Introducing conflict resolution and negotiation training into a biomedical sciences graduate curriculum.
Analysis of the biomedical workforce and graduate education have produced recommendations for modifications of pre-doctoral training to broadly prepare trainees for wider ranging scientific careers. Development of training in professional skills is widely recommended, but details of implementation are not widely available. In alignment with these recommendations, we have incorporated professional skills training into the biomedical science graduate curriculum at West Virginia University. An important component of the training is developing conflict resolution and negotiation skills. This training will provide useful skills for academic careers, non-academic careers and life situations outside of the workplace. Conflict resolution/negotiation skills are also relevant in managing issues in diversity, equity and inclusivity. We report our experience in developing this component of the training program, provide an overview of the approach to delivery and practice of skills, and provide an analysis of the reception and effectiveness of the training. Evaluation of effectiveness of training used the principals of the Kirkpatrick Four Level Model of Evaluation. At the end of the course, students completed a questionnaire about their perceptions of training and were asked how they would respond to different scenarios requiring conflict resolution/negotiation skills. Several months later, students were surveyed to determine if they used some of these skills and/or witnessed situations where these skills would be useful. We report our experience in developing conflict resolution/negotiation training in our graduate curriculum, provide an overview of the approach to delivery and practice of skills, and provide an analysis of the reception and effectiveness of the training. The results suggest this training meets a need and is effective. Importantly, these materials provide a template for others wishing to implement similar training in their curricula. Conflict resolution and negotiation training meets a need in graduate education. A mixed approach using didactic and interactive components spaced out over time appears to be an effective method of training.


Influence of PVP molecular weight on the microwave assisted in situ amorphization of indomethacin.
In situ amorphization is an approach that enables a phase transition of a crystalline drug to its amorphous form immediately prior to administration. In this study, three different polyvinylpyrrolidones (PVP K12, K17 and K25) were selected to investigate the influence of the molecular weight of the polymer on the degree of amorphization of the model drug indomethacin (IND) upon microwaving. Powder mixtures of crystalline IND and the respective PVP were compacted at 1:2 (w/w) IND:PVP ratios, stored at 54% RH and subsequently microwaved with a total energy input of 90 or 180kJ. After storage, all compacts had a similar moisture content (∼10% (w/w)). Upon microwaving with an energy input of 180kJ, 58±4% of IND in IND:PVP K12 compacts was amorphized, whereas 31±8% of IND was amorphized by an energy input of 90kJ. The drug stayed fully crystalline in all IND:PVP K17 and IND:PVP K25 compacts. After plasticization by moisture, PVP K12 reached a Tg below ambient temperature (16±2°C) indicating that the Tg of the plasticized polymer is a key factor for the success of in situ amorphization. DSC analysis showed that the amorphized drug was part of a ternary glass solution consisting of IND, PVP K12 and water. In dissolution tests, IND:PVP K12 compacts showed a delayed initial drug release due to a lack of compact disintegration, but reached a higher total drug release eventually. In summary, this study showed that the microwave assisted in situ amorphization was highly dependent on the Tg of the plasticized polymer.


Brain MRI lesion volume measurement reproducibility is not dependent on the disease burden in patients with multiple sclerosis.
We evaluated the potential effect of the lesion burden on the reproducibility of repeated lesion volume (LV) measurements from brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS). Dual-echo, conventional spin echo brain MRI scans were obtained from 107 patients with MS. On proton density-weighted images, LV was assessed three times by the same raters, using a semi-automated, local thresholding technique for lesion segmentation. Mean LV (MLV) was 16.1 mL (range = 0.7-57.3 mL). The mean intra-observer coefficient of variation (COV) for the three measurement replicates was 2.6% (range = 0.2-7.2%). The intra-observer measurement variance (Var) increased with MLV and the fitted model was Var = 0.00187 MLV1.84. This indicates that LV measurements can be considered as measures whose variances are proportional to the square of their mean values, i.e., these measures have constant COV. Using a semi-automated, local thresholding segmentation technique, the reproducibility of LV measurements from brain MRI scans of patients with MS is not significantly influenced by varying lesion burdens.


Bidentate Lewis Acid Catalyzed Domino Diels-Alder Reaction of Phthalazine for the Synthesis of Bridged Oligocyclic Tetrahydronaphthalenes.
A domino process consisting of an inverse and a normal electron-demand Diels-Alder reaction is presented for the formation of bridged tri- and tetracyclic 1,2,3,4-tetrahydronaphthalenes catalyzed by a bidentate Lewis acid. The products were synthesized in a one-pot reaction from commercially available starting materials and contain up to six stereogenic centers. The tetrahydronaphthalenes were isolated as single diastereomers and are derivatives of phenylethylamine, which is well-known as a scaffold of amphetamine or dopamine.


Setting the stage for debating the roles of risk assessment and life-cycle assessment of engineered nanomaterials.
Although technological and environmental benefits are important stimuli for nanotechnology development, these technologies have been contested from an environmental point of view. The steady growth of applications of engineered nanomaterials has heated up the debate on quantifying the environmental repercussions. The two main scientific methods to address these environmental repercussions are risk assessment and life-cycle assessment. The strengths and weaknesses of each of these methods, and the relation between them, have been a topic of debate in the world of traditional chemistry for over two decades. Here we review recent developments in this debate in general and for the emerging field of nanomaterials specifically. We discuss the pros and cons of four schools of thought for combining and integrating risk assessment and life-cycle assessment and conclude with a plea for action.


Fast domain wall motion in the vicinity of the angular momentum compensation temperature of ferrimagnets.
Antiferromagnetic spintronics is an emerging research field which aims to utilize antiferromagnets as core elements in spintronic devices. A central motivation towards this direction is that antiferromagnetic spin dynamics is expected to be much faster than its ferromagnetic counterpart. Recent theories indeed predicted faster dynamics of antiferromagnetic domain walls (DWs) than ferromagnetic DWs. However, experimental investigations of antiferromagnetic spin dynamics have remained unexplored, mainly because of the magnetic field immunity of antiferromagnets. Here we show that fast field-driven antiferromagnetic spin dynamics is realized in ferrimagnets at the angular momentum compensation point TA. Using rare earth-3d-transition metal ferrimagnetic compounds where net magnetic moment is nonzero at TA, the field-driven DW mobility is remarkably enhanced up to 20 km s-1 T-1. The collective coordinate approach generalized for ferrimagnets and atomistic spin model simulations show that this remarkable enhancement is a consequence of antiferromagnetic spin dynamics at TA. Our finding allows us to investigate the physics of antiferromagnetic spin dynamics and highlights the importance of tuning of the angular momentum compensation point of ferrimagnets, which could be a key towards ferrimagnetic spintronics.


Fetus in fetu: a case report and review of the literature.
A cystic tumor was first found in the abdomen of a Taiwanese girl at the age of 9 months. The tumor gradually increased in size and caused no symptoms until the girl was 7 years of age, when surgical removal was carried out. Pathological examination disclosed two "fetuses" within the fibrous sac. The pathogenesis of fetus in fetu and its differentiation from retroperitoneal teratoma are still controversial issues. Further work needs to be done to elucidate whether it is a natural progression of the twinning process to teratoma or the inclusion of a monozygotic diamniotic twin within the bearer.


Construction of refined staging classification systems integrating FIGO/T-categories and corpus uterine invasion for non-metastatic cervical cancer.
To investigate the prognostic value of corpus uterine invasion (CUI) in cervical cancer (CC), and determine the necessity to incorporate it for staging. A total of 809 cases of biopsy-proven, non-metastatic CC were identified from an academic cancer center. Recursive partitioning analysis (RPA) method was used to develop the refined staging systems with respect to overall survival (OS). Internal validation was performed by using calibration curve with 1000 bootstrap resampling. Performances of the RPA-refined stages were compared against the conventional FIGO 2018 and 9th edition TNM-stage classifications by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA). We identified that CUI was independently prognostic for death and relapse in our cohort. RPA modeling using a two-tiered stratification by CUI (positive and negative) and FIGO/T-categories divided CC into three risk groupings (FIGO I'-III'/T1'-3'), with 5-year OS of 90.8%, 82.1%, and 68.5% for proposed FIGO stage I'-III', respectively (p ≤ 0.003 for all pairwise comparisons), and 89.7%, 78.8%, and 68.0% for proposed T1'-3', respectively (p < 0.001 for all pairwise comparisons). The RPA-refined staging systems were well validated with RPA-predicted OS rates showed optimal agreement with actual observed survivals. Additionally, the RPA-refined stages outperformed the conventional FIGO/TNM-stage with significantly higher accuracy of survival prediction (AUC: RPA-FIGO vs. FIGO, 0.663 [95% CI 0.629-0.695] vs. 0.638 [0.604-0.671], p = 0.047; RPA-T vs. T, 0.661 [0.627-0.694] vs. 0.627 [0.592-0.660], p = 0.036). CUI affects the survival outcomes in patients with CC. Disease extended to corpus uterine should be classified as stage III/T3.


Drosophila retinal degeneration C (rdgC) encodes a novel serine/threonine protein phosphatase.
The Drosophila retinal degeneration C (rdgC) gene is required to prevent light-induced retinal degeneration. Molecular analysis shows that the rdgC transcription unit encodes a novel serine/threonine protein phosphatase. Amino acids 153-393 define a domain that has 30% identity with the catalytic domains of types 1, 2A, and 2B serine/threonine protein phosphatases. A putative regulatory domain is appended that contains multiple potential Ca(2+)-binding sites or "EF hand motifs." Thus, the analysis suggests that the rdgC protein is a novel type of serine/threonine protein phosphatase that is directly regulated by Ca2+. rdgC is expressed in the visual systems of the fly, as well as in the mushroom bodies of the central brain.


Utilization and outcomes of transcatheter coil embolization for various coronary artery lesions: Single-center 12-year experience.
Determining the outcomes of transcatheter coil embolization (TCE) for several coronary artery lesions. TCE has been used as a treatment modality for various lesions in the coronary circulation. However, data on the efficacy and safety of TCE to treat coronary artery fistula (CAF), left internal mammary artery (LIMA) side-branch, coronary artery perforation (CAP), coronary artery aneurysm (CAA), and coronary artery pseudoaneurysm (CAPA) are limited. We conducted a retrospective, descriptive analysis of all TCE devices in coronary lesions at our center from 2007 to 2019. Forty-one studied lesions included 25 CAF, 7 LIMA side-branch, 5 CAP, 2 CAA, and 2 CAPA. Short- and 1-year mortality and hospital readmission were reported, in addition to coil-related complications and procedural success. The utilization rate of TCE in coronary artery lesions at our center was found to be 33.8 per 100,000 percutaneous coronary intervention procedures over 12 years. Successful angiographic closure was achieved in 37 out of 41 (87.8%) cases (88, 100, 60, 100, and 100% of CAF, LIMA side-branch, CAP, CAA, and CAPA, respectively). No adverse events were directly related to TCE among the LIMA, CAA, and CAPA cases, and only one patient with CAF required reintervention at 3 months due to coil migration. Coil embolization in our institution was safe and effective in treating different coronary circulation abnormalities with a 87.8% overall success rate. Further study on the use of vascular plug devices in cases such as CAF or LIMA side-branch would be beneficial to understand the treatment options better.


Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels.
Rlip76 (Rlip) is a multifunctional membrane protein that facilitates the high metabolic rates of cancer cells through the efflux of toxic metabolites and other functions. Rlip inhibition or depletion results in broad-spectrum anti-cancer effects in vitro and in vivo. Rlip depletion effectively suppresses malignancy and causes global reversion of characteristic CpG island methylomic and transcriptomic aberrations in the p53-null mouse model of spontaneous carcinogenesis through incompletely defined signaling and transcriptomic mechanisms. The methylome and transcriptome are normally regulated by the concerted actions of several mechanisms that include chromatin remodeling, promoter methylation, transcription factor interactions, and miRNAs. The present studies investigated the interaction of Rlip depletion or inhibition with the promoter methylation and transcription of selected cancer-related genes identified as being affected by Rlip depletion in our previous studies. We constructed novel promoter CpG island/luciferase reporter plasmids that respond only to CpG methylation and transcription factors. We found that Rlip depletion regulated expression by a transcription factor-based mechanism that functioned independently of promoter CpG methylation, lipid peroxidation, and p53 status.


Analyzing the 22-item Sino-Nasal Outcome Test using item response theory.
The 22-item Sino-Nasal Outcome Test (SNOT-22) is a widely applied patient-reported outcome instrument used to assess the severity of symptoms associated with chronic rhinosinusitis. The purpose of this study was to evaluate the measurement performance of the SNOT-22 instrument on an item-level basis, in a sample of patients awaiting elective surgery for chronic rhinosinusitis. This study involved secondary analysis of SNOT-22 data that was prospectively collected from patients diagnosed with chronic rhinosinusitis and awaiting endoscopic sinus surgery in Vancouver, Canada. This study used classic test theory and a 2-parameter graded-response model to evaluate the SNOT-22 items' abilities to measure the severity of chronic rhinosinusitis in terms of patients' self-reported symptoms. This approach models each item's discriminability and difficulty, which provides insight into how well they respectively measure symptoms related to chronic rhinosinusitis. Factor analyses indicated that there are 5 domains of measurement in the SNOT-22. The majority of items demonstrated strong discriminability between symptom severities. Likewise, most of the items demonstrated strong difficulty measuring the symptoms across their range of levels. The exception was those items related to psychological symptoms. Differential item functioning demonstrated that very few of the SNOT-22 items were answered significantly differently by gender or age subgroups. This item-level analysis demonstrates that, in general, the SNOT-22 is a strong instrument. Items related to psychological symptoms require further investigation and warrant a supplemental patient-reported outcome instrument.


Risk Factors for Mortality Among Critical Acute Pancreatitis Patients with Carbapenem-Resistant Organism Infections and Drug Resistance of Causative Pathogens.
Carbapenem-resistant organisms (CRO) have emerged as a major global public health threat, but their role in critical acute pancreatitis (CAP) is still not defined. Our study aims to investigate risk factors associated with mortality and drug resistance among CAP patients with CRO infection. The clinical characteristics of CAP patients with CRO infection and drug resistance of causative pathogens from January 1, 2016, to October 1, 2021, were reviewed retrospectively. Independent risk factors for mortality were determined via univariate and multivariate analyses. Eighty-two CAP patients suffered from CRO infection, with mortality of 60.0%. The independent risk factors for mortality were procalcitonin > 5 ng/L (hazard ratio = 2.300, 95% confidence interval = 1.180-4.484, P = 0.014) and lactic acid > 2 mmol/L (hazard ratio = 2.101, 95% confidence interval = 1.151-3.836, P = 0.016). The pancreas was the main site of infection, followed by lung, bloodstream and urinary tract. Klebsiella pneumoniae and Acinetobacter baumannii were the main pathogenic bacteria of CRO strains with extensive antibiotic resistance (> 60%) to 6 of 8 common antibiotics, except sulfamethoxazole (56.3%) and tigecycline (33.2%). CRO infection has become a serious threat for CAP patients, with high rates of mortality. Procalcitonin and lactic acid represent two independent risk factors for mortality in CAP patients with CRO infection. Klebsiella pneumoniae and Acinetobacter baumannii are the primary categories of CRO pathogens. Greater efforts are needed for early prevention and prompt treatment of CRO infections in CAP patients.


Mechanism of action of Panax notoginoside against lung cancer in mice based on response to CTSB gene.
This study aimed to investigate the mechanism of action of Panax notoginoside (PNS) against lung cancer and inhibition of lung cancer cell proliferation by the drug at different concentrations in a mouse model, considering the cathepsin B (CTSB) gene as a target. The mice were randomly assigned into the following five groups: normal control, tumor-bearing, low-dose Panax notoginoside (TSPN), medium-dose TSPN, and high-dose TSPN. All mice were treated with physiological saline or TSPN at different concentrations for 28 days consecutively by gavage. The tumor size was measured, the tumor growth was observed, and the survival curve was drawn. At different time points, the expression of the CTSB gene was detected using quantitative fluorescent polymerase chain reaction, Western blot analysis, and indirect immunofluorescence. The serum indices, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and Soluble fragment of cytokeratin 19 (CYFRA21), were detected by enzyme-linked immunosorbent assay. In vivo, PNS could directly inhibit the expression of the CTSB gene in tumors of mice, limit tumor growth, and alter tumor-related indices, such as CEA, NSE, and CYFRA21 levels, in the serum to different extents simultaneously. CTSB gene was closely related to the pathogenesis of lung cancer. PNS could act on the CTSB gene, downregulate the expression of CTSB in lung cancer cells, inhibit the proliferation and invasion of tumors, and prolong the survival period.


A preliminary study on urban malaria during the minor transmission season: The case of Adama City, Oromia, Ethiopia.
The distribution of malaria shows considerable spatial heterogeneity globally, regionally and locally. For the design of effective malaria control and elimination, and for its implementation in Ethiopia, urban malaria should be given due attention. Therefore, the present study was aimed to examine the status of urban malaria during the minor transmission season in Adama city. A total of 2590 febrile patients were screened using the gold standard microscopy-based blood test for malaria diagnosis from seven purposively selected health facilities found in Adama City from April to July 2018. Socio-demographic data were collected from malaria positive patients to correlate predisposing factors; like previous malaria history, settlement, travel history, age, and other associated risk factors with malaria incidence. Climatological data, such as temperature and relative humidity, recorded during the study period were also collected from the data base of Adama meteorology center for analysis. The microscopic data indicated that from a total of 2590 febrile patients screened for malaria during the study period 3.7% (97/2590) of them were confirmed malaria positive. Adolescents and adults (≥15 years of age) were found to be most affected by Plasmodium vivax (66%) and Plasmodium falciparum (20.5%), and mixed (6%). Analysis of the climatological data revealed a rise in environmental temperature and relative humidity during the study that coincides with the increase of malaria cases, since it creates favorable mosquito breeding for malaria transmission in the city. P. vivax was found as a predominant species in causing malaria burden indicating its public health problem in Adama city affecting the productive age group of the community, adolescents and adults, during the minor transmission season of malaria. In addition to its public health importance by causing morbidity and mortality such kind of scenario may also exacerbates poverty.


The extrasplanchnic origin of blood dihydrotestosterone in elderly men.
The splanchnic extraction and interconversion of testosterone (T) and dihydrotestosterone (DHT) were studied in 5 elderly men undergoing cardiac catheterization using a constant infusion of [1,2-3H] testosterone and [4-14C] DHT. Metabolic clearance rate (MCR), splanchnic extraction (SE), splanchnic clearance (SC), extrasplanchnic clearance (ESC), transfer constant in blood ([p] T-DHT BB) and transfer constant across the liver ([p] T-DHT SB) were calculated. The MCRT was 675 +/- 108 (mean +/- SC) L/day and MCRDHT was 409 +/- 68 L/day. SET was 45.9 +/- 7.0% and SEDHT was 18.5 +/- 5.4%. When these values are compared with those recently reported by us for normal men, there is a 1/3 reduction in SET and 1/2 reduction for SEDHT in elderly men. The calculated SCT and ESCT were 355 +/- 72 L/day and 320 +/- 86 L/day, respectively. SCDHT and ESCDHT were 145 +/- 48 L/day and 263 +/- 77 L/day respectively, suggesting that a major fraction of DHT is metabolized in extrasplanchnic organs. No evidence for a net appearance of DHT by either mass or specific activity analysis in hepatic vein blood was observed indicating that the splanchnic compartment does not contribute DHT into the circulation either by de novo synthesis or via conversion from testosterone. This work indicates that conversion of testosterone to DHT in elderly men occurs entirely in extrasplanchnic tissue.


Spatial distribution and risk assessment of heavy metals in the coastal waters of the Gulf of Suez, Red Sea, Egypt.
To assess ecological and health risks connected with heavy metal contamination in the Gulf of Suez, Red Sea seawater during winter 2021. The selected heavy metals were detected using the "AAS" Technique. The results presented that; the average metal concentrations ranged between (0.57, 1.47, 0.76, 5.44, 0.95, 18.79, and 1.90 μg/l) for Cd, Pb, Zn, Mn, Fe, Cu, and Ni along the investigated area. Pollution Index for overall Gulf sectors <1, indicating a slightly and moderately affected region. Metal Index for the Gulf is >1, representing the existence of heavy metal pollution, which is alarming in this area. (HPI) Heavy metal pollution index <100 indicates low contamination of heavy metal "and is apposite for consumption. The Gulf's ecological risk index (Eri) mostly fell under the low-ecological risk. The risk health estimation revealed that CDI values for carcinogenic were (10-5 to10-7), (10-6 to10-8), and (10-9 to10-11) for ingestion, dermal, and inhalation, respectively. Ingestion for children is twice as high as the proportions documented for adults. At the same time, THQ values for non-carcinogenic ingestion, dermal, and inhalation were (10-5 to 10-8), (10-4 to 10-5), and (10-10 to 10-12), respectively. Also, the total hazard quotient (THQ ing. + THQ inh.) values were <1 acceptable limit, indicating no non-carcinogenic risk to the residents through dermal adsorption and oral water intake. The ingestion pathway was the main pathway for total risk. In conclusion, the overall hazard risks are lower than the permissible limit of <1 regarding heavy metals.


Induction therapy with basiliximab and full HLA mismatch.
Induction therapy reduces rejection episodes among patients at high immunologic risk. Antithymocyte globulins appear to be superior to basiliximab in this population, despite the greater potential risk of infection and neoplasia. The aim of this study was to evaluate graft function and acute rejection episodes in 6 HLA-mismatched patients who underwent induction with basiliximab but had no other immunologic risk factors. We analyzed retrospectively patients who were transplanted using basiliximab for induction therapy during a 4 year period, comparing patients with full HLA mismatches with those who had 5 or fewer mismatches. None of the patients had other immunological risk factors for rejection. We observed no significant differences between the groups concerning demographic features, cold ischemia times, and panel reactive antibodies. Graft function at 12 and 24 months was not different between both groups. Acute rejection episodes were also not different between groups. In this population of full HLA mismatches and no other immunological risk factors, induction immunosuppression therapy with basiliximab was safe in terms of graft function and acute rejection episodes.


Alpha-tricalcium phosphate hydrolysis to octacalcium phosphate: effect of sodium polyacrylate.
Alpha-Tricalcium phosphate (alpha-TCP) hydrolysis into octacalcium phosphate (OCP) has been investigated in phosphoric acid solution at different concentrations of sodium polyacrylate (NaPA). The hydrolysis process has been followed by powder X-ray diffraction, infrared absorption and scanning electron microscopy analyses. In the absence of the polyelectrolyte, alpha-TCP undergoes a complete transformation into OCP in 24 h. The presence of polyacrylate in solution inhibits the hydrolysis so that a NaPA concentration of 0.5 microm is sufficient to lengthen the time required to complete the hydrolysis to 4 days. The variation of Ca2+ concentration in the soaking solution suggests that the transformation occurs through alpha-TCP dissolution followed by OCP precipitation. The delayed OCP nucleation and growth in the presence of polyacrylate implies a preferential adsorption of the polyelectrolyte on the growing OCP crystals, which induces an anisotropic reduction of the coherence lengths of the perfect crystalline domains.


Adjuvant hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases.
We performed a prospective study of adjuvant hepatic arterial infusion chemotherapy after resection of colorectal liver metastases. We placed hepatic arterial infusion ports in 20 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5-fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months. Nine of the 18 evaluable patients (50%) have developed recurrent colorectal cancer. The liver was the only site of failure in 3 of 18 patients (17%), and extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without recurrence are alive. The median survival of the patients without recurrent disease is 39 months, compared with 27 months for those with recurrent metastatic disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion chemotherapy compared with historical controls treated with surgery alone, we have observed a decreased incidence of recurrent disease after liver resection for metastases. We recommend that patients who undergo hepatic resection for colorectal metastases be considered for postoperative adjuvant chemotherapy to decrease the likelihood of recurrence and to improve survival.


[Patient education in psychiatry: Representations of caregivers, patients and their families].
Why do caregivers working in psychiatry seem to wonder about their practices, in front of the recent mediatisation of patient education in France? Do our educational practices meet the needs and the expectations of patients and their families? These questions led us to carry out this qualitative and prospective study concerning the representations of patient education of the main actors in psychiatry. This work aims to assess the representations of patient education of the main actors in psychiatry, in particular to assess convergences and divergences. This is a qualitative and prospective study. Qualitative data are speeches from caregivers working in psychiatry, patients suffering from a psychiatric pathology and their families. The three populations studied were defined by precise characteristics. The sample was diversified by a variable related to the study theme: experience or not in patient education. Speeches were collected during interviews, which were carried out by the same person. Interviews were semi-structured by a thematic guide, which defined the themes to be explored. The three main themes are: the concept of patient education, the objectives of patient education, and the caregiver/patient relationship. We analysed the content of the speeches with a lexical reference table that we elaborated from the literature of experts in patient education. We also realised a transverse analysis in order to assess convergences and divergences between the different speeches. Thirty-two interviews were realised with fifteen caregivers (six psychiatrists and nine nurses), ten patients and seven families. In the speeches of the different populations, we found the expected element of language for all the themes explored. Unexpected ideas were also found in the speeches of the various groups. We could find convergences and divergences concerning these unexpected ideas between and within each group. Regarding convergences, all the groups mentioned the unexpected idea of the problem of social representations of psychiatric diseases. The three groups also approached the need to develop the work with families. Patients and families entrusted their feeling that there would be a lack of exchange with some caregivers. Patients and caregivers evoked the paternalistic attitude of some caregivers. Finally, both caregivers and family approached their questions regarding the caregiver/patient relationship during care without the patient's consent. We found several divergences in the caregivers' speeches. These divergences seemed to be correlated with the experience in patient education in psychiatry. They concerned the scope of patient education in psychiatry, the differences perceived between patient education in psychiatry or in somatic cares, and the diagnostic announcement to the patient. This last unexpected idea was the main point of divergence between caregivers and patients. Results of this study showed that the representations of caregivers, patients and their families correlate with the experts' ideas regarding patient education. The analysis of the different speeches highlighted several unexpected ideas, which constitute themes of reflection about patient education. Some of these themes concern in particular the medical domain of psychiatry such as the questions about caregiver/patient relationship during care without the patient's consent and restraint. Another theme of psychiatry specific reflection is the differences perceived by some caregivers between their practices and the patient education in somatic care. Others themes of reflection highlighted all the medical specialities: the need to develop the work with families, the problem of the social representations of diseases, the scopes of patient education and the diagnostic announcement to the patient. This study highlighted several themes of reflection about patient education in psychiatry. We should include this theme of reflection in our practices in order to respond more precisely to the needs and the expectations of the patients and their families.


An appraisal of blood trauma and blood-prosthetic interface during left ventricular bypass in the calf and humans.
Mechanical circulatory support was accomplished in 20 calves (mean, 140 days) and in 5 patients following operation for acquired heart disease (range, 1 hour to 8 days) employing a pneumatically actuated xenograft-valved assist pump interposed between the left ventricular apex and aorta. Following pump implantation in calves, hematocrit and platelets decreased transiently and returned to normal within 14 days. Plasma hemoglobin and erythrocyte mechanical fragility values were elevated for 48 hours. Platelet survival was slightly reduced, but erythrocyte survival values were similar to controls. In patients who received assist pumps, plasma hemoglobin and erythrocyte mechanical fragility were transiently elevated, but rapidly decreased to normal. Thrombocytopenia occurred only in the presence of bleeding and renal failure requiring hemodialysis. Pump flow of the left ventricular assist device was maintained above 2.0 L/min/m2 despite serious arrhythmias. Postmortem examination revealed no evidence of thromboemboli in the clinical patients although anticoagulant agents were not administered.


Adaptation of the central retina for high acuity vision: cones, the fovea and the avascular zone.
Presence of a fovea centralis is directly linked to molecular specification of an avascular area in central retina, before the fovea (or 'pit') begins to form. Modelling suggests that mechanical forces, generated within the eye, initiate formation of a pit within the avascular area, and its later remodelling in the postnatal period. Within the avascular area the retina is dominated by 'midget' circuitry, in which signals are transferred from a single cone to a single bipolar cell, then a single ganglion cell. Thus in inner, central retina there are relatively few lateral connections between neurons. This renders the region adaptable to tangential forces, that translocate of ganglion cells laterally/centrifugally, to form the fovea. Optical coherence tomography enables live imaging of the retina, and shows that there is greater variation in the morphology of foveae in humans than previously thought. This variation is associated with differences in size of the avascular area and appears to be genetically based, but can be modified by environmental factors, including prematurity. Even when the fovea is absent (foveal hypoplasia), cones in central retina adopt an elongated and narrow morphology, enabling them to pack more densely to increase the sampling rate, and to act as more effective waveguides. Given these findings, what then is the adaptive advantage of a fovea? We suggest that the advantages of having a pit in central retina are relatively few, and minor, but together work to enhance acuity.


Glare sensitivity and professional drivers' safety: a case of rod-cone dystrophy with negative electroretinogram.
To obtain a driver's licence certain requirements for visual acuity and visual field have to be fulfilled. Mesopic contrast and glare sensitivity are not regularly tested and are not crucial to passing the driving test. We report a case of a 39-year-old professional bus driver whose only complaint was increased glare sensitivity. After he had been involved in four traffic accidents, ophthalmological investigations revealed binocular annular scotomata and night blindness, leading to the diagnosis of rod-cone dystrophy. Enhanced glare sensitivity is a common complaint in elderly people or people with the beginnings of cataract but may also represent an initial symptom of a retinal disorder. It is therefore advisable for traffic safety if drivers with such complaints undergo a complete ophthalmological investigation including visual field testing.


Spinocerebellar projections from the cervical enlargement in the cat, as studied by anterograde transport of wheat germ agglutinin-horseradish peroxidase.
The projection fields of spinocerebellar tracts arising from the cervical enlargement were studied by the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in the cat. Following injections of WGA-HRP into the C5-C8 or T1 segments, labeled terminals were seen in lobule I to sublobule Vf of the anterior lobe, and lobule VI, sublobule VIIb, lobules VIII and IX, the simple lobule, crus II, and the paramedian lobule of the posterior lobe. In the sagittal plane of sublobules Ib-Vf and sublobules VIf and VId, the labeled terminals were distributed mainly in the superficial two thirds of the apicobasal extent. The labeled terminals in the anterior lobe accounted for about 70% of the total labeled terminals; the great majority were in lobule IV (17-20%) and lobule V (40%). The labeled terminals in the posterior lobe accounted for 30% of the total labeled terminals; the majority were in sublobules VIf (11-15%) and VId (6%). In the mediolateral extent, more than 50% of the total labeled terminals in each lobule were concentrated within 1.0 mm from the midline (the vermis) and 70-80% within 2.0 mm from the midline (the vermis and the medial part of the intermediate regions). A smaller number were also present in the intermediate region. Cases with lateral cordotomies revealed that the projections were bilateral but predominantly ipsilateral to the cells or origin and that the quantity of the ipsilateral projection was 66.5-75% of the total in each of sublobules IVb, Va, and VIf. The projection to the paramedian lobule was also predominantly ipsilateral. Projection fields in the horizontal plane were reconstructed from a series of transverse sections through each lobule. In sublobules Va-VIf labeled terminals were distributed in three areas: area 1 located within 0.25 mm from the midline in zone A1 of Voogd; area 2 located between 0.5 and 0.75 mm lateral to the midline in zones A1 and A2; and area 3, which appeared to be located between 0.75 and 1.5 mm lateral to the midline in zones A2-B. These areas extended longitudinally in the apical two thirds of the lobules. From the present and previous retrograde HRP studies it was suggested that the neuronal groups in the cervical enlargement (the medial lamina VI group and the central lamina VII group) project to lobules I-V of the anterior lobe and lobule VI, sublobule VIIb, and lobule VIII of the posterior lobe. They have strong projections to caudal lobules of the anterior lobe (lobules III-Va) and lobules facing the primary fissure (sublobules Vd-Vf and sublobules VIf and VId).


Torque-EMG-velocity relationship in female workers with chronic neck muscle pain.
The present study investigated the effect of chronic neck muscle pain (defined as trapezius myalgia) on neck/shoulder muscle function during concentric, eccentric and static contraction. Forty-two female office workers with trapezius myalgia (MYA) and 20 healthy matched controls (CON) participated. Isokinetic (-60, 60 and 180 degrees s(-1)) and static maximal voluntary shoulder abductions were performed in a Biodex dynamometer, and electromyography (EMG) obtained in the trapezius and deltoideus muscles. Muscle thickness in the trapezius was measured with ultrasound. Pain and perceived exertion were registered before and after the dynamometer test. The main findings were that shoulder abduction torque (at -60 and 60 degrees s(-1)) and trapezius EMG amplitude (at -60, 0 and 60 degrees s(-1)) were significantly lower in MYA compared with CON (p<0.001-0.05). Deltoideus EMG and trapezius muscle thickness were not significantly different between the groups. While perceived exertion increased in both groups in response to the test (p<0.0001), pain increased in MYA only (p<0.0001). In conclusion, having trapezius myalgia was associated with decreased strength capacity and lowered activity of the painful trapezius muscle. The most consistent differences-in terms of both torque and EMG-were found during slow concentric and eccentric contractions. Activity of the synergistic pain free deltoideus muscle was not significantly lower, indicating specific inhibitory feedback of the painful trapezius muscle only. Parallel increase in pain and perceived exertion among MYA were observed in response to the maximal contractions, emphasizing that heavy physical exertion provokes pain increase only in conditions of myalgia.


Biodegradable and injectable hydrogels as an immunosuppressive drug delivery system.
Cyclosporine A (CsA) is an extremely hydrophobic immunosuppressive drug, whose systemic administration to suppress the activity of T cells and T cell-based immune responses is frequently associated with a number of adverse drug reactions. Local delivery of CsA focused on a specific target organ has been proposed as a possible solution to this problem. In this study, we developed biodegradable sol-gel drug delivery systems, consisting of HA-Ca-Alg hydrogels combining hyaluronic acid calcium complex (HA-Ca) and sodium alginate (Alg-Na) components, for the local sustained delivery of CsA. A HA-Ca complex with very high degree of substitution was prepared by the acid-base reaction of hyaluronic acid and calcium acetate. The gelation was completed within about 2-45 min without external addition of calcium salts such as CaSO4 and CaCl2, indicating the high potential of the present hydrogel systems for drug delivery by injection in vivo. The HA-Ca system was characterized by high-resolution inductively coupled plasma-optical emission spectroscopy, 1H NMR, FT-IR, and thermogravimetric analysis methods. Moreover, the scanning electron microscopy analysis of the HA-Ca-Alg hydrogels showed an irregular porous morphology, with interconnected pores of 50-300 μm width. The sol-gel transition and the maximum viscosity (about 10,000 cP) of the HA-Ca-Alg hydrogels were characterized by examining the time evolution of the viscosity at 37 °C. The hydrolytic degradation of the HA-Ca-Alg hydrogel was also examined at 37 °C. CsA-encapsulated HA-Ca-Alg hydrogels exhibited sustained in vitro release of CsA over 14 days, which was confirmed through in vitro measurements of the activity of murine T cells over 2 weeks. These results show that the present injectable HA-Ca-Alg hydrogels can be used effectively for the sustained delivery of extremely hydrophobic immunosuppressive drugs, including CsA.


New insights into the fructosyltransferase activity of Schwanniomyces occidentalis ß-fructofuranosidase, emerging from nonconventional codon usage and directed mutation.
Schwanniomyces occidentalis β-fructofuranosidase (Ffase) releases β-fructose from the nonreducing ends of β-fructans and synthesizes 6-kestose and 1-kestose, both considered prebiotic fructooligosaccharides. Analyzing the amino acid sequence of this protein revealed that it includes a serine instead of a leucine at position 196, caused by a nonuniversal decoding of the unique mRNA leucine codon CUG. Substitution of leucine for Ser196 dramatically lowers the apparent catalytic efficiency (k(cat)/K(m)) of the enzyme (approximately 1,000-fold), but surprisingly, its transferase activity is enhanced by almost 3-fold, as is the enzymes' specificity for 6-kestose synthesis. The influence of 6 Ffase residues on enzyme activity was analyzed on both the Leu196/Ser196 backgrounds (Trp47, Asn49, Asn52, Ser111, Lys181, and Pro232). Only N52S and P232V mutations improved the transferase activity of the wild-type enzyme (about 1.6-fold). Modeling the transfructosylation products into the active site, in combination with an analysis of the kinetics and transfructosylation reactions, defined a new region responsible for the transferase specificity of the enzyme.


Corticolimbic mechanisms in the control of trial and error learning.
As learning progresses, human and animal studies suggest that a frontal executive system is strongly involved early in learning, whereas a posterior monitoring and control system comes online as learning progresses. In a previous study, we employed dense array EEG methodology to delineate the involvement of these two systems as human participants learn, through trial and error, to associate manual responses with arbitrary digit codes. The results were generally consistent with the dual-system learning model, pointing to the importance of both systems as learning progressed. In the present study, we replicate and extend the previous findings by examining the brain responses to error trials as well as examine the activity of these two systems' response to feedback processing. The results confirmed the role of these two systems in learning but they also provide a more complex view of their makeup and function. The frontal system includes ventral (inferior frontal gyrus, ventral anterior cingulate cortex, anterior temporal lobe) corticolimbic structures that are involved early in learning whereas the posterior system includes dorsal (anterior and posterior cingulate and medial temporal lobe) corticolimbic circuits that are engaged later in learning. Importantly, the engagement of each system during the course of learning is dependent on the nature of the events within the learning task.


Hearing results and control of vertigo after retrolabyrinthine vestibular nerve section.
To determine the effect of retrolabyrinthine vestibular nerve section (RVNS) on hearing, vertigo, and associated symptoms, we reviewed our experience in 48 patients. Of the 48, 39 responded to a questionnaire. Although RVNS appeared to have little effect on hearing in Meniere's patients, 91% of non-Meniere's patients had significant and often delayed postoperative sensorineural hearing loss. Our results for vertigo control compared favorably to previous reports with 96% of Meniere's patients and 69% of non-Meniere's patients reporting improvement. Presently, we more frequently recommend RVNS as the primary procedure for the control of severe vertigo in Meniere's patients. Patients with vertigo from other causes must be carefully selected.


Transcriptome profiling analysis of lung tissue of Chinese soft-shell turtle infected by Trionyx sinensis Hemorrhagic Syndrome Virus.
Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV) is the firstly discovered aquatic arterivirus inducing high mortality of Trionyx sinensis. So far, the lack of genomic resources has hindered further research on revealing the immunological characteristics of T. sinensis in response to TSHSV. In the present study, we performed a transcriptome analysis from the lungs of T. sinensis challenged by TSHSV using Illumina-based RNA-Seq. The validity of transcriptomic data was confirmed with the gradual increase of TSHSV RNA copies detected in lung. A total of 103079339 clean reads were generated, and 58374764 unique mapped reads were analyzed. Assembly of the sequence data allowed identifying 16383 unigenes consisting of 36 significant differentially expressed genes (DEGs). These DEGs were categorized into 30 GO-enriched bioprocesses and 9 KEGG pathways. The combinational analysis of GO-enriched bioprocesses and KEGG pathways demonstrated that TSHSV modulated several immune genes of T. sinensis related to various biological processes, including virus recognition (RIG-I/MDA-5), immune initiation (IFIT-1 and IFIT-5), endocytosis (CUBN, ENPP2 and LRP2) and steroid metabolism (FCNIL and STAR). In summary, the finding of this study revealed several immune pathways and candidated genes involved in the immune response of T. sinensis against TSHSV-infection. These results will provide helpful information to investigate molecular mechanism of T. sinensis in response to TSHSV.


Quantitation of intracellular oxidation in a renal epithelial cell line.
We quantitated the presence of intracellular oxidizing species in response to oxidative stimuli using fluorescent cell analytic techniques. The studies were performed with a laser-activated flow cytometry system using 2',7'-dichlorofluorescin diacetate (DCFDA) as a probe for intracellular oxidation events. Oxygen radical formation was initiated by the addition of FeCl2 or xanthine oxidase to the culture media. Xanthine oxidase and FeCl2 both increased intracellular DCFDA oxidation over control (p less than .001). Increases in intracellular DCFDA oxidation in response to xanthine oxidase exposure were inhibited by extracellular superoxide dismutase, catalase and dimethyl sulfoxide (p less than 0.001), implicating the superoxide anion, hydrogen peroxide, and the hydroxyl radical in producing the changes in intracellular dichlorofluorescein fluorescence. Increases in intracellular DCFDA oxidation in response to xanthine oxidase correlated with loss of cellular viability, as established by decreased plating efficiency. We conclude that relative intracellular oxidation can be quantitated within the cultured renal cell and that some extracellularly generated radicals may be capable of traversing the intact cell membrane to oxidize DCFDA in the cell interior.


Opinion of hepatic transplant waiting list patients regarding split liver transplantation.
Split liver transplantation (SLT) increases organ supply for hepatic transplantation. Long-term patient survival and complication rates seem to be equivalent between orthotopic liver transplantation (OLT) and SLT. There are controversies among transplant physicians due to an ethical dilemma between benefiting individual needs or those of society. Barshes and Goss (Am J Transplant 5:2047, 2005) demonstrated that the majority of adult liver transplant candidates are favorable to SLT. The aim of our study was to evaluate the opinions of patients at a Brazilian university hospital regarding SLT. A questionnaire with 14 questions was applied to 50 patients included in a hepatic transplant waiting list regarding SLT. The overall attitudes of 66% of the participants were classified as utilitarian, 31% were classified as self-preserving, and 3% were undecided. Ninety-one percent of patients would be willing to share even if their expected survival after SLT was shorter than that with OLT. For 77% of patients, children must have priority over adults. However, 83% were unaware of the donors for pediatric transplantations. SLT is a consistent solution for organ demand despite controversies among transplant physicians. The present study demonstrated that most patients were favorable to SLT. In conclusion, attitudes toward graft sharing are not barriers to SLT.


[The use of the Brøset Violence Checklist within forensic psychiatry].
It is well known that structured short-term risk assessment tools contribute to predicting physically aggressive behavior in patients in acute psychiatry. To research whether the Brøset-Violence-Checklist (BVC), an instrument for short-term prediction of violence of psychiatric inpatients, can be used in forensic psychiatry and how the use of the BVC is experienced. Twice every 24 hours at more or less fixed times, a BVC score was registered for all patients who stayed in a crisis department within a Forensic Psychiatric Center in 2019. The BVC total scores were then related to physically aggressive incidents. In addition, focus groups and interviews were conducted with sociotherapists to examine experiences with the use of the BVC. The analysis showed a significant predictive value of the BVC total score (AUC = 0.69; p < 0.01). Moreover, the sociotherapists experienced the BVC as user-friendly and efficient. The BVC has good predictive value to forensic psychiatry. This is especially true for those patients for whom personality disorder is not part of the primary classification.


A novel network for nonlinear modeling of neural systems with arbitrary point-process inputs.
This paper address the issue of nonlinear model estimation for neural systems with arbitrary point-process inputs using a novel network that is composed of a pre-processing stage of a Laguerre filter bank followed by a single hidden layer with polynomial activation functions. The nonlinear modeling problem for neural systems has been attempted thus far only with Poisson point-process inputs and using cross-correlation methods to estimate low-order nonlinearities. The specific contribution of this paper is the use of the described novel network to achieve practical estimation of the requisite nonlinear model in the case of arbitrary (i.e. non-Poisson) point-process inputs and high-order nonlinearities. The success of this approach has critical implications for the study of neuronal ensembles, for which nonlinear modeling has been hindered by the requirement of Poisson process inputs and by the presence of high-order nonlinearities. The proposed methodology yields accurate models even for short input-output data records and in the presence of considerable noise. The efficacy of this approach is demonstrated with computer-simulated examples having continuous output and point-process output, and with real data from the dentate gyrus of the hippocampus.


Calcium-induced fusion of proteoliposomes and protein-free liposomes. Effect of their phosphatidylethanolamine content on the structure of fused vesicles.
The acidic phospholipid cardiolipin was shown to be very efficient in promoting calcium-induced fusion of proteoliposomes. The degree of fusion was dependent on the phosphatidylethanolamine content of the vesicles. Addition of CaCl2 to proteoliposomes containing phosphatidylcholine and cardiolipin but without phosphatidylethanolamine did not induce fusion. Fusion of cytochrome oxidase vesicles, containing less than 50 mol% phosphatidylethanolamine resulted in monolamellar vesicles with a diameter of about 200 nm. The vesicles could be induced to fuse further by establishing an osmotic pressure across their membranes. When proteoliposomes containing more than 50 mol% phosphatidylethanolamine were fused, large vesicles with a diameter exceeding 1 micrometer were formed. They appeared in the electron microscope as a mixture of multilamellar and monolamellar vesicles. Fusion of corresponding liposomes resulted in formation of even larger structures appearing as dense multilamellar bodies and paracrystalline honeycomb-like lattices.


Transneuronal labeling of spinal interneurons and sympathetic preganglionic neurons after pseudorabies virus injections in the rat medial gastrocnemius muscle.
The distribution of retrogradely and transneuronally labeled neurons was studied in CNS of rats 4 days after injections of the Bartha strain of pseudorabies virus (PRV) into the medial gastrocnemius (MG) muscle. Tissue sections were processed for immunohistochemical detection of PRV. Retrogradely labeled cells were identified in the ipsilateral MG motor column in the caudal L4 and the L5 spinal segments. In order to evaluate the efficacy of PRV retrograde cell body labeling, the number of PRV retrogradely labeled neurons in the MG motor column was compared to the number labeled with two conventional retrograde cell body markers--Fluoro-Gold and cholera toxin-HRP. A ratio of 1:3 representing medium-sized (less than 30 microns) versus large neurons (greater than 30 microns) was found in the Fluoro-Gold dye experiments; a 1:2 ratio was seen in the PRV experiments. In contrast, when cholera toxin-HRP was used as a retrograde marker, mainly large neurons were labeled; the medium-to-large cell body ratio was 1:10 suggesting cholera toxin-HRP may have a greater affinity for the terminals of alpha-motoneurons as opposed to gamma-motoneurons. Transneuronally labeled cells were identified in the L1-L6 spinal gray matter, intermediolateral cell column (T11-L2), lateral spinal nucleus and medial part of lamina VII in C4 and C5 spinal segments, brainstem (caudal raphe nuclei, rostral ventrolateral medulla, A5 cell group, paralemniscal nucleus, locus coeruleus, subcoeruleus nucleus, red nucleus) and paraventricular hypothalamic nucleus. In the L5 spinal cord, transneuronally labeled neurons were seen in the ipsilateral spinal laminae I and II and bilaterally in spinal laminae IV-VIII, and X. Similar results were obtained in rats that had chronic unilateral L3-L6 dorsal rhizotomies indicating most of the labeling was due to retrograde transneuronal cell body labeling. In order to determine whether PRV was transported into the spinal cord by the dorsal root axons, the ipsilateral dorsal root ganglia (DRGs) were examined for PRV immunoreactivity; none was found. However, using the polymerase chain reaction, viral DNA was shown to be present in the ipsilateral DRGs indicating that some of spinal cord cell body labeling may have resulted from anterograde transneuronal labeling, as well.


Development of exploration of spatial-relational object properties in the second and third years of life.
Within a perception-action framework, exploration is seen as a driving force in young children's development. Through exploration, children become skilled in perceiving the affordances in their environment and acting on them. Using a perception-action framework, the current study examined the development of children's exploration of the spatial-relational properties of objects such as the possibility of containing or stacking. A total of 61 children, belonging to two age cohorts, were followed from 9 to 24 months and from 20 to 36 months of age, respectively. Exploration of a standard set of objects was observed in five home visits in each cohort conducted every 4 months. A cohort-sequential augmented growth model for categorical data, incorporating assumptions of item response theory, was constructed that fitted the data well, showing that the development of exploration of spatial-relational object properties follows an overlapping waves pattern. This is in line with Siegler's model (Emerging Minds, 1996), which suggested that skill development can be seen as ebbing and flowing of alternative (simple and advanced) behaviors. Although the probability of observing the more complex forms of exploration increased with age, the simpler forms did not disappear altogether but only became less probable. Findings support a perception-action view on development. Individual differences in observed exploration and their relations with other variables, as well as future directions for research, are discussed.


Radiation-Induced Cardiovascular Disease.
Thoracic radiation therapy is an effective treatment for several malignancies, such as Hodgkin's lymphoma and breast cancer. Over the years, however, the incidence of cardiovascular events has increased in these patients, notably in younger survivors who do not have traditional risk factors. This review summarizes the pathology, incidence, clinical presentation, and management of cardiac events after radiation therapy. Mediastinal radiation therapy accelerates the atherosclerosis process, resulting in early onset coronary artery disease. Valvular disease due to radiation therapy typically affects the left-sided valves, with aortic regurgitation being the most common. Rarely, it may lead to aortic stenosis requiring surgical interventions. Pericardial involvement includes acute and chronic pericardial disease and pericardial effusion. New studies are investigating the prevalence and pathogenesis of autonomic dysfunction in cancer survivors who have undergone mediastinal and neck radiation. Radiation therapy itself causes vascular endothelial dysfunction, resulting in clinical cardiovascular events, manifesting many years after completion of therapy. There remains little guidance regarding screening and therapies to prevent cardiovascular events in this population.


Analysis of axonal growth and cell migration in 3D hydrogel cultures of embryonic mouse CNS tissue.
This protocol uses rat tail-derived type I collagen hydrogels to analyze key processes in developmental neurobiology, such as chemorepulsion and chemoattraction. The method is based on culturing small pieces of brain tissue from embryonic or early perinatal mice inside a 3D hydrogel formed by rat tail-derived type I collagen or, alternatively, by commercial Matrigel. The neural tissue is placed in the hydrogel with other brain tissue pieces or cell aggregates genetically modified to secrete a particular molecule that can generate a gradient inside the hydrogel. The present method is uncomplicated and generally reproducible, and only a few specific details need to be considered during its preparation. Moreover, the degree and behavior of axonal growth or neural migration can be observed directly using phase-contrast, fluorescence microscopy or immunocytochemical methods. This protocol can be carried out in 4 weeks.


Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel.
Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 X 10(8) GBS/kg/h in ten 2- to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 +/- 2 to 34 +/- 4 torr (p less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01). Arterial hypoxemia developed (p less than 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Leucine Ingestion and Contraction on the Sestrin/GATOR2 Pathway and mTORC1 Activation in Rat Fast-Twitch muscle.
Leucine activates the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) in mammalian skeletal muscle. Recent studies have shown that Sestrin, a leucine sensor, might play a role in this process. However, it remains unknown whether Sestrin dissociates from GATOR2 in a dose- and time-dependent manner and whether an acute bout of muscle contraction augments this dissociation. This study aimed to examine the effects of leucine ingestion and muscle contraction on the interaction between Sestrin1/2 and GATOR2 and on mTORC1 activation. Male Wistar rats were randomly assigned to control (C), leucine 3 (L3), or leucine 10 (L10) groups. Intact gastrocnemius muscles were subjected to 30 repetitive unilateral contractions. The L3 and L10 groups were then orally administered 3 and 10 mmol/kg body weight of L-leucine 2 h after the end of the contractions, respectively. Blood and muscle samples were collected 30, 60, or 120 min after the administration. The blood and muscle leucine concentrations increased in a dose-dependent manner. The ratio of phosphorylated ribosomal protein S6 kinase (S6K) to total S6K (which indicates mTORC1 signaling activation) was markedly increased by muscle contraction and increased in a dose-dependent manner only in rested muscle. Leucine ingestion but not muscle contraction increased Sestrin1 dissociation from GATOR2 and Sestrin2 association with GATOR2. A negative relationship was observed between the blood and muscle leucine concentrations and the Sestrin1 association with GATOR2. The results suggest that Sestrin1, but not Sestrin2, regulates leucine-related mTORC1 activation via its dissociation from GATOR2 and that acute exercise-induced mTORC1 activation involves pathways other than the leucine-related Sestrin1/GATOR2 pathway.


PredicT-ML: a tool for automating machine learning model building with big clinical data.
Predictive modeling is fundamental to transforming large clinical data sets, or "big clinical data," into actionable knowledge for various healthcare applications. Machine learning is a major predictive modeling approach, but two barriers make its use in healthcare challenging. First, a machine learning tool user must choose an algorithm and assign one or more model parameters called hyper-parameters before model training. The algorithm and hyper-parameter values used typically impact model accuracy by over 40 %, but their selection requires many labor-intensive manual iterations that can be difficult even for computer scientists. Second, many clinical attributes are repeatedly recorded over time, requiring temporal aggregation before predictive modeling can be performed. Many labor-intensive manual iterations are required to identify a good pair of aggregation period and operator for each clinical attribute. Both barriers result in time and human resource bottlenecks, and preclude healthcare administrators and researchers from asking a series of what-if questions when probing opportunities to use predictive models to improve outcomes and reduce costs. This paper describes our design of and vision for PredicT-ML (prediction tool using machine learning), a software system that aims to overcome these barriers and automate machine learning model building with big clinical data. The paper presents the detailed design of PredicT-ML. PredicT-ML will open the use of big clinical data to thousands of healthcare administrators and researchers and increase the ability to advance clinical research and improve healthcare.


P2-purinoceptor-mediated inhibition of noradrenaline release in rat atria.
1. We looked for P2-purinoceptors modulating noradrenaline release in rat heart atria. Segments of the atria were preincubated with [3H]-noradrenaline and then superfused with medium containing desipramine (1 microM) and yohimbine (1 microM) and stimulated electrically, by 30 pulses/1 Hz unless stated otherwise. 2. The adenosine A1-receptor agonist, N6-cyclopentyl-adenosine (CPA; EC50 9.7 nM) and the nucleotides, ATP (EC50 6.6 microM) and adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S; EC50 4.8 microM), decreased the evoked overflow of tritium. The adenosine A2a-agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-a denosine (CGS-21680; 0.03-0.3 microM) and the P2x-purinoceptor agonist beta, gamma-methylene-L-ATP (30 microM) caused no change. 3. The concentration-response curve of CPA was shifted to the right by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX; 3 nM; apparent pKB value 9.7) but hardly affected by the P2-purinoceptor antagonist, cibacron blue 3GA (30 microM). In contrast, the concentration-response curves of ATP and ATP gamma S were shifted to the right by DPCPX (3 nM; apparent pKB values 9.3 and 9.4, respectively) as well as by cibacron blue 3GA (30 microM; apparent pKB values 5.0 and 5.1, respectively). Combined administration of DPCPX and cibacron blue 3GA caused a much greater shift of the concentration-response curve of ATP than either antagonist alone. The concentration-response curve of ATP was not changed by indomethacin, atropine or the 5'-nucleotidase blocker alpha, beta-methylene-ADP. 4. Cibacron blue 3GA (30 microM) increased the evoked overflow of tritium by about 70%. The increase was smaller when the slices were stimulated by 9 pulses/O00 Hz instead of 30 pulses/I Hz.5. The results indicate that the postganglionic sympathetic axons in rat atria possess P2-purinoceptors in addition to the known adenosine Al-receptor. Both mediate inhibition of noradrenaline release. Some adenine nucleotides such as ATP and ATP gamma S act at both receptors. The presynaptic P2-purinoceptor seems to be activated by an endogenous ligand, presumably ATP, under the condition of these experiments. This is the first evidence for presynaptic P2-purinoceptors at cardiac postganglionic sympathetic axons.


Role of cAMP, PKA and Rap1A in thyroid follicular cell survival.
Cyclic AMP (cAMP) rescues cells from apoptosis stimulated by diverse insults. We examined the role of cAMP as a survival factor, and the signaling pathways through which cAMP affords protection. Rat thyroid cells were selected for these studies given the predominant role of cAMP in thyrotropin (TSH)-stimulated proliferation and as an oncogene in thyroid cells. Wistar rat thyroid (WRT) cells perished via apoptosis following sodium nitroprusside (SNP) treatment. Elevations in cAMP following treatment with forskolin, 8BrcAMP or IBMX rescued cells from SNP-induced cell death. Notably, TSH prevented apoptosis, implicating an important role for this hormone as a survival factor. Cyclic AMP activates multiple signaling pathways including those mediated through PKA, PI3K, p70S6k and the Ras-related small G protein, Rap1. Intriguingly, multiple pathways modulate thyroid cell survival. Interference with cAMP-stimulated p70S6k, but not PI3K, activity abrogated cell survival. Treatment with PKA inhibitors was sufficient to stimulate apoptosis in hormone-deprived cells and markedly enhanced cell death in response to SNP. Cells expressing an activated Rap1A mutant exhibited an enhanced sensitivity to SNP-induced apoptosis, while those expressing dominant negative Rap1A were resistant to SNP-initiated cell death. Together, these findings establish an important role for PKA and Rap1 in the control of thyroid cell survival.


Production of natural IgM antibodies against oxidatively-modified proteins in milk fat globule epidermal growth factor 8 (MFG-E8) deficient mice.
Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8(-/-)) mice, and these mice develop an autoimmune disease. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8(-/-) mice. It was also revealed that the sera from the MFG-E8(-/-) mice exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ?6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8(-/-) mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells.


Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study.
Intracranial abscesses are relatively uncommon, but can result in significant mortality and morbidity. Whilst many potential causes of brain abscesses are recognised, in many cases the origin of infection remains clinically unidentified. Our objective was to investigate the role of bacteria found in the oral cavity in the development of brain abscesses. A retrospective analysis was performed using data from 87 patients admitted to a single UK neurosurgical unit with brain abscesses over a 16-year period. Using microbiological data obtained from abscess sampling and peripheral cultures, species of bacteria were categorised in patients where no primary source of infection was identified (NSI) for their brain abscess (n = 52), or where an infective source (ISI) was identified. The microbiological data was then screened to identify common oral bacteria in each group. Brain abscesses from the ISI group (n = 35) demonstrated a significantly lower preponderance of oral bacteria (n = 8), than the NSI group (n = 29) (p < 0.05). Brain abscesses from the NSI group also had significantly higher counts of Streptococcus anginosus compared to ISI (p < 0.05), with brain abscesses being most common in the frontal and parietal lobes for both ISI and NSI. These findings suggest that the oral cavity could be considered as a source of occult infection in cases of brain abscess where no clear cause has been identified. Future studies should include oral screening and microbiome analysis to better understand the mechanisms involved and develop approaches for prevention. Oral bacteria may be an under-recognised cause of brain abscesses. Careful review of oral health in brain abscess patients may help establish causation, particularly in patients with no cause for their abscess identified. Good levels of oral health may help prevent the development of brain abscesses in some individuals.


Thoracic herniation after lumbar spine fusion.
We report on a 65-year-old male patient with rapid onset of incomplete paraparesis, based on a massive thoracic herniation following adjacent instability of the thoracolumbar spine after lumbar fusions with transpedicular instrumentation.


Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis.
To study the humoral immune response directed at myelin oligodendrocyte glycoprotein (MOG)in pediatric patients with isolated and recurrent optic neuritis(ON). Observational prospective case series. Six pediatric hospitals in Germany and Austria. Thirty-seven patients 18 years or younger with single or recurrent episodes of ON were recruited from 6 different hospitals. Clinical features, magnetic resonance imaging findings, intrathecal IgG synthesis,and outcome were recorded. A live cell–based immunofluorescence assay was used to measure serum IgG antibodies to MOG and aquaporin 4. A single episode of ON was observed in 10 patients,and 15 experienced 2 to 12 episodes. The acute episode of ON was part of a clinically isolated syndrome in 12 patients, of whom 8 were subsequently classified as having multiple sclerosis. High-titer serum MOG-IgG antibodies (1:160) were detected in 17 patients (46%).In addition, high titers of MOG-IgG antibodies were more frequently observed in 12 of the 15 patients with recurrent episodes of ON (80%; median titer, 1:640)compared with 2 of the 10 patients with monophasic ON(20%; median titer, 0) and 3 of the 12 patients with ON as part of a clinically isolated syndrome (25%; median titer, 0). High-titer MOG-IgG antibodies are predominantly detected in pediatric patients with recurrent ON, indicating that anti-MOG-specific antibodies may exert a direct role in the pathogenesis of ON in this subgroup.


Identification of cannabinoid type 1 receptor expressing cocaine amphetamine-regulated transcript neurons in the rat hypothalamus and brainstem using in situ hybridization and immunohistochemistry.
Recent data have indicated that the neuropeptide cocaine amphetamine-regulated transcript (CART) may be a downstream mediator of the effect of CB1 receptor antagonist on appetite regulation. In order to identify possible interactions between CART and central CB1R expressing neurons, a detailed mapping of CART and CB1R expression and immunoreactivity in the brain was initiated. Single radioactive in situ hybridizations revealed a predominant overlap between CART and CB1R mRNA in hypothalamic and lower brainstem nuclei. Using double in situ hybridization, co-localization between CART and CB1R mRNA expressing neurons was observed to be most pronounced in the retrochiasmatic and lateral hypothalamic areas, as well as in all parts of the dorsal vagal complex. Further attempts to immunohistochemically characterize the distribution of CB1R were, however, deemed impossible as any of eight commercially available antibodies/antisera gave rise to non-specific staining patterns. Furthermore, the staining pattern obtained was not discriminate between CB1R knockout mice and wild type mice. Collectively, we demonstrate at the messenger level that CB1R expressing perikarya colocalize with CART expressing neurons in hypothalamic and brainstem areas known to be important in appetite control, whereas interactions at the protein level necessitate a demand for cautious interpretations of immunohistochemical results.


First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy.
We previously described safety of preschool peanut oral immunotherapy (P-OIT) in a real-world setting; 0.4% of patients experienced a severe reaction, and 4.1% received epinephrine, during build-up. To determine the effectiveness of preschool P-OIT after 1 year of maintenance. Preschoolers (9-70 months) with at least 1 objective reaction to peanut (during baseline oral food challenge (OFC) or P-OIT build-up) received a follow-up OFC to cumulative 4000 mg protein after 1 year on 300 mg peanut daily maintenance. Effectiveness of desensitization was defined as proportion of patients with a negative follow-up OFC. Symptoms and treatment at follow-up OFC were recorded. Of the 117 patients who successfully completed 1 year of P-OIT and subsequently underwent a cumulative 4000-mg follow-up OFC, 92 (78.6%) had a negative OFC and 115 (98.3%) tolerated a cumulative dose of greater than or equal to 1000 mg. For the 25 (21.4%) who reacted, their threshold increased by 3376 mg (95% CI, 2884-3868) from baseline to follow-up; 17 (14.5%) patients experienced grade 1 reactions, 7 (6.00%) grade 2, and 1 (0.85%) grade 3. Two patients (1.71%) received epinephrine associated with P-OIT, and 1 (0.85%) went to the emergency department. Our data demonstrate that real-world preschool P-OIT is effective after 1 year of maintenance for those who received a follow-up OFC. For those who reacted, their threshold increased sufficiently to protect against accidental exposures. P-OIT should be considered for preschoolers as an alternative to current recommendations to avoid peanut.


Olive oil increases the LIPC expression when associated with an Eastern pattern diet: An experimental study with Wistar rats.
Some nutrigenomic effects of extra virgin olive oil (EVOO) are described in the literature; however, it is unknown whether its interaction with lipid-related genes is independent of the combined diet. In this sense, our objective was to investigate whether EVOO consumption associated with Western or Eastern human-based chow modulates the expression of APOE, APOB, and LIPC genes in rats. In view of this, the hypothesis is that the consumption of olive oil may not have the same nutrigenomic effects, depending on the diet consumed. For this study, 56 female rats were randomly divided into four groups: Western diet with EVOO (WS), Western-diet control (WC), Eastern-diet with EVOO (ES), and Eastern-diet control (EC). After 15 weeks, the animals were anesthetized with an intraperitoneal injection of chloral hydrate 15% (1.5 mL/kg) and euthanized by guillotining, and adipose tissue, liver, and blood were extracted. Triglycerides, cholesterol, and glucose levels were obtained following standard protocols, and relative gene expressions were calculated using the ΔΔCt method after quantitative PCR. The EVOO consumption was associated with LIPC gene expression increase in the liver only in animals fed the Eastern diet, compared to EC and WS animals. The EVOO consumption, combined with the Eastern diet, was associated with decreased triglyceride levels compared to WC. Although final weight and weight gain were similar between groups, WS animals had lower daily energy consumption. Conclusion: Given these results, the authors suggested that the EVOO nutrigenomic effects were restricted to an Eastern human-based diet.


Validation of Indications for Surgery of European Evidence-Based Guidelines for Patients with Pancreatic Intraductal Papillary Mucinous Neoplasms.
Which patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical intervention remains a controversial issue. The aim of this retrospective study was to validate the new European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) for the management of IPMNs. One hundred fifty-eight patients with resected IPMNs at National Taiwan University Hospital between January 1994 and December 2016 were enrolled. Clinical information, including new-onset diabetes mellitus (DM) and preoperative CA 19-9 levels, were collected. All patients were stratified into three groups-absolute, relative indications, and conservative approach-according to EEBGPCN. The performance characteristics of EEBGPCN for high-grade dysplasia (HGD)/invasive carcinoma (IC) of IPMNs were calculated. One hundred seven (67.7%) patients with low-grade dysplasia and 51 patients with HGD/IC, including 10 HGD and 41 IC, were analyzed. The missed rate for HGD/IC by EEBGPCN was 1.9% (3/158). The sensitivity, specificity, positive and negative predictive values, and accuracy of the absolute or relative indications for resecting IPMN according to EEBGPCN were 94.1%, 28.0%, 38.4%, 90.9%, and 49.4%. Jaundice, enhancing mural nodule < 5 mm, cyst diameter > 40 mm, increased levels of serum CA 19-9, new-onset DM, and main pancreatic duct dilation were associated with HGD/IC. The missed rate for HGD/IC is low by EEBGPCN. Increased serum CA 19-9 and new-onset DM in EEBGPCN were verified as the indications for the surgical resection of IPMNs.


Synthesis, Characterisation, and Functionalisation of Charged Two-Dimensional MoS2.
The applications of exfoliated MoS2 are limited by its inert surface and poor interface. We have activated the surface of exfoliated 2H-MoS2 by reacting it with NaBH4 , forming an n-doped material as demonstrated by a negative zeta-potential value ζ=-25 mV and a 20 nm (0.05 eV) red-shift in its photoluminescence spectrum. The novel material's spectral properties were consistent with pristine 2H-MoS2 (as determined by HR-TEM, XPS, pXRD, DRIFT, TGA, and Raman spectroscopy). Importantly, it was readily dispersed in H2 O unlike 2H-MoS2 . Its dispersibility properties were explored for a variety of solvents and could be directly correlated with the relative permittivity of the respective solvents. The charged 2H-MoS2 reacted readily with an organo-iodide to deliver functionalized 2H-MoS2 . Our approach delivers aqueous dispersions of semiconducting 2H-MoS2 , without additives or chemical functionalities, and allows for controlled and facile functionalization of 2H-MoS2 opening multiple new avenues of semi-conducting MoS2 application.


Critically important antimicrobial resistant Enterobacteriaceae in Irish farm effluent and their removal in integrated constructed wetlands.
This study investigated the ability of Integrated Constructed Wetlands (ICWs) to remove critically important antimicrobial resistant organisms (AROs) from farm wastewater. Influent samples from the untreated farm waste and effluent samples taken at the end of the ICW system were collected monthly from four ICWs, serving four different farm types (suckler, dairy, dairy & poultry and pig). Using selective media to screen for the presence of carbapenemase resistant organisms, plasmid mediated and AmpC β-Lactamase producing organisms (ESBL/pAmpC) and fluoroquinolone resistant organisms, a total of 82 AROs were obtained with the majority being E. coli (n = 79). Statistically significant were the differences on the number of AROs isolated from influent (higher) compared to effluent, as well as a seasonal effect, with less AROs recovered during winter in comparison to other seasons (P < 0.05). On the other hand, there was no significant differences in the recovery of AROs on different farms. The majority of isolates from each of the farms (99%) were multi drug resistant, with 65% resistant to seven or more antimicrobials. A high incidence of tetracycline, trimethoprim/sulfamethoxazole, and ampicillin resistance was common to the isolates from all four farms but there were differences in ESBL levels with 63% of the isolates recovered from Farm 4 (piggery) being ESBLs compared to 18%, 36% and 4.5% recovered from Farms 1 (suckler), 2 (dairy) and 3 (dairy & poultry), respectively. No carbapenemase producing organisms were isolated. Our results showed that ICWs are effective in removing critically important AROs from farm wastewater on all four farm types.


Imaging protein structure in water at 2.7 nm resolution by transmission electron microscopy.
We demonstrate an in situ transmission electron microscopy technique for imaging proteins in liquid water at room temperature. Liquid samples are loaded into a microfabricated environmental cell that isolates the sample from the vacuum with thin silicon nitride windows. We show that electron micrographs of acrosomal bundles in water are similar to bundles imaged in ice, and we determined the resolution to be at least 2.7 nm at doses of ∼35 e/Å(2). The resolution was limited by the thickness of the window and radiation damage. Surprisingly, we observed a smaller fall-off in the intensity of reflections in room-temperature water than in 98 K ice. Thus, our technique extends imaging of unstained and unlabeled macromolecular assemblies in water from the resolution of the light microscope to the nanometer resolution of the electron microscope. Our results suggest that real-time imaging of protein dynamics is conceptually feasible.


Cerebrospinal fluid levels of oxytocin in Prader-Willi syndrome: a preliminary report.
Prader-Willi syndrome (PWS) is a genetic disorder characterized by mental retardation, appetite dysregulation, and a high risk for obsessive-compulsive disorder (OCD). Microscopic abnormalities of the hypothalamus have been described in PWS, and oxytocin has been implicated in both appetite regulation and OCD. Oxytocin and arginine vasopressin (AVP) were measured in the cerebrospinal fluid of 5 subjects with PWS (2 male, 3 female) and in 6 normal control subjects (all female). CSF oxytocin was elevated in PWS (9.2 +/- 3.9 pmol/L) as compared to normal control subjects (5.1 +/- 0.9 pmol/L, p = 0.045), a finding that was more significant when excluding male subjects from analysis (p = 0.02). AVP was not significantly different between the groups as a whole. These data provide further evidence for hypothalamic and oxytocinergic dysfunction in PWS. The associations between oxytocin, appetite regulation, and obsessive compulsive symptomatology in PWS warrant further investigation.


Thoracic endovascular aortic repair: Current evidence and challenges.
In 1987 Nikolay Volodos performed the world's first endovascular treatment of aortic aneurysms. Endovascular technology has progressed significantly since then. There are now many thoracic endovascular aortic repair (TEVAR) systems commercially available. By applying them, we can treat many pathologies: aneurysms, dissections, aortic ruptures, and penetrating aortic ulcers. However, TEVAR technology still has its limitations, namely the risk of a retrograde type A dissection, the issue of precise landing in the distal landing zone, and the risk of air embolism and paraplegia. Furthermore, there are no appropriate stent grafts widely available to treat acute dissections. Those currently used are designed for aneurysms, not for dissections. As a result, there are several challenges facing the future TEVAR surgical community, such as the need to develop new and more precise systems with retrograde deployment for the distal landing zone, as well as to introduce flexible stent grafts to treat dissections. The endo-Bentall is being developed as an alternative treatment method for acute type-A aortic dissection.


MDC1 interacts with Rad51 and facilitates homologous recombination.
Mediator of DNA damage checkpoint protein-1 (MDC1) is a recently identified nuclear protein that participates in DNA-damage sensing and signaling. Here we report that knockdown of MDC1 by RNA interference results in cellular hypersensitivity to the DNA cross-linking agent mitomycin C and ionizing radiation and in impaired homology-mediated repair of double-strand breaks in DNA. MDC1 forms a complex with Rad51 through a direct interaction with the forkhead-associated domain of MDC1, not the BRCA1 C-terminal domain. Depletion of MDC1 results in impaired formation of Rad51 ionizing radiation-induced foci, reduced amounts of nuclear and chromatin-bound Rad51, and a corresponding increase in Rad51 protein degradation. Together, our findings suggest that MDC1 functions in Rad51-mediated homologous recombination by retaining Rad51 in chromatin.


Bioremediation of polycyclic aromatic hydrocarbons in crude oil by bacterial consortium in soil amended with Eisenia fetida and rhamnolipid.
The present study investigated the concerted effort of Eisenia fetida and rhamnolipid JBR-425 in combination with a five-member bacterial consortium exhibiting elevated degradation levels of low and high molecular weight polycyclic aromatic hydrocarbons (PAH) from soil contaminated with Digboi crude oil. Application of bacterial consortium (G2) degraded 30-89% of selected PAH from the artificial soil after a 45-day post-exposure, in which chrysene showed the highest level of degradation with 89% and benzo(a)pyrene is the lowest with 30%, respectively. Moreover, an acute exposure study observed that earthworm biomass decreased, and mortality rates increased with increasing crude oil concentrations (0.25 to 2%). Earthworms with a 100% survival rate at 1% crude oil exposure suggest the tolerance potential and its mutual involvement in the bioremediation of crude oil with selected bacterial consortia. Bacterial consortium assisted with E. fetida (G3) showed 98% chrysene degradation with a slight change in benzo(a)pyrene degradation (35%) in crude oil spiked soil. Besides, the most dominant PAH in crude oil found in the current work, fluoranthene, undergoes 93% and 70% degradation in G3 and G5 groups, respectively. However, rhamnolipid JBR-425 coupled with the bacterial consortium (G5) has resulted in 97% degradation of chrysene and 33% for benzo(a)pyrene. Overall, bacterial consortium assisted with earthworm group has shown better degradation of selected PAH than bacterial consortium with biosurfactant. Catalase (CAT), glutathione reductase (GST) activity and MDA content was found to be reduced in earthworms after sub-lethal exposure, suggesting oxidative stress prevalence via reactive oxygen species (ROS). Hence, the findings of the present work suggest that the application of a bacterial consortium, along with earthworm E. fetida, has huge potential for field restoration of contaminated soil with PAH and ecosystem sustainability.


Inverse-orthostasis may induce elevation of blood pressure due to sympathetic activation.
Microgravity and simulated microgravity may cause cardiovascular deconditioning, but mechanisms of instantaneous responses to inverse-orthostasis are not studied. Hence, we investigated transient and steady state cardiovascular changes by combining the tilt technique with cardiovascular telemetry. Normotensive and NO-deprived hypertensive Wistar rats were used to analyze responses of mean arterial blood pressure, heart rate, contractility, spontaneous baroreflex sensitivity (sBRS), and autonomic balance. Inverse-orthostasis tests were carried out by 45 degrees head-down tilting (repeated 3 x 5 mins "R", or sustained for 120 mins "S"). In normotensive rats, horizontal control blood pressure was R111.3 +/- 1.7/S110.4 +/- 2.3 mm Hg and heart rate was R385.2 +/- 5.9/S371.1 +/- 6.1 BPM. Head-down tilt induced an increase in blood pressure by R5.9/S10.6 mm Hg, while heart rate, contractility, sBRS, and autonomic balance did not change. The hypertensive response was sustained, could be prevented by prazosin (10 mg/kgbw), and augmented by subanesthetic doses of chloralose (26 and 43 mg/kgbw). In NO-suppressed hypertension, control blood pressure and heart rate were R132.4 +/- 2.9/S130.0 +/- 4.1 mm Hg and R339.2 +/- 7.9/S307.2 +/- 23.6 BPM, respectively. Head-down tilt further increased blood pressure by R5.1/S10.5 mm Hg. These data demonstrate that conscious rats respond to inverse-orthostasis by sustained elevation of blood pressure independent of NO synthesis. This response is neither due to increased contractility and altered sBRS, nor due to non-specific stress, but probably due to sympathetic activation elicited by gravity-related reflexes, which increase peripheral resistance.


Congenital Stapes Ankylosis in Children: Surgical Findings and Results in 35 Cases.
To evaluate surgical findings and hearing results in children undergoing middle ear surgery for congenital stapes ankylosis with or without other ossicular malformations (Teunissen and Cremers class I and class II malformations). A nonrandomized, nonblinded case series of prospectively collected data. A tertiary referral center. Twenty-eight consecutive pediatric patients who underwent 35 surgical procedures for congenital stapes ankylosis with or without other ossicular malformations and had available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a Teflon piston, bucket handle prosthesis or total ossicular replacement prosthesis. Pre- and postoperative audiometric evaluation using four-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gaps (ABGs) were measured. Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months after surgery and at a yearly interval thereafter. Overall, a postoperative ABG closure of 10 dB or less was achieved in 73% of class I cases and in 50% of class II cases. A postoperative ABG closure of 20 dB or less was achieved in 77% of class I cases and 67% of class II cases. Postoperative sensorineural hearing loss occurred in one class I case (4%) and none of the class II cases. Stapedotomy is a safe and feasible treatment option in children with congenital stapes ankylosis.


Immunoglobulin subclass distribution of synovial plasma cells in rheumatoid arthritis determined by use of monoclonal anti-subclass antibodies.
The distribution of IgG and IgA subclass plasma cells among dissociated synovial cells from 14 rheumatoid arthritis (RA) synovia was examined by immunofluorescence using mouse monoclonal anti-human subclass antibodies. Of the IgG plasma cells 81 +/- 9% were IgG1, 4 +/- 2% IgG2, 14 +/- 9% IgG3, and 0.9 +/- 0.6% IgG4. While IgG1 predominated in all 14 synovia (which is similar to what is seen in normal tissues), in 5/14 20% or greater of IgG plasma cells were IgG3, suggesting a selective increase in IgG3 production in the synovia of certain RA patients. Among IgA plasma cells 89 +/- 5% were IgA1 and 8 +/- 3% were IgA2. This distribution is similar to the distribution in normal serum.


Moderate alcohol consumption and lipoprotein subfractions: a systematic review of intervention and observational studies.
Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. PROSPERO registration no. 98955.


Drinking variables, affective measures and neuropsychological performance: familial alcoholism and gender correlates.
The relationships between five measures of alcohol consumption and five summary measures of diverse neuropsychological test performances were studied in 76 male and 67 female alcoholics as a function of family history of alcoholism and affective symptomatology. No significant relationships were obtained between drinking variables and neuropsychological performance scores for the overall groups of male and female alcoholics. In family history positive (FH+) males, correlations between a number of drinking variables and neuropsychological measures neared significance. The Beck Depression Inventory (BDI) scores correlated most strongly with the overall impairment index in both family history positive (FH+) and family history negative (FH-) alcoholics. Depression and anxiety scores in the female alcoholics significantly correlated with three of the five alcohol consumption variables. Possible confounding factors in the relationships between alcohol intake measures and cognitive functioning were discussed.


Red cell mass during and after normal pregnancy.
Red cell mass, derived from plasma volume and haematocrit, was calculated serially in 45 healthy women during pregnancy and 4 to 6 months after delivery. Compared to the non-pregnant, postpartum value there was a reduction of approximately 100 ml at 12 weeks gestation. An increase in red cell mass occurred thereafter: at 36 weeks gestation values 180 ml greater than the non-pregnant were found. Iron and folic acid supplements almost doubled this increment to 349 ml of red cells.


A suggested classification of breast pain.
A system of classification based on the work of Preece et al. (1976) is described. The results of applying this classification over a 4 month period (representing 84 patients) are described.