Use of cultural consensus analysis to evaluate expert feedback of median safety.
Cultural consensus analysis is a statistical method that can be used to assess participant responses to survey questions. The technique concurrently estimates the knowledge of each survey participant and estimates the culturally correct answer to each question asked, based on the existence of consensus among survey participants. The main objectives of this paper are to present the cultural consensus methodology and apply it to a set of median design and safety survey data that were collected using the Delphi method. A total of 21 Delphi survey participants were asked to answer research questions related to cross-median crashes. It was found that the Delphi panel had agreeable opinions with respect to the association of average daily traffic (ADT) and heavy vehicle percentage combination on the risk of cross-median crashes; relative importance of additional factors, other than ADT, median width, and crash history that may contribute to cross-median crashes; and, the relative importance of geometric factors that may be associated with the likelihood of cross-median crashes. Therefore, the findings from the cultural consensus analysis indicate that the expert panel selected to participate in the Delphi survey shared a common knowledge pool relative to the association between median design and safety. There were, however, diverse opinions regarding median barrier type and its preferred placement location. The panel showed a higher level of knowledge on the relative importance regarding the association of geometric factors on cross-median crashes likelihood than on other issues considered. The results of the cultural consensus analysis of the present median design and safety survey data could be used to design a focused field study of median safety.


Adapting a triple-axis spectrometer for small angle neutron scattering measurements.
Small angle neutron scattering (SANS) instruments typically cover a q (scattering vector) range from 0.001 to 0.6 A(-1). This range in q is achieved through a combination of cold neutrons (lambda>4 A) and a highly collimated beam. However, as a direct result of the unavailability of a cold source at the Canadian Neutron Beam Centre (CNBC), we have resorted to adapting a triple-axis spectrometer to perform SANS measurements. This is achieved through the use of multiple converging incident beams which enhance the neutron flux on the sample by a factor of 20, compared to a single beam of the same spot size. Furthermore, smearing effects due to vertical divergence from the slit geometry are reduced through the use of horizontal Soller collimators. As a result, this modified triple-axis spectrometer enables SANS measurements to a minimum q value (q(min)) of approximately 0.006 A(-1). Data obtained from the modified triple-axis spectrometer are in good agreement with those data from the 30 m NG3-SANS instrument located at the National Institute of Standards and Technology (Gaithersburg, MD, USA).


The Predictive Value of Serum NT-proBNP on One-Year All-Cause Mortality in Geriatrics Hip Fracture: A Cohort Study.
Objective This study evaluated the association between N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and one-year mortality in geriatric patients with intertrochanteric and femoral neck fractures receiving the operative treatment. Methods Consecutive age ≥65 years patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. The multivariate logistic regression models were used to identify the association between preoperative NT-proBNP concentrations and mortality. All analyses were performed using EmpowerStats and the R software. Result One thousand two hundred nineteen patients were included in the study. The average age was 79.73±6.65 years (range 66-99 years). The mean NT-proBNP concentration was 616.09±1086.85 ng/L (median 313.40 ng/L, range 16.09-20123.00 ng/L). The follow-up was 35.39±15.09 months (median 35.78 months, range 0.10-80.14 months). One hundred and eleven (9.1%) patients died within one year. After adjusting for confounding factors, multivariate logistic regression models showed a curved association between preoperative NT-proBNP concentration and one-year mortality. When the NT-proBNP concentration was below 1099 ng/L, the mortality increased by 10% (OR=1.10, 95%CI: 1.03-1.17, P=0.0025) when NT-proBNP increased by 100 ng/L. When the NT-proBNP concentration was above 1099 ng/L, the mortality did not increase anymore when NT-proBNP increased (OR=1.00, 95%CI: 0.99-1.02, P=0. 7786). Thus, NT-proBNP was a valuable indicator to predict high one-year mortality in practice. Conclusion The NT-proBNP concentrations were nonlinearly associated with mortality in elderly hip fractures with a saturation effect, and NT-proBNP was a risk indicator of all-cause mortality. A well-designed controlled trial to show the role of mortality by decreasing the concentration of NT-proBNP is needed in the future.


Anastomotic aneurysms after surgical treatment of Takayasu's arteritis: a 40-year experience.
To evaluate the clinical characteristics of anastomotic aneurysms that develop in surgically treated patients with Takayasu's arteritis. Among 103 patients with Takayasu's arteritis treated surgically over 40 years, 91 patients with 259 anastomoses (allowing for exclusion of 12 operative deaths) participated in follow-up study from 1 month to 37.3 years with a mean value +/- SEM of 17.3 +/- 1.1 years with a follow-up completion rate of 93% at 30 years. The clinical characteristics of anastomotic aneurysms were clarified, and the influences of several factors (sites of anastomoses, occlusive or aneurysmal disease, suture material, preoperative systemic inflammation, and administration of corticosteroids) on formation of anastomotic aneurysms were analyzed by means of life-table method and Cox regression analysis. Twenty-two uninfected anastomotic aneurysms were found among 14 patients (22 of 259 anastomoses, 8.5%). The interval between the previous operation and diagnosis varied from 1.6 to 30 years with a mean value +/- SEM of 9.8 +/- 1.8 years. The cumulative incidence of anastomotic aneurysm at 20 years was 12.0%. Systemic inflammation or steroid administration had little influence on formation of anastomotic aneurysm. Instead, anastomotic aneurysm tended to occur after operations for aneurysmal lesions. Anastomotic aneurysm can occur anytime after operations for Takayasu's arteritis. The development of anastomotic aneurysm is not influenced by any factor specific to this disease except the presence of an aneurysmal lesion.


High ambient radiofrequency radiation in Stockholm city, Sweden.
We measured the radiofrequency (RF) radiation at central parts in Stockholm, Sweden in March and April 2017. The same measurement round tour was used each time. We used EME Spy 200 for the measurements as in our previous studies in Stockholm. The results were based on 11,482 entries, corresponding to more than 12 h measurements. The total mean level was 5,494 µW/m2 (median 3,346; range 36.6-205,155). The major contributions were down links from LTE 800 (4G), GSM + UMTS 900 (3G), GSM 1800 (2G), UMTS 2100 (3G) and LTE 2600 (4G). Regarding different places, the highest RF radiation was measured at the Hay Market with a mean level of 10,728 µW/m2 (median 8,578; range 335-68,815). This is a square used for shopping, and both retailers and visitors may spend considerable time at this place. Also, the Sergel Plaza had high radiation with a mean of 7,768 µW/m2. All measurements exceeded the target level of 30-60 µW/m2 based on non-thermal (no heating) effects, according to the BioInitiative Report. Based on short-term thermal effects, The International Commission on Non-Ionizing Radiation Protection established guideline 2 of 10 W/m2 (2,000,000-10,000,000 µW/m2) depending on frequency in 1998, and has not changed it despite solid evidence of non-thermal biological effects at substantially lower exposure levels. These environmental RF radiation levels are expected to increase with the introduction of 5G for wireless communication.


Membrane permeability related physicochemical properties of a novel gamma-secretase inhibitor.
Pharmaceutical profiling studies were conducted on a novel prototype gamma-secretase inhibitor, to determine the potential of its oral absorption. Such compounds can be of use in the treatment of Alzheimer's disease (AD). The studies included determination of solubility, dissociation constant (pK(a)), octanol/water partition coefficient (log P) and the capacity factor (k'(IAM)) on immobilized artificial membrane (IAM) chromatographic columns. The compound is very slightly solubility in water (120 +/- 50 microg/mL) but the solubility increased considerably in basic medium (270 +/- 60 microg/mL). The compound exhibited pK(a) of (10.36 +/- 0.11); and log P of (3.36 +/- 0.16) determined by shake-flask method and (3.31 +/- 0.01) determined by high performance liquid chromatography (HPLC). The experimentally determined log P values correlated well with the calculated one of 3.44. The observed log k'(IAM) value of (2.79 +/- 0.04) indicates that the compound can reasonably be expected to have high membrane permeability, and therefore, good absorption profile if taken orally. This conclusion is also supported by other parameters determined.


Microbial adjuvant and autoimmunity. I. Induction of antibody responses to syngeneic tissue extracts in mice treated with capsular polysaccharide of Klebsiella pneumoniae.
With the use of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as a powerful adjuvant, high precipitin responses could be induced in mice to syngeneic eyeball extracts and thyroid gland extracts which were normally nonimmunogenic. Only very weak responses were induced to eyeball extracts by Freund's complete adjuvant. Repeated administrations of the antigens mixed with CPS-K at time intervals of 30 days (more than twice for the eyeballs or more than three times for the thyroid glands) were required for induction of high precipitin responses. Antibody responses detectable by the immunofluorescent technique could be induced to syngeneic lymphoid tissue extracts by injecting the mixture of antigen and CPS-K more than five times at time intervals of 30 days. These findings suggest that repeated stimulation by autoantigens together with such a strong adjuvant as CPS-K can terminate natural tolerance against autoantigens.


Fertility in estrus-cycling and noncycling virgin heifers and suckled beef cows after induced ovulation.
A procedure was developed to either induce or synchronize ovulation in heifers and suckled cows. Beef females were assigned to two breeding programs: 1) two injections of prostaglandin F2alpha (PGF2alpha) given 14 d apart to synchronize estrus (PGF2alpha control; n = 179), with inseminations 12 to 16 h after detected estrus or at 80 h in the absence of estrus, or 2) two injections of PGF2alpha (d -14 and 0) plus 100 microg of GnRH on d -7 when 6 mg of norgestomet was implanted (PGF2alpha/NORG/GnRH treatment; n = 173). Implants were removed 24 h after the second PGF2alpha injection (d +1) and females were inseminated 12 to 16 h after detected estrus until 54 h after PGF2alpha. The remaining cattle were given a second 100-microg GnRH injection 54 h after PGF2alpha and inseminated 18 to 20 h later. Percentages of noncycling females with subsequently elevated progesterone (P4) on d 0 or +1 were not different between treatment groups (20.4 vs 25%), but conception rate was greater (P < .05) in noncycling treated females than in noncycling controls (55 vs 12.8%). Conception rates in cycling (59.2%) and noncycling (62.2%) treated females were similar to those in cycling controls (56.2%) but greater (P = .06) than those in noncycling controls (26.5%). Conception rates in treated females inseminated 12 to 16 h after detected estrus (63.1%) or at one fixed time (58.3%) were similar to those in controls inseminated 12 to 16 h after detected estrus (68.7%). This treatment procedure produced fertility after one timed insemination that was equal to controls inseminated after detected estrus and induced equally fertile ovulations in noncycling heifers and cows.


Developing Recommendations for Evidence-Based Clinical Preventive Services for Diverse Populations: Methods of the U.S. Preventive Services Task Force.
The U.S. Preventive Services Task Force (USPSTF) summarizes the principles and considerations that guide development of its recommendations for diverse U.S. populations. It uses these principles through each step in the evidence-based guideline process: developing the research plan, conducting the evidence review, developing the recommendation, and communicating to guideline users. Three recent recommendations provide examples of how the USPSTF has used these principles: the 2015 recommendation on screening for abnormal blood glucose and type 2 diabetes; the 2016 recommendation on screening for breast cancer; and the recommendation on screening for prostate cancer, which is currently in progress. A more comprehensive list of recommendations that includes considerations for specific populations is also provided.


Li80Ba39N9: the first Li/Ba subnitride.
The crystal structure of Li80Ba39N9, a new representative of alkali-alkaline-earth metal subnitrides prepared from the metals and barium azide, was investigated based on single-crystal X-ray diffraction data. The compound has a novel crystal structure with a tetragonal unit cell, space group I(-)42m, a = 16.0763(8) A, c = 32.267(2) A, Z = 2, and V = 8330.0(8) A3. The structure can be described in terms of subnitride clusters with internal ionic bonding and metallic bonding in the rest of the space. The compound contains a new cluster Li12Ba5N6 and polytetrahedral Li clusters based on centered Li13 icosahedra, which are typical for Li-rich intermetallic compounds.


Concentrations of prostaglandins D2, E2, F2 alpha, 6-keto-F1 alpha and thromboxane B2 in synovial fluid from patients with inflammatory joint disorders and osteoarthritis.
The concentrations of PGD2, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 in synovial fluid from patients with rheumatoid arthritis (RA), Reiter's disease (RD), acute gouty arthritis (GA) and osteoarthritis (OA) were measured by radioimmunoassay. PGE2 was found to be the most predominant prostanoid (pg/ml; Mean +/- S.E.M.): RA 887 +/- 85, RD 870 +/- 71, GA 1064 +/- 155 and OA 665 +/- 71. In patients with OA lower mean levels of all the prostanoids were found than compared to the other groups of patients. Only in patients with RA a slight correlation between PGD2/PGF2 alpha, PGE2/PGF2 alpha and PGE2/6-keto-PGF1 alpha could be demonstrated. No significant correlations between the leucocyte cell counts in the synovial fluid and the prostanoid concentrations were found. In patients with RA developing recurrent knee joint effusions within four weeks after the first sampling significantly lower levels of PGE2 and TXB2 were found in the recurrent samples (PGE2 792 +/- 183; TXB2 179 +/- 33) than compared with the original samples (PGE2 984 +/- 146; TXB2 239 +/- 32).


Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma.
HSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed ∼60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed ∼60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.


Reducing mortality from anthrax bioterrorism: strategies for stockpiling and dispensing medical and pharmaceutical supplies.
A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (<14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from 100,000 US dollars to 20,000 US dollars/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.


Thurstonian and Brunswikian origins of uncertainty in judgment: a sampling model of confidence in sensory discrimination.
As a preliminary step towards the presentation of a model of confidence in sensory discrimination, the authors propose a distinction between 2 different origins of uncertainty named after 2 of the great probabilists in the history of psychology, L.L. Thurstone and Egon Brunswik. The authors review data that suggest that there are empirical as well as conceptual differences between the 2 modes of uncertainty and thus that separate models of confidence are needed in tasks dominated by Thurstonian and Brunswikian uncertainty. The article presents a computational model for 1 class of tasks dominated by Thurstonian uncertainty: sensory discrimination with pair comparisons. The sensory sampling model predicts decisions, confidence assessments, and the complex pattern of response times in simple psychophysical discrimination tasks (J.V. Baranski and W.M. Petrusic, 1994). The model also accounts for the disposition towards underconfidence often observed in sensory discrimination with pair comparisons.


Pediatric cardiac catheterization.
The publications of 2000 and 2001 stress how interventional pediatric cardiology has moved from angioplasty to device placement. This review summarizes the important articles during the past year that evaluated the safety and efficacy of atrial septal defect devices, patent ductus occluders, and stents to treat coarctation of the aorta. The past year has also seen the emergence of old technologies that have been modified and expanded for new applications. The three areas of old technology reviewed are (1) using balloon angioplasty to palliate low birth weight infants with critical coarctation, (2) using coronary interventions in the pediatric patient, and (3) using balloon pulmonary angioplasty to treat patients with chronic thromboembolic pulmonary hypertension. Finally, this review describes the development of a new interventional technique, transcatheter implantation of a pulmonary valve, and outlines how real-time MRI in the next decade likely will replace x-ray fluoroscopy as the primary diagnostic and interventional imaging tool for the pediatric cardiologist.


[Erythema nodosum as a reaction pattern: a broad spectrum of underlying causes].
Erythema nodosum is a skin disorder that is characterised by the presence of painful erythematous nodules and plaques, mainly located on the shins. This disorder is associated with comorbidities and can be considered as an aspecific reaction pattern to a broad range of causes. However, an idiopathic variant also exists, which occurs in 22-72% of cases. Erythema nodosum is pre-eminently a skin disease which, due to its multifactorial pathogenesis, occurs in a wider field than dermatology alone. Therefore, knowledge of this disorder is important for all practicing physicians. To illustrate this we describe three patients with erythema nodosum attributable to different causes.


Working collaboratively across schools to promote oral health education through interprofessional education.
The Association of American Medical Colleges and American Dental Education Association have identified oral health knowledge, skills, and attitudes shared by both medical and dental professionals. Although oral health was deemed an essential competency for medical practitioners, our state struggled to ensure learners received proper training. This training deficit resulted in conducting a needs assessment and implementing an oral health interprofessional module at our schools. First-year medical students and clinical faculty were emailed surveys in 2016 to obtain baseline information. A team of faculty and students from the Schools of Medicine and Dentistry reviewed the curriculum to determine where to augment oral health content. An oral health module to teach a basic head, neck, and oral examination to first-year medical students during their patient-centered care small-group sessions was implemented and evaluated. Only 13.6% of faculty respondents were aware of national oral health competency recommendations, and <50% rated oral health important for primary care physicians (PCPs) to include in history, physical exam, or oral health counseling. On baseline, ≤25% of PCP respondents reported integrating the listed skills in their practice, and most indicated lacking expertise to teach oral health. Teaching sessions were rated helpful by students and faculty. After the teaching sessions, ratings on the importance of including oral health significantly increased from baseline. Collaboration between Schools of Dentistry and Medicine successfully integrated oral health into medical school curriculum and improved the tutors' attitudes of its importance.


Assessing Measurement Invariance of a Land Use Environment Construct Across Levels of Urbanicity.
Variation in the land use environment (LUE) impacts the continuum of walkability to car dependency, which has been shown to have effects on health outcomes. Existing objective measures of the LUE do not consider whether the measurement of the construct varies across different types of communities along the rural/urban spectrum. To help meet the goals of the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, we developed a national, census tract-level LUE measure which evaluates the road network and land development. We tested for measurement invariance by LEAD community type (higher density urban, lower density urban, suburban/small town, and rural) using multiple group confirmatory factor analysis. We determined that metric invariance does not exist; thus, measurement of the LUE does vary across community type with average block length, average block size, and percent developed land driving most shared variability in rural tracts and with intersection density, street connectivity, household density, and commercial establishment density driving most shared variability in higher density urban tracts. As a result, epidemiologic studies need to consider community type when assessing the LUE to minimize place-based confounding.


[Hypercalcemia in neoplastic and granulomatous diseases: pathogenesis and treatment options].
Hypercalcemia is a frequently observed laboratory phenomenon in clinical practice. It can occur in several diseases, among which it is associated most frequently with neoplasms, hyperparathyroidism and disorders of vitamin D metabolism. The appearance of hypercalcemia in neoplastic diseases is related to a poor prognosis in general. In most cases, malignant hypercalcemia is related to the secretion of parathormone-related protein, but other causes have also been described. Granulomatous diseases are associated with the hypersecretion of vitamin D metabolites. Fluid volume repletion, forced diuresis can be regarded as cornerstones in the therapy of acute hypercalcemia independent of its etiology, in addition, medications including bisphosphonates, calcitonin, gallium nitrate and glucocorticoids can be applied. In this review article, the authors present a brief synopsis of the pathogenesis of hypercalcemia associated with neoplastic and granulomatous diseases along with the treatment options, underlining the practical aspects.


Lupus-inducing drugs alter the structure of supercoiled circular DNA domains.
We analyzed the effects of procainamide (PROC), hydralazine (HYD), N-acetylprocainamide (NAPA), and L-canavanine (CAN) on circular supercoiled plasmids as models for chromosomal loop domains. The supercoil-dependent B-Z equilibrium in recombinant plasmids was used as an indicator of structural changes induced in circular DNA. Two-dimensional gel electrophoresis showed that PROC and HYD strongly inhibited supercoil-induced Z-DNA formation, whereas NAPA caused less pronounced changes in the B-Z equilibrium, and CAN had no effect. Gel retardation assays showed that the binding of a Z-DNA-specific autoimmune antibody to a Z-DNA-containing plasmid was strongly perturbed by HYD, but not influenced by CAN. Both PROC and NAPA showed moderate inhibition of antibody binding. Our results demonstrate the different potentials of these 4 drugs to interact with DNA and to alter the tertiary topology of DNA domains. It is conceivable that the in vivo capacity of PROC and HYD to induce antinuclear antibodies may be related to their ability to influence structural features in chromosomal DNA domains or nucleosomes, thus liberating antigenic structural epitopes in DNA and/or DNA-associated proteins.


Nature of quantum states created by one photon absorption: pulsed coherent vs pulsed incoherent light.
We analyze electronically excited nuclear wave functions and their coherence when subjecting a molecule to the action of natural, pulsed incoherent solar-like light and to that of ultrashort coherent light assumed to have the same center frequencies and spectral bandwidths. Specifically, we compute the spatiotemporal dependence of the excited wave packets and their electronic coherence for these two types of light sources, on different electronic potential energy surfaces. The resultant excited state wave functions are shown to be dramatically different, reflecting the light source from which they originated. In addition, electronic coherence is found to decay significantly faster for incoherent light than for coherent ultrafast excitation, for both continuum and bound wave packets. These results confirm that the dynamics observed from ultrashort coherent excitation does not reflect what happens in processes induced by solar-like radiation, and conclusions drawn from one do not, in general, apply to the other. These results provide further support to the view that the dynamics observed in studies using ultrashort coherent pulses can be significantly different than those that would result from excitation with natural incoherent light.


Immunological evidence for the occurrence of luteinizing hormone-releasing factor and the alpha-subunit of glycoprotein hormones in carcinoid tumors.
The immunoperoxidase technique was used to identify LRF and glycoprotein hormones or their subunits in 22 carcinoid tumors of various origins. All tumors were positive for both LRF and the alpha-subunit, whereas stainings with antisera against the beta-subunits of CG, LH, FSH, and TSH were negative. The binding of LRF and the alpha-subunit within the same malignant tissue raises the possibility of a functional relationship between the two.


Computed Tomography Fluoroscopy-guided Core Needle Biopsy of Abdominal Para-aortic Lesions: A Retrospective Evaluation of the Diagnostic Yield and Safety.
To retrospectively evaluate the diagnostic yield and safety of computed tomography (CT) fluoroscopy-guided biopsy of abdominal para-aortic lesions. CT fluoroscopy-guided biopsy was performed for 30 lesions (median long diameter 2.4 cm; range, 1.3-12.4 cm) in 30 patients (11 women and 19 men; median age 64.5 years; age range 37-90 years) using 18- and/or 20-gauge needles. The median length of the biopsy needle tracts was 9.3 cm (range, 5.5-13.0 cm). The median number of biopsy fires was 3 (range, 2-6). The median duration of the procedures was 33 min (range, 14-80 min). The diagnostic yield and adverse events (AEs) were retrospectively evaluated. The AEs were categorized using the Society of Interventional Radiology classification system. Technical success was determined by the acquisition of a sufficient number of specimens for pathological diagnosis. Diagnostic yield was defined as the match between the pathological and final diagnoses. In all 30 procedures, CT fluoroscopy-guided biopsies of the abdominal para-aortic lesions were technically successful. Twenty-six lesions were malignant (9 malignant lymphomas and 17 lymph node [LN] metastases) and four were benign (one schwannoma, one granular cell tumor, and two normal LNs). One case was insufficiently diagnosed as a B-cell lymphoma; thus, the diagnostic yield of the biopsy was 96.7%. AEs occurred in seven procedures (23.3%), including six cases of class A hemorrhage and one case of class B vasovagal reaction. CT fluoroscopy-guided biopsy of abdominal para-aortic lesions is a safe procedure and provides a high diagnostic yield.


Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections?
On 30 January 2020, the World Health Organisation identified COVID-19, caused by the virus SARS-CoV-2, to be a global emergency. The risk factors already identified for developing complications from a COVID-19 infection are age, gender and comorbidities such as diabetes, hypertension, obesity and cardiovascular disease. These risk factors, however, do not account for the other 52% of deaths arising from COVID-19 in often seemingly healthy individuals. This paper investigates the potential link between SARS-CoV-2 and bacterial load, questioning whether bacteria may play a role in bacterial superinfections and complications such as pneumonia, acute respiratory distress syndrome and sepsis. The connection between COVID-19 complications and oral health and periodontal disease is also examined, as the comorbidities at highest risk of COVID-19 complications also cause imbalances in the oral microbiome and increase the risk of periodontal disease. We explore the connection between high bacterial load in the mouth and post-viral complications, and how improving oral health may reduce the risk of complications from COVID-19.


Adverse and Advantageous Selection in the Medicare Supplemental Market: A Bayesian Analysis of Prescription drug Expenditure.
This paper develops an extended specification of the two-part model, which controls for unobservable self-selection and heterogeneity of health insurance, and analyzes the impact of Medicare supplemental plans on the prescription drug expenditure of the elderly, using a linked data set based on the Medicare Current Beneficiary Survey data for 2003-2004. The econometric analysis is conducted using a Bayesian econometric framework. We estimate the treatment effects for different counterfactuals and find significant evidence of endogeneity in plan choice and the presence of both adverse and advantageous selections in the supplemental insurance market. The average incentive effect is estimated to be $757 (2004 value) or 41% increase per person per year for the elderly enrolled in supplemental plans with drug coverage against the Medicare fee-for-service counterfactual and is $350 or 21% against the supplemental plans without drug coverage counterfactual. The incentive effect varies by different sources of drug coverage: highest for employer-sponsored insurance plans, followed by Medigap and managed medicare plans.


Mutualistic networks: moving closer to a predictive theory.
Plant-animal mutualistic networks sustain terrestrial biodiversity and human food security. Global environmental changes threaten these networks, underscoring the urgency for developing a predictive theory on how networks respond to perturbations. Here, I synthesise theoretical advances towards predicting network structure, dynamics, interaction strengths and responses to perturbations. I find that mathematical models incorporating biological mechanisms of mutualistic interactions provide better predictions of network dynamics. Those mechanisms include trait matching, adaptive foraging, and the dynamic consumption and production of both resources and services provided by mutualisms. Models incorporating species traits better predict the potential structure of networks (fundamental niche), while theory based on the dynamics of species abundances, rewards, foraging preferences and reproductive services can predict the extremely dynamic realised structures of networks, and may successfully predict network responses to perturbations. From a theoretician's standpoint, model development must more realistically represent empirical data on interaction strengths, population dynamics and how these vary with perturbations from global change. From an empiricist's standpoint, theory needs to make specific predictions that can be tested by observation or experiments. Developing models using short-term empirical data allows models to make longer term predictions of community dynamics. As more longer term data become available, rigorous tests of model predictions will improve.


Electron Energy Loss Processes in Methyl Methacrylate: Excitation and Bond Breaking.
Details of electron-induced chemistry of methyl methacrylate (MMA) upon complexation are revealed by combining gas-phase 2D electron energy loss spectroscopy with electron attachment spectroscopy of isolated MMA and its clusters. We show that even though isolated MMA does not form stable parent anions, it efficiently thermalizes the incident electrons via intramolecular vibrational redistribution, leading to autodetachment of slow electrons. This autodetachment channel is reduced in clusters due to intermolecular energy transfer and stabilization of parent molecular anions. Bond breaking via dissociative electron attachment leads to an extensive range of anion products. The dominant OCH3- channel is accessible via core-excited resonances with threshold above 5 eV, despite the estimated thermodynamic threshold below 3 eV. This changes in clusters, where MnOCH3- anions are observed in a lower-lying resonance due to neutral dissociation of the 1(n, π*) state and electron self-scavenging. The present findings have implications for electron-induced chemistry in lithography with poly(methyl methacrylate).


Microduplication of 3p26.3 in nonsyndromic intellectual disability indicates an important role of CHL1 for normal cognitive function.
Terminal deletions of chromosome 3p26.3 confined to the CHL1 gene have previously been described in children with intellectual disability and epilepsy. Here, we report for the first time, a 3p26.3 duplication including only the CHL1 gene in an intellectually disabled girl with epilepsy. The penetrance of both deletions and duplications in 3p26.3 is reduced because all chromosomal imbalances were inherited from healthy parents. Further studies are needed to specify the pathogenic mechanism of 3p26.3 imbalances and to estimate recurrence risks in genetic counseling. However, the description of both deletions and duplications of chromosome 3p26.3 in nonsyndromic intellectual disability suggests that CHL1 is a dosage-sensitive gene with an important role for normal cognitive development.


A DIC-Based Study on Compressive Responses of Concrete after Exposure to Elevated Temperatures.
This paper provides an experimental investigation on the cracking process and residual mechanical properties of concrete after exposure to elevated temperatures. A total of 36 standard concrete prism specimens were tested after exposure to high temperatures of up to 600 °C. The failure modes, cracking process, residual mechanical properties, deformation characteristics and the strain distribution on the surface during the loading procedure were presented. The influences of exposure temperature and water-cement ratio (w/c) were interpreted. The digital image correlation (DIC) method was applied to quantitatively and visually characterize the development of cracking and relative displacement on the concrete surface. The findings suggest that the residual compressive strength and elastic modulus of the concrete decreases gradually with the increasing temperature, especially in the specimens with lower w/c ratio. The DIC technique provides an effective means to measure very precise and detailed information, including the crack opening and distribution of strain on the concrete surface.


Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and IL-18.
Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity. However, some T cells also demonstrate innate functions, including non-Ag-specific IFN-gamma production in response to microbial products such as LPS or exposure to IL-12 and/or IL-18. In these studies we examined LPS-induced cytokine responses of CD8(+) T cells directly ex vivo. Following acute viral infection, 70-80% of virus-specific T cells will produce IFN-gamma after exposure to LPS-induced cytokines, and neutralization experiments indicate that this is mediated almost entirely through production of IL-12 and IL-18. Different combinations of these cytokines revealed that IL-12 decreases the threshold of T cell activation by IL-18, presenting a new perspective on IL-12/IL-18 synergy. Moreover, memory T cells demonstrate high IL-18R expression and respond effectively to the combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high cytokine concentrations. This demonstrates that the synergy between IL-12 and IL-18 in triggering IFN-gamma production by memory T cells is not simply due to up-regulation of the surface receptor for IL-18, as shown previously with naive T cells. Together, these studies indicate how virus-specific T cells are able to bridge the gap between innate and adaptive immunity during unrelated microbial infections, while attempting to protect the host from cytokine-induced immunopathology and endotoxic shock.


Diagnostic Approach to Cardiac Involvement in Idiopathic Inflammatory Myopathies.
Cardiac involvement in idiopathic inflammatory myopathies (IIMs) attracts more attention than it ever did because of its morbidity and impact on worse prognosis, although the accurate information needs further epidemiological studies. Early identification and intervention for the diseased heart may help improve the clinical outcomes of IIMs with cardiac involvement. Cardiac troponin assays, allowing for sensitive detection of minor myocardium injury, may provide a new way for early detection for heart involvement in IIMs. While elevated cardiac troponin I (cTnI) specifically indicates cardiomyocyte injury, the elevation of cardiac troponin T (cTnT) levels may not only derive from damaged heart but also diseased adult skeletal muscles in which cTnT could re-express in patients with IIMs. cTnI is the biomarker of choice for diagnosis of cardiac involvement and may also be a prognostic factor in IIMs. Meanwhile, electrocardiography (ECG), cardiac imaging (e.g., echocardiography, cardiac magnetic resonance) and histopathological techniques (e.g., endomyocardial biopsy) take on different degrees of importance for the diagnosis of cardiac involvement. We propose a diagnostic strategy combining the routine use of cTnI assay with other techniques (routine ECG and echocardiography, cardiac magnetic resonance, and or endomyocardial biopsy in necessity) and clinical investigation for early detection of heart involvement in IIMs. Future researches are required to validate the algorithm for performance.


N-Chlorotaurine and ammonium chloride: an antiseptic preparation with strong bactericidal activity.
The bactericidal activity of the endogenous antiseptic N-chlorotaurine (NCT) is significantly enhanced in the presence of ammonium chloride which induces the formation of monochloramine (NH(2)Cl) whose strong bactericidal activity is well known. In this study the properties of NCT plus ammonium chloride have been investigated. The reaction of active chlorine compounds like chloramine-T (N-chlorotoluene-sulfonamide sodium), chloroisocyanuric acid derivatives, hypochlorites (NaOCl, CaOCl(2)) with ammonium chloride did not stop at the stage of monochloramine, and the pungent smelling by-products di- and trichloramine, NHCl(2) and NCl(3), were also formed. This was not the case with NCT where only monochloramine was generated. The equilibrium constant of the reaction of NCT with ammonium was found to be [Formula: see text] , which allows to estimate the equilibrium concentration of monochloramine in aqueous solutions of NCT and ammonium chloride. At concentrations each ranging between 0.01% and 1.0% it comes to [NH(2)Cl]=3.5-254 ppm. As an unexpected result the monochloramine containing formulation turned out to be most stable in plain water without buffer additives. Quantitative killing assays revealed complete inactivation of 10(6) to 10(7)CFU/mL of seven bacterial strains by 0.1% NCT plus 0.1% ammonium chloride within 5 min, while with plain 0.1% NCT an incubation time of 2-4h was needed to achieve the same effect. The highly significant increase of bactericidal activity (200-300-fold) could be assigned to the presence of monochloramine which could be isolated by vacuum distillation. Aqueous solutions of NCT and ammonium chloride provide a highly effective and well tolerable antiseptic preparation appropriate to a treatment cycle of at least 1 month if stored in the refrigerator.


[Antigenic properties of glycine residue blocking aldehyde groups of cross-linking agent in peptide-protein conjugates].
Glutaraldehyde treatment of proteins and blocking free aldehyde groups by amines results in appearance of the antigen determinants, which include into their structure the residues both of glutaraldehyde and blocking agent (usually, glycine). The glycine-specific antibodies were detected and then selected by the immunosorbent glycine-oxyran-Sepharose. These antibodies have recognized glycine conjugated with proteins by glutaraldehyde and glycine conjugated with glycogen by bis-oxyran, however they have failed to recognized others amino acids in the analogical conjugates. It is assumed that glycine residue is a immunodominant group in the structure of epitope, which is recognized by these antibodies. Authors suppose that the proteins after the glutaraldehyde treatment can be used for obtaining the antibodies with high specificity to amino acids or other amines.


HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer.
HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease.


Applications of Photobiomodulation Therapy to Musculoskeletal Disorders and Osteoarthritis with Particular Relevance to Canada.
Background: Musculoskeletal disorders caused by osteoarthritis (MSDs/OA) are a growing problem in the modern industrialized society in Canada. Overall aging of the general population and a progressive lack of exercise contribute to this alarming increase. Moreover, a range of chronic conditions including cardiovascular and mental diseases show significantly higher comorbidity with MSDs/OA. Conventional medical treatment for MSDs/OA includes nonsteroidal anti-inflammatory drugs and opiate pain killers. These drugs have major drawbacks such as a relative lack of efficacy, potential for addiction, and even death (Vioxx scandal). Photobiomodulation (PBM) was discovered over 50 years ago but has still not attained widespread acceptance by the medical community. This is partly due to uncertainty about the precise molecular mechanisms of action and a bewildering array of different wavelengths and dosimetric parameters employed in reported studies. Objective: The goal of this review was to survey literature reports of PBM, also known as low-level laser therapy used for treatment of MSDs/OA, concentrating on the growth over time, different wavelengths employed, and application to different joints. Methods: We searched the PubMed database for publication of study on PBM to treat the most common joints. Results: We show that the field of PBM to treat MSDs/OA is expanding exponentially over the past 20 years. A trend has emerged over time for more power to achieve better effective treatments, and the understanding of the physiological effect of safe parameters has improved. There is, however, no consensus on the best set of parameters to treat a specific patient indication. Conclusions: Finally, we highlight gaps in our knowledge and the barriers to further clinical trials. We suggest that the growing body of evidence indicating efficacy, and the almost total lack of side effects, should encourage continued clinical research to support clinical applications where better rehabilitation treatments are much needed.


Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.
A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was "personalized" by estimating an individualized set of parameters from each participant's data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups ("fatigue-predominant" patients with CFS only versus "pain-predominant" patients with FM and comorbid chronic fatigue) from controls (all p's<.05), whereas daytime parameters and diurnal/nocturnal slopes did not. The same nocturnal parameters were significantly associated with somatic symptoms among patients (p's<.05). There was a significantly different pattern of association between nocturnal non-ACTH influences and sleep quality among patients versus controls (p<.05). Although speculative, the finding that patient somatic symptoms decreased when more cortisol was produced per unit ACTH, is consistent with cortisol's anti-inflammatory and sleep-modulatory effects. Patients' HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping "behavioral phenotypes" of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.


Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation.
Bone is a highly vascularized tissue and efficient bone regeneration requires neovascularization, especially for critical-sized bone defects. We developed a novel hybrid biomaterial comprising nanocalcium sulfate (nCS) and fibrin hydrogel to deliver mesenchymal stem cells (MSCs) and angiogenic factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor 9 (FGF9), to promote neovascularization and bone formation. MSC and growth factor(s)-loaded scaffolds were implanted subcutaneously into mice to examine their angiogenic and osteogenic potential. Micro CT, alkaline phosphatase activity assay, and histological analysis were used to evaluate bone formation, while immunohistochemistry was employed to assess neovessel formation. The presence of fibrin preserved the nCS scaffold structure and promoted de novo bone formation. In addition, the presence of bone morphogenic protein 2-expressing MSC in nCS and fibrin hydrogels improved bone regeneration significantly. While FGF9 alone had no significant effect, the combination FGF9 and VEGF conjugated in fibrin enhanced neovascularization and bone formation more than 4-fold compared to nCS with MSC. Overall, our results suggested that the combination of nCS (to support bone formation) with a fibrin-based VEGF/FGF9 release system (support vascular formation) is an innovative and effective strategy that significantly enhanced ectopic bone formation in vivo.


Isolation of membrane vesicles from prokaryotes: a technical and biological comparison reveals heterogeneity.
Prokaryotes release membrane vesicles (MVs) with direct roles in disease pathogenesis. MVs are heterogeneous when isolated from bacterial cultures so Density Gradient Centrifugation (DGC) is valuable for separation of MV subgroups from contaminating material. Here we report the technical variability and natural biological heterogeneity seen between DGC preparations of MVs for Mycobacterium smegmatis and Escherichia coli and compare these DGC data with size exclusion chromatography (SEC) columns. Crude preparations of MVs, isolated from cultures by ultrafiltration and ultracentrifugation were separated by DGC with fractions manually collected as guided by visible bands. Yields of protein, RNA and endotoxin, protein banding and particle counts were analysed in these. DGC and SEC methods enabled separation of molecularly distinct MV populations from crude MVs. DGC banding profiles were unique for each of the two species of bacteria tested and further altered by changing culture conditions, for example with iron supplementation. SEC is time efficient, reproducible and cost effective method that may also allow partial LPS removal from Gram-negative bacterial MVs. In summary, both DGC and SEC are suitable for the separation of mixed populations of MVs and we advise trials of both, coupled with complete molecular and single vesicle characterisation prior to downstream experimentation.


[Leopold Schönbauer and the Vienna Society of Physicians].
Schönbauer's merits for the Society of Physicians in Vienna not only concern the renovation of its building after the Second World War but also his active scientific co-operation during four decades. His lectures are primarily devoted to abdominal surgery and neuro-surgery.


Tracheal myxoma: a rare benign tracheal tumor.
Benign tracheal tumors are rare. We describe a 39-year-old man who underwent resection of a tracheal myxoma, a previously unrecognized benign tracheal neoplasm. He presented with a 9-month history of wheezing, cough, and dyspnea on exertion. Treatment with bronchodilators and corticosteroids administered by inhalation and systemically did not diminish his symptoms. Pulmonary function tests showed a pattern of airflow limitation consistent with variable extrathoracic obstruction. Chest radiography and computed tomography revealed a tracheal mass. Tracheal resection of the tumor with reconstruction was curative. The patient is free of disease 7 years after surgery.


Concentrations of Ag, Al, Au, Bi, Cd, Cu, Pb, Sb, and Se in cerebrospinal fluid of patients with cerebral neoplasms.
We measured the concentrations of nine trace elements in cerebrospinal fluid of 11 patients with malignant brain tumors, 11 with benign brain tumors, and 10 control patients, using flameless atomic absorption spectrophotometry. The mean and standard deviation for these concentrations (microgram/L) in the control group were 5.1 +/- 2.9 (silver), 326.6 +/- 171.2 (aluminum), 38.5 +/- 32.2 (gold), 36.6 +/- 23.7 (bismuth), 1.5 +/- 1.3 (cadmium), 39.8 +/- 24.7 (copper), 15.7 +/- 11.5 (lead), 20.9 +/- 3.8 (antimony), and 19.1 +/- 13.3 (selenium). Concentrations of silver and lead were markedly increased in patients with malignant cerebral neoplasms. The malignant-tumor/control patient concentration ratios were 2.31 for silver and 2.11 for lead. We observed no significant differences between the results for the benign tumor patients and the control group.


Red meat, processed meat, and other dietary protein sources and risk of overall and cause-specific mortality in The Netherlands Cohort Study.
Processed meat and red meat have been associated with increased mortality, but studies are inconsistent and few have investigated substitution by other protein sources. The relationship of overall and causes-specific mortality with red meat, processed meat, and other dietary protein sources was investigated in The Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years provided information on dietary and lifestyle habits. Mortality follow-up until 1996 consisted of linkage to statistics Netherlands. Multivariable case-cohort analyses were based on 8823 deaths and 3202 subcohort members with complete data on diet and confounders. Red meat (unprocessed) intake was not associated with overall and cause-specific mortality. Processed meat intake was significantly positively related to overall mortality: HR (95% CI) comparing highest versus lowest quintile, 1.21 (1.02-1.44) with Ptrend = 0.049. Significant associations were observed for cardiovascular [HR Q5 vs. Q1, 1.26 (1.01-1.26)] and respiratory [HR = 1.79 (1.19-2.67)], but not cancer mortality [HR = 1.16 (0.97-1.39)]. Adjustment for nitrite intake attenuated these associations which became nonsignificant: HRs Q5 versus Q1 (95% CI) were: 1.10 (0.77-1.55) for total, 1.09 (0.71-1.67) for cardiovascular, 1.44 (0.68-3.05) for respiratory, and 1.11 (0.78-1.58) for cancer mortality. Nitrite was significantly associated with overall, CVD and respiratory mortality. Poultry intake was significantly inversely related to cancer and overall mortality. While fish intake showed positive associations, nut intake showed inverse associations with all endpoints. Replacing processed meat with a combination of poultry, eggs, fish, pulses, nuts and low-fat dairy was associated with lower risks of overall, cardiovascular and respiratory mortality. Processed meat was related to increased overall, CVD and respiratory mortality, potentially due to nitrite. Substituting processed meat with other protein sources was associated with lower mortality risks.


Identifying specific needs in adult cystic fibrosis patients: a pilot study using a custom questionnaire.
Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams. We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items. Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m2. Mean FEV1% was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school. Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated. The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016.


[Mortality from malignant tumors in the industrial region of the province of Milan, 1980-1987].
For the period 1980-87 mortality data relating to residents of a densely populated area in the province of Milan was collected and elaborated. The area is heavily industrialised and had a particularly high immigration level in the 1960's and 70's. Malignant neoplasms represented the cause of death in 35.59% of male cases and 26.59% of female, with greater incidence in the former of tumours in respiratory organs and in the latter in the digestive tract. High mortality rates were noted for cancer of the lung in males over 35 years and for neoplasms of the digestive tract in those over 75 years but in females high mortality from breast cancer prevailed between 25-74 years and cancer of the stomach and intestine in those over 75 years. S.P.M.R. were elaborated with proportional mortality analysis showing an overall tendency to an increased death rate from malignant tumours that was statically significant in females, particularly at an advanced age. Increasing trends in tumours of the stomach and of the lympho-hematopoietic tissues were evident in females, in urinary organs in males, notably in elderly men, and in intestinal cancer in both sexes. The trend in mortality from breast cancer was however on the decline. As a whole, mortality was stationary in cases of cancer of the lung (although it was on the increase in females over 65 years), in cancer of the prostate (showing a decrease however in older subjects) and in cancer of the uterus and ovaries (but increasing in the latter case in elderly women). By means of S.M.R. elaboration the data was compared with that in Lombardy. In the area being taken into consideration a picture emerged of cancer mortality in general which was virtually the same as that found in Lombardy. However, the result of the comparison differs when considering sex and age groups. In fact in the 35-64 age group an inferior mortality rate to the Lombardian one was noted in the total population and in women, whilst for the age group 65 and over, a higher mortality rate emerged in men and in the total population. In males mortality was lower stomach tumours and higher for lung cancer, especially in more elderly subjects. Cancer of the colon-rectum, uterus and breast did not show statistically significant differences. The comparison with Italian data effected with direct age-standardisation has shown higher mortality from stomach, intestinal and lung cancer in the area being studied.(ABSTRACT TRUNCATED AT 400 WORDS)


[A "fast track" surgical concept realization in treatment of patients with acute pancreatitis].
Ten principles of a surgical concept of "fast track" surgery in the treatment of an acute pancreatitis (AP) were introduced in 57 patients, ageing from 34 to 67 yrs old, with the objective to study if it is affordable to realize this concept. In accordance to Atlanta's criteria (2007), AP of moderate severity was noted in 13 (23%) patients, and a severe one - in 44 (77%). Generally accepted principles of a "fast track" surgery were realized in the treatment program. Introduction of such a program have promoted the improvement of the patients quality of life. So, the duration of stationary treatment have had reduced by 4.7 days, and postoperative lethality - from 16.3 to 10.1%.


Extended Boari-flap technique as a reconstruction method of total ureteric avulsion.
Indication has led ureteroscopy to be a worldwide technique, with the expected appearance of multiple complications. The ureteral avulsion is an uncommon severe urological complication of ureteroscopy (URS). Surgery in patients with a total ureteral loss is a demanding challenge for urologist. It requires usually immediate open or laparoscopic intervention. This case report was to present the treatment modality after ureteral avulsion. We have presented a case of 58-year-old male patient who underwent a successful repair of an upper ureteral injury. We have comprehensively described the effectiveness of an extended Boari-flap procedure for reconstruction after iatrogenic ureteral trauma. Particularly in an unexpected and casual situations, the presented extended Boari flap modification can be a great alternative for reconstructing a total ureteral loss. In conclusion we have recommend useful tips, how to counteract such unwanted events.


Cutaneous reactions to substance P and histamine in atopic dermatitis.
The flare and weal reactions to intradermal injections of histamine and the peptide substance P were measured in a group of patients with atopic dermatitis and compared to reactions in a non-atopic control group. There was no significant difference in the flare areas between the controls and atopics with either reagent. The weal volumes after injection of substance P and histamine were significantly larger in the atopic group. As substance P causes mast cell histamine release, the increased weal volumes produced by substance P in the atopics may be entirely due to the exaggerated atopic weal reaction to histamine.


Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells.
Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [3H]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX. Exposure of primary human myotubes to palmitate impaired insulin-stimulated Akt-Ser473, AS160 and GSK-3β phosphorylation, induced ER stress signalling target PERK and stress kinase JNK 54 kDa isoform. These effects were virtually abolished by concomitant exposure of palmitate-treated myotubes to oleate. However, an exposure to palmitate, oleate or their combination reduced insulin-stimulated glucose uptake. This was associated with increased mitochondrial ROS production in palmitate-treated myotubes co-incubated with oleate, and was alleviated by antioxidants MitoTempo and Tempol. Thus, metabolic and intracellular signalling events diverge in myotubes treated with palmitate and oleate. Exposure of human myotubes to excess fatty acids increases ROS production and induces insulin resistance.


Data mining the NCI60 to predict generalized cytotoxicity.
Elimination of cytotoxic compounds in the early and later stages of drug discovery can help reduce the costs of research and development. Through the application of principal components analysis (PCA), we were able to data mine and prove that approximately 89% of the total log GI 50 variance is due to the nonspecific cytotoxic nature of substances. Furthermore, PCA led to the identification of groups of structurally unrelated substances showing very specific toxicity profiles, such as a set of 45 substances toxic only to the Leukemia_SR cancer cell line. In an effort to predict nonspecific cytotoxicity on the basis of the mean log GI 50, we created a decision tree using MACCS keys that can correctly classify over 83% of the substances as cytotoxic/noncytotoxic in silico, on the basis of the cutoff of mean log GI 50 = -5.0. Finally, we have established a linear model using least-squares in which nine of the 59 available NCI60 cancer cell lines can be used to predict the mean log GI 50. The model has R (2) = 0.99 and a root-mean-square deviation between the observed and calculated mean log GI 50 (RMSE) = 0.09. Our predictive models can be applied to flag generally cytotoxic molecules in virtual and real chemical libraries, thus saving time and effort.


[Specific silencing of PCNA gene expression in leukemic cell lines using siRNA].
Increased expression of PCNA gene was detected in chronic myeloid leukemia (CML) patients in our laboratory. The gene may participate in the disease development. The aim of the study was to develop appropriate conditions for PCNA-siRNA transfection into K562 and MOLM-7 cell lines (which both have the up-regulated PCNA gene) and to silence the increased expression. Key parameters of successful siRNA delivery into the cells are type and quantity of transfection reagent, cells and siRNA concentration or cultivation time before an expression analysis. Transfection reagents ExGene 500 (Fermentas), Metafectene (Biontex), Oligofectamine (Qiagen) and siPORT Amine (Ambion) were tested. Transfection efficiency was monitored by fluorescence microscopy of fluorescein labeled siRNA. Gene silencing was determined at mRNA level by real-time PCR and at protein level by western blots. As the most suitable reagent was chosen Oligofectamine, which achieved 70% decrease of PCNA mRNA level. Further, 50 nM siRNA concentration, 1 x 10(6) cells/ml and amount of Oligofectamine 4 microl per 1 ml of transfected cells were selected. The best cultivation time after siRNA delivery was 48 h. Based on the results of this study, transfection method for siRNA delivery into the K562 and MOLM-7 cell lines was proposed. The procedure can be transferred also on further selected genes potentially involved in CML and afterwards it will be possible to monitor the impact of siRNA-inhibition on expression profile. In the future siRNAs against some over-expressed genes would be used for gene therapy of CML.


Top-down suppression deficit underlies working memory impairment in normal aging.
In this study, we assess the impact of normal aging on top-down modulation, a cognitive control mechanism that supports both attention and memory by the suppression and enhancement of sensory processing in accordance with task goals. Using fMRI (functional magnetic resonance imaging), we show that healthy older adults demonstrated a prominent deficit in the suppression of cortical activity associated with task-irrelevant representations, whereas enhancement of task-relevant activity was preserved. Moreover, this suppression-specific attention deficit correlated with impaired working memory performance.


Reference cluster normalization improves detection of frontotemporal lobar degeneration by means of FDG-PET.
Positron emission tomography with [18F] fluorodeoxyglucose (FDG-PET) plays a well-established role in assisting early detection of frontotemporal lobar degeneration (FTLD). Here, we examined the impact of intensity normalization to different reference areas on accuracy of FDG-PET to discriminate between patients with mild FTLD and healthy elderly subjects. FDG-PET was conducted at two centers using different acquisition protocols: 41 FTLD patients and 42 controls were studied at center 1, 11 FTLD patients and 13 controls were studied at center 2. All PET images were intensity normalized to the cerebellum, primary sensorimotor cortex (SMC), cerebral global mean (CGM), and a reference cluster with most preserved FDG uptake in the aforementioned patients group of center 1. Metabolic deficits in the patient group at center 1 appeared 1.5, 3.6, and 4.6 times greater in spatial extent, when tracer uptake was normalized to the reference cluster rather than to the cerebellum, SMC, and CGM, respectively. Logistic regression analyses based on normalized values from FTLD-typical regions showed that at center 1, cerebellar, SMC, CGM, and cluster normalizations differentiated patients from controls with accuracies of 86%, 76%, 75% and 90%, respectively. A similar order of effects was found at center 2. Cluster normalization leads to a significant increase of statistical power in detecting early FTLD-associated metabolic deficits. The established FTLD-specific cluster can be used to improve detection of FTLD on a single case basis at independent centers - a decisive step towards early diagnosis and prediction of FTLD syndromes enabling specific therapies in the future.


Activated peripheral blood mononuclear cells detected in lupus patients using cDNA coding for proliferating cell nuclear antigen.
Abstract The expression of proliferating cell nuclear antigen (PCNA) mRNA in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) was measured by dot blot hybridization using a PCNA cDNA, and correlated with the percentage of PCNA-positive cells detected immunohistochemically using a monoclonal anti-PCNA antibody. PCNA-positive PBMCs were detected in 72.2% of SLE patients (n = 36), which is significantly more than among healthy controls. In addition, among those in whom PCNA expression was detected, the percentage of PBMCs expressing PCNA was significantly higher in SLE patients (mean 2.5% vs. 0.15%). The level of PCNA mRNA was increased in PBMCs from 83.3% of SLE patients, and was significantly correlated with the percentage of PCNA-positive cells (r = 0.54, P < 0.01) and with the disease activity score (r = 0.56, P < 0.01). A longitudinal study of two SLE patients confirmed that PCNA mRNA expression and the percentages of PCNA-positive cells varied in parallel with disease activity. Thus, an analysis of activated PBMCs from SLE patients using PCNA cDNA may be a useful method by which to estimate SLE disease activity.


[Retroperitoneal sarcomas. Report of five new cases and review of the current situation].
Soft-tissue sarcomas represent a heterogeneous group of rare tumors arising from the mesenchymal cells of the connective tissue. Approximately 15% of these tumors arise in the retroperitoneum. These neoplasms are locally aggressive and the only curative treatment is surgical resection "en-bloc". The main cause of mortality is locoregional recurrence. Five-year survival is 3-58%, depending on the histologic subtype and grade. Over a 5-year period (2001 to 2006), we performed surgery in five patients with retroperitoneal sarcomas. The mean age was 59 years (range, 46-76) with a male-to-female ratio of 3:2. The most frequent signs were abdominal pain and the appearance of a mass. In 2 patients, an incidental diagnosis was made during the surgical intervention. Surgical resection was performed in 5 patients but was incomplete in two patients. We removed 2 liposarcomas, 1 leiomyosarcoma, 1 chondrosarcoma and 1 fusocellular sarcoma arising in the kidney. Locoregional recurrence occurred in four patients, requiring between 1 and 2 new relaparotomies (using the retroperitoneal approach in 2 patients). There was one death. Retroperitoneal sarcomas are a heterogeneous group of tumors, in which the only common factor is the anatomical location. New randomized, prospective, multicenter trials are required to apply different therapeutic options according to the subtype of retroperitoneal sarcoma.


Trauma patients warrant upper and lower extremity venous duplex ultrasound surveillance.
Due to the high incidence of thromboembolic events (deep venous thrombosis [DVT] and pulmonary embolus [PE]) after injury, many trauma centers perform lower extremity surveillance duplex ultrasounds. We hypothesize that trauma patients are at a higher risk of upper extremity DVTs (UEDVTs) than lower extremity DVTs (LEDVTs), and therefore, all extremities should be evaluated. A retrospective chart and trauma registry review of Intensive Care Unit trauma patients with upper and LEDVTs detected on surveillance duplex ultrasound from January 2010 to December 2014 was carried out. Variables reviewed were age, gender, injury severity score, injury mechanism, clot location, day of clot detection, presence of central venous pressure catheter, presence of inferior vena cava filter, mechanical ventilation, and fracture. A total of 136 patients had a DVT in a 5-year period: upper - 71 (52.2%), lower - 61 (44.9%), both upper and lower - 4 (2.9%). Overall, 75 (55.2%) patients had a UEDVT. Upper DVT vein: Brachial (62), axillary (26), subclavian (11), and internal jugular (10). Lower DVT vein: femoral (58), popliteal (14), below knee (4), and iliac (2). 10.3% had a PE: UEDVT - 5 (6.7%) and LEDVT - 9 (14.8%) P = 0.159. The majority of the DVTs in the study were in the upper extremities. For trauma centers that aggressively screen the lower extremities with venous duplex ultrasound, surveillance to include the upper extremities is warranted.


rpsftm: An R Package for Rank Preserving Structural Failure Time Models.
Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard intention-to-treat analysis) can lead to biased estimates of treatment efficacy. The rank preserving structural failure time model (RPSFTM) is a method used to adjust for treatment switching in trials with survival outcomes. The RPSFTM is due to Robins and Tsiatis (1991) and has been developed by White et al. (1997, 1999). The method is randomisation based and uses only the randomised treatment group, observed event times, and treatment history in order to estimate a causal treatment effect. The treatment effect, ψ, is estimated by balancing counter-factual event times (that would be observed if no treatment were received) between treatment groups. G-estimation is used to find the value of ψ such that a test statistic Z(ψ) = 0. This is usually the test statistic used in the intention-to-treat analysis, for example, the log rank test statistic. We present an R package that implements the method of rpsftm.


Molecular characterization of 8-methoxyfluoroquinolone resistance in a clinical isolate of methicillin-resistant Staphylococcus aureus.
Activity of gatifloxacin against clinical isolates of fluoroquinolone-resistant Staphylococcus aureus is more potent than that of other fluoroquinolones such as norfloxacin and levofloxacin. To date, few reports have described high-level resistance to gatifloxacin in clinical isolates of S. aureus, although in vitro studies have shown that mutations in both DNA gyrase and topoisomerase IV were required for gatifloxacin resistance in S. aureus. Minimum inhibitory concentrations were determined for fluoroquinolones and other antimicrobials in a methicillin-resistant S. aureus isolate that was cultured from blood of a patient with septicemia. Fluoroquinolone resistance was characterized by DNA sequencing and microbiologic assay. The isolate showed high-level resistance to fluoroquinolones including an 8-methoxyfluoroquinolone, gatifloxacin (minimum inhibitory concentration 64 microg/ml). Amino acid mutations of Ser80Tyr and Glu84Lys in GrlA and Ser84Leu and Ser85Pro in GyrA were possibly related to this resistance in methicillin-resistant S. aureus HU2000-062, although efflux may play a minor role in resistance as well. GyrA and GrlA mutations mainly conferred to 8-methoxyfluoroquinolone resistance in this isolate.


Isosymmetrical phase transition in alpha-YbV4O8.
The structure of YbV4O8 is related to the CaFe2O4 structure type. VO6 octahedra form a three-dimensional framework with tunnels in which the Yb3+ ions are incorporated. Two different polymorphs alpha and beta are known and differ mainly in the arrangement of the Yb ions within the framework. We studied the structure and magnetic properties of alpha-YbV4O8 as a function of temperature. At approximately 70 K alpha-YbV4O8 undergoes a first-order isosymmetrical phase transition (P2(1)/n --> P2(1)/n). While in the high-temperature alpha phase the three V3+ and one V4+ are disordered over the four symmetrically independent octahedral sites, in the low-temperature alpha' phase complete charge ordering is observed. The transition is accompanied by a paramagnetic-paramagnetic anomaly in the magnetic susceptibility data which can be interpreted on the basis of spin-gap formation. The transition mechanism in the alpha polymorph is very similar to that observed earlier in the beta polymorph at 185 K.


Immunohistochemical studies on cholecystokinin (CCK)-immunoreactive neurons in the rat using sequence specific antisera and with special reference to the caudate nucleus and primary sensory neurons.
In the present immunohistochemical study the occurrence and distribution of CCK-immunoreactive neurons were analyzed in the brain, spinal cord and sensory ganglia using sequence specific antisera. Thus, antibodies directed towards the C-terminal portion of CCK-33, to the N-terminal portion of CCK-8 and to the mid portion of CCK-33 as well as monoclonal antibodies were used. For comparison antisera raised against calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and 5-hydroxytryptamine (5-HT) were used. Untreated, colchicine treated, 6-hydroxydopamine (6-OH-DA) treated and ibotenic acid treated rats were analyzed. The results indicate that most CCK systems in the rat central nervous system contain genuine CCK. These include, for example, the hippocampal formation, the hypothalamus, several subcortical forebrain areas, the ventral mesencephalon, nucleus tractus solitarii, some neurons in the ventral medulla oblongata as well as local and possibly descending neurons in the spinal cord. An exception was primary sensory neurons in which CCK-like immunoreactivity (LI) could only be demonstrated with C-terminally directed antisera and probably represents cross-reactivity with CGRP or a similar peptide. The central branches of such primary afferents were found both in the dorsal vagal complex, in the spinal trigeminal nucleus and in the dorsal horn of the spinal cord. Special attention was focused on CCK-LI in mesencephalic dopamine neurons and in their projection areas including nucleus accumbens, tuberculum olfactorium and particularly the caudate nucleus. In the latter structure CCK-LI exhibited a heterogenous pattern probably representing fibres of different types and origin. Thus, CCK-LI coexists with dopamine in two anatomically and morphologically distinguishable systems, one located in the periventricular area, increasing in size in the caudal direction to occupy most of the cauda, and a second system consisting of very fine dots in the medial half of the caudate nucleus. These two fibre types disappeared after 6-OH-DA treatment. A third system consisted of strongly fluorescent patches distributed at all levels of the caudate nucleus, mainly in its medial half. A diffuse, weakly fluorescent network of CCK-positive fibres was also found over the entire caudate nucleus. The latter two systems did not disappear after 6-OH-DA. Finally, local CCK-positive cell bodies were seen in small numbers, mainly in the ventral aspects of the caudate nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)


Variant CJD. 18 years of research and surveillance.
It is now 18 years since the first identification of a case of vCJD in the UK. Since that time, there has been much speculation over how vCJD might impact human health. To date there have been 177 case reports in the UK and a further 51 cases worldwide in 11 different countries. Since establishing that BSE and vCJD are of the same strain of agent, we have also shown that there is broad similarity between UK and non-UK vCJD cases on first passage to mice. Transgenic mouse studies have indicated that all codon 129 genotypes are susceptible to vCJD and that genotype may influence whether disease appears in a clinical or asymptomatic form, supported by the appearance of the first case of potential asymptomatic vCJD infection in a PRNP 129MV patient. Following evidence of blood transfusion as a route of transmission, we have ascertained that all blood components and leucoreduced blood in a sheep model of vCJD have the ability to transmit disease. Importantly, we recently established that a PRNP 129MV patient blood recipient with an asymptomatic infection and limited PrP(Sc) deposition in the spleen could readily transmit disease into mice, demonstrating the potential for peripheral infection in the absence of clinical disease. This, along with the recent appendix survey which identified 16 positive appendices in a study of 32,441 cases, underlines the importance of continued CJD surveillance and maintaining control measures already in place to protect human health.


Why does the APA recommend the use of serif fonts?
The publication norms of the American Psychological Association recommend the use of a serif font in the manuscripts (Times New Roman). However, there seems to be no well-substantiated reason why serif fonts would produce any advantage during letter/word processing. This study presents an experiment in which sentences were presented either with a serif or sans serif font from the same family while participants' eye movements were monitored. Results did not reveal any differences of type of font in eye movement measures -except for a minimal effect in the number of progressive saccades. There is no reason why the APA publication norms recommend the use of serif fonts other than uniformity in the elaboration/presentation of the manuscripts.


Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags.
The Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genus Bungarus have been well characterized, a detailed compositional analysis of B. flaviceps is currently lacking. Here, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of a B. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of beta-bungarotoxin), phospholipase A2 (including chain A of beta-bungarotoxin), natriuretic peptide (NP), CRISPs, and C-type lectin. The 3FTxs were found to be the major component of the venom (39%). We found eight groups of unique 3FTxs and most of them were different from the well-characterized 3FTxs. We found three groups of Kunitz-type serine protease inhibitors (SPIs); one group was comparable to the classical SPIs and the other two groups to chain B of beta-bungarotoxins (with or without the extra cysteine) based on sequence identity. The latter group may be functional equivalents of dendrotoxins in Bungarus venoms. The natriuretic peptide (NP) found is the first NP for any Asian elapid, and distantly related to Australian elapid NPs. Our study identifies several unique toxins in B. flaviceps venom, which may help in understanding the evolution of venom toxins and the pathophysiological symptoms induced after envenomation.


Host-Guest Recognition-Assisted Electrochemical Release: Its Reusable Sensing Application Based on DNA Cross Configuration-Fueled Target Cycling and Strand Displacement Reaction Amplification.
In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such a design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output, which could be trapped by cucurbit[8]uril methyl viologen (CB-8-MV2+) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection. Moreover, the nucleic acids products obtained from the process of cycling amplification could be utilized sufficiently, avoiding the waste and saving the experiment cost. Impressively, by resetting a settled voltage, the proposed biosensor could release S1-Trp and S2-Trp from the electrode surface, attributing that the guest ion methyl viologen (MV2+) was reduced to MV+· under this settled voltage and formed a more-stable CB-8-MV+·-MV+· complex. Once O2 was introduced in this system, MV+· could be oxidized to MV2+, generating the complex of CB-8-MV2+ for capturing S1-Trp and S2-Trp again in only 5 min. As a result, the simple and fast regeneration of biosensor for target detection was realized on the base of electrochemical redox-driven assembly and release, overcoming the challenges of time-consuming, burdensome operations and expensive experimental cost in traditional reusable biosensors and updating the construction method for a reusable bisensor. Furthermore, the biosensor could be reused for more than 10 times with a regeneration rate of 93.20%-102.24%. After all, the conception of this work provides a novel thought for the construction of effective reusable biosensor to detect miRNA and other biomarkers and has great potential application in the area requiring the release of nucleic acids or proteins.


External validation of an opioid misuse machine learning classifier in hospitalized adult patients.
Opioid misuse screening in hospitals is resource-intensive and rarely done. Many hospitalized patients are never offered opioid treatment. An automated approach leveraging routinely captured electronic health record (EHR) data may be easier for hospitals to institute. We previously derived and internally validated an opioid classifier in a separate hospital setting. The aim is to externally validate our previously published and open-source machine-learning classifier at a different hospital for identifying cases of opioid misuse. An observational cohort of 56,227 adult hospitalizations was examined between October 2017 and December 2019 during a hospital-wide substance use screening program with manual screening. Manually completed Drug Abuse Screening Test served as the reference standard to validate a convolutional neural network (CNN) classifier with coded word embedding features from the clinical notes of the EHR. The opioid classifier utilized all notes in the EHR and sensitivity analysis was also performed on the first 24 h of notes. Calibration was performed to account for the lower prevalence than in the original cohort. Manual screening for substance misuse was completed in 67.8% (n = 56,227) with 1.1% (n = 628) identified with opioid misuse. The data for external validation included 2,482,900 notes with 67,969 unique clinical concept features. The opioid classifier had an AUC of 0.99 (95% CI 0.99-0.99) across the encounter and 0.98 (95% CI 0.98-0.99) using only the first 24 h of notes. In the calibrated classifier, the sensitivity and positive predictive value were 0.81 (95% CI 0.77-0.84) and 0.72 (95% CI 0.68-0.75). For the first 24 h, they were 0.75 (95% CI 0.71-0.78) and 0.61 (95% CI 0.57-0.64). Our opioid misuse classifier had good discrimination during external validation. Our model may provide a comprehensive and automated approach to opioid misuse identification that augments current workflows and overcomes manual screening barriers.


Controlling Your "App"etite: How Diet and Nutrition-Related Mobile Apps Lead to Behavior Change.
In recent years, obesity has become a serious public health crisis in the United States. Although the problem of obesity is being addressed through a variety of strategies, the use of mobile apps is a relatively new development that could prove useful in helping people to develop healthy dietary habits. Though such apps might lead to health behavior change, especially when relevant behavior change theory constructs are integrated into them, the mechanisms by which these apps facilitate behavior change are largely unknown. The purpose of this study was to identify which behavior change mechanisms are associated with the use of diet- and nutrition-related health apps and whether the use of diet- and nutrition-related apps is associated with health behavior change. A cross-sectional survey was administered to a total of 217 participants. Participants responded to questions on demographics, use of diet and nutrition apps in the past 6 months, engagement and likability of apps, and changes in the participant's dietary behaviors. Regression analysis was used to identify factors associated with reported changes in theory and separately for reported changes in actual behavior, after controlling for potential confounding variables. The majority of study participants agreed or strongly agreed with statements regarding app use increasing their motivation to eat a healthy diet, improving their self-efficacy, and increasing their desire to set and achieve health diet goals. Additionally, majority of participants strongly agreed that using diet/nutrition apps led to changes in their behavior, namely increases in actual goal setting to eat a healthy diet (58.5%, 127/217), increases in their frequency of eating healthy foods (57.6%, 125/217), and increases in their consistency of eating healthy foods (54.4%, 118/217). Participants also responded favorably to questions related to engagement and likability of diet/nutrition apps. A number of predictors were also positively associated with diet-related behavior change. Theory (P<.001), app engagement (P<.001), app use (P<.003), and education (P<.010) were all positively associated with behavior change. Study findings indicate that the use of diet/nutrition apps is associated with diet-related behavior change. Hence, diet- and nutrition-related apps that focus on improving motivation, desire, self-efficacy, attitudes, knowledge, and goal setting may be particularly useful. As the number of diet- and nutrition-related apps continues to grow, developers should consider integrating appropriate theoretical constructs for health behavior change into the newly developed mobile apps.


Hope during the first months after acute spinal cord injury.
According to the general literature on hope, individuals who are hopeful live more positive lives than those who experience hopelessness. Hope has been defined as a positive orientation toward future improvements, and is associated with health and well-being. This paper reports a study that explored patients' experiences of hope following spinal cord injury. Data were collected by personal interviews (n = 10) at a rehabilitation institution in Norway. A phenomenological-hermeneutic approach was used to extract the meaningful content of patients' experiences. The analysis was performed as a spiral process that included a reading to gain a sense of the whole, followed by identification of meaningful parts and a comprehensive and understandable interpretation of the whole. Two themes emerged: 'images of the past and future', and 'balancing between inner emotional dichotomies' that were, mainly, related to experiences of courage/uncertainty and patience/restlessness. All participants experienced hope. The substance of hope--being able to walk again and hoping for recovery--was a universal experience among participants and was comprehended in terms of positive expectations. The process of hope involved continuous 'ups and downs'. Patients were in need of skilled nursing care to enable and foster hope during the first months following acute spinal cord injury. In conclusion, patients hoped for recovery and every improvement stimulated hope. The process of hope was future-oriented, characterized by dichotomies. Nurses need the skills to foster hope and enable recently injured patients to look beyond the immediate situation and direct their energies appropriately.


[Problems posed by the detection of familial medullary cancer of the thyroid in children].
The authors give the approach managing for medullary thyroid carcinoma in families afflicted by the multiple endocrine tumor syndromes, as defined by "G. E. T. C." (Groupe d'Etude des Tumeurs à Calcitonine), French Group based in Paris, 1983. Diagnosis of MEN II a usually follows investigations in a family of an adult patient found, at thyroid surgery, to have a MTC. Age related probability of development of hereditary MCT is stated. Investigations of the family must be most careful if the index patient is found to have medullary carcinoma on the both sides of the thyroid gland, and/or pheochromocytoma. Sequential monitoring (by means of blood calcitonin measurements following IV infusion of pentagastrin) of family members at risk between 5-35, allows diagnosis of C-cell hyperplasia and treatment of tumor in his earliest stages--MEN II b is usually recognizable in infancy or early childhood by clinical markers (mucosal neuromata, Marfanlike habitus and abnormalities of myenteric plexus). Report of patients in whom MTC was manifest as early as 18 months of age and metastasized at 2 years, require subjects at risk should be screened by CT immunoassay as soon as feasible and repeated annually until 35 years, and every 5 years after 35. The diagnosis of subjects at risk within a family is made easy by recognition of aforesaid clinical features and some more precocious abnormalities = disturbed intradermal histamine reaction and thickened corneal nerve fibers.


Establishing a Pharmacy-Based Patient Registry System: A Pilot Study for Evaluating Pharmacist Intervention for Patients with Long-Term Medication Use.
Background: In Japan, an increasing number of patients are prescribed a large amount of long-term medications by large hospitals that are then dispensed by a community pharmacy. This practice often leads to considerable wastage of medicine. As part of their professional role, community pharmacists are expected to contribute more to the appropriate use of medication by patients. Using a prospective cohort, we aimed to evaluate pharmacists' role in the community. Methods: We created a patient registry system for community pharmacies to monitor long-term medication use by patients with chronic conditions. Patient drug adherence and potential problems were monitored through regular home visits or telephone calls by the pharmacist at least once a month between patient hospital visits. Patient data were collected and stored in an internet-based system. Results: Over a one-year follow-up, 28 out of 37 registered patients from 14 community pharmacies were continuously monitored. In total, we extracted 19 problems relating to medication use, 17 to physical complaints, eight to patient concerns, and two others. Conclusion: The registry system was useful for identifying medication-related problems as well as patient concerns and changes in their condition. Pharmacists might play a key role in improving patient care in the community.


Reporter gene transfer induces apoptosis in primary cortical neurons.
Modern cell biologists typically use reporter genes either alone or co-expressed with a protein of interest to facilitate the localization or quantification of protein expression. Our work demonstrates that reporter genes should be used cautiously, as several common reporter gene products are toxic to primary cortical neuronal cultures. We used the herpes simplex virus-based viral amplicon vector to transduce cortical neurons with three different reporter genes and assessed whether any reporter gene products were toxic over time, by monitoring neurite disintegration and apoptosis. Toxicity varied as a function of the reporter gene, the gene product localization, and the level of reporter gene expression. Transduction of enhanced green fluorescent protein or nuclear-localized beta-galactosidase was more toxic than non-nuclear localized beta-galactosidase. This work underscores the need for careful design of gene expression constructs. Moreover, in studies where cell injury or toxicity is being evaluated, their use should be carefully considered.


PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis.
Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) as a PARL substrate. In apoptotic cells, Smac is released into the cytosol and promotes caspase activity by inhibiting inhibitors of apoptosis (IAPs). Intramembrane cleavage of Smac by PARL generates an amino-terminal IAP-binding motif, which is required for its apoptotic activity. Loss of PARL impairs proteolytic maturation of Smac, which fails to bind XIAP. Smac peptidomimetics, downregulation of XIAP or cytosolic expression of cleaved Smac restores apoptosis in PARL-deficient cells. Our results reveal a pro-apoptotic function of PARL and identify PARL-mediated Smac processing and cytochrome c release facilitated by OPA1-dependent cristae remodelling as two independent pro-apoptotic pathways in mitochondria.