More than just the gene: Investigating expression using a non-native plasmid and host and its impact on resistance conferred by ß-lactamase OXA-58 isolated from a hospital wastewater microbiome.

With the escalation of hospital-acquired infections by multi-drug resistant bacteria, understanding antibiotic resistance is of paramount importance. This study focuses on the ß-lactamase gene, blaOXA-58, an important resistance determinant identified in a patient-facing hospital wastewater system. This study aimed to characterise the behaviour of the OXA-58 enzyme when expressed using a non-native plasmid and expression host. blaOXA-58 was cloned using a pET28a(+)/Escherichia coli BL21(DE3) expression system. Nitrocefin hydrolysis and antimicrobial susceptibility of OXA-58-producing cells were assessed against penicillin G, ampicillin, meropenem, and amoxicillin. blaOXA-58 conferred resistance to amoxicillin, penicillin G, and ampicillin, but not to meropenem. This was unexpected given OXA-58's annotation as a carbapenemase. The presence of meropenem also reduced nitrocefin hydrolysis, suggesting it acts as a competitive inhibitor of the OXA-58 enzyme. This study elucidates the phenotypic resistance conferred by an antimicrobial resistance gene (ARG) obtained from a clinically relevant setting and reveals that successful functional expression of ARGs is multifaceted. This study challenges the reliability of predicting antimicrobial resistance based solely on gene sequence alone, and serves as a reminder of the intricate interplay between genetics and structural factors in understanding resistance profiles across different host environments.

Effects of chicken slurry inclusion on apparent total tract macronutrient digestibility, palatability, and fecal characteristics, microbiota, and metabolites of healthy adult dogs.

"Premium" pet foods are often formulated with meat slurries. Meat slurries are believed to be of higher quality than rendered meals, but inadequate research has been performed to test how their inclusion affects palatability, digestibility, or indicators of gastrointestinal health. Therefore, the objectives of this study were to determine how chicken slurry inclusion affected the palatability and apparent total tract macronutrient digestibility (ATTD) of dog foods and to assess their effects on the fecal characteristics, metabolites, and microbiota of dogs. A replicated 3x3 Latin square design digestibility study was conducted using 9 healthy adult dogs (age = 5.44 ± 0.53 yr) to test diets containing 0% (control; CON), 8% (low inclusion; LOW), and 16% (high inclusion; HIGH) chicken slurry. The experiment comprised three 21-day experimental periods (14 days of adaptation, 5 days of total fecal collection (used for ATTD calculations), and 2 days of blood collection). On the first day of fecal collections, one fresh sample was collected for measurement of pH, dry matter (DM) content, fermentative metabolite concentrations, and microbiota populations. A 2-day palatability study (n=20 dogs) was also conducted to compare CON vs. HIGH. Data were analyzed statistically by Mixed Models using SAS 9.4, with P<0.05 being significant. In the palatability study, dogs were shown to prefer (P<0.05) the HIGH diet by a ratio of 2:1. In the digestibility study, fecal output, scores, pH, and DM percentage were not different among diets. The ATTD of protein was higher (P<0.05) for the HIGH diet (84.6%) than for the LOW (82.7%) or CON (82.6%) diets. The ATTD of other nutrients and energy were not different among diets (all over 80%). Fecal propionate, butyrate, and total short-chain fatty acid concentrations were higher (P<0.05) in dogs fed the LOW diet (122.0, 67.4, and 408.2 ßmol/g, respectively) than those fed the HIGH diet (89.0, 46.9, and 338.2 ßmol/g, respectively). The other fecal metabolites (acetate, branched-chain fatty acids, ammonia, phenol, and indole) were not different among treatments. Few changes to the fecal microbiota were noted. However, the relative abundance of fecal Fusobacterium was higher (P<0.05) in dogs fed the CON diet than those fed the HIGH diet (25.% vs. 20.0% relative abundance). In summary, chicken slurry inclusion improved palatability but had minimal effects on nutrient digestibility and fecal characteristics, metabolites, and microbiota.

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.

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.

Success Rates with Preimplantation Genetic Testing for Aneuploidy (PGT-A) in Good Prognosis Patients is Dependent on Age.

OBJECTIVE: To evaluate cumulative live birth following preimplantation genetic testing for aneuploidy (PGT-A) with next generation sequencing (NGS) compared to morphology alone among patients aged 21-40 years undergoing single blastocyst transfer. DESIGN: Retrospective cohort study SUBJECTS: Patients aged 21 to 40 years undergoing first, autologous retrieval cycles resulting in ≥ 5 fertilized oocytes, with subsequent single blastocyst transfer in SART clinics from 2016 to 2019. EXPOSURE: PGT-A using NGS MAIN OUTCOME MEASURES: The primary outcome was cumulative live birth per retrieval. Secondary outcomes included clinical pregnancy, miscarriage, and live birth per transfer. RESULTS: A total of 56,469 retrieval cycles were included in the analysis. Retrieval cycles were stratified based on age (< 35, 35-37, and 38-40 years) and exposure to PGT-A with NGS. Modified Poisson regression modeling was used to evaluate the association between PGT-A and cumulative live birth per retrieval while controlling for covariates. In this cohort, most cycles did not utilize PGT-A (n=49,608; 88%). After adjusting for covariates, the use of PGT-A was associated with a slightly lower cumulative live birth in individuals aged <35 years (risk ratio [RR] 0.96; 95% CI: 0.93, 0.99) compared with no PGT, but higher cumulative live birth in ages 35-37 years (RR 1.04; 95% CI: 1.00, 1.08), and 38-40 years (RR 1.14; 95% CI: 1.07, 1.20). A subgroup analysis limited to freeze-all cycles (n=29,041) showed that PGT-A was associated with higher cumulative live birth in individuals aged ≥ 35 years and was similar to no PGT in individuals aged < 35 years. Miscarriage was significantly less likely in individuals aged ≥ 35 years utilizing PGT-A compared with no PGT-A. CONCLUSION: In this large national database study, success rates in cycles utilizing PGT-A were dependent on age. Cumulative live birth was observed to be significantly less likely in PGT-A cycles among individuals aged < 35 years and more likely among individuals aged 38 to 40 years, compared to no PGT-A. In individuals with no fresh transfer, results were similar. Moreover, miscarriage was significantly less likely with PGT-A among individuals aged 35-40 years in a subgroup analysis of freeze-all cycles.

Acanthamoebae as a protective reservoir for Pseudomonas aeruginosa in a clinical environment.

BACKGROUND: Pseudomonas aeruginosa is a growing concern in healthcare-associated infections and poses significant risk to those with serious underlying health conditions. The antimicrobial resistance traits of the pathogen and ability to form biofilms make effective mitigation and disinfection strategies difficult. Added to this challenge is the role that free-living amoebae such as Acanthamoeba play in the detection, disinfection and transmission of P. aeruginosa. P. aeruginosa can survive intracellularly within amoebae, which has the potential to limit detectability and permit transmission into high-risk areas. METHODS/FINDINGS: We screened for the presence of Acanthamoeba spp. and P. aeruginosa within a functioning general hospital in Scotland using a culture and molecular approach, noting their presence at several sites over a four-month period, particularly within floor drains connecting patient rooms. In addition, microbiome analysis revealed that amoebae harbour a unique microbial community comprised primarily of Pseudomonas spp. that were not readily detected using microbiome sequencing techniques on environmental swabs. Having demonstrated that both organisms were consistently present in hospital settings, we investigated the relationship between acanthamoeba and P. aeruginosa in the laboratory, showing that (i) acanthamoeba growth rate is increased in the presence of pseudomonas biofilms and viable pseudomonas persist within the amoebae and (ii) hydrogen peroxide-based disinfectants are significantly less effective against an isolate of P. aeruginosa in the presence of acanthamoeba than when the bacteria are incubated alone. CONCLUSIONS: These findings suggest that amoebae, and other protists, can influence the detection and persistence of P. aeruginosa in high-risk areas and should be considered when implementing mitigation strategies.

Cortico-hippocampal interactions underlie schema-supported memory encoding in older adults.

Although episodic memory is typically impaired in older adults (OAs) compared to young adults (YAs), this deficit is attenuated when OAs can leverage their rich semantic knowledge, such as their knowledge of schemas. Memory is better for items consistent with pre-existing schemas and this effect is larger in OAs. Neuroimaging studies have associated schema use with the ventromedial prefrontal cortex (vmPFC) and hippocampus (HPC), but most of this research has been limited to YAs. This fMRI study investigated the neural mechanisms underlying how schemas boost episodic memory in OAs. Participants encoded scene-object pairs with varying congruency, and memory for the objects was tested the following day. Congruency with schemas enhanced object memory for YAs and, more substantially, for OAs. FMRI analyses examined how cortical modulation of HPC predicted subsequent memory. Congruency-related vmPFC modulation of left HPC enhanced subsequent memory in both age groups, while congruency-related modulation from angular gyrus (AG) boosted subsequent memory only in OAs. Individual differences in cortico-hippocampal modulations indicated that OAs preferentially used their semantic knowledge to facilitate encoding via an AG-HPC interaction, suggesting a compensatory mechanism. Collectively, our findings illustrate age-related differences in how schemas influence episodic memory encoding via distinct routes of cortico-hippocampal interactions.

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, microbiota, and metabolite and bile acid (BA) concentrations 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 body weight twice daily). At week 4, cats were randomly allotted to one of 2 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 weeks 2, 4, 5, 6, 7, and 8 for measurement of pH, dry matter (DM) %, metabolites, and microbiota. Microbiota was 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 was 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.

The objective of this study was to determine how a veterinary gastrointestinal diet impacts the fecal characteristics, metabolites, and microbiota concentrations of adult cats treated with metronidazole. All cats were fed a leading grocery brand diet (GBD) during a 2-wk baseline, dosed orally with metronidazole (20 mg/kg BW twice daily) for 2 wk, then randomly allotted to one of 2 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 weeks 2, 4, 5, 6, 7, and 8 to assess fecal characteristics, microbiota populations, and metabolite and bile acid (BA) concentrations. Metronidazole increased fecal scores (looser stools), altered relative abundances of 78 bacterial genera and BA profiles (increased primary BA; reduced secondary BA), and increased dysbiosis index. Fecal outcomes varied during recovery. Recovery of 16 bacterial genera was impacted by diet. Dysbiosis index and bacterial alpha diversity were not affected by diet. Our data demonstrate that metronidazole is a powerful antibiotic and may have long-lasting effects on the gut microbiota and metabolites of cats. Feeding a gastrointestinal diet may aid in the recovery of several markers of microbial function (e.g., metabolites).

Cryobiopsy versus fine-needle aspiration for shape-sensing robotic-assisted sampling of small lung nodules.

INTRODUCTION: Shape-sensing Robotic-assisted Bronchoscopy (ssRAB) has emerged as a promising tool for improved performance when sampling pulmonary nodules (PPN). Previous studies suggest that the 1.1 mm cryoprobe is as effective compared to fine needle aspiration (FNA), for different lesions sizes. We aim to compare the 1.1 mm cryoprobe performance to FNA for sampling PPN < 20 mm with ssRAB. MATERIAL AND METHODS: We conducted a retrospective cohort study from November 2022 to February 2024 of patients who underwent ssRAB with cryobiopsy for evaluation of PPN. We compared the diagnostic yield and sensitivity for malignancy of cryobiopsy and FNA for the same PPN. Descriptive statistical analysis was conducted using the McNemar's Test and Comparison of proportion. Multivariate logistic regression assessed the impact of PPN characteristics on the yield of each tool. RESULTS: We included 256 patients, with a combined 284 procedures, and 324 nodules sampled. The median maximum and minimum nodule size was 1.6 cm (IQR 1.17-2.4) and 1.17 cm (IQR 0.86-1.7) respectively. The overall ssRAB diagnostic yield was 93.8 % and sensitivity for malignancy was 97.5 %. Cryobiopsy had a diagnostic yield of 92 % and sensitivity of 96 %, FNA had a 70.4 % and 79.29 % respectively (P < 0.001). Cryobiopsy had a significantly higher performance compared to FNA across the analyzed categories (P < 0.05), except for the sensitivity of mixed-type lesions (P = 0.11). PPN < 10 mm and ≥ 10 mm - <15 mm sampled with FNA, had lower odds of achieving a diagnosis compared to the ≥ 20 mm group (OR = 0.305 IC95%: 0.142-0.65, p < 0.001; OR = 0.497 IC95%: 0.263-0.939, p = 0.031, respectively). Complications occurred in 5.98 % (N = 17) of cases. CONCLUSION: Cryobiopsy demonstrates a statistically higher diagnostic yield and sensitivity for malignancy compared to FNA. Remarkably, FNA showed reduced diagnostic odds in PPN < 15 mm. ssRAB with cryobiopsy could enhance PPN diagnostic yield, leading to earlier lung cancer diagnosis and improve long-term survival rates.

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.

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.

Cross-site Validation of AI Segmentation and Harmonization in Breast MRI.

This work aims to perform a cross-site validation of automated segmentation for breast cancers in MRI and to compare the performance to radiologists. A three-dimensional (3D) U-Net was trained to segment cancers in dynamic contrast-enhanced axial MRIs using a large dataset from Site 1 (n = 15,266; 449 malignant and 14,817 benign). Performance was validated on site-specific test data from this and two additional sites, and common publicly available testing data. Four radiologists from each of the three clinical sites provided two-dimensional (2D) segmentations as ground truth. Segmentation performance did not differ between the network and radiologists on the test data from Sites 1 and 2 or the common public data (median Dice score Site 1, network 0.86 vs. radiologist 0.85, n = 114; Site 2, 0.91 vs. 0.91, n = 50; common: 0.93 vs. 0.90). For Site 3, an affine input layer was fine-tuned using segmentation labels, resulting in comparable performance between the network and radiologist (0.88 vs. 0.89, n = 42). Radiologist performance differed on the common test data, and the network numerically outperformed 11 of the 12 radiologists (median Dice: 0.85-0.94, n = 20). In conclusion, a deep network with a novel supervised harmonization technique matches radiologists' performance in MRI tumor segmentation across clinical sites. We make code and weights publicly available to promote reproducible AI in radiology.

Effects of a Veterinary Gastrointestinal Low-Fat Diet on Fecal Characteristics, Metabolites, and Microbiota Concentrations of Adult Dogs Treated with Metronidazole.

Antibiotics are known to cause loose stools, disrupt the fecal microbiota, and alter fecal bile acid (BA) profiles of dogs. Recovery may be aided by diet, but little research has been conducted. The objective of this study was to determine how a veterinary low-fat diet affected the fecal characteristics, metabolites, BA, and microbiota of dogs receiving antibiotics. Twenty-four healthy adult dogs [7.38 ± 1.95 yr; 7.67 ± 0.76 kg body weight (BW)] were used in an 8-wk completely randomized design study. During a 2-wk baseline, all dogs were fed a leading grocery brand dry kibble diet (GBD). Over the next 2 wk, dogs were fed GBD and received metronidazole orally (20 mg/kg BW twice daily). At wk 4, dogs were randomly allotted to one of two treatments [GBD or Blue Buffalo Natural Veterinary Diet GI Gastrointestinal Support Low-Fat (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 content, and metabolite and BA concentrations. Fecal microbiota populations were analyzed by 16S rRNA gene amplicon sequencing and qPCR-based dysbiosis index (DI). All data were analyzed as repeated measures using the Mixed Models procedure of SAS 9.4, testing for effects of treatment, time, and treatment*time and significance set at P<0.05. Metronidazole increased (P<0.0001) fecal scores (looser stools), reduced fecal short-chain fatty acid, branched-chain fatty acid, phenol, and indole concentrations, increased primary BA concentrations, and decreased secondary BA concentrations. Metronidazole also reduced fecal bacterial alpha diversity, altered the abundance of 58 bacterial genera, and increased DI. During antibiotic recovery, change in fecal pH, dry matter percentage, and metabolite and immunoglobulin A concentrations were altered (P<0.05) by diet. Fecal BA concentrations recovered quickly for all dogs. Change in lithocholic acid was affected (P<0.0001) by diet, but other BA were not. Recovery of over 25 bacterial genera was impacted by diet (P<0.05). While many bacterial taxa returned to baseline levels after 4 wk, others did not fully recover. DI and bacterial alpha diversity measures recovered quickly for all dogs, but were not impacted by diet. In conclusion, metronidazole drastically altered the fecal microbiota and metabolites of dogs. While most variables returned to baseline by wk 8, diet may be used to aid in recovery.

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.

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.

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.