Barriers and facilitators to implementing a motivational interviewing-based intervention: a multi-site study of organizations caring for youth living with HIV.

Understanding possible barriers and facilitators to effective implementation of evidence-based interventions to help high-risk youth prevent and manage HIV is crucial for their scale-up. This manuscript analyzes qualitative interview data collected during the early phase implementation of a motivational interviewing (MI) based intervention at 10 HIV care clinics in the United States providing services to youth. Using the Exploration-Preparation-Implementation-Sustainment (EPIS) framework to understand the implementation and the dynamic adaptation process (DAP) model to balance notions of intervention fidelity and flexibility, providers and stakeholders at each site (N = 97) were interviewed prior to implementation to gather their perspectives on organizational readiness for the intervention, as well as provider and client characteristics. The interviewers summarized their experience with rapid feedback forms (RFFs). Data extracted from the RFFs highlighted anticipated barriers to and facilitators of the proposed MI-based intervention, with the EPIS framework used to organize these findings. Study findings illustrate the inner and outer contextual factors that affect implementation and denote the points at which the MI-based intervention may be tailored to fit the unique context of a clinic while remaining faithful to the intervention's original design.

Efficacy of a multimodal nursing intervention strategy in the process of becoming a mother: A randomized controlled trial.

The lack of knowledge and skills for transitioning to motherhood places first-time mothers at greater risk of depression and stress, may lower their perceived self-efficacy and satisfaction with the maternal role, and potentially affects the mother-infant bond. The purpose of this study was to test the efficacy of a multimodal nursing intervention (AMACOMPRI), based on Mercer's Becoming a Mother Theory, in supporting the process of becoming a mother in first-time mothers of term infants. This study was a parallel-group, double-blind, randomized, controlled trial with a 4-month postpartum follow-up. The outcome measures were the process of becoming a mother, functional social support, mother-infant bond, and perceived maternal self-efficacy. Sixty-six first-time mothers completed the study: 33 in the intervention group and 33 in the control group. The intervention was effective in supporting the process of becoming a mother, with a large effect size (Cohen's d = 1.50) and higher scores on the Becoming-a-Mother Scale in the intervention group compared with the control group (intergroup difference 13.04 points; 95% confidence interval: 8.72-17.34). Participants in the intervention group demonstrated higher scores in functional social support, perceived maternal self-efficacy, and mother-infant bond. This study provides evidence for the efficacy of an innovative nursing intervention that supports the process of becoming a mother. Further testing of the intervention is required in different settings and first-time mothers of low and high risk newborns.

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension.

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase.

Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes TH2 responses through dendritic cell (DC) activation. Whether it also plays a role in human autoimmune inflammation and associated pathways is not known. OBJECTIVE: In this study we investigated the potential role of several epithelium-derived factors, including TSLP, in inducing IL-23 production by human DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23-associated skin autoimmune disease. METHODS: The study was performed in human subjects using primary cells and tissue samples from patients with psoriasis and healthy donors. We analyzed the production of IL-23 in vitro by blood and skin DCs. We studied the function for TSLP and its interaction with other components of the inflammatory microenvironment in situ and ex vivo. RESULTS: We found that TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23 production by primary blood and skin DCs. In situ TSLP was strongly expressed by keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we could demonstrate that IL-4, an important component of the TH2 inflammation seen in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP and CD40 ligand in a signal transducer and activator of transcription 6-independent manner. CONCLUSION: Our results identify TSLP as a novel player within the complex psoriasis cytokine network. Blocking TSLP in patients with psoriasis might contribute to decreasing DC activation and shutting down the production of pathogenic IL-23.

Formation of a tyrosine adduct involved in lignin degradation by Trametopsis cervina lignin peroxidase: a novel peroxidase activation mechanism.

LiP (lignin peroxidase) from Trametopsis cervina has an exposed catalytic tyrosine residue (Tyr181) instead of the tryptophan conserved in other lignin-degrading peroxidases. Pristine LiP showed a lag period in VA (veratryl alcohol) oxidation. However, VA-LiP (LiP after treatment with H2O2 and VA) lacked this lag, and H2O2-LiP (H2O2-treated LiP) was inactive. MS analyses revealed that VA-LiP includes one VA molecule covalently bound to the side chain of Tyr181, whereas H2O2-LiP contains a hydroxylated Tyr181. No adduct is formed in the Y171N variant. Molecular docking showed that VA binding is favoured by sandwich π stacking with Tyr181 and Phe89. EPR spectroscopy after peroxide activation of the pre-treated LiPs showed protein radicals other than the tyrosine radical found in pristine LiP, which were assigned to a tyrosine-VA adduct radical in VA-LiP and a dihydroxyphenyalanine radical in H2O2-LiP. Both radicals are able to oxidize large low-redox-potential substrates, but H2O2-LiP is unable to oxidize high-redox-potential substrates. Transient-state kinetics showed that the tyrosine-VA adduct strongly promotes (>100-fold) substrate oxidation by compound II, the rate-limiting step in catalysis. The novel activation mechanism is involved in ligninolysis, as demonstrated using lignin model substrates. The present paper is the first report on autocatalytic modification, resulting in functional alteration, among class II peroxidases.

Real-World Health Care Outcomes and Costs Among Patients With Juvenile Idiopathic Arthritis in Spain.

Background: Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. Objective: To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Methods: Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). Results: Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). Conclusion: JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.

The NUPHAC-EU Framework for Nurses' Role in Interprofessional Pharmaceutical Care: Cross-Sectional Evaluation in Europe.

Clear role descriptions promote the quality of interprofessional collaboration. Currently, it is unclear to what extent healthcare professionals consider pharmaceutical care (PC) activities to be nurses' responsibility in order to obtain best care quality. This study aimed to create and evaluate a framework describing potential nursing tasks in PC and to investigate nurses' level of responsibility. A framework of PC tasks and contextual factors was developed based on literature review and previous DeMoPhaC project results. Tasks and context were cross-sectionally evaluated using an online survey in 14 European countries. A total of 923 nurses, 240 physicians and 199 pharmacists responded. The majority would consider nurses responsible for tasks within: medication self-management (86-97%), patient education (85-96%), medication safety (83-95%), monitoring adherence (82-97%), care coordination (82-95%), and drug monitoring (78-96%). The most prevalent level of responsibility was 'with shared responsibility'. Prescription management tasks were considered to be nurses' responsibility by 48-81% of the professionals. All contextual factors were indicated as being relevant for nurses' role in PC by at least 74% of the participants. No task nor contextual factor was removed from the framework after evaluation. This framework can be used to enable healthcare professionals to openly discuss allocation of specific (shared) responsibilities and tasks.

Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease.

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid and a bioactive lipid that is synthesized by the enzyme autotaxin (ATX). The ATX-LPA axis has been associated with cognitive dysfunction and inflammatory diseases, mainly in a range of nonalcoholic liver diseases. Recently, preclinical and clinical evidence has suggested a role of LPA signaling in alcohol use disorder (AUD) and AUD-related cognitive function. However, the ATX-LPA axis has not been sufficiently investigated in alcoholic liver diseases. An exploratory study was conducted in 136 participants, 66 abstinent patients with AUD seeking treatment for alcohol (alcohol group), and 70 healthy control subjects (control group). The alcohol group was divided according to the presence of comorbid liver diseases (i.e., fatty liver/steatosis, alcoholic steatohepatitis, or cirrhosis). All participants were clinically evaluated, and plasma concentrations of total LPA and ATX were measured using enzyme-linked immunosorbent assays. Data were primarily analyzed using analysis of covariance (ANCOVA) while controlling for age, body mass index, and sex. Logistic regression models were created to assess the association of the ATX-LPA axis and AUD or liver disease. LPA and ATX were log10-transformed to fit the assumptions of parametric testing.The main results were as follows: total LPA and ATX concentrations were dysregulated in the alcohol group, and patients with AUD had significantly lower LPA (F(1,131) = 10.677, p = 0.001) and higher ATX (F(1,131) = 8.327, p = 0.005) concentrations than control subjects; patients with AUD and liver disease had significantly higher ATX concentrations (post hoc test, p < 0.05) than patients with AUD but not liver disease; significant correlations between AUD-related variables and concentrations of LPA and ATX were only found in the non-liver disease subgroup (the duration of alcohol abstinence with LPA and ATX (r = +0.33, p < 0.05); and the severity of AUD with ATX (rho = -0.33, p < 0.05)); and a logistic regression model with LPA, ATX, and AUD-related variables showed an excellent discriminative power (area under the curve (AUC) = 0.915, p < 0.001) for distinguishing patients with AUD and comorbid liver disease. In conclusion, our data show that the ATX-LPA axis is dysregulated in AUD and suggest this lipid signaling, in combination with relevant AUD-related variables, as a reliable biomarker of alcoholic liver diseases.

Deepening the knowledge on the removal of Cr(VI) by L. minuta Kunth: removal efficiency and mechanisms, lipid signaling pathways, antioxidant response, and toxic effects.

Lemna minuta Kunth was used to remove Cr(VI) from aqueous solutions, and some of the mechanisms involved in this process were analyzed. In addition, the cellular signaling mediated by phospholipase D activity as well as antioxidant responses was also evaluated during the process. Cr(VI) removal efficiencies were 40% for 0.5 mg/L, after 24 h, and up to 18% at metal concentrations as high as 5 mg/L. Removal mechanisms displayed by these macrophytes include bioadsorption to cell surfaces and, to a greater extent, Cr internalization and bioaccumulation within cells. Inside of them, Cr(VI) was reduced to Cr(III), a less toxic form of this metal. At the first hours of Cr(VI) exposure, plants were able to sense chromium, activating membrane signal transduction pathways mediated by phospholipase D and phosphatidic acid. Moreover, an increase in the activity of antioxidant enzymes such as superoxide dismutases and peroxidases was observed in the same time. These and other components of the antioxidant defense system would help to reduce the stress generated by the metal. The toxicity of the products formed during the removal process was assessed through Lactuca sativa L. and AMPHIAGU test. It was evidenced that Cr(VI) phytoremediation process by L. minuta plants did not generate acute toxicity neither for L. sativa seeds nor for embryos of Rhinella arenarum (Hensel, 1876). Thus, L. minuta plants could be considered as valuable species for the treatment of waters contaminated with Cr(VI).

Labor outcomes with epidural analgesia: an observational before-and-after cohort study comparing continuous infusion versus programmed intermittent bolus plus patient-controlled analgesia.

BACKGROUND: Scientific evidence shows that programmed intermittent epidural bolus (PIEB) for labor analgesia achieves good obstetric outcomes. After implementing our institutional standard for epidural analgesia, we compared PIEB + patient-controlled epidural analgesia (PCEA) versus continuous epidural infusion (CEI). METHODS: In an observational cohort study, we compared CEI with 0.2% ropivacaine + 100-µg fentanyl initial bolus versus PIEB+PCEA with 0.1% ropivacaine + 2 µg mL-1 fentanyl in primiparous women. The primary outcome was mode of delivery. Secondary outcomes were duration of the second stage of labor and total ropivacaine and fentanyl doses. Other outcomes, in the PIEB+PCEA group only, were motor block, use of PCEA and rescue bolus, maternal mobility and maternal satisfaction. Univariate statistical analysis was performed using the χ2 Test, analysis of variance or nonparametric Kruskal-Wallis Test. Multivariate analysis was performed using multiple logistic regression analysis. RESULTS: The study included 221 patients (CEI 116; PIEB+PCEA 105). Multiple logistic regression showed that the PIEB+PCEA group had significantly fewer caesarean sections (CEI [14%] vs. PIEB+PCEA [5%], P=0.015) and instrumental deliveries, after correcting for confounders (OR=0.49; 95% CI: 0.27-0.89). The second stage of labor did not significantly differ between groups. Total ropivacaine dose was significantly lower with PIEB+PCEA. There was no relationship between mild motor block and increased use of PCEA in the PIEB+PCEA group. Mode of delivery and duration of the second stage of labor were not influenced by motor block either. Maternal satisfaction was high. CONCLUSIONS: PIEB+PCEA offers obstetric and analgesic advantages over CEI in daily clinical practice.

Efficacy of intravitreal bevacizumab to treat retinal angiomatous proliferation stage II and III.

PURPOSE: To evaluate the efficacy of intravitreal bevacizumab to treat retinal angiomatous proliferation (RAP) stages II and III. METHODS: A retrospective, interventional, nonrandomized multicentric study was performed. The files, optical coherence tomography (OCT) scans, indocyanine green, and fluorescein angiograms of patients with RAP stages II and III who had been treated by intravitreal bevacizumab were retrospectively examined. Final visual acuity, number of injections, and appearance of adverse events were considered as main outcome indicators. RESULTS: Twenty-six eyes from 24 patients (9 male and 15 female) were treated by intravitreal bevacizumab. Fourteen eyes presented RAP stage II and 12 eyes presented RAP stage III. Mean age was 76+/-9 and 79+/-6 years, respectively. Mean initial best-corrected visual acuity (BCVA) was logMAR 0.60+/-0.24 and 1.13+/-0.37, respectively. Mean BCVA was 0.62+/-0.26 and 1.06+/-0.37, respectively, at 6 months (p=0.96 and 0.10, respectively, Student t test for paired data) and 0.63+/-0.26 and 1.04+/-0.37, respectively, at 12 months (p=0.82 and p=0.06, respectively, Student t test for paired data). The average number of injections during the first year was 3.4 and 3.2, respectively. CONCLUSIONS: Intravitreal bevacizumab may stabilize visual acuity during the first year in RAP lesion stage II and III. Visual prognosis seems to be better in RAP II lesions.

Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

BACKGROUND: The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. METHODS: The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). RESULTS: Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent unemployment, and percent of people with less than a high school degree) were less likely to report current ART use (OR: 0.85, 95% CI: 0.72-1.00, p = .05). Among current ART users, living in more disadvantaged areas was associated with greater likelihood of having used ART for ≥6 months. Participants living in counties with greater HIV prevalence among 13-24 year olds were more likely to report current ART use (OR: 1.32, 95% CI: 1.05-1.65, p = .02), ≥6 months ART use (OR: 1.32, 95% CI: 1.05-1.65, p = .02), and to be virally suppressed (OR: 1.50, 95% CI: 1.20-1.87, p = .001); however, youth in these areas were also more likely to report missed medical appointments (OR: 1.32, 95% CI: 1.07-1.63, p = .008). CONCLUSIONS: The findings underscore the multi-level and structural factors associated with ART use, missed HIV care appointments, and viral suppression for adolescents and young adults in the United States. Consideration of these factors is strongly recommended in future intervention, clinical practice, and policy research that seek to understand the contextual influences on individuals' health behaviors.

Essential requirement of reduced glutathione (GSH) for the anti-oxidant effect of the flavonoid quercetin.

We have analyzed the anti- or pro-oxidant effects of the flavonoid quercetin (QU) by evaluating, in U937 cell line, hydrogen peroxide (H(2)O(2)), superoxide anion reduced glutathione (GSH) content, mitochondrial membrane potential, DNA content, phosphatidylserine exposure on the outer face of the plasma membrane and cell viability. Polychromatic flow cytometry was used to evaluate in the same cells several functional parameters. For short periods of treatment QU exerted an anti-oxidant effect (decrease in H(2)O(2) levels), whereas for long periods it showed a pro-oxidant activity (increase in ). In these conditions, GSH content was reduced, and this correlated with a lack of anti-oxidant activity of QU, which in turn could be correlated with proapoptotic activity of this molecule. Thus, QU can exert different effects (anti-/prooxidant) depending on exposure times and oxidative balance, and in particular on stores of GSH.

Digital retinal images and teleophthalmology for detecting and grading diabetic retinopathy.

OBJECTIVE: Detecting and grading of diabetic retinopathy (DR) by means of digital retinal images sent via the Internet. RESEARCH DESIGN AND METHODS: Four nonstereoscopic digital retinal images (45 degrees field each) of 126 eye fundus images from 70 diabetic patients were obtained with a nonmydriatic camera at two peripheral units. The images were sent via the Internet using a web-based system to a reference center, where they were diagnosed and graded by one ophthalmologist. These results were compared with those obtained by two other ophthalmologists, one at each peripheral unit, after direct examination of the patients. A modified severity scale of Airlie House was used for grading DR in all cases. Agreement between observers was assessed using unweighted kappa for categorical data and the intraclass correlation coefficient (ICC) for continuous data. RESULTS: Presence of DR was detected in 69 eyes (55%). All eyes with DR (69 of 69, 100%) were correctly identified (kappa = 1) by inspecting the digital images. In 118 eyes (118 of 126, 94%), 57 with no DR and 61 with DR, there was an agreement between the gradation made after the direct examination and the gradation made after the inspection of the images (ICC = 0.92). In eight eyes with DR (8 of 126, 6%), there was disagreement in the grading made with both techniques. CONCLUSIONS: Inspection of digital retinal images sent via the Internet allowed diagnosis and grading of DR. The presence or absence of DR was correctly assessed by inspection of the images in all instances. We also found agreement, in most cases, between retinopathy gradation made from the images and the gradation made by direct examination of the eyes. These findings suggest that this technique is suitable for screening procedures.

Absceso tibial causado por histoplasma capsulatum / Tibial abscess caused by histoplasma capsulatum

La histoplasmosis diseminada es la forma más seria de enfermedad causada por el hongo Histoplasma capsulatum. La histoplasmosis fue descripta por primera vez por Darling en 1906 y es endémica en ciertas áreas de las regiones Central y Sudoeste de Estados Unidos y en la mayoría de los países de Latinoamérica, incluyendo la región de la Pampa húmeda y la Mesopotamia en Argentina, pero en otros continentes tiene una distribuición regional limitada. Los pulmones están implicados en el 90 porciento de los casos, pero H.capsulatum puede involucrar hueso y tejidos blandos. Las lesiones óseas sin otro signo de infección son raras y a menudo mal diagnosticadas como cáncer. Se irforma aquí un caso de histoplasmosis diseminada en un hombre con mielodisplasia quien presentó un absceso tibial izquierdo, sin evidencia clínica pulmonar. El paciente fue tratado con itraconazol en forma exitosa.

Bacteremia por Achromobacter xylosoxidans en un paciente con neumonía adquirida en la comunidad / Achromobacter xylosoxidans bacteremia in a patient with community-acquired pneumonia

La bacteriemia causada por Achromobacter xylosoxidans es rara y hay poca información con repecto a su tratamiento. La mayoría de los pacientes que han desarrollado bacteriemia por Achromobacter han presentado causas predisponentes a la infección. Se informa aquí un caso de bacteriemia y neumonía adquirida en la comunidad en un paciente previamente sano. Achromobacter es usualmente resistente a amplicilina, cefalosporinas de primera, segunda y tercera generación, aminoglucósidos y quinolomas. Piperacilina sola o en combinación con tazobactama, impenem y trimetoprima-sulfametozaxol inhiben la mayoría de los aislamientos.