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1.
Development ; 150(8)2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36975725

RESUMO

The transcription factor FOXN1 is essential for fetal thymic epithelial cell (TEC) differentiation and proliferation. Postnatally, Foxn1 levels vary widely between TEC subsets, from low/undetectable in putative TEC progenitors to highest in differentiated TEC subsets. Correct Foxn1 expression is required to maintain the postnatal microenvironment; premature downregulation of Foxn1 causes a rapid involution-like phenotype, and transgenic overexpression can cause thymic hyperplasia and/or delayed involution. We investigated a K5.Foxn1 transgene that drives overexpression in mouse TECs, but causes neither hyperplasia nor delay or prevention of aging-related involution. Similarly, this transgene cannot rescue thymus size in Foxn1lacZ/lacZ mice, which undergo premature involution as a result of reduced Foxn1 levels. However, TEC differentiation and cortico-medullary organization are maintained with aging in both K5.Foxn1 and Foxn1lacZ/lacZ mice. Analysis of candidate TEC markers showed co-expression of progenitor and differentiation markers as well as increased proliferation in Plet1+ TECs associated with Foxn1 expression. These results demonstrate that the functions of FOXN1 in promoting TEC proliferation and differentiation are separable and context dependent, and suggest that modulating Foxn1 levels can regulate the balance of proliferation and differentiation in TEC progenitors.


Assuntos
Regulação da Expressão Gênica , Timo , Animais , Camundongos , Diferenciação Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Camundongos Endogâmicos C57BL
2.
PLoS Pathog ; 19(3): e1011230, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36940219

RESUMO

In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.


Assuntos
Genoma de Protozoário , Leishmaniose Cutânea , Parasitologia , Pele , Genoma de Protozoário/genética , Humanos , Genética Populacional , Pele/parasitologia , Brasil , Leishmaniose Cutânea/parasitologia , Parasitologia/métodos , Leishmania braziliensis/genética
3.
Proc Natl Acad Sci U S A ; 119(41): e2202261119, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36206369

RESUMO

Global change is altering the vast amount of carbon cycled by microbes between land and freshwater, but how viruses mediate this process is poorly understood. Here, we show that viruses direct carbon cycling in lake sediments, and these impacts intensify with future changes in water clarity and terrestrial organic matter (tOM) inputs. Using experimental tOM gradients within sediments of a clear and a dark boreal lake, we identified 156 viral operational taxonomic units (vOTUs), of which 21% strongly increased with abundances of key bacteria and archaea, identified via metagenome-assembled genomes (MAGs). MAGs included the most abundant prokaryotes, which were themselves associated with dissolved organic matter (DOM) composition and greenhouse gas (GHG) concentrations. Increased abundances of virus-like particles were separately associated with reduced bacterial metabolism and with shifts in DOM toward amino sugars, likely released by cell lysis rather than higher molecular mass compounds accumulating from reduced tOM degradation. An additional 9.6% of vOTUs harbored auxiliary metabolic genes associated with DOM and GHGs. Taken together, these different effects on host dynamics and metabolism can explain why abundances of vOTUs rather than MAGs were better overall predictors of carbon cycling. Future increases in tOM quantity, but not quality, will change viral composition and function with consequences for DOM pools. Given their importance, viruses must now be explicitly considered in efforts to understand and predict the freshwater carbon cycle and its future under global environmental change.


Assuntos
Gases de Efeito Estufa , Vírus , Amino Açúcares/metabolismo , Bactérias/genética , Bactérias/metabolismo , Carbono/metabolismo , Ciclo do Carbono , Gases de Efeito Estufa/metabolismo , Lagos/microbiologia , Vírus/genética , Vírus/metabolismo , Água/metabolismo
4.
Emerg Infect Dis ; 30(3): 510-518, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38407142

RESUMO

Disseminated leishmaniasis (DL) is an emergent severe disease manifesting with multiple lesions. To determine the relationship between immune response and clinical and therapeutic outcomes, we studied 101 DL and 101 cutaneous leishmaniasis (CL) cases and determined cytokines and chemokines in supernatants of mononuclear cells stimulated with leishmania antigen. Patients were treated with meglumine antimoniate (20 mg/kg) for 20 days (CL) or 30 days (DL); 19 DL patients were instead treated with amphotericin B, miltefosine, or miltefosine and meglumine antimoniate. High levels of chemokine ligand 9 were associated with more severe DL. The cure rate for meglumine antimoniate was low for both DL (44%) and CL (60%), but healing time was longer in DL (p = 0.003). The lowest cure rate (22%) was found in DL patients with >100 lesions. However, meglumine antimoniate/miltefosine treatment cured all DL patients who received it; therefore, that combination should be considered as first choice therapy.


Assuntos
Leishmania braziliensis , Leishmania , Leishmaniose Cutânea , Fosforilcolina/análogos & derivados , Humanos , Antimoniato de Meglumina/uso terapêutico , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico
5.
Osteoarthritis Cartilage ; 32(8): 938-949, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38782253

RESUMO

OBJECTIVE: Traumatic meniscal injuries can cause acute pain, hemarthrosis (bleeding into the joint), joint immobility, and post-traumatic osteoarthritis (PTOA). However, the exact mechanism(s) by which PTOA develops following meniscal injuries is unknown. Since meniscus tears commonly coincide with hemarthrosis, investigating the direct effects of blood and its constituents on meniscus tissue is warranted. The goal of this study was to determine the direct effects of blood and blood components on meniscus tissue catabolism. METHODS: Porcine meniscus explants or primary meniscus cells were exposed to whole blood or various fractions of blood for 3 days to simulate blood exposure following injury. Explants were then washed and cultured for an additional 3 days prior to collection for biochemical analyses. RESULTS: Whole blood increased matrix metalloproteinase (MMP) activity. Fractionation experiments revealed blood-derived red blood cells did not affect meniscus catabolism. Conversely, viable mononuclear leukocytes induced MMP activity, nitric oxide (NO) production, and loss of tissue sulfated glycosaminoglycan (sGAG) content, suggesting that these cells are mediating meniscus catabolism. CONCLUSIONS: These findings highlight the potential challenges of meniscus healing in the presence of hemarthrosis and the need for further research to elucidate the in vivo effects of blood and blood-derived mononuclear leukocytes due to both hemarthrosis and blood-derived therapeutics.


Assuntos
Leucócitos Mononucleares , Meniscos Tibiais , Animais , Suínos , Leucócitos Mononucleares/metabolismo , Meniscos Tibiais/metabolismo , Óxido Nítrico/metabolismo , Lesões do Menisco Tibial/metabolismo , Glicosaminoglicanos/metabolismo , Metaloproteinases da Matriz/metabolismo , Células Cultivadas , Menisco/metabolismo , Sangue/metabolismo
6.
Mol Ecol ; 33(11): e17370, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38682799

RESUMO

The composition of mammalian gut microbiomes is highly conserved within species, yet the mechanisms by which microbiome composition is transmitted and maintained within lineages of wild animals remain unclear. Mutually compatible hypotheses exist, including that microbiome fidelity results from inherited dietary habits, shared environmental exposure, morphophysiological filtering and/or maternal effects. Interspecific hybrids are a promising system in which to interrogate the determinants of microbiome composition because hybrids can decouple traits and processes that are otherwise co-inherited in their parent species. We used a population of free-living hybrid zebras (Equus quagga × grevyi) in Kenya to evaluate the roles of these four mechanisms in regulating microbiome composition. We analysed faecal DNA for both the trnL-P6 and the 16S rRNA V4 region to characterize the diets and microbiomes of the hybrid zebra and of their parent species, plains zebra (E. quagga) and Grevy's zebra (E. grevyi). We found that both diet and microbiome composition clustered by species, and that hybrid diets and microbiomes were largely nested within those of the maternal species, plains zebra. Hybrid microbiomes were less variable than those of either parent species where they co-occurred. Diet and microbiome composition were strongly correlated, although the strength of this correlation varied between species. These patterns are most consistent with the maternal-effects hypothesis, somewhat consistent with the diet hypothesis, and largely inconsistent with the environmental-sourcing and morphophysiological-filtering hypotheses. Maternal transmittance likely operates in conjunction with inherited feeding habits to conserve microbiome composition within species.


Assuntos
Dieta , Equidae , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Animais , RNA Ribossômico 16S/genética , Quênia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Equidae/microbiologia , Hibridização Genética , Feminino , Microbiota/genética , Masculino
7.
Brain Behav Immun ; 117: 36-50, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38182037

RESUMO

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Infecções por Citomegalovirus , Demência , Animais , Camundongos , Infecções por Citomegalovirus/complicações , Cognição
8.
J Surg Res ; 294: 183-190, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37913725

RESUMO

INTRODUCTION: Uncontrolled hemorrhage models require sufficient quantities of donor blood products to support resuscitation. To that end, we describe a novel method of whole blood extraction from donor swine using resuscitative endovascular balloon occlusion of the aorta (REBOA) to support hemodynamics during terminal blood extraction and its impact on the quality of banked blood. METHODS: Ten adult Yorkshire-cross swine were anesthetized and instrumented with an REBOA catheter, femoral multistage venous cannula, and proximal/distal blood pressure monitoring. Hemodynamics during terminal blood extraction was supported with hand-titrated partial REBOA. Blood samples were taken at set time points for analysis. RESULTS: The median collected blood volume was 3912 mL, with all animals surviving through the planned blood collection of 60% estimated total blood volume (ETBV). Median lactate and potassium levels remained within normal limits for swine through collection of 40% of the ETBV. Median hemoglobin through collection of 40% ETBV did not significantly change from values measured at the start of hemorrhage. CONCLUSIONS: This method of whole blood extraction provided sufficient blood volume and blood quality appropriate for transfusion through 40% ETBV, with remaining collected blood likely still acceptable for allogeneic transfusion despite increased lactate levels. This method of whole blood extraction can efficiently provide a large volume of quality blood to support resuscitation for subsequent uncontrolled hemorrhage models.


Assuntos
Oclusão com Balão , Procedimentos Endovasculares , Choque Hemorrágico , Suínos , Animais , Pressão Arterial , Modelos Animais de Doenças , Hemorragia/etiologia , Hemorragia/terapia , Aorta , Ressuscitação/métodos , Oclusão com Balão/métodos , Lactatos , Choque Hemorrágico/terapia , Procedimentos Endovasculares/métodos
9.
J Anim Ecol ; 93(7): 876-890, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38778676

RESUMO

Interspecific interactions, including predator-prey, intraguild predation (IGP) and competition, may drive distribution and habitat use of predator communities. However, elucidating the relative importance of these interactions in shaping predator distributions is challenging, especially in marine communities comprising highly mobile species. We used individual-based models (IBMs) to predict the habitat distributions of apex predators, intraguild (IG) prey and prey. We then used passive acoustic telemetry to test these predictions in a subtropical marine predator community consisting of eight elasmobranch (i.e. shark and ray) species in Bimini, The Bahamas. IBMs predicted that prey and IG prey will preferentially select habitats based on safety over resources (food), with stronger selection for safe habitat by smaller prey. Elasmobranch space-use patterns matched these predictions. Species with predator-prey and asymmetrical IGP (between apex and small mesopredators) interactions showed the clearest spatial separation, followed by asymmetrical IGP among apex and large mesopredators. Competitors showed greater spatial overlap although with finer-scale differences in microhabitat use. Our study suggests space-use patterns in elasmobranchs are at least partially driven by interspecific interactions, with stronger spatial separation occurring where interactions include predator-prey relationships or IGP.


Assuntos
Ecossistema , Cadeia Alimentar , Comportamento Predatório , Tubarões , Animais , Tubarões/fisiologia , Rajidae/fisiologia , Bahamas , Modelos Biológicos , Distribuição Animal , Telemetria
10.
Med Mycol ; 62(7)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38918050

RESUMO

The increasing prevalence of Candida parapsilosis as a causative agent of fungal infections underscores the need to comprehensively understand its virulence factors. Secreted aspartic proteases (Saps) play a significant role in adhesion events, promoting biofilm formation, causing tissue damage and evading the host's immune response. In C. parapsilosis, three Saps have been identified: Sapp1, Sapp2 and Sapp3. The present study investigates the production dynamics of Sapp1 and Sapp2 across 10 clinical isolates of C. parapsilosis using various approaches. Each fungal isolate demonstrated the capability to utilize bovine serum albumin (BSA) as the sole nitrogen source, as evidenced by its degradation in a cell-free culture medium, forming low molecular mass polypeptides. Interestingly, the degradation of different proteinaceous substrates, such as BSA, human serum albumin (HSA), gelatin and hemoglobin, was typically isolate-dependent. Notably, higher proteolysis of HSA compared to BSA, gelatin and hemoglobin was observed. A quantitative assay revealed that the cleavage of a peptide fluorogenic substrate (cathepsin D) was isolate-specific, ranging from 44.15 to 270.61 fluorescence arbitrary units (FAU), with a mean proteolysis of 150.7 FAU. The presence of both Sapp1 and Sapp2 antigens on the cell surface of these fungal isolates was confirmed through immunological detection employing specific anti-Sapp1 and anti-Sapp2 antibodies. The surface levels of Sapp1 were consistently higher, up to fourfold, compared to Sapp2. Similarly, higher levels of Sapp1 than Sapp2 were detected in fungal secretions. This study provides insights into the dynamic expression and regulation of Sapps in C. parapsilosis, highlighting a known virulence factor that is considered a potential target for drug development against this increasingly prominent pathogen.


The fungal pathogen Candida parapsilosis can secrete aspartic proteases (Sapps) as part of its arsenal of virulence factors. We demonstrated that Sapps were able to cleave key host proteins, and the production of Sapp1 and Sapp2 antigens was typically dependent on the fungal isolate when grown in both planktonic- and biofilm-forming cells.


Assuntos
Ácido Aspártico Proteases , Candida parapsilosis , Candida parapsilosis/enzimologia , Candida parapsilosis/genética , Humanos , Ácido Aspártico Proteases/metabolismo , Ácido Aspártico Proteases/genética , Fatores de Virulência/metabolismo , Soroalbumina Bovina , Proteólise , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Candidíase/microbiologia , Meios de Cultura/química , Catepsina D/metabolismo , Proteases Aspárticas Secretedas
11.
J Asthma ; : 1-10, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38577973

RESUMO

BACKGROUND: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. OBJECTIVE: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. METHODS: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. RESULTS: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). CONCLUSIONS: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

12.
Neurosurg Rev ; 47(1): 174, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643293

RESUMO

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

13.
JAMA ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873723

RESUMO

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

14.
Odontology ; 112(3): 959-965, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38214844

RESUMO

This study aimed to evaluate the influence of the metal post composition, tooth location in the dental arch, and metal artifact reduction (MAR) on vertical root fracture (VRF) diagnosis in cone beam computed tomography (CBCT). Twenty-two unirradicular premolars (12 sound and 10 fractured) and two alveolar sockets of a mandible (anterior and posterior regions) composed the sample. CBCT scans of each tooth with a metal post placed into the root canal-silver-palladium (Ag-Pd), cobalt-chromium (Co-Cr), or nickel-chromium (Ni-Cr)-were individually acquired for each mandibular region, and two conditions of MAR, using a OP300 device (Instrumentarium, Finland). Images were assessed by five evaluators independently for VRF detection. Diagnostic values were calculated and compared among all groups using multi-way ANOVA with Tukey post hoc test to investigate the effect of post material, anatomical region, and MAR on VRF diagnosis (α = 0.05). Values of area under the receiver operating curve and specificity were not influenced by the studied factors (p > 0.05). Sensitivity was influenced by the MAR in both mandibular regions (p < 0.05). In the anterior region, sensitivity values increased when the MAR was enabled, regardless of the metal post material (p < 0.05). Similar behavior was noticed in the posterior region for Ni-Cr (p < 0.05) but not for Ag-Pd and Co-Cr posts (p > 0.05). The MAR improved the sensitivity in VRF diagnosis for all tested metal posts in the mandibular anterior region and for the Ni-Cr post in the mandibular posterior region. Therefore, for images obtained in the OP300 CBCT device, activation of the MAR is suggested in these cases.


Assuntos
Artefatos , Tomografia Computadorizada de Feixe Cônico , Técnica para Retentor Intrarradicular , Fraturas dos Dentes , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Fraturas dos Dentes/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/lesões , Dente Pré-Molar/diagnóstico por imagem , Arco Dental/diagnóstico por imagem , Metais , Técnicas In Vitro , Sensibilidade e Especificidade , Mandíbula/diagnóstico por imagem
15.
Ecol Lett ; 26(1): 170-183, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36318189

RESUMO

Managing ecological communities requires fast detection of species that are sensitive to perturbations. Yet, the focus on recovery to equilibrium has prevented us from assessing species responses to perturbations when abundances fluctuate over time. Here, we introduce two data-driven approaches (expected sensitivity and eigenvector rankings) based on the time-varying Jacobian matrix to rank species over time according to their sensitivity to perturbations on abundances. Using several population dynamics models, we demonstrate that we can infer these rankings from time-series data to predict the order of species sensitivities. We find that the most sensitive species are not always the ones with the most rapidly changing or lowest abundance, which are typical criteria used to monitor populations. Finally, using two empirical time series, we show that sensitive species tend to be harder to forecast. Our results suggest that incorporating information on species interactions can improve how we manage communities out of equilibrium.


Assuntos
Biota , Fatores de Tempo , Dinâmica Populacional , Previsões
16.
N Engl J Med ; 383(21): 2041-2052, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32706953

RESUMO

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).


Assuntos
Antivirais/administração & dosagem , Azitromicina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Brasil , COVID-19 , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , SARS-CoV-2 , Falha de Tratamento , Tratamento Farmacológico da COVID-19
17.
Curr Opin Infect Dis ; 36(5): 414-419, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527001

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to summarize the treatment of complicated intraabdominal infections (cIAIs) in premature infants. RECENT FINDINGS: Recent work has continued to define the complex nature of cIAIs and necrotizing enterocolitis (NEC). This includes new findings on the microbiome, breast milk and risk factors associated with NEC. The treatment of cIAIs employs a combination of both surgical and medical treatment. Further look at what type and timing of surgical intervention is used as well as the ideal antibiotic regimen. Upcoming research is highlighted in future directions of NEC treatment. SUMMARY: cIAIs in premature infants is a challenging disease with more research needed to further delineate the pathophysiology and treatment options.


Assuntos
Enterocolite Necrosante , Infecções Intra-Abdominais , Microbiota , Lactente , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Leite Humano , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/terapia , Infecções Intra-Abdominais/tratamento farmacológico
18.
Mol Ecol ; 32(11): 2985-2999, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36807953

RESUMO

The rhizosphere is a vital soil compartment providing key plant-beneficial functions. However, little is known about the mechanisms driving viral diversity in the rhizosphere. Viruses can establish lytic or lysogenic interactions with their bacterial hosts. In the latter, they assume a dormant state integrated in the host genome and can be awakened by different perturbations that impact host cell physiology, triggering a viral bloom, which is potentially a fundamental mechanism driving soil viral diversity, as 22%-68% of soil bacteria are predicted to harbour dormant viruses. Here we assessed the viral bloom response in rhizospheric viromes by exposing them to three contrasting soil perturbation agents: earthworms, herbicide and antibiotic pollutant. The viromes were next screened for rhizosphere-relevant genes and also used as inoculant on microcosms incubations to test their impacts on pristine microbiomes. Our results show that while post-perturbation viromes diverged from control conditions, viral communities exposed to both herbicide and antibiotic pollutant were more similar to each other than those influenced by earthworms. The latter also favoured an increase in viral populations harbouring genes involved in plant-beneficial functions. Post-perturbation viromes inoculated on soil microcosms changed the diversity of pristine microbiomes, suggesting that viromes are important components of the soil ecological memory driving eco-evolutionary processes that determine future microbiome trajectories according to past events. Our findings demonstrate that viromes are active players in the rhizosphere and need to be considered in efforts to understand and control the microbial processes towards sustainable crop production.


Assuntos
Herbicidas , Vírus , Rizosfera , Viroma , Microbiologia do Solo , Bactérias/genética , Vírus/genética , Solo , Antibacterianos
19.
Glob Chang Biol ; 29(11): 3039-3053, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36843502

RESUMO

Northern lakes disproportionately influence the global carbon cycle, and may do so more in the future depending on how their microbial communities respond to climate warming. Microbial communities can change because of the direct effects of climate warming on their metabolism and the indirect effects of climate warming on groundwater connectivity from thawing of surrounding permafrost, especially at lower landscape positions. Here we used shotgun metagenomics to compare the taxonomic and functional gene composition of sediment microbes in 19 peatland lakes across a 1600-km permafrost transect in boreal western Canada. We found microbes responded differently to the loss of regional permafrost cover than to increases in local groundwater connectivity. These results suggest that both the direct and indirect effects of climate warming, which were respectively associated with loss of permafrost and subsequent changes in groundwater connectivity interact to change microbial composition and function. Archaeal methanogens and genes involved in all major methanogenesis pathways were more abundant in warmer regions with less permafrost, but higher groundwater connectivity partly offset these effects. Bacterial community composition and methanotrophy genes did not vary with regional permafrost cover, and the latter changed similarly to methanogenesis with groundwater connectivity. Finally, we found an increase in sugar utilization genes in regions with less permafrost, which may further fuel methanogenesis. These results provide the microbial mechanism for observed increases in methane emissions associated with loss of permafrost cover in this region and suggest that future emissions will primarily be controlled by archaeal methanogens over methanotrophic bacteria as northern lakes warm. Our study more generally suggests that future predictions of aquatic carbon cycling will be improved by considering how climate warming exerts both direct effects associated with regional-scale permafrost thaw and indirect effects associated with local hydrology.


Assuntos
Lagos , Pergelissolo , Clima , Pergelissolo/microbiologia , Ciclo do Carbono , Archaea/metabolismo , Carbono/metabolismo
20.
Langmuir ; 39(30): 10464-10474, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37458993

RESUMO

The kinetics of UV radiation-induced fast collapse and recovery in thermally cycled and rehydrated light- and thermo- double-responsive copolymer films of poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-(4-phenylazophenoxy)hexyl acrylate), abbreviated as P(OEGMA300-co-PAHA), are probed by in situ neutron reflectivity (NR). The copolymer film is exposed to a thermal treatment starting at a temperature of 60 °C, which is well above its transition temperature (TT = 53 °C) before the temperature is rapidly decreased from 60 to 23 °C. Based on the applied protocol, the initially collapsed P(OEGMA300-co-PAHA) film is rehydrated due to the switching of polymer chains from a more hydrophobic to a more hydrophilic state when the temperature falls below its TT. The whole rehydration process can be divided into 3 stages: D2O absorption, chain rearrangement, and film reswelling. After rehydration, the thermally cycled P(OEGMA300-co-PAHA) film is switched by UV irradiation via setting the UV radiation on and off. Considering the UV-induced collapse and recovery, both processes are slower than those observed in freshly hydrated films without any thermal stimulus history. Therefore, the experienced thermal history of the film should be considered in the design of sensors and detectors based on double-responsive copolymer films.

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