Alcohol consumption and perceived sexual coercion: effects of gender and personality determinants.
Alcohol intoxication is a risk factor for being a perpetrator or victim of sexual coercion. Environmental factors (e.g., misperception of social cues), as well as dispositional factors (e.g., personality, gender), are believed to play an important role in linking alcohol consumption and sexual coercion. Sixty-three participants, chosen on the basis of being high or low on scales of hypermasculinity (men) or hyperfemininity (women), were randomly assigned to either an alcohol or nonalcohol condition. After viewing a video of an ambiguous heterosexual interaction, participants responded to questions assessing their accuracy of recall of cues from the interaction, positive bias in their recall of cues, and expectancies regarding 1) the future sexual behavior of the characters in the video and 2) their own conduct if they were in a similar situation. Alcohol was negatively related to accuracy in recall and positively related to the belief that the characters in the video would engage in sexual intercourse (both volitionally and forced). Gender was also important as women were less accurate in recalling cues and intoxicated women evinced a positive bias for cue recall. Traits of hypermasculinity and hyperfemininity were not robust predictors. Hypermasculine men did, however, endorse a substantially higher likelihood that they would have sexual intercourse if in a similar situation. Findings are placed in the context of potential preventive interventions.


Altered brain functional network topology in Obsessive-Compulsive Disorder: A comparison of patients with varying severity of depressive symptoms and the impact on psychosocial functioning.
Obsessive-compulsive disorder (OCD) is associated with psychosocial impairment, which can be exacerbated by depressive symptoms. In this study, we employed graph theory analysis to investigate the association among neuroimaging, clinical features, and psychosocial functioning in OCD patients, with a specific focus on the differential impact of depressive symptoms. 216 OCD patients were divided into two subgroups based on depressive symptoms. Resting-state functional MRI data were acquired from a subset of 106 OCD patients along with 77 matched healthy controls (HCs). We analyzed the topological characteristics of the entire brain and the cognition-related subnetworks and performed Pearson correlation analyses to further explore the relationship with psychosocial functioning. OCD patients with more severe depressive symptoms exhibited greater impairment across all dimensions of psychosocial functioning. Graph theory analysis revealed more pronounced reductions in network efficiency within the entire brain, the default mode network (DMN), and the cingulo-opercular network (CON) among patients with non or mild depressive symptoms. Lower nodal efficiency and degree centrality of the right superior temporal gyrus (STG) were found in OCD patients and these variables were positively correlated with psychosocial functioning impairment. This study revealed that the presence of depressive symptoms generally exacerbated psychosocial functioning impairment in OCD patients. Abnormalities in the functional integration of the entire brain, the DMN, and the CON in OCD patients may comprise the basis of cognitive deficits, while dysfunction of the right STG may affect the psychosocial functioning through its role in emotion, intention perception, and insight.


Differential cellular responses to protein adducts of naphthoquinone and monocrotaline pyrrole.
Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there is a correlation between protein adduction and target organ toxicity, a cause and effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts with a similar select group of proteins rich in reactive thiols. In this study, we treated human pulmonary artery endothelial cells (HPAEC) with NQ, MCTP, or preformed NQ or MCTP adducts to the protein galectin-1 (gal-1) and examined indicators of reactive oxygen species (ROS) oxidative injury, markers of apoptosis (caspase-3 and annexin V), and gene responses of cellular stress. ROS production was assayed fluorescently using CM-H(2)DCFDA. NQ adducts to gal-1 (NQ-gal) produced 183% more intracellular ROS than gal-1 alone (p < 0.0001). Caspase-3 activity and annexin V staining of phosphatidylserine were used to assess apoptotic activity in treated cells. HPAEC exposed to MCTP-gal had increases in both caspase-3 activation and membrane translocation of annexin V relative to gal-1 alone (p < 0.0001). Direct application of NQ produced significantly more ROS and induced significant caspase-3 activation, whereas MCTP did not. Human bronchial epithelial cells were also exposed to MCTP-gal and found to have significant increases in both caspase-3 activation and annexin V staining in comparison to that of gal-1 (p < 0.05). Western blot analysis showed that both NQ and MCTP significantly induced the Nrf2 mediated stress response pathway despite differences in ROS generation. ER stress was not induced by either adducts or parent compounds as seen by quantitative RT-PCR, but HOX-1 expression was significantly induced by NQ-gal and MCTP alone. Electrophile adduction to gal-1 produces different cytotoxic effects specific to each reactive intermediate.


Sensitivity of FEV1 response following one and two inhalations of albuterol: a pilot study.
Eleven patients entered a pilot study designed to evaluate the proportion of eligible responders following a single inhalation of albuterol aerosol, the degree of response, and the sensitivity to distinguish between one and two inhalations based on FEV1 response. Each patient received a single inhalation at 0 and 60 minutes. FEV1 was measured 30 and 60 minutes after each inhalation. Most patients (82%) responded to a single inhalation and the majority (73%) were capable of further response after two inhalations. This study design was able to distinguish FEV1 responses to one and two inhalations of albuterol and provide upward and downward sensitivity sufficient to detect major differences in products.


Biofilm detection with hematoxylin-eosin staining.
To demonstrate that hematoxylin-eosin staining can be used to detect the presence of bacterial biofilm in patients with chronic rhinosinusitis (CRS). A prospective study. The University of Southern California University Hospital and the Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Keck School of Medicine, Los Angeles. A total of 34 patients: 24 undergoing endoscopic sinus surgery for CRS and 10 undergoing septoplasty with or without turbinate reduction with no history of sinusitis, were enrolled in the study. Contiguous sections from patient samples were examined by both hematoxylin-eosin staining and fluorescence in situ hybridization (FISH) with the bacterial-specific probe EUB338 for evidence of bacterial biofilm. Biofilm was detected by hematoxylin-eosin staining in 15 of 24 patients with CRS and 1 of 10 control patients. In all cases, hematoxylin-eosin staining was found to be an accurate predictor of the presence or absence of biofilm using FISH as a control standard. Hematoxylin-eosin staining of surgical specimens is a reliable and available method for the detection of bacterial biofilm in chronic infectious disease.


Oxygen as attractant and repellent in bacterial chemotaxis.
Studies of bacterial chemotaxis to oxygen (aerotaxis) over a broad range of oxygen concentrations showed that at high concentrations, oxygen was a repellent of Salmonella typhimurium, Escherichia coli, and some bacilli, whereas it is known that at lower concentrations (less than or equal to 0.25 mM dissolved oxygen), oxygen is an attractant. In a temporal assay of aerotaxis, S. typhimurium in medium equilibrated with air (0.25 mM dissolved oxygen) and then exposed to pure oxygen (1.2 mM) tumbled continuously for approximately 20 s. The oxygen concentration that elicited a half-maximal negative (repellent) response was 1.0 mM for both S. typhimurium and E. coli. The receptor for the negative chemoresponse to high concentrations of oxygen is apparently different from the receptor for the positive chemoresponse to low concentrations of oxygen, since the oxygen concentration that elicits a half-maximal positive (attractant) response in S. typhimurium and E. coli is reported to be 0.7 microM. Adaptation to high concentrations of oxygen, like adaptation to low concentrations of oxygen, was independent of methylation of a transducer protein. Only the response to low oxygen concentrations, however, was altered by interaction with the amidated Tsr transducer in cheB mutants.


Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS.
Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute to sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) and high-mobility group box 1 (HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing inflammation and ARDS severity.We investigated neutrophil and NET clearance by macrophages from control and ARDS patients and examined how bronchoalveolar lavage (BAL) fluid from control and ARDS patients could affect NET formation and efferocytosis. Metformin (an AMPK activator) and neutralising antibody against HMGB1 were applied to improve efferocytosis and NET clearance.Neutrophils from ARDS patients showed significantly reduced apoptosis. Conversely, NET formation was significantly enhanced in ARDS patients. Exposure of neutrophils to ARDS BAL fluid promoted NET production, while control BAL fluid had no effect. Macrophage engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients. Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL fluid improved efferocytosis and NET clearance.In conclusion, restoration of AMPK activity with metformin or specific neutralisation of HMGB1 in BAL fluid represent promising therapeutic strategies to decrease sustained lung inflammation during ARDS.


Antibacterial Activity of Thai Medicinal Plant Extracts Against Microorganism Isolated from Post-Weaning Diarrhea in Piglets.
Post-weaning bacterial infections in piglets caused by resistant strains have increased dramatically. Thai medicinal plants such as Piper retrofractum, Piper leptostachyum, Piper sarmentosum, Zingiber officinale, Plumbago indica, Piper betle, Caesalpinia sappan, Garcinia mangostana etc have been widely used in Thai traditional medicine to treat diarrhea. Thus, these plants were investigated antimicrobial activity against gram negative strain isolated from piglets with diarrhea. To investigate antimicrobial activity of Thai medicinal plants and their isolated compounds in order to develop an alternative treatment against bacteria causing post-weaning diarrhea in piglets. Antimicrobial activity of some Thai medicinal plants and their compounds were tested using disc diffusion and broth dilution methods against bacteria associated with diarrheal disease including Escherichia coli and Salmonella spp. The extraction was performed by maceration in 95% ethanol. The results showed that all tested strains were sensitive to P. betle extract. As well as Plumbagin compound from Plumbago indica also showed antimicrobial activity against all microbes the same of P. betle extract with MIC between 5 to 10 mg/ml, which are different from the group of antibiotics with MIC values between 0.19-2.5 mg/ml, P. betle extracts inhibited Escherichia coli and Salmonella spp while some antibiotics can inhibit only some types. The results support the use of Thai medicinal plants for treatment of diarrhea caused by these bacteria. This study also provides basic knowledge on antimicrobial activity against diarrheal microbe isolated from piglets. These results lead to further development of an effective formula of Thai medicinal plants for diarrheal disease in post-weaned piglets and other infectious diseases in the future.


Ehrlichia infection in Italy.
Immunoglobulin M seroconversion to Ehrlichia chaffeensis was documented in U.S. citizens bitten by ticks in Sardinia. Seven cases of suspected ehrlichiosis in local residents were not confirmed by laboratory tests. In Alpine areas antibodies to E. phagocytophila were detected in persons at high risk, i.e., foresters (8.6%) and hunters (5.5%), and in controls (1.5%). Of 153 persons bitten by ticks, only one was Ehrlichia antibody-positive after 6 months.


A novel collaborative learning model for mixed dentition and fillings segmentation in panoramic radiographs.
It is critical for dentists to identify and differentiate primary and permanent teeth, fillings, dental restorations and areas with pathological findings when reviewing dental radiographs to ensure that an accurate diagnosis is made and the optimal treatment can be planned. Unfortunately, dental radiographs are sometimes read incorrectly due to human error or low-quality images. While secondary or group review can help catch errors, many dentists work in practice alone and/or do not have time to review all of their patients' radiographs with another dentist. Artificial intelligence may facilitate the accurate interpretation of radiographs. To help support the review of panoramic radiographs, we developed a novel collaborative learning model that simultaneously identifies and differentiates primary and permanent teeth and detects fillings. We used publicly accessible dental panoramic radiographic images and images obtained from the University of Missouri-Kansas City, School of Dentistry to develop and optimize two high-performance classifiers: (1) a system for tooth segmentation that can differentiate primary and permanent teeth and (2) a system to detect dental fillings. By utilizing these high-performance classifiers, we created models that can identify primary and permanent teeth (mean average precision [mAP] 95.32 % and performance [F-1] 92.50 %), as well as their associated dental fillings (mAP 91.53 % and F-1 91.00 %). We also designed a novel method for collaborative learning that utilizes these two classifiers to enhance recognition performance (mAP 94.09 % and F-1 93.41 %). Our model improves upon the existing machine learning models to simultaneously identify and differentiate primary and permanent teeth, and to identify any associated fillings. Human error can lead to incorrect readings of panoramic radiographs. By developing artificial intelligence and machine learning methods to analyze panoramic radiographs, dentists can use this information to support their radiograph interpretations, help communicate the information to patients, and assist dental students learning to read radiographs.


Piperlongumine attenuates angiotensin-II-induced cardiac hypertrophy and fibrosis by inhibiting Akt-FoxO1 signalling.
Cardiac hypertrophy and fibrosis are closely related to cardiac dysfunction, especially diastolic dysfunction. Limited medications can be used to simultaneously delay cardiac hypertrophy and fibrosis in clinical practice. Piperlongumine (PLG) is an amide alkaloid extracted from Piper longum and has been shown to have multiple biological effects, including anticancer and antioxidant effects. However, the role of PLG in cardiac hypertrophy and fibrosis is not clear. The aim of this study was to reveal the role of PLG in cardiac hypertrophy and fibrosis and the associated mechanism. Cardiac hypertrophy and fibrosis were induced by angiotensin II (Ang II) in vivo and in vitro. The effect of PLG in vivo, in vitro and its mechanism were investigated by proliferation and apoptosis assays, western blot, real-time PCR, immunofluorescence, histochemistry, echocardiography, flow cytometry and chromatin immunoprecipitation. Proliferation and apoptosis assays showed that 2.5 μM PLG slightly inhibited proliferation and did not promote apoptosis. Treatment with 5 mg/kg PLG obviously inhibited Ang II-induced cardiac hypertrophy and fibrosis in vivo. In vitro studies of neonatal rat cardiomyocytes (NRCMs) showed that the anti-hypertrophic effect of PLG was mediated by reducing the phosphorylation of Akt and thereby preserving the level of Forkhead box transcription factor O1 (FoxO1), since knockdown of FoxO1 by siRNA reversed the protective effect of PLG on NRCMs. In addition, PLG significantly decreased the Ang II-induced expression of profibrotic proteins in neonatal cardiac fibroblasts by reducing the expression of Krüppel-like factor 4 (KLF4) and the recruitment of KLF4 to the promoter regions of transforming growth factor-β and connective tissue growth factor. We demonstrate the cardioprotective effects of PLG in both cardiac hypertrophy and fibrosis and the potential value of PLG for developing novel medications for pathological cardiac hypertrophy and heart failure.


A Cross-Sectional Serosurvey of Anti-Orthopoxvirus Antibodies in Central and Western Africa.
Since the eradication of smallpox and the subsequent discontinuation of the worldwide smallpox vaccination program, other Orthopoxviruses beside Variola virus have been increasingly representing a risk to human health. To investigate the extent of natural contact with Orthopoxviruses and possible demographic risk factors for such an exposure, we performed a cross-sectional serosurvey of anti-Orthopoxvirus IgG antibodies in West and Central Africa. To this end, people living in forest regions in Côte d'Ivoire (CIV, n = 737) and the Democratic Republic of the Congo (COD, n = 267) were assigned into groups according to their likely smallpox vaccination status. The overall prevalence of anti-Orthopoxvirus antibodies was 51% in CIV and 60% in COD. High rates of seropositivity among the vaccinated part of the population (80% in CIV; 96% COD) indicated a long-lasting post vaccination immune response. In non-vaccinated participants, seroprevalences of 19% (CIV) and 26% (COD) indicated regular contact with Orthopoxviruses. Multivariate logistic regression revealed that the antibody level in the vaccinated part of the population was higher in COD than in CIV, increased with age and was slightly higher in females than males. In the unvaccinated part of the population none of these factors influenced antibody level significantly. In conclusion, our results confirm expectedly high anti-Orthopoxvirus seroprevalences in previously smallpox-vaccinated people living in CIV and the COD but more unexpectedly imply regular contact with Orthopoxviruses both in Western and Central Africa, even in the absence of recognized outbreaks.


COVID-19: Four Paediatric Cases in Malaysia.
This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.


May microbial ecological baseline exist in continental groundwater?
Microbes constitute almost the entire biological community in subsurface groundwater and play an important role in ecological evolution and global biogeochemical cycles. Ecological baseline as a fundamental reference with less human interference has been investigated in surface ecosystems such as soils, rivers, and ocean, but the existence of groundwater microbial ecological baseline (GMEB) is still an open question so far. Based on high-throughput sequencing information derived from national monitoring of 733 newly constructed wells, we find that bacterial communities in pristine groundwater exhibit a significant lateral diversity gradient and gradually approach the topsoil microbial latitudinal diversity gradient with decreasing burial depth of phreatic water. Among 74 phyla dominated by Proteobacteria in groundwater, Patescibacteria act as keystone taxa that harmonize microbes in shallower aquifers and accelerate decline in bacterial diversity with increasing well-depth. Decreasing habitat niche breadth with increasing well-depth suggests a general change in the relationship among key microbes from closer cooperation in shallow to stronger competition in deep groundwater. Unlike surface-water microbes, microbial communities in pristine groundwater are predominantly shaped by deterministic processes, potentially associated with nutrient sequestration under dark and anoxic environments in aquifers. By unveiling the biogeographic patterns and mechanisms controlling the community assembly of microbes in pristine groundwater throughout China, we firstly confirm the existence of GMEB in shallower aquifers and propose Groundwater Microbial Community Index (GMCI) to evaluate anthropogenic impact, which highlights the importance of GMEB in groundwater water security and health diagnosis. Video Abstract.


Design, synthesis, characterization, luminescence and non-linear optical (NLO) properties of multinuclear platinum(II) alkynyl complexes.
A series of luminescent multinuclear platinum(II) alkynyl complexes containing triethynylbenzene or 1,4-bis(3,5-diethynylphenyl)buta-1,3-diyne as cores has been successfully synthesized and characterized. The electronic absorption, emission, nanosecond transient absorption and electrochemical properties of these complexes have been reported. These complexes show long-lived emissions in degassed benzene solution and in alcoholic glass at 77 K. Moreover, they are found to exhibit two-photon absorption (2PA) and two-photon induced luminescence (TPIL) properties, and their two-photon absorption cross-sections have been determined to be 6-191 GM upon excitation at 720 nm. Through a systematic comparison, it has been found that tetra- and hexanuclear platinum(II) complexes show better 2PA and TPIL properties than their di- and trinuclear counterparts.


[Morphometric characteristics of the immunomorphological reactions in metastasizing and nonmetastasizing thyroid cancers].
Morphometrically, immunomorphological reactions have been studied on the intraoperative material from 70 patients with thyroid cancer of various histological pattern. It was found that metastasization of cancerous tumors proceeds on the background of suppressed antitumor immunity--a reduced index of the stroma lymphoid infiltration, diminishing of the T-dependent paracortical zone of regional lymph nodes and less content of T-lymphocytes and macrophages in it.


Fresh frozen plasma for cardiovascular surgery.
Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP. To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding. We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status. We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange. Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial. We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion. This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of patients with coagulopathies or those who are undergoing emergency surgery. There were no reported adverse events attributable to FFP transfusion, although there was a significant increase in the number of patients requiring red cell transfusion who were randomised to FFP. Variability in outcome reporting between trials precluded meta-analysis for many outcomes across all trials, and there was evidence of a high risk of bias in most of the studies. Further adequately powered studies of FFP, or comparable pro-haemostatic agents, are required to assess whether larger reductions in prothrombin time translate into clinical benefits. Overall the evidence from randomised controlled trials for the safety and efficacy of prophylactic transfusion of FFP for cardiac surgery is insufficient.


Self-Assembly of Bolaamphiphiles into 2D Nanosheets via Synergistic and Meticulous Tailoring of Multiple Noncovalent Interactions.
A bolaamphiphile possessing a hydrophobic skeleton and two hydrophilic groups at both ends represents an important class of building blocks toward a rich variety of self-assembled materials for use in ion transport, optoelectronic devices, and drug and gene delivery. Herein, we report a one-step synthesis of an array of rationally designed anionic bolaamphiphiles and unravel the correlation between molecular structure of anionic bolaamphiphiles and their disparate self-assemblies via synergistic and meticulous tailoring of a set of interactions. Intriguingly, by delicately regulating the interactions among these supramolecular interactions, two-dimensional (2D) nanosheets are crafted via self-assembly of anionic bolaamphiphiles. Particularly, single-layered 2D nanosheets are formed through the synergy of aromatic π-π stacking, hydrophobic, hydrogen-bonding, and electrostatic repulsion interactions. In contrast, the selective converting of anionic headgroups of bolaamphiphiles into nonpolar alkyl chain screens the electrostatic repulsion between neighboring bolaamphiphiles while keeping the other segments of bolaamphiphiles intact, thereby allowing them to self-assemble into multilayered 2D nanosheets. Interestingly, the intrinsically charged 2D nanosheets could anchor oppositely charged metal nanoparticles via electrostatic attraction. Conceptually, anionic bolaamphiphile-derived 2D nanosheets may function as a substrate to position a diversity of nanocrystals and conjugated polymers for a broad range of applications in catalysis, optical devices, and photothermal therapy.


[Interest in disinterestedness in the epidemiology of health systems and services].
This article intends to critique of the cultural authority of the medical sciences, opening up a discussion on its publicization from a political standpoint. At the same time, from a more technical standpoint, it proposes the implementation of an epidemiology of health systems and services. Based on Pierre Bourdieu's concept of interest in disinterestedness and Joseph Gusfield's notion of the cultural authority of public problems, it analyzes why epidemiological information is so rarely used in the evaluation and monitoring of clinical, population, institutional, and territorial practices. That is, why does the dominant culture of decision making eschew epidemiological information? Within this conceptual framework, a body of documental evidence is analyzed that sheds light on the weak scientific basis that upholds or that has underpinned certain practices in the health field at different historical moments. The discussion is organized around three major themes: assistentialist professional practice, medication, and biomedical technologies.


Patient Characteristics and Indicators of Treatment Initiation with Repository Corticotropin Injection in Patients with Rheumatoid Arthritis: A Claims Database Analysis.
Repository corticotropin injection (RCI) is indicated as adjunctive, short-term therapy in selected patients with RA. To characterize RCI users and identify predictors of RCI initiation in RA, we compared preindex characteristics, treatment patterns, comorbidities, healthcare resource utilization (HCRU), and costs for patients who had initiated RCI treatment (RCI cohort) versus patients with no RCI claims and ≥ 1 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD) claim (non-RCI ts/bDMARD cohort). We analyzed pharmacy and medical claims data from a large commercial and Medicare supplemental administrative database. Inclusion criteria were age ≥ 18 years, ≥ 1 inpatient or ≥ 2 outpatient claims with RA diagnosis (January 1, 2007-December 31, 2018), and 12-month continuous medical and pharmacy coverage preindex. Results from baseline cohort comparisons informed multiple logistic regression analysis. Compared with the non-RCI ts/bDMARD cohort (n = 162,065), the RCI cohort (n = 350) had a greater proportion of patients with higher Charlson comorbidity index (CCI) scores; higher mean claims-based index of RA severity and CCI scores; greater frequency of almost all comorbidities; higher use of nontraditional DMARDs, glucocorticoids, and opioids; higher all-cause HCRU; and higher medical and total costs. By multivariable analysis, the most significant predictors of RCI initiation were intermittent glucocorticoid use at any dose (odds ratio [OR] 1.67), extended-use glucocorticoids at medium (OR 2.03) and high doses (OR 2.99), nontraditional DMARD use (OR 2.09), anemia (OR 1.39), and renal disease (OR 2.45). Before RCI initiation, patients had more severe RA, higher comorbidity burden, greater use of glucocorticoids and opioids, and higher HCRU compared with non-RCI initiators. The most significant predictors for starting RCI in patients with RA were intermittent use of glucocorticoids at any dose, extended-use high-dose glucocorticoids, use of nontraditional DMARDs, and comorbid anemia and renal disease.


[The effect of tobacco smoking during pregnancy on concentration of pro-hepcidin and some parameters of iron metabolism in matched-maternal cord pairs].
Iron deficiency relatively observed in pregnant women is assumed to be enhanced by cigarette smoking. Hepcidin, a peptide hormone produced by the liver as pro-hepcidin, has recently emerged as a central mediator of iron metabolism. Hepcidin regulates intestinal iron absorption, macrophage iron release, and the placental passage of iron. Maternal smoking is associated with increased fetal iron requirements and stimulates fetal erythropoiesis. This is probably through a hypoxic effect on the fetus, and is dose related to the maternal smoking level. It is known that anemia and hypoxia suppress hepcidine mRNA expression. Therefore the aim of the study was to estimate the effect of tobacco smoking on serum pro-hepcidin levels and some iron parameters in pregnant women and umbilical cord blood. We also studied correlation between pro-hepcidin and others iron markers in mothers and their newborns. Healthy, pregnant women (n = 50), patients of Clinical Department of Obstetrics and Gynecology, Institute of Mother and Child were divided into groups nonsmoking and smoking according to questionnaire declaration. Serum concentrations of pro-hepcidin were determined by immunoenzymathic method using a commercial pro-hepcidin assay (DRG, Germany). Levels of ferritin and transferrin were measured by immunoturbidimetric method and iron by photometric test with ferrozine using HORIBA ABX kits (France) and Cobas Mira analyser (Roche, Switzerland). Levels of hemoglobin and hematocrite were determined using commercially available kits on Pentra 60 analyser (ABX, France). We observed that the mean concentration of pro-hepcidin in serum of smoking pregnant women was statistically lower than in tobacco abstinent (101.9 +/- 28.6 ng/ml vs 88.3 +/- 18.2 ng/ml; p < 0.01). Levels of others studied iron markers were similar in both group except total iron concentration, which was 20% lower in smoking mothers than in nonsmoking ones. In umbilical cord blood of infants born to smoking women level of pro-hepcidin was significantly lower than in tobacco abstinent (54.2 +/- 14.0 ng/ml vs 76.8 +/- 21.4 ng/ml, p < 0.0001). We observed positive correlation between concentrations of that prohormone in serum of mothers and cord blood of their newborns in nonsmoking group (r = 0.54; p < 0.02) as well as in smoking ones (r = 0.68; p < 0.05). In addition, concentrations of ferritin, transferin and total iron were lower by 30%, 13% and 20% respectively in cord blood of smoking than nonsmoking group. The differences were statistically significant (p < 0.05). Our analysis revealed no correlation between serum pro-hepcidin levels and other studied parameters of iron status both in the mothers and children groups. Our results indicate that tobacco smoking during pregnancy affected pro-hepcidine levels in serum of mothers and their newborns. Low concentrations of some iron markers in umbilical cord blood suggest that mother's smoking could lead to subclinical iron deficiency in fetus. No anemia were observed in both studied groups of mothers that could explain no relationships between pro-hepcidin and others parameters of iron status.


Having friends and Rett syndrome: how social relationships create meaningful contexts for limited skills.
The experiences of a teenage girl with Rett syndrome who was being educated in an inclusive middle school are described to provide a better understanding of how social relationships create meaningful contexts for individuals with limited skills. The case example is used to illustrate the principle that contexts (including expectancies, acceptance, philosophical principles) can be designed to support meaningful social relationships, despite social and intellectual disabilities. Naturalistic observations of social interactions over a two year period are reported to illustrate the possible types of social relationship between this young person and her adolescent friends and peers. While someone with this syndrome might be judged objectively to have minimal social skills, an accepting social environment willing to read minimal communicative cues provided the context for many typical social interactions. Since contexts require subjective judgement. the post-modern concept that disability represents a social construction can be viewed as a metaphor compatible with the reality that careful planning and structuring of the environment is in some instances the most appropriate intervention focus rather than the person with a disability. The sorts of positive friendship experiences described in this paper did not occur spontaneously, or by chance alone, nor were they the result of social skills instruction. Instead, they were associated with observable social behaviour by caregivers and peers who were extending their own repertoires to accommodate someone objectively determined to have a severe disability.


Tumor Necrosis Factor-Alpha Induces Proangiogenic Profiling of Cardiosphere-Derived Cell Secretome and Increases Its Ability to Stimulate Angiogenic Properties of Endothelial Cells.
Ischemic heart disease and its complications, such as myocardial infarction and heart failure, are the leading causes of death in modern society. The adult heart innately lacks the capacity to regenerate the damaged myocardium after ischemic injury. Multiple lines of evidence indicated that stem-cell-based transplantation is one of the most promising treatments for damaged myocardial tissue. Different kinds of stem cells have their advantages for treating ischemic heart disease. One facet of their mechanism is the paracrine effect of the transplanted cells. Particularly promising are stem cells derived from cardiac tissue per se, referred to as cardiosphere-derived cells (CDCs), whose therapeutic effect is mediated by the paracrine mechanism through secretion of multiple bioactive molecules providing immunomodulatory, angiogenic, anti-fibrotic, and anti-inflammatory effects. Although secretome-based therapies are increasingly being used to treat various cardiac pathologies, many obstacles remain because of population heterogeneity, insufficient understanding of potential modulating compounds, and the principles of secretome regulation, which greatly limit the feasibility of this technology. In addition, components of the inflammatory microenvironment in ischemic myocardium may influence the secretome content of transplanted CDCs, thus altering the efficacy of cell therapy. In this work, we studied how Tumor necrosis factor alpha (TNFa), as a key component of the pro-inflammatory microenvironment in damaged myocardium from ischemic injury and heart failure, may affect the secretome content of CDCs and their angiogenic properties. We have shown for the first time that TNFa may act as a promising compound modulating the CDC secretome, which induces its profiling to enhance proangiogenic effects on endothelial cells. These results allow us to elucidate the underlying mechanisms of the impact of the inflammatory microenvironment on transplanted CDCs and may contribute to the optimization of CDC efficiency and the development of the technology for producing the CDC secretome with enhanced proangiogenic properties for cell-free therapy.


Mechanism of gram variability in select bacteria.
Gram stains were performed on strains of Actinomyces bovis, Actinomyces viscosus, Arthrobacter globiformis, Bacillus brevis, Butyrivibrio fibrisolvens, Clostridium tetani, Clostridium thermosaccharolyticum, Corynebacterium parvum, Mycobacterium phlei, and Propionibacterium acnes, using a modified Gram regimen that allowed the staining process to be observed by electron microscopy (J. A. Davies, G. K. Anderson, T. J. Beveridge, and H. C. Clark, J. Bacteriol. 156:837-845, 1983). Furthermore, since a platinum salt replaced the iodine mordant of the Gram stain, energy-dispersive X-ray spectroscopy could evaluate the stain intensity and location by monitoring the platinum signal. These gram-variable bacteria could be split into two groups on the basis of their staining responses. In the Actinomyces-Arthrobacter-Corynebacterium-Mycobacterium-Propionibacterium group, few cells became gram negative until the exponential growth phase; by mid-exponential phase, 10 to 30% of the cells were gram negative. The cells that became gram negative were a select population of the culture, had initiated septum formation, and were more fragile to the stress of the Gram stain at the division site. As cultures aged to stationary phase, there was a relatively slight increase toward gram negativity (now 15 to 40%) due to the increased lysis of nondividing cells by means of lesions in the side walls; these cells maintained their rod shape but stained gram negative. Those in the Bacillus-Butyrivibrio-Clostridium group also became gram negative as cultures aged but by a separate set of events. These bacteria possessed more complex walls, since they were covered by an S layer. They stained gram positive during lag and the initial exponential growth phases, but as doubling times increased, the wall fabric underlying the S layer became noticeably thinner and diffuse, and the cells became more fragile to the Gram stain. By stationary phase, these cultures were virtually gram negative.


[Analysis of plasmid pUDKH by anion-exchange high performance liquid chromatogaphy].
pUDKH, a new plasmid DNA comprising human hepatocyte growth factor (HGF), was developed as a potential genetherapeutic product for peripheral arterial disease. An anion-exchange high performance liquid chromatographic (HPLC) method was developed to determine the proportion of plasmid DNA in both opened and supercoiled forms. A TSK gel DNA-NPR column was equilibrated with 50% buffer A (20 mmol/L Tris-HCl, pH 8.8) and 50% buffer B (buffer A with 1 mol/L NaCl added). pUDKH was analyzed by using a gradient HPLC with a mobile phase from 50% B to 80% B and with a UV detection at 260 nm. The flow rate was 0.5 mL/min. The method was also used to monitor the production procedures.


[The influence of 1-DOPA on emotional responses and serotonin metabolism in the rat brain].
Experiments were conducted on male Wistar rats. Intraperitoneal injection of 1-DOPA (.100 - 200 mg/kg increased the brain concentration of dopamine and homovanilinic acid and lowered the level of brain serotonin, with simultaneous elevation of its metabolite 5-HIAA. A decrease in serotonin level was accompanied by increased emotional reactivity and agressiveness in rats. L-DOPA (100 mg/kg) decreased the binding of serotonin formed from tryptophane (100 mg/kg), accelerating its catabolism in the brain; at the same time 1-DOPA eliminated the depressive action of tryptophane on the emotional reactivity and aggressiveness. It is supposed that increased emotional excitation elicited by 1-DOPA was partially mediated through the block of the serotoninergic system.


Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA).
This review summarizes the evidence for a hypertensinogenic effect of Erythropoietin (Epo) in normal human subjects and predialysis, hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD) patients. The possible mechanisms of Epo-induced hypertension are examined with in vivo animal and in vitro data, as well as pathophysiological human studies in both normal subjects and CKD patients. The evidence for a hypertensinogenic effect of erythropoiesis-stimulating agents (ESAs) in normal subjects, predialysis CKD, hemodialysis, and CAPD patients is compelling. Epo increases BP directly and notably independently of its erythropoietic effect and its effect on blood rheology. The potential for the development of future agents that might act as specific stimulators of erythropoiesis, devoid of direct hemodynamic side effects is underscored.


Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats.
Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10-1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats.


Scheuermann's kyphoscoliosis associated with Charcot-Marie-Tooth syndrome.
Much confusion and disagreement exists regarding the classification and characteristics of inherited disorders manifesting neurogenic muscular atrophy. Many authors consider Charcot-Marie-Tooth syndrome (CMTS) and Roussy Levy syndrome (RLS) forme fruste or variants of Friedreich's ataxia (FA). Familial kyphoscoliosis has often been described in FA and RLS but not with CMTS. The purpose of this paper is to present detailed clinical and laboratory findings in a family with three cases of Scheuermann's kyphoscoliosis and CMTS in three generations. In all cases Scheuermann's kyphoscoliosis was associated with pes cavus, markedly diminished vibratory and position sensation in the lower extremities, absent deep tendon reflexes and muscular atrophy, predominantly of the distal muscles. Fine rhythmic tremor of outstretched hands and positive Romberg sign were present in one case only. Serum creating phosphokinase was elevated in two cases. Motor nerve conduction studies revealed impaired function in the median, ulnar, tibial and peroneal nerves. Sensory nerve conduction wal also impaired in median and ulnar nerves. There was evidence of left ventricular hypertrophy in one case only. The nosology and relationship between CMTS, RLS and FA are discussed.


Protein-protein and protein-DNA interactions in the type I restriction endonuclease R.EcoR124I.
The type I restriction-modification system EcoR124I recognizes and binds to the split DNA recognition sequence 5'-GAAN(6)RTCG-3'. The methyltransferase, consisting of HsdM and HsdS subunits with the composition M2S, can interact with one or more subunits of the HsdR subunit to form the endonuclease. The interaction of the methyltransferase with HsdR has been investigated by surface plasmon resonance, showing that there are two non-equivalent binding sites for HsdR which differ in binding affinity by at least two orders of magnitude. DNA footprinting experiments using Exonuclease III suggest that the addition of HsdR to the methyltransferase (at a stoichiometry of either 1:1 or 2:1) increases the stability of the resulting DNA-protein complex but does not increase the size of the footprint. More extensive in situ footprinting experiments using copper-phenanthroline on the DNA-protein complexes formed by M2S, R1M2S and R2M2S also show no difference in the detailed cleavage pattern, with approximately 18 nucleotides protected on both strands in each complex. Thus the HsdR subunit(s) of the endonuclease stabilise the interaction of the M2S complex with DNA, but do not directly contribute to DNA binding. In addition, the thymidine nucleotide in the tetranucleotide recognition sequence GTCG is hyper-reactive to cleavage in each case, suggesting that the DNA structure in this region is altered in these complexes.


Formation of threohydrobupropion from bupropion is dependent on 11β-hydroxysteroid dehydrogenase 1.
Bupropion is widely used for treatment of depression and as a smoking-cessation drug. Despite more than 20 years of therapeutic use, its metabolism is not fully understood. While CYP2B6 is known to form hydroxybupropion, the enzyme(s) generating erythro- and threohydrobupropion have long remained unclear. Previous experiments using microsomal preparations and the nonspecific inhibitor glycyrrhetinic acid suggested a role for 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in the formation of both erythro- and threohydrobupropion. 11β-HSD1 catalyzes the conversion of inactive glucocorticoids (cortisone, prednisone) to their active forms (cortisol, prednisolone). Moreover, it accepts several other substrates. Here, we used for the first time recombinant 11β-HSD1 to assess its role in the carbonyl reduction of bupropion. Furthermore, we applied human, rat, and mouse liver microsomes and a selective inhibitor to characterize species-specific differences and to estimate the relative contribution of 11β-HSD1 to bupropion metabolism. The results revealed 11β-HSD1 as the major enzyme responsible for threohydrobupropion formation. The reaction was stereoselective and no erythrohydrobupropion was formed. Human liver microsomes showed 10 and 80 times higher activity than rat and mouse liver microsomes, respectively. The formation of erythrohydrobupropion was not altered in experiments with microsomes from 11β-HSD1-deficient mice or upon incubation with 11β-HSD1 inhibitor, indicating the existence of another carbonyl reductase that generates erythrohydrobupropion. Molecular docking supported the experimental findings and suggested that 11β-HSD1 selectively converts R-bupropion to threohydrobupropion. Enzyme inhibition experiments suggested that exposure to bupropion is not likely to impair 11β-HSD1-dependent glucocorticoid activation but that pharmacological administration of cortisone or prednisone may inhibit 11β-HSD1-dependent bupropion metabolism.


Indirect evidence for microbiota reduction through dietary mannanoligosaccharides in the pigeon, an avian species without functional caeca.
A feeding trial was conducted to evaluate the effects of mannanoligosaccharides (MOS) on nutrient digestibility, intestinal pH, gut morphology and faecal bacteriology of pigeons, as model for birds without functional caeca. Sixteen adult pigeons (Columba livia domestica) were randomly allotted to either an extruded pellet diet with or without 0.4% MOS. After an adaptation period of 24 days, excreta were collected during 4 days. Apparent nutrient digestibility coefficients were determined using total collection method. Further, excreta pH was measured and percentage of uric acid determined. Fresh excreta were cultured for measurement of colony-forming units for Escherichia coli. At the end, the gastrointestinal tract (GIT) was excised and pH measurements performed on the separate GIT sections. Finally, pancreas, liver, gizzard and abdominal fat pad were weighed, and standardised segments of duodenum and jejunum were removed for microscopic measurement of crypt depth, villus height and muscularis thickness. Feed intake and water intake were similar between control diet and MOS diet. Intestinal pH was unaffected by MOS supplementation; however, excreta pH was significantly lower in pigeons on the MOS diet. Although nutrient digestibility was similar between treatments, uric acid content of excreta was significantly higher in the MOS group in relation to the control group. Further, duodenal crypt depth, villus height and muscularis thickness, as well as jejunal muscularis thickness were all significantly reduced by MOS supplementation. No effect of MOS supplementation was seen on the counts of E. coli. Furthermore, despite marked differences on both GIT morphology and uric acid content of excreta, apparent digestibility coefficients, and organ weights, were similar between treatments. It is suggested that the MOS-induced changes on gut morphology and the reduced excreta pH reflect a reduced bacterial challenge in the intestine of pigeons. Supplementation of MOS, therefore, has potential as prebiotic strategy in birds without functional caeca.


Clinical and serologic study of Sjögren's syndrome in patients with progressive systemic sclerosis.
Fifty-eight patients with progressive systemic sclerosis (PSS) were evaluated clinically and by biopsy of the minor salivary glands of the lips for the presence of Sjögren's syndrome. Clinical findings included dry eyes in 38%, dry mouth in 32%, parotid enlargement in 4%, and an abnormal Schirmer's test in 34%. Histologic changes in lip biopsies included lymphocytic infiltrates characteristic of Sjögren's syndrome in 17 individuals (29%). In 19 (33%) there was periglandular and intraglandular fibrosis (PSS-fibrosis) without significant inflammation, an alteration characteristic of PSS per se. In the remaining 22 patients (38%) with PSS, no abnormality was found. Of those with PSS and Sjögren's syndrome, 53% had serum antibodies to SS-A and/or SS-B, while only 1 patient with a normal biopsy had either of these antibodies. Anti-SS-A and anti-SS-B were not detected in patients with glandular fibrosis alone. The mortality rate of the PSS-fibrosis group was higher due to a variety of severe internal manifestations related to PSS. Antibodies to SS-A and SS-B are useful serologic markers of the presence of Sjögren's syndrome in patients with PSS.


Preoperative embolization in the treatment of spinal metastasis.
Because of advances in the treatment of cancer, the average rate of patient survival is increasing. As patients with cancer live longer, the incidence of spinal metastasis also likely will increase. To help control pain and maintain function, some of these metastases will require surgical intervention. Because >60% of spinal metastases are hypervascular, preoperative embolization may be considered in order to decrease hemorrhage risk and improve outcomes. Embolization for spinal metastasis can be performed through the angiogram catheter. When such embolization is performed carefully, the complication rate is low.


Helping consumers to evaluate annual percentage rates (APR) on credit cards.
To help consumers make informed decisions, regulators often impose disclosure requirements on financial institutions. However, disclosures may not be informative for consumers if they contain difficult-to-evaluate attributes, such as annual percentage rates (APRs). To improve a consumer's ability to evaluate the relative attractiveness of products with difficult-to-evaluate attributes, evaluability theory suggests providing consumers with distributional information. Here, we tested whether credit card disclosures containing graphs of the distribution of APRs in the credit card market help consumers estimate the relative costs of credit and evaluate credit cards. In two studies, we found that consumers using standard credit card disclosures (without distributional information) underestimated the costs of credit card APRs relative to the market. We then built on the graph design literature to design different graphs for presenting distributional APR information. A comparison of the graphs we designed showed that a histogram was most successful at improving consumers' estimates of APR costs relative to the market and modifying consumers' evaluations of an expensive credit card. We discuss the implications of our findings for evaluability theory, graph design, and communication efforts that aim to provide consumers with meaningful financial disclosures. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Exploring the Effects of Prescribed Fire on Tick Spread and Propagation in a Spatial Setting.
Lyme disease is one of the most prominent tick-borne diseases in the United States, and prevalence of the disease has been steadily increasing over the past several decades due to a number of factors, including climate change. Methods for control of the disease have been considered, one of which is prescribed burning. In this paper, the effects of prescribed burns on the abundance of ticks present in a spatial domain are assessed. A spatial stage-structured tick-host model with an impulsive differential equation system is developed to simulate the effect that controlled burning has on tick populations. Subsequently, a global sensitivity analysis is performed to evaluate the effect of various model parameters on the prevalence of infectious nymphs. Results indicate that while ticks can recover relatively quickly following a burn, yearly, high-intensity prescribed burns can reduce the prevalence of ticks in and around the area that is burned. The use of prescribed burns in preventing the establishment of ticks into new areas is also explored, and it is observed that frequent burning can slow establishment considerably.


High frequency of virulence factor genes tdh, trh, and tlh in Vibrio parahaemolyticus strains isolated from a pristine estuary.
Virulence factor genes encoding the thermostable direct hemolysin (tdh) and the thermostable direct hemolysin-related hemolysin (trh) are strongly correlated with virulence of the emergent human pathogen Vibrio parahaemolyticus. The gene encoding the thermolabile hemolysin (tlh) is also considered a signature molecular marker for the species. These genes are typically reported in very low percentages (1 to 2%) of nonclinical strains. V. parahaemolyticus strains were isolated from various niches within a pristine estuary (North Inlet, SC) and were screened for these genes using both newly designed PCR primers and more commonly used primers. DNA sequences of tdh and trh were recovered from 48% and 8.3%, respectively, of these North Inlet strains. The recovery of pathogenic V. parahaemolyticus strains in such high proportions from an estuarine ecosystem that is virtually free of anthropogenic influences indicates the potential for additional, perhaps environmental roles of the tdh and trh genes.


Modification of the anterior iliofemoral approach to the hip.
This paper describes a modified iliofemoral surgical approach to the hip joint performed on 282 patients over a 26-year period. The surgical technique follows the anterior iliofemoral approach except that the lateral "bone overhang" of the iliac crest is osteotomized and dissected distally with the fascia lata to expose the hip capsule. The "six muscle glove" is sharply dissected off the greater trochanter, the hip capsule is opened and surgery is carried out, upon completion of which the operated leg is abducted. The osteotomized iliac crest bone-graft with the attached muscles is reapproximated to its anatomical position and fixed with permanent sutures through five holes drilled through the replaced bone graft and the intact ilium. The closure is rapidly performed, strong, and allows early functional return. Blood loss is relatively slight.


Preoperative Safety Briefing Project.
Increased media attention on surgical procedures that were performed on the wrong anatomic site or wrong patient has prompted the health care industry to identify and address human factors that lead to medical errors. To increase patient safety in the perioperative setting, our objective was to create a climate of improved communication, collaboration, team-work, and situational awareness while the surgical team reviewed pertinent information about the patient and the pending procedure. A team of doctors, nurses, and technicians used human factors principles to develop the Preoperative Safety Briefing for use by surgical teams, a briefing similar to the preflight checklist used by the airline industry. A six-month pilot of the briefing began in the Kaiser Permanente (KP) Anaheim Medical Center in February 2002. Four indicators of safety culture were used to measure success of the pilot: occurrence of wrong-site/wrong procedures, attitudinal survey data, near-miss reports, and nursing personnel turnover data. Wrong-site surgeries decreased from 3 to 0 (300%) per year; employee satisfaction increased 19%; nursing personnel turnover decreased 16%; and perception of the safety climate in the operating room improved from "good" to "outstanding." Operating suite personnel perception of teamwork quality improved substantially. Operating suite personnel perception of patient safety as a priority, of personnel communication, of their taking responsibility for patient safety, of nurse input being well received, of overall morale, and of medical errors being handled appropriately also improved substantially. Team members who work together and communicate well can quickly detect and more easily avoid errors. The Preoperative Safety Briefing is now standard in many operating suites in the KP Orange County Service Area. The concepts and design of this project are transferable, and similar projects are underway in the Departments of Radiology and of Labor and Delivery at KP Anaheim Medical Center.


Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.
The olfactory receptor (OR)-gene superfamily is the largest in the mammalian genome. Several of the human OR genes appear in clusters with > or = 10 members located on almost all human chromosomes, and some chromosomes contain more than one cluster. We demonstrate, by experimental and in silico data, that unequal crossovers between two OR gene clusters in 8p are responsible for the formation of three recurrent chromosome macrorearrangements and a submicroscopic inversion polymorphism. The first two macrorearrangements are the inverted duplication of 8p, inv dup(8p), which is associated with a distinct phenotype, and a supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent rearrangement and is associated with minor anomalies. We demonstrate that it is the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent 8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s originate consistently in maternal meiosis, we investigated the maternal chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of one subject with +der(8), by means of probes included between the two 8p-OR gene clusters. All the mothers were heterozygous for an 8p submicroscopic inversion that was delimited by the 8p-OR gene clusters and was present, in heterozygous state, in 26% of a population of European descent. Thus, inversion heterozygosity may cause susceptibility to unequal recombination, leading to the formation of the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements. Accordingly, it may be possible to develop a profile of the individual risk of having progeny with chromosome rearrangements.


Functional analysis of the α-1,3-glucan synthase genes agsA and agsB in Aspergillus nidulans: agsB is the major α-1,3-glucan synthase in this fungus.
Although α-1,3-glucan is one of the major cell wall polysaccharides in filamentous fungi, the physiological roles of α-1,3-glucan remain unclear. The model fungus Aspergillus nidulans possesses two α-1,3-glucan synthase (AGS) genes, agsA and agsB. For functional analysis of these genes, we constructed several mutant strains in A. nidulans: agsA disruption, agsB disruption, and double-disruption strains. We also constructed several CagsB strains in which agsB expression was controlled by the inducible alcA promoter, with or without the agsA-disrupting mutation. The agsA disruption strains did not show markedly different phenotypes from those of the wild-type strain. The agsB disruption strains formed dispersed hyphal cells under liquid culture conditions, regardless of the agsA genetic background. Dispersed hyphal cells were also observed in liquid culture of the CagsB strains when agsB expression was repressed, whereas these strains grew normally in plate culture even under the agsB-repressed conditions. Fractionation of the cell wall based on the alkali solubility of its components, quantification of sugars, and (13)C-NMR spectroscopic analysis revealed that α-1,3-glucan was the main component of the alkali-soluble fraction in the wild-type and agsA disruption strains, but almost no α-1,3-glucan was found in the alkali-soluble fraction derived from either the agsB disruption strain or the CagsB strain under the agsB-repressed conditions, regardless of the agsA genetic background. Taken together, our data demonstrate that the two AGS genes are dispensable in A. nidulans, but that AgsB is required for normal growth characteristics under liquid culture conditions and is the major AGS in this species.


No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).
Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients' immune systems remains undocumented. Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients. We performed a longitudinal analysis of the relationship between cannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy. Cannabis use was assessed using annual self-administered questionnaires in 955 patients (2386 visits) enrolled in the ANRS CO13-HEPAVIH cohort. The effect of cannabis use on circulating CD4 T-cell count and percentage was estimated using multivariate linear regression models with generalised estimating equations. Sensitivity analyses were conducted after excluding visits where (i) tobacco use and (ii) smoking >=10 tobacco cigarettes/day were reported. At the first visit, 48% of patients reported cannabis use during the previous four weeks, and 58% of these patients also smoked ≥10 tobacco cigarettes/day. After multiple adjustment, cannabis use was not significantly associated with either circulating CD4 T-cell count [model coefficient (95% confidence interval): 0.27 (-0.07; 0.62), P = 0.12] or percentage [-0.04 (-0.45; 0.36), P = 0.83]. Sensitivity analyses confirmed these results. Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients. In-depth immunological studies are needed to document whether cannabis has a harmful effect on CD4 levels in lungs and on cells' functional properties. [Marcellin F, Lions C, Rosenthal E, Roux P, Sogni P, Wittkop L, Protopopescu C, Spire B, Salmon-Ceron D, Dabis F, Carrieri MP, HEPAVIH ANRS CO13 Study Group. No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRSCO13-HEPAVIH French cohort). Drug Alcohol Rev 2017;36:227-238].


Transitioning Cell Culture CURE Labs from Campus to Online: Novel Strategies for a Novel Time.
Course-based undergraduate research experiences (CUREs) provide a way for students to gain research experience in a classroom setting. Few examples of cell culture CUREs or online CUREs exist in the literature. The Cell Biology Education Consortium (CBEC) provides a network and resources for instructors working to incorporate cell-culture based research into the classroom. In this article, we provide examples from six instructors from the CBEC network on how they structure their cell-culture CUREs and how they transitioned the labs to online in the spring semester of 2020. We intend for these examples to provide instructors with ideas for strategies to set up cell culture CUREs, how to change that design mid-term, and for creating online CUREs in the future.


Single-molecule RNA folding.
Single-molecule experiments significantly expand our capability to characterize complex dynamics of biological processes. This relatively new approach has contributed significantly to our understanding of the RNA folding problem. Recent single-molecule experiments, together with structural and biochemical characterizations of RNA at the ensemble level, show that RNA molecules typically fold across a highly rugged energy landscape. As a result, long-lived folding intermediates, multiple folding pathways, and heterogeneous conformational dynamics are commonly found for RNA enzymes. While initial results have suggested that stable secondary structures are partly responsible for the rugged energy landscape of RNA, a complete mechanistic understanding of the complex folding behavior has not yet been obtained. A combination of single-molecule experiments, which are well suited to analyze transient and heterogeneous dynamic behaviors, with ensemble characterizations that can provide structural information at a superior resolution will likely provide more answers.


Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes.
Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20-43 microM) increased with increasing glucose concentration (15-35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10-200 microM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15-35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. It is concluded that resorcinol inhibits glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding. The results indicate a link between glucuronidation and glucokinase translocation.


A novel cosmetic antifungal/anti-inflammatory topical gel for the treatment of mild to moderate seborrheic dermatitis of the face: an open-label trial utilizing clinical evaluation and erythema-directed digital photography.
Topical cosmetic agents may play a role in the management of facial seborrheic dermatitis by reducing inflammation and scale production. Advanced digital photography, equipped with technology able to provide a detailed evaluation of red skin components corresponding to vascular flare (erythema-directed digital photography), is a useful tool for evaluation of erythema in patients affected by inflammatory dermatoses. The aim of this study was to assess the efficacy and safety of a new cosmetic topical gel containing piroctone olamine, lactoferrin, glycero-phospho-inositol, and Aloe vera for the treatment of facial seborrheic dermatitis by clinical and advanced digital photography evaluation. An open-label, prospective, clinical trial was conducted on 25 patients with mild to moderate facial seborrheic dermatitis. Subjects were instructed to apply the gel twice daily for 45 days. The clinical efficacy was evaluated by measuring at baseline, at day 15 and 45 the degree of desquamation (by clinical examination) and erythema (by digital photography technology via VISIA-CR™ system equipped with RBX™), using a 5-point severity scale, and pruritus (by subject-completed Visual Analogue Scale; scale from 0 to 100 mm). Finally, at baseline and at the end of the study, IGA (Investigator Global Assessment) was performed using a 5-point severity scale (from 0 = worsening to 4 = excellent response). At the end of treatment, a significant reduction (P<0.001) of all considered parameters was observed. Moreover, an excellent response (>80% improvement) was recorded in 47.9% of patients, with no case of worsening. No signs of local intolerance were documented. The tested cosmetic topical gel was effective in treating mild to moderate seborrheic dermatitis of the face. Erythema-directed digital photography may represent a noteworthy tool for the therapeutic monitoring of facial seborrheic dermatitis and an important adjunct aid in the dermatologic clinical practice.


In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection.
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.


The Bristol Sponge Microbiome Collection: A Unique Repository of Deep-Sea Microorganisms and Associated Natural Products.
The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate novel products from marine organisms have, to date, focused predominantly on samples recovered from shallow seas. For this reason, the deep ocean remains a largely untapped resource of novel microbiological life and associated natural products. Here we report the establishment of the Bristol Sponge Microbiome Collection (BISECT), a unique repository of deep-sea microorganisms and associated metabolites isolated from the microbiota of marine sponges, recovered from previously unsurveyed regions of the mid Atlantic Ocean, at depths of 0.3-3 km. An integrated biodiscovery pipeline comprising molecular, genetic, bioinformatic and analytical tools is also described, which is being applied to interrogate this collection. The potential of this approach is illustrated using data reporting our initial efforts to identify antimicrobial natural product lead compounds. Prospects for the use of BISECT to address allied pharmaceutical needs, along with mechanisms of access to the collection are also discussed.


Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical laboratories.
A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.


Quantitative analysis of group II intron expression and splicing in Lactococcus lactis.
The group II intron Ll.ltrB is found within the ltrB relaxase gene of the conjugative element pRS01 in Lactococcus lactis. Precise splicing of the intron is essential for pRS01 transfer. The transcription regulation and in vivo splicing activity of Ll.ltrB have not been investigated thoroughly in L. lactis in the natural pRS01 context. We developed absolute quantitative real-time reverse transcription-PCR assays to quantify RNA levels of the 5' exon (ltrBE1) and the spliced relaxase (ltrB) and intron-encoded protein (ltrA) genes, as well as Ll.ltrB splicing activity under different physiological conditions. The mRNA levels for the ATP-binding protein OppD were assayed for comparison to the ltrB transcripts. The oppD mRNA ranged from 10- to 10,000-fold higher than ltrB region genes. ltrBE1 expression was growth-phase dependent. The mRNA level of ltrA was almost constant during all growth phases and in all media tested. Ll.ltrB in vivo splicing activity ranged from (6.5 +/- 2.1)% to (22.1 +/- 8.0)%. Acid challenge significantly decreased both ltrB region mRNA levels and intron splicing activity. The presence of recipient cells, different mating environments, and temperature stress had no significant effects on expression and splicing. Western blotting showed that the level of LtrB protein expressed from an intronless ltrB gene was much higher (about 20-fold) than the level of protein expressed from an intron-containing construct. Interestingly, LtrB protein showed a tendency to function in cis on its oriT target. The low level of ltrB transcript and relatively inefficient splicing of the intron may limit Ll.ltrB mobility and dissemination in nature.


[Public policies for the elderly in Brazil: an integrative review].
This paper is an integrative review analyzing the scientific production and legal documents regarding public policies for the elderly in Brazil. Research was conducted in the Virtual Health Library and Scopus databases, examining publications since 2003. Data were collected from June to September of 2011 using the following key words: "elderly" (idosos), "public policies" (políticas públicas), "elderly person" (pessoa idosa), "aging" (envelhecimento) and "civic participation" (participação cidadã). The search resulted in the selection of 15 articles and six legal documents targeted at the elderly in Brazil that were submitted to content analysis by categorization. The results revealed that aging in Brazil has occurred in the midst of adaptations entrenched in cultural biases, social, economic and educational discrepancies and the implementation of public welfare policies. There were few studies that indicated the importance of strengthening social movements that elicit discussion related to the elderly in Brazil. The conclusion reached is that the study will provide material for reflection about the construction of a new reality about aging in Brazil.


Double-attention Assisted Multi-task Learning for the Alzheimer's Disease Prediction from Mild Cognitive Impairment.
Alzheimer's disease (AD) is a progressive neurode-generative disease. Identifying the mild cognitive impairment (MCI) subjects who will convert to AD is essential for early intervention to slow the irreversible brain damage and cognitive decline. In this paper, we propose a novel double-attention assisted multi-task framework for the MCI conversion prediction task. By introducing an auxiliary grey matter segmentation task along with an adaptive dynamic weight average strategy to balance the impact of each task. Then, a double-attention module is incorporated to leverage both the classification and the segmentation attention information to guide the network to focus more on the structural alteration regions for better discrimination of AD pathology, as well as increase the interpretability of the network. Extensive experiments on a publicly available dataset demonstrate that the proposed method significantly outperforms the approaches using the same image modality.


Wolves in sheep's clothing: Is non-profit status used to signal quality?
Why do many firms in the healthcare sector adopt non-profit status? One argument is that non-profit status serves as a signal of quality when consumers are not well informed. A testable implication is that an increase in consumer information may lead to a reduction in the number of non-profits in a market. We test this idea empirically by exploiting an exogenous increase in consumer information in the US nursing home industry. We find that the information shock led to a reduction in the share of non-profit homes, driven by a combination of home closure and sector switching. The lowest quality non-profits were the most likely to exit. Our results have important implications for the effects of reforms to increase consumer provision in a number of public services.


Frequent association between MEN 2A and cutaneous lichen amyloidosis.
Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are genetic diseases due to activating mutations of the RET proto-oncogene. Affected patients develop medullary thyroid carcinoma (100%), in an isolated form (FMTC) or in association with phaeochromocytoma (30-50%), and primary hyperparathyroidism (10-20%) (MEN 2A). The presence of cutaneous lichen amyloidosis (CLA) has been anecdotally described in few families harbouring RET proto-oncogene mutation in codon 634. The aim of the study was to evaluate the incidence of CLA in MEN 2A/FMTC families. Ten MEN 2A/FMTC families were studied and RET gene mutations identified in all. Complete dermatological assessment was carried out in each family member. Skin biopsy for histological studies was performed in patients with CLA. Among 10 MEN 2A/FMTC families, the presence of CLA was found only in patients belonging to the three families with MEN 2A and RET mutation in codon 634. Nine of 25 patients (36%) with codon 634 mutation presented CLA, though two of them did not show CLA skin lesions but the typical neurological pruritus in the upper back. In all patients, neurological pruritus was present since infancy as a precocious marker of the disorder. The dermatological study of patients with CLA skin lesions added further evidence that pruritus has a pivotal role in the development of CLA, the amyloid deposition being the consequence of repeated scratching. Light microscopy revealed orthokeratotic hyperkeratosis, with elongation of the rete ridges, rare intramalpighian apoptic keratinocytes and deposits of amorphous material in the superficial dermis. Examination under ultraviolet light showed thioflavin T-positive staining, confirming the presence of amyloid in the papillary dermis. The use of Capsaicin at the dilution of 0.025% had a mild efficacy on the cutaneous symptoms. Among the members of the three families with MEN 2A and RET 634 mutation, the incidence of CLA was 36%, a figure similar to that reported in the literature for phaeochromocytoma (30-50%) and even higher than that for hyperparathyroidism (10-20%). The present data confirm that CLA is linked to codon 634 RET mutations and is a precocious marker of the disorder.


Bone substitutes in the Netherlands - a systematic literature review.
Autologous bone grafting is currently considered as the gold standard to restore bone defects. However, clinical benefit is not guaranteed and there is an associated 8-39% complication rate. This has resulted in the development of alternative (synthetic) bone substitutes. The aim of this systematic literature review was to provide a comprehensive overview of literature data of bone substitutes registered in the Netherlands for use in trauma and orthopedic surgery. Brand names of selected products were used as search terms in three available databases: Embase, PubMed and Cochrane. Manuscripts written in English, German or Dutch that reported on structural, biological or biomechanical properties of the pure product or on its use in trauma and orthopedic surgery were included. The primary search resulted in 475 manuscripts from PubMed, 653 from Embase and 10 from Cochrane. Of these, 218 met the final inclusion criteria. Of each product, structural, biological and biomechanical characteristics as well as their clinical indications in trauma and orthopedic surgery are provided. All included products possess osteoconductive properties but differ in resorption time and biomechanical properties. They have been used for a wide range of clinical applications; however, the overall level of clinical evidence is low. The requirements of an optimal bone substitute are related to the size and location of the defect. Calcium phosphate grafts have been used for most trauma and orthopedic surgery procedures. Calcium sulphates were mainly used to restore bone defects after tumour resection surgery but offer minimal structural support. Bioactive glass remains a potential alternative; however, its use has only been studied to a limited extent.


Beauty and the eye of the beholder: social consequences and personal adjustments for facial patients.
Patients' pre- and postoperative self-reports were compared with reports of non-medical observers to investigate whether improved self-esteem is a direct result of increased social acceptance in maxillo- and craniofacial patients. Twenty-two children and adolescents undergoing reconstructive surgery for a variety of facial deformities were asked to rate their physical appearance on the Hay's Scale and fill out the Piers-Harris Self-Concept Scale. Their ratings were compared with scores given by a panel of lay volunteers on random presentation of pre- and postoperative photographs of the same patients. Patients rated their appearance as noticeably improved after surgery, their self-esteem rose significantly and they reported more social adeptness and acceptance at home and school. Raters observed only relatively subtle changes. Apparently, quality of life improved for the postsurgical facial patient because of increased self-esteem and confidence, which free him to overcome social barriers.


Suppressive effects of exercise-conditioned serum on cancer cells: A narrative review of the influence of exercise mode, volume, and intensity.
Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.


Immune evasion by oncogenic proteins of acute myeloid leukemia.
PML-RARA and AML1-ETO are important oncogenic fusion proteins that play a central role in transformation to acute myeloid leukemia (AML). Whether these fusion proteins render the tumor cells with immune evasion properties is unknown. Here we show that both oncogenic proteins specifically downregulate the expression of CD48, a ligand of the natural killer (NK) cell activating receptor 2B4, thereby leading to decreased killing by NK cells. We demonstrate that this process is histone deacetylase (HDAC)-dependent, that it is mediated through the downregulation of CD48 messenger RNA, and that treatment with HDAC inhibitors (HDACi) restores the expression of CD48. Furthermore, by using chromatin immunoprecepitation (ChIP) experiments, we show that AML1-ETO directly interacts with CD48. Finally, we show that AML patients who are carrying these specific translocations have low expression of CD48.


Immunotherapy for the Treatment of Breast Cancer: Emerging New Data.
Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents. Immunotherapy has recently demonstrated significant breakthroughs in various types of cancers that are refractory to traditional therapies including melanoma and Non-Small Cell Lung Cancer (NSCLC). Breast cancer however remains one of the tumors that was initially least investigated because of being considered to have a low immunogenic potential and a low mutational load. Over the past few years, antiPD1/PDL1 drugs have started to make progress in the triple-negative subtype with more promising outcomes. In this report, we review the treatment of triple-negative breast cancer and specifically shed light on advances in immunotherapy and newly approved drugs in this challenging disease.


Effect of sodium hypochlorite on the bond strength of an adhesive system to superficial and deep dentin.
The objective of this study was to evaluate the bond strength to superficial (SU) and deep (D) dentin, accessed via apical (DA) or occlusal (DO), using One-Step adhesive system applied according to the manufacturer's instructions (C) or following deproteinization with 10% sodium hypochlorite (H) for 60s, after acid etching. Three sound extracted human molars were prepared for each experimental condition. Restorations were performed using Z100 in 2mm increments, each one being light-cured for 40s. Teeth were longitudinally sectioned to obtain stick-shaped specimens with a cross-sectional area of 0.8mm², which were submitted to bond strength test (0.6mm/min). Results obtained after statistical analysis using a two-way ANOVA (substrate vs. surface treatment) and Tukey's test were: SU (35.4 ± 12.3), DO (26.5 ± 8.5), DA (26.1 ± 10.2) following conventional surface treatment, and SU (28.82 ± 12.7), DO (24.3 ± 8.3) and DA (23.5 ± 8.5), after surface treatment using sodium hypochlorite. The interaction of the factors was not significant (p>0.05). However, the main factors were significant (p<0.05). Mean bond strength values in superficial dentin were statistically superior to deep dentin (p<0.05), although no statistically significant difference was observed between the two via of access to deep dentin (SU>DO=DA). The conventional surface treatment resulted in higher bond strength values than the sodium hypochlorite treatment (p<0.05). It was concluded: 1) bond strength values were higher in superficial dentin, 2) no difference was found between the two deep substrate preparations, and 3) the application of sodium hypochlorite following dentin acid etching may reduce bond strengths.