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Overexpression of EGFR drives glioblastomas (GBM) cell invasion but these tumours remain resistant to EGFR-targeted therapies such as tyrosine kinase inhibitors (TKIs). Endocytosis, an important modulator of EGFR function, is often dysregulated in glioma cells and is associated with therapy resistance. However, the impact of TKIs on EGFR endocytosis has never been examined in GBM cells. In the present study, we showed that gefitinib and other tyrosine kinase inhibitors induced EGFR accumulation in early-endosomes as a result of an increased endocytosis. Moreover, TKIs trigger early-endosome re-localization of another membrane receptor, the fibronectin receptor alpha5beta1 integrin, a promising therapeutic target in GBM that regulates physiological EGFR endocytosis and recycling in cancer cells. Super-resolution dSTORM imaging showed a close-proximity between beta1 integrin and EGFR in intracellular membrane compartments of gefitinib-treated cells, suggesting their potential interaction. Interestingly, integrin depletion delayed gefitinib-mediated EGFR endocytosis. Co-endocytosis of EGFR and alpha5beta1 integrin may alter glioma cell response to gefitinib. Using an in vitro model of glioma cell dissemination from spheroid, we showed that alpha5 integrin-depleted cells were more sensitive to TKIs than alpha5-expressing cells. This work provides evidence for the first time that EGFR TKIs can trigger massive EGFR and alpha5beta1 integrin co-endocytosis, which may modulate glioma cell invasiveness under therapeutic treatment.
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Endocitose/efeitos dos fármacos , Gefitinibe/farmacologia , Integrina alfa5beta1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Endossomos/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Integrina alfa5beta1/antagonistas & inibidores , Integrina alfa5beta1/genética , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismoRESUMO
The aim of this study was to determine the wound healing outcomes of patients with a plantar diabetic foot ulcer (DFU) treated with an interdisciplinary team approach, and to identify associated variables. A retrospective observational cohort study of 140 adult patients, with a plantar DFU, treated between 2012 and 2018 at a wound care clinic of a University affiliated hospital was conducted. Predictive and explicative analyses were conducted with logistic multivariate methods and with a Receiver Operating Characteristics curve. The best predictor of wound healing at 3 months was a 41.8% wound size reduction at 4 weeks (AUC: 0.86; sensitivity: 83.1%; specificity: 67.2%, positive predictive value: 72.8%; negative predictive value: 78.9%; positive and negative likelihood ratios: 2.53 and 0.25, respectively). Main baseline variables independently associated with this predictor were: a monophasic Doppler waveform (OR 7.52, 95% CI [2.64-21.39]), cigarette smoking (OR 4.7, 95% CI [1.44-15.29]), and male gender (OR 3.58, 95% CI [1.30-9.87]). The health care provider should be cautious and intensify its management of DFUs particularly with patients of male gender; smoking, having a monophasic waveform with a hand-held Doppler, and not achieving a minimal 41.8% wound area reduction at 4 weeks of treatment.
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Pé Diabético , Equipe de Assistência ao Paciente , Cicatrização , Adulto , Idoso , Canadá , Diabetes Mellitus , Pé Diabético/terapia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cancer stem cells (CSCs) have been reported in various cancers, including in skin squamous-cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here we find that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells, was the most upregulated transcription factor in the CSCs of squamous skin tumours in mice. SOX2 is absent in normal epidermis but begins to be expressed in the vast majority of mouse and human pre-neoplastic skin tumours, and continues to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In contrast to other SCCs, in which SOX2 is frequently genetically amplified, the expression of SOX2 in mouse and human skin SCCs is transcriptionally regulated. Conditional deletion of Sox2 in the mouse epidermis markedly decreases skin tumour formation after chemical-induced carcinogenesis. Using green fluorescent protein (GFP) as a reporter of Sox2 transcriptional expression (SOX2-GFP knock-in mice), we showed that SOX2-expressing cells in invasive SCC are greatly enriched in tumour-propagating cells, which further increase upon serial transplantations. Lineage ablation of SOX2-expressing cells within primary benign and malignant SCCs leads to tumour regression, consistent with the critical role of SOX2-expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing skin papilloma and SCC leads to tumour regression and decreases the ability of cancer cells to be propagated upon transplantation into immunodeficient mice, supporting the essential role of SOX2 in regulating CSC functions. Transcriptional profiling of SOX2-GFP-expressing CSCs and of tumour epithelial cells upon Sox2 deletion uncovered a gene network regulated by SOX2 in primary tumour cells in vivo. Chromatin immunoprecipitation identified several direct SOX2 target genes controlling tumour stemness, survival, proliferation, adhesion, invasion and paraneoplastic syndrome. We demonstrate that SOX2, by marking and regulating the functions of skin tumour-initiating cells and CSCs, establishes a continuum between tumour initiation and progression in primary skin tumours.
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Carcinoma de Células Escamosas , Transformação Celular Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Cutâneas , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adesão Celular/genética , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Deleção de Genes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Redes Reguladoras de Genes/genética , Camundongos , Camundongos Endogâmicos , Fatores de Transcrição SOXB1/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
PURPOSE: The aim of this study was to evaluate the effects of lumbar muscle delayed-onset muscle soreness (DOMS) on the ability of the trunk muscles to reproduce different levels of force. METHODS: Twenty healthy adults (10 males and 10 females) were recruited for this study. Force reproduction in trunk extension and flexion was assessed at 50 and 75% of participants' maximal isometric voluntary contraction in flexion and extension before and after a lumbar muscle DOMS protocol. Trunk proprioception was evaluated and compared between these conditions using different variables such as constant errors (CE), absolute errors (AE), variable errors (VE) and time to peak force (TPF). For each variable, repeated measure ANOVAs were conducted. RESULTS: AE were higher when participants had to reach the target post-DOMS protocol in extension compared to flexion and in the presence of higher demand of force (p = 0.02). For VE, results showed that participants were more variable in extension than in flexion when the required force was higher (p = 0.04). CE variable was higher when participants had to reach the force target in extension compared to flexion under the effect of DOMS (p = 0.02). Results also showed that participants took less time to reach the force target post-DOMS protocol in extension (0.62 ± 0.20 s) and in flexion (0.53 ± 0.19 s) than pre-DOMS protocol in extension (0.55 ± 0.15) and in flexion (0.50 ± 0.20) (p < 0.001). CONCLUSION: Lumbar muscle DOMS affects trunk proprioception during force reproduction tasks especially in trunk extension and at higher force.
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Exercício Físico , Mialgia/fisiopatologia , Propriocepção , Adulto , Feminino , Humanos , Região Lombossacral/fisiologia , Masculino , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Tronco/fisiologiaRESUMO
The large screening of exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene may lead to the discovery of rare, atypical molecular alterations for which the sensitivity to tyrosine kinase inhibitors (TKIs) remains uncertain. We are reporting a rare exon 18 EGFR mutation (p.E709_710 > D) that confers sensitivity to second-generation EGFR TKI (afatinib), lasting for 1 year. Tumor progression biopsy showed small cell lung cancer transformation, associated with a SMAD4 mutation. KEY POINTS: A rare exon 18 epidermal growth factor receptor mutation with sensitivity to afatinib is reported.Small cell transformation was observed at tumor progression.Acquisition of a SMAD4 mutation was observed at tumor progression.
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Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Adenocarcinoma de Pulmão/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , MutaçãoAssuntos
Conjuntivite Alérgica , Interleucina-5 , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Criança , Masculino , Feminino , Interleucina-5/antagonistas & inibidores , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico , AdolescenteRESUMO
Anorexia nervosa concerned, firstly, because this disorder is associated with many medical complications and secondly, because it is linked with a poor prognosis. Given these facts, it is imperative that effective treatments be available for anorexia nervosa. This article aims to present a systematic review of the literature on the best therapeutic modalities in the field of anorexia nervosa. Among these, we find outpatient treatment, importance of multidisciplinary team and various therapeutic approachs, like familial therapy.
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Anorexia Nervosa/terapia , Terapia Cognitivo-Comportamental , Internação Compulsória de Doente Mental , Terapia Familiar , HumanosRESUMO
Promising targeted therapy and personalized medicine are making molecular profiling of tumours a priority. For colorectal cancer (CRC) patients, international guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-epidermal growth factor receptor agents (anti-EGFR). Daily, new data emerge on the theranostic and prognostic role of molecular biomarkers, which is a strong incentive for a validated, sensitive and broadly available molecular screening test in order to implement and improve multi-modal therapy strategy and clinical trials. Next generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. Targeted NGS is a method that allows parallel sequencing of thousands of short DNA sequences in a single test offering a cost-effective approach for detecting multiple genetic alterations with a minimum amount of DNA. In the present review, we collected data concerning the clinical application of NGS technology in the setting of colorectal cancer.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Receptores ErbB/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Sequência de Bases , Biomarcadores Tumorais/genética , Cetuximab/uso terapêutico , Neoplasias Colorretais/patologia , Receptores ErbB/antagonistas & inibidores , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Panitumumabe , Análise de Sequência de DNARESUMO
AIMS: The assessment of thyroid nodules is a common clinical challenge. Fine-needle aspiration (FNA) is the standard pre-operative tool for thyroid nodule diagnosis. However, up to 30% of the samples are classified as indeterminate. This often leads to unnecessary surgery. In this study, we evaluated the added value of next-generation sequencing (NGS) for helping in the diagnosis of FNA samples. METHODS AND RESULTS: We analysed retrospectively 34 indeterminate FNA samples for which surgical resection was performed. DNA was obtained from cell blocks or from stained smears and subjected to NGS to analyse mutations in 50 genes. Mutations in BRAF, NRAS, KRAS and PTEN, that are known to be involved in thyroid cancer biology, were detected in seven FNA samples. The presence of a mutation in these genes was a strong indicator of cancer because five (71%) of the mutation-positive FNA samples had a malignant diagnosis after surgery. Moreover, there was only an 8% cancer risk in nodules with an indeterminate cytological diagnosis but with a negative molecular test. CONCLUSION: This study demonstrates that thyroid FNA can be analysed successfully by NGS. The detection of mutations known to be involved in thyroid cancer improves the sensitivity of thyroid FNA diagnosis.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Adulto , Biópsia por Agulha Fina , Análise Mutacional de DNA/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sequência de DNA/métodosRESUMO
Despite advances in diagnosis and treatment, the overall outcomes for patients with brain tumors remain unpredictable. New prognostic markers are still needed to identify high-risk patients for whom the standard treatment has poor outcomes and would thus be well suited for more aggressive therapies. Neovascularization has long been implicated as a salient feature of glioma progression. In fact, high-grade gliomas are among the most vascular of all solid tumors, and vascular proliferation is a pathological hallmark of glioblastomas. Galectins are known to play important roles in cancer biology, including cancer cell migration, tumor immune escape or tumor angiogenesis. Moreover, galectins were reported to be involved in glioma progression. Given the key role of angiogenesis in brain tumors, the expression of galectins in tumor-associated endothelial cells (EC) and the implication of galectins in angiogenesis, the present review will focus on the expression of galectins in ECs of normal brain and brain tumors.
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Neoplasias do Sistema Nervoso Central/genética , Galectinas/genética , Glioma/genética , Neovascularização Patológica/genética , Encéfalo/patologia , Movimento Celular/genética , Neoplasias do Sistema Nervoso Central/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Galectinas/biossíntese , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Neovascularização Patológica/patologiaRESUMO
Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through ß2-adrenoceptors (ß2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor α (TNFα) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on ß2-ARs expressed by non-neuronal satellite cells. This stimulation of ß2-ARs decreases the neuropathy-induced production of membrane-bound TNFα, resulting in relief of neuropathic allodynia. This indirect anti-TNFα action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the ß2-AR agonist terbutaline. Our data revealed an original therapeutic mechanism that may open novel research avenues for the management of painful peripheral neuropathies.
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Antidepressivos Tricíclicos/farmacologia , Gânglios Espinais/metabolismo , Neuralgia/tratamento farmacológico , Receptores Adrenérgicos beta 2/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anticorpos Monoclonais/farmacologia , Antidepressivos Tricíclicos/uso terapêutico , Etanercepte , Gânglios Espinais/patologia , Imunoglobulina G/farmacologia , Infliximab , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/metabolismo , Norepinefrina/metabolismo , Nortriptilina/farmacologia , Medição da Dor , Receptores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The COVID-19 pandemic exacerbated staffing challenges in intensive care units, with increased burnout and moral distress cited as major problems. A healthy work environment is critical to nurses' success and wellbeing. During the pandemic, a survey by the American Association of Critical-Care Nurses revealed decreased composite scores in each of the 6 critical elements of a healthy work environment. Hospital units that improved even 1 critical element reported higher job satisfaction. The use of telehealth tools by expert nurses expanded care delivery during the pandemic by improving response to acutely and critically ill patients while supporting hospital-based nurses. All of the critical elements of a healthy work environment are relevant to the tele-critical care nurse's role and challenges. This article describes how tele-critical care nurses were affected by the pandemic and how healthy work environment strategies promoted successful nurse and patient outcomes.
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Esgotamento Profissional , Enfermagem de Cuidados Críticos , Recursos Humanos de Enfermagem Hospitalar , Humanos , Condições de Trabalho , Pandemias , Unidades de Terapia Intensiva , Satisfação no EmpregoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0067029.].
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Background: The Obstetric Quality of Recovery-10 (ObsQoR-10) is a validated tool for assessing the quality of postpartum recovery. This study aimed to validate the French version of the ObsQoR-10 scale (ObsQoR-10-French). Methods: After translating the ObsQoR-10 into French, we conducted a psychometric validation involving internal consistency, convergent validity, construct validity, reliability, responsiveness, scaling properties, acceptability, and feasibility. French women who underwent either a vaginal delivery (spontaneous or induced labour), or an emergency or elective Caesarean section (C-section) were prospectively included. They completed the ObsQoR-10-French before delivery and at 24 h (H24) and 48 h (H48) after delivery. Results: Of the 500 women included, 431 (86%) completed the questionnaire at all three timepoints. A total of 352 women (82%) underwent vaginal delivery (with 228 [53%] experiencing spontaneous labour and 124 [29%] had labour induced), whereas 53 (12%) women underwent an emergency C-section and 26 (6%) an elective C-section. The ObsQoR-10-French demonstrated excellent internal consistency with a Cronbach's coefficient of 0.81, 95% confidence interval 0.78-0.84 at H24. The tool was correlated with an 11-item global health score (P<0.001). Of the list of hypotheses for evaluating the construct validity, 81% were confirmed (negative associations between ObsQoR-10-French and length of labour, hospital stay, the need for a C-section, and the emergency level of the C-section). The Cohen effect size at H24 was 0.58. The intra-class coefficient was 0.90, 95% confidence interval 0.86-0.93 at H24. Conclusion: The ObsQoR-10-French is a valid and reliable psychometric questionnaire, capable of assessing the quality of postpartum recovery in French-speaking populations. Clinical trial registration: NCT04489602.
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BACKGROUD: Management of severe COVID-19 patients admitted to ICU considerably evolved during the first months of the pandemic. It is unclear, however, whether these changes improved long-term survival of these critically ill patients. METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to a French ICU between February 2020 and January 2021, a timeframe that covered the first two waves of the pandemic. Primary outcome was to compare long-term survival between the first and second waves. Survival predictor were identified using a Cox proportional-hazards model. RESULTS: We included 265 patients in the cohort: 140 (52.8 %) and 125 (47.2 %) belonging to the first and second waves, respectively. Baseline characteristics of the patients were similar between the two waves. During W2, use of early corticotherapy increased (86.4% vs. 17.8 %; p <0.001), as well as high-flow oxygen therapy use (68.5% vs. 37.4 %; p<0.001). Need for invasive mechanical ventilation decreased (49.6% vs. 72.9 %; p <0.001) and ICU length of stay was shorter (11 [6-22] vs 19 [8-32]days; p = 0.008). ICU mortality was 32.8 % without significant difference between waves. Survival analysis revealed that 3 variables were independently associated with a worse long-term prognosis: a higher SAPS II score (1.05 [1.04-1.06]; p<0.001), a higher age (1.05 [1.01-1.08]; p = 0.005) and admission during W2 (2.22 [1.15-4.28]; p = 0.017). DISCUSSION: Despite substantial changes on management of severe COVID-19 patients, we observed a decreased long-term survival among patients admitted during the second wave. We also noted a shorter ICU length of stay.
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COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Estudos Retrospectivos , Unidades de Terapia Intensiva , Hospitalização , Respiração ArtificialRESUMO
A large number of drugs are known to bind with high affinity to sigma receptors (sigma-Rs) and have been used in the clinic to treat mental disorders for many years. However, recent publications highlighting sigma-R overexpression in many cancer tissues suggest potential applications for sigma-R ligands in cancer diagnosis and therapy. The present review focuses on the involvement of sigma-Rs in cancer biology and the potential therapeutic contributions of their pharmacologic ligands in oncology. After summarizing the current and general knowledge regarding sigma-Rs, we detail data reported in the particular context of oncology. We then investigate the potential and specific signal transduction pathways and mechanisms involved in the actions of sigma-R ligands in cancer biology. These processes include modulations of (1) the plasma membrane and lipid raft components, (2) intracellular calcium levels, (3) cytoskeletal protein functions, and (4) endoplasmic reticulum stress. Finally, we conclude by speculating on the roles of sigma-R overexpression and sigma-R ligands in cancer biology and offer perspectives on cancer therapy.
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Neoplasias/fisiopatologia , Receptores sigma/fisiologia , Cálcio/metabolismo , Proteínas do Citoesqueleto/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Ligantes , Microdomínios da Membrana/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Receptores sigma/uso terapêutico , Transdução de Sinais , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Oxytocin is a pleiotropic molecule which, in addition to its facilitating action during parturition and milk ejection, is involved in social and prosocial behaviors such as attachment. This article presents, after a brief historical review, the action of oxytocin during the milk ejection reflex. Oxytocin is indeed essential for this vital function in mammals. It is both a neurohormone released into the bloodstream by the axon terminals of the posterior pituitary and a neuromodulator released in the hypothalamus by the soma and dendrites of oxytocinergic magnocellular neurons. In addition, oxytocin is also released by the axon terminals of parvocellular neurons and axon collaterals of magnocellular neurons in the brain. Both maternal attachment in rats and ewes and attachment between sexual partners in the prairie vole, one of the few monogamous rodent species, are mediated by central oxytocin. However, neither administering oxytocin into the brain nor increasing expression of the oxytocin receptor in the nucleus accumbens using a gene transfer technique converts polygamous voles to monogamous ones. Unfortunately, translation of animal data to human remains problematic due to still unsolved difficulties in modifying the level of oxytocin in the brain.
Title: Comment, au fil du temps, l'ocytocine est devenue l'hormone de l'attachement. Abstract: L'ocytocine est une molécule pléiotrope qui, en plus de son action facilitatrice au cours de l'accouchement et de l'allaitement, est impliquée dans des comportements sociaux et prosociaux comme l'attachement. Cet article présente, après un bref rappel historique, l'action de l'ocytocine pendant le réflexe d'éjection de lait. L'ocytocine est en effet indispensable à cette fonction vitale chez les mammifères. Elle est à la fois une neurohormone, libérée dans la circulation sanguine par les terminaisons axonales de la post-hypophyse, et un neuromodulateur, libéré dans l'hypothalamus par le soma et les dendrites des neurones magnocellulaires ocytocinergiques. D'autre part, l'ocytocine est également libérée dans le cerveau par les terminaisons axonales des neurones parvocellulaires et des collatérales d'axones des neurones magnocellulaires. La libération centrale de l'ocytocine est à l'origine de ses effets dans l'attachement, qu'il s'agisse de l'attachement maternel comme chez la ratte et la brebis ou de l'attachement entre les partenaires sexuels chez le campagnol des prairies, une des rares espèces de rongeurs monogames. Toutefois, ni l'injection d'ocytocine dans le cerveau, ni l'augmentation de l'expression du récepteur de l'ocytocine dans le noyau accumbens grâce à une technique de transfert de gène, ne rendent monogames des campagnols polygames. La transposition à l'espèce humaine des données obtenues chez l'animal reste problématique en raison principalement de la difficulté à modifier le taux d'ocytocine dans le cerveau.
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Ocitocina , Receptores de Ocitocina , Animais , Feminino , Humanos , Ratos , Encéfalo/metabolismo , Neurônios , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , OvinosRESUMO
OBJECTIVES: To evaluate a testing algorithm for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that includes the use of PCR-based targeted single nucleotide polymorphism (SNP) detection assays preceded by a multiplex PCR sensitive to S-Gene Target Failure (SGTF). METHODS: PCR SNP assays targeting SARS-CoV-2 S-gene mutations ΔH69-V70, L452R, E484K, N501Y, H655Y and P681R using melting curve analysis were performed on 567 samples in which SARS-CoV-2 viral RNA was detected by a multiplex PCR. Viral whole-genome sequencing (WGS) was performed to confirm the presence of SNPs and to identify the Pangolin lineage. Additionally, 1133 SARS-CoV-2 positive samples with SGTF were further assessed by WGS to determine the presence of ΔH69-V70. RESULTS: The N501Y-specific assay (n = 567) had an overall percentage agreement (OPA) of 98.5%. The ΔH69-V70-specific (n = 178) and E484K-specific (n = 401) assays had OPA of 96.6% and 99.7%, respectively. Assessment of H655Y (n = 139) yielded a 100.0% concordance when applied in the proposed algorithm. The L452R-specific (n = 67) and P681R-specific (n = 62) assays had an OPA of 98.2% and 98.1%, respectively. The proposed algorithm identified six variants of concern/interest (VOC/VOI)-Alpha (n = 149), Beta (n = 65), Gamma (n = 86), Delta (n = 49), Eta (n = 6), Kappa (n = 6)-and 205 non-VOC/VOI strains-including the variants under monitoring B.1.214.2 (n = 43) and B.1.1.318 (n = 18) and Epsilon (n = 1). An excellent concordance was observed for the identification of all SARS-CoV-2 lineages evaluated. CONCLUSIONS: We present a flexible testing algorithm for the rapid detection of current and emerging SARS-CoV-2 VOC/VOIs, which can be easily adapted based on the local endemicity of specific variants.
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COVID-19/diagnóstico , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , Algoritmos , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação , Pandemias , Reação em Cadeia da Polimerase , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
OBJECTIVES: Post-COVID-19 symptoms experienced by many survivors have a further devastating effect. This study aimed to analyze the risk factors associated with long COVID-19 in a prospective cohort of hospitalized patients including those requiring intensive care unit (ICU) transfer, taking into account objective measures of COVID-19 severity. METHODS: Hospitalized patients with confirmed COVID-19 were enrolled. A structured follow-up visit was performed 4 months after hospital admission. Multivariable adjusted regression models were used to analyse the association between parameters at the acute phase and persistent symptoms. RESULTS: A follow-up visit was performed in 316 patients including 115 (36.4%) discharged from the ICU. Mean age was 64.1 years, and 201 patients (58.3%) were men. Female sex (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.17-3.22; P =.01), hypertension (OR, 2.01; 95% CI, 1.22-3.31; P <.01), and the number of initial symptoms (NIS) (OR, 1.35; 95% CI, 1.17-1.54; P <.001) were significantly associated with long COVID-19. Number of persistent symptoms was significantly associated with NIS (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.11-1.22; P <.001), female sex (aIRR, 1.56; 95% CI 1.29-1.87; P <.001), hypertension (aIRR, 1.23; 95% CI, 1.02-1.50; P =.03), and length of stay in hospital (aIRR, 1.01; 95% CI, 1.005-1.017; P <.001). CONCLUSION: Our study suggested that female sex, hypertension, and NIS had a significant impact on persistent symptoms in hospitalized patients in contrast to severity of acute COVID-19 infection.
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COVID-19 , Hipertensão , COVID-19/complicações , Feminino , Hospitalização , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58-1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients.