PLGA-TiO2 as a Carrier System for Drug Release.

This paper reports the results of the PLGA-TiO2 nanocomposite regarding the green synthesis of titanium dioxide nanoparticles using a natural extract, its characterization, and encapsulation with poly(lactic-co-glycolic acid) (PLGA). UV-visible spectrometry was used for the identification of terpenes present in the extracts. The morphology of the nanoparticles was determined by scanning electron microscopy. Infrared spectroscopy was used for the determination of functional groups, while X-ray diffraction was used to determine the crystal structure. The analysis of the extended release of the encapsulated extract in the matrix of the nanomaterial resulted in a maximum visible UV absorbance at approximately 260 nm and confirmed the synthesis of titanium dioxide nanoparticles. Moreover, terpenes enhance synthesis and stabilize titanium dioxide nanoparticles. The synthesized structures are spherical and amorphous, 44 nm in size, and encapsulated at 65 nm.

A Study of Zn-Ca Nanocomposites and Their Antibacterial Properties.

This study aimed to develop Ca2+ doped ZnO nanoparticles (NPs) and investigate their antibacterial properties against microorganisms of dental interest. Zn-Ca NPs were synthesized by the sol-gel method with different concentrations of Ca2+ (1, 3, and 5 wt. %) and subsequently characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis spectroscopy and Fourier transform infrared spectroscopy (FT-IR). The Kirby-Bauer method was used to measure antibacterial effects. NPs showed the wurzite phase of ZnO and bandgap energies (Eg) from 2.99 to 3.04 eV. SEM analysis showed an average particle size of 80 to 160 nm. The treatments that presented the best antibacterial activity were Zn-Ca 3% and Zn-Ca 5%. ZnO NPs represent an alternative to generate and improve materials with antibacterial capacity for dental applications.

Absence of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling protects against collagen-induced arthritis.

OBJECTIVE: Comprehending the mechanisms that regulate activation of autoreactive T cells and B cell antibody production is fundamental for understanding the breakdown in self-tolerance and development of autoimmunity. Here we studied the role of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling in the pathogenesis of collagen-induced arthritis (CIA). METHODS: CIA was induced in mice lacking Flt3L (Flt3L(-/-)) and wild-type (WT) littermates (C57/BL6, 8-10 weeks old). Mice were killed in the initial phase (acute phase: experiment 1) and late phase (chronic phase: experiment 2) of the disease. Arthritis severity was assessed using a semiquantitative scoring system (0-4), and histological analysis of cellular infiltration, cartilage destruction and peptidoglycan loss was performed. Phenotypic and functional analysis of T and B cells, FoxP3 expression, activation and lymphocyte costimulatory markers, and cytokine production were performed ex vivo by flow cytometry in lymph nodes. Serum collagen type II (CII)-specific antibodies were measured by ELISA. RESULTS: Flt3L(-/-) mice showed a marked decrease in clinical arthritis scores and incidence of arthritis in both acute and chronic phases of CIA compared with WT mice. Moreover, decreased synovial inflammation and joint destruction was observed. Both the magnitude and quality of T cell responses were altered in Flt3L(-/-). In the acute phase, the amount of CII-specific IgG2a antibodies was lower in Flt3L(-/-) than WT mice. CONCLUSIONS: These results strongly suggest a role for Flt3L signalling in the development of arthritis.

Predicting emergency health care demands due to respiratory diseases.

BACKGROUND: Timely care in the health sector is essential for the recovery of patients, and even more so in the case of a health emergency. In these cases, appropriate management of human and technical resources is essential. These are limited and must be mobilised in an optimal and efficient manner. OBJECTIVE: This paper analyses the use of the health emergency service in a city, Jaén, in the south of Spain. The study is focused on the most recurrent case in this service, respiratory diseases. METHODS: Machine Learning algorithms are used in which the input variables are multisource data and the target attribute is the prediction of the number of health emergency demands that will occur for a selected date. Health, social, economic, environmental, and geospatial data related to each of the emergency demands were integrated and related. Linear and nonlinear regression algorithms were used: support vector machine (SVM) with linear kernel and generated linear model (GLM), and the nonlinear SVM with Gaussian kernel. RESULTS: Predictive models of emergency demand due to respiratory disseases were generated with am absolute error better than 35 %. CONCLUSIONS: This model helps to make decisions on the efficient sizing of emergency health resources to manage and respond in the shortest possible time to patients with respiratory diseases requiring urgent care in the city of Jaén.

Influence of CMO pharmaceutical care model-based intervention on readmission rate in high risk HIV patients: the INFARDAR study.

OBJECTIVE: Many studies have indicated that hospitalization and readmissions occur frequently, especially among people living with HIV. The aim of the study was to determine the effectiveness of a programmed and structured pharmaceutical intervention, based on "CMO PC model" to reduce the readmission rate in high-risk HIV patients. METHODS: This was a single-center, prospective study based on a structured health intervention conducted between March-2017 and March-2018 with 12 months of follow-up at outpatient pharmacy services. At discharge, HIV patients included were classified according to the risk of readmission as low or high risk patients, being the latter proposed to participate. The selected patients were randomly assigned to a control group (usual care) or intervention group (including stratification-motivational interview and new technologies: CMO pharmaceutical care). The primary endpoint was readmission rate at one year of follow-up in each group. RESULTS: A total of 39 patients were included. As regards the main variable, in the intervention group, 21,4% (n=3) of patients were readmitted in the first year after discharge vs. 66,7% (n=6) in the control group (p=0,042). CONCLUSIONS: Tailored pharmaceutical care based on risk stratification, motivational interviewing, and new technologies has a positive influence to reduce the percentage of readmission in high risk HIV patients.

Clinical trial on the effect of tranexamic acid on bleeding and fibrinolysis in primary hip and knee replacement. / Ensayo clínico sobre el efecto del ácido tranexámico en el sangrado y la fibrinólisis durante la artroplastia simple de cadera y rodilla.

BACKGROUND: Tourniquet-induced ischaemia could increase fibrinolysis and enhance tranexamic acid (TXA) efficacy in total knee arthroplasty (TKA) compared to total hip arthroplasty (THA). The aims of this study are to compare the effect of TXA on bleeding and fibrinolysis in both types of surgery, and to record thromboembolic complications. METHODS: A prospective double-blind study was conducted on patients scheduled for TKA or THA who received TXA (2 bolus of 10mg/kg) or placebo. Bleeding and fibrinolysis were evaluated. Doppler-ultrasound and computed tomography were performed in order to assess any thromboembolic complications. RESULTS: A total of 44 patients were included (11 THA and 11 TKA treated with TXA; 11 THA and 11 TKA as controls). Blood losses were significantly lower in the TXA group (mean 921mL vs 1,383mL in THA and 969mL vs 1,223mL in TKA), and no transfusions were needed with TXA, whereas 5 blood units were transfused in controls. TXA was equally effecting in reducing bleeding in both surgeries (33% in THA and 21% in TKA). The significant mean increase in D-dimers from baseline to 6 hours after surgery (1,004 ug/L to 10,284 ug/L in THA and 571 ug/L to 6,480 ug/L in TKA) was attenuated by TXA (1,077 ug/L to 2,590 ug/L in THA and 655 ug/L to 2,535 ug/L in TKA). There were no differences in thromboembolic episodes. CONCLUSIONS: Prophylactic use of tranexamic acid is equally effective in reducing bleeding in TKA and THA. Both surgeries have a similar effect on fibrinolysis.

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals.

Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.

Hostility and helper T-cells in patients with bulimia nervosa.

OBJECTIVE: The study aimed to analyze the correlation between lymphocyte counts and several psychopathological variables associated with psychological instability (depression, hostility, impulsivity, self-defeating personality traits, and borderline personality symptoms) in patients with bulimia nervosa (BN). METHOD: Sixty BN patients were assessed, using specific scales for eating pathology, general psychopathology, impulsivity, depression, and borderline personality features. Lymphocyte and lymphocyte subset counts were performed. Plasma cortisol at 8:00, before and after administration of 1 mg of dexamethasone at 23:00, was determined. The influence of body weight, and the use of tobacco, alcohol, and caffeine was controlled. The relationship between each isolated variable and the number of immune cells was analyzed. In a second step, supplementary post-hoc analysis of the variables was introduced to confirm the accuracy of the psychopathological assessment. RESULTS: Hostility was negatively correlated with the number of helper T-cells (CD4+). Patients with high hostility had lower CD4+ cell counts and lower CD4+/CD8+ ratios. In the post-hoc control study, hostility was significantly related with other "interpersonal" items. CONCLUSIONS: These results support the idea that hostility, as an expression of disturbed interpersonal relationships, could play a role as a modulator of immune activity in patients with BN.

Real life study of sacubitril valsartan combined therapy in chronic heart failure / Estudio en vida real de la terapia combinada de sacubitril valsartán en insuficiencia cardíaca crónica

Objectives: Sacubitril/valsartan is a drug for chronic heart failure (CHF), approved by Drugs Regulatory Agencies based on the results of the PARADIGM-HF, which could have several limitations on internal validity and applicability. Furthermore, this drug has a high economic impact. The objectives of this study are to evaluate effectiveness and safety of sacubitril/valsartan in CHF, as well as to evaluate adequation to use criteria stablished in a Health Management Area (HMA). Methods: Retrospective, observational study including adult patients with CHF who were receiving sacubitril/valsartan during 2017 in an HMA. The treatment effectiveness was assesed by death and/or hospitalization rates related to CHF. Frequency of adverse events was used to safety evaluation. Furthermore, adequation rate was assessed. Findings: A total of 68 patients were included. Death or hospitalization rates due to CHF at 12 months were 32.3% globally (2.9% and 29.4% respectively). Among patients analyzed, 33.8% presented hypotension, during the first year after treatment initiation. Overall adequation rate was 67.6%. Conclusions: A high percentage of death and/or hospitalization due to CHF was observed. Hypotension is a frequent adverse event which leads to dose adjustment and/or drug withdrawal. Overall adequation rate of sacubitril/valsartan prescription is acceptable. (AU)

Objetivos: El sacubitril/valsartán es un medicamento para la insuficiencia cardíaca crónica (ICC), aprobado por las agencias reguladoras de medicamentos en base a los resultados del ensayo pivotal PARADIGM-HF, que podría tener varias limitaciones en la validez interna y la aplicabilidad. Además, este fármaco tiene un alto impacto económico. Los objetivos de este estudio son evaluar la efectividad y la seguridad de sacubitril/valsartán en la ICC, así como evaluar la adecuación a los criterios establecidos en un Área de Gestión de Salud (AGS). Métodos: Estudio observacional retrospectivo que incluye pacientes adultos con ICC que recibieron sacubitril/valsartán durante 2017 en una AGS. La efectividad del tratamiento fue evaluada mediante la tasa de mortalidad y/o hospitalización relacionadas con la ICC. La frecuencia de los eventos adversos se utilizó para la evaluación de seguridad. Además, se evaluó la tasa de adecuación. Resultados: Se incluyeron un total de 68 pacientes. Las tasas de mortalidad u hospitalización por ICC a los 12 meses fueron del 32,3% a nivel global (2,9% y 29,4%, respectivamente). Entre los pacientes analizados, el 33,8% presentó hipotensión durante el primer año después del inicio del tratamiento. La tasa de adaptación global fue del 67,6%. Conclusiones: Se observó un alto porcentaje de muerte y/o hospitalización por ICC. La hipotensión es un evento adverso frecuente que conduce al ajuste de la dosis y/o a la retirada del medicamento. La tasa general de adecuación de la prescripción de sacubitril/valsartán es aceptable. (AU)

Clinical presentation of Bacillus Calmette-Guérin infections in patients with immunodeficiency syndromes.

Nine children with immunodeficiency syndromes who developed persistent or disseminated Bacillus Calmette-Guérin (BCG) infections after BCG vaccination at birth were observed in Santiago, Chile, over a period of 10 years. This represents a risk for persistent or disseminated BCG infections of 3.4/1,000,000 vaccinated newborns. This may closely reflect the incidence of severe combined immunodeficiency syndromes, cellular immunodeficiency syndromes and chronic granulomatous disease in the study area. The clinical presentation and course of the infection varied considerably depending on the underlying immunodeficiency syndrome. Two patients with severe combined immunodeficiency presented with cutaneous nodules in the absence of any local reaction at the site of BCG vaccination. Both patients died of disseminated BCG infection within the first year of life. Four patients with cellular immunodeficiency syndromes presented with regional lymphadenitis resistant to treatment after the fifth month of life. Three of these patients had specific unresponsiveness to tuberculin and survived from 5 to 6 years of age. Two boys with X-linked chronic granulomatous disease presented with regional lymphadenitis in the first 3 months of life. A girl with autosomal recessive chronic granulomatous disease presented at 18 months of age with regional lymphadenitis. All three patients with chronic granulomatous disease had positive tuberculin reactions and died from infections other than BCG.

[Prophylaxis of infective complications of central venous catheters]. / Profilaxis de las complicaciones infecciosas de los catéteres venosos centrales.

Infections related to central venous cannulation present first-magnitude problems in recovery rooms and intensive care units. Catheter-related bloodstream infection (CRBSI) is the most serious complication because of its high frequency and a mortality rate that averages around 3%. Although infections arise for various reasons, point-of-insertion contamination is the main cause when catheters are implanted for periods of less than 10 days. Contaminating microorganisms (especially Staphyloccocus epidermidis) find refuge from the host's defenses in a biofilm that covers the catheter. Several factors participate in the formation of this biofilm, such as catheter composition, proteins of the host or type of microorganism. Biofilm bacteria are resistant to both antibiotics and the host's own defenses (e.g. phagocytes and antibodies). The microorganism can then begin to reproduce, possibly leading to bloodstream infection. The measures designed to prevent this process include recommendations for both catheter insertion and maintenance. Recent meta-analyses have led to certain conclusions but no unanimity among authors. Thus, there is agreement on the adoption of strict aseptic technique during catheter insertion, on the use of chlorhexidine as a skin antiseptic and on choice of the subclavian vein. Such measures significantly decrease the frequency of CRBSI. Maintenance techniques that have been shown to be effective are the use of connectors impregnated with antiseptic, catheters impregnated with antiseptics or antibiotics, and permeable dressings. Additionally, building an experienced infusion-therapy team to insert and maintain central venous catheters has been shown to be one of the most effective measures for preventing CRBSI.

Fms-like tyrosine kinase 3 ligand-dependent dendritic cells in autoimmune inflammation.

Dendritic cells (DCs) are specialized in capture, processing and presentation of antigens to T cells. Depending on the type of DC and its activation state, the interaction of DCs with naive T cells can lead to different types of immune response, or to T-cell tolerance. The existence of many specialized subtypes of DCs with particular functions has raised the need to distinguish DCs formed in steady-state from those produced during an inflammatory response. In patients with autoimmune disease and in experimental animal models of autoimmunity, DCs show abnormalities in both numbers and activation state, expressing immunogenic levels of co-stimulatory molecules and pro-inflammatory cytokines. Initial in vitro studies of cytokines in DC development revealed distinct and important roles for the receptor tyrosine kinases, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF, also called CSF1) and fms-like tyrosine kinase 3 ligand (Flt3L) in the generation of DCs. Flt3L is critical for instructing DC generation throughout different organs and regulates DC development from Flt3(+) lymphoid and myeloid-committed progenitors to DCs in vivo. The aim of this review is to provide an overview of the role of Flt3L-dependent DCs in the immunopathogenesis of autoimmunity and chronic inflammation and its potential as therapeutic targets.

[Influence of the grade of anxiety and level of cortisol on post-surgical recovery]. / Influencia del grado de ansiedad y el nivel de cortisol sobre la recuperación posquirúrgica.

INTRODUCTION: The objective is to analyze the influence of several biological and/or psychological factors on postsurgery recovery. METHOD: Our sample was made up of 42 inpatients waiting for surgery. The day before the intervention, they filled out Spielbergers' State/Trait Anxiety Inventory (STAI) and sample of saliva was collected at 8:00 in order to determine cortisol concentration. Recovery was codified as <> or <> using the Moix criteria (1995). RESULTS: Patients with higher scores on the STAI had higher levels of salivary cortisol and their recovery was worse compared with patients with low anxiety. CONCLUSIONS: Our results confirm the relationship between specific psychological variables, cortisol levels and the characteristics of the surgery recovery process of the patients.

Toxoplasma gondii: antigenic differences between endozoites and cystozoites defined by monoclonal antibodies.

The antigenic differences between endozoites and cystozoites of Toxoplasma gondii were analyzed by indirect immunofluorescent assay and Western blotting using monoclonal antibodies. An antigenic determinant of an antigen of 20 kDa mol. wt. that appeared to be localized in the cytoplasm was observed to be specific to cystozoites alone. The 20-kDa antigen was diffused throughout the parasite and was observed in cystozoites produced both in vivo and in vitro.

Cultivation of Plasmodium falciparum using animal serum (horse, calf and bovine) as human serum substitute.

Horse, calf and bovine serum were successfully used as human serum substitutes in the in vitro cultivation of Plasmodium falciparum. Positive results were obtained only after gradually adapting the parasites to the substitute serum. Adapted lines were established within 4-5 weeks. 10% horse serum was observed to be the best substitute with growth rates comparable or even surprising that obtained in human serum. Pure calf or bovine serum supported stable growths of 20-30% less which was enhanced to comparable levels after addition of 1% glucose-peptone to the medium. Direct transfers of adapted cultures to human serum showed enhanced growth rates. Lower growth rates of adapted cultures (i.e. horse serum-adapted cultures) in other substitute sera (i.e. calf or bovine sera) were improved in subsequent subcultures. Similarly, there were no adverse effects when they were returned back to the substitute serum they were originally adapted to.

Plasmodium falciparum: characterization of a 33-kDa soluble antigen.

A 33-kDa soluble antigen identified in the culture supernatant by patient serum and monoclonal antibodies was present in rings, trophozoites, schizonts, and merozoites of Plasmodium falciparum. The antigen which is released into the culture supernatant by growing parasites was also observed in the host cells of trophozoites and schizonts and could be localized on the host cell surface. Its specificity for the surface of trophozoites and schizonts was observed to decrease with increased duration without subculture. The antigen could then be detected on the surface of noninfected erythrocytes. The antigenicity of the 33-kDa antigen was destroyed by heating at 65 degrees C. Monoclonal and polyclonal specific antibodies weakly inhibited parasite growth in vitro. The antigen was present in both knob positive and knob negative parasites in all the P. falciparum isolates tested.

Subtype criteria for bulimia nervosa: short- versus long-term compensatory behaviors.

Weight control methods used by a group of bulimic patients were studied, analyzing the relationship among compensatory strategies and other clinical variables. Sixty-nine female consecutive patients who sought help for DSM-IV bulimia nervosa were recruited for the study. The prevalence and frequency of use of binge eating and six compensatory methods (vomiting, laxatives, diuretics, diet pills, fasting, and compulsive exercise) were assessed in each patient. Factor analysis was used to group the variables, and a cluster analysis was performed on a second step. The clinical variables were finally analyzed in each of the groups isolated through cluster analysis. According to the results of the factor analysis, the compensatory strategies were identified as short-term compensatory methods (vomiting), long-term methods (diet pills, diuretics, and laxatives), and nonpurging methods (dieting and exercise). Three groups of patients were isolated through cluster analysis: short-term purgers (vomiting), long-term purgers (laxatives + diet pills + diuretics), and a mixed group (vomiting + laxatives). Long-term purgers were older and heavier, had a greater prevalence of past overweight, and used more compensatory methods. These results confirm the necessity to continue investigating alternative ways of classifying bulimia nervosa patients based on compensatory behaviors, considering the existence of clinical dimensions rather than rigid clinical subtypes.