CXCR4(+)-targeted protein nanoparticles produced in the food-grade bacterium Lactococcus lactis

Lactococcus lactis is a Gram-positive (endotoxin-free) food-grade bacteria exploited as alternative to Escherichia coli for recombinant protein production. We have explored here for the first time the ability of this platform as producer of complex, self-assembling protein materials. Materials & methods: Biophysical properties, cell penetrability and in vivo biodistribution upon systemic administration of tumor-targeted protein nanoparticles produced in L. lactis have been compared with the equivalent material produced in E. coli. Results: Protein nanoparticles have been efficiently produced in L. lactis, showing the desired size, internalization properties and biodistribution. Conclusion: In vitro and in vivo data confirm the potential and robustness of the production platform, pointing out L. lactis as a fascinating cell factory for the biofabrication of protein materials intended for therapeutic applications.Award-winningPostprint (published version

Factores desencadenantes de ingresos hospitalarios de pacientes por insuficiencia cardíaca

Introduction: Heart failure is a serious public health problem and causes high rates of hospital admissions and readmissions, especially in patients over 60 years of age. Admissions can usually be avoided if the factors that cause them are identified. Objective: The objective of this study was, therefore, to identify associated factors influencing hospital admissions of patients with heart failure. Methodology: is a descriptive qualitative study by a systematic review of scientific articles that address the relationship between the causes and patients admitted with a diagnosis of heart failure in hospital centers, for which an exhaustive and coherent review and interpretation of scientific publications and meta-analyses was carried out. Results: From this review, 10 relevant studies that met the research objective were selected. The most frequent comorbidities were diabetes mellitus (40% to 50% of patients), hypertension (60%-80% of patients), dyslipidemia (30% to 50% of patients) and atrial fibrillation (40% to 50% of patients), and to a lesser extent obesity, anemia and smoking. Conclusions: The admissions and readmissions of patients with heart failure are mainly related to comorbidities and derived factors, which implies a higher risk of readmission, so it is necessary to identify and register them in order to propose prevention strategiesIntroducción: La insuficiencia cardíaca es un grave problema de salud pública provoca altas tasas de ingresos y reingresos hospitalarios en especial en pacientes mayores de 60 años. Generalmente los ingresos pueden evitarse si se identifican los factores que los provocan. Objetivo: Identificar los factores asociados que influyen en los ingresos hospitalarios de pacientes con insuficiencia cardíaca. Metodología: es un estudio cualitativo descriptivo mediante una revisión sistemática de artículos científicos que abordan la relación entre las causas y los pacientes ingresados con diagnóstico de insuficiencia cardíaca en los centros hospitalarios, para lo cual se realizó una revisión e interpretación exhaustiva y coherente de las publicaciones científicas y los metaanálisis. Resultados: De esta revisión, se seleccionaron 10 estudios relevantes que cumplían el objetivo de la investigación. Las comorbilidades más frecuentes fueron la diabetes mellitus (40% a 50% de pacientes), la hipertensión (60%-80% de pacientes) , la dislipidemia (30% a 50% de pacientes)  y la fibrilación auricular (40% a 50% de pacientes), y en menor medida la obesidad, la anemia y el tabaquismo. Conclusiones: los ingresos y reingresos de pacientes con insuficiencia se vinculan principalmente a comorbilidades y a factores derivados, lo cual implica un mayor riesgo  de reingreso, por lo cual es necesario la identificación y registro para plantear estrategias de prevención

Reevaluation of the Application Method and Efficacy of Propiconazole in Controlling Laurel Wilt in Avocado Orchards in South Florida

Propiconazole has fungistatic and fungicidal properties against Harringtonia lauricola, the causal agent of laurel wilt disease. Propiconazole injections are used by Florida, USA, farmers as a prophylactic method to manage the disease in avocado (Persea americana) trees, but its efficacy has remained questionable for more than a decade due to documented restricted mobility within the tree vascular system. This study was conducted to evaluate the absorption of propiconazole when using soil drenching as an alternative application method, assess the efficacy of propiconazole in controlling disease development when drenched or injected, and its synergistic effect on common cultural management practices used by the local farmers, such as branch removal and trunk cutting (“stumping”). To determine if propiconazole soil-drenching can provide better xylem coverage, potted and mature orchard trees were treated with different concentrations and artificially inoculated with the pathogen. Propiconazole translocation from the roots to above-the-ground tissue was confirmed in potted and orchard trees, but the concentrations in orchard trees were below the fungicidal threshold (1 ppm). Although none of the potted trees developed laurel wilt symptoms, all inoculated branches of the orchard trees did. Furthermore, noninoculated branches in more than 80% of the inoculated and propiconazole-treated orchard trees developed symptoms, even though the inoculated branch was cut at the early stages of disease development. To elucidate if propiconazole injections effectively control the disease, trees from a commercial orchard that were injected five times were challenged by artificial inoculation. Propiconazole concentration in trees was highly variable (ranging from < 0.01 to 294 ppm), but even in trees with a high concentration of propiconazole, inoculated and noninoculated branches developed symptoms. Even though drenched and injected trees were “stumped” soon after symptoms appeared in the noninoculated branches (4 to 5 months after inoculation), all of the stumps in the drenched plot and 80% of the injected trees, showed internal symptoms 5 and 4 months after the cut, respectively. Results demonstrate that the soil-drenching of propiconazole is an ineffective application method in orchard trees, and that the conventional injection does not prevent disease development after artificial inoculation. Moreover, because propiconazole does not prevent the movement of the pathogen to the trunk, the “stumping” of infected trees to reduce the disease in the orchard is an inadequate practice. This study highlights the critical need for other active ingredients with lower fungicidal thresholds, longer half-life, and higher xylem mobility

Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented the expansion of the perigonadal depot while at the same time exacerbating inflammation. PPARγ2KO pregnant mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential to promote healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness: BFU2012-33594 and BFU2013-47384-R to GMG; SAF2015- 64287-R to M. Ricote; and SAF2014-56671-R to MPR; predoctoral fellowship BES-2010- 038107 to YV; and grants S2010/BMD-2423 from the Community of Madrid to MPR and GMG. The authors thank Saverio Cinti for his helpful comments with histological samples, Antonio Vidal-Puig for his help in discussion and Lucia Torres for technical assistance.S

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

BackgroundRecurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population.Methods/designIn this single-blind randomized controlled trial, 516 adults (≥40&nbsp;years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90&nbsp;days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP &lt;130&nbsp;mmHg) at 1&nbsp;year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care.DiscussionIf this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings.Trial registrationClinicalTrials.gov Identifier NCT01763203

Methylthioadenosine reverses brain autoimmune disease

OBJECTIVE: To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis. METHODS: We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-kappaB modulation by Western blot. RESULTS: We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha) degradation and in the impaired activation transcription factor nuclear factor-kappaB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10). INTERPRETATION: MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases

Cadaveric and three-dimensional computed tomography study of the morphology of the scapula with reference to reversed shoulder prosthesis

<p>Abstract</p> <p>Purpose</p> <p>The purpose of this study is to analyze the morphology of the scapula with reference to the glenoid component implantation in reversed shoulder prosthesis, in order to improve primary fixation of the component.</p> <p>Methods</p> <p>Seventy-three 3-dimensional computed tomography of the scapula and 108 scapular dry specimens were analyzed to determine the anterior and posterior length of the glenoid neck, the angle between the glenoid surface and the upper posterior column of the scapula and the angle between the major craneo-caudal glenoid axis and the base of the coracoid process and the upper posterior column.</p> <p>Results</p> <p>The anterior and posterior length of glenoid neck was classified into two groups named "short-neck" and "long-neck" with significant differences between them. The angle between the glenoid surface and the upper posterior column of the scapula was also classified into two different types: type I (mean 50°–52°) and type II (mean 62,50°–64°), with significant differences between them (p < 0,001). The angle between the major craneo-caudal glenoid axis and the base of the coracoid process averaged 18,25° while the angle with the upper posterior column of the scapula averaged 8°.</p> <p>Conclusion</p> <p>Scapular morphological variability advices for individual adjustments of glenoid component implantation in reversed total shoulder prosthesis. Three-dimensional computed tomography of the scapula constitutes an important tool when planning reversed prostheses implantation.</p

Functionalization of breast implants by cyclodextrin in-situ polymerization: a local drug delivery system for augmentation mammaplasty

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: β-CD/citric acid and 2-hydroxypropyl-β-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa, revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants