Increased dominance of heat-tolerant symbionts creates resilient coral reefs in near-term ocean warming.

Climate change is radically altering coral reef ecosystems, mainly through increasingly frequent and severe bleaching events. Yet, some reefs have exhibited higher thermal tolerance after bleaching severely the first time. To understand changes in thermal tolerance in the eastern tropical Pacific (ETP), we compiled four decades of temperature, coral cover, coral bleaching, and mortality data, including three mass bleaching events during the 1982 to 1983, 1997 to 1998 and 2015 to 2016 El Niño heatwaves. Higher heat resistance in later bleaching events was detected in the dominant framework-building genus, Pocillopora, while other coral taxa exhibited similar susceptibility across events. Genetic analyses of Pocillopora spp. colonies and their algal symbionts (2014 to 2016) revealed that one of two Pocillopora lineages present in the region (Pocillopora "type 1") increased its association with thermotolerant algal symbionts (Durusdinium glynnii) during the 2015 to 2016 heat stress event. This lineage experienced lower bleaching and mortality compared with Pocillopora "type 3", which did not acquire D. glynnii. Under projected thermal stress, ETP reefs may be able to preserve high coral cover through the 2060s or later, mainly composed of Pocillopora colonies that associate with D. glynnii. However, although the low-diversity, high-cover reefs of the ETP could illustrate a potential functional state for some future reefs, this state may only be temporary unless global greenhouse gas emissions and resultant global warming are curtailed.

Insights into the early transcriptomic response against watermelon mosaic virus in melon.

BACKGROUND: Watermelon mosaic virus (WMV) is one of the most prevalent viruses affecting melon worldwide. Recessive resistance to WMV in melon has previously been reported in the African accession TGR-1551. Moreover, the genomic regions associated to the resistance have also been described. Nevertheless, the transcriptomic response that might infer the resistance to this potyvirus has not been explored. RESULTS: We have performed a comparative transcriptomic analysis using mock and WMV-inoculated plants of the susceptible cultivar "Bola de oro" (BO) and a resistant RIL (Recombinant inbred line) derived from the initial cross between "TGR-1551" and BO. In total, 616 genes were identified as differentially expressed and the weighted gene co-expression network analysis (WGCNA) detected 19 gene clusters (GCs), of which 7 were differentially expressed for the genotype x treatment interaction term. SNPs with a predicted high impact on the protein function were detected within the coding regions of most of the detected DEGs. Moreover, 3 and 16 DEGs were detected within the QTL regions previously described in chromosomes 11 and 5, respectively. In addition to these two specific genomic regions, we also observde large transcriptomic changes from genes spread across the genome in the resistant plants in response to the virus infection. This early response against WMV implied genes involved in plant-pathogen interaction, plant hormone signal transduction, the MAPK signaling pathway or ubiquitin mediated proteolysis, in detriment to the photosynthetic and basal metabolites pathways. Moreover, the gene MELO3C021395, which coded a mediator of RNA polymerase II transcription subunit 33A (MED33A), has been proposed as the candidate gene located on chromosome 11 conferring resistance to WMV. CONCLUSIONS: The comparative transcriptomic analysis presented here showed that, even though the resistance to WMV in TGR-1551 has a recessive nature, it triggers an active defense response at a transcriptomic level, which involves broad-spectrum resistance mechanisms. Thus, this study represents a step forward on our understanding of the mechanisms underlaying WMV resistance in melon. In addition, it sheds light into a broader topic on the mechanisms of recessive resistances.

Defining the Biology of Estrogen Receptor-Low-Positive Breast Cancer.

BACKGROUND: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score® (RS) assay in this population. METHODS: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1-10%), HER2- breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined. Finally, patients with ER-low+, HER2- breast cancer treated at DF/BCC from 2011 to 2020 without prior RS results and in whom tissue was available to perform the assay were identified. RS results, treatment, recurrence and breast cancer-specific survival (BCSS) were determined. RESULTS: Of 1033 patients in TCGA, ER percentage and PAM50 subtype were available for 342 (33.1%) patients. Forty-six (13.5%) had ER-low+/HER2- tumors, among whom 82.6% were basal and 4.3% were luminal A. Among 3423 patients with ER-low+/HER2- disease in the NCDB, RS results were available for 689 (20.1%) patients; 67% had an RS ≥26. In our institutional database, only two patients with ER-low+/HER2- disease and an RS were identified, both with RS ≥26. Among 37 patients in our institutional cohort without prior RS, 35 (97.4%) had an RS ≥26, determined with testing. After a median follow-up of 40 months (range 3-106), three patients, all treated with chemotherapy, recurred. Three-year BCSS was 97.0% (95% confidence interval 96.9-97.1%). CONCLUSIONS: Most ER-low+/HER2- breast cancers are basal-like, with RS ≥26 suggesting these tumors are similar to triple-negative disease.

Rubble persistence under ocean acidification threatened by accelerated bioerosion and lower-density coral skeletons.

As the balance between erosional and constructive processes on coral reefs tilts in favor of framework loss under human-induced local and global change, many reef habitats worldwide degrade and flatten. The resultant generation of coral rubble and the beds they form can have lasting effects on reef communities and structural complexity, threatening the continuity of reef ecological functions and the services they provide. To comprehensively capture changing framework processes and predict their evolution in the context of climate change, heavily colonized rubble fragments were exposed to ocean acidification (OA) conditions for 55 days. Controlled diurnal pH oscillations were incorporated in the treatments to account for the known impact of diel carbonate chemistry fluctuations on calcification and dissolution response to OA. Scenarios included contemporary pH (8.05 ± 0.025 diel fluctuation), elevated OA (7.90 ± 0.025), and high OA (7.70 ± 0.025). We used a multifaceted approach, combining chemical flux analyses, mass alteration measurements, and computed tomography scanning images to measure total and chemical bioerosion, as well as chemically driven secondary calcification. Rates of net carbonate loss measured in the contemporary conditions (1.36 kg m-2 year-1) were high compared to literature and increased in OA scenarios (elevated: 1.84 kg m-2 year-1 and high: 1.59 kg m-2 year-1). The acceleration of these rates was driven by enhanced chemical dissolution and reduced secondary calcification. Further analysis revealed that the extent of these changes was contingent on the density of the coral skeleton, in which the micro- and macroborer communities reside. Findings indicated that increased mechanical bioerosion rates occurred in rubble with lower skeletal density, which is of note considering that corals form lower-density skeletons under OA. These direct and indirect effects of OA on chemical and mechanical framework-altering processes will influence the permanence of this crucial habitat, carrying implications for biodiversity and reef ecosystem function.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

A cohort analysis of familial partial lipodystrophy from two Mediterranean countries.

AIM: To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications. MATERIALS AND METHODS: An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted. RESULTS: Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P = .01). Cardiovascular events were a major cause of death. CONCLUSIONS: Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances.

Tracking People Living with HIV in Loss to Follow Up in Central Brazil: A Call for Attention to Health Services.

Despite the effectiveness of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a global public health concern. However, weaknesses in its management regarding access to integrated HIV care include treatment gaps and loss to follow-up (LTFU) from antiretroviral treatment (ART). This study aimed to characterize the epidemiological and clinical profiles of people living with HIV/AIDS (PLHA) in LTFU from HIV care in Campo Grande, Central Brazil. This retrospective cross-sectional study was conducted between January 2021 and April 2022 using secondary data from PLHA who had LTFU in Campo Grande. A total of 852 patients with PLHA were included in this study. The majority of participants in LTFU were male (63.1%), had a CD4 cell count > 200 cells/mm3 (68.2%), and had been treated for ≥ 3 months (86.4%). Only 287 (33.7%) participants had undetectable HIV viral load. Of the total number of patients who returned to treatment during the study period, 448 (54.3%) were LTFU-positive. The tracking strategy was not applied to 556 (65.26%) patients, and 44.4% of the participants had been in spontaneous demand. These results highlight the relevance of patient-centered interventions and the need to ensure early treatment and promote retention in care systems with consequent viral suppression, impacting the healthcare indicators of the population, with emphasis on health managers and stakeholders in HIV care.

How to explain the beneficial effects of leukocyte- and platelet-rich fibrin.

The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.

High silent prevalence of human herpesvirus 1 (HSV-1) infection affecting the indigenous reservation of the municipality of Dourados, Central-West Brazil.

BACKGROUND: The indigenous population located in the central region of Brazil, is the second largest in terms of population size in the country. The Indigenous Reserve of Dourados has risk factors that increase the vulnerability of the indigenous population to infectious diseases, especially Human alphaherpesvirus (HSV-1), a neglected disease with high prevalence in priority populations in developing countries. The virus can also cause many more severe diseases, including widespread neonatal infections, herpetic keratitis, and herpes encephalitis, which can be fatal if left untreated. We estimated the prevalence of anti-HSV-1 antibodies and correlated it with the demographic and behavioral characteristics of the Indigenous population of the Jaguapirú and Bororó villages (Dourados, Mato Grosso do Sul (MS), Brazil). METHODS: Our approach was cross-sectional. From March 2017 to November 2018. Using anti-HSV-1 (Gg1) IgM and anti-HSV-1 (gG1) IgG Euroimmun and the detection and quantification of HSV-1 viral load in plasma samples, through real-time PCR. The maps were constructed using QGIS and the statistical analyses using R Studio software. RESULTS: A total of 1138 individuals (> 18 years old) were enrolled. The prevalence of anti-HSV-1 IgM and IgG were 20% and 97.5%, respectively. The prevalence of anti-HSV-1 antibodies for IgG was higher in both sexes. Anti-HSV-1 IgM antibodies were present in 17.1%, 21.2%, 12.5%, and 22% of the participants with urinary problems, genital wounds, genital warts, and urethral discharge, respectively. Real-time PCR was used for confirmatory testing; HSV-1 DNA was detected in 25.6% (54/211) of anti-HSV1 IgM-positive samples. Viral loads ranged from 5.99E + 02 to 3.36E + 13. CONCLUSIONS: The seroprevalence of HSV-1 IgM and detection of HSV-1 DNA in the Indigenous population confirmed high silent prevalence. Furthermore, the seroprevalence of HSV-1 in the Indigenous population was higher than that reported in the general adult Brazilian population. Various socioeconomic factors, drug use, and health and sexual behaviors could contribute to the facilitation of HSV-1 transmission in the Indigenous population. Our results may help develop culturally appropriate intervention programs that eliminate health access barriers and improve the implementation of public health policies aimed at promoting information regarding the prevention, treatment, and control of HSV-1 infection in Brazilian Indigenous populations.

How Imaging Advances Are Defining the Future of Precision Radiation Therapy.

Radiation therapy is fundamental in the treatment of cancer. Imaging has always played a central role in radiation oncology. Integrating imaging technology into irradiation devices has increased the precision and accuracy of dose delivery and decreased the toxic effects of the treatment. Although CT has become the standard imaging modality in radiation therapy, the development of recently introduced next-generation imaging techniques has improved diagnostic and therapeutic decision making in radiation oncology. Functional and molecular imaging techniques, as well as other advanced imaging modalities such as SPECT, yield information about the anatomic and biologic characteristics of tumors for the radiation therapy workflow. In clinical practice, they can be useful for characterizing tumor phenotypes, delineating volumes, planning treatment, determining patients' prognoses, predicting toxic effects, assessing responses to therapy, and detecting tumor relapse. Next-generation imaging can enable personalization of radiation therapy based on a greater understanding of tumor biologic factors. It can be used to map tumor characteristics, such as metabolic pathways, vascularity, cellular proliferation, and hypoxia, that are known to define tumor phenotype. It can also be used to consider tumor heterogeneity by highlighting areas at risk for radiation resistance for focused biologic dose escalation, which can impact the radiation planning process and patient outcomes. The authors review the possible contributions of next-generation imaging to the treatment of patients undergoing radiation therapy. In addition, the possible roles of radio(geno)mics in radiation therapy, the limitations of these techniques, and hurdles in introducing them into clinical practice are discussed. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Immunotherapy for Early-Stage Triple Negative Breast Cancer: Is Earlier Better?

PURPOSE OF REVIEW: In this narrative review, we discuss the optimal timing of immune checkpoint inhibitors (ICI) in early triple negative breast cancer (TNBC), the landscape of predictive biomarkers for the use of immunotherapy, and the mounting literature suggesting a benefit for an early use of ICI. RECENT FINDINGS: TNBC is associated with a poor prognosis relative to other breast cancer subtypes, and until recently, the treatment of TNBC was limited to cytotoxic chemotherapy. In 2021, the immune-checkpoint inhibitor, pembrolizumab, was approved in combination with neoadjuvant chemotherapy for patients with high-risk early stage TNBC. This approval changed the treatment paradigm of early TNBC concomitantly raised several challenges in clinical practice, pertaining to patient selection, toxicity management, and post-neoadjuvant treatment, among others. The introduction of neoadjuvant chemoimmunotherapy has transformed the treatment landscape for early TNBC. However, several challenges, including patient selection, toxicity management, and the identification of predictive biomarkers, need to be addressed. Future research should focus on refining the timing and duration of immunotherapy, optimizing the chemotherapy partner, and exploring novel predictive biomarkers of response or toxicity.

Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

The intestinal microbiome of infants with cow's milk-induced FPIES is enriched in taxa and genes of enterobacteria.

OBJECTIVES: Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis. METHODS: Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology. RESULTS: A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors. CONCLUSION: These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

Structure, governance and delivery of specialist training programs in periodontology and implant dentistry.

AIM: To update the competences and learning outcomes and their evaluation, educational methods and education quality assurance for the training of contemporary specialists in periodontology, including the impact of the 2018 Classification of Periodontal and Peri-implant Diseases and Conditions (2018 Classification hereafter) and the European Federation of Periodontology (EFP) Clinical Practice Guidelines (CPGs). METHODS: Evidence was gathered through scientific databases and by searching for European policies on higher education. In addition, two surveys were designed and sent to program directors and graduates. RESULTS: Program directors reported that curricula were periodically adapted to incorporate advances in diagnosis, classification, treatment guidelines and clinical techniques, including the 2018 Classification and the EFP CPGs. Graduates evaluated their overall training positively, although satisfaction was limited for training in mucogingival and surgical procedures related to dental implants. Traditional educational methods, such as didactic lectures, are still commonly employed, but they are now often associated with more interactive methods such as case-based seminars and problem-based and simulation-based learning. The evaluation of competences/learning outcomes should employ multiple methods of assessment. CONCLUSION: An update of competences and learning outcomes of specialist training in periodontology is proposed, including knowledge and practical application of the 2018 Classification and CPGs. Harmonizing specialist training in periodontology is a critical issue at the European level.

The Applications of Artificial Intelligence for Assessing Fall Risk: Systematic Review.

BACKGROUND: Falls and their consequences are a serious public health problem worldwide. Each year, 37.3 million falls requiring medical attention occur. Therefore, the analysis of fall risk is of great importance for prevention. Artificial intelligence (AI) represents an innovative tool for creating predictive statistical models of fall risk through data analysis. OBJECTIVE: The aim of this review was to analyze the available evidence on the applications of AI in the analysis of data related to postural control and fall risk. METHODS: A literature search was conducted in 6 databases with the following inclusion criteria: the articles had to be published within the last 5 years (from 2018 to 2024), they had to apply some method of AI, AI analyses had to be applied to data from samples consisting of humans, and the analyzed sample had to consist of individuals with independent walking with or without the assistance of external orthopedic devices. RESULTS: We obtained a total of 3858 articles, of which 22 were finally selected. Data extraction for subsequent analysis varied in the different studies: 82% (18/22) of them extracted data through tests or functional assessments, and the remaining 18% (4/22) of them extracted through existing medical records. Different AI techniques were used throughout the articles. All the research included in the review obtained accuracy values of >70% in the predictive models obtained through AI. CONCLUSIONS: The use of AI proves to be a valuable tool for creating predictive models of fall risk. The use of this tool could have a significant socioeconomic impact as it enables the development of low-cost predictive models with a high level of accuracy. TRIAL REGISTRATION: PROSPERO CRD42023443277; https://tinyurl.com/4sb72ssv.

Investigation of the involvement of platelet-activating factor in the control of hypertension by aerobic training. A randomized controlled trial.

Although studies have demonstrated the effectiveness of exercise in controlling systemic arterial hypertension (SAH), the mechanisms involved in this effect are still poorly understood. Thus, this study investigated the impact of aerobic training on the relationship between platelet-activating factor (PAF) circulating levels and blood pressure in hypertensives. Seventy-seven hypertensive subjects were enrolled in this randomized controlled trial (age 66.51 ± 7.53 years, body mass 76.17 ± 14.19 kg). Participants were randomized to two groups: the intervention group (IG, n = 36), composed of hypertensive individuals submitted to an aerobic training protocol, and the control group (CG, n = 41), composed of non-exercised hypertensives. Body mass index, arterial blood pressure, quality of life, respiratory muscle strength, and functional capacity were assessed before and after 12 weeks. PAF and plasma cytokine levels were also evaluated respectively by liquid chromatography coupled with mass spectrometry and enzyme-linked immunosorbent assay. Aerobic training promoted a significant reduction in blood pressure while functional capacity, expiratory muscle strength, and quality of life, PAFC16:0 and PAFC18:1 plasma levels were increased in comparison to the CG (p < 0.05). In addition, multiple correlation analysis indicated a positive correlation [F (3.19) = 6.322; p = 0.001; R2adjusted = 0.499] between PAFC16:0 levels and expiratory muscle strength after aerobic training. Taken together, our findings indicate that PAF may be involved in the indirect mechanisms that control SAH, being mainly associated with increased respiratory muscle strength in hypertensive subjects undergoing aerobic training.

Adjuvant Olaparib for Germline BRCA Carriers With HER2-Negative Early Breast Cancer: Evidence and Controversies.

In the OlympiA study, 1 year of adjuvant olaparib significantly extended invasive disease-free survival and overall survival. The benefit was consistent across subgroups, and this regimen is now recommended after chemotherapy for germline BRCA1/2 mutation (gBRCA1/2m) carriers with high-risk, HER2-negative early breast cancer. However, the integration of olaparib in the landscape of agents currently available in the post(neo)adjuvant setting-ie, pembrolizumab, abemaciclib, and capecitabine-is challenging, as there are no data suggesting how to select, sequence, and/or combine these therapeutic approaches. Furthermore, it is unclear how to best identify additional patients who could benefit from adjuvant olaparib beyond the original OlympiA criteria. Since it is unlikely that new clinical trials will answer these questions, recommendations for clinical practice can be made through indirect evidence. In this article, we review available data that could help guide treatment decisions for gBRCA1/2m carriers with high-risk, early-stage breast cancer.

Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. METHODS: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. RESULTS: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. CONCLUSIONS: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

Antibiotics reduce Pocillopora coral-associated bacteria diversity, decrease holobiont oxygen consumption and activate immune gene expression.

Corals are important models for understanding invertebrate host-microbe interactions; however, to fully discern mechanisms involved in these relationships, experimental approaches for manipulating coral-bacteria associations are needed. Coral-associated bacteria affect holobiont health via nutrient cycling, metabolic exchanges and pathogen exclusion, yet it is not fully understood how bacterial community shifts affect holobiont health and physiology. In this study, a combination of antibiotics (ampicillin, streptomycin and ciprofloxacin) was used to disrupt the bacterial communities of 14 colonies of the reef framework-building corals Pocillopora meandrina and P. verrucosa, originally collected from Panama and hosting diverse algal symbionts (family Symbiodiniaceae). Symbiodiniaceae photochemical efficiencies and holobiont oxygen consumption (as proxies for coral health) were measured throughout a 5-day exposure. Antibiotics altered bacterial community composition and reduced alpha and beta diversity, however, several bacteria persisted, leading to the hypothesis that these bacteria are either antibiotics resistant or occupy internal niches that are shielded from antibiotics. While antibiotics did not affect Symbiodiniaceae photochemical efficiency, antibiotics-treated corals had lower oxygen consumption rates. RNAseq revealed that antibiotics increased expression of Pocillopora immunity and stress response genes at the expense of cellular maintenance and metabolism functions. Together, these results reveal that antibiotic disruption of corals' native bacteria negatively impacts holobiont health by decreasing oxygen consumption and activating host immunity without directly impairing Symbiodiniaceae photosynthesis, underscoring the critical role of coral-associated bacteria in holobiont health. They also provide a baseline for future experiments that manipulate Pocillopora corals' symbioses by first reducing the diversity and complexity of coral-associated bacteria.

Nodal Positivity in Early-Stage Triple-Negative Breast Cancer: Implications for Preoperative Immunotherapy.

BACKGROUND: Adding pembrolizumab to preoperative chemotherapy improves event-free survival in patients with early-stage triple-negative breast cancer (TNBC). However, owing to potential toxicities, the risk-benefit ratio of pembrolizumab must be considered. There is consensus that the addition of immunotherapy should be recommended in node-positive patients. This study is undertaken to determine nodal positivity rates in patients with TNBC presenting with cT1-2N0 disease undergoing upfront surgery and to evaluate the utility of axillary ultrasound and biopsy in the setting of a negative clinical examination. PATIENTS AND METHODS: Patients with cT1-2N0 TNBC undergoing upfront surgery were identified from our institutional database (January 2016-February 2021; n = 343) and from the National Cancer Database (NCDB) (n = 46,015). Pathologic nodal status was determined. A second cohort of patients with cT1-T2 TNBC with a negative clinical examination was defined in our institutional database (n = 499), and utilization of axillary ultrasound was examined. RESULTS: For patients undergoing upfront surgery, pathologically positive nodes were found in 14.6% patients of our institutional cohort: 9.4% cT1a/b, 14.9% cT1c, and 20.8% cT2 tumors. In the NCDB cohort, 13.7% patients were node positive: 4.9% cT1a/b, 11.4% cT1c, and 19.7% cT2 tumors. For patients with a normal clinical examination undergoing axillary ultrasound, 7.5% of cT1c and 8.7% of cT2 had suspicious nodes biopsied and confirmed positive for metastasis. CONCLUSIONS: Pathologic node-positive disease is found in > 10 and 20% patients with cT1cN0 and cT2N0 TNBC, respectively. Axillary ultrasound can be used to identify patients presenting with a normal clinical examination for whom preoperative pembrolizumab should be considered.