Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution.

BACKGROUND: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. RESULTS: We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. CONCLUSIONS: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites.

Gut-gonad crosstalk in mice exposed to a "chemical cocktail" combining metabolomics and microbial profile by amplicon sequencing.

Testes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular metabolome and the possible influence in the gut-gonad crosstalk. For this, BALB/c mice were given flumequine and diclofenac orally in food and potentially toxic trace elements (Cd, Hg, As) in drinking water. A mice group was supplemented with selenium, a well-known antagonist against many pollutants. Our results revealed that the steroid 5-alpha-androstan-17-beta-ol propionate, suggested as a parameter of androgenicity independent of testosterone levels, proline that improves reproductive indicators in male rabbits affected by environmental stress) among others metabolites are only present after CC exposure with rodent and selenium supplemented diet. Selenium also antagonized the up-or down-regulation of anandamide (20:l, n-9) (p < 0.001 and FC 0.54 of CC vs C but p > 0,05 and FC 0.74 of CC-Se vs C), that regulates gonadotropin-releasing hormones in mammals, 2,3-dinor-11b-PGF2a (p < 0.001 and FC 0.12 of CC vs C but p > 0,05 and FC 0.34 of CC-Se vs C), which has been related with reproductive hormones, besides others testicular metabolites altered by the exposure to the CC and reversed the levels to control. Moreover, numerous significant associations between gut microbes and testicular metabolites indicated a possible impact of pollutants in the testes mediated by gut microbiota due to a gut-gonad crosstalk.

Role of vertical and horizontal microbial transmission of antimicrobial resistance genes in early life: insights from maternal-infant dyads.

Early life represents a critical window for metabolic, cognitive and immune system development, which is influenced by the maternal microbiome as well as the infant gut microbiome. Antibiotic exposure, mode of delivery and breastfeeding practices modulate the gut microbiome and the reservoir of antibiotic resistance genes (ARGs). Vertical and horizontal microbial gene transfer during early life and the mechanisms behind these transfers are being uncovered. In this review, we aim to provide an overview of the current knowledge on the transfer of antibiotic resistance in the mother-infant dyad through vertical and horizontal transmission and to highlight the main gaps and challenges in this area.

Predictors of surgical difficulty in upper third molar removal: a prospective cohort study.

BACKGROUND: Upper third molar (U3M) removal is a common surgical procedure. The aims of this study were to assess the patient-specific, radiological and surgical factors related to the difficulty of U3M removal, and to determine the incidence of intraoperative and postoperative complications. MATERIAL AND METHODS: A prospective cohort study was carried out in adult patients undergoing U3M removal. Operative time, surgeon-reported difficulty and the Parant classification were used to assess extraction difficulty. Clinical, radiological and surgical factors were recorded to determine their relationship with surgical difficulty. A descriptive, bivariate and multivariate statistical analysis was carried out. RESULTS: A total of 250 patients were included. The mean operative time was 10.4 (±12.3) minutes, mean surgeon-reported difficulty was 3.2/10 (±2.3). The multivariate analysis showed greater impaction against the second molar and greater soft tissue and bony impaction to significantly increase operative time and surgeon-perceived difficulty. Additionally, surgeon experience was related to perceived difficulty. The overall incidence of intraoperative complications was 0.8%, and no postoperative events were recorded. CONCLUSIONS: Upper third molars in close relation with the roots of the adjacent second molar and with soft tissue and bony impaction are significantly more difficult to extract. Perceived difficulty was related to surgeon experience. This procedure appears to produce few intra- and postoperative complications.

Noninvasive prediction models of intra-amniotic infection in women with preterm labor.

BACKGROUND: Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women. OBJECTIVE: This study modeled the best performing models, integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days. STUDY DESIGN: From 2015 to 2020, data from a cohort of women, who underwent amniocentesis to rule in or rule out intra-amniotic infection or inflammation, admitted with a diagnosis of preterm labor at <34 weeks of gestation at the Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, Spain, were used. At admission, transvaginal ultrasound was performed, and maternal blood and vaginal samples were collected. Using high-dimensional biology, vaginal proteins (using multiplex immunoassay), amino acids (using high-performance liquid chromatography), and bacteria (using 16S ribosomal RNA gene amplicon sequencing) were explored to predict the composite outcome. We selected ultrasound, maternal blood, and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing machine learning that was applied in a validation cohort. RESULTS: A cohort of 288 women with preterm labor at <34 weeks of gestation, of which 103 (35%) had a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days, were included in this study. The sample was divided into derivation (n=116) and validation (n=172) cohorts. Of note, 4 prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal interleukin 6 (using an automated immunoanalyzer), vaginal pH (using a pH meter), vaginal lactic acid (using a reflectometer), and vaginal Lactobacillus genus (using quantitative polymerase chain reaction), with areas under the receiving operating characteristic curve ranging from 82.2% (95% confidence interval, ±3.1%) to 85.2% (95% confidence interval, ±3.1%), sensitivities ranging from 76.1% to 85.9%, and specificities ranging from 75.2% to 85.1%. CONCLUSION: The study results have provided proof of principle of how noninvasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes while improving the use of resources and patient experience.

Impact of "chemical cocktails" exposure in shaping mice gut microbiota and the role of selenium supplementation combining metallomics, metabolomics, and metataxonomics.

Biological systems are exposed to a complex environment in which pollutants can interact through synergistic or antagonistic mechanisms, but limited information is available on the combined effects. To this end, conventional and antibiotic-treated (Abx) mice models were fed regular rodent or selenium (Se) supplemented diets and exposed to a "chemical cocktail" (CC) including metals and pharmaceuticals. Metallomics, metabolomics, and metataxomics were combined to delve into the impact on gut microbiota, plasma selenoproteome, metabolome, and arsenic metabolization. At the molecular level, Se decreased the concentration of the antioxidant glutathione peroxidase in plasma and increased the arsenic methylation rate, possibly favoring its excretion, but not in the Abx and also plasma metabolomes of Abx, and Abx-Se were not differentiated. Moreover, numerous associations were obtained between plasma selenoproteins and gut microbes. Se-supplementation partially antagonizes the gut microbiota alteration caused by Abx, and slightly by CC, but strongly altered profiles were observed in CC-Abx-Se, suggesting synergistic deleterious effects between pollutants, Abx and Se. Moreover, although CC and Abx changed gut microbiota, several common taxa were enriched in CC-Abx and control mice, indicating possible synergistic effects. Our results suggest a potential beneficial impact of supplementation, but mediated by gut microbes being reversed in their absence.

Genomic and biochemical analysis of repeatedly observed variants in DBT in individuals with maple syrup urine disease of Central American ancestry.

Maple syrup urine disease (MSUD) is an intoxication-type inherited metabolic disorder in which hyperleucinemia leads to brain swelling and death without treatment. MSUD is caused by branched-chain alpha-ketoacid dehydrogenase deficiency due to biallelic loss of the protein products from the genes BCKDHA, BCKDHB, or DBT, while a distinct but related condition is caused by loss of DLD. In this case series, eleven individuals with MSUD caused by two pathogenic variants in DBT are presented. All eleven individuals have a deletion of exon 2 (delEx2, NM_001918.3:c.48_171del); six individuals are homozygous and five individuals are compound heterozygous with a novel missense variant (NM_001918.5:c.916 T > C [p.Ser306Pro]) confirmed to be in trans. Western Blot indicates decreased amount of protein product in delEx2;c.916 T > C liver cells and absence of protein product in delEx2 homozygous hepatocytes. Ultrahigh performance liquid chromatography-tandem mass spectrometry demonstrates an accumulation of branched-chain amino acids and alpha-ketoacids in explanted hepatocytes. Individuals with these variants have a neonatal-onset, non-thiamine-responsive, classical form of MSUD. Strikingly, the entire cohort is derived from families who immigrated to the Washington, DC, metro area from Honduras or El Salvador suggesting the possibility of a founder effect.

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.

Mice brain metabolomics after the exposure to a "chemical cocktail" and selenium supplementation through the gut-brain axis.

Several environmental pollutants have been shown to damage brain and affect gut microbiota. Limited evidence is available about the impact of "chemical cocktails" (CC) of xenobiotics on brain metabolome and their possible influence in the gut-brain crosstalk. To this end, BALB/c mice were exposed to heavy metals (As, Hg, Cd) and pharmaceuticals (diclofenac and flumequine) under regular rodent diet or supplemented with selenium (Se). Selenium, an antioxidant well-known for its antagonism against the neurotoxicity of several pollutants, modulated several brain metabolic impairments caused by CC (e.g., brain levels of the excitatory amino acid N-acetyl aspartic acid) by influencing mainly the metabolisms of purine, glycosylate and dicarboxylate, glutamate, glycerophospholipid, alanine and aspartate. Numerous associations were obtained between brain metabolites and gut microbes and they changed after Se-supplementation (e.g., Lactobacillus was positively associated with a brain ceramide, phosphoserine, phosphocholine, vitamin D3 derivative, fatty acids, malic acid, amino acids, and urea after the exposure, but not after Se-supplementation). Our results showed numerous evidences about the impact of CC on brain metabolome, the potential role of Se as an antagonist and their impact on the gut-brain axis. Further research is needed to understand the complex mechanism of action implied on CC-brain-microbiota interactions.

Metallomic and Untargeted Metabolomic Signatures of Human Milk from SARS-CoV-2 Positive Mothers.

SCOPE: Lack of information about the impact of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the elemental and metabolomic profile of human milk (HM). METHODS AND RESULTS: An observational study on HM from mothers with COVID-19 is conducted including a prepandemic control group. Maternal-infant clinical records and symptomatology are recorded. The absolute quantification of elements and untargeted relative metabolomic profiles are determined by inductively coupled plasma mass spectrometry and gas chromatography coupled to mass spectrometry, respectively. Associations of HM SARS-CoV-2 antibodies with elemental and metabolomic profiles are studied. COVID-19 has a significant impact on HM composition. COVID-19 reduces the concentrations of Fe, Cu, Se, Ni, V, and Aluminium (Al) and increases Zn compared to prepandemic control samples. A total of 18 individual metabolites including amino acids, peptides, fatty acids and conjugates, purines and derivatives, alcohols, and polyols are significantly different in HM from SARS-CoV-2 positive mothers. Aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine, and linoleic acid pathways are significantly altered. Differences are obtained depending on COVID-19 symptomatic and asymptomatic status. CONCLUSIONS: This study provides unique insights about the impact of maternal SARS-CoV-2 infection on the elemental and metabolomic profiles of HM that warrants further research due the potential implications for infant health.

Intake of Natural, Unprocessed Tiger Nuts (Cyperus esculentus L.) Drink Significantly Favors Intestinal Beneficial Bacteria in a Short Period of Time.

Horchata is a natural drink obtained from tiger nut tubers (Cyperus esculentus L.). It has a pleasant milky aspect and nutty flavor; some health benefits have been traditionally attributed to it. This study evaluated the effects of an unprocessed horchata drink on the gut microbiota of healthy adult volunteers (n = 31) who consumed 300 mL of natural, unprocessed horchata with no added sugar daily for 3 days. Although there were no apparent microbial profile changes induced by horchata consumption in the studied population, differences could be determined when volunteers were segmented by microbial clusters. Three distinctive enterogroups were identified previous to consuming horchata, respectively characterized by the relative abundances of Blautia and Lachnospira (B1), Bacteroides (B2) and Ruminococcus and Bifidobacterium (B3). After consuming horchata, samples of all volunteers were grouped into two clusters, one enriched in Akkermansia, Christenellaceae and Clostridiales (A1) and the other with a remarkable presence of Faecalibacterium, Bifidobacterium and Lachnospira (A2). Interestingly, the impact of horchata was dependent on the previous microbiome of each individual, and its effect yielded microbial profiles associated with butyrate production, which are typical of a Mediterranean or vegetable/fiber-rich diet and could be related to the presence of high amylose starch and polyphenols.

Evaluación del impacto del confinamiento sobre la salud y el estilo de vida de las personas usuarias de los centros neurorrehabilitadores de Lleida y Reus de la Fundació Esclerosi Múltiple / Evaluation of the impact of lockdown on the health and lifestyle of users of the Fundació Esclerosi Múltiple’s neurorehabilitation centres in Lleida and Reus

Introducción: El día 13 de marzo de 2020 se decretó el estado de alarma con motivo de la pandemia de la COVID-19, lo que supuso un confinamiento domiciliario total en España. Los centros neurorrehabilitadores de la Fundació Esclerosi Múltiple (FEM) atienden a personas diagnosticadas de enfermedades neuroprogresivas con déficits de salud importantes. Analizamos cómo el confinamiento puede afectar a su forma de vida. Objetivos: Evaluar y gestionar el impacto del confinamiento en la persona con esclerosis múltiple (EM) y otras enfermedades neurodegenerativas. Pacientes y métodos: Estudio observacional analítico. Se aplicó un cuestionario anónimo a todas las personas que estaban en tratamiento rehabilitador integral en dos de los centros de la FEM, que incluía características demográficas y clínicas de los sujetos, junto con la evaluación del impacto de la pandemia en la esfera física, social y psicológica. Resultados: Se han analizado un total de 202 encuestas. La edad media de los participantes ha sido de 49,09 años. Un 77,8% presenta EM, mientras que un 22,2% tiene otras patologías. Los síntomas físicos que han aparecido más frecuentemente han sido debilidad muscular, pérdida de equilibrio y fatiga. La población estudiada se ha mantenido activa durante el confinamiento. Más de la mitad no refiere aumento en los síntomas cognitivos, pero sí que aparece, a nivel emocional, un aumento de la sensación de preocupación. Conclusiones: Podemos afirmar que las acciones desplegadas desde la FEM, para reducir las consecuencias del confinamiento, han sido efectivas y han bajado al máximo la aparición de conductas desadaptativas. El estudio también nos ha abierto la puerta a añadir nuevas líneas de intervención.(AU)

Introduction: On 13 March 2020, a state of alarm was declared due to the COVID-19 pandemic, resulting in total lockdown in Spain. The neurorehabilitation centres of the Fundació Esclerosi Múltiple (FEM) provide care for people diagnosed with neuroprogressive diseases with significant health deficits. We look at how lockdown can affect their way of life. Aims: To assess and manage the impact of lockdown on persons with multiple sclerosis (MS) and other neurodegenerative diseases. Patients and methods. Analytical observational study. An anonymous questionnaire was administered to all the patients undergoing comprehensive rehabilitation treatment at two of the FEM centres; the survey included questions on the demographic and clinical characteristics of the subjects, and an assessment of the impact of the pandemic on the physical, social and psychological spheres. Results: A total of 202 surveys were analysed. The average age of the participants was 49.09 years and 77.8% had MS, while 22.2% had other conditions. The most frequently reported physical symptoms were muscle weakness, loss of balance and fatigue. The study population remained active during lockdown. More than half of them did not report any increase in cognitive symptoms, but they did mention an increased sense of worry on an emotional level. Conclusions: We can state that the actions deployed by the FEM to reduce the consequences of lockdown have been effective and have minimised the occurrence of maladaptive behaviours. The study has also opened the door for us to add new lines of intervention.(AU)

[Evaluation of the impact of lockdown on the health and lifestyle of users of the Fundacio Esclerosi Multiple's neurorehabilitation centres in Lleida and Reus]. / Evaluación del impacto del confinamiento sobre la salud y el estilo de vida de las personas usuarias de los centros neurorrehabilitadores de Lleida y Reus de la Fundació Esclerosi Múltiple.

INTRODUCTION: On 13 March 2020, a state of alarm was declared due to the COVID-19 pandemic, resulting in total lockdown in Spain. The neurorehabilitation centres of the Fundacio Esclerosi Multiple (FEM) provide care for people diagnosed with neuroprogressive diseases with significant health deficits. We look at how lockdown can affect their way of life. AIMS: To assess and manage the impact of lockdown on persons with multiple sclerosis (MS) and other neurodegenerative diseases. PATIENTS AND METHODS: Analytical observational study. An anonymous questionnaire was administered to all the patients undergoing comprehensive rehabilitation treatment at two of the FEM centres; the survey included questions on the demographic and clinical characteristics of the subjects, and an assessment of the impact of the pandemic on the physical, social and psychological spheres. RESULTS: A total of 202 surveys were analysed. The average age of the participants was 49.09 years and 77.8% had MS, while 22.2% had other conditions. The most frequently reported physical symptoms were muscle weakness, loss of balance and fatigue. The study population remained active during lockdown. More than half of them did not report any increase in cognitive symptoms, but they did mention an increased sense of worry on an emotional level. CONCLUSIONS: We can state that the actions deployed by the FEM to reduce the consequences of lockdown have been effective and have minimised the occurrence of maladaptive behaviours. The study has also opened the door for us to add new lines of intervention.

TITLE: Evaluación del impacto del confinamiento sobre la salud y el estilo de vida de las personas usuarias de los centros neurorrehabilitadores de Lleida y Reus de la Fundació Esclerosi Múltiple.Introducción. El día 13 de marzo de 2020 se decretó el estado de alarma con motivo de la pandemia de la COVID-19, lo que supuso un confinamiento domiciliario total en España. Los centros neurorrehabilitadores de la Fundació Esclerosi Múltiple (FEM) atienden a personas diagnosticadas de enfermedades neuroprogresivas con déficits de salud importantes. Analizamos cómo el confinamiento puede afectar a su forma de vida. Objetivos. Evaluar y gestionar el impacto del confinamiento en la persona con esclerosis múltiple (EM) y otras enfermedades neurodegenerativas. Pacientes y métodos. Estudio observacional analítico. Se aplicó un cuestionario anónimo a todas las personas que estaban en tratamiento rehabilitador integral en dos de los centros de la FEM, que incluía características demográficas y clínicas de los sujetos, junto con la evaluación del impacto de la pandemia en la esfera física, social y psicológica. Resultados. Se han analizado un total de 202 encuestas. La edad media de los participantes ha sido de 49,09 años. Un 77,8% presenta EM, mientras que un 22,2% tiene otras patologías. Los síntomas físicos que han aparecido más frecuentemente han sido debilidad muscular, pérdida de equilibrio y fatiga. La población estudiada se ha mantenido activa durante el confinamiento. Más de la mitad no refiere aumento en los síntomas cognitivos, pero sí que aparece, a nivel emocional, un aumento de la sensación de preocupación. Conclusiones. Podemos afirmar que las acciones desplegadas desde la FEM, para reducir las consecuencias del confinamiento, han sido efectivas y han bajado al máximo la aparición de conductas desadaptativas. El estudio también nos ha abierto la puerta a añadir nuevas líneas de intervención.

Effect of music therapy on anxiety and pain in the critical polytraumatised patient.

OBJECTIVE: To determine the effectiveness of music therapy on anxiety and pain in critical polytraumatised patients admitted to the resuscitation unit of a tertiary level hospital in Spain. MATERIAL AND METHOD: Randomised clinical trial conducted in a tertiary level hospital, from June 2016 to May 2018. The study sample was 60 patients, 30 belonging to the intervention group (IG), and 30 to the control group (CG). The IG were given a 30-minute music session and heart rate (HR) and blood pressure (BP) were measured. The VAS (Visual Analogue Scale) was applied for anxiety and pain before and after each session. The same measures and scales were applied in the CG who did not receive a music session. The music session comprised 3 parts: the first was standard music selected by music therapists; the second was personalised, chosen by the patient and the third was a new standard. The intervention took place in a booth with headphones. RESULTS: Significant changes in anxiety levels (P<.01) were detected in the group of patients undergoing the intervention, measured with the VAS scale for anxiety, and pain levels (P<.01), measured with the VAS scale for pain. No significant differences were found in the physiological parameters of HR and BP. CONCLUSION: The use of music in critical polytraumatised patients reduces anxiety and pain levels, increasing the patient's well-being and improving the quality of care. Music therapy, therefore, is considered beneficial as a complementary measure in critical care units. It would be worthwhile to continue studies in this and other hospital areas.

Efecto de la musicoterapia sobre la ansiedad y el dolor en el paciente crítico politraumatizado / Effect of music therapy on anxiety and pain in the critical polytraumatised patient

Objetivo Determinar la efectividad de la musicoterapia sobre la ansiedad y el dolor en pacientes críticos politraumatizados ingresados en la unidad de reanimación de un hospital de tercer nivel en España. Material y método Ensayo clínico aleatorizado realizado en un hospital de tercer nivel, desde junio de 2016 a mayo de 2018. La muestra del estudio fue de 60 pacientes, 30 pertenecientes al grupo intervención y 30 al grupo control. El grupo intervención recibió una sesión musical de 30minutos y se midieron los parámetros de frecuencia cardiaca y presión arterial. Se aplicaron las escalas visuales analógicas (EVA) desarrolladas para la ansiedad y para el dolor antes y después de cada sesión. Al grupo control se le aplicaron las mismas medidas y escalas sin recibir sesión musical. La sesión musical estaba compuesta de 3 partes: primera parte de música estándar, seleccionada por musicoterapeutas; segunda parte personalizada, elegida por el paciente, y tercera parte de nuevo estándar. La aplicación de la intervención se realizó en el box mediante auriculares. Resultados Se detectaron cambios significativos en el grupo de pacientes que recibieron la intervención, tanto en los niveles de ansiedad (p<0,01), medidos con la escala EVA para la ansiedad, como en los niveles de dolor (p<0,01), medidos con la escala EVA para el dolor. No se encontraron diferencias significativas en los parámetros fisiológicos de frecuencia cardiaca y presión arterial. Conclusión El uso de la música en pacientes críticos politraumatizados reduce los niveles de ansiedad y dolor, aumentando el bienestar del paciente y mejorando la calidad en sus cuidados. Por ello se considera beneficiosa la musicoterapia como medida complementaria en las unidades de cuidados críticos, y sería conveniente la continuidad de los estudios en esta y otras áreas de hospitalización. (AU)

Objective To determine the effectiveness of music therapy on anxiety and pain in critical polytraumatised patients admitted to the resuscitation unit of a tertiary level hospital in Spain. Material and methodRandomised clinical trial conducted in a tertiary level hospital, from June 2016 to May 2018. The study sample was 60 patients, 30 belonging to the intervention group (IG), and 30 to the control group (CG). The IG were given a 30-minute music session and heart rate (HR) and blood pressure (BP) were measured. The VAS (Visual Analogue Scale) was applied for anxiety and pain before and after each session. The same measures and scales were applied in the CG who did not receive a music session. The music session comprised 3 parts: the first was standard music selected by music therapists; the second was personalised, chosen by the patient and the third was a new standard. The intervention took place in a booth with headphones. Results Significant changes in anxiety levels (P<.01) were detected in the group of patients undergoing the intervention, measured with the VAS scale for anxiety, and pain levels (P<.01), measured with the VAS scale for pain. No significant differences were found in the physiological parameters of HR and BP. Conclusion The use of music in critical polytraumatised patients reduces anxiety and pain levels, increasing the patient's well-being and improving the quality of care. Music therapy, therefore, is considered beneficial as a complementary measure in critical care units. It would be worthwhile to continue studies in this and other hospital areas. (AU)

Maternal diet during pregnancy and intestinal markers are associated with early gut microbiota.

BACKGROUND: Diet has an important role in host-microbiome interplay, which may result in intestinal permeability changes and physiopathological effects at a systemic level. Despite the importance of maternal microbiota as the main contributor to the initial microbial seeding, little is known about the effects of maternal diet during pregnancy on maternal-neonatal microbiota. OBJECTIVES: This study aimed at ascertaining the possible associations between maternal dietary intake during pregnancy and neonatal microbiota at birth and to evaluate the relationship with maternal intestinal markers. METHODS: In a nested cross-sectional study in the longitudinal MAMI cohort, maternal-neonatal microbiota profiling at birth (n = 73) was assessed by 16S rRNA gene sequencing. Maternal intestinal markers as zonulin, intestinal alkaline phosphatase (IAP) activity and faecal calprotectin were measured in faeces. Furthermore, maternal-neonatal clinical and anthropometric data, as well as maternal nutrient intake during pregnancy obtained by FFQ questionnaires, were collected. RESULTS: Maternal diet is associated with both maternal and neonatal microbiota at the time of birth, in a delivery mode-dependent manner. The existing link between maternal diet, intestinal makers and neonatal gut microbiota would be mainly influenced by the intake of saturated (SFA) and monounsaturated fatty acids (MUFA). Members of Firmicutes in the neonatal microbiota were positively associated with maternal fat intake, especially SFA and MUFA, and negatively correlated to fibre, proteins from vegetable sources and vitamins. CONCLUSIONS: Maternal diet during pregnancy, mainly fat intake (SFA and MUFA), was related to intestinal markers, thus likely shifting the microbial transmission to the neonate and priming the neonatal microbial profile with potential health outcomes. CLINICAL TRIAL REGISTRY: NCT03552939.

Effect of music therapy on anxiety and pain in the critical polytraumatised patient. / Efecto de la musicoterapia sobre la ansiedad y el dolor en el paciente crítico politraumatizado.

OBJECTIVE: To determine the effectiveness of music therapy on anxiety and pain in critical polytraumatised patients admitted to the resuscitation unit of a tertiary level hospital in Spain. MATERIAL AND METHOD: Randomised clinical trial conducted in a tertiary level hospital, from June 2016 to May 2018. The study sample was 60 patients, 30 belonging to the intervention group (IG), and 30 to the control group (CG). The IG were given a 30-minute music session and heart rate (HR) and blood pressure (BP) were measured. The VAS (Visual Analogue Scale) was applied for anxiety and pain before and after each session. The same measures and scales were applied in the CG who did not receive a music session. The music session comprised 3 parts: the first was standard music selected by music therapists; the second was personalised, chosen by the patient and the third was a new standard. The intervention took place in a booth with headphones. RESULTS: Significant changes in anxiety levels (P<.01) were detected in the group of patients undergoing the intervention, measured with the VAS scale for anxiety, and pain levels (P<.01), measured with the VAS scale for pain. No significant differences were found in the physiological parameters of HR and BP. CONCLUSION: The use of music in critical polytraumatised patients reduces anxiety and pain levels, increasing the patient's well-being and improving the quality of care. Music therapy, therefore, is considered beneficial as a complementary measure in critical care units. It would be worthwhile to continue studies in this and other hospital areas.

A review of the impact of xenobiotics from dietary sources on infant health: Early life exposures and the role of the microbiota.

Xenobiotics are worldwide distributed and humans are unavoidably exposed to multiple chemical compounds during life, from preconception to adulthood. The human microbiota is mainly settled during early life and modulate host health and fitness. One of the main routes for chemical exposure is by intake of contaminated food and water. Thus, the interplay between diet-xenobiotics-microbiota during pregnancy and perinatal period may have relevant consequences for infant and adult health. Maternal exposure to metal(oid)s, persistent organic pollutants, and some food additives can modify the infant's microbiota with unknown consequences for child or adult health. Toxicants' exposure may also modulate the maternal transfer of microorganisms to the progeny during birth and breastfeeding; however, scarce information is available. The rapid increase in releasing novel chemicals to the environment, the exposure to chemical mixtures, the chronic/low dose scenario, and the delay in science-stakeholders action call for novel and groundbreaking approaches to improve a comprehensive risk assessment in sensitive population groups like pregnant women and neonates, with emphasis on microbiota as modulating factor and target-organ of xenobiotic's toxicity.

Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function.

BACKGROUND: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. METHODS: Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. RESULTS: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. CONCLUSIONS: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. TRIAL REGISTRATION: NCT03552939 . Video Abstract.

Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes.

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are autosomal recessive disorders of propionyl-CoA (P-CoA) catabolism, which are caused by a deficiency in the enzyme propionyl-CoA carboxylase or the enzyme methylmalonyl-CoA (MM-CoA) mutase, respectively. The functional consequence of PA or MMA is the inability to catabolize P-CoA to MM-CoA or MM-CoA to succinyl-CoA, resulting in the accumulation of P-CoA and other metabolic intermediates, such as propionylcarnitine (C3), 3-hydroxypropionic acid, methylcitric acid (MCA), and methylmalonic acid (only in MMA). P-CoA and its metabolic intermediates, at high concentrations found in PA and MMA, inhibit enzymes in the first steps of the urea cycle as well as enzymes in the tricarboxylic acid (TCA) cycle, causing a reduction in mitochondrial energy production. We previously showed that metabolic defects of PA could be recapitulated using PA patient-derived primary hepatocytes in a novel organotypic system. Here, we sought to investigate whether treatment of normal human primary hepatocytes with propionate would recapitulate some of the biochemical features of PA and MMA in the same platform. We found that high levels of propionate resulted in high levels of intracellular P-CoA in normal hepatocytes. Analysis of TCA cycle intermediates by GC-MS/MS indicated that propionate may inhibit enzymes of the TCA cycle as shown in PA, but is also incorporated in the TCA cycle, which does not occur in PA. To better recapitulate the disease phenotype, we obtained hepatocytes derived from livers of PA and MMA patients. We characterized the PA and MMA donors by measuring key proximal biomarkers, including P-CoA, MM-CoA, as well as clinical biomarkers propionylcarnitine-to-acetylcarnitine ratios (C3/C2), MCA, and methylmalonic acid. Additionally, we used isotopically-labeled amino acids to investigate the contribution of relevant amino acids to production of P-CoA in models of metabolic stability or acute metabolic crisis. As observed clinically, we demonstrated that the isoleucine and valine catabolism pathways are the greatest sources of P-CoA in PA and MMA donor cells and that each donor showed differential sensitivity to isoleucine and valine. We also studied the effects of disodium citrate, an anaplerotic therapy, which resulted in a significant increase in the absolute concentration of TCA cycle intermediates, which is in agreement with the benefit observed clinically. Our human cell-based PA and MMA disease models can inform preclinical drug discovery and development where mouse models of these diseases are inaccurate, particularly in well-described species differences in branched-chain amino acid catabolism.