Long-Term Treatment with Alcaligenes faecalis A12C Improves Host Resistance to Pathogens in Septic Rats: Possible Contribution of Curdlan-Like Immune Trainer.

Curdlan, a ß-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1ß, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.

Vericiguat en insuficiencia cardíaca: de la evidencia científica a la práctica clínica / Vericiguat in heart failure: from scientific evidence to clinical practice

A pesar de los tratamientos actuales, el riesgo de muerte y hospitalizaciones en pacientes con insuficiencia cardíaca con fracción de eyección reducida (IC-FEr) sigue siendo elevado. La fisiopatología de la IC-FEr incluye activación neurohormonal caracterizada por la estimulación de las vías deletéreas (sistemas simpático y renina-angiotensina-aldosterona) y la supresión de las vías protectoras como las dependientes del óxido nítrico. La inhibición o estimulación de algunas de estas vías, pero no de todas, es insuficiente. En la IC-FEr existe una menor actividad de óxido nítrico, guanilato ciclasa soluble y GMPc que provoca efectos deletéreos a nivel miocárdico, vascular y renal. Vericiguat estimula la actividad de esta vía protectora. El estudio VICTORIA demostró, en pacientes con IC-FEr y descompensación reciente, que la adición de vericiguat al tratamiento médico óptimo reducía de forma significativa la incidencia del objetivo primario compuesto de muerte cardiovascular u hospitalización por IC, con un número de 24 pacientes que es necesario tratar, y una excelente tolerabilidad (AU)

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability (AU)

Grupo de seguridad del paciente del colegio oficial de farmacéuticos: 10 años de práctica colaborativa entre farmacias y centros sanitarios / Patient safety group of the official college of pharmacists: 10 years of collaborative practice between pharmacies and healthcare centres

JUSTIFICACIÓN: la colaboración entre centros sanitarios y farmacias es esencial para mejorar la seguridad de los pacientes y el estado de salud de la población. El Grupo de Seguridad del Paciente del Colegio Oficial de Farmacéuticos se constituyó en 2011 para fomentar la comunicación entre niveles asistenciales y mejorar la atención a los pacientes.OBJETIVOS: describir las actividades del Grupo, enfocadas a la práctica colaborativa entre farmacias y centros del Área Sanitaria del Servicio de Salud, para mejorar la seguridad de los pacientes.MATERIAL Y MÉTODOS: el Grupo lo integran profesionales de la farmacia comunitaria, hospitalaria, de atención primaria y del Centro de Información de Medicamentos colegial, que se reúnen mensualmente para elaborar documentos, promover acciones formativas y fomentar la mejora de la comunicación entre las farmacias y los centros sanitarios. También se revisan incidentes en la prescripción o dispensación de medicamentos, para evitar errores de seguridad en el ámbito extrahospitalario. Los materiales elaborados se difunden entre los colegiados, otros profesionales sanitarios y/o la población general.RESULTADOS/DISCUSIÓN: las principales actividades desarrolladas por el Grupo de Seguridad del Paciente han sido: -Elaboración de un protocolo de comunicación entre farmacias y centros sanitarios.-Difusión e implantación de un formulario de notificación de incidentes, para su posterior evaluación por el Grupo de Seguridad.-Revisión de incidencias relacionadas con errores de prescripción, errores de dispensación y problemas de funcionamiento de receta electrónica, que pueden dar lugar a errores de medicación. (AU)

Vericiguat in heart failure: From scientific evidence to clinical practice.

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability.

Drugs used during the COVID-19 first wave in Vitoria-Gasteiz (Spain) and their presence in the environment.

The city of Vitoria-Gasteiz was one of the probable first entrances of the SARS-CoV2 in Spain, one of the worst affected countries in the world during the first COVID 19 wave. Driven by the urgency of the situation, multiple drugs with antiviral activity were used off label. Sadly, most of these treatments were of little or no benefit and thus, the number of patients suffering from COVID-19 attended in intensive care units (ICUs) multiplied. After being administered to patients, a variable proportion of these drugs reach the environment where they may have detrimental effects, although this aspect is usually ignored by healthcare professionals. In this study we measured the patterns of hospital drug use in the city of Vitoria-Gasteiz (Spain) during the first COVID-19 wave pandemic, focusing on those with antiviral activity and those used in the ICUs. Subsequently, we measured concentrations of selected drugs in the city's wastewater treatment plant influent and effluent and estimated the potential risk for the environment. The hospital use of certain antivirals and drugs used for sedo-analgesia were dramatically increased during the first wave (cisatracurium was multiplied by 25 and lopinavir/ritonavir by 20). A mean of 1.632 daily defined doses of hydroxychloroquine were used during the period of February-May 2020. In this study we report the first positive detection of hydroxychloroquine ever in the environment. We also show the second positive report of lopinavir. Low risk was estimated for hydroxychloroquine, lopinavir and ritonavir (Risk quotients (RQ) <1), and medium risk for azithromycin (RQ 0f 0.146).

Effect of high-pressure treatment and storage temperature on top-quality (Montanera) Iberian dry-cured pork sausages (chorizo).

The stability after hydrostatic high pressure (HHP) (600 MPa/8 min/10 °C) and 180 days of storage at 4 and 20 °C was evaluated on Iberian dry-cured pork sausages (chorizo) packaged sliced or as half-pieces from pigs raised outdoors. Microbiological, physical-chemical, oxidative, and sensory changes were analyzed. The evolution of mesophilic aerobic and molds and yeasts counts was different in the half and sliced packaged pork sausages after processing and during storage. Sliced and half-packaged pork sausages had instrumental color stability after HHP and during storage. TBA-RS values were quite stable in both products. Protein oxidation values of pork sausage in half-products were increased by at 20 °C. In sliced pork sausage, both HPP and 20 °C storage favored the development of protein oxidation at the end of storage. In the sensory analysis, the sliced product developed more rancidity than the half-pieces during the storage. Therefore, the storage temperature has great importance for the preservation of dry-cured pork sausages, the increases of protein oxidation, and rancidity could reduce the shelf-life at these conditions. The presentation of the product is also relevant when HHP is applied, and this would also compromise the stability of the product when it is stored at room temperature. PRACTICAL APPLICATION: Chorizo is a traditional dry-fermented pork sausage that is generally considered to be microbiologically safe. However, the initial contamination of the raw materials, and some processes, such as the slicing or packaging, can compromise the safety of these products. Additionally, packaged dry-cured sausages require long shelf-life, and although they are normally stored at refrigeration temperature; sometimes, they are preserved at room temperature. The application of hydrostatic high pressure could increase the safety of dry-cured meat products even when they are stored at room temperature. Initial characteristics of each type of pork sausage could determine their technological behavior during processing or during storage under different conditions.

Defining tetrahydrobiopterin responsiveness in phenylketonuria: Survey results from 38 countries.

BACKGROUND: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. METHODS: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). RESULTS: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. CONCLUSION: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.

Survive or swim: different relationships between migration potential and larval size in three sympatric Mediterranean octocorals.

Knowledge about migration potential is key to forecasting species distributions in changing environments. For many marine benthic invertebrates, migration happens during reproduction because of larval dispersal. The present study aims to test whether larval size can be used as a surrogate for migration potential arising from larval longevity, competence, sinking, or swimming behavior. The hypothesis was tested using larvae of three sympatric gorgonian species that release brooded lecithotrophic larvae in the same season: Paramuricea clavata, Corallium rubrum and Eunicella singularis. Despite different fecundities and larval sizes, the median larval longevity was similar among the three species. Free-fall speed increased with larval size. Nevertheless, the only net sinkers were the P. clavata larvae, as swimming was more common than free fall in the other two species with larger larvae. For the other two species, swimming activity frequency decreased as larval size increased. Interestingly, maximum larval longevity was lowest for the most active but intermediately sized larvae. Larval size did not covary consistently with any larval traits of the three species when considered individually. We thus advise not using larval size as a surrogate for migration potential in distribution models. The three species exemplified that different mechanisms, i.e., swimming activity or larval longevity, resulting from a trade-off in the use of energy reserves can facilitate migration, regardless of life history strategy.

Correction to: PKU dietary handbook to accompany PKU guidelines.

An amendment to this paper has been published and can be accessed via the original article.

PKU dietary handbook to accompany PKU guidelines.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. MAIN BODY: In 2017 the first European PKU Guidelines were published. These guidelines contained evidence based and/or expert opinion recommendations regarding diagnosis, treatment and care for patients with PKU of all ages. This manuscript is a supplement containing the practical application of the dietary treatment. CONCLUSION: This handbook can support dietitians, nutritionists and physicians in starting, adjusting and maintaining dietary treatment.

Foliculitis por larvas de nematodo: una infrecuente causa de foliculitis en viajeros / Hookworm: An Uncommon Cause of Folliculitis in Travelers

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Resilience of Octocoral Forests to Catastrophic Storms.

After centuries of human-mediated disturbances, Caribbean reef communities are vastly different from those described in the 1950s. Many are functionally dominated by macroalgae, but this community state represents only one of several possibilities into which present-day coral reefs can transition. Octocorals have always been abundant on Caribbean reefs, but increases in their abundance over the last few decades suggest that arborescent octocorals have the potential to expand their populations on reefs that hitherto had been dominated by scleractinians. Here we show that octocoral-dominated communities at three sites on the fringing reefs of St. John, US Virgin Islands, were resilient to the effects of two Category 5 hurricanes in 2017. We describe the dynamics of octocoral communities over five years at three sites on shallow reefs (~9-m depth), and test for the effects of Hurricanes Irma and Maria. The hurricanes depressed the densities of juvenile and adult octocoral colonies as much as 47%. However, there were only weak effects on species richness and the relative abundances of the octocoral species. The hurricanes did not alter patterns of spatial variability in octocoral community structure that existed among sites prior to the storms. The density of octocoral recruits (individuals ≤ 5 cm high) was reduced in the year following the hurricanes, mainly due to a decline in abundance of recruits <0.5 cm, but returned to pre-storm densities in 2019. Persistently high octocoral recruitment provides a mechanism supporting ecological resilience of these communities. Continuing environmental degradation is a threat to all tropical marine communities, but the reefs of St. John illustrate how "octocoral forests" can persist as the structurally dominant community on Caribbean reefs.

PET/TC con 18F-FDG en la recaída extramedular de una leucemia aguda de linaje ambiguo / 18F-FDG PET/CT for extramedullary relapse of acute leukemia of ambiguous lineage

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Vitamina D e insuficiencia cardíaca. Fisiopatología, prevalencia, y asociación pronóstica / Vitamin D and heart failure. Pathophysiology, prevalence,and prognostic association

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Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Effects of Wood Density on Aquatic Insect Communities in a Cuban Montane Rainforest Stream.

We tested whether hardness or different wood carbon densities, considered as the concentration of carbon structural compounds, influence functional feeding groups and species richness of aquatic insects in a tropical stream. We expected that harder woods would harbor aquatic insect communities with species richness and functional food group profile different from softwoods. We also expected that collector-gatherers and collector-filterers will be more abundant in softwood because harder woods are less substrate suitable for biofilm production. Aquatic insects associated with the following plants were analyzed: Gomidesia lindeniana with high-density, Psychotria grandis with medium-density, and Meriania leucantha with low-density wood. Diptera and Ephemeroptera were the most abundant groups sampled in the woods. Psychotria grandis shows higher concentrations of lignin, cellulose, and hemicellulose, followed by G. lindeniana and M. leucantha. Breakdown rates are different among plant species with M. leucantha having four times highest breakdown rates and on average three more species in the species richness value. We did not find significant differences in the composition of insect species associated with the plants. We found evidence that the richness and functional organization of aquatic insect communities were mostly related to the breakdown rates and lignin amount of the woods. Plants that decompose faster on average have three more species and two more insect functional groups. Our findings suggest that the loss of high carbon density trees in tropical forests can affect aquatic biodiversity.

Human acute myeloid leukemia cells express Neurokinin-1 receptor, which is involved in the antileukemic effect of Neurokinin-1 receptor antagonists.

The substance P/neurokinin-1 receptor system has been implicated in tumor cell proliferation. Neurokinin-1 receptor has been identified in different solid tumors but not frequently in hematopoietic malignant cells. We investigated the presence of the Neurokinin-1 receptor in acute myeloid leukemia cell lines (KG-1 and HL-60), demonstrating that acute myeloid leukemia cell lines overexpress the truncated Neurokinin-1 receptor isoform compared with lymphocytes from healthy donors. Using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we demonstrated that substance P induced cell proliferation in both acute myeloid leukemia cell lines. We also observed that four different Neurokinin-1 receptor antagonists (L-733,060, L-732,138, CP 96-345 and aprepitant) elicited inhibition of acute myeloid leukemia cell growth lines in a concentration-dependent manner, while growth inhibition was only marginal in lymphocytes; the specific antitumor action of Neurokinin-1 receptor antagonists occurs via the Neurokinin-1 receptor, and leukemia cell death is due to apoptosis. Finally, administration of high doses of daily intraperitoneal fosaprepitant to NOD scid gamma mice previously xenografted with the HL60 cell line increased the median survival from 4 days (control group) to 7 days (treated group) (p = 0.059). Taken together, these findings suggest that Neurokinin-1 receptor antagonists suppress leukemic cell growth and may be considered to be potential antitumor drugs for the treatment of human acute myeloid leukemia.