[Prevention of transmission of multidrug-resistant bacteria].
The increase in multidrug-resistant bacteria (MDR) is a worldwide problem. Depending on the type of pathogen there are only a few and less effective treatment options available; therefore, effective infection prevention is of major importance. Which infection prevention and control measures are effective and feasible for the prevention of MDR transmission? Discussion and critical appraisal of current recommendations and the available literature. Studies evaluating infection control measures for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant Gram-negative bacteria differ with respect to the prevalence of MDR, screening methods, number of available personnel and compliance with hand hygiene measures. Many databases result from outbreak investigations and are not comparable with the endemic setting. In addition, the bundle approach makes it impossible to evaluate a single measure alone. The guidelines and recommendations for dealing with colonized and infected patients are of low evidential value and often difficult to implement in the clinical practice. The single most important measure to avoid transmission is still disinfection of the hands. Single room isolation and contact precautions are often recommended but the relevance is unclear; however, the disadvantages of patients being isolated are well studied and of major concern. Screening measures have to be adapted to the local situation. Full body washing of all patients in at-risk areas with chlorhexidine appears to be an attractive and effective alternative to screening and isolation.


Surfactant metabolism.
Alveolar surfactant pool sizes are small in the preterm animal with RDS, and these pool sizes probably increase to approximate those found in preterm animal without RDS by 3 to 4 days after birth. De novo synthesis and secretion of surfactant phospholipids are slow processes. Therefore, surfactant treatments are the only way to acutely increase the pool size. Surfactant phospholipids are very slowly catabolized in the preterm lung. The surfactant phospholipids used for treatment rapidly associate with lung tissue and are processed by recycling through lamellar bodies within type II cells. Surfactant proteins already present within the preterm lung can associate with the exogenous surfactant. These proteins have metabolic pathways quite different from those for the lipids. Surfactant treatments do not seem to interfere with endogenous metabolic pathways for surfactant synthesis and secretion. Surfactant treatments of infants with RDS are beneficial in part because of the favorable metabolism characterized by a preterm lung that can recycle surfactant and does not catabolize the exogenous surfactant.


Identification of schisandrin as a vascular endothelium protective component in YiQiFuMai Powder Injection using HUVECs binding and HPLC-DAD-Q-TOF-MS/MS analysis.
YiQiFuMai Powder Injection (YQFM) is a re-developed preparation based on the well-known traditional Chinese medicine formula Sheng-mai-san. It has been widely used for the treatment of cardiovascular disease with definite clinical efficacy in China, but its bioactive molecules remain obscure. In this study, an effective method has been employed as a tool for screening active components in YQFM, using human umbilical vein endothelial cells (HUVECs) extraction and liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Nine compounds, which could interact with HUVECs, were identified as ginsenosides Rb1, Rc, Rb2, Rd, 20(S)-Rg3, 20(R)-Rg3, Rk1/Rg5 and schisandrin by comparing with reference substances or literature. In vitro assays showed that schisandrin at concentrations of 10-100 μM protected HUVECs from hypoxia/reoxygenation (H/R) injury, increased cell viability, nitric oxide (NO) content and decreased lactate dehydrogenase (LDH) leakage, malonaldehyde (MDA) content and ROS generation. Moreover, schisandrin pretreatment inhibited cell apoptosis, as evidenced by inhibiting activation of caspase-3 and increasing the Bcl-2/Bax ratio. These data indicate that HUVECs biospecific extraction coupled with HPLC-ESI-Q-TOF-MS/MS analysis is a reliable method for screening potential bioactive components from traditional Chinese medicines. Meanwhile, the vascular endothelium protective property of schisandrin might be beneficial for the treatment of cardiovascular disease.


Right ventricular adaptation and maladaptation in chronic pulmonary arterial hypertension.
The right ventricle (RV) is not well suited to chronic pressure overload and often fails to adequately compensate. Mechanisms that allow the RV to respond to acute pressure overload often become maladaptive and contribute to its failure, including the effects of pulmonary hypertension on RV myocardial perfusion, the influence of interventricular dependence on RV function, and metabolic shifts in the RV myocardium from fatty acid to glycolysis. Medications to treat pulmonary hypertension have focused on pulmonary vasodilatation. Their effects on RV function may determine their effectiveness. How new medications affect right ventricular performance must be addressed.


Survival in chronic obstructive pulmonary disease after diagnosis of pulmonary hypertension related to long-term oxygen therapy.
Long-term oxygen therapy has proven increased survival rates of patients with severe chronic obstructive pulmonary lung disease and remains the only treatment so far to prolong life in these patients. No study has related hemodynamic measurements, lung function data, and age at beginning of long-term oxygen treatment to prognosis in these patients. In a retrospective study, we analyzed these parameters for 76 survivors and 51 deceased, starting supplemental oxygen therapy in 1981 and thereafter, concerning significant differences using the Proportional Hazards General Linear Model Procedure. A longer survival could be shown for PaP less than 30 mmHg when compared to PaP greater than 30 mmHg (p = 0.0442) and for the age less than 60 yrs compared to greater than 60 yrs (p = 0.0317). No contribution to prognosis could be made by FEV1, IVC, PaO2 and nationality. We conclude that hemodynamic measurements prior to long-term oxygen treatment are necessary since, besides age, they serve as the only indicator for prognosis in these patients.


Attitudes of the General Population Regarding Patient Information for a Chronic and Life-Threatening Disease: A Cross-Sectional Study.
The form of communication developed between the physician and the patient and between the physician and the patient's close relatives builds the foundation for the process of announcing unpleasant news, which is related to the diagnosis of chronic disease. The aim of this study was to investigate the attitudes of the general population regarding the information of patients for a chronic and life-threatening disease. It is a cross-sectional study. An anonymous questionnaire was used on a sample of 350 people. The 95.1% of participants considered that patients have the right to be fully informed about their health status and that the physician has the right to be informed. The 90.3% of the respondents argued that patients differ in their preferences. Totally, 60.3% of participants agreed that all patients would like to know the bad news about their health, while 44.5% argued that patients do not want to hear bad news about their health, and 32.3% believed that patients should be protected from the announcement of bad news. The majority of respondents (95.6%) were informed by the physician about their or their relevant chronic disease. The general population is of the opinion that patients should be informed about their health status. Due to the fact that each patient responds differently to the announcement of the unpleasant news, the respondents replied that the announcement of the unpleasant news should be personalized and carried out by the physician.


Dendritic localization of the transcriptional co-repressor Groucho/TLE1 in cortical and cerebellar neurons.
In the present study we show that the transcription factor Groucho/TLE1 (TLE1) is expressed in virtually all major cortical subdivisions, hippocampus, amygdala, and thalamus, as well as in the cerebellum of the adult rat brain. In both neocortex and subcortical structures, TLE1 expression was mostly localized to neurons. In addition to the expected nuclear localization, TLE1 immunoreactivity was also detected in apical dendritic shafts of neocortical layer III and V pyramidal cells and in Purkinje cell dendrites. These results demonstrate that TLE1 expression occurs in the mature nervous system and suggest that this protein may perform new functions outside of the nucleus in selected cortical and cerebellar neurons.


The Association of Syntax Score with Levels of Lipoprotein(a) and Inflammatory Biomarkers in Patients with Stable Coronary Artery Disease and Different Low-Density Lipoprotein Cholesterol Levels.
Lipoprotein(a) (Lp(a)) is associated with the severity of coronary lesions evaluated using Syntax score in patients with stable coronary artery disease (CAD). However, the effect of low-density lipoprotein cholesterol (LDL-C) levels on the association of Lp(a) levels with Syntax score remains unclear. A total of 646 patients with stable CAD were enrolled in the present study. Lp(a) levels were measured with an AU5800 Chemistry Analyzer. Syntax scores were calculated by two advanced interventional cardiologists. SPSS 22.0 was used for statistical analyses. The concentration of Lp(a) ranged from 1 to 192 mg/dL. Pearson's correlation analysis showed a positive correlation between Syntax score and the level of Lp(a) (r = 0.108, p = 0.006). The LDL-C ≥100 mg/dL group presented with a higher Lp(a) level, 16 (9-29) vs 13 (7-24). Pearson's correlation analysis identified a correlation between Lp(a) level and Syntax score (r = 0.249, p < 0.001) only in the LDL-C ≥100 mg/dL group. Multivariate logistic regression analysis revealed the positive predictive value of an Lp(a) level >30 mg/dL for a Syntax score ≥23 only in the LDL-C ≥100 mg/dL group, adjusted odds ratio 2.895, p = 0.010. A receiver operating characteristic curve analysis confirmed the predictive value of Lp(a) levels for a Syntax score ≥23 in the LDL-C ≥100 mg/dL group with a cutoff value for Lp(a) >30 mg/dL. The association between Lp(a) level and Syntax score was only maintained in the LDL-C ≥100 mg/dL group. An Lp(a) level >30 mg/dL was an independent predictor of a Syntax score ≥23 only in the LDL-C ≥100 mg/dL group. The effect of LDL-C levels on the association of Lp(a) levels with Syntax score requires further investigations.


Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7.
Insulin-dependent diabetes mellitus (IDDM) is characterized by autoimmune destruction of the insulin secreting beta-cells of the pancreas and subsequent disruption of glucose metabolism. The tendency of IDDM to cluster in families and the modest (36%) concordance rate in monozygotic twins indicates that both genetic and environmental factors contribute to IDDM susceptibility. Recent genome-wide searches using the affected sib-pair (ASP) approach have provided evidence for novel loci, in addition to HLA (IDDM1) and insulin (IDDM2), which show evidence of linkage to IDDM (P < 0.05). We have evaluated 35 microsatellite marker loci on human chromosome 7 for linkage to IDDM in 339 affected sib-pair families. Increased sharing of parental haplotypes in affected sib-pairs was detected for two microsatellite markers flanking glucokinase (GCK). Preferential transmission of alleles to affected offspring was observed at one of these marker loci, GCK3, indicating linkage disequilibrium between the marker and a disease susceptibility locus. This combination of linkage and disease association suggests that glucokinase, or a gene in the vicinity, plays an important part in IDDM susceptibility.


Cadmium in the Amazonian Guajará Estuary: distribution and remobilization.
Extremely high total cadmium concentrations (average about 500 mg/kg) together with very small (average of 1.1 microg/l) dissolved available cadmium have been found in the more acidic deeper layers of the bottom sediments of the Brazilian Amazonian Guajará Estuary. The paper shows that climatic changes and the periodic input of the Atlantic waters into the Estuary appear to have no direct influence on annual average total cadmium concentration, but they affect accumulation, distribution and remobilization of cadmium in different ways during the rainy season (February/March) and the dry season (November/December). Even if only a very small part of the total Cd is available, the concentrations of dissolved Cd in the Estuary are still high enough to cause environmental concern, if compared with concentrations in natural freshwater ecosystems.


Hormone changes in relation to the time of fetal death after prostaglandin-induced abortion.
The changes in unconjugated estradiol-17beta and estriol, progesterone and chorionic somatomammotropin (HCS) in peripheral plasma have been studied in 18 women at 30-minute intervals following intra-uterine prostaglandin E2 administration for therapeutic termination of second trimester pregnancy. The hormonal changes were related to the time of fetal death detected by the disappearance of fetal heart pulsations. Prostaglandin E2 was given by the intra-amniotic route with urea (5 patients) or with intravenous oxytocin (5 patients), or by the extra-amniotic route with intravenous oxytocin (8 patients). Fetal death occurred rapidly with intra-amniotic PGE2, but usually at a late stage with extra-amniotic PGE2. Three fetuses in the extra-amniotic group died at or just before abortion. A variety of fetal heart changes were noted and the time of fetal death did not appear to influence the time of abortion within each treatment subgroup. Estradiol and estriol showed a sligh but persistent fall over 24 hours prior to induction of abortion. A more rapid fall usually occurred after induction, with a consistent fall around the time of fetal death. Progesterone and HCS usually fell much less before and immediately after fetal death. A marked rise in estradiol sometimes occurred before fetal death, particularly in the intraamniotic PGE2 and urea subgroup. Estriol levels declined more rapidly before than after fetal death, whereas fetal death had less consistent effects on the other hormones. All hormones had usually fallen considerably at the time of abortion, and in some individuals marked fluctuations in hormone levels were seen.


MiR-148a regulates the growth and apoptosis in pancreatic cancer by targeting CCKBR and Bcl-2.
Our previous studies have revealed that miR-148a is downregulated in pancreatic cancer. Bioinformatics analysis has shown cholecystokinin-B receptor (CCKBR) and B cell lymphoma (Bcl-2) to be potential targets of miR-148a. But the pathophysiologic role of miR-148a and its relevance to the growth and development of pancreatic cancer are yet to be investigated. The purpose of this study is to elucidate the molecular mechanisms where miR-148a acts as a tumor suppressor in pancreatic cancer. Our results showed significant downregulation of miR-148a in 28 pancreatic cancer tissue samples and five pancreatic cancer cell lines, compared with their non-tumor counterparts by qRT-PCR. MiR-148a was found to not only inhibit the proliferation of pancreatic cancer cells (PANC-1 and AsPC-1) in vitro by MTT assay and colony formation assay, but also to promote cells apoptosis in vitro by Annexin V-FITC apoptosis detection and caspase activity assay. Using western blot and luciferase activity assay, CCKBR and Bcl-2 were identified as targets of miR-148a. Moreover, we also found that the expression of Bcl-2 lacking in 3'UTR could abrogate the pro-apoptosis function of miR-148a. These findings suggest the importance of miR-148a's targeting of CCKBR and Bcl-2 in the regulation of pancreatic cancer growth and apoptosis.


Ideotype breeding and genome engineering for legume crop improvement.
Ideotype breeding is a strategy whereby traits are modeled a priori and then introduced into a model or crop species to assess their impact on yield. Thus, knowledge about the connection between genotype and phenotype is required for ideotype breeding to be deployed successfully. The growing understanding of the genetic basis of yield-related traits, combined with increasingly efficient genome engineering tools, improved transformation efficiency, and high-throughput genotyping of regenerants paves the way for the widespread adoption of ideotype breeding as a complement to conventional breeding. We briefly discuss how ideotype breeding, coupled with such state-of-the-art biotechnological tools, could contribute to knowledge-based legume breeding and accelerate yield gains to ensure food security in the coming decades.


A gas-liquid chromatographic method for steric analysis of epoxy acids.
A gas-liquid chromatographic method for determination of the absolute configuration of the two chiral carbon atoms of epoxy fatty acids was developed. The method involved (1) conversion of the saturated epoxy ester into a pair of regioisomeric allylic alcohols by consecutive treatments with selenophenoxide anion and hydrogen peroxide, (2) oxidative ozonolysis performed on the (-)-menthoxycarbonyl derivatives of the allylic alcohols, and (3) steric analysis of the resulting two 2-hydroxy acids (methyl esters, (-)-menthoxycarbonyl derivatives) by gas-liquid chromatography using appropriate reference compounds. Application of the method for steric analysis of several synthetic epoxyoctadecanoates as well as (+)-vernolic acid derived from Vernonia galamensis is described.


A comparative study of cocaine-treatment completers and dropouts.
This study compared matched groups of completers and dropouts from residential treatment for cocaine abuse on a range of outcome measures, including cocaine and alcohol use, stress, coping, and social support characteristics. The most striking finding of this study was that treatment dropouts differed from treatment completers on only 2 of 14 dependent measures reflecting substance use, stress, coping, and social support characteristics during two 3-month follow-up periods. Both dropouts and completers demonstrated large decreases in cocaine and alcohol use from pretreatment to the first follow-up period. Completers and dropouts did not differ in level of substance use during either follow-up period.


Endovascular treatment of visceral artery aneurysms.
To review a 10-year experience with endovascular embolization of visceral artery aneurysms. Twenty-five patients (13 men; mean age 52.1 years, range 31-80) presented with VAAs of varying locations and etiologies: 10 splenic, 3 gastroduodenal, 2 pancreaticoduodenal, 3 hepatic, 3 superior mesenteric, 2 celiac, 1 left gastric, and 1 jejunoileal. Ten patients were asymptomatic; 7 aneurysms were ruptured. Transcatheter coil embolization was the treatment of choice in all patients. Coil placement was initially (<7 days) successful in 23 (92%) patients. One superior mesenteric artery aneurysm remained perfused, and recurrent bleeding occurred 2 days after intervention in 1 case, but repeated embolization excluded the aneurysm. One patient with necrotizing pancreatitis died from sepsis 10 days after endovascular treatment and surgery (4% 30-day mortality). Long-term follow-up revealed excellent results after an average 48.7 months (range 14-75) with only 1 recurrence after 12 months. Embolotherapy is the treatment of choice in visceral artery aneurysms, regardless of etiology, location, or clinical presentation.


Differential induction of help and suppression in mice by bifunctional antigens administered via different routes.
Bifunctional antigens composed of one L-tyrosine-p-azobenzenearsonate (Tyr-ABA) carrier epitope and one dinitrophenyl (DNP) haptenic epitope separated by 6-aminocaproyl or polyprolyl spacers induced weak IgM anti-DNP plaque-forming cell (PFC) responses in the spleens of mice immunized intraperitoneally, without detectable IgG PFC. However, the same antigens introduced into the footpads induced IgG PFC responses in the draining lymph nodes which rose to levels greater than 100/10(6) viable lymphocytes. Moreover, the response in the lymph nodes to booster injections of antigen was characteristic of secondary T-dependent antibody responses, whereas the splenic secondary response simply mirrored the primary. The magnitude of the IgG PFC response was influenced by the size of the spacer and by the strain of mice, although genetic control did not map to the major histocompatibility complex. Prior i.p. immunization suppressed the IgG response to subsequent immunization in the footpads. This suppression could be transferred to normal syngeneic recipient mice with spleen cells from suppressed donors. Suppressor activity was eliminated by treating the spleen cells with anti-Thy-1 antibody prior to transfer, establishing the T-cell dependency of suppression. Suppression was also induced by Tyr-ABA itself, but not by DNP-lysine, indicating the epitope specificity of the suppressor cells. Thus, bifunctional antigens induce dominant suppression in the spleen but significant help in lymph nodes.


Risk Factors for Post-Traumatic Stress Disorder Symptoms in Surrogate Decision-Makers of Patients with Chronic Critical Illness.
Chronically critically ill patients are often dependent on family members for surrogate decision-making, and these surrogates are at high risk for emotional distress. We hypothesized that patient- and surrogate-specific risk factors for surrogate post-traumatic stress disorder (PTSD) symptoms can be identified early in the course of chronic critical illness. To identify risk factors for PTSD symptoms in surrogate decision-makers of chronically critically ill patients. We performed a secondary analysis of the database from a multicenter randomized trial of a communication intervention for chronic critical illness patients and surrogates. Variables preselected for plausible mechanism for increasing PTSD symptoms and identifiable by Day 10 of mechanical ventilation were included in the analysis for association with surrogate PTSD symptoms at 90 days, as measured by the Impact of Events Score-Revised (IES-R). Patient factors included demographics, insurance status, baseline functional status, chronic comorbidities, illness severity, and presence of advance directive. Surrogate variables included demographics, education level and employment, religion, relationship to patient, and Hospital Anxiety and Depression Scale score measured at enrollment. Multivariable linear regression models were then constructed for 26 potential risk factors, including biologically or mechanistically plausible confounders for each, with IES-R score as the outcome. All models were adjusted for multiple respondents, using a mixed model, considering the patients as a random factor. Our analysis included 306 surrogates for 224 patients. A total of 49% of patients were female, and mean age was 59 years (95% confidence interval [CI], 56.4-60.7). A total of 71% of surrogates were female, and mean age was 51 years (95% CI, 49.3-52.4). After examining each potential risk factor in a separate multivariable model, only Day-10 surrogate Hospital Anxiety and Depression Scale score (β coefficient = 1.02; 95% CI, 0.73-1.30) and patient unresponsiveness (β coefficient = 8.39; 95% CI, 0.83-15.95) were associated with higher IES-R scores. Among surrogate decision-makers for chronically critically ill patients, high anxiety and depression scores and patient unresponsiveness on or near Day 10 of mechanical ventilation are risk factors for PTSD symptoms at 90 days.


Hand grip force as an assessment of recovery from neuromuscular block.
A simple hydraulic hand dynamometer was used to assess the hand grip force before and after general anesthesia. Eight patients received a general anesthetic of nitrous oxide and oxygen and an inhalational agent without relexants (non-relaxant group). Ten patients received a similar anesthetic of nitrous oxide and oxygen and an inhalational agent with non-depolarizing relaxants (relaxant group). The patients in the nonrelaxant group showed a mild depression to 77% of initial hand grip force by the time they could hold up their heads for 5 seconds. Patients in the relaxant group had a mean of only 29% of initial hand grip force when they could lift their heads. One hour later, hand grip force increased to 76% of preoperative force in the relaxant group. Hand grip force appears to be a sensitive measurement of residual relaxant effect.


A chance to cut is a chance to cure: complete resection of an atypical neurofibroma prevents further progression to malignancy.
Plexiform neurofibromas are the hallmark of neurofibromatosis type 1 (NF1) and significantly contribute to the overall burden of disease. While surgical excision has long been the only available therapy, the MEK inhibitor (MEKi) selumetinib has been approved as a non-surgical treatment option for these tumors in 2020 (USA) and 2021 (Europe), respectively. However, selumetinib will result in tumor shrinkage only after several months of therapy and might not prevent malignant transformation of a plexiform neurofibroma that occurs with a frequency of 10-15%. Here, we demonstrate that surgical excision might be the therapy of choice in some plexiform neurofibromas despite the availability of MEKi therapy.


Timing of postoperative chemotherapy in patients undergoing perioperative chemotherapy and gastrectomy for gastric cancer.
For patients who qualify for perioperative chemotherapy and gastrectomy for gastric cancer, the optimal timing of the postoperative chemotherapy (PC) seems equivocal. The aim of this study was to evaluate the influence of timing of PC on overall survival (OS) in patients receiving perioperative chemotherapy. Patients undergoing perioperative chemotherapy and gastrectomy with curative intent (2010-2014) were extracted from the nationwide population-based Netherlands Cancer Registry. Timing of PC was analyzed as a linear and categorical variable (<6 weeks, 6-8 weeks, and >8 weeks). Risk factors for a late start of PC (≥6 weeks), and the association between timing of PC and OS were assessed by multivariable regression analyses. Among 1066 patients who underwent perioperative chemotherapy and gastrectomy, 463 (43%) patients started PC. PC was administered within 6 weeks in 208 (45%) patients, within 6-8 weeks in 155 (33%) patients, and after 8 weeks in 100 (22%) patients. A total of 419 (91%) and 351 (76%) patients finished all cycles of preoperative and PC, respectively. A late start of PC was associated with a longer hospital stay (+1 hospital day: OR 1.15, 95% CI [1.08-1.23], p < 0.001). Timing of PC was not associated with OS (6-8 weeks vs. <6 weeks, HR 1.14, 95% CI [0.79-1.65], p = 0.471; >8 weeks vs. <6 weeks, HR 1.04, 95% CI [0.79-1.65], p = 0.872). Timing of postoperative chemotherapy does not influence survival in patients receiving perioperative chemotherapy for gastric cancer. The results suggest that the early postoperative period may be safely used for recovery and optimizing patients for the start of PC.


Total and pathogen-specific serum Immunoglobulin G concentrations in neonatal beef calves, Part 2: Associations with health and growth.
The association of poor transfer of passive immunity (TPI) with negative health outcomes is extensively researched in dairy calves. However, few field studies have examined the effect of total and particularly pathogen-specific Immunoglobulin G (IgG) concentrations on pre-weaning health and growth of beef calves. Hence, the objective of this study was to determine the association of total and pathogen-specific IgG concentrations against selected pathogens associated with neonatal calf diarrhea (NCD) and bovine respiratory disease (BRD) and the odds of pre-weaning treatments, mortality, and the growth of newborn beef calves. A total of 420 serum samples from 1- to 7-day old beef calves born on 6 farms in Alberta, Canada, were available for this observational study. Serum samples were analyzed by radial immunodiffusion for total IgG concentration and by enzyme-linked immunosorbent assays for pathogen-specific IgG concentrations against Escherichia coli (E. coli), bovine Rotavirus (BRoV), Cryptosporidium parvum (C. parvum), Bovine Viral Diarrhea Virus (BVDV), Parainfluenza Virus Type 3 (PI-3), Bovine Respiratory Syncytial Virus (BRSV), and Bovine Herpesvirus Type 1 (BHV-1). Data about the individual dam- and calf-level risk factors, calf treatments, mortality, and birth and weaning weights were collected. Multivariable multilevel logistic and linear regression models were built to evaluate the association of total and pathogen-specific IgG concentrations with the odds of mortality and average daily gain (ADG), respectively, while their association with the odds of pre-weaning treatment was established by univariable logistic regression analysis. The odds of calves with IgG concentrations < 10 g/L of getting treated (OR 7.9, 95 % CI 2.7-23.7) and dying (OR: 18.5, 95 % CI: 3.7-93.4) were higher than for their counterparts (P < 0.0001). Calves with IgG concentrations < 24 g/L also had higher odds of dying (OR: 10.1, 95 % CI: 2.6-40.2) and had lower ADG (-0.09 kg, SE: 0.03, P < 0.002) than calves with IgG concentrations ≥ 24 g/L. Higher BVDV-specific IgG concentration was protective against mortality (OR: 0.97, 95 % CI: 0.96-0.99, P < 0.001). This study highlights the negative association of inadequate TPI with health and growth of beef calves and thus, the need to refine protocols for dam vaccination and colostrum intervention in cow-calf operations to meet these higher IgG targets.


Persistent cross-species SARS-CoV-2 variant infectivity predicted via comparative molecular dynamics simulation.
Widespread human transmission of SARS-CoV-2 highlights the substantial public health, economic and societal consequences of virus spillover from wildlife and also presents a repeated risk of reverse spillovers back to naive wildlife populations. We employ comparative statistical analyses of a large set of short-term molecular dynamic (MD) simulations to investigate the potential human-to-bat (genus Rhinolophus) cross-species infectivity allowed by the binding of SARS-CoV-2 receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) across the bat progenitor strain and emerging human strain variants of concern (VOC). We statistically compare the dampening of atom motion across protein sites upon the formation of the RBD/ACE2 binding interface using various bat versus human target receptors (i.e. bACE2 and hACE2). We report that while the bat progenitor viral strain RaTG13 shows some pre-adaption binding to hACE2, it also exhibits stronger affinity to bACE2. While early emergent human strains and later VOCs exhibit robust binding to both hACE2 and bACE2, the delta and omicron variants exhibit evolutionary adaption of binding to hACE2. However, we conclude there is a still significant risk of mammalian cross-species infectivity of human VOCs during upcoming waves of infection as COVID-19 transitions from a pandemic to endemic status.


Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes.
It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates.


Neurology and psychiatry.
There has been a long historical relationship between neurology and psychiatry. This relationship has been nurtured by the common interest in the central nervous system and disturbed behavior associated with dysfunctions of the nervous system. This paper reviews the formal relationships between neurology and psychiatry and particularly looks at the behavioral aspects of neurological disease. For the past 10 years, both from a clinical and a theoretical viewpoint, the importance of understanding central nervous system functioning and dysfunctioning has become increasingly apparent to psychiatrists.


Attitude of medical school students in China towards genetic testing and counseling issues in FXS.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. However, genetic testing protocols and genetic counseling guidelines for FXS are not yet established in mainland China. In the present study, we conducted a comprehensive analysis using a self-administered questionnaire among students at the Xiangya medical school to investigate their attitude towards genetic testing and counseling issues of FXS. We have gained a general understanding of the attitudes of medical students towards these FXS issues in China. This information is of immense importance to develop appropriate genetic tests and to train counselors for FXS. As the medical school students surveyed are prospective physicians who will be a part of the Chinese health system, our survey was focused on the basic knowledge of FXS, population-based FXS screening, confidentiality and reproductive options for mutation carriers. The study demonstrated that only less than one third of the participants had heard about FXS. 94.6 % of participants were in favor of FXS screening for women in their reproductive age who had a genetic history of FXS. Furthermore, only half of the participants would inform their families about their genetic status in case of positive test results, and more than half of the participants supported natural conception and prenatal diagnosis for FXS mutation carriers. Additional findings and research implications are also discussed. This survey targeting potential doctors provides important information for the development of FXS genetic test and counselor training for the Chinese health system.


Effects of the botanical composition and weather conditions on mycotoxins in winter forage from grassland.
The paper focuses on possible effects of the botanical composition and weather conditions on the extend of zearalenone and ochratoxin A concentrations in various grass swards in winter pasture systems. Zearalenone is only detectable in pure stands ofLolium perenne or inLolio-Cynosuretum plant communities, respectively. The occurrence of ochratoxin A is more frequent and less specific concerning the botanical composition. This mycotoxin was found in both,Lolium perenne andFestuca arundinacea in varying years. The incidence of ochratoxin A depends on year and is apparently related to the weather conditions in autumn and winter. There was no evidence that particular locatio8/22/2008 12:57PMns have a higher or a lower risk for high ochratoxin A or zearalenone concentrations than others. Peak values in individual swards are not intermittent over the years.


An improved method for in vitro feeding of adult female Dermanyssus gallinae (poultry red mite) using Baudruche membrane (goldbeater's skin).
Dermanyssus gallinae, or poultry red mite (PRM), is an important ectoparasite in laying hen, having a significant effect on animal welfare and potentially causing economic loss. Testing novel control compounds typically involves in vitro methodologies before in vivo assessments. Historically, in vitro methods have involved PRM feeding on hen blood through a membrane. The use of hen blood requires multiple procedures (bleeds) to provide sufficient material, and the use of a larger species (e.g. goose) could serve as a refinement in the use of animals in research. The in vitro feeding device used was that which currently employs a Parafilm™ M membrane (Bartley et al.: Int J Parasitol. 45:819-830, 2015). Adult female PMR were used to investigate any differences in mite feeding, egg laying and mortality when fed goose or hen blood. Effects on these parameters when PRM were fed through either the Parafilm™ M membrane or the Baudruche membrane alone or through a combination of the membrane with an overlaid polyester mesh were tested using goose blood. Poultry red mites fed equally well on goose or hen blood through the Parafilm™ M membrane, and there were no significant differences in mortality of PRM fed with either blood type. A significant increase (t test: t = 3.467, df = 4, P = 0.03) in the number of eggs laid per fed mite was observed when goose blood was used. A 70% increase in PRM feeding was observed when the mites were fed on goose blood through a Baudruche membrane compared to when they were fed goose blood through the Parafilm™ M membrane. The addition of an overlaid polyester mesh did not improve feeding rates. A significant increase (analysis of variance: F(3, 20) = 3.193, P = 0.04) in PRM egg laying was observed in mites fed on goose blood through the Baudruche membrane compared to those fed goose blood through the Parafilm™ M membrane. A mean of 1.22 (standard error of the mean ± 0.04) eggs per fed mite was obtained using the Baudruche feeding device compared to only 0.87 (SEM ± 0.3) eggs per fed mite using the Parafilm™ M device when neither was combined with a polyester mesh overlay. The in vitro feeding of adult female PRM can be readily facilitated through the use of goose blood in feeding devices with the Baudruche membrane.


Intelligent hydrogel with both redox and thermo-response based on cellulose nanofiber for controlled drug delivery.
The purpose of this study is to develop a hydrogel with temperature and redox response to control drug delivery. However, the strength of temperature sensitive N-isopropylacrylamide (NIPAM) hydrogel is weak. Therefore, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized cellulose nanofiber (CNF) is introduced to improve this problem. The compressive strength of hydrogels increased by 360% after CNF addition. Meanwhile, N,N'-bis(acryloyl)cystamine (BACy) is introduced into the hydrogels as a cross-linker, imparting redox responsive properties to the hydrogels. Tumor therapeutic drugs are used as model drugs for in vitro release studies. The drug release rate of hydrogel is regulated by temperature and reducing environment. The maximum cumulative release rate of doxorubicin (DOX) is 39.56%, and the Berberine (BBR) is 99.50% after 60 h. The swelling and transparency of hydrogels showed dramatic changes in the range of 30-40 °C. Cytotoxicity experiments demonstrated that the hydrogel had almost no cytotoxicity.


A feasibility study of low-dose ketamine for acute management of suicidal ideation.
Mood disorders complicated by suicidal ideation (SI) frequently present to the emergency department (ED) for care. Currently, patients with SI in the ED do not typically receive targeted interventions. Ketamine may have a role in treating SI within the ED because subanesthetic doses have rapid-acting antidepressant and antisuicidal properties. This single-arm, open-label feasibility study enrolled 14 participants from the ED with acute SI who were awaiting voluntary admission to inpatient psychiatry to receive ketamine at 0.5 mg/kg, administered intravenously. Participants were assessed post administration to evaluate feasibility of administration in the ED and short-term effectiveness. Feasibility was determined by acceptability by patients and physicians as well as tolerability and ability to recruit participants into the study. Efficacy was assessed based on changes in (1) self-reported mood and (2) suicidal ideation pre- and postinfusion of ketamine. All patients reported severe depression and active SI at baseline. No serious adverse events were reported, and acceptability was rated highly by both participants and physicians (>70%). Two hours after receiving ketamine 0.5 mg/kg, the mean SI and somatic symptom burden were decreased compared to baseline (P < 0.001 and P = 0.005, respectively), and the mean self-reported mood was increased (P = 0.006). Improvements in mood and decreases in suicidality persisted at 6 hours. Overall, ketamine was well tolerated, considered feasible by both participants and physicians, and demonstrated short-term efficacy. There is a growing body of evidence demonstrating the feasibility of ketamine administration in the ED, and larger randomized trials should be conducted to establish treatment recommendations for patients with SI in the ED.


[Prevalence of plasmid-mediated quinolone resistance determinant aac(6')-Ib-cr among ESBL producing enterobacteria isolates from Chilean hospitals].
The frequency of aac(6')-Ib-cr gene in ESBL-producing strains of Klebsiella pneumoniae and Escherichia coli is unknown, in Chile. The aac(6')-Ib and aac(6')-Ib-cr genes were investigated using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and sequencing, in strains isolated from 10 Chilean hospitals between 2008-2009. The aac(6')-Ib-cr gene was detected in 54% of K. pneumoniae and 74% of E. coli strains. The CIM(50) of CIP was higher among strains harboring aac(6')-Ib-cr, 8 times higher in K. pneumoniae and 4 times higher in E. coli. Moreover, both aac(6')-Ib and aac(6')-Ib-cr were simultaneously found in 13 K. pneumoniae and 3 E. coli isolates. This is the first report of aac(6')-Ib-cr in ESBL-producing strains of K. pneumoniae and E. coli isolated from in-patients in Chilean hospitals located along an area of more than 2,800 Km.


Detection of the international lineage ST71 of methicillin-resistant Staphylococcus pseudintermedius in two cities in Rio de Janeiro State.
Staphylococcus pseudintermedius is the main coagulase-positive staphylococci associated with canine skin/soft tissue infections (SSTI), otitis externa, and surgical site infections. The international spread of an epidemic and multiresistant lineage of methicillin-resistant Staphylococcus pseudintermedius (MRSP), the so-called European clone-displaying sequence type (ST) 71-requires attention. The first isolation of an MRSP ST71 isolate in South America was reported in Rio de Janeiro city, in 2010; however, a limited number of canine isolates were analyzed. Thus, to have a better panel of the MRSP spread in this city, we were stimulated to continue this study and search for the presence of MRSP in 282 colonized or infected dogs in the city of Rio de Janeiro. Among the MRSP isolates collected (N = 17; 6.1%), the pulsed-field gel electrophoresis (PFGE) patterns were similar to those of European clone. All 17 isolates were classified as ST71 by multilocus sequence typing (MLST). In order to assess whether isolates of MRSP ST71 may have also spread to the Rio de Janeiro state countryside, we collected samples from 124 infected dogs in the city of Campos dos Goytacazes (232 km away from Rio de Janeiro city). Our data showed the presence of ST71 lineage in one isolate among three MRSP detected. S. pseudintermedius was isolated from 40.6% of the clinical samples (N = 165/406). A relatively high incidence of methicillin resistance, detected by a PCR-based method, was found in 12.1% of the S. pseudintermedius recovered from animals (N = 20/165). The resistance profile of these isolates was similar to that described for the international ST71 strains whose genomes are publicly available in the GenBank. The prospect of ST71 isolates being resistant to virtually all antimicrobials used in veterinary medicine is alarming and should be considered a central issue considering that MRSP ST71 spreads over large geographic distances and its transmission from animals to humans.


Otitis media and otitis interna. Etiology, diagnosis, and medical management.
In this article, the etiologies, clinical signs, diagnostic aids, and treatments for otitis media and interna are discussed. A review of the anatomy and physiology of the middle and inner ear structures precedes each discussion.


HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda.
To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified. Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria. Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.


Conjugative plasmid transfer from Escherichia coli is a versatile approach for genetic transformation of thermophilic Bacillus and Geobacillus species.
We previously demonstrated efficient transformation of the thermophile Geobacillus kaustophilus HTA426 using conjugative plasmid transfer from Escherichia coli BR408. To evaluate the versatility of this approach to thermophile transformation, this study examined genetic transformation of various thermophilic Bacillus and Geobacillus spp. using conjugative plasmid transfer from E. coli strains. E. coli BR408 successfully transferred the E. coli-Geobacillus shuttle plasmid pUCG18T to 16 of 18 thermophiles with transformation efficiencies between 4.1 × 10(-7) and 3.8 × 10(-2)/recipient. Other E. coli strains that are different from E. coli BR408 in intracellular DNA methylation also generated transformants from 9 to 15 of the 18 thermophiles, including one that E. coli BR408 could not transform, although the transformation efficiencies of these strains were generally lower than those of E. coli BR408. The conjugation was performed by simple incubation of an E. coli donor and a thermophile recipient without optimization of experimental conditions. Moreover, thermophile transformants were distinguished from abundant E. coli donor only by high temperature incubation. These observations suggest that conjugative plasmid transfer, particularly using E. coli BR408, is a facile and versatile approach for plasmid introduction into thermophilic Bacillus and Geobacillus spp., and potentially a variety of other thermophiles.


Optimal Placement of Colectomy in the Treatment of Ulcerative Colitis: a Markov Model Analysis.
Treatment for moderate-to-severe ulcerative colitis (UC) includes medical therapies such as immunosuppressive agents or surgical options such as colectomy. While prior studies have indicated a mortality benefit with elective surgery, the timing and effectiveness of colectomy in the UC treatment algorithm have not been assessed. We hypothesize that the ideal placement of colectomy occurs prior to the exhaustion of all medical therapies. We designed a Markov model to assess the ideal position of colectomy. The base case was a 50-year-old male with steroid-dependent moderate-to-severe UC without prior treatment with immunomodulator or biologic therapies. We developed 4 separate algorithms incorporating elective colectomy: (1) prior to biologics, (2) after infliximab monotherapy failure, (3) after infliximab and azathioprine combination therapy failure, and (4) after medically refractory to all medical therapies including vedolizumab. Transition probabilities were obtained from published literature. First-order Monte Carlo simulations of 100 trials of 100,000 individuals were used to calculate quality-adjusted life-year (QALY) estimates. One-way sensitivity analyses were conducted for all variables. Algorithm 3 (colectomy following combination therapy) was the preferred strategy with 1.864 QALYs (95% CI [1.863, 1.865]) over a 3-year period and the preferred strategy in the probabilistic sensitivity analysis 92.77% of the time. This simulation suggests that early incorporation of colectomy for patients medically refractory to infliximab and azathioprine combination therapy may yield greater quality of life for patients with steroid-dependent UC. These findings suggest avenues for more patient-centered preference work and a combined medical-surgical approach to UC.


Incidental detection of haemoglobin (Hb) variants during high performance liquid chromatography (HPLC) analysis of HbA1c: is it time for a standardised approach to reporting?
Haemoglobin (Hb) variants are genetic variations in the globin genes that code for an abnormal globin protein structure. The prevalence of Hb variants has increased in Ireland due to the number of emigrants from Africa and Southeast Asia. The rate of incidentally detected Hb variants, in laboratories employing HPLC to measure HbA1c, has increased in parallel. The presence of a Hb variant can compromise HbA1c measurement and interpretation. In such cases, HbA1c cannot be used to diagnose diabetes or to assess concordance with glycaemic targets. To establish the number of incidentally identified Hb variants during 10 months of routine HbA1c analysis, and the percentage of HbA1c reports alerting the requesting clinician to the presence of a Hb variant. The laboratory database was interrogated to extract all records of HbA1c requests and incidentally identified Hb variants from March to December 2012. A total of 32,636 HbA1c analyses were performed during the evaluation period. Seventy-three Hb variants were identified in a total of 46 patients. In 32.6% (15 of 46) the haemoglobinopathy status was known prior to testing and 97% of HbA1c reports communicated the presence of the Hb variant to the requesting clinician. Hb variants may invalidate the results of HbA1c analysis and could result in a missed diagnosis or a misdiagnosis of diabetes or mismanagement of a patient with diabetes mellitus. It is, therefore, imperative that a comment alerting the requesting clinician to the presence of the Hb variant is appended to the HbA1c result.


O-arm failure traps patient prone on a Jackson table.
The O-arm Surgical Imaging System (Medtronic Sofamor Danek, Memphis, TN, USA) is an increasingly popular tool for spinal surgical procedures that allows for intraoperative acquisition of multi-dimensional spinal imaging that can be used either to confirm placement of spinal instrumentation or to guide spinal screw placement in conjunction with a navigation system. The machine is typically placed open from the side of the patient positioned prone on the Jackson spinal table (Mizuho OSI, Union City, CA, USA) and then closed to complete a ring around the patient to acquire images. A failure of the O-arm opening mechanism can lead to a patient becoming effectively trapped within the device with limited physician access to the patient's body, a situation that may be remedied by using a manual opening procedure. This report highlights a patient safety issue encountered when a mechanical failure of the O-arm occurred and one of the two tools required for its manual opening was missing. We describe the improvised method employed to successfully open the device.


[Morphologic and histochemical responses of the body to introduction of C1. botulinum toxin. V. Response of locus coeruleus cells of the brain to introduction of the toxin of C1. botulinum type B].
After the per os administration of 1Dlm/ml of botulin, type B. there were observed at the period of development of the limb paralysis and myasthenia morphological changes in the locus coeruleus cells expressed in the development of a more pronounced than normal perinuclear clarification and some nuclear basophilia. Histochemical study of succinic dehydrogenase, acid phosphatase, cholinesterase, and catecholamines pointed to the intensified neuron metabolism of the locus coeruleus; this could serve as an indication of enhanced energopacemaker function of this nucleus in hypoxia which occurred.


Mesenchymal chondrosarcoma mimicking apical periodontitis.
This report describes the case of a patient with mesenchymal chondrosarcoma in the region of tooth #18 that mimicked apical periodontitis. Forty-five days after endodontic treatment, gingival swelling and intense pain were observed. The endodontist suspected a furcation lesion, and the treatment option that the patient chose was extraction of the tooth. Seven days after suture removal, a rapidly growing swelling was seen in the region. The patient was referred to an oral and maxillofacial surgeon, who recommended an incisional biopsy after evaluating imaging and clinical findings. Microscopic examination confirmed the diagnosis of mesenchymal chondrosarcoma. The patient underwent hemimandibulectomy with wide surgical margins. This clinical case draws attention to the fact that endodontic lesions should be carefully evaluated because malignant tumors such as mesenchymal chondrosarcoma might mimic apical periodontitis.


Peroxidation of brain lipids following cyanide intoxication in mice.
Lipid peroxidation of brain lipids as determined by the conjugated diene method was observed in mice following administration of sublethal doses of potassium cyanide (KCN). Conjugated diene production was dose- and time-dependent; 10 mg/kg KCN produced detectable levels of conjugated dienes at 30 min post cyanide, whereas, 15 mg/kg produced marked levels of conjugated dienes over a 10-60-min period after KCN. Pretreatment of mice with either diltiazem (600 micrograms/kg, i.v.) or allopurinol (25 mg/kg, i.v.) blocked the generation of conjugated dienes. These results suggest lipid peroxidation of neuronal membranes play a role in cyanide intoxication and this action is related to altered regulation of neuronal calcium homeostasis and activation of xanthine oxidase.


Is catastrophising associated with pain perception in early phase of orthodontic treatment? A cohort study.
This study aimed to investigate the association between pain perception and catastrophising at the beginning of orthodontic treatment; and the association between pain during orthodontic treatment and demographic, clinical and other psychological factors. A cohort study with 44 patients (28.9 ± 15.05 years old; 25 females and 19 males) under orthodontic treatment with fixed appliances had their pain perception evaluated through a visual analogue scale at baseline (before activation), 6 h, 24 h, 2nd day, 3rd day, 5th day and 7th day after activation. The scores at each evaluation period after the first (T1), second (T2) and third (T3) appointments were compared by analysis of variance. A multivariate Poisson regression analysis verified the association between pain perception and Pain Catastrophising Scale (PCS); and demographic (age, gender), clinical (tooth crowding, tooth loss, analgesic intake and archwire characteristics) and other psychological (dental anxiety and previous negative dental experiences) independent variables (p < .05). Catastrophising (RR = 1.03, 95%CI 1.01-1.05, p = .0001) showed a weak risk of pain perception at T1. The peak of pain occurred 24 h after activation at T1, T2 and T3. Significant higher scores were observed at T1 in comparison to T2 (FT1,T2 = 11.82, p = .005) and T3 (FT1,T3 = 5.09, p = .03). Wire diameter, tooth crowding and single-arch treatment were found as risk factors for pain. Patients without tooth loss had half of the risk of pain perception, while analgesics intake and older patients were also found with a weak protective association. Dental anxiety and negative dental experience were not associated with pain perception. Catastrophising has a mild influence on pain perception and only after the first orthodontic activation. Patients with tooth losses, tooth crowding and using thicker archwires are more likely to report pain after orthodontic activations.


Postural challenge affects motor cortical activity in young and old adults.
When humans voluntarily activate a muscle, intracortical inhibition decreases. Such a decrease also occurs in the presence of a postural challenge and more so with increasing age. Here, we examined age-related changes in motor cortical activity during postural and non-postural contractions with varying levels of postural challenge. Fourteen young (age 22) and twelve old adults (age 70) performed three conditions: (1) voluntary contraction of the soleus muscle in sitting and (2) leaning forward while standing with and (3) without being supported. Subthreshold transcranial magnetic stimulation was applied to the soleus motor area suppressing ongoing EMG, as an index of motor cortical activity. The area of EMG suppression was ~60% smaller (p<0.05) in unsupported vs. supported leaning and sitting, with no difference between these latter two conditions (p>0.05). Even though in absolute terms young compared with old adults leaned farther (p=0.018), there was no age effect or an age by condition interaction in EMG suppression. Leaning closer to the maximum without support correlated with less EMG suppression (rho=-0.44, p=0.034). We conclude that the critical factor in modulating motor cortical activity was postural challenge and not contraction aim or posture. Age did not affect the motor control strategy as quantified by the modulation of motor cortical activity, but the modulation appeared at a lower task difficulty with increasing age.


Regulation of apoptosis-related genes by nitric oxide in cancer.
Nitric oxide (NO) is a simple molecule with a complex and pleiotropic biological activity. NO or related species have been implicated in the regulation of many genes that participate in many diverse biological functions including programmed cell death or apoptosis. Apoptosis is a process that may potentially be disrupted in cancer cells conferring a survival advantage. In addition, malignant tumor cells can develop an intricate system of resistance to apoptotic stimuli. NO or related species have been shown to play a dual role in the regulation of apoptosis in malignant cells either promoting cell death or protecting cells from pro-apoptotic induction. However, the specific role of NO in the regulation of apoptosis/survival-related genes expression seems to tilt the balance toward the promotion of pro-apoptotic and the suppression of anti-apoptotic genes. Herein we have reviewed the most relevant aspects involving NO and/or reactive intermediates in the regulation of apoptosis-related genes--mainly--at the transcriptional level. We described the basic apoptotic molecules that potentially are affected by NO and how NO-mediated signaling gets transmitted to the transcriptional machinery that governs the expression of these genes. In addition, we discussed some of the fundamental functional consequences of the regulation of apoptosis-related genes by NO in cancer biology and its potential therapeutic implications.


[Chemotherapy in perioperative setting for infiltrative bladder cancer].
Despite an aggressive initial treatment, only 60% of patients with T2-staged bladder tumours, 50% with T3a and 15% with T3b staged-tumours will be alive at 5 years. The purpose of this review is to clarify the potential role of chemotherapy in localised urothelial tumours, which has not been clearly defined. To address this question, we reviewed published randomized trials of chemotherapy in urothelial tumours of the bladder in both neoadjuvant and adjuvant settings from 1980 and 2010 and corresponding meta-analyses in PubMed. In the neoadjuvant setting, a meta-analysis of individual data from 3005 patients demonstrated an absolute survival benefit of 5.5% at 5 years. Despite these results, neoadjuvant chemotherapy is very rarely proposed in this indication. Comparative trials performed in the adjuvant setting have been limited by major methodological weaknesses, preventing definitive conclusions. In a meta-analysis based on individual data from 491 patients, a 25% reduction in death risk was observed for an absolute gain of 9% at 3 years. In light of these data, chemotherapy should be offered early and proposed as a reasonable option for patients for tumours with extravesical extension or with nodal involvement detected postoperatively, neoadjuvant chemotherapy is the standard of care.


Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.
This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.


Comprehensive proficiency-based inanimate training for robotic surgery: reliability, feasibility, and educational benefit.
We previously developed a comprehensive proficiency-based robotic training curriculum demonstrating construct, content, and face validity. This study aimed to assess reliability, feasibility, and educational benefit associated with curricular implementation. Over an 11-month period, 55 residents, fellows, and faculty (robotic novices) from general surgery, urology, and gynecology were enrolled in a 2-month curriculum: online didactics, half-day hands-on tutorial, and self-practice using nine inanimate exercises. Each trainee completed a questionnaire and performed a single proctored repetition of each task before (pretest) and after (post-test) training. Tasks were scored for time and errors using modified FLS metrics. For inter-rater reliability (IRR), three trainees were scored by two raters and analyzed using intraclass correlation coefficients (ICC). Data from eight experts were analyzed using ICC and Cronbach's α to determine test-retest reliability and internal consistency, respectively. Educational benefit was assessed by comparing baseline (pretest) and final (post-test) trainee performance; comparisons used Wilcoxon signed-rank test. Of the 55 trainees that pretested, 53 (96 %) completed all curricular components in 9-17 h and reached proficiency after completing an average of 72 ± 28 repetitions over 5 ± 1 h. Trainees indicated minimal prior robotic experience and "poor comfort" with robotic skills at baseline (1.8 ± 0.9) compared to final testing (3.1 ± 0.8, p < 0.001). IRR data for the composite score revealed an ICC of 0.96 (p < 0.001). Test-retest reliability was 0.91 (p < 0.001) and internal consistency was 0.81. Performance improved significantly after training for all nine tasks and according to composite scores (548 ± 176 vs. 914 ± 81, p < 0.001), demonstrating educational benefit. This curriculum is associated with high reliability measures, demonstrated feasibility for a large cohort of trainees, and yielded significant educational benefit. Further studies and adoption of this curriculum are encouraged.


Pain Psychology and Pain Catastrophizing in the Perioperative Setting: A Review of Impacts, Interventions, and Unmet Needs.
This article provides a brief overview of the literature on perioperative pain psychology in terms of relevant factors and treatments. Where possible, the content emphasizes hand surgery or hand trauma populations, although this literature is notably limited, as well as the relevant musculoskeletal surgery literature. In addition, gaps in understanding and patient care are identified and discussed.


Expression of the membrane complement regulatory protein CD59 (protectin) is associated with reduced survival in colorectal cancer patients.
It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune-editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.


A telomerase regulation-related lncRNA signature predicts prognosis and immunotherapy response for gastric cancer.
Telomeres are involved in the development and progression of gastric cancer (GC). However, the association of telomerase regulation-related lncRNAs with prognosis and immunotherapy responsiveness in gastric cancer is unclear. This study systematically evaluated the relationship between lncRNAs co-expressed with 67 telomerase regulatory genes and gastric cancer prognosis. The risk scores of the samples were calculated based on telomerase regulation-related lncRNAs with prognostic value, and the samples were classified into high-/low-risk groups. The prognostic value of risk groups was then evaluated, a GC prognostic prediction model based on risk groups and clinical characteristics was established, and the prediction accuracy of the model was clarified by receiving operating characteristic (ROC) curves and calibration curves. Finally, the value of risk grouping in GC immunotherapy sensitivity was predicted by comparing MSI status and tumor mutation load between the high- and low-risk groups. We identified 13 lncRNAs with prognostic value co-expressed with telomerase regulatory genes and observed that the prognosis of the low-risk group was significantly better than that of the high-risk group. Meanwhile, a GC overall survival (OS) prediction model based on risk grouping and clinical characteristics was developed, and ROC curves and calibration curves confirmed the good predictive ability of the model. In addition, the low-risk group exhibited a higher tumor mutation load and MSI-H, suggesting a possible benefit of immunotherapy. We found that telomerase regulation-related lncRNAs have prognostic value in GC patients and contribute to the exploration of more effective immunotherapeutic strategies.


Multi-functional nanofilms capable of angiogenesis, near-infrared-triggered anti-bacterial activity and inflammatory regulation for infected wound healing.
Chronic infected wound healing is a critical challenge in clinical practice owing to the involvement of multiple physiological processes, including bacteria-related, inflammatory regulation and angiogenesis. Therefore, a multi-functional strategy with synergistic anti-bacterial, anti-inflammatory and pro-angiogenic effects should be developed. Owing to their biomimetic structural features and controlled delivery of active agents, electrospun nanofilms are promising biomaterials for the treatment of skin defects. In this study, we fabricated multi-functional nanofilms with pro-angiogenic, anti-bacterial and anti-inflammatory capacities. First, strontium (Sr) ions were incorporated into poly(L-lactic-co-caprolactone) (PLCL) nanofilms. Subsequently, polydopamine (PDA) and zinc oxide (ZnO) were decorated onto the surface of Sr-loaded PLCL nanofilms to prepare ZnO/PDA@PLCL@Sr nanofilms. In vitro results showed that ZnO/PDA@PLCL@Sr nanofilms were biocompatible, exhibited angiogenic activity and significantly inhibited the growth of Staphylococcus aureus and Escherichia coli upon near-infrared -light irradiation. Furthermore, ZnO/PDA@PLCL@Sr nanofilms were found to drive the transformation of macrophages into the M2 phenotype. In vivo results further validated that ZnO/PDA@PLCL@Sr nanofilms exhibited pro-angiogenic and anti-bacterial activities and regulated inflammation to accelerate wound -healing in a rat model of bacteria-infected skin defects. In conclusion, we successfully developed a multi-functional biomaterial with pro-angiogenic, anti-bacterial and anti-inflammatory capacities to treat chronic infected wounds.


Persistence and prediction of radiocaesium levels in animals grazing semi-natural environments.
In vivo monitoring of radiocaesium levels in a flock of mountain sheep grazing a heather-dominant peatland ecosystem was undertaken over a 3-year period from 1989 to 1991. Highest values were observed during summer and autumn and measurable radiocaesium activities were present throughout the year. Comparably high mean and maximum values recorded in November 1989 are thought to be a result of fungi consumption. Analysis of variance indicated that an increase of 4% occurred in radiocaesium levels in muscle between 1989 and 1990 followed by an overall decrease of 35% between 1990 and 1991. In order to test an existing model to predict radiocaesium levels in muscle from measured activities in faeces, an independent data set was produced. The radiocaesium content of faecal samples collected from the grazing range of a sheep flock was compared with the results of in vivo measurements on the same animals. The correlation over time between the predicted and observed flock mean and maximum values was found to be significant, thereby confirming the value of faeces sampling as an inexpensive and rapid means of assessing the distribution of radiocaesium activities in sheep flocks grazing semi-natural ecosystems.


Effect of an organizational change in a prehospital trauma care protocol and trauma transport directive in a large urban city: a before and after study.
Trauma systems and regionalized trauma care have been shown to improve outcome in severely injured trauma patients. The aim of this study was to evaluate the implementation of a prehospital trauma care protocol and transport directive, and to determine its effects on the number of primary admissions and secondary trauma transfers in a large Scandinavian city. We performed a retrospective observational study based on local trauma registries and hospital and ambulance records in Stockholm County; patients > 15 years of age with an Injury Severity Score (ISS) > 15 transported to any emergency care hospitals in the Stockholm area were included for the years 2006 and 2008. We also included secondary transferred patients to the regional trauma center during 2006, 2008, and 2013. A total of 693 primarily admitted trauma patients were included for the years 2006 and 2008. For the years 2006, 2008 and 2013, we included 114 secondarily transported trauma patients. The number of primary patient transports to the trauma center increased during the years by 20.2%, (p < 0.001); patients primarily transported to the trauma center had a significantly higher Injury Severity Score in 2008 than in 2006, and the number of patients transported secondarily to the trauma center in 2006 was higher compared to 2008 and to 2013 (p < 0.001, all 3 years). Our data indicate that implementation of a prehospital trauma care protocol may have an effect on transportation of severely injured trauma patients. A decrease in secondarily transported trauma patients to the regional trauma center was noted after 1 year and persisted at 7 years after the organizational change. Patients primarily admitted to the trauma center after the change had more severe injuries than patients transported to other emergency hospitals in the area even if 20 % of patients were not admitted primarily to a trauma center. This does not imply that the transport directives or the criteria were not followed but rather reveals the difficulties and uncertainties of field triage. With the introduction of a prehospital trauma transport directive in a large urban city, an increase in patients transported to the regional trauma center and a decrease in secondary transfers were detected, but a considerable number of severely injured patients were still transported to local hospitals.


Intratracheal instillation of automobile exhaust condensate in Syrian golden hamsters.
Male Syrian golden hamsters were intratracheally instilled with automobile exhaust condensate at dose levels of 0.306, 0.613, 1.25, 2.5, and 5.0 mg/hamster once a fortnight for 78 weeks. While a total of six tumors were found in the trachea and lung, hamsters treated with the vehicle only showed no respiratory tract neoplasms. Bronchiogenic adenomatous proliferations and hyperplastic nodules in the lung occurred in all groups, with a significant difference in incidence being seen between the high-dose groups and the controls.


Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease.
Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.


Single-puncture laparoscopic gastrostomy in children.
An original one-puncture technique of performing laparoscopic gastrostomy is described. The implications are analysed. The results of five operations are presented and the advantages and limitations are discussed in the light of current available methods.


Incorporation of curcumin-loaded lipid-based nano delivery systems into food: Release behavior in food simulants and a case study of application in a beverage.
Curcumin-loaded lipid-based nano delivery systems (nanoemulsions-NE, solid lipid nanoparticles-SLN and nanostructured lipid carriers-NLC) were subjected to different food simulants to evaluate curcumin's in vitro release kinetics and particlés stability. The nano delivery systems were also incorporated into a model beverage and their physicochemical properties were evaluated during storing period. Curcumin's bioaccessibility of beverages containing nano delivery systems were assessed through an in vitro digestion process. All nano delivery systems showed a higher curcumin's release and lower particle stability at 50 % ethanol (lipophilic food simulant) comparatively to hydrophilic food simulants. NLC and SLN showed a good particle's stability within the beverage during storing period, while NE presented high instability immediately after incorporation in the beverage. NLC and SLN did not affect beverage's stability relatively to pH, however the beverage with NLC was slightly more stable regarding color. Beverage with SLN presented higher curcumin bioaccessibility compared to the beverage with NLC, however it showed lower curcumin's stability.


Video-endoscope versus endoscope for paranasal sinus surgery: influence on stereoacuity.
A matter of debate is whether the use of a video-endoscope impairs visual orientation and manual precision in endonasal surgery. We investigated the influence of video-endoscopy compared to endoscopy on stereoacuity in a model of the nasal cavity. Twenty medical staff members were asked to touch defined points in a spatial model of the nasal cavity as quickly as possible and in correct order using 0 degree and 30 degrees endoscopes, looking directly through the endoscope or looking at a video monitor connected to a CCD camera on the endoscope. Time, number of omissions of points and faults in point sequence were recorded. Manipulations were significantly quicker when the "operative field" was seen directly through the endoscope compared to orientation from the monitor for both 0 degree endoscope 96 +/- 4.7 s. vs. 108 +/- 5.6 s. and 30 degrees endoscope 84 +/- 3.9 s. vs. 96 +/- 5.5 s. (+/- SEM). There was no difference in number of omissions and faults in sequence between "endoscope" and "video-endoscope." The fact that the use of a video-endoscope did not increase the number of faults in our experiment does not support the notion that performing endoscopic sinus surgery using a monitor is unsafe. In the hands of the participants who were experienced with the endoscope, however, the use of a video-endoscope slowed down manipulations to a significant degree. To which extent this may be due to the effect of training or to superiority of the endoscope per se will remain a matter of discussion until a group of experienced video-endoscopists will have repeated the study.


Selectivity of pirenzepine in the central nervous system. III. Differential effects of multiple pirenzepine and scopolamine administrations on muscarinic receptors as measured autoradiographically.
The effects of intrahippocampal injections of scopolamine and pirenzepine on muscarinic receptor binding were examined by quantitative autoradiographic techniques. Brain slices from animals which had received 7 injections of either scopolamine (n = 5) or pirenzepine (n = 5) over a 22-day injection schedule were compared with slices from 5 saline-injected controls for receptor binding to the whole slice and within selected regions of the brain as measured autoradiographically. The total number of receptors was determined from direct binding assays with 1-[3H]quinuclidinyl-benzilate ([3H]-1-QNB), while the binding of the selective ligands pirenzepine, carbamylcholine, and scopolamine was examined through inhibition studies. The data from the whole slices indicated that pirenzepine-treated animals contained more receptors for [3H]-1-QNB than either saline- or scopolamine-injected controls. Slices from the same animals also displayed a lower affinity for pirenzepine. Slices from scopolamine-injected animals revealed neither an increase in receptor number nor a decrease in antagonist affinity, although the binding of the agonist carbamylcholine was increased. Quantitative analysis of the autoradiograms generated from the slices indicated that the increase in receptor number for pirenzepine-injected animals was predominantly within the cerebral and cingulate cortices. The inhibition by pirenzepine was also lower in these areas in the same group of animals. Agonist inhibition was altered in the central layers of the cerebral cortex and in the pretectal area in scopolamine-treated animals. The results suggest separate mechanisms of drug action and adaptation for pirenzepine and scopolamine.


Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.
2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50=25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50=7.5 nM) and TNF-α production in mouse splenocytes (IC50=9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50=18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex.


Where, oh where, have my stem cells gone?
During the summer of 2001, Americans were treated to high political drama courtesy of the debate over embryonic and adult stem cell research. The popular press was flush with predictions about how neural stem cells would reverse, almost by magic, the devastation caused by diseases such as Alzheimer's, Parkinson's, stroke or spinal cord injury. Unfortunately, this promise remains unfulfilled because we have such a poor understanding of how stem cells function. With regard to adult stem cells, we are not even completely sure where they are, or how or when they got there. A provocative study by Ourednik et al. published in Science suggests that in primates, adult neural stem cells are allocated during early corticogenesis. The study also provides evidence for the existence of stem cells dispersed throughout the frontal cortex and striatum.


The effect of naloxone on cerebellar cGMP content. A possible GABA-antagonistic action?
Naloxone in high doses (60--240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5--10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by isoniazid. On the other hand, naloxone (5 mg/kg) partially antagonized the fall in cGMP elicited by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.


Fabrication of a sensitive amperometric sensor for NADH and H2O2 using palladium nanoparticles-multiwalled carbon nanotube nanohybrid.
Palladium nanoparticles decorated multiwalled carbon nanotubes (PdNPs-MWCNTs) were synthesized and simply cast on the surface of a glassy carbon electrode (GCE) to prepare an amperometric sensor. The fabricated sensor (PdNPs-MWCNTs/GCE) showed excellent electrocatalytic activity towards NADH and H2O2 oxidation and H2O2 reduction. A fast, linear and highly sensitive response was observed for NADH in the concentration range between 0.1 and 200 μM with a detection limit (S/N=3) of 32 nM. Also, the sensor exhibited fast and sensitive responses (<2 s) towards H2O2. The sensitivity and detection limit for H2O2 at the operating potential of +0.35 V were 167 nA μM(-1)cm(-2) and 1.2 μM, respectively and better than those obtained at the operating potential of -0.25 V (68 nA μM(-1)cm(-2) and 14 μM). Moreover, further modification of the proposed sensor by glucose oxidase led to the fabrication of a glucose biosensor with satisfactory performance.


Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies.
The tumor microenvironment is often overlooked when considering tumor response to chemotherapeutic agents. This environment consists of soluble factors, components of the extracellular matrix as well as cell-cell interactions. Recently, it has become clear that cell-cell and cell-matrix interactions result in cytoskeletal reorganization and the activation of multiple signal transduction pathways that directly influence cell survival, growth and differentiation. Experimental evidence shows that anti-apoptotic pathways initiated by cell adhesion are operative in tumor cells and, furthermore, cause resistance to mechanistically distinct cytotoxics. For hematopoietic tumors, cell adhesion to a single matrix, fibronectin is sufficient to inhibit apoptosis induced by mechanistically distinct cyctotoxics. Adhesion of hematopoietic tumors to this matrix blocks cell cycle progression, and for the human multiple myeloma 8226 cell line adhesion to fibronectin resulted in increased p27kip1 levels, which correlated with cell cycle arrest and drug resistance. A decrease in initial DNA damage induced by topoisomerase II inhibitors has also been observed in adherent hematopoietic tumor cell lines. Further studies investigating the mechanisms of cell adhesion mediated drug resistance may reveal novel targets directed at the reversal of de novo drug resistance.


Reflections of Dutch patients on IVF treatment in Belgium: a qualitative analysis of internet forums.
What information is shared on Dutch internet forums with regard to infertility treatment in Belgium? The online discussion mainly regards medical treatments, feelings and experiences, and financial implications. The general tone of the discussion on the forums about fertility treatment in Belgium is that Belgian clinics offer better quality of care. The internet is the most important source of information for cross-border patients. Many Dutch patients visit Belgian clinics for infertility treatment. This study comprised an inductive thematic analysis of eight Dutch internet forums about infertility. All the threads that were active in a 15-month period (October 2010-December 2011) were retrieved and checked for relevance. This resulted in 77 threads containing 1813 posts that were used for thematic analysis. Eight themes emerged after data analysis: medical expertise and testing, feelings and experiences, costs, trying out different clinics, travel and waiting times, treatments in the Netherlands, cooperation between clinics/physicians and laws and regulations. Our analysis of shared patient experiences indicates that patients identify respect for the person behind the patient as the fundamental reason why quality of care is higher in Belgium. They define this respect as active involvement in the medical decision-making process, which is considered a form of patient-centred care. The data from internet forums are not representative of the experience of Dutch IVF patients in Belgium. We are presenting a thematic analysis of information that circulates on the web, not making statements about IVF treatment in Belgium or the Netherlands. This is the first study on what information (future) cross-border patients are likely to find when they look for information online. W.V.H. has a Ph.D. grant and V.P. holds a Postdoctoral Mandate by the Flemish Foundation for Scientific Research (FWO-Vlaanderen). G.P. is supported by a full-time stipend at Ghent University. There are no competing interests. N/A.


Mechanical performance under dynamic loading of rubberized asphalt mixtures with highly-porous vesicular aggregate.
In volcanic regions, the use of certain abundant aggregates of scoriaceous nature with high porosity to manufacture bituminous paving mixtures is a major problem due to the excessive heterogeneity, absorption and limited strength of these aggregates. Consequently, the properties of the mixtures often do not meet technical specifications. The aim of this research is to study the improvement of the mechanical performance of asphalt mixtures with these residual volcanic aggregates by using binders modified with rubber from end-of-life tyres, since environmental and economic requirements make it necessary to reuse both types of waste. Laboratory studies determining the compactability, dynamic stiffness, fatigue resistance and elastic constants have made it possible to characterise the mechanical performance of these mixtures during production and in service, and to compare them with conventional mixtures. It was found that the use of tyre rubber modified bitumen makes compaction somewhat more difficult, but reduces the particle size degradation of the porous aggregates and improves the mixture performance and durability, showing higher stiffness moduli and increased resistance to fatigue.


Identification of transcription factors and gene clusters in rabbit smooth muscle cells during high flow-induced vascular remodeling via microarray.
Sustained blood flow, especially high blood flow causes the remodeling of arteries. The molecular mechanism of vascular remodeling has been mainly investigated in cultured cells. However, the in vivo molecular mechanism is poorly understood. In this study, we performed microarray analysis to explore the gene expression profile of smooth muscle cells (SMCs) during vascular remodeling. Transcriptional profiles indicated that 947 genes were differentially expressed in SMCs responding to high flow compared with the sham control, of which 617 genes were up-regulated and 330 genes were down-regulated. Gene ontology analysis revealed the special participation of extracellular matrix related genes during high flow-induced vascular remodeling. KEGG pathway analysis showed the enrichment of metabolism and immune function associated genes in SMCs exposed to high flow. Besides, we also identified 25 differentially expressed transcription factors potentially impacted by hemodynamic insult. Finally, we revealed FOXN4 as a novel transcription factor that could modulate MMP2 and MMP9 transcriptional activity. Collectively, our results revealed major gene clusters and transcription factors in SMCs during vascular remodeling which may provide an insight into the molecular mechanism of vascular remodeling and facilitate the screening of candidate genes for vascular diseases.


Individual and interactive role of Trichoderma viride and arbuscular mycorrhizal fungi on growth and pigment content of onion plants.
The study of interactions between beneficial micro-organisms associated with plant roots is important, because such interactions might either enhance or inhibit the beneficial effects of individual species. The effect of the combined inoculation of arbuscular mycorrhizal (AM) fungi and a biocontrol fungus (Trichoderma viride) on different growth parameters and chlorophyll a,b, carotenoids, total chlorophyll and total pigments of onion (Allium cepa) plants was studied under glasshouse conditions. The results proved that AM fungi and T. viride are compatible with each other and their combined use was effective not only in improving onion growth parameters such as fresh and dry weights, root and shoot lengths and leaf area but also increasing total chlorophyll, carotenoids and total pigments content in onion leaves. Where, inoculation of onion plants by AM fungi and T. viride alone or in combination significantly increased bulb diameters of onion plants 20, 12·5 and 17·5% increase; respectively, when compared with control ones. Also percentage of AM fungal colonization increased greatly with T. viride inoculation. Therefore, AM fungi and T. viride could be a good alternate of chemical fertilizer for improving the growth of onion. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: The need for increasing agricultural productivity and quality has led to an excessive use of chemical fertilizers; creating serious threats to human health and the environment. The use of biofertilizers is an alternative for sustaining high production with low ecological impact. Thus the goal of this study was to propose a biological technique using arbuscular mycorrhizal symbiosis and Trichoderma viride (plant-microbe interaction) for increasing plant growth that represent a great opportunities for recent agricultural practices. This may be an indication displaying the AM and Trichoderma significance for plant progress and growth.


The Bankart Performance Metrics Combined With a Shoulder Model Simulator Create a Precise and Accurate Training Tool for Measuring Surgeon Skill.
To determine if a dry shoulder model simulator coupled with previously validated performance metrics for an arthroscopic Bankart repair (ABR) would be a valid tool with the ability to discriminate between the performance of experienced and novice surgeons, and to establish a proficiency benchmark for an ABR using a model simulator. We compared an experienced group of arthroscopic shoulder surgeons (Arthroscopy Association of North America faculty) (n = 12) with a novice group (n = 7) (postgraduate year 4 or 5 orthopaedic residents). All surgeons were instructed to perform a diagnostic arthroscopy and a 3 suture anchor Bankart repair on a dry shoulder model. Each procedure was videotaped in its entirety and scored in blinded fashion independently by 2 trained reviewers. Scoring used previously validated metrics for an ABR and included steps, errors, and "sentinel" (more serious) errors. The inter-rater reliability among pairs of raters averaged 0.93. The experienced group made 63% fewer errors, committed 79% fewer sentinel errors, and performed the procedure in 42% less time than the novice group (all significant differences). The greatest difference in errors between the groups involved anchor preparation and insertion, suture delivery and management, and knot tying. The tool comprised by validated ABR metrics coupled with a dry shoulder model simulator is able to accurately distinguish between the performance of experienced and novice orthopaedic surgeons. A performance benchmark based on the mean performance of the experienced group includes completion of a 3 anchor Bankart repair, enacting no more than 4 total errors and 1 sentinel error. The combination of performance metrics and an arthroscopic shoulder model simulator can be used to improve the effectiveness of surgical skills training for an ABR. The methodology used may serve as a template for outcomes-based procedural skills training in general.