Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.
The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.


The effect of optimum, indication-specific imaging fields on the radiation exposure from CBCT examinations of impacted maxillary canines and mandibular third molars.
Objective Indication-specific optimum field-of-views (FOVs) have been assessed for CBCT scans of impacted maxillary canines and mandibular third molars, as 40∅ × 35 mm and 35∅ × 35 mm, respectively. The objective was to investigate possible changes in absorbed organs and effective doses, for these two imaging indications, performing CBCT examinations with optimum FOV sizes instead of commonly used FOVs. Additionally, radiation exposure-induced cancer risk was calculated for both imaging indications with optimum FOVs.Methods An adult female head phantom (ATOM 702-D, CIRS, Norfolk, VA, USA) was scanned using Planmeca Viso G7 CBCT-device (Planmeca, Helsinki, Finland). Scanning factors, different FOV sizes, dose-area product (DAP) values and anatomical FOV locations were used for Monte Carlo PCXMC-simulation and ImpactMC software. In the PCXMC- simulation, 10-year-old child and 30-year-old adult phantoms were used to estimating effective and absorbed organ doses.Results The effective dose varied from 58 µSv to 284 µSv for impacted maxillary canines, and from 38 µSv to 122 µSv for mandibular third molars, the lowest dose value for each corresponding to optimum FOV. Effective dose reduction between the optimum FOV and the smallest common FOV of 50∅ × 50 mm, maintaining other scanning factors constant, was 33% for impacted maxillary canines, and 45% for mandibular third molars. At all examinations, the highest absorbed organ doses were in salivary glands or in oral mucosa.Conclusions Optimum FOVs, 40∅ × 35 mm for impacted maxillary canine and 35∅ × 35 mm for mandibular third molar, could decrease effective doses received by young patients, and improve radiation safety in these common CBCT imaging procedures.


Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.
Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering. A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed. One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors. In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.


[Anthracycline-induced cardiotoxicity: report of fatal cases].
Anthracyclines are effective drugs in pediatrics cancer treatment. However, anthracycline-induced cardiotoxicity (AIC) is a serious adverse drug reaction that affects the survival in patients treated for childhood cancer. Case 1: Nine-year-old girl with stage IV Hodgkin lymphoma with 12 epirubicin doses and a cumulative dose of 576 mg/m2. After last chemotherapy dose, the patient was admitted with systemic inflammatory response, asthenia and adinamia. Echocardiography: LVEF of 22%, SF 11% and moderate mitral regurgitation. Patient died 2 days after diagnosed with dilated cardiomyopathy secondary to anthracyclines. Case 2: Fifteen-year-old girl with stage IV Burkitt lymphoma with two epirubicin doses and a cumulative dose of 90 mg/m2. After the last cycle, the patient developed several infectious foci. Echocardiography: LVEF of 49%, SF 20% and dilated left ventricle with septal flattening. Patient died 13 days after diagnosis of dilated cardiomyopathy by anthracyclines. AIC is a problem in pediatric patients receiving anthracyclines, monitoring is essential to detect the onset of cardiac damage to provide an intervention to prevent heart failure progress.


Using overseas registered nurses to fill employment gaps in rural health services: quick fix or sustainable strategy?
This study sought to identify and evaluate approaches used to attract internationally trained nurses from traditional and non-traditional countries and incentives employed to retain them in small rural hospitals in Gippsland, Victoria. An exploratory descriptive design. Small rural hospitals in Gippsland, Victoria. Hospital staff responsible for recruitment of nurses and overseas trained nurses from traditional and non-traditional sources (e.g. England, Scotland, India, Zimbabwe, Holland, Singapore, Malaysia). Recruitment of married overseas trained nurses is more sustainable than that of single registered nurses, however, the process of recruitment for the hospital and potential employees is costly. Rural hospitality diffuses some of these expenses by the employing hospitals providing emergency accommodation and necessary furnishings. Cultural differences and dissonance regarding practice create barriers for some of the overseas trained nurses to move towards a more sanguine position. On the positive side, single overseas registered nurses use the opportunity to work in rural Australian hospitals as an effective working holiday that promotes employment in larger, more specialized hospitals. Overall both the registered nurses and the employees believe the experience to be beneficial rather than detrimental.


[Clinical approach to constipation: proposal of a diagnostic and therapeutic protocol].
A study concerning constipation in children has been carried out in the University Department of Pediatrics and in the Division of Pediatric Surgery of Parma with the aim of reaching an homogeneus approach: it has been applied to 20 children up to now observed for such a problem. According to clinical and anamnestic criteria, children were divided into 3 groups on the basis of different degree of constipation: 1) moderate, 2) mild, 3) severe. Children belonging to the 2nd and 3rd group underwent barium enema and rectal manometry; two cases of ultrashort Hirschprung's disease and 7 cases of functional megarectum were diagnosed. Different treatment have been employed for each group and good results were observed in 18 cases. The AA. briefly discuss the different aspects concerning constipation and its therapy in childhood including diet, drugs, psychotherapy and surgical treatment.


Structural Engineering of the Barrier Oxide Layer of Nanoporous Anodic Alumina for Iontronic Sensing.
The hemispherical barrier oxide layer (BOL) closing the bottom tips of hexagonally distributed arrays of cylindrical nanochannels in nanoporous anodic alumina (NAA) membranes is structurally engineered by anodizing aluminum substrates in three distinct acid electrolytes at their corresponding self-ordering anodizing potentials. These nanochannels display a characteristic ionic current rectification (ICR) signal between high and low ionic conduction states, which is determined by the thickness and chemical composition of the BOL and the pH of the ionic electrolyte solution. The rectification efficiency of the ionic current associated with the flow of ions across the anodic BOL increases with its thickness, under optimal pH conditions. The inner surface of the nanopores in NAA membranes was chemically modified with thiol-terminated functional molecules. The resultant NAA-based iontronic system provides a model platform to selectively detect gold metal ions (Au3+) by harnessing dynamic ICR signal shifts as the core sensing principle. The sensitivity of the system is proportional to the thickness of the barrier oxide layer, where NAA membranes produced in phosphoric acid at 195 V with a BOL thickness of 232 ± 6 nm achieve the highest sensitivity and low limit of detection in the sub-picomolar range. This study provides exciting opportunities to engineer NAA structures with tailorable ICR signals for specific applications across iontronic sensing and other nanofluidic disciplines.


Immortalization and controlled in vitro differentiation of murine multipotent neural crest stem cells.
To isolate mouse neural crest stem cells, we have generated a rat monoclonal antibody to murine neurotrophin receptor (p75). We have immortalized p75+ murine neural crest cells by expression of v-myc, and have isolated several clonal cell lines. These lines can be maintained in an undifferentiated state, or induced to differentiate by changing the culture conditions. One of these cell lines, MONC-1, is capable of generating peripheral neurons, glia, and melanocytic cells. Importantly, most individual MONC-1 cells are multipotent when analyzed at clonal density. The neurons that differentiate under standard conditions have an autonomic-like phenotype, but under different conditions can express markers of other peripheral neuronal lineages. These lines therefore exhibit a similar differentiation potential as their normal counterparts. Furthermore, they can be genetically modified or generated from mice of different genetic backgrounds, providing a useful tool for molecular studies of neural crest development.


Predicting the microbial cause of community-acquired pneumonia: can physicians or a data-driven method differentiate viral from bacterial pneumonia at patient presentation?
Community-acquired pneumonia (CAP) requires urgent and specific antimicrobial therapy. However, the causal pathogen is typically unknown at the point when anti-infective therapeutics must be initiated. Physicians synthesize information from diverse data streams to make appropriate decisions. Artificial intelligence (AI) excels at finding complex relationships in large volumes of data. We aimed to evaluate the abilities of experienced physicians and AI to answer this question at patient admission: is it a viral or a bacterial pneumonia? We included patients hospitalized for CAP and recorded all data available in the first 3-h period of care (clinical, biological and radiological information). For this proof-of-concept investigation, we decided to study only CAP caused by a singular and identified pathogen. We built a machine learning model prediction using all collected data. Finally, an independent validation set of samples was used to test the pathogen prediction performance of: (i) a panel of three experts and (ii) the AI algorithm. Both were blinded regarding the final microbial diagnosis. Positive likelihood ratio (LR) values > 10 and negative LR values < 0.1 were considered clinically relevant. We included 153 patients with CAP (70.6% men; 62 [51-73] years old; mean SAPSII, 37 [27-47]), 37% had viral pneumonia, 24% had bacterial pneumonia, 20% had a co-infection and 19% had no identified respiratory pathogen. We performed the analysis on 93 patients as co-pathogen and no-pathogen cases were excluded. The discriminant abilities of the AI approach were low to moderate (LR+ = 2.12 for viral and 6.29 for bacterial pneumonia), and the discriminant abilities of the experts were very low to low (LR+ = 3.81 for viral and 1.89 for bacterial pneumonia). Neither experts nor an AI algorithm can predict the microbial etiology of CAP within the first hours of hospitalization when there is an urgent need to define the anti-infective therapeutic strategy.


The arachidonate-activatable, NADPH oxidase-associated H+ channel is contained within the multi-membrane-spanning N-terminal region of gp91-phox.
The generation of superoxide by the NADPH oxidase of neutrophils is accompanied by the efflux of H+ ions through a H+ channel. gp91-phox, a protein component of the oxidase, has been shown previously to function as a H+ channel [Henderson, Banting and Chappell (1995) J. Biol. Chem. 270, 5909-5916]. We have constructed a CHO cell line (CHO-N) that expresses an N-terminal fragment of gp91-phox containing the predicted multiple transmembrane domains of the protein. These cells exhibit H+ fluxes in response to an imposed proton motive force and in the presence of arachidonate (to open the channel). The H+ fluxes were indistinguishable from those observed in cells expressing full-length gp91-phox. Therefore the N-terminal 230 amino acids of gp91-phox contain all that is required to function as the NADPH oxidase-associated H+ channel.


Resilience and diabetes self-management among African-American men receiving primary care at an urban safety-net hospital: a cross-sectional survey.
Resilience is the ability to adapt to adverse life events. Studies that explore diabetes self-management interventions integrating resilience in African-Americans with diabetes include few African-American men, who have higher diabetes-related mortality and complication rates compared to African-American women. We conducted a cross-sectional study of African-American men with uncontrolled diabetes living in diabetes hotspots. We measured resilience levels using the General Self Efficacy Scale (GSES), adherence to diabetes self-management behaviors using the Diabetes Self-Management Questionnaire (DSMQ), and incarceration history by phone survey. We categorized participants as higher or lower resilience level and higher or lower adherence to diabetes self-management behaviors. Using multivariable logistic regression, we examined the relationship between resilience and adherence to diabetes self-management behaviors. Our model accounted for potential confounders, including age, incarceration history, and socioeconomic factors. Of 234 patients contacted by mail and phone, 94 (40.2%) completed the survey. Mean age was 60.6 years, 59.5% reported an annual household income of less than $20,000, and 29.8% reported a history of incarceration. The mean unadjusted GSES score was 25.0 (sd 5.2; range: 0-30, higher scores indicate greater resilience), and the mean DSMQ score was 7.34 (sd 1.78; range: 0-10, higher scores indicate greater adherence to diabetes self-management behaviors). In multivariable analyses, higher levels of resilience were associated with higher adherence to diabetes self-management behaviors (aOR = 9.68, 95% CI 3.01, 31.12). History of incarceration was negatively associated with higher adherence to diabetes self-management behaviors (aOR = 0.23, 95% CI 0.06, 0.81). Resilience and personal history of incarceration are associated with adherence to diabetes self-management behaviors among African-American men residing in diabetes hotspots. Future interventions should incorporate resilience training to improve diabetes self-management behaviors. At a societal level, social determinants of health that adversely affect African-American men, such as structural racism and mass incarceration, need to be eliminated.


Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.
G protein-coupled receptor kinase-6 (GRK6) is a serine/threonine kinase that is important in inflammatory processes. In this study, we examined the role of GRK6 in Escherichia coli-induced lung infection and inflammation using GRK6 knockout (KO) and wild-type (WT) mice. Intratracheal instillation of E. coli significantly enhanced bacterial load in the bronchoalveolar lavage (BAL) of KO compared with WT mice. Reduced bacterial clearance in the KO mice was not due to an intrinsic defect in neutrophil phagocytosis or killing but as a result of reduced neutrophil numbers in the KO BAL. Interestingly, neutrophil numbers in the lung were increased in the KO compared with WT mice, suggesting a potential dysfunction in transepithelial migration of neutrophils from the lungs to the bronchoalveolar space. This effect was selective for lung tissue because peritoneal neutrophil numbers were similar between the two genotypes following peritoneal infection. Although neutrophil expression of CXCR2/CXCR3 was similar between WT and KO, IL-17A expression was higher in the KO compared with WT mice. These results suggest that enhanced neutrophil count in the KO lungs but reduced numbers in BAL are likely due to transepithelial migration defect and/or altered chemokines/cytokines. Together, our studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.


[Update on the genetics of age-related macular degeneration].
The relationship between genetics and age-related macular degeneration is well established. Heritability has been estimated to be up to 70%. Recent studies have identified several chromosomal regions that are likely to contain susceptibility loci. Common variations in three genes (CFH, LOC 387715 and C2-FB) strongly influence the risk of age-related macular degeneration. New findings in the field of the genetics of age-related macular degeneration are a starting point toward understanding the causes of AMD and for future therapeutic studies.


Adjuvant Chemotherapy for Stage II and III Colon Cancer Following Complete Resection: A Cancer Care Ontario Systematic Review.
The objective of this systematic review was to provide current evidence regarding the use of adjuvant systemic chemotherapy for stage II and III colon cancer following curative intent surgery. MEDLINE and EMBASE databases and proceedings of American Society for Clinical Oncology and European Society of Medical Oncology/European Cancer Congress were searched through to August 2015. Systematic reviews (with or without meta-analyses) and randomised controlled trials were included. Patients with completely resected stage III colon cancer have an overall survival benefit from adjuvant chemotherapy. Combination chemotherapy (5-fluorouracil/leucovorin/oxaliplatin or capecitabine/oxaliplatin) provides a larger benefit than monotherapy but with additional toxicity. For stage II colon cancer, a clear overall survival benefit has not been shown. However, based on the subgroup analysis available, patients with high-risk stage II disease may benefit from adjuvant chemotherapy. Patients younger than 70 years of age may derive greater disease-free survival and overall survival benefit from adjuvant chemotherapy (in combination with oxaliplatin) compared with those older than 70 years. Stage II patients with microsatellite instability may have an overall survival detriment if given adjuvant chemotherapy.


Functional heartburn and non-erosive reflux disease.
Gastroesophageal reflux disease (GERD) is a common disorder in Western countries. For many years our attention has been focused on patients with erosive esophagitis, but in recent times we have realized that endoscopy-negative reflux disease is the most common presentation of this illness, affecting up to 70% of these individuals. Patients with the non-erosive form (NERD) are a heterogeneous group including various subpopulations with different mechanisms for their main symptom of heartburn: reflux of acidic and non-acidic gastric contents, mucosal hypersensitivity, intraesophageal distension by gas, intraduodenal infusion of fat, muscle contractions and psychological abnormalities. As to esophageal acid exposure, patients with NERD can be subdivided into those with abnormal and normal pH testing. The latter group includes patients with a positive correlation between symptoms and reflux events, in whom heartburn can be controlled by proton pump inhibitor (PPI) therapy. According to the recent Rome III criteria, they are still in the realm of GERD. An additional group is called functional heartburn, because this typical symptom is associated neither with an abnormal pH test nor with a positive symptom index. Their response to PPIs is very disappointing. Therefore, there is an increasing consensus on the fact that they do not have GERD and should be treated with drugs other than PPIs.


What becomes of medical students: the dark side.
In the cohort of 1337 former Johns Hopkins medical students from the classes of 1948 through 1964, there were 1248 graduates and 89 nongraduates. In follow-up studies of this cohort, 49 subjects, 3.1% of the graduates and 11.2% of the nongraduates, have been found to have died prematurely. Incipient mental illness and emotional disturbance appear to have contributed substantially to academic failure, poor performance during and after medical school, and premature death. These findings underscore the need for learning to identify and help medical students who are especially vulnerable to stress. Such insights would contribute to the prevention of premature disease and death, not only from mental illness but from other disorders.


Modulation of transport at the interface in the microporous layer for high power density proton exchange membrane fuel cells.
The proton exchange membrane (PEM) fuel cell is a device that demonstrates a significant potential for environmental sustainability, since it efficiently converts chemical energy into electrical energy. The microporous layer (MPL) in PEM fuel cells promotes gas transport and eliminates water. Nevertheless, the power density of PEM fuel cells is restricted by ohmic losses and mass transport losses in conventional MPLs. In this study, we enhanced the power density of proton exchange membrane (PEM) fuel cells through the identification of appropriate materials and the mitigation of mass transport losses occurring at the interface between the microporous layer and the catalyst layer. The incorporation of high electron conductivity, slip behavior at the interface between graphene and water, and rapid water evaporation facilitated by nanoporous graphene effectively address transport-related challenges. We evaluated two types of graphene as potential substitutes for carbon black in the microporous layer (MPL). The enhanced power density (up to 1.1 W cm-2) under all humidity conditions and reduced mass transport resistance (a 75 % reduction compared to carbon black MPL) make them promising candidates for next-generation PEM fuel cells. Furthermore, these findings provide guidance for controlling interfacial mass transport in colloidal systems.


Oxadiazole Derivatives as Anticancer and Immunomodulatory Agents: A Systematic Review.
Tumor plasticity processes impact the treatment of different types of cancer; as an effect of this, the bioprospecting of therapies from natural and/or synthetic compounds that can regulate or modulate the immune system has increased considerably. Oxadiazole derivatives are structures that exhibit diverse biological activities. Therefore, this review aimed to evaluate the activity of oxadiazole compounds against tumor cell lines and their possible immune-mediated mechanisms. A search in PubMed, Web of Science, and Science Direct databases was carried out on studies published from January 1, 2004, to January 31, 2022, using "oxadiazole" in combination with the other descriptors "cancer" and "macrophage". Only experimental in vitro and in vivo articles were included. A similar search strategy was used in the Derwent Innovation Index database for technology mapping. The search was performed on Drugbank using the descriptor oxadiazole for commercial mapping. 23 oxadiazole studies were included in this review, and some biological activities linked to antitumoral and immunomodulation were listed. Oxadiazole derivatives inhibited tumor cell growth and proliferation, blocked cell cycle, modulated mitochondrial membrane potential, presented immunoregulatory activity by different mechanisms reducing proinflammatory cytokines levels and acted directly as selective inhibitors of the COX enzyme. There was an increase in oxadiazole patent publications in the last 11 years, with emphasis on chemistry, pharmacy and biotechnology applied to microbiology areas. Compounds with 1,2,4-oxadiazole isomer are predominant in patent publications and approved drugs as observed in the technological and commercial mapping. Therefore, oxadiazole derivatives are therapeutic molecules that can be considered promising for the development of cancer therapies.


Osteoid osteoma treated with radiofrequency ablation in non-operating room anesthesia. A different way of approaching ablative therapy on osteoid osteoma.
The purpose of this study is to verify the effectiveness and complications occurrence of radiofrequency ablation (RFA) in the treatment of osteoid osteoma (OO) in non-operating room anesthesia (N.O.R.A.). From 2014 to 2017, 61 patients affected by OO (40 men and 21 women) with an age of 20.7 years on average (range, 4-51 years; 12 patients aged 20 years or younger) underwent computed tomography-guided percutaneous radiofrequency ablation (RFA) in N.O.R.A. (Non-Operating Room Anesthesia). Lesion sites treated were: femur (27), tibia (22), pelvis (2), talar bone (3), distal radius (1), and humerus (6). Mean follow-up time was 36 months. In each case, anesthesiologic support followed a new protocol (N.O.R.A. protocol), approved by our Institute. Primary success rate, complications, symptom-free intervals, and follow-up results were evaluated. Pain relief (evaluated with Visual Analogue Scale - VAS) was significant in 97% of patients; it disappeared within 24 hours of the procedure in 44 patients, within 3 days in 10 patients, and within 7 days in 7 patients. After 6 months of observation time, 60 of 61 patients were successfully treated and had no more complaints. In 2 patients, two major complications were found: infection of the site treated, healed with antibiotics, and a nerve lesion, healed with steroid therapy. No other complications were observed. RFA is a highly effective, efficient, minimally invasive and safe method for the treatment of OO following N.O.R.A.


[Normalizing effect of interferon on the system of mixed-function oxidases in the liver of mice with Lewis lung carcinoma].
The effect of interferon (IF) on the activity of multipurpose hepatic oxidases (MHO) in animals in the process of metastatic tumour development as well as interaction of IF and vinblastine (VBL) in the cell culture have been studied. IF activates MHO under conditions of their inhibition at the beginning of the tumour development and inhibits them to the normal level under activation in the postmetastatic period. Contrary to the data obtained in vivo IF does not decrease the toxicity of VBL for the tumour cells in vitro. The data obtained evidence for the modulating effect of IF on the MHO system under the tumour development.


[Disseminated inflammatory tinea: An unusual presentation.].
Tinea incognito represents a new entity caused basically by the careless application of corticosteroidal creams. We present a 71-year-old man with disseminated erythematous and squamous lesions treated with corticosteroid creams for seven months; the clinical aspect worsened and new pustular lesions appeared. The diagnosis of disseminated inflammatory tinea was confirmed by culture, with the growth of Trichophyton mentagrophytes. We comment on the clinical findings and the factors that contribute to spread the process.


[Application of advanced engineering technologies to medical and rehabilitation fields].
The words "Japan syndrome" can now be heard increasingly through the media. Facing the approach of an elderly-dominated society, Robot Technology(RT)is expected to play an important role in Japan's medical, rehabilitation, and daily support fields. The industrial robot, which has already spread through the world with a great success in certain isolated environments by doing the work which is specialized for the thing with the hard known characteristic. By comparison, in the medical and rehabilitation fields, environments always change intricately, and individual characteristics differ from person to person. Furthermore, there are many times when a robot will be asked to directly interact with people. Moreover, the relation between a robot and a person turns into a relation which should involve contact flexibly according to a situation, and also turns into a relation which should avoid contact. In our group, we have so far developed practical rehabilitation and medical robots which can respond to difficulties such as environmental change and individual specificity. In developing rehabilitation robots, it is especially important to consider intuitive operability and individual differences. In addition, in developing medical robots, it is important to replace the experimental knowledge of surgeons to the mechanical quantitative properties. In this article, we introduce some practical examples of rehabilitation and medical robots interweaving several detailed technologies we have so far developed.


Effect of different drugs and drug combinations on killing stationary phase and biofilms recovered cells of Bartonella henselae in vitro.
Bartonella henselae is a Gram-negative bacterium transmitted to humans by a scratch from cat in the presence of ectoparasites. Humans infected with B. henselae can result in various clinical diseases including local lymphadenopathy and more serious systemic disease such as persistent bacteremia and endocarditis. The current treatment of persistent B. henselae infections is not very effective and remains a challenge. To find more effective treatments for persistent and biofilm Bartonella infections, in this study, we evaluated a panel of drugs and drug combinations based on the current treatment and also promising hits identified from a recent drug screen against stationary phase and biofilm recovered cells of B. henselae. We evaluated 14 antibiotics and 25 antibiotic combinations for activity against stationary phase B. henselae (all antibiotics were at 5 μg/ml) and found that ciprofloxacin, gentamicin, and nitrofurantoin were the most active agents, while clofazimine and miconazole had poor activity. Drug combinations azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, and rifampin/methylene blue could rapidly kill stationary phase B. henselae with no detectable CFU after 1-day exposure. Methylene blue and rifampin were the most active agents against the biofilm B. henselae after 6 days of drug exposure. Antibiotic combinations (azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, rifampin/methylene blue) completely eradicated the biofilm B. henselae after treatment for 6 days. These findings may facilitate development of more effective treatment of persistent Bartonella infections in the future.


Novel approaches for preventing or limiting events in diabetic patients (Naples-diabetes) trial: a randomized comparison of 3 drug-eluting stents in diabetic patients.
To expand the paucity of data on the efficacy of various drug-eluting stents in diabetic patients. Type 2 diabetic patients treated in our institution from October 2005 to January 2007 presenting with of de novo lesions in native coronary arteries were randomly assigned to sirolimus-eluting stents (Cypher group; n=76); paclitaxel-eluting stents (Taxus group; n=75); and everolimus-eluting stents (Endeavor group; n=75). Poor metabolic control (HbA1c >7% and low-density lipoprotein cholesterol >100 mg/dL) and microvascular complications (retinopathy and/or nephropathy) were assessed. The primary end point was the 3-year composite of major adverse cardiac events (MACE), including death of any cause, myocardial infarction, and clinically driven target vessel revascularization. MACE-free survival was 86.8% in the Cypher group, 82.5% in the Taxus group, and 64.4% in the Endeavor group (P=0.006 by log-rank test). The post hoc comparisons showed no significant difference between Cypher versus Taxus groups (adjusted P=1.0) but a higher MACE rate in the Endeavor group versus both the Cypher group (adjusted P=0.012) and the Taxus group (adjusted P=0.075). Independent predictors of 3-year MACE at Cox analysis were treatment by Endeavor versus Cypher stent (2.35 [95% confidence interval, 1.07 to 5.41]; P=0.030), multivessel disease (hazard ratio, 1.78 [95% confidence interval, 1.06 to 2.66]; P=0.031), diabetic retinopathy (hazard ratio, 1.60; [95% confidence interval, 1.03 to 2.76]; P=0.038), and poor metabolic control (hazard ratio, 1.60; [95% confidence interval, 1.02 to 2.52]; P=0.048). The present pilot study suggests that in diabetic patients, the Endeavor stent is associated with a higher 3-year MACE rate when compared with Cypher and Taxus stents.


Relationship between Intralipid-induced hyperlipemia and pulmonary function.
One unit (500 ml) of 10% Intralipid (an intravenous soy bean oil-egg yolk lecithin preparation) was infused into 20 normal subjects over 4 hr. Serum triglyceride concentration and plasma optic density (at 700 nm) increased to maximal levels of 339 +/- 102 mg/100 ml and 1.14 +/- 0.41, respectively, at the completion of the infusion, and returned to basal levels in most subjects within 4 hr. Pulmonary membrane diffusion was decreased in six subjects at rest and with exercise at 25 and 50% maximum oxygen uptake. Only one subject showed a minor change in PO2 and none showed clinical signs of ischemia. The changes in pulmonary diffusion reverted to basal levels when serum lipids were cleared. Heparin (60 IU/kg) prevented the marked increase in serum lipids and, as a consequence, the changes in pulmonary function. Changes in pulmonary function from Intralipid-induced lipemia are similar to those known to result from diet-induced lipemia. The findings suggest that in the presence of normal vasculature and pulmonary function, Intralipid-induced lipemia should cause no clinical consequences. However, patients with preexisting pulmonary or vascular disease may be at greater risk after Intralipid-induced lipemia.


Liquid crystal holographic configurations for optically reconfigurable gate arrays.
An optically reconfigurable gate array (ORGA) system, which consists of an ORGA very large scale integration (VLSI), an easily rewritable liquid crystal holographic memory recording four configuration contexts, and a laser array, is proposed. Circuits on a gate array of the ORGA-VLSI can be programmed rapidly by exploiting large parallel connections between a holographic memory and a gate array VLSI; that programming can be executed even as it is being programmed. Consequently, the gate array can be switched from a certain circuit to another circuit instantaneously. We present a demonstration of the ORGA system and experimental results.


Mutations in the conserved carboxy-terminal hydrophobic region of glycoprotein gB affect infectivity of herpes simplex virus.
Glycoprotein gB is the most highly conserved glycoprotein in the herpesvirus family and plays a critical role in virus entry and fusion. Glycoprotein gB of herpes simplex virus type 1 contains a hydrophobic stretch of 69 aa near the carboxy terminus that is essential for its biological activity. To determine the role(s) of specific amino acids in the carboxy-terminal hydrophobic region, a number of amino acids were mutagenized that are highly conserved in this region within the gB homologues of the family HERPESVIRIDAE: Three conserved residues in the membrane anchor domain, namely A786, A790 and A791, as well as amino acids G743, G746, G766, G770 and P774, that are non-variant in Herpesviridae, were mutagenized. The ability of the mutant proteins to rescue the infectivity of the gB-null virus, K082, in trans was measured by a complementation assay. All of the mutant proteins formed dimers and were incorporated in virion particles produced in the complementation assay. Mutants G746N, G766N, F770S and P774L showed negligible complementation of K082, whereas mutant G743R showed a reduced activity. Virion particles containing these four mutant glycoproteins also showed a markedly reduced rate of entry compared to the wild-type. The results suggest that non-variant residues in the carboxy-terminal hydrophobic region of the gB protein may be important in virus infectivity.


Role of eicosanoids, histamine, and serotonin in the pathogenesis of Klebsiella pneumoniae-induced bovine mastitis.
By inoculating Klebsiella pneumoniae into the teat canals of mammary glands, coliform mastitis was induced experimentally in 6 lactating cows. Release of eicosanoids, histamine, and serotonin in plasma and milk was studied in response to 2 doses of K pneumoniae. A low dose (mean, 5,000 organisms/ml) was inoculated into cows 1 through 4, and a high dose (mean, 200,000 organisms/ml) was inoculated into cows 5 and 6. Milk and blood samples were collected before inoculation (0 hours), and hourly, from 3 to 24 hours after inoculation. Concentrations of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E (PGE), thromboxane B2 (TxB2), histamine, and serotonin were measured in plasma and milk obtained from control (NaCl solution-inoculated) and infected quarters. Fluorometric analysis of milk from infected quarters revealed significantly increased histamine and serotonin concentrations regardless of the dose of K pneumoniae. The mean (+/- SEM) peak concentrations of histamine were significantly (P less than 0.01) increased from the preinoculation value of 44 (+/- 12) ng/ml to 312 (+/- 104) ng/ml in milk from infected quarters and 72 (+/- 24) ng/ml in milk from control quarters. The mean peak concentration of serotonin increased significantly from the preinoculation concentration of 436 (+/- 37) ng/ml to 1,754 (+/- 662) ng/ml and 4,867 (+/- 1,248) ng/ml in milk from control (P less than 0.02) and infected (P less than 0.001) quarters, respectively. However, serotonin concentration in milk from infected quarters was approximately 2.8 times greater than that in milk from control quarters. Concentrations of PGF2 alpha, PGE, and TxB2 in milk and plasma were evaluated by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)


Neonatal infections in Asia.
To study the epidemiology (including incidence, antibiotic sensitivity and mortality) of neonatal unit infections in countries in Asia. One year prospective study of neonatal infections in eight neonatal units in Asia. There were 453 episodes of sepsis affecting 394 babies. Mortality from neonatal sepsis was 10.4%, with an incidence of 0.69 deaths/1000 live births. Group B streptococcus was the most common early-onset organism causing 38% of episodes of early-onset (<48 h old) sepsis, with a rate of 0.51 episodes per 1000 live births and a mortality of 22%. Gram-negative bacillary early-onset sepsis occurred at a rate of 0.15 episodes per 1000 live births with a mortality of 12%. There were 406 episodes of late-onset sepsis. The incidence was high at 11.6 per 1000 live births, and mortality was 8.9%. Coagulase-negative staphylococcus caused 34.1% of episodes, whereas Staphylococcus aureus caused only 5.4%. Gram-negative bacilli caused 189 episodes (46.6%). Only 44% of Gram-negative bacilli were sensitive to both gentamicin and a third-generation cephalosporin, whereas 30% were resistant to both antibiotics. Meningitis occurred in 17.2% of episodes of late sepsis, with a mortality of 20%. The incidence of late-onset sepsis was higher in Asia than in resource-rich countries, but the organisms isolated and mortality were similar. Over half of all Gram-negative bacilli were antibiotic resistant.


A culture system to study oligodendrocyte myelination processes using engineered nanofibers.
Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.


Phylogenetic relationships among cirrate octopods (Mollusca: Cephalopoda) resolved using mitochondrial 16S ribosomal DNA sequences.
PHYLOGENETIC RELATIONSHIPS AMONG THE CIRRATE OCTOPODS (MOLLUSCA: Cephalopoda) were investigated using partial sequences of the 16S rRNA mitochondrial gene. The derived phylogeny supports the traditional separation of cirrate families based on web form. Genera with a single web (Opisthoteuthis, Grimpoteuthis, Luteuthis, and Cirroctopus) are clearly distinct from those with an intermediate or secondary web (Cirroteuthis, Cirrothauma, and Stauroteuthis). The cirrates with a single web are separated into three groups. The first group is represented by Opisthoteuthis species, the second by Grimpoteuthis and Luteuthis, and the third by members of the genus Cirroctopus. There is no support for the isolation of Luteuthis in a separate family (Luteuthidae). There is, however, evidence of two groupings within the genus Opisthoteuthis. The data suggest the following revisions in the systematic classification of the cirrates: (1) Cirrothauma, Cirroteuthis, and Stauroteuthis be united in the Cirroteuthidae; (2) Grimpoteuthis and Luteuthis be placed in the Grimpoteuthidae; (3) Opisthoteuthis in the Opisthoteuthidae, and; (4) Cirroctopus be considered sufficiently distinct from both Opisthoteuthidae and Grimpoteuthidae to warrant placement in a new family.


Feasibility and acceptability of family administration of delirium detection tools in the intensive care unit: a patient-oriented pilot study.
Family-administered delirium detection tools may serve as valuable diagnostic adjuncts because family caregivers may be better able than providers to detect changes in patient cognition and behaviour from pre-illness levels of functioning. The aim of this pilot study was to assess the feasibility and acceptability of family-administered tools to detect delirium in critically ill patients. In this single-centre pilot tool validation study conducted in August and September 2017, eligible family caregivers used the Family Confusion Assessment Method (FAM-CAM) and the Sour Seven questionnaire to detect delirium during the patient's intensive care unit (ICU) stay. We calculated descriptive statistics for all study variables. Patients and family caregivers were involved as research partners throughout the study. A patient-orient research approach was taken, engaging patients and family caregivers as full partners. Of 141 patients admitted to the ICU, 75 were eligible, of whom 53 were approached; 21 patients (40%), 23/38 family caregivers (60%) and 17/38 dyads (i.e., patient and family caregiver enrolled together) (45%) consented to participate. The most common reason for nonenrolment was refusal by the family, who commonly reported feeling overwhelmed. The completion rate for the FAM-CAM and Sour Seven questionnaire was 74% (17/23). Among 13 dyads, family caregivers detected delirium in 5 patients (38%) using the FAM-CAM, and delirium or possible delirium in 8 patients (62%) using the Sour Seven questionnaire, whereas trained research assistants detected delirium in 8 patients (62%) using the Confusion Assessment Method for the Intensive Care Unit 7 and the Richmond Agitation-Sedation Scale (κ coefficient for agreement between the former and the FAM-CAM and Sour Seven questionnaire 0.62 and 0.85, respectively). Administration of the FAM-CAM and Sour Seven questionnaire by family caregivers to detect delirium in the ICU is feasible and acceptable, although, as with most family engagement strategies, it was not desired by all. Results from this pilot study support a definitive study with a larger sample to enable calculation of inferential statistics, but additional recruitment strategies are necessary to improve the response rate. Trial registration: Clinicaltrials.gov, no. NCT03379129.


The experience of accommodating privacy restrictions during implementation of a large-scale surveillance study of an osteoporosis medication.
To explore whether privacy restrictions developed to protect patients have complicated research within a 15-year surveillance study conducted with US cancer registries. Data from enrolling 27 cancer registries over a 10-year period were examined to describe the amount of time needed to obtain study approval. We also analyzed the proportion of patients that completed a research interview out of the total reported by the registries and examined factors thought to influence this measure. The average length of the research review process from submission to approval of the research was 7 months (range, <1 to 24 months), and it took 6 months or more to obtain approval of the research at 41% of the cancer registries. Most registries (78%) required additional permission steps to gain access to patients for research. After adjustment for covariates, the interview response proportion was 110% greater (ratio of response proportion = 2.1; 95% confidence interval: 1.3, 3.3) when the least restrictive versus the most restrictive permission steps were required. An interview was more often completed for patients (or proxies) if patients were alive, within a year of being diagnosed, or identified earlier in the study. Lengthy research review processes increased the time between diagnosis and provision of patient information to the researcher. Requiring physician permission for access to patients was associated with lower subject participation. A single national point of entry for use of cancer registry data in health research is worthy of consideration to make the research approval process efficient. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.


The covalent structure of an entire gammaG immunoglobulin molecule.
The complete amino acid sequence of a human gammaG1 immunoglobulin (Eu) has been determined and the arrangement of all of the disulfide bonds has been established. Comparison of the sequence with that of another myeloma protein (He) suggests that the variable regions of heavy and light chains are homologous and similar in length. The constant portion of the heavy chain contains three homology regions each of which is similar in size and homologous to the constant region of the light chain. Each variable region and each constant homology region contains one intrachain disulfide bond. The half-cystines participating in the interchain bonds are all clustered within a stretch of ten residues at the middle of the heavy chains.These data support the hypothesis that immunoglobulins evolved by gene duplication after early divergence of V genes, which specified antigen-binding functions, and C genes, which specified other functions of antibody molecules. Each polypeptide chain may therefore be specified by two genes, V and C, which are fused to form a single gene (translocation hypothesis). The internal homologies and symmetry of the molecule suggest that homology regions may have similar three-dimensional structures each consisting of a compact domain which contributes to at least one active site (domain hypothesis). Both hypotheses are in accord with the linear regional differential of function in antibody molecules.


Extended MRI findings of intersection syndrome.
The symptoms and physical findings of intersection syndrome have been well described in the clinical medical literature. However, the magnetic resonance imaging (MRI) findings in patients with intersection syndrome of the forearm have only recently been described in a small number of patients. We review our experience with imaging of intersection syndrome, describe previously unreported MRI findings, and emphasize modifications to MRI protocols for its evaluation. Institutional review board approval was obtained for this retrospective review of patients with MRI findings consistent with intersection syndrome of the forearm during the period from January 2004 to September 2006. Six patients were identified, three males and three females, with an average age of 39.3 years. The MRI examinations were reviewed to assess signal abnormalities within and adjacent to the first and second dorsal extensor tendon compartments (DETC): tendinosis, peritendinous edema or fluid, muscle edema, subcutaneous edema, and juxtacortical edema. The overall longitudinal extent of signal alterations was measured as well as the distance from Lister's tubercle to the crossover of the first and second DETC. Review of the MRIs showed increased intrasubstance tendon signal suggesting tendinosis in two of the six patients, peritendinous edema or fluid in all six patients, muscle edema in five of the six patients, and subcutaneous edema in three of the six patients. Juxtacortical edema was seen in one patient. Peritendinous edema or fluid extended distally beyond the radiocarpal joint in three of the six patients. The average distance from Lister's tubercle to the crossover of the first and second DETC was 3.95 cm, in keeping with recently published data. Intersection syndrome is an uncommon MRI diagnosis. In addition to the previously described MRI findings of edema adjacent to the first or second DETC, possibly with proximal extension and subcutaneous edema, we have identified additional abnormalities: tendinosis, muscle edema, and juxtacortical edema. In addition, our review shows that first and second DETC signal abnormalities in patients with intersection syndrome are not necessarily limited to the site of crossover but can extend distally beyond the radiocarpal joint. As standard wrist protocols may not include the area of intersection between the first and second DETC, coverage may need to be extended to the mid-forearm.


Switching ferroelectric domain configurations using both electric and magnetic fields in Pb(Zr,Ti)O3-Pb(Fe,Ta)O3 single-crystal lamellae.
Thin single-crystal lamellae cut from Pb(Zr,Ti)O3-Pb(Fe,Ta)O3 ceramic samples have been integrated into simple coplanar capacitor devices. The influence of applied electric and magnetic fields on ferroelectric domain configurations has been mapped, using piezoresponse force microscopy. The extent to which magnetic fields alter the ferroelectric domains was found to be strongly history dependent: after switching had been induced by applying electric fields, the susceptibility of the domains to change under a magnetic field (the effective magnetoelectric coupling parameter) was large. Such large, magnetic field-induced changes resulted in a remanent domain state very similar to the remanent state induced by an electric field. Subsequent magnetic field reversal induced more modest ferroelectric switching.


Diaphragmatic hernia mimicking hydropneumothorax: common error in emergency department.
Detection of diaphragmatic hernia in the acute setting is problematic and diagnosing diaphragmatic hernia as hydropneumothorax is not an uncommon mistake. We present a series of four such cases diagnosed over a 7-year period, from December 2004 to January 2011 and analyse them for how this mistake can be avoided. In case of all the patients reported by us the initial radiographs were technically compromised because the patient could not be positioned properly. Also they were examined by non-radiologists. We feel that treating surgeons in emergency department tend to overdiagnose pneumothorax as it is a life-threatening condition. We feel that in the appropriate setting suspicion of diaphragmatic hernia should be raised in patients having fractured ribs associated with homogenous opacity, which cannot be differentiated from the diaphragm. Evidence of loculation of hydropneumothorax in the appropriate setting should also raise the possibility of diaphragmatic hernia.


Mechanism of efflux of melphalan from L5178Y lymphoblasts in vitro.
The mechanism of efflux of melphalan from L5178Y lymphoblasts in vitro was investigated. Evidence was obtained that drug efflux occurs by a process different from the influx mechanism. A time course of efflux followed a first-order process for at least 5 min, with a rate constant K of 0.13 +/- 0.05 (S.D.) min-1, and approximately 80% of drug taken up by the cells was exchangeable. From a kinetic analysis of melphalan efflux, it was not possible to determine if the mechanism of drug efflux was simple diffusion or a technically nonsaturable carrier-mediated process. The Q10 for drug efflux varied from 1.2 to 1.8, values intermediate between those expected for simple diffusion and a carrier-mediated process. Furthermore, drug efflux was sodium independent and was not inhibited by the presence of amino acids on the same side of the membrane, findings which support the concept that efflux was by simple diffusion. The presence of a wide variety of amino acids in the extracellular medium was found to stimulate melphalan efflux. An evaluation of the structure-activity relationship disclosed that amino acids containing hydroxyl, acidic, or amide side chains were most active; however, a distinct pattern between amino acid structure and stimulation of efflux was not established. The stimulation process was concentration dependent and was not restricted to either L5178Y cells or to melphalan as transport substrate.


The role of the endocannabinoid system in female reproductive tissues.
There has been increasing interest in the role of endocannabinoids as critical modulators of the female reproductive processes. Endocannabinoids are natural ligands of cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. Together with their receptors, enzymes and downstream signaling targets, they form the endocannabinoid system (ECS). While the ECS is known to modulate pain and neurodevelopment, it is also known to impact the female reproductive system where it affects folliculogenesis, oocyte maturation, and ovarian endocrine secretion. In addition, the ECS affects oviductal embryo transport, implantation, uterine decidualization and placentation. There is a complex interplay between the ECS and the hypothalamic-pituitary-ovarian axis, and an intricate crosstalk between the ECS and steroid hormone production and secretion. Exogenous cannabinoids, derived from plants such as Cannabis sativa, are also ligands for cannabinoid receptors. These have been shown to have clinical outcomes related to ECS dysregulation, including multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis, along with adverse effects on female reproduction. The aim of this review is to describe and discuss data from human, animal, and in vitro studies that support the important role of the endocannabinoid system in female reproductive tissues and processes. In particular, we will discuss some of the mechanisms by which endocannabinoid signaling can affect ovarian function in both physiological and pathophysiological states.


Evidence that two stereochemically different alpha-2 adrenoceptors modulate norepinephrine release in rat cerebral cortex.
Cerebral cortex slices from the rat were loaded with [3H]norepinephrine ([3H]NE) and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. The (-)-isomer and the (+)-isomer of CH-38083 ([7,8-(methylenedioxy)-14- alpha-hydroxyalloberbane HCl), a selective alpha-2-adrenoceptor antagonist with an alloberbane skeleton, increased the electrically induced release of [3H]NE in a concentration-dependent manner, and a similar effect was observed with racemic CH-38083 and idazoxan. The stereoisomers of CH-38083 applied in a concentration range of 10(-8) to 10(-6) mol/l were equipotent in facilitating stimulation-evoked [3H]NE release: concentrations needed to enhance tritium outflow by 50% were 1.3 X 10(-7) mol/l for (-)-CH-38083 and 1.4 X 10(-7) mol/l for (+)-CH-38083. Exogenous NE decreased the electrically stimulated release of [3H]NE, and the stereoisomers of CH-38083 antagonized this inhibition with different potencies: the dissociation constant (KB) values for (-)-isomer and for (+)-isomer of CH-38083 were 14.29 and 97.18 nmol/l. These data indicate that presynaptic alpha-2 adrenoceptors that are available for NE released from axon terminals do not show stereospecificity toward enantiomers of CH-38083, whereas those that are occupied by exogenous NE are much more sensitive toward (-)-CH-38083. The alpha-1 adrenoceptor antagonist prazosin also differentiated between the alpha-2 adrenoceptor subtypes: prazosin (10(-6) mol/l) did not alter the increase of electrically induced [3H]NE release evoked by (-)- and (+)-CH-38083; however, in its presence, the stereoisomers of CH-38083 failed to antagonize the inhibitory effect of exogenous NE on its own release.(ABSTRACT TRUNCATED AT 250 WORDS)


Dietary Galactose Increases the Expression of Mitochondrial OXPHOS Genes and Modulates the Carbohydrate Oxidation Pathways in Mouse Intestinal Mucosa.
Prolonged lactation provides substantial health benefits, possibly because of galactose as part of milk sugar lactose. Isocaloric replacement of dietary glucose [16 energy%(en%)] with galactose within a normal diet (64en% carbohydrates) during a 3-wk postweaning period provided substantial benefits on short- and long-term physiologic and metabolic parameters at the whole-body level and liver in female mice, which might be attributable to intestinal function. This study aimed to investigate if partial dietary replacement of glucose with galactose alters intestinal metabolism underlying hepatic health effects. Proximal intestinal mucosa gene profiles in female mice were analyzed using RNAseq technology, validated, and correlated with hepatic health parameters. Transcriptome analysis revealed that the presence of galactose primarily affected the pathways involved in energy metabolism. A consistently higher expression was observed in the subset of mitochondrial transcripts (78 of 80, all P.adj < 0.1). Oxidative phosphorylation (OXPHOS) represented the most upregulated process (all top 10 pathways) independent of the total mitochondrial mass (P = 0.75). Moreover, galactose consistently upregulated carbohydrate metabolism pathways, specifically glycolysis till acetyl-CoA production and fructose metabolism. Also, the expression of transcripts involved in these pathways was negatively correlated with circulating serum amyloid A3 protein, a marker of hepatic inflammation [R (-0.61, -0.5), P (0.002, 0.01)]. Accordingly, CD163+ cells were decreased in the liver. Additionally, the expression of key fructolytic enzymes in the small intestinal mucosa was negatively correlated with triglyceride accumulation in the liver [R (-0.45, -0.4), P (0.03, 0.05)]. To our knowledge, our results show for the first time the role of galactose as an OXPHOS activator in vivo. Moreover, the concept of intestinal cells acting as the body's metabolic gatekeeper is strongly supported, as they alter substrate availability and thereby contribute to the maintenance of metabolic homeostasis, protecting other organs, as evidenced by their potential ability to shield the liver from the potentially detrimental effects of fructose.


Investigation of Antibacterial 1,8-Cineole-Derived Thin Films Formed via Plasma-Enhanced Chemical Vapor Deposition.
The need for low-fouling coatings for biomedical devices has prompted considerable interest in antibacterial compounds from natural and sustainable sources, such as essential oils. Herein, a tea tree oil-based precursor, 1,8-cineole, is used to fabricate antimicrobial films (denoted ppCin) by plasma-enhanced chemical vapor deposition. Film properties were comprehensively characterized using a variety of surface and bulk analytical tools, and the plasma gas phase is assessed using optical emission spectroscopy, which can be correlated to ppCin film properties. Notably, film wettability increases linearly with plasma pressure, yielding water contact angles ranging from ∼50° to ∼90°. X-ray photoelectron spectroscopy reveals less oxygen is incorporated at higher pressures, likely arising from the lower density of OH(g) species. Further, we utilized H2O(v) plasma surface modification of the ppCin films to improve wettability and find this results in a substantial increase in surface oxygen content. To elucidate the role of film wettability and antibacterial properties, both as-deposited and H2O(v) plasma-modified films were exposed to Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus using glass slides and hydrocarbon films deposited from 1,7-octadiene as positive controls. Overall, bacteria attach to a similar extent on all films, including controls, yet only essential oil-based films significantly prevent biofilm formation (4-7% coverage compared to ∼40% for controls).


Global quantitative predictions of complex laser dynamics.
We demonstrate unprecedented agreement between a theoretical two-dimensional bifurcation diagram and the corresponding experimental stability map of an optically injected semiconductor laser over a large range of relevant injection parameter values. The bifurcation diagram encompasses both local and global bifurcations mapping out regions of regular, chaotic, and multistable behavior in considerable detail. This demonstrates the power of dynamical systems modeling for the quantitative prediction of nonlinear dynamics and chaos of semiconductor lasers.


A Hybrid Dragonfly Algorithm for Efficiency Optimization of Induction Motors.
Induction motors tend to have better efficiency on rated conditions, but at partial load conditions, when these motors operate on rated flux, they exhibit lower efficiency. In such conditions, when these motors operate for a long duration, a lot of electricity gets consumed by the motors, due to which the computational cost as well as the total running cost of industrial plant increases. Squirrel-cage induction motors are widely used in industries due to their low cost, robustness, easy maintenance, and good power/mass relation all through their life cycle. A significant amount of electrical energy is consumed due to the large count of operational units worldwide; hence, even an enhancement in minute efficiency can direct considerable contributions within revenue saving, global electricity consumption, and other environmental facts. In order to improve the efficiency of induction motors, this research paper presents a novel contribution to maximizing the efficiency of induction motors. As such, a model of induction motor drive is taken, in which the proportional integral (PI) controller is tuned. The optimal tuning of gains of a PI controller such as proportional gain and integral gain is conducted. The tuning procedure in the controller is performed in such a condition that the efficiency of the induction motor should be maximum. Moreover, the optimization concept relies on the development of a new hybrid algorithm, the so-called Scrounger Strikes Levy-based dragonfly algorithm (SL-DA), that hybridizes the concept of dragonfly algorithm (DA) and group search optimization (GSO). The proposed algorithm is compared with particle swarm optimization (PSO) for verification. The analysis of efficiency, speed, torque, energy savings, and output power is validated, which confirms the superior performance of the suggested method over the comparative algorithms employed.


Non-dural-based spinal meningioma : the first case report of a fibrous subtype and a review of the literature.
Spinal meningiomas typically adhere to the dura matter. Non-dural based spinal meningiomas are rare and most are clear cell meningiomas. We report here the first case of a fibrous meningioma with non-dural attachment. The patient was a 49-year-old female, who complained of numbness in the legs and a gait disturbance. Magnetic resonance imaging revealed a 1.7×1.4-cm mass in the C7-T1 intra-dural extramedullary space, showing peripheral gadolinium enhancement without a "dural tail sign". A complete microsurgical resection was performed. The mass was covered with a white membrane but was not adhered to the dura, and its appearance was consistent with a neurilemmoma. The histopathological diagnosis was fibrous-type meningioma. The recovery of the patient was uneventful. No surgical complications and no recurrence of the tumor had occurred at the 6-month follow-up.


Construction of Mycoplasma hyopneumoniae P97 Null Mutants.
Mycoplasma hyopneumoniae is the causative agent of enzootic pneumonia, a world-wide problem in the pig industry. This disease is characterized by a dry, non-productive cough, labored breathing, and pneumonia. Despite years of research, vaccines are marginally effective, and none fully protect pigs in a production environment. A better understanding of the host-pathogen interactions of the M. hyopneumoniae-pig disease, which are complex and involve both host and pathogen components, is required. Among the surface proteins involved in virulence are members of two gene families called P97 and P102. These proteins are the adhesins directing attachment of the organism to the swine respiratory epithelium. P97 is the major ciliary binding adhesin and has been studied extensively. Monoclonal antibodies that block its binding to swine cilia have contributed extensively to its characterization. In this study we use recombination to construct null mutants of P97 in M. hyopneumoniae and characterize the resulting mutants in terms of loss of protein by immunoblot using monoclonal antibodies, ability to bind purified swine cilia, and adherence to PK15 cells. Various approaches to recombination with this fastidious mycoplasma were tested including intact plasmid DNA, single-stranded DNA, and linear DNA with and without a heterologous RecA protein. Our results indicate that recombination can be used to generate site-specific mutants in M. hyopneumoniae. P97 mutants are deficient in cilia binding and PK15 cell adherence, and lack the characteristic banding pattern seen in immunoblots developed with the anti-P97 monoclonal antibody.


[Status of higher nervous activity and various indices of experimental-psychological examinations of the aged].
On the basis of a comprehensive experimental-psychological examination of clinically healthy people of advanced age groups, the authors have established the main regularities of changes in mental activity with age. It is demonstrated that deterioration of memory, attention and apractognostic processes is largely due to a reduction in the tone of the brain cortex. The normative parameters of the functional mobility and mental working ability are presented for people aged 20 to 100 years.


Proteome composition and codon usage in spirochaetes: species-specific and DNA strand-specific mutational biases.
The genomes of the spirochaetes Borrelia burgdorferi and Treponema pallidum show strong strand-specific skews in nucleotide composition, with the leading strand in replication being richer in G and T than the lagging strand in both species. This mutation bias results in codon usage and amino acid composition patterns that are significantly different between genes encoded on the two strands, in both species. There are also substantial differences between the species, with T.pallidum having a much higher G+C content than B. burgdorferi. These changes in amino acid and codon compositions represent neutral sequence change that has been caused by strong strand- and species-specific mutation pressures. Genes that have been relocated between the leading and lagging strands since B. burgdorferi and T.pallidum diverged from a common ancestor now show codon and amino acid compositions typical of their current locations. There is no evidence that translational selection operates on codon usage in highly expressed genes in these species, and the primary influence on codon usage is whether a gene is transcribed in the same direction as replication, or opposite to it. The dnaA gene in both species has codon usage patterns distinctive of a lagging strand gene, indicating that the origin of replication lies downstream of this gene, possibly within dnaN. Our findings strongly suggest that gene-finding algorithms that ignore variability within the genome may be flawed.


A Dual-Energy Metal Artifact Redcution Method for DECT Image Reconstruction.
Metal implants are one of the culprits for image quality degradation in CT imaging, introducing so-called metal artifacts. With the help of the virtual-monochromatic imaging technique, dual-energy CT has been proven to be effective in metal artifact reduction. However, the virtual monochromatic images with suppressed metal artifacts show reduced CNR compared to polychromatic images. To remove metal artifacts on polychromatic images, we propose a dual-energy NMAR (deNMAR) algorithm in this paper that adds material decomposition to the widely used NMAR framework. The dual energy sinograms are first decomposed into water and bone sinograms, and metal regions are replaced with water on the reconstructed material maps. Prior sinograms are constructed by polyenergetically forward projecting the material maps with corresponding spectra, and they are used to guide metal trace interpolation in the same way as in the NMAR algorithm. We performed experiments on authentic human body phantoms, and the results show that the proposed deNMAR algorithm achieves better performance in tissue restoration compared to other compelling methods. Tissue boundaries become clear around metal implants, and CNR rises to 2.58 from ~1.70 on 80 kV images compared to other dual-energy-based algorithms.


Alpha Test of a Videogame to Increase Children's Vegetable Consumption.
This is a report of an alpha test with a computer of one episode of a casual videogame smartphone application, called Kiddio Food Fight™ (Archimage Inc., Houston, TX), targeted at training parents to increase their 3-5-year-old child's vegetable consumption. This was a qualitative study using semistructured interviews. Sixteen parents from three ethnic groups living with their 3-5-year-old child were recruited. Parents provided screening information and informed consent and played the videogame. Afterward, semistructured intensive interviews were conducted about their experience. Parents generally liked the game. Their suggestions included a reduced list of values, rewording of reasons statements, an improved storyline, and feedback during and at the end of the game. The scoring system was ignored or confusing. Problems with the tool bar and game navigation caused problems in performance. A tutorial was requested. Kiddio Food Fight could have positive acceptance among parents with minor modifications. A videogame play could help parents learn effective vegetable parenting practices.


The canonical Wg and JNK signaling cascades collaborate to promote both dorsal closure and ventral patterning.
Elaboration of the Drosophila body plan depends on a series of cell-identity decisions and morphogenetic movements regulated by intercellular signals. For example, Jun N-terminal kinase signaling regulates cell fate decisions and morphogenesis during dorsal closure, while Wingless signaling regulates segmental patterning of the larval cuticle via Armadillo. wingless or armadillo mutant embryos secrete a lawn of ventral denticles; armadillo mutants also exhibit dorsal closure defects. We found that mutations in puckered, a phosphatase that antagonizes Jun N-terminal kinase, suppress in a dose-sensitive manner both the dorsal and ventral armadillo cuticle defects. Furthermore, we found that activation of the Jun N-terminal kinase signaling pathway suppresses armadillo-associated defects. Jun N-terminal kinase signaling promotes dorsal closure, in part, by regulating decapentaplegic expression in the dorsal epidermis. We demonstrate that Wingless signaling is also required to activate decapentaplegic expression and to coordinate cell shape changes during dorsal closure. Together, these results demonstrate that MAP-Kinase and Wingless signaling cooperate in both the dorsal and ventral epidermis, and suggest that Wingless may activate both the Wingless and the Jun N-terminal kinase signaling cascades.


Understanding stress: characteristics and caveats.
Exposure to stressful situations is among the most common human experiences. These types of situations can range from unexpected calamities to routine daily annoyances. In response to stressors, a series of behavioral, neurochemical, and immunological changes occur that ought to serve in an adaptive capacity. However, if those systems become overly taxed, the organism may become vulnerable to pathology. Likewise, the biological changes, if sufficiently sustained, may themselves adversely affect the organism's well-being. Several factors may dictate an individual's response to environmental stressors, including characteristics of the stressor (i.e., type of stressor and its controllability, predictability, and chronicity); biological factors (i.e., age, gender, and genetics); and the subject's previous stressor history and early life experiences. Research on the physiological and psychological responses to different types of stressful stimuli is presented, focusing particularly on processes that may be relevant to the development of alcohol use disorders. Stressful events may profoundly influence the use of alcohol or other drugs (AODs). For example, the resumption of AOD use after a lengthy period of abstinence may reflect a person's attempt to self-medicate to attenuate the adverse psychological consequences of stressors (e.g., anxiety). Alternatively, stress may increase the reinforcing effects of AODs.


Social mobility and psychiatric disabilities: an assessment of the social causation and social selection hypotheses.
Social mobility is the movement of individuals, families and groups from one social position to another. Researchers indicate that people with psychiatric disabilities tend to come from lower socioeconomic status groups, and that the causal relationship between lower socioeconomic status and mental illness occurs through social mobility process. The purpose of this study was to examine the occupational social mobility process of a sample of self-identified psychiatrically disabled individuals who have been active members of the labor force for most of their adult lives. A total of 200 participants were recruited from the customers of a One-Stop Career Center in Gloucester County, New Jersey. The social mobility pattern of persons with psychiatric disabilities was compared to that of persons without psychiatric disabilities (n = 100 for each group). That is, the social selection and the social causation hypotheses were applied to the social mobility patterns of people with psychiatric disabilities. It was revealed that the social class distribution for fathers of people with psychiatric disabilities was not different from that of people without psychiatric disabilities and also there was no significant social mobility difference between the two groups. These findings do not support the social causation and the social selection hypotheses. Specifically, the findings demonstrate that occupational capabilities and skills of people with psychiatric disabilities have been stabilized and are similar to those of people without psychiatric disabilities. Furthermore, these results may dispute several biases and prejudices with regard to social mobility process of persons with psychiatric disabilities.


Paradoxical choice in rats: Subjective valuation and mechanism of choice.
Decision-makers benefit from information only when they can use it to guide behavior. However, recent experiments found that pigeons and starlings value information that they cannot use. Here we show that this paradox is also present in rats, and explore the underlying decision process. Subjects chose between two options that delivered food probabilistically after a fixed delay. In one option ("info"), outcomes (food/no-food) were signaled immediately after choice, whereas in the alternative ("non-info") the outcome was uncertain until the delay lapsed. Rats sacrificed up to 20% potential rewards by preferring the info option, but reversed preference when the cost was 60%. This reversal contrasts with the results found with pigeons and starlings and may reflect species' differences worth of further investigation. Results are consistent with predictions of the Sequential Choice Model (SCM), that proposes that choices are driven by the mechanisms that control action in sequential encounters. As expected from the SCM, latencies to respond in single-option trials predicted preferences in choice trials, and latencies in choice trials were the same or shorter than in single-option trials. We argue that the congruence of results in distant vertebrates probably reflects evolved adaptations to shared fundamental challenges in nature, and that the apparently paradoxical overvaluing of information is not sub-optimal as has been claimed, even though its functional significance is not yet understood.


Mycoplasma pneumoniae infections--does treatment help?
Mycoplasma pneumoniae is a common cause of respiratory tract infections (RTI's), especially in children. While severe M. pneumoniae infections are generally treated with antibiotics, the diagnosis as well as treatment of these infections should be reconsidered in the light of recent clinical findings. First, M. pneumoniae was found to be carried in the upper respiratory tract of a relatively high percentage of healthy, asymptomatic children. Clearly, this complicates the diagnosis of a suspected M. pneumoniae RTI and, thus, the decision when to initiate treatment. A complication in the treatment of these infections is that data on the efficacy of antibiotic treatment of M. pneumoniae RTI's are sparse and derived exclusively from comparative studies. A recent Cochrane review concluded that there is insufficient evidence about the efficacy of antibiotics for M. pneumoniae lower respiratory tract infections (LRTI) in children. Due to side effects associated with the use of tetracyclines and quinolones in children, only macrolides can be used to treat M. pneumoniae infections in young patients. The general applicability of macrolides, however, is currently threatened by the worldwide increase in macrolide-resistant M. pneumoniae strains. Finally, limited evidence is available that corticosteroids might have an additional benefit in the treatment of M. pneumoniae infections. In this review, the current issues related to the diagnosis and treatment of M. pneumoniae infections will be discussed.


Antimicrobial Activity of Ceftazidime-Avibactam Against Contemporary Pathogens From Urinary Tract Infections and Intra-abdominal Infections Collected From US Children During the 2016-2019 INFORM Surveillance Program.
Antibacterial activity of ceftazidime-avibactam (CAZ-AVI) was evaluated against bacterial isolates from children in the United States with a urinary tract infection (UTI) or intra-abdominal infection (IAI) during the 2016-2019 International Network for Optimal Resistance Monitoring program. Prevalence of isolates and susceptibility to CAZ-AVI in pediatric and adult patients were compared. Bacterial isolates were collected from children with a UTI or IAI at 70 US medical centers from 2016 to 2019. The antimicrobial activity of CAZ-AVI and comparator agents was tested by broth microdilution methods. The most prevalent Enterobacterales pathogens in children with UTIs were Escherichia coli (62.5%), Klebsiella pneumoniae (12.1%) and Proteus mirabilis (6.2%). Minimum inhibitory concentration 90% values for CAZ-AVI against Enterobacterales (0.25 μg/mL) and Pseudomonas aeruginosa (4 μg/mL) were identical for children and adults. The most prevalent Enterobacterales pathogens in children with IAIs were E. coli (57.4%), K. pneumoniae (11.1%) and Enterobacter cloacae species complex (9.3%). All isolates of Enterobacterales from pediatric patients with UTI and IAI were susceptible to CAZ-AVI, including extended-spectrum β-lactamase phenotypes. Susceptibility of P. aeruginosa isolates to CAZ-AVI was 96.2% in children and 98.4% in adults with a UTI: for IAI it was 100% and 97.2%, respectively. Contemporary UTI and IAI pathogens collected from US children from 2016 to 2019 exhibited similar prevalence and susceptibilities as isolates collected from adult patients. CAZ-AVI exhibited potent activity against these pathogens.


Posttraumatic syrinx formation: experimental study.
An experimental study was performed to examine posttraumatic spinal cord cavitation in an animal model by evaluating immediate and delayed computed tomographic (CT) scans obtained after administration of intrathecal contrast material. Four cats underwent midthoracic laminectomy and spinal cord contusion using a standard 400 g-cm model. All animals were studied by CT with intrathecal contrast enhancement before and 4-5 days, 3-4 weeks, and 7-13 weeks after experimental cord contusion. Either metrizamide or iopamidol was used as the contrast agent. Two of the four cats had CT and pathologic evidence of cord cavitation at the site of injury. Another animal had uptake of contrast material into the spinal cord without pathologic evidence of cyst formation, which was believed to represent malacic change. The fourth animal had a normal-appearing cord by both CT and pathologic criteria. Animals that received metrizamide after cord contusion had generalized myoclonic seizures. This did not occur when iopamidol was administered.


The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer.
SOX genes encode a family of high-mobility group transcription factors that play critical roles in organogenesis. The functional specificity of different SOX proteins and the tissue specificity of a particular SOX factor are largely determined by the differential partnership of SOX transcription factors with other transcription regulators, many of which have not yet been discovered. Virtually all members of the SOX family have been found to be deregulated in a wide variety of tumors. However, little is known about the cellular and molecular behaviors involved in the oncogenic potential of SOX proteins. Using cell culture experiments, tissue analysis, molecular profiling, and animal studies, we report here that SOX2 promotes cell proliferation and tumorigenesis by facilitating the G(1)/S transition and through its transcription regulation of the CCND1 gene in breast cancer cells. In addition, we identified beta-catenin as the transcription partner for SOX2 and demonstrated that SOX2 and beta-catenin act in synergy in the transcription regulation of CCND1 in breast cancer cells. Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, beta-catenin.


Membrane Emulsification Process as a Method for Obtaining Molecularly Imprinted Polymers.
The membrane emulsification process (ME) using a metallic membrane was the first stage for preparing a spherical and monodisperse thermoresponsive molecularly imprinted polymer (TSMIP). In the second step of the preparation, after the ME process, the emulsion of monomers was then polymerized. Additionally, the synthesized TSMIP was fabricated using as a functional monomer N-isopropylacrylamide, which is thermosensitive. This special type of polymer was obtained for the recognition and determination of trace bisphenol A (BPA) in aqueous media. Two types of molecularly imprinted polymers (MIPs) were synthesized using amounts of BPA of 5 wt.% (MIP-2) and 7 wt.% (MIP-1) in the reaction mixtures. Additionally, a non-imprinted polymer (NIP) was also synthesized. Polymer MIP-2 showed thermocontrolled recognition for imprinted molecules and a higher binding capacity than its corresponding non-imprinted polymer and higher than other molecularly imprinted polymer (MIP-1). The best condition for the sorption process was at a temperature of 35 °C, that is, at a temperature close to the phase transition value for poly(N-isopropylacrylamide). Under these conditions, the highest levels of BPA removal from water were achieved and the highest adsorption capacity of MIP-2 was about 0.5 mmol g-1 (about 114.1 mg g-1) and was approximately 20% higher than for MIP-1 and NIP. It was also observed that during the kinetic studies, under these temperature conditions, MIP-2 sorbed BPA faster and with greater efficiency than its non-imprinted analogue.


Defining expected mortality in occupational studies.
The mortality in a reference population for specific occupations was evaluated by means of occupational studies of different designs. The data originated from a random sample of 19,862 persons from among the total Finnish population. The age standardized mortality for those who had at any time belonged to the active work force in Finland was estimated to be 10% less than the average mortality for the total population. The difference was 20% if the currently active work force was compared with the total population. The standardized mortality ratio was 70% for those who had stayed for less than 10 years within the same occupational category and 80% for those with more than 10 years' work within the same occupational category. The expected mortality varied up to 50% depending on the broad occupational category and on the occupational history when compared with the total mortality in Finland.


Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.
To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.


Validation and reliability of Falls Risk for Hospitalized Older People (FRHOP): Taiwan version.
A comprehensive fall risk assessment can provide information for effective prevention and intervention measures and reduce falls among hospitalized elderly people. The purpose of this study was to develop a Chinese version of an inpatient fall risk assessment tool and evaluate its validity and reliability.This study employed the Falls Risk for Hospitalised Older People (FRHOP) assessment to construct a FRHOP-Taiwan Version (Tw-FRHOP) through forward, synthesized, and backward translation. A face validation was conducted by 5 clinical nurses and a content validation was conducted by 5 specialists using the content validity index (CVI) to validate the proposed model. Thirty hospitalized older adults in an internal care unit were selected for an interrater reliability assessment, conducted separately by specialists in 4 disciplines (i.e., nurses, physicians, occupational therapists, and physiotherapists) by using Cohen kappa statistic and intraclass correlation coefficients (ICCs). Specifically, the assessment rating developed in the Tw-FRHOP was compared with the Morse Fall Scale (MFS), St. Thomas Risk Assessment Tool in Falling Elderly Inpatients (STRATIFY), and the Hendrich II Fall Risk Model (HIIFRM) for criterion validation.According to the analysis results, the CVI was 0.94, and the indexes of criterion-related validity for the FRHOP-Taiwan Version, MFS, STRATIFY, and HIIFRM were 0.49, 0.63, and 0.54 (all P < .001), respectively. In addition, after interrater reliability testing was conducted, the results indicated that the index of response consistency in each discipline was 86.7% to 100%, and the values of Cohen kappa were 0.651 to 1.000. The ICCs of the discipline-related subscale were 0.97 to 1.00.The Tw-FRHOP is a multidisciplinary comprehensive fall risk assessment that can serve as a satisfactorily valid and reliable reference tool for medical personnel with full professional training, as well as inpatient fall prevention interventions for multidisciplinary teams in hospitals.


Effects of TNF-alpha blockade in monocrotaline-induced pulmonary hypertension.
TNF-alpha blockade in ischemic heart failure is still the subject of debate since clinical trials show conflicting results. However, its benefit in heart failure secondary to pulmonary hypertension has yet to be determined. It has been reported that transgenic rats overexpressing TNF-alpha develop pulmonary hypertension. The aim of this study was to assess the morphologic and hemodynamic effects of administration of an anti-TNF-alpha monoclonal antibody (etanercept) in rats with monocrotaline (MCT)-induced pulmonary hypertension. Adult Wistar rats were injected with MCT (60 mg/Kg sc), or vehicle only (day 0). Beginning one day later, the animals were randomly treated with etanercept (ETC, 0.03 mg/Kg sc, three times a week) or with a similar volume of vehicle. The study thus had four groups: Ctrl (n = 6), Ctrl + ETC (n = 6), MCT (n = 6) and MCT + ETC (n = 6). On days 22-23, the rats were instrumented to record right ventricular systolic and end-diastolic pressures, dP/dtmax and tau. At the end of each experiment the heart and lungs were weighed. Chronic administration of etanercept induced only a slight increase in relaxation velocity, with no effect on other hemodynamic parameters, including pulmonary hypertension, and no reduction in right ventricular hypertrophy. These results suggest that etanercept does not lead to a significant improvement in heart failure secondary to pulmonary hypertension.


Breeding success of a colony of Boat-billed Herons Cochlearius cochlearius (Ciconiiformes: Ardeidae) in pasturelands of Costa Rica.
The breeding success of a double-brooding colony of Boat-billed Herons Cochlearius cochlearius was studied in pasturelands of Costa Rica. Mean clutch size in the first clutches (2.9 eggs/nest) was higher than in second and repeat clutches (2.3 eggs/nest). Breeding success was similar in the first attempt and second attempts (20.7% and 21.7%, respectively). In both attempts earlier nests enjoyed a higher breeding success. Starvation of the youngest chicks within the nest and destruction of nests by bad weather conditions were the main factors related to nestling death. No effects of human activity on the reproduction of the breeding colony were observed.


Reproducibility of intravascular ultrasound radiofrequency data analysis: implications for the design of longitudinal studies.
The purpose of this study was to assess in vivo the reproducibility of tissue characterization using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data (IVUS-VH). Despite the need for reproducibility data to design longitudinal studies, such information remains unexplored. IVUS-VH (Volcano Corp., Rancho Cordova, USA) was performed in patients referred for elective percutaneous intervention and in whom a non-intervened vessel was judged suitable for a safe IVUS interrogation. The IVUS catheters used were commercially available catheters (20 MHz, Volcano Corp., Rancho Cordova, USA). Following IVUS-VH acquisition, and after the disengagement and re-engagement of the guiding catheter, an additional acquisition was performed using a new IVUS catheter. Fifteen patients with 16 non-significant lesions were assessed by 2 independent observers. The relative inter-catheter differences regarding geometrical measurements were negligible for both observers. The inter-catheter relative difference in plaque cross-sectional area (CSA) was 3.2% for observer 1 and 0.5% for observer 2. The limits of agreement for (observer 1 measurements) lumen, vessel, plaque and plaque burden measurements were 0.82, -1.10 mm(2); 0.80, -0.66 mm(2); 1.08, -0.66 mm(2); and 5.83, -3.89%; respectively. Limits of agreement for calcium, fibrous, fibrolipidic and necrotic core CSA measurements were 0.22, -0.25 mm(2); 1.02, -0.71 mm(2); 0.61, -0.65 mm(2); and 0.43, -0.38 mm(2) respectively. Regarding the inter-observer agreement, the limits of agreement for lumen, vessel, plaque and plaque burden measurements were 2.61, -2.09 mm(2); 2.20-3.03 mm(2); 1.70, -3.04 mm(2); and 9.16, -16.41%; respectively, and for calcium, fibrous, fibrolipidic and necrotic core measurements of 0.08, -0.09 mm(2); 0.89, -1.28 mm(2); 0.74, -1.06 mm(2); and 0.16, -0.20 mm(2); respectively. The present study demonstrates that the geometrical and compositional output of IVUS-VH is acceptably reproducible.


[High Expression Level of SP1, CSF1R, and PAK1 Correlates with Sensitivity of Leukemia Cells to the Antibiotic Mithramycin].
Acute myeloid leukemia (AML) is a genetically heterogeneous group of oncological diseases of the hematopoietic system, which are extremely difficult to treat. The development of new targeted drugs (Hylteritinib, Venetoclax) significantly improved the survival of patients, but resistance, as well as cytotoxic anti-leukemia drugs, often occurs. The search for new molecular targets for the development of effective approaches for the treatment of AML is very urgent. In blast cells of patients with AML, mutations, chromosomal rearrangements, and increased expression of a number of non-mutant genes, including transcription factor genes, are detected. The transcription factor Sp 1 binds to GC-rich regions of regulatory regions of various genes and thus controls their expression. Sp1 targets include genes responsible for proliferation, cell cycle regulation, and differentiation. In many malignant diseases, a high level of Sp1 gene expression is associated with an unfavorable prognosis, therefore, Sp1 is considered as a promising therapeutic target for cancer. In this paper, we estimated the expression levels of Sp1 in various malignant tissues. Increased Sp1 expression was detected in samples obtained from patients with AML, acute lymphoblastic leukemia, Ewing sarcoma, ovarian and kidney cancer. It is also shown that Sp1 expression correlates with the expression of genes encoding cytokine receptors and growth factors (CSF1R and IL6R), intracellular kinases (CSK, SYK, PAK1, ILK, JAK2), and transcription factor LMO2. The correlation between expression levels of Sp1 and CSF1R, SYK, Jak2 and LMO2 is also characteristic of transplanted human leukemia cells. We measured expression levels of Sp1, CSF1R, ILK, PAK1 in the cells of three transplantable lines of human leukemia and found increased levels of expression of these genes in Kasumi-1 cells. In addition, we showed that Kasumi-1 cells are most sensitive to Mitramycin, a drug that displaces Sp1 from its targets with DNA. Our data indicate the need to identify AML cells that are most sensitive to inhibition of Sp1 activity in order to assess the possibility of suppressing its activity in vivo.