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1.
Sci Immunol ; 9(96): eadk4893, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941480

RESUMO

Activation of natural killer (NK) cells with the cytokines interleukin-12 (IL-12), IL-15, and IL-18 induces their differentiation into memory-like (ML) NK cells; however, the underlying epigenetic and transcriptional mechanisms are unclear. By combining ATAC-seq, CITE-seq, and functional analyses, we discovered that IL-12/15/18 activation results in two main human NK fates: reprogramming into enriched memory-like (eML) NK cells or priming into effector conventional NK (effcNK) cells. eML NK cells had distinct transcriptional and epigenetic profiles and enhanced function, whereas effcNK cells resembled cytokine-primed cNK cells. Two transcriptionally discrete subsets of eML NK cells were also identified, eML-1 and eML-2, primarily arising from CD56bright or CD56dim mature NK cell subsets, respectively. Furthermore, these eML subsets were evident weeks after transfer of IL-12/15/18-activated NK cells into patients with cancer. Our findings demonstrate that NK cell activation with IL-12/15/18 results in previously unappreciated diverse cellular fates and identifies new strategies to enhance NK therapies.


Assuntos
Citocinas , Epigênese Genética , Memória Imunológica , Células Matadoras Naturais , Humanos , Células Matadoras Naturais/imunologia , Epigênese Genética/imunologia , Memória Imunológica/imunologia , Citocinas/imunologia , Regulação da Expressão Gênica/imunologia , Diferenciação Celular/imunologia , Interleucina-15/imunologia
2.
Nat Hum Behav ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862815

RESUMO

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.

3.
Glob Chang Biol ; 30(6): e17367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840430

RESUMO

Wildfire activity is increasing globally. The resulting smoke plumes can travel hundreds to thousands of kilometers, reflecting or scattering sunlight and depositing particles within ecosystems. Several key physical, chemical, and biological processes in lakes are controlled by factors affected by smoke. The spatial and temporal scales of lake exposure to smoke are extensive and under-recognized. We introduce the concept of the lake smoke-day, or the number of days any given lake is exposed to smoke in any given fire season, and quantify the total lake smoke-day exposure in North America from 2019 to 2021. Because smoke can be transported at continental to intercontinental scales, even regions that may not typically experience direct burning of landscapes by wildfire are at risk of smoke exposure. We found that 99.3% of North America was covered by smoke, affecting a total of 1,333,687 lakes ≥10 ha. An incredible 98.9% of lakes experienced at least 10 smoke-days a year, with 89.6% of lakes receiving over 30 lake smoke-days, and lakes in some regions experiencing up to 4 months of cumulative smoke-days. Herein we review the mechanisms through which smoke and ash can affect lakes by altering the amount and spectral composition of incoming solar radiation and depositing carbon, nutrients, or toxic compounds that could alter chemical conditions and impact biota. We develop a conceptual framework that synthesizes known and theoretical impacts of smoke on lakes to guide future research. Finally, we identify emerging research priorities that can help us better understand how lakes will be affected by smoke as wildfire activity increases due to climate change and other anthropogenic activities.


Assuntos
Ecossistema , Lagos , Fumaça , Incêndios Florestais , Fumaça/análise , América do Norte , Monitoramento Ambiental
4.
JCI Insight ; 9(12)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38912579

RESUMO

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.


Assuntos
Linfócitos T CD8-Positivos , Imunidade Inata , Macaca mulatta , Vacinas contra a SAIDS , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Vacinas contra a SAIDS/imunologia , Imunidade Inata/imunologia , Linfócitos T CD8-Positivos/imunologia , Anticorpos Antivirais/imunologia , Masculino , Vacinas Atenuadas/imunologia
5.
Urol Pract ; 11(4): 640-652, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38899638

RESUMO

INTRODUCTION: Financial toxicity associated with treatments for metastatic prostate cancer remains poorly defined. We sought to understand aspects of financial toxicity not captured in a commonly employed financial toxicity questionnaire and identify potential interventions to help alleviate financial toxicity through a convergent mixed methods approach. METHODS: Patients seen at our institution's advanced prostate cancer clinic were approached for completion of the Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire (quantitative analysis). A maximal variation purposive sample was chosen to participate in focus group discussions (qualitative analysis). Conventional content analysis was performed using an inductive approach. COST-FACIT scores were compared between patients experiencing high and low financial toxicity using Wilcoxon rank sum test. RESULTS: Three themes were identified through qualitative analysis: (1) workload, (2) coping strategies, and (3) communication. We found alignment with the existing theory of financial capacity across our findings. Two unique aspects of financial toxicity emerged that were not assessed quantitatively and deemed to be significant. Specifically, cost transparency (including health care teams knowledgeable about and willing to discuss costs) and inclusion of informal caregivers in financial toxicity screening and decision-making may guide future interventions aimed at limiting financial toxicity in this population. CONCLUSIONS: Prolonged treatment courses involving multiple lines of treatment with varying costs result in distinct financial toxicity components for patients with metastatic prostate cancer that are not assessed with COST-FACIT. Improving cost transparency, health care team knowledge and engagement, and providing resources to support informal caregivers may have a significant impact on the financial toxicity experienced by these patients.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/economia , Idoso , Pessoa de Meia-Idade , Metástase Neoplásica , Inquéritos e Questionários , Adaptação Psicológica , Grupos Focais , Efeitos Psicossociais da Doença , Carga de Trabalho
6.
bioRxiv ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38895480

RESUMO

The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP Sst+ ) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior. We find that EP Sst+ neurons are strongly engaged during this task and show bidirectional changes in activity during the choice and outcome periods of a trial. We then tested the effects of either permanently blocking cotransmission or modifying the GABA/glutamate ratio on behavior in well-trained animals. Neither manipulation produced detectable changes in behavior despite significant changes in synaptic transmission in the LHb, demonstrating that the outputs of these neurons are not required for on-going action-outcome updating in a probabilistic switching task.

7.
J Clin Invest ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805302

RESUMO

The surface receptor CD8α is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8α may impact critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models, compared to CD8α+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8α expression was induced on approximately 30% of previously CD8α- NK cells following IL-15 stimulation. These 'induced' CD8α+ ('iCD8α+') NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8α expression ('sustained CD8α+) or those that remained CD8α- ('persistent CD8α-'). These iCD8α+ cells originated from an IL-15Rß high NK cell population, with CD8α expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8α status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors.

8.
Oncoimmunology ; 13(1): 2348254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737793

RESUMO

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the NK cell responses to CRC. Compared to conventional (c) NK cells, ML NK cells displayed increased IFN-γ production against both CRC cell lines and primary patient-derived CRC spheroids. ML NK cells also exhibited improved killing of CRC target cells in vitro in short-term and sustained cytotoxicity assays, as well as in vivo in NSG mice. Mechanistically, enhanced ML NK cell responses were dependent on the activating receptor NKG2D as its blockade significantly decreased ML NK cell functions. Compared to cNK cells, ML NK cells exhibited greater antibody-dependent cytotoxicity when targeted against CRC by cetuximab. ML NK cells from healthy donors and mCRC patients exhibited increased anti-CRC responses. Collectively, our findings demonstrate that ML NK cells exhibit enhanced responses against CRC targets, warranting further investigation in clinical trials for mCRC patients, including those who have failed ICB.


Assuntos
Diferenciação Celular , Neoplasias Colorretais , Memória Imunológica , Células Matadoras Naturais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Humanos , Animais , Camundongos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Interferon gama/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Camundongos Endogâmicos NOD , Feminino
9.
Foods ; 13(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38790752

RESUMO

Microorganisms can play an important role in food production, especially through fermentation processes [...].

10.
Artigo em Inglês | MEDLINE | ID: mdl-38673338

RESUMO

This study is the first to examine factors in the utilization of physician services, dentist services, hospital care, and prescribed medications focusing exclusively on insured children in the United States. Data describing 48,660 insured children were extracted from the 2021 National Survey of Children's Health. Children in the present sample were covered by private health insurance, public health insurance, or other health insurance. Logistic regression results showed self-reported health to be negatively associated with physician visits, hospital-care use, and prescription use, but teeth condition to be positively associated with dentist visits. Physician visits were associated negatively with age, Hispanic ethnicity, Asian ethnicity, family income at or below 200% of the federal poverty level, and other health insurance, but positively with parental education and metropolitan residency. Dentist visits were associated positively with girls, age, and parental education, but negatively with Asian ethnicity and public health insurance. Use of hospital care was associated negatively with age and Asian ethnicity, but positively with parental education and public health insurance. Use of prescriptions was associated positively with age, Black ethnicity, parental education, and public health insurance, but negatively with Hispanic ethnicity, Asian ethnicity, and family income at or below 200% of the federal poverty level. Implications included the expansion of public health insurance, promotion of awareness of medicine discount programs, and understanding of racial/ethnic minorities' cultural beliefs in health and treatment.


Assuntos
Seguro Saúde , Humanos , Criança , Feminino , Estados Unidos , Masculino , Pré-Escolar , Lactente , Adolescente , Seguro Saúde/estatística & dados numéricos , Recém-Nascido , Medicamentos sob Prescrição/uso terapêutico
11.
Food Microbiol ; 120: 104488, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38431314

RESUMO

Agricultural practises such as conventional and organic farming can potentially affect the microbial communities in milk. In the present study, the bacterial diversity of milk was investigated using high-throughput sequencing on ten organic and ten conventional farms in the Azores, a region where milk production is largely based on year-round grazing systems. The microbiota of milk from both production systems was dominated by Bacillota, Pseudomonadota, Actinomycetota and Bacteroidota. The organic milk showed greater heterogeneity between farms, as reflected in the dispersion of diversity indices and the large variation in the relative abundances of the dominant genera. In contrast, conventionally produced milk showed a high degree of similarity within each season. In the conventional production system, the season also had a strong influence on the bacterial community, but this effect was not observed in the organic milk. The LEfSe analysis identified the genus Iamia as significantly (p < 0.05) more abundant in organic milk, but depending on the season, several other genera were identified that distinguished organic milk from conventionally produced milk. Of these, Bacillus, Iamia and Nocardioides were associated with the soil microbiota in organic farming.


Assuntos
Bactérias , Leite , Animais , Bovinos , Feminino , Leite/microbiologia , Bactérias/genética , Agricultura Orgânica , Agricultura , Fazendas
12.
PeerJ ; 12: e16779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38239293

RESUMO

Background: Microendemic species are species with very small geographic distributions (ranges). Their presence delimitates areas with microendemic species (AMs), denoting a spatial unit comprising at least one population of at least one microendemic species. AMs are assumed to be distributed distinctively and associated with specific ecological, historical, and anthropogenic attributes. However, the level of influence of these factors remains unclear. Thus, we studied the distribution patterns of microendemic species within the Brazilian Atlantic Forest to (a) identify the region's AMs; (b) evaluate whether ecological (latitude, altitude, distance from the coastline), historical (climate stability), and anthropogenic (ecological integrity) attributes distinguish AMs from non-AMs; and (c) assess the conservation status of the Atlantic Forest's AMs. Methods: We mapped the ranges of 1,362 microendemic species of angiosperms, freshwater fishes, and terrestrial vertebrates (snakes, passerine birds, and small mammals) to identify the region's AMs. Further, spatial autoregressive logit regression models were used to evaluate whether latitude, altitude, distance from the coastline, Climate Stability Index, and ecological integrity can be used to discern AMs from non-AMs. Moreover, the AMs' conservation status was assessed by evaluating the region's ecological integrity and conservation efforts (measured as the proportion of AMs in protected areas). Results: We identified 261 AMs for angiosperm, 205 AMs for freshwater fishes, and 102 AMs for terrestrial vertebrates in the Brazilian Atlantic Forest, totaling 474 AMs covering 23.8% of the region. The Brazilian Atlantic Forest is a large and complex biogeographic mosaic where AMs represent islands or archipelagoes surrounded by transition areas with no microendemic species. All local attributes help to distinguish AMs from non-AMs, but their impacts vary across taxonomic groups. Around 69% of AMs have low ecological integrity and poor conservation efforts, indicating that most microendemic species are under threat. This study provides insights into the biogeography of one of the most important global biodiversity hotspots, creating a foundation for comparative studies using other tropical forest regions.


Assuntos
Biodiversidade , Magnoliopsida , Animais , Florestas , Vertebrados , Clima , Brasil , Mamíferos
13.
Eur J Investig Health Psychol Educ ; 14(1): 203-214, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38248133

RESUMO

This secondary data analysis of 1731 low-birth-weight children and their parents in the United States investigated children's health and its associations with social disorganization, social structural factors, social relationships, health/mental health, and access to health insurance/services. The study drew on data from the 2021 National Survey of Children's Health. Logistic regression yielded results showing low-birth-weight children's excellent/very good/good health to be associated positively with parents' education and health. In turn, child health was associated negatively with being Black, having a family income at or below the 100% federal poverty level, difficulty parenting the child, child chronic health condition(s), parent mental health, and substance use in the family. The implications of the present findings in terms of interventions promoting maternal and child health as well as participation in government assistance programs for low-income families are discussed.

14.
Glob Chang Biol ; 30(1): e17061, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273537

RESUMO

Drier and hotter conditions linked with anthropogenic climate change can increase wildfire frequency and severity, influencing terrestrial and aquatic carbon cycles at broad spatial and temporal scales. The impacts of wildfire are complex and dependent on several factors that may increase terrestrial deposition and the influx of dissolved organic matter (DOM) from plants into nearby aquatic systems, resulting in the darkening of water color. We tested the effects of plant biomass quantity and its interaction with fire (burned vs. unburned plant biomass) on dissolved organic carbon (DOC) concentration and degradation (biological vs. photochemical) and DOM composition in 400 L freshwater ponds using a gradient experimental design. DOC concentration increased nonlinearly with plant biomass loading in both treatments, with overall higher concentrations (>56 mg/L) in the unburned treatment shortly after plant addition. We also observed nonlinear trends in fluorescence and UV-visible absorbance spectroscopic indices as a function of fire treatment and plant biomass, such as greater humification and specific UV absorbance at 254 nm (a proxy for aromatic DOM) over time. DOM humification occurred gradually over time with less humification in the burned treatment compared to the unburned treatment. Both burned and unburned biomass released noncolored, low molecular weight carbon compounds that were rapidly consumed by microbes. DOC decomposition exhibited a unimodal relationship with plant biomass, with microbes contributing more to DOC loss than photodegradation at intermediate biomass levels (100-300 g). Our findings demonstrate that the quantity of plant biomass leads to nonlinear responses in the dynamics and composition of DOM in experimental ponds that are altered by fire, indicating how disturbances interactively affect DOM processing and its role in aquatic environments.


Assuntos
Matéria Orgânica Dissolvida , Lagoas , Biomassa , Água Doce , Compostos Orgânicos/química
15.
Glob Chang Biol ; 30(1): e17058, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273540

RESUMO

Fire can lead to transitions between forest and grassland ecosystems and trigger positive feedbacks to climate warming by releasing CO2 into the atmosphere. Climate change is projected to increase the prevalence and severity of wildfires. However, fire effects on the fate and impact of terrestrial organic matter (i.e., terrestrial subsidies) in aquatic ecosystems are unclear. Here, we performed a gradient design experiment in freshwater pond mesocosms adding 15 different amounts of burned or unburned plant detritus and tracking the chronology of detritus effects at 10, 31, 59, and 89 days. We show terrestrial subsidies had time- and mass-dependent, non-linear impacts on ecosystem function that influenced dissolved organic carbon (DOC), ecosystem metabolism (net primary production and respiration), greenhouse gas concentrations (carbon dioxide [CO2 ], methane [CH4 ]), and trophic transfer. These impacts were shifted by fire treatment. Burning increased the elemental concentration of detritus (increasing %N, %P, %K), with cascading effects on ecosystem function. Mesocosms receiving burned detritus had lower [DOC] and [CO2 ] and higher dissolved oxygen (DO) through Day 59. Fire magnified the effects of plant detritus on aquatic ecosystem metabolism by stimulating photosynthesis and respiration at intermediate detritus-loading through Day 89. The effect of loading on DO was similar for burned and unburned treatments (Day 10); however, burned-detritus in the highest loading treatments led to sustained hypoxia (through Day 31), and long-term destabilization of ecosystem metabolism through Day 89. In addition, fire affected trophic transfer by increasing autochthonous nitrogen source utilization and reducing the incorporation of 15 N-labeled detritus into plankton biomass, thereby reducing the flux of terrestrial subsidies to higher trophic levels. Our results indicate fire chemically transforms plant detritus and alters the role of aquatic ecosystems in processing and storing carbon. Wildfire may therefore induce shifts in ecosystem functions that cross the boundary between aquatic and terrestrial habitats.


Assuntos
Incêndios , Incêndios Florestais , Ecossistema , Dióxido de Carbono , Florestas
16.
Cureus ; 15(10): e47799, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021526

RESUMO

Cardiovascular disease has remained one of the leading causes of mortality in the world. The basic pathophysiology of coronary artery disease (CAD) is a reduction of the blood flow in coronary vessels, leading to restricted blood flow to the heart muscle. Both modifiable and non-modifiable risk factors contribute to its multifactorial etiology. The clinical presentation ranges from asymptomatic to typical symptoms like chest pain, shortness of breath, and left arm or jaw pain. The purpose of this review is to investigate and analyze the variation of CAD depending on the biological sex, age, race, or ethnicity and how it might differ in the studied population while comparing the symptoms and prognosis of CAD. For this research, PubMed's database was used. A total of 926 articles were selected using pre-determined inclusion and exclusion criteria, with 74 articles eligible to be included in the narrative review. Studies were selected from the general population of patients with CAD, regardless of their severity, stage of diagnosis, and treatment plan. The scale for the assessment of non-systematic review articles (SANRA) was used to assess the quality of the study. As humans age, the incidence of CAD increases, and people over 75 are more likely to have multiple-vessel CAD. It has been observed that South Asians have the highest rate of CAD at 24%, while the White population has the lowest at 8%. The prevalence of CAD also depends on race, with the White population having the lowest rate at 3.2%, followed by Hispanics at 5%, Black women at 5.2%, and Black men at 5.7%. Younger Black women tend to have more chest pain. Men with CAD commonly experience chest pain, and women are more likely to present with atypical symptoms. Modifiable risk factors such as smoking and alcoholism are more commonly observed in young men than in young women. Coronary artery disease in the elderly, female, minority, and Black patients is associated with a higher mortality rate. Acknowledging the prevalence of certain risk factors, signs, results, and responses to treatment in certain socio-demographic groups, as well as the provision and accessibility of diagnosis and treatment, would lead to a better outcome for all individuals. The impact of this shift can range from an earlier diagnosis of CAD to a faster and more customized treatment plan tailored to each patient's individual requirements.

17.
bioRxiv ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37986885

RESUMO

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

18.
Eur J Investig Health Psychol Educ ; 13(10): 2251-2261, 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37887160

RESUMO

Applying the behavioral model of health services utilization to data from the United States, this study examined immigrant children's use of physician and dentist visits, hospital care, and prescribed medication. We employed data describing 9759 immigrant parents and children who participated in 2021's National Survey of Children's Health. Logistic regression results negatively linked physician visits to child health, child age, Asian children, fathers, lower parent education, lower family income, uninsured children, and parent's U.S. residence under 5 years. Dentist visits were positively associated with child age, girls, Hispanic children, parent education, family income, public/private health insurance coverage, and U.S.-born children, but such use was associated negatively with Asian children. Hospital use was positively associated with poor child health, Black children, children of "other" race/ethnicity, younger parent age, enrolled in health insurance, and parent's U.S. residence under 5 years. The use of prescribed medication was negatively associated with Asian children, younger child age, lower parent education, uninsured child, and lack of English proficiency. The paper's conclusion suggests policymakers expand Medicaid and CHIP eligibility among immigrant children and suggests community education to foster awareness of children's physical and oral health needs and of Medicaid, CHIP, and prescription assistance programs. The conclusion calls for healthcare providers and social workers to accommodate and respect immigrants' traditional health-related beliefs, showing cultural competence.

19.
Sci Rep ; 13(1): 18440, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891196

RESUMO

Drastic changes in vegetation structure caused by exceeding ecological thresholds have fueled the interest in tropical forest responses to climate and land-use changes. Here, we examine the potential successional trajectories experienced by the largest dry tropical forest region in South America, driven by climate conditions and human disturbance. We built potential distribution models for vertebrate taxa associated with forest or shrub habitats to estimate natural vegetation cover. Distribution patterns were compared to current vegetation across the entire region to identify distinct forest degradation levels. Our results indicate the region has climatic and soil conditions suitable for more forest cover than is currently found, even in some areas with limited precipitation. However, 11.04% of natural cover persists across such an immense region, with only 4.34% consisting of forest cover. Forest degradation is characterized by the dramatic expansion of shrubland (390%), farming, and non-vegetation cover due to changes in land-use, rather than climatic conditions. Although different climate conditions have been the principal drivers for natural forest distribution in the region, the forest seems unable to resist the consequences of land-use changes, particularly in lower precipitation areas. Therefore, land-use change has exceeded the ecological thresholds for the persistence of forests, while climate change may exacerbate vegetation-type transitions.


Assuntos
Ecossistema , Florestas , Humanos , América do Sul , Agricultura , Fazendas
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