Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, i.e., non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant. We evaluated whether UMs, as distinctive functional gut-microbiome signatures, could determine the potential effect of a pomegranate extract (PE) rich in ET-EA on the metabolism of BAs and cholesterol in mild dyslipidaemic overweight-obese individuals, with possible consequences on host-lipid homeostasis and gut health. At the baseline, UM-B presented the highest levels of faecal total and secondary BAs and coprostanol, suggesting that the lipid absorption capacity and gut cytotoxic risk could be augmented in UM-B. PE intake significantly reduced faecal coprostanol and BA production, especially secondary BAs, and modulated the gut microbiome, reducing the gut cytotoxic risk, especially in UM-B individuals. The lowering of faecal microbial coprostanol and BAs and some BA-metabolising bacteria was quantitatively correlated with Uro concentrations, mainly faecal Uro-A. This suggests that PE consumption could exert cardiovascular and gut protection through Uro-A production as a direct driver of the effects and indirectly by reducing the Coriobacteriaceae family and BA pool, known factors involved in the gut absorption of lipids.

Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma.

The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.

Discordant Humoral and T-Cell Response to mRNA SARS-CoV-2 Vaccine and the Risk of Breakthrough Infections in Women with Breast Cancer, Receiving Cyclin-Dependent Kinase 4 and 6 Inhibitors.

Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response.

Competencias sobre geriatría, modalidad de enseñanza y ageísmo en estudiantes de medicina en el contexto de la pandemia por COVID-19

Introducción. La pandemia por COVID-19 forzó a cambiar la educación médica a una modalidad virtual. Esta puede influenciar sobre la calidad de la enseñanza y la percepción que tienen los alumnos sobre los adultos mayores. Objetivo. Evaluar la percepción del auto reporte de cumplimiento de las competencias sobre geriatría (ACCG) y ageísmo, en estudiantes de medicina de universidades de Lima que llevaron el curso de geriatría en modalidad presencial y virtual. Métodos. Estudio transversal en estudiantes de 3 universidades de Lima, Perú que llevaron el curso de geriatría de forma presencial o virtual. El auto reporte de cumplimiento de competencias en geriatría fue medido mediante un puntaje y el ageísmo fue medido con la escala UCLA-GAS. Se realizó el análisis bivariado entre ACCG y el resto de las variables, finalmente se construyó un modelo de regresión lineal. Resultados. Se encontraron las medias del puntaje para ACCG fue de 0,72 (DE = 0,22) para la modalidad presencial y 0,75 (DE = 0,23) para la enseñanza virtual. No encontramos asociación estadística entre las variables de estudio (p = 0,39). La regresión lineal de auto reporte de cumplimiento de competencias en geriatría y ageísmo, fue ajustado por año de la carrera en que cursó geriatría y existencia de otro curso que aborde temas de geriatría, y se encontró que a mayor ACCG, mayor ageísmo. Conclusiones. Hasta el momento, no se puede afirmar que la educación virtual sea inferior a la presencial en lo que respecta generar al cumplimiento auto reportado de competencias en geriatría.

Introduction. The current COVID-19 pandemic has forced medical education to change to a virtual modality. This can influence the quality of teaching and the perception that students have about older adults. Objective. Our objective is to evaluate the perception of the self-report fulfillment of geriatric competencies (SRFGC) in medical students from universities in Lima-Peru, comparing face-to-face and virtual techniques. Methods. A cross-sectional study was designed including students from 3 universities in Lima, Peru who have taken the geriatrics course in person or virtually, measuring the main variables such as ACCG according to the recommendations of the pogoe web portal and ageing the UCLA-GAS scale. Averages and standard deviations were calculated for numerical variables and frequency for categorical variables. Bivariate analysis was also performed between ACCG and the rest of the variables measured. Results. Means 0.72 (SD=0.22) were found for the face-to-face modality and 0.75 (SD=0.23) for virtual teaching. We found no statistical association between the study variables (p value = 0.39), so there is no difference between the SRFGC between the virtual and face-to-face modalities. Through a linear regression model of SRFGC and ageism adjusted to statistically significant variables of the study, it was found that the greater the SRFGC, the greater the ageism. Conclusions. So far, it cannot be said that virtual education is inferior to face-to-face education with regard to the SRFGC.

Hemostatic Efficacy of Absorbable Gelatin Sponges for Surgical Nail Matrixectomy after Phenolization-A Blinded Randomized Controlled Trial.

Background: Some studies have recommended combining germinal matrix excision with phenol ablation in the treatment of onychocryptosis. Matrixectomy after phenolization has been shown to be an effective modification to reduce the drawbacks associated with phenolization alone, although it increases the risk of minor postoperative bleeding. The present study aims to assess the effectiveness and safety of gelatin sponges as hemostatic agents in partial matrixectomy after phenolization. Methods: A comparative clinical trial in parallel groups was designed in 74 halluces (44 patients) with stage I, II, and III onychocryptosis. All participants were randomly assigned to 3 groups: Group A (control group), Group B (conventional gelatin sponge), and Group C (high porosity gelatin sponge). Results: The quantified mean blood loss in the first 48 h after surgery in patients in both experimental groups was significantly lower compared to the control group. The lowest mean blood loss was recorded in Group C (p < 0.001) and followed by Group B (p = 0.005). No adverse effects were recorded in any of the patients included in the experimental groups. Conclusions: Hemostatic gelatin sponges were demonstrated to be effective and safe devices for the control of minor postoperative bleeding associated with matrixectomy after segmental phenolization.

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells' ABC-mediated chemoresistance.

Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

An Integrative Approach to Characterize the Early Phases of Dimethylhydrazine-Induced Colorectal Carcinogenesis in the Rat.

This study aimed to characterize an animal model of colorectal cancer (CRC) in the early stages of disease development. Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2), receiving EDTA-saline injections and two induced groups (CRC1 and CRC2), receiving 1,2-dimethylhydrazine (DMH) injections for seven consecutive weeks. CRC1 and CTRL1 were euthanized at the 11th week, while CRC2 and CTRL2 were euthanized at the 17th week. DMH treatment decreased microhematocrit values and IL-6, ghrelin, and myostatin serum levels. Histopathological analysis of intestinal sections showed that DMH-treated rats were characterized by moderate to severe epithelial dysplasia. An adenoma was observed in one animal (CRC2 group), and the presence of inflammatory infiltrate at the intestinal level was primarily observed in DMH-treated animals. DMH also induced Ki-67 immunoexpression. The gut microbiota analysis showed a higher abundance of Firmicutes, Clostridia, Clostridiales, Peptostreptococcaceae, Blautia, Romboutsia, and Clostridium sensu stricto in CRC than CTRL rats, whereas Prevotellaceae, Prevotella, Akkermansia, and Lactobacillus levels were more prevalent in CTRL animals. Our results suggest that this model could be helpful to investigate chemoprevention in the early stages of CRC.

Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota.

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.

Microfluidic Surgery in Single Cells and Multicellular Systems.

Microscale surgery on single cells and small organisms has enabled major advances in fundamental biology and in engineering biological systems. Examples of applications range from wound healing and regeneration studies to the generation of hybridoma to produce monoclonal antibodies. Even today, these surgical operations are often performed manually, but they are labor intensive and lack reproducibility. Microfluidics has emerged as a powerful technology to control and manipulate cells and multicellular systems at the micro- and nanoscale with high precision. Here, we review the physical and chemical mechanisms of microscale surgery and the corresponding design principles, applications, and implementations in microfluidic systems. We consider four types of surgical operations: (1) sectioning, which splits a biological entity into multiple parts, (2) ablation, which destroys part of an entity, (3) biopsy, which extracts materials from within a living cell, and (4) fusion, which joins multiple entities into one. For each type of surgery, we summarize the motivating applications and the microfluidic devices developed. Throughout this review, we highlight existing challenges and opportunities. We hope that this review will inspire scientists and engineers to continue to explore and improve microfluidic surgical methods.

Análisis clínico-tomográfico en obstrucción de intestino delgado por adherencias según el sitio de obstrucción en la tomografía / Clinical-tomographic analysis in adhesive small bowel obstruction according to obstruction site in the tomography

Introducción. Las adherencias postoperatorias son la causa más frecuente de obstrucción de intestino delgado. La clínica sugiere el diagnóstico, pero de manera poco precisa la causa y el sitio de la obstrucción. La tomografía computarizada contrastada es el estudio óptimo y permite identificar de manera oportuna a los pacientes que requieren intervención quirúrgica. El objetivo de este estudio fue analizar la correlación entre la clínica y el sitio de obstrucción detectado en la tomografía computarizada contrastada de abdomen, en pacientes con sospecha diagnóstica de obstrucción de intestino delgado por adherencias. Métodos. Estudio prospectivo, transversal y analítico de pacientes con sospecha clínica de obstrucción de intestino delgado por adherencias y antecedentes quirúrgicos y su correlación con el sitio de obstrucción detectado en la tomografía computarizada de abdomen contrastada, de pacientes atendidos entre marzo de 2016 y febrero de 2019 en un hospital de segundo nivel. Resultados. Se incluyeron 41 pacientes, la media de edad fue de 59 años y el género masculino el más comprometido (68,3 %, n=28); la ausencia de evacuaciones estuvo presente en 97,5 % (p=0,026). La tomografía computarizada contrastada mostró el sitio de obstrucción en 73 % de los pacientes y la localización de la obstrucción más prevalente fue en íleon distal (31,7 %, n=13). Se asoció a leucocitosis (p=0,041) y a dolor más intenso (p=0,049), sin presentar irritación peritoneal. Conclusión. La obstrucción localizada en el íleon distal se caracterizó por presentar más dolor y mayor recuento leucocitario, sin correlación como factor de riesgo para requerir tratamiento quirúrgico.

Introduction. Postoperative adhesions are the most common cause of small bowel obstruction. The clinical presentation suggests the diagnosis, but imprecisely the cause and the site of the obstruction. Contrast computed tomography is the optimal study and allows the timely identification of patients requiring surgical intervention. The objective of this study was to analyze the correlation between the symptoms and the obstruction site detected in the abdominal contrasted computed tomography in patients with suspected diagnosis of small bowel obstruction due to adhesions. Methods. Prospective, cross-sectional and analytical study of patients with clinical suspicion of small bowel obstruction due to adhesions and surgical history, and its correlation with the obstruction site detected in the abdominal contrasted computed tomography, during March 2016 to February 2019 in a secondary level hospital. Results. Forty-one patients were included, the mean age was 59 years and the male gender was the most frequent (68.3%, n=28); the absence of evacuations was present in 97.5% (p=0.026). Contrast computed tomography showed the obstruction site in 73% of the patients. The most prevalent location of the obstruction was in the distal ileum (31.7%, n=13). It was associated with leukocytosis (p=0.041) and more intense pain (p=0.049), without presenting peritoneal irritation. Conclusion. The obstruction located in the distal ileum was characterized by more pain and a higher white blood cell count, without correlation as a risk factor for requiring surgical treatment

Main drivers of (poly)phenol effects on human health: metabolite production and/or gut microbiota-associated metabotypes?

Despite the high human interindividual variability in response to (poly)phenol consumption, the cause-and-effect relationship between some dietary (poly)phenols (flavanols and olive oil phenolics) and health effects (endothelial function and prevention of LDL oxidation, respectively) has been well established. Most of the variables affecting this interindividual variability have been identified (food matrix, gut microbiota, single-nucleotide-polymorphisms, etc.). However, the final drivers for the health effects of (poly)phenol consumption have not been fully identified. At least partially, these drivers could be (i) the (poly)phenols ingested that exert their effect in the gastrointestinal tract, (ii) the bioavailable metabolites that exert their effects systemically and/or (iii) the gut microbial ecology associated with (poly)phenol metabolism (i.e., gut microbiota-associated metabotypes). However, statistical associations between health effects and the occurrence of circulating and/or excreted metabolites, as well as cross-sectional studies that correlate gut microbial ecologies and health, do not prove a causal role unequivocally. We provide a critical overview and perspective on the possible main drivers of the effects of (poly)phenols on human health and suggest possible actions to identify the putative actors responsible for the effects.

c-Abl regulates a synaptic plasticity-related transcriptional program involved in memory and learning.

Memory consolidation requires activation of a gene expression program that allows de novo protein synthesis. But the molecular mechanisms that favour or restrict that program are poorly understood. The kinase c-Abl can modulate gene expression through transcription factors and chromatin modifiers. Here, we show that c-Abl ablation in the brain improves learning acquisition and memory consolidation in mice. Its absence also affects gene expression profiles in the mouse hippocampus. We found that genes involved in synaptic plasticity and actin cytoskeleton dynamics, such as Arp2 and Thorase, are up-regulated at the mRNA and protein levels in trained c-Abl KO mice and by a chemical-LTP stimulus. Trained c-Abl KO mice also show that dendritic spines are larger than in wild-type mice and present at a higher density. These results indicate that c-Abl kinase is an important part of the mechanism that limits or restricts signalling of relevant gene programs involved in morphological and functional spine changes upon neuronal stimulation.

Tenosynovial Giant Cell Tumor in the Forefoot: Two Case Reports and Literature Review.

Tenosynovial giant cell tumor is the common term used to describe a group of soft-tissue tumors that share a common etiologic link. These tumors are relatively infrequent in the foot and ankle, and occasionally they may be the cause of destruction of the adjacent bone structures. We report the imaging appearance and pathologic findings of two patients with localized tenosynovial giant cell tumor of the forefoot. Both of these patients underwent surgical gross total resection. However, one of the patients experienced a recurrence. Their clinical, radiologic, and pathologic features, with their treatment protocol, are summarized retrospectively, and related literature is reviewed in an attempt to enhance the understanding of these tumor lesions. Clinicians should perform a careful preoperative and postoperative examination and complete tumor surgical resection with the aim of reducing local recurrence.

Analysis of emergency head computed tomography in critically ill oncological patients.

BACKGROUND: Critically ill cancer patients have an increased risk of developing acute neurological signs. The study objective was to evaluate the use and the usefulness of emergency head computed tomography (EHCT) in this category of patients. PATIENTS AND METHODS: This retrospective, single-centre, cohort study included patients with EHCT performed during Intensive Care Unit (ICU) admission for a period of three years. Indications, imagistic findings, type of malignancy, and outcome were evaluated to identify diagnostic yield and correlations between abnormal findings on positive scans, malignancy type, and mortality rate. RESULTS: Sixty-four EHCTs were performed in 54 critically ill cancer patients, with 32 scans (50%) showing previously unknown lesions and considered to be positive. The most frequent abnormal findings were ischemic (15 EHCTs, 47%) and haemorrhagic (13 EHCTs, 40%) lesions. Thirty-eight EHCTs (59%) were indicated for altered mental status, with a positivity rate of 50%. Eighteen EHCTs (48%) were performed in hematological malignancy patients: 9 (50%) of which were positive with 8/9 (89%) displaying hemorrhagic lesions. Twenty EHCTs were performed in solid tumour patients, 10 (50%) of which were positive, with 9/10 (90%) displaying ischemic lesions. Out of 54 patients, 30 (55%) died during ICU stay. The mortality rate was higher in patients with hematological malignancies and positive EHCT (78% vs. 58%). CONCLUSIONS: Diagnostic yield of EHCT in critically ill cancer patients is much higher than in other categories of ICU patients. We support the systematic use of EHCT in critically ill, mainly hemato-oncological patients with nonspecific neurological dysfunction, as it may lead to early identification of intracranial complications.

Pharmacological Therapy Determines the Gut Microbiota Modulation by a Pomegranate Extract Nutraceutical in Metabolic Syndrome: A Randomized Clinical Trial.

SCOPE: Poly-pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenols in poly-medicated MetS patients are unknown. METHODS AND RESULTS: A randomized, placebo-controlled, double-blinded, and crossover trial in poly-medicated MetS patients (n=50) explored whether the effects of a pomegranate extract nutraceutical (PE, 320 mg phenolics/day for 1 month) are affected by the drug therapy. Considering the lipid-lowering (LL-), anti-hypertensive (HP-) and(or) anti-diabetic (AD-) treatments: GM (16S rRNA sequencing), short-chain fatty acids, 40 inflammatory-metabolic and endotoxemia-related biomarkers, associations between biomarkers and GM with 53 cardiometabolic dysfunctions-related single-nucleotide polymorphisms (SNPs), and urolithin metabotypes (UMs) influence are evaluated. Representative SNPs-GM associations after PE include Lactococcus and ClostridiumXIVa with rs5443-GNB3 (G-protein-ß-polypeptide-3) and ClostridiumXIVa with rs7903146-TCF7L2 (transcription-factor-7-like-2) and rs1137101-LEPR (leptin-receptor). PE decreases sICAM-1 in LL-patients and the lipopolysaccharide-binding protein in all the patients. PE does not affect the other patients' markers as a group or stratifying by UMs. After PE, Lactococcus increases in AD-, LL-, and HP-patients, Bifidobacterium increases in LL- and AD-, while Clostridium XIVa decreases in non-LL- and non-HP-patients. CONCLUSION: The prebiotic effect of PE depends on the medication, mainly on HP-treatments. Targeting GM can complement MetS therapy, but the patients' drug therapy should be considered individually.

Urolithins in Human Breast Milk after Walnut Intake and Kinetics of Gordonibacter Colonization in Newly Born: The Role of Mothers' Urolithin Metabotypes.

The maternal-infant transmission of several urolithins through breast milk and the gut colonization of infants by the urolithin-producing bacterium Gordonibacter during their first year of life were explored. Two trials (proof-of-concept study: n = 11; validation study: n = 30) were conducted, where breastfeeding mothers consumed walnuts as a dietary source of urolithin precursors. An analytical method was developed and validated to characterize the urolithin profile in breast milk. Total urolithins ranged from 8.5 to 176.9 nM, while they were not detected in breast milk of three mothers. The mothers' urolithin metabotypes governed the urolithin profile in breast milk, which might have biological significance on infants. A specific quantitative polymerase chain reaction method allowed monitoring the gut colonization of infants by Gordonibacter during their first year of life, and neither breastfeeding nor vaginal delivery was essential for this. The pattern of Gordonibacter establishment in babies was conditioned by their mother's urolithin metabotype, probably because of mother-baby close contact.

Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes.

The full consensus on the role of dietary polyphenols as human-health-promoting compounds remains elusive. The two-way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols' effects. The identification of human metabotypes associated with a differential gut microbial metabolism of polyphenols has opened new research scenarios to explain the inter-individual variability upon polyphenols consumption. The metabotypes unequivocally identified so far are those involved in the metabolism of isoflavones (equol and(or) O-desmethylangolesin producers versus non-producers) and ellagic acid (urolithin metabotypes, including producers of only urolithin-A (UM-A), producers of urolithin-A, isourolithin-A, and urolithin-B (UM-B), and non-producers (UM-0)). In addition, the microbial metabolites (phenolic-derived postbiotics) such as equol, urolithins, valerolactones, enterolactone, and enterodiol, and 8-prenylnaringenin, among others, can exert differential health effects. The knowledge is updated and position is taken here on i) the two-way interaction between GM and polyphenols, ii) the evidence between phenolic-derived postbiotics and health, iii) the role of metabotypes as biomarkers of GM and the clustering of individuals depending on their metabotypes (metabotyping) to explain polyphenols' effects, and iv) the gut microbial metabolism of catecholamines to illustrate the intersection between personalized nutrition and precision medicine.

Urolithin Metabotypes can Anticipate the Different Restoration of the Gut Microbiota and Anthropometric Profiles during the First Year Postpartum.

The metabolism of dietary polyphenols ellagitannins by the gut-microbiota allows the human stratification in urolithin metabotypes depending on the final urolithins produced. Metabotype-A only produces urolithin-A, metabotype-B yields urolithin-B and isourolithin-A in addition to urolithin-A, and metabotype 0 does not produce urolithins. Metabotype-A has been suggested to be 'protective', and metabotype-B dysbiotic-prone to cardiometabolic impairments. We analyzed the gut-microbiome of 40 healthy women and determined their metabotypes and enterotypes, and their associations with anthropometric and gut-microbial changes after 3 weeks, 4, 6, and 12 months postpartum. Metabotype-A was predominant in mothers who lost weight (≥2 kg) (75%) versus metabotype-B (54%). After delivery, the microbiota of metabotype-A mothers changed, unlike metabotype-B, which barely changed over 1 year. The metabotype-A discriminating bacteria correlated to the decrease of the women's waist while some metabotype-B bacteria were inversely associated with a reduction of body mass index (BMI), waist, and waist-to-hip ratio. Metabotype-B was associated with a more robust and less modulating microbial and anthropometric profiles versus metabotype-A, in which these profiles were normalized through the 1-year follow-up postpartum. Consequently, urolithin metabotypes assessment could be a tool to anticipate the predisposition of women to normalize their anthropometric values and gut-microbiota, significantly altered during pregnancy and after childbirth.

Colecistitis hemorrágica: reporte de caso y revisión de la literatura / Hemorrhagic cholecystitis: case report and literature review

Resumen Introducción: La colecistitis hemorrágica es una complicación poco frecuente de la colecistitis aguda con una alta mortalidad. Materiales y Método: Paciente con dolor abdominal en hipocondrio derecho e ictericia. Los exámenes de laboratorio y ultrasonido hepatobiliar mostraron datos sugestivos de colecistitis aguda; durante su estancia hospitalaria presenta deterioro de su estado general, realizándose tomografía computarizada mostrando imágenes sugestivas de colecistitis hemorrágica y hemoperitoneo. Resultados: Laparotomía de urgencia, corroborando los hallazgos tomográficos y resolviéndose satisfactoriamente con la colecistectomía. Discusión: El diagnóstico de colecistitis hemorrágica es difícil ya que sus manifestaciones clínicas de inicio no difieren de la colecistitis aguda, por lo que la sospecha clínica y el adecuado estudio de imagen son importantes para su detección. Conclusión: A pesar que la colecistitis hemorrágica con perforación y hemoperitoneo es una patología muy poco común, de diagnóstico confuso, es importante establecer la realización de una tomografía computarizada abdominal con contraste endovenoso en pacientes con sospecha de colecistitis aguda grave.

Introduction: Hemorrhagic cholecystitis is a rare complication of acute cholecystitis with a high mortality. Materials and Method: Patient with abdominal pain in right hypochondrium and jaundice. Laboratory analyses and hepatobiliary ultrasound suggested acute cholecystitis, however, general worsening during hospital stay was observed and a computed tomography was performed, revealing hemorrhagic cholecystitis and hemoperitoneum. Results: Urgent laparotomy which confirmed tomographic results, successfully solved with cholecystectomy. Discussion: Hemorrhagic cholecystitis diagnosis is difficult as symptoms at the beginning do not differ from acute cholecystitis, then, clinical suspicion and a correct image analysis is crucial for its detection. Conclusion: Although, perforated hemorrhagic cholecystitis with hemoperitoneum is a very rare entity with confused diagnosis, an abdominal computed tomography with intravenous contrast is very important in any patient with severe acute cholecystitis suspicion.