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1.
Am J Psychiatry ; 178(10): 896-902, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34592843

RESUMO

Sleep disturbances and depression are closely linked and share a bidirectional relationship. These interconnections can inform the pathophysiology underlying each condition. Insomnia is an established and modifiable risk factor for depression, the treatment of which offers the critical opportunity to prevent major depressive episodes, a paradigm-shifting model for psychiatry. Identification of occult sleep disorders may also improve outcomes in treatment-resistant depression. Sleep alterations and manipulations may additionally clarify the mechanisms that underlie rapid-acting antidepressant therapies. Both sleep disturbance and depression are heterogeneous processes, and evolving standards in psychiatric research that consider the transdiagnostic components of each are more likely to lead to translational progress at their nexus. Emerging tools to objectively quantify sleep and its disturbances in the home environment offer great potential to advance clinical care and research, but nascent technologies require further advances and validation prior to widespread application at the interface of sleep and depression.


Assuntos
Depressão , Transtornos Intrínsecos do Sono , Depressão/fisiopatologia , Depressão/terapia , Humanos , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/tendências , Psicopatologia/métodos , Sono/fisiologia , Transtornos Intrínsecos do Sono/psicologia , Transtornos Intrínsecos do Sono/terapia
3.
Pan Afr Med J ; 39: 195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603576

RESUMO

Introduction: active ageing is the process of optimizing opportunities for health in order to enhance quality of life and wellbeing. It is influenced by physical activity, social participation and social network, cognitive and continuous learning and socio-economic factors. It involves disease prevention and promotion of healthy behaviours that can reduce the risk and occurrence of non-communicable diseases in middle age and also at old age. The study aimed to determine and compare the active ageing process and its determinants among middle-aged men in rural and urban areas in Nigeria. Methods: this was a comparative cross-sectional study among middle-aged men 40-60 years using mixed methods. A multi-stage sampling technique was used to select 720 respondents. A structured interviewer administered questionnaire and Key informant interviews were used to collect data. Results: respondents in the rural area were a little older compared to the respondents in the urban area with a mean age of 49.6 ± 6.3 years and 48.6 ± 6.2 years respectively. A higher proportion of the respondents in the rural area (83.2%) than the respondents in the urban area (73.8%) practice good active ageing processes in their lives. There was a significant association between education of respondent and the practice of active ageing among respondents in the urban and rural areas. Multivariate logistic regression showed that physical activity (aOR 7.62, 95% CI: 243-23.94, P = 0.001), life-long learning (aOR 51.73, 95% CI: 12.14-220.49, P = 0.000) and community participation (aOR 3.46, 95% CI: 2.51-4.77, P=0.000) are predictors of active ageing. Conclusion: the study showed that respondents in the rural area practice good active ageing compared to the respondents in the urban area and hence engaged more in sufficient active life in their daily activities, reducing the risk of non-communicable diseases.


Assuntos
Envelhecimento Saudável/fisiologia , Qualidade de Vida , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Envelhecimento/fisiologia , Estudos Transversais , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Fatores Socioeconômicos , Inquéritos e Questionários
4.
Pan Afr Med J ; 39: 206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603587

RESUMO

Introduction: type 2 diabetes mellitus has become a global public health crisis. The increment in the cases has contributed significantly to the parallel increase in the prevalence of overweight and obesity. This paper aimed to analyse the relationship between lipid profile, waist circumference and body mass index (BMI) with the glycaemic control of the diabetes patients in Kedah. Methods: a cross-sectional study was conducted, using the Kedah audit samples data extracted from the National Diabetes Registry (NDR) from the year 2014 to 2018. A total of 25,062 registered type 2 diabetes mellitus patients were selected using the inclusion and exclusion criteria from the registry. Only patients with complete data on their HbA1C, lipid profile, waist circumference and BMI were analysed using SPSS version 21. Results: the means for the age, BMI and waist circumference of the samples were 61.5 (±10.85) years, 27.3 (±5.05) kg/m2 and 89.46 (±13.58) cm, respectively. Poor glycaemic control (HbA1c>6.5%) was observed in 72.7% of the patients, with females having poorer glycaemic control. The BMI and waist circumference were found to be significantly associated with glycaemic control (P<0.001). The total cholesterol, triglycerides and low-density lipoproteins values showed positive correlation with glycaemic control (r = 0.178, 0.157, 0.145, p<0.001), while high-density lipoproteins values are negatively correlated (r = -0.019, p<0.001). Conclusion: implementing lifestyle changes such as physical activity and dietary modifications are important in the management of BMI, waist circumference and body lipids, which in turn results in improved glycaemic control.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/metabolismo , Lipídeos/sangue , Idoso , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Estilo de Vida , Malásia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sobrepeso , Sistema de Registros , Circunferência da Cintura/fisiologia
5.
BMC Pregnancy Childbirth ; 21(1): 670, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602060

RESUMO

BACKGROUND: Coronavirus currently cause a lot of pressure on the health system. Accordingly, many changes occurred in the way of providing health care, including pregnancy and childbirth care. To our knowledge, no studies on experiences of maternity care Providers during the COVID-19 Pandemic have been published in Iran. We aimed to discover their experiences on pregnancy and childbirth care during the current COVID-19 pandemic. METHODS: This study was a qualitative research performed with a descriptive phenomenological approach. The used sampling method was purposive sampling by taking the maximum variation possible into account, which continued until data saturation. Accordingly, in-depth and semi-structured interviews were conducted by including 12 participants, as 4 gynecologists, 6 midwives working in the hospitals and private offices, and 2 midwives working in the health centers. Data were analyzed using Colaizzi's seven stage method with MAXQDA10 software. RESULTS: Data analysis led to the extraction of 3 themes, 9 categories, and 25 subcategories. The themes were as follows: "Fear of Disease", "Burnout", and "Lessons Learned from the COVID-19 Pandemic", respectively. CONCLUSIONS: Maternal health care providers experience emotional and psychological stress and work challenges during the current COVID-19 pandemic. Therefore, comprehensive support should be provided for the protection of their physical and mental health statuses. By working as a team, utilizing the capacity of telemedicine to care and follow up mothers, and providing maternity care at home, some emerged challenges to maternal care services can be overcome.


Assuntos
COVID-19/psicologia , Pessoal de Saúde/psicologia , Serviços de Saúde Materna/estatística & dados numéricos , Assistência Perinatal/estatística & dados numéricos , Adulto , Esgotamento Psicológico/psicologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Emoções/fisiologia , Feminino , Ginecologia/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Recém-Nascido , Entrevistas como Assunto , Irã (Geográfico)/epidemiologia , Serviços de Saúde Materna/tendências , Pessoa de Meia-Idade , Tocologia/estatística & dados numéricos , Assistência Perinatal/organização & administração , Transtornos Fóbicos/psicologia , Gravidez , Pesquisa Qualitativa , SARS-CoV-2/genética , Estresse Psicológico/psicologia , Telemedicina/métodos
6.
Front Endocrinol (Lausanne) ; 12: 705214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594302

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health crisis affecting millions of people worldwide. SARS-CoV-2 enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2) after being cleaved by the transmembrane protease serine 2 (TMPRSS2). In addition to the lung, gastrointestinal tract and kidney, ACE2 is also extensively expressed in endocrine tissues, including the pituitary and adrenal glands. Although glucocorticoids could play a central role as immunosuppressants during the cytokine storm, they can have both stimulating and inhibitory effects on immune response, depending on the timing of their administration and their circulating levels. Patients with adrenal insufficiency (AI) or Cushing's syndrome (CS) are therefore vulnerable groups in relation to COVID-19. Additionally, patients with adrenocortical carcinoma (ACC) could also be more vulnerable to COVID-19 due to the immunosuppressive state caused by the cancer itself, by secreted glucocorticoids, and by anticancer treatments. This review comprehensively summarizes the current literature on susceptibility to and outcome of COVID-19 in AI, CS and ACC patients and emphasizes potential pathophysiological mechanisms of susceptibility to COVID-19 as well as the management of these patients in case of SARS-CoV-2. Finally, by performing an in silico analysis, we describe the mRNA expression of ACE2, TMPRSS2 and the genes encoding their co-receptors CTSB, CTSL and FURIN in normal adrenal and adrenocortical tumors (both adenomas and carcinomas).


Assuntos
COVID-19/complicações , COVID-19/virologia , Glucocorticoides/administração & dosagem , Insuficiência Adrenal/complicações , Insuficiência Adrenal/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , COVID-19/genética , COVID-19/imunologia , Síndrome de Cushing/complicações , Síndrome de Cushing/imunologia , Humanos , Neoplasias/complicações , Neoplasias/imunologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
7.
Nat Methods ; 18(10): 1181-1191, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594031

RESUMO

Cytokines are critical for intercellular communication in human health and disease, but the investigation of cytokine signaling activity has remained challenging due to the short half-lives of cytokines and the complexity/redundancy of cytokine functions. To address these challenges, we developed the Cytokine Signaling Analyzer (CytoSig; https://cytosig.ccr.cancer.gov/ ), providing both a database of target genes modulated by cytokines and a predictive model of cytokine signaling cascades from transcriptomic profiles. We collected 20,591 transcriptome profiles for human cytokine, chemokine and growth factor responses. This atlas of transcriptional patterns induced by cytokines enabled the reliable prediction of signaling activities in distinct cell populations in infectious diseases, chronic inflammation and cancer using bulk and single-cell transcriptomic data. CytoSig revealed previously unidentified roles of many cytokines, such as BMP6 as an anti-inflammatory factor, and identified candidate therapeutic targets in human inflammatory diseases, such as CXCL8 for severe coronavirus disease 2019.


Assuntos
COVID-19/imunologia , Citocinas/metabolismo , Bases de Dados de Proteínas , SARS-CoV-2 , COVID-19/metabolismo , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Regulação da Expressão Gênica/fisiologia , Humanos , Transdução de Sinais/fisiologia
8.
Anticancer Res ; 41(10): 4821-4836, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593431

RESUMO

BACKGROUND/AIM: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease. MATERIALS AND METHODS: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples. RESULTS: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells. CONCLUSION: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.


Assuntos
Carcinoma Ductal Pancreático/patologia , Genes Supressores de Tumor/fisiologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Subunidade beta de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Ribonucleosídeo Difosfato Redutase/genética , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de Sobrevida
9.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638545

RESUMO

Even in the face of global vaccination campaigns, there is still an urgent need for effective antivirals against SARS-CoV-2 and its rapidly spreading variants. Several natural compounds show potential as antiviral substances and have the advantages of broad availabilities and large therapeutic windows. Here, we report that lectin from Triticum vulgaris (Wheat Germ Agglutinin) displays antiviral activity against SARS-CoV-2 and its major Variants of Concern (VoC), Alpha and Beta. In Vero B4 cells, WGA potently inhibits SARS-CoV-2 infection with an IC50 of <10 ng/mL. WGA is effective upon preincubation with the virus or when added during infection. Pull-down assays demonstrate direct binding of WGA to SARS-CoV-2, further strengthening the hypothesis that inhibition of viral entry by neutralizing free virions might be the mode of action behind its antiviral effect. Furthermore, WGA exhibits antiviral activity against human coronavirus OC43, but not against other non-coronaviruses causing respiratory tract infections. Finally, WGA inhibits infection of the lung cell line Calu-3 with wild type and VoC viruses with comparable IC50 values. Altogether, our data indicate that topical administration of WGA might be effective for prophylaxis or treatment of SARS-CoV-2 infections.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Aglutininas do Germe de Trigo/farmacologia , Animais , Antivirais/química , COVID-19/virologia , Chlorocebus aethiops , Humanos , SARS-CoV-2/fisiologia , Triticum/química , Células Vero , Replicação Viral/efeitos dos fármacos , Aglutininas do Germe de Trigo/química
10.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639103

RESUMO

Various pathogens, such as Ebola virus, Marburg virus, Nipah virus, Hendra virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, are threatening human health worldwide. The natural hosts of these pathogens are thought to be bats. The rousette bat, a megabat, is thought to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Additionally, the rousette bat showed a transient infection in the experimental inoculation of SARS-CoV-2. In the current study, we established and characterized intestinal organoids from Leschenault's rousette, Rousettus leschenaultii. The established organoids successfully recapitulated the characteristics of intestinal epithelial structure and morphology, and the appropriate supplements necessary for long-term stable culture were identified. The organoid showed susceptibility to Pteropine orthoreovirus (PRV) but not to SARS-CoV-2 in experimental inoculation. This is the first report of the establishment of an expandable organoid culture system of the rousette bat intestinal organoid and its sensitivity to bat-associated viruses, PRV and SARS-CoV-2. This organoid is a useful tool for the elucidation of tolerance mechanisms of the emerging rousette bat-associated viruses such as Ebola and Marburg virus.


Assuntos
COVID-19/virologia , Quirópteros/virologia , Organoides/virologia , Orthoreovirus/fisiologia , Infecções por Reoviridae/virologia , SARS-CoV-2/fisiologia , Animais , COVID-19/veterinária , Técnicas de Cultura de Células , Células Cultivadas , Quirópteros/fisiologia , Humanos , Intestinos/citologia , Intestinos/virologia , Organoides/citologia , Infecções por Reoviridae/veterinária
11.
BMC Cancer ; 21(1): 1076, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34600510

RESUMO

BACKGROUND: Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R). METHODS: Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis. RESULTS: EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration. CONCLUSIONS: EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Eicosapentaenoico/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Receptores de Glucocorticoides/metabolismo , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Crioprotetores/farmacologia , Dexametasona/farmacologia , Dimetil Sulfóxido/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Glucocorticoides/farmacologia , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Sincalida/farmacologia
12.
Arch Insect Biochem Physiol ; 108(3): e21845, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34605064

RESUMO

With the wide cultivation of transgenic plants throughout the world and the rising risk of resistance to Bacillus thuringiensis crystal (Cry) toxins, it is essential to design an adaptive resistance management strategy for continued use. Neuropeptide F (NPF) of insects has proven to be valuable for the production of novel-type transgenic plants via its important role in the control of feeding behavior. In this study, the gene encoding NPF was cloned from the diamondback moth, Plutella xylostella, an important agricultural pest. Real-time quantitative reverse transcription-polymerase chain reaction and in situ hybridization showed a relatively high expression of P. xylostella-npf (P. x-npf) in endocrine cells of the midgut of fourth instar larvae, and it was found to participate in P. xylostella feeding behavior and Cry1Ac-induced feeding inhibition. Prokaryotic expression and purification provided structure unfolded P. x-npf from inclusion bodies for diet surface overlay bioassays and the results demonstrated a significant synergistic effect of P. x-npf on Cry1Ac toxicity by increasing intake of noxious food which contains Cry toxins, especially quick death at an early stage of feeding. Our findings provided a potential new way to efficiently control pests by increasing intake of lower dose Cry toxins and a novel hint for the complex Cry toxin mechanism.


Assuntos
Toxinas de Bacillus thuringiensis , Endotoxinas , Proteínas Hemolisinas , Mariposas , Neuropeptídeos , Animais , Toxinas de Bacillus thuringiensis/farmacologia , Endotoxinas/farmacologia , Comportamento Alimentar/fisiologia , Expressão Gênica , Genes de Insetos , Proteínas Hemolisinas/farmacologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/farmacologia , Mariposas/efeitos dos fármacos , Mariposas/genética , Mariposas/metabolismo , Mariposas/fisiologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Neuropeptídeos/farmacologia , Controle de Pragas/métodos
13.
Afr J Prim Health Care Fam Med ; 13(1): e1-e3, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34636616

RESUMO

A group of Vanguard Community Health Centre doctors embarked on a Health System's Improvement (HSI) project with the aim of reducing harm to renal function in patients who were either commenced on or switched to a dolutegravir (DTG)-based antiretroviral therapy (ART) regimen since 2019, when the usual monitoring and evaluation of ART-regimen switches were disrupted by the coronavirus disease 2019 (COVID-19) pandemic. This intended harm-reduction exercise, involving a reflective process that was facilitated by the family physician, led to the development of a Vanguard Renal Protection Surveillance tool, which is now used at Vanguard to detect and prevent renal decline.


Assuntos
COVID-19 , Infecções por HIV , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Rim/fisiologia , Oxazinas , Médicos de Família , Piperazinas , Piridonas , SARS-CoV-2
14.
Nat Commun ; 12(1): 5846, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615868

RESUMO

Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.


Assuntos
Oxigênio/química , Animais , Biomimética , Encapsulamento de Células , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Células Cultivadas , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Hidrogéis/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley
15.
Nat Commun ; 12(1): 5841, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615883

RESUMO

Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-ß strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Linfócitos/metabolismo , Subfamília D de Receptores Semelhantes a Lectina de Células NK/metabolismo , Perforina/metabolismo , Antígenos de Diferenciação de Linfócitos T/genética , Células Cultivadas , Doença de Crohn/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Imunidade Inata/genética , Imunidade Inata/fisiologia , Inflamação/imunologia , Inflamação/metabolismo , Linfócitos/imunologia , Perforina/genética , Reação em Cadeia da Polimerase em Tempo Real
16.
Front Immunol ; 12: 752612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616409

RESUMO

Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity. Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics. Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients. Results: The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10-CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1ß, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions. Conclusion: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.


Assuntos
COVID-19/complicações , Neutrófilos/imunologia , Receptores Depuradores Classe E/genética , Trombose/etiologia , Adulto , Idoso , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Estado Terminal , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-3/genética , Subunidade alfa de Receptor de Interleucina-3/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2/fisiologia , Receptores Depuradores Classe E/imunologia , Trombose/genética , Trombose/imunologia
17.
Medicine (Baltimore) ; 100(40): e27500, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622884

RESUMO

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has affected various aspects, including socioeconomic status and health. This retrospective study aimed to investigate the influence of the COVID-19 pandemic on oral health based on the number of teeth that contribute to mastication, and the nutritional status of elderly patients with digestive cancers.The authors defined the before and during COVID-19 periods in this study as January 2019 to December 2019 and January 2020 to December 2020, respectively. Patients with digestive cancer who underwent general, laboratory, and orthopantomograph examinations for preoperative oral health assessment before general anesthesia participated in this study. The authors investigated the following general characteristics: (1) sex, (2) age, and (3) the organ affected by disease and scheduled for surgery under general anesthesia. The authors collected information about (4) the number of teeth that could contribute to mastication as a clinical oral health parameter. The parameters: (5) body mass index, (6) serum total protein levels, and (7) serum albumin levels were used to indicate the nutritional status.A total of 233 elderly patients with digestive cancer participated in this study. There was no significant difference between the age of the patients with digestive cancer. There was also no significant difference in the number of teeth that could contribute to mastication. Additionally, there was no significant difference in nutritional status as indicated by the body mass index, serum total protein levels, and serum albumin levels.This study showed that the COVID-19 pandemic during 2020 did not have a significant influence on the oral health and nutritional status of elderly patients with digestive cancer. However, the influence of COVID-19 on community oral health may become apparent in the future. Thus, dental professionals should continue further research regarding the effects of COVID-19 on oral health.


Assuntos
COVID-19/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , Estado Nutricional , Saúde Bucal/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteínas Sanguíneas , Índice de Massa Corporal , Feminino , Nível de Saúde , Humanos , Japão/epidemiologia , Masculino , Mastigação/fisiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Albumina Sérica , Fatores Sexuais , Fatores Socioeconômicos , Perda de Dente/epidemiologia
18.
Nat Commun ; 12(1): 5827, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625553

RESUMO

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes.


Assuntos
Meiose/fisiologia , Animais , Pareamento Cromossômico/genética , Pareamento Cromossômico/fisiologia , Citometria de Fluxo , Recombinação Homóloga/genética , Recombinação Homóloga/fisiologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Meiose/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA-Seq , Espermatócitos/metabolismo
19.
Tohoku J Exp Med ; 255(2): 127-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34645738

RESUMO

Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.


Assuntos
COVID-19/complicações , Hospitalização , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Resultado do Tratamento , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/virologia
20.
Medicine (Baltimore) ; 100(39): e27383, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596159

RESUMO

ABSTRACT: The aim of this study was to develop an age and soccer-specific regression equation to estimate the peak power of children aged 12-14 from the height of their vertical jumps using a large sample (n = 188). This study included 188 male soccer players (age, 12.6 ±â€Š0.55; height, 153.31 ±â€Š8.38 cm; and body weight, 43.65 ±â€Š7.58 kg). Their actual peak power values obtained from vertical jumps were recorded using a force platform. The body weights of the participants were measured using Tanita. A regression model was developed using body weight and vertical jump values. All data were analyzed with the IBM SPSS (version 21) statistical analysis program. A multiple linear regression model was used to generate the best estimation of peak power. In this regression model, Power = -1714,116 + [(47.788 ∗ body weight (kg)] + [(58,976 ∗ Countermovement jump height (cm)]. Actual peak power is highly predictable for 12-14-year-old football players. In line with the new model, the actual peak power values obtained in this study were close to the estimated peak power values obtained with the Tufano formula. This may be because of the larger sample size and the same branch used for both equation models.


Assuntos
Força Muscular/fisiologia , Futebol/fisiologia , Adolescente , Peso Corporal , Criança , Estudos Transversais , Exercício Físico/fisiologia , Humanos , Masculino
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