Blood Pressure Control in Pregnant Patients with Chronic Hypertension and Diabetes: Should <130/80 be the Target?

BACKGROUND: The Chronic Hypertension and Pregnancy Study (CHAP) demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure (BP) <130/80 mm Hg. OBJECTIVE: We compared perinatal outcomes in patients with hypertension and diabetes who achieved BP <130/80 versus 130-139/80-89 mm Hg. STUDY DESIGN: This was a secondary analysis of a multi-center randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks' gestation and at least two recorded BP measurements prior to delivery. Average systolic and diastolic BP were calculated using ambulatory antenatal BPs. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). Comparisons were made between those with an average systolic BP <130 mm Hg and average diastolic BP <80 mm Hg and those with an average systolic blood pressure 130-139 mm Hg or diastolic blood pressure 80-89 mm Hg using Student's t-test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates. RESULTS: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed DM prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk (aRR) 0.43, 95% CI 0.30-0.61, p<0.01), with decreased risks specifically of preeclampsia with severe features (aRR 0.35, 95% CI 0.23-0.54) and indicated preterm birth prior to 35 weeks (aRR 0.44, 95% CI 0.24-0.79). The risk of NICU admission was lower in the lower blood pressure group (aRR 0.74, 95% CI 0.59-0.94). No differences were noted in cesarean delivery (aRR 1.04, 95% CI 0.90-1.20), fetal or neonatal death (aRR 0.59, 95% CI 0.12-2.92). SGA less than the 10th percentile was lower in the lower blood pressure group (aRR 0.37, 95% CI 0.14-0.96). CONCLUSION: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes.

Severe Hypertension in Pregnancy: Progress Made and Future Directions for Patient Safety, Quality Improvement, and Implementation of a Patient Safety Bundle.

Hypertensive disorders of pregnancy account for approximately 5% of pregnancy-related deaths in the United States and are one of the leading causes of maternal morbidity. Focus on improving patient outcomes in the setting of hypertensive disorders of pregnancy has increased in recent years, and quality improvement initiatives have been implemented across the United States. This paper discusses patient safety and quality initiatives for hypertensive disorders of pregnancy, with an emphasis on progress made and a patient safety tool: the Alliance for Innovation on Maternal Health's Severe Hypertension in Pregnancy patient safety bundle. Future patient safety and quality directions for the treatment of hypertensive disorders of pregnancy will be reviewed.

Effects of a Veterinary Gastrointestinal Diet on Fecal Characteristics, Metabolites, and Microbiota Concentrations of Adult Cats Treated with Metronidazole.

Antibiotics are used to treat gastrointestinal diseases or infections, but are known to negatively affect stool quality and gut microbiota in cats and dogs. Therefore, identifying dietary strategies that may aid in antibiotic recovery is of interest. The objective of this study was to determine how a veterinary gastrointestinal diet affected the fecal characteristics, metabolite and bile acid (BA) concentrations, and microbiota of cats recovering from metronidazole administration. Twenty-four healthy adult cats were used in an 8-wk completely randomized design study. During a 2-wk baseline, all cats consumed a leading grocery brand diet (GBD). Over the next 2 wk, cats consumed GBD and received metronidazole (20 mg/kg BW twice daily). At wk 4, cats were randomly allotted to one of two treatments [GBD; BLUE Natural Veterinary Diet GI Gastrointestinal Support (BB)] and fed for 4 wk. Fecal scores were recorded daily and fresh fecal samples were collected at wk 2, 4, 5, 6, 7, and 8 for measurement of pH, dry matter (DM) %, metabolites, and microbiota. Microbiota were analyzed by 16S rRNA gene sequencing and qPCR, which was used to calculate dysbiosis index. Data were analyzed as repeated measures using the Mixed Models procedure of SAS 9.4, testing for effects of diet, time and diet*time. Metronidazole had dramatic effects on all outcomes, including increased fecal scores (looser stools), reduced fecal pH and DM%, reduced fecal short-chain fatty acid, branched-chain fatty acid, ammonia, phenol, and indole concentrations, and altered fecal BA concentrations (increased primary BA; reduced secondary BA). Metronidazole reduced fecal bacterial alpha diversity, increased dysbiosis index, and altered the relative abundance of 78 bacterial genera. Fecal outcomes partially recovered over the next 4 wk, with some being impacted by diet. Fecal acetate concentrations were higher after metronidazole in cats fed BB. Dysbiosis index and alpha diversity measures slowly recovered over 4 wk, without diet differences. Recovery of 16 bacterial genera were impacted by diet. Fecal BA profiles demonstrated a prolonged impairment of primary to secondary BA conversion, with cholic acid being lower after metronidazole in cats fed BB. In conclusion, our data demonstrate that metronidazole is a powerful antibiotic that has long-lasting effects on the fecal microbiota and metabolites of cats. Outcome variables slowly recovered over time, but a gastrointestinal diet may aid in recovery.

Robotic-assisted bronchoscopy: a narrative review of systems.

Background and Objective: Robotic-assisted bronchoscopy (RAB) has emerged as an advanced technology for lung cancer diagnosis. This review explores the three approved robotic bronchoscopy systems: Ion™ Endoluminal (Intuitive Surgical, Sunnyvale, CA, USA), Monarch™ (Johnson & Johnson, Redwood City, CA, USA), and Galaxy System™ (Noah Medical, San Carlos, CA, USA), and their different operational systems. This narrative review aims to summarize their findings and outcomes for sampling peripheral pulmonary lesions (PPL) suspected of lung cancer. Methods: A search in PubMed and Google Scholar databases was conducted for articles and abstracts published between January 2018 to May 2024 using the terms "robotic bronchoscopy" or "robotic-assisted bronchoscopy" for biopsy of PPL. Key Content and Findings: Lung cancer is the leading cause of cancer-related mortality. The introduction of RAB aims to improve the feasibility and safety of sampling PPL. Current literature describes high diagnostic yields with low risk of complications, allowing concurrent hilar and mediastinal staging within the same procedure. RAB can potentially improve early diagnosis and treatment of pulmonary malignancies and survival rate in long term, while progressing towards therapeutic applications in the near future. Conclusions: As RAB evolves, its potential as a "one-stop shop" for diagnosis, staging, and treatment can positively impact lung cancer detection, focusing on improved patient-centered outcomes and reducing multiple diagnostic and therapeutic procedures.

Eliciting diverse perspectives to prioritize community actions for biodiversity conservation.

Communities have a strong role in protecting biodiversity. In addition to participation in restoration, a range of actions in the public or private sphere may support biodiversity. Despite this, there is a lack of clarity about what actions should be prioritized for behavior change campaigns. We developed and applied a method to prioritize community actions for biodiversity conservation that incorporates an expert-based assessment of impact and a community-informed measure of the likelihood of uptake. In stage 1, experts (n = 143) completed a survey that quantified the relative impact of actions based on best-worst scaling of perceived impact. In stage 2, surveyed community members (n = 3200) ranked the likelihood of adopting actions based on the ease or difficulty of performing each action, and the opportunity for change based on the proportion of respondents not yet engaging in each behavior. Experts gave the following actions the highest ranking for impact: voting for the environment (first), participating in restoration in ecological priority areas (second), and purchasing and protecting remnant bushland (third). When considering the disciplinary background and institutional background of experts, voting and participating in restoration activities remained in the upper ranked options. However, there was some divergence between these groups. For example, reducing beef consumption was ranked third by university-based experts but ranked 28th by experts based in state government. Overall, community members ranked the following behaviors as most likely to be adopted: following quarantine laws (first), reducing plastic use (second), and managing pets (third). Top likelihood ranking of actions was minimally affected by community characteristics (nature relatedness, gender, location). Integrating these findings, the action ranked most favorably for impact, likelihood, and opportunity was participating in restoration. Choosing actions for behavior change campaigns requires consideration of the entire social-ecological system-from social factors that enable or constrain adoption to the ecological impact of actions across relevant social and ecological contexts.

Inducción de perspectivas diversas para priorizar las acciones comunitarias a favor de la conservación de la biodiversidad Las comunidades juegan un papel importante en la protección de la biodiversidad. Además de participar en la restauración, existe una gama de acciones públicas y privadas que pueden ayudar a la biodiversidad. A pesar de esto, no está claro cuáles acciones deben priorizarse en las campañas de cambio conductual. Desarrollamos y aplicamos un método para priorizar las acciones comunitarias a favor de la conservación de la biodiversidad que incorpora la evaluación por experto del impacto y la medida comunitaria de la probabilidad de captación. En la fase 1, los expertos (n = 143) completaron una encuesta que cuantificó el impacto relativo de las acciones con base en una escala mejor­peor del impacto percibido. En la fase 2, los miembros de la comunidad (n = 3200) clasificaron la probabilidad del éxito de las acciones con base en la proporción de respondientes que todavía no participan en cada comportamiento. Los expertos otorgaron la clasificación más alta para el impacto a las siguientes acciones: votar por el ambiente (primero), participar en la restauración de áreas ecológicas prioritarias (segundo) y adquirir y proteger matorrales remanentes (tercero). Cuando consideramos la formación disciplinaria e institucional de los expertos, la votación y la participación en las actividades de restauración permanecieron en las opciones con clasificación más alta; sin embargo, existió una divergencia entre estos grupos. Por ejemplo, los expertos de las universidades clasificaron en tercero la reducción del consumo de carne de res, pero los expertos del gobierno estatal lo clasificaron en vigésimo octavo. En general, los miembros de la comunidad clasificaron los siguientes comportamientos como los más probables de ser adoptados: seguir las normas de cuarentena (primero), reducir el uso de plásticos (segundo) y el manejo de mascotas (tercero). Las características comunitarias (relación con la naturaleza, género, ubicación) afectaron en lo mínimo a la clasificación más alta de probabilidad de las acciones. Al integrar estos resultados, la acción mejor clasificada en cuanto a impacto, probabilidad y oportunidad fue la participación en la restauración. La selección de acciones para las campañas de cambio conductual requiere que se considere todo el sistema socio ecológico ­ desde los factores sociales que permiten o restringen la conservación hasta las acciones de impacto ecológico relevantes en los contextos sociales y ecológicos.

Effects of Antihypertensive Therapy During Pregnancy on Postpartum Blood Pressure Control.

OBJECTIVE: To compare differences in postpartum blood pressure (BP) control (BP below 140/90 mm Hg) for participants with hypertension randomized to receive antihypertensive treatment compared with no treatment during pregnancy. METHODS: This study was a planned secondary analysis of a multicenter, open-label, randomized controlled trial (The CHAP [Chronic Hypertension and Pregnancy] trial). Pregnant participants with mild chronic hypertension (BP below 160/105 mm Hg) were randomized into two groups: active (antihypertensive treatment) or control (no treatment unless severe hypertension, BP 160/105 mm Hg or higher). Study outcomes were BP control below 140/90 mm Hg (primary) and medication nonadherence based on a composite score threshold (secondary) at the 6-week postpartum follow-up visit. Participants without follow-up BP measurements were excluded from analysis of the BP control outcome. Participants without health care professional-prescribed antihypertensives at delivery were excluded from the analysis of the adherence outcome. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: Of 2,408 participants, 1,684 (864 active, 820 control) were included in the analysis. A greater percentage of participants in the active group achieved BP control (56.7% vs 51.5%; adjusted odds ratio [aOR] 1.22, 95% CI, 1.00-1.48) than in the control group. Postpartum antihypertensive prescription was higher in the active group (81.7% vs 58.4%, P<.001), and nonadherence did not differ significantly between groups (aOR 0.81, 95% CI, 0.64-1.03). CONCLUSION: Antihypertensive treatment of mild chronic hypertension during pregnancy was associated with better BP control below 140/90 mm Hg in the immediate postpartum period.

Mortality Among Children Under Five Years of Age Living With HIV on Antiretroviral Treatment From HIV Case Surveillance Data, Malawi, 2022.

From Malawi's HIV case surveillance, we report clinical characteristics and outcomes of 4461 children living with HIV on antiretroviral treatment aged <5 years from January to December, 2022. Among the 4% of children living with HIV who died, 43% were asymptomatic, 35% had advanced or severe symptoms at the time of HIV diagnosis and 50% died within 6 months of receiving an HIV diagnosis.

Clonal hematopoiesis: malignant implications, extrahematologic manifestations, and management.

As individuals age, their hematopoietic stem cells can sporadically acquire genetic mutations, known as clonal hematopoiesis. Although most of these genomic aberrations are of little consequence, particular changes in certain contexts can lead to the development of hematologic malignancies, such as myelodysplastic syndromes and acute myeloid leukemia. Owing to its pervasive extrahematologic interactions, clonal hematopoiesis is a recognized risk factor for and is causally implicated in the development of several chronic diseases of aging and/or inflammation, such as atherosclerotic cardiovascular disease. Here, we provide a review of the diagnosis and clinical implications of clonal hematopoiesis, as well as evolving management strategies in the absence of formal consensus guidelines.

Evaluating the role of sex-related structure-function differences on airway aerosol transport and deposition.

Several experimental studies have found that females have higher deposition of particles in the airways compared with males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of 1D ventilation distribution, particle transport, and deposition. The impact of gravity, inhalation flow rate, and dead space are evaluated in 12 structure-based models (seven female; five male). Females were found to have significantly higher total, bronchial, and alveolar deposition than males across a particle size range from 0.01 to 10 . Results suggest that higher deposition fraction in females is due to higher alveolar deposition for smaller particle sizes, and higher bronchial deposition for larger particles. Females had higher alveolar deposition in the lower lobes, and slightly lower particle concentration in the left upper lobe. Males were found to be more sensitive to changes due to gravity, showing greater reduction in bronchial deposition fraction. Males were also more sensitive to change in inhalation flow rate, and to scaling of dead space due to the larger male baseline airway size. Predictions of sex differences in particle deposition - that are consistent with the literature - suggest that sex-based characteristics of lung and airway size interacting with particle size gives rise to differences in regional deposition.

Effect of an Intrapartum Pelvic Dilator Device on Levator Ani Muscle Avulsion During Primiparous Vaginal Delivery: A Pilot Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery. METHODS: A multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months. RESULTS: A total of 214 women were randomized to Device (n = 113) or Control (n = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group (p = 0.040; two-tailed Fisher's test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related. CONCLUSIONS: The pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.

Risk Factors Associated with Occult Nodal Metastasis and Outcomes for cT1-2N0 Maxillary and Mandibular gingival Carcinoma: A Retrospective Study.

Objective: This study aims to identify the rate of occult nodal metastasis (ONM), risk factors associated with ONM, and compare regional recurrence (RR), 2-year disease-free survival (DFS) in patients treated with elective neck dissection (END) versus expectant management (OBS) for primary T1-T2 gingival squamous cell carcinoma (GSCC) of the maxilla and mandible. Methods: A retrospective analysis was conducted and included patients from 2014 to 2021 who were treated at a tertiary referral center. Results: Twenty patients underwent END and 36 were managed expectantly, with a mean follow-up period of 28 months. ONM was observed in 26% of the study cohort with 16.7% occurring in the maxilla and 36.4% in the mandible. No specific histopathologic features were predictive for ONM. No regional recurrence occurred. Local recurrence occurred in 5% and 2.8% of END and OBS groups, respectively. Two-year DFS were comparable between the END (93.8%) versus OBS (83.9%) as well as maxilla (90.9%) versus mandible (83.4%), P > 0.05. Conclusion: ONM remains variable in cT1-T2N0 GSCC with a greater incidence occurring in the mandible when compared to the maxilla, respectively. An END should be strongly considered for mandibular GSCC. Overall, END for the N0 neck has been shown to provide significant overall and disease-free survival benefits. However, further prospective randomized studies are needed to verify risk factors for ONM and validate the disease-related survival benefit of an elective neck dissection in this patient population.

Identification of Glyoxalase A in Group B Streptococcus and its contribution to methylglyoxal tolerance and virulence.

Group B Streptococcus (GBS) is a Gram-positive pathobiont that commonly colonizes the gastrointestinal and lower female genital tracts but can cause sepsis and pneumonia in newborns and is a leading cause of neonatal meningitis. Despite the resulting disease severity, the pathogenesis of GBS is not completely understood, especially during the early phases of infection. To investigate GBS factors necessary for blood stream survival, we performed a transposon (Tn) mutant screen in our bacteremia infection model using a GBS mariner transposon mutant library previously developed by our group. We identified significantly underrepresented mutations in 628 genes that contribute to survival in the blood, including those encoding known virulence factors such as capsule, the ß-hemolysin, and inorganic metal ion transport systems. Most of the underrepresented genes have not been previously characterized or studied in GBS, including gloA and gloB, which are homologs for genes involved in methylglyoxal (MG) detoxification. MG is a byproduct of glycolysis and a highly reactive toxic aldehyde that is elevated in immune cells during infection. Here, we observed MG sensitivity across multiple GBS isolates and confirm that gloA contributes to MG tolerance and invasive GBS infection. We show specifically that gloA contributes to GBS survival in the presence of neutrophils and depleting neutrophils in mice abrogates the decreased survival and infection of the gloA mutant. The requirement of the glyoxalase pathway during GBS infection suggests that MG detoxification is important for bacterial survival during host-pathogen interactions.

Lost in transition: A protocol for a retrospective, longitudinal cohort study for addressing challenges in opioid treatment for transition-age adults.

BACKGROUND: In the United States, there has been a concerning rise in the prevalence of opioid use disorders (OUD) among transition-age (TA) adults, 18 to 25-years old, with a disproportionate impact on individuals and families covered by Medicaid. Of equal concern, the treatment system continues to underperform for many young people, emphasizing the need to address the treatment challenges faced by this vulnerable population at a pivotal juncture in their life course. Pharmacotherapy is the most effective treatment for OUD, yet notably, observational studies reveal gaps in the receipt of and retention in medications for opioid use disorder (MOUD), resulting in poor outcomes for many TA adults in treatment. Few current studies on OUD treatment quality explicitly consider the influence of individual, organizational, and contextual factors, especially for young people whose social roles and institutional ties remain in flux. METHODS: We introduce a retrospective, longitudinal cohort design to study treatment quality practices and outcomes among approximately 65,000 TA adults entering treatment for OUD between 2012 and 2025 in New York. We propose to combine data from multiple sources, including Medicaid claims and encounter data and a state registry of substance use disorder (SUD) treatment episodes, to examine three aspects of OUD treatment quality: 1) MOUD use, including MOUD option (e.g., buprenorphine, methadone, or extended-release [XR] naltrexone); 2) adherence to pharmacotherapy and retention in treatment; and 3) adverse events (e.g., overdoses). Using rigorous analytical methods, we will provide insights into how variation in treatment practices and outcomes are structured more broadly by multilevel processes related to communities, treatment programs, and characteristics of the patient, as well as their complex interplay. DISCUSSION: Our findings will inform clinical decision making by patients and providers as well as public health responses to the rising number of young adults seeking treatment for OUD amidst the opioid and polysubstance overdose crisis in the U.S.

Exposures and conditions prior to age 16 are associated with dementia status among adults in the United States Health and Retirement Study.

Background: Dementia susceptibility likely begins years before symptoms. Early life has not been comprehensively tested for dementia associations. Method: In the US Health and Retirement Study (normal baseline cognition; n=16,509; 2008-2018 waves), 31 exposures before age 16 were retrospectively assessed with ten-year incident cognitive status (dementia, impaired, normal). Using parallel logistic models, each exposure was tested with incident cognition, adjusting for sex, baseline age, follow-up, race/ethnicity, personal/parental education. Result: 14.5% had incident impairment and 5.3% had dementia. Depression was associated with 1.71 (95%CI:1.28,2.26) times higher odds of incident impairment, relative to normal cognition. Headaches/migraines were associated with 1.63 (95%CI:1.18,2.22) times higher odds of incident impairment. Learning problems were associated with 1.75 (95%CI:1.05,2.79) times higher odds of incident impairment. Childhood self-rated health of fair (1.86, 95%CI:1.27,2.64) and poor (3.39, 95%CI:1.91,5.82) were associated with higher incident dementia odds, relative to excellent. Conclusion: Early life factors may be important for impairment or dementia, extending the relevant risk window.

Characteristics and outcomes of children, adolescent, and young adult patients with myelodysplastic neoplasms: A single-center retrospective analysis.

Myelodysplastic syndrome, or myelodysplastic neoplasms, are a rare finding in pediatric, adolescent, and young adult (AYA) patients. More literature is needed to highlight trends of survival or treatment resistance in subpopulations to improve treatment. Here we report a single center retrospective analysis of pediatric and AYA patients from 2000 to 2022 including molecular and cytogenetic data. Using the IPSS-R and IPSS-M, which have been reported exclusively in adults, and excluding patients with bone marrow failure syndromes, we analyzed 119 pediatric and AYA patients with myelodysplastic neoplasms. Therapy-related myelodysplastic neoplasms were present in 36 % of patients, and 31 % of patients developed acute myeloid leukemia. The 5-year overall survival (OS) rate for the entire cohort was 45 %. Contrary to young adults and older adults, mutations were not common in pediatrics. Those who underwent stem cell transplant (SCT)(at any time) had significantly longer median OS. Although SCT at any time improved OS in the de novo myelodysplastic neoplasm group, the choice of the initial treatment with intensive chemotherapy, hypomethylating agents, or SCT did not significantly alter OS. Median OS was shorter in the pediatric group (<18 years old) and longer for those with isolated deletion of 5q or TET2 mutation, but these were not significant findings. Median OS was significantly shorter in those with monosomy 7 or 7q deletion and those with therapy-related myelodysplastic neoplasms. These findings build on previously reported findings and encourage the use of SCT along with molecular and cytogenetic analysis.

Effects of yeast-enriched functionalized canola meal supplementation on apparent total tract macronutrient digestibility and fecal characteristics, fecal microbiota, and immune function of healthy adult dogs.

Brewer's dried yeast has a high nutritional value and has long been utilized by the animal feed industry as a source of protein, B-complex vitamins, and minerals. Brewer's dried yeast is also rich in bioactive compounds and may thereby be used as a functional ingredient, providing benefits beyond that of its nutrient content. Canola meal is a high-fiber ingredient that also has unique properties, especially when it is wetted and dried using a proprietary drying system that creates a "functionalized" canola meal. The objective of this experiment was to evaluate the effects of a yeast-enriched functionalized canola meal (FCM) on apparent total tract digestibility (ATTD) and the fecal quality, metabolite concentrations, and microbiota populations, and immune function of healthy adult dogs. Twelve adult female beagles (body weight [BW] = 7.6 ±â€…0.7 kg; age = 5.8 ±â€…1.3) were used in a replicated 4 × 4 Latin square design with 28-d periods. Each experimental period consisted of a 22-d adaptation phase, 5 d of total and fresh fecal collection, and blood collection on the last day. To start, all dogs were fed a basal diet to maintain BW for 14 d. Following fecal and blood collections at baseline (-1 d) to confirm health status, experimental periods began testing the following dietary treatments using a Latin square design experiment: 1) FCM only (no yeast inclusion), 2) FCM + low yeast dose, 3) FCM + medium yeast dose, and 4) FCM + high yeast dose. All treatments were top-dressed onto the basal diet at a rate estimated to be 1% of daily intake (as-is basis). Statistical analysis was performed using the PROC MIXED procedure of SAS with the main effect of treatment and the random effect of dog. Significance was declared at P ≤ 0.05, and trends reported if 0.05 < P ≤ 0.10. Supplementation with yeast-enriched FCM had no significant effect on the ATTD of macronutrients or energy or the fecal characteristics, metabolite concentrations, and microbiota populations of dogs. Additionally, no significant differences were observed in circulating immune cell counts or response to Toll-like receptor agonists among treatments. Our results suggest that the yeast-enriched FCM could be included in canine diets without negatively affecting stool quality, fecal metabolite concentrations, or ATTD. Further research is necessary to determine the effective dose of yeast-enriched FCM, potential mechanisms of action, and other potential implications it has on canine health.

Brewer's dried yeast has a high nutritional value and has long been utilized by the animal feed industry as a source of protein, B-complex vitamins, and minerals. Because yeast is rich in polyphenols, mannanoligosaccharides, and ß-glucans, it may also be used as a functional ingredient, providing benefits beyond that of its nutrient content. Canola meal is a high-fiber ingredient that also has unique properties, especially when it is wetted and dried using a proprietary drying system that creates a "functionalized" canola meal. In this experiment, functionalized canola meal was enriched with different levels of brewer's dried yeast, then fed to dogs to evaluate its effects on nutrient digestibility, stool characteristics, microbiota populations, and immunity. The results showed that the yeast-enriched functionalized canola meal had no impact on nutrient digestibility or fecal characteristics. Additionally, no differences were observed in immune cell counts or immune cell activation after challenge. In conclusion, yeast-enriched functionalized canola meal may be supplemented in canine diets without negatively affecting stool quality, fecal metabolite concentrations, or digestibility. Further research is necessary to determine the effective dose of yeast-enriched functionalized canola meal, potential mechanisms of action, and other potential implications it has on canine health.

The Interaction Effects of Sex, Age, APOE and Common Health Risk Factors on Human Brain Functions.

Importance: Nonlinear changes in brain function during aging are shaped by a complex interplay of factors, including sex, age, genetics, and modifiable health risk factors. However, the combined effects and underlying mechanisms of these factors on brain functional connectivity remain poorly understood. Objective: To comprehensively investigate the combined associations of sex, age, APOE genotypes, and ten common modifiable health risk factors with brain functional connectivities during aging. Design Setting and Participants: This analysis used data from 36,630 UK Biobank participants, aged 44-81, who were assessed for sex, age, APOE genotypes, 10 health risk factors, and brain functional connectivities through resting-state functional magnetic resonance imaging. Main Outcomes and Measures: Brain functional connectivities were evaluated through within- and between-network functional connectivities and connectivity strength. Associations between risk factors and brain functional connectivities, including their interaction effects, were analyzed. Results: Hypertension, BMI, and education were the top three influential factors. Sex-specific effects were also observed in interactions involving APOE4 gene, smoking, alcohol consumption, diabetes, BMI, and education. Notably, a negative sex-excessive alcohol interaction showed a stronger negative effect on functional connectivities in males, particularly between the dorsal attention network and the language network, while moderate alcohol consumption appeared to have protective effects. A significant negative interaction between sex and APOE4 revealed a greater reduction in functional connectivity between the cingulo-opercular network and the posterior multimodal network in male APOE4 carriers. Additional findings included a negative age-BMI interaction between the visual and dorsal attention networks, and a positive age-hypertension interaction between the frontoparietal and default mode networks. Conclusions and Relevance: The findings highlight significant sex disparities in the associations between age, the APOE-ε4 gene, modifiable health risk factors, and brain functional connectivity, emphasizing the necessity of jointly considering these factors to gain a deeper understanding of the complex processes underlying brain aging.

Fungal effectors: past, present, and future.

Fungal effector proteins function at the interfaces of diverse interactions between fungi and their plant and animal hosts, facilitating interactions that are pathogenic or mutualistic. Recent advancements in protein structure prediction have significantly accelerated the identification and functional predictions of these rapidly evolving effector proteins. This development enables scientists to generate testable hypotheses for functional validation using experimental approaches. Research frontiers in effector biology include understanding pathways through which effector proteins are secreted or translocated into host cells, their roles in manipulating host microbiomes, and their contribution to interacting with host immunity. Comparative effector repertoires among different fungal-host interactions can highlight unique adaptations, providing insights for the development of novel antifungal therapies and biocontrol strategies.