Role of hydroxypropyl-β-cyclodextrin on freeze-dried and gamma-irradiated PLGA and PLGA–PEG diblock copolymer nanospheres for ophthalmic flurbiprofen delivery

Poly(D,L-lactide-co-glycolide) and poly(D,L-lactide-co-glycolide) with poly(ethylene glycol) nanospheres (NSs) incorporating flurbiprofen (FB) were freeze-dried with several cryoprotective agents and sterilized by γ-irradiation. Only when 5.0% (w/v) hydroxypropyl-β-cyclodextrin (HPβCD) was used, a complete resuspension by manual shaking and almost identical particle size of the NSs was obtained after freeze-drying. In vitro drug release and ex vivo corneal permeation of NSs with and without HPβCD were evaluated. The presence of HPβCD resulted in a reduction of burst effect, providing a more sustained release of the drug. A significant decrease in the FB transcorneal permeation of NSs containing HPβCD was obtained, related to the slower diffusion of FB observed in the in vitro results. The uptake mechanism of the NSs was examined by confocal microscopy, suggesting that NSs penetrate corneal epithelium through a transcellular pathway. Ocular tolerance was assessed in vitro and in vivo by the Eytex™ and Draize test, respectively. Long-term stability studies revealed that γ-irradiated NSs stored as freeze-dried powders maintained their initial characteristics. Stability studies of the resuspended NSs after 3 months of storage in the aqueous form showed that NSs were stable at 4°C, while formulations stored at 25°C and 40°C increased their initial particle size

Optimization, biopharmaceutical profile and therapeutic efficacy of pioglitazone-loaded PLGA-PEG nanospheres as a novel strategy for ocular inflammatory disorders.

PURPOSE: The main goal of this study was to encapsulate Pioglitazone (PGZ), in biodegradable polymeric nanoparticles as a new strategy for the treatment of ocular inflammatory processes. METHODS: To improve their biopharmaceutical profile for the treatment of ocular inflammatory disorders, nanospheres (NSs) of PGZ were formulated by factorial design with poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). Interactions drug-polymer have been carried out by spectroscopic (X-ray spectroscopy, FTIR) and thermal methods (DSC). The PGZ-NSs were tested for their in vitro release profile, cytotoxicity, and ocular tolerance (HET-CAM® test); ex vivo corneal permeation, and in vivo inflammatory prevention and bioavailability. RESULTS: The optimized system showed a negative surface charge of -13.9 mV, an average particle size (Zav) of around 160 nm, a polydispersity index (PI) below 0.1, and a high encapsulation efficiency (EE) of around 92%. According to the DSC results, the drug was incorporated into the NSs polymeric matrix. The drug release was sustained for up to 14 h. PGZ-NSs up to 10 μg/ml exhibited no retinoblastoma cell toxicity. The ex vivo corneal and scleral permeation profiles of PGZ-NSs showed that retention and permeation through the sclera were higher than through the cornea. Ocular tolerance in vitro and in vivo demonstrated the non-irritant character of the formulation. CONCLUSION: The in vivo anti-inflammatory efficacy of developed PGZ-NSs indicates this colloidal system could constitute a new approach to prevent ocular inflammation. KEYWORDS: PLGA-PEG; drug delivery; nanospheres; ocular anti-inflammatory efficacy; pioglitazon

The effect of refeeding after starvation on the growth of sharpsnout seabream Diplodus puntazzo (Cetti, 1777)

Compensatory growth is rapid growth induced by hyperphagic behaviour after starvation. The present paper studies this phenomenon in sharpsnout seabream Diplodus puntazzo (Cetti, 1777). We used control groups (LC) feeding ad libitum and starvation-refeeding ad libitum groups (AR). AR growth was double that of LC after the refeeding period, and food intake was also higher. Although AR did not reach LC final weight, condition index K was achieved. These results suggest the need to test this hypothesis over longer starvation and refeeding periods which could lead to hyperphagic behavior.El crecimiento compensatorio se define como un crecimiento rápido provocado por un comportamiento hiperfágico después de un periodo de ayuno. El objetivo del trabajo es poner de manifiesto la existencia de estos fenómenos en Diplodus puntazzo (Cetti, 1777). Para ello se mantuvieron lotes de control alimentados a saciedad (LC) y lotes en ayuno y realimentados posteriormente a saciedad (AR). Se comprobó que la tasa de crecimiento se duplicó en el periodo de realimentación para los lotes AR con respecto a los lotes LC, siendo mayor, también, la tasa de alimentación de los lotes AR; sin embargo, estos lotes no alcanzan el peso de los lotes control, aunque sí recuperaron el factor de condición (K). Estos resultados sugieren la necesidad de comprobar este comportamiento para periodos de ayuno más prolongados que pudieran provocar una mayor respuesta hiperfágica.Instituto Español de Oceanografí

STI epidemic re-emergence, socio-epidemiological clusters characterisation and HIV coinfection in Catalonia, Spain, during 2017-2019 : A retrospective population-based cohort study

Objectives To describe the epidemiology of sexually transmitted infections (STIs), identify and characterise socio-epidemiological clusters and determine factors associated with HIV coinfection. Design Retrospective population-based cohort. Setting Catalonia, Spain. Participants 42 283 confirmed syphilis, gonorrhoea, chlamydia and lymphogranuloma venereum cases, among 34 600 individuals, reported to the Catalan HIV/STI Registry in 2017-2019. Primary and secondary outcomes Descriptive analysis of confirmed STI cases and incidence rates. Factors associated with HIV coinfection were determined using logistic regression. We identified and characterized socio-epidemiological STI clusters by Basic Health Area (BHA) using K-means clustering. Results The incidence rate of STIs increased by 91.3% from 128.2 to 248.9 cases per 100 000 population between 2017 and 2019 (p<0.001), primarily driven by increase among women (132%) and individuals below 30 years old (125%). During 2017-2019, 50.1% of STIs were chlamydia and 31.6% gonorrhoea. Reinfections accounted for 10.8% of all cases and 6% of cases affected HIV-positive individuals. Factors associated with the greatest likelihood of HIV coinfection were male sex (adjusted OR (aOR) 23.69; 95% CI 16.67 to 35.13), age 30-39 years (versus <20 years, aOR 18.58; 95% CI 8.56 to 52.13), having 5-7 STI episodes (vs 1 episode, aOR 5.96; 95% CI 4.26 to 8.24) and living in urban areas (aOR 1.32; 95% CI 1.04 to 1.69). Living in the most deprived BHAs (aOR 0.60; 95% CI 0.50 to 0.72) was associated with the least likelihood of HIV coinfection. K-means clustering identified three distinct clusters, showing that young women in rural and more deprived areas were more affected by chlamydia, while men who have sex with men in urban and less deprived areas showed higher rates of STI incidence, multiple STI episodes and HIV coinfection. Conclusions We recommend socio-epidemiological identification and characterisation of STI clusters and factors associated with HIV coinfection to identify at-risk populations at a small health area level to design effective interventions

Gestión de los residuos sanitarios en el ámbito hospitalario. Nivel de conocimiento y valoración global

Los residuos sanitarios representan un peligro potencial para los trabajadores sanitarios. Dado el alto riesgo de infección en los accidentes laborales, la gestión correcta de los residuos sanitarios minimiza el riesgo y mejora las condiciones labora­les y ambientales. OBJETIVOS. Identificar el nivel de conocimiento que tienen los profesionales sanitarios, en relación con la clasificación y ges­tión avanzada de los residuos sanitarios (RS) y valorar de for­ma global la gestión de los mismos. METODOLOGÍA. Estudio descriptivo transversal con 178 partici­pantes (auxiliares, enfermeras, médicos y técnicos de labora­torio), de 3 hospitales de la provincia de Barcelona. Se utilizó un cuestionario de elaboración propia, que anali­zaba las variables laborales, el conocimiento y la valoración global de la gestión de los RS. RESULTADOS. El nivel medio de conocimiento sobre los RS de los auxiliares, las enfermeras, los médicos y los técnicos de laboratorio, en una escala de 1 (valor mínimo) a 15 (valor máximo), es de 10.59, 10.61, 8.92 y 8.39, respectivamente. La valoración global que hacen los auxiliares, las enfermeras, los médicos y los técnicos de laboratorio de la gestión de los RS en una escala de 1 (valor mínimo) y 5 (valor máximo), es de 2.89, 2.93, 2.88, 2.94, respectivamente. C0NCLUSI0NES. Los resultados sugieren que las enfermeras y los auxiliares tienen un nivel de conocimiento aceptable con res­pecto a la gestión correcta de los RS. En cambio, los médicos y técnicos de laboratorio tienen un nivel de conocimiento infe­rior sobre la segregación y eliminación adecuada de los RS. En cuanto a la valoración global, se obtienen valores aceptables, y muy similares, entre las diferentes categorías de profesiona­les estudiadas, en relación con la gestión correcta de los RS en los centros asistenciales donde realizan su actividad laboral

Gestión de los residuos sanitarios en el ámbito hospitalario (2). Percepción de riesgo frente a la gestión

OBJETIVO. Identificar la percepción de riesgo que tienen los profesionales sanitarios, en relación con la clasificación y ges­tión avanzada de los residuos sanitarios (RS). METODOLOGIA. Estudio descriptivo y/o explicativo. El tamaño de la muestra fue de 177 participantes (técnicos auxiliares en cuidados de enfermería, enfermeras, médicos y técnicos de laboratorio) de tres hospitales de la provincia de Barcelona. Se utilizó un cuestionario de elaboración propia, para ana­lizar las variables laborales y de percepción de riesgo para la salud laboral y la seguridad personal, tanto para la población en general como para la salud pública, con preguntas en una escala tipo Likert y preguntas de asociación libre y espontá­nea y de frases incompletas. RESULTADOS. El nivel medio de percepción de riesgo de los téc­nicos auxiliares de cuidados de enfermería, las enfermeras, los médicos y los técnicos de laboratorio, en una escala de 1 (baja percepción) a 5 (alta percepción), es de 3.71, 3.75, 3.83 y 4.03, respectivamente. En referencia a los ítems con respuesta de asociación libre y espontánea, el 44.8 % de profesionales consideran los RS un riesgo biológico, el 29.6 % lo consideran material de desecho, el 22.1 % manifiestan que deben gestionarse correctamente y un 3.5 % los describen como residuos desconocidos. CONCLUSIONES. Los resultados sugieren que todos los profesio­nales de la salud tienen en general una percepción de riesgo alta, siendo los técnicos de laboratorio los que tienen una percepción más alta respecto al riesgo real de la gestión in­adecuada de los RS. El 63.2 % manifiesta que se ha de realizar una gestión adecuada para preservar su salud laboral; el 59 % responde que son un riesgo biológico para la población en general y el 47.8 % que son nocivos para la salud pública. Aunque cabe destacar que solo el 44.8 considera que los RS son tóxicos y peligrosos

Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.

Congenital disorders of glycosylation (CDG) are a heterogeneous and rapidly growing group of diseases caused by abnormal glycosylation of proteins and/or lipids. Mutations in genes involved in the homeostasis of the endoplasmic reticulum (ER), the Golgi apparatus (GA), and the vesicular trafficking from the ER to the ER-Golgi intermediate compartment (ERGIC) have been found to be associated with CDG. Here, we report a patient with defects in both N- and O-glycosylation combined with a delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex. TRAPPIII is implicated in the anterograde transport from the ER to the ERGIC as well as in the vesicle export from the GA. This report expands the spectrum of genetic alterations associated with CDG, providing new insights for the diagnosis and the understanding of the physiopathological mechanisms underlying glycosylation disorders

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

Association between use of enhanced recovery after surgery protocol and postoperative complications in colorectal surgery: the postoperative outcomes within enhanced recovery after surgery protocol (power) study

Importance: enhanced Recovery After Surgery (ERAS) care has been reported to be associated with improvements in outcomes after colorectal surgery compared with traditional care. Objective: to determine the association between ERAS protocols and outcomes in patients undergoing elective colorectal surgery. Design, setting, and participants: the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol (POWER) Study is a multicenter, prospective cohort study of 2084 consecutive adults scheduled for elective colorectal surgery who received or did not receive care in a self-declared ERAS center. Patients were recruited from 80 Spanish centers between September 15 and December 15, 2017. All patients included in this analysis had 1 month of follow-up. Exposures: colorectal surgery and perioperative management were the exposures. Twenty-two individual ERAS items were assessed in all patients, regardless of whether they were included in an established ERAS protocol. Main outcomes and measures: the primary study outcome was moderate to severe postoperative complications within 30 days after surgery. Secondary outcomes included ERAS adherence, mortality, readmissions, reoperation rates, and hospital length of stay. Results: between September 15 and December 15, 2017, 2084 patients were included in the study. Of these, 1286 individuals (61.7%) were men; mean age was 68 years (interquartile range [IQR], 59-77). A total of 879 patients (42.2%) presented with postoperative complications and 566 patients (27.2%) developed moderate to severe complications. The number of patients with moderate or severe complications was lower in the ERAS group (25.2% vs 30.3%; odds ratio [OR], 0.77; 95% CI, 0.63-0.94; P¿=¿.01). The overall rate of adherence to the ERAS protocol was 63.6% (IQR, 54.5%-77.3%), and the rate for patients from hospitals self-declared as ERAS was 72.7% (IQR, 59.1%-81.8%) vs non-ERAS institutions, which was 59.1% (IQR, 50.0%-63.6%; P¿<¿.001). Adherence quartiles among patients receiving the highest and lowest ERAS components showed that the patients with the highest adherence rates had fewer moderate to severe complications (OR, 0.34; 95% CI, 0.25-0.46; P¿<¿.001), overall complications (OR, 0.33; 95% CI, 0.26-0.43; P¿<¿.001), and mortality (OR, 0.27; 95% CI, 0.07-0.97; P¿=¿.06) compared with those who had the lowest adherence rates. Conclusions and relevance: an increase in ERAS adherence appears to be associated with a decrease in postoperative complications

Serum amyloid a1/toll-like receptor-4 Axis, an important link between inflammation and outcome of TBI patients

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability world-wide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patientsThis work was supported by grants from Fundación Mutua Madrileña and Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet CP14/00008; CPII19/00005; PI16/00735; PI19/00082) to JE, RYC2019-026870-I to JMR and PI18/01387 to A