Two-stage Bayesian hierarchical modeling for blinded and unblinded safety monitoring in randomized clinical trials.
Monitoring and reporting of drug safety during a clinical trial is essential to its success. More recent attention to drug safety has encouraged statistical methods development for monitoring and detecting potential safety signals. This paper investigates the potential impact of the process of the blinded investigator identifying a potential safety signal, which should be further investigated by the Data and Safety Monitoring Board with an unblinded safety data analysis. In this paper, two-stage Bayesian hierarchical models are proposed for safety signal detection following a pre-specified set of interim analyses that are applied to efficacy. At stage 1, a hierarchical blinded model uses blinded safety data to detect a potential safety signal and at stage 2, a hierarchical logistic model is applied to confirm the signal with unblinded safety data. Any interim safety monitoring analysis is usually scheduled via negotiation between the trial sponsor and the Data and Safety Monitoring Board. The proposed safety monitoring process starts once 53 subjects have been enrolled into an eight-arm phase II clinical trial for the first interim analysis. Operating characteristics describing the performance of this proposed workflow are investigated using simulations based on the different scenarios. The two-stage Bayesian safety procedure in this paper provides a statistical view to monitor safety during the clinical trials. The proposed two-stage monitoring model has an excellent accuracy of detecting and flagging a potential safety signal at stage 1, and with the most important feature that further action at stage 2 could confirm the safety issue.


Cost-effectiveness of an interdisciplinary intervention in geriatric inpatients to prevent malnutrition.
In order to reduce protein-energy malnutrition in older people during hospitalisation an early interdisciplinary intervention is needed. We developed a protocol which includes screening for malnutrition, dysphagia and dehydration on admission, followed by immediate interventions. To assess effectiveness of the protocol on nutritional status, hospital-acquired infections and pressure sores, and to evaluate the protocol s economical feasibility. Prospective, controlled study. The inpatient geriatric service of a university hospital (UMC Nijmegen) and a geriatric ward of a non-academic teaching hospital (Rijnstate Hospital, Arnhem). 298 older patients (>60 years). One of the geriatric wards applied the protocol (N=140) while the other provided standard care (N=158). All non-terminally ill patients admitted for more than two days were included. Body mass was measured on admittance and discharge and hospital-acquired infections and pressure sores were scored and costs related to nutrition, infections and length of hospital stay were assessed. There was a 0.8 kg loss (SEM 0.3 kg) in average weight in the standard care group and a 0.9 kg gain (SEM 0.2 kg) in the intervention group (p<0.001). The number of hospital acquired infections was significantly lower in the intervention group (33/140 versus 58/158, p=0.01) but no significant difference in number of patients with pressure sores (23/140 versus 33/158) was found. Costs were not significantly different: 7516 versus 7908 Euro/patient for intervention versus controls, respectively. An early interdisciplinary intervention approach can be effective in reducing protein-energy malnutrition and related hospital-acquired infections and appears to be economically feasible.


ACGME duty-hour restrictions decrease resident operative volume: a 5-year comparison at an ACGME-accredited university general surgery residency.
We compared the operative experience of chief residents at the Michigan State University Integrated Residency Program in General Surgery before and after duty-hour restrictions mandated by the Accreditation Council for Graduate Medical Education. Conflicting evidence exists regarding the influence of duty-hour restrictions upon resident operative experience. Resident self-reported operative experience submitted to the Residency Review Committee (RRC) for Surgery was tabulated. To control for a possible overall decrease in surgical procedures, for example, a decrease in referrals to the institution, the departmental database of surgical billings that is maintained independently from resident operative experience data also was reviewed. An overall decrease of nearly 20% occurred in resident operative volume after promulgation of duty-hour restrictions. All residents met minimum RRC operative experience requirements. Over the same period, no decrease was found in the number surgical procedures performed by the department. Our data suggest that restriction of resident duty hours is associated with a significant decrease in operative experience.


Abundance and composition of small floating plastics in the eastern and southern sectors of the Atlantic Ocean.
We report the distribution of floating plastics in the eastern and southern sectors of the Atlantic Ocean based on 35 neuston net trawl samples collected during two research cruises in 2016 and 2017. Plastic particles (>200 μm) were found in 69% of net tows, with median densities of 1583 items·km-2 and 5.1 g·km-2. Most particles (80% of 158) were microplastics (<5 mm) of secondary origin (88%), followed by industrial pellets (5%), thin plastic films (4%) and lines/filaments (3%). Due to the large mesh size we used, textile fibers were not considered in this study. μFTIR analysis revealed that most particles found in the net were made of polyethylene (63%), followed by polypropylene (32%) and polystyrene (1%). A transect between 0 and 18°E along 35°S in the South Atlantic Ocean revealed higher densities farther west, supporting the accumulation of floating plastics in the South Atlantic gyre, mainly west of 10°E.


Synthesis and SAR studies of urea and thiourea derivatives of gly/pro conjugated to piperazine analogue as potential AGE inhibitors.
Synthesis of a series of urea and thiourea derivatives of glycine and proline conjugated to 2,3-dichlorophenyl piperazine has been reported. The structures were confirmed by physical and spectroscopical measurements followed by characterization of antiglycation activity. All synthesized compounds were able to inhibit protein glycation, particularly halogen containing derivatives without preference of oxygen or sulphur at the urea function. The best analogues are nearly 20 fold (< 5 µM) more potent than the reference standard, rutin (41.9 µM).


Reconstruction of a tibial diaphyseal bone defect using the Masquelet technique. A case report.
Segmental bone defects in the lower limb may be treated by distraction osteogenesis, vascularized bone grafts, allografts, metal prostheses or amputation. The induced membrane technique, introduced by Masquelet, consists in induction of a pseudo-synovial membrane by local tissue reaction to a synthetic spacer, followed by application of bone allograft to the resulting cavity. This article describes the case of a 34-year-old male with severe multiple trauma. The patient's injuries included a Gustillo-Anderson type IIIa open tibial shaft fracture, treated by means of the fix and flap technique. Application of the fix and flap technique resulted in a 7 cm bone defect that was filled using the induced membrane technique. This case report includes a review of the existing literature and a description of the modifications that have been proposed to the original Masquelet technique, including the use of antibiotic-impregnated cement, extension of the interval between the two surgical stages, and the use of alternative osteosynthesis materials.


Alcohol consumption and risky sexual practices: the pattern of nursing students from the Spanish University.
to determine the prevalence of substance abuse and unsafe sexual practices and to analyze the relationship between them, in nursing students at the University of Seville. quantitative methodological approach with a descriptive cross-sectional design. The population was composed of first year nursing students in the University of Seville, during the academic year 2010-2011 (N=510), with consecutive opportunistic sampling composed of students who attended class on the scheduled day (n=291). a high prevalence of alcohol consumption, and increased likelihood of not using protective measures during sexual practices when alcohol had been consumed, was present. these findings are consistent with those obtained in the same population in Brazil, and highlight the need to strengthen in the nursing curriculum, the transverse axis related to the prevention of substance abuse, especially alcohol.


Angiomyolipoma of the liver: case report and collective review of cases diagnosed from fine needle aspiration biopsy specimens.
We experienced a rare case of primary angiomyolipoma (AML) of the liver, preoperatively diagnosed by fine needle aspiration biopsy (FNAB). Radiographic imaging revealed characteristic features of an angiomyolipoma. The diagnosis was confirmed by the presence of epithelioid smooth muscle cells, mature fat cells and blood vessels in the biopsy tissue. Our review of the literature showed this to be the eleventh case to be diagnosed in this way. Despite this preoperative diagnosis, the lesion was resected because of its pleomorphic histological features. Histologically, the epithelioid smooth muscle component included cells with a bizarre appearance and occasional hyperchromatic nuclei, and furthermore, occasional mitotic figures were observed. In own MEDLINE search of the literature we found 11 cases of AML of the liver for which the diagnoses were established by FNAB, and the same features were present in 5 cases for which surgical excision was contemplated.


Biological characterization of lead-enhanced exopolysaccharide produced by a lead resistant Enterobacter cloacae strain P2B.
A lead resistant bacterial strain isolated from effluent of lead battery manufacturing company of Goa, India has been identified as Enterobacter cloacae strain P2B based on morphological, biochemical characters, FAME profile and 16S rDNA sequence data. This bacterial strain could resist lead nitrate up to 1.6 mM. Significant increase in exopolysaccharide (EPS) production was observed as the production increased from 28 to 108 mg/L dry weight when exposed to 1.6 mM lead nitrate in Tris buffered minimal medium. Fourier-transformed infrared spectroscopy of this EPS revealed presence of several functional groups involved in metal binding viz. carboxyl, hydroxyl and amide groups along with glucuronic acid. Gas chromatography coupled with mass spectrometry analysis of alditol-acetate derivatives of acid hydrolysed EPS produced in presence of 1.6 mM lead nitrate demonstrated presence of several neutral sugars such as rhamnose, arabinose, xylose, mannose, galactose and glucose, which contribute to lead binding hydroxyl groups. Scanning electron microscope coupled with energy dispersive X-ray spectrometric analysis of this lead resistant strain exposed to 1.6 mM lead nitrate interestingly revealed mucous EPS surrounding bacterial cells which sequestered 17 % lead (as weight %) extracellularly and protected the bacterial cells from toxic effects of lead. This lead resistant strain also showed multidrug resistance. Thus these results significantly contribute to better understanding of structure, function and environmental application of lead-enhanced EPSs produced by bacteria. This lead-enhanced biopolymer can play a very important role in bioremediation of several heavy metals including lead.


Reliability map of individual differences reflected in inter-subject correlation in naturalistic imaging.
Understanding individual differences in brain function is an essential aim of neuroscience. Naturalistic imaging links neural activity to real-life contexts and reflects individual differences in brain response. These unique features make it a promising tool for individualized psychiatry. An essential prerequisite for the extensive use of this paradigm is the reliable representation of inter-individual relationships. We used a test-retest approach to examine whether the naturalistic paradigm reliably represents inter-individual differences, which brain regions have the superior capability, and whether the ability alters with the contents of the stimuli. We quantified the reliability of the inter-subject relationships in repeated scans of two movie clips: a natural sight view and an emotion-evoking story. Besides statistical inference, we included resting-state scans, behavioral tests, and questionnaires as references for the comparison. The results showed that over one-third area of the brain could reliably characterize the inter-individual relationship, and the superior temporal lobe demonstrated comparable reliability representation with the State and Trait Anxiety Inventory. Furthermore, the temporal lobe regions could retain this capability across emotional movies with different contents. This study provides a base for pushing the naturalistic imaging paradigm towards clinical applications and proposes reliable target brain regions for future studies.


Evaluation of the vasodilator vs inotropic effect of milrinone using an animal model of left ventricular failure: reversal of disopyramide depression of the myocardium with milrinone.
Milrinone (M) has been shown to improve left ventricular (LV) performance in animal and human studies. M has strong vasodilator action, and whether increased LV performance is due primarily to vasodilation or to a direct positive inotropic effect is unclear. Ten mongrel dogs were studied. Disopyramide caused a significant and sustained decrease in LV function and was a good model for myocardial depression. At equal reduction in systemic vascular resistance (SVR), M reversed this LV depression to a significantly greater degree than nitroprusside (NP) did. At equal levels of vasodilation, M produced significantly greater improvement in indices of LV function than NP did in our model of disopyramide-induced LV failure. This suggest that its effect on LV function is not due entirely to afterload reduction, or to reflex sympathetic stimulation, but has a substantial component of direct inotropic stimulation. This study also demonstrated a reversal of disopyramide-induced LV dysfunction by M, which may be clinically useful since, as in many antiarrhythmics, myocardial depression may be a limiting factor in its use.


Complicated parapneumonic effusion in Belgian children: increased occurrence before routine pneumococcal vaccine implementation.
An increased occurrence of complicated parapneumonic effusions in children has been reported from the UK and USA. Data from mainland Europe are scarce. We investigated the incidence of complicated parapneumonic effusion and empyaema in children admitted to the University Hospital of Leuven between 1993 and 2005, an era when pneumococcal conjugated vaccination had not yet been implemented. Sixty-eight cases were identified. The incidence increased from 20-55/100,000 hospital admissions to 120-130/100,000 hospital admissions in 2005, with 50% of the cases occurring from 2003 onwards (late cohort). This increase occurred later than that reported in the UK and US, but is of similar magnitude. The median patient age was 3.6 years (range 0.5-17 years). The median duration of symptoms before admission was 4 days (quartile values 3-7 days). The median white blood cell (WBC) count was 15,450 WBC/mm3 (quartile values 11,300-21,200 WBC/mm3) and the median C-reactive protein (CRP) level was 242 mg/L (quartile values 143-344 mg/L). Patients in the late cohort seemed to have worse disease compared to early cohort patients; significantly higher pleural lactate dehydrogenase (LDH) level (P = 0,02), higher pleural WBC, lower pleural glucose level and significantly longer duration of hospitalisation in the later cohort (P < 0,05), possibly reflecting more severe disease. In both cohorts, Streptococcus pneumoniae was the most frequently isolated pathogen, with serogroup 1 prevailing. The occurrence of complicated parapneumonic effusion increased in Belgian children before pneumococcal vaccination was added to routine childhood immunisations. This increase is pronounced from 2003 onwards (late cohort) and, thus, occurred later than that reported in the UK and USA; several parameters point towards the occurrence of more serious disease in the late cohort patients.


Expressional and regulatory characterization of Arabidopsis RNA-dependent RNA polymerase 1.
RNA-dependent RNA polymerase 1 (RDR1), a component of gene silencing, participates in plant pathogen defense. However, there are few reports on its expression pattern or regulatory mechanism. To clarify how the Arabidopsis RDR1 gene is regulated at the transcriptional level in response to various stresses, its native 1,303 bp promoter sequence upstream of the translational start site and five truncated regions were inserted upstream of a fused reporter gene (β-glucuronidase-green fluorescent protein) in Arabidopsis. Histochemical staining and fluorescent signal detection revealed that AtRDR1 was expressed primarily in the plant vascular tissue system and its expression was specifically localized in phloem cell layers in roots. Stress experiments showed that the AtRDR1 promoter has a broad-spectrum response to various stresses and is sensitive to 1-naphthaleneacetic acid, abscisic acid, and salicylic acid. Analysis of promoter derivatives revealed that the -1,088 to -690 region was involved in auxin and dehydration responsiveness, that -690 to -434 was responsive to cold treatment, and the intron in the 5'-untranslated region (5'-UTR) responded to jasmonic acid molecules. The 5'-UTR intron was functional in transcript accumulation. Together, our findings suggest that AtRDR1-associated pathogen defense is conducted mainly in the plant vascular tissue system and is under complex regulation.


Survey shows growing approval and acceptance of integrated, employed physicians.
Hundreds of physician leaders share their insights and opinions on the integrated employed physician models that are quickly rising up throughout the country.


Palladium-Catalyzed Carbonylative Annulation Reactions Using Aryl Formate as a CO Source: Synthesis of 2-Substituted Indene-1,3(2H)-dione Derivatives.
An efficient synthesis of 2-substituted indene-1,3(2H)-diones from stable and readily available 1-(2-halophenyl)-1,3-diones by employing phenyl formate as a CO source has been developed. The reaction occurred via palladium-catalyzed intramolecular carbonylative annulation using K3PO4 as a base and DMSO as a solvent at 95 °C. In this protocol, the reaction showed a broad substrate scope with good to excellent yields.


Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy: how did it get there?
An unusual case of retroperitoneal ectopic pregnancy is reported. The patient, a 34 year old nulligravida, underwent IVF/ET following bilateral salpingectomy. A small, degenerating, intrauterine gestational sac suggested failing intrauterine pregnancy. There was no intraperitoneal free fluid. On Day 41 after ET, the patient was hospitalized because of acute epigastric pains. A pseudocyst of the head of pancreas was demonstrated by CT scan. A day later, exploratory laparotomy, because of a precipitous drop in the hemoglobin, revealed a massive retroperitoneal hematoma and an embryo in the gestational sac attached to the head of pancreas and major blood vessels. The patient did well following surgery. The mechanisms of retroperitoneal embryo migration are discussed and literature is reviewed.


Identification of features of metaplastic cells in sputum for the detection of squamous-cell carcinoma of the lung.
Digitized images of 1,556 squamous metaplastic cells from the sputum of 15 patients with confirmed squamous-cell carcinoma of the lung and 13 subjects without apparent neoplasia were analyzed to determine if features existed within these relatively normal cells that could be used to differentiate between the two populations. Results indicate that such marker features do exist. A cross-validation study using an additional 465 cells confirmed the conclusion that squamous metaplastic cells from patients with squamous-cell carcinoma of the lung do differ from those of subjects without cancer. While such marker features alone are not reliable enough to assist pathologists in the diagnosis of squamous-cell carcinoma of the lung, they might, in sufficient numbers, be used to identify patients for whom follow-up testing would be advised.


Theoretical dynamics of competitors under predation.
Continuous population models of two prey species and a predator were explored by isocline analysis. When predator satiation and substitution between prey (with or without switching) are introduced in the models, many qualitatively different kinds of dynamic behaviour become possible. These depend in a complex but predictable way on competitive relations between prey and on predator feeding behaviour and efficiency. Under constant predation many cases of threshold responses between two or more alternate stable states are possibly; the numerical response of the predator population reduces some of the possibilities.Apparently contradictory community phenomena previously proposed, e.g. prey coexistence versus exclusion by addition of predator, exclusion versus stabilization by addition of alternate prey, are all possible as special cases. A prey which is relatively tolerant to predation can act as a keystone species, on which the existence of other prey species in the community depends, in either a positive or a negative sense. In certain conditions predator-induced obligatory mutualism between two prey species is theoretically possible.


Machine learning approaches reveal genomic regions associated with sugarcane brown rust resistance.
Sugarcane is an economically important crop, but its genomic complexity has hindered advances in molecular approaches for genetic breeding. New cultivars are released based on the identification of interesting traits, and for sugarcane, brown rust resistance is a desirable characteristic due to the large economic impact of the disease. Although marker-assisted selection for rust resistance has been successful, the genes involved are still unknown, and the associated regions vary among cultivars, thus restricting methodological generalization. We used genotyping by sequencing of full-sib progeny to relate genomic regions with brown rust phenotypes. We established a pipeline to identify reliable SNPs in complex polyploid data, which were used for phenotypic prediction via machine learning. We identified 14,540 SNPs, which led to a mean prediction accuracy of 50% when using different models. We also tested feature selection algorithms to increase predictive accuracy, resulting in a reduced dataset with more explanatory power for rust phenotypes. As a result of this approach, we achieved an accuracy of up to 95% with a dataset of 131 SNPs related to brown rust QTL regions and auxiliary genes. Therefore, our novel strategy has the potential to assist studies of the genomic organization of brown rust resistance in sugarcane.


Validity of test meals for determining binge eating.
Assessment of binge eating has been criticized because of serious doubts concerning the accuracy of self-report. This experiment tested the validity of a laboratory test meal as an indicator of binge eating. Eight individuals diagnosed with binge-eating disorder (BED), eight obese non-binge-eaters, and eight normal-weight non-binge-eaters ate a test meal under conditions designed to increase the likelihood of inducing a binge episode. Non-binge-eaters, regardless of weight, felt in control of their eating and ate a relatively small amount of the test meal, while participants with BED ate significantly more food and felt significantly more out of control. Eating behavior during test meals can be a useful indicator of BED diagnostic status and may be a useful method for objectively defining binge eating.


Arsenite (III) removal via manganese-decoration on cellulose nanocrystal -grafted polyethyleneimine nanocomposite.
The manganese is successfully induced as a "bridge joint" to fabricate a new adsorbent (CNC-Mn-PEI) connecting cellulose nanocrystal (CNC) and polyethyleneimine (PEI) respectively. It was used to remove As (III) from waste water. It has been proved that the incompact CNC and PEI were successfully connected by Mn ions, which induced the formation of O-Mn-O bonds and the removal efficiency is maintained in the broad pH range of 4-8, even with the influence of NO3- and CO32-. The CNC-Mn-PEI was characterized by Brunauer-Emmett-Telley (BET) method and the results showed that the nanoparticle of the specific surface area was 106.5753 m2/g, it has a significant improvement, compared with CNC-Mn-DW (0.1918 m2/g). The isotherm and kinetic parameters of arsenic removal on CNC-Mn-PEI were well-fitted by the Langmuir and pseudo-second-order models. The maximum adsorption capacities toward As (III) was 78.02 mg/g. After seven regeneration cycles, the removal of As (III) by the adsorbent decreased from 80.78% to 68.2%. Additionally, the hypothetical adsorption mechanism of "bridge joint" effect was established by FTIR and XPS, which provided the three activated sites from CNC-Mn-PEI can improve the arsenic removal efficiency, and providing a new stratagem for the arsenic pollution treatment.


Editor's Choice - Cerebral Hyperperfusion Syndrome After Carotid Artery Stenting: A Systematic Review and Meta-analysis.
Cerebral hyperperfusion syndrome (CHS) is a preventable cause of stroke after carotid endarterectomy (CEA). There are currently no pooled data available on the incidence of CHS after carotid artery stenting (CAS). The aim of this review was to assess the relevance of CHS in the procedural stroke rate following CAS. A systematic search on incidence rates of CHS after CAS was conducted in the MEDLINE, EMBASE, and Cochrane databases in November 2017. A meta-regression analysis was performed on CHS to explain heterogeneity and determine the impact of potential risk factors on observed CHS. The methodological quality of the included studies was assessed using the Cowley criteria. The pooled CHS risk across 33 studies concerning 8731 CAS patients was 4.6% (3.1-6.8%). Stroke occurred in 47% of CHS patients, of which 54% were fatal or disabling. Average time from procedure to symptoms was 12 h (IQR 8-36 h). Impaired cerebrovascular reserve (CVR) was associated with a higher risk of CHS after CAS (RR 5.18; 95% CI 1.0-26.8; p = .049). Symptomatic status was associated with a lower risk of CHS (RR 0.20; 95% CI 0.07-0.59; p = .001). CHS is a serious and frequent complication in patients undergoing carotid angioplasty with stenting, and is most likely to occur in the very early post-procedural period. Future studies are encouraged to investigate the effect of intensive haemodynamic monitoring, including blood pressure control and assessment of cerebral blood flow, on the incidence of stroke caused by CHS after CAS.


Effects of Chinese Language Learning Anxiety on the Mental Health of International Students in China: The Chain Mediating Effect of Campus Adaptation and Academic Resilience.
Studies have shown that Chinese language learning anxiety among international students in China can negatively affect their psychological adjustment. However, the specific effects and conditions of learning anxiety need to be further investigated. This study explored the mediating effects between Chinese language learning anxiety and psychological adjustment of international students in China. Chinese Learning Anxiety Scale, Campus Adaptability Scale for International Students in China, Academic Resilience Questionnaire for International Students in China, Zung's Self-Rated Depression Scale were administered to 307 international students from Nanjing Normal University in China, including 165 male students and 131 female students, aged 19-28 (M =21.42; SD = 1.528). Chinese language learning anxiety significantly predicted the psychological well-being of international students after controlling for gender and age variables. Furthermore, Chinese language learning anxiety predicted the mental health of students through the independent mediating effect of campus adaptation and academic resilience, as well as the chain mediating effect of campus adaptation and academic resilience. The study has theoretical and practical significance for improving international students' psychological adaptation and health, and implications for those involved in the management and teaching of international students in China. The research conclusions are as follows: firstly, when the Chinese learning anxiety of international students in China is strong, their campus adaptation and psychological resilience are reduced, and levels of depression increase; secondly, grades are significantly correlated with anxiety dimensions, and higher grades are associated with lower anxiety levels; finally, the mediating effects of campus adaptation and academic resilience were significant, together with a significant chain mediating effect of campus adaptation and academic resilience.


Neighborhood Socioeconomic Status and Health: A Longitudinal Analysis.
Higher income neighborhoods are associated with better health, a relation observed in many cross-sectional studies. However, prior research focused on the prevalence of health conditions, and examining the incidence of new health conditions may provide stronger support for a potential causal role of neighborhoods on health. We used the 2004 and 2014 waves of the Midlife in the United States Study (n = 1726; ages 34-83) to examine health condition incidence as a function of neighborhood income. Among participants who had lived in the same neighborhood across the time period, we hypothesized that higher neighborhood income would be associated with a lower incidence of health conditions ten years later. Health included 18 chronic conditions related to mental (anxiety, depression) and physical (cardiovascular, immune) health. Multinomial logistic regression analyses adjusting for individual income and sociodemographics indicated that the odds of developing two or more new health conditions (no new health conditions as referent), was significantly lower (OR = 0.92, CI: 0.86, 0.99) for every $10,000 increment in neighborhood income. Associations did not vary by age or neighborhood tenure. Results add to a literature documenting that higher neighborhood income is associated with better health.


Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process.
The infectious form of prion protein, PrP(Sc), self-propagates by its conversion of the normal, cellular prion protein molecule PrP(C) to another PrP(Sc) molecule. It has not yet been demonstrated that recombinant prion protein can convert prion protein molecules from PrP(C) to PrP(Sc). Here we show that recombinant hamster prion protein is converted to a second form, PrP(RDX), by a redox process in vitro and that this PrP(RDX) form seeds the conversion of other PrP(C) molecules to the PrP(RDX) form. The converted form shows properties of oligomerization and seeded conversion that are characteristic of PrP(Sc). We also find that the oligomerization can be reversed in vitro. X-ray fiber diffraction suggests an amyloid-like structure for the oligomerized prion protein. A domain-swapping model involving intermolecular disulfide bonds can account for the stability and coexistence of two molecular forms of prion protein and the capacity of the second form for self-propagation.


Data on the effects of ECM rigidity on actomyosin contractility and invadopodia activity in individual versus pairs of head and neck squamous cell carcinoma cells.
Migration through the extracellular matrix (ECM) is essential for cancer cells to escape the primary tumor and invade neighboring tissues with the potential for metastasis [1]. To penetrate tissue barriers, migrating cancer cells degrade the ECM with actin-rich membrane protrusions called invadopodia [2]. We have previously found that invadopodial ECM degradation is regulated by ECM rigidity in a process mediated by contractile forces in individual head and neck squamous cell carcinoma (HNSCC) cells [3], [4]. However, cancer cells often migrate together and interact with each other to alter their actomyosin contractility in response to the biomechanical properties of the ECM [5]. Therefore, we tested whether ECM rigidity promotes biomechanical interactions between cancer cells to enhance proteolytic activity. Using a minimal model of two HNSCC cells in physical contact, we provide data here that actomyosin contractility, invadopodia formation, and ECM degradation increase in response to ECM rigidity when cells are in pairs versus individual cells using traction force and invadopodia assays.


Continuous field flooding versus final one-shot CO2 insufflation in minimally invasive mitral valve repair.
Insufflation of carbon dioxide (CO2) into the operative field to prevent cerebral or myocardial damage by air embolism is a well known strategy in open-heart surgery. However, here is no general consensus on the best delivery approach. From January 2018 to November 2021, we retrospectively collected data of one hundred consecutive patients undergoing minimally invasive mitral valve repair (MIMVR). Of these, fifty patients were insufflated with continuous CO2 1 min before opening the left atrium and ended after its closure, and fifty patients were insufflated with one shot CO2 10 min before the start of left atrium closure. The primary outcome of the study was the incidence of transient post-operative cognitive disorder, in particular agitation and delirium at discontinuation of anesthesia, mechanical ventilation (MV) duration and intensive care unit (ICU) length of stay. In all patients that received continuous field flooding CO2, correction of ventilation for hypercapnia during cardiopulmonary bypass (CPB) was applied with an increase of mean sweep gas air (2.5 L) and monitoring of VCO2 changes. One patient vs. 9 patients of control group reported agitation at discontinuation of anesthesia (p = 0.022). MV duration was 14 ± 3 h vs. 27 ± 4 h (p = 0.016) and ICU length of stay was 33 ± 4 h vs. 42 ± 5 h (p = 0.029). A significant difference was found in the median number of total micro-emboli recorded from release of cross-clamp until 20 min after end of CPB (154 in the continuous CO2 group vs. 261 in the one-shot CO2 control group; p < 0.001). Total micro-emboli from the first 15 min after the release of cross-clamp was 113 in the continuous CO2 group vs. 310 in the control group (p < 0.001). In the continuous CO2 group, the median number of detectable micro-emboli after CPB fell to zero 9 ± 5 min after CPB vs. 19 ± 3 min in the control group (p = 0.85). Continuous field flooding insufflation of CO2 in MIMVR is associated with a lower incidence of micro-emboli and of agitation at discontinuation of anesthesia, along with improved MV duration and ICU length of stay.


Measuring the quality of motivational interviewing in primary health care encounters: The development and validation of the motivational interviewing assessment scale (MIAS).
Motivational interviewing (MI) is a collaborative, goal-oriented method to help patients change behaviour. Tools that are often used to measure MI are the motivational interviewing skills code' (MISC), the 'motivational interviewing treatment integrity' (MITI) and the 'behaviour change counselling index' (BECCI). The first two instruments have not been designed to be used in primary healthcare (PHC) settings. The BECCI actually is time-consuming. The motivational interviewing assessment scale (MIAS, 'EVEM' in Spanish) was developed to measure MI in PHC encounters as an alternative to the previous instruments. To validate MIAS as an instrument to assess the quality of MI in PHC settings. (a) Sixteen experts in MI participated in the design, face and consensus validity, using a Delphi-type methodology. (b) 27 PHC centres located in Spain. four experts in MI tested its psychometric properties with 332 video recordings coming from the Dislip-EM study (consultations provided by 37 practitioners). dimensionality, internal consistency, reliability (intra-class correlation coefficient-ICC), sensitivity to change and convergent validity with the BECCI scale. A 14-item scale was obtained after the validation process. Factor analysis: two factors explained 76.6% of the total variance. Internal consistency, α = 0.99. Reliability: intra-rater ICC = 0.96; inter-rater ICC = 0.97. Sensitivity to change: means before and after training were 23.63 versus 38.57 (P < 0.001). Spearman's coefficient between the MIAS and the BECCI scale was 0.98 (P < 0.001). The MIAS is a consistent and reliable instrument to assess the use of MI in PHC settings. [Box: see text].


The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study.
To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.


Effects of family coping and resources on family adjustment and parental stress in the acute phase of the NICU experience.
To determine the relationship between family coping and resources and family adjustment and parental stress in the acute phase of the NICU experience. Correlational study based on the Resiliency Model of Family Stress, Adjustment, and Adaptation. Main study instruments included the State Anxiety scale of the State-Trait Anxiety Inventory, the Family Inventory of Resources for Management, the Family Crisis Oriented Personal Evaluation Scales, and the General Functioning subscale of the McMaster Family Assessment Device. Data collected from 124 mother and father pairs within two to four days of their infant's admission to the NICU. Family adjustment and parental stress. Adequate resources were more strongly related to positive adjustment and decreased stress than were either coping or being a first-time parent. The relationships among the variables were generally the same for both parents. Mothers utilized more coping strategies than did fathers. PRACTICE RECOMMENDATIONS: Families with limited resources should be identified early to facilitate their adjustment to the NICU.


Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.
Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.


The content of internal medicine residency training and its relevance to the practice of medicine: implications for primary care curricula.
Using survey items from Kern et al. (1985), 192 former residents rated their preparation in, and the importance of, three content areas of their residency training ("basic skill and knowledge areas," "allied medical disciplines," and "areas related to the practice of medicine"). Mean ratings replicated those reported by Kern et al. (r = 0.70 to 0.97, p less than 0.004). Using additional data about current practice patterns, ratings by general internists were compared with ratings by subspecialists. Both groups identified basic skill and knowledge areas as most important and felt that many areas related to practice management had been underemphasized. Most allied medical disciplines, however, were more important to generalists. Exposure to non-internal medicine areas seems important for residents considering subspecialization. However, all residents may benefit from increased emphasis on basic clinical skills and practice management. Program directors may want to address these issues, given the recent decline in applications to internal medicine programs.


Teaching interactive signing in a dialogue situation to mentally retarded individuals.
Verbal prompts, modeling, physical guidance, positive reinforcement, fading, and chaining procedures were used to teach two nonverbal individuals, one severely and one moderately mentally retarded, an interactive signing dialogue in a naturalistic snack time setting. Both were required to initiate signed communication and to respond to signed communication with either action or manual signing. Using a multiple probe design across three dialogue situations, each client was successively taught his role in each dialogue with a staff member serving as his partner. After both trainees had mastered a dialogue role, signing competency was formally probed as they interacted with their staff partner in a maintenance situation and with the other trainee in a generalization situation. Results showed that clients could learn to use signed communication in each dialogue situation but that extensive training was required. Data also indicated that only partial generalization to the client-client situation occurred.


Feasibility and acceptability of a new web-based cognitive training platform for cognitively healthy older adults: the breakfast task.
Developing efficient cognitive training for the older population is a major public health goal due to its potential cognitive benefits. A promising training target is executive control, critical for multitasking in everyday life. The aim of this pilot study was to establish the feasibility and acceptability of the Breakfast Task training in older adults, a new web-based cognitive training platform that simulates real-life multitasking demands. A community-based sample of 24 cognitively healthy participants aged between 60 and 75 (M = 69.12, SD = 3.83) underwent 5-session cognitive training protocol, delivered online. Each session lasted 45 min and occurred twice a week at participant's homes. Performance was recorded, and participants completed questionnaires at baseline and after the intervention. Feasibility metrics showed overall high recruitment (82.7%), adherence and retention rates (100%). Acceptability was considered good based on participant's quantitative and qualitative responses. On average, participants rated the game as interesting, enjoyable and did not report difficulties in accessing the game online without supervision or in understanding the instructions. Participants showed a learning curve across sessions, suggesting improvement in the game outcomes and potential benefits from the emphasis change training approach. The study identified relevant areas that need improvements and adjustments, such as technical issues, session's structure, and dose. The findings provide preliminary support for the feasibility and acceptability of the web-based Breakfast Task training platform in cognitively healthy older adults. Results suggest the value of further research to investigate the Breakfast Task training features and dose-response relationship, as well as its potential efficacy in older adults via larger randomized controlled trials. ClinicalTrials.gov: NCT04195230 (Registered 11 December 2019).


Gluten-sensitive enteropathy in childhood.
Genetic and environmental factors (breast feeding, probably viral infections) play a role in the expression of the disease. Prevalence of GSE in childhood did not substantially decrease in the last 15 years in all European countries, where GSE is still more common in infantile age and presents frequently gastrointestinal symptoms. A decrease has been reported in childhood in several United Kingdom areas and in Finland, where the clinical presentation is changing, shifting upward with age and coming closer to the adult type of the disease. The following clinical problems have been reported in the recent literature: enamel hypoplasia; monosymptomatic short stature; arthritis and other immunologic diseases; association with diabetes, atopy, Iga deficiency, and probably Down's syndrome. Delay in puberty and other peculiar problems of the disease have been described in adolescents. Tests assessing the permeability of the small intestine and the blood levels of antigliadin antibodies have recently gained success as noninvasive tools for the diagnosis of the GSE. The gluten should be withdrawn from the diet and the challenge with gluten should be performed not before 12 months of gluten-free diet with an accurate timing of the biopsy on the basis of the antigliadin and antireticulin antibodies, to avoid clinical and growth damage. Celiac children do require a permanent gluten-free (and not poor) diet. In reality, too many celiac adolescents are off-diet.


Tumors of the pineal region in children and adolescents.
The treatment of tumors in the pineal area remains controversial. There are two main approaches: Conservative treatment, consisting in CSF shunting and radiotherapy, and direct surgical removal. We report on 25 children (22 boys and 3 girls) aged between 4 and 20 years who underwent conservative treatment. The follow-up period ranges from 1 to 11 years (mean, 4.8 years). 19 patients are still alive at a mean survival time of 5.8 years. 17 children are free of disease, two have severe neurological deficits. Our diagnostic and therapeutical concepts are presented.


Subcellular proteomic approach for identifying the signaling effectors of protein kinase C-β₂ under high glucose conditions in human umbilical vein endothelial cells.
The high glucose‑induced activation of protein kinase C‑β2 (PKC‑β2) has an essential role in the pathophysiology of diabetes‑associated vascular disease. In the present study, human umbilical vein endothelial cells (HUVECs) were cultured in high and normal glucose conditions prior to being infected with a recombinant adenovirus to induce the overexpression of PKC‑β2. The activity of PKC‑β2 was also decreased using a selective PKC‑β2 inhibitor. A series of two‑dimensional electrophoresis images detected ~800 spots in the nuclei, and ~600 spots in the cytosol. Following intra‑ and inter‑group cross‑matching, 38 significantly altered spots were identified as high glucose‑induced and PKC‑β2‑associated nuclear proteins. In addition to the observation that the regulation of key proteins involved in the nuclear factor (NF)‑κB signaling cascade occurred in the cytosol, various transcription factors, including peroxisome proliferator‑activated receptor δ (PPAR‑δ), were also altered in the nuclei. A human protein‑protein interaction network of potential connections of PKC‑β2‑associated proteins was constructed in the proteomics investigation using Biological General Repository for Interaction Datasets. The results indicated that PKC‑β2 may be involved in high glucose‑induced glucose and lipid crosstalk by regulating PPAR‑δ. In addition, NF‑κB inhibitor‑interacting Ras‑like protein 1 may be important in the PKC‑β2‑NF‑κB inhibitor‑NF‑κB signaling pathway in HUVECs under high‑glucose conditions.


Non-volatile resistive switching mechanism in single-layer MoS2 memristors: insights from ab initio modelling of Au and MoS2 interfaces.
Non-volatile memristive devices based on two-dimensional (2D) layered materials provide an attractive alternative to conventional flash memory chips. Single-layer semiconductors, such as monolayer molybdenum disulphide (ML-MoS2), enable the aggressive downscaling of devices towards greater system integration density. The "atomristor", the most compact device to date, has been shown to undergo a resistive switching between its high-resistance (HRS) and low-resistance (LRS) states of several orders of magnitude. The main hypothesis behind its working mechanism relies on the migration of sulphur vacancies in the proximity of the metal contact during device operation, thus inducing the variation of the Schottky barrier at the metal-semiconductor interface. However, the interface physics is not yet fully understood: other hypotheses were proposed, involving the migration of metal atoms from the electrode. In this work, we aim to elucidate the mechanism of the resistive switching in the atomristor. We carry out density functional theory (DFT) simulations on model Au and ML-MoS2 interfaces with and without the presence of point defects, either vacancies or substitutions. To construct realistic interfaces, we combine DFT with Green's function surface simulations. Our findings reveal that it is not the mere presence of S vacancies but rather the migration of Au atoms from the electrode to MoS2 that modulate the interface barrier. Indeed, Au atoms act as conductive "bridges", thus facilitating the flow of charge between the two materials.


Lycium ruthenicum Murr. alleviates nonalcoholic fatty liver in mice.
Oxidative stress and inflammation contribute to hypertriglyceridemia-induced nonalcoholic fatty liver disease (NAFLD). Cholesterol-enriched diets increase the risk of NAFLD. Lycium ruthenium Murr. (LRM) contains water-soluble antioxidant proanthocyanidins. Whether Lycium ruthenium Murr. improves NAFLD remains elusive. In this study, we established a model of NAFLD-induced by cholesterol-enriched high-fat diet (western diet) in ApoE -/- mice; oxidative stress and inflammation were examined and intervened by supplement of Lycium ruthenium Murr. (LRM) extracts. LRM supplement did not influence body weight gain, food intake, and lipotoxicity of mice. LRM supplement significantly alleviated triglyceride accumulation in liver, with reduced inflammation, elevated GSH-Px activity, and reduced MDA levels. The expression of fatty acids oxidative gene Scd1 was significantly increased, and fatty acids synthesis-related gene Pparγ was dramatically downregulated on mRNA level in liver of mice with LRM supplement. These data demonstrated that LRM supplement decreased ROS production and inflammation, increased fatty acids oxidation, and reduced fatty acids synthesis in liver, leading to ameliorate the development of NAFLD induced by high western diet. Thus, oxidative stress and inflammation also are involved in the pathogenesis of western diet-induced NAFLD, which is independent of obesity.


Phosphorus nuclear magnetic resonance studies on the effect of duration of contraction in bull-frog skeletal muscles.
1. Contraction and recovery of bull-frog skeletal muscles were studied using 31P nuclear magnetic resonance (NMR), with a time resolution of 16 s, at 4 degrees C. The muscles were stimulated tetanically for various periods (0.2-10 s) at a sarcomere length of 2.4 microns. Changes in the concentrations of inorganic phosphate (Pi), phosphocreatine (PCr) and other metabolites were studied for repeated cycles of contraction and recovery. 2. In resting muscles, bathed in a solution gassed with 95% O2 and 5% CO2, the concentration of Pi was 1.15 +/- 0.21 mmol kg-1 wet weight (mean +/- one S.D., n = 12), that of ATP was 3.32 +/- 0.15 mmol kg-1 (mean +/- one S.D., n = 12) and that of sugar phosphates was less than 0.5 mmol kg-1. The intracellular pH (pHi) was 7.22 +/- 0.01 (mean +/- one S.D., n = 12). These results are averages for fibres which probably have different values. 3. On stimulating the muscles pHi shifted in the alkaline direction and subsequently recovered. The extent of the alkaline shift was linearly related to the contraction duration (0.2-10 s) with a rate of 0.01 pH unit s-1. 4. The increase in Pi with stimulus duration was biphasic, consisting of an early burst, 0.38 +/- 0.10 mmol kg-1 (+/- 1 S.D., n = 5), complete within about 0.2-0.5 s, followed by a slower steady-state increase. The steady-state rate of Pi increase was 0.33 +/- 0.02 mmol kg-1 s-1 (+/- 1 S.D., n = 5) in agreement with the results of previous studies involving chemical analyses. 5. The time course of Pi recovery was well described by a single exponential. Intensities of ATP, sugar phosphates and the peaks in the phosphodiester region did not change during a 2 s tetanus. 6. The amount of PCr hydrolysed (-delta PCr), associated with contractions of various durations, coincided well with Pi increase (delta Pi). This was found during the whole recovery period except for the initial few minutes following relaxation when -delta PCr was significantly smaller than delta Pi. The difference was 0.35 +/- 0.03 mmol kg-1 (mean +/- 1 S.D., n = 3) immediately after a 2 s tetanus. 7. In contractions of 2 s or longer, the extent of the temporal separation between delta Pi and -delta PCr was almost the same, but in contractions of less than 2 s it was significantly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)


[Improved reliability of critical data exchange between the biological laboratory and clinical centres. Type of data to transfer and identification of the most relevant tools].
The reliability of the transfer of critical data between the biological laboratory and the clinical centres has to be reassessed. We have a legal constraint (GBEA and best practices) to make sure that the appropriate alert is issued for severe and urgent cases. In this paper, we present a study of the performances of data transfer tools, such as the comparison between regular phone and up to date available means like in line printers and network terminals. This paper focuses on the twenty-four hours duty in the hospital at the same level of reliability for alerts.


Rubeosis iridis and glaucoma associated with sickle cell retinopathy: a light and electron microscopic study.
The ultrastructure of rubeosis iridis in sickle cell-hemoglobin C disease is described for the first time. Findings included open interendothelial cell junctions, intraendothelial cytoplasmic attenuations (fenestrations), and pericyte formation. The ultrastructural appearance of rubeosis iridis gives no clue to the underlying etiology and is similar to that reported in rubeosis associated with diabetes mellitus, central retinal vein occlusion, and uveitis. The electron microscopic findings explain the functional incompetence of rubeotic vessels that are manifested by transmural leakage of fluorescein.


A systematic approach for stability-indicating HPLC method optimization for Nilotinib bulk through design of experiments: Application towards characterization of base degradation products by mass spectrometry.
A novel and reliable stability-indicating high-performance liquid chromatography method was developed using design of experiments. Under forced degradation conditions (hydrolysis, oxidative, photolytic and thermal) Nilotinib produced five major degradation products utilizing sodium hydroxide in base hydrolysis. The degradation products were separated by Hypersil ODS column (150×4.6mm i.d., 5μ) utilizing methanol and 10mM ammonium acetate (pH 3.0, adjusted with acetic acid) as mobile phase in gradient elusion mode at a flow rate of 1.2mL/min column temperature set at 35°C and UV detection at 263nm. Tandem mass spectrometry method was used to characterize the base degradation products by accurate mass measurements. The developed method was found to be linear, accurate, precise and selective for the separation of Nilotinib from its degradation products as per the International Conference on Harmonisation guidelines. The structures of the degradation products have been elucidated, of which three degradation products were reported for the first time.


Identification of plasma hsa_circ_0008673 expression as a potential biomarker and tumor regulator of breast cancer.
Cell-free circular RNAs (circRNAs) are stable and abundantly exist in body fluids. In this study, we aimed to investigate plasma cell-free circRNAs as a novel class of biomarkers for the diagnosis of breast cancer (BC). Differentially expressed circRNAs from 6 normal and 6 BC plasma samples were detected by microarray. Hsa_circ_0008673 was then screened and validated in the plasma of 102 normal and 378 BC samples. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The correlations between hsa_circ_0008673 expression and demographic characteristics, tumor features, and prognosis were analyzed. The effects of hsa_circ_0008673 on BC cell proliferation and metastasis were also measured. Of the top ten up-regulated (hsa_circ_0008673, hsa_circ_0008500, hsa_circ_0005260, hsa_circ_0003423, hsa_circ_0119881, hsa_circ_0000987, hsa_circ_0007386, hsa_circ_0000091, hsa_circ_0016601, and hsa_circ_0008549) and top ten down-regulated (hsa_circ_0000826, hsa_circ_0072697, hsa_circ_0004587, hsa_circ_0000471, hsa_circ_0007786, hsa_circ_0001417, hsa_circ_0005982, hsa_circ_0001566, hsa_circ_0003823, and hsa_circ_0003823) circRNAs from microarray, hsa_circ_0008673 was the most significantly up-regulated circRNA in BC, and represented a good diagnostic value. Hsa_circ_0008673 was remarkably down-regulated after breast mastectomy. Hsa_circ_0008673 expression was associated with larger tumor size, distant metastasis, positive estrogen receptor (ER) status, and positive progesterone receptor (PR) status. Additionally, hsa_circ_0008673 could serve as a prognostic predicator of overall survival (OS) and disease-specific survival (DSS). Cell assays proved that hsa_circ_0008673 knockdown contributed to inhibition of tumor cell proliferation and migration. Plasma cell-free hsa_circ_0008673 was up-regulated in BC, which was associated with poorer prognosis and promoted tumor proliferation and metastasis. Hsa_circ_0008673 is a promising biomarker for tumor diagnosis and prognostic assessment of BC patients.


Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment.
We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in-depth cognitive evaluation within a comprehensive geriatric assessment (CGA). Patients aged 70 years or older with a histologically confirmed diagnosis of cancer were evaluated with a full CGA, including CDT and Folstein Mini Mental State Examination (MMSE) as gold standard. Validation of the Freund CDT was defined in terms of diagnostic accuracy of the test through receiver operating characteristics (ROC)-analysis. To accept the Freund CDT as a screening tool, we estimated that the area under the ROC curve (AUC) had to differ significantly from 0.70 with an AUC of at least 0.85. Two hundred elderly cancer patients with a mean age of 79.0 years were included. Four patients were excluded from the analyses because of invalid results. Potential cognitive impairment (MMSE ≤23) was observed in 27.0% of patients. Based on of the AUC ± SE, the Freund CDT showed excellent diagnostic performance (0.95 ± 0.17). Furthermore, it provided excellent sensitivity (94.3%) and high specificity (87.4%). Our results indicate that the Freund CDT can be used as an initial screening tool to detect elderly cancer patients in need of a more in-depth cognitive assessment within CGA, instead of the MMSE.


A Pilot Study of a Measure of Parental Trust in Pediatric Emergency Department Care Teams.
To modify and test an existing measure of trust validated in a primary care setting for use in a pediatric emergency department (PED). The study population was parents/guardians who brought their child to an urban PED with a chief complaint of abdominal pain or head injury. We used a 2-phase design with modifications resulting from cognitive interviews with 15 participants followed by a field test with 150 participants. We measured usefulness by percent missing responses and ceiling effects. Cronbach's alpha and greatest lower bound measured reliability. As evidence of validity, we calculated a total trust score by summing the item scale values and correlating the score with measures of constructs shown to be positively associated with trust in other settings. We conducted a similar analysis to test a published shortened version of the same scale. Four items were modified prior to field testing. Ceiling effects for each item ranged from 53% to 67%. Missing data were minimal affecting only 2 items. The modified measure exhibited high reliability (Cronbach's alpha = .88, greatest lower bound = 0.93). Total trust scores ranged from 27 to 50 with mean (standard deviation) = 45.1 (4.9). The trust score exhibited a high positive correlation with communication and overall satisfaction, and moderate correlation with intent to adhere to physician recommendations. The short version of the scale performed similarly. This study provides evidence that the modified Wake Forest measure of trust is applicable and useful in the PED setting for this patient population.


Quantitative analysis of methanogenic community dynamics in three anaerobic batch digesters treating different wastewaters.
Quantitative changes in methanogenic community structures, associated with performance data, were investigated in three anaerobic batch digesters treating synthetic glucose medium, whey permeate, and liquefied sewage sludge. All digesters were initially seeded with anaerobic sludge obtained from a local municipal wastewater treatment plant. Dynamics of methanogenic populations were monitored, at order and family levels, using real-time PCR based on the 16S rRNA gene. The molecular monitoring revealed that, in each digester, the quantitative structure of methanogenic community varied continuously over treatment time and the variation corresponded well to the changes in chemical profiles. Biphasic production of methane, associated with successive increases in aceticlastic (mainly Methanosarcinaceae) and hydrogenotrophic (mainly Methanomicrobiales) methanogenic groups, was observed in each digester. This corresponded to the diauxic utilization of acetate and longer-chain volatile fatty acids (C(3)-C(6)), mainly propionate. Additionally, the non-metric multidimensional scaling (NMDS) analysis of the quantification results demonstrated that the community shift patterns in three digesters were totally different from each other. Considering that the operating conditions in all trials were identical except substrates, the differences in quantitative shift profiles were suggested to be due to the different substrate compositions. This implied that the composition of wastewater could affect the evolution of quantitative methanogenic community structure in an anaerobic process. Overall, our results suggested that more attention to quantitative as well as qualitative approaches on microbial communities is needed for fundamental understanding of anaerobic processes, particularly under dynamic or transitional conditions.


A meta-analysis of differentially expressed circulatory micro-RNAs in chronic traumatic encephalopathy and other tauopathies: A significant role of miR-181c-5p.
Micro-RNA (miRs) targeting kinases and phosphatases regulate the hyper-phosphorylation of tau protein, which is a characteristic feature of Chronic Traumatic Encephalopathy (CTE). Identification of lead dysregulated miR expressed in CTE, and other similar tauopathies. A search strategy was devised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to mine into multiple indexing databases such as Web of Science, Google Scholar, and PubMed spanning from 2005 to June 2022. Seven articles were screened out of 34,221 publications based on inclusion criteria and were categorized into two groups i.e., (1) CTE and its risk factors and (2) Age-related neurodegenerative disorders. Statistical analysis [RevMan 5.4.1] results showed that the overall risk ratio (RR) of the first group is significant (RR = 0.62, 95% CI = [0.38, 1.00], z = 1.95, p = 0.05) whereas, the second group favours the control population (RR = 1.64, 95% CI = [0.85, 3.16], z = 1.14, p = 0.14). We observed that among all other dysregulated miRs, miR-181c-5p is significantly overexpressed in Alzhimers disease (AD) and CTE. Further, we found that miR-210-3p is also upregulated notably in all groups. In sum, we conclude that these miRs can be considered as potential target and biomarker in the diagnosis and treatment of various tauopathies.


Ruthenium red-sensitive and -insensitive release of Ca2+ from uncoupled heart mitochondria.
The uncoupler-induced release of accumulated Ca2+ from heart mitochondria can be separated into two components, one sensitive and one insensitive to ruthenium red. In mitochondria maintaining reduced NAD(P)H pools and adequate levels of endogenous adenine nucleotides, the release of Ca2+ following addition of an uncoupler is virtually all inhibited by ruthenium red and can be presumed to occur via reversal of the Ca2+ uniporter. When ruthenium red is added to block efflux via this pathway, high rates of Ca2+ efflux can still be induced by an uncoupler, provided either NADH is oxidized or mitochondrial adenine nucleotide pools are depleted by prior treatment. This ruthenium red-insensitive Ca2+-efflux pathway is dependent on the level of Ca2+ accumulated and is accompanied by swelling of the mitochondria and loss of endogenous Mg2+. Loss of Ca2+ by this relatively nonspecific pathway is strongly inhibited by Sr2+ and by nupercaine, as well as by oligomycin and exogenous adenine nucleotides. The loss of Ca2+ from uncoupled heart mitochondria occurs via a combination of these two mechanisms except under conditions chosen specifically to limit efflux to one or the other pathway.


[Biochemistry of metallocenes. III. Thymus-affinity for (103Ru)-ruthenocenyl-3-phenyl-propen-1-one].
103Ru labelled 1-Ruthenocenyl-3-phenyl-propen-1-one was administered to mice introperitoneally. The organ distribution was determined in liver, spleen, lung, muscle, blood, kidney and thymus. The highest concentration was found in the thymus-up to 22% of the injected dose/g with corresponding thymus to muscle ratios of up to 364:1. The consequences for nuclear medicine are discussed.


The accuracy of three-dimensional prediction planning for the surgical correction of facial deformities using Maxilim.
The motivation for orthognathic surgery is to improve facial appearance and quality of life. This study aimed to validate a three-dimensional (3D) orthognathic planning programme (Maxilim) for predicting soft tissue changes following Le Fort I advancements. Cone beam computed tomography (CBCT) scans were taken before surgery (T(1)) and at 6-12 months after surgery (T(2)) for 13 patients. For each patient the 3D hard tissue changes between T(1) and T(2) were determined by CBCT superimposition on the cranial vault. Using Maxilim, each patient's skeletal movements were used to generate a 3D soft tissue prediction. The actual soft tissue mesh at T(2) was compared to the predicted mesh. The face was divided into areas: nose, right and left nares, right and left paranasal regions, upper and lower lip, and chin. The absolute distance between meshes for each region was calculated. A one-sample t-test showed the distances between the meshes for all of the areas were within 3 mm (P<0.05), except for the upper lip which was greater than 3 mm (P=0.577). Using Maxilim, 3D soft tissue predictions for Le Fort I advancements were clinically satisfactory in the regions assessed, but associated with marked errors around the region of the upper lip.


Is urine immunofixation electrophoresis necessary for monitoring myeloma patients who have undergone hematopoietic stem cell transplantation?
To investigate the role of urine immunofixation electrophoresis in detecting relapse in patients with myeloma who have undergone autologous and allogeneic hematopoietic stem cell transplantation (HSCT). The study included a total of 78 patients, comprising 49 males and 29 females, with progressive disease or relapse after HSCT. Serum protein electrophoresis (sPE), serum immunofixation electrophoresis (sIFE) and serum free light chain κ/λ ratio in addition to urine immunofixation (uIFE) were studied. sPE, sIFE and κ/λ ratio demonstrated relapse in 65.3%, 88.3% and 58.9% of the cases by theirselves respectively. The combination panel of sPE and sIFE demonstrated relapse in 88.3% of patients whereas sPE, sIFE and κ/λ ratio all together demonstrated relapse in 95.8% of the patients. In relapsed patients, urine immunofixation was found to be positive in 16.2% of the patients. No patients with relapsed disease were missed by omitting uIFE from serum studies (sPE, sIFE and sFLC). For evaluation of relapse in MM patients after HSCT, uIFE had no additional diagnostic capability compared to serum studies (sPE, sIFE, and sFLC). Therefore, urine studies should be performed more selectively.


DNA typing from single hairs.
The characterization of genetic variation at the DNA level has generated significant advances in gene and disease mapping, and in the forensic identification of individuals. The most common method of DNA analysis, that of restriction fragment length polymorphism (RFLP), requires microgram amounts of relatively undegraded DNA for multi-locus typing, and hundreds of nanograms for single-locus comparisons. Such DNA frequently cannot be obtained from forensic samples such as single hairs and blood stains, or from anthropological, genetic or zoological samples collected in the field. To detect polymorphic DNA sequences from single human hairs, we have used the polymerase chain reaction (PCR), in which specific short regions of a gene can be greatly amplified in vitro from as little as a single molecule of DNA. We have detected genetically variable mitochondrial and nuclear DNA sequences from the root region of shed, as well as freshly-plucked, single hairs; mitochondrial DNA (mtDNA) sequences have been detected in a sample from a single hair shaft. We have used three different means of DNA typing on these samples: the determination of amplified DNA fragment length differences, hybridization with allele-specific oligonucleotide probes, and direct DNA sequencing.


A case of thymoma protruding into the superior vena cava through the thymic vein.
We describe an unusual case of an invasive thymoma protruding into the superior vena cava and left brachiocephalic vein through the thymic veins in a 64-year-old patient. The tumor was resected with a bypass of the right brachiocephalic vein and right atrium. Although this type of growth form is rare for an invasive thymoma, this case suggests that in surgical procedures for thymomas, meticulous examination of the thymic veins is necessary to avoid leaving residual tumor.


Cytoplasmic Expression of Nanobodies with Formylglycine Generating Enzyme Tag and Conversion to a Bio-Orthogonal Aldehyde Group.
Nanobodies (Nbs) can be successfully retrieved following phage, bacterial, yeast, or ribosome display of immune, synthetic, or naïve libraries. However, after panning, multiple individual Nb clones need to be screened and assessed for solubility, antigen specificity, affinity, and potential biological function. Therefore, it is highly desirable to have a convenient expression strategy to obtain sufficient protein for in-depth characterization of the Nbs. The presence of a purification and detection tag, as well as a chemically reactive group to enable simple generation of Nb derivatives, would be of great help in this regard. Here, we provide a general protocol for high yield cytoplasmic expression and purification of formylglycine generating enzyme (FGE)-tagged Nbs. The cysteine within the FGE tag is easily converted to formylglycine by passing the FGE-tag containing Nb over a continuous-flow bio-catalysis system. The aldehyde group within the formylglycine side chain at the C-terminal end of the Nb is suitably located for subsequent bio-orthogonal reactions to fluorescent dyes, biotin, polyethylene glycol, or chromatography resins. We also include methods for production of high yield recombinant FGE, as well as conditions for its immobilization on Sepharose to produce the continuous-flow bio-catalysis system.


[Cultivation of bone marrow in a medium conditioned by lymphoid organ cells].
Conditioned media (CM) from short-term cultures of splenocytes or thymocytes stimulated by Con A inhibit the growth of fibroblast colonies and raise the survival of non-adherent cells (NAC) in primary monolayer cultures of mouse bone marrow. The double effect of the CM is dose-dependent. The self-renewal of NAC in CM cultures is effected during two weeks.


Statistical criteria for setting thresholds in medical school admissions.
In 2001, Dr Jordan Cohen, President of the AAMC, called for medical schools to consider using an Medical College Admission Test (MCAT) threshold to eliminate high-risk applicants from consideration and then to use non-academic qualifications for further consideration. This approach would seem to be consistent with the recent Supreme Court ruling on the University of Michigan admissions cases. Research to support a threshold approach has been reported in many different ways, making comparability problematic. This study examines an assortment of statistical indices that have been used to determine thresholds in undergraduate science grade point average (USGPA) and MCAT sub-scores and total sum and compares them in terms of their sensitivity and specificity for determining Medical Licensing Exam (USMLE Step 1) first time failure. Data for medical school entering classes of 1992-1998 (N=752) from a large Midwestern medical school are used to determine the set of statistics that provide the most useful information for this purpose. The results support plots of risk differences, odds-ratios, sensitivity and specificity for setting cut-scores.


Statistical analysis of the associations between polymorphisms within aldehyde dehydrogenase 2 (ALDH2), and quantitative and qualitative traits extracted from a large-scale database of Japanese single-nucleotide polymorphisms (SNPs).
A scan of 4,190 single-nucleotide polymorphisms (SNPs) in 199 different genes using 38 different quantitative traits to search for associations between genotypes and phenotypes detected an association between the genotypes at rs671 of ALDH2 and gamma-glutamyltranspeptidase (gamma-GTP) levels. We examined the associations between five factors such as gender, age, rs671 genotype, alcohol-drinking habit, and serum gamma-GTP level and found that all pairs were associated except for the pair of rs671 genotype and gender and rs671 genotype and age. We further analyzed the data by both multiple regression and subgroup analyses and found that the associations between rs671 genotype and alcohol-drinking habit, alcohol-drinking habit and gamma-GTP level, gender and gamma-GTP, and age and gamma-GTP were independent of other factors. Conversely, the association between rs671 genotype and gamma-GTP level was dependent on alcohol-drinking habit. Associations between genetic and environmental factors will become a focus of medical and biological studies. Our study has shown that (1) a large sample size combined with a replication study is necessary to overcome the multiple-comparison problem, and (2) subgroup analysis along with logistic and linear multiple regression analysis may be useful to dissect a complicated relationship.


Prolyl 4-hydroxylase alpha-related proteins in Drosophila melanogaster: tissue-specific embryonic expression of the 99F8-9 cluster.
The extracellular matrix (ECM) is proposed to play critical roles in organ morphogenesis through the stabilization and/or sequestration of signaling factors and adhesion molecules, and by maintaining organ integrity. As a first step toward understanding molecules involved in ECM modification and maturation, we have examined the embryonic expression profiles of ten prolyl 4-hydroxylase alpha subunit (PH4alpha)-related genes. Prolyl 4-hydroxylases (PH4) catalyze the formation of 4-hydroxyproline in collagens, the major components of the ECM, and are implicated in the hydroxylation of proline in several other secreted proteins. To date, two alpha subunit proteins have been described in both humans (PHalphaI and PHalphaII) and worms (PHY-1/DPY-18 and PHY-2), whereas only a single Drosophila alpha subunit has been identified. The ten PH4alpha-related genes described in this study are clustered in a 183-kb region near the tip of chromosome arm 3R and include the previously described Drosophila alpha subunit gene. Six of the ten PH4alpha genes in the cluster have tissue-specific embryonic expression. PH4alphaSG1 and PH4alphaSG2 are expressed in the salivary gland, PH4alphaMP is expressed in mouth-part precursors, PH4alphaPV is expressed in the proventriculus, and CG9698-E is expressed in the epidermis. PH4alphaEFB is expressed more broadly, with expression in the anterior and posterior midgut primordia, the fat body, the hemocytes and the epidermis. The expression profiles of these PH4alpha-related genes suggest that tissue-specific ECM modifications may be critical to organ formation and/or function.


Safety and tolerability of intravenous regadenoson in healthy subjects: A randomized, repeat-dose, placebo-controlled study.
Regadenoson is a selective A2A adenosine receptor agonist indicated for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. However, the safety, tolerability, and plasma concentrations associated with repeated doses have not previously been assessed. Healthy males and females were randomized to receive intravenous regadenoson [100 μg (3 doses), 200 μg (3 doses), or 400 μg (2 doses)], or placebo (2 or 3 doses; 0.9% sodium chloride); all doses 10 minutes apart. The primary endpoint was vital sign measurements (blood pressure and heart rate). Secondary endpoints included 12-lead electrocardiogram measurements, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and adverse events. Thirty-six subjects were randomized and completed the study. Plasma concentrations of regadenoson increased in a dose-related manner and with successive doses. No consistent effect was observed for systolic blood pressure, although diastolic blood pressure was slightly lower than placebo for all regadenoson groups. Transient, dose-dependent increases in heart rate were observed in all regadenoson groups. There were no serious adverse events; 27 adverse events occurred in 14 regadenoson-treated subjects vs two events in two placebo-treated subjects. Repeated doses of regadenoson appeared to be safe and well tolerated in healthy subjects.


Aspergillus section Flavi populations from field maize in Argentina.
Populations of Aspergillus section Flavi were studied from a commercial field of maize in Río Cuarto, Córdoba, Argentina. The Aspergillus species were isolated from soil, debris and insects during three periods: pre-planting, growing maize and post-harvest. The colony count from non-rhizospheric soil in the pre-planting period was higher than in growing maize and the post-harvest period. Debris samples analysed during all periods showed similar infection percentages for Aspergillus section Flavi. The samples of insects collected during the maize-growing period showed a lower percentage of Aspergillus isolates than the samples from soil and debris. Aflatoxigenic strains were present in lower levels in each component of the agroecosystem studied. All the strains that produced sclerotia were L strains. In this field agroecosystem, the only strains with a high probability for transfer to the storage agroecosystem were L strains with low toxigenic potential. Maize pre-harvest contamination with aflatoxigenic inoculum was not significant.


Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis.
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. The disease has an acute and a chronic phase in which approximately 30% of the chronic patients suffer from heart disease and/or gastrointestinal symptoms. The pathogenesis of the disease is multifactorial and involves the virulence of the strains, immunological factors and extracellular vesicles (EV) shed by the parasite which participate in cell-cell communication and evasion of the immune response. In this work, we present a transcriptomic analysis of cells stimulated with EV of the trypomastigote stage of T. cruzi. Results after EV-cell incubation revealed 322 differentially expressed genes (168 were upregulated and 154 were downregulated). In this regard, the overexpression of genes related to ubiquitin-related processes (Ube2C, SUMO1 and SUMO2) is highlighted. Moreover, the expression of Rho-GTPases (RhoA, Rac1 and Cdc42) after the interaction was analyzed, revealing a downregulation of the analyzed genes after 4 h of interaction. Finally, a protective role of EV over apoptosis is suggested, as relative values of cells in early and late apoptosis were significantly lower in EV-treated cells, which also showed increased CSNK1G1 expression. These results contribute to a better understanding of the EV-cell interaction and support the role of EV as virulence factors.


Operative strategy in combined coronary and carotid artery disease.
In the period between the opening of our heart center in November 1984 and May 1986, 2001 cardiac operations were performed with the aid of cardiopulmonary bypass. Almost three quarters (73.5%, n = 1471) of the patients had coronary artery disease and 20% (n = 359) had acquired valvular heart disease. In 47 of 1471 patients who underwent coronary artery bypass grafting, a simultaneous carotid endarterectomy was performed. They included 36 men and 11 women, aged between 51 and 78 years (mean 64 years). Preoperatively, 12 patients had cerebrovascular symptoms and 35 were neurologically asymptomatic. Twenty-three had unilateral carotid stenosis and 24 had bilateral or multiple vessel disease of the extracranial arteries. All except four patients had triple-vessel coronary artery disease. In three patients with aortic valve disease, coronary bypass, carotid endarterectomy, and aortic valve replacement were performed simultaneously. Cardiopulmonary bypass was instituted before carotid endarterectomy was performed, with mild hypothermia and hemodilution for added protection. Electroencephalographic monitoring was used throughout the operation. Forty-six of the 47 patients survived the operation without neurologic or cardiac complications. One patient had a neurologic deficit with hemiplegia and coma, which was lethal. We conclude that simultaneous endarterectomy of significant extracranial artery stenosis in candidates for coronary bypass is a method safe enough to justify its routine use.


Data from camera surveys identifying co-occurrence and occupancy linkages between fishers (Pekania pennanti), rodent prey, mesocarnivores, and larger predators in mixed-conifer forests.
These data provide additional information relevant to the frequency of fisher detections by camera traps, and single-season occupancy and local persistence of fishers in small patches of forest habitats detailed elsewhere, "Landscape Fuel Reduction, Forest Fire, and Biophysical Linkages to Local Habitat Use and Local Persistence of Fishers (Pekania pennanti) in Sierra Nevada Mixed-conifer Forests" [10]. The data provides insight on camera trap detections of 3 fisher predators (bobcat [Lynx rufus]). Coyote [Canis latrans], mountain lion [Puma concolor], 5 mesocarnivores in the same foraging guild as fishers (gray fox [Urocyon cinereoargenteus]) ringtail [Bassariscus astutus], marten [Martes americana], striped skunk [Mephitis mephitis] spotted skunk [Spilogale gracilis], and 5 Sciuridae rodents that fishers consume as prey (Douglas squirrel [Tamiasciurus douglasii]), gray squirrel [Sciurus griseus], northern flying squirrel [Glaucomys sabrinus], long-eared chipmunk [Neotamias quadrimaculatus], California ground squirrel [Spermophilus beecheyi]. We used these data to identify basic patterns of co-occurrence with fishers, and to evaluate the relative importance of presence of competing mesocarnivores, rodent prey, and predators for fisher occupancy of small, 1 km(2) grid cells of forest habitat.


Interspecific hybridization of plants and resistance to herbivores: hypotheses, genetics, and variable responses in a diverse herbivore community.
We studied the morphology, molecular genetics, and hebivory of two species of willows (Salix sericea and S. eriocephala) and their interspecific hybrids to test four alternative hypotheses concerning the effects of hybridization on plant resistance. Individually marked plants were identified using morphological traits in the field and measurements of stipule and leaf pubescence were made and compared using Canonical Discriminant Function Analysis. DNA was extracted from the leaves of a sample of the marked plants and RAPD-PCR analysis was performed to establish the genetic status of parental and hybrid plants. RAPD band analysis generally verified the genetic status of parental plants. Hybrid plants were usually correctly identified in the field with a few exceptions. However, the hybrid plants were a heterogeneous group of plants made up of most plants that appear to be F1s and a few plants that appear to be backcrosses to S. sericea. Morphological variables were useful for distinguishing S. sericea from S. eriocephala and hybrids, but were not as dependable in distinguishing between S. eriocephala and hybrids. We compared the densities of 11 herbivore species and the infection by a leaf rust pathogen (Melampsora sp.) on the leaves and stems of two parents and the hybrids in the field. We found support for the Additive hypothesis (3 species), the Dominance hypothesis (2 species) and the Hybrid Susceptibility hypothesis (7 species, 6 herbivores and the Melampsora rust). We found no evidence for the Hybrid Resistance hypothesis. Guild membership was not a good predictor of similar responses of species to hybrid versus parental plants. A Canonical Discriminant Function Analysis showed discrete separation of the taxa based on herbivore densities, illustrating different community structures on hybrid and parental plants. This study demonstrates the diversity of responses of phytophages in response to interspecific hybridization.


Repeat parathyroid operation associated with renal disease.
One hundred ten patients who had undergone operation for secondary and tertiary hyperparathyroidism have been described. Ninety patients had secondary disease and 20 patients had tertiary disease after renal transplantation. From these two groups, 18 patients had repeat operations for control of recurrent or persistent disease. The incidence of repeat operations was 14 percent. Causes were graft-dependent hyperparathyroidism, supernumerary glands in the neck or mediastinum, and incomplete identification of glands in the neck. The most important risk factor is continued long-term dialysis in functionally anephric patients. We recommend that patients with hyperparathyroidism associated with chronic renal failure undergo total parathyroidectomy with autotransplantation. If repeat operation is necessary, a reduction in glandular mass with autotransplantation is preferred. In selected patients, total parathyroidectomy can be considered because of the increased risk of aluminum bone disease.


Changes during travel in the composition and antibiotic resistance pattern of the intestinal Enterobacteriaceae flora: results from a study of mecillinam prophylaxis against travellers' diarrhoea.
A randomized double-blind study was carried out in a group of Danish students visiting Mexico for 2 weeks to investigate the efficacy of mecillinam when given orally in preventing travellers' diarrhoea. The subjects took either 200 mg mecillinam daily as a single dose or placebo for 14 days. Nine (56%) out of 16 taking placebo and 3 (19%) out of 16 taking mecillinam developed travellers' diarrhoea (p less than 0.05). The pathogenic aetiology was not ascertained. A complete change in the Enterobacteriaceae flora took place during travel. A highly antibiotic-resistant Enterobacteriaceae flora was acquired in Mexico in subjects on mecillinam prophylaxis as well as on placebo. Selection of mecillinam-resistant bacteria was minimal.


Excision of the spinal trigeminal tract. Electron microscopy.
In nine patients with trigeminal neuralgia excision of the trigeminal tract was performed instead of tractotomy. In eight of the patients neuralgia was cured. One female patient died due to occlusion of the middle cerebral artery. Electron microscopy disclosed first of all changes in the myelin sheaths. The majority of the changes were non-specific. Only degenerative hypermyelinization was considered to be characteristic for trigeminal neuralgia.


Ranking of Palliative Care Development in the Countries of the European Union.
There is growing interest in monitoring palliative care (PC) development internationally. One aspect of this is the ranking of such development for comparative purposes. To generate a ranking classification and to compare scores for PC development in the countries of the European Union, 2007 and 2013. PC "development" in this study is understood as a combination of the existence of relevant services in a country ("resources") plus the capacity to develop further resources in the future ("vitality"). "Resources" comprise indicators of three types of PC services per population (inpatient palliative care units and inpatient hospices, hospital support teams, and home care teams). "Vitality" of PC is estimated by numerical scores for the existence of a national association, a directory of services, physician accreditation, attendances at a key European conference and volume of publications on PC development. The leading country (by raw score) is then considered as the reference point against which all other countries are measured. Different weightings are applied to resources (75%) and vitality (25%). From this, an overall ranking is constructed. The U.K. achieved the highest level of development (86% of the maximum possible score), followed by Belgium and overall The Netherlands (81%), and Sweden (80%). In the resources domain, Luxembourg, the U.K., and Belgium were leading. The top countries in vitality were Germany and the U.K. In comparison to 2007, The Netherlands, Malta, and Portugal showed the biggest improvements, whereas the positions of Spain, France, and Greece deteriorated. The ranking method permitted a comparison of palliative care development between countries and shows changes over time. Recommendations for improving the ranking include improvements to the methodology and greater explanation of the levels and changes it reveals.


Highly efficient Cr(VI) remediation by cationic functionalized nanocellulose beads.
Applications of nanocellulose as a water treatment material are being actively pursued based on its interesting properties, such as renewability, large specific surface area, hydrophilic surface chemistry, and biodegradability. This study used carboxymethyl cellulose nanofibrils (CMCNFs) to prepare a typical bead-type adsorbent with improved structural stability as an actual water treatment restoration material. In addition, a cationized nanocellulose adsorbent was prepared by introducing polyethyleneimine (PEI) on the surface of the CMCNF (P/CMCNF), the removal efficiency of Cr(VI) was evaluated, and its mechanism was elucidated. As a result, the P/CMCNF beads showed an excellent Cr(VI) removal capacity of 1302.3 mg/g, the best result among cellulose-based adsorption materials. Cr(VI) was effectively removed by electrostatic attractions combined with chemical reduction and chelation mechanisms. Furthermore, the macrobead fabrication and PEI surface modification process improved the underwater stability of the P/CMCNF, and it showed excellent reuse efficiency.


A Randomized Controlled Trial of the Sources of Meaning Card Method: A New Meaning-Oriented Approach Predicts Depression, Anxiety, Pain Acceptance, and Crisis of Meaning in Patients with Chronic Pain.
Although considered the first-line psychological treatment for chronic pain, cognitive behavioral therapy has recently been criticized as being too limited, insufficient, and sometimes ineffective in the treatment of patients with chronic pain. Moreover, important existential perspectives are sparsely or not at all integrated into cognitive behavioral therapy. We therefore propose to complement chronic pain treatment with a meaning-based intervention, the Sources of Meaning Card Method (SoMeCaM). This study tested its efficacy. A randomized controlled trial was conducted with 42 patients with chronic pain. The trial compared an intervention group (standard care and participation in the SoMeCaM, a meaning-oriented approach) with a control group (standard care). We evaluated both groups at baseline and at 1 (t1) and 2 months (t2) after the intervention. The primary outcome assessed was pain acceptance, while depression, anxiety, pain intensity, pain medication, satisfaction with life, meaningfulness, and crisis of meaning were examined as secondary outcomes. Comparisons within and between groups showed significant treatment effects at t1. Higher increases in pain acceptance and decreases in anxiety, depression, and crisis of meaning were observed in the intervention group. Improvements in pain acceptance and anxiety persisted until t2, when pain intensity was also lower. Effect sizes at t2 were medium to large. Our preliminary work demonstrates the importance of the existential perspective in chronic pain therapy.


Accumulation of a glycine rich protein in auxin-deprived strawberry fruits.
Growth of strawberry (Fragaria ananassa Duch. cv. Ozark Beauty) receptacles is regulated by auxin supplied from the achenes. The receptacle growth can be stopped at any stage by deachening the fruits, and can be resumed by exogenous application of auxin. In our earlier studies we demonstrated auxin regulated polypeptide changes at different stages of strawberry fruit development. Removal of achenes from fruits and growing the receptacles without auxin resulted in the time-dependent accumulation of 52,000 Mr polypeptide. Amino acid analysis revealed that the protein is rich in glycine. Our studies, with normal and variant strawberry receptacles, indicate that the synthesis and accumulation of this glycine-rich protein correlates with cessation of receptacle growth. These results suggest a possible role for the glycine-rich protein in cessation of growth.


Kaposi sarcoma in a child after hematopoietic stem cell transplantation: Should pre-transplant HHV-8 screening be considered in recipients from high prevalence areas?
Kaposi sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8). We report the case of a 10-year-old male from a high HHV-8 prevalence area, diagnosed with severe aplastic anemia who underwent an upfront hematopoietic stem cell transplantation (HSCT). Five months after transplant, the patient was diagnosed with KS with skin, mucosae, lymph nodes and lung involvement. After withdrawal of immunosuppression the patient achieved complete remission without requiring further treatments. KS may occur after HSCT in patients from high HHV-8 prevalence areas. Considering that, we propose that screening of HHV-8 by antibody testing could be considered in HSCT donors/recipients from these areas.


Comparison of large scale purification processes of naproxen enantiomers by chromatography using methanol-water and methanol-supercritical carbon dioxide mobile phases.
This paper compares two methods used for the preparative purification of a mixture of (S)-, and (R)-naproxen on a Whelk-O1 column, using either high performance liquid chromatography or supercritical fluid chromatography. The adsorption properties of both enantiomers were measured by frontal analysis, using methanol-water and methanol-supercritical carbon dioxide mixtures as the mobile phases. The measured adsorption data were modeled, providing the adsorption isotherms and their parameters, which were derived from the nonlinear fit of the isotherm models to the experimental data points. The model used was a Bi-Langmuir isotherm, similar to the model used in many enantiomeric separations. These isotherms were used to calculate the elution profiles of overloaded elution bands, assuming competitive Bi-Langmuir behavior of the two enantiomers. The analysis of these profiles provides the basis for a comparison between supercritical fluid chromatographic and high performance liquid chromatographic preparative scale separations. It permits an illustration of the advantages and disadvantages of these methods and a discussion of their potential performance.