Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities.
Transgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Abeta42 production and provide a model of Alzheimer-type amyloidosis. Here, we examine cognition in 6- and 18-month old transgenic mice expressing APPswe and PS1dE9, alone and in combination. Spatial reference memory was assessed in a standard Morris Water Maze task followed by assessment of episodic-like memory in Repeated Reversal and Radial Water maze tasks. We then used factor analysis to relate changes in performance in these tasks with cholinergic markers, somatostatin levels, and amyloid burden. At 6 months of age, APPswe/PS1dE9 double-transgenic mice showed visible plaque deposition; however, all genotypes, including double-transgenic mice, were indistinguishable from nontransgenic animals in all cognitive measures. In the 18-month-old cohorts, amyloid burdens were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). APPswe/PS1dE9 mice performed all cognitive tasks less well than mice from all other genotypes. Factor and correlation analyses defined the strongest correlation as between deficits in episodic-like memory tasks and total Abeta loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Abeta associated with amyloid deposition can disrupt cognitive circuits when the cholinergic and somatostatinergic systems remain relatively intact; and that episodic-like memory seems to be more sensitive to the toxic effects of Abeta.


Self-Construals and Social Anxiety Among Asian American College Students: Testing Emotion Suppression as a Mediator.
Although past studies have revealed ethnic and cultural variations in social anxiety, little research addresses why these variations might arise. The present study addressed this gap by examining emotion regulation as an explanatory mechanism that may account for such differences. Drawing from a culture-specific (Kitayama, Karasawa, & Mesquita, 2004), as well as process-based (Gross, 1998) model of emotion regulation, we hypothesized that emotion suppression would mediate associations between self-construals (interdependent and independent) and social anxiety symptoms. The data analytic sample consisted of 784 self-identified Asian American college students from 20 colleges/universities in the United States. Participants completed the study measures via a confidential, online questionnaire. Structural equation modeling (SEM) analyses indicated a significant indirect effect of both types of self-construal on social anxiety through emotion suppression. Specifically, an interdependent self-construal was associated with more (whereas an independent self-construal was associated with less) emotion suppression, which in turn, was associated with higher levels of social anxiety. Clinically, these findings suggest that an individual's emotion regulation strategy could serve as a proximal target of intervention among Asian American young adults.


Assessment of velocity fields through open-channel flows with an empiric law.
Most sewer managers are currently confronted with the evaluation of the water discharges, that flow through their networks or go to the discharge system, i.e. rivers in the majority of cases. In this context, the Urban Hydraulic Systems laboratory of the ENGEES is working on the relation between velocity fields and metrology assessment through a partnership with the Fluid and Solid Mechanics Institute of Strasbourg (IMFS). The responsibility is clearly to transform a velocity profile measurement, given by a Doppler sensor developed by the IMFS team, into a water discharge evaluation. The velocity distribution in a cross section of the flow in a channel has attracted the interests of many researchers over the years, due to its practical applications. In the case of free surface flows in narrow open channels the maximum velocity is below the free surface. This phenomenon, usually called "dip-phenomenon", amongst other things, raises the problem of the area explored in the section of measurements. The work presented here tries to create a simple relation making possible to associate the flow with the velocity distribution. This step allows to insert the sensor position into the flow calculation.


Alteration in Expression of miR-32 and FBXW7 Tumor Suppressor in Plasma Samples of Patients with T-cell Acute Lymphoblastic Leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and malignant neoplasm that arises from the hematopoietic T-cell precursors. Inactivation of FBXW7 gene is frequently observed in T-cell acute lymphoblastic leukemia, suggesting a significant tumor-suppressive role for FBXW7 in the pathobiology of this leukemia. Considering the role of microRNAs in cell proliferation and regulation of apoptosis, the aim of this study was to identify novel oncogenic microRNAs that suppress FBXW7 in patients with T-ALL. The expression levels of two bioinformatically predicted microRNAs - miR-32 and miR-107 were compared in patients with T-ALL and a control group. A total of 80 plasma samples were subjected to RNA extraction, and the microRNA expression profiles were assessed by the RT-qPCR. The expression level of miR-103 was used as the endogenous reference for normalization of quantitative data. The plasma levels of miR-32 and miR-107 in patients with T-ALL were significantly higher (5.65, P < 0.001) and lower (0.432, P = 0.002), respectively. On the other hand, the expression levels of FBXW7 gene were significantly downregulated by -76.9 fold in T-ALL patients (P < 0.001). The results of the ROC curve analysis indicated that overexpression of miR-32 might be used to distinguish T-ALL patients with reasonable sensitivity and specificity. miR-32 is considered as a novel oncomir that targets FBXW7 and might have a role in the etiology or progression of T-ALL. Furthermore, miR-32 can potentially serve as a non-invasive biomarker for detection of T-ALL.


Liver Metastases and Immune Checkpoint Inhibitor Efficacy in Patients With Refractory Metastatic Colorectal Cancer: A Secondary Analysis of a Randomized Clinical Trial.
Immune checkpoint inhibitors (ICIs) have limited activity in microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer. Recent findings suggest the efficacy of ICIs may be modulated by the presence of liver metastases (LM). To investigate the association between the presence of LM and ICI activity in advanced MSS colorectal cancer. In this secondary analysis of the Canadian Cancer Trials Group CO26 (CCTG CO.26) randomized clinical trial, patients with treatment-refractory colorectal cancer were randomized in a 2:1 fashion to durvalumab plus tremelimumab or best supportive care alone between August 10, 2016, and June 15, 2017. The primary end point was overall survival (OS) with 80% power and 2-sided α = .10. The median follow-up was 15.2 (0.2-22.0) months. In this post hoc analysis performed from February 11 to 14, 2022, subgroups were defined based on the presence or absence of LM and study treatments. Durvalumab plus tremelimumab or best supportive care. Hazard ratios (HRs) and 90% CIs were calculated based on a stratified Cox proportional hazards regression model. Plasma tumor mutation burden at study entry was determined using a circulating tumor DNA assay. The primary end point of the study was OS, defined as the time from randomization to death due to any cause; secondary end points included progression-free survival (PFS) and disease control rate (DCR). Of 180 patients enrolled (median age, 65 [IQR, 36-87] years; 121 [67.2%] men; 19 [10.6%] Asian, 151 [83.9%] White, and 10 [5.6%] other race or ethnicity), LM were present in 127 (70.6%). For patients with LM, there was a higher proportion of male patients (94 of 127 [74.0%] vs 27 of 53 [50.9%]; P = .005), and the time from initial cancer diagnosis to study entry was shorter (median, 40 [range, 8-153] vs 56 [range, 14-181] months; P = .001). Plasma tumor mutation burden was significantly higher in patients with LM. Patients without LM had significantly improved PFS with durvalumab plus tremelimumab (HR, 0.54 [90% CI, 0.35-0.96]; P = .08; P = .02 for interaction). Disease control rate was 49% (90% CI, 36%-62%) in patients without LM treated with durvalumab plus tremelimumab, compared with 14% (90% CI, 6%-38%) in those with LM (odds ratio, 5.70 [90% CI, 1.46-22.25]; P = .03). On multivariable analysis, patients without LM had significantly improved OS and PFS compared with patients with LM. In this secondary analysis of the CCTG CO.26 study, the presence of LM was associated with worse outcomes for patients with advanced colorectal cancer. Patients without LM had improved PFS and higher DCR with durvalumab plus tremelimumab. Liver metastases may be associated with poor outcomes of ICI treatment in advanced colorectal cancer and should be considered in the design and interpretation of future clinical studies evaluating this therapy.


Health-related quality of life in indigenous Sami schoolchildren in Sweden.
To investigate health-related quality of life (HRQOL) in indigenous Sami schoolchildren in Sweden and its associations with sex, age, enculturation and ethnicity-related negative treatment. The study population was comprised of all children in grades 6-12 (ages 12-18 years) who attended specific Sami school programmes in Sweden. HRQOL was measured by the Kidscreen-52 self-report form, which was filled in at school (n = 121). The indigenous Sami children in Sweden experienced lower HRQOL than Swedish children in general, with regard to their school situation, financial resources, parents' relations, physical well-being and social support from peers. In Sami children, functioning and well-being generally decreased by older age group and girls reported lower physical well-being, more negative feelings and more negative self-perception than boys. Finally, more than half of the Sami children had experienced ethnicity-related negative treatment, and these children reported a robustly lower functioning and well-being compared with those without this experience. In some aspects of HRQOL, indigenous Sami schoolchildren with an explicit ethnic identity experienced less favourable functioning and well-being than Swedish children in general, which is worrisome. A high degree of ethnicity-related negative treatment may partly explain this lower HRQOL in Sami children.


Investigating women's preference for sildenafil or tadalafil use by their partners with erectile dysfunction: the partners' preference study.
Several preference studies comparing a short-acting with a longer-acting phosphodiesterase type 5 inhibitor have been conducted in men. Most men in those studies preferred tadalafil rather than sildenafil, and recent post hoc analysis of one study described several factors associated with men's treatment preference. No prospective studies have investigated the woman partners' preferences. To investigate the treatment preference of women who were partners of men using oral medications for erectile dysfunction (ED) in a single-center open-label crossover study. One hundred heterosexual couples in stable relationships, with male partners having ED based on the erectile function subscale of the International Index of Erectile Function, were randomly assigned to receive sildenafil or tadalafil for a 12-week phase, followed by another 12-week period using the alternate drug. Male and female participants completed sexual event diaries during both study phases, and the female participants were interviewed at baseline, midpoint, and end of study. Primary outcome data were the women's final interviews during which they were asked which drug they preferred and their reasons for that preference. A total of 79.2% of the women preferred their partners' use of tadalafil, while 15.6% preferred sildenafil. Preference was not affected by age or treatment order randomization. Women preferring tadalafil reported feeling more relaxed, experiencing less pressure, and enjoying a more natural or spontaneous sexual experience as reasons for their choice. Mean number of tablets used, events recorded, events per week, and days between events were not significantly different during each study phase. Women's preferences were similar to men when using these two drugs. While the women's reasons for preferring tadalafil emphasized relaxed, satisfying, longer-lasting sexual experiences, those preferring sildenafil focused on satisfaction and drug effectiveness for their partner.


Mechanisms of adverse drug reactions and interactions in veterinary medicine.
Rapid advances in research in basic pharmacology and the productivity of the pharmaceutical industry have resulted in the introduction of many new drugs for the veterinary profession. The availability of such a large number of drugs has stimulated their concomitant use with the hope that maximum therapeutic effectiveness will be achieved. Indeed, modern therapeutics in veterinary medicine often necessitates the simultaneous administration of several drugs. With the increased use of multiple drug therapy has come the problem of drug interactions, which necessitates greater professional awareness and responsibility on the part of the veterinarian. Drug interactions are essentially a problem of modern medicine.


Factors affecting bovine corneal endothelial cell density in vitro.
To examine factors influencing the density and contact inhibition of bovine corneal endothelial cells cultured in vitro. Cell counts were performed on bovine corneal endothelial cells cultured for various times in the presence of 10% fetal calf serum, with or without varying concentrations of growth factors, 5% dextran T-500, or 2% chondroitin sulphate, at 32 degrees C or 37 degrees C, and after treatment with beta galactosidase. Both basic fibroblast growth factor (FGFb) and retinal crude extract (RCE), but neither epidermal growth factor (EGF) nor acidic fibroblast growth factor (FGFa), increased endothelial cell density in vitro (p < 0.05). Continuous exposure to RCE resulted in a higher cell density than did a 24 hour pulse (p < 0.01), and higher cell densities were achieved at 37 degrees C than at 32 degrees C (p < 0.0001). In the absence of RCE, dextran T-500 increased cell density modestly (p < 0.05); in the presence of RCE, the addition of dextran T-500 had no effect on final cell density, whereas chondroitin sulphate significantly decreased final cell density (p < 0.01). In the absence of exogenous growth factors, beta galactosidase treatment resulted in a 50% increase in final cell density compared with controls (p < 0.0001). Bovine corneal endothelial cell growth can be augmented under conditions different from those used in corneal preservation systems. The final cell density in a confluent monolayer can be increased by treatment with beta galactosidase, suggesting that corneal endothelial cells may be contact inhibited through a beta galactosidase sensitive receptor system.


Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: kinetic analysis of covalent binding and DNA-induced hydrolysis.
The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via an SN2 reaction from an intercalated state. Although the epoxide hydrolyzes rapidly in H2O (0.6 s-1 at 25 degrees C), very high yields of DNA adduct result. Experimental binding data were fit to a model in which the epoxide forms a reversible complex with calf thymus DNA (Kd = 0.43 mg ml-1, or 1.4 mM monomer equivalents) and reacts with guanine with a rate of 35 s-1. Stopped-flow kinetic analysis revealed attenuation of fluorescence in the presence of DNA that was dependent on DNA concentration. Kinetic spectral analysis revealed that this process represents conjugation of epoxide with DNA, with an extrapolated rate maximum of 42 s-1 and half-maximal velocity at a DNA concentration of 1.8 mg ml-1 (5.8 mM monomer equivalents). The rate of hydrolysis of the epoxide was accelerated by calf thymus DNA in the range of pH 6-8, with a larger enhancement at the lower pH (increase of 0.23 s-1 at pH 6.2 with 0.17 mg DNA ml-1). The same rate enhancement effect was observed with poly[dA-dT].poly[dA-dT], in which the epoxide can intercalate but not form significant levels of N7 purine adducts, and with single-stranded DNA. The increased rate of hydrolysis by DNA resembles that reported earlier for epoxides of polycyclic hydrocarbons and is postulated to involve a previously suggested localized proton field on the periphery of DNA. The epoxide preferentially intercalates between base pairs, and the proton field is postulated to provide acid catalysis to the conjugation reaction.


Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review.
» Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.» The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.» Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.» Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.


Enhancing the Efficiency and Stability of Perovskite Solar Cells through Defect Passivation and Controlled Crystal Growth Using Allantoin.
In this study, we present a robust approach that concurrently manages crystal growth and defect passivation within the perovskite layer through the introduction of a small molecule additive─allantoin. The precise regulation of crystal growth in the presence of allantoin yields perovskite films characterized by enhanced morphology, larger grain size, and improved grain orientation. Notably, the carbonyl and amino groups present in allantoin passivate under-coordinated Pb2+ and I- defects, respectively, through molecular interactions. Trap density in the perovskite layer is measured, and it is 0.39 × 1016 cm-3 for the allantoin-incorporated device and 0.83 × 1016 cm-3 for the pristine device. This reduction in defects leads to reduced trap-assisted nonradiative recombination, as confirmed by the photoluminescence, transient photo voltage, and impedance measurements. As a result, when these allantoin-incorporated perovskite films are implemented as the active layer in solar cells, a noteworthy efficiency enhancement to 20.63% is attained, surpassing the 18.04% of their pristine counterparts. Furthermore, devices with allantoin exhibit remarkable operational stability, maintaining 80% of their efficiency even after 500 h of continuous illumination, whereas the pristine device degraded to 65% of its initial efficiency in 400 h. Also, allantoin-incorporated devices exhibited exceptional stability against high humidity and elevated temperatures.


From Precision Metapharmacology to Patient Empowerment: Delivery of Self-Care Practices for Epilepsy, Pain, Depression and Cancer Using Digital Health Technologies.
To improve long-term outcomes of therapies for chronic diseases, health promotion and lifestyle modifications are the most promising and sustainable strategies. In addition, advances in digital technologies provide new opportunities to address limitations of drug-based treatments, such as medication non-adherence, adverse effects, toxicity, drug resistance, drug shortages, affordability, and accessibility. Pharmaceutical drugs and biologics can be combined with digital health technologies, including mobile medical apps (digital therapeutics), which offer additional clinical benefits and cost-effectiveness. Promises of drug+digital combination therapies are recognized by pharmaceutical and digital health companies, opening opportunities for integrating pharmacotherapies with non-pharmacological interventions (metapharmacology). Herein we present unique features of digital health technologies which can deliver personalized self-care modalities such as breathing exercises, mindfulness meditation, yoga, physical activity, adequate sleep, listening to preferred music, forgiveness and gratitude. Clinical studies reveal how aforementioned complimentary practices may support treatments of epilepsy, chronic pain, depression, cancer, and other chronic diseases. This article also describes how digital therapies delivering "medicinal" self-care and other non-pharmacological interventions can also be personalized by accounting for: 1) genetic risks for comorbidities, 2) adverse childhood experiences, 3) increased risks for viral infections such as seasonal influenza, or COVID-19, and 4) just-in-time stressful and traumatic circumstances. Development and implementation of personalized pharmacological-behavioral combination therapies (precision metapharmacology) require aligning priorities of key stakeholders including patients, research communities, healthcare industry, regulatory and funding agencies. In conclusion, digital technologies enable integration of pharmacotherapies with self-care, lifestyle interventions and patient empowerment, while concurrently advancing patient-centered care, integrative medicine and digital health ecosystems.


The effect of chronic cadmium toxicity on blood pressure and plasma viscosity.
Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence of environmental and industrial pollution. The aim of this study was to investigate the effect of chronic Cd toxicity on blood pressure and plasma viscosity. Experimental group rats were given doses that contained 15 ppm CdCl(2) in drinking water for 8 weeks. The systolic blood pressure and heart rate were measured from rats' tails and recorded by plethysmography every two weeks. Blood samples were drawn, Cd levels were determined by atomic absorption spectrophotometer and plasma viscosity values by viscometer. Blood Cd levels were found to be significantly higher in the experimental group compared to the control group (p < 0.001). The whole blood analysis was made by an analyzer. Polymorphonuclear leukocytes and monocytes increased (p < 0.01) and lymphocyte number (p < 0.05) decreased in the experimental group. Viscosity values were 2.21 ± 0.54 and 1.62 ± 0.31 centipoises in the experimental and control groups, respectively (p < 0.001). In the experimental group, changes in systolic blood pressure between weeks were significant (p < 0.001) and were found to be correlated with plasma viscosity (p < 0.001). In the experimental group, changes in heart rate between weeks were significant (p < 0.001). According to our findings, Cd toxicity may lead to an increase in blood pressure by increasing plasma viscosity.


Glyphosate uncouples gas exchange and chlorophyll fluorescence.
Changes in chlorophyll fluorescence have often been advocated as a sensitive biomarker of plant stress, assuming that any kind of plant stress serious enough to affect plant growth will also affect photosynthesis. Glyphosate affects photosynthetic electron transport indirectly by inhibiting sink processes. The question is how fast this inhibition can be observed on CO(2) assimilation and ultimately on chlorophyll fluorescence? Experiments measuring CO(2) assimilation, conductance and chlorophyll fluorescence using four Kautsky curve parameters on barley (Hordeum vulgare L.) exposed to increasing doses of glyphosate showed a total cessation of CO(2) fixation and conductance without significant changes in chlorophyll fluorescence. The decrease in CO(2) fixation and conductance was significant 1 day after spraying and corresponded well to the decrease in biomass 5-7 days after spraying. A total cessation of CO(2) assimilation can take place without affecting chlorophyll fluorescence. Hypotheses concerning what happens to the energy from the photosynthetic apparatus that is not used for CO(2) assimilation are discussed. The results question the use of chlorophyll fluorescence as a universal indicator of stress on photosynthetic processes. Also, they demonstrate that changes in gas-exchange parameters are more sensitive biomarkers for glyphosate toxicity compared with chlorophyll fluorescence.


Biochemical mechanisms in the effects of kerosene on airways of experimental animals.
The biochemical mechanisms involved in the bronchoconstriction and airway hyperresponsiveness induced by the acute inhalation of aerosol of kerosene in experimental animals and the inflammatory changes induced by subchronic inhalation of the aerosol or smoke of kerosene were investigated. The results obtained indicate that the inhibition of the acetylcholinesterase activity in airways and the decrease in the efficiency of the calcium uptake by the sarcoplasmic reticulum are some of the mechanisms involved in the airway hyperreactivity induced by kerosene. The levels of cyclic nucleotides in lungs and trachea and the histamine concentration in blood did not change in the animals exposed to the aerosol of kerosene. The subchronic exposure to vapors of kerosene or its combustion fumes, induced an increase in the activity of lysosomal enzymes in lungs which can be an explanation of the inflammatory response induced in lungs by this agent.


Influence of acquisition parameters on the magnitude of cone beam computed tomography artifacts.
To evaluate the influence of kilovoltage (kVp) and metal artifact reduction tool (MAR) on the magnitude of cone beam CT (CBCT) artifacts. A titanium and zirconia implants were inserted alternately in a posterior region of a mandible. CBCT exams were acquired with ProMax 3D (Planmeca Oy, Helsinki, Finland) and Picasso Trio machines (Vatech, Hwaseong, South Korea) using 70 kVp, 80 kVp and 90 kVp with and without MAR activation. The other exposure factors remained fixed at 5mA, field of view 80 × 50 mm and voxel 0.20 mm. The scans were performed before and after the insertion of the implants. Regions of interest were determined in different distances from the artifact production area (15, 25 and 35 mm) in an axial image, in which standard deviation (SD) of grayscale values was measured and contrast-to-noise ratio (CNR) was calculated. Analysis of variance was used to compare the data. Overall, in cases where the artifact was pronounced, MAR was efficient in reducing SD values. MAR also improved the CNR of ProMax images, but did not affect the Picasso images. Additionally, the higher was the kVp, the lower was the SD value and the higher was the CNR in both machines. In both machines, increasing kVp and MAR are effective in decreasing the CBCT artifacts in all their magnitude when they are pronounced. Therefore, the professionals should choose one of those options or even both considering the purpose of the CBCT imaging and radiation dose for the patient.


The American Society of Thoracic Surgery Score versus EuroSCORE I and EuroSCORE II in Israeli Patients Undergoing Cardiac Surgery.
Recently, Israel established the first national-level adult cardiac surgery database, which was linked to the Society of Thoracic Surgeons (STS). To validate and compare the STS predicted risk of mortality (PROM) to logistic EuroSCORE I (LESI) and EuroSCORE II (ESII) in Israeli patients undergoing cardiac surgery. We retrospectively studied 1279 consecutive patients who underwent cardiac surgeries with a calculable PROM. Data were prospectively entered into our database and used to calculate PROM, LESI, and ESII. Scores were normalized and correlated using linear regression and Pearson's test. To examine model calibration, we plotted the total observed versus expected mortality for each score and across five risk-score subgroups. Model discrimination was assessed by measuring the area under the receiver operating curves. The observed 30-day operative mortality was 1.95%. The median (IQ1; IQ3) PROM, LESI, and the ESII scores were 1.45% (0.69; 3.22), 4.54% (2.28; 9.27), and 1.88% (1.18; 3.54), respectively, with observed over expected ratios of 0.63 (95% confidence interval [95%CI] 0.42-0.93), 0.59 (95%CI 0.40-0.87), and 0.24 (95%CI 0.17-0.36), respectively, (STS vs. ESII P = 0.36, STS vs. LESI P = 0.0001). There was good correlation among all scores. All models overestimated mortality. Model discrimination was high and similar for all three scores. Model calibration of the STS, PROM, and ESII were more accurate than the LESI, particularly in higher risk subgroups. All scores overestimated mortality. In Israeli patients, the STS, PROM, and ESII risk-scores were more reliable metrics than LESI, particularly in higher risk patients.


Adenovirus E1B 55-kilodalton oncoprotein inhibits p53 acetylation by PCAF.
The adenovirus E1B 55-kDa protein binds to cellular tumor suppressor p53 and inactivates its transcriptional transactivation function. p53 transactivation activity is dependent upon its ability to bind to specific DNA sequences near the promoters of its target genes. It was shown recently that p53 is acetylated by transcriptional coactivators p300, CREB bidning protein (CBP), and PCAF and that acetylation of p53 by these proteins enhances p53 sequence-specific DNA binding. Here we show that the E1B 55-kDa protein specifically inhibits p53 acetylation by PCAF in vivo and in vitro, while acetylation of histones and PCAF autoacetylation is not affected. Furthermore, the DNA-binding activity of p53 is diminished in cells expressing the E1B 55-kDa protein. PCAF binds to the E1B 55-kDa protein and to a region near the C terminus of p53 encompassing Lys-320, the specific PCAF acetylation site. We further show that the E1B 55-kDa protein interferes with the physical interaction between PCAF and p53, suggesting that the E1B 55-kDa protein inhibits PCAF acetylase function on p53 by preventing enzyme-substrate interaction. These results underscore the importance of p53 acetylation for its function and suggest that inhibition of p53 acetylation by viral oncoproteins prevent its activation, thereby contributing to viral transformation.


The practise and practice of Bourdieu: the application of social theory to youth alcohol research.
Some years ago Australian anthropologist David Moore criticised the predominant form of understanding youth alcohol consumption for residing with biomedical approaches that individualise and ultimately stigmatise drinking behaviour and 'ignore' the social context of consumption. Of interest here is the ongoing insufficient integration of alternative approaches to understanding young people's drinking. This paper presents theoretically informed qualitative research that investigates why young Australian females (aged 14-17) drink and how social and cultural context form the basis, rather than the periphery, of their drinking experience. We demonstrate the utility of Pierre Bourdieu's sociological framework for delving beyond the dichotomy of young people's drinking decisions as either a determination of their cultural environment or the singular result of a rational individual's independent decision-making. The paper is presented in two parts. First, we provide the interpretation, or 'practise', of Bourdieu's concepts through an outline and application of his complex theoretical constructs. Specifically, the concept of symbolic capital (or social power) is applied. Second, our explication of Bourdieu's 'practice', or epistemological contributions, offers a methodologically grounded example to other researchers seeking to attain more complete understandings of the social processes underpinning youth alcohol consumption. A sociological approach to exploring the complex relationship between drinking and contextual social factors amongst young Australian females is an unchartered area of enquiry. We contribute new theoretically supported insights to create a more complete picture of young females' drinking behaviours.


Preweaning iron deficiency increases non-contingent responding during cocaine self-administration in rats.
Iron deficiency (ID) is the most prevalent single-nutrient deficiency worldwide. There is evidence that ID early in development (preweaning in rat) causes irreversible neurologic, behavioral, and motor development deficits. Many of these effects have been attributed to damage to dopamine systems, including ID-induced changes in transporter and receptor numbers in the striatum and nucleus accumbens. These mesolimbic dopaminergic neurons are, in part, responsible for mediating reward and thus play a key role in addiction. However, there has been relatively little investigation into the behavioral effects of ID on drug addiction. In 2002, we found that rats made ID from weaning (postnatal day 21) and throughout the experiment acquired cocaine self-administration significantly more slowly than controls and failed to increase responding when the dose of the drug was decreased. In the present study, we assessed addiction for self-administered cocaine in rats with a history of preweaning ID only during postnatal days 4 through 21, and iron replete thereafter. The results showed that while ID did not affect the number of cocaine infusions or the overall addiction-like behavior score, ID rats scored higher on a measure of continued responding for drug than did iron replete controls. This increase in responding, however, was less goal-directed as ID rats also responded more quickly to the non-rewarded manipulandum than did control rats. Thus, while ID early in infancy did not significantly increase addiction-like behaviors for cocaine in this small study, the pattern of data suggests a possible underlying learning or performance impairment. Future studies will be needed to elucidate the exact neuro-behavioral deficits that lead to the increase in indiscriminate responding for drug in rats with a history of perinatal ID.


Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices.
The optimal management of ruptured gastric varices in patients with cirrhosis has not been codified yet. The present study reports the use of transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory gastric variceal bleeding. Thirty-two consecutive patients were included. All had been unresponsive to vasoactive agents infusion, sclerotherapy, and/or tamponade and were considered poor surgical candidates. They were followed-up until death, transplantation, or at least 1 year (median: 509 days; range 4 to 2,230). Hemostasis was achieved in 18 out of 20 patients actively bleeding at the time of the procedure. In the whole sample of 32 patients, rebleeding rates were 14%, 26%, and 31%, respectively at 1 month, 6 months, and 1 year. De novo encephalopathy was observed in 5 (16%) patients. Seven patients experienced complications and consequently 4 of these patients died. TIPS primary patency rates were 84%, 74%, and 51%, respectively, at 1 month, 6 months, and 1 year. For the same periods of time, survival rates were 75%, 62%, and 59%. These results suggest that TIPS can be used in cirrhotic patients with refractory gastric variceal bleeding and are effective in achieving hemostasis as well as in preventing rebleeding.


Human metabolic correlates of body mass index.
A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold (p<0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all Pheterogeneity >0.05). In total, 110 metabolites were associated with BMI at the p<0.05 level. These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between high BMIs and disease risk.


Hemophagocytic Lymphohistiocytosis and Pancreatic Cancer: A Rare Association.
Hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic syndrome (HPS) is a life-threatening and relatively rare condition that usually presents as a multisystem febrile illness. It is associated with excessive activation of the immune system and hypercytokinemia, leading to an unregulated aggregation of macrophages and lymphocytes. Here, we present the first likely case of HLH with metastatic pancreatic carcinoma being the underlying etiology. A 44-year-old male with past medical history significant for heart transplant for which he was on tacrolimus, End-Stage Renal Disease (ESRD) on hemodialysis, recently treated CMV viremia, and necrotizing pancreatitis presented to the emergency with complaints of chills, decreased appetite, worsening non-bloody emesis, and dull left upper quadrant abdominal pain with radiation to the back for four days. No shortness of breath, fever, diarrhea, or blood in the stool was reported. Vitals on admission were blood pressure of 90/61 mmHg, a heart rate of 110 beats per minute, temperature of 98.1 °F, and respiratory rate of 18 per minute. Physical exam was significant for scleral icterus, decreased bibasilar breath sounds, moderate abdominal tenderness in the left flank and left upper abdominal quadrant without any palpable mass, and 1+ bilateral pedal edema. The remainder of the physical examination was benign. Electrocardiogram (EKG) showed sinus tachycardia without any ischemic changes, and chest x-ray showed mild pulmonary edema. Initial blood workup revealed WBC at 8.3 k/uL, hemoglobin of 10.2 g/dL, platelet count of 90 k/uL, and BUN/creatinine of 45/5.8 (baseline 40/5.0). Cardiac workup showed an elevated high sensitivity troponin level of 2479 pg/mL and brain natriuretic peptide (BNP) of 600 (0-100 pg/mL). The hepatobiliary profile showed an aspartate transaminase (AST) level of 2645 U/L, an alanine transaminase (ALT) of 2935 U/L, alkaline phosphatase (ALP) of 106 U/L, and lipase of 61 U/L, with total and conjugated bilirubin of 3.5 mg/dL and 2.1 mg/dL, respectively. Transthoracic echocardiogram (TTE) showed reduced left ventricular size with hyperdynamic systolic function. Computerized tomography (CT) scan of the abdomen (Fig. 1) revealed numerous new pulmonary nodules, ring-enhancing lesions within the liver, hyperenhancement of the pancreas with walled-off necrosis, and splenomegaly. Microbiological work-up was positive for cytomegalovirus (CMV) serologies (IgM and IgG) but absent viral load on Polymerase Chain Reaction (PCR). The initial diagnosis was systemic inflammatory respiratory syndrome (SIRS), likely septic versus distributive in the setting of pancreatitis, demand mediated non-ST segment elevation myocardial infarction (NSTEMI), and shock liver. Tacrolimus was held, and the patient was started on broad-spectrum antibiotics including vancomycin and cefepime for sepsis of unknown origin along with vasopressors for hypotension, requiring admission to the medical intensive care unit. Blood and urine cultures were collected on admission which remained negative throughout the course of hospital. CA19-9 levels were found elevated at 5587 U/mL. Liver biopsy was consistent with poorly differentiated adenocarcinoma of pancreatic origin. Both Infectious Disease and Hematology were consulted due to broad differential diagnoses. Due to the patient's continued hemodynamic instability and nonresponsiveness to the antibiotics, HLH was suspected with supporting labs as follows: ferritin 55,740 ng/mL (22-322 ng/mL), triglycerides 177 mg/dL (30-150 mg/dL), and fibrinogen 244 mg/dL (173-454 mg/dL), thus conferring 70-80% probability of HPS based on H-score. Soluble IL-2 R levels came out at 19,188 pg/mL (ref range 175-858 pg/mL). The patient couldn't be started on HLH treatment due to initial concerns of underlying infection and the delay in results of soluble IL-2 Receptor (IL-2 R) levels. The infection as a possible etiology was ruled out due to negative blood and urine cultures and HLH was attributed to pancreatic cancer. A marrow biopsy couldn't be pursued as the patient died within a week of hospitalization. An autopsy was not performed as per family's request. HLH can occur secondary to solid cell malignancies including those from the pancreas and should be kept high in the differential in critically ill cancer patients who are nonresponsive to antibiotics. H-score has been reported to be a more sensitive tool compared to the HLH protocol, especially if used earlier during the presentation. Further research is needed to compare diagnostic efficacy for HLH protocol verses H-score especially in critically ill patients as they might benefit from steroid trial.


Colonic volvulus: presentation and management in metropolitan Minnesota, United States.
Management approaches for colonic volvulus are infrequently described in the literature in the United States, and many studies only report operative cases. The aim of this study was to define the demographics, diagnostic and treatment approaches, and outcomes for patients with this disorder in the United States. This study is a retrospective review. The study was conducted at a 7-hospital health system. All patients diagnosed with colonic volvulus by International Classification of Diseases, Ninth Revision code were included. The primary outcomes measured were recurrence, complications, and mortality. One hundred three cases of volvulus (50 sigmoid, 53 cecal) were identified in 92 patients. Compared with cecal volvulus, sigmoid volvulus was more common in men, patients with neurologic diagnoses, and residents of skilled nursing home. Eighty-five percent of the cases presented were acutely obstructed. The diagnosis was established by abdominal x-ray (17%), contrast enema study (27%), CT scan (35%), or laparotomy (17%). Abdominal x-rays were insufficient for definitive diagnosis in 85% of cecal and 49% of sigmoid cases (p = 0.002). All patients with cecal volvulus were treated surgically. Seventy-nine percent of patients with sigmoid volvulus underwent successful nonoperative reduction, of whom 38% had subsequent surgery. Fifty-eight percent of patients with sigmoid volvulus were treated operatively. Resection with primary anastomosis was chosen in most cases (78%). Resection with end ostomy (10%), reduction and pexy (7%), and reduction alone (4%) were other approaches. The mortality rate was 5% (cecal 0%, sigmoid 10%; p = 0.012). There were no readmissions for recurrent cecal volvulus. Nonoperative treatment for sigmoid volvulus often failed (48%). Complication rates were higher in sigmoid volvulus cases (cecal 17%, sigmoid 34%; p = 0.047). This study was limited by its retrospective, nonexperimental design. Although incidences of cecal and sigmoid volvulus are similar in the present series, sigmoid volvuli are more common in men, individuals with neurologic disease, and residents of nursing homes. Plain radiograph is insufficient to confirm cecal volvulus. The diagnosis is most often made with CT scans. The nonoperative management of sigmoid volvulus is associated with a high recurrence rate.


A computer-based incentivized food basket choice tool: Presentation and evaluation.
To develop and evaluate a low-cost computer-based tool to elicit dietary choices in an incentive compatible manner, which can be used on-line or as part of a laboratory study. The study was conducted with around 255 adults. Respondents were asked to allocate a fixed monetary budget across a choice of around a hundred grocery items with the prospect of receiving these items with some probability delivered to their home by a real supermarket. The tool covers a broad range of food items, allows inference of macro-nutrients and calories, and allows the researcher to fix the choice set participants can choose from. We compare the information derived from our incentivized tool, and compare it to alternative low-cost ways of measuring dietary intake, namely the food frequency questionnaire and a one-shot version of the 24-hour dietary recall, which are both based on self-reports. We compare the calorie intake indicators derived from each tool with a number of biometric measures for each subject, namely weight, body-mass-index (BMI) and waist size. The results show that the dietary information collected is only weakly correlated across the three methods. We find that only the calorie intake measure from our incentivized tool is positively and significantly related to each of the biometric indicators. Specifically, a 10% increase in calorie intake is associated with a 1.5% increase in BMI. By contrast, we find no significant correlations for either of the two measures based on self-reports. The computer-based tool is a promising new, low-cost measure of dietary choices, particularly in one-shot situations where such behaviours are only observed once, whereas other tools like 24-hour dietary recalls and food frequency questionnaires may be more suited when they are administered repeatedly. The tool may be useful for research conducted with limited time and budget.


Functional assessment of mycosporine-like amino acids in Microcystis aeruginosa strain PCC 7806.
The biological role of the widespread mycosporine-like amino acids (MAAs) in cyanobacteria is under debate. Here, we have constructed and characterized two mutants impaired in MAA biosynthesis in the bloom-forming cyanobacterium Microcystis aeruginosa PCC 7806. We could identify shinorine as the sole MAA type of the strain, which is exclusively located in the extracellular matrix. Bioinformatic studies as wells as polymerase chain reaction screening revealed that the ability to produce MAAs is sporadically distributed within the genus. Growth experiments and reactive oxygen species quantification with wild-type and mutant strains did not support a role of shinorine in protection against UV or other stress conditions in M. aeruginosa PCC 7806. The shinorine content per dry weight of cells as well as transcription of the mys gene cluster was not significantly elevated in response to UV-A, UV-B or any other stress condition tested. Remarkably, both mutants exhibited pronounced morphological changes compared with the wild type. We observed an increased accumulation and an enhanced hydrophobicity of the extracellular matrix. Our study suggests that MAAs in Microcystis play a negligible role in protection against UV radiation but might be a strain-specific trait involved in extracellular matrix formation and cell-cell interaction.


Efficacy of an Enterotoxigenic Escherichia coli (ETEC) Vaccine on the Incidence and Severity of Traveler's Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score.
The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers' Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score and alternative clinical endpoints were evaluated as part of an initial validation effort to access the efficacy of a vaccine intervention for the first time in travelers to an ETEC endemic area. A randomized, double-blind, placebo-controlled trial followed travelers to Guatemala or Mexico up to 28 days after arrival in the country following vaccination (two doses two weeks apart) with an ETEC vaccine. Fecal samples were collected upon arrival, departure, and during TD for pathogen identification. Serum was collected in a subset of subjects to determine IgA cholera toxin B subunit (CTB) antibody titers upon their arrival in the country. The ETEC vaccine's efficacy, utilizing a TD severity score and other alternative endpoints, including the relationship between antibody levels and TD risk, was assessed and compared to the per-protocol primary efficacy endpoint. A total of 1435 subjects completed 7-28 days of follow-up and had available data. Vaccine efficacy was higher against more severe (≥5 unformed stools/24 h) ETEC-attributable TD and when accounting for immunologic take (PE ≥ 50%; p < 0.05). The vaccine protected against less severe (3 and 4 unformed stools/24 h) ETEC-attributable TD when accounting for symptom severity or change in activity (PE = 76.3%, p = 0.01). Immunologic take of the vaccine was associated with a reduced risk of infection with ETEC and other enteric pathogens, and with lower TD severity. Clear efficacy was observed among vaccinees with a TD score of ≥4 or ≥5, regardless of immunologic take (PE = 72.0% and 79.0%, respectively, p ≤ 0.03). The vaccine reduced the incidence and severity of ETEC, and this warrants accelerated evaluation of the improved formulation (designated ETVAX), currently undergoing advanced field testing. Subjects with serum IgA titers to CTB had a lower risk of infection with ETEC and Campylobacter jejuni/coli. Furthermore, the TD severity score provided a more robust descriptor of disease severity and should be included as an endpoint in future studies.


Systematic characterization of short intronic splicing-regulatory elements in SMN2 pre-mRNA.
Intronic splicing enhancers and silencers (ISEs and ISSs) are two groups of splicing-regulatory elements (SREs) that play critical roles in determining splice-site selection, particularly for alternatively spliced introns or exons. SREs are often short motifs; their mutation or dysregulation of their cognate proteins frequently causes aberrant splicing and results in disease. To date, however, knowledge about SRE sequences and how they regulate splicing remains limited. Here, using an SMN2 minigene, we generated a complete pentamer-sequence library that comprises all possible combinations of 5 nucleotides in intron 7, at a fixed site downstream of the 5' splice site. We systematically analyzed the effects of all 1023 mutant pentamers on exon 7 splicing, in comparison to the wild-type minigene, in HEK293 cells. Our data show that the majority of pentamers significantly affect exon 7 splicing: 584 of them are stimulatory and 230 are inhibitory. To identify actual SREs, we utilized a motif set enrichment analysis (MSEA), from which we identified groups of stimulatory and inhibitory SRE motifs. We experimentally validated several strong SREs in SMN1/2 and other minigene settings. Our results provide a valuable resource for understanding how short RNA sequences regulate splicing. Many novel SREs can be explored further to elucidate their mechanism of action.


Oestradiol decreases rat apolipoprotein AI transcription via promoter site B.
Oestrogens protect against ischaemic heart disease in the post-menopausal female by increasing serum concentrations of apolipoprotein (apo) AI and the abundance of high-density lipoprotein particles. In men and experimental male animals, the administration of oestrogen has variable effects on apo AI expression. As the major mode of oestrogen action on target genes involves regulating promoter activity and hence transcription, oestrogen is expected to alter transcription of the apo AI gene. To test this hypothesis, the effect of 17beta-oestradiol (E(2)), on rat apo AI promoter activity in male hepatoma HuH-7 cells, was tested by co-transfecting a reporter template, pAI.474.CAT containing-474 to-7 of the rat apo AI promoter and an oestrogen receptor (ER) expression vector, pCMV-ER. Transfected cells exposed to E(2) showed a dose-dependent decrease in chloramphenicol acetyltransferase (CAT)-activity, with a maximum 91+/-1.5% reduction at 1 microM E(2). Deletional analysis of the promoter localized the inhibitory effect of ER and E(2) to site B (-170 to-144) with an adjacent 5' contiguous motif, site S (-186 to-171) acting as an amplifier. HuH-7 cell nuclear extracts showed binding activities with both sites S and B, but recombinant human ER did not. Furthermore, nuclear extracts from E(2)-treated HuH-7 cells showed weaker binding activity to site B, but not to site S. In summary, the inhibitory effect of ER and E(2) on rat apo AI gene activity is mediated by a promoter element, site B. This inhibitory effect arises from a mechanism that does not involve direct ER binding to the B-element. The conclusion that E(2) inhibits apo AI transcription was confirmed in vivo. Treatment of male adult Sprague-Dawley rats with up to 200 microg E(2) for 7 days decreased apo AI protein and hepatic mRNA by 72+/-21% and 68+/-1.4% respectively. Results of 'run-on' transcription of the apo AI gene in isolated hepatic nuclei showed a 55% decrease in hormone-treated male rats. These findings suggest that E(2) exerts primarily an inhibitory effect within male hepatic nuclei.


New insights into the immunomodulatory properties of poxvirus cytokine decoy receptors at the cell surface.
Poxviruses encode a set of secreted proteins that bind cytokines and chemokines as a strategy to modulate host defense mechanisms. These viral proteins mimic the activity of host cytokine decoy receptors but have unique properties that may enhance their activity. Here, we describe the ability of poxvirus cytokine receptors to attach to the cell surface after secretion from infected cells, and we discuss the advantages that this property may confer to these viral immunomodulatory proteins.


Hydrolyzed eggshell membrane immobilized on phosphorylcholine polymer supplies extracellular matrix environment for human dermal fibroblasts.
We have found that a water-soluble alkaline-digested form of eggshell membrane (ASESM) can provide an extracellular matrix (ECM) environment for human dermal fibroblast cells (HDF) in vitro. Avian eggshell membrane (ESM) has a fibrous-meshwork structure and has long been utilized as a Chinese medicine for recovery from burn injuries and wounds in Asian countries. Therefore, ESM is expected to provide an excellent natural material for biomedical use. However, such applications have been hampered by the insolubility of ESM proteins. We have used a recently developed artificial cell membrane biointerface, 2-methacryloyloxyethyl phosphorylcholine polymer (PMBN) to immobilize ASESM proteins. The surface shows a fibrous structure under the atomic force microscope, and adhesion of HDF to ASESM is ASESM-dose-dependent. Quantitative mRNA analysis has revealed that the expression of type III collagen, matrix metalloproteinase-2, and decorin mRNAs is more than two-fold higher when HDF come into contact with a lower dose ASESM proteins immobilized on PMBN surface. A particle-exclusion assay with fixed erythrocytes has visualized secreted water-binding molecules around the cells. Thus, HDF seems to possess an ECM environment on the newly designed PMBN-ASESM surface, and future applications of the ASESM-PMBN system for biomedical use should be of great interest.


[Ulcers in the area of the external saphenous vein].
The varicose or incompetent short saphenous vein is solely responsible for the ulcers with typical localizations. These ulcers, which are especially painful and less frequent than those caused by the long saphenous vein alone, or by the joint role of both saphenae, are easily cured, like any varicose ulcer, by direct action taken on the vein responsible. The author's conclusions are based on a study of 634 cases of venous ulcers.


Early Evidence of the Italian Parent-Report Strengths and Difficulties Questionnaire (SDQ-P).
The parent-report Strengths and Difficulties Questionnaire (SDQ-P) is a widely used scale that assesses children's and adolescents' strengths and difficulties. The present study applied this scale to Italian adolescents and compared the current results with previous Chinese findings and the United Kingdom norm. Participants were 422 Italian parents and their adolescent children. Parents and adolescents answered the parent-report and the self-report SDQ, respectively. Results showed that the five-factor first-order model was better than other competing models. Cronbach's alpha of emotional problems, conduct problems, hyperactivity, peer problems, prosocial behavior, and total difficulties was .63, .52, .69, .51, .59, and .77 respectively for mother-report measure, and .67, .48, .67, .46, .55, and .79 respectively for father-report measure. Parent-adolescent agreements ranged from low to medium, whereas mother-father agreements were large. Parents did not rate boys and girls as well as early-adolescence and mid-adolescence differently. Italian parents rated their adolescent children to have lower levels of hyperactivity, peer problems, total difficulties, and higher levels of prosocial behavior than Chinese parents; and Italian mothers rated their adolescent children to have lower levels of hyperactivity than United Kingdom parents. In conclusion, the current findings suggest both strengths and inadequacies of the SDQ-P for Italian adolescents.


Achievable goals and relevant endpoints in cancer treatment.
The goals of cancer treatment range from eliminating cancer to prolonging the time to recurrence, controlling local disease, and palliating symptoms. For many cancer patients, disease elimination is an unrealistic treatment goal at the time of diagnosis due to the presence of metastatic disease and the lack of effective systemic treatment. For other patients, treatment options with similar survival expectation but differing side effects may complicate treatment selection. There is a clear need for new cancer treatment endpoints to be developed so that the effects of cancer treatment may be appropriately monitored. Some recently developed cancer treatment endpoints are described, and their use in clinical trials is advocated.


[Registry Research Funding of the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC) and Research Funding Report 2019/2020].
Since 2015/16 the DGPRÄC collects, evaluates and publishes the research activities of academic sections, departments and clinics for plastic surgery at university hospitals in Germany, in order to raise the awareness of plastic surgical research performance. The directors of plastic surgical academic institutions were contacted via the DGPRÄC and asked to report any requested/approved and rejected research applications to public, non-public and industrial funding organizations. Data was collected in our previously established online database: https://docs.google.com/forms/d/e/1FAIpQLSe6F5xmTyw-k7VKJx_2jkPA4LBXsA0sgBGMrC3rx_4bHj6uzQ/viewform?usp=sf_link. In addition, applications were identified via the DFG's public database GEPRIS. A total of 41 funding applications to the public funding institutes DFG, BMBF, BMWi, BMG and EU were identified. 75.6 % (31/41) of the applications had already been approved at the time of data collection, of which 77.4 % (24/31) were DFG, 9.7 % (3/31) were BMWi, 6.5 % (2/31) were EU and 3.2 % (1/31) were BMBF or BMG applications. The average funding amounted to 358 301 Euro. In 50.0 % (12/24) of the cases, the approved DFG proposals were assigned to the subject review board 205-27 Orthopedics, Trauma Surgery, Reconstructive Surgery. The continuous publication of plastic surgical research funding reports submitted by the convention of university plastic surgeons of the DGPRÄC portraits the excellent, collaborative research activity in the field of plastic surgery.


Impaired circulating dendritic cell reconstitution identifies rejecting recipients after clinical heart transplantation independent of rejection therapy.
Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx). Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment of allograft function during EMB was performed to distinguish clinical necessity for rejection therapy within histologically rejecting patients (R). Myeloid (mDC) and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio were compared sequentially between non-rejecting (NR) recipients and R patients treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up. Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52; grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05) but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively). Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05). Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients, independent of rejection therapy. Defective DC subset reconstitution by dendritic cell profiling identifies patients at risk for AR after 3 months post-HTx. This finding may contribute to further optimization of immunosuppressive treatment strategies after clinical heart transplantation.


Mining Non-Redundant High Order Correlations in Binary Data.
Many approaches have been proposed to find correlations in binary data. Usually, these methods focus on pair-wise correlations. In biology applications, it is important to find correlations that involve more than just two features. Moreover, a set of strongly correlated features should be non-redundant in the sense that the correlation is strong only when all the interacting features are considered together. Removing any feature will greatly reduce the correlation.In this paper, we explore the problem of finding non-redundant high order correlations in binary data. The high order correlations are formalized using multi-information, a generalization of pairwise mutual information. To reduce the redundancy, we require any subset of a strongly correlated feature subset to be weakly correlated. Such feature subsets are referred to as Non-redundant Interacting Feature Subsets (NIFS). Finding all NIFSs is computationally challenging, because in addition to enumerating feature combinations, we also need to check all their subsets for redundancy. We study several properties of NIFSs and show that these properties are useful in developing efficient algorithms. We further develop two sets of upper and lower bounds on the correlations, which can be incorporated in the algorithm to prune the search space. A simple and effective pruning strategy based on pair-wise mutual information is also developed to further prune the search space. The efficiency and effectiveness of our approach are demonstrated through extensive experiments on synthetic and real-life datasets.


Skin substitutes and wound healing.
Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are not life threatening. Nowadays, more than 20 products are commercially available, more are undergoing clinical trials and a large number of new models are being investigated in various research laboratories worldwide. Many of the current products do not contain any living cells and vary in their capacity to harness the innate capacity of the body to heal itself. Others include living cells, of allogeneic or autologous origin, and are often referred to as 'cellular therapy' or 'tissue-engineered' products. Modifications and improvements are currently investigated that aim at improving the healing potential of those products through the use of recombinant growth factors and additional features such as microvascularization. Fundamental research into wound healing and scar-free regeneration raises the hope that we will eventually be able to restore almost completely the appearance and function of skin after the healing of wounds.


All-trans Retinoic Acid Augments Autophagy during Intracellular Bacterial Infection.
Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic-resistant TB is increasing globally; therefore, there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages, the niche cell for Mtb, metabolize vitamin A to all-trans retinoic acid (atRA), which influences host immune responses. We sought to determine the mechanistic effects of atRA on the host immune response to intracellular bacterial infection in primary human and murine macrophages. In this study, atRA promoted autophagy resulting in a reduced bacterial burden in human macrophages infected with Mtb and Bordetella pertussis, but not bacillus Calmette-Guérin (BCG). Autophagy is induced by cytosolic sensing of double-stranded DNA via the STING/TBK1/IRF3 axis; however, BCG is known to evade cytosolic DNA sensors. atRA enhanced colocalization of Mtb, but not BCG, with autophagic vesicles and acidified lysosomes. This enhancement was inhibited by blocking TBK1. Our data indicate that atRA augments the autophagy of intracellular bacteria that trigger cytosolic DNA-sensing pathways but does not affect bacteria that evade these sensors. The finding that BCG evades the beneficial effects of atRA has implications for vaccine design and global health nutritional supplementation strategies. The ability of atRA to promote autophagy and aid bacterial clearance of Mtb and B. pertussis highlights a potential role for atRA as a host-directed adjunctive therapy.


Multiethnic polygenic risk scores improve risk prediction in diverse populations.
Methods for genetic risk prediction have been widely investigated in recent years. However, most available training data involves European samples, and it is currently unclear how to accurately predict disease risk in other populations. Previous studies have used either training data from European samples in large sample size or training data from the target population in small sample size, but not both. Here, we introduce a multiethnic polygenic risk score that combines training data from European samples and training data from the target population. We applied this approach to predict type 2 diabetes (T2D) in a Latino cohort using both publicly available European summary statistics in large sample size (Neff = 40k) and Latino training data in small sample size (Neff = 8k). Here, we attained a >70% relative improvement in prediction accuracy (from R2 = 0.027 to 0.047) compared to methods that use only one source of training data, consistent with large relative improvements in simulations. We observed a systematically lower load of T2D risk alleles in Latino individuals with more European ancestry, which could be explained by polygenic selection in ancestral European and/or Native American populations. We predict T2D in a South Asian UK Biobank cohort using European (Neff = 40k) and South Asian (Neff = 16k) training data and attained a >70% relative improvement in prediction accuracy, and application to predict height in an African UK Biobank cohort using European (N = 113k) and African (N = 2k) training data attained a 30% relative improvement. Our work reduces the gap in polygenic risk prediction accuracy between European and non-European target populations.


Development of the testis in pre-pubertal boys with cancer after biopsy for fertility preservation.
Is testicular growth affected by a testicular biopsy intended for fertility preservation in pre-pubertal boys with cancer? Testicular growth of the biopsied testis is not impeded in comparison to the non-biopsied contralateral testis up until 1 year after surgery. Fertility preservation in pre-pubertal boys by means of testicular biopsy has been conducted for more than 15 years. Although immediate adverse effects of testicular biopsy are rare (1%), no data exist on the effect of biopsy on testicular growth. In this prospective cohort study, between March 2011 and February 2017, 93 parents of pre-pubertal boys were offered cryopreservation of testicular tissue of their son, of whom 78 consented. Sixty-four boys were included in this follow-up study. All boys with cancer at the paediatric oncology department of the Academic Medical Center (AMC) who needed gonadotoxic therapy and were unable to ejaculate were offered cryopreservation of testicular tissue prior to treatment. By testicular ultrasound before and after biopsy (1, 6 and 12 months after biopsy), volume and parenchymal abnormalities were assessed. Data were analysed using mixed-effects modelling. Of the 64 included boys all were followed up at 1 month, 58 at 6 months and 55 at 12 months. Mean testicular volumes after 1, 6 and 12 months after biopsy were 1.7 ± 2.1, 1.7 ± 2.2 and 1.9 ± 2.4 for the biopsied testis and 1.8 ± 2.2, 1.8 ± 2.3 and 2.0 ± 2.2 for the non-biopsied testis, respectively. Biopsy of the testis did not have a significant impact on testicular growth. Immediate adverse effects of the biopsy, i.e. wound infections, were seen in 3/78 boys (3.8%). Although it is the largest cohort available to date, the number of patients included in our follow-up is still relatively small. A larger cohort would be able to evaluate growth more precisely. Follow-up was discontinued in a significant portion of boys, 12/76 (15.8%), mainly because of death due to primary illness but also because they could not be reached or declined further follow-up. These reassuring data may be used in counselling future boys who are eligible for fertility preservation and their parents. Study funded by KIKA Foundation (Kika 86), Grant from the Netherlands Organisation for Health Research and Development (ZonMW TAS-116003002). The authors declare no conflict of interest. CCMO-register: NL27690.000.09.


Staphylococcus aureus nasal colonization among HIV-infected adults in Botswana: prevalence and risk factors.
We sought to determine the clinical and epidemiologic determinants of Staphylococcus aureus nasal colonization in HIV-infected individuals at two outpatient centers in southern Botswana. Standard microbiologic techniques were used to identify S. aureus and methicillin-resistant S. aureus (MRSA). In a sample of 404 HIV-infected adults, prevalence of S. aureus nasal carriage was 36.9% (n = 152) and was associated with domestic overcrowding and lower CD4 cell count. MRSA prevalence was low (n = 13, 3.2%), but more common among individuals with asthma and eczema. The implications of these findings for HIV management are discussed.


Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares.
The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with biphasic disposition. The total plasma clearance of probenecid averaged 1.18 +/- 0.49 ml/min/kg, whereas renal clearance accounted for 42.6 +/- 9.3% of the total clearance. The steady-state volume of distribution of probenecid averaged 116 +/- 28.2 ml/kg. Plasma protein binding of probenecid was extensive, with 99.9% of the drug bound at plasma probenecid concentrations of 10 micrograms/ml. The maximum plasma probenecid concentration after 10 mg/kg orally averaged nearly 30 micrograms/ml. The half-life of probenecid after oral administration was approximately 120 minutes. Oral bioavailability was good with greater than 90% of the dose absorbed. The effect of probenecid on tubular secretion of organic anions was evaluated by determining the pharmacokinetics of IV cefazolin (11 mg/kg) administered alone and 15 minutes after probenecid (10 mg/kg orally). Treatment with probenecid did not affect pharmacokinetic values of cefazolin. This failure of probenecid to alter the pharmacokinetics of cefazolin may be caused by insufficient plasma probenecid concentrations after the oral dose.


Hybrid Membrane Camouflaged Chemodrug-Gene Nanoparticles for Enhanced Combination Therapy of Ovarian Cancer.
Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.


Genetic diversity and structure in two protected Posidonia oceanica meadows.
Posidonia oceanica meadows growing along the west Mediterranean coastline are under continuous anthropogenic pressure. The way meadow health correlates with genetic and genotypic diversity in P. oceanica, is still under debate. Here we report a microsatellite analysis of two P. oceanica meadows living in protected areas of the Ligurian (Monterosso al Mare, MPA of "Cinque Terre") and central Tyrrhenian Sea (Santa Marinella, regional Site of Community Importance). Both meadows were recently classified as "disturbed", according to shoot density and other phenological parameters. Between the two meadows, Santa Marinella showed higher genetic diversity, while clear genetic substructure was present in both sites, reflecting high spatial heterogeneity. The present study suggests that genetic diversity does not match unequivocally with shoot density and leaf morphology and that small scale intra-meadow heterogeneity is an important factor to consider for establishing the relation between genetic/genotypic variability and health of natural seagrass meadows.


Yogurt Making as a Tool To Understand the Food Fermentation Process for Nonscience Participants.
Designing an outreach program concerning food fermentation for nonscience participants offers an opportunity to introduce the basic principles of microbiology and their application in food preservation. This program can be adapted to microbiology courses at the undergraduate level to help students understand the concept of food fermentation and its process control. Yogurt is a type of fermented milk that is commercially available in Indonesia. While yogurt fermentation is usually performed in a closed fermenter in an aseptically controlled room, yogurt can also be made at home using lactic acid bacteria culture starters, such as Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus, and applying proper hygiene and sanitation procedures. Yogurt making requires not only appropriate ingredients but also an understanding of the microbiological concepts of yogurt fermentation in order to enable control and modification of the fermentation process so that the end product is safe to consume. Through this activity, we provided training to residents from a nonscience background in Bogor, Indonesia, for simple and feasible homemade yogurt production using a variety of milk substrates and sources of starter culture. All participants prepared the ingredients and sanitized kitchen equipment, performed the yogurt fermentation process, and evaluated the product's sensory properties. Participants were challenged to explore the differences among various yogurt batches. This activity can be completed in two days, and the recipe could be modified once the participants have understood the concept of yogurt fermentation.


[State-of-the-art and prospects of high-tech medical aid to patients with cardiac arrhythmia based at military medical facilities].
Analysis of provision of high-tech medical aid to patients with cardiac arrhythmia based at military medical facilities showed that the available means and workforce are sufficient for the purpose. In order to facilitate access to high-tech medical aid it is necessary to equip arrhythmologic departments with up-to-date-instruments and set up cabinets of electrocardiostimulation in regional (naval) hospitals for implantation of temporary and permanent pacemakers. A program is pending for education (primary specialization) and advanced training of specialists in clinical cardiac electrophysiology, interventional and surgical arrhythmology.


The excised leader of human cytochrome c oxidase subunit I mRNA which contains the origin of mitochondrial DNA light-strand synthesis accumulates in mitochondria and is polyadenylated.
We identified a polyadenylated RNA species which contains the origin of human mitochondrial DNA light-strand synthesis and the surrounding complementary sequences of the four light-strand-encoded tRNAs. This RNA (RNA 9L) is probably derived from the leader portion of RNA 6 which is excised during the formation of the mature cytochrome c oxidase subunit mRNA (RNA 9). The high degree of secondary structure of this RNA is presumably responsible for its anomalous electrophoretic behavior in denaturing polyacrylamide gels.


Classification of patients by severity grades during triage in the emergency department using data mining methods.
To test the feasibility of classifying emergency department patients into severity grades using data mining methods. Emergency department records of 402 patients were classified into five severity grades by two expert physicians. The Naïve Bayes and C4.5 algorithms were applied to produce classifiers from patient data into severity grades. The classifiers' results over several subsets of the data were compared with the physicians' assessments, with a random classifier, and with a classifier that selects the maximal-prevalence class. Positive predictive value, multiple-class extensions of sensitivity and specificity combinations, and entropy change. The mean accuracy of the data mining classifiers was 52.94 ± 5.89%, significantly better (P < 0.05) than the mean accuracy of a random classifier (34.60 ± 2.40%). The entropy of the input data sets was reduced through classification by a mean of 10.1%. Allowing for classification deviations of one severity grade led to mean accuracy of 85.42 ± 1.42%. The classifiers' accuracy in that case was similar to the physicians' consensus rate. Learning from consensus records led to better performance. Reducing the number of severity grades improved results in certain cases. The performance of the Naïve Bayes and C4.5 algorithms was similar; in unbalanced data sets, Naïve Bayes performed better. It is possible to produce a computerized classification model for the severity grade of triage patients, using data mining methods. Learning from patient records regarding which there is a consensus of several physicians is preferable to learning from each physician's patients. Either Naïve Bayes or C4.5 can be used; Naïve Bayes is preferable for unbalanced data sets. An ambiguity in the intermediate severity grades seems to hamper both the physicians' agreement and the classifiers' accuracy.


Persistent neuropsychological impairment associated with West Nile virus infection.
West Nile virus infection can result in prolonged subjective complaints of cognitive and functional decline even in the absence of a neuroinvasive form of infection. Persistent cognitive and functional complaints could be a result of general somatic symptoms, emotional distress, or residual central nervous system damage or dysfunction. Most studies of cognition in postacute West Nile virus infection rely on self-report. This descriptive study aimed to document cognitive deficits in a sample of the 2003 infected population reported in New Mexico. Patients with clinically defined neuroinvasive disease or who were impaired on brief mental status screening were seen for comprehensive neuropsychological assessment. We found that one year after symptom onset, more than half of the sample had objectively measurable neuropsychological impairment in at least two cognitive domains. Impairment was not related to subjective complaints of physical or emotional distress, or premorbid intellectual abilities. Persistent cognitive impairment in West Nile virus infection may be due to prolonged or permanent damage to the central nervous system.


Total organic carbon concentrations in clastic cave sediments from Butler Cave, Virginia, USA: implications for contaminant fate and transport.
Clastic cave deposits are representative of sediments throughout the karst aquifer and thus are an abundant and accessible resource through which to study the chemistry of karst aquifer. Clastic cave sediments are attributed to depositional facies based on cave location, sorting, and particle size. These facies settings may influence different chemical parameters of the sediments, like concentrations of total organic carbon (TOC). The TOC concentrations in clastic cave sediments have not been well constrained nor has the role of clastic sediments in contaminant fate and transport through karst systems been well described. In this study, particle size, TOC, and total nitrogen were measured in sediments representing different facies in Butler Cave, Virginia, USA. TOC concentrations ranged from 0.08 - 0.87 weight percent and C:N molar ratio ranged from 3 - 15, indicating a possible terrestrial source of organic carbon in these sediments. The diamicton facies was sandier and but had similar TOC concentrations compared to the channel facies. TOC concentrations measured in Butler Cave were within the same range as those observed in above water, eogenetic clastic cave sediments from two caves in Puerto Rico. Estimated retardation factors calculated based on the TOC concentrations in the Butler Cave sediments indicate the range of TOC in this cave could be responsible for 39 - 987% increase in retardation of selected contaminants. This study highlights the importance of measuring the ranges of TOC in clastic cave sediments across different facies and their role in contaminant fate and transport.


Stenting of an anomalous left circumflex coronary artery arising from the right sinus of Valsalva.
Anomalous origin of coronary arteries is rare, occurring in about 1% of patients undergoing cardiac catheterization. Coronary atherosclerosis is not uncommon in these patients. Percutaneous angioplasty of anomalous coronary arteries poses a particular technical challenge secondary to the vessel characteristics. Stenting of the anomalous coronary arteries has not been described previously. We report a 47-year-old man with unstable angina in whom a MULTI-LINK coronary stent was placed successfully in an anomalous circumflex coronary artery.


The conceptualization of stigma within a rehabilitation framework using HIV as an example.
Stigma theory is concerned with inclusion and opportunities that influence well-being. Rehabilitation is also concerned with social inclusion and well-being. This is a central concern in one of the leading rehabilitation theories, the World Health Organization's International Classification of Functioning, Disability and Health. Despite these shared concerns, the relationship between the fields of stigma and rehabilitation has not been well theorized to date. Using human immunodeficiency virus (HIV) as an example, this article presents an analysis of three ways that stigma may be conceptualized within the context of the International Classification of Functioning, Disability and Health. Three broad spheres of stigma are described: enacted, self, and structural stigma. These three forms of stigma are then aligned in unique ways with three particular constructs of the International Classification of Functioning, Disability and Health: participation restrictions, environmental, and personal contextual factors. This conceptualization illustrates how rehabilitation professionals and other practitioners, policy makers and researchers can better understand the dynamic and nuanced forms of stigma and how they relate to rehabilitation. Implications for rehabilitation This article enables rehabilitation professionals to better understand stigma as it relates to rehabilitation and human immunodeficiency virus. Rehabilitation professionals have the important job of allies and advocates for persons experiencing restrictions in these domains as a result of stigma.


[Contact urticaria, rhinoconjunctivitis and bronchial asthma from occupational use of papain].
Papain is a plant protein with a wide pharmacological, domestic and industrial use. It leads a high sensitisation, being the most common rotue of entry the inhalation. The occupational allergy to papain in exposed workers was described some years ago, being presented with bronchial asthma, rhinitis or both. In most of the cases, the specific IgE was positive. We present a case contact urticaria, rhinoconjunctivitis and bronchial asthma per papain of occupational origin. Papain prick test, specific IgE and nasal challenge were positive. The peak flow record showed diary decreases during the working week and the basal spirometry showed obstruction to the airflow. The patient was moved away the place where papain was handled and this resolved the clinical symptoms and the spirometry returns to the normal values. We present a case of IgE-mediated allergy, vehicled by tow routes: contact and airborne. The latest produced clinical manifestations later. Papain was used as Cephalopoda softening, because of that it worth emphasising its seasonal use.


A Brodie's abscess caused by Salmonella give.
This report describes a typical Brodie's abscess caused by a Salmonella subspecies in an otherwise healthy individual. The rarity of the causative agent of this infection is stressed.


Effects of micro-sized biodegradable plastics on Microcystis aeruginosa.
Plethora of plastics are being used in current society, generating huge amounts of plastic waste. Non-biodegradability of conventional plastics is one of the main challenges to treat plastic waste. In an effort to increase the efficiency of plastic waste treatment, biodegradable plastics have gained attention. Although the use of biodegradable plastics has been increased, their potential effects on the environments are not fully elucidated yet. In this study, the impacts of micro-sized non-biodegradable plastic (i.e., polystyrene (PS)) and micro-sized biodegradable plastics (i.e., polycaprolactone (PCL) and polylactic acid (PLA)) on Microcystis aeruginosa were investigated. Regardless of microplastic (MP) types, MP treatments inhibited the growth of M. aeruginosa at the beginning (4 days) while significant dose-dependent effect was not observed in the range of 0.1 to 10 mg/L. However, after long-term exposure (12 days), micro-sized biodegradable plastics stimulated the growth of M. aeruginosa (up to 73 % increase compared to the control). The photosynthetic activity showed a similar trend to the cell growth. The MP treatments induced the production of extracellular polymeric substances (EPS). Indeed, micro-sized PCL and PLA stimulated the production of protein compounds in EPS. These might have affected the releases of chemicals from PCL and PLA, suggesting that the chemicals in biodegradable plastic leachates would promote the growth of M. aeruginosa in long-term exposure. The MP treatments also induced cyanotoxin (microcystin-LR) productions. Our results give a new insight into the cyanobacterial blooming and suggest a novel relationship between harmful algal blooms (HABs) and biodegradable plastics.


Intervention strategies to reduce musculoskeletal injuries associated with handling patients: a systematic review.
To report, analyse, and discuss the results of a systematic review looking at intervention strategies to reduce the risk factors associated with patient handling activities. A search strategy was devised to seek out research between 1960 and 2001. Inclusion/exclusion criteria limited the entry of papers into the review process. A checklist was selected and modified to include a wide range of study designs. Inter-rater reliability was established between six reviewers before the main review process commenced. Each paper was read by two reviewers and given a quality rating score, with any conflicts being resolved by a third reviewer. Papers were grouped by category: multifactor, single factor, and technique training based interventions. A total of 2796 papers were found, of which 880 were appraised. Sixty three papers relating to interventions are reported in this paper. The results are reported as summary statements with the associated evidence level (strong, moderate, limited, or poor). There is strong evidence that interventions predominantly based on technique training have no impact on working practices or injury rates. Multifactor interventions, based on a risk assessment programme, are most likely to be successful in reducing risk factors related to patient handling activities. The seven most commonly used strategies are identified and it is suggested that these could be used to form the basis of a generic intervention programme, with additional local priorities identified through the risk assessment process. Health care providers should review their policies and procedures in light of these findings.


Genetic Background but Not Intestinal Microbiota After Co-Housing Determines Hyperoxaluria-Related Nephrocalcinosis in Common Inbred Mouse Strains.
Calcium oxalate (CaOx) crystal formation, aggregation and growth is a common cause of kidney stone disease and nephrocalcinosis-related chronic kidney disease (CKD). Genetically modified mouse strains are frequently used as an experimental tool in this context but observed phenotypes may also relate to the genetic background or intestinal microbiota. We hypothesized that the genetic background or intestinal microbiota of mice determine CaOx crystal deposition and thus the outcome of nephrocalcinosis. Indeed, Casp1-/-, Cybb-/- or Casp1-/-/Cybb-/- knockout mice on a 129/C57BL/6J (B6J) background that were fed an oxalate-rich diet for 14 days did neither encounter intrarenal CaOx crystal deposits nor nephrocalcinosis-related CKD. To test our assumption, we fed C57BL/6N (B6N), 129, B6J and Balb/c mice an oxalate-rich diet for 14 days. Only B6N mice displayed CaOx crystal deposits and developed CKD associated with tubular injury, inflammation and interstitial fibrosis. Intrarenal mRNA expression profiling of 64 known nephrocalcinosis-related genes revealed that healthy B6N mice had lower mRNA levels of uromodulin (Umod) compared to the other three strains. Feeding an oxalate-rich diet caused an increase in uromodulin protein expression and CaOx crystal deposition in the kidney as well as in urinary uromodulin excretion in B6N mice but not 129, B6J and Balb/c mice. However, backcrossing 129 mice on a B6N background resulted in a gradual increase in CaOx crystal deposits from F2 to F7, of which all B6N/129 mice from the 7th generation developed CaOx-related nephropathy similar to B6N mice. Co-housing experiments tested for a putative role of the intestinal microbiota but B6N co-housed with 129 mice or B6N/129 (3rd and 6th generation) mice did not affect nephrocalcinosis. In summary, genetic background but not the intestinal microbiome account for strain-specific crystal formation and, the levels of uromodulin secretion may contribute to this phenomenon. Our results imply that only littermate controls of the identical genetic background strain are appropriate when performing knockout mouse studies in this context, while co-housing is optional.


Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines.
The administration of cancer chemotherapeutic agents results in an increase in the apoptotic cells in the tumor: therefore, it has been assumed that anticancer drugs exhibit their cytotoxic effects via apoptotic signaling pathways. Characteristics that confer sensitivity to drug-induced apoptosis are, a functional p53 protein and expression of the apoptosis-promoting protein, bax. The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD(50) concentrations of etoposide, vinblastine and estramustine. Cell death was monitored morphologically by fluorescent microscopy, and by flow cytometry (Annexin-V assay). Apoptotic morphology was rather low and ranged from 0.1% to 12.1%, 3.0% to 6.0% and 0.1% to 8.5% for etoposide, estramustine and vinblastine, respectively. Annexin-V binding and flow cytometry indicated apoptotic propensities of 0% to 4%, 0% to 3% and 0% to 5%, respectively. The percentage of cells responding to drug-induced apoptosis was, on average, higher in the tumor cell lines than in the normal cell lines, but showed no correlation with p53 status. The percentage of cells showing necrosis, assessed by Annexin binding and Propidium Iodide permeability in aqueous medium, tended to be much higher, and was found to be at the level of 5% to 30%. Immunoblotting demonstrated that bax and bcl-2 proteins were expressed at a basal level in all cell lines, but did not increase after exposure to TD(50) doses of the three drugs. The ratio of bax and bcl-2, measured by laser scanning densitometry, was not altered by the drug-induced DNA damage. The results suggest that apoptosis is not a major mechanism of drug-induced cell death in prostate cell lines and appears to be independent of p53 status and bax/bcl-2 expression.


Genome-Wide Association Study and Transcriptome Differential Expression Analysis of the Feather Rate in Shouguang Chickens.
The feather rate phenotype in chicks, including early-feathering and late-feathering phenotypes, are widely used as a sexing system in the poultry industry. The objective of this study was to obtain candidate genes associated with the feather rate in Shouguang chickens. In the present study, we collected 56 blood samples and 12 hair follicle samples of flight feathers from female Shouguang chickens. Then we identified the chromosome region associated with the feather rate by genome-wide association analysis (GWAS). We also performed RNA sequencing and analyzed differentially expressed genes between the early-feathering and late-feathering phenotypes using HISAT2, StringTie, and DESeq2. We identified a genomic region of 10.0-13.0 Mb of chromosome Z, which is statistically associated with the feather rate of Shouguang chickens at one-day old. After RNA sequencing analysis, 342 differentially expressed known genes between the early-feathering (EF) and late-feathering (LF) phenotypes were screened out, which were involved in epithelial cell differentiation, intermediate filament organization, protein serine kinase activity, peptidyl-serine phosphorylation, retinoic acid binding, and so on. The sperm flagellar 2 gene (SPEF2) and prolactin receptor (PRLR) gene were the only two overlapping genes between the results of GWAS and differential expression analysis, which implies that SPEF2 and PRLR are possible candidate genes for the formation of the chicken feathering phenotype in the present study. Our findings help to elucidate the molecular mechanism of the feather rate in chicks.