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1.
Genome Res ; 34(3): 498-513, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38508693

RESUMO

Hydractinia is a colonial marine hydroid that shows remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, Hydractinia symbiolongicarpus and Hydractinia echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell-type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinia's i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinia's stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from nonself.


Assuntos
Genoma , Hidrozoários , Animais , Hidrozoários/genética , Evolução Molecular , Transcriptoma , Células-Tronco/metabolismo , Masculino , Filogenia , Análise de Célula Única/métodos
2.
BMC Biol ; 21(1): 32, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782149

RESUMO

BACKGROUND: Sex determination occurs across animal species, but most of our knowledge about its mechanisms comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. RESULTS: In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used it to demonstrate that this species has an XX/XY sex determination system. We demonstrate that the X and Y chromosomes have pseudoautosomal and non-recombining regions. We then use the linkage map and a method based on the depth of sequencing coverage to identify genes encoded in the non-recombining region and show that many of them have male gonad-specific expression. In addition, we demonstrate that recombination rates are enhanced in the female genome and that the haploid chromosome number in Hydractinia is n = 15. CONCLUSIONS: These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination and the evolution of sex chromosomes.


Assuntos
Hidrozoários , Cromossomos Sexuais , Masculino , Feminino , Animais , Cromossomos Sexuais/genética , Mapeamento Cromossômico , Cromossomo Y/genética , Hidrozoários/genética , Evolução Molecular
3.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892238

RESUMO

Flavonoids are secondary metabolites that play important roles in the resistance of plants to abiotic stress. Despite the widely reported adverse effects of lead (Pb) contamination on maize, the effects of Pb on the biosynthetic processes of flavonoids in maize roots are still unknown. In the present work, we employed a combination of multi-omics and conventional assay methods to investigate the effects of two concentrations of Pb (40 and 250 mg/kg) on flavonoid biosynthesis in maize roots and the associated molecular regulatory mechanisms. Analysis using conventional assays revealed that 40 and 250 mg/kg Pb exposure increased the lead content of maize root to 0.67 ± 0.18 mg/kg and 3.09 ± 0.02 mg/kg, respectively, but they did not result in significant changes in maize root length. The multi-omics results suggested that exposure to 40 mg/kg of Pb caused differential expression of 33 genes and 34 metabolites related to flavonoids in the maize root system, while 250 mg/kg of Pb caused differential expression of 34 genes and 31 metabolites. Not only did these differentially expressed genes and metabolites participate in transferase activity, anthocyanin-containing compound biosynthetic processes, metal ion binding, hydroxyl group binding, cinnamoyl transferase activity, hydroxycinnamoyl transferase activity, and flavanone 4-reductase activity but they were also significantly enriched in the flavonoid, isoflavonoid, flavone, and flavonol biosynthesis pathways. These results show that Pb is involved in the regulation of maize root growth by interfering with the biosynthesis of flavonoids in the maize root system. The results of this study will enable the elucidation of the mechanisms of the effects of lead on maize root systems.


Assuntos
Flavonoides , Regulação da Expressão Gênica de Plantas , Chumbo , Raízes de Plantas , Estresse Fisiológico , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/metabolismo , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento , Flavonoides/biossíntese , Flavonoides/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Chumbo/toxicidade , Chumbo/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Fisiológico/genética , Metabolômica/métodos , Metaboloma/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
J Environ Manage ; 353: 120244, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38335599

RESUMO

On a global scale, the restoration of metal mine ecosystem functions is urgently required, and soil microorganisms play an important role in this process. Conventional studies frequently focused on the relationship between individual functions and their drivers; however, ecosystem functions are multidimensional, and considering any given function in isolation ignores the trade-offs and interconnectedness between functions, which complicates obtaining a comprehensive understanding of ecosystem functions. To elucidate the relationships between soil microorganisms and the ecosystem multifunctionality (EMF) of metal mines, this study investigated natural restoration of metal mines, evaluated the EMF, and used high-throughput sequencing to explore the bacterial and fungal communities as well as their influence on EMF. Bacterial community diversity and composition were more sensitive to mine restoration than fungal community. Bacterial diversity exhibited redundancy in improving N-P-K-S multifunctionality; however, rare bacterial taxa including Dependentiae, Spirochaetes, and WPS-2 were important for metal multifunctionality. Although no clear relationship between fungal diversity and EMF was observed, the abundance of Glomeromycota had a significant effect on the three EMF categories (N-P-K-S, carbon, and metal multifunctionality). Previous studies confirmed a pronounced positive association between microbial diversity and multifunctionality; however, the relationship between microbial diversity and multifunctionality differs among functions' categories. In contrast, the presence of critical microbial taxa exerted stronger effects on mine multifunctionality.


Assuntos
Ecossistema , Microbiota , Solo , Microbiologia do Solo , Bactérias/genética , Metais
5.
J Elder Abuse Negl ; 36(4): 413-422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449107

RESUMO

Elder mistreatment (EM) is a complex problem, with response and prevention requiring contributions from professionals from many disciplines. Community-based multi-disciplinary teams (MDTs) that conduct meetings to discuss challenging cases and coordinate services are a common strategy to ensure effective collaboration. Though they play an important role in EM identification, intervention, and prevention, hospitals and hospital-based healthcare professionals have been particularly difficult to engage in MDTs. Two hospitals in different communities recently launched Emergency Department (ED)/hospital-based response teams to consult in cases of potential EM, and both participate in MDTs. We explored similarities and differences between the MDTs in these communities including in the role of the ED/hospital-based response team. The comparison demonstrates both core common features as well as large variations. These differences reflect different circumstances in the models on which they were based, on MDT development in these communities, available resources and infrastructure, and the ED/hospital program's role.


Assuntos
Abuso de Idosos , Serviço Hospitalar de Emergência , Equipe de Assistência ao Paciente , Humanos , Equipe de Assistência ao Paciente/organização & administração , Serviço Hospitalar de Emergência/organização & administração , Idoso , Modelos Organizacionais
6.
J Elder Abuse Negl ; 36(4): 350-366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38117212

RESUMO

Interdisciplinary Emergency Department/hospital-based teams represent a promising care model to improve identification of and intervention for elder mistreatment. Two institutions, Weill Cornell Medicine/NewYork-Presbyterian Hospital and the University of Colorado Anschutz Medical Campus have launched such programs and are exploring multiple strategies for effective dissemination. These strategies include: (1) program evaluation research, (2) framing as a new model of geriatric care, (3) understanding the existing incentives of health systems, EDs, and hospitals to align with them, (4) connecting to ongoing ED/hospital initiatives, (5) identifying and collaborating with communities with strong elder mistreatment response that want to integrate the ED/hospital, (6) developing and making easily accessible high-quality, comprehensive protocols and training materials, (7) offering technical assistance and support, (8) communications outreach to raise awareness, and (9) using an existing framework to inform implementation in new hospitals and health systems.


Assuntos
Abuso de Idosos , Serviço Hospitalar de Emergência , Humanos , Abuso de Idosos/prevenção & controle , Idoso , Serviço Hospitalar de Emergência/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Avaliação de Programas e Projetos de Saúde
7.
J Elder Abuse Negl ; 36(4): 367-383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38602348

RESUMO

Elder mistreatment, including elder abuse and neglect, is a difficult diagnosis to make and manage for most providers. To address this, two elder abuse consultation teams were developed for patients in the hospital and emergency department settings. As these teams have developed, the providers involved have obtained specialized training and experience that we believe contributes to a new field of elder abuse geriatrics, a corollary to the well-established field of child abuse pediatrics. Providers working in this field require specialized training and have a specialized scope of practice that includes forensic evaluation, evaluation of cognition and capacity, care coordination and advocacy for victims of abuse, and collaboration with protective services and law enforcement. Here we describe the training, scope of practice, ethical role, and best practices for elder mistreatment medical consultation. We hope this will serve as a starting point for this new and important medical specialty.


Assuntos
Abuso de Idosos , Geriatria , Humanos , Abuso de Idosos/prevenção & controle , Abuso de Idosos/diagnóstico , Idoso , Encaminhamento e Consulta , Especialização , Avaliação Geriátrica/métodos
8.
J Elder Abuse Negl ; 36(4): 339-349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39051637

RESUMO

Elder mistreatment is common, serious, and under-recognized, with Emergency Department and hospital clinical encounters offering a potential but currently unrealized opportunity to identify and help older adults experiencing mistreatment. Interdisciplinary emergency department and hospital-based response teams represent a promising care model to address this. This manuscript describes two such teams and introduces a special issue dedicated to this work.


Assuntos
Abuso de Idosos , Serviço Hospitalar de Emergência , Humanos , Abuso de Idosos/prevenção & controle , Idoso , Consenso , Equipe de Assistência ao Paciente
9.
Clin Gerontol ; : 1-18, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622883

RESUMO

OBJECTIVES: This scoping review maps the literature on psychosocial distress and coping among nursing assistants (CNAs) in long-term care facilities (LTC) during the COVID-19 pandemic onto the Social Ecological Model (SEM) of Occupational Stress. METHODS: Searches yielded 862 unique studies. Inclusion criteria were sample CNAs or equivalent in LTC; includes psychosocial variable; and collect data from February 2020-. A multi-phasic, meta-synthesis was used to synthesize qualitative data. RESULTS: We identified 20 studies (13 quantitative, 7 qualitative) conducted between March 2020 and December 2021 from 14 countries. Prevalence rates were reported for perceived stress (31-33%; n = 1 study), post-traumatic stress (42%; n = 1), anxiety (53%; n = 1), depression (15-59%; n = 2), suicidal thoughts (11-15%; n = 1), and everyday emotional burnout (28%; n = 1). Qualitative studies identified factors contributing to psychosocial distress and coping at each SEM level (i.e. individual, microsystem, organization, and peri-/extra-organizational). Quantitative studies primarily measured factors relating to psychosocial distress and coping at the individual and organizational levels. CONCLUSIONS & CLINICAL IMPLICATIONS: This review identifies specific targets for intervention for psychosocial distress among CNAs in LTC at multiple levels, including job clarity; workload; facility culture; community relations; and policy. These intervention targets remain relevant to the LTC industry beyond the context of the COVID-19 pandemic.

10.
BMC Genomics ; 24(1): 575, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37759191

RESUMO

Comparative genomics is the comparison of genetic information within and across organisms to understand the evolution, structure, and function of genes, proteins, and non-coding regions (Sivashankari and Shanmughavel, Bioinformation 1:376-8, 2007). Advances in sequencing technology and assembly algorithms have resulted in the ability to sequence large genomes and provided a wealth of data that are being used in comparative genomic analyses. Comparative analysis can be leveraged to systematically explore and evaluate the biological relationships and evolution between species, aid in understanding the structure and function of genes, and gain a better understanding of disease and potential drug targets. As our knowledge of genetics expands, comparative genomics can help identify emerging model organisms among a broader span of the tree of life, positively impacting human health. This impact includes, but is not limited to, zoonotic disease research, therapeutics development, microbiome research, xenotransplantation, oncology, and toxicology. Despite advancements in comparative genomics, new challenges have arisen around the quantity, quality assurance, annotation, and interoperability of genomic data and metadata. New tools and approaches are required to meet these challenges and fulfill the needs of researchers. This paper focuses on how the National Institutes of Health (NIH) Comparative Genomics Resource (CGR) can address both the opportunities for comparative genomics to further impact human health and confront an increasingly complex set of challenges facing researchers.


Assuntos
Algoritmos , Genômica , Estados Unidos , Humanos , Hibridização Genômica Comparativa , Sistemas de Liberação de Medicamentos , National Institutes of Health (U.S.)
11.
Proc Natl Acad Sci U S A ; 117(10): 5358-5363, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32094163

RESUMO

Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.


Assuntos
Genoma Mitocondrial , Interações Hospedeiro-Parasita , Myxozoa/classificação , Myxozoa/genética , Salmão/parasitologia , Animais , Filogenia
12.
Ecotoxicol Environ Saf ; 250: 114498, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608568

RESUMO

The understanding of bacterial resistance to hexavalent chromium [Cr(VI)] are crucial for the enhancement of Cr(VI)-polluted soil bioremediation. However, the mechanisms related to plant-associated bacteria remain largely unclear. In this study, we investigate the resistance mechanisms and remediation potential of Cr(VI) in a plant-associated strain, AN-B15. The results manifested that AN-B15 efficiently reduced Cr(VI) to soluble organo-Cr(III). Specifically, 84.3 % and 56.5 % of Cr(VI) was removed after 48 h in strain-inoculated solutions supplemented with 10 and 20 mg/L Cr(VI) concentrations, respectively. Transcriptome analyses revealed that multiple metabolic systems are responsible for Cr(VI) resistance at the transcriptional level. In response to Cr(VI) exposure, strain AN-B15 up-regulated the genes involved in central metabolism, providing the reducing power by which enzymes (ChrR and azoR) transformed Cr(VI) to Cr(III) in the cytoplasm. Genes involved in the alleviation of oxidative stress and DNA repair were significantly up-regulated to neutralize Cr(VI)-induced toxicity. Additionally, genes involved in organosulfur metabolism and certain ion transporters were up-regulated to counteract the starvation of sulfur, molybdate, iron, and manganese induced by Cr(VI) stress. Furthermore, a hydroponic culture experiment showed that toxicity and uptake of Cr(VI) by plants under Cr(VI) stress were reduced by strain AN-B15. Specifically, strain AN-B15 inoculation increased the fresh weights of the wheat root and shoot by 55.5 % and 18.8 %, respectively, under Cr(VI) stress (5 mg/L). The elucidation of bacterial resistance to Cr(VI) has an important implication for exploiting microorganism for the effective remediation of Cr(VI)-polluted soils.


Assuntos
Cromo , Pseudomonas , Pseudomonas/genética , Pseudomonas/metabolismo , Cromo/análise , Bactérias/metabolismo , Ferro/metabolismo , Biodegradação Ambiental
13.
Ecotoxicol Environ Saf ; 266: 115527, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37806135

RESUMO

Understanding Cd-resistant bacterial cadmium (Cd) resistance systems is crucial for improving microremediation in Cd-contaminated environments. However, these mechanisms are not fully understood in plant-associated bacteria. In the present study, we investigated the mechanisms underlying Cd sequestration and resistance in the strain AN-B15. These results showed that extracellular Cd sequestration by complexation in strain AN-B15 was primarily responsible for the removal of Cd from the solution. Transcriptome analyses have shown that the mechanisms of Cd resistance at the transcriptional level involve collaborative processes involving multiple metabolic pathways. The AN-B15 strain upregulated the expression of genes related to exopolymeric substance synthesis, metal transport, Fe-S cluster biogenesis, iron recruitment, reactive oxygen species oxidative stress defense, and DNA and protein repair to resist Cd-induced stress. Furthermore, inoculation with AN-B15 alleviated Cd-induced toxicity and reduced Cd uptake in the shoots of wheat seedlings, indicating its potential for remediation. Overall, the results improve our understanding of the mechanisms involved in Cd resistance in bacteria and thus have important implications for improving microremediation.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/metabolismo , Pseudomonas/genética , Pseudomonas/metabolismo , Plântula/metabolismo , Ferro/metabolismo , Estresse Oxidativo , Bactérias/metabolismo , Poluentes do Solo/análise , Raízes de Plantas/metabolismo
14.
Int J Mol Sci ; 24(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298252

RESUMO

Stomata are one of the important structures for plants to alleviate metal stress and improve plant resistance. Therefore, a study on the effects and mechanisms of heavy metal toxicity to stomata is indispensable in clarifying the adaptation mechanism of plants to heavy metals. With the rapid pace of industrialization and urbanization, heavy metal pollution has been an environmental issue of global concern. Stomata, a special physiological structure of plants, play an important role in maintaining plant physiological and ecological functions. Recent studies have shown that heavy metals can affect the structure and function of stomata, leading to changes in plant physiology and ecology. However, although the scientific community has accumulated some data on the effects of heavy metals on plant stomata, the systematic understanding of the effects of heavy metals on plant stomata remains limited. Therefore, in this review, we present the sources and migration pathways of heavy metals in plant stomata, analyze systematically the physiological and ecological responses of stomata on heavy metal exposure, and summarize the current mechanisms of heavy metal toxicity on stomata. Finally, the future research perspectives of the effects of heavy metals on plant stomata are identified. This paper can serve as a reference for the ecological assessment of heavy metals and the protection of plant resources.


Assuntos
Metais Pesados , Poluentes do Solo , Metais Pesados/metabolismo , Plantas/metabolismo , Poluição Ambiental , Fenômenos Fisiológicos Vegetais , Poluentes do Solo/metabolismo , Solo/química
15.
J Elder Abuse Negl ; : 1-11, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37691425

RESUMO

The emergency department and hospital provide a unique and important opportunity to identify elder mistreatment and offer intervention. To help manage these complex cases, multi-disciplinary response teams have been launched. In developing these teams, it quickly became clear that social workers play a critical role in responding to elder mistreatment. Their unique skillset allows them to establish close connections with community resources, collaborate with various hospital stakeholders, support patients/families/caregivers through challenging situations, navigate the legal and protective systems, and balance patient safety and quality of life in disposition decision-making. The role of the social worker on these multi-faceted teams includes conducting a comprehensive biopsychosocial assessment, helping to develop a safe discharge plan, and making appropriate referrals, among other responsibilities. Any institution considering developing a multi-disciplinary program should recognize the critical importance of social work.

16.
Cancer Causes Control ; 33(7): 1013-1018, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35441278

RESUMO

The development of nasopharyngeal carcinoma (NPC) and its unique geographic distribution have long been attributed to a combination of dietary intake of salt-preserved fish, inherited susceptibility, and early-life infection with the Epstein-Barr virus (EBV). New findings from our large, rigorously designed, population-based case-control study of NPC in southern China have enabled substantial revision of this causal model. Here, we briefly summarize these results and provide an updated model of the etiology of NPC. Our new research identifies two EBV genetic variants that may be causally involved in the majority of NPC in southern China, and suggests the rise of modern environmental co-factors accompanying cultural and economic transformation in NPC-endemic regions. These discoveries can be translated directly into clinical and public health advances, including improvement of indoor air quality and oral health, development of an EBV vaccine, enhanced screening strategies, and improved risk prediction. Greater understanding of the roles of environmental, genetic, and viral risk factors can reveal the extent to which these agents act independently or jointly on NPC development. The history of NPC research demonstrates how epidemiology can shed light on the interplay of genes, environment, and infections in carcinogenesis, and how this knowledge can be harnessed for cancer prevention and control.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Estudos de Casos e Controles , China/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/etiologia
17.
Osteoarthritis Cartilage ; 30(9): 1278-1286, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35714760

RESUMO

OBJECTIVE: Both obesity and synovitis are independently associated with knee osteoarthritis (KOA) progression. We examined whether synovitis mediates the relationship between body mass index (BMI) and KOA radiographic progression in the Osteoarthritis Initiative (OAI) cohort. DESIGN: We conducted a case-control study within the OAI. Cases (n = 315) were right knees with an increase of ≥1 Kellgren-Lawrence from baseline to 48 months of follow-up. Controls (n = 315) were right knees with no KL change. Cases and controls were matched by age, sex, race, and baseline KL. MRI Osteoarthritis Knee Score (MOAKS) at baseline and at 2 years was used for a semi-quantitative scoring (0-3) of effusion-synovitis and Hoffa-synovitis. Conditional logistic regression estimated associations between BMI and synovitis with KOA progression. Mediation analysis was used to assess the mediating effects of synovitis. RESULTS: The mean age of participants was 61 years, 70.8% were women, and 87% were White. KOA progression was associated with higher BMI (adjusted OR 1.05; 95%CI 1.01-1.09) and effusion-synovitis relative to no effusion-synovitis (adjusted OR 2.2; 95%CI 1.6-3.1). Associations between effusion-synovitis worsening and KOA progression were more pronounced among obese individuals (OR 34.1; 95%CI 4.2-274.8; P = 0.001) compared to normal weight (OR 3.2; 95%CI 0.8-12.8, P=0.096) individuals. Effusion-synovitis at 2 years, but not at baseline, mediated the relationship between BMI and KOA progression over a 4-year period. CONCLUSIONS: We found that effusion-synovitis worsening mediated the association between BMI and KOA progression and was associated with increased risk of KOA progression, particularly among obese individuals.


Assuntos
Osteoartrite do Joelho , Sinovite , Índice de Massa Corporal , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Sinovite/diagnóstico por imagem
18.
Anticancer Drugs ; 33(7): 696-700, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35324529

RESUMO

Treatment options for heavily treated anaplastic lymphona kinase (ALK )-positive nonsmall cell lung cancer (NSCLC) patients, who typically bear-resistant mechanisms to ALK tyrosine kinase inhibitors (TKIs), are usually limited to chemotherapy, which elicits limited clinical benefit and may incur severe toxicity. It is clinically relevant to explore other revenues for these patients. poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib are currently approved to treat BReast CAncer gene 1/2 ( BRCA1/2 )-mutated patients in a few tumor types. There have been a trial and two case reports of an olaparib-containing regimen in treating epidermal growth factor receptor (EGFR)-positive or driver-negative NSCLC. We report a case of a 27-year-old female nonsmoker diagnosed with ALK -rearranged metastatic lung adenocarcinoma. She was treated with alectinib and acquired ALK p.I1171N and p.V1180L mutations. Germline BRCA2 p.F2801fs was also identified. After sequential lines of ceritinib and chemotherapy, lorlatinib was chosen as the fourth-line therapy and maintained control for 6 months. Shortly after progression, the patient was admitted to the ICU due to critically severe stenosis caused by a tracheal mass and soon relieved by embolization and stenting. Afterward lorlatinib plus olaparib was started and elicited a rapid response within 1 month. The progression-free survival was 6 months as of the latest follow-up, with the best response of partial response. To the best of our knowledge, this case is the first to provide clinical evidence of antitumor activity of olaparib plus ALK TKI in ALK -positive, g BRCA -mutated metastatic NSCLC. Together with previous reports in EGFR -positive or driver-negative patients, our finding warrants further studies on PARP inhibition in BRCA1/2 -mutated NSCLC.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estenose Traqueal , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adulto , Aminopiridinas , Quinase do Linfoma Anaplásico/genética , Proteína BRCA2/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB , Feminino , Humanos , Lactamas , Lactamas Macrocíclicas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Ftalazinas , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Pirazóis , Receptores Proteína Tirosina Quinases/genética , Estenose Traqueal/tratamento farmacológico
19.
Hong Kong Med J ; 28(1): 7-15, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35249888

RESUMO

INTRODUCTION: Because of the ageing population in Hong Kong, there is an increasing incidence of total knee arthroplasties (TKA) conducted in patients aged >80 years. METHODS: This retrospective case-control study enrolled all patients who were aged >80 years and underwent fast-track primary TKA between 2011 and 2015. Their outcomes were compared with the outcomes of a matched control group of younger patients who underwent fast-track TKA in the same period. RESULTS: In total, 220 patients were included in this study with a follow-up period of at least 2 years (mean=3.2 years; range, 2-5 years); 112 (51%) were octogenarians and 108 (49%) were non-octogenarians. Greater improvement in Knee Society Score was found in the octogenarian group at 1 year after surgery (46 ± 19 vs 39 ± 16, P=0.018). The incidence of complications was higher in the octogenarian group (15.2% vs 4.6%, P=0.009). There were no significant differences in the incidence of major complications, the rate of intensive care unit admission, or the 1-year mortality rate between the two groups. After adjustment for confounding factors, Charlson Comorbidity Index >5, history of major cerebrovascular accident, and history of peptic ulcer disease were predictive of complications after fast-track TKA (P=0.039, P=0.016, and P=0.007, respectively); octogenarian status was not predictive of complications. CONCLUSIONS: Octogenarians had greater improvement in Knee Society Score at 1 year after fast-track TKA, compared with non-octogenarians, but there were no significant differences in the incidences of mortality or major complications.


Assuntos
Artroplastia do Joelho , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Estudos de Casos e Controles , Humanos , Incidência , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
20.
Osteoarthritis Cartilage ; 29(8): 1173-1180, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33882334

RESUMO

OBJECTIVE: Meniscal degeneration is strongly associated with osteoarthritis (OA). We aimed to evaluate a 3D ultrashort-echo-time Cones magnetization transfer (UTE-Cones-MT) sequence for quantification of macromolecular fraction (MMF) and MT ratio (MTR) in menisci of healthy volunteers and patients with different degrees of OA. METHODS: Patients with mild OA (n = 19; 37-86 years; 10 males) or advanced OA (n = 12; 52-88 years; 4 males) and healthy volunteers (n = 17; 20-49 years; 7 males) were scanned with T2-FSE and UTE-Cones-MT sequences at 3T. Morphological assessment was performed using meniscal whole-organ magnetic resonance imaging score (WORMS). MMF and MTR were calculated for menisci, and correlated with age and meniscal WORMS scores. The diagnostic efficiency was performed by using receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses. RESULTS: Decreased MMF and MTR were observed in menisci of patients with mild or advanced OA compared with healthy subjects, and in menisci with tears (Grade 2-4) compared with normal menisci (Grade 0). Significant negative correlations were observed between MMF (r = -0.769, P < 0.01), MTR (r = -0.320, P < 0.01), and meniscal WORMS score. There was a mild negative correlation between MMF (r = -0.438, P < 0.01), MTR (r = -0.289, P < 0.01), and age. The AUC values of MMF and MTR in the four horns of meniscus and the posterior horn medial meniscus for differentiating OA patients from healthy volunteers were 0.762 and 0.699, and 0.835 and 0.883, respectively. CONCLUSION: The 3D UTE-Cones-MT biomarkers of MTR and especially MMF can detect compositional changes in meniscus and differentiate healthy subjects from patients with mild or advanced knee OA.


Assuntos
Imageamento por Ressonância Magnética/métodos , Meniscos Tibiais/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Lesões do Menisco Tibial/diagnóstico por imagem , Adulto Jovem
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