RESUMO
Due to the complex nature of noncovalent interactions and their long-range effects, analyzing protein conformations using network theory can be enlightening. Protein Structure Networks (PSNs) provide a convenient formalism to study protein structures in relation to essential properties such as key residues for structural stability, allosteric communication, and the effects of modifications of the protein. PSNs can be defined according to very different principles, and the available tools have limitations in input formats, supported models, and version control. Other outstanding problems are related to the definition of network cutoffs and the assessment of the stability of the network properties. The protein science community could benefit from a common framework to carry out these analyses and make them easier to reproduce, reuse, and evaluate. We here provide two open-source software packages, PyInteraph2 and PyInKnife2, to implement and analyze PSNs in a reproducible and documented manner. PyInteraph2 interfaces with multiple formats for protein ensembles and incorporates different network models with the possibility of integrating them into a macronetwork and performing various downstream analyses, including hubs, connected components, and several other centrality measures, and visualizes the networks or further analyzes them thanks to compatibility with Cytoscape.PyInKnife2 that supports the network models implemented in PyInteraph2. It employs a jackknife resampling approach to estimate the convergence of network properties and streamline the selection of distance cutoffs. We foresee that the modular structure of the code and the supported version control system will promote the transition to a community-driven effort, boost reproducibility, and establish common protocols in the PSN field. As developers, we will guarantee the introduction of new functionalities and maintenance, assistance, and training of new contributors.
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Proteínas , Software , Reprodutibilidade dos Testes , Proteínas/química , Conformação ProteicaRESUMO
BACKGROUND: Preoperative intravenous iron administration is a frequently used patient blood management procedure. If the timeframe of intravenous iron administration before surgery is short, (1) the concentration of the intravenous iron compound might still be high in patients' plasma when undergoing surgery and (2) this iron in patients' plasma is at risk to be lost due to blood loss. The aim of the current study was, therefore, to track the iron compound ferric carboxymaltose (FCM) before, during, and after cardiac surgery requiring cardiopulmonary bypass, with an emphasis on intraoperative iron losses in shed blood and potential recovery through autologous cell salvage. METHODS: Concentrations of FCM were analyzed in patients' blood using a hyphenation of liquid chromatography and inductively coupled plasma-mass spectrometry to distinguish between pharmaceutical compound FCM and serum iron. In this prospective, single-center pilot trial, 13 anemic and 10 control patients were included. Anemic patients with hemoglobin levels ≤12/13 g/dL in women and men were treated with 500 milligrams (mg) intravenous FCM 12 to 96 hours before elective on-pump cardiac surgery. Patients' blood samples were collected before surgery and at days 0, 1, 3, and 7 after surgery. One sample each was taken of the cardiopulmonary bypass, the autologous red blood cell concentrate generated by cell salvage, and the cell salvage disposal bag. RESULTS: Patients who had received FCM <48 hours before surgery had higher FCM serum levels (median [Q1-Q3], 52.9 [13.0-91.6]) compared to ≥48 hours (2.1 [0.7-5.1] µg/mL, P = .008). Of 500-mg FCM administered <48 hours, 327.37 (257.96-402.48) mg were incorporated compared to administration ≥48 hours with 493.60 (487.78-496.70) mg. After surgery, patients' plasma FCM concentration in the FCM <48 hours group was decreased (-27.1 [-30 to -5.9] µg/mL). Little FCM was found in the cell salvage disposal bag (<48 hours, 4.2 [3.0-25.8] µg/mL, equivalent to 29.0 [19.0-40.7] mg total; equivalent to 5.8% or 1/17th of the 500 mg FCM initially administered), almost none in the autologous red blood cell concentrate (<48 hours, 0.1 [0.0-0.43] µg/mL). CONCLUSIONS: The data generate the hypotheses that nearly all FCM is incorporated into iron stores with administration ≥48 hours before surgery. When FCM is given <48 hours of surgery, the majority is incorporated into iron stores by the time of surgery, although a small amount may be lost during surgical bleeding with limited recovery by cell salvage.
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Anemia , Procedimentos Cirúrgicos Cardíacos , Masculino , Humanos , Feminino , Ferro , Estudos Prospectivos , Projetos Piloto , Compostos Férricos , Administração Intravenosa , MaltoseRESUMO
PURPOSE: This study aimed to compare the tomographic features of the cornea on elevation maps between obstructive sleep apnea syndrome (OSAS) and keratoconus (KC) patients and to investigate the presence of susceptibility to ectatic corneal diseases in OSAS patients. DESIGN: This is a comparative cross-sectional case-control study. METHODS: This study included 84 eyes of 42 patients diagnosed with severe OSAS using polysomnography (apnea/hypopnea index > 30), 84 eyes of 56 patients diagnosed with keratoconus, and 84 eyes of 42 healthy subjects as control group and evaluated in three groups. Elevation maps of all the groups were performed using Pentacam, and topometric, pachymetric, and deviation indices were recorded. RESULTS: The study included 252 eyes of 130 participants divided in three groups. Comparing all the tomographic keratometric values, a significant difference was found among the three groups. All keratometric values were found to be higher in the OSAS patients group compared to those in the control group. Also topometric indices and Belin-Ambrosio enhanced ectasia display (BAD) were observed to be higher as in subclinical keratoconus and statistically significant when compared to those in the control group. CONCLUSION: The study reveals the tomographic corneal characteristics and topometric and pachymetric indices of patients with severe OSAS at the time of diagnosis; these findings statistically significantly differ from the control group. In addition to the known association of floppy eyelid in OSAS patients, the suspicion of keratoconus should be kept in mind.
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Ceratocone , Apneia Obstrutiva do Sono , Estudos de Casos e Controles , Córnea , Paquimetria Corneana/métodos , Topografia da Córnea/métodos , Estudos Transversais , Humanos , Ceratocone/complicações , Ceratocone/diagnóstico , Curva ROC , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Given its geometric similarity to large-scale production plants and the excellent possibilities for precise process control and monitoring, the classic stirred tank bioreactor (STR) still represents the gold standard for bioprocess development at a laboratory scale. However, compared to microbioreactor technologies, bioreactors often suffer from a low degree of process automation and deriving key performance indicators (KPIs) such as specific rates or yields often requires manual sampling and sample processing. A widely used parallelized STR setup was automated by connecting it to a liquid handling system and controlling it with a custom-made process control system. This allowed for the setup of a flexible modular platform enabling autonomous operation of the bioreactors without any operator present. Multiple unit operations like automated inoculation, sampling, sample processing and analysis, and decision making, for example for automated induction of protein production were implemented to achieve such functionality. The data gained during application studies was used for fitting of bioprocess models to derive relevant KPIs being in good agreement with literature. By combining the capabilities of STRs with the flexibility of liquid handling systems, this platform technology can be applied to a multitude of different bioprocess development pipelines at laboratory scale.
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Automação Laboratorial , Reatores Biológicos , Corynebacterium glutamicum/crescimento & desenvolvimento , Modelos Biológicos , Robótica , LaboratóriosRESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging, fast-spreading, highly mortal and worldwide infectious disease. The pulmonary system was defined as the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mortality concept of this disease presented with more severe and systemic disease. The present study investigated the relationship between the patient characteristics at the initial hospital administration and fatality in COVID-19 patients. METHODS: In this retrospective and comparative cohort study, all the 767 hospitalised COVID-19 patients, treated between 18 March and 15 May 2020 in the Covid Clinics of Gulhane Training and Research Hospital in Ankara, Turkey, were evaluated. RESULTS: The fatality rate was significantly increased in patients with any comorbid disease except asthma. The initial laboratory test results indicated highly significant differences according to the patient's outcome. A multifactor logistic regression analysis was performed to calculate the adjusted odds ratios for predicting patient outcomes. Being older than 60 years increased the death risk with an adjusted OR of 7.2 (95% CI: 2.23-23.51; P = .001). The presence of a cancer and the extended duration of intensive care unit treatment were other significant risk factors for nonsurvival. Azithromycin treatment was determined as significantly reduced the death ratio in these patients (P = .002). CONCLUSION: It was revealed that being older than 60 years, presence of a cancer and extended duration of ICU treatment were the major risk factors for predicting fatality rate in hospitalised COVID-19 patients.
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COVID-19 , Pandemias , Estudos de Coortes , Mortalidade Hospitalar , Hospitalização , Hospitais , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , SARS-CoV-2 , Atenção Terciária à SaúdeRESUMO
AIMS: This study aimed to investigate the clinical and chest computed tomography (CT) features associated with clinical parameters for coronavirus disease (COVID-19) in the capital of Turkey, Ankara. MATERIALS AND METHODS: Epidemiological, clinical features, laboratory findings and radiological characteristics of 1563 hospitalised patients with COVID-19 in Ankara were collected, reviewed and analysed in this study. The risk factors associated with disease severity were investigated. RESULTS: Non-severe (1214; 77.7%) and severe cases (349; 22.3%) were enrolled in the study. Compared with the non-severe group, the severe group were significantly older and had more comorbidities (ie, hypertension, diabetes mellitus, cardiovascular disease and chronic kidney disease). Smoking was more common in the severe group. Severe patients had higher respiratory rates and higher incidences of cough and dyspnoea compared with non-severe patients. Compared with the non-severe patients, the severe patients had increased C-reactive protein (CRP), procalcitonin, neutrophil to lymphocyte ratio (NLR) and CRP/albumin ratio and decreased albumin. The occurrence rates of consolidation, subpleural sparing, crazy-paving pattern, cavity, halo sign, reversed halo sign, air bronchogram, pleural thickening, micronodule, subpleural curvilinear line and multilobar and bilateral involvement in the CT finding of the severe patients were significantly higher than those of the non-severe patients. CONCLUSIONS: Many factors are related to the severity of COVID-19, which can help clinicians judge the severity of the patient and evaluate the prognosis. This cohort study revealed that male sex, age (≥55 years), patients with any comorbidities, especially those with cardiovascular disease, dyspnoea, increased CRP, D-dimer and NLR, and decreased lymphocyte count and CT findings of consolidation and multilobar involvement were predictors of severe COVID-19.
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COVID-19 , Pulmão , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: The lung volume reduction coil treatment is a minimally invasive bronchoscopic treatment option for emphysema patients who suffer from severe hyperinflation. Previous studies have reported successful outcomes in selected cases using coil for bronchoscopic lung volume reduction (BLVR). Our aim is to determine the changes in respiratory function tests, perception of dyspnea and exercise capacities after 12 months in patients treated with endobronchial coil. MATERIALS AND METHODS: The data of patients with severe emphysema and treated with coils between 2014-2017 were evaluated retrospectively. Dynamic and static lung volume capacities at baseline and 12 months, modified Medical Research Council (mMRC) questionnaire and six-minute walk test (6-MWT) results were recorded. RESULT: BLVR was performed in thirty patients (one female, twenty-nine males). Five patients were treated bilaterally and twentyfive unilaterally. One patient died after 7 days and 4 patients died during follow-up. Five patients were lost to follow-up. A total of twenty patients with available data were included in the study. A statistically significant difference was found in mMRC results in pre-treatment and 12-month evaluations. There was no significant difference in FEV1, TLC and RV values at the end of 12 months. There was an increase of 18.9 meters (± 83.5 m) between the baseline and 12 months in 6-MWT. 45% of the patients improved their walking distance over 26 meters which is known as minimal clinically important difference (MCID). CONCLUSIONS: Although no significant changes were observed in pulmonary function tests and lung volumes, the increase in exercise capacity and decreased perception of dyspnea indicate the efficacy of endobronchial coil.
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Broncoscopia/métodos , Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Dispneia/etiologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/complicações , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Although metastasis of extrapulmonary solid organ malignant tumors to the lungs is very common, endobronchial metastases are very rare. The most common extrapulmonary tumors that make endobronchial metastases are breast, kidney and colorectal carcinomas. MATERIALS AND METHODS: In this study, we retrospectively examined the data of eleven renal cell carcinoma patients who underwent endobronchial metastases in an eight-year period. RESULT: Ten of the patients were male and the mean age was 55 ± 1 (41-71) years. The most common symptom was cough (45.5%, n= 5), on the other hand 18.2% (n= 2) of the patients had no complaints. Right bronchial system, left bronchial system and tracheal distribution rates of endobronchial lesions were 45.5% (n= 5), 63.6% (n= 7) and 27.3% (n= 3) respectively. The mean time from diagnosis of primary renal cell carcinoma to endobronchial metastases was 47.5 ± 32 (5.2-100.5) months. A total of twenty two interventional procedures were performed. All except one patient underwent endobronchial treatment. Argon plasma coagulation was most commonly used as the endobronchial metastases option (n= 10, 100%). The mechanical resection (n= 6, 60%), laser (n= 5, 50%), cryoextraction (n= 5, 50%) and cryotherapy (n= 4, 40%) methods were used other than argon plasma coagulation. The mean survival time was 19.4 ± 15.7 (3.2-40.5) months after endobronchial metastases and 54.0 ± 40.4 (8.7-107.6) months after renal cell carcinoma diagnosis. CONCLUSIONS: Extrathoracic malignancy that most metastasis to the airways is renal cell carcinoma. Endobronchial treatment procedures for endobronchial metastasis of renal cell carcinoma can be performed with low complication rates.
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Neoplasias Brônquicas/secundário , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Adulto , Idoso , Neoplasias Brônquicas/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pneumologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Tracheobronchial stents (TBS) are the principal modalities in the management of central airway obstruction with intrinsic tracheobronchial pathology and extrinsic airway compression. The aim of the study is to assess the indications, surveillance management, complications, and long-term outcomes of the TBS managed by rigid bronchoscopy (RB) in our 10-year experience. MATERIALS AND METHODS: The files of all patients who underwent stenting in two centers from November 2008 to September 2018 were reviewed for background data, type of disease, and indication for the placement of stents, symptoms, treatment, complications and outcome. RESULT: 305 patients were stented with 342 TBS. TBS were placed in both malignant (n= 223) and benign airway diseases (n= 82). The median length of stent stay was 88 (34-280) days in patients with malignancies and 775 (228-2085) days in benign diseases. There was no stent-related mortality. Mucostasis (19%) and granulation tissue formation (17%) were the most common stentrelated complications. Benign nature of the disease, tumors metastatic to tracheobronchial tree, lenght of stent stay, and shape of stent were associated with the development of complications. CONCLUSIONS: TBS offer a safe and effective therapy for patients with both benign and malign tracheobronchial pathologies.
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Obstrução das Vias Respiratórias/etiologia , Broncoscopia/efeitos adversos , Stents/efeitos adversos , Adulto , Idoso , Broncopatias/etiologia , Broncoscopia/métodos , Constrição Patológica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents/estatística & dados numéricos , Resultado do TratamentoRESUMO
Background/aim: The increasing number of lung diseases and particularly pulmonary malignancies has intensified the need for diverse interventions in the field of interventional pulmonology. In recent years we have seen many new developments and expanding applications in the field of interventional pulmonology. This has resulted in an increased number and variety of performed procedures and differing approaches. The purpose of the present study is to provide information on patient characteristics, range of interventions, complication rates, and the evolving approach of an experienced center for interventional pulmonology. Materials and methods: We retrospectively examined the records of 1307 patients who underwent a total of 2029 interventional procedures in our interventional pulmonology department between January 2008 and December 2017. Results: About half of the interventional procedures (47.2%) were performed on patients with airway stenosis due to malignant disease. Among patients with benign airway stenosis, the most frequent reason for intervention was postintubation tracheal stenosis. The number of patients who developed complications was 81 (6.2%), and the most common complication was hemorrhage (n = 31, 2.99%); 94.9% (n = 1240) of interventional procedures were performed under general anesthesia, without complications or deaths associated with anesthesia. Only one death (0.076%) occurred in the perioperative period. A total of 18 patients (1.38%) died in the 30-day perioperative and postoperative period. None of the patients with benign airway stenosis died. Conclusion: Interventional bronchoscopy is an invasive but considerably safe and efficient procedure for selected cases and effective treatment modality for airway obstructions, massive hemoptysis, and foreign body aspiration. Interventional pulmonology is a field of pulmonary medicine that needs effort to progress and provide an opportunity to witness relevant developments, and increase the number of competent physicians and centers.
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Pneumopatias/terapia , Neoplasias Pulmonares/cirurgia , Procedimentos Cirúrgicos Pulmonares/métodos , Procedimentos Cirúrgicos Pulmonares/tendências , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosAssuntos
Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 6/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Citocinas/metabolismo , Hepcidinas/metabolismo , Proteínas Musculares/metabolismo , Animais , Células Cultivadas , Células HEK293 , Hepatócitos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Multimerização ProteicaRESUMO
Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is a well-established technique for assessing lesions near the central airway. While EBUS is typically used via the airway, the esophageal approach known as endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA) has gained popularity for evaluating previously inaccessible lesions. This study aimed to assess the safety and diagnostic contribution of EUS-B-FNA in elderly patients. This retrospective study included elderly patients (≥65 years) who underwent EUS-B-FNA with concurrent convex probe-EBUS (C-EBUS) between June 2019 and December 2022. Inclusion criteria were age >64, having chest computed tomography (CT) or FDG-PET/CT, and undergoing C-EBUS, with the exclusion of patients with prior malignancy diagnoses and undergoing EBUS-TBNA. Among 68 patients who underwent combined EBUS and EUS-B-FNA, 31 met the inclusion criteria. The mean age was 71.7 years and 74.2% were male. All EUS-B-FNA material provided adequate material for histopathological analysis. Among patients, 67.7% received a malignancy diagnosis. Samples were obtained from mass lesions (58.1%) and lymph nodes (41.9%), primarily from the subcarinal (station 7) and left paratracheal (station 4L) regions. The mean number of needle passes was 2.83, with an average procedure duration of 9.4 min. No significant complications occurred. EUS-B-FNA is a safe and effective diagnostic method in elderly patients, offering an alternative when the transbronchial approach is not feasible. This underscores the importance of bronchoscopists' training in the transesophageal approach via EBUS scope.
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Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Idoso , Masculino , Feminino , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Broncoscopia/métodos , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagemRESUMO
Introduction: This study explores the impact of vascular diameters on mortality risk in Coronavirus disease-2019 (COVID-19) patients. COVID-19, caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and is associated with thrombosis. Materials and Methods: In this study, we retrospectively examined the data of patients who were hospitalized and treated in our hospital between September 1, 2020, and November 30, 2020, and whose COVID-19 diagnosis was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The diameters of the ascending aorta, main pulmonary artery, and right and left pulmonary arteries were measured from the chest computed tomography (CT) scans taken at the time of admission. The aim of the study was to investigate the impact of vascular diameters on the course of the disease. Result: Of 1.705 patients, 840 were eligible for the study. We concluded that 36 of the patients (4.3%) died, and among the non-survivors patients, 12 (33.3%) were females, and 24 (66.7%) were males. Hospitalization duration was 7.1 ± 3.1 vs. 6.1 ± 2 days (p= 0.004) in surviving and non-surviving patients respectively. On the other hand, we found the mean diameters of the right pulmonary artery in the chest CT of patients to be 2.17 ± 0.35 vs. 2.44 ± 0.29 cm in survivors and non-survivors, respectively (p< 0.001). In addition, we found the mean diameters of the left pulmonary artery 2.12 ± 0.32 vs. 2.34 ± 0.28 cm in survivors and non-survivors, respectively (p< 0.001). Mean diameters of the ascending aorta were 3.53 ± 0.46 vs. 3.72 ± 0.34 cm in survivors and non-survivors, respectively (p= 0.017). Conclusions: The study underscores the potential prognostic value of vascular diameters, especially in the ascending aorta and main pulmonary artery, as indicators of mortality risk in COVID-19 patients. The association between vascular dilation and severity of COVID-19, coupled with elevated D-dimer levels, suggests a link between thrombosis and vascular involvement.
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Aorta , COVID-19 , Artéria Pulmonar , Humanos , COVID-19/mortalidade , COVID-19/complicações , Masculino , Feminino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Aorta/diagnóstico por imagem , Idoso , SARS-CoV-2 , Tempo de Internação/estatística & dados numéricos , Tomografia Computadorizada por Raios X , Hospitalização/estatística & dados numéricos , Turquia/epidemiologia , AdultoRESUMO
INTRODUCTION: Interstitial lung disease is one of the most critical manifestations of connective tissue diseases that may cause morbidity and mortality. This study aimed to evaluate the clinical and demographic characteristics and treatment of the patients with connective tissue disease-related interstitial lung disease. METHOD: This retrospective observational study included patients from the Gulhane Rheumatology Interstitial Lung Disease cohort between October 2016 and June 2023. The patients were assessed retrospectively. RESULTS: A total of 173 patients were included in the study with a mean age of 63.4 ± 11.9 years. The frequencies of CTD were 34.1% Sjogren's syndrome, 30.1% rheumatoid arthritis, 25.4% systemic sclerosis, 5.8% undifferentiated connective tissue disease, 2.9% idiopathic inflammatory myositis, 1.2% mixt connective tissue disease, and 0.6% systemic lupus erythematosus in decreasing frequencies. Nonspecific interstitial pneumonia, which was the most common interstitial lung disease pattern in 103 (59.5%) patients, was most frequent among patients with SS and SSc (p < 0.001 vs. p < 0.001). Usual interstitial pneumonia was most frequent among patients with RA (p < 0.001). All patients received immunosuppressive treatment, most commonly azathioprine. 57.2% were using immunosuppressives for ILD. Six patients had mortality, and infections were the leading cause. CONCLUSIONS: As a critical manifestation of connective tissue diseases, immunosuppressive treatment is indispensable in the management of interstitial lung diseases especially those at an increased risk for progression. The treatment approaches should be assessed in a patient-based way. The patients under immunosuppressive treatment should be cautiously followed for infections. Key Points ⢠Interstitial lung disease is a noteworthy manifestation of connective tissue diseases. ⢠The clinical findings, treatment requirements, and progression vary according to the severity of the disease. ⢠Immunosuppressive treatment may be essential in patients with worsening symptoms, impaired pulmonary function tests, and radiological findings.
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Doenças do Tecido Conjuntivo , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças do Tecido Conjuntivo/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Imunossupressores/uso terapêuticoRESUMO
ABSTRACT: Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.
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Proteínas Ligadas por GPI , Proteína da Hemocromatose , Hepcidinas , Animais , Camundongos , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/genética , Hepcidinas/metabolismo , Hepcidinas/genética , Proteína da Hemocromatose/metabolismo , Proteína da Hemocromatose/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Fígado/metabolismo , Ferro/metabolismo , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/genética , Receptores de Ativinas Tipo I/metabolismo , Receptores de Ativinas Tipo I/genética , Receptores de Activinas Tipo IIRESUMO
Over the past two decades, endobronchial ultrasound (EBUS) has become a crucial tool for diagnosing pulmonary diseases. The most common indication of EBUS usage is the diagnosis and staging of lung cancer. Additionally, there have been significant improvements in the application of convex probe EBUS in line with the increase in experience and knowledge about EBUS and the developments in medicine and technology. To enhance diagnostic accuracy and acquire larger tissue samples, techniques such as cryo-biopsy guided by endobronchial ultrasound (EBUS) and intranodal forceps biopsy have been developed. Additionally, elastography functionality has been integrated into the EBUS application to improve the assessment of targeted lesions. Moreover, its utilization for evaluating and sampling pulmonary vascular structures has expanded. It has also found applications in guiding intratumoral therapy, positioning fiducial markers, and facilitating the drainage of pleural or pericardial effusions. This review aims to provide an overview of the extended applications of convex probe EBUS beyond its conventional uses.
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Neoplasias Pulmonares , Derrame Pericárdico , Humanos , Biópsia , Neoplasias Pulmonares/diagnóstico por imagemRESUMO
In this study, polyvinyl alcohol (PVA) and polyacrylic acid (PAA) nanofibers loaded with boron nitride nanoparticles (mBN) were fabricated by using electrospinning and crosslinked by heat treatment. The physical, chemical, and mechanical properties, hydrophilic behavior, and degradability of composite nanofibers were evaluated. The mechanical properties such as elastic modulus, elongation percentage at the break, and mechanical strength of PVA/PAA nanofibers improved with mBN loading. The thermal conductivity of composite nanofibers reached 0.12 W/m·K at mBN content of 1.0 wt% due to the continuous heat conduction pathways of mBN. In the meantime, while there was no cytotoxicity recorded for both L929 and HUVEC cell lines for all composite nanofibers, the antimicrobial efficiency improved with the incorporation of mBN compared with PVA/PAA and recorded as 68.8% and 75.1% for Escherichia coli and Staphylococcus aureus, respectively. On this basis, the present work proposes a promising biomaterial for biomedical applications such as dual drug delivery, particularly including both hydrophobic and hydrophilic drugs or wound dressing.
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Nanofibras , Álcool de Polivinil , Álcool de Polivinil/química , Nanofibras/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
OBJECTIVE: Identification of unmet psychiatric needs, protective and risk factors for suicide are crucial for people with traumatic spinal cord injury (SCI). In this study, we aimed to explore depression, post-traumatic stress disorder (PTSD) status (non-PTSD, partial-PTSD, full-PTSD), resilience, suicidal ideation (SI) and to examine predictors and clinical correlates of current SI in traumatic SCI. METHOD: Sixty-three individuals with traumatic SCI who were at least 3 months post-injury were included in the study. The participants were evaluated in terms of PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5), depression, SI, and resilience using the PCL-5, the Patient Health Questionnaire-9, the Brief Resilience Scale, and sociodemographic measures. RESULTS: 33% of our sample (n = 21) had SI over the past two weeks. 71.4% of the patients with SI (n = 15) had depression. A total of 52.4% of the patients with SI (n = 11) were diagnosed with full PTSD. Resilience was found to be significantly lower in individuals with depression and individuals with SI. While depression predicted SI in traumatic SCI, resilience stands as a protective factor against SI. CONCLUSION: SI is quite common in individuals with traumatic SCI and is accompanied by substantial psychiatric comorbidities such as depression and PTSD. Along with depression and PTSD, resilience - which has protective and predictive values and is inversely associated with SI - constitutes a significant psychotherapeutic intervention and screening area.
Assuntos
Traumatismos da Medula Espinal , Transtornos de Estresse Pós-Traumáticos , Humanos , Ideação Suicida , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Depressão/etiologia , Depressão/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , ComorbidadeRESUMO
AIM: This study aimed to investigate the effectiveness of disposable continuous positive airway pressure (DCPAP) system in decreasing the partial pressure of carbon dioxide (PaCO2) levels in patients with acute hypercapnic respiratory failure (AHRF). MATERIAL AND METHODS: This retrospective observational study included patients treated in the emergency department (ED) with respiratory distress and PaCO2 > 45 mmHg. Patients were divided into two groups (DCPAP and non-DCPAP), depending on the treatment received to treat AHRF. The difference between the baseline PaCO2 levels in the first blood gas obtained from patients at the time of admission and the follow-up blood gas after treatment. Then, the calculated PaCO2 decrease was divided by the time elapsed to obtain the rate of decrease in PaCO2 levels in mmHg/min. The statistical analyses were performed using SPSS version 18.0 software. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 61 patients were included in the study, 31 patients in the DCPAP group and 30 patients in the non-DCPAP group. The mean age of the patients was 74.03 ± 10.04, and the male/female was 23/38. The study demonstrated a statistically significant difference between the DCPAP and non-DCPAP groups in terms of PaCO2 decreasing rate, and it was found to be twice higher in the DCPAP group (0.11 ± 0.07 mmHg/min) than in the non-DCPAP group (0.05 ± 0.06 mmHg/min). CONCLUSION: The study demonstrated that the treatment of AHRF patients with a DCPAP provides a faster decrease in PaCO2 levels in hypercapnic patients compared to standard medical therapy alone.
Assuntos
Dióxido de Carbono , Insuficiência Respiratória , Humanos , Feminino , Masculino , Pressão Positiva Contínua nas Vias Aéreas , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Hipercapnia/etiologia , Hipercapnia/terapia , DispneiaRESUMO
In this study, the production and characterization of silver-doped hydroxyapatite (AgHA) reinforced Xanthan gum (XG) and Polyethyleneimine (PEI) reinforced semi-interpenetrating polymer network (IPN) biocomposite, known to be used as bone cover material for therapeutic purposes in bone tissue, were performed. XG/PEI IPN films containing 2AgHA nanoparticles were produced by simultaneous condensation and ionic gelation. Characteristics of 2AgHA-XG/PEI nanocomposite film were evaluated by structural, morphological (SEM, XRD, FT-IR, TGA, TM, and Raman) and biological activity analysis (degradation, MTT, genotoxicity, and antimicrobial activity) techniques. In the physicochemical characterization, it was determined that 2AgHA nanoparticles were homogeneously dispersed in the XG/PEI-IPN membrane at high concentration and the thermal and mechanical stability of the formed film were high. The nanocomposites showed high antibacterial activity against Acinetobacter Baumannii (A.Baumannii), Staphylococcus aureus (S.aureus), and Streptococcus mutans (S.mutans). L929 exhibited good biocompatibility for fibroblast cells and was determined to support the formation of MCC cells. It was shown that a resorbable 2AgHA-XG/PEI composite material was obtained with a high degradation rate and 64% loss of mass at the end of the 7th day. Physico-chemically developed biocompatible and biodegradable XG-2AgHA/PEI nanocomposite semi-IPN films possessed an important potential for the treatment of defects in bone tissue as an easily applicable bone cover. Besides, it was noted that 2AgHA-XG/PEI biocomposite could increase cell viability, especially in dental-bone treatments for coating, filling, and occlusion.