Photodynamic inactivation of Staphylococcus aureus by ecological antibacterial solutions associating LED (ʎ 450 ± 10 nm) with curcumin and olive leaf extracts.

Antimicrobial resistance is a problem in contemporary society, with Staphylococcus aureus standing out as a threat due to its ability to colonize, its pathogenicity, and its expression of several virulence factors. In this context, antimicrobial photodynamic inactivation (aPDI) emerges as an alternative to conventional microbicidal or microbiostatic systems, enabling numerous and successive applications without developing side effects and microbial resistance. In this context, an aPDI system against cultures of S. aureus based on a water-in-oil (W/O) emulsion incorporating curcumin as the photosensitizer (PS), with and without olive leaf extract (OLE), was developed and the antibacterial efficacy evaluated under LED activation (ʎ450 ± 10 nm) by depositing an energy density of 14 J/cm2. The produced emulsified systems showed no significant differences in the droplet size and morphology, remaining stable along the tested period of 30 days. The bacterial reduction achieved after the first aPDI application for the emulsions added with curcumin and curcumin combined with the OLE was 5 log10 CFU.mL-1 and 6 log10 CFU.mL-1, respectively, revealing a significant difference between the two groups (p < 0.0001). After the second aPDI application, an increased microbial reduction (7 log10 CFU.mL-1) was observed for both studied groups even with a low significant difference (p < 0.05). The PS loading through an emulsified system for aPDI obtained a bactericidal action against S. aureus, increased by applying two aPDI, showing a significant synergy between photodynamic inactivation, OLE delivery and antibacterial activity. In addition, the developed solutions were produced using natural products by an ecologically correct process.

Microalgae-Derived Pigments: A 10-Year Bibliometric Review and Industry and Market Trend Analysis.

Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments and microalgal sources by gathering trends from a 10-year bibliometric survey, a patents search, and an industrial and market analysis built from available market reports, projects and companies' webpages. The performed analysis pointed out chlorophylls, phycocyanin, astaxanthin, and ß-carotene as the most relevant pigments, and Chlorella vulgaris, Spirulina platensis, Haematococcus pluvialis, and Dunaliella salina, respectively, as the most studied sources. Haematococcus is referred in the highest number of patents, corroborating a high technological interest in this microalga. The biorefinery concept, investment in projects and companies related to microalgae cultivation and/or pigment extraction is increasingly growing, particularly, for phycocyanin from Spirulina platensis. These pieces of evidence are a step forward to consolidate the microalgal pigments market, which is expected to grow in the coming years, increasing the prospects of replacing synthetic pigments by natural counterparts.

Urban vegetation and particle air pollution: Experimental campaigns in a traffic hotspot.

This work presents the main results of two experimental campaigns carried out in summer and winter seasons in a complex pollution hotspot near a large park, El Retiro, in Madrid (Spain). These campaigns were aimed at understanding the microscale spatio-temporal variation of ambient concentration levels in areas with high pollution values to obtain data to validate models on the effect of urban trees on particulate matter concentrations. Two different measuring approaches have been used. The first one was static, with instruments continuously characterizing the meteorological variables and the particulate matter concentration outside and inside the park. During the summer campaign, the particulate matter concentration was clearly influenced by a Saharan dust outbreak during the period 23 June to 10 July 2016, when most of the particulate matter was in the fraction PM2.5-10. During the winter campaign, the mass concentrations were related to the meteorological conditions and the high atmospheric stability. The second approach was a dynamic case with mobile measurements by portable instruments. During the summer campaign, a DustTrak instrument was used to measure PM10 and PM2.5 in different transects close to and inside the park at different distances from the traffic lane. It was observed a decrease in the concentrations up to 25% at 20 m and 50% at 200 m. High PM10 values were linked to dust resuspension caused by recreational activities and to a Saharan dust outbreak. The highest PM values were measured at the Independencia square, an area with many bus stops and high traffic density. During the winter campaign, three microaethalometers were used for Black Carbon measurement. Both pollutants also showed a reduction in their concentrations when moving towards inside the park. For PM10 and PM2.5, reductions up to 50% were observed, while for BC this reduction was smaller, about 20%.

Preparation of nano-hydroxyapatite/chitosan aqueous dispersions: From lab scale to continuous production using an innovative static mixer.

Chitosan is widely used in the preparation of organic-inorganic composite materials, such as n-HAp/CS composites, which find application for bone regeneration. The methods for their preparation are various, and usually based on the preparation of intermediate n-HAp/CS dispersions, which can greatly influence the final properties of the resulting composites since it is expected that homogenous and stable dispersions lead to composite materials with improved final properties. This work hypothesizes that, additionally to process parameters such as pH, n-HAp/CS weight ratio, mixing conditions and the presence of salts, chitosan itself has a high impact on dispersions stability. Thus, the importance of properly control the preparation of the n-HAp/CS intermediate dispersions is highlighted by doing a systematic study where relevant processing parameters were studied at lab scale using ultrasonication, alone or in the presence of chitosan, namely on particle size and zeta potential. Furthermore, and based on the best laboratorial conditions, the production of n-HAp/CS nanocomposite dispersions in continuous mode was attempted through NETmix® technology, an innovative static mixer and reactor developed at the Associate Laboratory LSRE-LCM of the Faculty of Engineering of the University of Porto (FEUP).

Supercritical CO2 assisted process for the production of high-purity and sterile nano-hydroxyapatite/chitosan hybrid scaffolds.

Hybrid scaffolds composed of hydroxyapatite (HAp), in particular in its nanometric form (n-HAp), and chitosan (CS) are promising materials for non-load-bearing bone graft applications. The main constraints of their production concern the successful implementation of the final purification/neutralization and sterilization steps. Often, the used purification strategies can compromise scaffold structural features, and conventional sterilization techniques can result in material's thermal degradation and/or contamination with toxic residues. In this context, this work presents a process to produce n-HAp/CS scaffolds mimicking bone composition and structure, where an innovative single step based on supercritical CO2 extraction was used for both purification and sterilization. A removal of 80% of the residual acetic acid was obtained (T = 75°C, p = 8.0 MPa, 2 extraction cycles of 2 h) giving rise to scaffolds exhibiting adequate interconnected porous structure, fast swelling and storage modulus compatible with non-load-bearing applications. Moreover, the obtained scaffolds showed cytocompatibility and osteoconductivity without further need of disinfection/sterilization procedures. Among the main advantages, the proposed process comprises only three steps (n-HAp/CS dispersion preparation; freeze-drying; and supercritical CO2 extraction), and the supercritical CO2 extraction show clear advantages over currently used procedures based on neutralization steps. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 965-975, 2018.

Assessing the direction of climate interactions by means of complex networks and information theoretic tools.

An estimate of the net direction of climate interactions in different geographical regions is made by constructing a directed climate network from a regular latitude-longitude grid of nodes, using a directionality index (DI) based on conditional mutual information (CMI). Two datasets of surface air temperature anomalies-one monthly averaged and another daily averaged-are analyzed and compared. The network links are interpreted in terms of known atmospheric tropical and extra-tropical variability patterns. Specific and relevant geographical regions are selected, the net direction of propagation of the atmospheric patterns is analyzed, and the direction of the inferred links is validated by recovering some well-known climate variability structures. These patterns are found to be acting at various time-scales, such as atmospheric waves in the extratropics or longer range events in the tropics. This analysis demonstrates the capability of the DI measure to infer the net direction of climate interactions and may contribute to improve the present understanding of climate phenomena and climate predictability. The work presented here also stands out as an application of advanced tools to the analysis of empirical, real-world data.

Impact of reperfusion strategy on outcomes in very elderly patients with acute myocardial infarction.

AIM: The best reperfusion strategy for patients of advanced age (either primary-angioplasty or thrombolysis) after a ST-segment elevation myocardial infarction (STEMI) remains controversial. Aim of the study was to test differences in morbidity and mortality regarding the reperfusion strategy adopted. METHODS: From 2007-2012, 182 patients ≥85 year-old with STEMI were admitted to the coronary care unit of two tertiary centers. Data regarding baseline characteristics, clinical presentation, reperfusion strategy adopted and outcomes were retrospectively reviewed. The relation between the type of reperfusion therapy and outcomes was evaluated. RESULTS: Median age was 86.8±6.9 years (range 85-96). Most patients (54.4%) were woman. Anterior wall STEMI was the main electrocardiographic location (45.1%). A conservative treatment was seen in 64 patients (35.2%), thrombolysis in 41 (22.5%) and primary-angioplasty in the remaining 77 patients (42.3%). A total of 56 patients died (30.8%). The mortality rate in the thrombolysis group (21.9%) was similar than that found in the primary-angioplasty group (15.6%) (P=0.45). No difference was found in a subgroup analysis of high risk patients (i.e. anterior wall STEMI, Killip class ≥2). Morbidity rates were also similar between both therapeutic groups (thrombolisys 58.5% vs. primary-angioplasty 46.7%, P=0.22). Morbidity and mortality rates were much higher among those patients treated conservatively than that found in patients who received any of the reperfusion strategies (54.6% vs. 17.8%, P<0.0001 and 79.7% vs. 50.8%, P<0.0001, respectively). CONCLUSIONS: Mortality and morbidity among very elderly patients with STEMI are extremely high. No differences were found between primary-angioplasty and fibrinolysis with regard to outcomes. A conservative treatment was associated with a worse prognosis.

[Prevention of medication errors in healthcare transition of patients treated with apomorphine]. / Intervenciones farmacéuticas relacionadas con la prevención de errores de medicación en la transición asistencial de pacientes tratados con apomorfina.

The transition of patients between different levels of care process is a particular risk in the production of medication errors. The aim of this paper is to analyze the role of the pharmacist in preventing errors transition care to ensure a safe and cross pharmacotherapy of patients.Transversal, observational and descriptive study in a University Hospital that has a pharmacy service that integrates specialized inpatient care and health centers. Transition of care a patient treated with Apormorfina was analyzed to determine the keypoints of action of the pharmacist. Demographics, disease and medication history, and care transition episodes were collected through the pharmacy program and electronics history.The pharmacist did tasks adapting, reconciliation, management and reporting of medication to the health care team to prevent medication errors in care transition of patients treated with drugs requiring special handling .In conclusion, this work represents perfectly the key role of the pharmacist as coordinator of safe and transverse pharmacotherapy of patients.

La transición de los pacientes entre los diferentes niveles asistencialesconstituye un proceso de especial riesgo en la producciónde errores de medicación. El objetivo de este trabajo esmostrar el papel del farmacéutico en la prevención errores paragarantizar una farmacoterapia segura y transversal de lospacientes.Estudio transversal, observacional y descriptivo en un ComplejoHospitalario Universitario que cuenta con un Servicio de Farmaciaque integra atención especializada a pacientes hospitalizadosy a residentes de centros sociosanitarios. Se analizó la transiciónasistencial de una paciente tratada con Apomorfina paradeterminar los puntos clave de actuación del farmacéutico. Serecogieron datos demográficos, patología e historia farmacoterapéutica,así como los episodios de transición asistencial, a travésdel programa de Farmacia y la historia electrónica.El farmacéutico realizó tareas de adecuación, conciliación, gestióne información de la medicación al equipo asistencial paraprevenir errores de medicación en la transición asistencial depacientes tratados con fármacos de especial manejo.En conclusión este trabajo representa los puntos críticos deintervención del farmacéutico como coordinador de la farmacoterapiasegura y transversal de los pacientes.

Titanium compacts produced by the pulvimetallurgical hydride-dehydride method for biomedical applications.

Titanium powder production by the hydride-dehydride method has been developed as a non-expensive process. In this work, commercially pure grade two Ti specimens were hydrogenated. The hydrided material was milled in a planetary mill. The hydrided titanium powder was dehydrided and then sieved to obtain a particle size between 37 and 125 microm in order to compare it with a commercial powder produced by chemical reduction with a particle size lower than 150 microm. Cylindrical green compacts were obtained by uniaxial pressing of the powders at 343 MPa and sintering in vacuum. The powders and the density of sintered compacts were characterized, the oxygen content was measured and in vivo tests were performed in the tibia bones of Wistar rats in order to evaluate their biocompatibility. No differences were observed between the materials which were produced either with powders obtained by the hydride-dehydride method or with commercial powders produced by chemical reduction regarding modifications in compactation, sintering and biological behaviour.

Kidney androgen-regulated protein transgenic mice show hypertension and renal alterations mediated by oxidative stress.

BACKGROUND: Kidney androgen-regulated protein (KAP), a proximal tubule androgen-regulated gene, codes for a protein of unknown function. METHODS AND RESULTS: To investigate the consequences of KAP overexpression in kidney, we produced KAP transgenic mice and performed microarray expression analyses in kidneys of control and transgenic males. Downregulation of the androgen-sensitive Cyp4A14 monooxygenase gene in KAP transgenic mice prompted us to analyze blood pressure levels, and we observed that transgenic mice were hypertensive. Inhibition of 20-hydroxyeicosatetraenoic acid synthesis by N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) reduced the increased 20-hydroxyeicosatetraenoic acid levels in urine and normalized arterial pressure in transgenic mice, as did the NADPH oxidase inhibitor apocynin. Increased oxidative stress in transgenic mice was demonstrated by (1) enhanced excretion of urinary markers of oxidative stress, 8-iso-prostaglandin F2alpha, 8-hydroxydeoxyguanosine, and thiobarbituric acid-reacting substances; (2) augmented mitochondrial DNA damage and malondialdehyde levels in kidneys; and (3) diminished catalase and glutathione peroxidase activity in transgenic kidneys. Mice exhibited renal defects that included focal segmental glomerulosclerosis, proteinuria, glycosuria, and fibrosis. CONCLUSIONS: Taken together, these results indicate that KAP expression is critical for cardiovascular-renal homeostasis maintenance and that hypertension is associated with increased oxidative stress. This is the first report showing that overexpression of an androgen-regulated, proximal tubule-specific gene induces hypertension. These observations may shed light on the molecular pathophysiology of gender differences in the prevalence and severity of hypertension and chronic renal disease.

Novel expression and direct effects of adiponectin in the rat testis.

Adiponectin is an adipocyte hormone, with relevant roles in lipid metabolism and glucose homeostasis, recently involved in the control of different endocrine organs, such as the placenta, pituitary and, likely, the ovary. However, whether as described previously for other adipokines, such as leptin and resistin, adiponectin is expressed and/or conducts biological actions in the male gonad remains unexplored. In this study, we provide compelling evidence for the expression, putative hormonal regulation, and direct effects of adiponectin in the rat testis. Testicular expression of adiponectin was demonstrated along postnatal development, with a distinctive pattern of RNA transcripts and discernible protein levels that appeared mostly located at interstitial Leydig cells. Testicular levels of adiponectin mRNA were marginally regulated by pituitary gonadotropins but overtly modulated by metabolic signals, such as glucocorticoids, thyroxine, and peroxisome proliferator-activated receptor-gamma, whose effects were partially different from those on circulating levels of adiponectin. In addition, expression of the genes encoding adiponectin receptor (AdipoR)-1 and AdipoR2 was detected in the rat testis, with developmental changes and gonadotropin regulation for AdipoR2 mRNA, and prominent levels of AdipoR1 in seminiferous tubules. Moreover, recombinant adiponectin significantly inhibited basal and human choriogonadotropin-stimulated testosterone secretion ex vivo, whereas it failed to change relative levels of several Sertoli cell-expressed mRNAs, such as stem cell factor and anti-Müllerian hormone. In summary, our data are the first to document the expression, regulation and functional role of adiponectin in the rat testis. Taken together with its recently reported expression in the ovary and its effects on LH secretion and ovarian steroidogenesis, these results further substantiate a multifaceted role of adiponectin in the control of the reproductive axis, which might operate as endocrine integrator linking metabolism and gonadal function.

[CARD15 mutations are poorly related to Crohn's disease phenotypes in Asturias]. / Las mutaciones del gen CARD15 presentan escasa relación con los fenotipos de la enfermedad de Crohn en Asturias.

BACKGROUND: the association between the three common CARD15 gene mutations (R702W, G908R, L1007fs) and the genetic susceptibility to Crohn s disease (CD) have been confirmed by several studies, with some differences found, in relation to geographic areas and ethnic groups. OBJECTIVES: To analyze the prevalence of CARD15 gen and its polymorphisms in patients with CD in Asturias and its possible correlation with the different genotypes of the disease. METHODS: a total of 216 CD patients recruited from Asturias (North of Spain) and 86 ethnically matched healthy controls, were typed using Hybprobes on a LightCycler instrument for CARD15 mutations. Patients were subdivided according to Vienna classification. We have studied the frequency of these mutations in the different subgroups of CD patients and analyzed its contribution to the disease clinical characteristics and progression. RESULTS: carrier frequencies for CARD15 mutations in our CD patients were similar to controls (17.8 vs. 17.4%) respectively (NS). CD patients exhibited frequencies of 8.8, 3.0 and 6.0% for the R702, G908R and L1007fs polymorphisms respectively, whereas our control population had allele frequencies of 11.6, 2.3 and 3.5% for the three mutations respectively (NS). We did not find any relationship between CARD15 mutations and the different phenotypes of Crohn s disease, according to Vienna classification. CONCLUSIONS: in our CD population, other factors (i.e. environmental), in addition to genetics, must be mainly involved in the development of the disease.

Role of leptin and ghrelin in the regulation of gonadal function.

Gonadal development and function is sustained by the complex interaction of an array of regulatory signals that operate directly on the gonads and/or indirectly via modulation of gonadotropin secretion. During the last decade, different factors primarily involved in the control of food intake and energy balance have been demonstrated as putative modulators of different elements of the reproductive axis, including the gonads, thus helping to define the neuroendocrine basis for the link between body energy stores and fertility. These factors include not only the adipocyte-derived hormone leptin, which is indispensable for proper energy balance and reproduction, but also a number of neuropeptides and hormones of central and peripheral origin. In the latter, growing evidence strongly suggests the involvement of the stomach-secreted peptide ghrelin in the control of several aspects of gonadal function. Interestingly, leptin and ghrelin have been proposed as reciprocally related regulators of energy homeostasis; however, their potential interplay in the control of reproduction remains ill defined. This work will summarize the most salient findings concerning the potential roles of leptin and ghrelin in the functional control of the gonads. In addition, open issues regarding the reproductive facets of these metabolic signals will be highlighted. Overall, the authors propose that through complementary or antagonistic actions, leptin and ghrelin may jointly cooperate to modulate a wide set of reproductive functions, thereby contributing to the physiologic integration of energy balance and reproduction.

The Pliocene paradox (mechanisms for a permanent El Niño).

During the early Pliocene, 5 to 3 million years ago, globally averaged temperatures were substantially higher than they are today, even though the external factors that determine climate were essentially the same. In the tropics, El Niño was continual (or "permanent") rather than intermittent. The appearance of northern continental glaciers, and of cold surface waters in oceanic upwelling zones in low latitudes (both coastal and equatorial), signaled the termination of those warm climate conditions and the end of permanent El Niño. This led to the amplification of obliquity (but not precession) cycles in equatorial sea surface temperatures and in global ice volume, with the former leading the latter by several thousand years. A possible explanation is that the gradual shoaling of the oceanic thermocline reached a threshold around 3 million years ago, when the winds started bringing cold waters to the surface in low latitudes. This introduced feedbacks involving ocean-atmosphere interactions that, along with ice-albedo feedbacks, amplified obliquity cycles. A future melting of glaciers, changes in the hydrological cycle, and a deepening of the thermocline could restore the warm conditions of the early Pliocene.

[Expression of CD10 and renal cell carcinoma marker in clear cell renal cell carcinoma: analysis on tissue arrays]. / Expresión de CD10 y del marcador de carcinoma renal en el carcinoma renal de células claras: análisis en matrices tisulares.

OBJECTIVES: CD10 and renal cell carcinoma (RCC) marker antibodies react against proteins of the epithelium of the renal proximal tubule, being expressed by renal cell carcinomas. The frequence and pattern of expression of both markers are analysed in a series of clear cell renal cell carcinomas. METHOD: Two tissue arrays were used, which were composed of cylinders obtained with a 16G needle from 40 paraffin blocks that corresponded to clear cell renal cell carcinomas. The labeled streptavidin-biotin technique was performed (LSAB2, Dako) using CD10 and RCC monoclonal antibodies (Novocastra), testing different antigen retrieval methods for RCC. Immunoreactivity was evaluated as + (isolated cells or focal staining); ++ (moderate) and +++ (extense). RESULTS: Thirty cases (75%) were positive for CD10: 12 +; 5 ++ and 13 +++. The best antigen retrieval method for RCC was a double enzyme digestion (trypsin + protease). Twenty cases (50%) were positive for RCC: 7 +; 5 ++ and 8 +++. Four cases out of the 20 immunoreactive for RCC were negative for CD10. The 16 remaining cases also expressed CD10. CONCLUSIONS: CD10 and RCC are often expressed by clear cell renal cell carcinomas, and they may be useful markers to suggest a renal origin of carcinomas. RCC is less sensitive than CD10. Staining for both of them is usually focal, and thus sensitivity of these techniques decreases when small samples are investigated, such as tissue arrays. The antigen retrieval method is essential for RCC immunohistochemical detection, obtaining the best results with the use of proteolytic enzymes.

Protective and antioxidant effects of Rhizophora mangle L. against NSAID-induced gastric ulcers.

The bark of Rhizophora mangle, the red mangrove, has been used traditionally in folk medicine of Caribbean countries due to its antiseptic, astringent, haemostatic and antifungal properties. Aqueous extracts are rich in tannins and have been proven experimentally to possess antibacterial, wound healing and antiulcerogenic effects. This work was designed to determine the gastroprotective effect of Rhizophora mangle in a model of diclofenac-induced ulcers in rats and to study the mechanisms involved, using the proton pump inhibitor omeprazole as a comparison. The lyophilized extract was given by oral gavage (125 and 62.5mg/kg) three times at 12h intervals before administering diclofenac 100mg/kg. Pretreatment with the extract resulted in a significant decrease of the ulcerated area (P<0.01). Rhizophora mangle induced a recovery of PGE(2) levels, which had been depleted by diclofenac. No anti-inflammatory effect was observed ex vivo or in vitro. The highest dose of the extract provoked a marked increase in glutathione peroxidase and superoxide dismutase activity, which was comparable to omeprazole. Furthermore, lipid peroxidation levels were inhibited in a dose-dependent manner. These results suggest that the gastroprotective effect of Rhizophora mangle in this experimental model appears through an antioxidant and prostaglandin-dependent way.