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1.
Psychooncology ; 33(5): e6348, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38730533

RESUMO

BACKGROUND: Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS: Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS: Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS: Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION: Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION: The case is made for further routinization of ongoing developmental screening in pediatric oncology care.


Assuntos
Deficiências do Desenvolvimento , Neoplasias , Melhoria de Qualidade , Encaminhamento e Consulta , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Neoplasias/diagnóstico , Neoplasias/terapia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/terapia , Adolescente , Programas de Rastreamento , Pediatria/normas , Oncologia , Lactente , Atenção Primária à Saúde
2.
Artigo em Inglês | MEDLINE | ID: mdl-38818044

RESUMO

Participation in authentic research in the field and online through Community and Citizen Science (CCS) has shown to bring learning benefits to volunteers. In online CCS, available platforms present distinct features, ranging from scaffolding the process of data collection, to supporting data analysis and enabling volunteers to initiate their own studies. What is yet not well understood is how best to design CCS programmes that are educational, inclusive, and accessible by diverse volunteers, including young people and those with limited prior science experiences who are rather few in CCS. In this study, we interviewed 31 young people, aged 7-20 years old, who used iNaturalist, an online biodiversity monitoring platform, and identified how different forms of participation online and in the field facilitated (or inhibited) certain forms of learning, as defined by the Environmental Science Agency framework. Findings revealed that iNaturalist enabled participation of young people including those with limited science experiences and facilitated science learning such as the development of science competence and understanding. A blended learning framework for biodiversity monitoring in CCS is presented as a means to support the development of hybrid, educational, and inclusive CCS programmes for young people.

3.
J Clin Psychol Med Settings ; 31(2): 304-315, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615281

RESUMO

It is well established that the integration of behavioral healthcare into the medical home model improves patient outcomes, reduces costs, and increases resident learning. As academic health centers increasingly integrate behavioral healthcare, targeted training for interprofessional collaboration around behavioral healthcare is needed. Simulation educational approaches potentially can provide this training. Health service psychologists are well-poised to support this because of their specialized training in integrated healthcare. The present exploratory study aimed to evaluate existing simulation programs and develop recommendations for integrated behavioral health training and evaluation. Directors of ACGME accredited residency programs that are high utilizers of the medical home model (Pediatrics, Internal Medicine, Medicine/Pediatrics, Family Medicine) as well as Psychiatry residencies and medical schools with membership in the Society for Simulation in Healthcare were recruited to complete a 26-item survey to assess program usage of psychologists as part of simulation training for integrated behavioral healthcare services. Of 79 participants who completed initial items describing their training program, only 32 programs completed the entire survey. While many academic health centers offered integrated team and behavioral health simulations, few utilized psychology faculty in design, implementation, and evaluation. Other behavioral health providers (psychiatrists, social workers) were often involved in medical school and pediatric residency simulations. Few institutions use standardized evaluation. Qualitative feedback and faculty-written questionnaires were often used to evaluate efficacy. Survey responses suggest that psychologists play limited roles in integrated behavioral healthcare simulation despite their expertise in interdisciplinary training, integrated behavioral healthcare, and program evaluation.


Assuntos
Treinamento por Simulação , Humanos , Treinamento por Simulação/métodos , Inquéritos e Questionários , Internato e Residência/métodos , Psicologia/educação , Docentes de Medicina , Prestação Integrada de Cuidados de Saúde , Medicina do Comportamento/educação
4.
Toxicology ; 504: 153786, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522819

RESUMO

This study evaluated the effect of pharmacological inhibition of galectin 3 (Gal-3) with modified citrus pectin (MCP) on the heart and kidney in a model of cisplatin-induced acute toxicity. Male Wistar rats were divided into four groups (n = 6/group): SHAM, which received sterile saline intraperitoneally (i.p.) for three days; CIS, which received cisplatin i.p. (10 mg/kg/day) for three days; MCP, which received MCP orally (100 mg/kg/day) for seven days, followed by sterile saline i.p. for three days; MCP+CIS, which received MCP orally for seven days followed by cisplatin i.p. for three days. The blood, heart, and kidneys were collected six hours after the last treatment. MCP treatment did not change Gal-3 protein levels in the blood and heart, but it did reduce them in the kidneys of the MCP groups compared to the SHAM group. While no morphological changes were evident in the cardiac tissue, increased malondialdehyde (MDA) levels and deregulation of the mitochondrial oxidative phosphorylation system were observed in the heart homogenates of the MCP+CIS group. Cisplatin administration caused acute tubular degeneration in the kidneys; the MCP+CIS group also showed increased MDA levels. In conclusion, MCP therapy in the acute model of cisplatin-induced toxicity increases oxidative stress in cardiac and renal tissues. Further investigations are needed to determine the beneficial and harmful roles of Gal-3 in the cardiorenal system since it can act differently in acute and chronic diseases/conditions.


Assuntos
Antineoplásicos , Cisplatino , Galectina 3 , Rim , Pectinas , Ratos Wistar , Animais , Cisplatino/toxicidade , Pectinas/farmacologia , Masculino , Galectina 3/metabolismo , Galectina 3/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Antineoplásicos/toxicidade , Ratos , Cardiotoxicidade , Miocárdio/metabolismo , Miocárdio/patologia , Malondialdeído/metabolismo , Coração/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Galectinas/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nefropatias/prevenção & controle
6.
Methods Mol Biol ; 2750: 143-163, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38108975

RESUMO

Overexpression of recombinant protein in mammalian cells is widely used for producing biologics, as protein maturation and post-translational modifications are similar to human cells. Some therapeutics, such as mRNA vaccines, target nonnative cells that may contain inefficient secretory machinery. For example, gene replacement therapies for alpha-1 antitrypsin (AAT), a glycoprotein normally produced in hepatocytes, are often targeted to muscle cells due to ease of delivery. In this chapter, we define methods for expressing AAT in representative cell types such as Huh-7; hepatocytes; Chinese hamster ovarian cells (CHO), a common host to produce biologics; and C2C12, a muscle progenitor cell line. Methods for metabolically labeling AAT to monitor secretion in these cell lines are described along with the use of proteostasis activators to increase the amount of AAT secreted in both C2C12 myoblasts and differentiated myotubes. Assays to assess the activity and glycan composition of overexpressed AAT are also presented. The usage of the proteostasis activator SAHA provided a 40% improvement in expression of active AAT in muscle-like cells and may be an advantageous adjuvant for recombinant production of proteins delivered by mRNA vaccines.


Assuntos
Produtos Biológicos , Vacinas de mRNA , Animais , Cricetinae , Humanos , Hepatócitos , Fibras Musculares Esqueléticas , Células CHO , Mamíferos
7.
J Biol Chem ; 300(1): 105574, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38110031

RESUMO

The 70 kDa heat shock proteins (Hsp70s) play a pivotal role in many cellular functions using allosteric communication between their nucleotide-binding domain (NBD) and substrate-binding domain, mediated by an interdomain linker, to modulate their affinity for protein clients. Critical to modulation of the Hsp70 allosteric cycle, nucleotide-exchange factors (NEFs) act by a conserved mechanism involving binding to the ADP-bound NBD and opening of the nucleotide-binding cleft to accelerate the release of ADP and binding of ATP. The crystal structure of the complex between the NBD of the Escherichia coli Hsp70, DnaK, and its NEF, GrpE, was reported previously, but the GrpE in the complex carried a point mutation (G122D). Both the functional impact of this mutation and its location on the NEF led us to revisit the DnaK NBD/GrpE complex structurally using AlphaFold modeling and validation by solution methods that report on protein conformation and mutagenesis. This work resulted in a new model for the DnaK NBD in complex with GrpE in which subdomain IIB of the NBD rotates more than in the crystal structure, resulting in an open conformation of the nucleotide-binding cleft, which now resembles more closely what is seen in other Hsp/NEF complexes. Moreover, the new model is consistent with the increased ADP off-rate accompanying GrpE binding. Excitingly, our findings point to an interdomain allosteric signal in DnaK triggered by GrpE binding.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Proteínas de Choque Térmico HSP70 , Proteínas de Choque Térmico , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Regulação Alostérica , Cristalografia por Raios X , Escherichia coli/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Mutagênese , Mutação Puntual , Ligação Proteica , Domínios Proteicos , Reprodutibilidade dos Testes , Rotação
8.
Mol Cell ; 83(24): 4524-4537.e5, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38052210

RESUMO

N-glycans act as quality control tags by recruiting lectin chaperones to assist protein maturation in the endoplasmic reticulum. The location and composition of N-glycans (glyco-code) are key to the chaperone-selection process. Serpins, a class of serine protease inhibitors, fold non-sequentially to achieve metastable active states. Here, the role of the glyco-code in assuring successful maturation and quality control of two human serpins, alpha-1 antitrypsin (AAT) and antithrombin III (ATIII), is described. We find that AAT, which has glycans near its N terminus, is assisted by early lectin chaperone binding. In contrast, ATIII, which has more C-terminal glycans, is initially helped by BiP and then later by lectin chaperones mediated by UGGT reglucosylation. UGGT action is increased for misfolding-prone disease variants, and these clients are preferentially glucosylated on their most C-terminal glycan. Our study illustrates how serpins utilize N-glycan presence, position, and composition to direct their proper folding, quality control, and trafficking.


Assuntos
Chaperonas Moleculares , Dobramento de Proteína , Humanos , Chaperonas Moleculares/metabolismo , Lectinas/metabolismo , Polissacarídeos/química , Controle de Qualidade
9.
iScience ; 26(12): 108409, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38058311

RESUMO

Given the importance of the kinin B1 receptor in insulin and leptin hormonal regulation, which in turn is crucial in maternal adaptations to ensure nutrient supply to the fetus, we investigated the role of this receptor in maternal metabolism and fetoplacental development. Wild-type and kinin B1 receptor-deficient (B1KO) female mice were mated with male mice of the opposite genotype. Consequently, the entire litter was heterozygous for kinin B1 receptor, ensuring that there would be no influence of offspring genotype on the maternal phenotype. Maternal kinin B1 receptor blockade reduces adiponectin secretion by adipose tissue ex vivo, consistent with lower adiponectin levels in pregnant B1KO mice. Furthermore, fasting insulinemia also increased, which was associated with placental insulin resistance, reduced placental glycogen accumulation, and heavier offspring. Therefore, we propose the combination of chronic hyperinsulinemia and reduced adiponectin secretion in B1KO female mice create a maternal obesogenic environment that results in heavier pups.

10.
Endocrinology ; 165(1)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37980602

RESUMO

Cancer-associated cachexia occurs in 50% to 80% of cancer patients and is responsible for 20% to 30% of cancer-related deaths. Cachexia limits survival and treatment outcomes, and is a major contributor to morbidity and mortality during cancer. Ovarian cancer is one of the leading causes of cancer-related deaths in women, and recent studies have begun to highlight the prevalence and clinical impact of cachexia in this population. Here, we review the existing understanding of cachexia pathophysiology and summarize relevant studies assessing ovarian cancer-associated cachexia in clinical and preclinical studies. In clinical studies, there is increased evidence that reduced skeletal muscle mass and quality associate with worse outcomes in subjects with ovarian cancer. Mouse models of ovarian cancer display cachexia, often characterized by muscle and fat wasting alongside inflammation, although they remain underexplored relative to other cachexia-associated cancer types. Certain soluble factors have been identified and successfully targeted in these models, providing novel therapeutic targets for mitigating cachexia during ovarian cancer. However, given the relatively low number of studies, the translational relevance of these findings is yet to be determined and requires more research. Overall, our current understanding of ovarian cancer-associated cachexia is insufficient and this review highlights the need for future research specifically aimed at exploring mechanisms of ovarian cancer-associated cachexia by using unbiased approaches and animal models representative of the clinical landscape of ovarian cancer.


Assuntos
Neoplasias , Neoplasias Ovarianas , Animais , Camundongos , Humanos , Feminino , Caquexia/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Neoplasias/patologia , Inflamação/patologia , Músculo Esquelético/patologia , Atrofia Muscular/etiologia
11.
An Acad Bras Cienc ; 95(suppl 2): e20230365, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37909611

RESUMO

Obesity and depression, disorders associated with inflammation, have high incidences in women. Understanding the derangements present in the initial phase of obesity may point to factors that could help avoiding disease aggravation. The present study aimed at investigating the effects of a 6-months interdisciplinary therapy for weight loss in women with grade I obesity. Before and after the therapy, 37 middle-aged women donated blood and responded to questionnaires for depression and anxiety symptoms. Inflammatory parameters were evaluated in serum and a preliminary screening of the plasma proteome was performed. The therapy decreased anthropometric, psychological scores, and serum levels of inflammatory parameters. Depression and anxiety scores correlated positively with some inflammatory parameters. The proteomic analysis showed changes in proteins related to cholesterol metabolism and inflammatory response. Interdisciplinary therapy improves anthropometric and inflammatory statuses and ameliorating psychological symptoms. The decrease of MCP-1 levels after interdisciplinary therapy has not been reported so far, at the best of our knowledge. The present demonstration of positive associations of inflammatory markers and psychological scores indicate that these mediators may be useful to monitor psychological status in obesity. The present proteome data, although preliminary, pointed to plasma alterations indicative of improvement of inflammation after interdisciplinary therapy.


Assuntos
Proteoma , Proteômica , Pessoa de Meia-Idade , Humanos , Feminino , Obesidade , Inflamação/terapia , Inflamação/complicações , Estilo de Vida
12.
Artigo em Inglês | MEDLINE | ID: mdl-37573715

RESUMO

BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal. METHOD: Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry. RESULTS: Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants. CONCLUSIONS: The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.


Assuntos
Lipodistrofia Generalizada Congênita , Humanos , Desjejum , Lipidômica , Tecido Adiposo , Lipídeos
13.
bioRxiv ; 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37163105

RESUMO

Many multi-domain proteins including the serpin family of serine protease inhibitors contain non-sequential domains composed of regions that are far apart in sequence. Because proteins are translated vectorially from N- to C-terminus, such domains pose a particular challenge: how to balance the conformational lability necessary to form productive interactions between early and late translated regions while avoiding aggregation. This balance is mediated by the protein sequence properties and the interactions of the folding protein with the cellular quality control machinery. For serpins, particularly α1-antitrypsin (AAT), mutations often lead to polymer accumulation in cells and consequent disease suggesting that the lability/aggregation balance is especially precarious. Therefore, we investigated the properties of progressively longer AAT N-terminal fragments in solution and in cells. The N-terminal subdomain, residues 1-190 (AAT190), is monomeric in solution and efficiently degraded in cells. More ß-rich fragments, 1-290 and 1-323, form small oligomers in solution, but are still efficiently degraded, and even the polymerization promoting Siiyama (S53F) mutation did not significantly affect fragment degradation. In vitro, the AAT190 region is among the last regions incorporated into the final structure. Hydrogen-deuterium exchange mass spectrometry and enhanced sampling molecular dynamics simulations show that AAT190 has a broad, dynamic conformational ensemble that helps protect one particularly aggregation prone ß-strand from solvent. These AAT190 dynamics result in transient exposure of sequences that are buried in folded, full-length AAT, which may provide important recognition sites for the cellular quality control machinery and facilitate degradation and, under favorable conditions, reduce the likelihood of polymerization.

14.
PeerJ ; 11: e15119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37009161

RESUMO

Methane seeps are highly abundant marine habitats that contribute sources of chemosynthetic primary production to marine ecosystems. Seeps also factor into the global budget of methane, a potent greenhouse gas. Because of these factors, methane seeps influence not only local ocean ecology, but also biogeochemical cycles on a greater scale. Methane seeps host specialized microbial communities that vary significantly based on geography, seep gross morphology, biogeochemistry, and a diversity of other ecological factors including cross-domain species interactions. In this study, we collected sediment cores from six seep and non-seep locations from Grays and Quinault Canyons (46-47°N) off Washington State, USA, as well as one non-seep site off the coast of Oregon, USA (45°N) to quantify the scale of seep influence on biodiversity within marine habitats. These samples were profiled using 16S rRNA gene sequencing. Predicted gene functions were generated using the program PICRUSt2, and the community composition and predicted functions were compared among samples. The microbial communities at seeps varied by seep morphology and habitat, whereas the microbial communities at non-seep sites varied by water depth. Microbial community composition and predicted gene function clearly transitioned from on-seep to off-seep in samples collected from transects moving away from seeps, with a clear ecotone and high diversity where methane-fueled habitats transition into the non-seep deep sea. Our work demonstrates the microbial and metabolic sphere of influence that extends outwards from methane seep habitats.


Assuntos
Microbiota , Água do Mar , Metano/química , RNA Ribossômico 16S/genética , Biodiversidade , Microbiota/genética
15.
Int J Endocrinol ; 2023: 7625720, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37101600

RESUMO

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

16.
Trends Ecol Evol ; 38(6): 485-489, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37088666

RESUMO

Amidst attention towards improving equality, inclusivity, and diversity, citizen science is woefully anachronistic in its name. There is a critical need for this field to distance itself from the exclusionary nature of the term 'citizen'. We provide reasoning for abandoning this term and an outline for adopting a new name.


Assuntos
Ciência do Cidadão , Humanos , Participação da Comunidade
17.
Eur Heart J Case Rep ; 7(1): ytad026, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36727140

RESUMO

Background: Tick-borne illness are becoming increasingly common, in a spreading geographic area. Lyme disease is a well-known cause of cardiovascular disease, but anaplasmosis has previously had relatively little reported association with conduction and myocardial disease. Case Summary: A 65-year-old man with fever and malaise was admitted to the intensive care unit in shock. Electrocardiogram showed new atrial fibrillation and conduction abnormalities. Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction but significant right ventricle dysfunction. Cardiac magnetic resonance imaging findings were consistent with myopericarditis. Workup revealed human granulocytic anaplasmosis without Lyme. He recovered with doxycycline. Conclusion: To our knowledge, this is one of the first reported cases of anaplasmosis causing electrical conduction and myocardial disease with haemodynamic instability in an isolated infection. Treatment with appropriate antibiotics and supportive care allowed the patient to recover to his functional baseline within a month from being discharged from the hospital. Recognition of anaplasmosis in the absence of Lyme disease as a potential cause of electrical and myocardial disease is important in the context of increasing anaplasmosis incidence across the United States.

18.
Clin Exp Rheumatol ; 41(2): 238-246, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36226626

RESUMO

OBJECTIVES: Until now, researchers have not provided a well-defined muscle histological pattern for antisynthetase syndrome (ASSD). Therefore, we aimed to analyse the muscle biopsies of patients with anti-Jo-1 ASSD. METHODS: This study included 26 patients with anti-Jo-1 ASSD admitted for investigation of the disease and obligatorily with muscle impairment, from 2010 to 2021, whose serial frozen muscle sections were analysed. RESULTS: Patients' mean age at disease diagnosis was 42.8±11.6 years, and the female gender was most predominant. Concerning muscle biopsies, cell infiltrates were present in 76.9% of the samples, and they were mainly located at the endomysium area (70%), with a predominance of macrophages (92.9%). Fiber muscle necrosis was present in 92.3% and was diffused in 54.2%. Expression of MHC-I was seen in all samples. Samples were mostly marked by the presence of CD68+ and discreet/low CD4+ and CD8+ staining, which is consistent with a higher predominance of observed necrosis and macrophage cell infiltrates. In general, 38.5% of patients had a necrotising myopathy pattern in muscle biopsies, whereas 34.6% and 26.9% had a general inflammatory myopathy pattern and nonspecific myopathy, respectively. This necrotising myopathy pattern was not associated with the demographic, clinical, or laboratory data. CONCLUSIONS: Our data show that almost 40% of patients with well-defined anti-Jo-1 ASSD with objective muscle impairment have a necrotising myopathy pattern in their muscle biopsies. Although this pattern is more classically related to immune-mediated necrotising myopathies, in association with clinical manifestations and the presence of anti-Jo-1 autoantibodies, this characteristic may lead to ASSD diagnosis.


Assuntos
Doenças Musculares , Miosite , Humanos , Feminino , Prevalência , Miosite/diagnóstico , Doenças Musculares/diagnóstico , Músculos/patologia , Biópsia , Necrose , Autoanticorpos
19.
J Paediatr Child Health ; 59(1): 134-143, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36354053

RESUMO

AIM: The purpose of this study was to evaluate whether a neurology outreach teaching programme delivered via video-teleconferencing (6 × 60 min live sessions every 6-8 weeks) is acceptable, contributes to understanding and meets the neurology learning needs of Australian paediatricians from metropolitan, rural and remote areas. METHODS: A sample of six NSW sites that joined the neurology outreach programme between 2017 and 2019 (Arm 1) and six interstate sites from QLD, WA and TAS who commenced the programme in 2020 (Arm 2) participated. A mixed-methods survey explored participants' learning needs and value of the programme. RESULTS: Forty-six participants submitted programme evaluation surveys (26 arm 1, 20 arm 2); 9 were removed due to insufficient data (n = 37). Quantitative and qualitative data showed the programme was acceptable in format, relevant to practice, appropriate for clinician learning needs, and engaging. Clinicians reported improvement in understanding and confidence. Participants felt more connected/less isolated and up-to-date. Participants reported a positive impact from the programme on approach to neurological problems and ensuing consults, and more differentiated and appropriate paediatric neurology referrals. CONCLUSION: This study validates the live video-teleconference outreach model as an acceptable, effective and important means of providing continuing neurology education for Australian paediatricians.


Assuntos
Aprendizagem , Pediatras , Criança , Humanos , Austrália , Estudos Longitudinais , Avaliação de Programas e Projetos de Saúde
20.
Tropical Biomedicine ; : 444-452, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1011360

RESUMO

@#This paper describes the occurrence of multiple parasitic infection with special reference to emerging haemotropic Mycoplasma ovis. A cross-sectional survey of four selected goat flocks was conducted to collect samples and management information. Blood samples were processed using microhaematocrit centrifugation to determine the packed cell volume (PCV). Detection and morphological identification of blood protozoa and haemotropic Mycoplasma ovis from Giemsa-stained smears were done microscopically. M. ovis infection was classified mild (1-29% infected cells), moderate (30-59% infected cells), or severe (above 60% infected cells). Faecal floatation and McMaster faecal egg count were used to detect and classify strongyle infections as negative (no eggs/oocysts), light (< 500 epg), Moderate (500 – 1000 epg), or severe (>1000 epg) and coccidia infection as light (<1800 opg), moderate (1800 – 6000 opg), or severe (>6000 opg). There were 149 goats with blood protozoa (57.98%; 95% CI: 51.87 – 63.85) and 204 goats with GI parasites (79.38%; 95% CI: 74.02 - 83.87) involved in single (15.8%; 95% CI: 11.7 – 21.0) or multiple (84.2%; 95% CI: 79.0 – 88.3) infections. The risk of Strongyles increases by 2.49 (95% CI: 1.24 – 4.99) in females versus males and 6.79 (95% CI: 3.25 – 14.18, p =0.000) in adults versus young. The risk of Eimeria species increases by 7.32 (95% CI: 3.45 – 15.50, p =0.000) in adults versus young, while M. ovis coinfection risk increases by 4.51 (95% CI: 1.40 – 14.50, p =0.000) in female versus males. Thin animals had a significantly higher (p<0.05) mean burden of Strongyle (1370.37 ± 345.49) and Eimeria (1594.12 ± 695.26) than the moderate and fat goats. The PCV was negatively associated with mean faecal egg count (FEC) (p<0.05) such that a lower PCV was recorded in animals with a higher Strongyle epg output. A severe burden of M. ovis was accompanied by an increased nematode FEC and decreased haematocrit (p<0.05). Coinfections of Strongyles, or Eimeria species involving M. ovis were associated with a higher parasitaemia compared with single infections (p<0.05). This study highlights the importance of M. ovis and Strongyle or Eimeria species coinfections among goat flocks and provides valuable data for developing and implementing an integrated herd health management program for parasite control among low-input smallholder flocks.

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