Farmworker Mobility and COVID-19 Vaccination Strategies: Yuma County, Arizona, 2021.

Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

Safety and feasibility of transradial access for percutaneous coronary intervention in chronic total occlusions.

INTRODUCTION AND OBJECTIVES: Transfemoral access is the most frequently used vascular approach in chronic total occlusion percutaneous coronary interventions (CTO-PCI). The aim of this study was to evaluate the safety and feasibility of a transradial access CTO-PCI program and its impact on angiographic and clinical results and length of hospital stay. METHODS: Retrospective multicenter cohort study including 2550 consecutive CTO-PCI procedures included in a multicenter registry with accurate information on vascular access. A total of 896 procedures were performed as radial-only access while 1654 were performed through at least 1 femoral puncture. Clinical and angiographic data were collected. RESULTS: The mean age was 66.3± 11.4 years. The mean Japan-chronic total occlusion score (2.7±0.3) was similar in the 2 groups. Successful revascularization was achieved in 2009 (79.6%) cases, 78.2% and 82.1% in the femoral and radial access cohorts, respectively (P=.002). Periprocedural in-hospital complications were observed in 5.1% and 2.3% (P=.02), with fewer access site-dependant vascular complications in the transradial cohort (2.3% vs 0.2%; P=.009). The mean length of hospital stay was significantly shorter in the transradial access group (0.89±1.4 vs 2.2±3.2 days, P<.001). CONCLUSIONS: A transradial program for CTO-PCI is safe and effective in most CTO lesions. The transradial strategy has fewer vascular complications and shorter length of hospital stay without compromising the success rate.

Can an ultrathin strut stent design and a polymer free, proendothelializing probucol matrix coating improve early strut healing? The FRIENDLY-OCT trial. An intra-patient randomized study with OCT, evaluating early strut coverage of a novel probucol coated polymer-free and ultra-thin strut sirolimus-eluting stent compared to a biodegradable polymer sirolimus-eluting stent.

BACKGROUND: incomplete strut coverage determines the risk of stent thrombosis in the first months after stent implantation. AIMS: To evaluate the potential better early healing of a novel probucol coated polymer free ultra-thin strut sirolimus eluting stent (PF-SES). [Clinical trial unique identifier: NCT02785237]. METHODS: Patients with two (angiographically similar) lesions with clinical indication for PCI were enrolled. The investigated stent was compared to a thin strut, bioresorbable polymer, sirolimus eluting stent (BP-SES). Every patient received both stents, one in each lesion, assigned in a randomized sequence. OCT was systematically performed at 3 months. Primary end point was the difference in the proportion of covered struts at 3 months (defined as ≥20 µm of tissue coverage). Secondary end points included differences in percentage of uncovered struts (0 µm coverage), mean strut coverage thickness, and malapposed struts' coverage proportion. Major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 12 months were also evaluated. RESULTS: 70 patients were included. At 3 months, a consistent and significantly higher strut coverage rate (≥20 µm) was observed in PF-SES as compared to BP-SES, both for well apposed (87.3% versus 79.1%, p < 0.001) and malapposed struts (50.4% vs 37.8%, p 0.00). Uncoverage rate (0 µm) was also significantly lower for the PF-SES (3.1% vs 5.3%, p < 0.001). There were no differences in clinical endpoints. CONCLUSION: The probucol coated non-polymeric ultra-thin strut sirolimus eluting stent showed a significantly better early strut coverage at 3 months.

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.

AIM: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. METHODS AND RESULTS: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. CONCLUSION: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03321032.

Clinical Outcomes Following Urgent vs. Elective Percutaneous Mitral Valve Repair.

AIM: To examine procedural and clinical outcomes among patients undergoing percutaneous mitral valve repair (PMVR) within an admission for acute-decompensated heart failure (ADHF). METHODS AND RESULTS: Prospective registry of all consecutive patients with symptomatic mitral regurgitation (MR) grade 3+ or 4+ who underwent PMVR our centre and classified in 2 groups: elective group and urgent PMVR group (within the index admission for ADHF). Echocardiographic, procedural and clinical outcomes were compared between groups. 85 patients (median age 77.0 [67.8-83.4] years, 64.7% male) were treated within the recruitment period. Among them, 17 (20%) underwent urgent MitraClip®. Urgent PMVR were at a higher risk for conventional surgery (p = 0.002) and had worse estimated prognosis according to HF risk scores (p < 0.001). Overall technical success was 100%, without differences between groups. At 30 days, no differences were found in mortality, MR reduction and in NYHA functional improvement between groups. Cumulative estimated survival free from all-cause death was 92.9% (82.4% vs. 95.6%), 89.4% (82.4% vs. 91.1%), 76.3% (82.4 vs. 74.9%) at 6 months, 1-year and 2-years, respectively, with no significant differences between urgent or elective PMVR (p = 0.769). CONCLUSION: MitraClip® implantation can be considered as an urgent therapy during admission for ADHF.

Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies.

New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.

Early Downregulation of p75NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington's Disease Mice.

Deficits in striatal brain-derived neurotrophic factor (BDNF) delivery and/or BDNF/tropomyosin receptor kinase B (TrkB) signaling may contribute to neurotrophic support reduction and selective early degeneration of striatal medium spiny neurons in Huntington's disease (HD). Furthermore, we and others have demonstrated that TrkB/p75NTR imbalance in vitro increases the vulnerability of striatal neurons to excitotoxic insults and induces corticostriatal synaptic alterations. We have now expanded these studies by analyzing the consequences of BDNF/TrkB/p75NTR imbalance in the onset of motor behavior and striatal neuropathology in HD mice. Our findings demonstrate for the first time that the onset of motor coordination abnormalities, in a full-length knock-in HD mouse model (KI), correlates with the reduction of BDNF and TrkB levels, along with an increase in p75NTR expression. Genetic normalization of p75NTR expression in KI mutant mice delayed the onset of motor deficits and striatal neuropathology, as shown by restored levels of striatal-enriched proteins and dendritic spine density and reduced huntingtin aggregation. We found that the BDNF/TrkB/p75NTR imbalance led to abnormal BDNF signaling, manifested as a diminished activation of TrkB-phospholipase C-gamma pathway but upregulation of c-Jun kinase pathway. Moreover, we confirmed the contribution of the proper balance of BDNF/TrkB/p75NTR on HD pathology by a pharmacological approach using fingolimod. We observed that chronic infusion of fingolimod normalizes p75NTR levels, which is likely to improve motor coordination and striatal neuropathology in HD transgenic mice. We conclude that downregulation of p75NTR expression can delay disease progression suggesting that therapeutic approaches aimed to restore the balance between BDNF, TrkB, and p75NTR could be promising to prevent motor deficits in HD.

No Differences in Levels of Circulating Progenitor Endothelial Cells or Circulating Endothelial Cells Among Patients Treated With Ticagrelor Compared With Clopidogrel During Non- ST -Segment-Elevation Myocardial Infarction.

Background Ticagrelor use during acute coronary syndromes demonstrated a decrease in all-cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non-platelet-derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non-ST-segment-elevation myocardial infarction. Methods and Results In this multicenter, randomized study ( NCT 02244710), patients were considered for inclusion after non-ST-segment-elevation myocardial infarction whenever they were P2Y12-inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28-64), 50 (33-63), and 38 (23-62) cells/mL, respectively, for clopidogrel and 38 (29-60), 45 (32-85), and 35 (24-71) cells/mL, respectively, for ticagrelor ( P=0.6). Endothelial progenitor cell levels were 29 (15-47), 27 (15-33), and 18 (10-25) cells/mL, respectively, for clopidogrel and 20 (11-33), 22 (12-32), and 18 (11-29) cells/mL, respectively, for ticagrelor ( P=0.9). No differences in intraindividual changes were found. Conclusions Patients treated with ticagrelor during non-ST-segment-elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02244710.

Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels.

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.SIGNIFICANCE STATEMENT BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD.

Seguridad y eficacia de nuevos modelos de stents liberadores de sirolimus con polímero biodegradable en el modelo preclínico / Safety and efficacy of new biodegradable polymer-based sirolimus-eluting stents in a preclinical model

Introducción y objetivos: Los nuevos stents farmacoactivos (SFA), diseñados para solventar las limitaciones de los existentes, han de someterse inicialmente al análisis preclínico. El objetivo es analizar la eficacia y la seguridad de nuevos SFA con polímero biodegradable en comparación con stents convencionales (SC) y SFA comercializados en el modelo de arteria coronaria sana porcina. Métodos: Se implantaron aleatoriamente 101 stents (SC y stents liberadores de sirolimus con polímero biodegradable: 3 formulaciones test [BD1, BD2 y BD3], Orsiro, Biomime y Biomatrix) en las arterias coronarias de 34 cerdos domésticos. Se completó estudio angiográfico e histomorfométrico al mes (n = 83) y a los 3 meses (n = 18). Resultados: Los stents se implantaron en proporción stent/arteria de 1,31 ± 0,21, sin diferencias entre grupos. Al mes, los nuevos stents (BD1, BD2 y BD3) mostraron menos pérdida tardía y reestenosis angiográfica, así como menor área neointimal y reestenosis histológica (p < 0,0005) que los SC. No se observaron diferencias significativas entre los nuevos stents y los SC en endotelización, daño vascular o inflamación; solo se encontró mayor persistencia de fibrina en los nuevos (p = 0,0006). A los 3 meses, todas estas diferencias desaparecieron, excepto una menor área neointimal con el nuevo stent BD1 (p = 0,027). No hubo diferencias en ningún parámetro al mes ni a los 3 meses entre los nuevos stents y los comercializados. Conclusiones: En este modelo preclínico, los nuevos SFA con polímero biodegradable estudiados presentan menos reestenosis que los SC, sin diferencias significativas en seguridad y eficacia respecto a SFA comercializados (AU)

Introduction and objectives New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. Methods: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. Results: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. Conclusions: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES (AU)

Decreasing incidence and mortality among hospitalized patients suffering a ventilator-associated pneumonia: Analysis of the Spanish national hospital discharge database from 2010 to 2014.

The aim of this study was to describe trends in the incidence and outcomes of ventilator-associated pneumonia (VAP) among hospitalized patients in Spain (2010-2014).This is a retrospective study using the Spanish national hospital discharge database from year 2010 to 2014. We selected all hospital admissions that had an ICD-9-CM code: 997.31 for VAP in any diagnosis position. We analyzed incidence, sociodemographic and clinical characteristics, procedures, pathogen isolations, and hospital outcomes.We identified 9336 admissions with patients suffering a VAP. Incidence rates of VAP decreased significantly over time (from 41.7 cases/100,000 inhabitants in 2010 to 40.55 in 2014). The mean Charlson comorbidity index (CCI) was 1.08 ±â€Š0.98 and it did not change significantly during the study period. The most frequent causative agent was Pseudomonas and there were not significant differences in the isolation of this microorganism over time. Time trend analyses showed a significant decrease in in-hospital mortality (IHM), from 35.74% in 2010 to 32.81% in 2014. Factor associated with higher IHM included male sex, older age, higher CCI, vein or artery occlusion, pulmonary disease, cancer, undergone surgery, emergency room admission, and readmission.This study shows that the incidence of VAP among hospitalized patients has decreased in Spain from 2010 to 2014. The IHM has also decreased over the study period. Further investigations are needed to improve the prevention and control of VAP.

Effect of Type 2 Diabetes on In-Hospital Postoperative Complications and Mortality After Primary Total Hip and Knee Arthroplasty.

BACKGROUND: We aimed to compare in-hospital postoperative complications (IHPC) and in-hospital mortality between patients with and without type 2 diabetes mellitus (T2DM) undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: We analyzed data from the Spanish National Hospital Discharge Database, 2010-2014. We selected patients who had undergone THA (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 81.51) and TKA (code 81.54). Diabetic patients with THA and TKA were matched by year, age, sex, and the comorbidities included in the modified Elixhauser Comorbidity Index with a nondiabetic patient. RESULTS: We identified 115,234 THA patients and 195,355 TKA patients, 12.4% and 15.6% with T2DM, respectively. We matched 10,777 and 26,640 pairs of diabetic and nondiabetic patients. In T2DM patients who had undergone THA, the incidence of urinary tract infection was higher than in nondiabetic patients (1.50% vs 1.09%, P = .007), as was that of "any IHPC" (9.68% vs 8.98%, P = .038). In patients who had undergone TKA, the incidence of postoperative anemia was significantly higher in diabetic patients (4.90% vs 4.53, P = .040), as was that of urinary tract infection (0.80% vs 0.53%, P = .025) and "any IHPC" (7.30% vs 6.76%, P = .014). In both procedures, mean length of hospital stay was significantly higher in diabetic patients; for TKA, in-hospital mortality was higher in diabetic patients (0.09% vs 0.02%, P = .002). Previous comorbidities, age, and obesity predict a higher incidence of IHPC among diabetic patients. CONCLUSIONS: This study confirms the higher risk of IHPC among T2DM patients after joint arthroplasty. IHPC may result in a higher risk of mortality in patients undergoing TKA.

Safety and Efficacy of New Biodegradable Polymer-based Sirolimus-Eluting Stents in a Preclinical Model.

INTRODUCTION AND OBJECTIVES: New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. METHODS: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. RESULTS: The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. CONCLUSIONS: In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.

Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3).

Ubiquitination of the TrkA neurotrophin receptor in response to NGF is critical in the regulation of TrkA activation and functions. TrkA is ubiquitinated, among other E3 ubiquitin ligases, by Nedd4-2. To understand mechanistically how TrkA ubiquitination is regulated, we performed a siRNA screening to identify deubiquitinating enzymes and found that USP36 acts as an important regulator of TrkA activation kinetics and ubiquitination. However, USP36 action on TrkA was indirect because it does not deubiquitinate TrkA. Instead, USP36 binds to Nedd4-2 and regulates the association of TrkA and Nedd4-2. In addition, depletion of USP36 increases TrkA·Nedd4-2 complex formation, whereas USP36 expression disrupts the complex, resulting in an enhancement or impairment of Nedd4-2-dependent TrkA ubiquitination, respectively. Moreover, USP36 depletion leads to enhanced total and surface TrkA expression that results in increased NGF-mediated TrkA activation and signaling that augments PC12 cell differentiation. USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation. Our results demonstrate that USP36 binds to and regulates the actions of Nedd4-2 over different substrates affecting their expression and functions.

El trastorno por déficit de atención con/sin hiperactividad en España: crónica de los últimos 15 años / Attention deficit hyperactivity disorder in Spain: chronicle of the last 15 years

El trastorno por déficit de atención con/sin hiperactividad tiene una gran relevancia en la infancia y puede perdurar en la adolescencia y en la edad adulta. Cada vez se conoce más y mejor en España esta afección, y desde hace más de una década su diagnóstico ha aumentado, así como los medios para su asistencia, tanto sanitaria como educativa. Tras hacer una breve historia de esta enfermedad, en esta revisión se actualizan los datos de prevalencia y del diagnóstico precoz, así como de los tratamientos disponibles actualmente. Asimismo, se comentan algunos aspectos de la realidad asistencial y cómo se está planificando el futuro (AU)

Attention deficit hyperactivity disorder is getting increasingly better known in Spain. It is of great relevance in children and may remain in adolescence and in adulthood. For over a decade its diagnosis has been going up, as well as the means for its assistance, both health-related and educational. After obtaining a short medical history we updated the statistics of prevalence and early diagnosis, as well as the drugs available to date. Finally there is a short remark on some aspects of today’s assistance and how the future is being planned out (AU)

Binational Dengue Outbreak Along the United States-Mexico Border - Yuma County, Arizona, and Sonora, Mexico, 2014.

Dengue is an acute febrile illness caused by any of four dengue virus types (DENV-1-4). DENVs are transmitted by mosquitos of the genus Aedes (1) and are endemic throughout the tropics (2). In 2010, an estimated 390 million DENV infections occurred worldwide (2). During 2007-2013, a total of three to 10 dengue cases were reported annually in Arizona and all were travel-associated. During September-December 2014, coincident with a dengue outbreak in Sonora, Mexico, 93 travel-associated dengue cases were reported in Arizona residents; 70 (75%) cases were among residents of Yuma County, which borders San Luis Río Colorado, Sonora, Mexico. San Luis Río Colorado reported its first case of locally acquired dengue in September 2014. To investigate the temporal relationship of the dengue outbreaks in Yuma County and San Luis Río Colorado and compare patient characteristics and signs and symptoms, passive surveillance data from both locations were analyzed. In addition, household-based cluster investigations were conducted near the residences of reported dengue cases in Yuma County to identify unreported cases and assess risk for local transmission. Surveillance data identified 52 locally acquired cases (21% hospitalized) in San Luis Río Colorado and 70 travel-associated cases (66% hospitalized) in Yuma County with illness onset during September-December 2014. Among 194 persons who participated in the cluster investigations in Yuma County, 152 (78%) traveled to Mexico at least monthly during the preceding 3 months. Four (2%) of 161 Yuma County residents who provided serum samples for diagnostic testing during cluster investigations had detectable DENV immunoglobulin M (IgM); one reported a recent febrile illness, and all four had traveled to Mexico during the preceding 3 months. Entomologic assessments among 105 households revealed 24 water containers per 100 houses colonized by Ae. aegypti. Frequent travel to Mexico and Ae. aegypti colonization indicate risk for local transmission of DENV in Yuma County. Public health officials in Sonora and Arizona should continue to collaborate on dengue surveillance and educate the public regarding mosquito abatement and avoidance practices. Clinicians evaluating patients from the U.S.-Mexico border region should consider dengue in patients with acute febrile illness and report suspected cases to public health authorities.