Osteoradionecrosis--a review of current concepts in defining the extent of the disease and a new classification proposal.
Osteoradionecrosis (ORN) is potentially a debilitating and serious consequence of radiotherapy to the head and neck. Although it is often defined as an area of exposed bone that does not heal, it can also exist without breaching the mucosa or the skin. Currently, 3 classifications of ORN are in use, but they depend on the use of hyperbaric oxygen or are too complicated to be used as a simple aide-mémoire, and include features that do not necessarily influence its clinical management. We propose a new classification to cover these shortcomings and to take into account the increasingly widespread use of antifibrotic medical treatment. We classified a series of 85 patients with varying severities of ORN into 4 groups. An analysis of the outcomes of the series showed that the classification staged the severity of the condition simply and that the stage was relevant to both treatment and outcome. The new classification was therefore verified by the series presented.


Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells.
The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal 'starburst' amacrine cells is one of the several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ~3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Taken together, these results provide direct support for the 'space-time wiring' model for direction selectivity.


Synthesis of thromboxane B2 and 6-keto-prostaglandin F1 alpha by bovine gastric mucosal and muscle microsomes.
Bovine gastric mucosal and muscle microsomes synthesize prostaglandins and thromboxane b/ (TXB2) from aratchidonic acid (AA). TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were the majro products synthesized by pylorus, body, and cardiac region of the gastric mucosa. Gastric muscle mainly synthesized 6-keto-PGF1 alpha. TXB2 and 6-keto-PGF1 alpha synthesis occurs at an appreciable rate from endogenous precursors but more rapidly with added arachidonate. Prostaglandins E2, F2 alpha and D2 were synthesized in smaller amounts under the conditions studied.


Paradoxical motion of the posterior left ventricular wall seen in healthy subjects in the upright position.
Paradoxical motion of the posterior left ventricular wall in patients in the upright but not in the supine position was demonstrated in a high percentage of normal volunteers. There was no significant difference in age, body surface area, heart rate, and blood pressure between the groups, with or without paradoxical motion. This echocardiographic finding probably represents a physiologic phenomenon and should be taken into consideration during the interpretation of upright exercise echocardiograms.


Orbital lymphangioma in a child: a diagnostic dilemma.
We report a case of significant unilateral left proptosis after a fall in a 10-year old child. Magnetic resonance imaging showed an extraconal hyperintense orbital mass extending into the maxillary sinus which was opacified. After drainage the proptosis resolved. The cause of the acute proptosis was haemorrhage within an orbital lymphangioma.


Regulatory differences between Ca(2+)-ATPase in plasma membranes from chicken (nucleated) and pig (anucleated) erythrocytes.
Kinetic and regulatory properties of the plasma membrane Ca(2+)-ATPase activity from chicken (nucleated) erythrocytes were studied and compared to those from pig (anucleated) erythrocytes. In the absence of known activators: (1) Ca(2+) affinity for the Ca(2+)-ATPase activity from nucleated erythrocytes was 12-fold higher than that from pig erythrocytes, and thus the enzyme is sensitive to physiological Ca(2+) concentrations; (2) the enzyme from chicken erythrocytes showed two apparent Km values for ATP, as compared to one apparent Km value displayed by pig erythrocytes; (3) Ca(2+)-ATPase inserted in chicken erythrocyte membranes showed a low sensitivity to activation by phosphatidylinositol-4-phosphate; (4) when p-NPP was used as substrate, the activity of chicken erythrocytes was high, similar to that attained by pig erythrocytes, but barely sensitive to activation by dimethylsulfoxide and calmodulin. ATP hydrolysis was 10-fold lower than that displayed by pig erythrocytes and the maximal velocity was activated three-fold by calmodulin. The enzyme was insensitive to alkaline phosphatase treatment and showed a single phosphorylation band in electrophoresis, ruling out the possibility of previous modulation by endogenous kinases and/or by partial proteolysis. The differences may be attributed to some endogenous modulator, to distinct isoforms, or to a difference in the E(1)/E(2) states of the enzyme.


Implementation of an Acute Care Surgery Service Facilitates Modern Clinical Practice Guidelines for Gallstone Pancreatitis.
Current practice guidelines for management of gallstone pancreatitis (GSP) recommend early cholecystectomy for patient stabilization and bile duct clearance, preferably at index admission. Historically, this has been difficult to achieve due to lack of emergency surgical resources. We investigated whether implementation of an acute care surgery (ACS) model would allow better adherence to current practice guidelines for GSP. A retrospective review was conducted of all patients admitted with the diagnosis of GSP to 2 tertiary care university teaching hospitals from January 2002 to October 2013. Diagnosis was confirmed on review of clinical, biochemical, and radiographic criteria. Patients were divided into pre-ACS (2002 to 2009) and post-ACS (2010 to 2013) eras. Only 1 of the 2 hospitals implemented an ACS service in the latter era. Data were collected on demographics, admissions, cholecystectomy timing, and emergency department visits. Before implementation of an ACS service, the rate of index cholecystectomy was 3% at both hospital sites. The rate of index cholecystectomy increased significantly with the addition of ACS, from 2.4% to 67% (p < 0.001). The presence of an ACS team was highly predictive of index cholecystectomy (odds ratio = 10.4; 95% CI 2.0 to 55.1). Patients who did not undergo cholecystectomy during the index admission had an overall readmission rate of 24.9% at both sites. In the ACS hospital, repeat emergency department visits decreased from 24.8% to 8.3% (p < 0.001) and readmission rate decreased from 16.8% to 7.3% (p = 0.04) in the pre-and post-ACS eras, respectively. Implementation of an ACS service resulted in a higher rate of index cholecystectomy and decreased emergency department visits and readmissions for biliary disease, and allowed for increased adherence to clinical practice guidelines for GSP.


Optimization of S-Nitrosocaptopril Monohydrate Storage Conditions Based on Response Surface Method.
From unstable crystals to relatively stable monohydrate crystals, many researchers have been working on S-nitrosocaptopril for more than two decades. S-nitrosocaptopril monohydrate (Cap-NO·H2O) is a novel crystal form of S-nitrosocaptopril (Cap-NO), and is not only a nitric oxide (NO) donor, but also an angiotensin-converting enzyme inhibitor (ACEI). Yet, a method for long-term storage has never been reported. In order to determine the optimal storage conditions, Plackett-Burman (PB) design was performed to confirm the critical factors. Response surface methodology (RSM) was employed to determine the optimal Cap-NO·H2O storage condition, based on the rough interval determined by the path of steepest ascent experiment. The optimized storage condition was denoted as nitrogen purity of 97%, temperature of -10 °C and 1.20 g deoxidizer. In this case, a final preservation rate of 97.91 ± 0.59% could be obtained. In specific storage conditions, Cap-NO·H2O was found to be stable for at least 6 months in individual PE package, procreating a potentially applicable avenue.


Personality pattern of patients with chronic gastric ulcer. Study of neuroticism and extroversion in a gastric ulcer and a control population.
Forty-four patients with chronic gastric ulcer were compared with a control group matched for age, sex, and place of residence. The personality pattern was studied by the Eysenck Personality Inventory and personality assessed in terms of neuroticism and extroversion. The relevance of social class was also studied. The gastric ulcer population did not differ from the control group except among the male population, in which the gastric ulcer population was significantly more neurotic and less extroverted than their controls.


Glucose tolerance predicts short-term refeeding outcome in females with anorexia nervosa.
Little is known about biologic predictors of refeeding outcome in anorexia nervosa (AN). Because nutritional status mirrors glucose metabolism during an oral glucose tolerance test (OGTT) in AN, this study investigated whether pretreatment glucose response patterns during the OGTT might be associated with refeeding progress in patients with AN. Sixty-four female patients with anorexia (33 restrictors and 31 binge/purgers) and 13 healthy control subjects underwent an OGTT before nutritional rehabilitation, including desensitization to fear of energy intake of 1000 to 1600 kcal/day. Patients were divided into flat-type responders, impaired glucose tolerance (IGT)-type responders, and normal-type glucose responders. Daily energy intake, weekly weight gain, and the duration of desensitization period were evaluated until the 12th week. The patients with anorexia consisted of 20 flat-type, 21 IGT-type, and 23 normal- type responders. Normal-type responders required a shorter time to complete the desensitization period than other responders (p = .003 for restrictors, p < .001 for binge/purgers). In terms of refeeding progress, significant group effects for daily energy intake and weekly weight gain were evident in restrictors (p = .006, p = .028, respectively) and binge/purgers (p < .001, p = .003, respectively); normal-type responders showed good refeeding progress compared with other responders in both AN subtypes. The present study found a close relationship between pretreatment glucose responses, therapeutic progress of desensitization to fear of energy intake, and refeeding progress in both AN subtypes. Our findings suggest that glucose tolerance may be a useful predictor of short-term refeeding outcome in this disorder.


Changed course of cytotoxic reaction as a result of modification of target cell membrane.
We studied the sensitivity of K-562 erythromyeloblasts cultured for a long time in a nutrient media of common composition (control) or medium modified by proline-rich hexapeptide, to cytolysis mediated by natural killers. On day 2 of culturing the cytotoxicity of human natural killers towards targets maintained in the modified medium was almost 2-fold higher than in the control. By day 30 this difference was retained at the effector:target ratio of 50:1 and 12:1. By day 90 of the experiment activity of natural killers towards K-562 cells cultured in modified medium was lower than in the control. The results are discussed in the context of hydration of the target cell surface structures at the expense of bound water brought by proline-rich open type sequences into the distal regions of extracellular sites of adhesion receptors and target determinants recognized by natural killers.


Sister chromatid exchange (SCE) in human lymphocytes. Effect of UV C irradiation and age.
The number of sister chromatid exchanges (SCE) per metaphase was determined in normal human lymphocytes by the Hoechst-Giemsa procedure. UV C irradiation promotes SCE dose-dependent in the range of 0-40 mJ/cm2. No difference of this phenomenon may be observed, compairing young volunteers (20-40 years) with a 60-80-year-old group.


TGF-beta1 impairs homocysteine metabolism in human renal cells: possible implications for transplantation.
We hypothesized that TGF-beta1 influences the metabolism of homocysteine (Hcy) and increases its cellular export, which may lead to hyperhomocysteinemia in patients with renal transplants. We exposed human renal proximal tubule epithelial cells (huRPTECs) to different concentrations of TGF-beta1, IL-1alpha, IL-10, or methionine and measured total Hcy (tHcy) in culture supernatants. We then examined the relationship between plasma levels of tHcy and TGF-beta1 in renal graft recipients. In multivariate analysis, the factors mediator (TGF-beta1, IL-1alpha, IL-10), mediator concentration, methionine concentration, and "mediator x concentration" interaction independently influenced tHcy concentrations in culture supernatants. A 31% increase in tHcy was observed after exposure of huRPTECs to TGF-beta1 compared to medium alone. However, TGF-beta1 plasma levels in kidney graft recipients showed no independent association with tHcy plasma concentrations. We demonstrated that the release of Hcy from huRPTECs is enhanced by TGF-beta1, but that TGF-beta1 plasma levels in renal graft recipients show no independent relationship with hyperhomocysteinemia.


Phenotypic flexibility of skeletal muscles during long-distance migration of garden warblers: muscle changes are differentially related to body mass.
Mass changes of skeletal muscles occur in a variety of species during the migratory period. Phenotypic flexibility of flight muscle mass is considered to represent adaptations of the flight muscle to changing power requirements associated with changes in body mass. We analyzed the relationship between muscle masses and body mass for garden warblers (Sylvia borin) sampled during spring migration in Tanzania, Ethiopia, and Egypt, and during autumn migration in Turkey. Flight muscle mass was positively related to body mass of warblers at only one of the four sites, in Egypt where warblers had just arrived after a long migratory flight. Analysis of covariance (ANCOVA) revealed a significant interaction term between sampling site and body mass (P < .001), indicating that flight muscle and body mass differed from site to site. We therefore question the idea that changing power requirements associated with changes in body mass cause mass changes of the flight muscle. We further suggest that different migration strategies across different landscapes shape the relationship between flight muscle and body mass. Flights across major ecological barriers may cause substantial catabolism of flight muscle protein until the limit necessary for flight, while migration across "common landscape," which enables a bird to land and to feed and/or drink, may occur without the need to catabolize flight muscle protein. However, a differential relationship between flight muscle mass and body mass described here for a long-distance migrant seems as well to occur in a short-distance migrant and is therefore unlikely to be part of an adaptive syndrome typical for long-distance migration.


An appraisal of healthcare accreditation agencies and programs: similarities, differences, challenges and opportunities.
The study, following similar reviews in 2000 and 2010, presents an update of knowledge about external evaluation agencies and accreditation programs. The study aim was to investigate the current profile of external evaluation agencies identifying their program features, and significant changes and challenges.


Transport of glycerol by Pediococcus pentosaceus isolated from wine.
Pediococcus pentosaceus N(5)p is a strain isolated from wine that uses glycerol as its sole carbon source, mainly via the glycerol kinase pathway. The transport of glycerol was investigated in resting cells of this strain. Glycerol uptake followed a Michaelis-Menten relationship with an observed apparent K(m) of 33 microM and a V(max) of 2.5 nmol/min/mg of cell protein. The transport system was specific for glycerol, which was present in the cells grown either on glycerol or glucose suggesting its constitutive nature. The presence of uptake when resting cells were treated with HgCl(2) and the absence of counterflow indicate that facilitated diffusion is not involved in glycerol transport. On the other hand, glycerol uptake was inhibited by the metabolic poisons that affect ATP availability by acting on either electron transport or ATPase activity, and by the proton-conducting uncouplers without any effect on glycerol kinase activity. The restoration of glycerol uptake in de-energized cells by the addition of glucose and low concentration of cyanide-m-chlorophenyl hydrazone was achieved. These results, the first in the genus Pediococcus, provide evidence for an energy-dependent uptake of glycerol that involves the proton motive force directly or coupled with ATP synthesis.


Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism.
Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools.


In vivo absorption and disposition of cefadroxil after escalating oral doses in wild-type and PepT1 knockout mice.
To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. The absorption and disposition kinetics of [3H]cefadroxil were determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil were also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil were not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs.


HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice.
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammation that is a risk factor for many gastrointestinal cancers. Exosomes are gradually gaining attention as an emerging treatment method for IBD due to their important biological characteristics. NF-κB is an important pro-inflammatory transcription factor kept inactive by IκB protein in the cytoplasm by masking the nuclear localization signal of NF-κB. The deterioration of IκB is mainly ubiquitination, and this depends on neddylation. In this study, we established a dextran sulfate sodium (DSS)-induced IBD model in BABL/C mice to evaluate the effect of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exosomes, hucMSC-Ex) on the repair of IBD. At the same time, human colorectal mucosa cells (FHC) were stimulated by LPS (lipopolysaccharide) in vitro to activate the inflammatory environment to study the mechanism of hucMSC-Ex regulating neddylation. The microRNA (miRNA) obtained by sequencing and transfection with hucMSC-Ex was used to verify the role of miR-326/neddylation/IκB/NF-κB signaling pathway in IBD repair. HucMSC-Ex inhibited the process of neddylation in relieving DSS-induced IBD in mice. The binding of NEDD8 (neural precursor cell-expressed, developmentally downregulated gene 8) to cullin 1 and the activation of NF-κB signaling pathway were suppressed along with reduced expression levels of neddylation-related enzyme molecules. The same phenomenon was observed in FHC cells. The miRNA comparison results showed that miR-326 was highly expressed in hucMSC-Ex and played an important role in inhibiting the neddylation process. The therapeutic effect of hucMSC-Ex with high expression of miR-326 on IBD mice was significantly stronger than that of ordinary hucMSC-Ex. HucMSC-Ex relieves DSS-induced IBD in a mouse model by inhibiting neddylation through miR-326.


Research articles published in clinical radiology journals: trend of contribution from different countries.
To determine different countries' trend of contribution to clinical radiology journals and its relationship with impact factor. All the journals, which publish articles on clinical radiology, were selected from the category of Radiology and Nuclear Medicine group of journals, and articles published in these journals between 1991 and 2000 were searched for the authors' affiliation using the Medline database. Then, share of research output of the top-ranking 20 countries was determined along with the trend over time. Also, the relationship of different countries' contribution with the impact factor of journals was examined by cross-sectional time-series linear model. Of total articles (38,359), the United States' share for the selected journals in clinical radiology was 43.2% (16,582 articles) and ranked top in the world, followed by the United Kingdom (9.9%) and Japan (8.0%). The recent increase in the share was statistically significant for Japan, France, Germany, Italy, South Korea, Turkey, Spain, Switzerland, Austria, and China. On the other hand, the United States, United Kingdom, and Canada showed a significant negative trend. Among the top-ranking 10 countries, the US contribution was significantly higher to journals with high-impact factors, whereas the opposite was true for France. The United States, United Kingdom, and Canada showed a negative trend over the last decade in terms of proportion of contribution of articles to the clinical radiology journals. However, only the United States published more articles in high-impact factor journals.


bSTH and IGF-I levels in blood and milk of black and white dairy cows before and after application of recombinantly derived bovine somatotropin.
In an 8 week trial period six black and white dairy cows were injected with Optiflex, a slow release formulation of recombinantly derived bovine somatotropin (BST). Three cows each were injected at two-weeks (BST-14) or four weeks (BST-28) intervals. The dosage was 640 mg BST per injection. Average milk yield increased by 18.3% and 13.8% in groups BST-14 and BST-28 respectively. Blood plasma levels of bSTH and IGF-I increased till day 10 post-injection; thereafter they declined, except IGF-I levels in group BST-14 which persisted continuously elevated with minor variations. No bSTH above detection level could be assayed in the milk of treated animals. The IGF-I level in milk was slightly elevated after BST-application but stayed within the normal range.


Examining the Relationships Between Air Pollutants and the Incidence of Acute Aortic Dissection with Electronic Medical Data in a Moderately Polluted Area of Northwest China.
This paper explored whether air pollutants influenced acute aortic dissection (AAD) incidence in a moderately polluted area. A total of 494 AAD patients' data from 2013 to 2016 were analyzed. The results showed that AAD had the strongest associations with PM10, SO2, NO2, CO, and O3 on the day before an AAD incident (lag1) and with PM2.5 two days before an incident (lag2) in single-pollutant model. In the three-pollutant model, PM10 was associated with the highest risk of adverse effects (RR = 1.37, 95% CI: 1.22, 1.53), whereas PM2.5 was associated with the lowest risk (RR = .83, 95% CI: .79, .88). Both PM2.5 and PM10 were affected by season, and SO2 was significantly different between heating and non-heating seasons as well. This study revealed significant associations between short-term PM2.5, PM10, and SO2 exposure and daily AAD incidence, showing that PM10 and SO2 were strong predictors of AAD incidence in a moderately polluted area.


Carcinoma of the prostate: clinical and pathological staging and prognosis.
Clinical and pathological staging furnishes valuable information upon which the clinician can base his treatment and compare results. Staging refinements occur as we learn more about the natural history of the disease and the efficacy of our treatment. We observed that clinical stage B patients with minimal (less than twice normal) elevation of the serum acid phosphatase have similar pathologic stage B (75%) and disease-free survival rates following total prostatectomy as stage B patients with normal acid phosphatases. Intraglandular crystalloids were found in 26% of clinical stage B patients treated by total prostatectomy, and none of this subgroup of patients has had a recurrence of disease. Pathologic staging frequently confirms the presence of a greater extent of tumor than was clinically anticipated. In general, prognosis for patients with a small tumor mass will be more favorable than that for patients with a large tumor mass. Staging permits the estimation of prognosis of groups of patients with similar tumor burdens; however, the survival of an individual within any such group is unpredictable.


The determination of bromazepam in plasma by reversed-phase high-performance liquid chromatography.
A reversed-phase high-performance liquid chromatographic method has been developed for the determination of bromazepam, an anxiolytic benzodiazepine, in plasma. After a single-step extraction from alkalinized plasma with diethyl-ether in the presence of an internal standard (alpha-hydroxy-triazolam), the residues were chromatographed on a reversed-phase Nova Pak 5 microns C18 column, with a mobile phase of acetonitrile-water-triethylamine (700:300:4, v/v/v) adjusted to pH 7.4 with orthophosphoric acid. The limit of detection was 50 ng ml-1, using a 20 microliters injection with UV detection at 240 nm. Between-day and within-day relative standard deviations were lower than 6%. Studies of drug stability during sample storage at -20 degrees C and at +4 degrees C showed no degradation of bromazepam. However, bromazepam seemed to be degraded at ambient temperature, without any influence of light. This method is applied to the determination of bromazepam plasma levels in analytical toxicology.


Autonomic nervous system concomitants of short-term abstinence in alcoholics; Pupillometric studies. II.
During rest, stress and homeostatic recovery, drinking and nondrinking alcoholics showed impaired pupillary contraction, but the pupillary dilation in drinking alcoholics was slower and more attenuated than that in nondrinking alcoholics and nonalcoholics.


Tumors can teem with microbes. But what are they doing there?
New study suggests microbiomes can promote cancer by suppressing immune response and seeding metastase.


Genetic improvement of n-butanol tolerance in Escherichia coli by heterologous overexpression of groESL operon from Clostridium acetobutylicum.
Strain tolerance to toxic metabolites remains an important issue in the production of biofuels. Here we examined the impact of overexpressing the heterologous groESL chaperone from Clostridium acetobutylicum to enhance the tolerance of Escherichia coli against several stressors. Strain tolerance was identified using strain maximum specific growth rate (μ) and strain growth after a period of solvent exposure. In comparison with control strain, the groESL overexpressing strain yielded a 27 % increase in growth under 0.8 % (v/v) butanol, a 9 % increase under 1 % (v/v) butanol, and a 64 % increase under 1.75 (g/l) acetate. Moreover, after 10 h, groESL overexpression resulted in increase in relative tolerance of 58 % compared with control strain under 0.8 % (v/v) butanol, 56 % increase under 1 % (v/v) butanol, 42 % increase under 1 % (v/v) isobutanol, 36 % increase under 4 % (v/v) ethanol, 58 % increase under 1.75 (g/l) acetate. These data demonstrate that overexpression of the groESL from C. acetobutylicum in E. coli increased tolerance to several stressors. Solvent tolerant strain of E. coli was developed to be used as a basic strain for biofuel production.


Physical activity, sitting time and sleep duration before and during pregnancy and pregnancy outcomes: A prospective panel study.
To examine how changes in physical activity, sitting time and sleep duration through pre-, mid- and late pregnancy are in association with Caesarean section, medically indicated Caesarean section and small for gestational age. While circadian activities could change throughout pregnancy, studies exploring the effect of change in those activities on pregnancy outcomes remain limited. This study applied a prospective panel design. A self-reported questionnaire was used to assess the three activities before and during pregnancy and was administered three times from August 2015-July 2017. Multiple logistic regression models were used. The analysis included 488, 477 and 455 participants in the models for Caesarean section, medically indicated Caesarean section and small for gestational age, respectively. This study followed the STROBE guidelines. The mean age of participants was 32.18 years, and more than half (54.90%) were primiparous. Sleep duration of >8 hr/day before pregnancy and experiencing a decrease in mid-pregnancy was a risk factor for Caesarean section and medically indicated Caesarean section. Sitting ≥8 hr/weekday in pre-, mid- and late pregnancy had a protective effect for Caesarean section and medically indicated Caesarean section. Sitting <8 hr in mid-pregnancy and experiencing a decrease in late pregnancy was a risk factor for small-for-gestational-age infants. Physical activity was not significantly related to pregnancy outcomes. Sleep duration of 7-8 hr and sitting time of more than 8 hr/day seem beneficial for women both before and during pregnancy. Health professionals could assess pregnant women or those intending to become pregnant regarding their sleep and sitting behaviour and provide relevant interventions.


Sequences enhancing cassava mosaic disease symptoms occur in the cassava genome and are associated with South African cassava mosaic virus infection.
Cassava is an important food security crop in Sub-Saharan Africa. Two episomal begomovirus-associated sequences, named Sequences Enhancing Geminivirus Symptoms (SEGS1 and SEGS2), were identified in field cassava affected by the devastating cassava mosaic disease (CMD). The sequences reportedly exacerbated CMD symptoms in the tolerant cassava landrace TME3, and the model plants Arabidopsis thaliana and Nicotiana benthamiana, when biolistically co-inoculated with African cassava mosaic virus-Cameroon (ACMV-CM) or East African cassava mosaic virus-UG2 (EACMV-UG2). Following the identification of small SEGS fragments in the cassava EST database, the intention of this study was to confirm their presence in the genome, and investigate a possible role for these sequences in CMD. We report that multiple copies of varying lengths of both SEGS1 and SEGS2 are widely distributed in the sequenced cassava genome and are present in several other cassava accessions screened by PCR. The endogenous SEGS1 and SEGS2 are in close proximity or overlapping with cassava genes, suggesting a possible role in regulation of specific biological processes. We confirm the expression of SEGS in planta using EST data and RT-PCR. The sequence features of endogenous SEGS (iSEGS) are unique but resemble non-autonomous transposable elements (TEs) such as MITEs and helitrons. Furthermore, many SEGS-associated genes, some involved in virus-host interactions, are differentially expressed in susceptible (T200) and tolerant TME3) cassava landraces infected by South African cassava mosaic virus (SACMV) of susceptible (T200) and tolerant (TME3) cassava landraces. Abundant SEGS-derived small RNAs were also present in mock-inoculated and SACMV-infected T200 and TME3 leaves. Given the known role of TEs and associated genes in gene regulation and plant immune responses, our observations are consistent with a role of these DNA elements in the host's regulatory response to geminiviruses.


Follow-up study of 232 patients with stage Ia1 and 411 patients with stage Ia2 squamous cell carcinoma of the cervix (microinvasive carcinoma).
This report retrospectively analyzes 643 patients with microinvasive squamous cell carcinoma of the cervix who were followed-up for 3-17 years. The cases were classified according to the FIGO definition adopted in 1985 which includes a subdivision into Stage Ia1 and Stage Ia2. It is concluded that the new FIGO system has definite advantages for the decision of therapy in microinvasive carcinoma. Unnecessary radical treatment can be avoided.


Prognosis of Bell's palsy in children--analysis of 29 cases.
We report 29 children with 32 episodes of Bell's palsy admitted to a university affiliated hospital during an 8-year period (1995-2003). The peak age of onset was under 3 years. Three (10.3%) had recurrent attacks. Complete recovery occurred in all 32 episodes except 1 (3.1%) with partial recovery, having MRI evidence of parotitis shown in the contralateral side. The recovery rate within 3 weeks was 68.8%. There was statistically significant increase in the duration of complete recovery for those with positive virological confirmation or mycoplasma infection. There was no significant difference between the rate of recovery in those treated with a short course of steroid (N = 23 attacks) than those without steroid treatment (N = 9 attacks). As there were few studies in the natural course of children with Bell's palsy, evidence based trials should be done to assess the natural course rather than giving steroid empirically as those with more protracted recovery might be viral in origin.


Bronchoscopy can be done safely in patients with thrombocytopenia.
Prophylactic platelet (PLT) transfusions are often administered to patients before bronchoscopy or bronchoalveolar lavage (BAL) to prevent bleeding. There is a paucity of data to validate this approach, with a commonly suggested PLT transfusion threshold of fewer than 50 × 10(9) /L, largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in patients with thrombocytopenia undergoing bronchoscopy. We identified 150 consecutive patients with PLT counts of not more than 100 × 10(9) /L who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. The British Thoracic Society (BTS) guidelines were used to categorize bleeding associated with bronchoscopy. Infection (40%) was the primary indication for bronchoscopy with BAL. Fifty-eight of 89 (65%) patients with baseline PLT counts of not more than 50 × 10(9) /L received prophylactic transfusions compared to 8% of those with PLT counts of more than 50 × 10(9) /L. The PLT count did not increase to more than 50 × 10(9) /L in many patients who received transfusions. Seventy-two patients had counts of less than 50 × 10(9) /L at the time of bronchoscopy, with 15 patients having counts of less than 20 × 10(9) /L. Only one patient with a PLT count of 61 × 10(9) /L had bleeding that required continuous suctioning but then resolved spontaneously (termed "mild bleeding" by BTS criteria). Bloody lavage that resolved spontaneously without continuous suctioning (termed "no bleeding" by the BTS criteria) was observed in nine (6%) patients. The very low incidence of bleeding complications from bronchoscopy with or without BAL even in patients with PLT counts of not more than 30 × 10(9) /L (no episodes of clinically significant bleeding in 35 patients) demonstrates that bronchoscopy can be done safely in patients with severe thrombocytopenia.


Spectroscopic and biological studies on newly synthesized nickel(II) complexes of semicarbazones and thiosemicarbazones.
Nickel(II) complexes, having the general composition Ni(L)2X2, have been synthesized [where L: isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC) and 4-aminoacetophenone thiosemicarbazone (LLD) and X=Cl-, 1/2SO(4)2-]. All the Ni(II) complexes reported here have been characterized by elemental analyses, magnetic moments, IR, electronic and mass spectral studies. All the complexes were found to have magnetic moments corresponding to two unpaired electrons. The possible geometries of the complexes were assigned on the basis of electronic and infrared spectral studies. Newly synthesized ligand and its nickel(II) complexes have been screened against different bacterial and fungal growth.


Mitosis may be an obligatory route to terminal differentiation in the Friend erythroleukemia cell.
In previous studies, it was shown that treatment of Friend erythroleukemia (FEL) cells with dimethylsulfoxide (DMSO) and the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide (3AB) blocked the differentiation pathway just prior to commitment. These studies show that the exposure of DMSO(+3AB)-induced cells to the mitotic inhibitors colcemid or nocodazole resulted in commitment to terminal differentiation. Expression of differentiated phenotype required further incubation without the mitotic inhibitors. Microscopic examination indicated that the number of cells blocked in mitosis and those that differentiated were approximately equivalent. These observations suggest that commitment had occurred during mitosis and that expression of the differentiated state occurred after completion of mitosis. Since commitment was not inhibited by blocking DNA replication by aphidicolin or cytokinesis by cytochalasin B, mitosis may be the only phase of the cell cycle required for commitment.


Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in aldosteronism.
Aldosteronism, or chronic elevation in plasma aldosterone (ALDO) (inappropriate for dietary Na(+) intake), is accompanied by an adverse structural remodeling of the heart and vasculature. Herein, we bring forward a new perspective in which parathyroid hormone (PTH) is identified as a crucial mediator of pathologic cardiac remodeling in aldosteronism. Secondary hyperparathyroidism (SHPT) appears because of the marked urinary and fecal losses of Ca(2+) and Mg(2+) that accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia, providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked to restore extracellular Ca(2+) and Mg(2+) homeostasis, elevations in plasma PTH lead to paradoxical intracellular Ca(2+) overloading of diverse tissues. In the case of cardiomyocytes, the excessive intracellular Ca(2+) accumulation involves both cytosolic free and mitochondrial domains with a consequent induction of oxidative stress by these organelles and lost ATP synthesis. The ensuing opening of their inner membrane permeability transition pore (mPTP) accounts for the osmotic swelling and structural degeneration of mitochondria followed by programed cell necrosis. Tissue repair, invoked to preserve the structural integrity of myocardium accounts for a replacement fibrosis, or scarring, which is found scattered throughout the right and left heart; it represents a morphologic footprint of earlier necrosis. Multiple lines of evidence are reviewed that substantiate the PTH-mediated paradigm and the mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis.


Biomechanical Weakening of Paper and Plant Cell Walls by Bacterial Expansins.
Expansins are proteins that loosen plant cell walls but lack enzymatic activity. Here we describe two protocols tailored to measure the biomechanical activity of bacterial expansin. The first assay relies on the weakening of filter paper by expansin. The second assay is based on induction of creep (long-term, irreversible extension) of plant cell wall samples.


The certainty of the evidence in oral health has not improved according to GRADE: a meta-epidemiological study.
The aim of this meta-epidemiological study was to provide an update of the certainty of the evidence in oral health by using the GRADE rating reported in oral health Cochrane systematic reviews (CSR). All interventional oral health CSR published between 2003-2021 were sourced. Study characteristics were extracted at the level of the CSR and the outcome/meta-analysis. One-hundred-five CSR were eligible and analysed. Almost a third of CSR (n=67) were excluded as a GRADE rating was not available. The most prevalent type of primary studies included in the CSR were randomized studies (93.4%) and the most used measure of effect was the risk ratio (67.3%). Overall, the certainty of the evidence according to the GRADE rating for all examined outcomes was very low/low (88%). The two most common reasons for downgrading the confidence in the evidence were study limitations (Risk of bias) and imprecision. The odds of moderate/high vs. low/very low-GRADE rating are higher for the primary compared to the secondary outcomes after adjusting for year and number of trials (OR 2.49; 95% CI: 1.09, 5.65; P=0.02). Per year (2010-2021 period) the odds of moderate/high vs. low/very low-GRADE rating decrease (OR 0.73; 95% CI: 0.60, 0.90; P=0.01), and as the number of trials per comparison increase the odds of moderate/high vs. low/very low GRADE rating increase (OR 1.13; 95% CI: 1.01, 1.25; P=0.001). The certainty of the evidence in oral health when assessed with the GRADE rating remains predominantly low or very low.


Considerations on the possible structrual basis of neuronal integrated functions.
Different types of dendro-dendritic and dendro-somatic contacts in several species are described. They are classified in five varieties: (a) parallel dendro-dendritic contacts; (b) crossed dendro-dendritic contacts; (c) perisomatic interdendritic contacts; (d) perivascular interdendritic contacts; (e) dendro-somatic contacts. It is hypothetically postulated, in agreement with other authors, that the structurally differentiated interdendritic and dendro-somatic contacts could act as functional junctions for the electrotonic spread of stimuli between neighbour neuronal elements.


Functionalized PVA-silk blended nanofibrous mats promote diabetic wound healing via regulation of extracellular matrix and tissue remodelling.
Chronic cutaneous ulcers, a complex pathophysiological diabetic condition, represent a critical clinical challenge in the current diabetes mellitus pandemic. Consequently, there is a compelling need for bioactive dressings that can trigger healing processes for complete wound repair. Silk fibroin (SF), a natural protein polymer from mulberry and non-mulberry silkworms, has properties that support accelerated wound healing rate. SF from non-mulberry variety possesses additional cell-binding motifs (arginine, glycine, and aspartate), offering cell-material interactions. This study is aimed to investigate wound healing efficacy of dressings made up of various SF varieties blended with poly(vinyl alcohol) biopolymer in alloxan-induced diabetic rabbit model. The nanofibrous mats have been developed using electrospinning and functionalized with growth factors and LL-37 antimicrobial peptide for sustained delivery. Following post 14-day treatment, non-mulberry SF (NMSF)-based dressings healed the wounds faster, in comparison with their mulberry Bombyx mori SF, poly(vinyl alcohol), and control counterparts (p < .01). NMSF-based dressings also supported faster granulation tissue development, angiogenesis, and reepithelialization of wounds. Gene expression study of matrix metalloproteinases and collagen proteins affirmed higher extent of tissue remodelling during the repair process. Furthermore, there was organized extracellular matrix deposition (collagen type I, collagen type III, elastin, and reticulin) and higher wound breaking strength in NMSF compared with other groups after 4 weeks. These results validated the potential of NMSF-based bioactive dressings to regulate extracellular matrix deposition leading to faster and complete repair of chronic diabetic cutaneous wounds.


Trauma during pregnancy.
Traumatic injuries in pregnancy are both common and burdensome. Optimal management includes proper triage, maternal resuscitation, fetal monitoring, and diagnostic imaging.


Sympathetic ophthalmia in Singapore: new trends in an old disease.
Sympathetic ophthalmia (SO) is an uncommon uveitic condition that occurs after injury to the uvea of one eye and may occur after accidental ocular trauma or ocular surgery. We sought to investigate the common causes of SO in Singapore and the demographic profile as well as the final visual acuity after treatment in these patients. This was a retrospective, non-comparative case series in which patients with SO were identified from the Singapore National Eye Centre uveitis database in the period between 1993 and 2003. The patients' case records were examined for a history of ocular trauma or surgery and subsequent development of bilateral or contralateral uveitis consistent with SO or histopathological evidence of SO in enucleated eyes. The medical records of these patients were reviewed for details of the inciting event, presentation, treatment, and visual acuity. A total of ten patients (six men and four women) were diagnosed with SO in the period of study. SO occurred after accidental trauma in three patients and following ocular surgery in seven. Vitreoretinal surgery was responsible for four of these cases, and diode laser cyclophotoablation for another two, whereas neodymium:yttrium-aluminium-garnet (Nd:YAG) laser cyclotherapy was the cause in the last patient. Overall, six of ten patients underwent at least one vitreoretinal procedure. Four of the patients had a final visual acuity of 6/15 or better, whereas five had a visual acuity of 6/30 or worse. Good final visual acuity appeared to be associated with early initiation of immunosuppressive therapy. In this series, ocular surgery, especially vitreoretinal surgery, had overtaken non-surgical trauma as the major cause of SO. A good outcome was possible in most cases if an early diagnosis was made and immunosuppressive treatment started promptly.


Anticipating care needs of patients after discharge from hospital: Frail and elderly patients without physiological abnormality on day of admission are more likely to require social services input.
Acute admissions to hospital are rising. As a part of a service evaluation we examined pathways of patients following hospital discharge depending on data available on admission to hospital. We merged data available on admission to the Wrexham Maelor hospital from an existing data-base in the Acute Medical Unit with follow up data from local social services as part of a data sharing agreement. Patients requiring support by social services post-discharge were matched with patients not requiring social services from the same post-code. Stepwise logistic regression analysis identified candidate variables predicting likely support need. Decision tree analysis identified sub-groups of patients with higher likelihood to require support by social services after discharge from hospital. We found patients with normal physiology on admission as evidenced by a value of zero for the National Early Warning Score who were frail or older than 85years were most likely to require support after discharge. Information available on admission to hospital might inform long term care needs. Prospective testing is needed. The algorithms are prone to be dependent on availability of local services but our methodology is expected to be transferable to other organizations.


Complex evaluation of secretin-pancreozymin test data by multivariate statistical pattern recognition methods.
Complex evaluation of secretin-pancreozymin test data with multivariate statistical methods was performed in patients with pancreatic insufficiency and in controls. The centroid, the nearest neighbour methods and the linear discriminant analysis led to the correct diagnosis in 84, 77 and 92%, respectively, when the overall responses to synthetic secretin plus cholecystokinin-octapeptide were evaluated. Results of individual stimulations were less precise. The linear discriminant analysis also successfully separated the patients with mild chronic pancreatitis from the healthy subjects, and seems to provide a useful support in medical diagnosis, particularly in controversial cases.


The discourse functions of grammatical constructions explain an enduring syntactic puzzle.
Each grammatical construction serves a function, such as conveying that part an utterance is at-issue or is backgrounded. When multiple constructions combine to produce an utterance, their functions must be compatible. This preregistered study (N = 680) addresses the enigmatic case of "syntactic island constraints": Long-distance dependency constructions (LDDs) do not combine equally well with all base constructions. While widely presumed to require unlearned syntactic constraints, we test the idea that it is infelicitous to make an element both prominent (via an LDD construction) and backgrounded (via the base construction). Using 10 base constructions of English (144 base stimuli), results confirm two independent measures of backgroundedness strongly correlate with acceptability ratings on each of three LDD constructions. Results indicate that "island" constraints arise from a clash between the functions of the constructions being combined.


Evaluation of p16 hypermethylation in oral submucous fibrosis: A quantitative and comparative analysis in buccal cells and saliva using real-time methylation-specific polymerase chain reaction.
The aim of this study was to quantitatively investigate the hypermethylation of p16 gene in buccal cells and saliva of oral submucous fibrosis (OSMF) patients using real-time quantitative methylation-specific polymerase chain reaction (PCR) and to compare the values of two methods. A total of 120 samples were taken from 60 subjects selected for this study, of which 30 were controls and 30 patients were clinically and histopathologically diagnosed with OSMF. In both groups, two sets of samples were collected, one directly from the buccal cells through cytobrush technique and the other through salivary rinse. We analyzed the samples for the presence of p16 hypermethylation using quantitative real-time PCR. In OSMF, the hypermethylation status of p16 in buccal cells was very high (93.3%) and in salivary samples, it was partially methylated (50%). However, no hypermethylation was found in controls suggesting that significant quantity of p16 hypermethylation was present in buccal cells and saliva in OSMF. This study indicates that buccal cell sampling may be a better method for evaluation than the salivary samples. It signifies that hypermethylation of p16 is an important factor to be considered in epigenetic alterations of normal cells to oral precancer, i.e. OSMF.


Microbial Proteome Profiling and Systems Biology: Applications to Mycobacterium tuberculosis.
Each year, 1.3 million people die from tuberculosis, an infectious disease caused by Mycobacterium tuberculosis. Systems biology-based strategies might significantly contribute to the knowledge-guided development of more effective vaccines and drugs to prevent and cure infectious diseases. To build models simulating the behaviour of a system in response to internal or external stimuli and to identify potential targets for therapeutic intervention, systems biology approaches require the acquisition of quantitative molecular profiles on many perturbed states. Here we review the current state of proteomic analyses in Mycobacterium tuberculosis and discuss the potential of recently emerging targeting mass spectrometry-based techniques which enable fast, sensitive and accurate protein measurements.


Autologous tissues for dural grafting in children: a report of 56 cases.
Diverse materials have been used for dural closure, including grafts of cadaveric origin. Some 168 cases of Creutzfeldt-Jakob disease have been reported following the implant of human dura mater. A few publications have addressed the use of dural grafts in children, but none has analyzed the feasibility of autologous tissues for this purpose. Since 1994, the authors have utilized autologous tissues for dural grafting in children undergoing neurosurgical procedures, aimed at studying the feasibility of its use in this age group. We studied 56 children submitted to neurosurgical procedures who underwent an implant of a patch of autologous tissue for dural closure. Epidemiological, clinical, and neuroimaging data were processed using statistical methods. The study group was composed of 29 boys and 27 girls, with ages ranging from 1 month to 17 years (mean 7.6 years). The procedures corresponded to lesions at the posterior cranial fossa (n = 41), supratentorial cranial compartment (n = 12), and spine (n = 3). Seventy-five percent of the children had no complication. Four patients had adverse effects unrelated to dural grafting, while ten children had complications that might be associated with it. The most frequent complication was pseudomeningocele (n = 6), followed by infection (n = 3) and CSF leak (n = 1). Although hydrocephalus seemed to have an influence on the occurrence of complications, their incidence in patients without hydrocephalus did not differ statistically. Autologous grafts of fascia or pericranium can be safely used for dural reconstruction in children. Given the reported complications associated with the use of foreign materials for duraplasty, the authors recommend the use of autologous tissues for dural repair, reserving other types of dural grafts for cases in which its usage is unavoidable.


Screening for major depression among alcoholics: an application of receiver operating characteristic analysis.
When comparing several screening tests designed to detect the same disease, methodological problems arise in determining which is most accurate. We have previously demonstrated that receiver operating characteristic (ROC) methodology can provide a set of statistical procedures which allow for objective comparisons of screening tests. In this report, ROC methodology is brought to a different substantive area: the detection of clinical depression among treated alcoholics. In a sample of hospitalized alcoholics, we compared the accuracies of several commonly used screening tests for depressive disorders, as well as comparing each of these with a screening test for anxiety disorders. No test offered a statistically significant advantage over any other, and all did poorly in detecting clinically diagnosed major depression. The performance of the screening tests was worst when the non-depressed comparison group included subjects with remitted disorder, but was still poor when the comparison group did not include such potentially 'noisy' subjects. Factors contributing to the difficulty of screening for clinical depression are discussed, as well as suggestions for improvements in future screening efforts.


PET image denoising using a synergistic multiresolution analysis of structural (MRI/CT) and functional datasets.
PET allows the imaging of functional properties of the living tissue, whereas other modalities (CT, MRI) provide structural information at significantly higher resolution and better image quality. Constraints for injected radioactivity, technologic limitations of current instrumentation, and inherent spatial uncertainties on the decaying process affect the quality of PET images. In this article we illustrate how structural information of matched anatomic images can be used in a multiresolution model to enhance the signal-to-noise ratio of PET images. The model states a flexible relation between function and structure in the brain and replaces high-resolution information of PET images with appropriately scaled MRI or CT local detail. The method can be naturally extended to other functional imaging modalities (SPECT, functional MRI). The methodology is based on the multiresolution property of the wavelet transform (WT). First, the coregistered structural image (MRI/CT) is downgraded to the resolution of the PET volume through appropriate filtering. Second, a redundant version of the WT is applied to both volumes. Third, a linear model is applied to the set of local coefficients of both image volumes and resulting parameters are recorded. The overall set of linear coefficients is then modeled as a mixture of multivariate gaussian distributions and fitted through a k-means algorithm. Finally, the local wavelet coefficients of the PET image are substituted by the corresponding values of the MRI/CT set calibrated according to the resulting clustering. The methodology was validated on digital simulated images and clinical data to evaluate its quantitative potential for individual as well as group analysis. Application to real and simulated datasets shows very effective noise reduction (15% SD) while resolution is preserved. The methodology is robust to errors in the coregistration parameters, practical to implement, and computationally fast.


Cyber-infrastructure and epidemic precautionary policy: evidence from China.
The application of technology supported by cyber infrastructure has emerged as a critical factor influencing city management. This study aims to investigate whether the development of cyber infrastructure can enhance cities' confidence in responding to potential epidemic threats in the context of COVID-19. China serves as a good example for both COVID-19 management and smart city construction. We take advantage of a special time point, the 2022 Chinese New Year, to observe cities' precautionary epidemic policies. We utilize choice models and data from 188 Chinese cities to examine the impact of internet coverage on the degree of policy relaxation. We found that cities with higher internet coverage tend to adopt looser policies. In the benchmark regression, for every 1 percentage point increase in internet coverage, the likelihood of implementing loose measures increases by 0.9 percentage points. This result remains robust across different classifications of policies. We also addressed potential endogeneity issues by using the instrumental variables method. Our study indicates that effective management of epidemics in the modern era requires not only the utilization of traditional medical resources but also the incorporation of new city features, such as information technology infrastructure.


Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway.
To investigate the role of Hedgehog (Hh) signaling pathway in the invasion and metastasis of human hepatocellular carcinoma (HCC). Eighty six HCC tissues samples and HCC cell line Bel-7402 were examined. The protein expression of sonic hedgehog (Shh), nuclear glioma-associated oncogene-1 (Gli1), MMP-9 and p-ERK1/2 in HCC was analyzed using immunohistochemistry and Western blot analysis. Boyden chamber assay and wound-healing assay were used to quantify the invasion and metastasis of Bel-7402 cells. In 86 HCC tissue samples, the positive ratio of Shh and nucleus Gli1 was 67.44% (58/86) and 60.47% (52/86), respectively; the expression of nucleus Gli1 was correlated with the tumor pathological grade (P=0.034), and with the ability of the tumor to invade and metastasize (P=0.001); the expression of nucleus Gli1 was also correlated with p-ERK1/2 (P=0.031) and with MMP-9 (P=0.034). Neither Shh, nor nucleus Gli1 was observed in normal liver tissue. KAAD-cyclopamine (KAAD-cyc), a specific inhibitor of the Hh pathway, at the concentrations of 1 and 4 μmol/L inhibited the invasion and migration of Bel-7402 cells and decreased the expression of Gli1 in nucleus and MMP-9, p-ERK1/2 proteins in Bel-7402 cells. On the other hand, Shh, a ligand of the Hh pathway, at the concentration of 0.5 μg/mL produced opposite effects. The MAPK pathway inhibitors U0126 and PD98059 at the concentrations of 5 and 10 μmol/L inhibited invasion and metastasis of Bel-7402 cells induced by Shh, and decreased the expression of p-ERK1/2 and MMP-9. However, U0126 and PD98059 had no effect on the expression of Gli1. Hh signaling pathway mediates invasion and metastasis of human HCC by up-regulating the protein expression of MMP-9 via ERK pathway.


A study of condylar movement by bilateral simultaneous videofluorography.
To analyse the condylar movements of patients with temporomandibular disorders and investigate the mutual interaction between both temporomandibular joints (TMJs) by comparing bilateral simultaneous videofluorography with the disk position on MRI. Fifty-two patients who had been diagnosed as having internal derangement in one or both TMJs on the base of the clinical symptoms underwent bilateral simultaneous videofluorography and MRI. The TMJs were classified from the MRI into three categories: superior disk position (SDP), reducing disk displacement (RDD) and nonreducing disk displacement (NDD). Condylar movements of the TMJs were analysed from the videofluorography and correlated with the MR diagnoses. The range of condylar movement of NDD joints was significantly shorter than that of SDP or RDD joints at maximum mouth opening (P < 0.001), but not at maximum protrusion and lateral protrusion. Based on the sagittal condylar path during maximum mouth opening and closing, three patterns of condylar movement were identified: normal, deflected and short. Sixty-nine per cent of the normal pattern were SDP, 55% of the deflected RDD and 77% of the short NDD. The condylar movement of a NDD or RDD joint could influence the range and pattern of movement of the contralateral joint. Analysis of condylar movement was helpful in assessing the state of the disk because they were closely related. The range and pattern of condylar movement of both TMJs were mutually interrelated. Patients with signs and symptoms of internal derangement should have both sides examined for an accurate and complete diagnosis.


Effect of antacid medication on the pharmacokinetics of temafloxacin.
The effect of an antacid drug (Maalox 70) on the pharmacokinetics of temafloxacin was studied in 12 healthy young volunteers. The study was designed as a randomised open 2-period crossover trial in which temafloxacin was administered alone and with Maalox 70. In both treatments, temafloxacin was administered as a single oral 400mg dose on the morning of day 2. In the antacid regimen, 8 doses of Maalox 70 were administered every 2h on day 1, starting at 8am and ending with the last dose at 10pm; 5 doses were given on day 2, at 2.5 and 1h before administration of temafloxacin and 1, 3 and 5h after the temafloxacin dose. With coadministration of Maalox 70, peak plasma temafloxacin concentrations (Cmax) were reduced to 44.6% (+/- 24.5), and AUC(0-infinity) was reduced to 39.8% (+/- 17.4) of the corresponding values obtained when temafloxacin was given alone. Urinary excretion of temafloxacin was reduced to 46.0% (+/- 13.7) of that observed when temafloxacin was administered alone. Time to peak plasma concentration (tmax = 1.8h) was not affected by antacid administration. Comparable or greater antacid-associated reductions in relative bioavailability have been reported for other quinolones. As with other quinolones, the concurrent administration of temafloxacin and antacids should be avoided.


Comment on perceptual defense in anxiety disorders.
This paper is intended to lend support to the 2003 findings of Poloni, Riquier, Zimmermann, and Borgeat. Further, some extensions of these and other findings with respect to perceptual defense are suggested.


Factors influencing dietary practices in a transitioning food environment: a cross-sectional exploration of four dietary typologies among rural and urban Ugandan women using Photovoice.
Healthy and sustainable dietary practices offer a possible solution to competing tensions between health and environmental sustainability, particularly as global food systems transition. To encourage such dietary practices, it is imperative to understand existing dietary practices and factors influencing these dietary practices. The aim of this study was to identify multi-level factors in lived rural and urban Ugandan food environments that influence existing dietary practices among women of reproductive age (WRA). A mixed methods study was conducted. Multiple correspondence analysis followed by hierarchical cluster analysis were performed on dietary data collected among a sample (n = 73) of Ugandan WRA in Kampala (urban) and Wakiso (rural) districts to elicit dietary clusters. Dietary clusters, which were labelled as dietary typologies based on environmental impact and nutrition transition considerations, were reflective of dietary practices. Following this, a smaller sample of WRA (n = 18) participated in a Photovoice exercise and in-depth interviews to identify factors in their social, physical, socio-cultural and macro-level environments influencing their enactment of the identified dietary typologies, and therefore dietary practices. Four dietary typologies emerged: 'urban, low-impact, early-stage transitioners', 'urban, medium-impact, mid-stage transitioners', 'rural, low-impact, early-stage transitioners' and 'rural, low-impact, traditionalists'. Although experienced somewhat differently, the physical environment (access, availability and cost), social networks (parents, other family members and friends) and socio-cultural environment (dietary norms) were cross-cutting influences among both urban and rural dietary typologies. Seasonality (macro-environment) directly influenced consumption of healthier and lower environmental impact, plant-based foods among the two rural dietary typology participants, while seasonality and transportation intersected to influence consumption of healthier and lower environmental impact, plant-based foods among participants in the two urban dietary typologies. Participants displayed a range of dietary typologies, and therefore dietary practices. Family provides an avenue through which interventions aimed at encouraging healthier and lower environmental impact dietary practices can be targeted. Home gardens, urban farming and improved transportation could address challenges in availability and access to healthier, lower environmental impact plant-based foods among urban WRA.


Theophylline effects on cellular response in protein-energy malnourished neonatal rat brain.
The present study employed an animal model in an attempt to document effects on brain growth of long-term exposure to theophylline in the presence or absence of malnutrition. One group of dams was randomly divided into half. One-half was fed a 20% protein diet and the other half a 6% protein diet. Similarly, a second group of dams was also randomly divided into two groups. These were pair-fed with rats of the first group, receiving diets comparable to those in group one but to which theophylline was added in amounts calculated to provide daily doses of 2 mg/100 g of body weight. Theophylline supplementation in the dams' 6% protein diet decreased the body weight of the pups consistently from d 3 to the end of the study at d 15 in comparison to the non-theophylline group. In contrast, the presence of theophylline in the control diet increased the body weight of the pups at d 15 compared with that of the non-theophylline group. Brain weight was essentially identical in the normal controls and the normally nourished group given theophylline. No difference in brain weight was noted between the malnourished group and the malnourished group given theophylline. We found a significant reduction in DNA content per brain or per mg of brain weight in the normally nourished group given theophylline compared with non-theophylline group. DNA values per mg of brain weight from the controls that received theophylline were not different from either malnourished group.(ABSTRACT TRUNCATED AT 250 WORDS)


Change in Profile of Entrants in a Brazilian Large Cardiovascular Rehabilitation Service.
There are references regarding physical activity and cardiovascular disease since the nineteenth century. New evidences support that cardiac rehabilitation is closely related to therapeutic success after major coronary events. Although the benefits of cardiac rehabilitation programs are well established, referencing and enrolment in such services remain low. The aim of this paper is to describe the profile changes throughout the years in a large cardiac rehabilitation service in Brazil. This is a retrospective analysis of medical records of all patients referred to cardiac rehabilitation service of the Institute of Sports Medicine, University of Caxias do Sul from March 2003 to July 2014. Data collection was carried out using SPSS software and the statistical analysis with Student's t-test, ANOVA test and chi square test. It has seen a substantial increase of patients, mostly routed via universal health system, also an increase of post-myocardial infarction patients and ex-smokers. Also, it was seen few patients in the 7th and 8th life decades, and men were in majority since the beginning. An increase in the number of patients referred by universal health system occurred because there is a governmental interest in this type of program. About tobacco, hospitalizations appear to be influential in the decision of abandonment. There was a substantial increase of patients with more severe disease which is in accordance with the latest guidelines of Cardiovascular and Metabolic Rehabilitation.


Oxidative DNA damage drives carcinogenesis in MUTYH-associated-polyposis by specific mutations of mitochondrial and MAPK genes.
MUTYH is a DNA-base-excision-repair gene implicated in the activation of nuclear and mitochondrial cell-death pathways. MUTYH germline mutations cause an inherited polyposis, MUTYH-associated-polyposis, characterized by multiple adenomas and increased susceptibility to colorectal cancer. Since this carcinogenesis remains partially unknown, we searched for nuclear and mitochondrial gene alterations that may drive the tumorigenic process. Ninety-six adenomas and 7 carcinomas from 12 MUTYH-associated-polyposis and 13 classical/attenuated adenomatous polyposis patients were investigated by sequencing and pyrosequencing for the presence of mutations in KRAS, BRAF, MT-CO1/MT-CO2 and MT-TD genes. KRAS mutations were identified in 24% MUTYH-associated-polyposis vs 15% classical/attenuated familial polyposis adenomas; mutated MUTYH-associated-polyposis adenomas exhibited only c.34G>T transversions in codon 12, an alteration typically associated with oxidative DNA damage, or mutations in codon 13; neither of these mutations was found in classical/attenuated familial polyposis adenomas (P<0.001). Mutated MUTYH-associated-polyposis carcinomas showed KRAS c.34G>T transversions, prevalently occurring with BRAFV600E; none of the classical/attenuated familial polyposis carcinomas displayed these alterations. Comparing mitochondrial DNA from lymphocytes and adenomas of the same individuals, we detected variants in 82% MUTYH-associated-polyposis vs 38% classical/attenuated familial polyposis patients (P=0.040). MT-CO1/MT-CO2 missense mutations, which cause aminoacid changes, were only found in MUTYH-associated-polyposis lesions and were significantly associated with KRAS mutations (P=0.0085). We provide evidence that MUTYH-associated-polyposis carcinogenesis is characterized by the occurrence of specific mutations in both KRAS and phylogenetically conserved genes of mitochondrial DNA which are involved in controlling oxidative phosphorylation; this implies the existence of a colorectal tumorigenesis in which changes in mitochondrial functions cooperate with RAS-induced malignant transformation.


Global risks, the macroeconomy, and asset prices.
We propose a novel index of global risks awareness (GRAI) based on the most concerning risks-classified in five categories (economic, environmental, geopolitical, societal, and technological)-reported by the World Economic Forum (WEF) according to the potential impact and likelihood occurrence. The degree of public concern toward these risks is captured by Google search volumes on topics having the same or similar wording of that one of the WEF Global Risk Report. The dynamics of our GRAI exhibits several spillover episodes and indicates that concerns on the five different categories of global risks are-on average-highly interconnected. We further examine the interconnection between global risks perceptions and the macroeconomy and find that concerns on economic-, geopolitical-, and societal-related risks are net shock transmitters, whereas the macroeconomic variables are largely net receivers. Finally, we perform standard cross-sectional asset pricing tests and provide evidence that rising interconnection among global risks awareness commands a positive and statistically significant risk premium.


Serum D-dimer as a predictor of mortality in patients with acute spontaneous intracerebral hemorrhage.
It has been found that the hemostatic system is activated following a brain injury. To explore the role of D-dimer in spontaneous intracerebral hemorrhage (ICH), this prospective study aimed to evaluate the association between serum D-dimer concentration, clinical outcome and radiographic findings of ICH patients in the emergency department (ED). Patients with acute (<24 hours) spontaneous ICH were enrolled in this study. The D-dimer concentration was related to: baseline ICH volume (r=0.198, p=0.01); Glasgow Coma Scale (GCS) score 3-8 (p=0.01); GCS score 13-15 (p=0.002); midline shift >15 mm (p=0.016); and to subarachnoid extension of the blood (p<0.0001). Diabetes mellitus (odds ratio [OR]: 2.93; 95% confidence interval [CI]: 1.1-7.76, p=0.031), ICH volume (OR: 1.16; 95% CI: 1.07-1.27, p<0.0001) and D-dimer concentration (OR: 2.72; 95% CI: 1.08-6.9, p=0.002) were associated with 30-day mortality. This study shows that in patients with spontaneous ICH, a higher initial D-dimer concentration is associated with higher 30-day mortality.


The effect of glucagon on infusion cholangiography.
The study was undertaken to assess the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min-1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min-1 over 30 min. Radiographs were taken in both series, immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series than assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography.


[Expression and clinical significance of p27 protein and cyclinD1 protein in gastrointestinal stromal tumors].
To investigate the expression of p27 and cyclin D1 protein in gastrointestinal stromal tumors (GIST), and discuss the relationship between their expression and clincopathological characteristics. Immunohistochemical staining was used to detect the expression of p27 and cyclin D1 in 48 cases of GIST and corresponding normal tissues. In 48 cases GIST, the expression of p27 and cyclin D1 protein were 54.16% and 58.33% respectively. The low level expression of p27 protein was inversely correlated with the degree of differentiation and tumor recurrence of GIST (both P < 0.01). The expression of p27 protein was positively relatied to that of cyclin D1 (r = 0.573, P < 0.01). These data shows the expression of p27 and cyclin D1 expression are related to the ontogenesis and progression of GIST. p27 and cyclin D1 may be prognostic indicators in GIST.


Skin test reactivity in inflammatory bowel disease in the United States and Czechoslovakia.
Inflammatory bowel disease (IBD) patients in the United States of America (USA) and Czechoslovakia (CSSR) were categorized by clinical, pathological, and radiological criteria as having Crohn's disease (CD) or ulcerative colitis (UC) and were tested with five skin test antigens [Candida, mumps, purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), and trichophytin] at two different dilutions in an attempt to elicit some evidence of anergy. No significant differences were encountered between the USA and CSSR populations or between any patient group and its controls.


Role of the tertiary and quaternary structure in the formation of bis-histidyl adducts in cold-adapted hemoglobins.
All tetrameric hemoglobins from Antarctic fish, including that from Trematomus bernacchii, HbTb form in the ferric state, promptly and distinctively from all the other tetrameric hemoglobins, a mixture of aquo-met at the α subunits and bis-histidyl adduct (hemichrome) at the β subunits. The role of the tertiary and quaternary structure in the hemichrome formation is unknown. Here we report the cloning, expression, purification, spectroscopic and computational characterization of the β-chain of HbTb (β-HbTb). Similarly to the human β-chains, β-HbTb self-assembles to form the homotetramer β(4)-HbTb; however, the latter quantitatively forms reversible ferric and ferrous bis-histidyl adducts, which are only partially present in the human tetramer (β(4)-HbA). A molecular dynamics study of the isolated β subunit of the two Hbs indicates that the ability to form hemichrome is an intrinsic feature of the chain; moreover, the greater propensity of β-HbTb to form the bis-histidyl adduct is probably linked to the higher flexibility of the CD loop region. On the bases of these experimental and computational results on the isolated chain, the influence of the quaternary structure on the stability of the endogenous ferrous and ferric hexa-coordination is also discussed.


Alloplastic materials in rhinoplasty.
This review examines implant materials currently used in rhinoplasty. In revision cases, the most desirable autogenous grafts from the septum are often unavailable in adequate quantities. The 'ideal' implant has strict requirements concerning biocompatibility, plasticity, stability of form, resistance to infection, and removability. Silicone implants continue to be used in spite of frequent reports of rejection. In spite of its described absorption, conserved cartilage can help in preserving profiles. Increasingly, good results are being reported with porous polyethylene, although Proplast is sometimes used in its place. Despite the fact that AlloDerm is partially absorbed, it can still be useful. GoreTex is effective for smaller defects. Mersilene mesh is not absorbed and retains its stability of shape. 'Turkish Delight' (diced cartilage with a wrapping) seems to be absorbed when the wrapping is made of Surgicel, but a wrapping of autogenous fascia provides lasting results. Several alloplastic materials do have a place in nasal surgery. Provided that the correct techniques are employed, side effects from their use are no greater than the complications resulting from the use of autogenous costal cartilage, with the intervention necessary for its harvesting.


Correlation between KRAS mutation subtypes and prognosis in Chinese advanced non-squamous non-small cell lung cancer patients.
The relationship between mutant KRAS and the risk of disease progression and death in advanced non-squamous non-small cell lung cancer (NSCLC) is still controversial among current studies, and the effects of distinct KRAS mutations on prognosis may be different. This study aimed to further investigate the association between them. Of the 184 patients eventually included in the study, 108 had KRAS wild type (WT) and 76 had KRAS mutant type (MT). Kaplan-Meier curves were plotted to describe the survival for patients among groups, while log-rank tests were conducted to evaluate the survival differences. The univariate and multivariate Cox regression were performed to identify predictors, and subgroup analysis was used to verify the interaction effect. Similar efficacy of first-line therapy was observed for KRAS MT and WT patients (p = 0.830). The association between KRAS mutation and progression-free survival (PFS) was not significant in univariate analysis (hazard ratio [HR] = 0.94; 95% CI, 0.66-1.35), and no KRAS mutation subtype significantly affected PFS. However, KRAS mutation and KRAS non-G12C were associated with increased risk of death compared to KRAS WT in univariate and multivariate analysis. Univariate and multivariate analysis also confirmed that chemotherapy combined with antiangiogenesis or immunotherapy in the KRAS mutation group was associated with decreased risk of disease progression. However, the overall survival (OS) among KRAS mutant patients received different first-line treatments did not significantly differ. KRAS mutations and their subtypes are not independent negative predictors of PFS, while KRAS mutation and KRAS non-G12C were independent prognostic factors for OS. Chemotherapy combined with antiangiogenesis or immunotherapy conferred decreased risk of disease progression to KRAS mutation patients compared to single chemotherapy.


The sea anemone Bunodosoma cangicum as a potential biomonitor for microplastics contamination on the Brazilian Amazon coast.
This study reports for the first time the ingestion of meso- (5.01-25 mm) and microplastics (1 μm-5 mm) by the sea anemone Bunodosoma cangicum, the most abundant actiniarian species on the Amazon coast. At three sites on the coast of Pará, Brazil, anemones were collected from beachrocks in the intertidal zone (30 at each site), measured (pedal disc diameter, mm) and weighed (wet weight, g). The contents of the gastrovascular cavity were extracted and analyzed under a stereoscope. The recovered plastic particles were characterized by Fourier Transform Infrared (FTIR) spectroscopy. Overall, 139 microplastic and 2 mesoplastic items were identified in 68 individuals (75.6%) among the 90 examined, with a mean of 1.6 (±1.5) items per individual. Plastic fibers comprised about 84% of the ingested plastics, followed by fragments (∼12%) and films (∼4%). Particle diameters ranged from 0.10 to 9.17 mm (1.57 ± 1.23 mm). A weak positive correlation was found between the weight of anemones and the number of plastic particles in the gastrovascular cavity (p = 0.03) and between the number of prey items and the number of plastic particles in the gastrovascular cavity (p < 0.01). The main polymers identified by FTIR analysis were polyethylene terephthalate (PET), polypropylene (PP), polyamide (PA), polyurethane (PU), polyethylene (PE), acrylonitrile butadiene styrene (ABS), polystyrene (PS) and rayon. Sea anemones ingested significantly more plastic debris at the most urbanized and populous sampling sites. This study provides the first evidence of microplastics contamination of marine invertebrates from the Amazon coast. Abundant species such as B. cangicum have the potential to monitor the levels of plastic contamination in the region. Our results support this potential, as the species showed a high frequency of plastic ingestion and allowed detection of plastic contamination even in the best-preserved area where anemones were collected.


Early Outcomes of Two Treatment Modes of PresbyLASIK: Monocular vs. Micro-Monovision.
To report the visual, refractive and subjective outcomes of presbyLASIK for the correction of presbyopia. Monocular (20 eyes) or micro-monovision (12 eyes) presbyLASIK was performed on a total of 32 eyes in 16 patients (50% female, average age 55±4.6 years) using the Zeiss VisuMax 400Hz femtosecond and Schwind Amaris 1050RS excimer laser platform. Predictability, safety and efficacy were assessed and compared at 4-6 weeks, 3 months and 6 months. Results were considered significant if P < 0.05. For monocular treatments, average postoperative spherical equivalent (SE) was 0.1±0.1 D and -0.86±0.5 D at 4-6 weeks postoperatively for distance and near eyes respectively; 90% eyes achieved SE ±1.0 D of the target. Postoperative binocular uncorrected distance (UDVA), intermediate (UIVA) and near visual acuity (UNVA) were -0.03±0.1 LogMAR (20/20), 0.09±0.26 LogMAR (N4) and 0.29±0.11 LogMAR (N6) respectively with 90% patients achieving binocular UDVA of 20/20 or better. For micro-monovision treatments, average postoperative SE was -0.33±0.51 D and -1.60±0.78 D at 4-6 weeks postoperatively for distance and near eyes respectively; 100% eyes achieved SE ±1.0 D of the target. Postoperative binocular UDVA, UIVA and UNVA were 0.05±0.16 LogMAR (20/20), -0.02±0.10 LogMAR (N3) and 0.23±0.08 LogMAR (N5) respectively with 67% patients achieving binocular UDVA of 20/20 or better. Monocular and micro-monovision presbyLASIK are both effective options for the treatment of presbyopia. Monocular treatments are more likely to be well tolerated by patients who prefer to preserve exceptional distance vision, while micro-monovision treatments may be better suited to patients who can tolerate compromises in distance vision in order to attain greater intermediate vision function.


Organizational wellbeing: A model of a new Apulian COVID-19 designated hospital.
Work environment characteristics have an important impact on organizational wellbeing in health care facilities. In the Apulia Region, a new COVID-19 hospital was planned, designated and built in a few weeks for the treatment of patients infected with SARS-CoV-2. To our knowledge, this hospital, together with "Fiera Hospital" in Milan, are two of the few buildings worldwide that have been converted into new health care facilities with intensive care center units to treat COVID-19 patients, and this is the first study assessing organizational wellbeing in a newly designated COVID-19 hospital. To detect and assess the strong points, criticality, and perceptions of wellbeing/discomfort of health care workers engaged in the management of the current health emergency. The study was conducted on 188 health care workers, with the "Multidimensional Organizational Health Questionnaire." We found an overall positive level of organizational wellbeing. The more positive dimensions were "Collaboration between colleagues," "Organizational efficiency" and "Room Comfort." Conflict situations in the workplace were poorly perceived. A very low rate of absenteeism from work was also observed. Our results show the effectiveness of the organizational model adopted in the management of the COVID-19 hospital, especially in view of the work and emotional overload of the personnel called to face the epidemiological emergency on the frontline, which did not adversely affect the psychophysical conditions of the workers. The success of this model is related to the coexistence of all levels of care required during any type of health emergency in a single structure, paying particular attention to the architectural, functional, and procedural aspects of health care and to the so-called "humanization" of care.


Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.
Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from pediatric cancer patients in developed countries may be generalizable to pediatric cancer patients in developing countries.


Detection of Respiratory Syncytial Virus or Rhinovirus Weeks After Hospitalization for Bronchiolitis and the Risk of Recurrent Wheezing.
In severe bronchiolitis, it is unclear if delayed clearance or sequential infection of respiratory syncytial virus (RSV) or rhinovirus (RV) is associated with recurrent wheezing. In a 17-center severe bronchiolitis cohort, we tested nasopharyngeal aspirates (NPA) upon hospitalization and 3 weeks later (clearance swab) for respiratory viruses using PCR. The same RSV subtype or RV genotype in NPA and clearance swab defined delayed clearance (DC); a new RSV subtype or RV genotype at clearance defined sequential infection (SI). Recurrent wheezing by age 3 years was defined per national asthma guidelines. Among 673 infants, RSV DC and RV DC were not associated with recurrent wheezing, and RSV SI was rare. The 128 infants with RV SI (19%) had nonsignificantly higher risk of recurrent wheezing (hazard ratio [HR], 1.31; 95% confidence interval [CI], .95-1.80; P = .10) versus infants without RV SI. Among infants with RV at hospitalization, those with RV SI had a higher risk of recurrent wheezing compared to children without RV SI (HR, 2.49; 95% CI, 1.22-5.06; P = .01). Among infants with severe bronchiolitis, those with RV at hospitalization followed by a new RV infection had the highest risk of recurrent wheezing.


Maximum Lyapunov exponent revisited: Long-term attractor divergence of gait dynamics is highly sensitive to the noise structure of stride intervals.
The local dynamic stability method (maximum Lyapunov exponent) can assess gait stability. Two variants of the method exist: the short-term divergence exponent (DE), and the long-term DE. Only the short-term DE can predict fall risk. However, the significance of long-term DE has been unclear so far. Some studies have suggested that the complex, fractal-like structure of fluctuations among consecutive strides correlates with long-term DE. The aim, therefore, was to assess whether the long-term DE is a gait complexity index. The study reanalyzed a dataset of trunk accelerations from 100 healthy adults walking at preferred speed on a treadmill for 10 min. By interpolation, the stride intervals were modified within the acceleration signals for the purpose of conserving the original shape of the signal, while imposing a known stride-to-stride fluctuation structure. Four types of hybrid signals with different noise structures were built: constant, anti-correlated, random, and correlated (fractal). Short- and long-term DEs were then computed. The results show that long-term DEs, but not short-term DEs, are sensitive to the noise structure of stride intervals. For example, it was that observed that random hybrid signals exhibited significantly lower long-term DEs than hybrid correlated signals did (0.100 vs 0.144, i.e. a 44% difference). Long-term DEs from constant hybrid signals were close to zero (0.006). Conversely, short-term DEs of anti-correlated, random, and correlated hybrid signals were closely grouped (2.49, 2.50, and 2.51). The short-term DE and the long-term DE, although they are both computed from divergence curves, should not be interpreted in a similar way. The long-term DE is very likely an index of gait complexity, which may be associated with gait automaticity or cautiousness. Consequently, to better differentiate between short- and long-term DEs, the use of the term attractor complexity index (ACI) is proposed for the latter.


Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case-Control Study in the Iranian Kurdish Ethnic Group.
Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter-308 G/A polymorphism with T2DM. In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods. The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype. Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population.


Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities.
Activation of the coagulation cascade is a critical, evolutionarily conserved mechanism that maintains hemostasis by rapidly forming blood clots in response to blood-borne infections and damaged blood vessels. Coagulation is a key component of innate immunity since it prevents bacterial dissemination and can provoke inflammation. The term immunothrombosis describes the process by which the innate immune response drives aberrant coagulation, which can result in a lethal condition termed disseminated intravascular coagulation, often seen in sepsis. In this review, we describe the recently uncovered molecular mechanisms underlying inflammasome- and STING-driven immunothrombosis induced by bacterial and viral infections, culminating in tissue factor (TF) activation and release. Current anticoagulant therapeutics, while effective, are associated with a life-threatening bleeding risk, requiring the urgent development of new treatments. Targeting immunothrombosis may provide a safer option. Thus, we highlight preclinical tools which target TF and/or block canonical (NLRP3) or noncanonical (caspase-11) inflammasome activation as well as STING-driven TF release and discuss clinically approved drugs which block key immunothrombotic processes and, therefore, may be redeployed as safer anticoagulants.