Estimates of cancer burden in Sicily.
Estimates are complementary epidemiological measures which allow to present data on cancer burden, especially in geographical areas where measurements of cancer occurrence are not supported by exhaustive statistics on incidence, mortality and survival. The aim of this paper is to provide cancer incidence, mortality and prevalence estimates and projections for the major cancers in the period 1970-2015 for the entire region of Sicily. The estimates were computed by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Published data from the Italian cancer registries were modeled in order to estimate the regional cancer survival. In 2012 the most common cancers were breast cancer in women, colorectal cancer in both sexes, and prostate cancer in men, with about 4,000, 3,500 and 3,000 estimated new cases, respectively. The highest crude mortality rates were estimated for lung cancer in men (63.6 per 100,000) and breast cancer in women (30.8 per 100,000) and the lowest for skin melanoma (both sexes) and cancer of the cervix uteri. For colorectal, lung and stomach cancer and skin melanoma, all the indicators were higher in men than women. The prevalence figures in women were more than 9 times the incidence figures for breast cancer and more than 10 times the incidence figures for skin melanoma. The prevalence was twice the incidence for lung cancer in both sexes. The prevalence increased for all the considered cancers except cervical cancer. According to our analyses in Sicily we expect about 14,000 new diagnoses and 5,500 deaths for the major cancer types in a year, while about 92,000 persons with a diagnosis of the considered cancers were alive in 2012. We expect an increase in cancer survival and contemporary aging of the population: both expectations will inflate the cancer prevalence, causing more demand for oncology facilities.


[Case description of the abnormally big pseudoaneurysm in a patient after myocardial infarction].
Authors present a case of a 72 years old woman with an abnormally big left ventricular pseudoaneurysm as a consequence of a rupture of the left ventricular wall during myocardial infarction. Pseudoaneurysm threatens its carrier with both sudden death as a result of the rupture and a progressing heart failure. The patient mentioned has undergone an infero-lateral myocardial infarction complicated with beginning cardiogenic shock in July 2001. Based on coronarography examination which proved only peripheral stenoses in coronary bed a conservative procedure was indicated. In June 2002 the patient was admitted to a hospital for progressive dyspnoea, nonspecific chest and epigastric pain, and dyspeptic complaints. Transtoracal echocardiography examination proved a large pseudoaneurysm coming from periapical bottom wall of the left ventricle. Diagnosis was further confirmed and specified by ventriculography and the patient was indicated for surgery. Authors present a range of clinical signs of pseudoaneurysm, an approach to an examination, differential diagnostics and treatment procedure in patients with this unusual complication.


Microbial Biotechnology is 15! An adventure in journal parenting.
This year, 2022, Microbial Biotechnology (MBT) celebrates its 15th birthday. In journal terms, 15 is adulthood. It has been a privilege to develop the idea, launch the journal, nurture it in its infancy and stimulate and support it during its adolescence and early adulthood. The success of MBT - its growth over the last 4 years averaging > 30%, and the highest impact factor in the field, making it the leading research journal in applied microbiology/microbial biotechnology and the most attractive to publish in - gives us enormous pleasure and satisfaction, and not a little pride.


Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons.
The analgesic effects of Cannabis sativa are mediated by ∆9 tetrahydrocannabinol (THC), but the contributions of other bioactive complex components, including cannabigerol (CBG) and cannabidiol (CBD), are unclear. We describe the individual and combined effects of CBG, CBD and THC, on blocking capsaicin responses in dorsal root ganglion (DRG) neurons, in an in vitro model of nociceptor hypersensitivity. Adult rat DRG were dissected and enzyme digested to obtain a neuronal suspension in BSF2 medium containing 2% fetal calf serum, and the neurotrophic factors NGF and GDNF. After 48 h, cultured neurons were loaded with Fura-2 AM, to determine the effects of cannabinoids on capsaicin responses using calcium imaging. In control experiments, neurons were treated with vehicle, followed by 1 µM capsaicin. In cannabinoid treated cultures, CBG, CBD or THC were applied individually, or combined (1:1:1 ratio), followed by 1 µM capsaicin. Data from n = 6 experiments were analysed with Student's t-test and Pearson's correlation coefficient. CBG, CBD and THC, applied individually, elicited dose-related calcium influx in a subset of DRG neurons, and a corresponding dose-related reduction of subsequent responses to capsaicin. Maximum inhibition of capsaicin responses was observed at 30 µM CBG, 100 µM CBD, and 100 µM THC individually, and with combined CBD+CBG+THC (1:1:1) at 90 µM. THC+CBD+CBG combined in a 1:1:1 proportion has the potential to enhance the potency of these compounds applied individually. There was a high correlation between cannabinoid-mediated calcium influx and reduction of capsaicin responses: CBG = -0.88, THC = -0.97, CBD = -0.99 and combined CBG + THC + CBD = -1.00. CBG, CBD and THC demonstrated potent dose-related inhibition of capsaicin responses in DRG neurons when applied individually in vitro, and enhanced when applied in combination, being most effective at 90 μM. Thus, efficacy and tolerability of THC could be improved in combination with CBG and CBD at optimal concentrations, which deserve further studies in vivo.


A case of lupus nephritis showing good clinical course and apoptosis in glomerular cells detected by the nick end labeling method.
We report here an adult patient with lupus nephritis who had a good clinical course under long-term observation. Apoptotic bodies in the glomeruli were determined in serial renal biopsy specimens by the nick end labeling method. Apoptotic bodies in the proliferated glomerular cells were detected in the 3rd renal biopsy but not in the 2nd biopsy. The clinical activities of lupus nephritis fluctuated until the time of the 3rd renal biopsy. The 3rd renal biopsy was performed because of increased proteinuria and an increased amount of hyaline, granular and red blood cell casts, with impairment of renal function. The levels of proteinuria, creatinine clearance and serum complements were improved after the 3rd renal biopsy. It appears that apoptosis might control glomerular cell proliferation and also influence the clinical course of lupus nephritis.


A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.
The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.


Impact of Salmonella Control Programmes in Poultry on Human Salmonellosis Burden in Greece.
Since 2008, veterinary authorities in Greece have implemented national control programmes (NSCPs) targeting S. Enteritidis (SE) and S. Typhimurium (ST) in poultry. We assessed the effect of the programs on the reported number of human isolates. Using monthly data for 2006-2017, we defined two groups (SE, ST) and one control group with serotypes unrelated to poultry or eggs. For SE we also analysed data for 2006-2015 due to a multi-county SE outbreak in 2016. We performed an interrupted time series analysis and used a negative binominal regression model. For both SE and ST, there was no significant trend of the isolation rate before or after NSCPs' introduction. After the NSCPs' introduction there was an increasing rate (IRR: 1.005, 95% CI: 1.001-1.008) for control serotypes and a decreasing one for SE (IRR: 0.990, 95% CI: 0.986-0.995) (for 2009 to 2015 analysis). From 2006 to 2017, NSCPs had a statistically significant impact on the number of SE isolates that decreased by 49% (IRR:0.511, 95% CI: 0.353-0.739). No impact was shown on the number of ST (p-value = 0.741) and control isolates (p = 0.069). As a conclusion, NSCP's implementation was associated with decreased SE isolates and overall burden of salmonellosis; however further measures aiming at human salmonellosis due to ST, should be considered.


Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice.
Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the effect of CREG1 on aging-associated phenotypes. In this study, we investigated the effects of CREG1 on age-related obesity and renal dysfunction in Tg mice. Increased brown fat formation was detected in aged Tg mice, in which age-associated metabolic phenotypes such as body weight gain and increases in blood glucose were improved compared with those in wild-type (WT) mice. Blood CREG1 levels increased significantly in WT mice with age, whereas the age-related increase was suppressed, and its levels were reduced, in the livers and kidneys of Tg mice relative to those in WT mice at 25 months. Intriguingly, the mRNA levels of Ink4a, Arf, and senescence-associated secretory phenotype (SASP)-related genes and p38MAPK activity were significantly lowered in the aged kidneys of Tg mice, in which the morphological abnormalities of glomeruli as well as filtering function seen in WT kidneys were alleviated. These results suggest the involvement of CREG1 in kidney aging and its potential as a target for improving age-related renal dysfunction.


Comparison of Two Bayesian Methods in Evaluation of the Absence of the Gold Standard Diagnostic Tests.
The Bayesian model plays an important role in diagnostic test evaluation in the absence of the gold standard, which used the external prior distribution of a parameter combined with sample data to yield the posterior distribution of the test characteristics. However, the correlation between diagnostic tests has always been a problem that cannot be ignored in the Bayesian model evaluation. This study will discuss how different Bayesian model, correlation scenarios, and prior distribution affect the outcome. The data analyzed in this study was gathered during studies of patients presenting to the Nanjing Chest Hospital with suspected tuberculosis. The diagnostic character of T-SPOT.Tb and KD38 tuberculosis antibody test were evaluated in different Bayesian model, and discharge diagnosis as a gold standard was used to verify the model results in the end. The comparison of four models under the conditional independence situation found that Bayesian probabilistic constraint model was consistent with the Conditional Covariance Bayesian model. The results were mainly affected by prior information. The sensitivity and specificity of the two tests in Conditional Covariance Bayesian model in prior constraint situation were considerably higher than the Bayesian probabilistic constraint model in prior constraint situation. The results of the four models under the conditional dependence situation were similar to the conditional independence situation; pD was also negative with no prior constraint situation in both model Bayesian probabilistic constraint model and Conditional Covariance Bayesian model. The Deviance Information Criterion of Bayesian probabilistic constraint model was close to model Conditional Covariance Bayesian model, but pD of Conditional Covariance Bayesian model in Prior constraint situation (pD=2.40) was higher than the Bayesian probabilistic constraint model in Prior constraint situation (pD=1.66). The result of Conditional Covariance Bayesian model in prior constraint with conditional independence situation was closest to the result of gold standard evaluation in our data. Both of the two Bayesian methods are the feasible way for the evaluation of diagnostic test in the absence of the gold standard diagnostic. Prior source, priority number, and conditional dependencies should be considered in the method selection, the accuracy of posterior estimation mainly depending on the prior distribution.


Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study.
Polycystic ovary syndrome (PCOS) represents a serious reproductive and endocrine condition and is associated with high incidence rates. H19 is a compelling long noncoding RNA (lncRNA) which carries out a range of biological functions. However, prior to this study, little was known as to whether there was an association between lncRNA H19 and PCOS. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine lncRNA H19 expression levels in peripheral blood leukocytes from patients with PCOS and compared this data with that derived from normal controls. We also screened data for potential relationships between lncRNA H19 and a range of endocrine variables in PCOS. The expression of lncRNA H19 was significantly higher in cases of PCOS than in controls. Individuals exhibiting higher expression levels of lncRNA H19 were associated with a significantly higher risk of PCOS than those with lower expression levels. Moreover, lncRNA H19 expression was positively correlated with fasting plasma glucose levels; this was the case with both raw data, and after adjustment for age and BMI in the PCOS group. However, lncRNA H19 expression showed no significant correlation with total testosterone or insulin resistance in either PCOS cases or the controls. In conclusion, we demonstrate the first evidence to indicate that lncRNA H19 is associated with PCOS, suggesting that elevated lncRNA H19 levels are a risk factor for PCOS. For susceptible individuals, lncRNA H19 may represent a useful biomarker of the early stages of endocrine and metabolic disorders in PCOS.


[Hygiene and methods of decontamination, disinfection and sterilization in dental offices in Yaounde].
Hygiene and asepsis of the dental office depend on medical ethics and legal obligation. The survey done with the participation of 33 practitioners over the 42 practicing in Yaounde allows apprehending the reality of the daily hygiene. The ways of cleaning, decontamination, disinfection or of sterilization of the premises, the dental equipment and instruments, hand-washing, disposable materials and the vaccination protection of the practitioners were analyzed. The cleaning of the floor and door mats is daily (100%); disinfection is done daily in 83% of the departments in all of the centers. The cleaning and disinfection of the dental chair is daily and is done using soap (23%) and/or bleaching-water (56%). Cleaning or disinfection of the suction machine is done with soap (24%) or with bleaching-water (47%). The hand-pieces and the turbines are cleaned and/or disinfected after each usage in (94%) with alcohol (17%) or with bleaching-water (32%) and sterilized with a heat sterilizer (45%), an autoclave(40%) or cold disinfected(15%). The frequency of the treatment of the instruments is well-respected (83%). Nevertheless the products used are very varied and are not always used in the prescribed order. Hand-washing is systematic after each patient; 50% of the practitioners use soap bars or powered soap and 50% use an antiseptic or a disinfectant solutions. With the regard to the vaccination, only 3 practitioners were properly vaccinated against hepatitis B, tetanus, diphtheria, poliomyelitis and tuberculosis. With regard to the protection of the practitioners, 72% do not wear caps, 56% do not wear eyeglasses, 40% do not wear masks, 95% do not use rubber dams, 56% do not disinfect the radiographic films and 37% do not disinfect the impressions; the habitual attire consists of a smock worn over street clothes (78%) and street shoes (90%). The debris is burnt in 35% of the centers. Better knowledge of the different stages (cleaning, decontamination, disinfection or sterilization and the products used, absolute respect of the disposable materials, optimal vaccination protection and the elaboration of the correct procedures written and posted up in the different departments are fundamental points for quality treatment. As a matter of fact, negligence and ignorance of the rules of hygiene and asepsis should not be part and parcel of the therapeutic hazard in the dental department.


Prediction of low haemoglobin levels in whole blood donors.
Each year, a relevant proportion of whole blood donors is deferred from donation because of low haemoglobin (Hb) levels. Such temporary deferrals are demoralizing, and donors may never return for a donation. Reliable predictions of Hb levels may guide the decision whether donors can be invited for the next donation. In this study, a prediction model was developed for the risk of low Hb levels. Individual data from 5191 whole blood donors were analysed; 143 donors had a low Hb level. Eleven candidate predictors were considered in logistic regression models to predict low Hb levels. The performance of the prediction model was studied with the receiver operating characteristic (ROC) curve. Internal validity was assessed with a bootstrap procedure. Strong predictors were sex, seasonality, Hb level measured at the previous visit, difference in Hb levels between the previous two visits, time since the previous visit, deferral at the previous visit, and the total number of whole blood donations in the past 2 years. Internal validation showed an area under the ROC curve of 0·87. The developed prediction model provides accurate discrimination between donors with low and appropriate Hb levels. The model predictions may be valuable to determine whether donors can be invited for a next donation, or whether some interventions such as postponement of the invitation are warranted. Potentially, this could decrease the number of donor deferrals for low Hb levels.


Respiratory Syncytial Virus Disease Severity in Young Children.
Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children. Children aged <5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children's Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children. From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B. RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children.


Residents' practices and perceptions about do not resuscitate orders and pronouncing death: an opportunity for clinical training.
Although ''Do not resuscitate'' (DNR) orders are among the most commonly discussed patient preference treatment measures, few studies have assessed internal medicine residents' views on this complex topic. Our objective was to assess resident practices in establishing code status. We also examined resident training and experiences in pronouncing death. An 18-question survey addressing DNR discussions and pronouncing death was emailed to internal medicine residents in the state of Illinois. Each question had multiple-choice options. A total of 175 residents completed the questionnaire (22% response rate). Seventy-eight percent of the residents had discussed DNR status with patients or their families at least 9 times. However, only one third of the residents felt very comfortable in such discussions. Only 26% of the residents had been observed by a faculty member during a code status discussion and fewer (16%) while pronouncing death. Do not resuscitate discussions rarely occurred in an outpatient clinic (27%). Most residents (90%) thought they would benefit from formal training in DNR discussion. Although most residents discuss DNR status with patients and families, only a quarter are observed in such discussions by attending physicians and only a third feel comfortable with this aspect of clinical care. Developing a structured residency program curriculum to address resident skills in end-of-life care would benefit residency training.


There's more than one frog in the pond: a survey of the Amphibia and their contributions to developmental biology.
The study of developmental biology has benefited greatly from the insights gained using amphibians as experimental models. Although Xenopus is currently the predominant model, much of our embryological knowledge derives from research on other amphibians. I will review some of these discoveries, made through astute choice of model organism, and I will examine the reasons behind the adoption of Xenopus as the standard for amphibian research. Additionally, I will discuss the diversity in developmental and reproductive strategies that exists within the Amphibia, and consider some of the recent advances in our understanding of the mechanisms underlying this developmental diversity.


Ozone disinfection of waterborne pathogens and their surrogates: A critical review.
Viruses, Giardia cysts, and Cryptosporidium parvum oocysts are all major causes of waterborne diseases that can be uniquely challenging in terms of inactivation/removal during water and wastewater treatment and water reuse. Ozone is a strong disinfectant that has been both studied and utilized in water treatment for more than a century. Despite the wealth of data examining ozone disinfection, direct comparison of results from different studies is challenging due to the complexity of aqueous ozone chemistry and the variety of the applied approaches. In this systematic review, an analysis of the available ozone disinfection data for viruses, Giardia cysts, and C. parvum oocysts, along with their corresponding surrogates, was performed. It was based on studies implementing procedures which produce reliable and comparable datasets. Datasets were compiled and compared with the current USEPA Ct models for ozone. Additionally, the use of non-pathogenic surrogate organisms for prediction of pathogen inactivation during ozone disinfection was evaluated. Based on second-order inactivation rate constants, it was determined that the inactivation efficiency of ozone decreases in the following order: Viruses >> Giardia cysts > C. parvum oocysts. The USEPA Ct models were found to be accurate to conservative in predicting inactivation of C. parvum oocysts and viruses, respectively, however they overestimate inactivation of Giardia cysts at ozone Ct values greater than ∼1 mg min L-1. Common surrogates of these pathogens, such as MS2 bacteriophage and Bacillus subtilis spores, were found to exhibit different inactivation kinetics to mammalian viruses and C. parvum oocysts, respectively. The compilation of data highlights the need for further studies on disinfection kinetics and inactivation mechanisms by ozone to better fit inactivation models as well as for proper selection of surrogate organisms.


Selective enrichment and detection of mycobacterial DNA in paucibacillary specimens.
A major challenge for tuberculosis control is mycobacterial detection in paucibacillary disease, particularly in pediatric, extrapulmonary and smear-negative pulmonary infections. We developed a simple and efficient DNA extraction and real-time quantitative PCR (qPCR) protocol for mycobacterial detection and quantification in paucibacillary specimens. The method was refined using an in vitro model mimicking blood specimens which are characterized by the presence of numerous qPCR inhibitors. Mycobacterial DNA detection in blood is of interest given the high sensitivity we previously reported using conventional PCR in blood of patients with tuberculosis lymphadenitis. Mechanical lysis of mycobacteria in the presence of an organic solvent provided the highest sensitivity. Mycobacterial DNA amplification was compromised when the human:bacterial genome ratio was at least 190:1. Separation of the specimen into bacterial- and host-rich fractions prior to DNA extraction improved mycobacterial DNA detection by 30%. Preliminary testing of our protocol in smear-negative, culture-positive specimens (gastric and lymph node aspirates, pleural and cerebrospinal fluid, and blood) confirmed the applicability of our technique to a range of paucibacillary specimens for the detection, quantification and speciation (M. tuberculosis versus M. avium) of mycobacteria, several weeks before culture results were available. Our protocol provides a novel, efficient and simple strategy to improve the performance of qPCR in paucibacillary specimens, including those with excess human DNA background. This tool is useful to study the pathophysiology of early pulmonary or occult tuberculosis, and for more rapid and accurate diagnosis in difficult to diagnose infections.


Successful recanalization of acute superior mesenteric artery thrombotic occlusion with primary aspiration thrombectomy.
Prompt revascularization of the superior mesenteric artery (SMA) thrombotic occlusion can prevent intestinal infarction and decrease necrosis of the bowel segment. Herein, we describe two cases who underwent successful endovascular recanalization for acute SMA thrombosis using a primary aspiration thrombectomy because of possible consequent laparotomy for survey of bowel viability. The two patients had dramatic pain relief immediately after the procedure and remained symptom-free during the follow-up period.


Generalized partial dynamical symmetry in nuclei.
We introduce the notion of a generalized partial dynamical-symmetry for which part of the eigenstates have part of the dynamical symmetry. This general concept is illustrated with the example of Hamiltonians with a partial dynamical O(6) symmetry in the framework of the interacting boson model. The resulting spectrum and electromagnetic transitions are compared with empirical data in 162Dy.


Course of intellectual functioning in schizophrenia and bipolar disorder: a 10-year follow-up study.
Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls. We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment. Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period. Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.


Comparisons of various acidic treatments of bovine serum on insulin-like growth factor-I immunoreactivity and binding activity.
Untreated serum exhibited two forms of insulin-like growth factor-I (IGF-I)-binding protein complexes during gel chromatography: one of Mr 150,000 and the other of Mr 40,000-45,000. The majority of the immunoreactive IGF-I was associated with the Mr 150,000 complex. Following acid-ethanol extraction of serum, the binding activity at Mr 150,000 disappeared and a reduced binding activity appeared in the albumin size range. Acid incubation of serum was slightly less effective than acid-ethanol extraction in reducing the binding activity. Acid-ethanol-extracted or acid-incubated serum were parallel to IGF-I standard in the dose-response displacement of iodinated IGF-I. Gel filtration of serum with 1 mol acetic acid/l almost completely separated IGF-I and the binding proteins. Binding-protein fractions from gel filtration interfered with the immunoreactivity of IGF-I with its antibodies, causing a non-parallel displacement curve in the radioimmunoassay (RIA). Serum IGF-I could be isolated as a single peak by high performance C18 reverse-phase liquid chromatography (HPLC). The concentrations of IGF-I measured in bovine sera by RIA were similar between acid gel filtration and HPLC; the concentrations by acid-ethanol extraction and acid incubation being about 30% smaller than those measured with former methods. The lower concentration of IGF-I measured in bovine serum with acid-ethanol extraction or acid incubation appears to be due to interference of IGF-binding proteins not removed by either treatment.


Improving suicide risk prediction via targeted data fusion: proof of concept using medical claims data.
Reducing suicidal behavior among patients in the healthcare system requires accurate and explainable predictive models of suicide risk across diverse healthcare settings. We proposed a general targeted fusion learning framework that can be used to build a tailored risk prediction model for any specific healthcare setting, drawing on information fusion from a separate more comprehensive dataset with indirect sample linkage through patient similarities. As a proof of concept, we predicted suicide-related hospitalizations for pediatric patients in a limited statewide Hospital Inpatient Discharge Dataset (HIDD) fused with a more comprehensive medical All-Payer Claims Database (APCD) from Connecticut. We built a suicide risk prediction model for the source data (APCD) and calculated patient risk scores. Patient similarity scores between patients in the source and target (HIDD) datasets using their demographic characteristics and diagnosis codes were assessed. A fused risk score was generated for each patient in the target dataset using our proposed targeted fusion framework. With this model, the averaged sensitivities at 90% and 95% specificity improved by 67% and 171%, and the positive predictive values for the combined fusion model improved 64% and 135% compared to the conventional model. We proposed a general targeted fusion learning framework that can be used to build a tailored predictive model for any specific healthcare setting. Results from this study suggest we can improve the performance of predictive models in specific target settings without complete integration of the raw records from external data sources.


Understanding the Dynamics of the Developing Adolescent Brain Through Team Science.
One of the major goals for research on adolescent development is to identify the optimal conditions for adolescents to grow up in a complex social world and to understand individual differences in these trajectories. Based on influential theoretical and empirical work in this field, achieving this goal requires a detailed understanding of the social context in which neural and behavioral development takes place, along with longitudinal measurements at multiple levels (e.g., genetic, hormonal, neural, behavioral). In this perspectives article, we highlight the promising role of team science in achieving this goal. To illustrate our point, we describe meso (peer relations) and micro (social learning) approaches to understand social development in adolescence as crucial aspects of adolescent mental health. Finally, we provide an overview of how our team has extended our collaborations beyond scientific partners to multiple societal partners for the purpose of informing and including policymakers, education and health professionals, as well as adolescents themselves when conducting and communicating research.


Temporal clustering of neuroblastic tumours in children and young adults from Ontario, Canada.
The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England. We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained. Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005). The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs.


Heteromodal connections supporting multisensory integration at low levels of cortical processing in the monkey.
While multisensory integration is thought to occur in higher hierarchical cortical areas, recent studies in man and monkey have revealed plurisensory modulations of activity in areas previously thought to be unimodal. To determine the cortical network involved in multisensory interactions, we performed multiple injections of different retrograde tracers in unimodal auditory (core), somatosensory (1/3b) and visual (V2 and MT) cortical areas of the marmoset. We found three types of heteromodal connections linking unimodal sensory areas. Visuo-somatosensory projections were observed originating from visual areas [probably the ventral and dorsal fundus of the superior temporal area (FSTv and FSTd), and middle temporal crescent (MTc)] toward areas 1/3b. Somatosensory projections to the auditory cortex were present from S2 and the anterior bank of the lateral sulcus. Finally, a visuo-auditory projection arises from an area anterior to the superior temporal sulcus (STS) toward the auditory core. Injections in different sensory regions allow us to define the frontal convexity and the temporal opercular caudal cortex as putative polysensory areas. A quantitative analysis of the laminar distribution of projecting neurons showed that heteromodal connections could be either feedback or feedforward. Taken together, our results provide the anatomical pathway for multisensory integration at low levels of information processing in the primate and argue against a strict hierarchical model.


[Role of twin reversed arterial perfusion syndrome in the development of fetus acardius].
Monochorionic multiple pregnancy has a higher risk for obstetric complications, including those due to the development of twin-to-twin transfusion syndrome and reversed arterial perfusion syndrome (TRAP sequence). The latter occurs in 0.1% of all monochorionic pregnancies. The basis for TRAP sequence is a relationship between arterial and venous anastomoses from the appropriate placental areas, causing a recipient fetus to develop at the expense of a donor fetus. The presence of abnormal anastomoses is considered to be a main cause of acardia. The prognosis for a donor fetus is also unfavorable: the mortality rates in the absence of intrauterine correction are as high as 55%.


Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Correlations of outcome with clinical and radiological data.
Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.


Health care-associated infections.
The incidence of postoperative infections in surgery can be reduced by 20% to 34% through adoption of "safe" patient care practices. Moreover, some of the recently highlighted epidemiologic features of infections in surgery, such as the increasing prevalence of antibiotic-resistant organisms, are strongly associated with questionable clinical choices. In recent years, several governments and scientific institutions have launched initiatives aimed at improving the safety of surgery, a key component of which is the availability of surveillance data. In 2003, an audit was performed in the Emilia-Romagna region of Italy on a random sample of general, orthopedic, and gynecologic surgical units to explore the knowledge, perceptions, and practices of surgeons and nurses regarding control of surgical site infections (SSI). The Emilia-Romagna regional audit found good agreement between the infectioncontrol standards and knowledge (70%), claimed practices (73%), and observed practices (78%). Surgical hand antisepsis was applied consistently, and surgical attire was used widely, but surgeons and nurses paid little attention to keeping operating room doors closed and limiting the number of people. Handwashing and sterile technique for postoperative incision care were the recommendations least frequently followed. Greater attention to proven methods of infection control and availability of surveillance data should reduce the incidence of SSI.


[Influence of metal-ceramic fixed dental restorations on the occurrence of discoloration of gingiva].
Adverse effects of dental cast alloys on the health of patients are the problem in clinical practice. The aim of this paper was to describe the case of a patient with discolorated gingivae in the presence of fixed dental restorations and used diagnostic and therapeutic procedures. A 30-year old pacient, presented with the complaints about unsatisfactory esthetic of his fixed dental restorations. He complained about the greyish discoloration of gingivae, inappropriate color of the crowns, and a larger space between the central incisors. Both discolorated and normal gingivae around the fixed dental restorations were taken by excision and the samples of gingivae were examined histopathologically, and by using the Atomic Absorption Spectrophotometry test (AAS). Histopathological examination of the discolorated gingivae showed the presence of non-specific inflammation with a foreign body. AAS revealed the presence of various metals in the samples and the higher metal contents in the samples of discolorated gingivae as compared with the samples of normal gingivae. New metal-ceramic crowns were made for the patient. A main cause of greyish discoloration of gingivae was presence of a metal in gingival tissue. After the excision of discolorated gingivae old metal-ceramic crowns should be replaced with new crowns.


Synthesis of Hybrid-Polypeptides m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) and Study of Their Structure and Aggregation. Influence of Hydrophobic Copolypeptides on the Properties of Poly(L-histidine).
The highly diverse and sophisticated action of proteins results from their equally diverse primary structure, which along with the nature of interactions between the amino acids, defines the higher self-assembly of proteins. The interactions between amino acids can be very complicated, and their understanding is necessary in order to elucidate the protein structure-properties relationship. A series of well-defined hybrid-polypeptidic diblock copolymers of the type m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) was synthesized through the ring opening polymerization of the N-carboxyanhydrides of the corresponding amino acids, with a molar ratio of the hydrophobic peptide to histidine at 10%, 20% and 40%. The excellent purity of the monomers combined with the high vacuum techniques resulted in controlled polymerization with high molecular and compositional homogeneity. FT-IR, as well as circular dichroism, were employed to investigate the secondary structure of the polymers, while DLS, SLS and ζ-potential were utilized to study the aggregates formed in aqueous solutions, as well as their pH responsiveness. The results revealed that the randomly distributed monomeric units of glycine or alanine significantly influence L-histidine's structure. Depending on the pH, aggregates with a different structure, different molecular characteristics and a different surface charge are formed, potentially leading to very interesting bioapplications.


[The factor of intra-abdominal pressure in patients with morbid obesity].
Pathogenetic peculiarities of chronic intraabdominal hypertension syndrome (CHIHS) in patients, suffering morbid obesity (MO), to whom bariatric operative interventions were performed, were studied. The intraabdominal pressure factor impact on the concurrent diseases and postoperative period course in patients, suffering MO, was analyzed.


Efficacy of continuous renal replacement on acute renal injury developed in severe sepsis.
Sepsis is a systemic inflammatory response that can further develop into severe sepsis (septic shock), which eventually leads to multiple organ dysfunction syndrome (MODS). This study aimed to assess the effects of continuous renal replacement therapy (CRRT) on acute renal injury caused by severe sepsis by monitoring biochemical parameters. A total of 60 patients with septic shock and acute kidney injury were included. The control group (30 cases) was treated with routine treatment and intermittent renal replacement therapy (IRRT). The experimental group (30 cases) was treated with routine treatment and continuous renal replacement therapy CRRT. The changes in inflammation and biochemical indexes and APACHE- II score were evaluated before the treatment and 1, 3, and 7days after the treatment. The inflammatory markers (neutrophil percentage, C-reactive protein (CRP) and procalcitonin (PCT) levels) in the experimental group decreased significantly after treatment. In the control group, the index of inflammation still increased one day after treatment and decreased on day 3 of treatment. After treatment, blood lactate, serum creatinine and urea nitrogen levels decreased, but the urine volume increased. After treatment, the vasoactive dose in the experimental group was significantly lower than that of the control group (P less than 0.05). CRRT is a good treatment for septic shock-related acute kidney injury, which improves biochemical indicators and protects kidney function.


Non-Hodgkin's lymphomas of primary follicle/mantle zone origin.
Recent immunopathologic studies have demonstrated that primary follicles and the mantle zones of secondary follicles are composed largely of virgin B lymphocytes which migrate from the bone marrow to these areas, and are the precursor cells of germinal centers. Non-Hodgkin's lymphomas corresponding to these immature B cells include mantle zone lymphoma (MZL), a primary follicle variant of MZL without reactive germinal centers, and diffuse intermediate lymphocytic (centrocytic) lymphoma. Diffuse intermediate lymphocytic lymphoma (DILL) is considered a late stage in the progression of MZL. Cytologically, these lymphomas usually resemble their normal cellular counterparts and consist predominantly of atypical small lymphoid cells with slightly-irregular and indented nuclei, moderately-coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Small lymphocytic, cerebriform and blastic variants have also been described. In smears and touch preparations, the neoplastic cells are usually prolymphocytes. Immunologically, the cells have features of virgin B cells, bearing pan-B cell antigens along with monoclonal surface IgM, with or without surface IgD, and CD5 (Leu 1) antigen, and lacking common acute lymphocytic leukemia associated (CALLA) antigen. Cytogenetically, the t(11;14)(q13;q32) has been associated with this group of lymphomas, and expression of the putative cellular oncogene bcl-1 (11q13) has been demonstrated in 30-50% of cases. Clinically, the patients have a median age of 60 years and usually present with advanced stage disease. Splenomegaly, often massive, is present in 80% of those with MZL. Patients with MZL have a significantly longer median survival (74-77 months) than those with DILL (30-33 months), and survival in both groups is significantly prolonged if a complete clinical remission is attained. Based on clinical studies, MZL should be considered a low grade lymphoma and DILL should be considered an intermediate grade lymphoma by Working Formulation criteria. The lymphomas of primary follicle/mantle zone origin are a distinct clinicopathologic entity biologically analogous to the follicular and diffuse lymphomas of germinal center origin, from which they should be distinguished in current and future classifications of non-Hodgkin's lymphoma.


Factorial structure of the 17-item Hamilton Depression Rating Scale.
The Hamilton Depression Rating Scale was applied to 60 depressed inpatients diagnosed using the Composite International Diagnostic Interview. The information to rate the scale was obtained with a semistructured interview to standardize the scale administration method. Items were factorized using principal components analysis with Varimax rotation. Three factors were obtained with the simulation method, accounting for 47% of variance. The first includes the core symptoms of depression. The symptoms of patients having an isolated mood disorder were compared with those having comorbidity with other diagnoses. The comorbidity did not affect the first factor but modified the second factor (anxiety) and the third factor (insomnia).


[The enhancement of electric field distribution in one-dimensional metallic-dielectric photonic crystals].
The authors theoretically study the transmission properties and electric filed distribution in one-dimensional metallic-dielectric photonic crystals with the transfer matrix method. The results show that the physical properties can be improved considerably after the introduction of antireflection layer and optimizing structural parameters, e. g., 77% electric file distribution in metal layers can be obtained under 19% transmittance, and 72% transmittance can be obtained with 28% electric field distribution in metal layers. These photonic crystal structures, whose transmission properties and electric field in metal layers are tunable, could be widely used in nonlinear photon device based on the enhancement of electric field in metal layers.


Hematuria in rabbits.
A nine year retrospective study of hematuria in 14 New Zealand White rabbits was conducted to classify possible etiologies of this clinical finding. Physical examination, laboratory tests, radiography and postmortem examination were utilized in most cases to verify the presence of hematuria and to determine its etiology. Uterine adenocarcinoma was diagnosed in two rabbits. Three rabbits had uterine polyps with hemorrhage. Renal infarction with hemorrhage was diagnosed in three rabbits. Urolithiasis with secondary urethral obstruction and hemorrhagic cystitis was identified as the cause of hematuria in four rabbits. Other causes of hematuria included chronic cystitis, disseminated intravascular coagulation, bladder polyps and pyelonephritis. Hematuria of undetermined origin was observed in one rabbit. This last [corrected] case was negative for both blood and porphyrin in the urine, but positive for excess levels of urobilin, the oxidative product of urobilinogen. This case illustrates that hyperpigmented urine should be a rule out in all cases of suspected hematuria in rabbits.


Evidence-based clinical practice in falls prevention: a randomised controlled trial of a falls prevention service.
Evidence-based guidelines recommend a range of treatments for falls and injury prevention. We undertook a randomised trial of a falls prevention service to screen for falls risk factors and recommend to GPs an evidenced base prescription for falls prevention. All patients who presented with a fall to the Emergency Department at Flinders Medical Centre over a 22-week period were considered for the study. We excluded patients with dementia, resident in high care or those transferred to other hospitals and outside our catchment area. Of those who consented, we randomised patients between usual care or to an intervention consisting of a falls risk assessment and writing of an evidence-based prescription faxed to their GP for action. Patients were followed for six months and uptake of advice and fall rates were monitored. Four hundred and fifty patients presented with a fall-related attendance and of these 261 patients were eligible for inclusion in the trial. Of these 261 patients, 140 consented and were enrolled in the trial. Over the six months patients in the intervention group were more likely to uptake preventative advice (OR=12.3; 95%CI=4.2-35.9). We were unable to show a reduction in falls (OR= 1.7; 95%CI=0.7-4.4). A patient centered evidence-based approach is feasible and effective in increasing uptake of falls prevention advice. Long term compliance with advice needs further exploration.


Sternal reconstruction with omental and pectoralis flaps: a review of 415 consecutive cases.
Sternal wound infections are a life-threatening complication of cardiovascular surgery, and management can present a great challenge for the plastic surgeon. Successful treatment involves a multidisciplinary approach, immediate detection, meticulous debridement, and delivery of vascularized tissue to the infected wound bed. Twenty-nine years experience of a single surgeon in 415 sternal wound reconstructions is retrospectively analyzed. Flap choice was based on the amount of vascularized tissue required. Low-risk, early infections were treated with debridement and a single flap. Large, high-risk wounds were treated with multiple debridements and covered with a combination of flaps to reduce infection and eliminate dead space. Immediate wound closure with aggressive debridement and flap coverage in a single-stage early in the series (first 12 patients, 1980-1981) led to a mortality rate of 25% due to sepsis and cardiovascular instability. Thereafter, treatment was altered, and patient stability and wound preparation were emphasized, often requiring multiple debridements (91% of all patients). Nine percent of patients, with early low-risk infections, underwent single-stage rewiring and coverage with pectoralis or omental flaps. Coverage of multiple debrided purulent wounds was performed using pectoralis major flap (37% of total number of patients), omentum (18%), a pectoralis/omentum combination (34%), or rectus abdominis flap (2%). A multistage approach and use of 2 flaps for coverage resulted in a 1.5% mortality due to sepsis, 2.5% infection rate, 1.5% skin necrosis rate, and 1.5% hematoma/seroma rate. The use of multiple flaps in large, complex wounds resulted in a complication rate similar to smaller wounds covered with a single flap. In all, 3.5% of the patients required a salvage operation with alternate flaps. This large series demonstrates the importance of early detection of infection, meticulous staged debridement of nonviable tissue, and elimination of dead space with multiple vascularized flaps.


Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study.
The objective of this study was to assess pharmacokinetic (PK) and safety profiles of 2 fixed-dose combinations in development for the treatment of chronic obstructive pulmonary disease (COPD): budesonide/glycopyrronium/formoterol fumarate dihydrate metered-dose inhaler (BGF MDI; triple combination) and glycopyrronium/formoterol fumarate dihydrate (GFF MDI; dual combination). The PK and safety profiles of BGF MDI and GFF MDI were assessed for the first time in healthy Chinese adults after single and repeated (7-day) dosing. This Phase I, randomized, double-blind, parallel-group study was conducted at a single site in Shanghai, China. Male or female Chinese subjects, 18-45 years of age and in good general health, were randomized 1:1:1 to receive BGF MDI 320/14.4/10 μg, BGF MDI 160/14.4/10 μg, or GFF MDI 14.4/10 μg. PK parameters were assessed after a single dose (day 1) and at steady state (day 8), and included AUC0-12, Cmax, and Tmax. Tolerability was assessed using physical examination findings, adverse events reporting, 12-lead ECG, vital signs, and clinical laboratory values. Ninety-six subjects (mean age, 25.6 years; 83.3% male) were randomized and received treatment. All randomized subjects were included in the safety and PK populations. After single and repeated dosing, budesonide AUC0-12 and Cmax were increased dose proportionally from BGF MDI 160/14.4/10 μg to BGF MDI 320/14.4/10 μg, respectively (single dose: AUC0-12, 811.8 vs 1748 h · pg/mL; Cmax, 224.3 vs 459.3 pg/mL; repeated dosing: AUC0-12, 1250 vs 2510 h · pg/mL; Cmax, 315.4 vs 626.4 pg/mL). After single and repeated dosing, glycopyrronium AUC0-12 and Cmax were similar across all treatments (single dose: AUC0-12, 27.20-29.40 h · pg/mL; Cmax, 4.884-5.674 pg/mL; repeated dosing: AUC0-12, 69.49-77.08 h · pg/mL; Cmax, 11.30-13.12 pg/mL) and formoterol (single dose: AUC0-12, 46.49-53.58 h · pg/mL; Cmax 9.651-10.62 pg/mL; repeated dosing: AUC0-12, 81.94-85.32 h · pg/mL; Cmax, 16.13-17.71 pg/mL), suggesting that the addition of budesonide did not appreciably alter the PK properties of GFF MDI. All treatment-emergent adverse events were mild in severity and rates were similar across groups (range, 50.0%-56.3%). There were no new or unexpected findings on tolerability. Overall, all treatments were well tolerated and PK parameters were generally comparable to those previously reported in Western and Japanese healthy subjects, suggesting that the doses of BGF MDI and GFF MDI in development globally for COPD are also appropriate for Chinese patients with COPD. ClinicalTrials.gov identifier: NCT03075267.


Common cold among young adults in China without a history of asthma or allergic rhinitis - associations with warmer climate zone, dampness and mould at home, and outdoor PM10 and PM2.5.
This paper studied associations between reported common cold and home dampness and mould, cleaning habits and ventilation, climate and outdoor air pollution in China among young adults without asthma or allergic rhinitis. Parents of children attending day care in eight Chinese cities answered a questionnaire on their health and home environment (75% response rate). We restricted the population to subject without asthma or allergic rhinitis (N = 37,275). Temperature and air pollution data was obtained from monitoring stations. Associations were estimated by multilevel logistic regression. Totally 12.5% reported common cold (≥3 colds) and 1.6% frequent common cold (≥5 colds) in the past 12 months. Female gender (OR = 1.53; 95% CI 1.37-1.71), residents in southern China (OR = 1.89; 95% CI 1.16-3.07) and living in homes with water leakage (OR = 1.32; 95% CI 1.16-1.50), mould odour (OR = 1.48; 95% CI 1.28-1.72), indoor mould (OR = 1.47; 95% CI 1.28-1.70), condensation on window panes (OR = 1.42; 95% CI 1.32-1.52) and damp bed clothing (OR = 1.19; 95% CI 1.11-1.28) were associated with common cold. Having many signs of dampness increased ORs. Daily cleaning (OR = 0.91; 95% CI 0.85-0.97) and mechanical ventilation in kitchen or bathroom (OR = 0.75; 95% CI 0.64-0.89) were protective. Higher mean ambient temperature (OR = 1.11 per °C; 95% CI 1.02-1.21), PM10 (OR = 1.17 per 10 μg/m3; 95% CI 1.14-1.21) and PM2.5 (OR = 1.28 per 10 μg/m3; 95% CI 1.20-1.37) were associated with common cold. The association with particulate air pollution was stronger in southern China. Similar associations were found for frequent common cold. In conclusion, indoor dampness and mould, a warmer climate and PM10 and PM2.5 can be associated with reported common cold. Further intervention and prospective studies are needed to verify causality of observed association in this cross-sectional study.


Cloning and molecular characterization of CnTEF1 which encodes translation elongation factor 1alpha in Cryptococcus neoformans.
Degenerate PCR primers were synthesized based upon known translation factor 1alpha (TEF1) sequences. Touchdown PCR with these primers utilizing Cryptococcus neoformans strain M1-106 genomic DNA as template produced a DNA fragment containing a portion of CnTEF1. This DNA fragment was used as a hybridization probe to clone a cDNA version of CnTEF1 from C. neoformans strain B3501. Comparison of the genomic and cDNA nucleotide sequences revealed the presence of six introns in CnTEF1. The nucleotide sequence of CnTEF1 from these two strains of C. neoformans were 98% identical. Codon bias for most amino acids encoded by CnTEF1 was similar to that observed in Saccharomyces cerevisiae for highly expressed genes. This codon bias was also observed in the C. neoformans ACT gene. CnTEF1 encoded a protein (CnEF-1alpha) consisting of 459 amino acids with a calculated MW of 50.3 kDa from C. neoformans strain B3501. CnTEF1 from strain M1-106 encoded a protein with one additional aa. Both C. neoformans proteins possessed a high degree of identity throughout their length to fungal, human, and plant EF-1alpha proteins.


[To pay attention to clinical limitations of accommodative and multifocal intraocular lens].
Clinical application of accommodative and multifocal intraocular lens (IOL) were comparatively successful in recent years. However, we must notice the limitations of these kinds of IOL and the related clinical problems, such as very limited accommodative ability of accommodative IOL and glare or haloes and reduced contrast sensitivity of multifocal IOL. We must pay attention to these clinical problems from these IOL and the unexpected prognosis of these kinds of lens. We must choose the indications strictly, and avoid the misuse.


Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.
Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were compared with controls for spatial, auditory, and olfactory serial reversal learning (SRL); spatial matching to sample (MTS); auditory go-no-go discrimination; and open-field exploration. PTD rats made more errors reaching criterion for SRL in all modalities but showed normal transfer effects between problems. PTD rats were also impaired in learning the go-no-go and MTS tasks and showed consistent alterations in exploratory activity. It is argued that the PTD rat, like human Korsakoff patients, have impairments of learning and memory (but spared capacity for reference memory) that extend across sensory modalities. Postmortem analyses showed normal indices of cortical cholinergic, noradrenergic, dopaminergic, and serotonergic function and consistent bilateral lesions of the thalamus, which were centered on the internal medullary lamina, and the medial mammillary nucleus.


Crystal Transition Behavior and Thermal Properties of Thermal-Energy-Storage Copolymer Materials with an n-Behenyl Side-Chain.
In this paper, we synthesized MC(BeA-co-MMA) copolymer microcapsules through suspension polymerization. The pendent n-behenyl group of BeA is highly crystalline, and it acts as the side-chain in the structure of BeA-co-MMA copolymer. The highly crystalline n-behenyl side-chain provides BeA-co-MMA copolymer thermal-energy-storage capacity. In order to investigate the correlation between the thermal properties and crystal structure of the BeA-co-MMA copolymer, the effects of monomer ratio, temperature changing and the changing rate, as well as synthesis method were discussed. The monomer ratio influenced crystal transition behavior and thermal properties greatly. The DSC results proved that when the monomer ratio of BeA and MMA was 3:1, MC(BeA-co-MMA)3 showed the highest average phase change enthalpy ΔH (105.1 J·g-1). It indicated that the n-behenyl side-chain formed a relatively perfect crystal region, which ensured a high energy storage capacity of the copolymer. All the DSC and SAXS results proved that the amount of BeA had a strong effect on the thermal-energy-storage capacity of the copolymer and the long spacing of crystals, but barely on the crystal lamella. It was found that MMA units worked like defects in the n-behenyl side-chain crystal structure of the BeA-co-MMA copolymer. Therefore, a lower fraction of MMA, that is, a higher fraction of BeA, contributed to a higher crystallinity of the BeA-co-MMA copolymer, providing a better energy storage capacity and thermoregulation property. ST(BeA-co-MMA) copolymer sheets with the same ingredients as microcapsules were also prepared through light-induced polymerization aiming at clarifying the effect of the synthesis method. The results proved that the synthesis method mainly influenced the copolymer chemical component, but lightly on the crystal packing of the n-behenyl side-chain.


Observation of suppression of morphology-dependent resonances in singly levitated micrometer-sized droplets.
Suppression of morphology-dependent resonances of the light elastically scattered by a laser-illuminated, micrometer-sized droplet is reported. A single nonabsorbing droplet is levitated by using an electrodynamic quadrupole trap, and the scattered light is monitored as the droplet slowly evaporates. The size of the droplet is approximated by using the instability characteristics of the electrodynamic trap. To determine the refractive index and droplet radius precisely, the experimental scattering curve is fitted to a scattering curve that is generated from Mie theoretical calculations. The procedure is then repeated for absorbing droplets. The quality factor Q of each experimental resonance is determined and used to quantify the suppression effect. A dramatic suppression of narrow resonances occurs with increased absorption, whereas little or no effect is seen in moderate to broad resonances.


Comparison of the responses of corn root tissue to fusicoccin and washing.
A comparison has been made of the effects of fusicoccin with those of washing on segments of corn (Zea mays L.) root tissue. Both fusicoccin and washing caused increases in K(+)((86)Rb) influx, net H(+) efflux, and electrogenic cell membrane potential, but with no effect on respiration rate. The similarity was most evident with fresh tissue during the initial phases of washing, prior to the developmental changes which augment the anion and general solute transport rates of the tissue. After the development of enhanced transport capacity the proportional response to fusicoccin was much diminished. It is suggested that the fusicoccin-like response to washing may be a manifestation of recovery from injury.


It's no accident: Our bias for intentional explanations.
Three studies tested the idea that our analyses of human behavior are guided by an "intentionality bias," an implicit bias where all actions are judged to be intentional by default. In Study 1 participants read a series of sentences describing actions that can be done either on purpose or by accident (e.g., "He set the house on fire") and had to decide which interpretation best characterized the action. To tap people's initial interpretation, half the participants made their judgments under speeded conditions; this group judged significantly more sentences to be intentional. Study 2 found that when asked for spontaneous descriptions of the ambiguous actions used in Study 1 (and thus not explicitly reminded of the accidental interpretation), participants provided significantly more intentional interpretations, even with prototypically accidental actions (e.g., "She broke the vase"). Study 3 examined whether more processing is involved in deciding that something is unintentional (and thus overriding an initial intentional interpretation) than in deciding that something is unpleasant (where there is presumably no initial "pleasant" interpretation). Participants were asked to judge a series of 12 sentences on one of two dimensions: intentional/unintentional (experimental group) or pleasant/unpleasant (control group). People in the experimental group remembered more unintentional sentences than people in the control group. Findings across the three studies suggest that adults have an implicit bias to infer intention in all behavior. This research has important implications both in terms of theory (e.g., dual-process model for intentional reasoning), and practice (e.g., treating aggression, legal judgments).


Acute physical exercise increases PI3K-p110α protein content in the hypothalamus of obese mice.
The anatomy of the hypothalamus includes many nuclei and a complex network of neurocircuits. In this context, some hypothalamic nuclei reside closer to the blood-brain barrier, allowing communication with the peripheral organs through some molecules, such as leptin. Leptin is considered the main adipokine for energy homeostasis control. Furthermore, leptin signalling in the hypothalamus can communicate with insulin signalling through the activation of phosphoinositide 3-kinase (PI3k). Previous data suggest that isoforms of PI3k are necessary to mediate insulin action in the hypothalamus. However, obese animals show impairment in the central signalling of these hormones. Thus, in the current study, we evaluated the role of acute exercise in the leptin and insulin pathways in the hypothalamus, as well as in food intake control in obese mice. Although acute physical exercise was not able to modulate leptin signalling, this protocol suppressed the increase in the suppressor of cytokine signalling 3 (SOCS3) protein levels. In addition, acute exercise increased the content of PI3k-p110α protein in the hypothalamus. The exercised animals showed a strong tendency to reduction in cumulative food intake. For the first time, our results indicate physical exercise can increase PI3k-p110α protein content in the hypothalamus of obese mice and regulate food intake.


Phylogenetic relationships of Argentinean Creole horses and other South American and Spanish breeds inferred from mitochondrial DNA sequences.
South American horses constitute a direct remnant of the Iberian horses brought to the New World by the Spanish conquerors. The source of the original horses was Spain, and it is generally assumed that the animals belonged to the Andalusian, Spanish Celtic, Barb or Arabian breeds. In order to establish the relationship between Argentinean and Spanish horses, a portion of the mitochondrial D-loop of 104 animals belonging to nine South American and Spanish breeds was analysed using SSCP and DNA sequencing. The variability found both within and between breeds was very high. There were 61 polymorphic positions, representing 16% of the total sequence obtained. The mean divergence between a pair of sequences was 2.8%. Argentinean Creole horses shared two haplotypes with the Peruvian Paso from Argentina, and the commonest haplotype of the Creole horses is identical to one of the Andalusian horses. Even when there was substantial subdivision between breeds with highly significant Wright's Fixation Index (FST), the parsimony and distance-based phylogenetic analyses failed to show monophyletic groups and there was no clear relationship in the trees between the South American and any of the other horses analysed. Although this result could be interpreted as mixed ancestry of the South American breeds with respect to the Spanish breeds, it is probably indicating the retention of very ancient maternal lineages in the breeds analysed.


Cimetidine protection against lethal tumor challenge in mice.
Cimetidine, a histamine type-2 receptor antagonist, has been shown to augment proliferative responses of lymphocytes in man and mouse and to increase in vitro-generated murine cell-mediated cytotoxicity. It has been suggested by others that histamine receptors are involved in modulating the immune response through mediation of suppressor cell function. We have previously described a murine tumor model in which suppressor function increases with advancing tumor burden. We now have examined the in vivo effect of cimetidine on survival in this tumor-bearing murine model. Cimetidine was administered in the drinking water to C57BL/6 mice after an intraperitoneal injection of an LD90 dose of EL4 tumor cells. The survival rate was noticeably improved (56%) with an optimal dose of cimetidine (100 mg/kg/day) after 30 days, compared to that of water-treated control mice (10%). This protective effect was present with young (2 months old) as well as older (8 months old) mice. Rechallenge of cimetidine-treated survivors with a six times LD100 tumor dose and continuation of cimetidine produced a 33% survival rate. Comparison of cimetidine (100 mg/kg/day) with different doses of diphenhydramine (histamine type-1 antagonist) showed the protective effect to be more type-2 specific. The mechanism of action of cimetidine remains unclear, but based on this work and work by others, we think that cimetidine probably modulates suppressor cell function. Cimetidine may have potential as an immunomodulator.


The evaluation of factors affecting the castability of metal ceramic alloy--investment combinations.
An evaluation of the castability of metal ceramic alloy-investment combinations using a mesh test and utilizing a factorial design concept has shown that different metal ceramic alloys (gold-based, palladium-based, and nickel-chromium-based alloys) react differently, as far as castability is concerned, to various factors involved in the casting process. These factors were divided into two groups: procedural factors, that included sprue diameter, investing technique, and melting and casting method; and operator factors, which included alloy casting temperature, mould temperature, and heat-soak times. Each of these factors had two or three levels.


A routine third trimester growth ultrasound in the obese pregnant woman does not reliably identify fetal growth abnormalities: A retrospective cohort study.
In response to the challenges of assessing fetal growth in obese women, guidelines recommend routine third trimester ultrasound scans. The aim of this study was to assess the diagnostic performance of this routine scan in obese women (body mass index (BMI) ≥ 35 kg/m2 ). A retrospective cohort study of 1008 pregnancies with maternal BMI ≥ 35 kg/m2 born after 37 weeks gestation at a Victorian hospital from 2015 to 2017. Multiple pregnancies and those affected by diabetes were excluded. Growth ultrasounds were performed between 34 + 0 and 36 + 6 weeks gestation. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of large for gestational age (LGA > 90%) and small for gestational age (SGA < 10%) were calculated using ultrasound estimated fetal weight (EFW) or abdominal circumference (AC) and compared with gestational age and gender-based birthweight percentiles. Using EFW, sensitivity for detecting SGA at birth was 8.1% (six of 74) with a PPV of 100%. Sensitivity for detecting LGA at birth was 61.0% (119 of 195), PPV 54.8%. Sensitivity, specificity, PPV and NPV percentages were all lower using AC. Only 40% of actual birthweight percentiles (405/1008) were within ±10 percentiles of their growth ultrasound EFW percentile. The performance of a routine third trimester ultrasound in women with BMI ≥ 35 kg/m2 suggests limited utility in helping identify aberrant fetal growth. This has important implications for the management of obese pregnant women.


Manipulating Assemblies in Metallosupramolecular Gels, Driven by Isomeric Ligands, Metal Coordination, and Adaptive Binary Gelator Systems.
Metallosupramolecular gel (MSG) is a unique combination of metal-ligand coordination chemistry and supramolecular gel chemistry with extraordinary adaptivity and softness. Such materials find broad uses in industry, pharmaceutical and biomedical sectors, and in technology generation among many others. Pyridyl-appended bis(urea) gelator systems have been extensively studied as potential MSG-forming materials in the presence of various metal ions. The previous molecular engineering approaches depicted competitive intermolecular and intramolecular binding modes involving urea and pyridyl groups and further fine-tuned by the presence of various molecular spacers. In those studies, formation of intermolecular hydrogen bonding among urea moieties to form urea tape was found to be the key factor in one-dimensional assembly and gel formation. In the present study, we show how two isomeric pyridyl-appended bis(urea) ligands can be designed appropriately to essentially eliminate the interference of competitive factors, leaving the intermolecular urea assembly practically unaffected even in the presence of metal ions. We found that one of the two ligands (L2) and the mixed ligand (L1 + L2) assemblies formed gel in the presence and absence of various metal ions. A metal ion with a linear coordination geometry significantly strengthened the gels. Moreover, an inherently weak L1 + L2 assembly appears to be more adaptive in accommodating larger metal ions especially with nonlinear coordination geometry preferences. Small-angle neutron scattering and rheological, spectroscopic, and morphological characterizations, collectively, capture a detailed interplay among ligand assembly, metal-ligand coordination, and adaptivity, driven by the pure versus mixed ligand assemblies. The knowledge gathered from the present study would be highly beneficial in engineering the metallosupramolecular polymeric assemblies toward their functional applications.


Impact of automated peritoneal dialysis on initial graft function after renal transplantation.
In this retrospective study, we evaluated the impact of automated peritoneal dialysis (APD) on initial graft function after cadaveric renal transplantation. Each patient on APD was matched for donor age, donor serum creatinine, and cold ischemia time with one control patient on HD. The study sample consisted of 67 cases and 67 controls. The rate of delayed graft function--defined as a need for dialysis within the first week following renal transplantation-was 16% in the APD group and 10% in the HD group [p = nonsignificant (NS)]. The proportion of patients with a creatinine clearance below 10 mL/min 6 days after renal transplantation was 7% in the APD group and 3% in the HD group. Of the 67 APD patients, 12 had slow graft function as compared with 13 of the 67 HD patients (p=NS). Weight changes 3 days after transplantation were +2.1% +/- 3.7% of dry weight in HD patients and -0.1% +/- 4.6% of dry weight in APD patients (p < 0.05). The total amount of fluid infused during the surgical procedure was similar in the two groups (55.8 +/- 14.3 mL/kg vs. 60.7 +/- 14.8 mL/kg). Compared with HD, APD was not associated with a lower rate of delayed graft function.


Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A.
In mammals, methionine metabolism occurs mainly in the liver via methionine adenosyltransferase-catalyzed conversion to S-adenosylmethionine. Of the two genes that encode methionine adenosyltransferase(MAT1Aand MAT2A), MAT1A is mainly expressed in adult liver whereas MAT2A is expressed in all extrahepatic tissues. Mice lacking MAT1A have reduced hepatic S-adenosylmethionine content and hyperplasia and spontaneously develop nonalcoholic steatohepatitis. In this study, we examined whether chronic hepatic S-adenosylmethionine deficiency generates oxidative stress and predisposes to injury and malignant transformation. Differential gene expression in MAT1A knockout mice was analyzed following the criteria of the Gene Ontology Consortium. Susceptibility of MAT1A knockout mice to CCl4-induced hepatotoxicity and malignant transformation was determined in 3- and 18-month-old mice, respectively. Analysis of gene expression profiles revealed an abnormal expression of genes involved in the metabolism of lipids and carbohydrates in MAT1A knockout mice, a situation that is reminiscent of that found in diabetes, obesity, and other conditions associated with nonalcoholic steatohepatitis. This aberrant expression of metabolic genes in the knockout mice was associated with hyperglycemia, increased hepatic CYP2E1 and UCP2 expression and triglyceride levels, and reduced hepatic glutathione content. The knockout animals have increased lipid peroxidation and enhanced sensitivity to CCl4-induced liver damage, which was largely due to increased CYP2E1 expression because diallyl sulfide, an inhibitor of CYP2E1, prevented CCl4-induced liver injury. Hepatocellular carcinoma developed in more than half of the knockout mice by 18 months of age. Taken together, our findings define a critical role for S-adenosylmethionine in maintaining normal hepatic function and tumorigenesis of the liver.


Different inhibitory actions of IGFBP-1, -2 and -4 on IGF-I effects in vascular smooth muscle cells.
IGF-I is involved in the regulation of metabolism, growth and migration of vascular smooth muscle cells (VSMCs). We have studied how IGFBP-1, -2 and -4 modulate IGF-I-induced DNA and protein synthesis in cultured rat VSMCs. DNA and protein synthesis were measured as incorporation of [3H]thymidine and [3H]leucine into DNA and protein respectively. Western immunoblot was used to detect IGFBPs in conditioned medium and solution hybridization was used to measure IGFBP gene expression. IGF-I stimulated DNA synthesis with an EC50 of 44 pM, reaching a maximal effect at 1 nM. An IGF-I concentration of 1 nM was subsequently used in the experiments with IGFBPs. IGFBP-1 and IGFBP-4 acted in an inhibitory manner on IGF-I-induced DNA synthesis with calculated IC50 values of 1.6 nM and 6.2 nM respectively. IGFBP-2 (16 nM) also inhibited the growth response to IGF-I, but this effect could only be obtained if the two peptides were pre-incubated together for 2 h prior to addition to the cells. IGFBP-1, -2 and -4 inhibited IGF-I-induced protein synthesis in a similar way. Immunoblot of the incubation medium showed little degradation of IGFBP-2 and -4 for up to 24 h. mRNA for IGFBP-2 and -4, but not for IGFBP-1 was detected in the VSMCs. Endogenous IGFBP-2 and -4 could be detected by immunoblot in the conditioned medium but only if it was concentrated. In conclusion, IGFBP-1, -2 and -4, of which IGFBP-2 and -4 may be locally derived, act as inhibitors with different potencies on IGF-I effects in VSMCs.


[Treatment of diabetic neuropathic defect at the surgery department and at the center for diabetic foot care].
The aim of the study was to evaluate the treatment of neuropathic diabetic ulcer at the surgery department and the treatment at the diabetic foot centre at dismissal time and 3 months after the dismissal. For assessment of treatment success parameters of glucose control were used (average of daily blood glucose values, glycosylated haemoglobin--HbA1C and glycosylated protein), healing of ulcers (Wagner classification), hospitalisation time and number of amputations. 22 diabetic patients at the centre and 17 patients at the surgical department were observed in this investigation. There was no difference between the groups as for the age, glucose control (HbA1C), and severity of diabetic ulcers (Wagner 3-4). Local and antibiotic therapies were the same ones. Results as median and difference 75th and 25th percentile were evaluated by Wilcoxon test for paired data within the groups and by Man-Whitney test between both of the groups. In the both group the diabetic control and ulcer healing were significantly improved during hospitalisation period, 3 months after discharge deteriorate diabetic control and ulcer healing stagnated, however, only in the group treated at the surgical department. The hospitalisation time was significantly longer in the surgical group in comparison with the centre group [median 52 days (35)] vs. [median 31 days (38)], p < 0.01. Amount of transmetatarsal and higher amputations was lower at the foot centre in comparison with the surgical group (1 vs. 7). Statistical evaluation was not used for low amount of amputations. Team approach at the centre of diabetic foot is effective in the treatment of diabetic foot ulcers, significantly shortened the hospital stay, probably decrease amount of amputations. Three months after discharge the diabetic control and ulcer healing were significantly better in patients treated at the diabetic foot centre.


Formation of heterocyclic amines in Chinese marinated meat: effects of animal species and ingredients (rock candy, soy sauce and rice wine).
Heterocyclic aromatic amines (HAAs) are one type of neo-formed contaminants in protein-rich foods during heat processing. Recently, accumulative studies have focused on the formation of HAs in Western foods. However, there is little knowledge about the occurrence of HAAs in traditional Chinese foods. The objective of this study was to determinate the contents of main HAs in traditional marinated meat products by UPLC-MS/MS, and to investigate the effects of animal species and the ingredients (soy sauce, rock candy, and rice wine) on the formation of HAAs in marinated meats. Five HAs - 2-amino-3-methylimidazo[4,5-f]-quinolone (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline (MeIQ), 9H-pyrido[3,4-b]indole (Norharman) and l-methyl-9H-pyrido[3,4-b]indole (Harman) - were detected in 12 marinated meats, but 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was only found in three chicken marinates. The animal species and ingredients (soy sauce, rock candy and rice wine) have significant influence on the formation of HAAs in meat marinates. Beef had the highest content of total HAAs compared with pork, mutton and chicken. Meanwhile, soy sauce contributed to the formation of HAAs more greatly than rock candy, soy sauce, and rice wine. Choice of raw materials and optimisation of ingredients recipe should be become a critical point to control the HAAs formation in marinated meats. © 2017 Society of Chemical Industry.


Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety.
A combination of demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), with a platinum moiety has produced a series of TCM-based platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, which demonstrate selective cytotoxicity toward SK-Hep-1 (human liver) cell line, and circumvention of cross-resistance. The inclusion of demethylcantharidin rendered the compounds highly active as protein phosphatase (PP2A) inhibitors. The new TCM-Pt compounds may possess a novel dual mechanism of antitumor action: inhibition of PP2A and platination of DNA.


[Results of fundoplication in reflux esophagitis].
A retrospective study of 71 patients treated with Nissen-Rossetti fundoplication for a symptomatic esophagitis shows that 82% of the patients are satisfied and symptom-free 2 1/2 years after surgery. 18% have recurrent reflux disease, 15% need medicamentous therapy to control their symptoms, 3% were reoperated on. Possible explantation for recurrent reflux disease are wrap dislocation and wrap disrupture. With one exception recurrences occurred within the first 12 months after operation.


NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation.
Cancer cells can survive and maintain their high proliferation rate in spite of their hypoxic environment by deploying a variety of adaptative mechanisms, one of them being the reorientation of cellular metabolism. A key aspect of this metabolic rewiring is the promotion of the synthesis of antioxidant molecules in order to counter-balance the hypoxia-related elevation of reactive oxygen species (ROS) production and thus combat the onset of cellular oxidative stress. However, opposite to their negative role in the inception of oxidative stress, ROS are also key modulatory components of physiological cellular metabolism. One of the major physiological cellular ROS sources is the NADPH oxidase enzymes (NOX-es). Indeed, NOX-es produce ROS in a tightly regulated manner and control a variety of cellular processes. By contrast, pathologically elevated and unbridled NOX-derived ROS production is linked to diverse cancerogenic processes. In this respect, NOX4, one of the members of the NOX family enzymes, is of particular interest. In fact, NOX4 is closely linked to hypoxia-related signaling and is a regulator of diverse metabolic processes. Furthermore, NOX4 expression and function are altered in a variety of malignancies. The aim of this review is to provide a synopsis of our current knowledge concerning NOX4-related processes in the oncogenic metabolic adaptation of cancer cells.


Specific loss of toll-like receptor 2 on bone marrow derived cells decreases atherosclerosis in LDL receptor null mice.
Innate immunity and, notably, Toll-like receptors (TLR), have an important role in atherogenesis. We have tested the hypothesis that the selective loss of TLR-2 by cells of bone marrow (BM) origin will protect low-density receptor-deficient (Ldlr (-/-)) mice from both early- and late-stage atherosclerosis. BM cells from Tlr2(+/+) and Tlr2(-/-) littermates were used to reconstitute lethally irradiated Ldlr(-/-) mice. Following a recovery period, mice were placed either on a diet containing 21% saturated fat - 0.15% cholesterol for 8 weeks to study early-stage atherosclerosis, or on a diet richer in cholesterol (1.5%) for 16 weeks to study late-stage atherosclerosis. Donor cell Tlr2 genotype did not alter serum cholesterol levels or lipoprotein profiles in recipient animals. After 8 weeks on the 0.15% cholesterol diet, deficiency of TLR-2 expression on cells of BM origin reduced atherosclerosis in the aortic root and the aortic arch in both genders of mice. In contrast, the BM recipients who received the 1.5% cholesterol diet for 16 weeks showed much larger lesions in the aortic root, and TLR-2 deficiency in BM cells failed to provide protection. Thus, TLR-2 expression in BM-derived cells contributes primarily to early stage atherosclerosis.


[Efficacy of the APimicos-B to control and prevent chalkbrood disease in honey bees].
Chalkbrood disease in Apis mellifera is a fungal disease affecting developing brood, infested larvae become mummified. As it is a factorial disease, studies on this pathology are obstructed by the need of some predisposing conditions which must occur for such disease to develop. Thus, many questions are yet to be answered about which treatments to apply. The aim of this work is to evaluate the efficacy of the Apimicos-B, a treatment against chalk brood. To induce the disease, some pieces of combs containing susceptible worker brood both from infected and treated colonies and from infected and untreated colonies were cooled. No significant differences were registered (53.12% and 59.58% of mummification respectively).


The use of bone morphogenetic protein in lumbar spine surgery.
Creating a solid lumbar spinal fusion remains a challenge. Despite advances in fixation, a pseudarthrosis still may occur. Recently, attention has focused on creating a more biologically favorable environment to enhance fusion rate. Bone morphogenetic proteins (BMPs) are a group of secreted growth factors that belong to the transforming growth factor-beta superfamily. Two recombinant BMP proteins, rhBMP-2 and rhBMP-7 (OP-1), have been used successfully in preclinical and clinical trials and are commercially available for clinical applications.


Distribution of the HLA-DQ alpha alleles and genotypes in a sample of a population from Barcelona (Spain).
Allele and genotype frequencies at the HLA-DQ alpha locus were determined by the use of polymerase chain reaction (PCR) and the reverse dot blot format. 6 HLA-DQ alpha alleles and 21 genotypes were detected among the 178 unrelated individuals from Barcelona. A fair agreement was found between observed and expected numbers assuming a Hardy-Weinberg equilibrium. The Barcelona population is statistically similar to the Finnish population, but differs significantly from the Japanese, Black and Caucasoid series.


Community Profile and Drivers of Predatory Myxobacteria under Different Compost Manures.
Myxobacteria are unique predatory microorganisms with a distinctive social lifestyle. These taxa play key roles in the microbial food webs in different ecosystems and regulate the community structures of soil microbial communities. Compared with conditions under conventional management, myxobacteria abundance increases in the organic soil, which could be related to the presence of abundant myxobacteria in the applied compost manure during organic conditions. In the present study,16S rRNA genes sequencing technology was used to investigate the community profile and drivers of predatory myxobacteria in four common compost manures. According to the results, there was a significant difference in predatory myxobacteria community structure among different compost manure treatments (p < 0.05). The alpha-diversity indices of myxobacteria community under swine manure compost were the lowest (Observed OTU richness = 13.25, Chao1 = 14.83, Shannon = 0.61), and those under wormcast were the highest (Observed OTU richness = 30.25, Chao1 = 31.65, Shannon = 2.62). Bacterial community diversity and Mg2+ and Ca2+ concentrations were the major factors influencing the myxobacteria community under different compost manure treatments. In addition, organic carbon, pH, and total nitrogen influenced the community profile of myxobacteria in compost manure. The interaction between myxobacteria and specific bacterial taxa (Micrococcales) in compost manure may explain the influence of bacteria on myxobacteria community structure. Further investigations on the in-situ community profile of predatory myxobacteria and the key microorganism influencing their community would advance our understanding of the community profile and functions of predatory microorganisms in the microbial world.