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1.
Nature ; 608(7923): 552-557, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948636

RESUMO

As the climate changes, warmer spring temperatures are causing earlier leaf-out1-3 and commencement of CO2 uptake1,3 in temperate deciduous forests, resulting in a tendency towards increased growing season length3 and annual CO2 uptake1,3-7. However, less is known about how spring temperatures affect tree stem growth8,9, which sequesters carbon in wood that has a long residence time in the ecosystem10,11. Here we show that warmer spring temperatures shifted stem diameter growth of deciduous trees earlier but had no consistent effect on peak growing season length, maximum growth rates, or annual growth, using dendrometer band measurements from 440 trees across two forests. The latter finding was confirmed on the centennial scale by 207 tree-ring chronologies from 108 forests across eastern North America, where annual ring width was far more sensitive to temperatures during the peak growing season than in the spring. These findings imply that any extra CO2 uptake in years with warmer spring temperatures4,5 does not significantly contribute to increased sequestration in long-lived woody stem biomass. Rather, contradicting projections from global carbon cycle models1,12, our empirical results imply that warming spring temperatures are unlikely to increase woody productivity enough to strengthen the long-term CO2 sink of temperate deciduous forests.


Assuntos
Aquecimento Global , Estações do Ano , Temperatura , Árvores , Aclimatação , Biomassa , Dióxido de Carbono/metabolismo , Sequestro de Carbono , Modelos Climáticos , Florestas , Aquecimento Global/estatística & dados numéricos , América do Norte , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Caules de Planta/crescimento & desenvolvimento , Caules de Planta/metabolismo , Fatores de Tempo , Árvores/anatomia & histologia , Árvores/classificação , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Madeira/crescimento & desenvolvimento , Madeira/metabolismo
2.
Mol Cell ; 78(6): 999-1001, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32559429

RESUMO

In a breakthrough study in a recent issue of Cell, Michealraj et al. (2020) demonstrate that posterior fossa A ependymoma, a lethal pediatric brain tumor with a silent genome, is dependent upon metabolic changes associated with hypoxia that drive the tumor's characteristic epigenetic dysregulation.


Assuntos
Neoplasias Encefálicas , Ependimoma/genética , Neoplasias Infratentoriais/genética , Criança , Epigenoma , Epigenômica , Humanos
3.
Proc Natl Acad Sci U S A ; 120(51): e2312057120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38085776

RESUMO

Neoepitopes arising from amino acid substitutions due to single nucleotide polymorphisms are targets of T cell immune responses to cancer and are of significant interest in the development of cancer vaccines. However, understanding the characteristics of rare protective neoepitopes that truly control tumor growth has been a challenge, due to their scarcity as well as the challenge of verifying true, neoepitope-dependent tumor control in humans. Taking advantage of recent work in mouse models that circumvented these challenges, here, we compared the structural and physical properties of neoepitopes that range from fully protective to immunologically inactive. As neoepitopes are derived from self-peptides that can induce immune tolerance, we studied not only how the various neoepitopes differ from each other but also from their wild-type counterparts. We identified multiple features associated with protection, including features that describe how neoepitopes differ from self as well as features associated with recognition by diverse T cell receptor repertoires. We demonstrate both the promise and limitations of neoepitope structural analysis and predictive modeling and illustrate important aspects that can be incorporated into neoepitope prediction pipelines.


Assuntos
Neoplasias , Humanos , Animais , Camundongos , Epitopos , Neoplasias/genética , Linfócitos T , Peptídeos/metabolismo , Antígenos de Neoplasias
4.
Trends Genet ; 38(7): 708-723, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35314082

RESUMO

Mosquitoes bring global health problems by transmitting parasites and viruses such as malaria and dengue. Unfortunately, current insecticide-based control strategies are only moderately effective because of high cost and resistance. Thus, scalable, sustainable, and cost-effective strategies are needed for mosquito-borne disease control. Symbiont-based and genome engineering-based approaches provide new tools that show promise for meeting these criteria, enabling modification or suppression approaches. Symbiotic bacteria like Wolbachia are maternally inherited and manipulate mosquito host reproduction to enhance their vertical transmission. Genome engineering-based gene drive methods, in which mosquitoes are genetically altered to spread drive alleles throughout wild populations, are also proving to be a potentially powerful approach in the laboratory. Here, we review the latest developments in both symbionts and gene drive-based methods. We describe some notable similarities, as well as distinctions and obstacles, relating to these promising technologies.


Assuntos
Culicidae , Tecnologia de Impulso Genético , Malária , Wolbachia , Animais , Culicidae/genética , Malária/genética , Malária/prevenção & controle , Mosquitos Vetores/genética , Wolbachia/genética
5.
Cancer ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837334

RESUMO

BACKGROUND: Despite mandated insurance coverage since 2006 and robust health infrastructure in urban settings with high concentrations of minority patients, race-based disparities in prostate cancer (PCa) treatment persist in Massachusetts. In this qualitative study, the authors sought to identify factors driving inequities in PCa treatment in Massachusetts. METHODS: Four hospitals offering PCa treatment in Massachusetts were selected using a case-mix approach. Purposive sampling was used to conduct semistructured interviews with hospital stakeholders. Additional interviews were conducted with representatives from grassroots organizations providing PCa education. Two study staff coded the interviews to identify major themes and recurrent patterns. RESULTS: Of the 35 informants invited, 25 participated in the study. Although national disparities in PCa outcomes were readily discussed, one half of the informants were unaware that PCa disparities existed in Massachusetts. Informants and grassroots organization representatives acknowledged that patients with PCa are willing to face transportation barriers to receive treatment from trusted and accommodating institutions. Except for chief equity officers, most health care providers lacked knowledge on accessing or using metrics regarding racial disparities in cancer outcomes. Although community outreach was recognized as a potential strategy to reduce treatment disparities and engender trust, informants were often unable to provide a clear implementation plan. CONCLUSIONS: This statewide qualitative study builds on existing quantitative data on the nature and extent of disparities. It highlights knowledge gaps in recognizing and addressing racial disparities in PCa treatment in Massachusetts. Improved provider awareness, the use of disparity metrics, and strategic community engagement may ensure equitable access to PCa treatment. PLAIN LANGUAGE SUMMARY: Despite mandated insurance and urban health care access, racial disparities in prostate cancer treatment persist in Massachusetts. This qualitative study revealed that, although national disparities were acknowledged, awareness about local disparities are lacking. Stakeholders highlighted the importance of ancillary services, including translators, rideshares, and navigators, in the delivery of care. In addition, whereas hospital stakeholders were aware of collected equity outcomes, they were unsure whether and who is monitoring equity metrics. Furthermore, stakeholders agreed that community outreach showed promise in ensuring equitable access to prostate cancer treatment. Nevertheless, most interviewed stakeholders lacked clear implementation plans.

6.
Environ Microbiol ; 26(2): e16576, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38192175

RESUMO

The mosquito microbiome is critical for host development and plays a major role in many aspects of mosquito biology. While the microbiome is commonly dominated by a small number of genera, there is considerable variation in composition among mosquito species, life stages, and geography. How the host controls and is affected by this variation is unclear. Using microbiome transplant experiments, we asked whether there were differences in transcriptional responses when mosquitoes of different species were used as microbiome donors. We used microbiomes from four different donor species spanning the phylogenetic breadth of the Culicidae, collected either from the laboratory or the field. We found that when recipients received a microbiome from a donor reared in the laboratory, the response was remarkably similar regardless of donor species. However, when the donor had been collected from the field, many more genes were differentially expressed. We also found that while the transplant procedure did have some effect on the host transcriptome, this is likely to have had a limited effect on mosquito fitness. Overall, our results highlight the possibility that variation in mosquito microbiome communities is associated with variability in host-microbiome interactions and further demonstrate the utility of the microbiome transplantation technique for investigating host-microbe interactions in mosquitoes.


Assuntos
Aedes , Microbiota , Animais , Aedes/genética , Transcriptoma/genética , Filogenia , Microbiota/genética
7.
Genome Res ; 31(3): 512-528, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33419731

RESUMO

Although mosquitoes are major transmission vectors for pathogenic arboviruses, viral infection has little impact on mosquito health. This immunity is caused in part by mosquito RNA interference (RNAi) pathways that generate antiviral small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). RNAi also maintains genome integrity by potently repressing mosquito transposon activity in the germline and soma. However, viral and transposon small RNA regulatory pathways have not been systematically examined together in mosquitoes. Therefore, we developed an integrated mosquito small RNA genomics (MSRG) resource that analyzes the transposon and virus small RNA profiles in mosquito cell cultures and somatic and gonadal tissues across four medically important mosquito species. Our resource captures both somatic and gonadal small RNA expression profiles within mosquito cell cultures, and we report the evolutionary dynamics of a novel Mosquito-Conserved piRNA Cluster Locus (MCpiRCL) made up of satellite DNA repeats. In the larger culicine mosquito genomes we detected highly regular periodicity in piRNA biogenesis patterns coinciding with the expansion of Piwi pathway genes. Finally, our resource enables detection of cross talk between piRNA and siRNA populations in mosquito cells during a response to virus infection. The MSRG resource will aid efforts to dissect and combat the capacity of mosquitoes to tolerate and spread arboviruses.


Assuntos
Culicidae/genética , Culicidae/virologia , Elementos de DNA Transponíveis/genética , Genômica , RNA Interferente Pequeno/genética , Vírus , Animais
8.
Neuropathol Appl Neurobiol ; 50(2): e12972, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38502287

RESUMO

AIMS: We applied the 2021 consensus criteria for both chronic traumatic encephalopathy neuropathological change and traumatic encephalopathy syndrome in a small case series of six former elite-level Australian rugby code players. METHODS: Neuropathological assessment of these cases was carried out at the Sydney and Victorian Brain Banks. Clinical data were collected via clinical interviews and health questionnaires completed by the participants and/or their next of kin, and neuropsychological testing was conducted with participants who were capable of completing this testing. RESULTS: All cases exhibited progressive cognitive impairment during life. Chronic traumatic encephalopathy neuropathological change was identified in four out of the six cases. However, coexisting neuropathologies were common, with limbic-predominant age-related TDP-43 encephalopathy and ageing-related tau astrogliopathy seen in all cases, intermediate or high Alzheimer's disease neuropathological change seen in four cases and hippocampal sclerosis seen in two of the six cases. CONCLUSION: The presence of multiple neuropathologies in these cases complicates clinical diagnostic efforts for traumatic encephalopathy syndrome. It will be important for further clinicopathological studies on larger groups to report all neuropathological comorbidities found in cases diagnosed with either chronic traumatic encephalopathy neuropathological change and/or traumatic encephalopathy syndrome.


Assuntos
Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Demência , Humanos , Encefalopatia Traumática Crônica/complicações , Rugby , Austrália , Encéfalo/patologia , Demência/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia
9.
Glob Chang Biol ; 30(8): e17474, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39162051

RESUMO

Forests around the world are experiencing changes due to climate variability and human land use. How these changes interact and influence the vulnerability of forests are not well understood. In the eastern United States, well-documented anthropogenic disturbances and land-use decisions, such as logging and fire suppression, have influenced forest species assemblages, leading to a demographic shift from forests dominated by xeric species to those dominated by mesic species. Contemporarily, the climate has changed and is expected to continue to warm and produce higher evaporative demand, imposing stronger drought stress on forest communities. Here, we use an extensive network of tree-ring records from common hardwood species across ~100 sites and ~1300 trees in the eastern United States to examine the magnitude of growth response to both wet and dry climate extremes. We find that growth reductions during drought exceed the positive growth response to pluvials. Mesic species such as Liriodendron tulipifera and Acer saccharum, which are becoming more dominant, are more sensitive to drought than more xeric species, such as oaks (Quercus) and hickory (Carya), especially at moderate and extreme drought intensities. Although more extreme droughts produce a larger annual growth reduction, mild droughts resulted in the largest cumulative growth decreases due to their higher frequency. When using global climate model projections, all scenarios show drought frequency increasing substantially (3-9 times more likely) by 2100. Thus, the ongoing demographic shift toward more mesic species in the eastern United States combined with drier conditions results in larger drought-induced growth declines, suggesting that drought will have an even larger impact on aboveground carbon uptake in the future in the eastern United States.


Assuntos
Mudança Climática , Secas , Florestas , Árvores , Árvores/crescimento & desenvolvimento , Estados Unidos , Clima
10.
Phys Rev Lett ; 132(15): 153402, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38682986

RESUMO

We report the first observation of the quantum Joule-Thomson (JT) effect in ideal and unitary Fermi gases. We study the temperature dynamics of these systems while they undergo an energy-per-particle conserving rarefaction. For scale-invariant systems, whose equations of state satisfy the relation U∝PV, this rarefaction conserves the specific enthalpy, which makes it thermodynamically equivalent to a JT throttling process. We observe JT heating in an ideal Fermi gas, a direct consequence of Pauli blocking. In a unitary Fermi gas, we observe that the JT heating is marginal in the temperature range 0.2≲T/T_{F}≲0.8 as the repulsive quantum-statistical effect is lessened by the attractive interparticle interactions.

11.
Environ Sci Technol ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323876

RESUMO

Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.

12.
Med Vet Entomol ; 38(2): 138-147, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38469658

RESUMO

Microplastics (plastic particles <5 mm) permeate aquatic and terrestrial ecosystems and constitute a hazard to animal life. Although much research has been conducted on the effects of microplastics on marine and benthic organisms, less consideration has been given to insects, especially those adapted to urban environments. Here, we provide a perspective on the potential consequences of exposure to microplastics within typical larval habitat on mosquito biology. Mosquitoes represent an ideal organism in which to explore the biological effects of microplastics on terrestrial insects, not least because of their importance as an infectious disease vector. Drawing on evidence from other organisms and knowledge of the mosquito life cycle, we summarise some of the more plausible impacts of microplastics including physiological, ecotoxicological and immunological responses. We conclude that although there remains little experimental evidence demonstrating any adverse effect on mosquito biology or pathogen transmission, significant knowledge gaps remain, and there is now a need to quantify the effects that microplastic pollution could have on such an important disease vector.


Assuntos
Culicidae , Microplásticos , Animais , Microplásticos/toxicidade , Culicidae/efeitos dos fármacos , Culicidae/fisiologia , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/fisiologia , Larva/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
13.
PLoS Genet ; 17(12): e1009970, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34941884

RESUMO

Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids, and a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance.


Assuntos
Anopheles/genética , Resistência a Inseticidas/genética , Malária/genética , Transcriptoma/genética , Animais , Anopheles/patogenicidade , Inseticidas/farmacologia , Malária/transmissão , Controle de Mosquitos , Mosquitos Vetores/genética , Mosquitos Vetores/patogenicidade , Piretrinas/farmacologia , RNA-Seq , Sequenciamento Completo do Genoma/métodos
14.
Neurosurg Focus ; 57(1): E9, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38950448

RESUMO

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.


Assuntos
Atletas , Traumatismos em Atletas , Concussão Encefálica , Estudantes , Humanos , Masculino , Feminino , Concussão Encefálica/epidemiologia , Adolescente , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Recuperação de Função Fisiológica/fisiologia , Fatores Sexuais , Aprendizagem/fisiologia , Estudos de Coortes , Estudos Prospectivos , Instituições Acadêmicas , Retorno à Escola , Volta ao Esporte
15.
Acta Neurochir (Wien) ; 166(1): 144, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38514587

RESUMO

PURPOSE: The objective was to determine the incidence of surgically treated chronic subdural hematoma (cSDH) within six months after head trauma in a consecutive series of head injury patients with a normal initial computed tomography (CT). METHODS: A total of 1941 adult patients with head injuries who underwent head CT within 48 h after injury and were treated at the Tampere University Hospital's emergency department were retrospectively evaluated from medical records (median age = 59 years, IQR = 39-79 years, males = 58%, patients using antithrombotic medication = 26%). Patients with no signs of acute traumatic intracranial pathology or any type of subdural collection on initial head CT were regarded as CT negative (n = 1573, 81%). RESULTS: Two (n = 2) of the 1573 CT negative patients received surgical treatment for cSDH. Consequently, the incidence of surgically treated cSDH after a normal initial head CT during a six-month follow-up was 0.13%. Both patients sustained mild traumatic brain injuries initially. One of the two patients was on antithrombotic medication (warfarin) at the time of trauma, hence incidence of surgically treated cSDH among patients with antithrombotic medication in CT negative patients (n = 376, 23.9%) was 0.27%. Additionally, within CT negative patients, one subdural hygroma was operated shortly after trauma. CONCLUSION: The extremely low incidence of surgically treated cSDH after a normal initial head CT, even in patients on antithrombotic medication, supports the notion that routine follow-up imaging after an initial normal head CT is not indicated to exclude the development of cSDH. Additionally, our findings support the concept of cSDH not being a purely head trauma-related disease.


Assuntos
Traumatismos Craniocerebrais , Hematoma Subdural Crônico , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/epidemiologia , Hematoma Subdural Crônico/cirurgia , Estudos Retrospectivos , Incidência , Fibrinolíticos , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/cirurgia , Tomografia Computadorizada por Raios X/efeitos adversos
16.
Brain Inj ; 38(6): 425-435, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38329020

RESUMO

PRIMARY OBJECTIVE: We evaluated whether photobiomodulation with red/near infrared light applied transcranially via light emitting diodes (LED) was associated with reduced symptoms and improved cognitive functioning in patients with chronic symptoms following mild traumatic brain injury. RESEARCH DESIGN: Participants (3 men, 6 women; 22-61 years-old) underwent a 6-week intervention involving 18 40-minute transcranial LED treatment sessions. METHODS AND PROCEDURES: Reliable change indices were calculated for 10 neuropsychological test scores and 3 self-report questionnaires of subjective cognition, post-concussion symptoms, and depression at baseline and following treatment. Questionnaires were also administered after 2-week sham and at 1-month and 2-month follow-ups. MAIN OUTCOME AND RESULTS: Only 2 participants improved on neuropsychological testing. On questionnaires, 4 reported improved cognition, 5 reported improved post-concussion symptoms, and 3 reported improved depression. Significant improvement in 2 or more domains was reported by 4 participants and mostly maintained at both follow-ups. CONCLUSIONS: Most participants did not improve on neuropsychological testing. A minority self-reported improvement in symptoms, potentially explained by the intervention, psychiatric medication changes, placebo effects, or other factors. Selecting participants with different clinical characteristics, and dosing and delivery system changes, may produce different results. A study design accounting for placebo effects appears warranted in future trials.


Assuntos
Concussão Encefálica , Terapia com Luz de Baixa Intensidade , Síndrome Pós-Concussão , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Concussão Encefálica/complicações , Concussão Encefálica/radioterapia , Concussão Encefálica/diagnóstico , Síndrome Pós-Concussão/radioterapia , Síndrome Pós-Concussão/psicologia , Projetos Piloto , Cognição
17.
Clin J Sport Med ; 34(5): 404-410, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38780403

RESUMO

OBJECTIVE: To examine whether a personal history of migraines is associated with worse acute symptom burden after sport-related concussion (SRC). DESIGN: Retrospective cohort study. SETTING: National Collegiate Athletic Association Division III collegiate programs. PARTICIPANTS: Collegiate athletes from a prospective concussion surveillance system between 09, 2014, and 01, 2023. INTERVENTION: Preinjury migraines (yes/no) were self-reported by athletes. MAIN OUTCOME MEASURES: Post-Concussion Symptom Scale (PCSS) were collected within 3 days postinjury. Mann-Whitney U tests compared total PCSS scores and individual symptom scores between athletes with and without preinjury migraines. Chi-squared tests were used to compare proportions of athletes endorsing individual symptoms (ie, item score ≥1) between 2 groups. Multivariable regression analyzed potential predictors of PCSS scores. RESULTS: Of 1190 athletes with SRC, 93 (7.8%) reported a preinjury history of migraines. No significant difference in total PCSS scores was found between athletes with and without preinjury migraines (22.0 ± 16.4 vs 20.5 ± 15.8, U = 48 719.0, P = 0.471). Athletes with preinjury migraines reported greater severity of "sensitivity to light" (1.59 ± 1.59 vs 1.23 ± 1.41, P = 0.040) and "feeling more emotional" (0.91 ± 1.27 vs 0.70 ± 1.30; P = 0.008) and were more likely to endorse "feeling more emotional" (45.2% vs 29.5%, P = 0.002). No differences were found across all other symptoms, including headaches (migraine = 87.1% vs no migraine = 86.3%, P = 0.835). In a multivariable model, a history of migraine was not a significant predictor of acute PCSS scores, but those with a history of psychological disorders (ß = 0.12, P <0 .001) and greater number of days to symptom evaluation (ß = 0.08, P = 0.005) had higher PCSS scores. CONCLUSIONS: Collegiate athletes with a pre-existing history of migraines did not have higher acute symptom burden after SRC.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Transtornos de Enxaqueca , Humanos , Masculino , Feminino , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/diagnóstico , Estudos Retrospectivos , Adulto Jovem , Síndrome Pós-Concussão/diagnóstico , Atletas , Universidades , Adolescente
18.
J Environ Manage ; 351: 119692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38039589

RESUMO

Chemical contaminants, such as pesticides, pharmaceuticals and industrial compounds are ubiquitous in surface water and sediment in areas subject to human activity. While targeted chemical analysis is typically used for water and sediment quality monitoring, there is growing interest in applying effect-based methods with in vitro bioassays to capture the effects of all active contaminants in a sample. The current study evaluated the biological effects in surface water and sediment from two contrasting catchments in Aotearoa New Zealand, the highly urbanised Whau River catchment in Tamaki Makaurau (Auckland) and the urban and mixed agricultural Koreti (New River) Estuary catchment. Two complementary passive sampling devices, Chemcatcher for polar chemicals and polyethylene (PED) for non-polar chemicals, were applied to capture a wide range of contaminants in water, while composite sediment samples were collected at each sampling site. Bioassays indicative of induction of xenobiotic metabolism, receptor-mediated effects, genotoxicity, cytotoxicity and apical effects were applied to the water and sediment extracts. Most sediment extracts induced moderate to strong estrogenic and aryl hydrocarbon (AhR) activity, along with moderate toxicity to bacteria. The water extracts showed similar patterns to the sediment extracts, but with lower activity. Generally, the polar Chemcatcher extracts showed greater estrogenic activity, photosynthesis inhibition and algal growth inhibition than the non-polar PED extracts, though the PED extracts showed greater AhR activity. The observed effects in the water extracts were compared to available ecological effect-based trigger values (EBT) to evaluate the potential risk. For the polar extracts, most sites in both catchments exceeded the EBT for estrogenicity, with many sites exceeding the EBTs for AhR activity and photosynthesis inhibition. Of the wide range of endpoints considered, estrogenic activity, AhR activity and herbicidal activity appear to be the primary risk drivers in both the Whau and Koreti Estuary catchments.


Assuntos
Rios , Poluentes Químicos da Água , Humanos , Rios/química , Água/análise , Poluentes Químicos da Água/análise , Agricultura , Bioensaio , Polietileno , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química
19.
J Biol Chem ; 298(10): 102417, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037967

RESUMO

Γ-Crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults are associated with cataract formation. Therefore, drugs that increase their stability should have anticataract properties. To this end, we screened 2560 Federal Drug Agency-approved drugs and natural compounds for their ability to suppress or worsen H2O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, closantel (C), an antihelminthic drug, and gambogic acid (G), a xanthonoid, attenuated thermal-induced protein unfolding and aggregation as shown by turbidimetry fluorescence spectroscopy dynamic light scattering and electron microscopy of human or mouse recombinant crystallins. Furthermore, binding studies using fluorescence inhibition and hydrophobic pocket-binding molecule bis-8-anilino-1-naphthalene sulfonic acid revealed static binding of C and G to hydrophobic sites with medium-to-low affinity. Molecular docking to HγD and other γ-crystallins revealed two binding sites, one in the "NC pocket" (residues 50-150) of HγD and one spanning the "NC tail" (residues 56-61 to 168-174 in the C-terminal domain). Multiple binding sites overlap with those of the protective mini αA-crystallin chaperone MAC peptide. Mechanistic studies using bis-8-anilino-1-naphthalene sulfonic acid as a proxy drug showed that it bound to MAC sites, improved Tm of both H2O2 oxidized and native human gamma D, and suppressed turbidity of oxidized HγD, most likely by trapping exposed hydrophobic sites. The extent to which these drugs act as α-crystallin mimetics and reduce cataract progression remains to be demonstrated. This study provides initial insights into binding properties of C and G to γ-crystallins.


Assuntos
Materiais Biomiméticos , Catarata , Cristalino , Chaperonas Moleculares , Agregação Patológica de Proteínas , Salicilanilidas , Xantonas , alfa-Cristalinas , gama-Cristalinas , Animais , Bovinos , Humanos , Camundongos , alfa-Cristalinas/metabolismo , Catarata/tratamento farmacológico , Catarata/prevenção & controle , Catarata/genética , gama-Cristalinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Cristalino/metabolismo , Chaperonas Moleculares/metabolismo , Simulação de Acoplamento Molecular , Naftalenos/metabolismo , Ácidos Sulfônicos/metabolismo , Salicilanilidas/química , Salicilanilidas/farmacologia , Salicilanilidas/uso terapêutico , Xantonas/química , Xantonas/farmacologia , Xantonas/uso terapêutico , Agregação Patológica de Proteínas/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/uso terapêutico
20.
Appl Environ Microbiol ; 89(11): e0121923, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37902315

RESUMO

IMPORTANCE: The COVID-19 pandemic spurred research on the persistence of SARS-CoV-2 and its surrogates. Here we highlight the importance of evaluating viral surrogates and experimental methodologies when studying pathogen survival in the environment.


Assuntos
Bacteriófagos , COVID-19 , Humanos , SARS-CoV-2 , Água , Pandemias
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