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1.
Ecol Evol ; 14(10): e70385, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39381195

RESUMEN

Optimal foraging theory (OFT) and the energy maximization hypothesis (EMH) have long been essential when examining wildlife habitat selection. At high latitudes and altitudes, animals in winter face greater limitations in availability and accessibility of forage. Here we explore the foraging behavior of wood bison (Bison bison athabascae) during winter within the Ronald Lake bison herd in northeastern Alberta, Canada, and examine the trade-offs they face due to limitations in forage abundance and availability (snow conditions), as well as the need to minimize predation risk. We used Global Positioning System (GPS) location data collected from 70 female wood bison to identify winter foraging sites and craters selected by bison to access forage beneath the snow. Within wetlands used by bison we selected 190 pairs of used (foraged) and random (available) sites to test eight a priori hypotheses explaining how bison traded-off between forage availability, accessibility, and minimizing predation risk. We found with matched-paired logistic regression that Carex atherodes was 1.21-times more likely to be selected per unit increase in ground cover, compared to 1.17-times per unit ground cover for C. aquatilis and C. utriculata. However, all Carex species showed an increase in selection when cover was > 50% cover within individual craters. While the importance of Carex was clear, forage site selection was still inversely related to snow depth. There is also a neutralizing combined effect of snow depth and Carex species ground cover which suggests that bison maximized their energy return by avoiding areas with deep snow (> 30 cm) that demanded intensive cratering, even when highly selected forage was accessible beneath. Avoidance of forage areas with deep snow demonstrates that wood bison employed a foraging strategy that considers both forage availability and environmental conditions, with snow depth being a limiting factor. We highlight the relationship between optimal foraging based on food availability and the trade-offs within an energy restrictive winter season, furthering the understanding of how large herbivores forage strategically to maximize energy intake in northern environments.

2.
J Am Vet Med Assoc ; : 1-6, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39362266

RESUMEN

OBJECTIVE: To evaluate outcome in 60 dogs with cystine urolithiasis treated with surgical removal with and without castration and postoperative therapeutic diet to determine frequency of recurrence and urolith-free duration. METHODS: Patient records were reviewed for dogs with documented cystine urolithiasis from September 2010 to December 2020. Medical records, client interviews, and referring veterinarians were contacted to document the absence of clinical signs associated with subsequent urolith formation and to evaluate risk factors for urolith reoccurrence. RESULTS: 80 patients were identified with cystine uroliths, with 60 qualifying for inclusion in the study. Seven dogs were neutered prior to surgery, and 25 dogs were neutered at the time of the first surgery. Recurrence occurred in 20 dogs; 17 of those patients were intact (85%) at the time of recurrent urinary signs. Of the 20 dogs with recurrence, 50% (10 of 20) were being treated with dietary modifications. CONCLUSIONS: The risk of recurrence among neutered pets was 23% versus 47% for intact pets, but this difference was not statistically significant; however, neutered pets had a longer urolithiasis-free duration. There was no statistically significant difference in risk of recurrence and urolith-free duration between pets with and without therapeutic diet management, (30% vs 32.5%) respectively. Multivariant analysis showed no significant interaction between surgical intervention with therapeutic diet, with nonsignificant hazard ratios (HRs) for neuter status (HR = 0.503), diet (HR = 1.056), and their interaction (HR = 4.32 to 9). CLINICAL RELEVANCE: Sexually intact (vs castrated) male dogs should be monitored more closely for recurrence of surgical cystine urolithiasis.

3.
J Learn Disabil ; : 222194241263649, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092930

RESUMEN

We created and tested a family-based intervention with families of children in Grades 1 and 2 with reading and behavioral difficulties to investigate its impact on text comprehension. Developed with input from parents, reading experts, and behavior specialists, Family-RISE (Reading Intervention with Supports for Engagement) integrates evidence-based practices for enhancing students' knowledge of narrative texts with effective behavioral supports to maximize student engagement and minimize disruptive behaviors to help parents engage successfully in shared storybook reading. We assessed the effects of Family-RISE on children's narrative text comprehension using a multiple-baseline design. A functional relation was established between Family-RISE and narrative text comprehension, indicating Family-RISE substantially improved narrative text comprehension. Furthermore, nonoverlap of all pairs, Tau-U, and standard mean difference effect sizes were all considered large in favor of the intervention. Family members reported that the intervention was highly usable, feasible to implement, and socially valid. These findings underscore the promise of the Family-RISE intervention and the value of developing interventions that simultaneously support reading and behavior for children with co-occurring difficulties in these areas.

4.
Mol Metab ; 89: 102013, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39182840

RESUMEN

OBJECTIVES: The mitochondrial enzyme L-2-hydroxyglutarate dehydrogenase (L2HGDH) regulates the abundance of L-2-hydroxyglutarate (L-2HG), a potent signaling metabolite capable of influencing chromatin architecture, mitochondrial metabolism, and cell fate decisions. Loss of L2hgdh activity in humans induces ectopic L-2HG accumulation, resulting in neurodevelopmental defects, altered immune cell function, and enhanced growth of clear cell renal cell carcinomas. To better understand the molecular mechanisms that underlie these disease pathologies, we used the fruit fly Drosophila melanogaster to investigate the endogenous functions of L2hgdh. METHODS: L2hgdh mutant adult male flies were analyzed under normoxic and hypoxic conditions using a combination of semi-targeted metabolomics and RNA-seq. These multi-omic analyses were complemented by tissue-specific genetic studies that examined the effects of L2hgdh mutations on the Drosophila renal system (Malpighian tubules; MTs). RESULTS: Our studies revealed that while L2hgdh is not essential for growth or viability under standard culture conditions, L2hgdh mutants are hypersensitive to hypoxia and expire during the reoxygenation phase with severe disruptions of mitochondrial metabolism. Moreover, we find that the fly renal system is a key site of L2hgdh activity, as L2hgdh mutants that express a rescuing transgene within the MTs survive hypoxia treatment and exhibit normal levels of mitochondrial metabolites. We also demonstrate that even under normoxic conditions, L2hgdh mutant MTs experience significant metabolic stress and are sensitized to aberrant growth upon Egfr activation. CONCLUSIONS: These findings present a model in which renal L2hgdh activity limits systemic L-2HG accumulation, thus indirectly regulating the balance between glycolytic and mitochondrial metabolism, enabling successful recovery from hypoxia exposure, and ensuring renal tissue integrity.


Asunto(s)
Drosophila melanogaster , Hipoxia , Mitocondrias , Animales , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Mitocondrias/metabolismo , Masculino , Hipoxia/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Oxidorreductasas de Alcohol/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Glutaratos/metabolismo , Riñón/metabolismo , Mutación
5.
Microbiol Spectr ; 12(10): e0051624, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39166864

RESUMEN

Since the discovery of complete ammonia oxidizers (comammox) within the genus Nitrospira, their distribution and abundance across habitats have been intensively studied to better understand their ecological significance. Many primers targeting their ammonia monooxygenase subunit A gene (amoA) have been designed to detect and quantify comammox bacteria and to describe their community structure. We identified 38 published primers, but only few had high coverage and specificity for all known comammox Nitrospira or one of the two described subclades. For each target group, we comprehensively evaluated selected primer pairs using in silico analyses, endpoint PCRs, qPCRs, and amplicon sequencing on samples from various environments. Endpoint PCRs and qPCRs showed that the most commonly used primer pairs (comaA-244F/659R, comaB-244F/659R, and Ntsp-amoA162F/359R) produced several bands, which likely inflated quantifications via qPCR. In contrast, the recently published primer combinations CA377F/C576R, CB377F/C576R, and CA-CB377F/C576R resulted mostly in a single band. Furthermore, amplicon sequencing demonstrated that these primer combinations also captured the highest richness of comammox Nitrospira. Taken together, our results indicate that few existing comammox amoA primer combinations have both high specificity and coverage and that the choice of these high-specificity and high-coverage primer pairs substantially impacts the accurate detection, quantification, and community description of comammox bacteria. We, therefore, recommend using the CA377F/C576R, CB377F/C576R, and CA-CB377F/C576R primer pairs.IMPORTANCEBacteria that can fully convert ammonia via nitrite to nitrate, the complete ammonia oxidizers (comammox), were recently discovered and are found in many natural and engineered environments. PCR-based tools to study their abundance and diversity were rapidly developed, resulting in a plethora of primers available, many of which are widely used. The presence of comammox bacteria in an environment can, however, only be correctly determined if the used primers detect all members of this group while not detecting any other guilds. This study assesses the coverage and specificity of existing primers targeting comammox bacteria using both computational and standard molecular techniques, revealing large differences in their performance. The uniform usage of well-performing primers across studies could aid in generating comparable and generalizable data to better understand the importance of comammox bacteria in the environment.


Asunto(s)
Amoníaco , Cartilla de ADN , Oxidación-Reducción , Oxidorreductasas , Amoníaco/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Cartilla de ADN/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Filogenia , Bacterias/genética , Bacterias/enzimología , Bacterias/clasificación , Bacterias/metabolismo
6.
Res Sq ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39149494

RESUMEN

Background: The gut microbiome has emerged as a clear player in health and disease, in part by mediating host response to environment and lifestyle. The urobiome (microbiota of the urinary tract) likely functions similarly. However, efforts to characterize the urobiome and assess its functional potential have been limited due to technical challenges including low microbial biomass and high host cell shedding in urine. Here, to begin addressing these challenges, we evaluate urine sample volume (100 ml - 5 mL), and host DNA depletion methods and their effects on urobiome profiles in healthy dogs, which are a robust large animal model for the human urobiome. We collected urine from seven dogs and fractionated samples into aliquots. One set of samples was spiked with host (canine) cells to model a biologically relevant host cell burden in urine. Samples then underwent DNA extraction followed by 16S rRNA gene and shotgun metagenomic sequencing. We then assembled metagenome assembled genomes (MAGs) and compared microbial composition and diversity across groups. We tested six methods of DNA extraction: QIAamp BiOstic Bacteremia (no host depletion), QIAamp DNA Microbiome, Molzym MolYsis, NEBNext Microbiome DNA Enrichment, Zymo HostZERO, and Propidium Monoazide. Results: In relation to urine sample volume, 3 3.0 mL resulted in the most consistent urobiome profiling. In relation to host depletion, individual (dog) but not extraction method drove overall differences in microbial composition. DNA Microbiome yielded the greatest microbial diversity in 16S rRNA sequencing data and shotgun metagenomic sequencing data, and maximized MAG recovery while effectively depleting host DNA in host-spiked urine samples. As proof-of-principle, we then mined MAGs for core metabolic functions and environmental chemical metabolism. We identified long chain alkane utilization in two of the urine MAGs. Long chain alkanes are common pollutants that result from industrial combustion processes and end up in urine. Conclusions: This is the first study, to our knowledge, to demonstrate environmental chemical degradation potential in urine microbes through genome-resolved metagenomics. These findings provide guidelines for studying the urobiome in relation to sample volume and host depletion, and lay the foundation for future evaluation of urobiome function in relation to health and disease.

8.
Mol Ecol ; 33(14): e17432, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38887831

RESUMEN

Atmospheric CO2 and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological and behavioural responses of aquatic organisms. Further, spring snowmelt may cause transient increases of pCO2 in many freshwater systems. We examined the behavioural, physiological and transcriptomic responses of an ancient fish, the lake sturgeon (Acipenser fulvescens) to projected levels of warming and pCO2 during its most vulnerable period of life, the first year. Specifically, larval fish were raised in either low (16°C) or high (22°C) temperature, and/or low (1000 µatm) or high (2500 µatm) pCO2 in a crossed experimental design over approximately 8 months. Following overwintering, lake sturgeon were exposed to a transient increase in pCO2 of 10,000 µatm, simulating a spring melt based on data in freshwater systems. Transcriptional analyses revealed potential connections to otolith formation and reduced growth in fish exposed to high pCO2 and temperature in combination. Network analyses of differential gene expression revealed different biological processes among the different treatments on the edges of transcriptional networks. Na+/K+-ATPase activity increased in fish not exposed to elevated pCO2 during development, and mRNA abundance of the ß subunit was most strongly predictive of enzyme activity. Behavioural assays revealed a decrease in total activity following an acute CO2 exposure. These results demonstrate compensatory and compounding mechanisms of pCO2 and warming dependent on developmental conditions in lake sturgeon. Conserved elements of the cellular stress response across all organisms provide key information for how other freshwater organisms may respond to future climate change.


Asunto(s)
Dióxido de Carbono , Peces , Lagos , Temperatura , Animales , Dióxido de Carbono/metabolismo , Peces/genética , Transcriptoma , Cambio Climático , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Larva/genética
9.
J Clin Invest ; 134(13)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743486

RESUMEN

Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule l-2-hydroxyglutarate (l-2HG) is elevated in the most common histology of renal cancer. Similarly to other oncometabolites, l-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that l-2HG remodels amino acid metabolism in renal cancer cells through combined effects on histone methylation and RNA N6-methyladenosine. The combined effects of l-2HG result in a metabolic liability that renders tumors cells reliant on exogenous serine to support proliferation, redox homeostasis, and tumor growth. In concert with these data, high-l-2HG kidney cancers demonstrate reduced expression of multiple serine biosynthetic enzymes. Collectively, our data indicate that high-l-2HG renal tumors could be specifically targeted by strategies that limit serine availability to tumors.


Asunto(s)
Glutaratos , Neoplasias Renales , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Glutaratos/metabolismo , Humanos , Animales , Ratones , Línea Celular Tumoral , Serina/metabolismo , Epigenoma , Transcriptoma , Histonas/metabolismo , Histonas/genética , Regulación Neoplásica de la Expresión Génica , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Epigénesis Genética , Adenosina/análogos & derivados
10.
Front Physiol ; 15: 1376628, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559573

RESUMEN

The objective of the present study was to determine the effect of a novel (4th generation) phytase supplementation as well as its mode of action on growth, meat quality, and incidence of muscle myopathies. One-day old male broilers (n = 720) were weighed and randomly allocated to 30 floor pens (24 birds/pen) with 10 replicate pens per treatment. Three diets were fed from hatch to 56- days-old: a 3-phase corn-soy based diet as a positive control (PC); a negative control (NC) formulated to be isocaloric and isonitrogenous to the PC and with a reduction in Ca and available P, respectively; and the NC supplemented with 2,000 phytase units per kg of diet (NC + P). At the conclusion of the experiment, birds fed with NC + P diet were significantly heavier and had 2.1- and 4.2-points better feed conversion ratio (FCR) compared to birds offered NC and PC diets, respectively. Processing data showed that phytase supplementation increased live weight, hot carcass without giblets, wings, tender, and skin-on drum and thigh compared to both NC and PC diets. Macroscopic scoring showed that birds fed the NC + P diet had lower woody breast (WB) severity compared to those fed the PC and NC diets, however there was no effect on white striping (WS) incidence and meat quality parameters (pH, drip loss, meat color). To delineate its mode of action, iSTAT showed that blood glucose concentrations were significantly lower in birds fed NC + P diet compared to those offered PC and NC diets, suggesting a better glucose uptake. In support, molecular analyses demonstrated that the breast muscle expression (mRNA and protein) of glucose transporter 1 (GLUT1) and glucokinase (GK) was significantly upregulated in birds fed NC + P diet compared to those fed the NC and PC diets. The expression of mitochondrial ATP synthase F0 subunit 8 (MT-ATP8) was significantly upregulated in NC + P compared to other groups, indicating intracellular ATP abundance for anabolic pathways. This was confirmed by the reduced level of phosphorylated-AMP-activated protein kinase (AMPKα1/2) at Thr172 site, upregulation of glycogen synthase (GYS1) gene and activation of mechanistic target of rapamycin and ribosomal protein S6 kinase (mTOR-P70S6K) pathway. In conclusion, this is the first report showing that in-feed supplementation of the novel phytase improves growth performance and reduces WB severity in broilers potentially through enhancement of glucose uptake, glycolysis, and intracellular ATP production, which used for muscle glycogenesis and protein synthesis.

11.
Front Vet Sci ; 11: 1382535, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605922

RESUMEN

Powered by consumer taste, value, and preferences, natural products including phytogenics and algae are increasingly and separately used in the food systems where they have been reported to improve growth performance in poultry and livestock. The present study aimed to determine the effects of a new feed additive, microencapsulated NUQO© NEX, which contains a combination of phytogenic and phycogenic, on broiler growth performance, blood chemistry, bone health, meat quality and sensory profile. Male Cobb500 chicks (n = 1,197) were fed a 3-phase feeding intervals; 1-14d starter, 15-28d grower, and 29-40d finisher. The dietary treatments included a corn-soy basal Control (CON), basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 28d then 75 g/ton from d 28 to 40 (NEX75), and basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 40d (NEX100). The NEX100 supplemented birds had 62 g more BWG increase and 2.1-point improvement in FCR compared with CON in the finisher and overall growth phase (p < 0.05), respectively. Day 40 processing body weights and carcass weights were heavier for the NEX100 supplemented birds (p < 0.05). The incidences of muscle myopathies were also higher in NEX treatments, which could be associated with the heavier weights, but the differences were not detected to be significant. The NEX75 breast filets had more yellowness than other dietary treatments (p = 0.003) and the NEX 100 treatment reduced the levels of breast filet TBARS at 7 days-post harvest (p = 0.053). Finally, both NEX treatments reduced the incidence of severe bone (tibia and femur) lesions. In conclusion, the supplementation of the phytogenic NUQO© NEX improved finisher performance parameters, whole phase FCR, processing carcass weights, and breast filet yellowness, at varying inclusion levels.

12.
Nature ; 627(8004): 546-552, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38467896

RESUMEN

The generation of spectrally pure microwave signals is a critical functionality in fundamental and applied sciences, including metrology and communications. Optical frequency combs enable the powerful technique of optical frequency division (OFD) to produce microwave oscillations of the highest quality1,2. Current implementations of OFD require multiple lasers, with space- and energy-consuming optical stabilization and electronic feedback components, resulting in device footprints incompatible with integration into a compact and robust photonic platform3-5. Here we demonstrate all-optical OFD on a photonic chip by synchronizing two distinct dynamical states of Kerr microresonators pumped by a single continuous-wave laser. The inherent stability of the terahertz beat frequency between the signal and idler fields of an optical parametric oscillator is transferred to a microwave frequency of a Kerr soliton comb, and synchronization is achieved via a coupling waveguide without the need for electronic locking. OFD factors of N = 34 and 468 are achieved for 227 GHz and 16 GHz soliton combs, respectively. In particular, OFD enables a 46 dB phase-noise reduction for the 16 GHz soliton comb, resulting in the lowest microwave noise observed in an integrated photonics platform. Our work represents a simple, effective approach for performing OFD and provides a pathway towards chip-scale devices that can generate microwave frequencies comparable to the purest tones produced in metrological laboratories.

13.
Urol Oncol ; 42(5): 158.e11-158.e16, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38365461

RESUMEN

INTRODUCTION: Prostate cancer screening has routinely identified men with very low- or low-risk disease, per the National Comprehensive Cancer Network guidelines. Current literature has demonstrated that the most appropriate management strategy for these patients is active surveillance (AS). The mainstay of AS includes periodic biopsies and biannual prostate-specific antigen tests. However, multiparametric magnetic resonance imaging (mpMRI) is uniquely posed to improve patient surveillance. This study aimed to evaluate the utility of an annual mpMRI in patients on AS, focusing on radiologic upgrading and Prostate Imaging-Reporting and Data System (PI-RADS) trends as indicators of clinically significant disease. METHODS: This prospective, single intuition, study enrolled 208 patients on AS who had at least two biopsies and 1 mpMRI with a median follow-up of 5.03 years. The main outcome variable was time to Gleason grade (GG) reclassification. RESULTS: After delineating patients on their initial PI-RADS score, men with score 3 and 5 lesions at first MRI had comparable GG reclassification-free survival to their counterparts. Conversely, men with initial PI-RADS 4 lesions showed a lower 5-year GG reclassification-free survival compared to those with PI-RADS score 1-2. The cohort was then subset to 70 patients who obtained ≥2 mpMRIs on protocol. Men experiencing uptrending mpMRI scores had an increased risk of GG reclassification, with a 35.4% difference in 5 year GG reclassification-free survival probability on the Kaplan-Meier curve analysis. CONCLUSION: In conclusion, this study demonstrates that for men on AS with stable recapitulated disease, an annual MRI may replace repeat biopsies after confirmatory sampling has been obtained. On the other hand, men who initiate AS with PI-RADS 4 and/or who display uptrending mpMRI scores require periodic biopsies along with repeat imaging. This study highlights the utility of integrating an annual MRI into AS protocols, thus promising a more effective approach to management.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Antígeno Prostático Específico , Estudios Prospectivos , Detección Precoz del Cáncer , Biopsia Guiada por Imagen/métodos , Estudios Retrospectivos
14.
Brain Res ; 1829: 148772, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38244754

RESUMEN

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age- and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17ß-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.


Asunto(s)
Enfermedad de Alzheimer , Microglía , Persona de Mediana Edad , Humanos , Masculino , Femenino , Ratones , Animales , Anciano , Microglía/metabolismo , Enfermedad de Alzheimer/metabolismo , Envejecimiento , Encéfalo/metabolismo , Estrógenos/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo
15.
Neurobiol Stress ; 28: 100597, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38213318

RESUMEN

Dominance status has extensive effects on physical and mental health, and an individual's relative position can be shaped by experiential factors. A variety of considerations suggest that the experience of behavioral control over stressors should produce winning in dominance tests and that winning should blunt the impact of later stressors, as does prior control. To investigate the interplay between competitive success and stressor control, we first examined the impact of stressor controllability on subsequent performance in a warm spot competition test modified for rats. Prior experience of controllable, but not physically identical uncontrollable, stress increased later effortful behavior and occupation of the warm spot. Controllable stress subjects consistently ranked higher than did uncontrollable stress subjects. Pharmacological inactivation of the prelimbic (PL) cortex during behavioral control prevented later facilitation of dominance. Next, we explored whether repeated winning experiences produced later resistance against the typical sequelae of uncontrollable stress. To establish dominance status, triads of rats were given five sessions of warm spot competition. The development of stable dominance was prevented by reversible inactivation of the PL or NMDA receptor blockade in the dorsomedial striatum. Stable winning blunted the later stress-induced increase in dorsal raphe nucleus serotonergic activity, as well as prevented uncontrollable stress-induced social avoidance. In contrast, endocrine and neuroimmune responses to uncontrollable stress were unaffected, indicating a selective impact of prior dominance. Together, these data demonstrate that instrumental control over stress promotes later dominance, but also reveal that winning experiences buffer against the neural and behavioral outcomes of future adversity.

16.
Arthroscopy ; 40(1): 124-132, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37355190

RESUMEN

PURPOSE: To compare the time-zero biomechanical properties of hamstring graft preparations with or without suture augmentation for anterior cruciate ligament reconstruction (ACLR) in a full-construct cadaveric model. METHODS: Hamstring grafts were harvested from 24 fresh frozen human cadavers and prepared in 1 of 3 ways: quadrupled SemiTendinosus (SemiT), and quadrupled SemiT with suture augmentation (SemiT+2.0-mm tape or SemiT+1.3-mm tape; n = 8 per group). Adjustable loop suspensory implants and cortical buttons were used for fixation on a porcine tibia and acrylic block. Testing included force-controlled cyclic loading at 250 N and 400 N followed by load to failure. RESULTS: The 2 suture augmentation groups had less total elongation and increased stiffness compared to the nonsuture-augmented group (P = .025). The SemiT+2.0-mm tape group had 36% less total elongation and 34% increased stiffness compared to SemiT+1.3mm tape (P < .001). CONCLUSIONS: Suture augmentation improves construct biomechanics at time zero following hamstring tendon ACLR. Augmentation with 2.0-mm tape suture improves construct biomechanics compared to 1.3-mm tape suture. CLINICAL RELEVANCE: Independent suture augmentation of a quadrupled SemiT graft improves ACLR construct biomechanics. Outcomes were improved with augmentation using 2.0-mm tape suture compared to 1.3-mm tape suture.


Asunto(s)
Ligamento Cruzado Anterior , Músculos Isquiosurales , Humanos , Porcinos , Animales , Ligamento Cruzado Anterior/cirugía , Músculos Isquiosurales/trasplante , Tibia/cirugía , Fenómenos Biomecánicos , Suturas
17.
Behav Modif ; 48(2): 150-181, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38142355

RESUMEN

In this study we tested the usability, feasibility, social validity, and effectiveness of Engaged Learners, a behavior support program designed to be integrated into small group reading interventions. Participants included eight Grade 3 to 5 students with co-occurring reading difficulties and inattention. A concurrent multiple-baseline design was utilized to test the effects of Engaged Learners on engagement outcomes. Visual analysis and effect sizes indicated an improvement in engagement for seven students. Interventionists and students viewed the Engaged Learners program to be effective and socially valid. Limitations included lower than expected levels of fidelity for one interventionist and high student absenteeism. More research is needed to identify the extent to which Engaged Learners can support reading outcomes. Educators seeking an effective behavior support program that requires minimal training and coaching may consider integrating Engaged Learners into their small group reading instruction.


Asunto(s)
Tutoría , Lectura , Humanos , Estudiantes , Cognición
18.
Arthroscopy ; 40(8): 2229-2235.e1, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38161048

RESUMEN

PURPOSE: To quantify progression of chondral and meniscal injuries between primary and revision anterior cruciate ligament (ACL) surgery. METHODS: Patients who underwent both index and revision ACL reconstruction between 2000 and 2020 at our institution were identified, and dates of injury and surgery, demographics, and clinical data were obtained from operative reports. Outerbridge grade was recorded in each compartment, along with presence and location of meniscal injury. The frequency of each injury between first and second cases was calculated. Differences in injury and progression were compared over time as well as between patient sex and age. RESULTS: The study included 189 patients (96 female, 93 male). Age at first surgery was 31.7 ± 13.2 years. Mean time to second injury was 3.3 ± 3.0 years. In total, 116 patients had a new or previous chondral injury (odds ratio, 1.6; 95% CI, 1.2-2.1). The medial femoral condyle (31%) and the patella (21%) accounted for the highest proportion of new injury to articular surfaces, whereas new injury to menisci was comparable between the medial (25%) and lateral (23%) meniscus. At the time of revision ACL reconstruction, females had a high prevalence of chondral injuries to the lateral compartment, whereas males had a high prevalence of chondral injury to the medial femoral condyle. The prevalence of new chondral injuries was comparable between sexes, with males having a slightly higher proportion. While time between surgeries, sex, and age had graphical evidence of moderating risk, the effects were small and imprecise. CONCLUSIONS: Revision ACL reconstruction carried a 1.6 increase in the odds for new or progressive chondral lesions in our cohort. At the time of revision, females had a relatively higher proportion of lateral-sided chondral injuries, whereas males had a relatively higher proportion of medial femoral condyle injuries. The greatest increase in the prevalence of new and progressive lesions was observed in the medial femoral condyle and trochlea. This progression appeared to be moderated by time between surgeries, patient sex, and age; however, the differences were small and imprecise. LEVEL OF EVIDENCE: Level IV, therapeutic case series.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Cartílago Articular , Progresión de la Enfermedad , Reoperación , Humanos , Masculino , Femenino , Adulto , Reoperación/estadística & datos numéricos , Lesiones del Ligamento Cruzado Anterior/cirugía , Factores Sexuales , Cartílago Articular/lesiones , Cartílago Articular/cirugía , Adulto Joven , Lesiones de Menisco Tibial/cirugía , Estudios Retrospectivos , Adolescente , Persona de Mediana Edad
19.
bioRxiv ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38076915

RESUMEN

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age-and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17ß-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.

20.
Can J Vet Res ; 87(4): 290-296, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37790270

RESUMEN

Cranial cruciate ligament (CCL) disease is the leading cause of canine lameness. Diagnosis is based on physical examination and diagnostic imaging findings. Limitations of diagnostic modalities, including patient temperament, cost, availability, and need for general anesthesia, preclude their use for many patients. Infrared thermography is an easy, non-invasive diagnostic screening technique with use in both human and veterinary musculoskeletal conditions. The objective of this study was to investigate the utility of infrared thermography to diagnose CCL disease in a large population of client-owned dogs and investigate for correlations between ability of thermography to diagnose CCL deficiency and recorded explanatory factors. A commercial grade thermal imaging camera was used to collect preoperative images of both stifles in 50 dogs with surgically confirmed CCL rupture in one stifle and a normal opposite stifle. The average maximum temperatures of the affected and unaffected stifles were collected from these images and used for statistical analysis. Infrared thermography was not successful in differentiating between CCL-deficient and unaffected stifles in this cohort. No significant differences in average maximal temperature were observed between stifles when comparing to explanatory factors or variables. Use of infrared thermography should not be relied upon to diagnose canine CCL disease.


La pathologie du ligament croisé crânien (CCL) est la principale cause de boiterie canine. Le diagnostic repose sur l'examen physique et les résultats de l'imagerie diagnostique. Les limites des modalités de diagnostic, y compris le tempérament du patient, le coût, la disponibilité et la nécessité d'une anesthésie générale, empêchent leur utilisation pour de nombreux patients. La thermographie infrarouge est une technique de dépistage diagnostique simple et non invasive, utilisable dans les conditions musculosquelettiques humaines et vétérinaires. L'objectif de cette étude était d'étudier l'utilité de la thermographie infrarouge pour diagnostiquer les problèmes de CCL dans une grande population de chiens appartenant à des clients et d'étudier les corrélations entre la capacité de la thermographie à diagnostiquer une déficience du CCL et les facteurs explicatifs enregistrés. Une caméra d'imagerie thermique de qualité commerciale a été utilisée pour collecter des images préopératoires des deux grassets chez 50 chiens avec une rupture du CCL confirmée chirurgicalement dans un grasset et un grasset opposé normal. Les températures maximales moyennes des grassets affectés et non affectés ont été recueillies à partir de ces images et utilisées pour l'analyse statistique. La thermographie infrarouge n'a pas réussi à différencier les grassets avec atteintes du CCL des grassets non affectés dans cette cohorte. Aucune différence significative dans la température maximale moyenne n'a été observée entre les grassets lors de la comparaison avec des facteurs ou variables explicatifs. L'utilisation de la thermographie infrarouge ne doit pas être utilisée pour diagnostiquer les pathologie du CCL canin.(Traduit par Docteur Serge Messier).


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Enfermedades de los Perros , Humanos , Perros , Animales , Ligamento Cruzado Anterior/cirugía , Termografía/veterinaria , Lesiones del Ligamento Cruzado Anterior/veterinaria , Rodilla de Cuadrúpedos/cirugía , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/cirugía
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