A Novel Acquired t(2;4)(q36.1;q24) with a Concurrent Submicroscopic del(4)(q23q24) in An Adult with Polycythemia Vera.
Background: Polycythemia vera (PV) is a clonal myeloid stem cell disease characterized by a growth-factor independent erythroid proliferation with an inherent tendency to transform into overt acute myeloid malignancy. Approximately 95% of the PV patients harbor the JAK2V617F mutation while less than 35% of the patients harbor cytogenetic abnormalities at the time of diagnosis. Methods and Results: Here we present a JAK2V617F positive PV patient where G-banding revealed an apparently balanced t(2;4)(q35;q21), which was confirmed by 24-color karyotyping. Oligonucleotide array-based Comparative Genomic Hybridization (aCGH) analysis revealed an interstitial 5.4 Mb large deletion at 4q23q24. Locus-specific fluorescent in situ hybridization (FISH) analyses confirmed the mono-allelic 4q deletion and that it was located on der(4)t(2;4). Additional locus-specific bacterial artificial chromosome (BAC) probes and mBanding refined the breakpoint on chromosome 2. With these methods the karyotype was revised to 46,XX,t(2;4)(q36.1;q24)[18]/46,XX[7]. Conclusions: This is the first report on a PV patient associated with an acquired novel t(2;4)(q36.1;q24) and a concurrent submicroscopic deletion del(4)(q23q24). The study also underscores the benefit of combined usage of FISH and oligo-based aCGH analysis in characterizing chromosomal abnormalities. The present findings provide additional clues to unravel important molecular pathways in PV to obtain the full spectrum of acquired chromosomal and genomic aberrations, which eventually may improve treatment options.


Impact of Seismic Activity on Access to Health Care in Hispanic/Latino Cancer Patients from Puerto Rico.
On 7 January 2020, the southern region of Puerto Rico was struck by a 6.4 magnitude earthquake, followed by continual seismic activity. Our team performed secondary analyses to explore the relationship between exposure to seismic activity, protection (support) received, and barriers to health care access for cancer patients. Methods: The research team collected data from the database of a longitudinal case-control cohort parent study concerning the impact of Hurricane Maria in Puerto Rican cancer patients. The participants from the parent study were recruited in community clinics. The extracted data was collected from 51 cancer patients who completed the parent study's interviews from January−July 2020 (seismic activity period). Barriers to health care were assessed using the Barrier to Care Questionaries (BCQ), which is composed of five subscales: skills, marginalization, knowledge and beliefs expectations, and pragmatics. Exposure to seismic activity and protection was assessed using their respective subscales from the Scale of Psychosocial Impact of Disasters. Results: The results showed a significant relationship between exposure to seismic activity and barriers to health care (p < 0.001) and its five subscales (p < 0.01). These results shed light on potential access to care barriers that could hinder cancer patient treatment in the event of a natural disaster.


Organic photoconductive layers sensitized with triarylcarbonium salts.
The electrophotographic layer consisting of poly-3,6-dibromo-N-vinylcarbazole was sensitized with twenty-seven kinds of triarylcarbonium salts. The carbonium salt compounds used have the formula: [equation] The novel sensitizers differ in two points from the well-known triphenylmethane dyestuffs sensitizers for the organic electrophotoconductors. First, the triphenylmethane dyestuffs have at least two radicals such as amino or dimethylamino radical. The novel sensitizers have not such a radical. Second, the novel sensitizers have an extreme ability to increase the photosensitivity of organic photoconductors. When the photoconductive polymer sensitized with carbonium salts is applied to semitransparent paper, cellophane papers or plastic sheet, a transparent electrophotographic material can be obtained. These materials are superior to sensitized zinc oxide paper in photosensitivity. Such a transparent material can be used as a master for diazo copy, for overhead projection copy, or for slides.


[Occurrence of organizing pneumonia after radiation therapy for postoperative breast cancer].
Three cases of organizing pneumonia (OP) that occurred after planned radiation therapy for postoperative breast cancer are reported. All patients received tangential radiation therapy and adjuvant tamoxifen (TAM) for postoperative breast cancer. Two patients developed fever and cough; one was asymptomatic. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field. Bronchoalveolar lavage showed an elevated total cell count with a high percentage of lymphocytes, as well as elevated eosinophil levels in two cases. Transbronchial lung biopsy revealed a histologic pattern consistent with organizing pneumonia. For the two symptomatic cases, treatment with corticosteroids reduced clinical symptoms promptly and improved imaging findings. The single asymptomatic case improved without treatment. The number of such reported cases has increased in recent years, but the etiology is unclear. In the three cases presented, TAM combined with radiation therapy may have been the cause of the OP.


T lymphocyte antigen 4-modified dendritic cell therapy for asthmatic mice guided by the CCR7 chemokine receptor.
The CD80/CD86-CD28 axis is a critical pathway for immuno-corrective therapy, and the cytotoxic T lymphocyte antigen 4 (CTLA4) is a promising immunosuppressor targeting the CD80/CD86-CD28 axis; however, its use for asthma therapy needs further optimization. A human CTLA4 fused with the IgCγ Fc (CTLA4Ig) and mouse CC chemokine receptor type7 (CCR7) coding sequences were inserted into a recombinant adenovirus (rAdV) vector to generate rAdV-CTLA4Ig and rAdV-CCR7. The naive dendritic cells (DCs) were infected with these rAdVs to ensure CCR7 and CTLA4Ig expression. The therapeutic effects of modified DCs were evaluated. rAdV-CTLA4Ig and rAdV-CCR7 infected DCs improved all asthma symptoms. Inflammatory cell infiltration and cytokine analysis showed that rAdV-CTLA4Ig and rAdV-CCR7-modified DC therapy reduced the number of eosinophils and lymphocyte and neutrophil infiltration in the lung. Interestingly, assessment of the humoral immunity showed that the IL-4 and IFNγ levels of the rAdV-CTLA4Ig and rAdV-CCR7-modified DC-treated mice decreased significantly and did not reverse the Th1/Th2 balance. DCs expressing CCR7 displayed guidance ability for DC migration, primarily for DCs in the inflammatory lung. Additionally, the rAdVs caused an inflammatory response by inducing DC differentiation, inflammatory cell infiltration and changes in cytokines; however, mice transplanted with rAdV-green fluorescent protein (GFP)-infected DCs displayed no asthma manifestations. In conclusion, CTLA4Ig-modified DCs exhibited a therapeutic effect on asthma, and CCR7 may guide DC homing. The combination of these two molecules may be a model for precision-guided immunotherapy.


[Rupture of the quadriceps tendon (author's transl)].
Whereas a spontaneous rupture of the quadriceps tendon was seldom observed in earlier times, this injury seems to be occurring more frequently in recent years, a fact which may be explained by the rising average age of the population. Metabolic disturbances, rheumatic diseases, repeated traumata and aging processes can produce a certain disposition to rupture by degenerative changes in tendon tissue. Only very rarely does a trauma directly affecting the tendon come into consideration as the actual cause of the rupture. Early operative treatment of the rupture by suture of the extensor apparatus is unavoidable for restoration of the extensor function. Subsequently temporary immobilization and physiotherapy as soon as possible generally lead to a good result without any essential impairment of function being expected.


Cardiac and renal dysfunction in chronic heart failure: relation to neurohumoral activation and prognosis.
In chronic heart failure (CHF), cardiac dysfunction is considered the major determinant of neurohumoral activation but the role of renal impairment has not been defined. We investigated the relationship between both cardiac and renal dysfunction and neurohumoral activation, and their possible influence on prognosis. Hemodynamics, renal function, plasma neurohormones, and long-term follow-up were evaluated in 148 CHF patients, grouped according to systolic volume index (SVI) and serum creatinine (CRE) values: SVI > 28 mL/m2 and CRE < 1.5 mg/dL (group I, n = 55), SVI < 28 mL/m2 and CRE < 1.5 mg/dL (group II, n = 37), SVI > 28 mL/m2 and CRE > 1.5 mg/dL (group III, n = 25), SVI < 28 mL/m2 and CRE > 1.5 mg/dL (group IV, n = 31). Neurohormones progressively increased from Group I through IV and correlated with both cardiac and renal function. The hemodynamic pattern was similar in patients with normal or abnormal renal function, whereas neurohormones were only moderately increased in the former group and markedly increased in the latter group. Long-term survival progressively decreased from Group I through IV and was significantly poorer in patients with renal dysfunction. Our study confirms that, in CHF, neurohumoral activation is strictly related to long-term survival and that many factors contribute to its development and progression; among these, cardiac and renal dysfunction seem to play a major role.


Comparative efficacy of BioUD to other commercially available arthropod repellents against the ticks Amblyomma americanum and Dermacentor variabilis on cotton cloth.
BioUD is an arthropod repellent that contains the active ingredient 2-undecanone originally derived from wild tomato plants. Repellency of BioUD was compared with five commercially available arthropod repellents against the ticks Amblyomma americanum (L.) and Dermacentor variabilis Say in two-choice bioassays on treated versus untreated cotton cheesecloth. Overall mean percentage repellency against both species was greatest for and did not differ significantly between BioUD (7.75% 2-undecanone) and products containing 98.1% DEET, 19.6% IR3535, and 30% oil of lemon eucalyptus. Products containing 5% and 15% Picaridin and 0.5% permethrin were also repellent compared with untreated controls but to a lesser degree than BioUD. The four most active repellents at the same concentrations used before were directly compared in head-to-head bioassays on cotton cheesecloth. BioUD provided significantly greater overall mean percentage repellency than IR3535 for A. americanum and D. variabilis. BioUD was significantly more repellent than oil of lemon eucalyptus for A. americanum but did not differ significantly in repellency against D. variabilis. No statistically significant difference in overall mean percentage repellency was found between BioUD and DEET for A. americanum or D. variabilis. In a 7-week time course bioassay, BioUD applied to cotton cheesecloth and held at room temperature provided 5 weeks of > 90% repellency against A. americanum.


Efficacy and safety of bromelain: A systematic review and meta-analysis.
Background: Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. Aim: This systematic review and meta-analysis aimed to assess clinical evidence concerning the efficacy and safety of bromelain. Methods: A systematic search was conducted from conception to August 2022 using CINAHL Complete, MEDLINE, ScienceDirect, Scopus, and Thai Journal Online (TJO). The risk of bias was assessed using Risk of Bias 2 or ROBIN-I. A random-effect model with inverse variance weighting and DerSimonian and Laird method was used for meta-analysis. The heterogeneity was evaluated by I2 statistics. Results: We included 54 articles for qualitative summary and 39 articles for meta-analysis. The systematic review found that bromelain presented in serum with retained proteolytic activity after oral absorption. Bromelain may be effective against sinusitis but was not effective for cardiovascular diseases. Pain reduction from oral bromelain was slightly but significantly better than controls (mean difference in pain score = -0.27; 95% CI: -0.45, -0.08; n = 9; I2 = 29%). Adverse events included flatulence, nausea, and headache. Topical bromelain significantly reduced the time to complete debridement (mean difference in time = -6.89 days; 95% CI: -7.94, -5.83; n = 4; I2 = 2%). Adverse events may be irrelevant and include burning sensation, pain, fever, and sepsis. Conclusions: Moderate-quality studies demonstrated the potential of oral bromelain in pain control and topical bromelain in wound care. Major health risks were not reported during the treatment with bromelain.


Terrestrial carbon disturbance from mountaintop mining increases lifecycle emissions for clean coal.
The Southern Appalachian forest region of the U.S.--a region responsible for 23% of U.S. coal production--has 24 billion metric tons of high quality coal remaining of which mountaintop coal mining (MCM) will be the primary extraction method. Here we consider greenhouse gas emissions associated with MCM terrestrial disturbance in the life-cycle of coal energy production. We estimate disturbed forest carbon, including terrestrial soil and nonsoil carbon using published U.S. Environmental Protection Agency data of the forest floor removed and U.S. Department of Agriculture--Forest Service inventory data. We estimate the amount of previously buried geogenic organic carbon brought to the soil surface during MCM using published measurements of total organic carbon and carbon isotope data for reclaimed soils, soil organic matter and coal fragments. Contrary to conventional wisdom, the life-cycle emissions of coal production for MCM methods were found to be quite significant when considering the potential terrestrial source. Including terrestrial disturbance in coal life-cycle assessment indicates that indirect emissions are at least 7 and 70% of power plant emissions for conventional and CO(2) capture and sequestration power plants, respectively. To further constrain these estimates, we suggest that the fate of soil carbon and geogenic carbon at MCM sites be explored more widely.


From Passive Targeting to Personalized Nanomedicine: Multidimensional Insights on Nanoparticles' Interaction with the Tumor Microenvironment.
Nanomedicine is revolutionizing the treatment of cancer and has achieved unprecedented outcomes over the past decades. The accumulation of Nanoparticles (NPs) in different tumors relies mainly on the Enhanced Permeability and Retention (EPR) effect benefiting from the wide fenestrae of the tumor vasculature and the lack of lymphatic drainage. However, the EPR effect is recognized as a heterogeneous phenomenon resulting in heterogeneous outcomes of clinical trials. Extensive efforts are exerted to enhance the outcomes of nanomedicine in a larger cohort of patients by employing active targeting strategies. However, actively targeted NPs accumulate in tumors by the EPR effect and hence fail to achieve convincing therapeutic outcomes. These obstacles are gradually being removed by improving the understanding of the Tumor Microenvironment (TME) and the mechanistic interaction of the NPs with its different components. In this review, we provide detailed insights into the past concerns of drug targeting, the current trends of TME reengineering, and the future implications for overcoming past hurdles. Strategies explored in this regard included the use of companion diagnostics and the modulation of the protein corona associated with the systemic administration of NPs and their interaction with biological macromolecules.


Learning Hand Kinematics for Parkinson's Disease Assessment Using a Multimodal Sensor Glove.
Hand dysfunctions in Parkinson's disease include rigidity, muscle weakness, and tremor, which can severely affect the patient's daily life. Herein, a multimodal sensor glove is developed for quantifying the severity of Parkinson's disease symptoms in patients' hands while assessing the hands' multifunctionality. Toward signal processing, various algorithms are used to quantify and analyze each signal: Exponentially Weighted Average algorithm and Kalman filter are used to filter out noise, normalization to process bending signals, K-Means Cluster Analysis to classify muscle strength grades, and Back Propagation Neural Network to identify and classify tremor signals with an accuracy of 95.83%. Given the compelling features, the flexibility, muscle strength, and stability assessed by the glove and the clinical observations are proved to be highly consistent with Kappa values of 0.833, 0.867, and 0.937, respectively. The intraclass correlation coefficients obtained by reliability evaluation experiments for the three assessments are greater than 0.9, indicating that the system is reliable. The glove can be applied to assist in formulating targeted rehabilitation treatments and improve hand recovery efficiency.


Exposure to fluoride aggravates the impairment in learning and memory and neuropathological lesions in mice carrying the APP/PS1 double-transgenic mutation.
Alzheimer's disease (AD) is responsible for 60-70% of all cases of dementia. On the other hand, the tap water consumed by hundreds of millions of people has been fluoridated to prevent tooth decay. However, little is known about the influence of fluoride on the expression of APP and subsequent changes in learning and memory and neuropathological injury. Our aim here was to determine whether exposure to fluoride aggravates the neuropathological lesions in mice carrying the amyloid precursor protein (APP)/presenilin1 (PS1) double mutation. These transgenic or wide-type (WT) mice received 0.3 ml of a solution of fluoride (0.1 or 1 mg/ml, prepared with NaF) by intragastric administration once each day for 12 weeks. The learning and memory of these animals were assessed with the Morris water maze test. Senile plaques, ionized calcium binding adaptor molecule 1 (Iba-1), and complement component 3 (C3) expression were semi-quantified by immunohistochemical staining; the level of Aβ42 was detected by Aβ42 enzyme-linked immunosorbent assays (ELISAs); the levels of synaptic proteins and enzymes that cleave APP determined by Western blotting; and the malondialdehyde (MDA) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) measured by biochemical procedures. The untreated APP mice exhibited a decline in learning and memory after 12 weeks of fluoride treatment, whereas treatment of these some animals with low or high levels of fluoride led to such declines after only 4 or 8 weeks, respectively. Exposure of APP mice to fluoride elevated the number of senile plaques and level of Aβ42, Iba-1, and BACE1, while reducing the level of ADAM10 in their brains. The lower levels of synaptic proteins and enhanced oxidative stress detected in the hippocampus of APP mice were aggravated to fluoride. These findings indicate that exposure to fluoride, even at lower concentration, can aggravate the deficit in learning and memory and neuropathological lesions of the mice that express the high level of APP.


Elevated expression of inhibin alpha in prostate cancer.
Less than 50% of men who undergo radical prostatectomy for prostate cancer are cured of disease. We evaluate tumor expression of inhibin alpha, a putative tumor suppressor, and the related protein, follistatin, to determine whether expression correlated with failure to be cured by surgery. Tissues were selected from an archival collection of 379 prostatectomy specimens from men with followup of at least 5 years after surgery. Since previous studies showed that such men with only Gleason grade 3 cancer had a greater than 95% chance of no biochemical recurrence (increase in serum prostate specific antigen), our investigation was confined to 174 men with 2% or greater grade 4/5 cancer. These men had an intermediate rate of failure, providing an opportunity to analyze the potential contribution of inhibin alpha or follistatin to progression. Intensity of immunohistochemical labeling for inhibin alpha and follistatin in each cancer was compared with that in normal glands within the same tissue section. The majority of cases showed more intense expression of inhibin alpha in cancer than in normal glands. Those individuals whose cancers had the most elevated expression of inhibin alpha had a higher risk of recurrence, although this association was not statistically significant. Follistatin was expressed equivalently in normal and cancer cells in the majority of cases and did not correlate with recurrence. Our finding that inhibin alpha is frequently overexpressed in high grade prostate cancer suggests that the role of inhibin alpha as a tumor suppressor needs to be reevaluated. Furthermore, assessment of inhibin alpha as a serum marker of prostate cancer, as used to diagnose ovarian cancer, may be warranted.


Late hemodynamic effects of the preserved papillary muscles during mitral valve replacement.
The late hemodynamic effects of preserving the papillary muscles during mitral valve replacement have not been evaluated. Sixteen patients who had chronic mitral regurgitation due to myxomatous degeneration were randomized to preservation (Pres group, n = 8) or no preservation (No Pres group, n = 8) of the chordae tendineae and papillary muscles during mitral valve replacement. Rest and exercise nuclear ventriculograms were performed early (3 months) and late (5 years) after surgery. Early after surgery, the No Pres group had lower ejection fractions and stroke work indexes (P < .05 by repeated-measures [rm] ANOVA) than the Pres group did at similar end-diastolic volume indexes. The No Pres group had similar cardiac indexes after exercise because heart rate increased (P < .005 by rm ANOVA). Late after surgery, ejection fraction was greater at similar end-diastolic volume indexes (P < .005 by rm ANCOVA), and preload recruitable stroke work indexes (P < .001 by rm ANCOVA) were better in the Pres group. Preserving chordal attachments enhanced the late hemodynamic recovery after mitral valve replacement for mitral regurgitation.


Physical Activity Protects Men but Not Women for Sarcopenia Development.
Objective: Sarcopenia is among the most deleterious effects of aging. The objective of this study was to analyze the relationship between performance tests and muscular volume over the life span of male and female participants. Method: A correlation study was conducted with healthy individuals (50 males and 47 females) between the ages of 20 and 94; the study group included active older people, sedentary younger people, and young athletes. Muscular volume was determined by tomography and muscular performance (4-meter speed tests [4 MSTs], chair test, and handgrip test), and a correlation analysis between the groups was performed. Results: Sex-related differences were observed between the variables; in males, muscle volume and functional parameters were closely related with age and physical activity, whereas in females, they were not related at all. Conclusion: Male and female muscle volume and performance demonstrate strong differences, which should be considered during clinical evaluations of sarcopenia.


Persistence of replicating coxsackievirus B3 in the athymic murine heart is associated with development of myocarditic lesions.
Coxsackievirus B3 (CVB3)-induced myocarditis was studied in euthymic (nu/+) and athymic (nu/nu) C3H/HeN (H-2k) mice. Mice were inoculated intraperitoneally with 10(6) p.f.u. of CVB3 (Nancy strain) and sacrificed at intervals up to 92 days post-inoculation (p.i.). Viraemia peaked at day 2 to 3 p.i. and ceased at day 5 to 7 p.i. in a synchronized manner in both sets of mice. Very few infectious particles were detected in the blood of nu/nu mice after day 14 p.i. In nu/nu mice, CVB3 persisted in myocardial tissue with constant titres between 2.7 +/- 1.9 x 10(4) and 7.6 +/- 5.2 x 10(4) p.f.u./mg from day 3 to 92 p.i., which were comparable to those of nu/+ mice in the acute phase. In nu/+ mice, the virus was recovered from all animals examined by day 11 p.i. and from three out of 13 mice between days 14 and 21 p.i., yet no virus was recovered from nu/+ mice at day 42 p.i. In nu/nu mice, sense and antisense RNA for CVB3 was detected in the myocardial tissue up to day 42 p.i. by in situ hybridization and up to day 92 p.i. by reverse transcriptase-PCR. Neither sense nor antisense RNA was detected after day 21 p.i. in nu/+ mice with the same techniques. Myocardial tissue damage was analysed morphologically. At day 92 p.i., the area of myocardial injury peaked at 23% of the section in nu/nu mice. In contrast, less than 0.6% of tissue sections contained lesions in nu/+ mice. A neutralizing antibody response to CVB3 was observed in both nu/nu and nu/+ mice. The mean titre of neutralizing antibody was significantly higher at day 21 p.i. in nu/+ mice, but similar at day 42 p.i. with nu/nu and nu/+ mice. Perforin-producing natural killer-like cells, which are considered to play an important role in causing acute myocarditic lesions in immunocompetent mice, were found in the lesions of nu/nu mice persistently infected with CVB3. Prolonged tumour necrosis factor-alpha mRNA synthesis detected in nu/nu mice appears to reflect the continuous activation of macrophages, which extend phagocytic reactions to virus-infected myocytes. These immunological results suggested that the host immune response devoid of antigen-specific T cell function is not sufficient to terminate CVB3 infection in nu/nu mice. Also, it appears that competent cellular immunity, on the whole, plays a role in curing rather than in aggravating myocarditis in nu+mice.(ABSTRACT TRUNCATED AT 400 WORDS)


Do students mandated to intervention for campus alcohol-related violations drink more than nonmandated students?
It is often assumed that "mandated students" (i.e., those who violate campus alcohol policies and are mandated to receive an alcohol intervention) drink more than students from the general population. To test this assumption empirically, we compared alcohol-use levels of a sample of students mandated for alcohol violations (n = 435) with a representative sample of nonmandated students from the same university (n = 1,876). As expected, mandated students were more likely to be male, younger, first-year students, and living in on-campus dorms, and they reported poorer academic performance (i.e., grade point averages). With respect to alcohol use, after controlling for demographic differences, they reported more drinks per week than those in the general university sample but they did not report drinking heavily more frequently than nonmandated students. Within the mandated student sample, there was considerable variability in drinking level; that is, the frequency of heavy drinking covered the full range from never to 10+ times in the past month, and there was a larger standard deviation for drinks per week among mandated students than among those in the general sample. These results challenge the assumption that mandated students drink heavily more often but do provide empirical support for the assumption that students who violate alcohol policies drink at higher quantities, justifying the need for an alcohol use reduction intervention.


Moderately lipophilic 2-(Het)aryl-6-dithioacetals, 2-phenyl-1,4-benzodioxane-6-dithioacetals and 2-phenylbenzofuran-5-dithioacetals: Synthesis and primary evaluation as potential antidiabetic AMPK-activators.
Since the 1950's, AMP-kinase (AMPK) has been used as a promising target for the development of antidiabetic drugs against Type 2 diabetes mellitus (T2D). Indeed, the canonical antidiabetic drug metformin recruits, at least partially, AMPK activation for its therapeutic effect. Herein we present design and synthesis of 20 novel relatively polar cyclic and acyclic dithioacetals of 2-(Het)arylchroman-6-carbaldehydes, 2-phenyl-1,4-benzodioxane-6-carbaldehyde, and 2-phenylbenzofuran-5-carbaldehyde, which were developed as potential AMPK activators. Three of the synthesized dithioacetals demonstrated significant enhancement (≥70%) of glucose uptake in rat L6 myotubes. Noteworthy, one of the dithioacetals, namely 4-(6-(1,3-dithian-2-yl)chroman-2-yl)pyridine, exhibited high potency comparing to other molecules. It increased the rate of glucose uptake in rat L6 myotubes and augmented insulin secretion from rat INS-1E cells in pharmacological relevant concentrations (up to 2 μM). Both effects were mediated by activation of AMPK. In addition, the compound showed excellent pharmacokinetic profile in healthy mice, including maximal oral bioavailability. Such bifunctionality (increased glucose uptake and insulin secretion) can be used as a starting point for the development of a novel class of antidiabetic drugs with dual activity that is relevant for T2D treatment.


[The value of intraoperative ultrasonography during surgery for pancreatitis related changes of the pancreas].
The main purpose of this work was to examine the value of intraoperative ultrasonography (IOS) for decision-making in patients with complications of chronic pancreatitis and pancreatic adenocarcinoma. High-resolution intraoperative ultrasound scanning using B-mode real time (Capasee SSA-220A, Toshiba, Tokyo, Japan) and 7.5 MHz T-type transducer was performed in 48 patients (18 women and 30 men) treated at the Second Department of General Surgery between 1996 and 1998. The size, echogenicity and location of pancreatic lesions was studied, as well as the structure of liver, bile ducts and regional lymph nodes. The value of IOS was assigned to one of three categories: 1) very helpful--the scheduled operative procedure was modified in the light of IOS findings; 2) helpful--the operative procedure was carried out under IOS guidance; and 3) not helpful. The patients were divided into three groups basing on the histologic changes: Group I--26 patients operated for pancreatic carcinoma; group II--19 patients with cystic lesions and inflammatory tumors of the pancreas; group III--3 patients operated for preoperatively diagnosed pancreatic carcinoma not confirmed during surgery. In group I eight resections were performed, including five Whipple duodenopancreatectomies, two pancreatectomies, and one subtotal pancreatectomy. Very helpful information was obtained from IOS in four (16%) patients, helpful information in 11 (42%), not helpful in 11 (42%). Two nonpalpable masses were revealed by ultrasonography. In all cases the spread of the carcinoma to peripancreatic vessels: portal vein, superior mesenteric artery and inferior caval vein was correctly assessed (Figs. 1, 2). IOS provided mainly topographic information in group II, with very helpful and helpful data for 89% of the operations. Three cystic lesions in the inflammatory infiltrate and three hitherto undetected minor cysts were found. IOS facilitated drainage in 11 cases by reducing tissue trauma and operative time (Fig. 3). In six patients with suspected inflammatory lesions ultrasound served to guide needle biopsy. In group III the information was of diagnostic value. All patients in this group were intraoperatively diagnosed with extrapancreatic primary neoplasm spreading to the hepatoduodenal ligament. IOS served to inert a prosthesis of the common bile duct in one patient. Overall, IOS was very helpful for decision-making in 22.9% and helpful in 50% of the procedures (Tab. 1).


Association of PELI1 polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population.
Studies in animal models have indicated that Pellino 1 is involved in inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE). The current study was designed to determine whether PELI1 confers genetic susceptibility to SLE in humans, as assessed in a Chinese Han population. Blood samples were drawn from patients diagnosed with SLE and healthy volunteers. Three single nucleotide polymorphism (SNP) loci with a minor allele frequency of at least 0.05 were chosen to evaluate the correlation between PELI1 genotype and the incidence of SLE. There was a significant difference in the frequency distribution of the rs329497 allele between the SLE patients and the healthy controls (A vs. G; Bonferroni corrected p = 0.036, odds ratio = 0.75, 95% confidence interval = 0.60-0.94). No differences in the genotype and allele frequencies of other SNP loci were observed between the two groups. Furthermore, the alleles and genotypes of the three SNPs were not associated with lupus nephritis. In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility.


Moving healthcare reform forward: a complex and challenging transition.
As a long-time advocate of primary-care reform and a participant in the present implementation of the Ontario Primary Care Reform (PCR) pilot projects, I am sympathetic to the perspectives of Rosser and Kasperski. The model for reform that they propose has added fuel to the debate on PCR initiatives. However, the future strategic direction for primary care will be determined at the conclusion of the implementation and testing period for the pilot sites and after evaluating models in other provincial jurisdictions. Although the investment of resources over the past four years by government and the profession has clearly been significant, the methodical planning and breadth of consultation and review on many issues may not be apparent to observers.


Advances in reprogramming to pluripotency.
Pluripotent stem cells (PSCs) derived from somatic cells represent a powerful experimental tool for investigating the molecular mechanisms underlying the disease phenotype; with prospects to advance medical therapies. They also have significant potential as a renewable source of autologous cells for cellular therapy. Various approaches for PSC derivation from somatic cells have been reported in the literature. The method used for reprogramming is particularly relevant as it may affect the characteristics and quality of PSCs. This review will present an overview of the basic strategies and methods for reprogramming to pluripotency. These strategies will be briefly discussed in the context of how the mechanism of reprogramming could influence PSC characteristics with respect to safety and quality. Aspects of the reprogramming approach that can influence PSC properties, such as culture conditions and donor cell source, are also discussed.


Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring.
Human health is dependent upon environmental exposures, yet the diversity and variation in exposures are poorly understood. We developed a sensitive method to monitor personal airborne biological and chemical exposures and followed the personal exposomes of 15 individuals for up to 890 days and over 66 distinct geographical locations. We found that individuals are potentially exposed to thousands of pan-domain species and chemical compounds, including insecticides and carcinogens. Personal biological and chemical exposomes are highly dynamic and vary spatiotemporally, even for individuals located in the same general geographical region. Integrated analysis of biological and chemical exposomes revealed strong location-dependent relationships. Finally, construction of an exposome interaction network demonstrated the presence of distinct yet interconnected human- and environment-centric clouds, comprised of interacting ecosystems such as human, flora, pets, and arthropods. Overall, we demonstrate that human exposomes are diverse, dynamic, spatiotemporally-driven interaction networks with the potential to impact human health.


Current operative morbidity associated with elective surgical resection for lung cancer.
To determine the current operative morbidity for elective surgery of lung cancer, the authors reviewed the charts of 1076 consecutive patients who underwent pulmonary resection between 1978 and 1984 at two major Canadian teaching hospitals. Of these patients, 731 (68%) had a normal course. Minor complications occurred in 206 patients (19%); the majority were supraventricular arrhythmias (100 events) and atelectasis (41 events). Nonfatal major complications occurred in 105 patients (9.8%). The overall operative death rate was 3.2%. If supraventricular arrhythmias are excluded, nearly 80% of patients had a smooth postoperative course. In order to correlate the occurrence of complications with pre- and perioperative data, several possible risk factors were analysed. For major complications and death, the age, the forced expiratory volume, weight loss, coexisting disease, stage of cancer and extent of resection were significant risk factors (p less than 0.05). The data show that elective pulmonary surgery can be done safely and complications prevented. The necessary requirements are: proper selection of patients, a well-performed operation and prompt treatment of potential problems.


Comparison of phenotyping and genotyping of lymphoid neoplasms.
Comparison of phenotyping (PT) and genotyping (GT) of lymphoid neoplasms was performed on 51 specimens including lymph nodes, bone marrows, and body fluids. PT was performed with a flow cytometer using a large monoclonal antibody panel. GT included the testing for gene rearrangements of heavy chain, kappa and lambda light chains, and T-cell receptor beta-chain genes with DNA probes. The results obtained from these two techniques were generally compatible in terms of clonality and cell lineage. Only one case of B-cell lymphoma was not diagnosed by PT but showed gene rearrangement. For T-cell lymphoma, GT offers a more definitive diagnosis than does PT. Biclonality was demonstrated in one case of hairy cell leukemia by GT only. The rearranged band also offers a definitive clonal identification based on electrophoretic mobility. GT can detect a monoclonal population as small as 5% and can be performed on old or fresh specimens. PT requires 20% abnormal cells and a fresh specimen. It is concluded that GT is superior to PT for lymphoid tumor diagnosis, but it should be reserved as a supplementary test at this stage because of its technical complexity.


Best Practices for Reducing Unplanned Acute Care for Patients With Cancer.
Variation and cost in oncology care represent a large and growing burden for the US health care system, and acute hospital care is one of the single largest drivers. Reduction of unplanned acute care is a major priority for clinical transformation in oncology; proposed changes to Medicare reimbursement for patients with cancer who suffer unplanned admissions while receiving chemotherapy heighten the need. We conducted a review of best practices to reduce unplanned acute care for patients with cancer. We searched PubMed for articles published between 2000 and 2017 and reviewed guidelines published by professional organizations. We identified five strategies to reduce unplanned acute care for patients with cancer: (1) identify patients at high risk for unplanned acute care; (2) enhance access and care coordination; (3) standardize clinical pathways for symptom management; (4) develop new loci for urgent cancer care; and (5) use early palliative care. We assessed each strategy on the basis of specific outcomes: reduction in emergency department visits, reduction in hospitalizations, and reduction in rehospitalizations within 30 days. For each, we define gaps in knowledge and identify areas for future effort. These five strategies can be implemented separately or, with possibly more success, as an integrated program to reduce unplanned acute care for patients with cancer. Because of the large investment required and the limited data on effectiveness, there should be further research and evaluation to identify the optimal strategies to reduce emergency department visits, hospitalizations, and rehospitalizations. Proposed reimbursement changes amplify the need for cancer programs to focus on this issue.


Decision by sampling implements efficient coding of psychoeconomic functions.
The theory of decision by sampling (DbS) proposes that an attribute's subjective value is its rank within a sample of attribute values retrieved from memory. This can account for instances of context dependence beyond the reach of classic theories that assume stable preferences. In this paper, we provide a normative justification for DbS that is based on the principle of efficient coding. The efficient representation of information in a noiseless communication channel is characterized by a uniform response distribution, which the rank transformation implements. However, cognitive limitations imply that decision samples are finite, introducing noise. Efficient coding in a noisy channel requires smoothing of the signal, a principle that leads to a new generalization of DbS. This generalization is closely connected to range-frequency theory, and helps descriptively account for a wider set of behavioral observations, such as how context sensitivity varies with the number of available response categories. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


A quantitative assay for aggrecanase activity.
Aggrecanase activities of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases were measured with a recombinant aggrecan fragment and two monoclonal antibodies. Recombinant human aggrecan interglobular domain was first incubated in the presence of ADAMTS enzymes. The aggrecan peptide with the N-terminal sequence ARGSVIL released upon hydrolysis was then quantified in an enzyme-linked immunosorbent assay (ELISA) with an anti-neoepitope antibody specific for the N-terminal ARGSVIL sequence and a second anti-aggrecan peptide antibody. For higher sensitivity of the assay, P1-P5 residues of the aggrecanase site within the aggrecan substrate were changed by in vitro mutagenesis. Specific activities of recombinant truncated ADAMTS1 and ADAMTS4 estimated with authentic aggrecan interglobular domain amounted to 2.4 +/- 0.4 and 21.7 +/- 9.5 nmoles hydrolyzed substrate/min.mg, respectively. The values were 10.3 +/- 5.1 and 151.5 +/- 93.5 nmoles/min.mg for hydrolysis of the modified substrate. The aggrecanase activity assay can be used for (1) kinetic characterization of aggrecanase activities of human and animal ADAMTS, (2) screening of inhibitors for aggrecan hydrolyzing ADAMTS, and (3) estimation of aggrecanase activities in biological samples.


IL-1alpha, IL-1beta and TNF-alpha secretion during in vivo/ex vivo cellular interactions with titanium and copper.
Titanium (Ti) and copper (Cu) were used to evaluate cytokine secretion around materials with different chemical properties. Ti disks were coated with Cu or left uncoated. The disks were inserted subcutaneously in rats for 1, 3, 12, 18, 24 and 48 h. Interleukin-1alpha (IL-1alpha), IL-1beta and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in vivo around the materials, in sham operated sites, and after ex vivo incubation of surface adherent cells. Ti and Cu revealed distinct cytokine expression patterns. Cu recruited cells showed higher and prolonged release of IL-1alpha than Ti at longer times (>24 h), whereas Ti exhibited a transient IL-1alpha response at earlier periods (<24 h). An early enhanced secretion of TNF-alpha characterized Ti. Low amounts of IL-1beta were found around both materials. Sham site recruited cells produced lower levels of cytokines. The results after ex vivo incubations were similar to those in vivo. This study shows that material chemical properties influence early cytokine production. The Ti-associated transient rise of IL-1alpha and TNF-alpha may be of importance for the early tissue response around biocompatible materials, while a delayed high IL-1alpha expression could be a marker of inflammation induced by toxic materials.


Leaf chemical changes induced in Populus trichocarpa by enhanced UV-B radiation and concomitant effects on herbivory by Chrysomela scripta (Coleoptera: Chrysomelidae).
To assess the potential impact of enhanced ultraviolet-B (UV-B) radiation over two trophic levels, we monitored key leaf chemical constituents and related changes in their concentration to dietary preference and performance of a specialist insect herbivore. Ramets of Populus trichocarpa Torr. & Gray (black cottonwood) were subjected to near zero (0X), ambient (1X) or twice ambient (2X) doses of biologically effective UV-B radiation (UV-B(BE)) in a randomized block design using either a square-wave (greenhouse) or a modulated (field) lamp system. After a 3-month treatment period, apparent photosynthesis was determined in situ and plants were harvested for biomass determination. Leaf subsamples were analyzed for nitrogen, sulfur, chlorophylls, UV-absorbing compounds and protein-precipitable tannins. Effects of changes in these constituents on feeding by Chrysomela scripta Fab. (cottonwood leaf beetle) were determined by (1) adult feeding preference trials and (2) larval growth rate trials. Enhanced UV-B(BE) radiation had minimal effects on photosynthesis, growth, leaf area and biomass distribution. In the greenhouse study, concentrations of foliar nitrogen and chlorophylls increased, but tannins decreased slightly in young leaves exposed to enhanced UV-B(BE) radiation. There were no significant effects on these parameters in the field study. The concentration of methanol-extractable foliar phenolics increased in plants grown with enhanced UV-B(BE) radiation in both the greenhouse and field studies. In feeding preference trials, adult C. scripta chose 2X-treated tissue almost twice as often as 1X-treated tissue in both greenhouse and field studies, but differences were not statistically significant (P = 0.12). In the field study, first instar larvae grown to adult eclosion on 2X-treated leaves had a significant (P < 0.001) reduction in consumption efficiency compared with larvae grown on 1X-treated leaves. We conclude that effects of enhanced UV-B(BE) radiation at the molecular-photochemical level can elicit significant responses at higher trophic levels that may ultimately affect forest canopy structure, plant competitive interactions and ecosystem-level processes.


Relating body condition to inorganic contaminant concentrations of diving ducks wintering in coastal California.
In wild waterfowl, poor winter body condition may negatively affect migration, survival, and reproduction. Environmental contaminants have been shown to adversely affect the body condition of captive birds, but few field studies have examined body condition and contaminants in wild birds during the winter. We assessed the body condition of carcasses from a collection of canvasbacks (Aythya valisineria) and lesser (A. affinis) and greater scaup (A. marila) wintering in coastal California. We used Akaike information criterion (AIC) to select the model with the best balance of parsimony and goodness of fit that related indices of body condition with concentrations of Cd, Cu, Hg, Se, and Zn. Total ash-free protein in canvasbacks decreased with increasing Se concentrations, and pancreas mass decreased with increasing Hg. We combined the closely related lesser and greater scaup in analyses and found that total carcass fat, pancreas mass, and carcass mass decreased with increasing Zn concentrations, and pancreas mass decreased with increasing Hg. Our AIC analysis indicated that some indices of body condition in diving ducks were inversely related to some environmental contaminants in this collection, but additional AIC analyses should be conducted across a wider range of contaminant concentrations to corroborate our findings.


Clozapine induced myopericarditis: early recognition improves clinical outcome.
Clozapine is an atypical dibenzodiazepine antipsychotic used for resistant schizophrenia. Uncommonly, it is associated with myocarditis. We report a case of myopericarditis masquerading as an acute myocardial infarction based on presenting electrocardiogram and cardiac markers. Emergent coronary angiography confirmed the absence of epicardial coronary occlusion and revealed severe left ventricular systolic dysfunction. Immediate discontinuation of the clozapine, along with aggressive supportive care resulted in complete recovery to baseline. Cardiovascular health professionals should be aware of this uncommon but serious side effect of clozapine since failure to recognize the association may result in adverse clinical outcome and inappropriate therapy.


Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice.
An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS. After 14-day acclimation, the grouped ApoE-/- mice were immunized four times (day 0, day 7, day 14, day 28) with different spike-protein-derived peptides (coupled with KLH) or KLH via subcutaneous injection. Antibody level, state of glial cells, gene expression, prepulse inhibition, locomotor activity, and spatial working memory were assessed from day 21. An increased level of anti-S1-111 IgG was measured in their sera and brain homogenate after the immunization. Crucially, anti-S1-111 IgG increased the density of microglia, activated microglia, and astrocytes in the hippocampus, and we observed a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among S1-111-immunized mice. Transcriptome profiling showed that up-regulated genes in S1-111-immunized mice were mainly associated with synaptic plasticity and mental disorders. Our results show that the non-neutralizing antibody anti-S1-111 IgG induced by the spike protein caused a series of psychotic-like changes in model mice by activating glial cells and modulating synaptic plasticity. Preventing the production of anti-S1-111 IgG (or other non-neutralizing antibodies) may be a potential strategy to reduce CNS manifestations in COVID-19 patients and vaccinated individuals.


An immunohistochemical staining of epidermal Langerhans' cells in tinea cruris.
Epidermal Langerhans' cells (LC) were investigated in fresh cryostat sections of ten biopsies from patients with mycologically proven tinea cruris, using OKT6 monoclonal antibodies and avidin-biotin-immunoperoxidase. Compared to the controls, more epidermal LC and an increased number of LC in the upper half of the epidermis were found in the sections from tinea patients. In a double staining method for both OKT6-positivity and hyphae, a tendency towards a gathering of LC and fungal elements was found. The results of this study are in agreement with the theory that epidermal LC are responsible for the antigen uptake in dermatophytosis.


Highly enantioselective hydrogenation of alpha-dehydroamino acids by rhodium complexes with new unsymmetric P-chirogenic bisphosphine ligands.
[figure: see text] New rhodium catalysts with unsymmetric P-chirogenic bis(phosphino)ethanes, BisP*-Rh, exhibited very high enantioselectivity (98-99%) in the hydrogenation of alpha-dehydroamino acid derivatives. Such high enantioselectivity should result from the asymmetric environment around the Rh atom, as was shown in the molecular structure of the catalyst analyzed by X-rays. The asymmetry can be controlled by the combination of the alkyl groups on the two phosphorus atoms.


Artificial intelligence analysis of paraspinal power spectra.
OBJECTIVE: As an aid to discrimination of sufferers with back pain an artificial intelligence neural network was constructed to differentiate paraspinal power spectra. DESIGN: Clinical investigation using surface electromyography. METHOD: The surface electromyogram power spectra from 60 subjects, 33 non-back-pain sufferers and 27 chronic back pain sufferers were used to construct a back propagation neural network that was then tested. Subjects were placed on a test frame in 30 degrees of lumbar forward flexion. An isometric load of two-thirds maximum voluntary contraction was held constant for 30 s whilst surface electromyograms were recorded at the level of the L(4-5). Paraspinal power spectra were calculated and loaded into the input layer of a three-layer back propagation network. The neural network classified the spectra into normal or back pain type. RESULTS: The back propagation neural was shown to have satisfactory convergence with a specificity of 79% and a sensitivity of 80%. CONCLUSIONS: Artificial intelligence neural networks appear to be a useful method of differentiating paraspinal power spectra in back-pain sufferers.


Laparoscopic management of colovesical fistula in different clinical scenarios.
Colovesical fistula (CVF) is a condition with various aetiologies and presentations. Surgical treatment is necessary in most cases. Due to its complexity, open approach is preferred. However, laparoscopic approach is reported in the management of CVF due to diverticular disease. The aim of this study was to analyse the management and outcome of patients with CVF of different aetiologies treated with laparoscopic approach. This was a retrospective study. We retrospectively reviewed all patients undergoing elective laparoscopic management of CVF from March 2015 to December 2019. None. Nine patients underwent laparoscopic management of CVF. There were no intraoperative complications or conversions to open surgery. A sigmoidectomy was performed in eight cases. In one patient, a fistulectomy with sigmoid and bladder defect closure was performed. In two cases of locally advanced colorectal cancer with bladder invasion, a multi-stage procedure with temporary colostomy was chosen. In three cases, with no intraoperative leakage, we did not perform bladder suture. Four Clavien I-II complications were recorded. Two fragile patients died in the post-operative period. No patients required re-operation. At a median follow-up of 21 months (interquartile range: 6-47), none of the patients had recurrence of fistula. CVF can be managed with laparoscopic approach by skilled laparoscopic surgeons in different clinical scenarios. Bladder suture is not necessary if leakage is absent. Informed counselling to the patient must be guaranteed concerning the risk of major complications and mortality in case of CVF due to malignant disease.


Differential expression of cyclic-AMP responsive element modulator (CREM) mRNA isoforms during testicular development of boars.
The cyclic-AMP responsive element modulator (CREM) transcription factor, a key regulator of spermatogenesis, can activate or repress gene expression by differential expression of alternatively spliced mRNA isoforms. The objective of this study was to report the sequences of the predominant CREM mRNA isoforms with leader exons B, θ1, θ2, in addition to the relative expression of these transcripts, in immature and adult boar testes. Activator CREM isoforms τγ (containing the B exon), θ1τγ and θ2τγ, were expressed in the adult boar testes, but not in immature testes. The CREM θ2τγ isoform had the highest expression levels in the adult boar testes compared to the τγ and θ1τγ isoforms (θ2τγ = 4.94 ± 1.49 in contrast to τγ = 1.66 ± 0.79 and θ1τγ = 2.32 ± 0.72; mean ± SD; P < 0.01). Interestingly, the predominant CREM mRNA isoforms in adult boar testes contained the C and γ exons; these exons are not present in human and rodent CREM mRNA, demonstrating species-specific expression. In contrast to the adult CREM isoforms, only CREM mRNA isoforms with the B exon (τ1 and α) were amplified in the 21 d (immature) boar testes. Further understanding of CREM mRNA isoform expression and regulation during boar spermatogenesis could contribute to our knowledge of spermatogenic efficiency in this species.


Control of Bovine Leukemia Virus in Three US Dairy Herds by Culling ELISA-Positive Cows.
The objective of this trial was to evaluate a test-and-cull approach to controlling bovine leukemia virus (BLV) in US dairy herds with a low BLV prevalence. Despite worldwide distribution of the virus, 21 nations have eradicated BLV from their dairy cattle and are currently considered 'BLV-free.' In contrast, the US has attempted no industry-wide BLV control programs and has experienced an increase in BLV prevalence among dairy cows to about 40%. This raises concerns about production efficiency, herd health, and sustainability. In a pilot field trial with three Midwestern-US dairy herds, a test-and-cull approach using ELISA screening of milk samples was successful in reducing BLV prevalence in two herds. In the third herd, BLV prevalence increased following the introduction of infected heifers that were raised at an out-of-state calf raising facility. This trial demonstrated that a test-and-cull approach to BLV control can be successful in US dairy herds with low BLV prevalence, but ongoing surveillance is necessary to prevent reintroduction of the virus.


Higher-order dimensions of personality disorder: hierarchical structure and relationships with the five-factor model, the interpersonal circle, and psychopathy.
Two studies examined the higher-order factor structure of DSM-IV personality disorders using the International Personality Disorder Examination in male forensic psychiatric patients. In Study 1 (N = 168), exploratory factor analysis at the level of individual personality disorder criteria indicated nine primary factors. Exploratory and confirmatory factor analyses of these first-order factors supported a hierarchical structure in which two of three second-order factors covaried to yield a third-order factor. The two resulting superordinate factors were labelled Anxious-Inhibited and Acting Out. In Study 2 (N = 160), we used exploratory and confirmatory factor analyses to test hypotheses of common dimensions underlying these superordinate factors of personality disorder and superordinate factors of the five-factor model of personality, dimensions of the interpersonal circle, and psychopathy. Of three common factors, one combined Anxious-Inhibited disorders, "neurotic introversion," and hostile-submission. The other two factors of Acting Out/ psychopathy and antagonism/hostile-dominance covaried to yield a superordinate factor. Possible substrates underlying two superordinate dimensions common to normal and abnormal personality were identified in the theoretical literature.


Random Boolean network models and the yeast transcriptional network.
The recently measured yeast transcriptional network is analyzed in terms of simplified Boolean network models, with the aim of determining feasible rule structures, given the requirement of stable solutions of the generated Boolean networks. We find that, for ensembles of generated models, those with canalyzing Boolean rules are remarkably stable, whereas those with random Boolean rules are only marginally stable. Furthermore, substantial parts of the generated networks are frozen, in the sense that they reach the same state, regardless of initial state. Thus, our ensemble approach suggests that the yeast network shows highly ordered dynamics.


Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision).
Congenital adrenal hyperplasia is a category of disorders characterized by impaired adrenocortical steroidogenesis. The most frequent disorder of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is caused by pathogenic variants of CAY21A2 and is prevalent between 1 in 18,000 and 20,000 in Japan. The clinical guidelines for 21-hydroxylase deficiency in Japan have been revised twice since a diagnostic handbook in Japan was published in 1989. On behalf of the Japanese Society for Pediatric Endocrinology, the Japanese Society for Mass Screening, the Japanese Society for Urology, and the Japan Endocrine Society, the working committee updated the guidelines for the diagnosis and treatment of 21-hydroxylase deficiency published in 2014, based on recent evidence and knowledge related to this disorder. The recommendations in the updated guidelines can be applied in clinical practice considering the risks and benefits to each patient.


Analysis of precursors to wine odorant 3-mercaptohexan-1-ol using HPLC-MS/MS: resolution and quantitation of diastereomers of 3-S-cysteinylhexan-1-ol and 3-S-glutathionylhexan-1-ol.
A method has been developed and validated for the analysis of the individual diastereomers of 3-S-cysteinylhexan-1-ol (Cys-3-MH) and 3-S-glutathionylhexan-1-ol (Glut-3-MH) extracted from grape juice and wine. The method uses stable isotope dilution analysis (SIDA) combined with solid-phase extraction (SPE) and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for quantitation. These compounds have been considered as potential precursors to the important wine odorant 3-mercaptohexan-1-ol (3-MH). This constitutes the first analytical method where (1) Glut-3-MH has been accurately quantified in grape juice and wine and (2) the individual Cys- and Glut-3-MH diastereomers were separated and quantified by a single HPLC-MS/MS method. The use of deuterium-labeled internal standards has resulted in an accurate and precise method that can achieve quantitation limits of <0.5 microg/L for the individual Cys- and Glut-3-MH diastereomers in grape juice and white wine. The method has been applied to the determination of 3-MH precursor diastereomers in various white juice and wine samples. Overall, Glut-3-MH was always more abundant than Cys-3-MH in the juices and wines examined, regardless of grape variety. Stereochemically, (S)-Glut-3-MH generally dominated over the (R)-diastereomer in the juices and wines, but there was not such a marked difference between the distribution of Cys-3-MH diastereomers. These results have important implications for understanding the formation of wine flavor, and the application of this method will allow further exploration of precursors to the varietal thiol 3-MH.


Three-dimensional mesoporous gold film to enhance the sensitivity of electrochemical detection.
Cell-cell and cell-extracellular matrix (ECM) adhesion are fundamental and important in the development of a cell-based chip. In this study, a novel, simple, rapid, and one-step technique was developed for the fabrication of a uniform three-dimensional mesoporous gold thin film (MPGF) onto a gold (Au) coated glass plate based on an electrochemical deposition method. Scanning electron microscopy images demonstrated that the resulting MPGF electrode had uniformly distributed pores with diameters of about 20 nm. The cyclic voltammetric behavior of [Fe(CN)(6)](4-/3-) coupled onto MPGF and Au electrodes demonstrated that the MPGF electrode had a higher electrocatalytic sensitivity and reversibility than the bare Au electrode. The Arg-Gly-Asp (RGD) sequence containing the peptide was immobilized on the MPGF and bare Au substrates. HeLa cancer cells were then cultured on the RGD peptide layer. The successful immobilization of the peptide and cells was confirmed by atomic force microscopy. The cell proliferation and viability were evaluated by cyclic voltammetry and Trypan blue dyeing assay. These results indicated that the RGD/MPGF modified electrodes showed an electrochemical sensitivity in the detection of cancer cells which is approximately three times higher, especially at low cell density, than RGD/Au electrodes. This much improved sensitivity of the MPGF modified electrode demonstrates the potential for the fabrication of a highly sensitive and low-cost cell-based chip for rapid cancer detection.


Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome.
The purpose of this study was to investigate demographic and clinical aspects of a group of Italian patients with Chronic Fatigue Syndrome (CFS) which have not yet been described, in order to compare them with International literature, and to better define certain clinical aspects of the syndrome with respect to the Fukuda et al. case definition. A detailed questionnaire was sent to patients with certified CFS diagnosed in a referral center and the data were collected two weeks later. Besides persistent fatigue, a clinical syndrome with infectious, neurological and rheumatological characteristics is outlined from the data. Demographic characteristics of Italian patients are very similar to those described in international literature. Therapy has yet to be validated with evidence-based studies in Italy. Studies on the prevalence of CFS in Italy are lacking and would be useful to better define the syndrome in this Mediterranean population.


[Clinical trials in the European Union and the Czech Republic in the years 2006, 2009 and 2012].
The aim of this paper is to analyze clinical trials conducted in the European Union and the Czech Republic in the years 2006, 2009 and 2012. The analysis has two main points of interest: characterization of the study population (the attention is paid to the age and gender profile of the subjects population as well as to the fact whether healthy volunteers and/or patients were enrolled) and clinical trials focus (the phases of clinical trials and therapeutic areas the trials were focused on). In addition, the aim of this paper is to discover possible differences between the EU and the CR and to find out if the implementation of Directive 2001/20/EC of the European Parliament and Council from 4th of April 2001 had any influence on the number of clinical trials being conducted (per therapeutic area and time). clinical trials focus participant population healthy volunteers placebo.


The impact of the World Health Organization classification and clonality assessment of posttransplant lymphoproliferative disorders on disease management.
The World Health Organization classification of posttransplant lymphoproliferative disorders divides them into 4 main categories. To classify cases of posttransplant lymphoproliferative disorders diagnosed in our institution according to the World Health Organization scheme and correlate the classification and clonality with clinical data. Cases of posttransplant lymphoproliferative disorders were reviewed. They were classified according to the World Health Organization scheme. Clonality was determined by flow cytometry and/or polymerase chain reaction. Patients' charts were reviewed. Thirty-one cases were identified. Median age was 33 years. There were 19 cases of kidney, 8 cases of liver, and 4 cases of bone marrow transplant. Immunosuppression consisted of cyclosporin A and prednisone (N = 24) or FK506 and prednisone (N = 7). Twenty cases (63%) were World Health Organization type 3, 7 cases (23%) type 2, 3 cases (6.4%) type 1, and 1 case type 4 posttransplant lymphoproliferative disorder. Ten patients received chemotherapy, 20 patients had reduction of immunosuppression, and 1 had no treatment. Follow-up was available on 25 patients. Seven (43.75%) of 16 with type 3 lesions with available follow-up died of their disease. Five of these patients received reduction of immunosuppression alone. Only 2 of 9 patients with type 3 disease who received chemotherapy died of disease. Two patients with type 2 disease died of unrelated causes. One patient is alive with disease; the remaining patients with types 1 and 2 disease are alive with no disease. The World Health Organization classification of posttransplant lymphoproliferative disorders is valuable in the identification of subtypes. It helps identify early lesions (1 and 2) requiring reduction of immunosuppression and type 3 disease, which requires chemotherapy from the outset.


Implementation intentions and efficient action initiation.
Implementation intentions ("If I encounter Situation X, then I'll perform Behavior Y!") are postulated to instigate automatic action initiation. In 4 studies, the hypothesis was tested that implementation intentions lead to immediate action initiation once the specified situation is encountered, even under conditions of high cognitive load. First, individuals whose action control is known to be hampered by disruptive cognitive business, such as opiate addicts under withdrawal (Study 1) and schizophrenic patients (Study 2), benefited from forming implementation intentions. Second, the beneficial effect of implementation intentions was also found in 2 experiments with university students (Studies 3 and 4) in which cognitive load was experimentally induced by using dual task paradigms. Results of the 4 studies suggest that forming implementation intentions instigates immediate action initiation that is also efficient.


Physician roles in aeromedical evacuation: current practices in USAF operations.
Physicians play an increasingly important role in the critical medical process of aeromedical evacuation (AE). Incomplete or inappropriate preparation for AE can result in increased patient discomfort, and in the worst cases, potentially serious or insurmountable in-flight medical problems. During military operations and in response to natural disasters, physicians are responsible for four processes necessary for a successful AE mission. These include: 1) AE screening, including determination of appropriate classification, precedence, and special medical requirements; 2) validation; 3) medical preparation; and 4) clearance. Physicians responsible for preparing patients for AE need to understand both the patient evacuation system and the unique medical aspects associated with AE. The U.S. military patient evacuation system is comprised of three principal transportation phases: casualty evacuation; inter-theater AE; and intra-theater AE. Important elements of the USAF AE system are patient movement requirements centers, the validating flight surgeon, aeromedical staging facilities, AE liaison teams, aeromedical crews, and critical care air transport (CCAT) teams. Important medical aspects unique to AE include the effects of flight physiology on medical conditions, oxygen limitations, and distinctive medication and supplies requirements.


Steep HIV prevalence declines among young people in selected Zambian communities: population-based observations (1995-2003).
Understanding the epidemiological HIV context is critical in building effective setting-specific preventive strategies. We examined HIV prevalence patterns in selected communities of men and women aged 15-59 years in Zambia. Population-based HIV surveys in 1995 (n = 3158), 1999 (n = 3731) and 2003 (n = 4751) were conducted in selected communities using probability proportional to size stratified random-cluster sampling. Multivariate logistic regression and trend analyses were stratified by residence, sex and age group. Absence, <30% in men and <15% in women in all rounds, was the most important cause of non-response. Saliva was used for HIV testing, and refusal was <10%. Among rural groups aged 15-24 years, prevalence declined by 59.2% (15.7% to 6.4%, P < 0.001) in females and by 44.6% (5.6% to 3.1%, P < 0.001) in males. In age-group 15-49 years, declines were less than 25%. In the urban groups aged 15-24, prevalence declined by 47% (23.4% to 12.4%, P < 0.001) among females and 57.3% (7.5% to 3.2%, P = 0.001) among males but were 32% and 27% in men and women aged 15-49, respectively. Higher educated young people in 2003 had lower odds of infection than in 1995 in both urban [men: AOR 0.29(95% CI 0.14-0.60); women: AOR 0.38(95% CI 0.19-0.79)] and rural groups [men: AOR 0.16(95% CI 0.11-0.25), women: AOR 0.10(95% CI 0.01-7.34)]. Although higher mobility was associated with increased likelihood of infection in men overall, AOR, 1.71(95% CI 1.34-2.19), prevalence declined in mobile groups also (OR 0.52 95% CI 0.31-0.88). In parallel, urban young people with > or =11 school years were more likely to use condoms during the last casual sex (OR 2.96 95% CI 1.93-4.52) and report less number of casual sexual partners (AOR 0.33 95% CI 0.19-0.56) in the last twelve months than lower educated groups. Steep HIV prevalence declines in young people, suggesting continuing declining incidence, were masked by modest overall declines. The concentration of declines in higher educated groups suggests a plausible association with behavioural change.


A multi-hospital system for disaster situations*.
From a review of the literature, it can be concluded that it is always advantageous and usually necessary to distribute the casualties of a disaster to several hosp-hospitals rather than allowing 1 hospital, the nearest to the scene, to bear the whole load. The potential of these hospitals would be enhanced if their preparedness and planning included anticipation of their functioning as part of a framework of the entire capacity of the medical services of an entire small country, or a region of a larger one. For the smooth functioning of this framework, central co-ordination and control of the distribution of the load, the movements within it, the strengthening of its various component parts is necessary and services other than medical (transport, communications, etc.) are essential. The establishment of a multihospital system for disaster situations for a whole region is suggested. This would integrate all medical facilities and services of the region, as well as promoting additional services, first horizontally integrated and later vertically, and would have a central governing body with full authority to prepare the system for the calamity and to execute the implementation of the plan when disaster occurs. This body may find it useful to base some of its decision in the planning as well as the implementing stage, on an assumed population of casualties that is characteristic for the region and on implications that may be drawn from the population.


Ambiguous genitalia.
To review the relevant publications since 2004 on surgery for female pseudohermaphroditism. Current controversies exist regarding the timing and technical aspects of female genital reconstruction and indeed the wisdom of performing these procedures in childhood. Nine articles, published between 2004 and the present time, were found worthy of being included in this review. The topics include surgical technique, short-term and long-term results, voiding function after feminizing genitoplasty, and the timing of surgery. Although results for surgery for congenital adrenal hyperplasia have been less than satisfactory when adults who had surgery in childhood are evaluated, all present reports include patients operated on using a variety of techniques many years ago. Rather than abandoning the efforts to repair this malformation early, we favor the continued development of more refined surgical techniques that may yield better results in the future.


[Research on functional diversity of microorganisms on jujube fruit surface in storage].
Disease during storage caused by microbial infection is a serious problem of jujube fruits. The aim of the study was to characterize the microbial diversity in stored jujube fruits. I used Biolog in experiment. The types of micro-plates were Filamentous Fungi micro-plate and Economicmicro-plate. There was much difference in microbial functional diversity on the surface of stored jujube fruit. The microbial functional diversity of stored 30 days was richer than it of stored 15 days. The diversity, homogeneity and average well color development of jujube used by fruit perservatives were lower than it not used by fruit preservatives. There were six kinds of the characteristic carbon. Our study firstly showed microbial diversity on the surface of stored jujube fruit. Biolog could be applied in the research on microbial functional diversity of fruit surface.


[Multiple sclerosis with higher cerebral dysfunction: a case report].
Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.


Receptor-mediated uptake of hypertriglyceridaemic VLDL remnants by mouse macrophages in vitro.
Following incubation of the VLDL isolated from hypertriglyceridaemic patients with normal human postheparin plasma VLDL remnants were obtained. 125I-VLDL remnants were taken up and catabolized by mouse macrophages in vitro. This was a receptor-dependent process. Unlabelled VLDL remnants added to the incubation medium inhibited the degradation of 125I-VLDL remnants in the cells. This could not be produced by the presence of VLDL or acetyl-LDL in the medium. It shows that mouse macrophages bind VLDL remnants by means of an other receptor than that for acetyl-LDL. The cell cholesterol content increased after incubation of the cells with VLDL remnants or acetyl-LDL, but not with native VLDL or LDL.


Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice.
Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus versus intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity.
The dentate gyrus is one of the few areas of the adult brain that continues to produce neurons and to express the embryonic polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown that mature granule cells require corticosterone for their survival. Thus, the aim of our work was to investigate the respective role of the different corticosteroid receptors on these three parameters in adrenalectomized rats. It was found that treatment with a low dose of the mineralocorticoid receptor agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell death. Treatment with a higher dose of aldosterone normalized cell proliferation whereas PSA-NCAM expression was normalized only by treatment with the glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of the mineralocorticoid receptor is sufficient to mediate the effects of corticosterone on neurogenesis and to protect mature cells from cell death whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA-NCAM expression.


Highly Sensitive Capacitive Flexible Pressure Sensor Based on a High-Permittivity MXene Nanocomposite and 3D Network Electrode for Wearable Electronics.
With the fast development of consumer electronic and artificial intelligence equipment, flexible pressure sensors (FPSs) have become a momentous component in the application of wearable electronic, electronic skin, and human-machine interfacing. The capacitive FPS possesses the merits of low energy consumption, high resolution, and fast dynamic response, so it is ideal for mobile and wearable electronics. However, capacitive FPS is vulnerable to electromagnetic interference and parasitic capacitance due to its low sensitivity. Microstructure or porous dielectric materials have been applied to improve the sensitivity of the capacitive FPS, but the high sensitivity is just limited to a narrow region. In this work, we propose a different strategy that incorporates a high-permittivity MXene nanocomposite dielectric with a 3D network electrode (3DNE) to improve the sensing performance of the capacitive FPS. Thanks to the high permittivity of the dielectric layer and hierarchical deformation of the electrode, the fabricated capacitive FPS exhibits a high sensitivity of 10.2 kPa-1 in the low pressure range (0-8.6 kPa) and still maintains a relatively high sensitivity of 3.65 kPa-1 with a near-linear response in a wide pressure range (8.6-100 kPa). In addition, the capacitive FPS can withstand over 20,000 times pressure loads without significant signal damping. Furthermore, the working mechanism of the capacitive FPS is illustrated by the finite element analysis (FEA) method and theoretical calculation. The application potential of the sensor in wearable electronics was demonstrated by human pulse wave monitoring and pressure mapping tests with a 4 × 6 sensor microarray.


Conduction disorders using the Evolut R prosthesis compared with the CoreValve: has anything changed?
We compared early postprocedural and midterm evolution of atrioventricular and intraventricular conduction disorders following implantation of the new generation Evolut R (ER) prosthesis in comparison with the previous generation CoreValve (CV) system using routinely recorded ECG up to 6-month follow-up. All consecutive patients treated by transcathether aortic valve implantation (TAVI) using the Medtronic self-expanding devices for symptomatic severe aortic stenosis in a single centre between October 2011 and February 2016 were considered for inclusion. ECGs recorded at baseline, day 1 after TAVI, discharge and 6 months were retrospectively analysed. At each time-point, intrinsic rhythm, PR interval, QRS axis and duration, and atrioventricular and intraventricular conduction were analysed. Atrioventricular and intraventricular conduction following TAVI at discharge and at 6 months were compared intrasubject at the different time intervals and between patients receiving the ER versus the CV prosthesis. Among the 113 patients included in the analysis (51% female, 83.3±6.2 years), 60 (53%) patients received the CV and 53 (47%) patients received the ER. Compared with patients in the CV group, those in the ER group had a lower Society of Thoracic Surgeons score (6.3±3.1vs 4.8±3.6, P=0.02). Patients in the ER group in comparison with those in the CV group more frequently had postprocedural PR interval (57%vs23%, respectively, P=0.004) and QRS prolongation (76%vs50%, P=0.03) at discharge. Incidence of complete atrioventricular block was similar between both groups (9%vs18%, P=0.3) up to 6-month follow-up. No difference in term of new left bundle branch block (LBBB) (34%vs28%, P=0.8) or permanent pacemaker implantation rates (32.1%vs31.7%, P=1.0) was reported. Patients with the ER had greater postprocedural atrioventricular and intraventricular conduction delays than those with the CV at discharge, with however similar incidence of high-degree atrioventricular block, new LBBB and permanent pacemaker implantation up to 6-month follow-up.


Excimer Laser Assisted Non-occlusive Anastomosis (ELANA). Our experience with a training model in vivo.
In this study the ELANA Technique has been reproduced in our experimental laboratory in order to verify its feasibility and reproducibility, the percentage of patent anastomosis in acute at different steps along the learning curve of the surgical team, specific problems related to the surgical technique. In 20 rabbits New Zealand 4kg body weight the training model in vivo proposed by Tulleken and coworkers has been reproduced, realizing 40 ELANA anastomosis. The model consists in the realization of two different end-to-side anastomosis on the abdominal aorta of each experimental animal, assisted by a special designed suction/excimer laser catheter, then connected by an end-to-end suture. After a few hours the animals are sacrificed and the by-pass site withdrawn and examined in order to verify the percentage of patency in acute. In the first 5 animals (group A), the anastomosis were realized using a jugular vein graft and the procedure results successful in only 3 cases out of ten (30%). For the following experiments - groups B, C and D where an aorta artery graft was used, the percentage of arterial flap retrieval was respectively 50%, 60% and 80%. ELANA is a feasible fascinating microsurgical technique for the realization of high flow, non-occlusive anastomosis. The rate of success results progressively higher along the learning curve of the surgical team. In our opinion, before the application of the ELANA technique on humans, a period of propaedeutic training in vivo on laboratory animals is essential for the dedicated team.


New mutant types at the ade3 locus of Saccharomyces cerevisiae.
Six mutants, allelic to ade3, were isolated after mutagenic treatment of a prototrophic strain of yeast. All six grow on medium supplemented with adenine alone and four respond to histidine. Supplementation with adenine plus histidine or methionine inhibits growth, but a mixture of these three is stimulatory. Heteroallelic diploids formed by the new mutants with the standard ade3 can resemble either parent or show an intermediate phenotype. The new mutants, unlike standard ade3, are not fully epistatic to ade2. The activities of three enzymes concerned in tetrahydrofolate metabolism have been assayed in the new and standard ade3 mutants and wild type. The only difference detected between the new and standard ade3 was in the levels of 10-formyltetrahydrofolate synthetase. Activity in the new mutants ranged from 36 to 109% of wild type compared with 10 to 12% in the standard ade3. Possible mechanisms to account for the varied phenotypes at the ade3 locus are discussed.


Learning from pairwise constraints by Similarity Neural Networks.
In this paper we present Similarity Neural Networks (SNNs), a neural network model able to learn a similarity measure for pairs of patterns, exploiting a binary supervision on their similarity/dissimilarity relationships. Pairwise relationships, also referred to as pairwise constraints, generally contain less information than class labels, but, in some contexts, are easier to obtain from human supervisors. The SNN architecture guarantees the basic properties of a similarity measure (symmetry and non negativity) and it can deal with non-transitivity of the similarity criterion. Unlike the majority of the metric learning algorithms proposed so far, it can model non-linear relationships among data still providing a natural out-of-sample extension to novel pairs of patterns. The theoretical properties of SNNs and their application to Semi-Supervised Clustering are investigated. In particular, we introduce a novel technique that allows the clustering algorithm to compute the optimal representatives of a data partition by means of backpropagation on the input layer, biased by a L(2) norm regularizer. An extensive set of experimental results are provided to compare SNNs with the most popular similarity learning algorithms. Both on benchmarks and real world data, SNNs and SNN-based clustering show improved performances, assessing the advantage of the proposed neural network approach to similarity measure learning.


Deciphering the effects of genotype and climatic factors on the performance, active ingredients and rhizosphere soil properties of Salvia miltiorrhiza.
Salvia miltiorrhiza Bunge is an important medicinal herb, which is widely cultivated in most parts of China. It has attracted considerable attention because of its pharmacological properties and potential health benefits. We used a field experiment to determine the effects of different genotypes and climatic factors on the performance (plant biomass, morphological parameters), active ingredients, rhizosphere soil physicochemical properties and microbial composition of S. miltiorrhiza at five cultivation locations. The results showed that these parameters were significantly different in the six different genotypes of S. miltiorrhiza from five producing areas. Genotype and soil physicochemical properties were the main factors affecting the growth traits of S. miltiorrhiza, while genotype, climate and soil physicochemical properties were the main factors affecting the content of active components of S. miltiorrhiza. Microbial phospholipid fatty acid analysis showed that the biomass of Gram-positive and Gram-negative bacteria was affected by the genotypes of S. miltiorrhiza plants, while the biomass of arbuscular mycorrhizal fungi, fungi, Gram-positive and Gram-negative bacteria was affected by climate factors. Based on the main results, DS993 was the most suitable genotype for S. miltiorrhiza in the five producing areas from the perspective of comprehensive growth traits and medicinal components, while DS993 and DS2000 were suitable for planting in Shandong province from the perspective of origin. DS996 is not suitable for all of the above production areas. These results are helpful to understand the ecological adaptability of different genotypes of S. miltiorrhiza resources, and to select appropriate S. miltiorrhiza genotypes for specific planting areas, so as to maximize yield and quality.


MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio.
Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.


Rapid single-molecule imaging in cyclic olefin copolymer channels.
Rapid preparation of high quality capture surfaces is a major challenge for surface-based single-molecule protein binding assays. Here we introduce a simple method to activate microfluidic chambers made from cyclic olefin copolymer for single-molecule imaging with total internal reflection fluorescence microscopy. We describe a surface coating protocol and demonstrate single-molecule imaging in off-the-shelf microfluidic parts that can be activated for binding assays within a few minutes. As the first example, biotinylated protein directly captured on the neutravidin-coated surface was detected using fluorescently labeled antibody. We then showed detection of a fusion construct containing green fluorescence protein and verified its single fluorophore behavior by observing stepwise photobleaching events. Finally, a target protein was identified in the crude cell lysate using antibody-sandwich complex formation. In all experiments, controls were completed to ensure that nonspecific binding to the surface was minimal. Based on our results, we conclude that the simple surface preparation described in this paper enables single-molecule imaging assays without time-consuming coating procedures.


Addressing the amorphous content issue in quantitative phase analysis: the certification of NIST standard reference material 676a.
A non-diffracting surface layer exists at any boundary of a crystal and can comprise a mass fraction of several percent in a finely divided solid. This has led to the long-standing issue of amorphous content in standards for quantitative phase analysis (QPA). NIST standard reference material (SRM) 676a is a corundum (α-Al(2)O(3)) powder, certified with respect to phase purity for use as an internal standard in powder diffraction QPA. The amorphous content of SRM 676a is determined by comparing diffraction data from mixtures with samples of silicon powders that were engineered to vary their specific surface area. Under the (supported) assumption that the thickness of an amorphous surface layer on Si was invariant, this provided a method to control the crystalline/amorphous ratio of the silicon components of 50/50 weight mixtures of SRM 676a with silicon. Powder diffraction experiments utilizing neutron time-of-flight and 25 keV and 67 keV X-ray energies quantified the crystalline phase fractions from a series of specimens. Results from Rietveld analyses, which included a model for extinction effects in the silicon, of these data were extrapolated to the limit of zero amorphous content of the Si powder. The certified phase purity of SRM 676a is 99.02% ± 1.11% (95% confidence interval). This novel certification method permits quantification of amorphous content for any sample of interest, by spiking with SRM 676a.


Asthma and obesity in the Middle East region: An overview.
This paper aims to cover the current status of asthma and obesity in the Middle East, as well as to introduce the various studies tying the two diseases; further expanding on the proposed mechanisms. Finally, the paper covers recent literature related to sphingolipids and its role in asthma, followed by recommendations and future directions. In preparation of this paper, we searched PubMed and Google Scholar, with no restrictions, using the following terms; asthma, obesity, Middle East, sphingolipids. We also used the reference list of retrieved articles to further expand on the pool of articles that were used for this review.


Relationship between hemispheric cerebral blood flow, central conduction time, and clinical grade in aneurysmal subarachnoid hemorrhage.
The relationship between central conduction time (CCT) and hemispheric cerebral blood flow (CBF) has been examined in 20 patients presenting with subarachnoid hemorrhage. A total of 63 combined CCT/CBF recordings were performed at various times throughout the hospital course of these patients, and the findings were correlated to clinical status. The initial-slope index of the CBF (CBF isi) was found to correlate well with clinical grade, and a gradation in flow was noted between the different neurological grades. Patients in Grades I and II (Hunt and Hess classification) had the highest flows (mean CBF isi = 47.2 +/- 8.1); Grade III patients had intermediate flows (mean CBF isi = 39.6 +/- 7.8); and Grade IV patients had the lowest flows (mean CBF isi = 32.0 +/- 6.4). While CCT tended to become increasingly prolonged with worsening grade, a significant difference could not be demonstrated between Grade I, II, and III patients. Only when Grade IV status was reached was the CCT significantly prolonged. When CBF isi and CCT were examined, a threshold relationship was noted between CBF isi and CCT prolongation. At flow values above 30, little change was noted in CCT, and CCT remained in the normal range. However, at flow values below 30, CCT became increasingly prolonged as blood flow diminished. The degree of CCT prolongation appeared to be directly proportional to the degree of blood flow diminution at flows below threshold.