Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.

In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highly metabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletal muscle. Rats were randomly allocated into a normoxia control group (n = 10) and a hypoxia group (n = 30), divided into three groups (0, 6, and 24 h post-MHH). The normoxia situation was recapitulated at the University of Granada, at 662 m above sea level. The MHH situation was performed at the High-Performance Altitude Training Centre of Sierra Nevada located in Granada at 2320 m above sea level. We found a significant increase in mitochondrial supercomplex assembly in the heart as soon as the animals reached 2320 m above sea level and their levels are maintained 24 h post-exposure, but not in skeletal muscle. Furthermore, in skeletal muscle, at 0 and 6 h, there was increased dynamin-related protein 1 (Drp1) expression and a significant reduction in Mitofusin 2. In conclusion, mitochondria from the muscle and heart respond differently to MHH: mitochondrial supercomplexes increase in the heart, whereas, in skeletal muscle, the mitochondrial pro-fission response is trigged. Considering that skeletal muscle was not actively involved in the ascent when the heart was beating faster to compensate for the hypobaric, hypoxic conditions, we speculate that the different responses to MHH are a result of the different energetic requirements of the tissues upon MHH. KEY POINTS: The heart and the skeletal muscle showed different mitochondrial responses to moderate hypobaric hypoxia. Moderate hypobaric hypoxia increases the assembly of the electron transport chain complexes into supercomplexes in the heart. Skeletal muscle shows an early mitochondrial pro-fission response following exposure to moderate hypobaric hypoxia.

Human adaptation to heat in the context of climate change: A conceptual framework.

Climate change is causing serious damage to natural and social systems, as well as having an impact on human health. Among the direct effects of climate change is the rise in global surface temperatures and the increase in the frequency, duration, intensity and severity of heat waves. In addition, understanding of the adaptation process of the exposed population remains limited, posing a challenge in accurately estimating heat-related morbidity and mortality. In this context, this study seeks to establish a conceptual framework that would make it easier to understand and organise knowledge about human adaptation to heat and the factors that may influence this process. An inductive approach based on grounded theory was used, through the analysis of case studies connecting concepts. The proposed conceptual framework is made up of five components (climate change, vulnerability, health risks of heat, axes of inequality and health outcomes), three heat-adaptation domains (physiological, cultural and political), two levels (individual and social), and the pre-existing before a heat event. The application of this conceptual framework facilitates the assistance of decision-makers in planning and implementing effective adaptation measures. Recognizing the importance of addressing heat adaptation as a health problem that calls for political solutions and social changes. Accordingly, this requires a multidisciplinary approach that would foster the participation and collaboration of multiple actors for the purpose of proposing effective measures to address the health impact of the rise in temperature.

The Effects of Acute Deep Seawater Supplementation on Muscle Function after Triathlon.

(1) Background: Trainers and athletes have always sought to reduce the failure of muscle function during long endurance events. However, nowadays, it is a topic that is generating much debate in the scientific field. Currently, deep-sea water (DSW) intake seems to be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to determine whether DSW consumption during a triathlon event could preserve muscle function after exercise. (2) Methods: Nineteen trained male triathletes (age = 39.0 ± 4.25 years; BMI = 23.67 ± 1.81 kg/m2) randomly performed three triathlons, one of them consuming DSW (Totum SPORT 30 AB, Laboratories Quinton International, S.L., Spain), the other consuming isotonic placebo and the last with tap water-hydration. A vertical jump test with countermovement and an isometric muscle strength test were conducted before and after the triathlon test. (3) Results: There was a significant difference between treatment × time during the isometric muscle strength test. Based on the Tukey post hoc analysis, the peak net force decreased statistically in the placebo (p = 0.045) and control conditions (p = 0.026), but not in the experimental condition (p = 0.121). In addition, all of the conditions studied obtained similar results in the countermovement vertical jump after exercise. (4) Conclusions: As a result, consumption of DSW seems to delay the failure of muscle function specifically in isometric exercises but does not improve performance in sports. Thus, DSW does not alter muscle capacity in a negative way; therefore, its consumption may be recommended.

Impact of drought on mental and behavioral disorders, contributions of research in a climate change context. A narrative review.

Mental and behavioral disorders are an important public health problem and constitute a priority for the WHO, whose recommendations include the surveillance of their risk factors. On the other hand, drought episodes have been increasing in frequency and severity in Europe since 1980. Therefore, to review the present knowledge about the impact of drought on mental and behavioral disorders, in the present climate change context, and to underline potential research gaps, could be of major interest. Thus, we performed a narrative review using online academic databases with the aim of identifying relevant literature about the impact of drought on mental and behavioral disorders. To the best of our knowledge, no study in Europe quantifies the potential association between drought and mental disorders. A limited number of studies have found significant associations between droughts (with different temporal ranges) and various measures of mental health. However, according to our review, only three of them quantified the association between drought and objective mental health outcomes, such as number of emergencies due to clinically diagnosed mental disorders or suicides. Additionally, few studies used specific indices as a measure of drought; and finally, as far as authors are aware, none of them has analyzed this relationship adjusting for various other potential environmental confounders. Moreover, the eventual association could vary between different geographical areas within the same country. Therefore, national and regional studies would be especially necessary. Thus, there is a need for specific national and regional studies, in Europe and globally, that assess the impact of specific indices of drought (with different temporal ranges) on objective mental health outcomes controlling for potential environmental confounders. Moreover, the quantification of its cost would be necessary for health prioritization, evidence-based policies and strategic health planning.

Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification.

Antioxidant defenses in biological systems ensure redox homeostasis, regulating baseline levels of reactive oxygen and nitrogen species (ROS and RNS). Oxidative stress (OS), characterized by a lack of antioxidant defenses or an elevation in ROS and RNS, may cause a modification of biomolecules, ROS being primarily absorbed by proteins. As a result of both genome and environment interactions, proteomics provides complete information about a cell's proteome, which changes continuously. Besides measuring protein expression levels, proteomics can also be used to identify protein modifications, localizations, the effects of added agents, and the interactions between proteins. Several oxidative processes are frequently used to modify proteins post-translationally, including carbonylation, oxidation of amino acid side chains, glycation, or lipid peroxidation, which produces highly reactive alkenals. Reactive alkenals, such as 4-hydroxy-2-nonenal, are added to cysteine (Cys), lysine (Lys), or histidine (His) residues by a Michael addition, and tyrosine (Tyr) residues are nitrated and Cys residues are nitrosylated by a Michael addition. Oxidative and nitrosative stress have been implicated in many neurodegenerative diseases as a result of oxidative damage to the brain, which may be especially vulnerable due to the large consumption of dioxygen. Therefore, the current methods applied for the detection, identification, and quantification in redox proteomics are of great interest. This review describes the main protein modifications classified as chemical reactions. Finally, we discuss the importance of redox proteomics to health and describe the analytical methods used in redox proteomics.

A Clustering Study of Dietary Patterns and Physical Activity among Workers of the Uruguayan State Electrical Company.

Recent studies have shown that certain nutrients, specific food groups, or general dietary patterns (DPs) can promote health and prevent noncommunicable chronic diseases (NCCDs). Both developed and developing countries experience a high prevalence of NCCDs due to poor lifestyle habits, DPs, and low physical activity levels. This study aims to examine the dietary, physical activity, sociodemographic, and lifestyle patterns of Uruguayan State Electrical Company workers (the IN-UTE study). A total of 2194 workers participated in the study, providing information about their sociodemographics, lifestyles, and dietary habits through different questionnaires. To identify DPs from 16 food groups, principal component analysis (PCA) was performed. A hierarchical cluster algorithm was used to combine food groups and sociodemographic/lifestyle variables. Four DPs were extracted from the data; the first DP was related to the intake of energy-dense foods, the second DP to the characteristics of the job, the third DP to a Mediterranean-style diet, and the fourth DP to age and body mass index. In addition, cluster analysis involving a larger number of lifestyle variables produced similar results to the PCA. Lifestyle and sociodemographic factors, including night work, working outside, and moderate and intense PA, were significantly correlated with the dietary clusters, suggesting that working conditions, socioeconomic status, and PA may play an important role in determining DPs to some extent. Accordingly, these findings should be used to design lifestyle interventions to reverse the appearance of unhealthy DPs in the UTE population.

Concurrencia de trastorno por consumo de sustancias y de otro trastorno mental en personas en tratamiento por alguno de ellos en España / Co-occurrence of substance use disorders and other mental disorders in people undergoing specific treatment for any of them in Spain

La concurrencia de trastornos por consumo de sustancias (TUS) y de otros trastornos mentales (OTM) es desconocida en su conjunto en España, y su abordaje se hace desde diferentes redes asistenciales. El objetivo del presente estudio era conocer la prevalencia de esta comorbilidad tanto en las redes de tratamiento de las adicciones como en las de salud mental. Se diseñó un estudio observacional, transversal, multicéntrico, con una muestra aleatorizada de pacientes en tratamiento por TUS u OTM en diferentes Comunidades Autónomas (N=1.783). Se completó un cuestionario ad hoc on-line recogiendo variables sociodemográficas, sobre uso de sustancias, y de diagnósticos de TUS y de OTM. Los datos obtenidos en la encuesta arrojan una importante concurrencia de diagnósticos TUS y OTM. Se encontró una elevada prevalencia de OTM en aquellos en tratamiento en redes de adicciones por su TUS (71%) y también tanto de diagnósticos de T.U. de cualquier sustancia (68,9%) como de consumo activo de sustancias (50%, exceptuando tabaco) en las personas en tratamiento por diagnósticos de OTM en redes de salud mental. Y, además, relaciones significativas entre la adicción a determinadas sustancias y trastornos mentales concretos: trastorno de personalidad con todos los TUS; trastornos psicóticos con trastorno por uso de cannabis, pero no de cocaína; trastornos afectivos con trastornos por consumo de cocaína, y trastorno de ansiedad con trastorno por uso de cannabis. Este estudio aporta información preliminar sobre la elevada coexistencia en la práctica clínica habitual de trastornos adictivos y otros trastornos mentales en España, tanto en redes asistenciales de salud mental como específicas de adicciones. (AU)

The co-occurrence of substance use disorders (SUD) and other mental disorders (OMD) is assumed to be high but is, in fact, unknown in Spain; and it is approached from different healthcare networks. The objective of the present study was to know the prevalence of this co-occurrence, both in specific addiction treatment networks and in mental health networks, in Spain. An observational, multicenter cross study, with a randomized sample, of patients under treatment for SUD or OMD in different Autonomous Communities of Spain was carried out (N=1,783). A specific ad hoc online questionnaire collecting sociodemographic variables, substance use and diagnoses of SUD and OMD was completed. The data obtained in the survey show a significant concurrence of SUD and OMD diagnoses (in more than 60% of the patients). A high prevalence of OMD was found in those patients receiving treatment for their SUD (71%), and also of diagnoses of any SUD (68.9%) and active substance use (50%, except tobacco) in people receiving treatment for diagnoses of OMD. Also were found significant relationships between addiction to certain substances and specific mental disorders: personality disorders with all SUDs; psychotic disorders with cannabis use disorder, but not cocaine use disorder; affective disorders with cocaine use disorder, and anxiety disorders with cannabis use disorder. This study provides preliminary information about the high coexistence in routine clinical practice of addictive disorders and other mental disorders in different treatment settings in Spain. (AU)

Protocolos de rehabilitación y fisioterapia en pacientes afectados por COVID-19

La COVID-19 representa una emergencia internacional por los crecientes números de contagiados y fallecidos a nivel mundial. Los pacientes recuperados pueden sufrir afectaciones y secuelas respiratorias, cardiacas y neurológicas, lo que afecta su calidad de vida. El objetivo de este artículo consistió en reconstruir los protocolos de rehabilitación y fisioterapia respiratoria, cardiovascular, neurológica y neuromuscular para pacientes afectados por COVID-19, a partir de evidencias científicas reportadas. Para ello, se realizó una revisión bibliográfica en las principales bases de datos internacionales (PubMed, SciELO, Google Académico, ente otras). Para la búsqueda se utilizaron las palabras claves: COVID-19, síndrome de distrés respiratorio agudo, fisioterapia, rehabilitación respiratoria, Rehabilitación cardiovascular, rehabilitación neuromuscular y neurológica, en inglés y en español. Estos protocolos atribuyen mejorías significativas de las secuelas y en la calidad de vida de los pacientes. Se recomiendan ejercicios de fisioterapia respiratoria en posición decúbito-prono, entrenamiento de músculos inspiratorios, ejercicios aeróbicos y entrenamiento moderado de fuerza muscular. Los resultados de la aplicación de estos protocolos son satisfactorios en la recuperación de los pacientes.

A COVID-19 representa uma emergência internacional devido ao número crescente de pessoas infectadas e falecidas em todo o mundo. Os pacientes recuperados podem sofrer efeitos e sequelas respiratórias, cardíacas e neurológicas, o que afeta sua qualidade de vida. O objetivo deste artigo foi reconstruir os protocolos de reabilitação respiratória, cardiovascular, neurológica e neuromuscular e de fisioterapia para pacientes afetados pela COVID-19, com base em evidências científicas relatadas. Para tanto, foi realizada uma revisão bibliográfica nas principais bases de dados internacionais (PubMed, SciELO, Google Scholar, entre outras). As palavras-chave foram utilizadas para a busca: COVID-19, síndrome do desconforto respiratório agudo, fisioterapia, reabilitação respiratória, reabilitação cardiovascular, reabilitação neuromuscular e neurológica, nos idiomas inglês e espanhol. Esses protocolos atribuem melhorias significativas nas sequelas e na qualidade de vida dos pacientes. São recomendados exercícios de fisioterapia respiratória em posição prona, treinamento muscular inspiratório, exercícios aeróbicos e treinamento moderado de força muscular. Os resultados da aplicação desses protocolos são satisfatórios na recuperação dos pacientes.

The COVID-19 represents an international emergency due to the increasing numbers of infected and deceased people worldwide. Recovered patients may suffer respiratory, cardiac and neurological effects and sequelae, which affects their quality of life. The objective of this article was to reconstruct the respiratory, cardiovascular, neurological and neuromuscular rehabilitation and physiotherapy protocols for patients affected by COVID-19, based on reported scientific evidence. For it, a bibliographic review was carried out in the main international databases (PubMed, sciELO, Google Scholar, among others). The key words were used for the search: COVID-19, acute respiratory distress syndrome, physiotherapy, respiratory rehabilitation, cardiovascular rehabilitation, neuromuscular and neurological rehabilitation, in English and Spanish. These protocols attribute significant improvements in sequelae and in the quality of life of patients. Respiratory physiotherapy exercises in the prone position, inspiratory muscle training, aerobic exercises and moderate muscle strength training are recommended. The results of the application of these protocols are satisfactory in the recovery of patients.

Unbridled Threat of Gas Gangrene in a Patient With Uncontrolled Diabetes Mellitus: A Compelling Case Report of Clostridium perfringens Infection.

Clostridium perfringens, a Gram-positive anaerobic bacterium, is well-known for its association with gas gangrene, a severe and rapidly progressing infection characterized by tissue gas production and necrosis. In this case report, we present the instance of a 64-year-old male with poorly controlled diabetes mellitus who developed a C. perfringens-related infection following a traumatic foot wound. The report emphasizes the critical significance of early diagnosis and aggressive treatment in C. perfringens infections, particularly in patients with underlying risk factors. Detailed accounts of clinical findings, laboratory results, computed tomography, and surgical interventions are provided. A multidisciplinary approach proved essential for successful management. The inherent scholarly value of this case is substantiated by its meticulous documentation of the clinical trajectory, diagnostic modalities, and treatment modalities employed. The intricate collaboration across diverse medical disciplines, the uncommon manifestation of the infection following a traumatic foot wound, and the favorable outcome achieved through prompt and multidisciplinary intervention collectively contribute to the exceptional nature and didactic significance of this case. The dissemination of such clinical experiences assumes paramount importance in advancing medical scholarship, cultivating awareness, and engendering a profound comprehension of the complexities associated with C. perfringens infections, thereby enriching the wider scientific and medical community.

Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.

Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.

Rapidly developed, optimized, and applied wastewater surveillance system for real-time monitoring of low-incidence, high-impact MPOX outbreak.

Recent MPOX viral resurgences have mobilized public health agencies around the world. Recognizing the significant risk of MPOX outbreaks, large-scale human testing, and immunization campaigns have been initiated by local, national, and global public health authorities. Recently, traditional clinical surveillance campaigns for MPOX have been complemented with wastewater surveillance (WWS), building on the effectiveness of existing wastewater programs that were built to monitor SARS-CoV-2 and recently expanded to include influenza and respiratory syncytial virus surveillance in wastewaters. In the present study, we demonstrate and further support the finding that MPOX viral fragments agglomerate in the wastewater solids fraction. Furthermore, this study demonstrates that the current, most commonly used MPOX assays are equally effective at detecting low titers of MPOX viral signal in wastewaters. Finally, MPOX WWS is shown to be more effective at passively tracking outbreaks and/or resurgences of the disease than clinical testing alone in smaller communities with low human clinical case counts of MPOX.

Long-term antibody titers variation in unvaccinated patients receiving convalescent plasma or placebo for severe SARS-CoV-2 pulmonary infection.

BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.

Delayed estrogen actions diminish food consumption without changing food approach, motor activity, or hypothalamic activation elicited by corticostriatal µ-opioid signaling.

Mu-opioid receptor (µ-OR) signaling in forebrain sites including nucleus accumbens (Acb) and ventromedial prefrontal cortex (vmPFC) modulates reward-driven feeding and may play a role in the pathophysiology of disordered eating. In preclinical models, intra-Acb or intra-vmPFC µ-OR stimulation causes overeating and vigorous responding for food rewards. These effects have been studied mainly in male animals, despite demonstrated sex differences and estrogen modulation of central reward systems. Hence, the present study investigated sex differences and estrogen modulation of intra-Acb and intra-vmPFC µ-OR-driven feeding behaviors. First, the dose-related effects of intra-Acb and intra-vmPFC infusions of the µ-OR-selective agonist, DAMGO, were compared among intact female, ovariectomized (OVX) female, and intact male rats. The DAMGO feeding dose-effect function was flattened in intact females relative to the robust, dose-dependent effects observed in OVX females and intact males. Thus, in intact females, intra-Acb DAMGO failed to elevate food intake relative to vehicle, while intra-vmPFC DAMGO elevated food intake, but to a smaller degree compared to males and OVX females. Next, to explore the possible role of estrogen in mediating the diminished DAMGO response observed in intact females, OVX rats were given intra-Acb or intra-vmPFC infusions of DAMGO either immediately after a subcutaneous injection of 17-beta-estradiol 3-benzoate (EB; 5 µg/0.1 mL) or 24 h after EB injection. Intra-Acb DAMGO effects were not changed at the immediate post-EB time point. At the delayed post-EB timepoint, significant lordosis was noted and the duration of intra-Acb DAMGO-driven feeding bouts was significantly reduced, with no change in the number of bouts initiated, locomotor hyperactivity, or Fos immunoreactivity in hypothalamic feeding and arousal systems. Similarly, EB failed to alter the motor-activational effects of intra-vmPFC DAMGO while reducing feeding. These findings indicate that delayed, presumably genomically mediated estrogen actions modulate the µ-OR-generated motivational state by reducing consummatory activity while sparing goal-approach and general arousal/activity. The results additionally suggest that EB regulation of consummatory activity occurs outside of forebrain-µ-OR control of hypothalamic systems.

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity.

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesity-metabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (inter-tissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population.

From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players.

It is estimated that 25% of the world's population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota.

The relative abundance of fecal bacterial species belonging to the Firmicutes and Bacteroidetes phyla is related to plasma levels of bile acids in young adults.

BACKGROUND: Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults. METHODS: Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA. RESULTS: Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA. CONCLUSIONS: The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans.

The Interplay between Microbiota and Chemotherapy-Derived Metabolites in Breast Cancer.

The most common cancer in women is breast cancer, which is also the second leading cause of death in this group. It is, however, important to note that some women will develop or will not develop breast cancer regardless of whether certain known risk factors are present. On the other hand, certain compounds are produced by bacteria in the gut, such as short-chain fatty acids, secondary bile acids, and other metabolites that may be linked to breast cancer development and mediate the chemotherapy response. Modeling the microbiota through dietary intervention and identifying metabolites directly associated with breast cancer and its complications may be useful to identify actionable targets and improve the effect of antiangiogenic therapies. Metabolomics is therefore a complementary approach to metagenomics for this purpose. As a result of the combination of both techniques, a better understanding of molecular biology and oncogenesis can be obtained. This article reviews recent literature about the influence of bacterial metabolites and chemotherapy metabolites in breast cancer patients, as well as the influence of diet.

Porous 8YSZ Ceramics Prepared with Alkali Halide Sacrificial Additives.

8 mol% Y2O3-stabilized ZrO2 (8YSZ) ceramics were prepared with KCl and LiF additions to obtain porous specimens with high skeletal density. Thermogravimetric and differential thermal analyses (TG/DTA) were carried out on 8YSZ and on 8YSZ mixed to 5 wt.% KCl or 5 wt.% LiF as sacrificial pore formers that were thermally removed during sintering. The melting and evaporation of the alkali halides were evaluated by differential thermal analysis. Dilatometric analysis was also carried out following the same TG/DTA temperature profile with results suggesting rearrangement of the 8YSZ particles during LiF and KCl melting. The dilatometric data of 8YSZ green pellets mixed to KCl or LiF exhibited an initial expansion up to the melting of the alkali halide, followed by shrinkage due to sintering evolution with grain growth and pore elimination. The time that the alkali halide molten phase was kept during sintering was found to be an important parameter for obtaining 8YSZ-sintered specimens with specific pore content; bulk density and open porosity could then be tuned by controlling the time the alkali halide remained liquid during sintering. Scanning electron microscopy images of the pellet fracture surfaces showed pores that contributed to increasing the electrical resistivity as evaluated by impedance spectroscopy analysis.

Innova 2020: A Follow-Up Study of the Fecal Microbiota of Infants Using a Novel Infant Formula between 6 Months and 12 Months of Age.

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant's primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period.