Effect of chitosan on weight loss in overweight and obese individuals: a systematic review of randomized controlled trials.
This article aims to determine whether chitosan, a popular, over-the-counter, weight loss supplement, is an effective treatment for overweight and obesity. It is designed as a systematic review of randomized controlled trials. The data sources include the electronic databases Medline, EMBASE, Biosis, CINAHL and Cochrane Central Register of Controlled Trials (CCTR); the specialized websites Controlled Trials, International Bibliographic Information on Dietary Supplements (IBIDS), System for Information on Grey Literature in Europe (SIGLE), Reuter's Health Service, Natural Alternatives International and Pharmanutrients; and bibliographies of relevant journal articles. Included were randomized controlled trials of chitosan with a minimum duration of 4 weeks in adults who were overweight or obese and/or had hypercholesterolaemia at baseline. Fourteen trials involving a total of 1071 participants were included in the review. Analyses involving all trials indicated that chitosan preparations result in a small but statistically significant greater reduction in body weight (weighted mean difference -1.7 kg; 95% confidence interval -2.1, -1.3 kg, P < 0.00001) compared with placebo. Analyses restricted to high-quality studies showed that reductions in weight [-0.6 (-1.2, 0.1) kg, P = 0.11] were less than in lower quality studies [-2.3 (-2.7, -1.8) kg, P < 0.00001]. Results obtained from high-quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance.


The effect of three gums on the retrogradation of indica rice starch.
Retrograded starch (RS(3)) was produced from indica rice starch with three kinds of gums (konjac glucomannan, KGM; carrageenan, CA, USA; and gellan, GA, USA) by autoclaving, respectively, and the effect of the gums on the retrogradation behavior of starch was estimated. The influences of polysaccharide concentration, sodium chloride concentration, autoclaving time, refrigerated time, and pH value on RS(3) formation were discussed. Except for sodium chloride's persistent restraint on RS(3), the others all forced RS(3) yields higher at first, but lowered it after the peak value. The influencing sequence of these impact factors was: sodium chloride concentration > polysaccharide concentration > autoclaving time > refrigerated time > pH value. The results also proved that in the three gums, KGM plays the most significant role in RS(3) changing. It was concluded that the incorporation of each of these three gums into starch, especially KGM, results in an increase or decrease of RS(3) under different conditions. This phenomenon could be taken into consideration when developing starchy food with appropriate amount of RS(3).


Effectiveness of physical activity programs at worksites with respect to work-related outcomes.
This paper systematically reviews the literature on the effectiveness of physical activity programs at worksites with respect to work-related outcomes. A computerized literature search, a reference search, and a manual search of personal databases were performed using the following inclusion criteria: randomized controlled or controlled trial, working population. worksite intervention program to promote physical activity or physical fitness, and work-related outcomes. The study quality was evaluated using nine methodological criteria. Conclusions were based on a 5-level rating system of evidence. Eight studies (4 randomized controlled trials and 4 controlled trials) were identified, but their methodological quality was generally poor. The outcomes were absenteeism, job satisfaction, job stress, productivity, and employee turnover. The evidence of an effect was limited for absenteeism, inconclusive for job satisfaction, job stress and employee turnover, and nil for productivity. The scientific evidence on the effectiveness of physical activity programs at worksites is still limited. Because of the few high-quality randomized controlled trials, it is strongly suggested that this type of study be carried out. Future randomized controlled trials should pay special attention to the description of randomization, inclusion criteria, compliance, and analyses according to intention to treat.


In vitro assessments of reverse glenoid stability using displacement gages are misleading - recommendations for accurate measurements of interface micromotion.
Baseplate micromotion of the reverse shoulder glenoid component can lead to implant loosening. We hypothesized that a remotely positioned displacement gage measures elastic deformation of the system rather than actual micromotion at the implant/bone interface. Reverse glenoid components were implanted into polyurethane blocks of 3 different densities. A 700 N compressive load was maintained and a vertical 700 N shear load was applied for 1000 cycles. In addition to the typical gage measurement, a digital image analysis of micromotion at the implant/block interface using high resolution cameras was performed. The measurements were validated on human specimens. A finite element model was implemented to study the isolated effect of block deformation on baseplate displacements. With the gage, typically reported micromotions were measured. Two orders of magnitude lower micromotions were detected using interface image-based analysis. The finite element simulation showed that elastic deformation alone can cause micromotion magnitudes as measured with displacement gages. Polyurethane blocks of 20 and 15 lbs per cubic foot density best reproduced micromotions as measured on human specimens. We found considerably less relative micromotion at the implant/bone interface than previously assumed. Gage measurements quantify elastic deformation and not true interface micromotion. High resolution digital imaging at the implant/bone interface is strongly recommended for an accurate assessment of reverse glenoid component micromotion. Tests should further adopt 20 or 15 pcf bone test surrogates. Further studies are required to identify the failure modes encountered in vivo, and a corresponding in vitro testing methodology can then be developed.


Automated in vivo quantification of emphysema.
A computer program to automatically determine lung volume and percentage of emphysema from computed tomographic (CT) chest sections was developed. To test it, the authors reviewed scans obtained in 89 patients. Any computer errors in identification of normal or emphysematous lungs were corrected manually by tracing the boundaries of the lungs or eliminating areas of nonemphysematous lung with a roller ball. The corrected values were compared with the uncorrected values. In 33 patients from the study group, lung volumes and the percentage of emphysema were calculated by using a currently available "voxel highlighting" program. Successful computerized analysis of entire lungs was performed in 1 minute, compared to more than 1 hour for manual analysis. Correlation was high (r = .99) between results obtained manually and those obtained with the computer. Although the difference between uncorrected and corrected values of the percentage of emphysema was statistically significant, this converted to a correction of only 0.1%. The computer program allowed quick, accurate, and reproducible quantification of emphysema.


Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54-75 Years.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. Exposures: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and Measures: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. Among Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.


Hepatic differentiation of mouse embryonic stem cells and induced pluripotent stem cells during organoid formation in hollow fibers.
We have focused on pluripotent stem cells as a potential source of a hybrid-type artificial liver (HAL) and tried to develop a method for differentiating the pluripotent stem cells into cells of a hepatic lineage. In this study, we investigated the hepatic differentiation of mouse embryonic stem (ES) cells and induced pluripotent stem (iPS) cells by applying hollow fiber (HF)/organoid culture method, in which cultured cells form a cellular aggregate called an "organoid" in the lumen of the HF. ES and iPS cells were injected into HFs to induce organoid formation, and cells were cultured. To induce hepatic differentiation, we added differentiation-promoting agents to the culture medium. The expression levels of differentiation-related genes were up-regulated, with cell proliferation and organoid formation inside HFs. Since we were able to achieve a high cell density in culture, the maximum levels of liver-specific functions per unit volume in the differentiating ES and iPS cells reached a level comparable to or better than that of primary mouse hepatocytes. In conclusion, ES and iPS cells have the potential to be a cell source for a HAL, and the HF/organoid culture method, therefore, has promise as a basic technology for the development of a HAL.


Inhibition of malignant human bladder cancer phenotypes through the down-regulation of the long non-coding RNA SNHG7.
There is abundant evidence that long non-coding RNAs play important roles in the development of tumors. In the present study, our main aim was to explore the relationship between lncRNA SNHG7 and human bladder cancer cells, thus finding a novel target for bladder cancer therapy and diagnosis. Expression of lncRNA SNHG7 was evaluated using real-time quantitative polymerase chain reaction in bladder tumor tissues and paired adjacent normal tissues from 72 patients diagnosed with urothelial bladder carcinoma. We analyzed the differences in expression according to grading and staging. Human bladder cancer cell lines UMUC, 5637, T24 and SW780 were transiently transfected with lncRNA SNHG7-specific siRNA and negative control siRNA. The changes in malignant phenotypes in transfected bladder cancer cells were determined using CCK-8 assay, wound-healing assay and ELISA. We found that lncRNA SNHG7 was correlated with human bladder cancer. lncRNA SNHG7 was overexpressed in bladder cancer tissues compared to paired normal tissues and expression of SNHG7 was higher in high-grade than low-grade tumors. The malignant phenotypes were significantly inhibited when we inhibited expression of lncRNA SNHG7 in several bladder cell lines. SNHG7 plays an oncogenic role in human bladder cancer and may be a potential novel therapeutic target for treating bladder cancer.


Hepatitis C virus infection can affect lymphoproliferative disorders only as a cofactor for Epstein-Barr virus in liver transplant recipients: PTLD.Int survey.
Hepatitis C virus infection has a 10.5% frequency in liver transplant posttransplant lymphoproliferative disorders. Studies have suggested that hepatitis C virus infection plays a role in developing posttransplant lymphoproliferative disorders. Pooling data of posttransplant lymphoproliferative disorders developing in liver recipients from the literature, we analyzed and compared characteristics, behavior, and prognoses of posttransplant lymphoproliferative disorders arising in hepatitis C virus-positive versus negative liver graft recipients. We conducted a search for the available data though PubMed and Google Scholar for reports of posttransplant lymphoproliferative disorders and hepatitis C virus infection in liver transplant recipients. Overall, 29 studies were found and their data are included in the analyses. Overall, data of 212 liver transplant patients were included. Sixty-three percent were male. No difference was found between hepatitis C virus-positive liver transplant patients with posttransplant lymphoproliferative disorders compared to their hepatitis C virus-negative counterparts regarding sex, time from transplant to lymphoma development, lymphoma cell type, remission, mortality rate, multiorgan involvement, disseminated posttransplant lymphoproliferative disorders, and histopathologic evaluations (P > .1 for all). Hepatitis C virus-positive liver transplant recipients representing posttransplant lymphoproliferative disorders who were concomitantly positive for Epstein-Barr virus were significantly more likely to develop lymphomas in the early posttransplant period (26 [67%] vs 16 [40%]; P = .024) and to complicate liver (19 [63%] vs 8 [30%]; P = .017) than hepatitis C virus-/Epstein-Barr virus+ patients. Hepatitis C virus infection alone has no significant effect on lymphoproliferative disorders after liver transplant; but when combined with Epstein-Barr virus infection, it represents some significant different presentations of the disease. However, no survival effect was found for hepatitis C virus with or without simultaneous Epstein-Barr virus infection, in the posttransplant lymphoproliferative disorders setting. Future prospective studies are needed for confirming our results.


Tactile perception of the roughness of the end of a tool: what role does tool handle roughness play?
We investigated whether the perceived roughness of the end of a tool is influenced by the texture of the handle used to hold it. Participants rated the roughness of the ends (caps) of a series of tools by rubbing them along their forearm, and indicated the perceived roughness of the tool's cap by means of an anchored visual scale. The caps of the tools had one of eight different levels of roughness varying from very smooth (sample 1) to very rough (sample 8). The participants held the tool handle in one hand while rubbing the cap of the tool against their contralateral forearm. The tool handle was either smooth (similar in smoothness to sample 1) or else very rough (matched in roughness to sample 8). Overall, participants were remarkably good at ignoring the roughness of the tool's handle when discriminating the roughness of the tool's cap. Nevertheless, the roughness of the tool handle was shown to modulate roughness judgments concerning the tool cap under certain conditions: in particular, tool caps at the rougher end of the scale (6 and 7) were rated as being significantly less rough when the participants held tools with a rough handle than when they held tools with a smooth handle. Our results therefore demonstrate a small but significant effect of the roughness of the handle of a tool on the perceived roughness of its cap.


Therapeutic uses of magnesium.
Magnesium is an essential mineral for optimal metabolic function. Research has shown that the mineral content of magnesium in food sources is declining, and that magnesium depletion has been detected in persons with some chronic diseases. This has led to an increased awareness of proper magnesium intake and its potential therapeutic role in a number of medical conditions. Studies have shown the effectiveness of magnesium in eclampsia and preeclampsia, arrhythmia, severe asthma, and migraine. Other areas that have shown promising results include lowering the risk of metabolic syndrome, improving glucose and insulin metabolism, relieving symptoms of dysmenorrhea, and alleviating leg cramps in women who are pregnant. The use of magnesium for constipation and dyspepsia are accepted as standard care despite limited evidence. Although it is safe in selected patients at appropriate dosages, magnesium may cause adverse effects or death at high dosages. Because magnesium is excreted renally, it should be used with caution in patients with kidney disease. Food sources of magnesium include green leafy vegetables, nuts, legumes, and whole grains.


The enolase of Borrelia burgdorferi is a plasminogen receptor released in outer membrane vesicles.
The agent of Lyme disease, Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles of B. burgdorferi contain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination.


LRP5 associates with specific subsets of macrophages: Molecular and functional effects.
Innate and acquired immunity is involved in the progression of atherosclerosis. The molecular mechanisms ruling monocyte to macrophage (Mø) differentiation are not yet fully understood. Different subtypes of plaque macrophages that have differentiated from monocytes recruited from circulating blood, have been characterized based on surface epitopes. We have recently shown that LRP5, a member of the LDL receptor superfamily supporting Wnt signalling, has an important role in monocyte to macrophage differentiation. The aim of this study was to investigate whether the CD16- and CD16+ macrophage subsets found in human atherosclerotic plaques have a differential LRP5 expression/function and Wnt signalling potential. We show for the first time that LRP5 expression is significantly higher in human CD16+Mø derived from CD14(+)CD16(+) monocytes than in CD16-Mø macrophages derived from CD14(+)CD16(-) monocytes. LRP5 is not found in human healthy vessel or arterial intimal thickening but is found in advanced human atherosclerotic lesions co-localizing only with the CD16+Mø macrophage subset. LRP5 expressing macrophages infiltrate the deep layers of atherosclerotic plaques towards the intima-media boundaries showing increased migratory activity and higher phagocytic activity. The equivalent for human patrolling CD14(+)CD16(+) monocytes in mice, CD115(+)GR1(low) monocytes, also show an increased expression of LRP5. In summary, classical CD14(+)CD16(-)monocytes that differentiate into CD16-Mø do not express LRP5. Instead, human monocytes expressing LRP5 differentiate into CD16+Mø antiinflammatory macrophages. These antiinflammatory macrophages are found in advanced atherosclerotic human plaques. Thus LRP5 is a signature of the anti-inflammatory defensive phenotype of macrophages.


The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children.
One-third of all individuals with epilepsy are resistant to antiepileptic drug (AED) treatment. Antiepileptic treatment response has been suggested to be modulated by genetic polymorphisms of drug efflux transporters. Several polymorphic variants within the multidrug resistance 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein, have been proposed to be associated with AED resistance in epilepsy patients. The aim of this study was to evaluate the effect of C3435T and G2677T/A polymorphisms of MDR1 on AED resistance in Turkish children with epilepsy. MDR1 C3435T and G2677T/A were genotyped in 152 patients with epilepsy, classified as drug-resistant in 69 and drug-responsive in 83. Genotypes of the C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction followed by restriction fragment length polymorphism. Genotype and allele frequencies of C3435T and G2677T/A polymorphisms of the MDR1 gene did not differ between drug-resistant and drug-responsive epilepsy patients. Our results suggest that MDR1 C3435T and G2677T/A polymorphisms are not associated with AED resistance in Turkish epileptic patients. To clarify the exact clinical implication of the MDR1 polymorphisms on the multidrug resistance in epilepsy, further investigations in various ethnic populations would be necessary.


The effectiveness of exercise therapy for temporomandibular dysfunction: a systematic review and meta-analysis.
To investigate the effectiveness of exercise therapy on pain, function, and mobility outcomes in patients with temporomandibular joint dysfunction. Systematic review with meta-analysis. A systematic review and meta-analysis undertaken following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that met the inclusion criteria: (1) randomized controlled trials; (2) a population with the diagnosis of temporomandibular joint dysfunction; and (3) interventions that included exercise therapy were considered for review. When studies demonstrated homogeneity on outcome measures, the mean differences or standardized mean differences with 95% confidence interval were calculated and pooled in a meta-analysis for pooled synthesis. Six articles with a total of 419 participants were included in the review and only four studies were included in the meta-analysis. Mobility and mixed exercise therapy approaches appear to be the most common exercise approaches utilized for management of temporomandibular joint dysfunction. Exercise therapy and the associated dosage provide moderate short-term and varying long-term benefits in reduction of pain and improvement of range of motion of the in patients with temporomandibular joint dysfunction. Included studies suggest a mobility or a mixed approach to exercise therapies have impact on reducing pain, significant impact for increasing range of motion, but lack a significant impact for functional improvement. Therapy, level 1a-.


The Impact of Music on the Self in Dementia.
In this review, we consider how the onset and progression of dementia can disrupt one's sense of self, and propose that music is an ideal tool for alleviating this distressing symptom. Various aspects of the self can be impaired in people with dementia, depending on how the self is defined. There are anecdotal reports that music can 'bring people back to themselves' in the face of dementia, but there have been scarce empirical investigations of this topic. Motivated by a consideration of the existing literature, we outline a novel theoretical framework that accounts for the relationship between music and the self in people with dementia. We propose that music has a number of 'design features' that make it uniquely equipped to engage multiple aspects of the self. We suggest that each design feature interacts with different aspects of the self to varying degrees, promoting overall wellbeing. We discuss how existing research on music and dementia fits within this framework, and describe two case studies in which music was an ideal stimulus for reaffirming their sense of self. Our framework may be useful for the diagnosis and treatment of impairments of self in people with dementia, and highlights how music, given its ability to engage all aspects of the self simultaneously, can result in an overall enhanced sense of self.


"Pinning strategy": a novel approach for predicting the backbone structure in terms of protein blocks from sequence.
The description of protein 3D structures can be performed through a library of 3D fragments, named a structural alphabet. Our structural alphabet is composed of 16 small protein fragments of 5 C alpha in length, called protein blocks (PBs). It allows an efficient approximation of the 3D protein structures and a correct prediction of the local structure. The 72 most frequent series of 5 consecutive PBs, called structural words (SWs)are able to cover more than 90% of the 3D structures. PBs are highly conditioned by the presence of a limited number of transitions between them. In this study, we propose a new method called "pinning strategy" that used this specific feature to predict long protein fragments. Its goal is to define highly probable successions of PBs. It starts from the most probable SW and is then extended with overlapping SWs. Starting from an initial prediction rate of 34.4%, the use of the SWs instead of the PBs allows a gain of 4.5%. The pinning strategy simply applied to the SWs increases the prediction accuracy to 39.9%. In a second step, the sequence-structure relationship is optimized, the prediction accuracy reaches 43.6%.


CDK-1 and two B-type cyclins promote PAR-6 stabilization during polarization of the early C. elegans embryo.
In the C. elegans embryo, formation of an antero-posterior axis of polarity relies on signaling by the conserved PAR proteins, which localize asymmetrically in two mutually exclusive groups at the embryonic cortex. Depletion of any PAR protein causes a loss of polarity and embryonic lethality. A genome-wide RNAi screen previously identified two B-type cyclins, cyb-2.1 and cyb-2.2, as suppressors of par-2(it5ts) lethality. We found that the loss of cyb-2.1 or cyb-2.2 suppressed the lethality and polarity defects of par-2(it5ts) mutants and that these cyclins act in cell polarity with their cyclin-dependent kinase partner, CDK-1. Interestingly, cyb-2.1; cyb-2.2 double mutants did not show defects in cell cycle progression or timing of polarity establishment, suggesting that they regulate polarity independently of their typical role in cell cycle progression. Loss of both cyclin genes or of cdk-1 resulted in a decrease in PAR-6 levels in the embryo. Furthermore, the activity of the cullin CUL-2 was required to achieve suppression of par-2 lethality when both cyclins were absent. Our results support a model in which CYB-2.1/2/CDK-1 antagonize CUL-2 activity to promote stabilization of PAR-6 levels during polarization of the early C. elegans embryo. They also suggest that CYB-2.1 and CYB-2.2 contribute to the coupling of cell cycle progression and asymmetric segregation of cell fate determinants.


Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells.
Stromal derived factor-1 (SDF-1) is a chemokine signaling molecule that binds to its transmembrane receptor CXC chemokine receptor-4 (CXCR4). While we previously detected that SDF-1 was co-required with bone morphogenetic protein 2 (BMP2) for differentiating mesenchymal C2C12 cells into osteoblastic cells, it is unknown whether SDF-1 is similarly involved in the osteogenic differentiation of mesenchymal stem cells (MSCs). Therefore, here we examined the role of SDF-1 signaling during BMP2-induced osteogenic differentiation of primary MSCs that were derived from human and mouse bone marrow. Our data showed that blocking of the SDF-1/CXCR4 signal axis or adding SDF-1 protein to MSCs significantly affected BMP2-induced alkaline phosphatase (ALP) activity and osteocalcin (OCN) synthesis, markers of preosteoblasts and mature osteoblasts, respectively. Moreover, disrupting the SDF-1 signaling impaired bone nodule mineralization during terminal differentiation of MSCs. Furthermore, we detected that blocking of the SDF-1 signaling inhibited the BMP2-induced early expression of Runt-related factor-2 (Runx2) and osterix (Osx), two "master" regulators of osteogenesis, and the SDF-1 effect was mediated via intracellular Smad and Erk activation. In conclusion, our results demonstrated a regulatory role of SDF-1 in BMP2-induced osteogenic differentiation of MSCs, as perturbing the SDF-1 signaling affected the differentiation of MSCs towards osteoblastic cells in response to BMP2 stimulation. These data provide novel insights into molecular mechanisms underlying MSC osteogenesis, and will contribute to the development of MSC therapies for enhancing bone formation and regeneration in broad orthopaedic situations.


Receptivity to protobacco media and its impact on cigarette smoking among ethnic minority youth in California.
Adolescents from different ethnic groups show different cigarette smoking prevalence rates, suggesting potential differences in receptivity to and influences from protobacco media. Understanding these differences will be helpful in tailoring smoking prevention and cessation programs for diverse adolescent populations in the United States. Data from cross-sectional surveys of 20,332 randomly sampled California boys and girls, 12-17 years of age, were analyzed. Results indicate that receptivity to protobacco media was lower among African Americans, Asian Americans, and Hispanics than among White youth. There was a consistent dose-response relationship between receptivity to protobacco media and 30-day cigarette smoking across ethnic groups. Having a cigarette brand preference was associated with the highest risk for cigarette smoking, having a favorite tobacco ad showed the lowest risk, while having received or being willing to use tobacco promotional items was associated with a moderate risk. After controlling for 13 covariates, the odds ratio for receptivity to protobacco media and 30-day cigarette smoking was significant for Whites (RR = 1.38, p < 0.01) and Hispanics (RR = 1.46, p < 0.01), but not for African American (RR = 1.05, p > 0.05) and Asian American (RR = 1.17, p > 0.05) youth. African American, Asian American, and Hispanic adolescents have a lower level of receptivity to protobacco media than do Whites. The association between media receptivity and 30-day cigarette smoking exists for all four ethnic groups without controlling for other smoking predictor variables, but only for Hispanics and Whites when other variables are controlled. Protecting adolescents from protobacco advertising influences is an important element in tobacco control among ethnic minority youth.


High systemic immune-inflammation index represents an unfavorable prognosis of malignant pleural mesothelioma.
Background: Malignant pleural mesothelioma (MPM) represents a fatal disease with high aggressiveness, and limited biomarkers have yet been identified for MPM. The present study aims to explore potential serum prognostic factors of MPM. Materials and methods: A retrospective analysis of 97 pathologically diagnosed MPM was performed. The optimal cutoff value of pretreatment systemic immune-inflammation index (SII) was determined by receiver operating characteristic curve. Kaplan-Meier curves and Cox regression analysis were performed to assess the potential prognostic roles of parameters. Results: A total of 59.8% (n=58) patients are male, with a median age of 56.0 years (range 18-77). The optimal cutoff value of SII was 988.6×109/L. High and low SII were found in 44 (45.4%) and 53 (54.6%) patients, respectively. Median survival time for total 97 cases was 18.5 months. The median overall survival for patients with low and high SII was 47.0 and 13.0 months, respectively. The 1-, 2- and 3-year survival rates for patients with low SII were 85.8%, 57.8% and 52.0% compared to that of 53.9%, 23.6% and 13.8% in patients with high SII. On univariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS)<2 points, low SII and adjuvant treatment (P<0.05) were found to be closely correlated with a better prognosis of MPM. Only ECOG PS (P=0.036) and SII (P=0.009) held statistical significance on multivariate analysis. Conclusion: Pretreatment SII is easy to access to, and it represents an efficiency and noninvasive biomarker of MPM. High SII represents an unfavorable independent prognostic factor of MPM, and this needs to be validated in further studies.


Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women.
A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p<0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women.


Selective impact of disease on short-term and long-term components of self-reported memory: a population-based HUNT study.
Subjective memory is commonly considered to be a unidimensional measure. However, theories of performance-based memory suggest that subjective memory could be divided into more than one dimension. To divide subjective memory into theoretically related components of memory and explore the relationship to disease. In this study, various aspects of self-reported memory were studied with respect to demographics and diseases in the third wave of the HUNT epidemiological study in middle Norway. The study included all individuals 55 years of age or older, who responded to a nine-item questionnaire on subjective memory and questionnaires on health (n=18 633). A principle component analysis of the memory items resulted in two memory components; the criterion used was an eigenvalue above 1, which accounted for 54% of the total variance. The components were interpreted as long-term memory (LTM; the first component; 43% of the total variance) and short-term memory (STM; the second component; 11% of the total variance). Memory impairment was significantly related to all diseases (except Bechterew's disease), most strongly to brain infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary disease and whiplash. For most diseases, the STM component was more affected than the LTM component; however, in cancer, the opposite pattern was seen. Subjective memory impairment as measured in HUNT contained two components, which were differentially associated with diseases.


Low field-relevant tebufenozide concentrations affect reproduction in Chironomus riparius (Diptera: Chironomidae) in a long-term toxicity test.
A few studies reporting the effects of tebufenozide, a non-steroidal ecdysone agonist that mimics natural moulting hormones in chironomids exist in the literature. However, nothing is known about its chronic or multigenerational effects on the reproduction of aquatic insects, although tebufenozide is present in aquatic ecosystems. Here, we investigated the chronic toxicity of tebufenozide in two successive generations of Chironomus riparius using nominal concentrations that ranged from 4 to 26.2 μg/L. We started the test from the first instar larvae in the parental (P) generation, quantifying life cycle parameters (emergence, sex ratio, development rate, fecundity and fertility) until the emergence in the subsequent F1 generation. Results showed a reduction in reproduction and a significant decrease in male developmental rate of midges for all treatments, in the F1 generation compared with the P generation (paired t test; p<0.001). Two-way analysis of variance revealed a significant exposure × generation effect on male fraction with male fraction increasing (P generation) or decreasing (F1 generation) with increasing exposure. These effects on C. riparius underline the importance of conducting long-term studies with environmentally relevant concentrations to investigate population-level endpoints for endocrine disrupting chemicals.


Organophosphorus pesticides decrease M2 muscarinic receptor function in guinea pig airway nerves via indirect mechanisms.
Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. Intravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS)-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity.


Investigating the role of stigma on fertility desire among HIV-positive women in Bangkok, Thailand: a qualitative study.
The Thai Ministry of Public Health is committed to reaching the United Nations' goal of zero new HIV infections, zero AIDS-related deaths, and zero discrimination towards people living with HIV by 2030. While significant progress has been made towards the first two targets, stigma against women living with HIV (WLHIV), particularly in the context of their desire to have and raise children, remains an issue. We conducted interviews with WLHIV (n=10) who expressed a desire to have a child or delivered an infant within 2 years of the study date, and key informants (KI) involved in their medical care and social support. We asked women about their HIV diagnosis, thoughts about pregnancy, desires to have children, and perceived stigma. KIs were asked about their perceptions of stigma towards WLHIV and policies or recommended actions to reduce discrimination towards this population. While the WLHIV reported that their healthcare providers had generally been supportive of them having children, internalised stigma and the perceived risk of or actual discrimination by community members negatively impacted fertility desire and peripartum experiences among the study participants. KIs confirmed similar sources of discrimination, emphasising more internalised and community-based stigma rather than from healthcare providers. Both groups highlighted the importance of increasing community education and awareness about HIV to reduce stigma. Complex issues around stigma and discrimination specific to women with HIV should be addressed at the community level in order to reach the goal of zero discrimination against all people living with HIV in Thailand.


Low levels of DNA polymerase alpha induce mitotic and meiotic instability in the ribosomal DNA gene cluster of Saccharomyces cerevisiae.
The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between both homologues and sister chromatids, about five-fold in mitotic cells and 30-fold in meiotic cells. This stimulation is independent of Fob1p, a protein required for the programmed replication fork block (RFB) in the rDNA. We observed that the fob1 mutation alone significantly increased meiotic, but not mitotic, rDNA recombination, suggesting a meiosis-specific role for this protein. We found that meiotic cells with low polymerase alpha had decreased Sir2p binding and increased Spo11p-catalyzed double-strand DNA breaks in the rDNA. Furthermore, meiotic crossover interference in the rDNA is absent. These results suggest that the hyper-Rec phenotypes resulting from low levels of DNA polymerase alpha in mitosis and meiosis reflect two fundamentally different mechanisms: the increased mitotic recombination is likely due to increased double-strand DNA breaks (DSBs) resulting from Fob1p-independent stalled replication forks, whereas the hyper-Rec meiotic phenotype results from increased levels of Spo11-catalyzed DSBs in the rDNA.


Is Post-Traumatic Stress Disorder Associated with Premature Senescence? A Review of the Literature.
Post-traumatic stress disorder (PTSD) has major public health significance. Evidence that PTSD may be associated with premature senescence (early or accelerated aging) would have major implications for quality of life and healthcare policy. We conducted a comprehensive review of published empirical studies relevant to early aging in PTSD. Our search included the PubMed, PsycINFO, and PILOTS databases for empirical reports published since the year 2000 relevant to early senescence and PTSD, including: 1) biomarkers of senescence (leukocyte telomere length [LTL] and pro-inflammatory markers), 2) prevalence of senescence-associated medical conditions, and 3) mortality rates. All six studies examining LTL indicated reduced LTL in PTSD (pooled Cohen's d = 0.76). We also found consistent evidence of increased pro-inflammatory markers in PTSD (mean Cohen's ds), including C-reactive protein = 0.18, Interleukin-1 beta = 0.44, Interleukin-6 = 0.78, and tumor necrosis factor alpha = 0.81. The majority of reviewed studies also indicated increased medical comorbidity among several targeted conditions known to be associated with normal aging, including cardiovascular disease, type 2 diabetes mellitus, gastrointestinal ulcer disease, and dementia. We also found seven of 10 studies indicated PTSD to be associated with earlier mortality (average hazard ratio: 1.29). In short, evidence from multiple lines of investigation suggests that PTSD may be associated with a phenotype of accelerated senescence. Further research is critical to understand the nature of this association. There may be a need to re-conceptualize PTSD beyond the boundaries of mental illness, and instead as a full systemic disorder.


Strain effects on oxygen migration in perovskites.
Fast oxygen transport materials are necessary for a range of technologies, including efficient and cost-effective solid oxide fuel cells, gas separation membranes, oxygen sensors, chemical looping devices, and memristors. Strain is often proposed as a method to enhance the performance of oxygen transport materials, but the magnitude of its effect and its underlying mechanisms are not well-understood, particularly in the widely-used perovskite-structured oxygen conductors. This work reports on an ab initio prediction of strain effects on migration energetics for nine perovskite systems of the form LaBO3, where B = [Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Ga]. Biaxial strain, as might be easily produced in epitaxial systems, is predicted to lead to approximately linear changes in migration energy. We find that tensile biaxial strain reduces the oxygen vacancy migration barrier across the systems studied by an average of 66 meV per percent strain for a single selected hop, with a low of 36 and a high of 89 meV decrease in migration barrier per percent strain across all systems. The estimated range for the change in migration barrier within each system is ±25 meV per percent strain when considering all hops. These results suggest that strain can significantly impact transport in these materials, e.g., a 2% tensile strain can increase the diffusion coefficient by about three orders of magnitude at 300 K (one order of magnitude at 500 °C or 773 K) for one of the most strain-responsive materials calculated here (LaCrO3). We show that a simple elasticity model, which assumes only dilative or compressive strain in a cubic environment and a fixed migration volume, can qualitatively but not quantitatively model the strain dependence of the migration energy, suggesting that factors not captured by continuum elasticity play a significant role in the strain response.


Cloning of heat shock protein genes (hsp90 and hsc70) and their expression during larval diapause and cold tolerance acquisition in the rice stem borer, Chilo suppressalis Walker.
The complete cDNA sequences of heat shock protein 90 (hsp90) and of heat shock cognate protein 70 (hsc70) were cloned by reverse transcription polymerase chain reaction from the rice stem borer, Chilo suppressalis Walker. They potentially encode a 717-amino-acids (hsp90) and a 652-amino-acids (hsc70) protein, with calculated molecular weight of 82.5 and 71.3 kDa, respectively. The deduced amino acid sequence of hsp90 showed the highest homology of 97.2% to Spodoptera frugiperda hsp90. The closest match of C. suppressalis hsc70 was with Manduca sexta hsc70 at 98.0% identity. Expression of hsp90 in diapausing larvae was higher than that in non-diapausing larvae. No such up-regulation in diapausing larvae was observed for hsc70. In non-diapausing larvae, but not in diapausing ones, hsp90 expression was up-regulated by cold acclimation. Hsc70 expression slightly decreased during cold acclimation irrespective of the state of diapause. Involvement of hsp90 and hsc70 in larval diapause and cold tolerance acquisition in C. suppressalis is discussed.


Light collimation and focusing by a thin flat metallic slab.
We present experimental and theoretical work showing that a flat metallic slab can collimate and focus light impinging on the slab from a point source. The effect is optimized when the radiation is around the bulk, not at the surface, plasma frequency. Also, the smaller the imaginary part of the permittivity is, the better the collimation. Experiments for Ag in the visible as well as calculations are presented. We also discuss the interesting case of Al, whose imaginary part of permittivity is very small at the plasma frequency in UV radiation. Generalization to other materials and radiations are also discussed.


Increasing incidence of childhood leukaemia: a controversy re-examined.
We provide evidence of a gradual increase in the incidence of childhood leukaemia over the twentieth century from examination of trends in both incidence and mortality in England and Wales. We conclude that much of the recorded increase is likely to be real.


[CD30-negative diffuse large B-cell lymphoma expressing ALK].
A 33-years-old man was diagnosed as having undifferentiated carcinoma presenting with right neck lymphadenopathy in December 2000. He obtained complete remission (CR) following chemotherapy, radiation and lymphadenectomy on the right neck. He had multiple para-aorta lymphadenopathy and splenomegaly in December 2001. An open-abdominal lymph node biopsy was performed from which a diagnosis of anaplastic large cell lymphoma was made. CR was achieved with biweekly CHOP, however, the patient suffered from a relapse twice. He underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sister while in non-CR in November 2002. Engraftment was achieved on day 14, and at the same time, complete chimerism was confirmed. Acute grade III graft-versus-host disease (GVHD) developed and was controlled with cyclosporine A and prednisolone. Extensive chronic GVHD was subsequently observed and required systemic immunosuppression. His condition returned to CR after the PBSCT and he sustained complete chimerism. He suddenly died of fulminant thrombotic microangiopathy seven months after the PBSCT. The tumor cells were ALK-positive, CD30-negative and JH rearrangement was detected, and were therefore classified as diffuse large B-cell lymphoma with expression of ALK according to the WHO classification, though they differed from this subtype in some points. Although this case was refractory for chemotherapy with a complex karyotype, the graft-versus-lymphoma effect might have contributed to the sustained CR following the PBSCT.


Exercise prescription for the prevention and treatment of cardiovascular diseases: part I.
Epidemiological, clinical and laboratory studies have provided definitive evidence that physical activity is able to improve fitness and reduce cardiovascular morbidity and mortality. Moreover, physical exercise also seems to significantly reduce the risk of developing other chronic diseases such as obesity, osteoporosis, diabetes, tumours and depression. Promoting physical activity in the general population is therefore one of the primary objectives of our healthcare institutions. Although the benefits of an active lifestyle have been demonstrated by numerous scientific data, only a few numbers of Italians and Europeans take up regular physical exercise. To promote physical activity, both in the general population and in subjects affected by cardiovascular diseases, the Italian Federation of Sports Medicine, the Italian Society of Sports Cardiology, the Italian Association of Hospital Cardiologists, the Italian Society of Cardiology, the Italian Association of Out-of-Hospital Cardiologists and the Italian Group of Cardiac Rehabilitation have promoted the constitution of a Task Force made up of experts in the fields of sports cardiology. The document produced by the Task Force is intended for healthcare professionals and deals with the role of physical activity in the prevention and treatment of cardiovascular diseases. It examines the beneficial effects of physical activity on the cardiovascular system, while analysing the possible risks involved and how they can be avoided. The rational principles underlying the prescription of physical activity in the cardiologic setting are described, as are the modalities for prescribing such activity.


Resuscitation of eleven-year VBNC Citrobacter.
Citrobacter freundii strain WA1 was stressed by incubation in seawater microcosms for eleven years. After two years of starvation, no culturable strain was observed. Incubation of samples in nutrient-rich broth medium not supplemented with growth factors, however, allowed resuscitation of VBNC cells so that subsequent plating yielded observable colonies for significantly extended periods of time. Recovery of VBNC Citrobacter freundii was obtained by incubation in nutrient broth even after eleven years of starvation. To see whether the samples contained the same strain of Citrobacter freundii inoculated 11 years ago. The complete 16S rRNA gene was PCR amplified and sequenced from initial, stressed and revived strains of Citrobacter freundii strain WA1.The 16S rRNA gene sequences from eleven-year stressed strains were homologous with a high degree of similarity to the GenBank reference strain and were identical to each other.


Impaired Communication Between the Dorsal and Ventral Stream: Indications from Apraxia.
Patients with apraxia perform poorly when demonstrating how an object is used, particularly when pantomiming the action. However, these patients are able to accurately identify, and to pick up and move objects, demonstrating intact ventral and dorsal stream visuomotor processing. Appropriate object manipulation for skilled use is thought to rely on integration of known and visible object properties associated with "ventro-dorsal" stream neural processes. In apraxia, it has been suggested that stored object knowledge from the ventral stream may be less readily available to incorporate into the action plan, leading to an over-reliance on the objects' visual affordances in object-directed motor behavior. The current study examined grasping performance in left hemisphere stroke patients with (N = 3) and without (N = 9) apraxia, and in age-matched healthy control participants (N = 14), where participants repeatedly grasped novel cylindrical objects of varying weight distribution. Across two conditions, object weight distribution was indicated by either a memory-associated cue (object color) or visual-spatial cue (visible dot over the weighted end). Participants were required to incorporate object-weight associations to effectively grasp and balance each object. Control groups appropriately adjusted their grasp according to each object's weight distribution across each condition, whereas throughout the task two of the three apraxic patients performed poorly on both the memory-associated and visual-spatial cue conditions. A third apraxic patient seemed to compensate for these difficulties but still performed differently to control groups. Patients with apraxia performed normally on the neutral control condition when grasping the evenly weighted version. The pattern of behavior in apraxic patients suggests impaired integration of visible and known object properties attributed to the ventro-dorsal stream: in learning to grasp the weighted object accurately, apraxic patients applied neither pure knowledge-based information (the memory-associated condition) nor higher-level information given in the visual-spatial cue condition. Disruption to ventro-dorsal stream predicts that apraxic patients will have difficulty learning to manipulate new objects on the basis of information other than low-level visual cues such as shape and size.


Long-term culture-initiating cell expansion is dependent on frequent medium exchange combined with stromal and other accessory cell effects.
Despite considerable effort, the expansion of long-term culture-initiating cells (LTC-ICs) in cultures of purified hematopoietic cells has not yet been achieved. In contrast, LTC-IC expansion has been attained in cultures of bone marrow mononuclear cells (MNC) using frequent medium exchange. The use of frequent medium exchange was, therefore, examined in cultures of CD34-enriched cells. In stromal-free, CD34-enriched cell cultures, medium exchange intervals ranging from 2 days to no feeding for 14 days gave similar results. Six different growth factor combinations, reported by other groups to give optimal expansion of CD34-enriched cells, were tested in comparison with the control combination of IL-3/GM-CSF/Epo/SCF. None of the combinations resulted in improved colony-forming unit-granulocyte macrophage (CFU-GM) expansion or LTC-IC maintenance, although two were equivalent. All stromal-free cultures resulted in loss of LTC-IC to half of input. Because of the limited effect of medium exchange and growth factor variations on CD34-enriched cell cultures, the effect of preformed stroma was next examined. Preformed stroma increased cell (3-fold), CFU-GM (5-fold), and LTC-IC (3-fold) output, but only when the medium was exchanged every other day. Under these conditions, the number of LTC-IC was maintained near input level. The lack of LTC-IC expansion in CD34-enriched cell cultures prompted experiments to examine the effect of cell purification. Parallel cultures were performed at CD34+lin- cell purities of 20%, 40%, 70%, and 95%, with each well containing exactly 4,000 CD34+lin- cells in addition to the CD34- accessory cells required to give the desired percentage. Also, MNC from the same source (approximately 2% CD34+lin-) were cultured at a concentration to give 4,000 CD34+lin- cells per well. As CD34+lin- cell purity was decreased from 95% to 2%, the output of cells, CFU-GM, and LTC-IC increased by threefold to fivefold. The loss of culture performance with purification was likely due to the removal of important accessory cells, because the levels of endogenously produced leukemia inhibitory factor and IL-6 were found to decline significantly with increasing CD34+lin- cell purity. In summary, preformed stroma abrogated the decrease in cell and CFU-GM output from cultured CD34-enriched cells and led to LTC-IC maintenance. In contrast, MNC inocula resulting in a growing stromal layer during the culture led to LTC-IC expansion (3.2-fold).(ABSTRACT TRUNCATED AT 400 WORDS)


A dyadic analysis of loneliness and health-related quality of life in Latinas with breast cancer and their informal caregivers.
The primary aim of this investigation is to provide a novel dyadic test of a model of loneliness and health-related quality of life (HRQoL) in a sample of Latinas with breast cancer and their informal caregivers. At baseline, dyads completed measures of loneliness and HRQoL. At a 3-month follow-up, they returned to complete the HRQoL measure. Associations were tested with the Actor-Partner Interdependence Model. About 234 Latinas with breast cancer diagnosed within the past year and their informal caregivers participated in the investigation. Loneliness was concurrently and negatively associated with HRQoL at baseline for both survivors and caregivers. Survivors' baseline loneliness, controlling for their baseline HRQoL, negatively predicted their HRQoL at 3 months. Survivors' HRQoL at baseline also predicted caregivers' HRQoL at 3 months. Loneliness is a risk factor for declines in HRQoL among cancer survivors. Their caregivers are also at risk for degraded HRQoL when the survivor experiences compromised HRQoL. Loneliness complicates the HRQoL of the cancer survivor-caregiver dyad.


PROMIS Paediatric Mobility tool is correlated with accelerometer-measured physical activity in children with hip diseases.
The reduction in mobility due to hip diseases in children is likely to affect their physical activity (PA) levels. Physical inactivity negatively influences quality of life and health. Our aim was to objectively measure PA in children with hip disease, and correlate it with the Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility Score. A total of 28 children (12 boys and 16 girls) with hip disease aged between 8and 17 years (mean 12 (SD 3)) were studied between December 2018 and July 2019. Children completed the PROMIS Paediatric Item Bank v. 2.0 - Mobility Short Form 8a and wore a hip accelerometer (ActiGraph) for seven consecutive days. Sedentary time (ST), light PA (LPA), moderate to vigorous PA (MVPA), and vigorous PA were calculated from the accelerometers' data. The PROMIS Mobility score was classified as normal, mild, and moderate functions, based on the PROMIS cut scores on the physical function metric. A one-way analysis of covariance (ANCOVA) was used to assess differences among mobility (normal; mild; moderate) and measured PA and relationships between these variables were assessed using bivariate Pearson correlations. Children classified as normally functioning on the PROMIS had less ST (p = 0.002), higher MVPA, (p = 0.002) and VPA (p = 0.004) compared to those classified as mild or moderate function. A moderate correlation was evident between the overall PROMIS score and daily LPA (r = 0.462, n = 28; p = 0.013), moderate-to-vigorous PA (r = 0.689, n = 28; p = 0.013) and vigorous PA (VPA) (r = 0.535, n = 28; p = 0.013). No correlation was evident between the mean daily ST and overall PROMIS score (r = -0.282, n = 28; p = 0.146). PROMIS Pediatric Mobility tool correlates well with experimentally measured levels of physical activity in children with hip disease. We provide external validity for the use of this tool as a measure of physical activity in children. Cite this article: Bone Joint J 2021;103-B(2):405-410.


Association study between candidate genes and obesity-related phenotypes using a sample of lumberjacks.
Complex traits such as obesity are modulated by genetic and environmental factors and lead to varied clinical presentations.The aim of this study was to investigate associations between candidate genes and obesity-related phenotypes using a sample of 252 lumberjacks issued from a founder population and sharing a common and circumscribed environment. Thirty-seven variants in 18 genes were genotyped. The restriction fragment length polymorphism method and the template-directed dye-terminator incorporation assay with fluorescence polarization detection were employed for the genotyping assays. Multivariate logistic regression models were built in order to calculate the relative odds of exhibiting obesity-related phenotypes associated with the presence of the studied polymorphism. Among them, 21 single nucleotide polymorphisms were tested for associations with obesity phenotypes. Significant associations were found between carriers of the minor alleles of APOE-epsilon2, FABP2-A54T, UCP1-L229M, LPL-HindIII, LPL-S447X and LPL-T1973C, patients bearing a combination of LPL-D9N, LPL-N291S and LPL-P207L and obesity-related phenotypes. The present results suggest that a particular population such as lumberjacks, sharing the same environment, could help target genes involved in complex traits.


Crystal structure of human CDK4 in complex with a D-type cyclin.
The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. Among the cyclin/CDKs, CDK4 and cyclin D1 are the most frequently activated by somatic genetic alterations in multiple tumor types. Thus, aberrant regulation of the CDK4/cyclin D1 pathway plays an essential role in oncogenesis; hence, CDK4 is a genetically validated therapeutic target. Although X-ray crystallographic structures have been determined for various CDK/cyclin complexes, CDK4/cyclin D1 has remained highly refractory to structure determination. Here, we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A. Although CDK4 is bound to cyclin D1 and has a phosphorylated T-loop, CDK4 is in an inactive conformation and the conformation of the heterodimer diverges from the previously known CDK/cyclin binary complexes, which suggests a unique mechanism for the process of CDK4 regulation and activation.


Evaluation of sepsis/systemic inflammatory response syndrome, acute kidney injury, and RIFLE criteria in two tertiary hospital intensive care units in Turkey.
Sepsis is a common cause of acute renal failure in intensive care units (ICU) with mortality rates as high as 60%. In this study, the clinical and laboratory predictors of acute kidney injury (AKI) in critically ill Turkish patients with sepsis/systemic inflammatory response syndrome were identified. We studied 139 (67 females/72 males) patients admitted to our ICUs with sepsis/systemic inflammatory response syndrome without renal failure. The clinical and laboratory parameters and treatments were recorded. Patients were classified as those without AKI (n = 60; 43.20%) and those with AKI (n = 79; 56.80%) based on the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria. Those with AKI were further classified as: risk in 27 (19%), injury in 25 (17.9%), failure in 25 (17.9%), and loss in 2 (1.4%). We found that the mortality rate increased with the severity of renal involvement: 56% in risk, 68% in injury, 72% in failure, and 100% in loss categories. Patients with AKI had a more positive fluid balance, higher central venous pressure, more vasopressor use, and lower systolic blood pressure. In multivariate analysis, the sequential organ failure assessment score, blood pressure, serum creatinine, and fluid balance were risk factors for the development of AKI. In this population, the incidence of AKI was higher and contrary to previous knowledge. A positive fluid balance also carries a risk for AKI and mortality in septic ICU patients. The RIFLE criteria were found to be applicable to our ICU population.


Test-retest reliability of value-driven attentional capture.
Attention is biased toward learned predictors of reward. The degree to which attention is automatically drawn to arbitrary reward cues has been linked to a variety of psychopathologies, including drug dependence, HIV-risk behaviors, depressive symptoms, and attention deficit/hyperactivity disorder. In the context of addiction specifically, attentional biases toward drug cues have been related to drug craving and treatment outcomes. Given the potential role of value-based attention in psychopathology, the ability to quantify the magnitude of such bias before and after a treatment intervention in order to assess treatment-related changes in attention allocation would be desirable. However, the test-retest reliability of value-driven attentional capture by arbitrary reward cues has not been established. In the present study, we show that an oculomotor measure of value-driven attentional capture produces highly robust test-retest reliability for a behavioral assessment, whereas the response time (RT) measure more commonly used in the attentional bias literature does not. Our findings provide methodological support for the ability to obtain a reliable measure of susceptibility to value-driven attentional capture at multiple points in time, and they highlight a limitation of RT-based measures that should inform the use of attentional-bias tasks as an assessment tool.


Immunomodulation in hepatocellular cancer.
Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the United States in relation to mortality. HCC relies on a complex immunosuppressive network to modify the host immune system and evade destruction. Intrinsic to the liver's function and anatomy, native hepatic and immune cells produce many inhibitory cytokines that promote tolerogenicity and limit immune response. Since the introduction of sorafenib in 2008, no treatment has been able to demonstrate improved survival in patients with advanced HCC post disease progression treated with sorafenib. More recent studies have shown that sorafenib has an immunomodulatory function in addition to inhibition of multiple tyrosine kinases. Clinical trials have aimed to further enhance this immunomodulatory function with other treatments, most promisingly immune checkpoint inhibitors. Additionally, ongoing studies are using combinatorial approaches with immunomodulatory treatment and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation. This article will review recent data describing the immunosuppressive network in HCC, recent results of immunotherapies, and combinatorial approaches to treat advanced HCC.


Mechanism of the delayed puberty onset in offspring of rats that consumed aqueous extract of Hibiscus sabdariffa during pregnancy.
Consumption of extracts of Hibiscus sabdariffa (family: malvaceae) during pregnancy has been shown to cause maternal malnutrition which has been linked to various adverse conditions like increased postnatal weight gain, delayed puberty onset and elevated body weight and body mass index at onset of puberty in the female offspring. The present study was designed to investigate the possible mechanism underlying this. Eighteen in-bred pregnant Sprague-Dawley rats were on day 1 of pregnancy, randomly divided into three groups of six animals each. Group A (control) was given tap water to drink. Group B was given 0.6g extract/100ml while Group C was given 1.8g extract/100ml as their drinking solution. All groups received normal rat chow and their drinking solution ad libitum. Fluid and food intake and dam weights were measured daily throughout pregnancy. On gestational day 18, blood sample was withdrawn from each rat for estimation of plasma Na ion and corticosterone levels. On the day of delivery, the solutions of the extracts of Hibiscus sabdariffa were withdrawn and replaced with tap water. After 21 days, the pups were weaned to tap water and food ad libitum. Pups weight and age and body mass index at onset of puberty were measured. The results of the present study showed that the increased postnatal weight gain, delayed puberty onset and elevated body mass index at onset of puberty in the offspring of rats that consumed HS during pregnancy was associated with elevated maternal plasma Na ion and corticosterone levels during pregnancy.


Report on The Society for Fetal Urology panel discussion on the selection criteria and intervention for fetal bladder outlet obstruction.
The Society for Fetal Urology panel section at the 2016 Fall Congress featured a multidisciplinary discussion on appropriate patient selection, the conservative versus surgical management, and postnatal renal outcome of fetuses with lower urinary tract obstruction (LUTO). Rodrigo Ruano shared his experience of prenatal intervention, presenting the outcome of 111 fetuses with severe LUTO treated with vesicoamniotic shunting (VAS) (n = 16), cystoscopy (n = 34) or no intervention (n = 61) in a non-randomized series. Multivariate analysis at the 6-month follow-up suggested a significantly higher probability of survival with fetal intervention versus no intervention. A clear trend for normal renal function was present in the fetal cystoscopy group, but not in the VAS group. In cases in which there was a postnatal diagnosis of posterior urethral valves (n = 57), fetal cystoscopy was effective in improving both the 6-month survival rate and renal function, while VAS was associated with an improvement in the 6-month survival rate. In an attempt to better define which fetuses would benefit from intervention, Michael Braun explained the proposed LUTO classification system that incorporates: (1) fetal urinary biomarkers of renal injury; (2) amniotic fluid levels as a surrogate for the severity of obstruction; and (3) imaging studies to identify signs of renal dysplastic or cystic changes. Intervention was not recommended in patients at low risk of either renal disease or pulmonary hypoplasia (Stage 1). Vesicoamniotic shunting was performed in patients at high risk of either progressive renal injury or pulmonary hypoplasia without evidence of severe pre-existing renal damage (Stage 2). For those patients, who at the time of evaluation had evidence of severe renal disease (Stage 3), fetal intervention was individualized and often based on bladder capacity and bladder refilling after vesicocentesis. He went on to present the nephrologic outcome of fetuses managed over the last 3 years utilizing the selection criteria. Craig Peters supported the concept of selective criteria and discussed the cautious viewpoint, namely: (1) the procedure may be unnecessary, as it is possible for patients to do well, in spite of severe prenatal obstruction; and (2) the risk of giving partial treatment by allowing the baby to survive to delivery with the daunting postnatal journey of renal and pulmonary insufficiency. Standardized patient selection utilizing a staging system is undoubtedly the way forward and will enable comparable long-term renal and bladder functional outcome studies.


A New Pathway for Mannitol Metabolism in Yeasts Suggests a Link to the Evolution of Alcoholic Fermentation.
The yeasts belonging to the Wickerhamiella and Starmerella genera (W/S clade) share a distinctive evolutionary history marked by loss and subsequent reinstatement of alcoholic fermentation mediated by horizontal gene transfer events. Species in this clade also share unusual features of metabolism, namely the preference for fructose over glucose as carbon source, a rare trait known as fructophily. Here we show that fructose may be the preferred sugar in W/S-clade species because, unlike glucose, it can be converted directly to mannitol in a reaction with impact on redox balance. According to our results, mannitol is excreted to the growth medium in appreciable amounts along with other fermentation products such as glycerol and ethanol but unlike the latter metabolites mannitol production increases with temperature. We used comparative genomics to find genes involved in mannitol metabolism and established the mannitol biosynthesis pathway in W/S-clade species Starmerella bombicola using molecular genetics tools. Surprisingly, mannitol production seems to be so important that St. bombicola (and other W/S-clade species) deploys a novel pathway to mediate the conversion of glucose to fructose, thereby allowing cells to produce mannitol even when glucose is the sole carbon source. Using targeted mutations and 13C-labeled glucose followed by NMR analysis of end-products, we showed that the novel mannitol biosynthesis pathway involves fructose-6-phosphate as an intermediate, implying a key role for a yet unknown fructose-6-P phosphatase. We hypothesize that mannitol production contributed to mitigate the negative effects on redox balance of the ancient loss of alcoholic fermentation in the W/S clade. Presently, mannitol also seems to play a role in stress protection.


Group size and nest spacing affect Buggy Creek virus (Togaviridae: Alphavirus) infection in nestling house sparrows.
The transmission of parasites and pathogens among vertebrates often depends on host population size, host species diversity, and the extent of crowding among potential hosts, but little is known about how these variables apply to most vector-borne pathogens such as the arboviruses (arthropod-borne viruses). Buggy Creek virus (BCRV; Togaviridae: Alphavirus) is an RNA arbovirus transmitted by the swallow bug (Oeciacus vicarius) to the cliff swallow (Petrochelidon pyrrhonota) and the introduced house sparrow (Passer domesticus) that has recently invaded swallow nesting colonies. The virus has little impact on cliff swallows, but house sparrows are seriously affected by BCRV. For house sparrows occupying swallow nesting colonies in western Nebraska, USA, the prevalence of BCRV in nestling sparrows increased with sparrow colony size at a site but decreased with the number of cliff swallows present. If one nestling in a nest was infected with the virus, there was a greater likelihood that one or more of its nest-mates would also be infected than nestlings chosen at random. The closer a nest was to another nest containing infected nestlings, the greater the likelihood that some of the nestlings in the focal nest would be BCRV-positive. These results illustrate that BCRV represents a cost of coloniality for a vertebrate host (the house sparrow), perhaps the first such demonstration for an arbovirus, and that virus infection is spatially clustered within nests and within colonies. The decreased incidence of BCRV in sparrows as cliff swallows at a site increased reflects the "dilution effect," in which virus transmission is reduced when a vector switches to feeding on a less competent vertebrate host.


Training for eye contact modulates gaze following in dogs.
Following human gaze in dogs and human infants can be considered a socially facilitated orientation response, which in object choice tasks is modulated by human-given ostensive cues. Despite their similarities to human infants, and extensive skills in reading human cues in foraging contexts, no evidence that dogs follow gaze into distant space has been found. We re-examined this question, and additionally whether dogs' propensity to follow gaze was affected by age and/or training to pay attention to humans. We tested a cross-sectional sample of 145 border collies aged 6 months to 14 years with different amounts of training over their lives. The dogs' gaze-following response in test and control conditions before and after training for initiating eye contact with the experimenter was compared with that of a second group of 13 border collies trained to touch a ball with their paw. Our results provide the first evidence that dogs can follow human gaze into distant space. Although we found no age effect on gaze following, the youngest and oldest age groups were more distractible, which resulted in a higher number of looks in the test and control conditions. Extensive lifelong formal training as well as short-term training for eye contact decreased dogs' tendency to follow gaze and increased their duration of gaze to the face. The reduction in gaze following after training for eye contact cannot be explained by fatigue or short-term habituation, as in the second group gaze following increased after a different training of the same length. Training for eye contact created a competing tendency to fixate the face, which prevented the dogs from following the directional cues. We conclude that following human gaze into distant space in dogs is modulated by training, which may explain why dogs perform poorly in comparison to other species in this task.


Workplace pedometer interventions for increasing physical activity.
The World Health Organization (WHO) recommends undertaking 150 minutes of moderate-intensity physical activity per week, but most people do not. Workplaces present opportunities to influence behaviour and encourage physical activity, as well as other aspects of a healthy lifestyle. A pedometer is an inexpensive device that encourages physical activity by providing feedback on daily steps, although pedometers are now being largely replaced by more sophisticated devices such as accelerometers and Smartphone apps. For this reason, this is the final update of this review. To assess the effectiveness of pedometer interventions in the workplace for increasing physical activity and improving long-term health outcomes. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Occupational Safety and Health (OSH) UPDATE, Web of Science, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from the earliest record to December 2016. We also consulted the reference lists of included studies and contacted study authors to identify additional records. We updated this search in May 2019, but these results have not yet been incorporated. One more study, previously identified as an ongoing study, was placed in 'Studies awaiting classification'. We included randomised controlled trials (RCTs) of workplace interventions with a pedometer component for employed adults, compared to no or minimal interventions, or to alternative physical activity interventions. We excluded athletes and interventions using accelerometers. The primary outcome was physical activity. Studies were excluded if physical activity was not measured. We used standard methodological procedures expected by Cochrane. When studies presented more than one physical activity measure, we used a pre-specified list of preferred measures to select one measure and up to three time points for analysis. When possible, follow-up measures were taken after completion of the intervention to identify lasting effects once the intervention had ceased. Given the diversity of measures found, we used ratios of means (RoMs) as standardised effect measures for physical activity. We included 14 studies, recruiting a total of 4762 participants. These studies were conducted in various high-income countries and in diverse workplaces (from offices to physical workplaces). Participants included both healthy populations and those at risk of chronic disease (e.g. through inactivity or overweight), with a mean age of 41 years. All studies used multi-component health promotion interventions. Eleven studies used minimal intervention controls, and four used alternative physical activity interventions. Intervention duration ranged from one week to two years, and follow-up after completion of the intervention ranged from three to ten months. Most studies and outcomes were rated at overall unclear or high risk of bias, and only one study was rated at low risk of bias. The most frequent concerns were absence of blinding and high rates of attrition. When pedometer interventions are compared to minimal interventions at follow-up points at least one month after completion of the intervention, pedometers may have no effect on physical activity (6 studies; very low-certainty evidence; no meta-analysis due to very high heterogeneity), but the effect is very uncertain. Pedometers may have effects on sedentary behaviour and on quality of life (mental health component), but these effects were very uncertain (1 study; very low-certainty evidence). Pedometer interventions may slightly reduce anthropometry (body mass index (BMI) -0.64, 95% confidence interval (CI) -1.45 to 0.18; 3 studies; low-certainty evidence). Pedometer interventions probably had little to no effect on blood pressure (systolic: -0.08 mmHg, 95% CI -3.26 to 3.11; 2 studies; moderate-certainty evidence) and may have reduced adverse effects (such as injuries; from 24 to 10 per 100 people in populations experiencing relatively frequent events; odds ratio (OR) 0.50, 95% CI 0.30 to 0.84; low-certainty evidence). No studies compared biochemical measures or disease risk scores at follow-up after completion of the intervention versus a minimal intervention. Comparison of pedometer interventions to alternative physical activity interventions at follow-up points at least one month after completion of the intervention revealed that pedometers may have an effect on physical activity, but the effect is very uncertain (1 study; very low-certainty evidence). Sedentary behaviour, anthropometry (BMI or waist circumference), blood pressure (systolic or diastolic), biochemistry (low-density lipoprotein (LDL) cholesterol, total cholesterol, or triglycerides), disease risk scores, quality of life (mental or physical health components), and adverse effects at follow-up after completion of the intervention were not compared to an alternative physical activity intervention. Some positive effects were observed immediately at completion of the intervention periods, but these effects were not consistent, and overall certainty of evidence was insufficient to assess the effectiveness of workplace pedometer interventions. Exercise interventions can have positive effects on employee physical activity and health, although current evidence is insufficient to suggest that a pedometer-based intervention would be more effective than other options. It is important to note that over the past decade, technological advancement in accelerometers as commercial products, often freely available in Smartphones, has in many ways rendered the use of pedometers outdated. Future studies aiming to test the impact of either pedometers or accelerometers would likely find any control arm highly contaminated. Decision-makers considering allocating resources to large-scale programmes of this kind should be cautious about the expected benefits of incorporating a pedometer and should note that these effects may not be sustained over the longer term. Future studies should be designed to identify the effective components of multi-component interventions, although pedometers may not be given the highest priority (especially considering the increased availability of accelerometers). Approaches to increase the sustainability of intervention effects and behaviours over a longer term should be considered, as should more consistent measures of physical activity and health outcomes.


Towards resolving Lamiales relationships: insights from rapidly evolving chloroplast sequences.
In the large angiosperm order Lamiales, a diverse array of highly specialized life strategies such as carnivory, parasitism, epiphytism, and desiccation tolerance occur, and some lineages possess drastically accelerated DNA substitutional rates or miniaturized genomes. However, understanding the evolution of these phenomena in the order, and clarifying borders of and relationships among lamialean families, has been hindered by largely unresolved trees in the past. Our analysis of the rapidly evolving trnK/matK, trnL-F and rps16 chloroplast regions enabled us to infer more precise phylogenetic hypotheses for the Lamiales. Relationships among the nine first-branching families in the Lamiales tree are now resolved with very strong support. Subsequent to Plocospermataceae, a clade consisting of Carlemanniaceae plus Oleaceae branches, followed by Tetrachondraceae and a newly inferred clade composed of Gesneriaceae plus Calceolariaceae, which is also supported by morphological characters. Plantaginaceae (incl. Gratioleae) and Scrophulariaceae are well separated in the backbone grade; Lamiaceae and Verbenaceae appear in distant clades, while the recently described Linderniaceae are confirmed to be monophyletic and in an isolated position. Confidence about deep nodes of the Lamiales tree is an important step towards understanding the evolutionary diversification of a major clade of flowering plants. The degree of resolution obtained here now provides a first opportunity to discuss the evolution of morphological and biochemical traits in Lamiales. The multiple independent evolution of the carnivorous syndrome, once in Lentibulariaceae and a second time in Byblidaceae, is strongly supported by all analyses and topological tests. The evolution of selected morphological characters such as flower symmetry is discussed. The addition of further sequence data from introns and spacers holds promise to eventually obtain a fully resolved plastid tree of Lamiales.


Identification of a novel benzimidazole that inhibits bacterial biofilm formation in a broad-spectrum manner.
Bacterial biofilm formation causes significant industrial economic loss and high morbidity and mortality in medical settings. Biofilms are defined as multicellular communities of bacteria encased in a matrix of protective extracellular polymers. Because biofilms have a high tolerance for treatment with antimicrobials, protect bacteria from immune defense, and resist clearance with standard sanitation protocols, it is critical to develop new approaches to prevent biofilm formation. Here, a novel benzimidazole molecule, named antibiofilm compound 1 (ABC-1), identified in a small-molecule screen, was found to prevent bacterial biofilm formation in multiple Gram-negative and Gram-positive bacterial pathogens, including Pseudomonas aeruginosa and Staphylococcus aureus, on a variety of different surface types. Importantly, ABC-1 itself does not inhibit the growth of bacteria, and it is effective at nanomolar concentrations. Also, coating a polystyrene surface with ABC-1 reduces biofilm formation. These data suggest ABC-1 is a new chemical scaffold for the development of antibiofilm compounds.


Quantification of anticipation of excitement with a three-axial model of emotion with EEG.
Multiple facets of human emotion underlie diverse and sparse neural mechanisms. Among the many existing models of emotion, the two-dimensional circumplex model of emotion is an important theory. The use of the circumplex model allows us to model variable aspects of emotion; however, such momentary expressions of one's internal mental state still lacks a notion of the third dimension of time. Here, we report an exploratory attempt to build a three-axis model of human emotion to model our sense of anticipatory excitement, 'Waku-Waku' (in Japanese), in which people predictively code upcoming emotional events. Electroencephalography (EEG) data were recorded from 28 young adult participants while they mentalized upcoming emotional pictures. Three auditory tones were used as indicative cues, predicting the likelihood of the valence of an upcoming picture: positive, negative, or unknown. While seeing an image, the participants judged its emotional valence during the task and subsequently rated their subjective experiences on valence, arousal, expectation, and Waku-Waku immediately after the experiment. The collected EEG data were then analyzed to identify contributory neural signatures for each of the three axes. A three-axis model was built to quantify Waku-Waku. As expected, this model revealed the considerable contribution of the third dimension over the classical two-dimensional model. Distinctive EEG components were identified. Furthermore, a novel brain-emotion interface was proposed and validated within the scope of limitations. The proposed notion may shed new light on the theories of emotion and support multiplex dimensions of emotion. With the introduction of the cognitive domain for a brain-computer interface, we propose a novel brain-emotion interface. Limitations of the study and potential applications of this interface are discussed.


Occurrence of imposex in Thais haemastoma: possible evidence of environmental contamination derived from organotin compounds in Rio de Janeiro and Fortaleza, Brazil.
There are indications that the widespread use of organotin compounds (TBT and TPT) as antifoulings, as stabilizers in plastic and as pesticides, has severely affected several species of marine organisms. The most striking effect of TBT and TPT as hormonal disruptors is the development of male organs in females of gastropods, currently denominated imposex. This syndrome can lead to the sterilization and death of affected organisms. The present work gives an overview of the present state of knowledge on imposex occurrence and reports results of a survey conducted in Guanabara Bay, Rio de Janeiro and in several sites along the coast of Fortaleza, Ceará State. Different stages of imposex development were verified in this survey, however, the most prominent levels appeared associated to known spot sources of TBT and TPT.


Isolation and characterization of cDNA clones encoding pig gastric mucin.
Polyclonal antibodies raised to deglycosylated pig gastric mucin were used to screen a cDNA library constructed with pig stomach mucosal mRNA. Immunocytochemistry indicated that the antibody recognizes intracellular and secreted mucin in surface mucous cells of pig gastric epithelium. A total of 70 clones producing proteins immunoreactive to this antibody were identified, two of which (PGM-2A,9B) were fully sequenced from both ends. Clone PGM-9B hybridized to a polydisperse mRNA (3-9 kb) from pig stomach, but not liver, intestine or spleen, nor to mRNA from human, mouse, rabbit or rat stomach. Sequence analysis indicated that PGM-9B encodes 33 tandem repeats of a 16-amino-acid consensus sequence rich in serine (46%) and threonine (17%). Using the restriction enzyme MwoI, which has a single target site in the repeat, it was demonstrated that PGM-9B consists entirely of this tandem repeat. Southern-blot analysis indicated that the repeat region is contained in a 20 kb HindIII-EcoRI fragment, and BamHI digestion suggested that most of the repeats are contained in a 10 kb fragment. In situ hybridization with an antisense probe to PGM-9B showed an intense signal in the entire gastric gland. Clone PGM-2A also contains the same repeat sequence as 9B, but, in addition, has a 64-amino-acid-long non-repeat region at its 5' end. Interestingly the non-repeat region of PGM-2A has five cysteine residues, the arrangement of which is identical with that reported for human intestinal mucin gene MUC2.


Modification of Ran GTPase-activating protein by the small ubiquitin-related modifier SUMO-1 requires Ubc9, an E2-type ubiquitin-conjugating enzyme homologue.
Covalent modification of the Ran GTPase-activating protein RanGAP1 with the ubiquitin-related protein SUMO-1 promotes its association with Nup358, a component of the cytoplasmic fibrils emanating from the nuclear pore complex (1,2). In Xenopus egg extracts, Nup358 can be found in a complex with Ubc9 (3), a structural homologue of the E2-type ubiquitin-conjugating enzymes (UBCs). Here we show that a subset of the human homologue of Ubc9 (HsUbc9) colocalizes with RanGAP1 at the nuclear envelope. HsUbc9 forms thiolester conjugates with recombinant SUMO-1, but not with recombinant ubiquitin, indicating that it is functionally distinct from E2-type UBCs. Finally, HsUbc9 is required for the modification of RanGAP1 by SUMO-1. These results suggest that HsUbc9 is a component of a novel enzymatic cascade that modifies RanGAP1, and possibly other substrates, with SUMO-1.


Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes.
We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated.


A follow-up of 130 patients with acromegaly in a single centre.
Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly. 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy. We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up. There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease.


A triterpenoid-enriched extract of bitter melon leaves alleviates hepatic fibrosis by inhibiting inflammatory responses in carbon tetrachloride-treated mice.
Liver fibrosis is a progression of chronic liver disease characterized by excess deposition of fibrillary collagen. The aim of this study was to investigate the protective effect of a triterpenoid-enriched extract (TEE) from bitter melon leaves against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. Male ICR mice received TEE (100 or 150 mg kg-1) by daily oral gavage for one week before starting CCl4 administration and throughout the entire experimental period. After intraperitoneal injection of CCl4 for nine weeks, serum and liver tissues of the mice were collected for biochemical, histopathological and molecular analyses. Our results showed that TEE supplementation reduced CCl4-induced serum aspartate aminotransferase and alanine aminotransferase activities. Histopathological examinations revealed that CCl4 administration results in hepatic fibrosis, while TEE supplementation significantly suppressed hepatic necroinflammation and collagen deposition. In addition, TEE supplementation decreased α-smooth muscle actin (α-SMA)-positive staining and protein levels of α-SMA and transforming growth factor-β1. TEE-supplemented mice had lower mRNA expression levels of interleukin-6, tumor necrosis factor-α, and toll-like receptor 4. Moreover, TEE (150 mg kg-1) supplementation significantly reduced intrahepatic inflammatory Ly6C+ monocyte infiltration. We demonstrated that TEE could ameliorate hepatic fibrosis by regulating inflammatory cytokine secretion and α-SMA expression in the liver to reduce collagen accumulation.