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Objective: To conduct a pragmatic randomized controlled trial to test the effectiveness of an ADHD question prompt list with video intervention to increase youth question-asking and provider education about ADHD during visits., Methods: English-speaking youth ages 11-17 with ADHD and their caregivers were enrolled from two pediatric clinics. Youth were randomized to intervention or usual care groups. Intervention group adolescents watched the video and then completed an ADHD question prompt list before their visits. Multivariable regression was used to analyze the data., Results: Twenty-one providers and 102 of their patients participated. Intervention group youth were significantly more likely to ask one or more questions about ADHD and its treatment than usual care youth (odds ratio=5.4, 95 % Confidence Interval (CI)= 1.8, 15.9). Providers were significantly more likely to educate youth who asked one or more questions during visits about more ADHD medication areas (unstandardized beta=0.98, 95 % CI=0.31 to 1.64) and more non-medication strategies for ADHD (unstandardized beta=0.50, 95 % CI=0.13 to 0.88)., Conclusion: The intervention increased youth question-asking about ADHD and its treatment. Providers provided more education to youth who asked one or more questions about ADHD and its treatment., Practice Implications: Providers and practices should consider having youth complete ADHD question prompt lists and watch the video before visits to increase youth question-asking during visits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain., Methods: All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher's exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders., Results: Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51)., Conclusion: Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to identify what best practices facilitate implementation of Entrustable Professional Activities (EPAs) into surgical training programs., Design: This is a mixed methods study utilizing both survey data as well as semi-structured interviews of faculty and residents involved in the American Board of Surgery (ABS) EPA pilot study., Setting: From 2018 to 2020, the ABS conducted a pilot that introduced five EPAs across 28 general surgery training programs., Participants: All faculty members and residents at the 28 pilot programs were invited to participate in the study., Results: About 117 faculty members and 79 residents responded to the survey. The majority of faculty (81%) and residents (66%) felt that EPAs were useful and were a valuable addition to training. While neither group felt that EPAs were overly time consuming to complete, residents did report difficulty incorporating them into their daily workflow (44%). Semi-structured interviews found that programs that focused on faculty and resident -development and utilized frequent reminders about the importance and necessity of EPAs tended to perform better., Conclusions: EPA implementation is feasible in general surgery training programs but requires significant effort and engagement from all levels of program personnel. As EPAs are implemented by the ABS nationally a focus on resident and faculty development will be critical to success., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Wildfires, controlled burns, and biofuel combustion (biomass burning or BB) are major contributors to particulate matter in the atmosphere and thus have an impact on climate, human health, and ecosystems. Once emitted, the particulate matter derived from BB can be taken up by the oceans. However, the fate and impact of BB in the marine biological carbon pump, and carbon cycle are largely unknown. This work presents the first attempt to investigate the bioavailability of two BB tracers, levoglucosan and galactosan, in seawater inoculated with marine prokaryotes. Levoglucosan and galactosan were incubated with a marine bacterial inoculum and monitored for six weeks under controlled laboratory conditions. Along with the anhydrosugar concentrations, multiple chemical and biological parameters were monitored over time. The results indicate that levoglucosan and galactosan can be assimilated by marine prokaryotes as their concentrations decreased by 97 ± 4 % and 36 ± 21 % (n = 3) of their initial values. However, this decrease occurred only after a 9 and 15 days from the beginning of the experiment, respectively. The decrease in the levoglucosan and galactosan concentrations was accompanied by an increase in both heterotrophic prokaryotic production, and abundance. These results demonstrate that these anhydrosugars have the potential to be assimilated by heterotrophic prokaryotes and thus contribute to the microbial food web functioning. Under our experimental conditions, levoglucosan exhibited a bacterial growth efficiency of 17 ± 5 % (n = 3), suggesting that most of the levoglucosan is mineralized into CO 2 . Prokaryotic diversity analyses revealed the predominance of a few bacterial genera from the Roseobacter clade that were selected after the addition of the anhydrosugars. The presence of this widespread marine bacterial clade reflects its ability to process semilabile compounds (here levoglucosan and galactosan) originating from BB and contribute to the dissolved organic matter pool in surface seawaters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To examine whether non-adherent African American patients with glaucoma who received a question prompt list and video intervention were more likely to be given treatment options, have their input included into treatment regimens, and rate their providers as using more of a participatory decision-making style., Methods: African American patients with glaucoma taking one or more glaucoma medications and reported being non-adherent were randomized to a pre-visit video and glaucoma question prompt list intervention or usual care., Results: 189 African American patients with glaucoma participated. Providers gave patients treatment choices during 5.3% of visits and included patient input into treatment regimen decisions during 2.1% of visits. Male patients and patients with more years of education were significantly more likely to rate their providers as using more of a participatory decision-making style., Conclusion: African American patients with glaucoma rated their providers high on using a participatory decision-making style. Yet, providers infrequently presented non-adherent patients with medication treatment options, and it was rare for providers to include patient input into treatment decisions., Practice Implications: Providers should provide non-adherent patients with different glaucoma treatment options. Non-adherent African American patients with glaucoma should be encouraged to ask their providers for different medication treatment options., Competing Interests: Conflict of interest There are no competing interest that relate to any authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This paper looks at experiential feedback and the technical and scientific challenges tied to the MERITE-HIPPOCAMPE cruise that took place in the Mediterranean Sea in spring 2019. This cruise proposes an innovative approach to investigate the accumulation and transfer of inorganic and organic contaminants within the planktonic food webs. We present detailed information on how the cruise worked, including 1) the cruise track and sampling stations, 2) the overall strategy, based mainly on the collection of plankton, suspended particles and water at the deep chlorophyll maximum, and the separation of these particles and planktonic organisms into various size fractions, as well as the collection of atmospheric deposition, 3) the operations performed and material used at each station, and 4) the sequence of operations and main parameters analysed. The paper also provides the main environmental conditions that were prevailing during the campaign. Lastly, we present the types of articles produced based on work completed by the cruise that are part of this special issue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tγδ large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent Tαβ LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by Tγδ LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in ∼20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of Tγδ cases were also compared with a recently published Tαβ cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, Tγδ cases more frequently presented with neutropenia (P = .0161), anemia (P < .0001), severe anemia (P = .0065), and thrombocytopenia (P = .0187). Moreover, Vδ2- cases displayed higher frequency of symptomatic disease. Overall, Tγδ cases displayed reduced survival with respect to Tαβ cases (P = .0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tγδ LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with Tαβ LGLL., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Along with their important diversity, coastal ecosystems receive various amounts of nutrients, principally arising from the continent and from the related human activities (mainly industrial and agricultural activities). During the 20th century, nutrients loads have increased following the increase of both the global population and need of services. Alongside, climate change including temperature increase or atmospheric circulation change has occurred. These processes, Ecosystem state changes are hard to monitor and predict. To study the long-term changes of nutrients concentrations in coastal ecosystems, eleven French coastal ecosystems were studied over 20 years as they encompass large climatic and land pressures, representative of temperate ecosystems, over a rather small geographical area. Both univariate (time series decomposition) and multivariate (relationships between ecosystems and drivers) statistical analyses were used to determine ecosystem trajectories as well as typologies of ecosystem trajectories. It appeared that most of the French coastal ecosystems exhibited trajectories towards a decrease in nutrients concentrations. Differences in trajectories mainly depended on continental and human influences, as well as on climatic regimes. One single ecosystem exhibited very different trajectories, the Arcachon Bay with an increase in nutrients concentrations. Ecosystem trajectories based on ordination techniques were proven to be useful tools to monitor ecosystem changes. This study highlighted the importance of local environments and the need to couple uni- and multi-ecosystem studies. Although the studied ecosystems were influenced by both local and large-scale climate, by anthropogenic activities loads, and that their trajectories were mostly similar based on their continental influence, non-negligible variations resulted from their internal functioning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Here we assessed the subsurface ultraphytoplanktonic (< 10 μm) community along a North-South round-trip Mediterranean transect as part of a MERITE-HIPPOCAMPE cruise campaign in April-May 2019. Temperature, salinity, and nutrient concentrations in subsurface waters (2-5 m depth) were also measured along the transect. The subsurface ultraphytoplankton community structure was resolved with a spatial resolution of few kilometers and temporal resolution of 30-min intervals using automated pulse shape recording flow cytometry. The subsurface waters were clustered into seven areas based on temperature and salinity characteristics. Synechococcus were by far the most abundant group in all prospected zones, and nanoeukaryotes were the main biomass component, representing up to 51 % of ultraphytoplanktonic carbon biomass. Apparent net primary productivity (NPP) followed a decreasing gradient along the transect from north to south and was mostly sustained by Synechococcus in all zones. These findings are likely to have implications in terms of the trophic transfer of contaminants in planktonic food webs, as they highlight the potential role of nanoplankton in contaminants bioaccumulation processes and the potential role of Synechococcus in a likely transfer via grazing activities., (Copyright © 2022. Published by Elsevier Ltd.)

CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19- (pre)-leukemic cells represent an "early progenitor origin-related" mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19-CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19-CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19-CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19-CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19- relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged., (© 2022 by The American Society of Hematology.)

Purpose: The aim of this study is to assess factors that influence adolescent asthma responsibility and how patient- and parent-reported asthma responsibility changes over a 12-month period., Methods: One hundred sixty-four adolescents and their parents completed questionnaires at baseline and 12 months, including the asthma responsibility questionnaire, in which higher scores indicate greater adolescent responsibility. Multiple linear regression was used to assess how baseline asthma responsibility, self-efficacy, outcome expectations, and demographic characteristics were associated with 12-month asthma responsibility., Results: Asthma responsibility as reported by both adolescents and parents shifted significantly toward the adolescent over the study period (p < .001). Most individual scale items (e.g., noticing signs and symptoms of asthma, starting treatment when symptoms occur) also showed significant shifts toward greater adolescent responsibility. In the regression models, higher baseline asthma responsibility and older age were significant predictors of both higher adolescent- and parent-reported 12-month asthma responsibility, while female gender and mild asthma severity also predicted higher parent-reported asthma responsibility., Conclusions: Asthma responsibility shifted toward adolescents over a 12-month period. Regardless of age and gender, all types of adolescents were able to improve their responsibility level based on adolescent-reported results. Older females, according to parent-reported results, were more likely to improve their responsibility. Providers need to make sure adolescents are learning all the necessary skills to manage asthma independently before they reach adulthood., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Platelets are a reservoir of growth factors, cytokines and chemokines involved in spontaneous wound repair. In this study, a platelet-rich and fibrin-rich hydrogel was generated from expired platelet components that would have otherwise been transfused. The material contained physiological concentrations of transforming growth factor β1 (TGF-β1, platelet-derived growth factor AB (PDGF-AB), PDGF-BB, insulin-like growth factor-1 (IGF-1), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF). The effect of the hydrogel on wound repair was investigated in SKH-1 mice. Full thickness dorsal wounds were created on the mice and treated with the hydrogel at various concentrations. Immunohistochemical staining with CD31 (endothelial cell marker) revealed that wounds treated with the hydrogel showed significantly enhanced vascularisation in the wound bed. Moreover, high levels of interleukin-6 (IL-6) and KC (IL-8 functional homologue) in treated wounds were sustained over a longer period of time, compared to untreated wounds. We postulate that sustained IL-6 is a driver, at least partly, of enhanced vascularisation in full thickness wounds treated with the hydrogel. Future work is needed to explore whether this hydrogel can be utilised as a treatment option when vascularisation is a critical limitation. STATEMENT OF SIGNIFICANCE: The economic cost of wound repair is estimated in billions of dollars each year. In many cases time required to vascularise wounds is a major contributor to slow wound repair. In this study, we developed a blood-derived platelet- and fibrin-rich hydrogel. It contains a number of growth factors actively involved in spontaneous wound healing. This hydrogel significantly improved dermal repair and vascularisation in a full-thickness wound mouse model. This study provides an action mechanism for modulation of localised inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Adolescents experience challenges managing their chronic conditions, partly owing to limited involvement in medical visits. Because adolescents are "digital natives," providing a specific Web site with educational resources may support better adolescent-provider communication. Our purpose was to determine adolescents' opinions about a health communication-focused Web site., Methods: Sixty English-speaking adolescents aged 11-17 years with a chronic health condition (mean age: 13.3 years; SD 1.9) were enrolled at a pediatric clinic in rural North Carolina., Results: Adolescents most commonly accessed YouTube and Google for online health information. Nearly all adolescents supported the creation of a Web site and resources on how to communicate with their healthcare provider. Adolescents most often wanted to talk to specialists about their health and to pharmacists about their medications., Conclusions: A Web site and educational resources are currently being codeveloped with adolescents. It is essential that we find ways to engage adolescents in their healthcare management., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: OSA, a common comorbidity in interstitial lung disease (ILD), could contribute to a worsened course if untreated. It is unclear if adherence to CPAP therapy improves outcomes., Research Question: Does adherence to CPAP therapy improve outcomes in patients with concurrent interstitial lung disease and OSA?, Study Design and Methods: We conducted a 10-year retrospective observational multicenter cohort study, assessing adult patients with ILD who had undergone polysomnography. Subjects were categorized based on OSA severity into no/mild OSA (apnea-hypopnea index score < 15) or moderate/severe OSA (apnea-hypopnea index score ≥ 15). All subjects prescribed and adherent to CPAP were deemed to have treated OSA. Cox regression models were used to examine the association of OSA severity and CPAP adherence with all-cause mortality risk and progression-free survival (PFS)., Results: Of 160 subjects that met inclusion criteria, 131 had OSA and were prescribed CPAP. Sixty-six patients (41%) had no/mild untreated OSA, 51 (32%) had moderate/severe untreated OSA, and 43 (27%) had treated OSA. Subjects with no/mild untreated OSA did not differ from those with moderate/severe untreated OSA in mean survival time (127 ± 56 vs 138 ± 93 months, respectively; P = .61) and crude mortality rate (2.9 per 100 person-years vs 2.9 per 100 person-years, respectively; P = .60). Adherence to CPAP was not associated with improvement in all-cause mortality risk (hazard ratio [HR], 1.1; 95% CI, 0.4-2.9; P = .79) or PFS (HR, 0.9; 95% CI, 0.5-1.5; P = .66) compared with those that were nonadherent or untreated. Among subjects requiring supplemental oxygen, those adherent to CPAP had improved PFS (HR, 0.3; 95% CI, 0.1-0.9; P = .03) compared with nonadherent or untreated subjects., Interpretation: Neither OSA severity nor adherence to CPAP was associated with improved outcomes in patients with ILD except those requiring supplemental oxygen., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend anticoagulation using warfarin with bridging parenteral anticoagulation or one of the non-vitamin K antagonist oral anticoagulants (NOACs) to prevent thromboembolic events in patients undergoing cardioversion for atrial fibrillation (AF). We aimed to compare by meta-analytical techniques, the safety and efficacy of NOACs versus warfarin in patients undergoing cardioversion., Methods: PUBMED, EMBASE, Cochrane CENTRAL and CINAHL were searched electronically in addition to manual search for randomized controlled trials (RCTs) comparing NOACs and warfarin in patients undergoing cardioversion for AF. Mortality, major bleeding and ischemic and hemorrhagic stroke were compared between the two agents., Results: A total of 7 trials with 7588 total patients were included in the meta-analysis. NOACs, as compared to warfarin, resulted in similar risk of ischemic stroke [odds ratio (OR): 0.49 (95% confidence interval (CI): 0.20-1.19; P = 0.12], major bleeding [0.71 (0.37-1.38), P = 0.32], mortality [0.73 (0.32-1.67); P = 0.45], and hemorrhagic stroke [0.96 (0.11-8.70); P = 0.97]. The results were consistent across subgroup analyses., Conclusions: Based on the current meta-analysis, NOACs and warfarin have comparable efficacy and safety in patients with atrial fibrillation undergoing cardioversion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma associated with chemoresistance and a poor prognosis. Various nonsynonymous mutations in the R172 residue of IDH2 are present in 20% to 30% of AITL patients. In addition to their diagnostic value, these mutations are potentially targetable, especially by isocitrate dehydrogenase (IDH) 2 inhibitor, and therefore their identification in a routine setting is clinically relevant. However, in AITL, the neoplastic cells may be scarce, making the identification of molecular anomalies difficult. We evaluated the diagnostic value of different methods to detect IDH2 mutations in formalin-fixed, paraffin-embedded tumor samples. Immunohistochemistry with an anti-IDH2 R172K antibody, Sanger sequencing, high-resolution melting PCR, allele-specific real-time quantitative PCR, and next-generation sequencing (NGS) were applied to biopsy specimens from 42 AITL patients. We demonstrate that the IDH2 R172K antibody is specific to this amino acid substitution and highly sensitive for the detection of the IDH2 R172K variant, the most frequent substitution in this disease. In our study, NGS and allele-specific real-time quantitative PCR displayed a good sensitivity, detecting 96% and 92% of IDH2 mutations, respectively, in contrast to Sanger sequencing and high-resolution melting PCR, which showed a significantly lower detection rate (58% and 42%, respectively). These results suggest that a combination of immunohistochemistry and AS-PCR or NGS should be considered for the identification of IDH2 mutations in AITL in a routine setting., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: We conducted a pragmatic randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to increase youth question-asking and provider education during visits., Methods: English or Spanish-speaking youth ages 11-17 with persistent asthma and their parents were enrolled from four rural and suburban pediatric clinics. Youth were randomized to the intervention or usual care groups. Intervention group adolescents watched the video on an iPad and then completed an asthma question prompt list before their visits. Generalized estimating equations were used to analyze the data., Results: Forty providers and 359 patients participated. Intervention group youth were significantly more likely to ask one or more questions about medications, triggers, and environmental control than usual care youth. Providers were significantly more likely to educate intervention group youth about rescue medications, triggers, and environmental control. Intervention group caregivers were not significantly more likely to ask questions., Conclusion: The intervention increased youth question-asking and provider education about medications, triggers, and environmental control. The intervention did not impact caregiver question-asking., Practice Implications: Providers/practices should consider having youth complete question prompt lists and watch the video with their parents before visits to increase youth question-asking during visits., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The objectives of this study were to: (a) describe teen feedback on an asthma question prompt list/video intervention designed to motivate teens to be more engaged during visits and (b) examine teen demographics associated with teen acceptance of the intervention., Methods: Two hundred and fifty-nine teens ages 11 to 17 with persistent asthma were enrolled into a randomized, controlled trial and assigned to either a standard care or an intervention group where they watched an educational video with their parents and received a prompt list to complete before visits. Teens were interviewed after visits., Results: Of the 185 teens randomized to the intervention group: 93% said teens should complete the prompt lists before visits; 95% recommended teens should watch the video before visits; teens with moderate/severe persistent asthma were significantly more likely to find the prompt list useful; non-White teens were significantly more likely to find the prompt list and video more useful., Conclusions: Teens exposed to the question prompt list/video had very positive feedback about the intervention., Practice Implications: Providers/practices should consider having teens complete question prompt lists during pre-visit wait time for use during visits and watch the video with their parents before visits., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data. Patients with HPRT deficiency present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. We present a 9-year-old boy who experienced an episode of macroscopic hematuria with dysuria and left flank pain. He presented hyperuricemia and hyperuricosuria. HPRT and APRT activities were both normal in hemolysate; however, HPRT activity assayed in intact erythrocytes was 50% of control levels. A new missense point mutation c.424 A>G (T142A) was found in the HPRT1 gene. The apparent Michaelis constant (Km) for 5-phosphoribosyl-pyrophosphate assayed in patient hemolysate was 20-fold of control levels. In conclusion, we report a patient with HPRT deficiency who presented with both normal HPRT and APRT activity in hemolysate, in which the enzyme activity determined in intact erythrocytes was of diagnostic utility., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives:: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol., Methods:: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis., Results:: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor., Conclusions:: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Dissolved aliphatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs) were analysed from surface water collected in continental, harbour and off-shore marine sites from Marseilles coastal area (Northwestern Mediterranean Sea) from February 2011 to February 2012. AH and PAH concentrations were in the range of 0.04-0.53 μgl(-1) and 8.1-405 ngl(-1), respectively. They both displayed seasonal and spatial variations in their concentrations and molecular composition. The lowest AH concentrations were found in summer and the highest PAH concentrations in winter. Both natural and anthropogenic (pyrogenic and petrogenic) hydrocarbon sources were identified. In winter, concentrations and composition patterns highlighted an increase in the signature of unburned and combusted fossil fuels, while they suggested an enhancement of weathering processes in summer months. Hydrocarbon inputs to the dissolved phase seemed to originate mainly from the atmosphere and the Rhône River. Hydrocarbon additional sources were identified only at the harbour site, emphasising the intense shipping traffic and industrial activities occurring in one of the most important Mediterranean harbours. This study underscores the strong dynamics of dissolved hydrocarbons and the uncoupling of the sources, transport and removing processes affecting AHs and PAHs. It also demonstrates the pertinence of taking this dynamics into account for the budget assessments of organic pollutants in coastal environments., (© 2013.)

The Berre lagoon receives freshwater from two natural rivers but the implementation of the hydroelectric power plant led to strong changes in the ecosystem structure and functioning. Sediments are important sites for nitrogen cycling because the O(2) sharp gradient allows oxic nitrification as well as anoxic denitrification and anammox to operate in close proximity. Seasonal and short-term variations in the coastal nitrogen processes were quantified at two stations: SA1 located in the northern part of the lagoon directly under the inflows of freshwater and SA3 in the southern part of the lagoon influenced mainly by the marine water inflows. Results revealed that most of the nitrate formed by nitrification was denitrified. Total denitrification was the main N(2) removal process. The high primary production based on N-NH(4)(+) might be explained by mineralization rates, while the primary production based on N-NO(3)(-) was not fully explained by nitrification., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In order to advance in the understanding of CI in pepper fruits, the cell ultrastructure alterations induced by CI and the physiological and metabolic changes have been studied along with the proteomic study. When stored at low temperatures bell pepper (Capsicum annuum) fruits exhibited visual CI symptoms and important alterations within the cell ultrastructure, since peroxisomes and starch grains were not detected and the structure of the chloroplast was seriously damaged in chilled tissues. Physiological and metabolic disorders were also observed in chilled fruits, such as higher ethylene production, increased MDA content, changes in sugar and organic acids and enzymatic activities. The comparative proteomic analysis between control and chilled fruits reveals that the main alterations induced by CI in bell pepper fruits are linked to redox homeostasis and carbohydrate metabolism. Thus, protein abundance in the ascorbate-glutathione cycle is altered and catalase is down-regulated. Key proteins from glycolysis, Calvin cycle and Krebs cycle are also inhibited in chilled fruits. Enolase and GAPDH are revealed as proteins that may play a key role in the development of chilling injury. This study also provides the first evidence at the protein level that cytosolic MDH is involved in abiotic stress., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.

Nitrite and (29)N(2) productions in slurry incubations of anaerobically sediment after (15)NO(3) or (15)NH(4) labelling in the presence of Mn-oxides suggested that anaerobic Mn-oxides mediated nitrification coupled with denitrification in muddy intertidal sediments of Arcachon Bay (SW Atlantic French coast). From this sediment, bacterial strains were isolated and physiologically characterized in terms of Mn-oxides and nitrate reduction as well as potential anaerobic nitrification. One of the isolated strain, identified as Marinobacter daepoensis strain M4AY14, was a denitrifier. Nitrous oxide production by this strain was demonstrated in the absence of nitrate and with Mn-oxides and NH(4) amendment, giving indirect proof of anaerobic nitrate or nitrite production. Anaerobic Mn-oxide-mediated nitrification was confirmed by (29)N(2) production in the presence of (15)NO(3) and (14)NH(4) under denitrifying conditions. Anaerobic nitrification by M4AY14 seemed to occur only in the absence of nitrate, or at nitrate levels lower than that of Mn-oxides. Most of the other isolates were affiliated with the Shewanella genus and were able to use both nitrate and Mn-oxides as electron acceptors. When both electron acceptors were present, whatever their concentrations, nitrate and Mn-oxide reduction co-occurred. These data indicate that bacterial Mn-oxide reduction could be an important process in marine sediments with low oxygen concentrations, and demonstrate for the first time the role of bacteria in anaerobic Mn-mediated nitrification., (Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is the most frequent nodal T-cell lymphoma and is characterized by a polymorphic lymph node infiltrate, various dysimmune disorders, and a poor prognosis. Regulatory T-cells (Treg) play an emerging role in the prognosis of non-Hodgkin B-cell lymphoma and mediate significant autoreactive T-cell suppression. In this report, we demonstrate that numbers of Treg are significantly decreased in AITL lymph nodes [n = 30, 91 (40-195) per high power fields] compared with follicular lymphoma [n = 19, 179 (86-355)] and reactive lymph nodes [n = 8, 186 (140-265)]. Moreover, the few Treg in lymph nodes of AITL are resting Treg (rTreg) and have a naive CD45RA+, PD1-, and ICOS- phenotype [n = 5, 57% of Treg are CD45RA+ (16-96)], in contrast to the Treg in follicular lymphomas [n = 5, 7.4% (1-13)] or reactive lymph nodes [n = 7, 18.6% (6-48)]. Interestingly, Treg depletion was not observed in AITL peripheral blood at diagnosis. Altogether, these data suggest that Treg depletion could contribute to the nodal neoplastic T(FH) expansion and dysimmune symptoms in AITL.

The objective was to determine whether ethnic composition of neighborhoods is associated with number and type of food stores in an urban, Mexican American US community. Data were from a commercial food store data source and the US Census. Multivariate count models were used to test associations with adjustment for neighborhood demographics, income, and commercialization. Neighborhoods at the 75th percentile of percent Mexican American (76%) had nearly four times the number of convenience stores (RR=3.9, 95% CI: 2.2-7.0) compared with neighborhoods at the 25th percentile (36%). Percent Mexican American in the neighborhood was not associated with the availability of other food store types (supermarkets, grocery stores, specialty stores, convenience stores with gas stations) in the adjusted model. The impact of greater access to convenience stores on Mexican American residents' diets requires exploration., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Despite the development of multi-drug regimens for HIV, palliative care and quality-of-life issues in patients with advanced AIDS remain important areas of clinical investigation., Objective: Authors assessed the impact of treatment for depression on desire for hastened death in patients with advanced AIDS., Method: Patients with advanced AIDS (N=372) were interviewed shortly after admission to a palliative-care facility, and were reinterviewed monthly for the next 2 months. Patients diagnosed with a major depressive syndrome were provided with antidepressant treatment and reinterviewed weekly. Desire for hastened death was assessed with two questionnaire measures., Results: Desire for death was highly associated with depression, and it decreased dramatically in patients who responded to antidepressant treatment. Little change in desire for hastened death was observed in patients whose depression did not improve. Although improved depression was not significantly associated with the use of antidepressant medication, those individuals prescribed antidepressant medication showed the largest decreases in desire for hastened death., Discussion: Successful treatment for depression appears to substantially decrease desire for hastened death in patients with advanced AIDS. The authors discuss implications of these findings for palliative-care treatment and the physician-assisted suicide debate.

Biopsies and cell lines of natural killer/T-cell lymphoma, nasal type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor alpha and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase-signal transducers and activators of transcription, and nuclear factor-kappaB pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44], IL6R [1q21.3], CCL2 [17q12], TNFRSF21 [6p12.3]). Several features of NKTCL uncovered by this analysis suggest perturbation of angiogenic pathways. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets.

Oval cells participate in liver regeneration when hepatocyte replication is impaired. These precursor cells proliferate in periportal regions and organize in ductules. They are surrounded by a basement membrane, the degradation of which by matrix metalloproteinases (MMP) might trigger their terminal differentiation into hepatocytes. We studied the expression of MMP-2 and MMP-9 and that of one of their tissue inhibitors (TIMP-1) in a model of hepatic regeneration from precursor cells. Regeneration was induced by treating rats with 2-acetylaminofluorene followed by partial hepatectomy. MMP-2 and MMP-9 hepatic expression paralleled oval cell number with a peak at day 9-14 after hepatectomy. They were mainly detected in oval cells. TIMP-1 mRNA and oncostatin M receptor mRNA, a major regulator of TIMP-1 synthesis, markedly increased from day 1 after surgery until day 9 and then declined; they were mainly detected in interlobular bile duct cells and oval cells until day 14. In agreement with the in vivo data, the WB-F344 liver precursor cell line expressed MMP-2 and MMP-9, as well as TIMP-1 and oncostatin M receptor. These data suggest that (a) early increased TIMP-1 synthesis by biliary and oval cells favors basement membrane deposition around proliferating ductular structures through MMP inhibition, (b) delayed increased MMP expression, concomitant to decreased TIMP-1 synthesis, leads to basement membrane degradation, preceding oval cell differentiation, (c) the oncostatin M pathway might play a major role in increased TIMP-1 synthesis.

Objective: Urachal anomalies are rare. Variable presentations can be a diagnostic challenge. We combine our series with a review of literature to delineate the most common presentations, highest yield diagnostic studies and a diagnostic algorithm., Methods: We reviewed records of 22 boys and 15 girls with the diagnosis of a urachal anomaly from 2000 through 2005. This revealed 19 cysts, seven patent urachuses, five sinuses, four patients with unspecified "urachal anomalies," and two patients with no urachal anomaly by surgical exploration. Ultrasound was the most common diagnostic study, followed by computed tomography (CT), voiding cystourethrogram and sinogram. Thirty-five of 37 patients underwent surgery., Results: Clinical presentation included periumbilical leakage in 54%, pain in 30%, periumbilical mass in 22% and irritative voiding symptoms in 14%. In many patients diagnosis was made on clinical examination alone. When an ultrasound was used it was diagnostic for 82% of cysts, 100% of sinuses and 100% of patent urachuses. A voiding cystourethrogram was diagnostic for 100% of patent urachuses, but less successful in the other anomalies. CT scans correctly diagnosed 71% of cysts. Overall complication rate was 9%, all wound infections., Conclusion: Reviewing the results of this and four other large series showed that the most common anomaly is the urachal cyst followed by urachal sinus and patent urachus. Periumbilical drainage is the most common presentation. Physical exam alone can be diagnostic. When this is not possible ultrasound is our recommended initial study, followed by a CT scan if unsuccessful.

PURPOSE: Despite extensive research, the molecular basis of hypospadias and anorectal malformations is poorly understood, likely due to a multifactorial basis. The incidence of hypospadias is increasing, thus making research in this area warranted and timely. This review presents recent molecular work broadening our understanding of these disorders. MATERIALS AND METHODS: A brief review of our recent work and the literature on the role of Eph/ephrin signaling in hypospadias and anorectal malformations is presented. RESULTS: Genetically engineered mice mutant for ephrin-B2 or EphB2;EphB3 manifest a variety of genitourinary and anorectal malformations. Approximately 40% of adult male heterozygous mice demonstrate perineal hypospadias. Although homozygous mice die soon after birth, 100% of homozygous males demonstrate high imperforate anus with urethral anomalies and 100% of homozygous females demonstrate persistent cloaca. Male mice compound homozygous for EphB2(ki/ki);EphB3(Delta/Delta)/ also demonstrate hypospadias. CONCLUSIONS: These mouse models provide compelling evidence of the role of B-class Eph/ephrin signaling in genitourinary/anorectal development and add to our mechanistic and molecular understanding of normal and abnormal embryonic development. As research on the B-class Ephs and ephrins continues, they will likely be shown to be molecular contributors to the multifactorial basis of hypospadias and anorectal malformations in humans as well.

Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5-/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression.

Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

The recent debate over legalization of physician-assisted suicide has fueled interest in understanding factors that lead medically ill patients to seek a hastened death. The authors investigated the prevalence and predictors of desire for hastened death in 372 patients with advanced AIDS who were newly admitted to a palliative-care facility. Clinician-rated and self-report measures of desire for hastened death, depression, hopelessness, spiritual well-being, social support, pain, and physical symptom burden were administered to assess the factors that correspond to a high desire for death. The prevalence ranged from 4.6% to 8.3%, significantly lower than in previous studies of patients with advanced or terminal cancer. Multivariate models revealed significant and unique effects for both hopelessness and depression, with these variables accounting for a large proportion of the variance in each model. Authors discuss the implications of these findings for palliative care practice and the assisted-suicide debate.

Purpose: To estimate ethnic-specific all-cause mortality risk following ischemic stroke and to compare mortality risk by ethnicity., Methods: DATA from the Brain Attack Surveillance in Corpus Christi Project, a population-based stroke surveillance study, were used. Stroke cases between January 1, 2000 and December 31, 2002 were identified from emergency department (ED) and hospital sources (n = 1,234). Deaths for the same period were identified from the surveillance of stroke cases, the Texas Department of Health, the coroner, and the Social Security Death Index. Ethnic-specific all-cause cumulative mortality risk was estimated at 28 days and 36 months using Kaplan Meier analysis. Cox proportional hazards regression was used to compare mortality risk by ethnicity., Results: Cumulative 28-day all-cause mortality risk for Mexican Americans (MAs) was 7.8% and for non-Hispanic whites (NHWs) was 13.5%. Cumulative 36-month all-cause mortality risk was 31.3% in MAs and 47.2% in NHWs. MAs had lower 28-day (RR = 0.58; 95% CI: 0.41, 0.84) and 36-month all-cause mortality risk (RR = 0.79, 95% CI: 0.64, 0.98) compared with NHWs, adjusted for confounders., Conclusions: Better survival after stroke in MAs is surprising considering their similar stroke subtype and severity compared with NHWs. Social or psychological factors, which may explain this difference, should be explored.