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2.
Cell Mol Life Sci ; 79(1): 64, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013841

RESUMO

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5 binds to α7nAChRs and plays a role in nicotine-induced α7nAChRs upregulation and surface expression. We find that chronic exposure to 1 µM nicotine upregulated α7, ß2-contained nAChRs and PDLIM5 in cultured hippocampal neurons, and the upregulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, in primary hippocampal neurons, α7nAChRs and ß2nAChRs display distinct patterns of expression, with α7nAChRs colocalized more with PDLIM5. Furthermore, PDLIM5 interacts with α7nAChRs, but not ß2nAChRs in native brain neurons. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs. In primary hippocampal neurons, using shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs-mediated currents. Proteomics analysis and isothermal titration calorimetry (ITC) results show that PDLIM5 interacts with α7nAChRs through the PDZ domain, and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in the regulation of α7nAChRs, which may be relevant to plastic changes in the nervous system.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hipocampo/metabolismo , Proteínas com Domínio LIM/metabolismo , Nicotina/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Comportamento Aditivo/fisiopatologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Células HEK293 , Hipocampo/citologia , Humanos , Proteínas com Domínio LIM/genética , Neurônios/metabolismo , Domínios Proteicos/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Fumar , Regulação para Cima , Receptor Nicotínico de Acetilcolina alfa7/biossíntese
5.
Cell Mol Life Sci ; 79(1): 35, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989866

RESUMO

Multiple representatives of eulipotyphlan mammals such as shrews have oral venom systems. Venom facilitates shrews to hunt and/or hoard preys. However, little is known about their venom composition, and especially the mechanism to hoard prey in comatose states for meeting their extremely high metabolic rates. A toxin (BQTX) was identified from venomous submaxillary glands of the shrew Blarinella quadraticauda. BQTX is specifically distributed and highly concentrated (~ 1% total protein) in the organs. BQTX shares structural and functional similarities to toxins from snakes, wasps and snails, suggesting an evolutional relevancy of venoms from mammalians and non-mammalians. By potentiating thrombin and factor-XIIa and inhibiting plasmin, BQTX induces acute hypertension, blood coagulation and hypokinesia. It also shows strong analgesic function by inhibiting elastase. Notably, the toxin keeps high plasma stability with a 16-h half-life in-vivo, which likely extends intoxication to paralyze or immobilize prey hoarded fresh for later consumption and maximize foraging profit.


Assuntos
Analgesia/métodos , Hipocinesia/fisiopatologia , Musaranhos/metabolismo , Toxinas Biológicas/metabolismo , Peçonhas/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Pressão Sanguínea/efeitos dos fármacos , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Humanos , Macaca mulatta , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dor/induzido quimicamente , Dor/fisiopatologia , Dor/prevenção & controle , Homologia de Sequência de Aminoácidos , Musaranhos/genética , Trombina/antagonistas & inibidores , Trombina/metabolismo , Toxinas Biológicas/administração & dosagem , Toxinas Biológicas/genética , Peçonhas/genética
6.
Respir Res ; 23(1): 7, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022054

RESUMO

BACKGROUND: The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP. METHODS: Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model. RESULTS: 367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant). CONCLUSIONS: The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients' anthropometric characteristics.


Assuntos
COVID-19/terapia , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapia , Idoso , Antropometria , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Capacidade Residual Funcional , Interações Hospedeiro-Patógeno , Humanos , Pulmão/fisiopatologia , Pulmão/virologia , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Resultado do Tratamento
7.
Am J Phys Med Rehabil ; 101(2): 164-169, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35026778

RESUMO

ABSTRACT: A growing number of studies have documented a wide variety of neurological manifestations associated with the novel SARS-CoV-2 (COVID-19). Of the available literature, cranial neuropathies and central nervous system disorders, such as encephalopathy and ischemic strokes, remain the predominant discussion. Limited investigations exist examining peripheral neuropathies of those with COVID-19. This case series discusses eight patients who tested positive for COVID-19 and presented with localized weakness after a prolonged course of mechanical ventilation (>21 days). We retrospectively reviewed all patients' charts who received electrodiagnostic evaluation between March and November 2020 in the outpatient clinic or in the acute care hospital at the JFK Medical Center/JFK Johnson Rehabilitation Institute and Saint Peter's University Hospital of New Jersey. A total of eight COVID-19-positive patients were identified to have a clinical presentation of localized weakness after a prolonged course of mechanical ventilation. All patients were subsequently found to have a focal peripheral neuropathy of varying severity that was confirmed by electrodiagnostic testing. Patient demographics, clinical, and electrodiagnostic findings were documented. The findings of local weakness and focal peripheral neuropathies after diagnosis of COVID-19 raise significant questions regarding underlying pathophysiology and overall prognosis associated with COVID-19.


Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso Periférico/virologia , SARS-CoV-2 , Adulto , Idoso , COVID-19/fisiopatologia , Eletrodiagnóstico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Respiração Artificial/efeitos adversos , Estudos Retrospectivos
8.
JAMA Netw Open ; 5(1): e2143781, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-35029662

RESUMO

Importance: Myopia progression has been found to be worsening during the COVID-19 pandemic. It is important to control the rapid myopia progression in this period. Objective: To analyze the association of COVID-19-related lockdown measures with myopia progression in schoolchildren and to compare the performance of defocus incorporated multiple segments (DIMS) lens with that of single vision lens (SVL) treatment in reducing myopia progression. Design, Setting, and Participants: This cohort study involved an exploratory, prespecified, comparison of 2 independent longitudinal studies performed at the same institute beginning in 2019. Data from Hong Kong schoolchildren (aged 7-13 years) were gathered and analyzed. Data analysis was performed from June to July 2021. Exposure: Schoolchildren in study 1 wore a DIMS lens for 18 months, and those in study 2 wore a SVL for 24 months. Main Outcomes and Measures: Cycloplegic spherical equivalent refraction and axial length were measured. Studies 1 and 2 started before the start of lockdown measures and continued throughout the lockdown. In both studies, periods of fewer and more COVID-19-related lockdown measures were identified. Because COVID-19 lockdown caused deviations from the visit schedule, myopia progression was normalized to 12-month change, which were compared between DIMS and SVL groups, also during the periods with less and more lockdown time. Results: There were 115 participants (58 girls [50.4%]; mean [SD] age, 10.3 [1.5] years) in the DIMS group; their mean (SD) baseline refraction was -4.02 (1.46) D. There were 56 participants (29 girls [51.8%]; mean [SD] age, 10.8 [1.5] years) in the SVL group; their mean (SD) baseline refraction was -2.99 (1.06) D. After controlling for the covariates, DIMS treatment was significantly associated with 34% less axial elongation (0.19 mm [95% CI, 0.16 to 0.22 mm] vs 0.30 mm [95% CI, 0.25 to 0.35 mm]; P < .001) and 46% less myopic progression after 12 months (-0.31 D [95% CI, -0.39 to -0.23 D] vs -0.57 D [95% CI, -0.69 to -0.45 D]; P = .001) compared with SVL treatment. In both the DIMS and SVL groups, more lockdown time was associated with significantly more spherical equivalent refraction (-0.54 D [95% CI, -0.64 to 0.44 D] vs -0.34 D [95% CI, -0.44 to -0.25 D]; P = .01) and axial length (0.29 mm [95% CI, 0.25 to 0.32 mm] vs 0.20 mm [95% CI, 0.16 to 0.24 mm]; P = .001) compared with less lockdown time. No significant interaction between treatment type and lockdown time was observed. Conclusions and Relevance: In this exploratory analysis, myopia progressed more rapidly in schoolchildren during the period when there were more COVID-19-related lockdown measures. However, optical treatment with DIMS was significantly associated with slower myopia progression compared with SVL treatment during the lockdown period.


Assuntos
Óculos , Miopia/terapia , COVID-19/epidemiologia , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Miopia/fisiopatologia , Pandemias , Quarentena , Refração Ocular , SARS-CoV-2 , Isolamento Social
9.
Medicine (Baltimore) ; 101(1): e27559, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029870

RESUMO

ABSTRACT: Most postoperative patients with herniated lumbar disc complained of lower leg radiating pain (LRP), referred buttock pain (RBP), and low back pain (LBP). When discectomy is performed, improvement in LRP is observed due to spinal nerve irritation. However, long-term LBP due to degenerative changes in the disc may occur postoperatively. In addition, limited research has been reported on the short-term (within 1 year) improvement in LBP after discectomy. This study aimed to evaluate the effectiveness of discectomy in reducing LBP within 1 year postoperatively.Among the 183 patients who underwent discectomy performed by a single surgeon from January 2010 to December 2016, 106 who met the inclusion and exclusion criteria were enrolled. In the 106 patients who underwent lumbar discectomy, 3 types of spine-related pain were pre-operatively assessed and 3, 6, and 12 months postoperatively. Functional outcomes were evaluated, and quality of life was assessed 12 months postoperatively by using the Short-Form 36 questionnaire, which was subdivided into mental and physical components.LBP showed both statistical and clinical improvement within the first 3 months postoperatively, but the improvement was not observed until 12 months postoperatively. RBP and LRP showed both statistical and clinical improvement within the first 3 months and further consistently showed statistical improvement. LBP improved clinically only until 3 months postoperatively regardless of the type of herniation.LBP showed improvement within the first 3 months postoperatively and plateaued afterward, and RBP and radiculopathy showed consistent improvement until 12 months postoperatively. This may explain why patients from 12-month follow-up showed improvement in RBP and radiculopathy but not LBP.


Assuntos
Discotomia/efeitos adversos , Discotomia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Disco Intervertebral/cirurgia , Dor Lombar , Radiculopatia , Adulto , Feminino , Humanos , Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/psicologia , Dor Lombar/etiologia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Qualidade de Vida , Radiculopatia/etiologia , Radiculopatia/cirurgia , Resultado do Tratamento
10.
Cell Mol Life Sci ; 79(2): 74, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038030

RESUMO

Friedreich Ataxia (FA) is a rare neuro-cardiodegenerative disease caused by mutations in the frataxin (FXN) gene. The most prevalent mutation is a GAA expansion in the first intron of the gene causing decreased frataxin expression. Some patients present the GAA expansion in one allele and a missense mutation in the other allele. One of these mutations, FXNI154F, was reported to result in decreased content of mature frataxin and increased presence of an insoluble intermediate proteoform in cellular models. By introducing this mutation into the murine Fxn gene (I151F, equivalent to human I154F) we have now analyzed the consequences of this pathological point mutation in vivo. We have observed that FXNI151F homozygous mice present low frataxin levels in all tissues, with no evidence of insoluble proteoforms. Moreover, they display neurological deficits resembling those observed in FA patients. Biochemical analysis of heart, cerebrum and cerebellum have revealed decreased content of components from OXPHOS complexes I and II, decreased aconitase activity, and alterations in antioxidant defenses. These mitochondrial alterations are more marked in the nervous system than in heart, precede the appearance of neurological symptoms, and are similar to those observed in other FA models. We conclude that the primary pathological mechanism underlying the I151F mutation is frataxin deficiency, like in patients carrying GAA expansions. Therefore, patients carrying the I154F mutation would benefit from frataxin replacement therapies. Furthermore, our results also show that the FXNI151F mouse is an excellent tool for analyzing tissue-specific consequences of frataxin deficiency and for testing new therapies.


Assuntos
Ataxia de Friedreich/genética , Proteínas de Ligação ao Ferro/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/genética , Mutação Puntual , Alelos , Animais , Comportamento Animal , Biomarcadores/metabolismo , Códon , Modelos Animais de Doenças , Feminino , Ataxia de Friedreich/fisiopatologia , Células HEK293 , Humanos , Íntrons , Proteínas de Ligação ao Ferro/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Mitocondriais/fisiopatologia , Mutação , Mutação de Sentido Incorreto , Fenótipo , Proteômica , Ganho de Peso
11.
PLoS One ; 17(1): e0262756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35041692

RESUMO

BACKGROUND: Previous models that assess quality-of-Life (QoL) in patients with rheumatic diseases have a strong biomedical focus. We evaluated the impact of COVID-19 related-health care interruption (HCI) on the physical, psychological, social relationships and environment QoL-dimensions, and explored factors associated with QoL when patients were reincorporated to the outpatient clinic, and after six-month follow-up. PATIENTS AND METHODS: Study phase-1 consisted of a COVID-19 survey administered from June 24th-October 31st 2020, to outpatients with rheumatic diseases who had face-to-face consultation at outpatient clinic reopening. Study phase-2 consisted of 3 consecutive assessments of patient´s QoL (WHOQOL-BREF), disease activity/severity (RAPID-3), and psychological comorbidity/trauma (DASS-21 and IES-R) to patients from phase-1 randomly selected. Sociodemographic, disease and treatment-related information, and comorbidities were obtained. Multiple linear regression analysis identified factors associated with the score assigned to each WHOQOL-BREF dimension. RESULTS: Patients included (670 for phase-1 and 276 for phase-2), had primarily SLE and RA (44.2% and 34.1%, respectively), and all the dimensions of their WHOQOL-BREF were affected. There were 145 patients (52.5%) who referred HCI, and they had significantly lower dimensions scores (but the environment dimension score). Psycho-emotional factors (primarily feeling confused, depression and anxiety), sociodemographic factors (age, COVID-19 negative economic impact, years of scholarship, HCI and having a job), and biomedical factors (RAPID-3 score and corticosteroid use) were associated with baseline QoL dimensions scores. Psycho-emotional factors showed the strongest magnitude on dimensions scores. Most consistent predictor of six-month follow-up QoL dimensions scores was each corresponding baseline dimension score, while social determinants (years of scholarship and having a job), emotional factors (feeling bored), and biomedical aspects (RAPID 3) had an additional impact. CONCLUSIONS: HCI impacted the majority of patient´s QoL dimensions. Psycho-emotional, sociodemographic and biomedical factors were consistently associated with QoL dimensions scores, and these consistently predicted the QoL trajectory.


Assuntos
COVID-19/psicologia , Pandemias , Qualidade de Vida , Doenças Reumáticas/psicologia , SARS-CoV-2 , Adulto , COVID-19/epidemiologia , COVID-19/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/fisiopatologia , Doenças Reumáticas/terapia
12.
PLoS One ; 17(1): e0262332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35041712

RESUMO

BACKGROUND: The COVID-19 pandemic lockdowns have affected daily lives of the communities worldwide. This study aims to determine the lifestyle behaviours and their associations with body weight changes among Malaysian adults during the Movement Control Order (MCO) due to COVID-19 pandemic. METHODS: A total of 1319 Malaysian adults participated in this cross-sectional online survey. Information on anthropometric data including body weight and height, and lifestyle behaviours including eating pattern, physical activity, and sleep pattern were self-reported by the respondents. A multivariable generalised linear mixed model was used to assess the associations between lifestyle behaviours and body weight changes with adjustment of confounding factors; namely, age, sex, ethnicity, and body weight status before MCO. RESULTS: During MCO, 41.2% of the respondents perceived that their eating patterns were healthier, but 36.3% reduced their physical activities, and 25.7% had a poorer sleep quality. Further, the proportion of adults who reported having lose weight (32.2%) was almost similar to those who reported having gained weight (30.7%). Lifestyle behaviours including less frequent practice of healthy cooking methods and lunch skipping were associated with weight gain, while less frequent consumption of high fat foods, more frequent physical activity, and good sleep latency were associated with lower risk of weight gain. In contrast, practicing healthy eating concept, skipped lunch, and more frequent physical activity were significantly associated with weight loss. CONCLUSION: Lifestyle behaviours were associated with body weight changes during MCO. While the COVID-19 pandemic lockdown is necessary to prevent further spread of the disease, promoting healthy lifestyle practices during lockdown should be implemented for a healthy weight and better health.


Assuntos
COVID-19 , Exercício Físico , Comportamento Alimentar , Estilo de Vida , Pandemias/prevenção & controle , Quarentena , SARS-CoV-2 , Mídias Sociais , Ganho de Peso , Adulto , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/prevenção & controle , Estudos Transversais , Feminino , Humanos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Autorrelato
13.
BMJ ; 376: e068041, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045969

RESUMO

OBJECTIVE: To assess wrist function, quality of life, and complications in adult patients with a dorsally displaced fracture of the distal radius, treated with either a moulded cast or surgical fixation with K-wires. DESIGN: Multicentre randomised clinical superiority trial, SETTING: 36 hospitals in the UK National Health Service (NHS). PARTICIPANTS: 500 adults aged 16 or over with a dorsally displaced fracture of the distal radius, randomised after manipulation of their fracture (255 to moulded cast; 245 to surgical fixation). INTERVENTIONS: Manipulation and moulded cast was compared with manipulation and surgical fixation with K-wires plus cast. Details of the application of the cast and the insertion of the K-wires were at the discretion of the treating surgeon, according to their normal clinical practice. MAIN OUTCOME MEASURES: The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months (five questions about pain and 10 about function and disability; overall score out of 100 (best score=0 and worst score=100)). Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for surgery due to loss of fracture position in the first six weeks. RESULTS: The mean age of participants was 60 years and 417 (83%) were women; 395 (79%) completed follow-up. No statistically significant difference in the PRWE score was seen at 12 months (cast group (n=200), mean 21.2 (SD 23.1); K-wire group (n=195), mean 20.7 (22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66), P=0.87). No difference was seen at earlier time points. In the cast group, 33 (13%) of participants needed surgical fixation for loss of fracture position in the first six weeks compared with one revision surgery in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10). CONCLUSIONS: Among patients with a dorsally displaced distal radius fracture that needed manipulation, surgical fixation with K-wires did not improve patients' wrist function at 12 months compared with a cast. TRIAL REGISTRATION: ISRCTN registry ISRCTN11980540.


Assuntos
Fios Ortopédicos , Moldes Cirúrgicos/estatística & dados numéricos , Fixação de Fratura/estatística & dados numéricos , Fraturas do Rádio/terapia , Adolescente , Adulto , Feminino , Fixação de Fratura/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas do Rádio/fisiopatologia , Resultado do Tratamento , Reino Unido , Articulação do Punho/fisiopatologia , Articulação do Punho/cirurgia , Adulto Jovem
14.
Cytokine ; 150: 155790, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34991059

RESUMO

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.


Assuntos
COVID-19/imunologia , Citocinas/fisiologia , Hospitalização , Receptores de Citocinas/fisiologia , SARS-CoV-2 , Adulto , Área Sob a Curva , Biomarcadores , Proteína C-Reativa/análise , COVID-19/fisiopatologia , COVID-19/terapia , Quimiocinas/sangue , Quimiocinas/fisiologia , Citocinas/sangue , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Humanos , Interleucina-6/sangue , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Receptores de Quimiocinas/fisiologia , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Bull Exp Biol Med ; 172(3): 364-367, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35001305

RESUMO

The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O2 gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O2 gas mixture relieved manifestations of ventilation insufficiency and increased SpO2 and pneumatization of the terminal parts of the lungs.


Assuntos
COVID-19/complicações , Oxigênio/administração & dosagem , Insuficiência Respiratória/terapia , Terapia Respiratória/métodos , Xenônio/administração & dosagem , Administração por Inalação , Anestésicos Inalatórios/administração & dosagem , COVID-19/etiologia , COVID-19/reabilitação , COVID-19/terapia , Combinação de Medicamentos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Respiração/efeitos dos fármacos , Insuficiência Respiratória/etiologia , Federação Russa , SARS-CoV-2
16.
Int J Mol Sci ; 23(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35008922

RESUMO

The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies' datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Amplificação de Genes , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Mitocondriais/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Proteínas Nucleares/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/fisiopatologia , Prognóstico , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , RNA-Seq
17.
Invest Ophthalmol Vis Sci ; 63(1): 3, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34982147

RESUMO

Purpose: Amblyopia is diagnosed as a reduced acuity in an otherwise healthy eye, which indicates that the deficit is not happening in the eye, but in the brain. One suspected mechanism explaining these deficits is an elevated amount of intrinsic blur in the amblyopic visual system compared to healthy observers. This "internally produced blur" can be estimated by the "equivalent intrinsic blur method", which measures blur discrimination thresholds while systematically increasing the external blur in the physical stimulus. Surprisingly, amblyopes do not exhibit elevated intrinsic blur when measured with an edge stimulus. Given the fundamental ways in which they differ, synthetic stimuli, such as edges, are likely to generate contrasting blur perception compared to natural stimuli, such as pictures. Because our visual system is presumably tuned to process natural stimuli, testing artificial stimuli only could result in performances that are not ecologically valid. Methods: We tested this hypothesis by measuring, for the first time, the perception of blur added to natural images in amblyopia and compared discrimination performance for natural images and synthetic edges in healthy and amblyopic groups. Results: Our results demonstrate that patients with amblyopia exhibit higher levels of intrinsic blur than control subjects when tested on natural images. This difference was not observed when using edges. Conclusions: Our results suggest that intrinsic blur is elevated in the visual system representing vision from the amblyopic eye and that distinct statistics of images can generate different blur perception.


Assuntos
Ambliopia/fisiopatologia , Erros de Refração/fisiopatologia , Percepção Visual/fisiologia , Adulto , Idoso , Esotropia/fisiopatologia , Exotropia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Refração Ocular/fisiologia , Limiar Sensorial/fisiologia , Acuidade Visual/fisiologia , Adulto Jovem
18.
Invest Ophthalmol Vis Sci ; 63(1): 7, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34989761

RESUMO

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy. Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain. Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation. Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.


Assuntos
Analgésicos/administração & dosagem , Modelos Animais de Doenças , Síndromes do Olho Seco/fisiopatologia , Dor Ocular/fisiopatologia , Pregabalina/administração & dosagem , Administração Oftálmica , Animais , Astrócitos/patologia , Canais de Cálcio Tipo L/metabolismo , Doença Crônica , Córnea/inervação , Síndromes do Olho Seco/tratamento farmacológico , Dor Ocular/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Microglia/patologia , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Soluções Oftálmicas , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo/metabolismo , Nervo Trigêmeo/patologia
19.
Invest Ophthalmol Vis Sci ; 63(1): 6, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34989762

RESUMO

Purpose: To assess whether monocular contrast sensitivity and stereoacuity impairments remain when visual acuity is fully recovered in children with refractive amblyopia. Methods: A retrospective review of 487 patients diagnosed with refractive amblyopia whose visual acuity improved to 0.08 logMAR or better in both eyes following optical treatment was conducted. Measurements of monocular contrast sensitivity and stereoacuity had been made when visual acuity normalized. All patients had been treated with refractive correction for approximately 2 years following diagnosis. No other treatments were provided. Monocular contrast sensitivity was measured using the CSV-1000E chart for children 6 years of age or younger and a psychophysical technique called the quick contrast sensitivity function in older children. Stereoacuity was measured using the Random Dot Test that includes monocular cues and the Randot Stereoacuity Test that does not have monocular cues. Results: Statistically significant interocular differences in contrast sensitivity were observed. These differences tended to occur at higher spatial frequencies (12 and 18 cycles per degree). Stereoacuity within the age-specific normal range was achieved by 47.4% of patients for the Random Dot Test and only 23.1% of patients for the Randot Stereoacuity Test. Conclusions: Full recovery of visual acuity following treatment for refractive amblyopia does not equalize interocular contrast sensitivity or restore normal stereopsis. Alternative therapeutic approaches that target contrast sensitivity and/or binocular vision are required.


Assuntos
Ambliopia/terapia , Sensibilidades de Contraste/fisiologia , Percepção de Profundidade/fisiologia , Óculos , Hiperopia/terapia , Miopia/terapia , Ambliopia/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Hiperopia/fisiopatologia , Masculino , Miopia/fisiopatologia , Estudos Retrospectivos , Privação Sensorial , Testes Visuais/métodos , Visão Binocular , Acuidade Visual
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