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.

[Assessment of blood eosinophil count in respiratory disease from primary care]. / Valoración del recuento sanguíneo de eosinófilos en la patología respiratoria desde atención primaria.

Most physicians in general, and family physicians in particular, are familiar with certain parameters when ordering a hematological study, such as hemoglobin (including hematocrit and its features), leukocytes (including lymphocytes) and platelets. Nevertheless, there are two values that we use to overlook which are eosinophils and basophils. Specifically, eosinophils have a tendency to increase with allergic pathology. This article focuses on this type of cells, helping to interpret the values obtained and highlighting their importance in two of the most frequent respiratory pathologies in primary care: asthma and COPD. In addition to observing how the increase or normality of these parameters condition the diagnosis, phenotype and even the treatment.

Influence of Application Modes on Increasing Bond Strength Longevity of Self-etching and Universal Adhesive Systems to Enamel.

The present study aimed to evaluate the influence of application mode on the short-term microshear bond strength longevity of self-etching and universal adhesive systems to enamel, the failure mode, and the resulting enamel surface micromorphology. Ninety enamel surfaces were obtained from sound third molars, planed, and randomly assigned to nine groups, according to the application mode and the adhesive system (n=10). There were three primer application modes: according to the manufacturer's recommended application time (control), using double the application time recommended for the primer and selective enamel etching. The adhesive systems used were: Clearfil SE Bond (Kuraray), FL-Bond II (SHOFU), and Futurabond U (Voco). At least two resin-bonded composite cylinders (Grandioso Light Flow, Voco) were placed on each enamel surface, and then evaluated for microshear bond strength at 24 hours and 180 days of storage in solution body fluid (SBF) at pH 7.4. Failure modes were evaluated with a stereoscopic microscope at 20× magnification. A micromorphological analysis of the enamel surface was performed under a scanning electron microscope at 5000× magnification before and after the treatments. Mixed models for repeated measures over time showed significant interaction among application modes, adhesive systems, and time periods (p=0.0331). The bond strength of FL-Bond II adhesive to enamel observed after performing selective enamel etching was significantly higher than that observed after applying the control treatment (p=0.0010) at both 24 hours and 180 days. However, no significant difference was observed between the application of this same adhesive at double the time recommended by the manufacturer and the other two application modes (p>0.05). There was also no significant difference in the microshear bond strength for the enamel treatments applied using Clearfil SE Bond and Futurabond U (p>0.05). A significant reduction in bond strength to enamel was observed at the 180-day storage time for all the adhesive systems when selective enamel etching was performed (p<0.0001). No significant association was observed between the adhesive system failure mode and the enamel treatments (p=0.1402 and p=0.7590 for 24 hours and 180 days, respectively). The most prevalent failure was the adhesive type.

Using machine learning with passive wearable sensors to pilot the detection of eating disorder behaviors in everyday life.

BACKGROUND: Eating disorders (ED) are serious psychiatric disorders, taking a life every 52 minutes, with high relapse. There are currently no support or effective intervention therapeutics for individuals with an ED in their everyday life. The aim of this study is to build idiographic machine learning (ML) models to evaluate the performance of physiological recordings to detect individual ED behaviors in naturalistic settings. METHODS: From an ongoing study (Final N = 120), we piloted the ability for ML to detect an individual's ED behavioral episodes (e.g. purging) from physiological data in six individuals diagnosed with an ED, all of whom endorsed purging. Participants wore an ambulatory monitor for 30 days and tapped a button to denote ED behavioral episodes. We built idiographic (N = 1) logistic regression classifiers (LRC) ML trained models to identify onset of episodes (~600 windows) v. baseline (~571 windows) physiology (Heart Rate, Electrodermal Activity, and Temperature). RESULTS: Using physiological data, ML LRC accurately classified on average 91% of cases, with 92% specificity and 90% sensitivity. CONCLUSIONS: This evidence suggests the ability to build idiographic ML models that detect ED behaviors from physiological indices within everyday life with a high level of accuracy. The novel use of ML with wearable sensors to detect physiological patterns of ED behavior pre-onset can lead to just-in-time clinical interventions to disrupt problematic behaviors and promote ED recovery.

Adherencia terapéutica de pacientes con riesgo cardiovascular en atención primaria. Proyecto REAAP / Therapeutic adherence of patients with cardiovascular risk in primary care. REAAP project

Objetivo Describir las percepciones y las experiencias cotidianas de los médicos de atención primaria (AP) en el abordaje de la falta de adherencia terapéutica en pacientes con riesgo cardiovascular, así como sus expectativas y las posibles áreas de mejora. Material y métodos Estudio cualitativo (en el marco del proyecto REAAP: Red de Expertos en Adherencia de Atención Primaria) realizado en varias comunidades autónomas de España a partir de un cuestionario de respuesta abierta completado por médicos de AP. Los escritos se analizaron mediante el método marco o Framework Analysis para orientar la codificación de los temas. Resultados Participaron 18 médicos, de cuyas respuestas se identificaron tres temas principales: abordaje de la adherencia durante la práctica clínica, barreras que dificultan una correcta adherencia e intervenciones para mejorar la adherencia. Las estrategias más señaladas para facilitar la adherencia terapéutica de los pacientes fueron: mejorar la comunicación médico-paciente y la continuidad asistencial, involucrar a las farmacias comunitarias y simplificar el tratamiento prescribiendo fármacos a combinaciones fijas. Conclusiones Los médicos asistenciales de AP apuntan a que no existe una estrategia ideal que por sí sola facilite la adherencia terapéutica, siendo necesario combinar varias intervenciones para optimizarla. Conocer la problemática y las herramientas disponibles y ausentes en la práctica habitual permitirá un mejor abordaje de la adherencia de los pacientes. En esta línea, iniciativas como el proyecto REAAP son un medio importante para que el personal sanitario, y el resto de actores implicados reconozcan la importancia que merece esta cuestión (AU)

Objective To describe the perceptions and daily experiences of primary care (PC) physicians in dealing with the lack of therapeutic adherence in patients with cardiovascular risk, as well as their expectations and possible areas for improvement. Material and methods A qualitative study (within the framework of the REAAP project: Network of Experts in Adherence in Primary Care) carried out in several autonomous communities in Spain using an open-ended questionnaire completed by PC physicians and analyzed using the framework analysis method to guide the coding of the topics. Results Eighteen physicians participated, and three main themes were identified from their responses: an approach to adherence during clinical practice, barriers that hinder the appropriate adherence, and interventions to improve it. The strategies most frequently mentioned to facilitate patients’ therapeutic adherence were improving physician-patient communication and continuity of care, involving community pharmacies, and simplifying treatment by prescribing drugs in fixed combinations. Conclusions There is no single ideal strategy to facilitate therapeutic adherence, and it is necessary to combine several interventions to optimize it. The first step is to understand the problems and the tools available. Initiatives such as the REAAP project are an important means to improve patient adherence, and for healthcare personnel to recognize the importance that this issue deserves (AU)

Proteome of Agave angustifolia Haw.: Uncovering metabolic alterations, over-accumulation of amino acids, and compensatory pathways in chloroplast-deficient albino plantlets.

Amino acids (AA) are essential molecules for plant physiology, acting as precursor molecules for proteins and other organic compounds. Chloroplasts play a vital role in AA metabolism, yet little is known about the impact on AA metabolism of albino plants' lack of chloroplasts. In this study, we conducted a quantitative proteome analysis on albino and variegated somaclonal variants of Agave angustifolia Haw. to investigate metabolic alterations in chloroplast-deficient plants, with a focus on AA metabolic pathways. We identified 82 enzymes involved in AA metabolism, with 32 showing differential accumulation between the somaclonal variants. AaCM, AaALS, AaBCAT, AaIPMS1, AaSHMT, AaAST, AaCGS, and AaMS enzymes were particularly relevant in chloroplast-deficient Agave plantlets. Both variegated and albino phenotypes exhibited excessive synthesis of AA typically associated with chloroplasts (aromatic AAs, BCAAs, Asp, Lys, Pro and Met). Consistent trends were observed for AaBCAT and AaCM at mRNA and protein levels in albino plantlets. These findings highlight the critical activation and reprogramming of AA metabolic pathways in plants lacking chloroplasts. This study contributes to unraveling the intricate relationship between AA metabolism and chloroplast absence, offering insights into survival mechanisms of albino plants.

[Therapeutic adherence of patients with cardiovascular risk in primary care. REAAP project]. / Adherencia terapéutica de pacientes con riesgo cardiovascular en atención primaria. Proyecto REAAP.

OBJECTIVE: To describe the perceptions and daily experiences of primary care (PC) physicians in dealing with the lack of therapeutic adherence in patients with cardiovascular risk, as well as their expectations and possible areas for improvement. MATERIAL AND METHODS: A qualitative study (within the framework of the REAAP project: Network of Experts in Adherence in Primary Care) carried out in several autonomous communities in Spain using an open-ended questionnaire completed by PC physicians and analyzed using the framework analysis method to guide the coding of the topics. RESULTS: Eighteen physicians participated, and three main themes were identified from their responses: an approach to adherence during clinical practice, barriers that hinder the appropriate adherence, and interventions to improve it. The strategies most frequently mentioned to facilitate patients' therapeutic adherence were improving physician-patient communication and continuity of care, involving community pharmacies, and simplifying treatment by prescribing drugs in fixed combinations. CONCLUSIONS: There is no single ideal strategy to facilitate therapeutic adherence, and it is necessary to combine several interventions to optimize it. The first step is to understand the problems and the tools available. Initiatives such as the REAAP project are an important means to improve patient adherence, and for healthcare personnel to recognize the importance that this issue deserves.

Emerging alternatives against Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a significant worry within healthcare institutions and the community. It is one of the leading agents causing severe diarrhea worldwide. Effective management is critical since the morbidity and mortality attributed to CDI have increased exponentially over the past 20 years. Currently, antibiotics are the standard treatment for primary C. difficile infection, but at the same time, they are associated with disease relapse and increased drug resistance. CDI's high recurrence rates, spore generation, and antimicrobial resistance are currently significant challenges that urge the development of new options to combat this infection. This review describes up-and-coming alternatives and how they can mitigate the challenges associated with CDI. Here we have discussed the advantages and challenges of current and experimental alternatives against CDI.

SNAI1-expressing fibroblasts and derived-extracellular matrix as mediators of drug resistance in colorectal cancer patients.

Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.

Chloroplastic pentatricopeptide repeat proteins (PPR) in albino plantlets of Agave angustifolia Haw. reveal unexpected behavior.

BACKGROUND: Pentatricopeptide repeat (PPR) proteins play an essential role in the post-transcriptional regulation of genes in plastid genomes. Although important advances have been made in understanding the functions of these genes, there is little information available on chloroplastic PPR genes in non-model plants and less in plants without chloroplasts. In the present study, a comprehensive and multifactorial bioinformatic strategy was applied to search for putative PPR genes in the foliar and meristematic tissues of green and albino plantlets of the non-model plant Agave angustifolia Haw. RESULTS: A total of 1581 PPR transcripts were identified, of which 282 were chloroplastic. Leaf tissue in the albino plantlets showed the highest levels of expression of chloroplastic PPRs. The search for hypothetical targets of 12 PPR sequences in the chloroplast genes of A. angustifolia revealed their action on transcripts related to ribosomes and translation, photosystems, ATP synthase, plastid-encoded RNA polymerase and RuBisCO. CONCLUSIONS: Our results suggest that the expression of PPR genes depends on the state of cell differentiation and plastid development. In the case of the albino leaf tissue, which lacks functional chloroplasts, it is possible that anterograde and retrograde signaling networks are severely compromised, leading to a compensatory anterograde response characterized by an increase in the expression of PPR genes.

Lysine crotonylation: A challenging new player in the epigenetic regulation of plants.

Lysine crotonylation (Kcr) is a newly discovered post-translational modification, which is structurally and functionally different from the widely studied lysine acetylation. Kcr is found on histones and non-histone proteins, participating in many biological processes through the regulation of chromatin remodeling, metabolism, cell cycle and cellular organization. Among plants, Kcr in histones is not found in the same lysine residues but increases gene expression when it is co-localized with lysine acetylation. Kcr in non-histone proteins is mainly found in the chloroplast, which provides new insight into photosynthesis. In this review, we discuss recent findings on plant Kcr in histone and non-histone proteins, highlighting its biological implications. These findings not only point to new functions for Kcr, but also reveal the mechanisms by which crotonylation regulates cellular processes in plants and may even change the general direction of epigenome and plant regulation.

Properties of the avocado oil extracted using centrifugation and ultrasound-assisted methods.

The aim of this work was to evaluate the technologies effect of cold extraction by centrifugation (CE) and ultrasound-assisted (US-CE) methods without adding water, on the avocado oil yield, nutritional composition, physicochemical characteristics, oxidative stability (oxidation temperature and time, besides activation energy) and accelerated shelf life regarding hexane extraction (control). The US-CE improved the physicochemical properties such as acidity, peroxides, and iodine indexes regarding CE and Control. US-CE improved the yield, nutritional quality of fatty acids, oxidative stability, shelf life, and ω-6/ω-3 ratio regarding CE. Furthermore, US-CE improved the ratio yield/time extraction of the oil and increased the oxidation temperature regarding control. The main advantage of oils extracted using CE and US-CE concerning control was higher oxidative stability. The most representative polyunsaturated fatty acids identified in all treatments were γ-linolenic and conjugated α-linolenic acids. α-linolenic acid was only detected in US-CE and control. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00940-w.

Biopsia selectiva de ganglio centinela en el carcinoma escamoso de vulva. Análisis de seguimiento a 10 años / Sentinel lymph node biopsy procedure in squamous vulvar cancer. 10 years follow-up analysis

OBJETIVO: Aplicación de la biopsia selectiva de ganglio centinela (BSGC) en el carcinoma de vulva en estadios iniciales y análisis de los resultados, recurrencias y complicaciones. MATERIAL Y MÉTODOS: Se revisaron retrospectivamente 40 pacientes con cáncer de vulva y BSGC entre 2008 y 2018. El día de la intervención se rastrearon las cadenas ganglionares inguinales mediante sonda gammadetectora para identificar los ganglios centinela que se extirparon y remitieron para estudio anatomopatológico intraoperatorio. Posteriormente, se realizó seguimiento a largo plazo con análisis de complicaciones, recaída y mortalidad. RESULTADOS: De las 40 pacientes (edad media: 72 años [47-86]), la tasa de detección global por paciente fue del 95%, con un total de 129 ganglios centinela (GC) (3,22 GC/paciente). En tres de 25 pacientes con lesiones tumorales laterales el drenaje fue bilateral y en dos de 15 con lesiones de línea media fue unilateral. De las 40 linfogammagrafías 16 presentaban drenaje bilateral y 24 unilateral. Se obtuvieron un total de 119 GC- y 10 GC+, realizándose vaciamiento en ocho. En el grupo de GC- se incluyeron un caso de bloqueo linfático y un falso negativo. En 12 de 40 pacientes hubo complicaciones posquirúrgicas, cuatro de ellas linfedemas. Durante una mediana de seguimiento de 40 meses, recayeron seis de 10 con GC+ (40% mortalidad) y siete de 30 GC- (16% mortalidad). CONCLUSIONES: La BSGC en cáncer de vulva es la técnica de elección para una correcta estadificación y tratamiento locorregional. Es importante una adecuada estadificación ganglionar previa a la cirugía para evitar posibles bloqueos linfáticos que puedan inducir falsos negativos

AIM: Application of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. MATERIAL AND METHODS: 40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. RESULTS: 40 patients (mean age: 72 years [47-86], the overall detection rate per patient was 95% and a total of 129 Sentinel Lymph Nodes (SLNs) were removed (3.22 SLN/patient). In 3 out of 25 patients with lateral tumour lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN- and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN- group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN- (16% mortality) had recurrences. CONCLUSIONS: SLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN

18F-FDG PET/CT y el síndrome de intolerancia inmunológica en el injerto renal no funcionante / 18F-FDG PET/CT and non-functioning renal graft intolerance syndrome

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