Explore the vast range of titles available.

Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a “stem-like” population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.

Background Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. Results Results showed that Firmicutes was the dominant phylum in the gut, comprising 40–60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

Boron is an essential micronutrient for plants found in different compartments with a high variable content from rocks and soils to waters. Boron is one of the less abundant elements in the earth’s crust. The 10 B, a naturally occurring isotope of boron, has a high neutron capture cross-section. This property makes boron an effective neutron absorber, useful for various environmental, geological and agronomic applications. For example, the B detection in different matrices is key for irrigation and fertilization, waste management or prospection of new deposits, among others. In the present research a number of seven different materials are simulated to calibrate and optimize the signals for boron quantification. The three signals that are sensitive to boron content are calculated at different points for varying geometries in order to increase the sensitivity to boron content. Calibration curves are obtained for varying B contents, and some applications of these are discussed. The conclusions drawn provide a basis for the assessment of the viability of neutron and gamma detectors as calibrating tools within simulated setups.

Sarcopenia is a clinical syndrome characterized by the loss of muscle mass and strength. Hormonal changes that occur early in women may influence protein synthesis and promote muscle atrophy, leading to probable sarcopenia, defined as a loss of muscle strength without an obvious decrease in muscle mass. Various types of exercise have already proven effective in treating sarcopenia. Power training (PT), a subtype of resistance training performed at high speed, has not yet been studied in this population group. A randomized controlled trial will be conducted with three parallel groups: a PT group, a multicomponent training (MT) group, and a no-exercise group. The inclusion criteria will be women over 65 years of age who meet the diagnostic criteria for probable sarcopenia (Hand grip test less than 16 kg and Five Times Sit to Stand Test more than 15 s) according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Two assessments will be conducted at the beginning and at the end of the 32 weeks of intervention, in which variables of body composition (muscle, fat and weight) and functionality (strength and physical performance) will be collected. There will be 3 sessions of 50 minutes per week in each intervention group. The masking strategy will be double-blind. The analysis of intergroup differences will be conducted using multivariate and univariate analysis of variance (MANOVA and ANOVA), as well as pairwise comparisons (Bonferroni corrections). Changes in the degree of sarcopenia and how many women eliminate the risk of sarcopenia (no probable sarcopenia) after the different interventions will be tested. The study aims to investigate the impact of PT in older women at risk of sarcopenia. The expected results are that PT will significantly improve functionality and body composition compared to other forms of exercise (MT) and no physical activity. The results may represent a significant advance in understanding and addressing sarcopenia before it becomes established, providing preventive treatment and new tools whose clinical applicability has been studied.

Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome.

To perform a pilot study to characterize the effect of clinical parameters on the ocular surface microbiome (OSM) in children and adults using 16s ribosomal RNA sequencing. Prospective, cross-sectional study using 16s sequencing to evaluate the OSM. Comparisons were made in bacterial composition by 1) age, 2) gender, 3) sampling location of the ocular and periocular surfaces, and 4) topical drop use. 16s sequencing was performed using Illumina MiSeq 250 and analyzed using Qiime. Thirty patients (15 children [mean 3.7 years], 15 adults [mean 60.4 years]) were sampled. Both principal coordinate analysis and unifrac distance analysis showed significant differences in the composition between the pediatric and adult OSMs (both =0.001). The eyelid margin microbiota did not show any distinct clustering compared to conjunctiva within the pediatric samples but tended to show a distinction between anatomic sites in adult samples. No differences in OSM were noted by topical drop use. 16s sequencing is a useful tool in evaluating the OSM in patients of all ages, showing a distinct difference between pediatric and adult microbiomes.

Chronic lymphocytic leukaemia (CLL) is frequently associated with frailty, impaired physical function, and reduced quality of life. Evidence on the role of exercise in this population is limited. This pilot randomised clinical trial evaluated the effects of a supervised resistance training programme, combined with a home-based physical activity plan, on frailty, body composition, strength, fatigue, quality of life, and mental health in patients with CLL receiving active treatment. Thirty-six patients were randomised to either a home-based physical activity group plus a supervised resistance training programme group ( n  = 18) or a home-based physical activity group ( n  = 14) for eight weeks. The primary outcome was frailty assessed with the Short Physical Performance Battery. Secondary outcomes included body composition, grip strength, fatigue, quality of life, anxiety and depression, and sleep quality. Non-parametric analyses were performed, and effect sizes calculated. No differences between-group were found in frailty. However, participants in the supervised group showed significant improvements in lean mass ( p  = 0.047), dominant hand grip strength ( p  = 0.004), cognitive fatigue ( p  = 0.008), and sleep disturbance ( p  = 0.010). Effect sizes were moderate for anxiety and sleep quality, and small for depression. Adherence exceeded 80% in both groups, and no adverse events related to exercise were reported. Supervised resistance training combined with home-based physical activity is feasible, safe, and well tolerated in patients with CLL. The intervention was associated with preliminary improvements in muscle mass, strength, fatigue, and sleep-related outcomes. Larger and longer trials are needed to confirm these findings.

Nuclear and mitochondrial genomes coexist within cells but are subject to different tempos and modes of evolution. Evolutionary forces such as drift, mutation, selection, and migration are expected to play fundamental roles in the origin and maintenance of diverged populations; however, divergence may lag between genomes subject to different modes of inheritance and functional specialization. Herein, we explore whole mitochondrial genome data and thousands of nuclear single nucleotide polymorphisms to evidence extreme mito-nuclear discordance in the small black-tailed brush lizard, Urosaurus nigricaudus, of the Peninsula of Baja California, Mexico and southern California, USA, and discuss potential drivers. Results show three deeply divergent mitochondrial lineages dating back to the later Miocene (ca. 5.5 Ma) and Pliocene (ca. 2.8 Ma) that likely followed geographic isolation due to trans-peninsular seaways. This contrasts with very low levels of genetic differentiation in nuclear loci (FST < 0.028) between mtDNA lineages. Analyses of protein-coding genes reveal substantial fixed variation between mitochondrial lineages, of which a significant portion comes from non-synonymous mutations. A mixture of drift and selection is likely responsible for the rise of these mtDNA groups, albeit with little evidence of marked differences in climatic niche space between them. Finally, future investigations can look further into the role that mito-nuclear incompatibilities and mating systems play in explaining contrasting nuclear gene flow.

Polyphenols have been shown to be effective against many chronic diseases. These compounds could have a beneficial effect at the cognitive level. The exact mechanism by which they provide positive effects at the cognitive level is not well known, but it is believed that they could counteract neuroinflammation. The objective of this study is to review nutritional interventions that include foods or supplements rich in flavanols, flavonols, or stilbenes to the usual diet on cognitive deterioration in people over 50 years of age. Clinical trials published in PubMed and Web of Science from 1 March 2010 to 1 March 2020 were explored, from which 14 studies were selected. All of them showed some improvement after the intervention. In interventions with flavanols and stilbenes, relevant improvements have been observed both in healthy patients and in patients with established cognitive impairment. Most studies agree that the greatest benefits are found with high doses and longer duration treatments. The changes were fundamentally assessed through cognitive tests, and in some of the studies, through magnetic resonance imaging (fMRI). The type of cognitive test used to assess the effect of the intervention was revealed to be critical. Several studies have also shown improvements in analytical parameters and blood pressure.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198–569) and 628 days (95% CI 579–676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282–391 days), and 402 days (95% CI 286–517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.