Development and evaluation of the EOL-ICDQ as a measure of experiences, attitudes and knowledge in end-of-life in patients living with an implantable cardioverter defibrillator.
Due to extended indications and resynchronization therapy, many implantable cardioverter defibrillator (ICD) recipients will experience progressive co-morbid conditions and will be more likely to die of causes other than cardiac death. It is therefore important to elucidate the ICD patients' preferences when nearing end-of-life. Instead of avoiding the subject of end-of-life, a validated questionnaire may be helpful to explore patients' experiences and attitudes about end-of-life concerns and to assess knowledge of the function of the ICD in end-of-life. Validated instruments assessing patients' perspective concerning end-of-life issues are scarce. The purpose of this study was to develop and evaluate respondent satisfaction and measurement properties of the 'Experiences, Attitudes and Knowledge of End-of-Life Issues in Implantable Cardioverter Defibrillator Patients' Questionnaire' (EOL-ICDQ). The instrument was tested for validity, respondent satisfaction, and for homogeneity and stability in the Swedish language. An English version of the EOL-ICDQ was validated, but has not yet been pilot tested. The final instrument contained three domains, which were clustered into 39 items measuring: experiences (10 items), attitudes (18 items), and knowledge (11 items) of end-of-life concerns in ICD patients. In addition, the questionnaire also contained items on socio-demographic background (six items) and ICD-specific background (eight items). The validity and reliability properties were considered sufficient. The EOL-ICDQ has the potential to be used in clinical practice and future research. Further studies are needed using this instrument in an Anglo-Saxon context with a sample of English-speaking ICD recipients.


Sex and race or ethnicity disparities in opioid prescriptions for dental diagnoses among patients receiving Medicaid.
The objective of this study was to identify specific factors (sex, race or ethnicity, and health care provider type) associated with patient receipt of an opioid prescription after a dental diagnosis. The authors used Medicaid claims dated from January 1, 2013, through September 30, 2015, for 13 US states in this study. The authors identified oral health-related conditions by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes 520.0 through 529.9. During the 2013-2015 study period, among the more than 890,000 Medicaid patients with a dental diagnosis, 23% received an opioid within 14 days of diagnosis. Female patients were 50% more likely to receive an opioid for pain management of a dental condition than were men (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.52 to 1.55). Non-Hispanic whites and African Americans were approximately twice as likely to receive opioids than were Hispanics (OR, 2.11; 95% CI, 2.05 to 2.17 and OR, 1.88; 95% CI, 1.83 to 1.93, respectively). Patients receiving oral health care in an emergency department were nearly 5 times more likely to receive an opioid prescription than were patients treated in a dental office (OR, 4.66; 95% CI, 4.59 to 4.74). Patients with a dental condition diagnosed were nearly 3 times as likely to receive an opioid from a nurse practitioner as from a dentist (OR, 2.64; 95% CI, 2.57 to 2.70). Opioid use was substantially higher among African American female patients (OR, 3.29; 95% CI, 3.18 to 3.40) and non-Hispanic white female patients (OR, 3.24; 95% CI, 3.14 to 3.35) than among Hispanic female patients. Opioid prescribing patterns differ depending on patient race or ethnicity, sex, and health care provider source in patients with a dental diagnosis in the United States. Dentists are providing substantially less opioid prescriptions compared to their medical colleagues for pain treatment following a dental diagnosis in the Medicaid population. When considering pain management for dental and related conditions, dentists should continue with conservative prescribing practices as recommended.


A 40 % paddy surface soil organic carbon increase after 5-year no-tillage is linked with shifts in soil bacterial composition and functions.
Soil organic carbon (SOC) is related to soil fertility, crop yield, and climate change mitigation. Paddy soil is a significant carbon (C) sink, but its C sequestration potential has not been realized as the various driving factors are still not fully understood. We performed a 5-year paddy field experiment in southern China to estimate tillage effects on SOC accumulation and its relation with soil bacteria. The C input from rice residue, SOC content, CO2 flux, soil bacterial community composition, and predicted functions were analyzed. No-tillage (NT) increased (p < 0.05) rice residue C inputs (by 12.6 %-15.9 %), SOC (by 40 % at the surface soil layer compared with conventional tillage, CT), and CO2 fluxes compared with reduced tillage (RT) and CT. Also, NT significantly altered the soil bacterial community. The random forest model showed that the predicted bacterial functions of "Degradation/Utilization/Assimilation Other", "C1 Compound Assimilation", and "Amin and Polyamine Degradation" were the most important functions associated with SOC accumulation. Analysis of metabolic pathway differences indicated that NT significantly decreased the BENZCOA-PWY (anaerobic aromatic compound degradation) and the AST-PWY (L-arginine degradation II). Therefore, the rapid paddy SOC increase is associated with both residue C input (from higher rice yields) and the degradation functions regulated by soil bacteria.


Kinetics of glucocorticoid exposure in developing zebrafish: A tracer study.
In the current study the dynamics of glucocorticoid uptake by zebrafish chorionated embryos from the surrounding medium were studied, using 2.5 μM cortisol or dexamethasone solutions complemented with their tritiated variant. We measured the uptake of radioactive cortisol by embryos during a 1 h submersion. Interestingly, the signal in chorionated embryos was 85% (exposure: 1-2 hpf) or 78% (exposure: 48-49 hpf) of the signal present in an equal volume medium. By comparing embryos measured without chorion, we found that 18-20% of the radioactivity present in chorionated embryos is actually bound to the chorion or located in the perivitelline space. Consequently, embryonic tissue contains radioactivity levels of 60% of a similar volume of medium after 1 h incubation. During early developmental stages (1-48 hpf) exposure of more than 24 h in cortisol was needed to achieve radioactivity levels similar to an equal volume of medium within the embryonic tissue and more than 48 h for dexamethasone. In glucocorticoid-free medium, radioactivity dropped rapidly below 10% for both glucocorticoids, suggesting that the major portion of the embryonic radioactivity was a result of simple diffusion. During later developmental stages (48-96 hpf) initial uptake dynamics were similar, but showed a decrease of tissue radioactivity to 20% of an equal volume of medium after hatching, probably due to development and activation of the hypothalamic pituitary interrenal axis. Uptake is dependent on the developmental stage of the embryo. Furthermore, the presence of the chorion during exposure should be taken into account even when small lipophilic molecules are being tested.


Identification of the long-sought common-envelope events.
Common-envelope events (CEEs), during which two stars temporarily orbit within a shared envelope, are believed to be vital for the formation of a wide range of close binaries. For decades, the only evidence that CEEs actually occur has been indirect, based on the existence of systems that could not be otherwise explained. Here we propose a direct observational signature of CEEs arising from a physical model where emission from matter ejected in a CEE is controlled by a recombination front as the matter cools. The natural range of time scales and energies from this model, as well as the expected colors, light-curve shapes, ejection velocities, and event rate, match those of a recently recognized class of red transient outbursts.


Prognostic Influence of the Time Interval between Surgery and Chemotherapy in Epithelial Ovarian Cancer.
The influence of time to chemotherapy (TTC) on recurrence and survival among epithelial ovarian cancer (EOC) patients still remains unknown. This single center retrospective cohort study was conducted on 489 EOC patients who underwent surgery followed by taxane- plus platinum-based chemotherapy in the Shengjing Hospital of China Medical University between 2011 and 2015. The Multivariate cox proportional regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) after adjustment for potential confounders. The median follow-up duration was 2.97 years (inter-quartile range from 2.11 to 4.13 years). The recurrence and mortality rate of the all patients was 50.9% (249/489) and 43.6% (213/489), respectively. Having comorbidity, residual disease, ascites, and advanced FIGO stage (III-IV) was associated worse PFS and OS of EOC patients. Compared to TTC less than 14 days, delayed TTC (more than 28 days) was associated with a worse PFS (HR=1.36; 95%CI: 0.96-1.92) and OS (HR=1.38; 95%CI: 0.95-2.00). Notably, in EOC patients with advanced stage, delayed TTC (more than 28 days) was associated with worse PFS (HR=1.51; 95%CI: 1.02-2.24) and OS (HR=1.53; 95%CI: 1.01-2.32) when comparing to TTC less than 14 days. In conclusion, delayed TTC was associated with higher rates of EOC recurrence and survival among these patients with advanced stage. The findings of the present study may provide evidence for gynecologist as well as these ovarian cancer patients to make further decision for the treatment.


Electrocardiographic and electrophysiological characteristics of premature ventricular complexes associated with left ventricular dysfunction in patients without structural heart disease.
The mechanism responsible for premature ventricular complex (PVC)-mediated left ventricular (LV) dysfunction remains unclear. We sought to determine the electrocardiographic and electrophysiological characteristics of PVC-mediated LV dysfunction. One hundred and twenty-seven patients who underwent radiofrequency catheter ablation (RFCA) for frequent PVCs (PVCs burden ≥10%/24 h) and had no significant structural heart disease were investigated. Left ventricular dysfunction (ejection fraction < 50%) was present in 28 of 127 patients (22.0%). The mean PVC burden (31 ± 11 vs. 22 ± 10%, P < 0.001), the presence of non-sustained ventricular tachycardia (53.6 vs. 33.3%, P = 0.05), and the presence of a retrograde P-wave following a PVC (64.3 vs. 30.3%, P = 0.001) were significantly greater in those with LV dysfunction than in those with normal LV function. The cut-off PVC burden related to LV dysfunction was 26%/day, with a sensitivity of 70% and a specificity of 78%. The PVC morphology, QRS axis, QRS width, coupling interval, the presence of interpolation, and PVC emergence pattern during exercise electrocardiogram were not significantly different between the two groups. The origin sites of PVCs, the acute success rate, and the recurrence rate during follow-up after RFCA were similar. In a multivariate analysis, the PVC burden (odds ratio 2.94, 95% confidence interval 0.90-3.19, P = 0.006) and the presence of retrograde P-waves (odds ratio 2.79, 95% confidence interval 1.08-7.19, P = 0.034) were independently associated with PVC-mediated LV dysfunction. A higher PVC burden (>26%/day) and the presence of retrograde P-waves were independently associated with PVC-mediated LV dysfunction.


Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.
Background: Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines. Methods and Analysis: We will apply transcriptomic, proteomic, metabolomic, multiplex cytokine/chemokine, adenosine deaminase, and flow cytometry immune cell phenotyping to delineate early cellular and molecular signatures that correspond to vaccine immunogenicity. This approach will be applied to a neonatal cohort in The Gambia (N ~ 720) receiving at birth: (1) Hepatitis B (HepB) vaccine alone, (2) Bacille Calmette Guerin (BCG) vaccine alone, or (3) HepB and BCG vaccines, (4) HepB and BCG vaccines delayed till day 10 at the latest. Each study participant will have a baseline peripheral blood sample drawn at DOL0 and a second blood sample at DOL1,-3, or-7 as well as late timepoints to assess HepB vaccine immunogenicity. Blood will be fractionated via a "small sample big data" standard operating procedure that enables multiple downstream systems biology assays. We will apply both univariate and multivariate frameworks and multi-OMIC data integration to identify features associated with anti-Hepatitis B (anti-HB) titer, an established correlate of protection. Cord blood sample collection from a subset of participants will enable human in vitro modeling to test mechanistic hypotheses identified in silico regarding vaccine action. Maternal anti-HB titer and the infant microbiome will also be correlated with our findings which will be validated in a smaller cohort in Papua New Guinea (N ~ 80). Ethics and Dissemination: The study has been approved by The Gambia Government/MRCG Joint Ethics Committee and The Boston Children's Hospital Institutional Review Board. Ethics review is ongoing with the Papua New Guinea Medical Research Advisory Committee. All de-identified data will be uploaded to public repositories following submission of study output for publication. Feedback meetings will be organized to disseminate output to the study communities. Clinical Trial Registration: Clinicaltrials.gov Registration Number: NCT03246230.


Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion.
Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.


Neurofeedback-based motor imagery training for brain-computer interface (BCI).
In the present study, we propose a neurofeedback-based motor imagery training system for EEG-based brain-computer interface (BCI). The proposed system can help individuals get the feel of motor imagery by presenting them with real-time brain activation maps on their cortex. Ten healthy participants took part in our experiment, half of whom were trained by the suggested training system and the others did not use any training. All participants in the trained group succeeded in performing motor imagery after a series of trials to activate their motor cortex without any physical movements of their limbs. To confirm the effect of the suggested system, we recorded EEG signals for the trained group around sensorimotor cortex while they were imagining either left or right hand movements according to our experimental design, before and after the motor imagery training. For the control group, we also recorded EEG signals twice without any training sessions. The participants' intentions were then classified using a time-frequency analysis technique, and the results of the trained group showed significant differences in the sensorimotor rhythms between the signals recorded before and after training. Classification accuracy was also enhanced considerably in all participants after motor imagery training, compared to the accuracy before training. On the other hand, the analysis results for the control EEG data set did not show consistent increment in both the number of meaningful time-frequency combinations and the classification accuracy, demonstrating that the suggested system can be used as a tool for training motor imagery tasks in BCI applications. Further, we expect that the motor imagery training system will be useful not only for BCI applications, but for functional brain mapping studies that utilize motor imagery tasks as well.


Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics.
To identify novel CSF biomarkers in GRN-associated frontotemporal dementia (FTD) by proteomics using mass spectrometry (MS). Unbiased MS was applied to CSF samples from 19 presymptomatic and 9 symptomatic GRN mutation carriers and 24 noncarriers. Protein abundances were compared between these groups. Proteins were then selected for validation if identified by ≥4 peptides and if fold change was ≤0.5 or ≥2.0. Validation and absolute quantification by parallel reaction monitoring (PRM), a high-resolution targeted MS method, was performed on an international cohort (n = 210) of presymptomatic and symptomatic GRN, C9orf72 and MAPT mutation carriers. Unbiased MS revealed 20 differentially abundant proteins between symptomatic mutation carriers and noncarriers and nine between symptomatic and presymptomatic carriers. Seven of these proteins fulfilled our criteria for validation. PRM analyses revealed that symptomatic GRN mutation carriers had significantly lower levels of neuronal pentraxin receptor (NPTXR), receptor-type tyrosine-protein phosphatase N2 (PTPRN2), neurosecretory protein VGF, chromogranin-A (CHGA), and V-set and transmembrane domain-containing protein 2B (VSTM2B) than presymptomatic carriers and noncarriers. Symptomatic C9orf72 mutation carriers had lower levels of NPTXR, PTPRN2, CHGA, and VSTM2B than noncarriers, while symptomatic MAPT mutation carriers had lower levels of NPTXR and CHGA than noncarriers. We identified and validated five novel CSF biomarkers in GRN-associated FTD. Our results show that synaptic, secretory vesicle, and inflammatory proteins are dysregulated in the symptomatic stage and may provide new insights into the pathophysiology of genetic FTD. Further validation is needed to investigate their clinical applicability as diagnostic or monitoring biomarkers.


Functional morbidity following latissimus dorsi flap breast reconstruction.
According to the National Institutes of Health, more than 230,000 new cases of breast cancer will be diagnosed in 2014 alone. Following mastectomy, several reconstructive options exist for women with breast cancer. The timing and approach for reconstruction must be addressed rapidly. Although abdominal tissue transfer is described as the preferred method, it may not be best suited to all patients. The latissimus dorsi (LD) muscle flap is a widely available, proven, and reliable modality. The majority of studies support that shoulder functional morbidity is minimal, but this should be more accurately quantified to allow patients to assess the possible impact on their daily lives. A critical appraisal of the available evidence was undertaken to determine the incidence of new functional morbidity involving the ipsilateral arm following LD pedicled flap breast reconstruction. The process for identifying articles included preappraised and secondary literature sources published between 2005 and 2013. Randomized controlled trials, evidence-based practice, clinical guidelines, and systematic reviews were the quality filters applied. This literature review confirmed that LD muscle transfer does lead to measurable reductions in shoulder joint stability, strength, range of motion, and general functionality. However, these deficiencies resolve in the vast majority of women within 6 to 12 months. Ultimately, the consequences of shoulder function morbidity must be considered and discussed with patients prior to making a final decision.


Latino beliefs about diabetes.
To describe Latino beliefs about diabetes and assess heterogeneity in beliefs across different groups. This study comprised a survey of 161 representative Latino adults from four diverse communities: Hartford, Connecticut; Edinburg, Texas; Guadalajara, Mexico; and rural Guatemala. A 130-item questionnaire covered causes symptoms, and treatments for diabetes. Information on demographics and acquaintanceship with someone with diabetes was also collected. The cultural consensus model was used to analyze the variation in responses to determine whether the degree of consistency within and between samples was sufficient to warrant aggregation and description as a single set of beliefs. Homogeneous beliefs were present within each of the four samples. Although variability in responses increased significantly from Connecticut to Guatemala (P < 0.00005), there was significant agreement between samples on the answers (P < 0.0005). Answers tended to be concordant with the biomedical description of diabetes. Greater acculturation, higher educational attainment, and higher diabetes prevalence were associated with greater cultural knowledge about diabetes. In Connecticut, greater knowledge correlated with longer mainland U.S. residency (P < 0.05). In Mexico, those with average educational attainment knew more (P < 0.05). Finally, average knowledge levels were higher in communities with greater diabetes prevalence. The cultural consensus model facilitated assessment of cultural beliefs regarding diabetes and diabetes management. Overall, Latino cultural beliefs about diabetes were concordant with the biomedical model. Variation in responses tended to characterize less knowledge or experience with diabetes and not different beliefs.


Race/ethnicity and the socioeconomic status gradient in women's cancer screening utilization: a case of diminishing returns?
Using three years (2006, 2008, 2010) of nationally representative data from the Behavioral Risk Factor Surveillance System, I assessed the socioeconomic status (SES) gradient for odds of receiving a mammogram in the past two years and a Pap test in the past three years among White, Black, Hispanic, and Asian women living in the U.S. Mammogram and Pap test utilization were less likely among low-SES women. However, women of color experience less benefit than Whites from increasing SES for both screenings; as income and education increased, White women experienced more pronounced increases in the likelihood of being screened than did women of color. In what might be referred to as paradoxical returns, Asian women actually experienced a decline in the likelihood of obtaining a recent Pap test at higher levels of education. My findings suggest that women of color differ from Whites in the extent to which increasing socioeconomic resources is associated with increasing cancer screening utilization.


BCR-ABL1-like acute lymphoblastic leukaemia: From bench to bedside.
Acute lymphoblastic leukaemia (ALL) occurs in approximately 1:1500 children and is less frequently found in adults. The most common immunophenotype of ALL is the B cell lineage and within B cell precursor ALL, specific genetic aberrations define subtypes with distinct biological and clinical characteristics. With more advanced genetic analysis methods such as whole genome and transcriptome sequencing, novel genetic subtypes have recently been discovered. One novel class of genetic aberrations comprises tyrosine kinase-activating lesions, including translocations and rearrangements of tyrosine kinase and cytokine receptor genes. These newly discovered genetic aberrations are harder to detect by standard diagnostic methods such as karyotyping, fluorescent in situ hybridisation (FISH) or polymerase chain reaction (PCR) because they are diverse and often cryptic. These lesions involve one of several tyrosine kinase genes (among others, v-abl Abelson murine leukaemia viral oncogene homologue 1 (ABL1), v-abl Abelson murine leukaemia viral oncogene homologue 2 (ABL2), platelet-derived growth factor receptor beta polypeptide (PDGFRB)), each of which can be fused to up to 15 partner genes. Together, they compose 2-3% of B cell precursor ALL (BCP-ALL), which is similar in size to the well-known fusion gene BCR-ABL1 subtype. These so-called BCR-ABL1-like fusions are mutually exclusive with the sentinel translocations in BCP-ALL (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and KMT2A (MLL) rearrangements) and have the promising prospect to be sensitive to tyrosine kinase inhibitors similar to BCR-ABL1. In this review, we discuss the types of tyrosine kinase-activating lesions discovered, and the preclinical and clinical evidence for the use of tyrosine kinase inhibitors in the treatment of this novel subtype of ALL.


The concepts of rechallenge and retreatment with immune checkpoint blockade in melanoma patients.
Forty to 60% of patients with advanced or metastatic melanoma respond to first-line immune checkpoint inhibitors (ICI) and half of all patients in the metastatic setting eventually progress. This review evaluated the latest long-term data from clinical trials. It also considered data from recent retrospective studies, as these address important questions for clinical practice. 'Retreatment' defined as 'repeated treatment with the same therapeutic class following relapse after adjuvant treatment has ended' and showed activity in selected patients with recurrence after regular completion of adjuvant PD-1 treatment. In melanoma patients with adjuvant PD-1 monotherapy who recur during adjuvant treatment, further treatment with PD-1 monotherapy seems to have no clinical utility, indicating the need for a therapy switch or escalation in these patients. Targeted therapy with BRAF/MEK inhibitors and ipilimumab-based therapy (alone or combined with PD-1 blockade) show clinical activity in patients who recur during and after adjuvant treatment. 'Rechallenge', defined as 'repeated treatment with the same therapeutic class following disease progression in patients who had clinical benefit with prior treatment for unresectable or metastatic disease', with pembrolizumab at progression in the advanced setting achieving additional disease control. If possible, 'escalation' (PD-1 inhibitors combined with additional agents) should be preferred to PD-1 inhibitor monotherapy rechallenge as higher response rates were demonstrated. The combination of PD-1 plus CTLA-4 was found to be more effective but not more toxic than CTLA-4 alone. Promising antitumor activity was observed for escalation to lenvatinib plus pembrolizumab, entinostat plus pembrolizumab, and relatlimab plus nivolumab. Retreatment, rechallenge and escalation are available options for patients with melanoma who relapse in the adjuvant or advanced setting.


Exploring the ideal combination of activity satisfaction and burden among health promotion volunteers: a cross-sectional study in Japan.
Health promotion volunteers (HPVs) who are expected to function as leaders in promoting community health in Japan feel both satisfaction and burden associated with their community engagement activities. The purposes of this study were 1) to describe the prevalence of volunteers with differing levels of activity satisfaction and burden; 2) to examine the association between satisfaction and burden with activity involvement and persistence, and life satisfaction; and 3) to explore associated factors by satisfaction/burden levels among Japanese HPVs. The research question for this study was as follows: What is the relationship between activity satisfaction and burden among HPV? A mail-in self-administered questionnaire survey was distributed to 604 HPVs in the cities of Konan and Koka, Shiga Prefecture, central Japan, in September 2005. Questions encompassed demographic data, variables regarding HPV activity such as organizational environment, social support, and the relationship with the neighborhood association, and overall satisfaction and burden related to the activity. The analyzed sample comprised 422 HPVs. Those with high satisfaction/low burden represented the largest number of study participants (group A; 38.4%). HPVs with high satisfaction/high burden (group B), low satisfaction/low burden (group C), and low satisfaction/high burden (group D) represented 23.0%, 11.1%, and 27.5% of participants, respectively. HPVs in groups A and B reported a greater total number of activities undertaken than those in group C. However, HPVs in group A had higher life satisfaction than those in groups C and D. Multinomial logistic regression analysis used to explore group differences showed that HPVs in group B had lower initial motivation and received less social support from colleagues, and those in group C felt the head of the neighborhood association was uncooperative. Those in group D had lower initial motivation, rated their organizational climate as worse, and considered the head of the neighborhood association uncooperative compared with group A. We found that feeling satisfied and lightly burdened facilitated HPVs' active participation in community-based activities. Findings suggest the importance of improving activity environments surrounding HPVs.


Marine Reserve Targets to Sustain and Rebuild Unregulated Fisheries.
Overfishing threatens the sustainability of coastal marine biodiversity, especially in tropical developing countries. To counter this problem, about 200 governments worldwide have committed to protecting 10%-20% of national coastal marine areas. However, associated impacts on fisheries productivity are unclear and could weaken the food security of hundreds of millions of people who depend on diverse and largely unregulated fishing activities. Here, we present a systematic theoretic analysis of the ability of reserves to rebuild fisheries under such complex conditions, and we identify maximum reserve coverages for biodiversity conservation that do not impair long-term fisheries productivity. Our analysis assumes that fishers have no viable alternative to fishing, such that total fishing effort remains constant (at best). We find that realistic reserve networks, which protect 10%-30% of fished habitats in 1-20 km wide reserves, should benefit the long-term productivity of almost any complex fishery. We discover a "rule of thumb" to safeguard against the long-term catch depletion of particular species: individual reserves should export 30% or more of locally produced larvae to adjacent fishing grounds. Specifically on coral reefs, where fishers tend to overexploit species whose dispersal distances as larvae exceed the home ranges of adults, decisions on the size of reserves needed to meet the 30% larval export rule are unlikely to compromise the protection of resident adults. Even achieving the modest Aichi Target 11 of 10% "effective protection" can then help rebuild depleted catch. However, strictly protecting 20%-30% of fished habitats is unlikely to diminish catch even if overfishing is not yet a problem while providing greater potential for biodiversity conservation and fishery rebuilding if overfishing is substantial. These findings are important because they suggest that doubling or tripling the only globally enforced marine reserve target will benefit biodiversity conservation and higher fisheries productivity where both are most urgently needed.


Esteya vermicola Controls the Pinewood Nematode, Bursaphelenchus xylophilus, in Pine Seedlings.
Esteya vermicola (Ophiostomataceae) is an endoparasitic fungus that has great potential as a biological control agent against the pinewood nematode Bursaphelenchus xylophilus which causes pine wilt disease. We tested E. vermicola for control of pine wilt disease by spraying E. vermicola conidia on artificial wounds on pine seedlings, and the optimum E. vermicola treatment density and application time were also investigated in the greenhouse. The wounds were similar to those made by sawyer beetles (Coleoptera: Cerambycidae). Esteya vermicola treatments significantly increased the survival rate of pine seedlings that were infected by pinewood nematodes. Wounded plants sprayed with 107 CFU/ml E. vermicola had a 73.0% greater survival rate than nonwounded pine seedlings treated similarly. The treatment of pine seedlings with 107 CFU/ml E. vermicola 14 d before nematode infection increased their survival rate by 90.0%. The number of pinewood nematodes isolated from dead pine seedlings sprayed with E. vermicola was 76% less than the number of pinewood nematodes in the controls. Moreover, infected nematodes and the hyphae of E. vermicola were detected in the dead or wilting pine seedlings. Therefore, spraying E. vermicola on the wounds of pine seedlings made by sawyer beetles provides good control of the pine wilt disease that is caused by pinewood nematodes.


Stress-Induced Dinoflagellate Bioluminescence at the Single Cell Level.
One of the characteristic features of many marine dinoflagellates is their bioluminescence, which lights up nighttime breaking waves or seawater sliced by a ship's prow. While the internal biochemistry of light production by these microorganisms is well established, the manner by which fluid shear or mechanical forces trigger bioluminescence is still poorly understood. We report controlled measurements of the relation between mechanical stress and light production at the single cell level, using high-speed imaging of micropipette-held cells of the marine dinoflagellate Pyrocystis lunula subjected to localized fluid flows or direct indentation. We find a viscoelastic response in which light intensity depends on both the amplitude and rate of deformation, consistent with the action of stretch-activated ion channels. A phenomenological model captures the experimental observations.


Effects of dietary glucocerebrosides from sea cucumber on the brain sphingolipid profiles of mouse models of Alzheimer's disease.
Herein, we investigated the potential relationship between sphingolipids and Alzheimer's disease (AD) with special attention to the relationship between dietary sea cucumber glucocerebrosides (SCGs) and sphingolipid metabolism. We assessed animal behavior using the Morris water maze test, determined Aβ1-42 concentration in the hippocampus using ELISA, and assessed the sphingolipid profile of the hippocampus and the cortex in normal mice (SAMR1), AD mice (SAMP8), and AD mice (SAMP8) fed with SCG using liquid chromatography-triple quadrupole mass spectrometry. We found that the SAMP8 mice had impaired memory and an SCG diet significantly rescued spatial memory deficits in these mice. As expected, we found that the profiles of sphingolipid species and the levels of total cerebrosides (CBS), ceramides (Cer), and sulfatides (ST) were significantly different in both the hippocampus and the cortex between the three groups; moreover, there were significantly lower ST levels and higher Cer and CBS levels in these regions in the SAMP8 mice. In the AD-SCG group, Cer and ST levels were altered only in the hippocampus, in contrast to the AD group. The major molecular species ST (d18:1-C24:1) and Cer (d18:1/18:0) were especially different between those of the two groups. Unexpectedly, sphingolipid profiles, including the nonhydroxylated fatty acid-ST/hydroxylated fatty acid-ST, very long fatty acid-galactocerebroside/long fatty acid-galactocerebroside, nonhydroxylated fatty acid-galactocerebroside/hydroxylated fatty acid-galactocerebroside and galactocerebroside/glucocerebroside ratios, were affected by AD. Thus, the ST and Cer levels and the profiles of sphingolipid species in the AD-SCG group were significantly different compared to those of the AD model group. Therefore, SCG has potential ameliorative effects in AD, and exogenous sphingolipid intake may potentially influence sphingolipid metabolism in vivo.


The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence.
Two-component regulatory systems have been widely implicated in bacterial virulence. To investigate the role of one such system in Mycobacterium tuberculosis, a strain was constructed in which the senX3-regX3 system was deleted by homologous recombination. The mutant strain (Tame15) showed a growth defect after infection of macrophages and was attenuated in both immunodeficient and immunocompetent mice. Competitive hybridization of total RNA from the wild-type and mutant strains to a whole-genome microarray was used to identify changes in gene expression resulting from the deletion. One operon was highly up-regulated in the mutant, indicating that regX3 probably has a role as a repressor of this operon. Other genes which were up- or down-regulated were also identified. Many of the genes showing down-regulation are involved in normal growth of the bacterium, indicating that the mutant strain is subject to some type of growth slow-down or stress. Genes showing differential expression were further grouped according to their pattern of gene expression under other stress conditions. From this analysis 50 genes were identified which are the most likely to be controlled by RegX3. Most of these genes are of unknown function and no obvious motifs were found upstream of the genes identified. Thus, it has been demonstrated that the senX3-regX3 two-component system is involved in the virulence of M. tuberculosis and a number of genes controlled by this system have been identified.


Root Canal Transportation and Centering Ability of Nickel-Titanium Rotary Instruments in Mandibular Premolars Assessed Using Cone-Beam Computed Tomography.
The aim of this study was to evaluate, using cone-beam computed tomography (CBCT), transportation and centralization of different nickel-titanium (NiTi) rotary instruments. One hundred and twenty eight mandibular premolars were selected and instrumented using the following brands of NiTi files: WaveOne, WaveOne Gold, Reciproc, ProTaper Next, ProTaper Gold, Mtwo, BioRaCe and RaCe. CBCT imaging was performed before and after root canal preparation to obtain measurements of mesial and distal dentin walls and calculations of root canal transportation and centralization. A normal distribution of data was confirmed by the Kolmogorov-Smirnov and Levene tests, and results were assessed using the Kruskal-Wallis test. Statistical significance was set at 5%. ProTaper Gold produced the lowest canal transportation values, and RaCe, the highest. ProTaper Gold files also showed the highest values for centering ability, whereas BioRaCe showed the lowest. No significant differences were found across the different instruments in terms of canal transportation and centering ability (P > 0.05). Based on the methodology employed, all instruments used for root canal preparation of mandibular premolars performed similarly with regard to canal transportation and centering ability.


Neural mechanisms of visual object priming: evidence for perceptual and semantic distinctions in fusiform cortex.
Previous functional imaging studies have shown that facilitated processing of a visual object on repeated, relative to initial, presentation (i.e., repetition priming) is associated with reductions in neural activity in multiple regions, including fusiform/lateral occipital cortex. Moreover, activity reductions have been found, at diminished levels, when a different exemplar of an object is presented on repetition. In one previous study, the magnitude of diminished priming across exemplars was greater in the right relative to the left fusiform, suggesting greater exemplar specificity in the right. Another previous study, however, observed fusiform lateralization modulated by object viewpoint, but not object exemplar. The present fMRI study sought to determine whether the result of differential fusiform responses for perceptually different exemplars could be replicated. Furthermore, the role of the left fusiform cortex in object recognition was investigated via the inclusion of a lexical/semantic manipulation. Right fusiform cortex showed a significantly greater effect of exemplar change than left fusiform, replicating the previous result of exemplar-specific fusiform lateralization. Right fusiform and lateral occipital cortex were not differentially engaged by the lexical/semantic manipulation, suggesting that their role in visual object recognition is predominantly in the visual discrimination of specific objects. Activation in left fusiform cortex, but not left lateral occipital cortex, was modulated by both exemplar change and lexical/semantic manipulation, with further analysis suggesting a posterior-to-anterior progression between regions involved in processing visuoperceptual and lexical/semantic information about objects. The results are consistent with the view that the right fusiform plays a greater role in processing specific visual form information about objects, whereas the left fusiform is also involved in lexical/semantic processing.


Plasma 25-hydroxyvitamin d levels in operative patella fractures.
Patella fractures have not traditionally been considered "fragility" fractures. The purpose of this study was to examine the demographic patterns (age and gender distribution) and plasma 25-hydroxyvitamin D levels of a cohort of patients with operative patella fractures. Medical records were reviewed on all consecutive patients presenting to our institution with operative patella fractures from 2003 to 2009. Seventy-eight operative patella fractures (25 male, 53 female) were identified with a mean age of 58 years (range, 22-89 years). The majority of patients with patella fractures in this series were females over the age of 50 years who sustained low-energy falls from a standing height or less. Twenty-four patients (80%) had vitamin D insufficiency or deficiency at the time of injury. For 68 patients (87%), the patella fracture represented their first fracture. Patients with known osteoporosis risk factors did not have higher rates of vitamin D insufficiency/deficiency. The age and gender distribution, as well as the prevalence of vitamin D insufficiency/deficiency, of operative patella fractures, suggest that these patients likely have abnormal vitamin D levels and should undergo a metabolic bone work-up.


Neurotransmission in lower esophageal sphincter of W/Wv mutant mice.
To address the controversy surrounding the role of interstitial cells of Cajal (ICC) in nitrergic neurotransmission to gastrointestinal smooth muscle, circular smooth muscle from the lower esophageal sphincter (LES) of W/W(v) wild-type and mutant (ICC-deficient) mice were studied by using intracellular and tension recordings in vitro. Resting membrane potential was more negative, and the spontaneous unitary potentials diminished in mutant mice. In wild-type mice, nerve stimulation induced a biphasic inhibitory junction potential (IJP) consisting of a fast initial IJP followed by a long-lasting slow IJP (LSIJP). The IJP was markedly impaired in a significant proportion of mutant mice, whereas in others it was normal. Pharmacological studies in the mice with markedly impaired IJPs revealed that cholinergic and purinergic components of the nerve-mediated responses appeared intact. In wild-type mice, caffeine hyperpolarized smooth muscle cells, inhibited the initial fast IJP, and completely abolished the LSIJP. In mutant mice, caffeine depolarized smooth muscle cells and abolished the impaired LSIJP but did not affect the initial fast IJP. Immunohistochemical staining for c-Kit confirmed deficiency of ICC in mutant mice with a normal nitrergic IJP. Rings of LES circular smooth muscle from W/W(v) mutant mice generated significantly less spontaneous tone than controls. When tone was restored with carbachol, normal nitrergic LES relaxation was recorded. These data suggest that 1) there is significant variability in the generation of nitrergic neurotransmission in the LES of W/W(v) mutant mice, whereas purinergic and cholinergic neurotransmission are intact; 2) the altered nitrergic responses appear to be associated with abnormal Ca2+-dependent signaling initiated by spontaneous Ca2+ release from sarcoplasmic reticulum in smooth muscle cells; and 3) c-Kit-positive ICC are not essential for nitrergic neurotransmission in mouse LES smooth muscle.


Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: model for postadherence events in endovascular infections.
We examined the interaction of Staphylococcus aureus with cultured bovine aortic endothelial cells as a model for the initial events in the pathogenesis of endovascular infections. Confluent monolayers of cultured endothelial cells were incubated with S. aureus. Cell-associated bacteria were measured by washing away nonadherent organisms, disrupting the monolayers, and performing quantitative cultures. Phagocytosis was differentiated from adherence by treating the cells with lysostaphin; approximately 60% of cell-associated bacteria was found to be intracellular. Phagocytosis could be blocked by using cytochalasin B, which interferes with microfilament function. Addition of fibronectin resulted in a 63% increase in adherence of S. aureus to the endothelial cells but did not increase ingestion. Transmission electron microscopy demonstrated a sequence of events similar to that which occurs during ingestion by professional phagocytes, including: adherence of bacteria to the endothelial cell; formation and elongation of surface extensions of the endothelial cell to surround the adherent bacteria; and complete enclosure within apparent phagosomes. Phagocytosis of bacteria by endothelial cells, followed by intracellular persistence, may be an important postadherence event in the pathogenesis and pathophysiology of endovascular infections.


Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis.
Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information for Asian populations is lacking. We searched four electronic databases including PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov. We reviewed selected manuscripts and extracted the pooled relative risk (RR) from immunogenicity and safety information on HPV vaccination among women in Asian countries. We identified two quadrivalent-vaccine studies and eight bivalent-vaccine studies conducted in Asian countries. Analysis across these studies suggested that the HPV vaccines significantly enhanced HPV16- and HPV18-specific antibody among both uninfected (RR 85.69; 95% confidence interval (CI) 31.51-233.04 and 62.77; 95% CI 37.4-105.51) and infected individuals (RR 8.60; 95% CI 6.95-10.64 and RR 8.13; 95% CI 5.96-11.11). Furthermore, HPV vaccination among Asian populations has a favorable safety profile, with only slightly higher risks of local (RR: 1.89; 95% CI 1.65-2.17) and systemic (RR: 1.33; 95% CI 1.18-1.50) adverse events in vaccinated individuals compared with controls. For Asian populations, HPV vaccines enhance the level of HPV16- and HPV18-specific antibodies for both uninfected and infected individuals. Also, the risk of adverse events related to vaccination are acceptable. More data are needed to establish vaccine efficacy with regard to prevention of HPV infection and further outcomes including cervical intraepithelial neoplasia (CIN) and cervical cancer.


Modeling Photonastic Materials: A First Computational Study.
Photonastic materials present a directional and repeatable deformation of the material shape due to transduction from light energy to mechanical energy. Among these materials, light-responsive polymers, composed of photochromic molecules embedded in a polymer matrix, are of high interest. The present work aims at laying the foundation stone of the modeling of the photomechanical behavior of such systems by proposing a computational strategy that is able to investigate (i) the impact of the polymer matrix on the photochromic properties of a dithienylethene (DTE) switch and (ii) the impact of the photochromic reaction on the polymer environment. Contrary to previous approaches, the present model is able to propose a realistic arrangement of the photochrome embedded in the polymer film, thanks to the adaptation of the so-called "controlled-like polymerization algorithm" [Lemarchand, C. A.; J. Chem. Phys. 2019, 50, 224902]. Our strategy relies on molecular dynamics (MD) simulations and time-dependent density functional theory (DFT) calculations. Careful analysis of MD trajectories and comparison with simulations in solution have shown the rigidification of the DTE molecule due to the presence of the polymer chains, which hindered the interconversion between the DTE open-form isomers and can probably modify the photocyclization quantum yield. Besides, the UV-vis absorption properties of the DTE open-form isomers are more impacted by the polymer embedding than its closed-form counterpart. Concerning the impact of the photoreaction on the polymer matrix, the time evolution of the pressure tensor and of the atomic displacements in the matrix have shown that (i) the cyclization reaction has a negligible impact; (ii) the cycloreversion reaction induces a locally large and anisotropic pressure increase and leads to a collective displacement of the polymer matrix away from the reactive center; and (iii) the characteristic time scale associated with these coupled processes is below 1 ps. Therefore, the two processes involved in photonastic motions, namely, the photoreaction and the relaxation of the polymer matrix after the photoswitch structural change, cannot be decoupled.


Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression.
Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal, medial prefrontal areas and hypothalamic autonomic centers were also connected with the amygdala. Descending pathways from orbitofrontal and medial prefrontal cortices, which are also linked with the amygdala, provide the means for speedy influence of the prefrontal cortex on the autonomic system, in processes underlying appreciation and expression of emotions.


The unseen sample in cohort studies: estimation of its size and effect. Multicenter AIDS Cohort Study.
Recruitment of disease-free subjects into cohort studies and measurement of their time from exposure/infection to disease selectively excludes individuals (the unseen sample) who had earlier exposure and who have shorter times to disease. The unseen and observed samples may differ in other characteristics in addition to incubation period and exposure/infection time. For data with known truncation times, we develop non-parametric maximum likelihood estimates of the size, exposure/infection dates and distribution of incubation time in the unseen sample. We provide procedures to estimate and compensate for the biasing effects due to exclusion of the unseen sample in descriptive and survival analysis. We give consistency properties of these estimates and assess variability using bootstrap methods. One can use imputation to derive the above estimates from data with unknown truncation times that have been estimated parametrically. Application is made to an AIDS cohort study of over 5000 homosexual men. Important estimates obtained from this application are the annual seroconversion rates from 1978 to 1983, not otherwise obtainable in this study population.


Heterogeneous shedding of influenza by human subjects and its implications for epidemiology and control.
Heterogeneity of infectiousness is an important feature of the spread of many infections, with implications for disease dynamics and control, but its relevance to human influenza virus is still unclear. For a transmission event to occur, an infected individual needs to release infectious particles via respiratory symptoms. Key factors to take into account are virus dynamics, particle release in relation to respiratory symptoms, the amount of virus shed and, importantly, how these vary between infected individuals. A quantitative understanding of the process of influenza transmission is relevant to designing effective mitigation measures. Here we develop an influenza infection dynamics model fitted to virological, systemic and respiratory symptoms to investigate how within-host dynamics relates to infectiousness. We show that influenza virus shedding is highly heterogeneous between subjects. From analysis of data on experimental infections, we find that a small proportion (<20%) of influenza infected individuals are responsible for the production of 95% of infectious particles. Our work supports targeting mitigation measures at most infectious subjects to efficiently reduce transmission. The effectiveness of public health interventions targeted at highly infectious individuals would depend on accurate identification of these subjects and on how quickly control measures can be applied.


Testicular damage and farming environments - An integrative ecotoxicological link.
The exposure to agrochemicals during farming activities affects the function of the reproductive system, as revealed by the increasing worldwide evidence of male infertility amongst farmers. The main objective of this study was to untangle the link between agricultural practices and male reproductive impairment due to chronic exposure to xenobiotics (such as agrochemicals) in conventional and organic farming environments. For this purpose, male wild mice (Mus musculus) populations from sites representing two distinct farming practices (conventional and organic farming systems) were used as bioindicators for observable effects of testicular damage, namely on a set of histological and cellular parameters: (i) relative volumetric density of different spermatogenic cells and interstitial space; (ii) damage in the seminiferous tubules and (iii) apoptotic cells in the germinal epithelium. Results showed that mice from the conventional farming site bioaccumulated higher Pb hepatic loads, while mice from the organic farming site tend to bioaccumulate higher Cd hepatic loads. In general, for the analyzed testicular damage related parameters, mice from the organic farming site showed a similar performance than mice from the reference site. Mice from the conventional farming site stood out not only by underperforming in most studied parameters, while displaying an association between Pb hepatic loads and the observed testicular structural and functional disruption, but also by the increased stress index (Integrated Biomarker Response value). This study highlights the potential damaging effects of conventional farming practices on testicular structure and function, under natural conditions, raising concern about ensuing fertility risks for farmers.


Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.
Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies. We have built an RP-specific network (RPGeNet) by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space. In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.


Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.
According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.


The treatment of chronic hepatitis C with peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed patients awaiting renal transplant.
We undertook a pilot study to investigate the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed chronic HCV patients awaiting renal transplant. Patients received peginterferon alfa-2a 135 microg/week plus ribavirin 200 mg/day for 24 or 48 weeks (genotype non-1 and 1, respectively). The dose of ribavirin was tailored according to plasma concentrations and to haemoglobin levels. Outcomes in treated patients were compared with those of a matched untreated control group. Thirty-five patients received treatment, while 35 served as untreated controls. Thirty patients completed treatment; patients were withdrawn due to transplantation (n=2), severe anaemia (n=1), dermatitis (n=1) and non-response (n=1) resulting in a drop-out rate of 14%. Overall, 34/35 treated patients were HCV RNA negative at week 4 and had undetectable RNA at the end of treatment, compared with none of the untreated controls (ETR 97% vs 0%; p<0.001). Moreover, all achieved sustained virological response after 24 weeks of treatment-free follow-up versus no control patients (SVR 97% vs 0 %; p<0.001). In this study, we have shown for the first time in a large cohort of patients that HCV-patients on haemodialysis can be treated successfully with peginterferon alfa-2a (40 kDa) plus ribavirin.


Nanowire perovskite solar cell.
Organolead iodide perovskite, CH3NH3PbI3, was prepared in the form of nanowire by means of a small quantity of aprotic solvent in two-step spin-coating procedure. One-dimensional nanowire perovskite with the mean diameter of 100 nm showed faster carrier separation in the presence of hole transporting layer and higher lateral conductivity than the three-dimensional nanocuboid crystal. Reduction in dimensionality resulted in the hypsochromic shift of both absorption and fluorescence spectra, indicative of more localized exciton states in nanowires. The best performing device employing nanowire CH3NH3PbI3 delivered photocurrent density of 19.12 mA/cm(2), voltage of 1.052 V, and fill factor of 0.721, leading to a power conversion efficiency (PCE) of 14.71% at standard AM 1.5G solar illumination. A small I-V hysteresis was observed, where a PCE at forward scan was measured to be 85% of the PCE at reverse scan.


Prevalence and risk factors for anemia severity and type in Malawian men and women: urban and rural differences.
The global burden of anemia is large especially in sub-Saharan Africa, where HIV is common and lifestyles are changing rapidly with urbanization. The effects of these changes are unknown. Studies of anemia usually focus on pregnant women or children, among whom the burden is greatest. We describe prevalence and risk factors for anemia among rural and urban men and women of all ages in Malawi. We analyzed data from a population-wide cross-sectional survey of adults conducted in two sites, Karonga (rural) and Lilongwe (urban), commencing in May 2013. We used multinomial logistic regression models, stratified by sex to identify risk factors for mild and moderate-to-severe anemia. Anemia prevalence was assessed among 8,926 men (age range 18-100 years) and 14,978 women (age range: 18-103 years). Weighted prevalence levels for all, mild, and moderate-to-severe anemia were 8.2, 6.7 and 1.2% in rural men; 19.4, 12.0 and 7.4% in rural women; 5.9, 5.1 and 0.8% in urban men; and 23.4, 13.6 and 10.1% in urban women. Among women, the odds of anemia were higher among urban residents and those with higher socioeconomic status. Increasing age was associated with higher anemia prevalence in men. Among both men and women, HIV infection was a consistent risk factor for severity of anemia, though its relative effect was stronger on moderate-to-severe anemia. The drivers of anemia in this population are complex, include both socioeconomic and biological factors and are affecting men and women differently. The associations with urban lifestyle and HIV indicate opportunities for targeted intervention.


Statins and Risk of Lower Limb Revision Surgery: The Influence of Differences in Study Design Using Electronic Health Records From the United Kingdom and Denmark.
Previous observational studies on statins have shown variable results based on the methodology used. Our objective was to study the association between statins and orthopedic implant failure and to explore the influence of methodological differences in study design. Our study base consisted of patients with a primary total joint replacement in Denmark and the United Kingdom (n = 189,286; 1987-2012). We used 4 study designs: 1) case-control (each patient with revision surgery matched to 4 controls), 2) time-dependent cohort (postoperative statin use as a time-varying exposure variable), 3) immortal time cohort (misclassifying the time postoperatively before statin use), and 4) time-exclusion cohort (excluding the time postoperatively before statin use). Cox proportional hazards models and logistic regression were used to estimate incidence rate ratios. In the time-dependent cohort design, statin use was associated with a decreased risk of revision surgery (adjusted incidence rate ratio (IRR) = 0.90, 95% confidence interval (CI): 0.85, 0.96), which was similar to our case-control results (IRR = 0.87, 95% CI: 0.81, 0.93). In contrast, both time-fixed cohort designs yielded substantially lower risk estimates (IRR = 0.36 (95% CI: 0.34, 0.38) and IRR = 0.65 (95% CI: 0.63, 0.68), respectively). We discourage the use of time-fixed cohort studies, which may falsely suggest protective effects. The simple choice of how to classify exposure can substantially change results from biologically plausible to implausible.


Coarse-Grained Prediction of Peptide Binding to G-Protein Coupled Receptors.
In this study, we used the Martini Coarse-Grained model with no applied restraints to predict the binding mode of some peptides to G-Protein Coupled Receptors (GPCRs). Both the Neurotensin-1 and the chemokine CXCR4 receptors were used as test cases. Their ligands, NTS8-13 and CVX15 peptides, respectively, were initially positioned in the surrounding water box. Using a protocol based on Replica Exchange Molecular Dynamics (REMD), both opening of the receptors and entry of the peptides into their dedicated pockets were observed on the μs time-scale. After clustering, the most statistically representative orientations were closely related to the X-ray structures of reference, sharing both RMSD lower than 3 Å and most of the native contacts. These results demonstrate that such a model, that does not require access to tremendous computational facilities, can be helpful in predicting peptide binding to GPCRs as well as some of the receptor's conformational changes required for this key step. We also discuss how such an approach can now help to predict, de novo, the interactions of GPCRs with other intra- or extracellular peptide/protein partners.


Balancing Water Sustainability and Productivity Objectives in Microalgae Cultivation: Siting Open Ponds by Considering Seasonal Water-Stress Impact Using AWARE-US.
Microalgae have great potential as an energy and feed resource. Here we evaluate the water use associated with freshwater algae cultivation and find it is possible to scale U.S. algae biofuel production to 20.8 billion liters of renewable diesel annually without significant water-stress impact. Among potential sites, water-stress is significantly more variable than algae productivity across location and season. Thus, it is possible to reduce water-stress impact, quantified as water scarcity footprint, through the choice of algae site location. We test three site-selection criteria based on (1) biomass productivity, (2) water-use efficiency, and (3) water-stress impact and find that adding water-stress constraints to productivity-based ranking of suitable sites reduces water-stress impact by 97% and water consumption by half, compared with biomass-productivity ranking alone, with little productivity impact (<1.7% per-site on average). With 20.8 billion liters, algae could meet 19.7% of U.S. jet fuel demand with a freshwater demand of less than 1.4% of U.S. irrigation consumption. Evaluating water-stress impact is important because the impact of unit water consumption on water stress varies significantly across regions and seasons. Considering seasonal water balances allows producers to understand the combined seasonal effects of hydrologic flows and productivity, thereby avoiding potential short-term water stress.


Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion.
Although neoplasia is a major cause of mortality in humans and domestic animals, it has rarely been described in wildlife species. One of the few examples is a highly prevalent urogenital carcinoma in California sea lions (CSLs). Although the aetiology of this carcinoma is clearly multifactorial, inbreeding depression, as estimated using levels of microsatellite multilocus heterozygosity, is identified as predictive for this neoplasia. On further analysis, this relationship appears to be largely driven by one marker, suggesting that a single locus might be associated with the occurrence of this disease in CSLs. In a case-control study, carcinoma was significantly associated with homozygosity at the Pv11 microsatellite locus. Pv11 was mapped to intron 9 of the heparanase 2 gene (HPSE2) locus, a very large gene encoding heparanase 2, which in humans is associated with multiple carcinomas. Correspondingly, immunohistochemical labelling in tissues was present in carcinoma cases within a single homozygous Pv11 genotype. To our knowledge, this is the first report of an individual locus being associated with cancer in any wildlife species. This adds emphasis to the study of HPSE2 in other species, including humans and will guide future studies on this sentinel species that shares much of its diet and environment with humans.


Progress Evaluation for the Restaurant Industry Assessed by a Voluntary Marketing-Mix and Choice-Architecture Framework That Offers Strategies to Nudge American Customers toward Healthy Food Environments, 2006-2017.
Consumption of restaurant food and beverage products high in fat, sugar and sodium contribute to obesity and non-communicable diseases. We evaluated restaurant-sector progress to promote healthy food environments for Americans. We conducted a desk review of seven electronic databases (January 2006-January 2017) to examine restaurant strategies used to promote healthful options in the United States (U.S.). Evidence selection (n = 84) was guided by the LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and verified by data and investigator triangulation. A marketing-mix and choice-architecture framework was used to examine eight voluntary strategies (i.e., place, profile, portion, pricing, promotion, healthy default picks, priming or prompting and proximity) to evaluate progress (i.e., no, limited, some or extensive) toward 12 performance metrics based on available published evidence. The U.S. restaurant sector has made limited progress to use pricing, profile (reformulation), healthy default picks (choices), promotion (responsible marketing) and priming and prompting (information and labeling); and some progress to reduce portions. No evidence was available to assess progress for place (ambience) and proximity (positioning) to promote healthy choices during the 10-year review period. Chain and non-chain restaurants can apply comprehensive marketing-mix and nudge strategies to promote healthy food environments for customers.


γ-Actin regulates cell migration and modulates the ROCK signaling pathway.
Cell migration plays a crucial role in numerous cellular functions, and alterations in the regulation of cell migration are required for invasive transformation of a tumor cell. While the mechanistic process of actin-based migration has been well documented, little is known as to the specific function of the nonmuscle actin isoforms in mammalian cells. Here, we present a comprehensive examination of γ-actin's role in cell migration using an RNAi approach. The partial suppression of γ-actin expression in SH-EP neuroblastoma cells resulted in a significant decrease in wound healing and transwell migration. Similarly, the knockdown of γ-actin significantly reduced speed of motility and severely affected the cell's ability to explore, which was, in part, due to a loss of cell polarity. Moreover, there was a significant increase in the size and number of paxillin-containing focal adhesions, coupled with a significant decrease in phosphorylated paxillin in γ-actin-knockdown cells. In addition, there was a significant increase in the phosphorylation of cofilin and myosin regulatory light chain, suggesting an overactivated Rho-associated kinase (ROCK) signaling pathway in γ-actin-knockdown cells. The alterations in the phosphorylation of paxillin and myosin regulatory light chain were unique to γ-actin and not β-actin knockdown. Inhibition of the ROCK pathway with the inhibitor Y-27632 restored the ability of γ-actin-knockdown cells to migrate. This study demonstrates γ-actin as a potential upstream regulator of ROCK mediated cell migration.


Evaluation of the molecular bacterial load assay for detecting viable Mycobacterium tuberculosis in cerebrospinal fluid before and during tuberculous meningitis treatment.
New tools to monitor treatment response and predict outcome from tuberculous meningitis (TBM) are urgently required. We retrospectively evaluated the 16S rRNA-based molecular bacterial load assay (MBLA) to quantify viable Mycobacterium tuberculosis in serial cerebrospinal fluid (CSF) from adults with TBM. 187 CSF samples were collected before and during the first two months of treatment from 99 adults TBM, comprising 56 definite, 43 probable or possible TBM, and 18 non-TBM and preserved at -80°C prior to MBLA. We compared MBLA against MGIT culture, GeneXpert MTB/RIF (Xpert) and Ziehl-Neelsen (ZN) smear. Before treatment, MBLA was positive in 34/99 (34.3%), significantly lower than MGIT 47/99 (47.5%), Xpert 51/99 (51.5%) and ZN smear 55/99 (55.5%). After one month of treatment, MBLA and MGIT were positive in 3/38 (7.9%) and 4/38 (10.5%), respectively, whereas Xpert and ZN smear remained positive in 19/38 (50.0%) and 18/38 (47.4%). In summary, MBLA was less likely to detect CSF bacteria before the start of treatment compared with MGIT culture, Xpert and ZN smear. MBLA and MGIT positivity fell during treatment because of detecting only viable bacteria, whereas Xpert and ZN smear remained positive for longer because of detecting both live and dead bacteria. Sample storage and processing may have reduced MBLA-detectable viable bacteria; and sampling earlier in treatment may yield more useful results. Prospective studies with CSF sampling after 1-2 weeks are warranted.


Wavefront aberration of the eye: a review.
The concept of monochromatic wavefront aberration is discussed in relation to ray aberration, and methods for its measurement in the case of the eye are described. Examples are given of the measured aberration in individual eyes: in general the aberration falls within the Rayleigh quarter-wavelength criterion for pupil diameters less than 2 to 3 mm but significantly degrades image quality for larger pupils. The use of wavefront data to explore both the modulation and phase transfer functions of the eye as a function of pupil diameter and focus is described, together with typical results. Potential applications to clinical problems such as the effects of contact lenses, intraocular implants, refractive surgery, and pathology on the optical quality of the eye are outlined.


Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC). To evaluate the dynamics of oral HPV DNA detection and associations with disease outcomes in patients with HPV-positive and HPV-negative HNSCC. This prospective, 2-institution, tertiary referral center study of 396 patients with newly diagnosed oral cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis and at completion of primary therapy. Weekly oral rinse samples were collected during radiotherapy. Purified tumor and oral rinse sample DNA were evaluated for 37 HPV types, and viral load was quantified by type-specific real-time polymerase chain reaction. Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type. Prevalence of HPV DNA before, during, and after therapy. Associations between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free and overall survival were evaluated. Of the 396 patients (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; and 354 [89.4%] white race/ethnicity), 217 had oropharyngeal cancer; 170, oral cavity cancer; and 9, unknown primary HNSCC. The prevalence of oral HPV detection at diagnosis was higher among patients with HPV-positive compared with HPV-negative HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%]; P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive HNSCC. The prevalence and load of tumor-type HPV decreased significantly during primary therapy with odds ratio for probability of infection with each increasing month after diagnosis (0.41; 95% CI, 0.33-0.52; P < .001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62). Current smoking was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93). Two-year overall survival was significantly lower among the HPV-positive patients with persistent detection of tumor-type HPV after therapy than among those without detectable tumor-type DNA after therapy (68% vs 95%; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was recurrence-free survival (55% vs 88%; adjusted HR, 3.72; 95% CI, 1.71-8.09; P < .001). No associations were observed for nontumor type HPV DNA among patients with HPV-positive or HPV-negative HNSCC. Prevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.


Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype.
Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies. To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels. Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport. Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels.


Fluid and imaging biomarkers for Huntington's disease.
Huntington's disease is a chronic progressive neurodegenerative condition for which there is no disease-modifying treatment. The known genetic cause of Huntington's disease makes it possible to identify individuals destined to develop the disease and instigate treatments before the onset of symptoms. Multiple trials are already underway that target the cause of HD, yet clinical measures are often insensitive to change over typical clinical trial duration. Robust biomarkers of drug target engagement, disease severity and progression are required to evaluate the efficacy of treatments and concerted efforts are underway to achieve this. Biofluid biomarkers have potential advantages of direct quantification of biological processes at the molecular level, whilst imaging biomarkers can quantify related changes at a structural level in the brain. The most robust biofluid and imaging biomarkers can offer complementary information, providing a more comprehensive evaluation of disease stage and progression to inform clinical trial design and endpoints.


Influence of chemical and physical properties of activated carbon powders on oxygen reduction and microbial fuel cell performance.
Commercially available activated carbon (AC) powders made from different precursor materials (coal, peat, coconut shell, hardwood, and phenolic resin) were electrochemically evaluated as oxygen reduction catalysts and tested as cathode catalysts in microbial fuel cells (MFCs). AC powders were characterized in terms of surface chemistry and porosity, and their kinetic activities were compared to carbon black and platinum catalysts in rotating disk electrode (RDE) tests. Cathodes using the coal-derived AC had the highest power densities in MFCs (1620 ± 10 mW m(-2)). Peat-based AC performed similarly in MFC tests (1610 ± 100 mW m(-2)) and had the best catalyst performance, with an onset potential of E(onset) = 0.17 V, and n = 3.6 electrons used for oxygen reduction. Hardwood based AC had the highest number of acidic surface functional groups and the poorest performance in MFC and catalysis tests (630 ± 10 mW m(-2), E(onset) = -0.01 V, n = 2.1). There was an inverse relationship between onset potential and quantity of strong acid (pKa < 8) functional groups, and a larger fraction of microporosity was negatively correlated with power production in MFCs. Surface area alone was a poor predictor of catalyst performance, and a high quantity of acidic surface functional groups was determined to be detrimental to oxygen reduction and cathode performance.


Antifibrotic Effects of Hepatocyte Growth Factor on Endothelial-to-Mesenchymal Transition via Transforming Growth Factor-Beta1 (TGF-β1)/Smad and Akt/mTOR/P70S6K Signaling Pathways.
BACKGROUND The related mechanisms involved in allograft interstitial fibrosis and chronic allograft dysfunction (CAD), following renal transplant, remain largely unknown. Here, we explored the role of hepatocyte growth factor (HGF) treatment on the endothelial-to-mesenchymal transition (EndMT) as a new way to target and prevent kidney fibrosis and improve outcomes for renal transplant recipients. MATERIAL AND METHODS We extracted proteins and mRNAs from human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs) treated with transforming growth factor-beta1 (TGF-β1) and/or varying doses of HGF, and assessed the effect of HGF on the EndMT using western blotting, qRT-PCR, and ELISA assays. We utilized cell motility and migration assays to evaluate cell movement, and applied western blotting to assess the mechanism by which TGF-β1 induced the EndMT. RESULTS HGF significantly attenuated the development of TGF-β1-induced EndMT in a concentration-dependent way, and weakened the abilities of motility and migration of both HUVECs and HRGECs. Moreover, our results reveal that the antifibrotic effect of HGF on the EndMT was associated with the TGF-β/Smad and Akt/mTOR/p70S6K signaling pathways. CONCLUSIONS Our study suggests that HGF treatment significantly attenuates the development of EndMT induced by TGF-β1 via the TGFb/Smad and Akt/mTOR/P70S6K signaling, which provides novel insights into the prevention and treatment of interstitial fibrosis and CAD following renal transplant.


Visual crowding effect in the parvocellular and magnocellular visual pathways.
The crowding effect, defined as the detrimental effects of nearby items on visual object recognition, has been extensively investigated. Previous studies have primarily focused on finding the stage(s) in the visual hierarchy where crowding starts to limit target processing, while little attention has been focused on potential differences between the parvocellular (P) and magnocellular (M) pathways in crowding mechanisms. Here, we investigated the crowding effect in these parallel visual pathways. In Experiment 1, stimuli were designed to separately engage the P or M pathway, by tuning stimulus and background features (e.g., temporal frequency and color) to activate the targeted pathway and saturate the other pathway, respectively. Results showed that at the same eccentricity and with the same tasks, targets processed in the M pathway appeared to be more vulnerable to crowding effect. In Experiment 2, crowding effects were studied using three different types of stimuli and visual tasks (form, color, and motion), presumably with different degrees of dependence on the P and M pathways. Results revealed that color, motion, and form discrimination were increasingly more affected by crowding. We conclude that processing in the M and P pathways are differentially impacted by crowding; and importantly, crowding seems to affect processing of spatial forms more than other stimulus properties.


Reported maternal tendencies predict the reward value of infant facial cuteness, but not cuteness detection.
The factors that contribute to individual differences in the reward value of cute infant facial characteristics are poorly understood. Here we show that the effect of cuteness on a behavioural measure of the reward value of infant faces is greater among women reporting strong maternal tendencies. By contrast, maternal tendencies did not predict women's subjective ratings of the cuteness of these infant faces. These results show, for the first time, that the reward value of infant facial cuteness is greater among women who report being more interested in interacting with infants, implicating maternal tendencies in individual differences in the reward value of infant cuteness. Moreover, our results indicate that the relationship between maternal tendencies and the reward value of infant facial cuteness is not due to individual differences in women's ability to detect infant cuteness. This latter result suggests that individual differences in the reward value of infant cuteness are not simply a by-product of low-cost, functionless biases in the visual system.


Enhancing the effectiveness of diabetes self-management education: the diabetes literacy project.
Patient empowerment through self-management education is central to improving the quality of diabetes care and preventing Type 2 Diabetes. Although national programs exist, there is no EU-wide strategy for diabetes self-management education, and patients with limited literacy face barriers to effective self-management. The Diabetes Literacy project, initiated with the support of the European Commission, aims to fill this gap. The project investigates the effectiveness of diabetes self-management education, targeting people with or at risk of Type 2 Diabetes in the 28 EU Member States, as part of a comprehensive EU-wide diabetes strategy. National diabetes strategies in the EU, US, Taiwan, and Israel are compared, and diabetes self-management programs inventorized. The costs of the diabetes care pathway are assessed on a per person basis at national level. A comparison is made of the (cost)-effectiveness of different methods for diabetes self-management support, and the moderating role of health literacy, organization of the health services, and implementation fidelity of education programs are considered. Web-based materials are developed and evaluated by randomized trials to evaluate if interactive internet delivery can enhance self-management support for people with lower levels of health literacy. The 3-year project started in December 2012. Several literature reviews have been produced and protocol development and research design are in the final stages. Primary and secondary data collection and analysis take place in 2014. The results will inform policy decisions on improving the prevention, treatment, and care for persons with diabetes across literacy levels.


Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer.
Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (greater than 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p less than 0.01). Of those nine patients with bulky tumor (residual greater than 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (less than 2 cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (less than 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated greater than 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p less than 0.001). These data support the concept that interleukin-6 may be a useful tumor marker in some patients with epithelial ovarian cancer, as it correlates with the tumor burden, clinical disease status, and survival.


Behavioral correlates of fruit and vegetable intake in Puerto Rico: results from the Health Information National Trends Survey.
A diet high in fruit and vegetables (FV) is associated with a decreased risk for chronic diseases, such as cancer. Limited information exists regarding the factors associated with FV intake in persons living in Puerto Rico. The objective of this study was to examine sociodemographic, behavioral, and health-belief factors associated with dietary habits in Puerto Rico. Secondary data analysis of adults aged 18 years and older from the Puerto Rico Health Information National Trends Survey (HINTS-PR) conducted in 2009. Multivariate logistic regression models were used to identify factors associated with meeting the established recommendations for FV consumption. Only 14.5% of the adults in Puerto Rico met the recommendations for daily FV intake, and the vast majority (90.9%) were unaware of current recommendations. Bivariate analyses demonstrated that being obese, having lower than a high school education, and not knowing the recommendations were significantly associated with not meeting these recommendations. In the multivariate logistic regression analysis, being obese (OR = 3.77; 95% CI = 1.41-10.08) and not being aware of the current dietary recommendations (OR = 9.26; 95% CI = 3.77-22.73) continued to be significantly associated with not meeting the FV intake recommendations. The Puerto Rican population is far from meeting FV consumption recommendations, with prevalence estimates of consumption that are below the US median. Low FV intake might put the population in Puerto Rico at increased risk of developing cancer as well as a number of other chronic diseases that are secondary both to improper nutrition and to obesity.


Multidrug-resistant tuberculosis in north-west of Iran and Republic of Azerbaijan: a major public health concern for Iranian people.
Republic of Azerbaijan is considered as an area with high prevalence of multi-drug resistant tuberculosis. Uncontrolled travelling of Azerbaijanis people to Iran is the issue that needs to be considered as an important issue. This study was conducted on 32 patients with tuberculosis from Baku-Nakhchivan and 48 patients from Iran during 2012 to 2014. Colonies of Mycobacterium tuberculosis were examined after isolating them from patients using proportional method on Lowenstein-Jensen media regarding resistance encounter with Rifampin, Isoniazid and Ethambutol. Among M. tuberculosis isolates belonging to 32 foreign patients; 69%, 72% and 56% of them were resistant to Rifampin, Isoniazid and Ethambutol, respectively (multidrug resistance tuberculosis: MDR-TB: 62.5%). From 48 isolates of Iranian patients; 8%, 4% and 4% were resistant to Rifampin, Isoniazid and Ethambutol, respectively (MDR-TB: 2.1%). Resistant strains are common in Baku-Nakhchivan's people. To prevent the transmission of these strains to Iranians, strategies such as; establishing a medical campus in border lines of both countries for clinical examinations and conducting screening tests regarding tuberculosis infection in applicants for entering Iran must be taken in to account.


Intestinal inflammatory profile shows increase in a diversity of biomarkers in irritable bowel syndrome.
Background: It has been proposed that irritable bowel syndrome (IBS) is a low-grade mucosal inflammatory disease.Objective: To characterize the intestinal inflammatory profile in IBS patients with or without fructose intolerance.Design: Patients referred to colonoscopy with IBS complaints were screened for participation. IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were included in the study. One subgroup was patients included in a fructose-reduced diet study for 2 months with effects based on VAS symptom scores. Healthy controls were subjects under investigation of colorectal cancer screening with no IBS or other gastrointestinal diseases. All patients included had normal histology from rectum. Mucosal cytokines, chemokines and growth factors were measured by multiplex technology.Results: Of 27 inflammatory markers tested in the mucosal tissue, 13 were significantly increased and none was significantly decreased in IBS as compared to controls. Significantly increased were the proinflammatory cytokines tumor necrosis factor, the typical TH1 markers IFNγ, IL-1β, IL-2 and RANTES, the typical TH2 markers IL-5 and IL-9, the TH17 marker IL-17, TNF, the pleiotropic IL-15, and the growth factors bFGF and GM-CSF. In IBS patients with fructose intolerance only IL-5 was significantly increased compared to patients without fructose intolerance.Conclusions: A dysregulated mucosal inflammatory profile with an increased level of TH1, TH2 and TH17 markers, and growth factors were observed in bowel mucosa in of IBS patients when compared to healthy controls.