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1.
Proc Natl Acad Sci U S A ; 121(28): e2318691121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968121

ABSTRACT

Dietary lipids play an essential role in regulating the function of the gut microbiota and gastrointestinal tract, and these luminal interactions contribute to mediating host metabolism. Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are a family of lipids with antidiabetic and anti-inflammatory properties, but whether the gut microbiota contributes to their beneficial effects on host metabolism is unknown. Here, we report that treating chow-fed female and male germ-free (GF) mice with PAHSAs improves glucose tolerance, but these effects are lost upon high fat diet (HFD) feeding. However, transfer of feces from PAHSA-treated, but not vehicle-treated, chow-fed conventional mice increases insulin sensitivity in HFD-fed GF mice. Thus, the gut microbiota is necessary for, and can transmit, the insulin-sensitizing effects of PAHSAs in HFD-fed GF male mice. Analyses of the cecal metagenome and lipidome of PAHSA-treated mice identified multiple lipid species that associate with the gut commensal Bacteroides thetaiotaomicron (Bt) and with insulin sensitivity resulting from PAHSA treatment. Supplementing live, and to some degree, heat-killed Bt to HFD-fed female mice prevented weight gain, reduced adiposity, improved glucose tolerance, fortified the colonic mucus barrier and reduced systemic inflammation compared to HFD-fed controls. These effects were not observed in HFD-fed male mice. Furthermore, ovariectomy partially reversed the beneficial Bt effects on host metabolism, indicating a role for sex hormones in mediating the Bt probiotic effects. Altogether, these studies highlight the fact that PAHSAs can modulate the gut microbiota and that the microbiota is necessary for the beneficial metabolic effects of PAHSAs in HFD-fed mice.


Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome , Insulin Resistance , Obesity , Animals , Male , Female , Mice , Gastrointestinal Microbiome/drug effects , Obesity/metabolism , Obesity/microbiology , Obesity/etiology , Diet, High-Fat/adverse effects , Mice, Inbred C57BL , Stearic Acids/metabolism , Palmitic Acid/metabolism , Feces/microbiology , Mice, Obese
2.
Alzheimers Dement ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39030746

ABSTRACT

INTRODUCTION: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin-6 [IL-6], S100 calcium-binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase-3-like protein 1 [YKL-40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α-synuclein [α-Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]). METHODS: This Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate-adjusted multivariate regression examined relationships between age (mean-split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL-VSHET (N = 122) and non-carriers (KL-VSNC; N = 332). RESULTS: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age-stratified analyses, KL-VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL-6, S100B, Ng, and α-Syn (Ps ≥ 0.13) in KL-VSHET. Although age-related differences in GFAP, sTREM2, and YKL-40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL-VSNC. DISCUSSION: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL-VSHET. HIGHLIGHTS: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction. KLOTHO KL-VS non-carriers exhibit this same pattern, which is does not significantly differ between younger and older KL-VS heterozygotes for interleukin-6, S100 calcium-binding protein B, neurogranin, and total α-synuclein. Although age-related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase-3-like protein 1 are evident for both KL-VS groups, the magnitude of the effect is markedly stronger for KL-VS non-carriers. Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL-VS heterozygotes.

3.
J Pharm Pract ; : 8971900241263164, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030931

ABSTRACT

Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.

4.
ArXiv ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38947926

ABSTRACT

Objective: Neighborhood disadvantage is associated with worse health and cognitive outcomes. Morphological similarity network (MSN) is a promising approach to elucidate cortical network patterns underlying complex cognitive functions. We hypothesized that MSNs could capture intricate changes in cortical patterns related to neighborhood disadvantage and cognitive function, potentially explaining some of the risk for later life cognitive impairment among individuals who live in disadvantaged contexts. Methods: This cross-sectional study included cognitively unimpaired participants (n=524, age=62.96±8.377, gender (M:F)=181:343, ADI(L:H) =450,74) from the Wisconsin Alzheimer's Disease Research Center or Wisconsin Registry for Alzheimer's Prevention. Neighborhood disadvantage status was obtained using the Area Deprivation Index (ADI). Cognitive performance was assessed through six tests evaluating memory, executive functioning, and the modified preclinical Alzheimer's cognitive composite (mPACC). Morphological Similarity Networks (MSN) were constructed for each participant based on the similarity in distribution of cortical thickness of brain regions, followed by computation of local and global network features. We used linear regression to examine ADI associations with cognitive scores and MSN features. The mediating effect of MSN features on the relationship between ADI and cognitive performance was statistically assessed. Results: Neighborhood disadvantage showed negative association with category fluency, implicit learning speed, story recall and mPACC scores, indicating worse cognitive function among those living in more disadvantaged neighborhoods. Local network features of frontal and temporal brain regions differed based on ADI status. Centrality of left lateral orbitofrontal region showed a partial mediating effect between association of neighborhood disadvantage and story recall performance. Conclusion: Our findings suggest differences in local cortical organization by neighborhood disadvantage, which also partially mediated the relationship between ADI and cognitive performance, providing a possible network-based mechanism to, in-part, explain the risk for poor cognitive functioning associated with disadvantaged neighborhoods. Future work will examine the exposure to neighborhood disadvantage on structural organization of the brain.

5.
Cancer Cell ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39029467

ABSTRACT

Dendritic cells are critical inducers of adaptive anti-tumor immunity. However, their maturation, activation, and migration are often compromised in the tumor microenvironment. In this issue, You et al. demonstrate a novel axis of suppression of dendritic cell function mediated by interaction with regulatory T cells in perilymphatic niches.

6.
Health Commun ; : 1-12, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847325

ABSTRACT

Clinician racial bias has been associated with less patient-centered communication, but little is known about how it affects trainees' communication. We investigated genetic counseling students' communication during sessions with Black or White standardized patients (SPs) and the extent to which communication was associated with SP race or student scores on the Race Implicit Association Test (IAT). Sixty students conducted a baseline SP session and up to two follow-up sessions. Students were randomly assigned to a different White or Black SP and one of three clinical scenarios for each session. Fifty-six students completed the IAT. Session recordings were coded using the Roter Interaction Analysis System. Linear regression models assessed the effects of IAT score and SP race on a variety of patient-centered communication indicators. Random intercept models assessed the within-student effects of SP race on communication outcomes during the baseline session and in follow-up sessions (n = 138). Students were predominantly White (71%). Forty students (71%) had IAT scores indicating some degree of pro-White implicit preference. Baseline sessions with White relative to Black SPs had higher patient-centeredness scores. Within-participant analyses indicate that students used a higher proportion of back-channels (a facilitative behavior that cues interest and encouragement) and conducted longer sessions with White relative to Black SPs. Students' stronger pro-White IAT scores were associated with using fewer other facilitative statements during sessions with White relative to Black SPs. Different patterns of communication associated with SP race and student IAT scores were found for students than those found in prior studies with experienced clinicians.

7.
Langmuir ; 40(26): 13583-13595, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38907731

ABSTRACT

The growing reliance on pesticides for pest management in agriculture highlights the need for new analytical methods to detect these substances in food and water. Our research introduces a SPRWG-(C18H37) lipopeptide (LP) as a functional analog of acetylcholinesterase (AChE) for glyphosate detection in environmental samples using phosphatidylcholine (PC) monolayers. This LP, containing hydrophilic amino acids linked to an 18-carbon aliphatic chain, alters lipid assembly properties, leading to a more flexible system. Changes included reduced molecular area and peak pressure in Langmuir adsorption isotherms. Small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) analyses provided insights into the LP's structural organization within the membrane and its interaction with glyphosate (PNG). Structural and geometric parameters, as derived from in silico molecular dynamics simulations (MD), substantiated the impact of LP on the monolayer structure and the interaction with PNG. Notably, the presence of the LP and glyphosate increased charge transfer resistance, indicating strong adherence of the monolayer to the indium tin oxide (ITO) surface and effective pesticide interaction. A calibration curve for glyphosate concentration adjustment revealed a detection limit (LOD) of 24 nmol L-1, showcasing the high sensitivity of this electrochemical biosensor. This LOD is significantly lower than that of a similar colorimetric biosensor in aqueous media with a detection limit of approximately 0.3 µmol L-1. Such an improvement in sensitivity likely stems from adding a polar residue to the amino acid chain of the LP.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine , Glycine , Glyphosate , Lipopeptides , Molecular Dynamics Simulation , Glycine/chemistry , Glycine/analogs & derivatives , Glycine/analysis , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Lipopeptides/chemistry , Lipopeptides/analysis , Water/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Surface Properties
8.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167315, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897255

ABSTRACT

Anti-ganglioside antibodies (anti-Gg Abs) have been linked to delayed/poor clinical recovery in both axonal and demyelinating forms of Guillain-Barrè Syndrome (GBS). In many instances, the incomplete recovery is attributed to the peripheral nervous system's failure to regenerate. The cross-linking of cell surface gangliosides by anti-Gg Abs triggers inhibition of nerve repair in both in vitro and in vivo axon regeneration paradigms. This mechanism involves the activation of the small GTPase RhoA, which negatively modulates the growth cone cytoskeleton. At present, the identity/es of the receptor/s responsible for transducing the signal that ultimately leads to RhoA activation remains poorly understood. The aim of this work was to identify the transducer molecule responsible for the inhibitory effect of anti-Gg Abs on nerve repair. Putative candidate molecules were identified through proteomic mass spectrometry of ganglioside affinity-captured proteins from rat cerebellar granule neurons (Prendergast et al., 2014). These candidates were evaluated using an in vitro model of neurite outgrowth with primary cultured dorsal root ganglion neurons (DRGn) and an in vivo model of axon regeneration. Using an shRNA-strategy to silence putative candidates on DRGn, we identified tumor necrosis factor receptor 1A protein (TNFR1A) as a transducer molecule for the inhibitory effect on neurite outgrowth from rat/mouse DRGn cultures of a well characterized mAb targeting the related gangliosides GD1a and GT1b. Interestingly, lack of TNFr1A expression on DRGn abolished the inhibitory effect on neurite outgrowth caused by anti-GD1a but not anti-GT1b specific mAbs, suggesting specificity of GD1a/transducer signaling. Similar results were obtained using primary DRGn cultures from TNFR1a-null mice, which did not activate RhoA after exposure to anti-GD1a mAbs. Generation of single point mutants at the stalk region of TNFR1A identified a critical amino acid for transducing GD1a signaling, suggesting a direct interaction. Finally, passive immunization with an anti-GD1a/GT1b mAb in an in vivo model of axon regeneration exhibited reduced inhibitory activity in TNFR1a-null mice compared to wild type mice. In conclusion, these findings identify TNFR1A as a novel transducer receptor for the inhibitory effect exerted by anti-GD1a Abs on nerve repair, representing a significant step forward toward understanding the factors contributing to poor clinical recovery in GBS associated with anti-Gg Abs.

9.
Nano Lett ; 24(27): 8217-8231, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38848540

ABSTRACT

Theranostic medicine combines diagnostics and therapeutics, focusing on solid tumors at minimal doses. Optically activated photosensitizers are significant examples owing to their photophysical and chemical properties. Several optotheranostics have been tested that convert light to imaging signals, therapeutic radicals, and heat. Upon light exposure, conjugated photosensitizers kill tumor cells by producing reactive oxygen species and heat or by releasing cancer antigens. Despite clinical trials, these molecularly conjugated photosensitizers require protection from their surroundings and a localized direction for site-specific delivery during blood circulation. Therefore, cell membrane biomimetic ghosts have been proposed for precise and safe delivery of these optically active large molecules, which are clinically relevant because of their biocompatibility, long circulation time, bypass of immune cell recognition, and targeting ability. This review focuses on the role of biomimetic nanoparticles in the treatment and diagnosis of tumors through light-mediated diagnostics and therapy, providing insights into their preclinical and clinical status.


Subject(s)
Biomimetic Materials , Neoplasms , Photosensitizing Agents , Theranostic Nanomedicine , Humans , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/therapy , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/therapeutic use , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Animals , Biomimetics , Nanomedicine/methods
10.
J Am Geriatr Soc ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822739

ABSTRACT

BACKGROUND: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age-Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient-centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices. METHODS: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9-month virtual LC. It consisted of 4 synchronous, 1.5-h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre-post survey. Documentation of ACP in the EHR was collected after at least one plan-do-study-act cycle. RESULTS: We enrolled 17 participants from 6 PC practices (3 hospital-affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre-mean 2.9 [SD = 0.7]/post-mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post-collaborative (median 16.3%, IQR 1.3%-36.9%). CONCLUSIONS: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change.

11.
Stroke ; 55(8): 2139-2150, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38920050

ABSTRACT

BACKGROUND: Preconditioning by intermittent fasting is linked to improved cognition and motor function, and enhanced recovery after stroke. Although the duration of fasting was shown to elicit different levels of neuroprotection after ischemic stroke, the impact of time of fasting with respect to the circadian cycles remains unexplored. METHODS: Cohorts of mice were subjected to a daily 16-hour fast, either during the dark phase (active-phase intermittent fasting) or the light phase (inactive-phase intermittent fasting) or were fed ad libitum. Following a 6-week dietary regimen, mice were subjected to transient focal cerebral ischemia and underwent behavioral functional assessment. Brain samples were collected for RNA sequencing and histopathologic analyses. RESULTS: Active-phase intermittent fasting cohort exhibited better poststroke motor and cognitive recovery as well as reduced infarction, in contrast to inactive-phase intermittent fasting cohort, when compared with ad libitum cohort. In addition, protection of dendritic spine density/morphology and increased expression of postsynaptic density protein-95 were observed in the active-phase intermittent fasting. CONCLUSIONS: These findings indicate that the time of daily fasting is an important factor in inducing ischemic tolerance by intermittent fasting.


Subject(s)
Circadian Rhythm , Dendritic Spines , Fasting , Animals , Fasting/physiology , Mice , Circadian Rhythm/physiology , Dendritic Spines/pathology , Male , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Mice, Inbred C57BL , Recovery of Function/physiology , Intermittent Fasting
13.
Am J Perinatol ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38810899

ABSTRACT

This study aimed to investigate and present a review of the literature on long-term neurodevelopmental outcomes in children with gastroschisis. Gastroschisis is the most common abdominal wall defect. Children with gastroschisis are at high risk for premature birth, intestinal failure, sepsis, and repeated anesthesia exposure, which collectively increase the risk for adverse long-term neurodevelopmental outcomes. The existing literature on neurodevelopmental outcomes is limited in number, quality, and generalizability, creating a gap in clinical knowledge and care. Five internet databases were searched by a professional research librarian: Ovid MEDLINE, Scopus, Web of Science, PsycINFO, and Cochrane Library. Included articles were (1) published in English, (2) included postneonatal hospital discharge neurodevelopmental outcomes of children with gastroschisis, and (3) included patients under the age of 18 years. No date parameters were applied. The paucity of literature on long-term neurodevelopmental outcomes in gastroschisis children has left large gaps in the body of knowledge on post-hospital care of such children. In this review, 37 articles were found evaluating neurodevelopmental outcomes in gastroschisis and, while conclusions were contradictory, the literature broadly indicated the potential for neurodevelopmental deficits in the gastroschisis pediatric population. A significant limitation of this review was the heterogeneous samples included in available literature, which confounded the ability to determine cognitive risk of gastroschisis independent of other abdominal wall defects. Findings of this review demonstrate potential risk for neurodevelopmental deficits in the pediatric gastroschisis population exist, yet additional research is needed to definitively predict the significance, type, onset, and trajectory of neurodevelopmental impairment in this population. The significant gaps in long-term outcomes data have elucidated the need for prospective, longitudinal investigation of various cognitive domains in homogenous gastroschisis populations to properly evaluate prevalence of neurodevelopmental deficits and guide recommendations for long-term clinical care. KEY POINTS: · Limited literature exists regarding long-term neurodevelopmental outcomes in gastroschisis.. · There is some evidence to suggest worse cognitive behavioral outcomes in gastroschisis over time.. · Developmental surveillance, screening, and evaluation may be beneficial for gastroschisis patients..

14.
Nat Nanotechnol ; 19(6): 867-878, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750164

ABSTRACT

Owing to their distinct physical and chemical properties, inorganic nanoparticles (NPs) have shown promising results in preclinical cancer therapy, but designing and engineering them for effective therapeutic purposes remains a challenge. Although a comprehensive database of inorganic NP research is not currently available, it is crucial for developing effective cancer therapies. In this context, machine learning (ML) has emerged as a transformative tool, but its adaptation to nanomedicine is hindered by inexistent or small datasets. Here we assembled a large database of inorganic NPs, comprising experimental datasets from 745 preclinical studies in cancer nanomedicine. Using descriptive statistics and explainable ML models we mined this database to gain knowledge of inorganic NP design patterns and inform future NP research for cancer treatment. Our analyses suggest that NP shape and therapy type are prominent features in determining in vivo efficacy, measured as a percentage of tumour reduction. Moreover, our database provides a large-scale open-access resource for discriminative ML that the broader nanotechnology community can utilize. Our work blueprints data mining for translational cancer research and offers evidence for standardizing NP reporting to accelerate and de-risk inorganic NP-based drug delivery, which may help to improve patient outcomes in clinical settings.


Subject(s)
Machine Learning , Nanomedicine , Nanoparticles , Neoplasms , Nanoparticles/chemistry , Humans , Neoplasms/drug therapy , Animals , Nanomedicine/methods , Mice , Databases, Factual , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage
15.
Am J Occup Ther ; 78(4)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38768096

ABSTRACT

IMPORTANCE: Although research has examined early identification of autism spectrum disorder (ASD), few studies have found behavioral markers during midinfancy associated with later ASD diagnosis. OBJECTIVE: To examine infants' play behaviors and atypical positions at age 6 mo and later outcome classification among infants at elevated likelihood (EL) and typical likelihood (TL) for ASD. Atypical positions refer to movement patterns indicative of motor delays or deviations, including atypical extension and flexion, poor weight shift and rotation, hypertonicity or hypotonicity, and the presence of primitive reflex patterns. DESIGN: Observational cohort longitudinal design using blinded video analysis. PARTICIPANTS: Fifty-eight infants (41 EL infants and 17 TL infants) 6 mo of age. RESULTS: Infants later diagnosed with ASD needed more support to engage in play at age 6 mo compared with infants who did not receive an ASD diagnosis (U = 130, z = -2.29, p < .05, r = .31). Atypical positions at 6 mo of age were not associated with a later diagnosis of ASD. CONCLUSIONS AND RELEVANCE: Play behaviors may be early indicators of developmental differences for infants later diagnosed with ASD. The results of this pilot study suggest the need to observe the quality of interaction with a caregiver and objects during early play, which may serve as potential early indicators of ASD. Plain-Language Summary: Few studies have found behavioral markers during midinfancy that are associated with a later diagnosis of autism spectrum disorder (ASD). The results of this study showed that infants who were later diagnosed with ASD were found to have differences in play behaviors compared to infants who were not later diagnosed with ASD. Thus, early play behaviors may be an early indicator of developmental differences for infants who are later diagnosed with ASD.


Subject(s)
Autism Spectrum Disorder , Play and Playthings , Humans , Infant , Male , Female , Longitudinal Studies , Infant Behavior
16.
Alzheimers Res Ther ; 16(1): 102, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38725033

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.


Subject(s)
Alzheimer Disease , Polysomnography , Sleep Apnea, Obstructive , Sleep, REM , Humans , Female , Male , Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Alzheimer Disease/complications , Middle Aged , Sleep, REM/physiology , Aged , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/genetics , Risk Factors , Verbal Learning/physiology , Apolipoprotein E4/genetics , Memory/physiology , Severity of Illness Index , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/physiopathology , Sleep Apnea Syndromes/genetics
17.
Nat Commun ; 15(1): 4605, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816388

ABSTRACT

Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.


Subject(s)
Adipocytes , Diet, High-Fat , Inflammation , Insulin Resistance , Interferon Regulatory Factor-3 , Mice, Knockout , Obesity , Animals , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-3/genetics , Male , Obesity/metabolism , Mice , Diet, High-Fat/adverse effects , Inflammation/metabolism , Adipocytes/metabolism , Mice, Inbred C57BL , Glucose/metabolism , 3T3-L1 Cells
18.
Heliyon ; 10(8): e29657, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38655364

ABSTRACT

The need to find alternative materials to replace aqueous amine solutions for the capture of CO2 in post-combustion technologies is pressing. This study assesses the CO2 sorption capacity and CO2/N2 selectivity of three dicationic ionic liquids with distinct anions immobilized in commercial mesoporous silica support (SBA- 15). The samples were characterized by UART-FTIR, NMR, Raman, FESEM, TEM, TGA, Magnetometry (VSM), BET and BJH. The highest CO2 sorption capacity and CO2/N2 selectivity were obtained for sample SBA@DIL_2FeCl4 [at 1 bar and 25 °C; 57.31 (±0.02) mg CO2/g; 12.27 (±0.72) mg CO2/g]. The results were compared to pristine SBA-15 and revealed a similar sorption capacity, indicating that the IL has no impact on the CO2 sorption capacity of silica. On the other hand, selectivity was improved by approximately 3.8 times, demonstrating the affinity of the ionic liquid for the CO2 molecule. The material underwent multiple sorption/desorption cycles and proved to be stable and a promising option for use in industrial CO2 capture processes.

19.
J Sci Food Agric ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578668

ABSTRACT

Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. We conducted a systematic review of scientific articles published up to the year 2021, which included in vivo pre-clinical tests and clinical trials involving patients with acute infectious diarrhea to verify the antidiarrheal, antibacterial and antispasmodic effects of galenic preparations or phytopharmaceuticals from P. guajava. PRISMA and Rayyan were used as tools for the selection of studies collected in four databases (Pubmed, Scopus, Web of Science and Science Direct). The keywords used to carry out the search were: 'Psidium guajava', 'guava', 'antidiarrhe*' and 'diarrhe*', joined by Boolean operators 'OR' or 'AND'. The characteristics of studies in animal models of acute diarrhea induction, as well as in vivo and in vitro motility and microbiological tests linked with its main pathophysiological mechanisms, were collected. Twenty-three articles were included. Twenty (87%) of these reported heterogenic preclinical studies, predominating pharmacological studies of efficacy against conventional antidiarrheal agents, which utilized relevant outcomes and models of infectious diarrhea from the top pathogens in the clinic along with classical castor oil-induced diarrhea associated with motility tests. Only three articles (13%) corresponded to clinical trials investigating the efficacy, dose and safety of these preparations. Most studies reported positive results and significant mechanistic evidence from antibacterial, anti-motility, anti-secretory and protective/anti-inflammatory perspectives. However, further studies are needed to define the clinical significance and safety treatment with P. guajava extracts. © 2024 Society of Chemical Industry.

20.
Int J Exerc Sci ; 17(5): 13-24, 2024.
Article in English | MEDLINE | ID: mdl-38665138

ABSTRACT

Coach leadership style has long been positively correlated with athlete experiences such as motivation, health (i.e., burnout), and performance outcomes (i.e., enhanced execution time to complete tasks) (24). More recently, grit (18) has been positively correlated with athlete experiences such as engagement (39) and decreased burnout (32). Given the impact coaches have on their athletes and the positive psychological benefits of grit, it is reasonable to explore the intersections of coaching behaviors and grit. As such, the purpose of the current study was to examine the relationship between athlete perceptions of coach leadership behaviors and athlete grit. Intercollegiate athletes completed measures of grit and the leadership behaviors of their coach. A significant positive relationship was observed between the grit perseverance subscale and the leadership behavior of training and instruction (r =.30, p < .05). Additional analyses revealed that athletes' perceptions of coach positive feedback significantly predicted their perseverance. Taken together, these findings suggest a link between positive coach feedback and athlete perseverance. Implications of these results for professional practice and future research are discussed.

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