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ABSTRACT: Recent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured l-carnitine and acyl-carnitines in 13 091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation study. Genome-wide association studies against 879 000 polymorphisms identified critical genetic factors contributing to interdonor heterogeneity in end-of-storage carnitine levels, including common nonsynonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, and SLC16A9); carnitine synthesis (FLVCR1 and MTDH) and metabolism (CPT1A, CPT2, CRAT, and ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying 2 alleles of the rs12210538 SLC22A16 single-nucleotide polymorphism exhibited the lowest l-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice, and Percoll density gradients of human RBCs, showed age-dependent depletions of l-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process after chemically induced membrane lipid damage. Supplementation of stored murine RBCs with l-carnitine boosted posttransfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.
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Carnitina , Eritrócitos , Hemólise , Carnitina/metabolismo , Humanos , Animais , Camundongos , Eritrócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Envelhecimento Eritrocítico , Estudo de Associação Genômica Ampla , Masculino , Feminino , Membro 5 da Família 22 de Carreadores de Soluto/genética , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Preservação de Sangue/métodosRESUMO
NSG-SGM3 and NOG-EXL mice combine severe immunodeficiency with transgenic expression of human myeloid stimulatory cytokines, resulting in marked expansion of myeloid populations upon humanization with CD34+ hematopoietic stem cells (HSCs). Humanized NSG-SGM3 mice typically develop a lethal macrophage activation syndrome and mast cell hyperplasia that limit their use in long-term studies (e.g., humanization followed by tumor xenotransplantation). It is currently unclear to what extent humanized NOG-EXL mice suffer from the same condition observed in humanized NSG-SGM3 mice. We compared the effects of human CD34+ HSC engraftment in these two strains in an orthotopic patient-derived glioblastoma model. NSG-SGM3 mice humanized in-house were compared to NOG-EXL mice humanized in-house and commercially available humanized NOG-EXL mice. Mice were euthanized at humane or study endpoints, and complete pathological assessments were performed. A semiquantitative multiparametric clinicopathological scoring system was developed to characterize chimeric myeloid cell hyperactivation (MCH) syndrome. NSG-SGM3 mice were euthanized at 16 weeks after humanization because of severe deterioration of clinical conditions. Humanized NOG-EXL mice survived to the study endpoint at 22 weeks after humanization and showed less-severe MCH phenotypes than NSG-SGM3 mice. Major differences included the lack of mast cell expansion and limited tissue/organ involvement in NOG-EXL mice compared to NSG-SGM3 mice. Engraftment of human lymphocytes, assessed by immunohistochemistry, was similar in the two strains. The longer survival and decreased MCH phenotype severity in NOG-EXL mice enabled their use in a tumor xenotransplantation study. The NOG-EXL model is better suited than the NSG-SGM3 model for immuno-oncology studies requiring long-term survival after humanization.
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Antígenos CD34 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Camundongos Transgênicos , Células Mieloides , Animais , Camundongos , Humanos , Células-Tronco Hematopoéticas/patologia , Antígenos CD34/metabolismo , Células Mieloides/patologia , Fenótipo , Modelos Animais de DoençasRESUMO
Antarctica's extreme environmental conditions impose selection pressures on microbial communities. Indeed, a previous study revealed that bacterial assemblages at the Cierva Point Wetland Complex (CPWC) are shaped by strong homogeneous selection. Yet which bacterial phylogenetic clades are shaped by selection processes and their ecological strategies to thrive in such extreme conditions remain unknown. Here, we applied the phyloscore and feature-level ßNTI indexes coupled with phylofactorization to successfully detect bacterial monophyletic clades subjected to homogeneous (HoS) and heterogenous (HeS) selection. Remarkably, only the HoS clades showed high relative abundance across all samples and signs of putative microdiversity. The majority of the amplicon sequence variants (ASVs) within each HoS clade clustered into a unique 97% sequence similarity operational taxonomic unit (OTU) and inhabited a specific environment (lotic, lentic or terrestrial). Our findings suggest the existence of microdiversification leading to sub-taxa niche differentiation, with putative distinct ecotypes (consisting of groups of ASVs) adapted to a specific environment. We hypothesize that HoS clades thriving in the CPWC have phylogenetically conserved traits that accelerate their rate of evolution, enabling them to adapt to strong spatio-temporally variable selection pressures. Variable selection appears to operate within clades to cause very rapid microdiversification without losing key traits that lead to high abundance. Variable and homogeneous selection, therefore, operate simultaneously but on different aspects of organismal ecology. The result is an overall signal of homogeneous selection due to rapid within-clade microdiversification caused by variable selection. It is unknown whether other systems experience this dynamic, and we encourage future work evaluating the transferability of our results.
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Microbiota , Áreas Alagadas , Filogenia , Regiões Antárticas , Bactérias/genéticaRESUMO
ABSTRACT: In the field of transfusion medicine, the clinical relevance of the metabolic markers of the red blood cell (RBC) storage lesion is incompletely understood. Here, we performed metabolomics of RBC units from 643 donors enrolled in the Recipient Epidemiology and Donor Evaluation Study, REDS RBC Omics. These units were tested on storage days 10, 23, and 42 for a total of 1929 samples and also characterized for end-of-storage hemolytic propensity after oxidative and osmotic insults. Our results indicate that the metabolic markers of the storage lesion poorly correlated with hemolytic propensity. In contrast, kynurenine was not affected by storage duration and was identified as the top predictor of osmotic fragility. RBC kynurenine levels were affected by donor age and body mass index and were reproducible within the same donor across multiple donations from 2 to 12 months apart. To delve into the genetic underpinnings of kynurenine levels in stored RBCs, we thus tested kynurenine levels in stored RBCs on day 42 from 13 091 donors from the REDS RBC Omics study, a population that was also genotyped for 879 000 single nucleotide polymorphisms. Through a metabolite quantitative trait loci analysis, we identified polymorphisms in SLC7A5, ATXN2, and a series of rate-limiting enzymes (eg, kynurenine monooxygenase, indoleamine 2,3-dioxygenase, and tryptophan dioxygenase) in the kynurenine pathway as critical factors affecting RBC kynurenine levels. By interrogating a donor-recipient linkage vein-to-vein database, we then report that SLC7A5 polymorphisms are also associated with changes in hemoglobin and bilirubin levels, suggestive of in vivo hemolysis in 4470 individuals who were critically ill and receiving single-unit transfusions.
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Doadores de Sangue , Hemólise , Humanos , Cinurenina/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Eritrócitos/metabolismo , Metabolômica , Preservação de Sangue/métodosRESUMO
3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.
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Pulsatile lavage is utilized to copiously irrigate contaminated wounds; however, the current devices can cause significant splashing and increase the risk of contaminated fluid exposure to healthcare professionals. To create a larger splash guard for the standard pulsatile lavage device, we use heavy scissors to remove the end of a plastic light handle. We then place the nozzle of the lavage device through the open end to create a larger splash guard. This method provides a quick, accessible way to decrease the risk of splash exposure due to pulsatile lavage irrigation.
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BACKGROUND: Belize is a middle-income Caribbean country with poorly described cancer epidemiology and no comprehensive cancer care capacity. In 2018, GO, Inc., a US-based NGO, partnered with the Ministry of Health and the national hospital in Belize City to create the first public oncology clinic in the country. Here, we report demographics from the clinic and describe time intervals to care milestones to allow for public health targeting of gaps. PATIENTS AND METHODS: Using paper charts and a mobile health platform, we performed a retrospective chart review at the Karl Heusner Memorial Hospital (KHMH) clinic from 2018 to 2022. RESULTS: During this time period, 465 patients with cancer presented to the clinic. Breast cancer (28%) and cervical cancer (12%) were most common. Most patients (68%) presented with stage 3 or 4 disease and were uninsured (78%) and unemployed (79%). Only 21% of patients ever started curative intent treatment. Median time from patient-reported symptoms to a biopsy or treatment was 130 and 189 days. For the most common cancer, breast, similar times were seen at 140 and 178 days. Time intervals at the clinic: <30 days from initial visit to biopsy (if not previously performed) and <30 days to starting chemotherapy. CONCLUSION: This study reports the first clinic-based cancer statistics for Belize. Many patients have months between symptom onset and treatment. In this setting, the clinic has built infrastructure allowing for minimal delays in care despite an underserved population. This further affirms the need for infrastructure investment and early detection programs to improve outcomes in Belize.
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Neoplasias da Mama , Mama , Feminino , Humanos , Belize/epidemiologia , Estudos Retrospectivos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , DemografiaRESUMO
Coastal social-ecological systems in the Caribbean are affected by pelagic Sargassum spp. influxes and decomposition, but most satellite monitoring efforts focus on offshore waters. We developed a method to detect and spatial-temporally assess sargassum accumulations and their decaying stages along the shoreline and nearshore waters. A multi-predictor Random Forest model combining Sentinel-2 MultiSpectral Instrument reflectance bands and several vegetation, seaweed, water, and water quality indices was developed within the online Google Earth Engine platform. The model achieved 97 % overall accuracy and identified both fresh and decomposing sargassum, as well as the Sargassum-brown-tide generated from decomposing sargassum. We identified three hotspots of sargassum accumulation in La Parguera, Puerto Rico and found that sargassum was present every month in at least one of its forms during the entire time series (September 2015-January 2022). This research provides information to understand sargassum impacts and areas where mitigation efforts need to focus.
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Sargassum , Porto Rico , Ferramenta de Busca , Índias Ocidentais , EcossistemaRESUMO
The accumulation of unfolded proteins within the Endoplasmic Reticulum (ER) activates a signal transduction pathway termed the unfolded protein response (UPR), which attempts to restore ER homoeostasis. If this cannot be done, UPR signalling ultimately induces apoptosis. Ca2+ depletion in the ER is a potent inducer of ER stress. Despite the ubiquity of Ca2+ as an intracellular messenger, the precise mechanism(s) by which Ca2+ release affects the UPR remains unknown. Tethering a genetically encoded Ca2+ indicator (GCamP6) to the ER membrane revealed novel Ca2+ signalling events initiated by Ca2+ microdomains in human astrocytes under ER stress, induced by tunicamycin (Tm), an N-glycosylation inhibitor, as well as in a cell model deficient in all three inositol triphosphate receptor isoforms. Pharmacological and molecular studies indicate that these local events are mediated by translocons and that the Ca2+ microdomains impact (PKR)-like-ER kinase (PERK), an UPR sensor, activation. These findings reveal the existence of a Ca2+ signal mechanism by which stressor-mediated Ca2+ release regulates ER stress.
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Estresse do Retículo Endoplasmático , eIF-2 Quinase , Apoptose , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Humanos , Transdução de Sinais , Resposta a Proteínas não Dobradas , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismoRESUMO
BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).
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Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
OBJECTIVES: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS. METHODS: All patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed. RESULTS: Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002). CONCLUSIONS: Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.
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Síndrome de DiGeorge , Gastroenteropatias , Cardiopatias Congênitas , Comorbidade , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/genética , Feminino , Gastroenteropatias/complicações , Gastroenteropatias/genética , Humanos , Masculino , Fenótipo , Estudos RetrospectivosRESUMO
For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species-season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds.
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Migração Animal , Aves , Animais , Estações do Ano , América do SulRESUMO
Background: Faculty development for nurse and physician educators has a limited evidence base in high income countries, and very little research from low- and middle-income countries. Health professions educators in many global settings do not receive training on how to educate effectively. Objective: To pilot and assess a faculty development program aimed at nurse and physician educators at a teaching hospital in rural Haiti. Methods: We developed a program covering a total of 22 topics in health professions education, including applied learning theory as well as nurse and physician targeted topics. We assessed impact through participant assessment of personal growth, participant evaluation of the program, knowledge testing pre and post program, and structured observations of program participants providing teaching during the program. Findings: Nineteen out of 37 participants completed the program. While participant reviews were uniformly positive, a pre- and post-test on general educational topics showed no significant change, and the effort to institute observation and feedback of teaching did not succeed. Conclusions: Our project showcases some benefits of faculty development, while also demonstrating the challenges of instituting faculty development in situations where participants have limited time and resources. We suspect more benefits may emerge as the program evolves to fit the learners and setting.
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Docentes , Ocupações em Saúde , Currículo , Haiti , Hospitais de Ensino , Humanos , Desenvolvimento de Programas , EnsinoRESUMO
To analyze the etiological factors behind the malocclusion of a Late Pleistocene woman (named Naia), who is the best-preserved of the earliest individuals of the American continent. The examination of Naia's malocclusion was performed through cephalometric and occlusal analyses, and by measuring her mandible. Her data were then compared to published data for modern, medieval, and postmedieval samples and seven Late Pleistocene individuals. Naia presented her permanent dentition fully erupted, except for the impacted mandibular third molars. She presented a class II molar malocclusion with crowding. The dental widths and mandible measurements were similar to or smaller than modern standards. The degree of dental wear was light. The cephalometric analysis confirmed a skeletal class II relationship, with a retrusive mandible and protruded upper incisors. Naia's mild level of dental wear is consistent with a low masticatory force, in a time when the norm was a high amount of grinding. The low masticatory forces help explain Naia's small jaws and crowding. However, it does not clarify Angle's class II relationship. Naia is an example that environmental factors are insufficient to explain the onset of malocclusions and emphasizes the importance of understanding hereditary factors' role.
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Má Oclusão Classe II de Angle , Má Oclusão , Desgaste dos Dentes , Cefalometria , Feminino , Humanos , Recém-Nascido , Mandíbula , MéxicoRESUMO
As functional traits are conserved at different phylogenetic depths, the ability to detect community assembly processes can be conditional on the phylogenetic resolution; yet most previous work quantifying their influence has focused on a single level of phylogenetic resolution. Here, we have studied the ecological assembly of bacterial communities from an Antarctic wetland complex, applying null models across different levels of phylogenetic resolution (i.e. clustering ASVs into OTUs with decreasing sequence identity thresholds). We found that the relative influence of the community assembly processes varies with phylogenetic resolution. More specifically, selection processes seem to impose stronger influence at finer (100% sequence similarity ASV) than at coarser (99%-97% sequence similarity OTUs) resolution. We identified environmental features related with the ecological processes and propose a conceptual model for the bacterial community assembly in this Antarctic ecosystem. Briefly, eco-evolutionary processes appear to be leading to different but very closely related ASVs in lotic, lentic and terrestrial environments. In all, this study shows that assessing community assembly processes at different phylogenetic resolutions is key to improve our understanding of microbial ecology. More importantly, a failure to detect selection processes at coarser phylogenetic resolution does not imply the absence of such processes at finer resolutions.
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Ecossistema , Áreas Alagadas , Regiões Antárticas , Bactérias/genética , FilogeniaAssuntos
Fibrilação Atrial , Coração Auxiliar , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Humanos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Varfarina/efeitos adversosRESUMO
INTRODUCTION: Fracture nonunion remains a devastating complication and may occur for several reasons, though the microbial contribution remains poorly estimated. Next-generation sequencing (NGS) techniques, including 16S rRNA gene profiling, are capable of rapid bacterial detection within clinical specimens. Nonunion cases may harbor microbes that escape detection by conventional culture methods that contribute to persistence. Our aim was to investigate the application of NGS pathogen detection to nonunion diagnosis. METHODS: In this prospective multicenter study, samples were collected from 54 patients undergoing open surgical intervention for preexisting long-bone nonunion (n = 37) and control patients undergoing fixation of an acute fracture (n = 17). Intraoperative specimens were sent for dual culture and 16S rRNA gene-based microbial profiling. Patients were followed for evidence of fracture healing, whereas patients not healed at follow-up were considered persistent nonunion. Comparative analyses aimed to determine whether microbial NGS diagnostics could discriminate between nounions that healed during follow-up versus persistent nonunion. RESULTS: Positive NGS detection was significantly correlated with persistent nonunion, positive in 77% more cases than traditional culture. Nonunion cases were observed to have significantly increased diversity and altered bacterial profiles from control cases. DISCUSSION: NGS seems to be a useful adjunct in identification of organisms that may contribute to nonunion. Our findings suggest that the fracture-associated microbiome may be a significant risk factor for persistent nonunion. Ongoing work aims to determine the clinical implications of isolated organisms detected by sequencing and to identify robust microbial predictors of nonunion outcomes. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Fraturas não Consolidadas , Microbiota , Consolidação da Fratura , Fraturas não Consolidadas/cirurgia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microbiota/genética , Estudos Prospectivos , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We report a draft genome assembly of the causal agent of tomato vascular wilt, Fusarium oxysporum f. sp. lycopersici isolate 59, obtained from the Andean region in Colombia.
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Low-income Latina/o immigrants are very likely to experience intense contextual challenges in the USA, such as limited exposure to culturally relevant parent training (PT) prevention interventions. This prevention study consisted of an exploratory randomized controlled trial, aimed at empirically testing the implementation feasibility and initial efficacy of a culturally adapted version of the evidence-based PT intervention known as GenerationPMTO©. The parenting intervention was adapted to overtly address immigration-related stressors, discrimination, and challenges associated with biculturalism. Seventy-one Mexican-origin immigrant mothers participated in this study and were allocated to one of two conditions: (a) culturally adapted GenerationPMTO (i.e., CAPAS-Youth) or (b) wait-list control. Measurements were completed at baseline (T1) and intervention completion (T2). When compared to mothers in the control condition at T2, CAPAS-Youth participants reported significant improvements on four of the core parenting practices delivered in the CAPAS-Youth intervention. As hypothesized, no significant differences in limit-setting skills were identified at T2. With regards to adolescents' outcomes, mothers exposed to CAPAS-Youth reported significant improvements in youth internalizing and externalizing behaviors at T2 when compared to a wait-list control condition. Mothers in both conditions also reported significant reductions in levels of immigration-related stress. Current findings indicate the feasibility of implementing CAPAS-Youth within a context of considerable adversity, as well as the beneficial impacts of the parent-based intervention on salient parenting and youth outcomes.
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Emigrantes e Imigrantes , Poder Familiar , Adolescente , Emigração e Imigração , Feminino , Hispânico ou Latino , Humanos , MãesRESUMO
Individuals with PTSD have an increased risk of drug use disorders. Conversely, we aim to evaluate how early onset of alcohol, tobacco and psychoactive drugs use are associated with PTSD later in life. 2,193 brazilian young adults completed modularized assessments: The Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist-Civilian Version (PCL-C, transformed to PCL-5 through a crosswalk procedure), the Barratt Impulsivity Scale; and a survey on drug use with self-report questions about first use, current use, frequency, quantity, and interpersonal consequences. Bayesian inference and multivariate regression models were used to examine the effects on the risk of PTSD, considering different assumptions of information flow. Raw and unbiased (multivariate) estimates consistently revealed that earlier age of onset of alcohol and tobacco use increased risk for PTSD (Odds-ratios between 2.39 and 3.19 (Alcohol) and 1.82 to 2.05 (Tobacco). Among those who had PTSD (310), 10.3% (32) were very precocious at the onset age (12 to 18 years) of alcohol consumption (No-PTSD: 89 out 1883, 4.7%). Data supports a model in which age of onset effects are partially mediated by the number of trauma exposures. Early intoxication might suggest vulnerability for qualifying trauma events, or it may increase chances of exposure. Also, PTSD may be more likely to occur among trauma-exposed individuals with early intoxicating experiences due to alcohol or drug self-administration. The last possibility resonates with the idea that early intoxication might disrupt adolescent brain development, with a subsequent reduction in resilience when qualifying trauma events occur.