Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.902
Filtrar
1.
J Fish Biol ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965998

RESUMO

Acoustic telemetry has been used to monitor the movement of aquatic animals in a broad range of aquatic environments. Despite their importance, mangrove habitats are understudied for the spatial ecology of elasmobranchs, with acoustic telemetry rarely used inside mangrove habitats. One reason for this may be a general assumption that acoustic signals would not be able to be detected by receivers in such shallow, structurally complex, environments. This study tested whether acoustic receivers can be used inside mangrove habitats to track the movement of sharks and rays. Thirty-eight receivers were deployed in a mangrove system in Pioneer Bay, Orpheus Island, Great Barrier Reef, including inside mangroves, mangrove edges, and adjacent reef flat areas. The detection range and receiver performance metrics, such as code detection efficiency, rejection coefficient, and noise quotient, were examined and tested among habitats. The results highlighted that the signal from transmitters was successfully detected inside mangrove habitats as well as on the adjacent reef flat. The range to detect at least 50% of transmissions was up to 20 m inside mangroves and up to 120 m outside mangroves. The performance metrics of acoustic receivers inside the mangrove habitat were characterized by low background noise, low rejection rates, and reasonably high code detection efficiency. Furthermore, this study tested the application of this method on juvenile blacktip reef shark Carcharhinus melanopterus and mangrove whipray Urogymnus granulatus, and demonstrated that it can be used to successfully track animals inside mangrove habitat. This novel method could reveal further information on how sharks and rays use mangrove habitats.

2.
J Biol Chem ; : 107569, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009342

RESUMO

Loss of glycogen myophosphorylase (PYGM) expression results in an inability to break down muscle glycogen, leading to McArdle disease-an autosomal recessive metabolic disorder characterized by exercise intolerance and muscle cramps. While previously considered relatively benign, this condition has recently been associated with pattern dystrophy in the retina, accompanied by variable sight impairment, secondary to retinal pigment epithelial (RPE) cell involvement. However, the pathomechanism of this condition remains unclear. In this study, we generated a PYGM-null induced pluripotent stem cell (iPSC) line, and differentiated it into mature RPE to examine structural and functional defects, along with metabolite release into apical and basal media. Mutant RPE exhibited normal photoreceptor outer segment phagocytosis but displayed elevated glycogen levels, reduced transepithelial resistance, and increased cytokine secretion across the epithelial layer compared to isogenic wildtype controls. Additionally, decreased expression of the visual cycle component, RDH11, encoding 11-cis-retinol dehydrogenase, was observed in PYGM-null RPE. While glycolytic flux and oxidative phosphorylation levels in PYGM-null RPE were near normal, the basal oxygen consumption rate (OCR) was increased. OCR in response to physiological levels of lactate was significantly greater in wildtype compared to PYGM-null RPE. Inefficient lactate utilization by mutant RPE resulted in higher glucose dependence and increased glucose uptake from the apical medium in the presence of lactate, suggesting a reduced capacity to spare glucose for photoreceptor use. Metabolic tracing confirmed slower 13C-lactate utilization by PYGM-null RPE. These findings have key implications for retinal health since they likely underlie the vision impairment in individuals with McArdle disease.

3.
JMIR Ment Health ; 11: e59198, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38967418

RESUMO

Background: Paranoia is a spectrum of fear-related experiences that spans diagnostic categories and is influenced by social and cognitive factors. The extent to which social media and other types of media use are associated with paranoia remains unclear. Objective: We aimed to examine associations between media use and paranoia at the within- and between-person levels. Methods: Participants were 409 individuals diagnosed with schizophrenia spectrum or bipolar disorder. Measures included sociodemographic and clinical characteristics at baseline, followed by ecological momentary assessments (EMAs) collected 3 times daily over 30 days. EMA evaluated paranoia and 5 types of media use: social media, television, music, reading or writing, and other internet or computer use. Generalized linear mixed models were used to examine paranoia as a function of each type of media use and vice versa at the within- and between-person levels. Results: Of the 409 participants, the following subgroups reported at least 1 instance of media use: 261 (63.8%) for using social media, 385 (94.1%) for watching TV, 292 (71.4%) for listening to music, 191 (46.7%) for reading or writing, and 280 (68.5%) for other internet or computer use. Gender, ethnoracial groups, educational attainment, and diagnosis of schizophrenia versus bipolar disorder were differentially associated with the likelihood of media use. There was a within-person association between social media use and paranoia: using social media was associated with a subsequent decrease of 5.5% (fold-change 0.945, 95% CI 0.904-0.987) in paranoia. The reverse association, from paranoia to subsequent changes in social media use, was not statistically significant. Other types of media use were not significantly associated with paranoia. Conclusions: This study shows that social media use was associated with a modest decrease in paranoia, perhaps reflecting the clinical benefits of social connection. However, structural disadvantage and individual factors may hamper the accessibility of media activities, and the mental health correlates of media use may further vary as a function of contents and contexts of use.


Assuntos
Transtorno Bipolar , Avaliação Momentânea Ecológica , Transtornos Paranoides , Esquizofrenia , Mídias Sociais , Humanos , Feminino , Masculino , Transtorno Bipolar/psicologia , Transtorno Bipolar/epidemiologia , Adulto , Esquizofrenia/epidemiologia , Esquizofrenia/diagnóstico , Mídias Sociais/estatística & dados numéricos , Pessoa de Meia-Idade , Transtornos Paranoides/psicologia , Transtornos Paranoides/epidemiologia
4.
Eur J Intern Med ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39034174

RESUMO

OBJECTIVES: To evaluate whether the timing of initial antibiotic administration in patients with sepsis in hospital affects mortality. METHODS: This systematic review and meta-analysis included studies from inception up to 19 May 2022. Interventional and observational studies including adult human patients with suspected or confirmed sepsis and reported time of antibiotic administration with mortality were included. Data were extracted by two independent reviewers. Summary estimates were calculated by using random-effects model. The primary outcome was mortality. RESULTS: We included 42 studies comprising 190,896 patients with sepsis. Pooled data showed that the OR for patient mortality who received antibiotics ≤1 hr was 0.83 (95 %CI: 0.67 to 1.04) when compared with patients who received antibiotics >1hr. Significant reductions in the risk of death in patients with earlier antibiotic administration were observed in patients ≤3 hrs versus >3 hrs (OR: 0.80, 95 %CI: 0.68 to 0.94) and ≤6 hrs vs 6 hrs (OR: 0.57, 95 %CI: 0.39 to 0.82). CONCLUSIONS: Our findings show an improvement in mortality in sepsis patients with early administration of antibiotics at <3 and <6 hrs. Thus, these results suggest that antibiotics should be administered within 3 hrs of sepsis recognition or ED arrival regardless of the presence or absence of shock.

5.
Epilepsy Behav ; 158: 109928, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38959747

RESUMO

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

7.
Genet Med ; : 101211, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39011766

RESUMO

PURPOSE: An early genetic diagnosis can guide the time-sensitive treatment of individuals with genetic epilepsies. However, most genetic diagnoses occur long after disease onset. We aimed to identify early clinical features suggestive of genetic diagnoses in individuals with epilepsy through large-scale analysis of full-text electronic medical records (EMR). METHODS: We extracted 89 million time-stamped standardized clinical annotations using Natural Language Processing from 4,572,783 clinical notes from 32,112 individuals with childhood epilepsy, including 1,925 individuals with known or presumed genetic epilepsies. We applied these features to train random forest models to predict SCN1A-related disorders and any genetic diagnosis. RESULTS: We identified 47,774 age-dependent associations of clinical features with genetic etiologies a median of 3.6 years prior to molecular diagnosis. Across all 710 genetic etiologies identified in our cohort, neurodevelopmental differences between 6-9 months increased the likelihood of a later molecular diagnosis fivefold (P<0.0001, 95% CI=3.55-7.42). A later diagnosis of SCN1A-related disorders (AUC=0.91) or an overall positive genetic diagnosis (AUC=0.82) could be reliably predicted using random forest models. CONCLUSION: Clinical features predictive of genetic epilepsies precede molecular diagnoses by up to several years in conditions with known precision treatments. An earlier diagnosis facilitated by automated EMR analysis has the potential for earlier targeted therapeutic strategies in the genetic epilepsies.

8.
J Biomed Mater Res B Appl Biomater ; 112(7): e35438, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38923755

RESUMO

Volumetric muscle loss (VML) injury causes irreversible deficits in muscle mass and function, often resulting in permanent disability. The current standard of care is physical therapy, but it is limited in mitigating functional deficits. We have previously optimized a rehabilitation technique using electrically stimulated eccentric contraction training (EST) that improved muscle mass, strength, and size in VML-injured rats. A biosponge scaffold composed of extracellular matrix proteins has previously enhanced muscle function postVML. This study aimed to determine whether combining a regenerative therapy (i.e., biosponge) with a novel rehabilitation technique (i.e., EST) could enhance recovery in a rat model of VML. A VML defect was created by removing ~20% of muscle mass from the tibialis anterior muscle in adult male Lewis rats. Experimental groups included VML-injured rats treated with biosponge with EST or biosponge alone (n = 6/group). EST was implemented 2 weeks postinjury at 150 Hz and was continued for 4 weeks. A linear increase in eccentric torque over 4 weeks showed the adaptability of the VML-injured muscle to EST. Combining biosponge with EST improved peak isometric torque by ~52% compared with biosponge treatment alone at 6 weeks postinjury. Application of EST increased MyoD gene expression and the percentage of large (>2000 µm2) type 2B myofibers but reduced fibrotic tissue deposition in VML-injured muscles. Together, these changes may provide the basis for improved torque production. This study demonstrates the potential for combined regenerative and rehabilitative therapy to improve muscle recovery following VML.


Assuntos
Músculo Esquelético , Ratos Endogâmicos Lew , Animais , Masculino , Ratos , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Regeneração , Modelos Animais de Doenças , Terapia por Estimulação Elétrica , Contração Muscular , Doenças Musculares/patologia , Doenças Musculares/reabilitação
9.
Environ Sci Technol ; 58(26): 11718-11726, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38889109

RESUMO

Mountaintop removal coal mining is a source of downstream pollution. Here, we show that mountaintop removal coal mining also pollutes ecosystems downwind. We sampled regional snowpack near the end of winter along a transect of sites located 3-60 km downwind of coal mining in the Elk River valley of British Columbia, Canada. Vast quantities of polycyclic aromatic compounds (PACs), a toxic class of organic contaminants, are emitted and transported atmospherically far from emission sources. Summed PAC (ΣPAC) snowpack concentrations ranged from 29-94,866 ng/L. Snowpack ΣPAC loads, which account for variable snowpack depth, ranged from <10 µg/m2 at sites >50 km southeast of the mines to >1000 µg/m2 at sites in the Elk River valley near mining operations, with one site >15,000 µg/m2. Outside of the Elk River valley, snowpack ΣPAC loads exhibited a clear spatial pattern decreasing away from the mines. The compositional fingerprint of this PAC pollution matches closely with Elk River valley coal. Beyond our study region, modeling results suggest a depositional footprint extending across western Canada and the northwestern United States. These findings carry important implications for receiving ecosystems and for communities located close to mountaintop removal coal mines exposed to air pollution elevated in PACs.


Assuntos
Minas de Carvão , Neve , Colúmbia Britânica , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental
10.
Int J Obes (Lond) ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849462

RESUMO

BACKGROUND: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential. METHODS: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires. RESULTS: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found. CONCLUSIONS: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.

11.
Conserv Biol ; : e14311, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853694

RESUMO

Conducting conservation research and establishing protected areas (PAs) based on research results are critical to biodiversity conservation. However, the effect of research and PAs on conservation of threatened species has rarely been evaluated simultaneously. We collected data on PAs from 2000 for 2021 and determined the number of publications on global primates (published from 1950 to 2021) to assess the effect of PAs, research, and biological and socioeconomic factors on the current International Union for Conservation of Nature endangered status and change in status. We used the MCMCglmm package to conduct a phylogenetic comparative analysis to control the phylogenetic relationship of primate species. The status of 24.6% (82 of 333) of species assessed at least twice declined. Only the black lion tamarin (Leontopithecus chrysopygus) had an improved status. Species with status declines mostly occurred on the south coast of West Africa and in Madagascar. PAs covered 22.1% of each species' range. Forest loss in PAs (5.5%) was significantly lower than forest loss within 5 km outside PAs (13.8%), suggesting PAs effectively mitigated forest loss. Both the median number of total publications and conservation publications on critically endangered species were higher than those of other categories. Models showed that PA coverage and number of publications or conservation-focused publications were not related to current status or change in status over time. A decline in status was not related to creation of PAs or increase of research since the last assessment. Our results suggest that current PAs and research are not reversing the extinction crisis of global primates. Doing more conservation-oriented research, strengthening management of current PAs, and expanding PAs will be needed to protect primates globally.


Efectos de la cobertura e investigación de áreas protegidas sobre el estado de conservación de los primates a nivel mundial Resumen La investigación para la conservación y la creación de áreas protegidas (AP) con base en sus resultados son de suma importancia para conservar la biodiversidad. Sin embargo, pocas veces se ha analizado de forma simultánea el efecto de la investigación y las AP sobre la conservación de especies amenazadas. Recolectamos datos sobre las AP entre el 2000 y el 2021 y determinamos el número de artículos sobre primates publicados entre 1950 y 2021 para evaluar el efecto de las AP, la investigación y los factores biológicos y socioeconómicos sobre el estado actual de en peligro y de cambio de estatus de la Unión Internacional para la Conservación de la Naturaleza. Usamos el paquete MCMCglmm para realizar un estudio filogenético comparativo para analizar la relación filogenética del estado de las especies y del cambio de estatus de primates. El estatus del 24.6% (82 de 333) de las especies analizadas declinó al menos dos veces. Solamente el tití leoncito (Leontopithecus chrysopygus) tuvo una mejoraría en su estado. Las especies con declinación en su estado se ubicaron principalmente en la costa sur del Oeste de África y en Madagascar. Las AP cubrieron el 22.1% de la distribución de cada especie. La pérdida de bosques en las AP (5.5%) fue mucho menor que la pérdida dentro de los primeros 5 km fuera de las AP (13.8%), lo que sugiere que las AP mitigan eficientemente la pérdida de bosque. Tanto el número medio de publicaciones totales como el de publicaciones sobre la conservación de especies en peligro crítico fue mayor que aquellos de cualquier otra categoría. Los modelos mostraron que la cobertura de AP y el número de publicaciones o de publicaciones enfocadas en la conservación no estaban relacionados con el estado actual o el cambio de estado. La declinación del estado no estuvo relacionada con la creación de AP o el incremento en la investigación desde nuestro último análisis. Nuestros resultados sugieren que la investigación y las AP actuales no están revirtiendo la crisis mundial de extinción de primates. Para proteger a los primates se necesitará realizar más investigación orientada a la conservación, fortalecer el manejo actual de las AP, así como expandirlas.

12.
JMIR Med Educ ; 10: e54071, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38889065

RESUMO

Background: Health care professionals must learn continuously as a core part of their work. As the rate of knowledge production in biomedicine increases, better support for health care professionals' continuous learning is needed. In health systems, feedback is pervasive and is widely considered to be essential for learning that drives improvement. Clinical quality dashboards are one widely deployed approach to delivering feedback, but engagement with these systems is commonly low, reflecting a limited understanding of how to improve the effectiveness of feedback about health care. When coaches and facilitators deliver feedback for improving performance, they aim to be responsive to the recipient's motivations, information needs, and preferences. However, such functionality is largely missing from dashboards and feedback reports. Precision feedback is the delivery of high-value, motivating performance information that is prioritized based on its motivational potential for a specific recipient, including their needs and preferences. Anesthesia care offers a clinical domain with high-quality performance data and an abundance of evidence-based quality metrics. Objective: The objective of this study is to explore anesthesia provider preferences for precision feedback. Methods: We developed a test set of precision feedback messages with balanced characteristics across 4 performance scenarios. We created an experimental design to expose participants to contrasting message versions. We recruited anesthesia providers and elicited their preferences through analysis of the content of preferred messages. Participants additionally rated their perceived benefit of preferred messages to clinical practice on a 5-point Likert scale. Results: We elicited preferences and feedback message benefit ratings from 35 participants. Preferences were diverse across participants but largely consistent within participants. Participants' preferences were consistent for message temporality (α=.85) and display format (α=.80). Ratings of participants' perceived benefit to clinical practice of preferred messages were high (mean rating 4.27, SD 0.77). Conclusions: Health care professionals exhibited diverse yet internally consistent preferences for precision feedback across a set of performance scenarios, while also giving messages high ratings of perceived benefit. A "one-size-fits-most approach" to performance feedback delivery would not appear to satisfy these preferences. Precision feedback systems may hold potential to improve support for health care professionals' continuous learning by accommodating feedback preferences.


Assuntos
Retroalimentação , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Pessoal de Saúde/psicologia , Melhoria de Qualidade
13.
Biol Psychol ; 191: 108826, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38862067

RESUMO

Studies of COMT Val158Met suggest that the neural circuitry subserving inhibitory control may be modulated by this functional polymorphism altering cortical dopamine availability, thus giving rise to heritable differences in behaviors. Using an anatomically-constrained magnetoencephalography method and stratifying the sample by COMT genotype, from a larger sample of 153 subjects, we examined the spatial and temporal dynamics of beta oscillations during motor execution and inhibition in 21 healthy Met158/Met158 (high dopamine) or 21 Val158/Val158 (low dopamine) genotype individuals during a Go/NoGo paradigm. While task performance was unaffected, Met158 homozygotes demonstrated an overall increase in beta power across regions essential for inhibitory control during early motor preparation (∼100 ms latency), suggestive of a global motor "pause" on behavior. This increase was especially evident on Go trials with slow response speed and was absent during inhibition failures. Such a pause could underlie the tendency of Met158 allele carriers to be more cautious and inhibited. In contrast, Val158 homozygotes exhibited a beta drop during early motor preparation, indicative of high response readiness. This decrease was associated with measures of behavioral disinhibition and consistent with greater extraversion and impulsivity observed in Val homozygotes. These results provide mechanistic insight into genetically-determined interindividual differences of inhibitory control with higher cortical dopamine associated with momentary response hesitation, and lower dopamine leading to motor impulsivity.

15.
Nature ; 630(8017): 744-751, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867042

RESUMO

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.


Assuntos
Dano ao DNA , Reparo do DNA , DNA Polimerase Dirigida por DNA , DNA , Mutagênese , Mutação , Animais , Humanos , Camundongos , Alquilação/efeitos da radiação , Linhagem Celular , DNA/química , DNA/genética , DNA/metabolismo , DNA/efeitos da radiação , Adutos de DNA/química , Adutos de DNA/genética , Adutos de DNA/metabolismo , Adutos de DNA/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/fisiologia , Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Mutagênese/genética , Mutagênese/efeitos da radiação , Mutação/genética , Mutação/efeitos da radiação , Neoplasias/genética , Transcrição Gênica , Raios Ultravioleta/efeitos adversos
16.
NPJ Precis Oncol ; 8(1): 124, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822082

RESUMO

Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refined to attain a stably resistant phenotype. Mechanistic and translational studies reveal that resistance to dual-mechanism ERK/MAPK inhibition is broadly susceptible to manipulation of the epigenetic machinery, and that Mediator kinase, in particular, can be co-targeted at a bottleneck point to prevent diverse, cell line-specific resistance programs.

17.
Compr Psychiatry ; 133: 152495, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38728844

RESUMO

INTRODUCTION: Recent technology has enabled researchers to collect ecological momentary assessments (EMA) to examine within-person correlates of suicidal thoughts. Prior studies examined generalized temporal dynamics of emotions and suicidal thinking over brief periods, but it is not yet known how variable these processes are across people. METHOD: We use data EMA data delivered over two weeks with youth/young adults (N = 60) who reported past year self-injurious thoughts/behaviors. We used group iterative multiple model estimation (GIMME) to model group- and person-specific associations of negative emotions (i.e., fear, sadness, shame, guilt, and anger) and suicidal thoughts. RESULTS: 29 participants (48.33%) reported at least one instance of a suicidal thought and were included in GIMME models. In group level models, we consistently observed autoregressive effects for suicidal thoughts (e.g., earlier thoughts predicting later thoughts), although the magnitude and direction of this link varied from person-to-person. Among emotions, sadness was most frequently associated with contemporaneous suicidal thoughts, but this was evident for less than half of the sample, while other emotional correlates of suicidal thoughts broadly differed across people. No emotion variable was linked to future suicidal thoughts in >14% of the sample, CONCLUSIONS: Emotion-based correlates of suicidal thoughts are heterogeneous across people. Better understanding of the individual-level pathways maintaining suicidal thoughts/behaviors may lead to more effective, personalized interventions.


Assuntos
Avaliação Momentânea Ecológica , Emoções , Ideação Suicida , Humanos , Feminino , Masculino , Adulto Jovem , Adolescente , Adulto , Tristeza/psicologia , Ira , Vergonha , Medo/psicologia , Culpa
18.
Nat Ecol Evol ; 8(6): 1118-1128, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38769434

RESUMO

Many shark populations are in decline around the world, with severe ecological and economic consequences. Fisheries management and marine protected areas (MPAs) have both been heralded as solutions. However, the effectiveness of MPAs alone is questionable, particularly for globally threatened sharks and rays ('elasmobranchs'), with little known about how fisheries management and MPAs interact to conserve these species. Here we use a dedicated global survey of coral reef elasmobranchs to assess 66 fully protected areas embedded within a range of fisheries management regimes across 36 countries. We show that conservation benefits were primarily for reef-associated sharks, which were twice as abundant in fully protected areas compared with areas open to fishing. Conservation benefits were greatest in large protected areas that incorporate distinct reefs. However, the same benefits were not evident for rays or wide-ranging sharks that are both economically and ecologically important while also threatened with extinction. We show that conservation benefits from fully protected areas are close to doubled when embedded within areas of effective fisheries management, highlighting the importance of a mixed management approach of both effective fisheries management and well-designed fully protected areas to conserve tropical elasmobranch assemblages globally.


Assuntos
Conservação dos Recursos Naturais , Recifes de Corais , Pesqueiros , Tubarões , Rajidae , Animais , Conservação dos Recursos Naturais/métodos
19.
Health Promot Chronic Dis Prev Can ; 44(5): 197-207, 2024 May.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-38748477

RESUMO

INTRODUCTION: The goal of this study was to examine potential disparities in positive mental health (PMH) among adults in Canada by sexual orientation and gender modality. METHODS: Using 2019 Canadian Community Health Survey (CCHS) Annual Component data (N = 57 034), we compared mean life satisfaction and the prevalence of high self-rated mental health (SRMH), happiness and community belonging between heterosexual and sexual minority adults, and between cisgender and gender minority adults. We used 2019 CCHS Rapid Response on PMH data (N = 11 486) to compare the prevalence of high psychological well-being between heterosexual and sexual minority adults. Linear and logistic regression analyses examined the between-group differences in mean life satisfaction and the other PMH outcomes, respectively. RESULTS: Sexual minority (vs. heterosexual) adults reported lower mean life satisfaction (B = -0.7, 95% CI: -0.8, -0.5) and were less likely to report high SRMH (OR = 0.4, 95% CI: 0.3, 0.5), happiness (OR = 0.4, 95% CI: 0.3, 0.5), community belonging (OR = 0.6, 95% CI: 0.5, 0.7) and psychological well-being (OR = 0.4, 95% CI: 0.3, 0.6). Differences were not always significant for specific sexual minority groups in sexstratified analyses. Gender minority adults reported lower mean life satisfaction and were less likely to report high SRMH and happiness than cisgender adults. CONCLUSION: Future research could investigate how these PMH disparities arise, risk and protective factors in these populations, how other sociodemographic factors interact with sexual orientation and gender identity to influence PMH and changes in disparities over time.


Assuntos
Saúde Mental , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Canadá/epidemiologia , Adulto , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Satisfação Pessoal , Disparidades nos Níveis de Saúde , Inquéritos Epidemiológicos , Felicidade , Adulto Jovem , Heterossexualidade/estatística & dados numéricos , Heterossexualidade/psicologia , Adolescente , Idoso
20.
J Particip Med ; 16: e56204, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781010

RESUMO

BACKGROUND: Peer specialists are hired, trained, and accredited to share their lived experience of psychiatric illness to support other similar individuals through the recovery process. There are limited data on the role of peer specialists in suicide prevention, including their role in intervention development. OBJECTIVE: To better understand peer specialists within the Veterans Health Administration (VHA), we followed partnership community engagement and a formative research approach to intervention development to (1) identify barriers, facilitators, and perceptions of VHA peer specialists delivering a suicide prevention service and (2) develop and refine an intervention curriculum based on an evidence-informed preliminary intervention framework for veterans with serious mental illness (SMI). METHODS: Following the community engagement approach, VHA local and national peer support and mental health leaders, veterans with SMI, and veteran peer specialists met to develop a preliminary intervention framework. Next, VHA peer specialist advisors (n=5) and scientific advisors (n=6) participated in respective advisory boards and met every 2-4 months for more than 18 months via videoconferencing to address study objectives. The process used was a reflexive thematic analysis after each advisory board meeting. RESULTS: The themes discussed included (1) the desire for suicide prevention training for peer specialists, (2) determining the role of VHA peer specialists in suicide prevention, (3) integration of recovery themes in suicide prevention, and (4) difficulties using safety plans during a crisis. There were no discrepancies in thematic content between advisory boards. Advisor input led to the development of Suicide Prevention by Peers Offering Recovery Tactics (SUPPORT). SUPPORT includes training in general suicide prevention and a peer specialist-delivered intervention for veterans with SMI at an increased suicide risk. This training aims to increase the competence and confidence of peer specialists in suicide prevention and the intervention supports veterans with SMI at an increased suicide risk through their recovery process. CONCLUSIONS: This paper intends to document the procedures taken in suicide prevention intervention development, specifically those led by peer specialists, and to be a source for future research developing and evaluating similar interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05537376; https://classic.clinicaltrials.gov/ct2/show/NCT05537376.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...