Identification of age-dependent features of human bronchi using explainable artificial intelligence.
Ageing induces functional and structural alterations in organs, and age-dependent parameters have been identified in various medical data sources. However, there is currently no specific clinical test to quantitatively evaluate age-related changes in bronchi. This study aimed to identify age-dependent bronchial features using explainable artificial intelligence for bronchoscopy images. The present study included 11 374 bronchoscopy images, divided into training and test datasets based on the time axis. We constructed convolutional neural network (CNN) models and evaluated these models using the correlation coefficient between the chronological age and the "bronchial age" calculated from bronchoscopy images. We employed gradient-weighted class activation mapping (Grad-CAM) to identify age-dependent bronchial features that the model focuses on. We assessed the universality of our model by comparing the distribution of bronchial age for each respiratory disease or smoking history. We constructed deep-learning models using four representative CNN architectures to calculate bronchial age. Although the bronchial age showed a significant correlation with chronological age in each CNN architecture, EfficientNetB3 achieved the highest Pearson's correlation coefficient (0.9617). The application of Grad-CAM to the EfficientNetB3-based model revealed that the model predominantly attended to bronchial bifurcation sites, regardless of whether the model accurately predicted chronological age or exhibited discrepancies. There were no significant differences in the discrepancy between the bronchial age and chronological age among different respiratory diseases or according to smoking history. Bronchial bifurcation sites are universally important age-dependent features in bronchi, regardless of the type of respiratory disease or smoking history.


Variation in postoperative analgesic requirements in the morbidly obese following gastric bypass surgery.
Patient-controlled analgesia is a relatively new method of administering intravenous narcotics for postoperative pain relief. The technique involves the self-administration of a given analgesic in a bolus dose with the aid of a timed infusion and sequencing device. Ten morbidity obese patients undergoing elective gastric bypass surgery were treated in a prospective, unblinded, pilot project to evaluate the efficacy of patient-controlled analgesia. Analgesic therapy was satisfactory in all patients. The mean total dose of morphine sulfate administered during the first 36 hours postoperatively was 66 mg, an average of 1.7 mg/hr. There was a tenfold variation (17.5-175 mg) in the 36 hr total dose. The total dose was not related to body surface area, age, sex, dose per injection, or anesthetic agent. The large variation in individual narcotic analgesic requirements could be a major factor in the suboptimal management of postoperative pain with conventional dosing. Patient-controlled analgesia may circumvent these problems.


MR imaging-guided focal laser ablation for prostate cancer: phase I trial.
To evaluate the feasibility and safety of magnetic resonance (MR) imaging-guided laser-based thermotherapy in men with clinically low-risk prostate cancer and a concordant lesion at biopsy and MR imaging. This HIPAA-compliant phase I prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Transperineal MR imaging-guided focal laser ablation for clinically low-risk prostate cancer was performed in patients with a Gleason score of 7 or less in three or fewer cores limited to one sextant obtained with transrectal ultrasonography (US)-guided biopsy and a concordant lesion at MR imaging. Lesions were targeted with a laser ablation system. Periprocedural complications were recorded. The International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) score were collected before and after the procedure. MR imaging-guided biopsy of the ablation zone was performed 6 months after treatment. The prostate-specific antigen level, IPSS, and SHIM score before and after ablation were compared by using the Wilcoxon signed rank test. Treatment was successfully completed in nine patients (procedure duration, 2.5-4 hours; mean laser ablation duration, 4.3 minutes). Immediate contrast-enhanced posttreatment MR imaging showed a hypovascular defect in eight patients. Self-resolving perineal abrasion and focal paresthesia of the glans penis each occurred in one patient. The mean (± standard deviation) IPSS and SHIM score at baseline were 5.8 ± 5.3 and 19.0 ± 8.0, respectively. Average score changes were not significantly different from zero during follow-up (P = .18-.99). MR imaging-guided biopsy of the ablation zone showed no cancer in seven patients (78%) and Gleason grade 6 cancer in two (22%). Transperineal MR imaging-guided focal laser ablation appears to be a feasible and safe focal therapy option for clinically low-risk prostate cancer.


Subsidence and carbon dioxide emissions in a smallholder peatland mosaic in Sumatra, Indonesia.
Most attention in quantifying carbon dioxide (CO2) emissions from tropical peatlands has been on large-scale plantations (industrial timber, oil palm (Elaeis guinensis)), differing in drainage and land-use practices from those of smallholder farms. We measured subsidence and changes in bulk density and carbon organic content to calculate CO2 emissions over 2.5 years in a remnant logged-over forest and four dominant smallholder land-use types in Tanjung Jabung Barat District, Jambi Province, Sumatra, Indonesia: (1) simple rubber (Hevea brasiliensis) agroforest (> 30 years), (2) mixed coconut (Cocos nucifera) and coffee gardens (Coffea liberica) (> 40 years), (3) mixed betel nut (Areca catechu) and coffee gardens (> 20 years), and (4) oil palm plantation (1 year). We quantified changes in microtopography for each site for greater accuracy of subsidence estimates and tested the effects of nitrogen and phosphorus application. All sites had a fibric type of peat with depths of 50 to > 100 cm. A recently established oil palm had the highest rate of peat subsidence and emission (4.7 cm year-1 or 121 Mg CO2 ha-1 year-1) while the remnant forest had the lowest (1.8 cm year-1 or 40 Mg CO2 ha-1 year-1). Other land-use types subsided by 2-3 cm year-1, emitting 70-85 Mg CO2 ha-1 year-1. Fertilizer application did not have a consistent effect on inferred emissions. Additional emissions in the first years after drainage, despite groundwater tables of 40 cm, were of the order of belowground biomass of peat forest. Despite maintaining higher water tables, smallholder landscapes have CO2 emissions close to, but above, current IPCC defaults.


Synthetic mimics of surfactant proteins B and C: in vitro surface activity and effects on lung compliance in two animal models of surfactant deficiency.
Synthetic surfactant peptides SP-B1-78 and SP-C1-31 in a standard phospholipid mixture have been employed to examine the correlation between in vitro surface activity and in vivo function of synthetic surfactant preparations in the isolated rat lung and premature rabbit models of respiratory distress syndrome. Monolayer techniques showed that SP-B peptides have a high propensity for association with a phospholipid structure. By dynamic respreading, synthetic SP-B and SP-C showed rapid spreading and attained low surface tensions. Used as replacement surfactants in two animal models, these synthetic surfactant preparations partially restored lung compliance in lavaged rats and premature rabbits better than a pure phospholipid preparation and to a degree comparable to clinical surfactant, measured by pressure/volume curves. Our data confirm that in vitro functional determinations of synthetic surfactant peptides are instrumental in the preparation of replacement surfactants, and that dispersions thus selected represent viable therapeutic alternatives to current treatments for respiratory distress syndrome.


Oxidative stress-induced miRNAs modulate AKT signaling and promote cellular senescence in uterine leiomyoma.
Uterine leiomyomas (ULM) grow under high oxidative stress due to a hypoxic microenvironment and defects in redox metabolism. AKT is one major pathway activated by reactive oxygen species (ROS) that maintains ULM growth and survival. We previously reported that AKT inactivated by AKT inhibitors can significantly induce cellular senescence in ULM cells. Since some miRNAs are induced by AKT inhibitors in an ROS-dependent manner, we proposed that these miRNAs may modulate AKT function and cellular senescence in ULM. We therefore established ex vivo models of a three-dimensional ULM spheroid culture system to study the role of miRNAs in cellular senescence. Four miRNAs, miR-29b, miR-181a, miR-182, and miR-200c, were found to induce cellular senescence in primary ULM and myometrium spheroid cultures when stably overexpressed. miR-181a and miR-182 were found to repress AKT3 and CCND2, respectively. Correspondingly, RNAi of AKT3 or CCND2 also induced cellular senescence and G0/G1 arrest. Thus, miR-181a and miR-182 may drive cellular senescence in ULM by repressing AKT3 and CCND2 activity, respectively. We further demonstrated that senescent ULM cells can be effectively removed by BH3 mimetic ABT263, which provides a new therapeutic venue for the treatment of ULM. Our findings suggest that miRNAs are potent modulators in regulating the ROS-AKT-cell cycle axis in uterine leiomyoma. A subset of oxidative stress-induced miRNAs is involved in AKT signaling in uterine leiomyoma. Overexpression of miR-181a and miR-182 resulted in cellular senescence in leiomyoma through repression of AKT3 and CCND2, respectively. Silencing of AKT3 and CCND2 drives leiomyoma cell into senescence and cycle arrest. Application of our newly developed 3D leiomyoma spheroids can provide a quick and reliable ex vivo model for cytopathologic and functional analysis. BH3 mimetics can effectively reduce the viability of miRNA-mediated senescent cells in leiomyoma.


Sustained improvement in drug documentation, compliance, and disease control. A four-year analysis of an ambulatory care model.
We analyzed the effectiveness of an intervention program involving a clinical pharmacist and nurse clinician in improving drug documentation in medical records, patient compliance, and disease control. Medical records and prescription files were reviewed for patients in a rheumatology and renal clinic. Compliance was estimated by examining prescription refill patterns. Reviews were performed before intervention (control group), nine months after intervention (study group 1), and four years nine months after our intervention program began (study group 2). A six-month retrospective analysis at each review point demonstrated a significant improvement in drug documentation, compliance, and disease control--BP--for both study groups. A significant correlation was found between compliance (refill patterns) and BP control--correlation coefficient phi for the control group, 67 for study group 1, and .89 for study group 2. Cost reductions associated with our intervention program suggest that this program is cost-effective.


GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial function.
This study sought to determine the effects of endogenous tetrahydrobiopterin (BH4) bioavailability on endothelial nitric oxide synthase (eNOS) coupling, nitric oxide (NO) bioavailability, and vascular superoxide production in patients with coronary artery disease (CAD). GTP-cyclohydrolase I, encoded by the GCH1 gene, is the rate-limiting enzyme in the biosynthesis of BH4, an eNOS cofactor important for maintaining enzymatic coupling. We examined the associations between haplotypes of the GCH1 gene, GCH1 expression and biopterin levels, and the effects on endothelial function and vascular superoxide production. Blood samples and segments of internal mammary arteries and saphenous veins were obtained from patients with CAD undergoing coronary artery bypass grafting (n = 347). The GCH1 haplotypes were defined by 3 polymorphisms: rs8007267G<A, rs3783641A<T, and rs10483639C<G (X haplotype: A, T, G; O haplotype: any other combination). Vascular superoxide (+/- the eNOS inhibitor N(G)-nitro-L-arginine methyl ester [L-NAME]) was measured by lucigenin-enhanced chemiluminescence, whereas the vasorelaxations of saphenous veins to acetylcholine were evaluated ex vivo. Haplotype frequencies were OO 70.6%, XO 27.4%, and XX 2.0%. The X haplotype was associated with significantly lower vascular GCH1 messenger ribonucleic acid expression and substantial reductions in both plasma and vascular BH4 levels. In X haplotype carriers both vascular superoxide and L-NAME-inhibitable superoxide were significantly increased, and were associated with reduced vasorelaxations to acetylcholine. GCH1 gene expression, modulated by a particular GCH1 haplotype, is a major determinant of BH4 bioavailability both in plasma and in the vascular wall in patients with CAD. Genetic variation in GCH1 underlies important differences in endogenous BH4 availability and is a determinant of eNOS coupling, vascular redox state, and endothelial function in human vascular disease.


The effect of selected plant extracts on the development of single-species dental biofilms.
To determine the effect of a mixture of plant extracts on the adherence and retention of bacteria in dental biofilm. Experimental study. Department of Oral Biology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia, from December 2009 to December 2011. For determination of adhering ability, experimental pellicle was first treated with the Plant Extracts Mixture (PEM) before inoculating it with individual bacterial species (S. mitis / S. sanguinis / S. mutans). For the determination of retention ability, the procedure was repeated with the experimental pellicle being inoculated first with the individual bacterial species and then treating it with the PEM. These two experiments were repeated with deionized distilled water(negative control) and Thymol (0.64%) (positive control). The bacterial populations in biofilms for the two experiments were expressed as Colony Forming Unit (CFU) / mL x 10(4) and the corresponding values were expressed as mean ± SD. The effect of the Plant Extracts Mixture (PEM) for the two experiments was compared with that of Thymol and deionized distilled water. It was shown that there is a reduced adherence of bacteria to PEM-treated and Thymol (0.064%) treated experimental pellicle compared with the negative control (p < 0.001). It was also found that the retention of bacteria in both treated biofilms is also lower than that of negative control (p < 0.001). Plant Extracts Mixture (PEM) may influence the development of dental biofilm by affecting the adhering and retention capacities of the bacterial species in the dental biofilms.


Factors in homeowners' willingness to adopt nitrogen-reducing innovative/alternative septic systems.
When environmental mitigation requires individual adoption, engagement approaches centered on cost effectiveness and technological efficiency alone are often insufficient. Through focus groups with adopters and prospective adopters, this research identifies factors influencing homeowners' willingness to adopt Innovative/Alternative (I/A) septic systems for nitrogen reduction. We apply concepts from technology adoption and behavior change models as a framework for illustrating the homeowner decision-making process around I/A adoption. The perceived needs to replace an old/failing septic system, comply with local regulations, and protect local water quality synergistically catalyzed adoption. Adoption was further influenced by the larger context within which it is taking place, perceived characteristics of I/A systems and the installation process, system aesthetics concerns, and homeowners' attitudes and beliefs. Considering how these factors affect adoption could enable resource managers to design more targeted interventions to encourage adoption through behavior change strategies such as social marketing, and to improve how these systems are communicated. If I/A systems are to be used as a tool to achieve water quality goals, the considerations influencing homeowners' willingness to install these systems will be critical to incentivizing voluntary adoption. Many of these factors are relevant to the adoption of other individual-level environmental management strategies, which are being increasingly deployed in response to complex, nonpoint source pollution issues.


Analysis of radiation pneumonitis and radiation-induced lung fibrosis in breast cancer patients after breast conservation treatment.
We examined radiation pneumonitis in breast cancer patients after breast conservation treatment (BCT) and analysed the degree of radiation-induced lung fibrosis by computed tomographies of the chest (chest CT). Fifty-two breast cancer patients were treated with BCT, including breast irradiation and chemotherapy. These patients symptomatic of radiation pneumonitis were examined every two to four weeks. Chest X-rays and chest CT were performed about one year after irradiation. symptoms due to radiation pneumonitis was registered in 9.6% of patients. lungs showed fibrotic changes by chest CT in 90% of the cases. Concurrent or alternative chemotherapy increased the incidence of symptomatic radiation pneumonitis and, to a certain extent, the degree of fibrotic change in the lung after BCT.


Glaucoma in a captive-bred great horned owl (Bubo virginianus virginianus).
A captive-bred adult great horned owl (Bubo virginianus virginianus) behaved as though it was bilaterally blind. An ophthalmological examination showed that it had an increased intraocular pressure in both eyes and gonioscopy showed an abnormality of the iridocorneal angles. Retinal changes were also observed. Treatment was not attempted and the owl was euthanased. Histopathology confirmed the abnormal iridocorneal angles, but the exact aetiology of the primary glaucoma was not identified.


Molecular beam brightening by shock-wave suppression.
Supersonic beams are a prevalent source of cold molecules used in the study of chemical reactions, atom interferometry, gas-surface interactions, precision spectroscopy, molecular cooling, and more. The triumph of this method emanates from the high densities produced in relation to other methods; however, beam density remains fundamentally limited by interference with shock waves reflected from collimating surfaces. We show experimentally that this shock interaction can be reduced or even eliminated by cryocooling the interacting surface. An increase of nearly an order of magnitude in beam density was measured at the lowest surface temperature, with no further fundamental limitation reached. Visualization of the shock waves by plasma discharge and reproduction with direct simulation Monte Carlo calculations both indicate that the suppression of the shock structure is partially caused by lowering the momentum flux of reflected particles and significantly enhanced by the adsorption of particles to the surface. We observe that the scaling of beam density with source pressure is recovered, paving the way to order-of-magnitude brighter, cold molecular beams.


Guided Growth With Temporary Hemiepiphysiodesis to Treat Ankle Valgus in a Skeletally Immature Individual: A Case Report.
Guided growth is useful in correcting pediatric angular deformities. Ankle valgus is a coronal plane deformity and is often seen in skeletally immature patients with congenital or acquired lower extremity pathologic features. Temporary hemiepiphysiodesis with a percutaneous transphyseal medial malleolar screw is a surgical treatment capable of correcting the angular deformity and can offer effective correction. In the present case study, a 12-year-old male with dorsal-lateral peritalar subluxation and ankle valgus underwent a reconstructive procedure and temporary hemiepiphysiodesis with a percutaneous medial malleolar screw. After removal of the screw, reduction of his peritalar subluxation was achieved, improving his lateral-distal tibial angle from 81° preoperatively to 89° at the final follow-up examination. The patient returned to his preoperative sporting activities and ambulated comfortably and pain free in sneakers with orthotics. In conclusion, temporary hemiepiphysiodesis with a transphyseal medial malleolar screw is an effective treatment option for ankle valgus in a skeletally immature individual.


Unhelmeted Injured Cyclists in a Canadian Emergency Department: Cycling Behavior and Attitudes Towards Helmet Use.
We seek to characterize unhelmeted injured cyclists presenting to the emergency department: demographics, cycling behavior, and attitudes towards cycling safety and helmet use. This was a prospective case series in a downtown teaching hospital. Injured cyclists presenting to the emergency department were recruited for a standardized survey if not wearing a helmet at time of injury and over age 18. Exclusion criteria included inability to consent (language barrier, cognitive impairment) or admission to hospital. We surveyed 72 UICs (unhelmeted injured cyclists) with mean age of 34.3 years (range 18-68, median 30, IQR 15.8 years). Most UICs cycled daily or most days per week in non-winter months (88.9%, n = 64). Most regarded cycling in Toronto as somewhat dangerous (44.4%, n = 32) or very dangerous (5.9%, n = 4). Almost all (98.6%, n = 71) had planned to cycle when departing home that day. UICs reported rarely (11.1%, n = 8) or never (65.3%, n = 47) wearing a helmet. Reported factors discouraging helmet use included inconvenience (31.9%, n = 23) and lack of ownership (33.3%, n = 24), but few characterized helmets as unnecessary (11.1%, n = 7) or ineffective (1.4%, n = 1). Unhelmeted injured cyclists were frequent commuter cyclists who generally do not regard cycling as safe yet choose not to wear helmets for reasons largely related to convenience and comfort. Initiatives to increase helmet use should address these perceived barriers, and further explore cyclist perception regarding risk of injury and death.


Hypoxia- and vascular endothelial growth factor-induced stromal cell-derived factor-1alpha/CXCR4 expression in glioblastomas: one plausible explanation of Scherer's structures.
The morphological patterns of glioma cell invasion are known as the secondary structures of Scherer. In this report, we propose a biologically based mechanism for the nonrandom formation of Scherer's secondary structures based on the differential expression of stromal cell-derived factor (SDF)-1alpha and CXCR4 at the invading edge of glioblastomas. The chemokine SDF-1alpha was highly expressed in neurons, blood vessels, subpial regions, and white matter tracts that form the basis of Scherer's secondary structures. In contrast, the SDF-1alpha receptor, CXCR4, was highly expressed in invading glioma cells organized around neurons and blood vessels, in subpial regions, and along white matter tracts. Neuronal and endothelial cells exposed to vascular endothelial growth factor up-regulated the expression of SDF-1alpha. CXCR4-positive tumor cells migrated toward a SDF-1alpha gradient in vitro, whereas inhibition of CXCR4 expression decreased their migration. Similarly, inhibition of CXCR4 decreased levels of SDF-1alpha-induced phosphorylation of FAK, AKT, and ERK1/2, suggesting CXCR4 involvement in glioma invasion signaling. These studies offer one plausible molecular basis and explanation of the formation of Scherer's structures in glioma patients.


Preparation of core-shell magnetic molecularly imprinted polymer nanoparticles for recognition of bovine hemoglobin.
Imprinting nanoparticles: Core-shell bovine hemoglobin (BHb) imprinted magnetic nanoparticles (MNPs) with a mean diameter of 210 nm have been synthesized for the first time. The imprinted magnetic nanoparticles could easily reach the adsorption equilibrium and magnetic separation under an external magnetic field, thus avoiding problems related to the bulk polymer. In this work, the core-shell bovine hemoglobin (BHb) imprinted magnetic nanoparticles (MNPs) with a mean diameter of 210 nm were synthesized for the first time. In this protocol, the initial step involved co-precipitation of Fe(2+) and Fe(3+) in an ammonia solution. Silica was then coated on the Fe(3)O(4) nanoparticles using a sol-gel method to obtain silica shell magnetic nanoparticles. Subsequently, 3-aminophenylboronic acid (APBA), which is the functional and cross-linking monomer, and poly(APBA) thin films were coated onto the silica-modified Fe(3)O(4) surface through oxidation with ammonium persulfate in an aqueous solution in the presence or absence of protein. The morphology, adsorption, and recognition properties of the magnetic molecularly imprinted nanomaterial were investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Rebinding experiments were carried out to establish the equilibrium time and to determine the specific binding capacity and selective recognition. The protein adsorption results showed that poly(APBA) MIPs-coated magnetic nanoparticles have high adsorption capacity for template protein BHb and comparatively low non-specific adsorption. The imprinted magnetic nanoparticles could easily reach the adsorption equilibrium and magnetic separation under an external magnetic field, thus avoiding problems related to the bulk polymer. We believe that the imprinted polymer-coated magnetic nanoparticles can be one of the most promising candidates for various applications, which include chemical and biochemical separation, cell sorting, recognition elements in biosensors, and drug delivery.


European brown hare syndrome in England.
The livers from 50 brown hares (Lepus europaeus) were examined by electron microscopy for calicivirus-like particles typical of the virus of European brown hare syndrome (EBHS). The virus was visible in 23 of the livers which included four taken from hares which died in 1982 and 1985 and which had been stored at -20 degrees C. The clinical histories, post mortem and other findings associated with these 23 hares were similar to those described in cases of European brown hare syndrome in other European countries. The findings were compared with those associated with viral haemorrhagic disease (VHD) of rabbits which, although it did not occur in the United Kingdom until 1992, is also caused by a calicivirus believed to be related to EBHS virus. The finding of the virus in hares which died from the disease in 1982 is the earliest recorded isolation of the organism and predates the description of VHD virus and VHD in China in 1984. A retrospective review of post mortem reports revealed cases of disease between 1976 and 1977 which may have been due to EBHS and it is considered that the disease has occurred sporadically in England for several years. The results from suspected and confirmed cases of EBHS in England between 1976 and 1990 are reported and the epidemiology and emergence of the disease is considered.


[Fluorescein, indocyanine green and optical coherence tomography angiography in patients with native exudative age-related macular degeneration].
The newly developed optical coherence tomography angiography (OCT-A) has provided new means to depict the vascular plexus in neovascular age-related macular degeneration (nAMD). If these images are to be used as a basis for therapeutic decisions, it is of vital importance to classify choroidal neovascularization (CNV) as either classical or occult. This study aimed at comparing the findings in OCT-A imaging of CNV with the traditional multimodal imaging through fluorescein angiography (FLA) and indocyanine green angiography (ICGA). For this investigation 13 eyes from 13 patients with CNV on the basis of untreated nAMD were studied using FLA, ICGA, spectral domain OCT and OCT-A. All CNV were classified on the basis of SD-OCT and OCT-A images by two independent raters. Thereafter FLA and ICGA images were analyzed to set the gold standard for the classification and the ratings were compared to the previous SD-OCT and OCT-A results. 88% of eyes were correctly classified as either classical or occult CNV on the basis of SD-OCT and OCT-A images. Based on the CNV subgroups, 93% of classical CNV were identified using OCT-A images. In contrast occult CNV was correctly classified in 83% of patients. The interrater agreement was 77%. In general it was noted that the more the retina was pathologically altered, e. g. by edema or vascular pigment epithelium detachment, the harder it became to correctly classify the CNV. These results show that OCT-A can be used as an interesting addition in the diagnosis of CNV in nAMD. All CNV could be visualized using OCT-A and especially classical CNV could be clearly recognized in most cases. In contrast occult CNV could be identified in slightly fewer cases.


Teamwork Assessment Tools in Modern Surgical Practice: A Systematic Review.
Introduction. Deficiencies in teamwork skills have been shown to contribute to the occurrence of adverse events during surgery. Consequently, several teamwork assessment tools have been developed to evaluate trainee nontechnical performance. This paper aims to provide an overview of these instruments and review the validity of each tool. Furthermore, the present paper aims to review the deficiencies surrounding training and propose several recommendations to address these issues. Methods. A systematic literature search was conducted to identify teamwork assessment tools using MEDLINE (1946 to August 2015), EMBASE (1974 to August 2015), and PsycINFO (1806 to August 2015) databases. Results. Eight assessment tools which encompass aspects of teamwork were identified. The Nontechnical Skills for Surgeons (NOTSS) assessment was found to possess the highest level of validity from a variety of sources; reliability and acceptability have also been established for this tool. Conclusions. Deficits in current surgical training pathways have prompted several recommendations to meet the evolving requirements of surgeons. Recommendations from the current paper include integration of teamwork training and assessment into medical school curricula, standardised formal training of assessors to ensure accurate evaluation of nontechnical skill acquisition, and integration of concurrent technical and nontechnical skills training throughout training.


Implementation of human-machine synchronization control for active rehabilitation using an inertia sensor.
According to neuro-rehabilitation practice, active training is effective for mild stroke patients, which means these patients are able to recovery effective when they perform the training to overcome certain resistance by themselves. Therefore, for rehabilitation devices without backdrivability, implementation of human-machine synchronization is important and a precondition to perform active training. In this paper, a method to implement this precondition is proposed and applied in a user's performance of elbow flexions and extensions when he wore an upper limb exoskeleton rehabilitation device (ULERD), which is portable, wearable and non-backdrivable. In this method, an inertia sensor is adapted to detect the motion of the user's forearm. In order to get a smooth value of the velocity of the user's forearm, an adaptive weighted average filtering is applied. On the other hand, to obtain accurate tracking performance, a double close-loop control is proposed to realize real-time and stable tracking. Experiments have been conducted to prove that these methods are effective and feasible for active rehabilitation.


How to Avoid Stereotypes? Evaluation of a Strategy based on Self-Regulatory Processes.
Based on research on the motivational processes involved in preventing and controlling stereotypes, we aimed to assess whether temporary activation of egalitarian goals - by means of a task that gives respondents exposure to a text on gender inequality - can prevent stereotyped answers on the task. The task asks participants to place women and men into a hierarchical organizational structure. Two specific objectives were established: first, to control the effect of prejudice and egalitarian commitment on the dependent variable; and second, to study gender differences in task responses. The study included 474 college students, 153 men and 321 women. Their mean age was 20.04 (SD = 4.43). ANCOVA indicated main effects of condition, F(1) = 4.15, p = .042, η2 = .081 (control condition without goal activation vs. experimental condition with goal activation) and sex, F(1) = 40.46, p < .001, η2 = .081, on the dependent variable (female candidates placed in the chart). Specifically, responses from participants in the experimental condition avoided stereotyped answers more than participants in the control condition. Furthermore, women's performance on the task was more egalitarian than men's. Finally, there was a significant interaction effect of condition and type of organization, F(2) = 3.97, p = .019, η2 = .017; participants assigning candidates to the feminized organization differed the most across conditions.


[Male sterility. Experience of an andrologist].
Male sterility is taken as a paradigm for a new approach to andrology. Although known about since Antiquity, responsibility of man in conjugal sterility has only been recognized in the last half century. All the same, even to day, it is not always accepted: although apparently obsolete since women's sexual liberation, this denial often manifests itself in patients behaviour, as well as in their doctor's. Until now, as far as we know, no andrologist has taken into account this strange denial. The aim of this paper is to draw attention to the need for the andrologist to be aware of it in his approach to the sterile man. History of male sterility emphasizes the coexistence, since Antiquity, of two opposite preoccupations, those of doctors thoughtful of proving male sterility existence and those of philosophers, often determined to deny it. Steps of knowledge as well as social structures institutionalizing its dissembling are described. Sexual liberation which claimed to put and end to women's dependence on men is often illusory; acceptance of equality of sexes by men is often more apparent that real. At present, the medicalization of male sterility leads some patients and even some doctors to an activist behaviour which demonstrate their inability to accept even the concept of man sterility. In our opinion, to be an andrologist in the full sense of the word means not only to know the biology of reproduction and the progresses of research in this domain, but also and mainly to be aware of the permanence of prejudices and fantasies infallibly conveyed by the idea of sterility in every one, andrologist included.(ABSTRACT TRUNCATED AT 250 WORDS)


Capture of algae promotes growth and propagation in aquatic Utricularia.
Some carnivorous plants trap not only small animals but also algae and pollen grains. However, it remains unclear if these trapped particles are useless bycatch or whether they provide nutrients for the plant. The present study examines this question in Utricularia, which forms the largest and most widely spread genus of carnivorous plants, and which captures prey by means of sophisticated suction traps. Utricularia plants of three different species (U. australis, U. vulgaris and U. minor) were collected in eight different water bodies including peat bogs, lakes and artificial ponds in three regions of Austria. The prey spectrum of each population was analysed qualitatively and quantitatively, and correlated with data on growth and propagation, C/N ratio and δ(15)N. More than 50 % of the prey of the Utricularia populations investigated consisted of algae and pollen, and U. vulgaris in particular was found to capture large amounts of gymnosperm pollen. The capture of algae and pollen grains was strongly correlated with most growth parameters, including weight, length, budding and elongation of internodes. The C/N ratio, however, was less well correlated. Other prey, such as moss leaflets, fungal hyphae and mineral particles, were negatively correlated with most growth parameters. δ(15)N was positively correlated with prey capture, but in situations where algae were the main prey objects it was found that the standard formula for calculation of prey-derived N was no longer applicable. The mass capture of immotile particles confirms the ecological importance of autonomous firing of the traps. Although the C/N ratio was little influenced by algae, they clearly provide other nutrients, possibly including phosphorus and trace elements. By contrast, mosses, fungi and mineral particles appear to be useless bycatch. Correlations with chemical parameters indicate that Utricularia benefits from nutrient-rich waters by uptake of inorganic nutrients from the water, by the production of more traps per unit of shoot length, and by the capture of more prey particles per trap, as nutrient-rich waters harbour more prey organisms.


Moths on the Flatbed Scanner: The Art of Joseph Scheer.
During the past decade a few artists and even fewer entomologists discovered flatbed scanning technology, using extreme resolution graphical arts scanners for acquiring high magnification digital images of plants, animals and inanimate objects. They are not just for trip receipts anymore. The special attributes of certain scanners, to image thick objects is discussed along with the technical features of the scanners including magnification, color depth and shadow detail. The work of pioneering scanner artist, Joseph Scheer from New York's Alfred University is highlighted. Representative flatbed-scanned images of moths are illustrated along with techniques to produce them. Collecting and preparing moths, and other objects, for scanning are described. Highlights of the Fulbright sabbatical year of professor Scheer in Arizona and Sonora, Mexico are presented, along with comments on moths in science, folklore, art and pop culture. The use of flatbed scanners is offered as a relatively new method for visualizing small objects while acquiring large files for creating archival inkjet prints for display and sale.


[Initial results in man of immunolymphoscintigraphy of cancer of the prostate].
The loco-regional investigation of carcinoma of the prostate usually comprises ilio-obturator lymphadenectomy. This procedure carries a significant morbidity. Immunolymphoscintigraphy may provide a non-invasive alternative to this operation. Monoclonal (MAB) 227 A anti-prostatic acid phosphatase antibodies have been produced and selected for their affinity and specificity. This MAB was fragmented to its F (ab')2 form and marked with Iodine 123. Fifteen patients with prostate cancer were given 100 to 400 micrograms of the MAB by periprostatic perineal injection. The region was scanned 1 hr, 3 hrs, 6 hrs and 24 hrs after the injection. The results of the immunolymphoscintigraphy were compared with the histology of the ganglia removed at surgery or needle biopsy guided by CT scanning. In 13 cases the results were concordant for the two techniques (10 negatives and 3 positives). Two patients showed extra-prostatic fixation whilst the histology remained negative. Immunolymphoscintigraphy may therefore provide a simple method of detecting local metastases of carcinoma of the prostate if these initial results are confirmed.


Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides.
Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells' proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.


Stable establishment of cotyledon identity during embryogenesis in Arabidopsis by ANGUSTIFOLIA3 and HANABA TARANU.
In seed plants, the shoot apical and root apical meristems form at the apical and basal poles of the embryonic axis, and leaves form at the flanks of the shoot apical meristem. ANGUSTIFOLIA3/GRF INTERACTING FACTOR1 (AN3/GIF1) encodes a putative transcriptional co-activator involved in various aspects of shoot development, including the maintenance of shoot apical meristems, cell proliferation and expansion in leaf primordia, and adaxial/abaxial patterning of leaves. Here, we report a novel function of AN3 involved in developmental fate establishment. We characterised an an3-like mutant that was found to be an allele of hanaba taranu (han), named han-30, and examined its genetic interactions with an3. an3 han double mutants exhibited severe defects in cotyledon development such that ectopic roots were formed at the apical region of the embryo, as confirmed by pWOX5::GFP expression. Additionally, gif2 enhanced the ectopic root phenotype of an3 han. Although the auxin accumulation pattern of the embryo was correct in an3 han-30, based on DR5rev::GFP expression at the globular stage, expression of the PLETHORA1 (PLT1), a master regulator of root development, expanded from the basal embryonic region to the apical region during the same developmental stage. Furthermore, the plt1 mutation suppressed ectopic root formation in an3 han. These data suggest that establishing cotyledon identity requires both AN3 and HAN to repress ectopic root formation by repressing PLT1 expression.


Fluorescent carbon dot-gated multifunctional mesoporous silica nanocarriers for redox/enzyme dual-responsive targeted and controlled drug delivery and real-time bioimaging.
A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CDHA). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CDHA). The as-prepared MSN-SS-CDHA exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors. Upon loading the antitumor drug, doxorubicin (DOX), into the mesoporous channels of MSN nanoparticles, CDHA with a diameter size of 3nm completely blocked the pore entrance of DOX-encapsulated MSN nanoparticles with a pore size of about 3nm, thus preventing the premature leakage of DOX and increasing the antitumor activity until being triggered by specific stimuli in the tumor environment. The results of the cell imaging and cytotoxicity studies demonstrated that the redox/enzyme dual-responsive DOX-encapsulated MSN-SS-CDHA nanoparticles can selectively deliver and control the release of DOX into tumor cells. Ex vivo fluorescence images showed a much stronger fluorescence of MSN-SS-CDHA-DOX in the tumor site than in normal tissues, greatly facilitating the accumulation of DOX in the target tissue. However, its counterpart, MSN-SH-DOX exhibited no or much lower tumor cytotoxicity and drug accumulation in tumor tissue. In addition, MSN-SS-CD was also used as a control to investigate the ability of MSN-SS-CDHA to target A549 cells. The results obtained indicated that MSN-SS-CDHA possessed a higher cellular uptake through the CD44 receptor-mediated endocytosis compared with MSN-SS-CD in the A549 cells. Such specific redox/enzyme dual-responsive targeted nanocarriers are a useful strategy achieving selective controlled and targeted delivery of therapeutic reagents with real-time bioimaging, and may also facilitate the development of drug delivery systems for a number of clinical applications.


Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma.
The effect of repeated consumption of virgin olive oil on endogenous phenolic metabolites of fasting plasma is unknown. For this reason, we hypothesized that regular long-term virgin olive oil intake could have an indirect protection effect on the endogenous phenols. Thus, the aim of the study was to determine the phenolic profile of human plasma in a fasting state of long-term regular virgin olive oil consumers, using the fasting plasma of non-consumers as a natural control. Forty participants living in the area of Reus (Catalonia, Spain) were selected, 20 life-long regular consumers of virgin olive oil and a natural control of 20 non-consumers, the latter being Rumanians who dislike the taste of olive oil. The diet was obtained from 3-day food records. The results showed similar phenolic composition of fasting plasmas of the two volunteer groups. Of special interest is that more of the compounds quantified showed higher concentration in fasting plasma from habitual virgin olive oil consumers. The compounds were semi-quantified using caffeic acid as the calibration standard. The quantification of fasting consumer's plasma showed higher concentration of a hydroxyflavanone type compound (2.90+/-0.04 microM vs 1.5+/-0.04 microM) and a catecholamine derivative (0.70+/-0.03 microM vs 0.56+/-0.03 microM) than the plasma of non-consumers (P<0.05). The results suggest an indirect protective mechanism of long-term regular virgin olive oil consumption related to the protection of the endogenous antioxidant system.


Genetic Variability of Grapevine Pinot gris virus and Its Association with Grapevine Leaf Mottling and Deformation.
The role of Grapevine Pinot gris virus (GPGV) in the etiology of grapevine leaf mottling and deformation was investigated by biological and molecular assays. A survey on different cultivars from the Trentino Region in Italy showed a widespread distribution of GPGV, which was associated with symptomatic (79%) but also with symptomless (21%) vines. Symptomatic and GPGV-infected 'Pinot gris' vines induced symptoms on grafted vines of healthy Pinot gris or 'Traminer', whereas GPGV-infected but symptomless vines did not. High-throughput sequencing of small RNA (sRNA) populations of two infected Pinot gris accessions confirmed the existence of nearly overlapping viromes in vines with or without symptoms but phylogenetic analyses of the genomes of seven GPGV isolates from Italy and the Czech and Slovak Republics clearly differentiated those infecting symptomatic vines. The involvement of Grapevine rupestris vein feathering virus (GRVFV) in the disease, which was only infecting the symptomatic vine, was ruled out by reverse-transcription polymerase chain reaction studies. Maximum likelihood and Bayesian phylogenetic analysis of two GPGV genomic regions, encompassing part of the movement protein (MP) and coat protein gene sequences and the RNA-dependent RNA polymerase domain of the replicase gene, showed that isolates from symptomatic vines form a lineage distinct from that of symptomless vines. Moreover, the presence or lack of the MP stop codon identified in viral isolates from symptomatic or symptomless vines, respectively, is likely responsible for an MP six amino acids longer in symptomless isolates.


An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: biomonitoring.
This investigation randomly sampled a fluorochemical manufacturing employee population to determine the distribution of serum fluorochemical levels according to employees' jobs and work areas. Previous analyses of medical surveillance data have not shown significant associations between fluorochemical production employees' clinical chemistry and hematology tests and their serum PFOS and perfluorooctanoate (PFOA, C(7)F(15)COO(-)) concentrations, but may have been subject to nonparticipation bias. A random sample of the on-site film plant employee population, where fluorochemicals are not produced, determined their serum concentrations also. Of the 232 employees randomly selected for serum sampling, 186 (80%) employees participated (n=126 chemical plant; n=60 film plant). Sera samples were extracted using an ion-pairing extraction procedure and were quantitatively analyzed for seven fluorochemicals using high-pressure liquid chromatography electrospray tandem mass spectrometry methods. Geometric means (in parts per million) and 95% confidence intervals (in parentheses) of the random sample of 126 chemical plant employees were: PFOS 0.941 (0.787-1.126); PFOA 0.899 (0.722-1.120); perfluorohexanesulfonate 0.180 (0.145-0.223); N-ethyl perfluorooctanesulfonamidoacetate 0.008 (0.006-0.011); N-methyl perfluorooctanesulfonamidoacetate 0.081 (0.067-0.098); perfluorooctanesulfonamide 0.013 (0.009-0.018); and perfluorooctanesulfonamidoacetate 0.022 (0.018-0.029). These geometric means were approximately one order of magnitude higher than those observed for the film plant employees.


Immunosuppressive activity of the ethanol extract of Siegesbeckia orientalis on the immune responses to ovalbumin in mice.
The in vitro and in vivo immunosuppressive activity of the ethanol extract of Siegesbeckia orientalis (EESO) was studied on the immune responses in mice. EESO significantly suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a concentration-dependent manner. ICR Mice were immunized subcutaneously with ovalbumin (OVA) on days 0 and 14. Beginning on the day of immunization, the mice were administered intraperitoneally with EESO at a single dose of 0.25, 0.5, and 1.0 mg at intervals of 7 days. On day 28, OVA-specific antibodies in serum, and mitogen- and OVA-induced splenocyte proliferation were measured. EESO significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA-immunized mice in a dose-dependent manner. The OVA-specific serum IgG, IgG1, and IgG2b levels in the OVA-immunized mice were also significantly reduced by EESO. Moreover, reducing effect on the IgG1 antibody of EESO at the dose of 1.0 mg was more significant than that of cyclosporin A (CsA; positive drug). The results suggest that EESO could suppress the cellular and humoral response to ovalbumin in mice, and deserve further investigations to be developed as immunosuppressant.


[Circadian rhythms of antibacterial resistance, coagulase and antilysozyme activity of Staphylococcus aureus].
To determine daily dynamics of antibacterial resistance as well as antilysozyme and coagulase activity of S. aureus strains. On an example of clinical strains of S.aureus isolated from patients with surgical infections daily dynamics of biological characteristics of staphylococci was studied. After 12 hours of incubation strains were tested for coagulase activity by standard method (test tube method), antilysozyme activity by photometric method, and antibacterial resistance by method of serial dilutions in agar. Tests were repeated each 3-hours during a day. Variation of levels of studied biological characteristics of staphylococci during a day was revealed. Structures of coagulase and antilysozyme circadian rhythms had some differences in different S. aureus strains. Alongside with it, similarity in temporal expression of such biological characteristics of staphylococci as antibacterial resistance and antilysozyme activity was noted. Obtained data open prospect to use biorhythmological approach in study of biological characteristics of microorganisms during evaluation of their mechanisms of adaptation to changing environmental conditions. Chronobiological approach allows to reveal periods of maximal expression of S. aureus characteristics that could be used for increasing of effectiveness of antibacterial treatment by the choice of optimal time for administration of antibiotic.


Crystallographic and spectroscopic characterization and reactivities of a mononuclear non-haem iron(III)-superoxo complex.
Mononuclear non-haem iron(III)-superoxo species (Fe(III)-O2(-·)) have been implicated as key intermediates in the catalytic cycles of dioxygen activation by non-haem iron enzymes. Although non-haem iron(III)-superoxo species have been trapped and characterized spectroscopically in enzymatic and biomimetic reactions, no structural information has yet been obtained. Here we report the isolation, spectroscopic characterization and crystal structure of a mononuclear side-on (η(2)) iron(III)-superoxo complex with a tetraamido macrocyclic ligand. The non-haem iron(III)-superoxo species undergoes both electrophilic and nucleophilic oxidation reactions, as well as O2-transfer between metal complexes. In the O2-transfer reaction, the iron(III)-superoxo complex transfers the bound O2 unit to a manganese(III) analogue, resulting in the formation of a manganese(IV)-peroxo complex, which is characterized structurally and spectroscopically as a mononuclear side-on (η(2)) manganese(IV)-peroxo complex. The difference in the redox distribution between the metal ions and O2 in iron(III)-superoxo and manganese(IV)-peroxo complexes is rationalized using density functional theory calculations.


Granulomatous pigmented purpura: report of a case and review of the literature.
The pigmented purpuric dermatoses (PPD) are a group of diseases characterized by petechiae and bronze discoloration of the skin on the lower extremities. Histopathologically, extravasation of erythrocytes with hemosiderin deposition, a perivascular lymphocytic infiltrate centered on the superficial capillaries and endothelial cell swelling are seen. The granulomatous variant of PPD (GPPD) was described in 1996 and only 10 cases have been reported since in the literature, almost exclusively in patients of East Asian descent only involving the extremities. We present a case of GPPD in a Caucasian, North American Ashkenazi Jewish woman involving the thighs, back, forearms and wrists with concomitant non-granulomatous PPD of the shins. She presented with an asymptomatic, spreading, cayenne pepper-like rash. This rash intermittently involved the lower extremities and back for 15 years, but now involves the thighs with accompanying pink papules on the back, wrists and forearms. Histopathology of the thigh and back lesions revealed superficial lichenoid granulomatous dermatitis with palisading lymphocytes and focal interface changes. Extravasated erythrocytes were seen, but vasculitis was absent. No lymphocytic atypicality was noted and T-cell gene rearrangement studies were non-clonal. This is the second reported case of GPPD in a non-Asian patient and the first case involving sites other than the extremities.


Revisiting Trypanosoma rangeli Transmission Involving Susceptible and Non-Susceptible Hosts.
Trypanosoma rangeli infects several triatomine and mammal species in South America. Its transmission is known to occur when a healthy insect feeds on an infected mammal or when an infected insect bites a healthy mammal. In the present study we evaluated the classic way of T. rangeli transmission started by the bite of a single infected triatomine, as well as alternative ways of circulation of this parasite among invertebrate hosts. The number of metacyclic trypomastigotes eliminated from salivary glands during a blood meal was quantified for unfed and recently fed nymphs. The quantification showed that ~50,000 parasites can be liberated during a single blood meal. The transmission of T. rangeli from mice to R. prolixus was evaluated using infections started through the bite of a single infected nymph. The mice that served as the blood source for single infected nymphs showed a high percentage of infection and efficiently transmitted the infection to new insects. Parasites were recovered by xenodiagnosis in insects fed on mice with infections that lasted approximately four months. Hemolymphagy and co-feeding were tested to evaluate insect-insect T. rangeli transmission. T. rangeli was not transmitted during hemolymphagy. However, insects that had co-fed on mice with infected conspecifics exhibited infection rates of approximately 80%. Surprisingly, 16% of the recipient nymphs became infected when pigeons were used as hosts. Our results show that T. rangeli is efficiently transmitted between the evaluated hosts. Not only are the insect-mouse-insect transmission rates high, but parasites can also be transmitted between insects while co-feeding on a living host. We show for the first time that birds can be part of the T. rangeli transmission cycle as we proved that insect-insect transmission is feasible during a co-feeding on these hosts.


MiR-4262 promotes cell apoptosis and inhibits proliferation of colon cancer cells: involvement of GALNT4.
A role of microRNA-4262 (miR-4262) in the carcinogenesis of colon cancer remains undetermined. In this study, we studied the effects and mechanisms of miR-4262 to the colon cancer cell proliferation and apoptosis. We found that the levels of miR-4262 significantly down-regulated in colon cancer tissue, compared to the paired adjacent non-tumor colon tissue. The miR-4262 levels in colon cancer cell lines were significantly lower than those in control normal colon tissues. Transfection with the miR-4262 mimic decreased the cell proliferation and increased cell apoptosis in colon cancer cells, while transfection with the antisense of miR-4262 (as-miR-4262) increased cell proliferation and suppressed cell apoptosis in colon cancer cells. Bioinformatics analyses showed that GALNT4 was a potential target gene of miR-4262. The luciferase activities assay and Western blot verified that miR-4262 targeted GALNT4 mRNA to modulate its protein levels. When we treated cells with miR-4262 and GALN4 siRNA, the cell viability was significantly decreased. Together, our study suggests that aberrantly expressed miR-4262 may affect cell apoptosis and proliferation of human colon cancer cells via GALNT4, which appears to be a promising therapeutic target for colon cancer.


Electric-Field-Driven Spin Resonance by On-Surface Exchange Coupling to a Single-Atom Magnet.
Coherent control of individual atomic and molecular spins on surfaces has recently been demonstrated by using electron spin resonance (ESR) in a scanning tunneling microscope (STM). Here, a combined experimental and modeling study of the ESR of a single hydrogenated Ti atom that is exchange-coupled to a Fe adatom positioned 0.6-0.8 nm away by means of atom manipulation is presented. Continuous wave and pulsed ESR of the Ti spin show a Rabi rate with two contributions, one from the tip and the other from the Fe, whose spin interactions with Ti are modulated by the radio-frequency electric field. The Fe contribution is comparable to the tip, as revealed by its dominance when the tip is retracted, and tunable using a vector magnetic field. The new ESR scheme allows on-surface individual spins to be addressed and coherently controlled without the need for magnetic interaction with a tip. This study establishes a feasible implementation of spin-based multi-qubit systems on surfaces.


Dietary Intervention through Flipped Learning as a Techno Pedagogy for the Promotion of Healthy Eating in Secondary Education.
Technological progress in the educational field has led to the application of active and innovative teaching methods, such as flipped learning, including in the field of dietary education. This is considered a mixed formative approach that combines face-to-face and outside the classroom education. The objective of this research was to analyze the effectiveness of flipped learning methodology on a traditional training practice in dietary training, both in the sixth grade of primary education and in the fourth level of secondary education. A quasi-experimental design was adopted with two experimental groups, two control groups and only posttest. The final sample was composed of 115 students divided into four groups, two of each educational stage mentioned. A didactic unit consisting of six sessions in all groups was applied. Two different training methodologies were followed according to the nature of the group (control-traditional; experimental-flipped learning). The results reveal that flipped learning is effective both in primary education and in secondary education, being more influential in student development in this last stage. It is concluded that the flipped learning approach has meant an improvement of the academic indicators evaluated after a diet education program.


Social trust, firearm prevalence, and homicide.
Past research suggests that Americans arm themselves when they do not trust one another. We reexamine the relationship between social trust and firearm prevalence with improved data and methods. We also control for conditions, including area homicide rates, that other research showed to be related to both social trust and firearm prevalence. We use structural equation models to assess reciprocal effects of social trust, firearm prevalence, and homicide rates for a nationally representative sample of counties and county clusters (n = 99). We found no direct relationship between social trust and firearm prevalence. Social trust is related to firearm prevalence indirectly through its influence on homicide rates. Areas with low levels of social trust have high homicide rates, which, in turn, increase firearm prevalence. Americans arm themselves in response to high levels of firearm violence. Because greater social trust is related to lower homicide rates, public health researchers should be concerned with the community conditions that promote social trust.


A durable microsecond solid-state pulsed power system.
An all-solid-state microsecond pulsed power system has been tested in this paper. It can produce larger than 50 kV and microsecond-range pulses continuously for more than 9 × 104 shots into a resistive load at a repetition rate of 10 pps. The whole device has accumulatively operated more than 15 000 pulses at 100 Hz and 3 × 105 pulses at 10 Hz. This all-solid-state pulsed power system consists of a repetitive power supply, a four-stage Marx generator, a pulse forming network, and a resistive load. The repetitive power supply of the pulsed power system is calculated and analyzed first, followed by the introduction of the Marx generator and the three-section anti-resonance network. A polymer box of sodium chloride solution is applied as a resistive load with an impedance of 200 Ω. Repetitive experiments showed that this system is able to operate stably at 100 Hz repetition rate without failure.


Targetable IDH1 mutation identified in a rare case of pancreatic serous cystadenocarcinoma but not a series of serous cystadenomas.
Serous cystadenocarcinoma (SCAC) of the pancreas is rare, with only 35 cases reported in the literature. We present a case of SCAC, comparing the clinical presentation, management and molecular features of this case to a series of serous cystadenoma (SCA), which may be a precursor. Compared with SCAs (n = 5), SCAC was larger (11.5 vs median 3.6 cm). The case of SCAC invaded the spleen and exhibited distant metastasis, a requirement for diagnosis since pathologic features are otherwise indistinguishable from SCA. VHL mutations have been reported in about half of SCA in the literature. Accordingly, we identified either somatic or germline VHL mutations in 3 of 5 SCAs (60%), yet no pathogenic mutation was identified in the SCAC. A somatic mutation in IDH1 was found in SCAC only. This has been associated with multiple malignancies, is targetable with the drug ivosidenib and should be studied as a progression factor in SCAC.


Subclinical hypothyroidism.
Clinical and biochemical indices of thyroid function were compared in 18 euthyroid control subjects and 54 patients at risk of developing hypothyroidism, and the assessment repeated after a four-week trial of oral triiodothyronine (T3) 40 microgram daily. Patients with minor elevation of the pre-treatment serum TSH concentration (5-15 microU/ml) showed significant reduction in the free thyroxine index (FTI), prolongation of the basal ankle reflex half-relasation time (ART), and shortening of the ART after oral T3 treatment, when compared either to control subjects or to patients with a normal TSH level. It is concluded that patients with minimal TSH elevation have minor but parallel abnormalities of both thyroid hormone concentration and action.


Short Sleep Duration is Associated with Prolonged Virus Shedding in SARS-CoV-2 Omicron-Infected Patients.
Sleep disturbance has been implicated in poor prognosis of coronavirus disease 2019 (COVID-19), but less is known about the influence of short sleep duration on COVID-19 outcomes. We aim to investigate whether short sleep duration is associated with prolonged virus shedding duration in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-infected patients. A total of 270 patients with a laboratory confirmed COVID-19 diagnosis during SARS-CoV-2 Omicron-predominant period were recruited. Self-reported sleep duration of the patients was collected. The two-way analysis of variance (ANOVA) was used to determine the interactions between sleep duration and variables, and multivariate logistic regression analysis was used to analyze the effect of independent variables on longer virus shedding duration. The two-way ANOVA revealed a significant sleep duration × snoring interaction effect for virus shedding duration, and a sleep duration × sex interaction effect for virus shedding duration. Multivariate logistic regression model illustrated that patients sleeping <6 h were at greater risk of prolonged virus shedding duration compared to those sleeping ≥6 hours (OR = 1.80, 95% CI = 1.01-3.26), independent of age, sex, co-existing diseases, vaccination condition, and antiviral treatment. Short sleep duration (<6 h) was associated with increased virus shedding in SARS-CoV-2 Omicron-infected patients.


Low rate of transmitted drug resistance may indicate low access to antiretroviral treatment in Maranhão State, northeast Brazil.
The Brazilian AIDS epidemic is characterized by significant geographic contrasts: a reduction in incidence and mortality in the epicenter (southeast) and an increase in the northeast. HIV-1-transmitted drug resistance (TDR) and genetic diversity were investigated among 106 antiretroviral (ARV)-naive patients from Maranhão State, northeast. The HIV-1 protease (PR) and reverse transcriptase (RT) regions were sequenced; subtypes were assigned by REGA/phylogenetic analysis. TDR to the nucleoside/nonnucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and protease inhibitor (PI) was identified by the Calibrated Population Resistance tool (Stanford). The median age was 31 years (range 18-72), with 54.7% women, 78.3% heterosexual transmission, and 17.9% men who have sex with men (MSM). Around 30% had <350 CD4(+) T cells/μl and 47.2% had plasma viral loads ≤10,000 copies/ml. The TDR rate was 3.8% (4/106; CI 95%, 1.2-8.9%) (three males, two of them MSM). Only single class mutations to NRTI (M184V; T215S) or NNRTI (K103S/N) were detected. Subtype B represented 81.1% (86/106), F1 1.9% (2/106), and C 2.8% (3/106); 14.2% were mosaics: 13 BF1 and 2 BC. Surveillance of TDR and HIV-1 genetic diversity is important to improve control strategies regionally.


Peritoneal dialysis in chronic renal failure.
The long-term results of intermittent peritoneal dialysis in long-term treatment of renal disease have yet to equal those of intermittent hemodialysis. However, further exploration and refinement of this technique is justified. Performed in acute stages of disease, both peritoneal dialysis and hemodialysis relieve the symptoms of uremia and specifically "buy time" for the patient so that proper medical or surgical therapy may be instituted. In acute situations, peritoneal dialysis is the procedure of choice, and is an important adjunct to more conventional treatment for chronic renal disease. It may be useful sometimes even in chronically hemodialyzed patients-for example, when the hemodialysis cannula for one reason or another is inaccessible because of clots, replacement, or infection. It is especially valuable when the hemorrhagic complications of uremia contraindicate hemodialysis treatment. Its use in chronic uremia remains sharply limited in time, but for brief periods chronic peritoneal dialysis appears to be a reasonably satisfactory means of prolonging life while awaiting homotransplant or decision for maintenance hemodialysis therapy.


Obliterative portal venopathy: A histopathologic finding associated with chronic antibody-mediated rejection in pediatric liver allografts.
The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV. Clinical status, liver biochemistry, the presence of DSA, and available non-HLA antibody testing, as well as histopathologic features of chronic AMR, were assessed. All four patients with OPV had class II DSA and histopathologic features of chronic AMR based on the Banff criteria. Two patients were noted to have non-HLA antibodies. Three patients are undergoing treatment with IVIG but have persistent DSA. Two patients have graft failure and are awaiting retransplantation. In conclusion, OPV is a histopathologic finding associated with chronic AMR in pediatric LT recipients. Further studies are needed to elucidate whether OPV is reversible and/or amenable to medical therapy.


Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization.
When the skin is injured, keratinocytes proliferate, migrate, and differentiate to regenerate the epidermis. We recently showed that ablation of the vitamin D receptor (Vdr) in keratinocytes delays wound re-epithelialization in mice also fed a low-calcium diet, implicating a cooperative role of Vdr and calcium signaling in this process. In this study, we examined the role of vitamin D and calcium signaling in wound healing by deleting their receptors, Vdr and the calcium-sensing receptor (Casr). Gene expression profiling of neonatal epidermis lacking both Vdr and Casr [Vdr and Casr double knockout (DKO)] specifically in keratinocytes revealed that DKO affects a number of pathways relevant to wound healing, including Vdr, β-catenin, and adherens junction (AJ) signaling. In adult skin, DKO caused a significant delay in wound closure and re-epithelialization, whereas myofibroblast numbers and matrix deposition were unaffected. The injury-induced proliferation of epidermal keratinocytes was blunted in both epidermis and hair follicles, and expression of β-catenin target genes was reduced in the DKO. Expression of E-cadherin and desmoglein 1 was reduced in the shortened leading edges of the epithelial tongues re-epithelializing the wounds, consistent with the decreased migration rate of DKO keratinocytes in vitro. These results demonstrate that Vdr and Casr are required for β-catenin-regulated cell proliferation and AJ formation essential for re-epithelialization after wounding. We conclude that vitamin D and calcium signaling in keratinocytes are required for a normal regenerative response of the skin to wounding.


Contrast-Enhanced CT-Based Radiomics for the Differentiation of Nodular Goiter from Papillary Thyroid Carcinoma in Thyroid Nodules.
Papillary thyroid carcinoma (PTC) and nodular goiter (NG) represent the most commonly malignant and benign diseases of thyroid nodules and are often confused in diagnosis. CT examination has a certain diagnostic value for the diagnosis of suspected malignant thyroid nodules. The application of machine learning to radiomics features provides a new diagnostic approach, which has been widely used in ultrasound examination of the thyroid, but there are few literatures on CT examination. To explore the efficacy of a diagnostic model aided by machine learning for preoperative differentiation of nodular goiter and papillary thyroid carcinoma thyroid nodules on the basis of 3D arterial-phase contrast-enhanced computed tomography (CECT) features. We collected the data of 193 NG and 214 PTC thyroid nodules from 407 patients in CT examinations. Together with the pathologist findings and radiology diagnosis, we built a radiomics model using the 1218 features extracted from the arterial phase of CECT images. By comparing the diagnostic performance of the radiomics model with that of the clinical diagnosis, we assessed the performance of the radiomics model. The radiomics model was developed based on multivariable logistic regression with the optimal 12 radiomics features after feature dimension reduction. The radiomics model performed well on the classification accuracy of the PTC and NG thyroid nodules in the training group and validation group. The radiomics model based on the 3D arterial phase of CECT features performed better than the group of experienced radiologists in differentiating NG and PTC thyroid nodules.


Anti-malaria drug mefloquine induces motor learning deficits in humans.
Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans. The main aim of this study was to investigate the effect of mefloquine on olivary-related motor performance and motor learning tasks in humans. We subjected nine participants to voluntary motor timing (dart throwing task), perceptual timing (rhythm perceptual task) and reflex timing tasks (eye-blink task) before and 24 h after the intake of mefloquine. The influence of mefloquine on motor learning was assessed by subjecting participants with and without mefloquine intake (controls: n = 11 vs mefloquine: n = 8) to an eye-blink conditioning task. Voluntary motor performance, perceptual timing, and reflex blinking were not affected by mefloquine use. However, the influence of mefloquine on motor learning was substantial; both learning speed as well as learning capacity was impaired by mefloquine use. Our data suggest that mefloquine disturbs motor learning skills. This adverse effect can have clinical as well as social clinical implications for mefloquine users. Therefore, this side-effect of mefloquine should be further investigated and recognized by clinicians.


Changes in Sleep Predict Changes in Affect in Older Caregivers of Individuals with Alzheimer's Dementia: A Multilevel Model Approach.
Understanding predictors of older dementia caregivers' mood could provide insight into potential treatments which may delay institutionalization of their care recipient. Research with older noncaregivers has shown that nights characterized by better subjective sleep were associated with days characterized by higher positive and lower negative affect, and vice versa. Examining daily relationships is important, as sleep and affect are state-like behaviors that fluctuate within individuals, across time. This study was a preliminary examination of whether a sample with a greater proportion of older dementia caregivers exhibits similar daily sleep/affect associations. Sleep diaries, actigraphy, and affect data were collected concurrently for 7 days in 55 community-dwelling, dementia caregivers (M = 62.80 years, SD = 12.21; 77.8% female). Sleep and affect were examined within- (day-to-day level) and between-persons (mean level). Findings for older noncaregivers were replicated for negative affect only. Specifically, nights characterized by better subjective sleep were characterized by lower negative affect, and vice versa. Examining older caregivers' daily sleep/affect association is important, because caregiving-related awakenings are unavoidable, often unpredictable, and can impact mood. Future research is needed to examine whether regularization in awakenings and/or negative affect represent important secondary, or even target, treatment outcomes for this vulnerable population.


Anti-leukemic effects of the V-ATPase inhibitor Archazolid A.
Prognosis for patients suffering from T-ALL is still very poor and new strategies for T-ALL treatment are urgently needed. Our study shows potent anti-leukemic effects of the myxobacterial V-ATPase inhibitor Archazolid A. Archazolid A reduced growth and potently induced death of leukemic cell lines and human leukemic samples. By inhibiting lysosomal acidification, Archazolid A blocked activation of the Notch pathway, however, this was not the mechanism of V-ATPase inhibition relevant for cell death induction. In fact, V-ATPase inhibition by Archazolid A decreased the anti-apoptotic protein survivin. As underlying mode of action, this work is in line with recent studies from our group demonstrating that Archazolid A induced S-phase cell cycle arrest by interfering with the iron metabolism in leukemic cells. Our study provides evidence for V-ATPase inhibition as a potential new therapeutic option for T-ALL.


[Experience with the elimination of a cholera focus in a psychiatric clinic and the measures for its prevention].
The epidemic process of cholera in a mental-hospital setting is to a great extent influenced by specific factors. In view of a danger of cholera being brought into a mental in-patient facility the authors insist, based on their own experience, that in summer and autumn seasons in South regions and urban settlements with unstable, in respect of cholera, epidemic situation, not only patients with intestinal disfunction be examined for cholera but all those individuals to be managed at above facility. It is all-important for a mental hospital to have a plan at their disposal of primary antiepidemic measures to be instituted in case dangerous infections will pose too difficult a problem to deal with, with pharmacy being envisaged, provided with all the stores required.


Zika virus infection acquired during brief travel to Indonesia.
Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease.


[Regression analysis in the study of dynamics of 5-nucleotidase activity in mouse peritoneal exudate macrophages].
The time course of the activity of 5-nucleotidase of peritoneal exudate macrophages (PEM) was studied on mice. Regression models of in time changes in the activity of PEM 5-nucleotidase after intraperitoneal administration of 2 immunostimulators: salmosan and blastolysine were constructed by the results of the study. Within the experimentally chosen periods of the study the time changes in the enzyme activity after administration of either salmosan or blastolysine could be adequately approximated by linear regression. The models enabled predicting the enzyme activity levels at various moments within wide ranges after administration of the immunostimulators. Moreover, it is recommended that the regression models of changes in 5-nucleotidase activity after intraperitoneal administration of the immunostimulators be used for quantitative comparison of their efficacy.


Insular Cell Integrity Markers Linked to Weight Concern in Anorexia Nervosa-An MR-Spectroscopy Study.
An insular involvement in the pathogenesis of anorexia nervosa (AN) has been suggested in many structural and functional neuroimaging studies. This magnetic resonance spectroscopy (MRS) study is the first to investigate metabolic signals in the anterior insular cortex in patients with AN and recovered individuals (REC). The MR spectra of 32 adult women with AN, 21 REC subjects and 33 healthy controls (HC) were quantified for absolute N-acetylaspartate (NAA), glutamate + glutamine (Glx), total choline, myo-inositol, creatine concentrations (mM/L). After adjusting the metabolite concentrations for age and partial gray/white matter volume, group differences were tested using one-way multivariate analyses of variance (MANOVA). Post-hoc analyses of variance were applied to identify those metabolites that showed significant group effects. Correlations were tested for associations with psychometric measures (eating disorder examination), duration of illness, and body mass index. The MANOVA exhibited a significant group effect. The NAA signal was reduced in the AN group compared to the HC group. The REC and the HC groups did not differ in metabolite concentrations. In the AN group, lower NAA and Glx signals were related to increased weight concern. We interpret the decreased NAA availability in the anterior insula as a signal of impaired neuronal integrity or density. The association of weight concern, which is a core feature of AN, with decreased NAA and Glx indicates that disturbances of glutamatergic neurotransmission might be related to core psychopathology in AN. The absence of significant metabolic differences between the REC and HC subjects suggests that metabolic alterations in AN represent a state rather than a trait phenomenon.


The self-locking Balgrist hip socket for cementless fixation: biomechanical principles and clinical results.
The Balgrist hip socket, initially made entirely of HDPE (high molecular weight polyethylene), now made of outer titanium alloy shell that faces the bone of the acetabulum has been in clinical use for 10 years. The purpose of this presentation is to illustrate the biomechanical principles that have governed this unique design and to present the clinical results that we have obtained until the end of 1991 with 717 implants. From 1982 to 1987 Balgrist HDPE sockets had been implanted for 346 hips, from 1984 to 1991 Balgrist Titanium alloy sockets have been implanted for 371 hips. The number of revision are 55 of 717 hips. 48 hips out of 55 were with Balgrist HDPE sockets. On the contrary, only 7 hips were with Balgrist titanium socket. The greatest benefit of Balgrist Titanium socket is the excellent mechanical lock with subchondral bone of the acetabulum.


A new diagnostic method for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma based on serum metallothionein, copper, and zinc levels.
Serum metal levels and their ratios are frequently reported to be good signals for diagnosing various diseases. These parameters are not always specific to the disease, however, it is necessary to use other serum parameters for an exact diagnosis. We examined whether the monitoring of these serum parameters such as metallothionein, copper, and zinc levels are useful in diagnosing hepatic disorders. Metallothionein levels of patients with liver cirrhosis and hepatocellular carcinoma were found to be significantly lower than those of patients with chronic hepatitis and those of controls. In contrast, copper levels of the patients with liver cirrhosis and hepatocellular carcinoma were significantly higher than those with chronic hepatitis and controls. Zinc levels of the patients with chronic hepatitis and hepatocellular carcinoma were lower than those of controls. Using these three parameters, we are introducing a new parameter, (Cu/Zn)/MT, by which we can discriminate between patients in the [control+miscellaneous diseases+chronic hepatitis] group and those in the [liver cirrhosis+hepatocellular carcinomal group. The new parameter does not, however, allow us to clearly distinguish between the liver cirrhosis and hepatocellular carcinoma groups. Multivariate discriminant analysis was found to be very useful, with combinations of two discriminant functions having been designed to discriminate both between chronic hepatitis and liver cirrhosis and between liver cirrhosis and hepatocellular carcinoma. This method recognizes the differences between hepatic disorder, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma groups. On the basis of these results, we propose here that the diagnosis of hepatic disorders should be made based on a combination of three serum levels such as those of metallothionein, copper, and zinc.


Relationships between the electrostatic potential, epoxide hydrase inhibition and carcinogenicity for some hydrocarbon and halogenated hydrocarbon epoxides.
For a group of nine hydrocarbon and halogenated hydrocarbon epoxides, there is shown to be a good correlation between their abilities to inhibit epoxide hydrase and the quantity Vmin /Es, where Vmin is the most negative value of the molecule's electrostatic potential in the neighborhood of the epoxide oxygen and Es is a factor that takes account of steric effects. It is also demonstrated that carcinogenicity, for thirteen epoxides, appears to be associated with Vmin having a relatively large negative value. On this basis, several other epoxides are predicted to be carcinogenic. The electrostatic potentials used in developing these relationships have been computed by an ab initio self-consistent-field molecular orbital procedure, using optimized molecular geometries.


Intracellular pH (pHi) in gastric surface epithelium is more susceptible to serosal than mucosal acidification.
Intracellular microelectrode techniques were used to examine the effects of mucosal or serosal acidification on intracellular pH (pHi) in gastric surface epithelial cells. Necturus antrum was mounted in a modified Ussing chamber, and pHi was determined from the difference between the potentials recorded by intracellular conventional and pH-sensitive microelectrodes. In tissues bathed with bicarbonate-buffered Ringer's solution (pH 7), acidification of the mucosal solution to pH 4.5 by isotonic replacement of the NaHCO3 with NaCl had no significant effects on pHi. In contrast, acidification of the serosal solution to pH 4.5 by replacing the bicarbonate reduced pHi from 7.32 +/- 0.04 to 6.95 +/- 0.06 (p less than 0.001, n = 8). Similarly, in tissues bathed with HEPES-buffered Ringer's solution (pH 7.0), pHi was unaffected by reducing the mucosal solution pH to 4.5 with HCl but fell 0.21 +/- 0.05 pH units (p less than 0.01, n = 7) during acidification of the serosal solution to pH 6. These results suggest that gastric epithelium is more sensitive to acidification from the serosal than the mucosal side. Such a finding is consistent with the concept of a gastric mucosal barrier to luminal acid. It may also explain the gastric epithelium's greater sensitivity to acute ulceration during systemic acidosis.


Effect of low-dose propantheline on food-stimulated gastric acid secretion: comparison with an "optimal effective dose" and interaction with cimetidine.
We evaluated the widely held notion that anticholinergic drugs must be used in near toxic doses to inhibit gastric acid secretion effectively. Nine patients with duodenal ulcer were studied after a low dose (15 mg) and after a near toxic dose (averaging 48 mg) of the anticholinergic, propantheline. Mean (+/- S.E.) inhibition of food-stimulated acid secretion was identical with the two doses of propantheline: 29 +/- 10 and 29 +/- 11 per cent, respectively. In addition, when 15 mg of propantheline was combined with the histamine H2-receptor antagonist, cimetidine, acid secretion was suppressed to a greater degree than with either drug alone. A low dose of propantheline is as effective as a near toxic dose in suppressing food-stimulated acid secretion and augments the inhibitory effect of cimetidine.


[Postoperative histologic evaluation of hepatocarcinoma treated using chemo-embolization].
Transcatheter arterial chemoembolization (TAE) is generally considered to be an effective palliative treatment in patients with inoperable hepatocellular carcinoma (HCC). Recently, TAE has also been performed on operable cases, in order to reduce the chances of recurrence. This study was aimed at evaluating the histopathologic changes following chemoembolization in surgically resected HCCs. Chemoembolization was performed by selective intra-arterial injection of Lipiodol-chemotherapeutic agent (Adriamycin), followed by terminal embolization with Spongostan, in 5 patients with operable HCC. All patients underwent Computed Tomography (CT) follow-up and subsequent partial hepatectomy. CT after chemoembolization accurately demonstrated no increase in tumor size in all patients. In all HCCs a thick fibrous capsule was found. Histopathology of the surgically resected HCCs demonstrated complete necrosis of the primary tumor in 4/5 cases; 1 HCC remained viable and tumor cells were found in a few daughter nodules surrounding the tumor. In 1 case there were viable tumor emboli in the small portal vessels around the tumor. In patients with resectable HCC, TAE was useful in preventing tumor growth and in thickening the capsule, thus making surgery safer and reducing the chances of recurrence.


Porcine reproductive and respiratory syndrome in hybrid wild boars, china.
We conducted a serologic investigation of porcine reproductive and respiratory syndrome virus (PRRSV) in hybrid wild boar herds in China during 2008-2009. PRRSV isolates with novel genetic markers were recovered. Experimental infection of pigs indicated that hybrid wild boars are involved in the epidemiology of PRRSV.


Enzymologic studies on patients with methylmalonic aciduria: basis for a clinical trial of deoxyadenosylcobalamin in a hydroxocobalamin-unresponsive patient.
Eleven patients with methylmalonic aciduria have been classified on the basis of detailed enzymology on cultured skin fibroblasts. Nine were classified as mutase deficiencies and were unresponsive to hydroxocobalamin in vivo or in vitro. One was classified as a Cbl A variant and was responsive to hydroxocobalamin therapy in vitro and in vivo. Patient 11 was classified as having deoxyadenosyltransferase deficiency (Cbl B). However, a clinical therapeutic trial of deoxyadenosylcobalamin resulted in no clinical or biochemical improvement. Further studies on the patient's cultured fibroblasts suggested that deoxyadenosylcobalamin fails to reach the mitochondria in an intact form. These studies show that detailed enzymologic classification is essential for the reliable evaluation of the response to therapeutic maneuvers; complementation studies alone may be inadequate to completely classify these patients. Therapy with deoxyadenosylcobalamin offers no advantages over the use of hydroxocobalamin in the treatment of patients with methylmalonic aciduria.


Mixed Reality Supporting Modern Medical Education.
The paper presents new learning support for medical students exemplifying with several 3D applications for training on specific topics in medicine and investigates the impact on medical students. The applications were built using new concepts: Virtual Reality, Augmented Reality, as environments agreed by young people, and gamification to make learning easy and fun. Leap Motion and the VR headset are the devices to control the applications and provide a better human-computer/mobile phone interaction as compared to the current ones. The concepts and the new technologies to display/visualize the applications are the core of the Mixed Reality concept resulting from combining the 4 applications implemented for medical education.


Monitoring the effect of targeted therapies in a gastrointestinal stromal tumor xenograft using a clinical PET/CT.
The purpose of this study is to assess treatment responses induced by the two tyrosine kinase inhibitors, Imatinib and Sunitinib, in a gastrointestinal stromal tumor (GIST) xenograft using a clinical positron emission tomography/computed tomography (PET/CT) scanner. Nude mice bearing human GIST xenografts with mutations in exons 11 and 17 were randomly allocated to treatment with Imatinib, Sunitinib, or placebo daily for seven consecutive days. 2-deoxy-2-[(18)F]fluoro-D: -glucose PET ((18)F-FDG-PET/CT) was performed in a clinical PET/CT scanner at baseline (day 0) and 1 and 7 days after onset of treatment. Treatment response was assessed by measuring tumor volumes and by calculation of tumor-to-liver (18)F-FDG uptake ratios. Minor reductions in tumor volume were observed in both treatment groups. For the two treatment groups, significantly decreased tumor-to-liver uptake ratios were observed both at day 1 (Imatinib, -41%, p = .002; Sunitinib, -55%, p < .001) and at day 8 (Imatinib, -35%, p < .001; Sunitinib, -50%, p < .001), when compared to individual baseline values. For the control tumors, neither tumor volumes nor tumor-to-liver uptake ratios were altered during the 8 days the experiment lasted. Significant anti-tumor effects were demonstrated following treatment with both Imatinib and Sunitinib. Decreased tumor-to-liver uptake ratios were more pronounced than tumor volume reductions. Effects of novel targeted therapies can be evaluated in the GIST xenograft model using a clinical PET/CT scanner.


Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet-Role of PPARγ and PPARα.
In India syzygium cumini (Myrtaceae) is commonly used traditional medicine to treat diabetes. The present study was undertaken to assess an investigation of antihyperglycemic and antidyslipidemic properties of aqueous extract of Syzigium Cumini (SC) in diabetic rats fed a high cholesterol diet. The aqueous extract of SC was screened for antihyperglycemic and antidyslipidemic activity by streptozotocin induced diabetes in rats. Animals were treated with 100, 200 and 400mg/kg body weight of aqueous extract of SC. Metformin were used as reference antihyperglycemic drugs for comparison. Administration of aqueous extract of SC or metformin for 21days resulted in a significant (P<0.05) reduction in serum glucose, insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) compared with diabetic controls. Treatment with 100mg/kg/day aqueous extract of SC did not result in a significant reduction in serum insulin levels, but 200mg/kg/day and 400mg/kg/day, aqueous extract of SC and metformin showed significant reductions 17.89%, 19.60% and 24.40%, respectively. Furthermore, administration of 100, 200 and 400mg/kg/day, aqueous extract of SC and metformin resulted in significant decrease in insulin resistance of 19.20%, 41.59%, 51.55% and 68.68%, respectively. In high fat diet- streptozotocin (HFD - STZ) treated rats β-cells function (HOMA-B) were markedly reduced (5.8-fold), however observed a significant (P<0.01) improvement of β-cell function with aqueous extract of SC (400mg/kg/day) and metformin. The aqueous extract of SC seeds exhibits significant insulin-sensitizing, antidyslipidemic, antioxidant, anti-inflammatory and β-cell salvaging activity in HFD-STZ-induced type 2 diabetic rats via overexpression of PPARγ and PPARα activity, affirming its potential to be used in the prevention and treatment of type 2 diabetes mellitus (T2DM). Further isolation and characterization of active components in SC seed extract are needed to explore the other possible mechanisms and pathways that are involved in its anti-diabetic effect.


Acute effects of captopril on blood pressure and regional blood flows in two types of renovascular hypertensive rats in conscious state.
Mean arterial pressure and three regional blood flows--renal, superior mesenteric, and hindquarter flows--were monitored in conscious normotensive control rats (NCR), in two-kidney, one-clip (two-kidney), and in one-kidney, one-clip (one-kidney) hypertensive rats. After administering captopril, an angiotensin-converting enzyme inhibitor, mean arterial pressure decreased in all three groups. However, lowering of arterial pressure was not statistically significant in any of the groups. Renal flow increased significantly in the intact artery of two-kidney hypertensive rats, whereas it did not significantly increase in the clipped artery of one-kidney hypertensive rats and in the intact artery of NCR. Superior mesenteric flow increased significantly only in one-kidney hypertensive rats. Hindquarter flow did not significantly change in the three groups. Regional resistance reduced significantly in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it did not reduce significantly in these two vascular areas in one-kidney hypertensive rats and in NCR. The present findings show that the renin-angiotensin-mediated vasoconstriction plays a role in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it hardly plays a role in these three vascular beds in one-kidney hypertensive rats.