for 9 h thereafter, for measuring serum insulin and glucose. Hyperglycemia developed within 1 h from the onset of operation and lasted 9 h. The administration of 75 g glucose the preoperative night prevented surgery-induced hyperglycemia. Insulin profile analyzed by deconvolution analysis was similar between fasted patients and those who received 75 g glucose. Serum insulin was suppressed at the beginning of the surgery and reached baseline values 4 h thereafter. Hyperglycemia occurred within 1 h from the beginning of surgery and sustained for at least 9 h while insulin levels are suppressed or unaltered compared to baseline values in euglycemia. The administration of 75 g glucose the preoperative night prevents surgery-induced hyperglycemia without altering the profile of insulin secretion.


The anxiolytic effect of testosterone in the rat is mediated via the androgen receptor.
Endogenous and exogenous testosterone affects several behavioural traits as shown in human and animal studies. The effects of testosterone can be mediated via androgen or oestrogen receptors, but also via rapid non-genomic effects. The aim of this study was to evaluate whether a single testosterone injection has effects, mediated via the androgen receptor, on anxiety in intact male rats. We hypothesised that administration of testosterone will have an anxiolytic effect, mediated by the androgen receptor. Intact adult male Wistar rats were divided into groups: control, flutamide, testosterone and testosterone with flutamide. Testosterone and flutamide (as an androgen receptor blocker) were applied once, intramuscularly, at a dose of 5mg/kg. Twenty four hours later, rats underwent the following behavioural tests to analyse anxiety: open field test, elevated plus maze and light-dark box. Testosterone was measured in plasma to confirm elevated levels in groups that received testosterone. The levels of testosterone were 2.5-3 fold higher amongst rats administered with testosterone compared to controls. Flutamide did not affect plasma testosterone concentrations. Testosterone administration had no effect on anxiety in the open field and elevated plus maze. In the light-dark transition task, testosterone increased the time spent in the light part of the maze by 80%, an effect which was blocked by flutamide, and which was in support of our hypothesis. Flutamide-treated rats spent more time in the central square of the open field. Using the light-dark box we have shown that a single injection of testosterone decreases anxiety in adult male rats. This effect of increased testosterone was mediated via the androgen receptor as flutamide blocked the anxiolytic effect of exogenous testosterone. Treatment with flutamide blocked the effects of endogenous testosterone and had anxiolytic effects in the open field, suggesting a non-linear relationship between genomic effects of T and anxiety.


Extended Q-range small-angle neutron scattering to understand the morphology of proton-exchange membranes: the case of the functionalized syndiotactic-polystyrene model system.
Semi-crystalline polymers exhibit microphase separation into crystalline and amorphous domains characterized by multiple structural levels with sizes ranging from ångströms to hundreds of nanometres. The combination of small-angle (SANS) and wide-angle (WANS) neutron scattering on the same beamline enables reliable in situ characterization of such materials under application-relevant conditions, with the unique advantage of contrast variation by controlled labelling, allowing the structure of such multi-component systems to be resolved in detail. This paper reports a structural analysis performed on deuterated polymer membranes based on syndiotactic polystyrene (sPS) using an extended Q-range SANS and WANS combination, always with the same neutron scattering instrument, either a pinhole SANS diffractometer installed at a research reactor or a 'small- and wide-angle' time-of-flight diffractometer installed at a neutron spallation source. sPS is a semi-crystalline material that becomes hydrophilic and proton conducting when suitable functionalization is achieved by thin film sulfonation, and can form various co-crystalline complexes (clathrates) with small organic molecules stored in the crystalline phase as guests in the vacancies between the polymer helices. Therefore, this material is interesting not only for its conducting properties but also for its versatility as a model system to evaluate the usefulness of extended Q-range neutron scattering in such studies. Variation of neutron contrast was achieved in the amorphous hydrophilic phase by using H2O or D2O to hydrate the membranes and in the crystalline phase by loading the clathrates with deuterated or protonated guest molecules. The experimental approach, the advantages and limitations of the two types of instrumentation used in such analyses, and the main results obtained with respect to the structural characterization of sulfonated sPS membranes under different hydration and temperature conditions are reported, and the potential of this method for similar structural studies on other semi-crystalline polymeric materials is discussed.


Heterosexual Young Adults' Interest, Attitudes, and Experiences Related to Mixed-Gender, Multi-Person Sex.
There has been little research on threesomes, a form of multi-person sex that involves sexual activity with two other people simultaneously. Therefore, we examined young adults' attitudes toward, interest in, and experiences with one form of threesome, mixed-gender threesomes (MGTs), defined as sexual activity involving three people where at least one member of each gender is present. Participants were 274 (202 women, 72 men) heterosexual young adults who completed an online survey. Overall, 13 % of participants (24 % of men and 8 % of women) reported experience and 64 % reported some interest in engaging in an MGT. However, the overall level of interest was quite low and varied according to contextual variables (i.e., what other persons were involved). Men's interest remained unaffected by third person status as long as the MGT involved familiar others (friends and acquaintances) rather than strangers, whereas women preferred familiar others only for MGTs with which they were the third person, not for those involving a romantic partner. Participants also reported fairly neutral attitudes toward MGTs. Compared to the women, the men reported significantly more positive attitudes and greater interest, and were more likely to report MGT experience. In addition, attitudes, interest, and experience were all positively associated with each other. Taken together, these results suggest that young people are not judgmental about others engaging in MGTs but are not highly motivated to do so themselves. Implications for researchers and sexual health educators are discussed.


Influence of growth substrate and contaminant mixtures on the degradation of BTEX and MTBE by Rhodococcus rhodochrous ATCC strain 21198.
The degradation of the prevalent environmental contaminants benzene, toluene, ethylbenzene, and xylenes (BTEX) along with a common co-contaminant methyl tert-butyl ether (MTBE) by Rhodococcus rhodochrous ATCC Strain 21198 was investigated. The ability of 21198 to degrade these contaminants individually and in mixtures was evaluated with resting cells grown on isobutane, 1-butanol, and 2-butanol. Growth of 21198 in the presence of BTEX and MTBE was also studied to determine the growth substrate that best supports simultaneous microbial growth and contaminants degradation. Cells grown on isobutane, 1-butanol, and 2-butanol were all capable of degrading the contaminants, with isobutane grown cells exhibiting the most rapid degradation rates and 1-butanol grown cells exhibiting the slowest. However, in conditions where BTEX and MTBE were present during microbial growth, 1-butanol was determined to be an effective substrate for supporting concurrent growth and contaminant degradation. Contaminant degradation was found to be a combination of metabolic and cometabolic processes. Evidence for growth of 21198 on benzene and toluene is presented along with a possible transformation pathway. MTBE was cometabolically transformed to tertiary butyl alcohol, which was also observed to be transformed by 21198. This work demonstrates the possible utility of primary and secondary alcohols to support biodegradation of monoaromatic hydrocarbons and MTBE. Furthermore, the utility of 21198 for bioremediation applications has been expanded to include BTEX and MTBE.


Removal of N-nitrosodimethylamine precursors by cation exchange resin: The effects of pH and calcium.
Cation exchange resins have proved to be efficient in removing precursors of N-nitrosodimethylamine (NDMA). NDMA is a probable human carcinogen with a calculated lifetime cancer risk of 10-6 at 0.7 ng/L in drinking water. This paper investigated the effect of pH and calcium levels on the removal of NDMA precursors using a cation exchange resin. At pH 5 and 7, 30-50% of NDMA precursors, measured by formation potentials (FPs) changes before and after the treatment, were removed by Plus resin. However, increases in NDMA FPs were observed after the treatment at pH 10 indicating that NDMA precursors were released from the resin. NDMA FPs removals in samples containing 15 and 115 mg/L Ca2+ were 40% and -10% after the ion exchange treatments at pH 7, respectively. It was found that in the presence of high concentration of calcium only one out of four cation exchange resins released NDMA precursors (probably due to manufacturing impurities). Also, the release of NDMA precursors depended on the calcium concentration and the contact time of the resin with the solution containing calcium. Nonetheless, NDMA precursors release from the resin subsided significantly with increasing the number of regeneration cycles of the resin.


Cervical Lymph Nodes: A Hotbed For Metastasis in Malignancy.
The aim of this study was to find semblance between cervical lymph node metastasis and various malignancies. Objective was to estimate the incidence of neck node metastasis (NNM) from malignancies arising from infraclavicular region reported at a tertiary cancer centre over 10 years. Retrospective data was obtained from Hospital Management Software system from March 2012 to March 2017. 4000 patients were analysed and based on inclusion and exclusion criteria 68 patients were identified with clinically palpable and/or enlarged cervical lymph nodes. Results 41.7% patients had lung as a primary malignancy, 17.64% had breast carcinoma, 20.58% patients were with head and neck malignancy other than oral cavity malignancy, 7.3% of patients had primary malignancy in cervix. 2.94% patients had endometrial malignancy and renal malignancy each. Primary malignancies of gall bladder, pancreas, skin, prostate and vagina constituted 1.47% for each type. Conclusion understanding the pertinence of cervical lymph nodes specially supraclavicular lymph nodes with different primary tumor sites enables to plan interdisciplinary management of patients and also to correlate with the prognosis of patient.


Reduction of radiation exposure in cryoballoon ablation procedures: a single-centre study applying intracardiac echocardiography and other radioprotective measures.
The population treated with cryoballoon (CB) ablation is relatively young, and radiation protection is of major importance. We aimed to demonstrate that radiation exposure can be markedly reduced by intracardiac echocardiography (ICE) and optimized settings of the X-ray system. We analysed 100 patients undergoing CB pulmonary vein isolation (PVI) for treatment of paroxysmal atrial fibrillation. In 50 consecutive patients (25 male, 59 ± 13 years; Group 1), we used ICE, skipped PV angiography prior to CB inflation, and avoided fluoroscopy whenever possible. Furthermore, we reduced the frame rate, minimized distance between patient and detector, and consequently applied collimation. These patients were compared with 50 similar preceding patients in Group 2 (29 male, 61 ± 12 years). Total fluoroscopy time was reduced from 18 ± 6 min in Group 2 to 12 ± 5 min in Group 1 (P < 0.001). Moreover, the dose area product was significantly lower (1555 ± 1219 vs. 4935 ± 2094 cGycm2, P < 0.001), total freezing time was significantly shortened (1855 ± 399 vs. 2121 ± 756 s, P = 0.031), and contrast media use was significantly reduced (66 ± 25 vs. 109 ± 27 mL, P < 0.001). At the same time, total procedure duration and complication rates did not differ significantly between both groups. After a 12 months follow-up, a similar percentage of patients was free from recurrences (74% in Group 1 vs. 78% in Group 2, P = 0.640). Radiation exposure in CB PVI can be markedly reduced without prolonging procedure times, affecting the outcome or complication rates. Moreover, ICE seems to shorten total freezing time.


Multi-resource collaborative scheduling problem of automated terminal considering the AGV charging effect under COVID-19.
Since the COVID-19 ravaged the global terminals, the Automated Container Terminal (ACT) has become one of important approach to promote the stronger quick response capacity to deal with the uncertainty that COVID-19 brought to the terminal. This research takes Automated Guided Vehicle (AGV) and their effects into account the multi-resource collaborative scheduling model to tradeoff ACT operational efficiency and energy savings. Firstly, the dual-cycle strategy of QC and the pooling strategy of AGV are given, which coordinates the scheduling of Quay Cranes (QCs), Yard Cranes (YCs) and other equipment. Furthermore, a multi-resource collaborative scheduling optimization model is proposed which roots from the principle of the Blocking-type Hybrid Flow Shop Problem (B-HFSP) with the objectives of minimizing the makespan of QC and the transportation energy consumption. And simultaneously, a mixed algorithm SA-GA is designed for solving this mixed integer programming model by an optimizing effect of Simulated Annealing on Genetic algorithms. Numerical experiments show that the model in this research is effective. The convergence of SA-GA is effective for small-scale cases and superior for large-scale cases. Considering both goals of high efficiency and energy saving, the Pareto solution set and collaborative scheduling solution take a priority to ensure that the bottlenecked QC runs efficiently. Here and now the average idle rate of QC is about [14%, 35%] lower than that of other equipment. The collaborative scheduling model constructed above not only has reference value for other multi-device and multi-stage scheduling problem, but also enhance the integrated decision-making ability of the ACT in the post-epidemic era.


Gaucher disease: unmet treatment needs.
Gaucher disease is a multisystemic metabolic disorder arising from a deficiency of lysosomal glucocerebrosidase. The predominant clinical manifestations of the disease are hepatosplenomegaly, peripheral blood cytopenias and skeletal disease. Treatment with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) has been shown to be effective in improving organ volume, anaemia, thrombocytopenia, bone markers and biomarkers in patients with Gaucher disease. However, some patient needs remain unmet because of the limited availability of treatment, the inaccessibility of certain disease sites and emerging disease manifestations. An increase in haematological, lymphoreticular and immune system malignancies has been observed in patients with Gaucher disease, but mechanisms underlying the development of these are not fully understood. Mild neurological manifestations may also affect patients with type 1 Gaucher disease, but treatment with ERT or SRT does not improve neurological function. Potential new treatments for Gaucher disease include small molecules, which may penetrate tissues that are not accessible by ERT. ERT currently remains the most effective treatment for Gaucher disease. New treatments are emerging, but deficiencies in understanding basic pathophysiological mechanisms hinder progress.


Fatal chickenpox in a patient with nephrotic syndrome.
We report our experience with two patients with adult onset of chickenpox in the setting of longstanding steroid therapy for nephrotic syndrome. Ours is a 430-bed tertiary care teaching hospital, The Wellesley Hospital, Toronto, Ontario. Both patients presented as self-referrals to the emergency department. The clinical suspicion of chickenpox was rapidly confirmed in both cases by a Tzanck smear preparation, by viral cultures of the vesicle, serology, and skin biopsy. In both patients therapy with high dose acyclovir, 10 mg/kg q8h, intravenously, was instituted based on clinical presentation. Delay in clinical recognition and treatment in our first case resulted in death due to multiorgan failure (MOF). Improved awareness and rapid treatment of the second patient had a favorable outcome with no sequelae. Chickenpox is not only a childhood illness. Although rare in the adult population, it is associated even in the nonimmunocompromised host with increased morbidity and mortality. Steroid therapy predisposes to early dissemination and a potentially fatal outcome. Adults with immunosuppression should receive prompt systemic treatment with acyclovir.


Patient-health care provider communication among patients with newly diagnosed prostate cancer: findings from a population-based survey.
To examine the multidimensional concept of patient-health care provider (HCP) communication, its effects on patient satisfaction with oncology care services, and related racial differences. The current analysis draws from a population-based survey sample of 1011 African American and 1034 Caucasian American men with newly diagnosed prostate cancer. The variables of satisfaction with health care services, interpersonal treatment, contextual knowledge of the patient, and prostate cancer communication were analyzed using multiple-group structural equation modeling. Regardless of race, patient-HCP communication was related positively to interpersonal treatment by the HCP, HCP's contextual knowledge of the patient, and prostate cancer communication. More positive patient-HCP communication was related to more satisfaction with health care services. Racial differences were significant in the relationships between patient-HCP communication and prostate cancer communication. Content and interpersonal relationships are important aspects of patient-HCP communication and affect patient satisfaction with oncologic care for prostate cancer. HCPs need to integrate the transfer of information with emotional support and interpersonal connection when they communicate with men with newly diagnosed prostate cancer.


Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.
To evaluate the effect of pregestational metformin administration on abortion risk in polycystic ovary syndrome (PCOS) patients. Systematic review and meta-analysis. Academic Department of Obstetrics and Gynecology in Italy. Women affected by PCOS receiving pregestational metformin. Systematic review of randomized controlled trials (RCTs) published up to June 2008 and subsequent meta-analysis. Abortion rate. Seventeen RCTs were included in the final analysis. Overall, no effect of the metformin administration was detected on the abortion risk. No statistically significant effect of metformin on the abortion risk was observed in any comparison when subgrouping the RCTs according to received treatment. Metformin has no effect on the abortion risk in PCOS patients when administered before pregnancy.


Reliability and relationship of radiographic measurements in hallux valgus.
Although various radiographic measurements have been developed and used for evaluating hallux valgus, not all are universally believed to be necessary and their relationships have not been clearly established. Determining which are related could provide some insight into which might be useful and which would not. We investigated the reliability of eight radiographic measurements used to evaluate hallux valgus, and determined which were correlated and which predicted the hallux valgus angle. We determined eight radiographic indices for 732 patients (mean age, 51 years; SD, 17 years; 107 males and 625 females) with hallux valgus: hallux valgus angle, intermetatarsal angle, hallux interphalangeal angle, distal metatarsal articular angle, proximal phalangeal articular angle, simplified metatarsus adductus angle, first metatarsal protrusion distance, and sesamoid rotation angle. Intraobserver and interobserver reliabilities of each radiographic measurement were analyzed on 36 feet from 36 randomly selected patients. Correlations among the radiographic measurements were analyzed. Radiographic measurements predicting hallux valgus angle were evaluated using multiple regression analysis. Hallux valgus angle had the highest reliability, whereas the distal metatarsal articular angle and simplified metatarsus adductus angle had the lowest. Distal metatarsal articular angle, intermetatarsal angle, and sesamoid rotation angle had the highest correlations with hallux valgus angle. Distal metatarsal articular angle correlated with sesamoid rotation angle. The intermetatarsal angle, interphalangeal angle, distal metatarsal articular angle, first metatarsal protrusion distance, sesamoid rotation angle, and metatarsus adductus angle predicted the hallux valgus angle. We suggest using hallux valgus angle, intermetatarsal angle, interphalangeal angle, sesamoid rotation angle, and first metatarsal protrusion distance considering their reliability and prediction of the deformity.


Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides.
The inhibitory effect of antisense phosphorothioate oligodeoxynucleotides (S-ODN) on hepatitis C viral gene expression and analyzed in an in vitro test system and in cell culture. S-ODN were directed against different stem loop structures in the 5'noncoding region (NCR) of the hepatitis C virus, (HCV) RNA and against a nucleotide stretch, including the start codon of the polyprotein precursor. The inhibitory effect of these S-ODN was quantified employing a viral RNA consisting of the first 407 nucleotides of a HCV type 1b genome fused to the coding sequence of the firefly luciferase gene. For in vitro assays this RNA was generated by in vitro transcription and used as a template in a rabbit reticulocyte lysate in vitro translation system. The production of active luciferase in the absence or presence of S-ODN was monitored using an enzymatic assay. The best results were obtained with S-ODN 4 directed against nucleotides 326 to 348, comprising the start AUG of the polyprotein coding sequence. With this oligonucleotide, a specific and dose-dependent effect was observed with a maximal inhibition of 96 +/- 1% at a S-ODN concentration of 4.14 mumol/L. For cell culture experiments, the hepatoblastoma cell line HepG2 was transfected with a plasmid expressing the HCV-luciferase fusion RNA. In this assay system S-ODN 2, complementary to nucleotides 264 to 282 of the HCV RNA, and S-ODN 4 were most efficient and reduced the viral translation by 96 +/- 0.4% and 94 +/- 0.7%, respectively, at a concentration of 0.3 mumol/L. The inhibition was specific (1) because the expression of the HCV-luciferase fusion RNA was not significantly impaired by the control S-ODN and (2) because the expression of an unrelated messenger RNA was not or only slightly downregulated. These data suggest that HCV gene expression can be inhibited effectively by antisense S-ODN. Therefore, this approach represents a promising perspective for the treatment of hepatitis C.


Influence of resident involvement on fluoroscopy time and ionizing radiation exposure in fluoroscopy-guided spinal procedures.
Fluoroscopic guidance has become the standard for a variety of medical procedures. Mastering these techniques requires practice, which may entail additional radiation for patients and providers. Despite their widespread use, the literature examining factors influencing radiation exposure in fluoroscopically guided pain procedures is scarce. To evaluate the influence of resident involvement on radiation exposure during fluoroscopy-guided spinal interventions. Single-center, observational study. Outpatient physiatry clinic in a teaching hospital. All patients who received cervical or lumbar facet block(s) (FBs), transforaminal epidural steroid injection(s) (TFESIs) without digital subtraction, or a caudal epidural (CE) during the study period were included. Resident involvement in the procedures: absent, observing, or participating. Machine-indicated fluoroscopy time (seconds) and radiation dose (milligrays [mGy]). Two hundred ninety six procedures were included: 188 FBs (58 cervical, 130 lumbar), 48 CEs, and 60 TFESIs. For lumbar FBs, fluoroscopy time and radiation dose increased significantly when residents performed them (meantime = 24.5 s, confidence interval [CI] = 20.4-28.7; meandose = 3.53 mGy, CI = 2.57-4.49) compared to when they observed (meantime = 9.9 s, CI = 8.1-11.7; meandose = 1.28 mGy, CI = 0.98-1.59) (mean difference: time = 14.63 s, CI = 9.31-19.94; dose = 2.25 mGy, CI = 1.17-3.33) and were absent during the procedure (meantime = 12.9 s, CI = 11.1-14.6; meandose = 1.65 mGy, CI = 1.40-1.89) (mean difference: time = 11.67 s, CI = 7.35-15.98; dose = 1.88 mGy, CI = 1.01-2.76). In the case of TFESIs, time, but not dose, increased significantly when residents observed (meantime = 39.1 s, CI = 30.7-47.6; meandose = 6.73 mGy, CI = 3.39-10.07) compared to when they were absent (meantime = 27.1 s, CI = 22.4-31.8; meandose = 4.41 mGy, CI = 3.06-5.76 (mean difference: time = 11.99 s, CI = 1.37-22.61; dose = 2.32 mGy, CI = -1.20-5.84). Finally, resident involvement did not significantly affect the outcomes for CEs (ptime = .032, pdose = .74) and cervical FBs (ptime = .64, pdose = .68). Resident participation affected lumbar FBs the most, with an increase in both fluoroscopy time and radiation dose.


The biotransformation of thioridazine to thioridazine 5-sulfoxide stereoisomers in phenobarbital induced rats.
The disposition and urinary elimination of thioridazine 5-sulfoxide (ring sulfoxide) following subacute administration of thioridazine was investigated in control and phenobarbital (Pb) induced rats. The ring sulfoxide exists as two stereoisomeric pairs, identified by high performance liquid chromatography as fast eluting (RSF) and slow eluting (RSS) ring sulfoxide. No major differences were detected in the distribution in serum or tissue of the ring sulfoxide between control and induced animals. The ring sulfoxide accumulated in all tissues studied. RSF tissue concentrations were significantly greater than those of RSS in both groups. However, stereoselective formation and elimination of the two ring sulfoxides was not noted in either group. Pb inducible cytochrome P-450 drug metabolizing enzymes do not appear to play a major role in the biotransformation of thioridazine to the ring sulfoxide.


Family history as a predictor of uptake of cancer preventive procedures by women with a BRCA1 or BRCA2 mutation.
Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast and ovarian cancer; however, it is unclear to what extent family history influences the uptake of cancer prevention options. Women with a BRCA1/2 mutation completed a follow-up questionnaire that assessed uptake of cancer preventive options. The pedigree of each woman was reviewed, and information was recorded on cancers diagnosed in relatives. Five hundred and seventeen women were included in the study. Women with a sister with breast cancer were more likely to have a prophylactic mastectomy than those without a sister with breast cancer [odds ratios (OR) = 2.4, p = 0.003]. Uptake of prophylactic mastectomy was significantly lower in women with a mother with ovarian cancer compared with those whose mother did not have ovarian cancer (OR = 0.4, p = 0.01). Having a mother or sister with ovarian cancer significantly predicted the uptake of prophylactic oophorectomy (OR = 1.6, p = 0.04). Women with a BRCA2 mutation were less likely to have a prophylactic oophorectomy than those with a BRCA1 mutation (OR = 0.49, p = 0.0004). Among women with a BRCA1 or BRCA2 mutation, family history predicts the uptake of prophylactic mastectomy and prophylactic oophorectomy.


Survival kinetics, membrane integrity and metabolic activity of Salmonella enterica in conventionally and osmotically dehydrated coconut flakes.
Many outbreaks involving Salmonella enterica in dehydrated coconut have been reported. Little is known about the survival of S. enterica in dehydrated coconut flakes at common retail or domestic storage conditions. This study evaluated the behavior of a S. enterica cocktail (S. Enteritidis PT4, S. Typhimurium PT4, S. Bredeney, S. Muenster and S. Agona) in conventionally and osmotically dehydrated coconut flakes under four storage regimes: 25 °C for 120 days, 25 °C for 30 days then 7 °C for 90 days, 7 °C for 30 days then 25 °C for 90 days, and 7 °C for 120 days. S. enterica membrane integrity (using with propidium iodide and bis-1,3-dibutylbarbutyric acid) and metabolic activity (using 5-cyano-2,3-ditolyl tetrazolium chloride) were assessed by flow cytometry analysis after dehydration and storage at 7 °C or 25 °C for 120 days. Lower S. enterica inactivation rates (kmax 0.02 to 0.04 1/days) were observed in conventionally dehydrated coconut flakes compared to osmotically dehydrated coconut flakes (kmax 0.16 to 0.20 1/days). Changes in storage temperature did not affect the behavior of S. enterica in conventionally or osmotically dehydrated coconut flakes. Results show that S. enterica inactivation in conventionally dehydrated coconut flakes could be described by log-linear with tail models. S. enterica inactivation in osmotically dehydrated coconut flakes could be described by log-linear with shoulder and tail models. Subpopulations of S. enterica cells with damaged membranes and without metabolic activity were larger in conventionally (32.1% and 90.9%, respectively) than osmotically dehydrated coconut (18.5% and 82.2%, respectively) flakes at the beginning of the storage. Subpopulations of S. enterica cells with damaged membrane decreased by 9.4-14.4%, while cells with membrane potential and intact membrane increased by 23.7 and 24.2% in conventionally dehydrated coconut flakes after 120 days of storage at 7 °C or 25 °C, respectively. Subpopulations of S. enterica with damaged membranes did not change significantly in osmotically dehydrated coconut flakes. Our findings suggest that S. enterica populations decline during storage occurs due in part to membrane integrity losses. These data can contribute to the development of risk management strategies for S. enterica in dehydrated coconut flakes.


Selective accumulation of the first component of complement and leukocytes in ischemic canine heart muscle. A possible initiator of an extra myocardial mechanism of ischemic injury.
Myocardial concentrations of C1q, a subunit of the first component of complement, were measured 5-120 minutes after ligation of a coronary artery in dogs injected with 125I-labeled human C1q and 131I-labeled human albumin. The 131I-labeled human serum albumin was used as a plasma protein marker. Ischemic regions of myocardium were defined by measuring regional myocardial blood flow by the reference sample method at intervals after coronary artery occlusion. Significant accumulations of 125I-C1q were demonstrated in the ischemic myocardium after coronary artery occlusions lasting 45 minutes. Some localization of C1q in ischemic myocardium was observed after a 15-minute occlusion, but the accumulations of C1q achieved in this case were not statistically significant. After coronary artery occlusions lasting greater than or equal to 45 minutes, left ventricular concentrations of C1q correlated reciprocally with regional myocardial blood flow. Moreover, high concentrations of C1q persisted in formerly ischemic segments after reperfusion. Radiolabeled neutrophils also accumulated selectively in ischemic segments relatively rich in C1q. It is suggested that complement activation may initiate the neutrophil-dependent portion of ischemic injury, delineated in recent years, that is associated with free radical release by phagocytic cells.


An Analysis of Psychoactive Medications Initiated in the ICU but Continued Beyond Discharge: A Pilot Study of Stewardship.
Psychoactive medications (PM) are frequently administered in the intensive care unit (ICU) to provide comfort. Interventions focused on preventing their continuation after the acute phase of illness are needed. To determine the frequency that patients with ICU-initiated PM are continued upon ICU and hospital discharge. This single-center, prospective, observational study assessed consecutive adult ICU patients who received scheduled PM. Frequency of PM continued at ICU and hospital discharge was recorded. The patient's primary treatment team was contacted by the pharmacist within 72 hours of ICU discharge to establish rationale for continued use or to suggest discontinuation. Of the 60 patients included, 72% were continued on PM at ICU discharge and 30% at hospital discharge. The pharmacist contacted 40% of treatment teams after ICU discharge and intervention resulted in PM discontinued in 50% of patients. Post ICU discharge, the indication of 41% of patients' PM was unknown by the non-ICU care team or incorrect. Medical ICU patients or those transferred to an outside facility were more likely remain on PM at hospital discharge. PM are frequently continued during transitions of care and often without knowledge of the initial indication. Future studies should establish effective PM stewardship methods.


Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota.
To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis. C57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing. S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased. S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.


Domains of Students' Concerns in Oral Diagnosis and Surgery Clinic.
Oral diagnosis and surgery education is the main educational subject in dental schools. Due to its importance and the demand to achieve a proper level of training, dental students might have some concerns related to this subject. The study aims to investigate domains related to students' concerns in oral surgery clinics. An online questionnaire of five domains was circulated to 211 fourth, and fifth-year students. The domains include; the benefit of oral surgery lectures in oral surgery clinic; the importance of oral surgery clinic, what they fear the most during their oral surgery training; difficulty domain, and importance domain. It was distributed to a sample of 211 fourth-, and fifth-year students at the Ibn Sina College of Dentistry, Baghdad, Iraq in January, and February 2022. In the domain of "benefit of oral surgery lectures in the oral surgery clinic" Half of the respondents think theory lectures are useful. About one-third of the students believe it is essential. The most important item in the domain of "most factors students' fear" was the item of nerve injury (42.1%). Incomplete tooth removal was reported in (32.7%), whereas post-extraction bleeding was reported by (19.2%). In the domain "the most difficult" 71% of students stated that it is dealing with uncooperative patients was the most important item. Similarly, in the domain "the most important" the majority of students reported that correct surgical diagnosis (70.1%) is the most important item, followed by master extraction technique (26.2%), and master anesthesia technique (3.7%). This study evaluated the "fear", "difficulty", and "importance" domains of students' concerns during oral surgery training. There is a noticeable shift in students' attention toward clinical reasoning compared to the technical aspects of surgical training. This positive shift reflects the perceived importance of diagnosis for proper clinical practice. This needs to be encouraged by the teaching staff.


Inhibition of iNOS protects the aging heart against beta-adrenergic receptor stimulation-induced cardiac dysfunction and myocardial ischemic injury.
beta-adrenergic receptor (AR) and aging are two major contributors to pathogenesis of perioperative myocardial ischemia and infarction. This study compared the response to beta-AR stimulation in the young and aging heart and examined the role of inducible nitric oxide synthase (iNOS) in aging related myocardial ischemic injury and its relation to beta-AR stimulation. Isolated perfused hearts from young (3-5 months) and aging (24-25 months) rats were subjected to 60 min of 50% coronary flow reduction and 30 min of isoproterenol (Iso) stimulation starting at 30 min of ischemia. The rats were randomized to receive vehicle or 1400W (a selective iNOS inhibitor) at 24 h (2 mg/kg, i.p.) and 1 h (1 mg/kg, i.p.) pre-ischemia. The 30 min of myocardial ischemia resulted in cardiac dysfunction as indicated by a 13 to 45% of reduction in left ventricular developed pressure (LVDP) and +/- dp/dtmax in either young or aging rats. Infusion of Iso for 30 min caused a partial recovery of cardiac function in hearts from young animals receiving either vehicle or 1400W as evidenced by improvements in LVDP and +/- dp/dtmax. In striking contrast, Iso infusion to hearts from aging animals receiving vehicle not only failed to improve ischemia-induced cardiac depression but worsened cardiac function as indicated by a 43 to 60% further reduction in LVDP and +/- dp/dtmax at the end of 30-min Iso infusion, which was also associated with a significant increase in myocardial NO production, ONOO- formation, caspase-3 activation and creatine kinase (CK) release. However, the treatment with a selective iNOS inhibitor-1400W blocked NO production and ONOO- formation, attenuated caspase-3 activation and CK release, and improved LV function in the aging heart, demonstrating a critical link between iNOS generated NO production and aging myocardial ischemic injury. A significant increase of iNOS protein expression, activity and immunoreactivity was found in the baseline aging LV tissues versus their young counterparts. Aging induces phenotypic up-regulation of iNOS in the heart, in which beta-AR stimulation interacts with ischemia and triggers a markedly increased NO production, which creates a nitrative stress, generates toxic peroxynitrite, activates apoptosis, and eventually causes cardiac dysfunction and myocardial injury. An iNOS inhibitor-1400W can markedly attenuate these adverse effects in the aging heart.


An EMTALA primer: the impact of changes in the emergency medicine landscape on EMTALA compliance and enforcement.
Tiana Lee's article provides an overview and update on the latest in the Emergency Medical Treatment and Active Labor Act (EMTALA). Reviewing the history of the statute, explaining some of the relevant regulations, and exploring government enforcements efforts to date, Ms. Lee highlights the benefits and drawbacks of the statute and recommends ways to ameliorate EMTALA's weaknesses.


Multiple distinct intracranial tumors: association of pinealoma and craniopharyngioma. Case report.
We report the case of a patient with multiple primary brain neoplasms. A pinealoma was treated with radiotherapy and surgical resection in 1983. In 1987, a craniopharyngioma was resected surgically. Various possible determinants of multiple brain tumors have been described in the literature and are discussed. The possibility of an unknown underlying pathologic mechanism predisposing to multiple malignancies must be considered, but we are unable to conclude that this particular occurrence is more than a random chance finding.


NAD-dependent ADP-ribosylation of arginine and proteins by Escherichia coli heat-labile enterotoxin.
Escherichia coli heat-labile enterotoxin (labile toxin, LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide and the ADP-ribosylation of arginine (Moss, J., and Richardson, S.H. (1978) J. Clin. Invest. 62, 281-285). Analysis of the product of the ADP-ribosylation of arginine by nuclear magnetic resonance spectroscopy indicated that the reaction was stereospecific and resulted in the formation of alpha-ADP-ribosyl-L-arginine. This reaction product rapidly anomerized to yield a mixture of the alpha and beta forms. In the presence of [adenine-U-14C]NAD, E. coli enterotoxin catalyzed the transfer of the radiolabel to proteins; the ADP-ribosylation of proteins was inhibited by arginine methyl ester, an alternative substrate. Digestion of the 14C-protein with snake venom phosphodiesterase released predominantly 5'-AMP. No product was obtained with a mobility similar to that of 2'-(5''-phosphoribosyl)-5'-AMP. This result is consistent with the covalent attachment by the enterotoxin of ADP-ribose rather than poly(ADP-ribose) to protein. Thus, LT is catalytically equivalent to choleragen, an enterotoxin of Vibrio cholerae, and activates adenylate cyclase through a similar stereospecific ADP-ribosylation reaction.


Sex-age-specific handgrip strength and mortality in an incident hemodialysis cohort: The risk explained by nutrition and comorbidities.
To investigate associations of sex-age-specific handgrip strength by a dynamometer with all-cause mortality and the percent excess risk explained (%ERE) by comorbidities and nutritional indicators in incident maintenance hemodialysis patients. Prospective cohort of 413 adult patients (165 women, 248 men, 299 <60 years and 114 ⩾60 years) with <6 months (82% <3 months) on dialysis enrolled in PROHEMO in Salvador, Brazil. Low and high handgrip strength groups were based on sex-age-specific cutoffs (17.8 kg for women <60 years, 13.8 kg for women ⩾60 years, 29.5 kg for men <60 years, and 21.9 kg for men ⩾60 years). We used Cox regression to estimate the mortality hazard ratio. The %ERE was determined by the equation (HR1 - HR2)/(HR1 - 1) × 100, in which HR1 represented the hazard ratio in a model with a smaller number of covariates and HR2 represented the hazard ratio in a subsequent model with the inclusion of new covariates plus the variables included in the previous model. The mortality hazard ratio comparing low and high handgrip strength was 2.58 (95% confidence interval: 1.73, 3.85) in the model with sociodemographic factors and vintage and 2.25 (95% confidence interval: 1.49, 3.43) with addition of comorbidities, corresponding to a %ERE of 21%. The hazard ratio was 1.98 (95% confidence interval: 1.29, 3.06) after addition of nutritional indicators corresponding to %ERE of 38%. Results stratified by age and gender followed similar patterns. These results provide support for the assessment of handgrip strength in all maintenance hemodialysis patients for early identification of those who may require special care to improve nutritional status and survival.


Treating mother with statins could reduce negative effects of stress hormone on fetus.
Statins could protect fetuses from the effects of maternal stress, research suggests.


An expert system for synoptic interpretation of lung function tests.
We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing.


A simple polar deacetylated caloporoside derivative is a positive modulator of the GABA(A) chloride channel complex in cortical mammalian neurones.
Synthesis of octyl-O-beta-D-mannopyranoside, a caloporoside analogue was achieved by the activation of 2,3,4,6-rerra-O-benzyl-1-O-1',3'2'-dioxaphosphacyclohexane-a lpha,beta-D-mannopyranosyl-2-oxide with TMSOTf (Trimethyl silyl triflate) and subsequent debenzylation. At 100 microM the molecule significantly and reversibly increased the magnitude of GABA(A) currents evoked in cultured rat pyramidal neurones whilst concomitantly reducing the incidence of spontaneous synaptic activity. These results contradict earlier proposals that such molecules bind to the TBPS (tert-Butylbicyclophosphorothionate) site to block the chloride channel.


A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns].
The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]


The impact of age-related syndromes on ICU process and outcomes in very old patients.
In this narrative review, we describe the most important age-related "syndromes" found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment.


Alcohol and drug use by alcohol and drug abusers when incarcerated: clinical and research implications.
Alcohol (n = 24) and drug (n = 60) abusers reported frequent alcohol and/or drug use while incarcerated in hospitals, jails, and residential treatment programs. Although substance use by addicts while incarcerated may be a "well-known" clinical phenomenon, there are virtually no published data regarding the range and frequencies of such behaviors. The clinical and research implications of frequent drug and alcohol use by alcohol and drug abusers when incarcerated are discussed.


One pot synthesis and characterization of gold nanocatalyst using Sacha inchi (Plukenetia volubilis) oil: Green approach.
In this report, a simple and cost-effective methodology has been developed to obtain gold nanoparticles (AuNPs) using Sacha inchi (Plukenetia volubilis) oil in the presence of sunlight. The spectroscopic and morphological properties of AuNPs were characterized by using UV-vis spectroscopy, transmission electron microscopy (TEM), particle size analyzer, and X-ray diffraction (XRD). UV-vis and TEM reveal that the nanostructure of the gold particles has surfaced plasmon resonance at 515-520nm and is almost spherical in shape with an average size of 5-15nm. XRD studies confirmed the face cubic center (fcc) unit cell structure of AuNPs. The as-synthesized AuNPs showed remarkable photocatalytic decomposition of the methylene blue (>75%) without using any reducing agent and weak antioxidant activity (21-16%) against 1,1-diphenyl-2-picrylhydrazyl at the different sunlight exposure times. The experimental approach is promising and suggested that the sunlight is a good source of energy for enhancement of AuNP synthesis via Sacha inchi oil and its photocatalytic activity.


Tumors of the alimentary tract.
Neoplasms of the canine and feline alimentary tract represent diagnostic and therapeutic challenges for the veterinarian in practice. Careful attention to historical details and thorough and repeated examination are of paramount importance in evaluating animals with chronic digestive disturbances. By judicious use of ancillary studies such as plain and contrast radiography, endoscopy, and exploratory surgery, the clinician may arrive at a diagnosis earlier in the course of a neoplasm. This in turn may facilitate more efficacious treatment. A particularly interesting aspect of tumors of the gastrointestinal tract is their frequent association with environmental carcinogens. By being aware of these relationships, veterinarians stand a better chance of reaching the ultimate goal of cancer therapists--the prevention of malignant disease.


Fast spark discharge-laser-induced breakdown spectroscopy method for rice botanic origin determination.
A simple, fast, and efficient spark discharge-laser-induced breakdown spectroscopy (SD-LIBS) method was developed for determining rice botanic origin using predictive modeling based on support vector machine (SVM). Seventy-two samples from four rice varieties (Guri, Irga 424, Puitá, and Taim) were analyzed by SD-LIBS. Spectral lines of C, Ca, Fe, Mg, N and Na were selected as input variables for prediction model fitting. The SVM algorithm parameters were optimized using a central composite design (CCD) to find the better classification performance. The optimum model for discriminating rice samples according to their botanical variety was obtained using C = 5.25 and γ = 0.119. This model achieved 96.4% of correct predictions in test samples and showed sensitivities and specificities per class within the range of 92-100%. The developed method is robust and eco-friendly for rice botanic identification since its prediction results are consistent and reproducible and its application does not generate chemical waste.


Deterioration of muscle function in the human esophagus with age.
Most studies on the effect of aging on esophageal motor function have shown that peristaltic function deteriorates with age. Esophageal motor function is traditionally studied by means of manometry and radiography. Distension of the esophagus with evaluation of active and passive mechanical parameters have become available during recent years. In this study, we did a manometric swallow analysis and used the distension method to study esophageal properties and function during aging. An impedance planimetric probe with a bag for distension was placed in the distal esophagus of 25 healthy volunteers with a median age of 35 (range 23-86) years. Distensions were done at an infusion rate of 25 ml min(-1) with and without relaxation of neuromuscular activity with butylscopolamine. The infusion was reversed when moderate pain was experienced by the subjects. Swallow-induced contraction amplitudes decreased as function of age for persons older than 40 years (P < 0.05). The total and passive tension showed an exponential increase as function of the change in radius, whereas the active tension increased until it reached a local maximum point. The maximum active tension deteriorated as a function of age after the age of 40 years (P < 0.05). Furthermore, esophagus became stiffer with age. In conclusion, age-related changes of increased stiffness and reduced primary and secondary peristalsis were found in the human esophagus with a deterioration of esophageal function after the age of 40 years. Such changes may contribute to the high prevalence of reflux disease in elderly.


Bilateral malignant lymphoma of the breast in patients with a familial history of cancer: a report of three cases.
We report three cases of bilateral malignant lymphoma of the breast in patients with a familial history of cancers. All the patients had B-cell malignant lymphoma and were treated by a radical mastectomy and polychemotherapy. Bilateral tumors were detected synchronously in one case, whereas the second tumors in the other cases occurred 4 years and 8 years after the initial treatment. Although the patients had no relevant past history, these cases were notable for the fact that all were associated with a familial history of cancers. One patient had a definite familial history of breast cancer, that is to say, her mother, sister and brother all suffered from this disease. The brother of another patient died of gastric cancer while two of her uncles each suffered from sarcoma of the lower extremities and a brain tumor, respectively. As for the remaining patient, one of her maternal uncles and an aunt also died of prostate cancer and leukemia, respectively. However, only one out of seven patients with unilateral malignant lymphoma of the breast used for comparison had a familial history of cancer. A possible relationship between bilateral primary malignant lymphoma of the breast and a familial history of cancer is suggested.


Runoff control simulation and comprehensive benefit evaluation of low-impact development strategies in a typical cold climate area.
With the acceleration of urbanization, the proportion of surface imperviousness is increasing continuously in cities, resulting in frequent waterlogging disasters. In this context, storm water management, based on the low-impact development (LID) concept, offers an effective measure for the management of urban storm waters. First, the storm water management model (SWMM) was built for a typical cold climate city (Changchun) in China. Next, the two-stage calibrated model was employed to explore the surface runoff and storm sewer control effects of four LID combination plans. Finally, these plans were put through a "cost-benefit" evaluation through an analytic hierarchy process. According to the results, after using four LID plans, the reduction rates of peak runoff exceeded 40% and the problem of overflow load of the storm sewage was significantly mitigated. The infiltration-oriented Plan I proved to be the optimal plan, with the lowest proportions of the overflow nodes and full-load pipe sections in each return period, as well as with maximum overall performance. This study offers technical and conformed methodological support to cold cities for the prevention and control of waterlogging disasters and recycling of rainwater resources.


Metabolic regulation by p53 family members.
The function of p53 is best understood in response to genotoxic stress, but increasing evidence suggests that p53 also plays a key role in the regulation of metabolic homeostasis. p53 and its family members directly influence various metabolic pathways, enabling cells to respond to metabolic stress. These functions are likely to be important for restraining the development of cancer but could also have a profound effect on the development of metabolic diseases, including diabetes. A better understanding of the metabolic functions of p53 family members may aid in the identification of therapeutic targets and reveal novel uses for p53-modulating drugs.


Blood pressure variability and brain morphology in elderly women without cardiovascular disease.
To examine the relationship between blood pressure (BP) variability (BPV), brain volumes, and cognitive functioning in postmenopausal women with few modifiable cardiovascular risk factors. Study participants consisted of postmenopausal women enrolled in the Women's Health Initiative Memory MRI study (WHIMS-MRI) without cardiovascular disease, diabetes mellitus, hypertension, or current smoking at baseline (1996-1999). BP readings were taken at baseline and each annual follow-up visit. BPV was defined as the SD associated with a participant's mean BP across visits and the SD associated with the participant's regression line with BP regressed across visits. Brain MRI scans were performed between 2004 and 2006. Cognitive functioning was assessed at baseline and annually thereafter with the Modified Mini-Mental State Examination (3MSE) scoring until 2008. The final sample consisted of 558 women (mean age 69 years, median follow-up time [interquartile range] 8 [0.8] years). In adjusted models including mean systolic BP, women in the highest tertile of systolic BPV had lower hippocampal volumes and higher lesion volumes compared to women in the lowest tertile. No relationship between BPV and 3MSE scoring was detected. In postmenopausal women with few modifiable cardiovascular risk factors, greater visit-to-visit systolic BPV was associated with reductions in hippocampal volume and increases in lesion volumes at later life. These data add evidence to the emerging importance of BPV as a prognostic indicator even in the absence of documented cardiovascular risk factors.


Laparoscopic rectosigmoid resection with transanal colonic pull-through and delayed coloanal anastomosis: a new approach to adult Hirschsprung disease.
Hirschsprung disease in adults is a rare and frequently misdiagnosed cause of long-standing, refractory constipation. Surgical procedures initially developed for pediatric patients have been applied to adults with varying degrees of success. Our aim was to describe a new surgical procedure consisting of laparoscopic rectosigmoid resection with a transanal colonic pull-through followed by a delayed coloanal anastomosis for the treatment of Hirschsprung disease in adults and to present our preliminary results with this technique. This was a descriptive observational study of treatment outcome conducted at the colorectal surgical unit of a university teaching hospital in France. Patients were adults with confirmed Hirschsprung disease treated from October 2006 through February 2009. Laparoscopic rectosigmoid resection was performed with a transanal colonic pull-through followed by a delayed coloanal anastomosis. Clinical and functional data (Cleveland Clinic Florida incontinence scale and Fecal Incontinence Quality of Life scale) were obtained at postoperative visits. Five patients underwent the procedure. One patient died of postoperative cardiovascular complications. No patient had to be reoperated. No anastomotic leakage occurred. One patient developed anastomotic stricture requiring dilatation. No sexual or urinary dysfunction was reported. Postoperative analysis (mean follow-up 16 months) showed good functional outcomes in 3 (75%) of the 4 evaluable patients. This study had only a small number of patients and no controls other comparison with cases reported in the literature. Laparoscopic rectosigmoid resection with a transanal colonic pull-through followed by delayed coloanal anastomosis represents a valid alternative in the treatment of Hirschsprung disease in adult patients, because it involves minimally invasive surgery, does not require a preventive diverting stoma, and shows anastomotic security.


AFM imaging and analysis of local mechanical properties for detection of surface pattern of functional groups.
In this work we evaluate the applicability of different atomic force microscopy (AFM) modes, such as Phase Shift Imaging, Atomic Force Acoustic Microscopy (AFAM) and Force Spectroscopy, for mapping of the distribution pattern of low-molecular-weight biomimetic groups on polymer biomaterial surfaces. Patterns with either random or clustered spatial distribution of bioactive peptide group derived from fibronectin were prepared by surface deposition of functional block copolymer nano-colloids and grafted with RGDS peptide containing the sequence of amino acids arginine-glycine-aspartic acid-serine (conventionally labeled as RGDS) and carrying biotin as a tag. The biotin-tagged peptides were labeled with 40nm streptavidin-modified Au nanospheres. The peptide molecules were localized through the detection of bound Au nanospheres by AFM, and thus, the surface distribution of peptides was revealed. AFM techniques capable of monitoring local mechanical properties of the surface were proved to be the most efficient for identification of Au nano-markers. The efficiency was successfully demonstrated on two different patterns, i.e. random and clustered distribution of RGDS peptides on structured surface of the polymer biomaterial.


Corrigendum: Effects of weight divisions in time-motion of female high-level Brazilian Jiu-jitsu combat behaviors.
[This corrects the article DOI: 10.3389/fpsyg.2023.1048642.].


Effects of culture (China vs. US) and task on perceived hazard: Evidence from product ratings, label ratings, and product to label matching.
In the current study, 44 Chinese and 40 US college students rated their perceived hazard in response to warning labels and products and attempted to match products with warning labels communicating the same level of hazard. Chinese participants tended to provide lower ratings of hazard in response to labels, but hazard perceived in response to products did not significantly differ as a function of culture. When asked to match a product with a warning label, Chinese participants' hazard perceptions appeared to be better calibrated, than did US participants', across products and labels. The results are interpreted in terms of constructivist theory which suggests that risk perceptions vary depending on the "frame of mind" evoked by the environment/context. Designers of warnings must be sensitive to the fact that product users' cognitive representations develop within a culture and that risk perceptions will vary based on the context in which they are derived.


Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo.
Infantile fibrosarcoma is a rare childhood tumour that originates in the fibrous connective tissue of the long bones for which there is an urgent need to identify novel therapeutic targets. This study aims to clarify the role of the extracellular matrix component hyaluronan in the invasion of child fibroblasts and Infantile fibrosarcoma into the surrounding environment. Using nanoscale super-resolution STED (Stimulated emission depletion) microscopy followed by computational image analysis, we observed, for the first time, that invasive child fibroblasts showed increased nanoscale clustering of hyaluronan at the cell periphery, as compared to control cells. Hyaluronan was not observed within focal adhesions. Bioinformatic analyses further revealed that the increased nanoscale hyaluronan clustering was accompanied by increased gene expression of Hyaluronan synthase 2, reduced expression of Hyaluronidase 2 and CD44, and no change of Hyaluronan synthase 1 and Hyaluronidases 1, 3, 4 or 5. We further observed that the expression of the Hyaluronan synthase 1, 2 and 3, and the Hyaluronidase 3 and 5 genes was linked to reduced life expectancy of fibrosarcoma patients. The invasive front of infantile fibrosarcoma tumours further showed increased levels of hyaluronan, as compared to the tumour centre. Taken together, our findings are consistent with the possibility that while Hyaluronan synthase 2 increases the levels, the Hyaluronidases 3 and 5 reduce the weight of hyaluronan, resulting in the nanoscale clustering of hyaluronan at the leading edge of cells, cell invasion and the spread of Infantile fibrosarcoma.


Life Cycle Assessment and Environmental Life Cycle costing of a unitised regenerative fuel cell stack.
Life Cycle Assessment (LCA) and Environmental Life Cycle Costing (eLCC) are useful methods for evaluating the environmental, energy and economic performances of innovative energy storage technologies. By using these methods, the production process of a small Polymer Electrolyte Membrane Unitized Regenerative Fuel Cell (PEM-URFC) stack has been investigated, aiming to assess its environmental, energy and economic impacts at the early design stage and to identify the contributions of its various components on these impacts. Indeed, the PEM-URFC stack includes Critical Raw Materials that affect the product's sustainability. Results show that the highest contributions are associated with the platinum group metals used for the catalyst and, to a lesser degree, the materials and energy used for the bipolar plates and porous transport layers. However, considering that the datasets for representing the impacts of one of the electrocatalysts (Iridium Ruthenium Oxide) are still missing in LCA commercial databases and literature, a sensitivity analysis is performed assuming its impact to be similar to that of other Platinum Group Metals (PGMs) extracted with them (e.g., Platinum, Nickel, Palladium, etc.). The analysis shows a high difference in results due to data and methodological assumptions, making the assimilation of Iridium Ruthenium Oxide to Rhodium the worst scenario, increasing environmental impacts by 37.54 %, energy impacts by 40.48 % and environmental price by 45.08 %. Moreover, the study identified issues for applying life cycle thinking approaches on URFC devices that must be resolved in future studies (e.g., increase the reliability of catalyst inventory data or improve guidelines on energy storage technologies).