Anti-inflammatory effects of a methanol extract from Montanoa grandiflora DC. (Asteraceae) leaves on in vitro and in vivo models.

BACKGROUND: Montanoa grandiflora, a plant species native from Mexico to Central America, locally known as "Teresita" in Yucatán, México, is used to alleviate anxiety, rheumatism, and stomach issues. This study aims to investigate the anti-inflammatory properties of the methanol extract of Montanoa grandiflora leaves (MMG) in experimental models of inflammation. METHODS: Gas chromatography-mass spectroscopy was used to characterize the MMG; cytotoxicity was assessed by MTT assay on murine macrophages and hemolysis assay. The in vitro anti-inflammatory activity was evaluated on LPS-stimulated murine macrophages by measuring of pro- and anti-inflammatory cytokines, NO and H2O2 release. The in vivo anti-inflammatory activity was evaluated using carrageenan-induced mouse paw edema, 12-O-tetradecanoylphorbol 13-acetate induced-ear edema, and 1-fluoro-2,4-dinitrobenzene induced-delayed-type hypersensitivity. In addition, the serum levels of prostaglandins and leukotrienes were assessed. RESULTS: The main compounds found in MMG were terpenes (i.e., ß-caryophyllene, (-)-α-cubebene, alloaromadendrene, ( +)-δ-cadinene, ß-eudesmol), alkaloid (( ±)-nor-ß-hydrastine), cyclic polyol (quinic acid), carbohydrates and their derivatives, and fatty acids (octadecatrienoic acid and octadecanoic acid). MMG did not exhibit cytotoxic or hemolytic activity. However, it demonstrated in vitro anti-inflammatory effects by increasing the production of IL-10, decreasing the levels of TNF-α, IL-1ß, IL-6, NO and H2O2. MMG significantly reduced carrageenan-induced paw edema, TPA-induced ear edema, and DNFB-induced delayed-type hypersensitivity in mice with effects comparable to those of standard drugs, as well as serum levels of prostaglandins and leukotrienes. CONCLUSION: The anti-inflammatory activity of MMG is associated with increased IL-10 levels and inhibiting inflammatory cell migration mechanisms, without causing cytotoxic or hemolytic damage in both in vitro and in vivo assays.

A Patent-Pending Ointment Containing Extracts of Five Different Plants Showed Antinociceptive and Anti-Inflammatory Mechanisms in Preclinical Studies.

Background/Objectives: The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus, Curcuma longa, Hamamelis virginiana, Echinacea purpurea, and Zingiber officinale were evaluated. Methods: Plant extracts were chemically characterized by gas chromatography-mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results: The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v/v) and ketoprofen gel (2.5% v/v). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1ß, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment's plant mixture, corroborated the in vivo results. Conclusions: The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1ß and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study.

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6-18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

Gestational and postnatal exposure to wildfire smoke and prolonged use of respiratory medications in early life.

As wildfire frequency and severity increases, smoke exposures will cause increasingly more adverse respiratory effects. While acute respiratory effects of smoke exposure have been documented in children, longer term sequelae are largely unstudied. Our objective here was to examine the association between gestational and postnatal exposure to wildfire smoke and prolonged use of prescription medication for respiratory conditions in early childhood. Using Merative MarketScan claims data, we created cohorts of term children born in western states between 1 January 2010-31 December 2014 followed for at least three years. Using NOAA Hazard Mapping System data, we determined the average number of days a week that >25% of the population in a metropolitan statistical area (MSA) was covered by smoke within each exposure period. The exposure periods were defined by trimester and two 12 week postnatal periods. Medication use was based on respiratory indication (upper respiratory, lower respiratory, or any respiratory condition) and categorized into outcomes of prolonged use (⩾30 d use) (PU) and multiple prolonged uses (at least two prolonged uses) (MPU). We used logistic regression models with random intercepts for MSAs adjusted for child sex, birth season, and birth year. Associations differed by exposure period and respiratory outcome, with elevated risk of MPU of lower respiratory medications following exposure in the third trimester and the first 12 postnatal weeks (RR 1.15, 95% CI 0.98, 1.35; RR 1.21, 95% CI 1.05, 1.40, respectively). Exposure in the third trimester was associated with an increase in MPU of any respiratory among males infants only (male RR 1.22, 95% CI 1.00, 1.50; female RR 0.93, 95% CI 0.66, 1.31). Through novel use of prescription claims data, this work identifies critical developmental windows in the 3rd trimester and first 12 postnatal weeks during which environmental inhalational disaster events may impact longer-term respiratory health.

A technology acceptance model to predict anesthesiologists' clinical adoption of virtual reality.

BACKGROUND: Virtual reality (VR) is a novel tool with demonstrated applications within healthcare; however its integration within clinical practice has been slow. Adoption patterns can be evaluated using a technology acceptance model (TAM). The primary study aim was to use VR TAM to assess factors that influence anesthesiologists' acceptance of VR for preoperative anxiolysis. The secondary aim assessed the model's reliability. METHODS: 109 clinical anesthesiologists at Stanford were exposed to a VR application developed as a distraction tool to reduce preoperative patient anxiety. Anesthesiologists were surveyed about their attitudes, beliefs, and behaviors as predictors of their likelihood to clinically use VR. The primary outcome assessed predictive validity using descriptive statistics, construct validity using confirmatory factor analysis, and standardized estimates of model relationships. The secondary outcome assessed reliability with Cronbach's α and composite reliability. RESULTS: Construct validity and reliability was assessed, where all values established acceptable fit and reliability. Hypothesized predictors of consumer use were evaluated with standardized estimates, looking at perceptions of usefulness, ease of use, and enjoyment in predicting attitudes and intentions toward using and purchasing. Past use and price willing to pay did not predict perceived usefulness. Participants in lower age ranges had higher levels of perceived ease of use than those >55 years. CONCLUSION: All confirmatory factor analysis testing for construct validity had good fit. Perceptions of usefulness and enjoyment predicted an anesthesiologist's attitude toward using and intention to purchase, while perceived ease of use predicted perceived usefulness and enjoyment, attitude toward purchasing and using, and intention to use. Past use and price willing to pay did not influence perceptions of usefulness. Lower age predicted greater perceived ease of use. All scales in the model demonstrated acceptable reliability. With good validity and reliability, the VR-TAM model demonstrated factors predictive of anesthesiologist's intentions to integrate VR into clinical settings.

Prevalence of syphilis among people living with HIV who attend a large urban antiretroviral therapy clinic in Panama: a cross-sectional epidemiological study.

Background: Syphilis is a serious global public health challenge. Despite prior progress in syphilis control, incidence has been increasing in recent years. Syphilis is a common coinfection among people living with HIV (PLHIV). In Panama, few data describe syphilis prevalence among PLHIV. We describe syphilis antibody and high-titer (⩾1:8) active syphilis prevalence and associated factors among individuals who attended an antiretroviral clinic. Methods: A cross-sectional study was undertaken during February-March 2022 and September-October 2022 for adults (⩾18 year) assigned male and female at birth, respectively. Participants provided peripheral blood samples and self-administered a questionnaire. Samples were screened using immunochromatography; antibody-positive samples were tested using rapid plasma regain to 1:512 dilutions. Logistic regression was used to identify factors associated with syphilis antibody and high-titer active syphilis. Results: In all, 378 participants gave blood samples; 377 individuals participated in the questionnaire (216 self-reported male sex [males], 158 female [females], and three intersex individuals). Median age was 36 years (interquartile range: 28-45 years). Overall, syphilis antibody prevalence was 32.3% (122/378) (males, 50.7% [108/2013]; females, 5.7% [9/158]; intersex individuals, 100.0% (3/3)], p < 0.01. High-titer active syphilis was found among 24.6% (n = 30) of samples with positive antibody test (males 27.8% [n = 30], females 0.0% [0/9], intersex individuals 0.0% [0/3]). Antibody positivity was associated in the multivariable model with males (50.7%, AOR = 24.6, 95%CI: 1.57-384.53). High-titer active syphilis was associated with younger participant age (18-30 years, 13.2%, OR = 4.82, 95%CI: 1.17-19.83); 31-40 years, 7.8%, OR = 4.24, 95%CI: 1.04-17.21 versus 3.2% >40 years), homosexual identity (16.0% OR = 34.2, 95%CI: 4.50-259.27 versus 0.6% among heterosexual identity); in the multivariable model, associated with sexual identity (bisexual 19.1%, AOR = 10.89, 95%CI: 1.00-119.06) compared to heterosexual identity (0.6%) and weakly associated with concurrency (⩾1 ongoing sexual relationships, 15.9%, AOR = 3.09, 95%CI: 0.94-10.14). Conclusion: This study found very high prevalence of syphilis antibodies and high-titer syphilis among PLHIV in Panama. Those most affected are males, younger in age, those who practice concurrent sexual relationships, and those who reported homosexual and bisexual identity. Targeted interventions should include repetitive testing and treatment, especially among individuals who may be at increased infection risk.

Prevalence of syphilis among people living with HIV who attend a large antiretroviral therapy clinic, Panama, 2022 Syphilis is a significant health challenge worldwide. On a global scale, yearly syphilis incidence is increasing, including in Panama. However, there are no current data to explain syphilis prevalence and who is most affected among people living with HIV in Panama. In order to understand syphilis in Panama and create targeted interventions among specific groups of people, it is important to describe how many people are infected, and who is most affected by this infection. Therefore, we conducted a study among 378 people living with HIV at a treatment clinic in Panama City, Panama. Blood samples and demographic data were collected. In all, syphilis antibodies were found in 32.3% of individuals (50.7% of those who self-report as males, 5.7% as females, and 100% of those who self-report as intersex. Of those with positive antibody tests, 24.6% of individuals also had active syphilis. Only individuals who identify as male had active syphilis. Our findings show high syphilis prevalence among people with HIV in Panama City, particularly among males, those who are younger, those who report sexual identity as homosexual or bisexual, and those with ongoing sexual relationships with more than one individual. Targeted interventions are needed among people living with HIV, especially among the groups most affected. These interventions could include testing more often for syphilis and providing timely treatment, especially among individuals who may be at increased risk of infection.

Virtual Reality Facilitated Exercise Increases Sympathetic Activity and Reduces Pain Perception: A Randomized Crossover Study.

OBJECTIVE: Both virtual reality (VR) and exercise reduce pain while avoiding the risks of traditional pharmacotherapy. The aim of this study was to assess how VR-facilitated exercise modulates sympathetic activity and pain perception. DESIGN: Healthy adult volunteers were randomized by hand dominance and then subjected to a standardized cold pressor test while experiencing a VR application. After a 5-minute washout, participants were crossed-over and repeated the test on their other hand while undergoing a VR-facilitated exercise application. Sympathetic activation, pain sensation, and pain tolerance data were collected identically during both conditions. RESULTS: 110 participants were analyzed. Sympathetic activity increased in both conditions but was higher in the VR-facilitated exercise condition (p < 0.0001). Pain sensation scores were initially higher with VR-facilitated exercise but dropped below the VR-only condition by the end of the intervention (p = 0.0175). There were no differences in pain tolerance between conditions (p = 0.18). CONCLUSION: The decrease in pain perception with VR-facilitated exercise condition compared to VR alone indicates VR-facilitated exercise can be a useful tool for managing pain. Though this effect did not translate into higher pain tolerance, VR-facilitated exercise may be a useful intervention in the setting of physical therapy or for patients with chronic pain.

Diagnostic Accuracy of Grammaticality and Utterance Length in Bilingual Children.

PURPOSE: The purpose of this study was to investigate the diagnostic accuracy of two measures derived from spontaneous language samples, mean length of utterance in words (MLUw) and percentage of grammatical utterances (PGU), in identifying developmental language disorder (DLD) in Spanish-English bilingual children. We examined two approaches: best language and total language. METHOD: The participants in this study included 74 Spanish-English bilingual children with (n = 36) and without (n = 38) DLD. Language samples were elicited through a story retell and story generation task using Frog wordless picture books in English and Spanish. Stories were transcribed and coded using the Systematic Analysis of Language Samples (Miller & Iglesias, 2020) to extract MLUw and PGU in both languages. RESULTS: Logistic regression analyses suggested that a model that included PGU, MLUw, and age achieved the best diagnostic accuracy in predicting group membership. Both approaches, best language and total language, had fair diagnostic accuracy. CONCLUSIONS: In combination, PGU and MLUw seem to be useful diagnostic tools to differentiate bilingual children with and without DLD. Clinical implications and usability are discussed.

Inhaled endotoxin induces a systemic neutrophil response without affecting cardiovascular measures in a randomized cross-over exposure study.

OBJECTIVE: The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures. MATERIALS AND METHODS: In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis. RESULTS: In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp. DISCUSSION AND CONCLUSIONS: In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

Prehospital Pediatric Emergency Training Using Augmented Reality Simulation: A Prospective, Mixed Methods Study.

OBJECTIVE: Pediatric emergencies are high-stakes yet low-volume clinical encounters for emergency medical services (EMS) clinicians, necessitating innovative approaches to training. We sought to explore the acceptability, usability, and ergonomics of a novel augmented reality (AR) software for EMS crisis management training. METHODS: This was a prospective, mixed-methods study employing qualitative and quantitative analyses. We enrolled emergency medical technicians (EMTs) and paramedics at a municipal fire service in Northern California. We ran the Chariot Augmented Reality Medical simulation software (Stanford Chariot Program, Stanford University, Stanford, CA) on the ML1 headset (Magic Leap, Inc., Plantation, FL), which enabled participants to view an AR image of a patient overlaid with real-world training objects. Participants completed a simulation of a pediatric hypoglycemia-induced seizure and cardiac arrest. Participants subsequently engaged in structured focus group interviews assessing acceptability, which we coded and thematically analyzed. We evaluated the usability of the AR system and ergonomics of the ML1 headset using previously validated scales, and we analyzed findings with descriptive statistics. RESULTS: Twenty-two EMS clinicians participated. We categorized focus group interview statements into seven domains after an iterative thematic analysis: general appraisal, realism, learning efficacy, mixed reality feasibility, technology acceptance, software optimization, and alternate use cases. Participants valued the realism and the mixed reality functionality of the training simulation. They reported that AR could be effective for practicing pediatric clinical algorithms and task prioritization, building verbal communication skills, and promoting stress indoctrination. However, participants also noted challenges with integrating AR images with real-world objects, the learning curve required to adapt to the technology, and areas for software improvement. Participants favorably evaluated the ease of use of the technology and comfortability of wearing the hardware; however, most participants reported that they would need technical support. CONCLUSION: Participants positively evaluated the acceptability, usability, and ergonomics of an AR simulator for pediatric emergency management training, and participants identified current technological limitations and areas for improvement. AR simulation may serve as an effective training adjunct for prehospital clinicians.

Assessment of Pregnancy-Related Telehealth Interventions in the United States: A 10-Year Scoping Review.

Introduction: Telehealth use in obstetrics has been demonstrated to improve efficiency, access to care, and pregnancy outcomes. Despite reported successful implementation of these programs, information regarding the program variations and its impact on health care costs and outcomes are scarce. Methods: This is a scoping review of pregnancy-related telehealth studies to understand the current landscape of pregnancy-related telehealth interventions as well as to subset those that are used in high-risk pregnancies. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to guide this review. Results: A total of 70 articles were included in this scoping review. Of those, 53 (75.7%) studies included a pregnant population and 17 (24.3%) studies focused on a rural and/or urban population. Most studies (n = 56; 80%) included some form of synchronous interaction between provider and participant. Patient outcomes included maternal/infant health outcomes (n = 41; 44.1%), patient satisfaction (n = 9; 9.7%), and attendance/compliance (n = 5; 5.4%). Provider-level outcomes included knowledge change (n = 11; 11.8%) and self-efficacy (n = 3; 3.2%). Other outcomes included assessment of costs and patient/provider feasibility and acceptability of the intervention. Overall, there has been a growing trend in articles published on pregnancy-related telehealth studies since 2011, with 2018 having the most publications in a single year. Conclusion: This review suggests a steadily growing body of literature on pregnancy-related telehealth interventions; however, more research is needed to better understand outcomes of telehealth for pregnancy-related care, especially related to patient satisfaction, health disparities, and cost-benefit.

Adolescent Asthma Monitoring: A Preliminary Study of Audio and Spirometry Modalities.

Asthma patients' sleep quality is correlated with how well their asthma symptoms are controlled. In this paper, deep learning techniques are explored to improve forecasting of forced expiratory volume in one second (FEV1) by using audio data from participants and test whether auditory sleep disturbances are correlated with poorer asthma outcomes. These are applied to a representative data set of FEV1 collected from a commercially available sprirometer and audio spectrograms collected overnight using a smartphone. A model for detecting nonverbal vocalizations including coughs, sneezes, sighs, snoring, throat clearing, sniffs, and breathing sounds was trained and used to capture nightly sleep disturbances. Our preliminary analysis found significant improvement in FEV1 forecasting when using overnight nonverbal vocalization detections as an additional feature for regression using XGBoost over using only spirometry data.Clinical relevance- This preliminary study establishes up to 30% improvement of FEV1 forecasting using features generated by deep learning techniques over only spirometry-based features.

Using Cost Conversations to Address Financial Toxicity in Pediatric Asthma Care: Findings From a Survey of Caregivers.

INTRODUCTION: Asthma care teams are well-positioned to help caregivers address financial toxicity in pediatric asthma care, although discussing cost can be challenging. We sought to characterize cost conversations in pediatric asthma specialty care. METHOD: We surveyed 45 caregivers of children aged 4-17 with asthma. Eligible caregivers reported costs concerns and had accompanied their child to a multisite asthma specialty practice in North Carolina. RESULTS: About one-third of caregivers reported a cost conversation (36%). Cost conversations were less common among caregivers whose child had public versus private health insurance (16% vs. 56%), who attended a telehealth versus in-person visit (6% vs. 52%), or who did not versus did want a conversation (19% vs. 77%, all p < .05). Common cost conversation topics were medications and equipment like spacers. DISCUSSION: Our findings suggest cost conversations may be relatively uncommon in pediatric asthma care, particularly for publicly insured patients and telehealth visits.

A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation. Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans. Methods: This was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol-enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates. Results: Short-course γ-tocopherol intervention did not reduce wood smoke-induced neutrophilic airway inflammation, but it did prevent wood smoke-induced eosinophilic airway inflammation. Conclusion: γ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.

Racial/Ethnic Disparities in Misidentification of Dementia in Medicare Claims: Results from the Washington Heights-Inwood Columbia Aging Project.

BACKGROUND: Misidentification of dementia in Medicare claims is quite common. OBJECTIVE: We examined potential race/ethnic disparities in misidentification of dementia in Medicare claims in a diverse cohort of older adults who underwent careful clinical assessment. METHODS: Participants were enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multiethnic, population-based, prospective study of cognitive aging in which dementia status was assessed using a rigorous clinical protocol. ICD-9-CM and ICD-10-CM diagnosis codes in all available Medicare claims (1999-2019) were compared to clinical dementia diagnosis and categorized into three mutually exclusive groups: 1) congruent-, 2) over-, and 3) under- identification during the study period. Multinomial logistic regression model was used to examine the relationship between race (White, African American/Black, other) and ethnicity (Hispanic/Latinx, non-Hispanic/Latinx) and congruency of dementia identification after controlling for clinical (cognition, function, comorbidities) and demographic characteristics (age, sex, education), and inpatient and outpatient utilization. RESULTS: Across all person-years, 88.4% had congruent identification of dementia compared to clinical diagnosis, in 4.1% of the times participants were over-identified with dementia, and 7.5% of the times the participants were under-identified. Rates of misidentification was higher in minority participants than in White, non-Hispanic participants. Multivariable estimation results showed that the probability of over-identification with dementia was 2.2% higher for African American/Black than White (p = 0.05) and 2.7% higher for Hispanic participants than non-Hispanics (p = 0.03) participants. Differences in under-identification by race/ethnicity were not statistically significant. CONCLUSIONS: African American/Black and Hispanic participants were more likely over-identified with dementia in Medicare claims.

Phenotypic and Genomic Characterization of Streptomyces pakalii sp. nov., a Novel Species with Anti-Biofilm and Anti-Quorum Sensing Activity in ESKAPE Bacteria.

The increasing number of infections caused by antimicrobial multi-resistant microorganisms has led to the search for new microorganisms capable of producing novel antibiotics. This work proposes Streptomyces pakalii sp. nov. as a new member of the Streptomycetaceae family. The strain ENCB-J15 was isolated from the jungle soil in Palenque National Park, Chiapas, Mexico. The strain formed pale brown, dry, tough, and buried colonies in the agar with no diffusible pigment in GAE (glucose-asparagine-yeast extract) medium. Scanning electron micrographs showed typical mycelium with long chains of smooth and oval-shaped spores (3-10 m). The strain grew in all of the International Streptomyces Project (ISP)'s media at 28-37 °C with a pH of 6-9 and 0-10% NaCl. S. pakalii ENCB-J15 assimilated diverse carbon as well as organic and inorganic nitrogen sources. The strain also exhibited significant inhibitory activity against the prodigiosin synthesis of Serratia marcescens and the inhibition of the formation and destruction of biofilms of ESKAPE strains of Acinetobacter baumannii and Klebsiella pneumoniae. The draft genome sequencing of ENCB-J15 revealed a 7.6 Mb genome with a high G + C content (71.6%), 6833 total genes, and 6746 genes encoding putative proteins. A total of 26 accessory clusters of proteins associated with carbon sources and amino acid catabolism, DNA modification, and the antibiotic biosynthetic process were annotated. The 16S rRNA gene phylogeny, core-proteome phylogenomic tree, and virtual genome fingerprints support that S. pakalii ENCB-J15 is a new species related to Streptomyces badius and Streptomyces globisporus. Similarly, its average nucleotide identity (ANI) (96.4%), average amino acid identity (AAI) (96.06%), and virtual DNA-DNA hybridization (67.3%) provide evidence to recognize it as a new species. Comparative genomics revealed that S. pakalli and its closest related species maintain a well-conserved genomic synteny. This work proposes Streptomyces pakalii sp. nov. as a novel species that expresses anti-biofilm and anti-quorum sensing activities.

Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-dwelling Older Adults with Dementia.

BACKGROUND AND OBJECTIVES: Neuropsychiatric symptoms (NPS), including psychotic symptoms (hallucinations, illusions, delusions), agitation/aggression, and depressed mood, are common in individuals with Alzheimer's disease (AD) and predict poorer outcomes, including faster disease progression. We aimed to evaluate associations between NPS and cognition and dependence in a multi-ethnic sample of community-dwelling older adults with AD. METHODS: Predictors 3 (P3) is a cohort study of AD disease courses recruiting older adults aged 65 and above residing in upper Manhattan. A total of 138 of 293 participants had probable AD at the study baseline. We fit linear mixed models to examine longitudinal associations of time-varying NPS (psychotic symptoms, agitation/aggression, and depressed mood) with dependence and cognition, adjusted for race-ethnicity, sex, education, age, clinical dementia rating score, APOE-ε4, and comorbidity burden; separate interaction models were fit for age, Hispanic ethnicity, and sex. RESULTS: Psychotic symptoms were associated with faster rates of increasing dependence and declining cognition over time, agitation/aggression with faster rates of declining cognition, and depressed mood with faster rates of increasing dependence. Among psychotic symptoms, delusions, but not hallucinations or illusions, were associated with worse outcome trajectories. Depressed mood predicted an accelerated increase in dependence in males but not females. CONCLUSION: Our results confirm and extend prior results in clinic-based samples. The presence of NPS was associated with worse trajectories of dependence and cognition in this muti-ethnic sample of older adults with AD. Importantly, sex modified the association between depressed mood and dependence. Our results on NPS as predictors of differential AD progression in a community-dwelling, ethnically diverse sample serve to better inform the clinical care of patients and the future development of AD therapies.