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1.
World J Surg Oncol ; 22(1): 226, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39192281

RESUMO

BACKGROUND: Surgeries for sarcomas in the abdominal wall require wide resections, often radical en bloc resections, which generate major defects involving a very complex repair. The combined use of porcine dermal xenografts, together with composite meshes, may assist in the repair of these defects with minimal complications. METHOD: We present a series of 19 patients (10 males and 9 females), with a mean age of 53.2 years (range: 11-86 years) treated in the Sarcoma Unit of the Virgen de la Arrixaca University Hospital from January 2015 to December 2021. Histopathologically, there were four chondrosarcomas (21%), three Ewing sarcomas (15.7%), two desmoid tumours (10.5%), two undifferentiated pleomorphic sarcomas (10.5%), two well-differentiated liposarcomas (10.5%), two leiomyosarcomas (10.5%), one synovial sarcoma, one dermatofibrosarcoma protuberans, one fibromyxoid sarcoma (or Evans tumour), and one metastasis from an adenocarcinoma of unknown origin. All the patients were resected following surgical oncology principles and reconstructed by means of the combined use of a composite mesh acting as a neoperitoneum and a porcine dermal xenograft acting as an abdominal neofascia. RESULTS: The mean size of the defects generated after surgery for tumour excision was 262.8 cm2 (range: 150-600 cm2). After a mean follow-up of 38 months, six patients (31.5%) developed complications-two cases of wound dehiscence, one case of surgical wound infection, one case of graft partial necrosis, one case of anastomotic leak and one death due to multiorgan failure secondary to massive bronchoaspiration. CONCLUSION: Surgeries for sarcomas of the abdominal wall require wide oncological resections, which generate major abdominal wall defects. The repair of these defects by means of the combined use of synthetic and biological meshes is a technique associated with minimal complications and excellent medium-term results.


Assuntos
Parede Abdominal , Derme Acelular , Procedimentos de Cirurgia Plástica , Sarcoma , Telas Cirúrgicas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Adolescente , Parede Abdominal/cirurgia , Parede Abdominal/patologia , Idoso de 80 Anos ou mais , Criança , Adulto Jovem , Sarcoma/cirurgia , Sarcoma/patologia , Procedimentos de Cirurgia Plástica/métodos , Seguimentos , Prognóstico , Animais
4.
Vet Res ; 49(1): 21, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29467018

RESUMO

The aim of this work was to evaluate the immunogenicity and efficacy of DNA and MVA vaccines encoding the RVFV glycoproteins Gn and Gc in an ovine model of RVFV infection. Adult sheep of both sexes were challenged 12 weeks after the last immunization and clinical, virological, biochemical and immunological consequences, were analyzed. Strategies based on immunization with homologous DNA or heterologous DNA/MVA prime-boost were able to induce a rapid in vitro neutralizing antibody response as well as IFNγ production after in vitro virus specific re-stimulation. In these animals we observed reduced viremia levels and less clinical signs when compared with mock-immunized controls. In contrast, sheep inoculated with a homologous MVA prime-boost showed increased viremia correlating with the absence of detectable neutralizing antibody responses, despite of inducing cellular responses after the last immunization. However, faster induction of neutralizing antibodies and IFNγ production after challenge were found in this group when compared to the mock vaccinated group, indicative of a primed immune response. In conclusion, these results suggest that vaccination strategies based on DNA priming were able to mount and maintain specific anti-RVFV glycoprotein immune responses upon homologous or heterologous booster doses, warranting further optimization in large animal models of infection.


Assuntos
Febre do Vale de Rift/prevenção & controle , Vírus da Febre do Vale do Rift/imunologia , Doenças dos Ovinos/prevenção & controle , Vacinação/veterinária , Vacinas de DNA/farmacologia , Vacinas Virais/farmacologia , Animais , Feminino , Masculino , Febre do Vale de Rift/virologia , Ovinos , Doenças dos Ovinos/virologia
5.
Helicobacter ; 23(2): e12462, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29316052

RESUMO

BACKGROUND: Helicobacter pylori is a gut bacterium that is the primary cause of gastric cancer. H. pylori infection has been consistently associated with lack of access to sanitation and clean drinking water. In this study, we conducted time-series sampling of drinking water in Lima, Peru, to examine trends of H. pylori contamination and other water characteristics. MATERIALS AND METHODS: Drinking water samples were collected from a single faucet in Lima's Lince district 5 days per week from June 2015 to May 2016, and pH, temperature, free available chlorine, and conductivity were measured. Quantities of H. pylori in all water samples were measured using quantitative polymerase chain reaction. Relationships between the presence/absence and quantity of H. pylori and water characteristics in the 2015-2016 period were examined using regression methods accounting for the time-series design. RESULTS: Forty-nine of 241 (20.3%) of drinking water samples were contaminated with H. pylori. Statistical analyses identified no associations between sampling date and the likelihood of contamination with H. pylori. Statistically significant relationships were found between lower temperatures and a lower likelihood of the presence of H. pylori (P < .05), as well as between higher pH and higher quantities of H. pylori (P < .05). CONCLUSIONS: This study has provided evidence of the presence of H. pylori DNA in the drinking water of a single drinking water faucet in the Lince district of Lima. However, no seasonal trends were observed. Further studies are needed to determine the presence of H. pylori in other drinking water sources in other districts in Lima, as well as to determine the viability of H. pylori in these water sources. Such studies would potentially allow for better understanding and estimates of the risk of infection due to exposure to H. pylori in drinking water.


Assuntos
Água Potável/microbiologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/genética , Peru , Abastecimento de Água
6.
Gut ; 66(8): 1369-1381, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27196595

RESUMO

OBJECTIVE: Lymphotoxin ß receptor (LTßR) signalling has been implicated in inflammation-associated tumour development in different tissues. We have analysed the role of LTßR and alternative NF-κB signalling in Helicobacter pylori-mediated gastric inflammation and pathology. DESIGN: We analysed several ligands and receptors of the alternative NF-κB pathway, RelB, p52 nuclear translocation and target genes in tissue samples of H. pylori-infected patients with different degrees of gastritis or early gastric tumours by in situ hybridisation, immunohistochemistry, Western blot and real-time PCR analyses. Molecular mechanisms involved in LTßR activation by H. pylori were assessed in vitro using human gastric cancer cell lines and distinct H. pylori isolates. The effects of blocking or agonistically activating LTßR on gastric pathology during challenge with a human pathogenic H. pylori strain were studied in a mouse model. RESULTS: Among the tested candidates, LT was significantly increased and activated alternative NF-κB signalling was observed in the gastric mucosa of H. pylori-infected patients. H. pyloriinduced LTßR-ligand expression in a type IV secretion system-dependent but CagA-independent manner, resulting in activation of the alternative NF-κB pathway, which was further enhanced by blocking canonical NF-κB during infection. Blocking LTßR signalling in vivo suppressed H. pylori-driven gastritis, whereas LTßR activation in gastric epithelial cells of infected mice induced a broadened pro-inflammatory chemokine milieu, resulting in exacerbated pathology. CONCLUSIONS: LTßR-triggered activation of alternative NF-κB signalling in gastric epithelial cells executes H. pylori-induced chronic gastritis, representing a novel target to restrict gastric inflammation and pathology elicited by H. pylori, while exclusively targeting canonical NF-κB may aggravate pathology by enhancing the alternative pathway.


Assuntos
Quimiocinas/metabolismo , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Receptor beta de Linfotoxina/metabolismo , NF-kappa B/metabolismo , Sistemas de Secreção Tipo IV/metabolismo , Animais , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL2/metabolismo , Quimiocina CCL20/metabolismo , Quimiocina CXCL10/metabolismo , Células Epiteliais/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Humanos , Receptor beta de Linfotoxina/antagonistas & inibidores , Receptor beta de Linfotoxina/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro , Transdução de Sinais , Fator de Transcrição RelB/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
7.
Yale J Biol Med ; 90(2): 245-259, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28656011

RESUMO

Human immunodeficiency virus type 1 (HIV-1) disease is pandemic, with approximately 36 million infected individuals world-wide. For the vast majority of these individuals, untreated HIV eventually causes CD4+ T cell depletion and profound immunodeficiency, resulting in morbidity and mortality. But for a remarkable few (0.2 to 0.5 percent), termed elite controllers (ECs), viral loads (VLs) remain suppressed to undetectable levels (< 50 copies/ml) and peripheral CD4+ T cell counts remain high (200 to 1000/µl), all in the absence of antiretroviral therapy (ART). Viremic controllers (VCs) are a similar but larger subset of HIV-1 infected individuals who have the ability to suppress their VLs to low levels. These patients have been intensively studied over the last 10 years in order to determine how they are able to naturally control HIV in the absence of medications, and a variety of mechanisms have been proposed. Defective HIV does not explain the clinical status of most ECs/VCs; rather these individuals appear to somehow control HIV infection, through immune or other unknown mechanisms. Over time, many ECs and VCs eventually lose the ability to control HIV, leading to CD4+ T cell depletion and immunologic dysfunction in the absence of ART. Elucidating novel mechanisms of HIV control in this group of patients will be an important step in understanding HIV infection. This will extend our knowledge of HIV-host interaction and may pave the way for the development of new therapeutic approaches and advance the cure agenda.


Assuntos
Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Fármacos Anti-HIV/uso terapêutico , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Humanos , Imunidade Celular , Linfócitos T/imunologia , Linfócitos T/fisiologia , Carga Viral/imunologia , Viremia/imunologia , Viremia/virologia
8.
Nanomedicine ; 12(5): 1185-92, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26970026

RESUMO

In this work we have tested the potential antiviral activity of silver nanoparticles formulated as Argovit™ against Rift Valley fever virus (RVFV). The antiviral activity of Argovit was tested on Vero cell cultures and in type-I interferon receptor deficient mice (IFNAR (-/-) mice) by two different approaches: (i) different dilutions of Argovit were added to previously infected cells or administrated to animals infected with a lethal dose of virus; (ii) virus was pre-incubated with different dilutions of Argovit before inoculation in mice or cells. Though the ability of silver nanoparticles to control an ongoing RVFV infection in the conditions tested was limited, the incubation of virus with Argovit before the infection led to a reduction of the infectivity titers both in vitro and in vivo. These results reveal the potential application of silver nanoparticles to control the infectivity of RVFV, which is an important zoonotic pathogen.


Assuntos
Antivirais/farmacologia , Nanopartículas/uso terapêutico , Vírus da Febre do Vale do Rift/efeitos dos fármacos , Prata/uso terapêutico , Animais , Camundongos , Febre do Vale de Rift/prevenção & controle , Vírus da Febre do Vale do Rift/patogenicidade
9.
Cir Esp ; 93(9): 589-93, 2015 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26277461

RESUMO

BACKGROUND: After pneumonectomy, the development of a new lung cancer or a recurrence in the residual lung is a challenge. Surgery often is considered contraindicated. The goal of our study is to assess the morbidity and mortality of lung resection on a single lung. METHODS: All patients who underwent lung resection after pneumonectomy from January 1996 through December 2012 were reviewed. RESULTS: There were 12 patients (10 men and 2 women). Mean age was 71 years (range, 54-81 years). Mean preoperative FEV1 was 1,470 ml (52%) and preoperative FVC 2,153 ml (61,5%). Subsequent pulmonary resection was performed after a median follow-up of 34,5 months. Wedge resection was performed in all patients. Diagnosis was pulmonary mestastatic lung cancer in 2 patients, metachronous lung cancer in 6, metastatic extrathoracic cancer in 3 and benign nodule in one. Complications occurred in 4 patients (33,4%) while operative mortality was nil. CONCLUSIONS: Lung resection on a single lung is a safe procedure associated with acceptable morbidity and mortality. Careful patient selection is very important.


Assuntos
Pneumonectomia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Segunda Neoplasia Primária/etiologia , Seleção de Pacientes , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
10.
Sci Rep ; 14(1): 10396, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710724

RESUMO

Regulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors.


Assuntos
Neoplasias da Mama , Linfócitos T Reguladores , Transcriptoma , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Prognóstico
11.
Arch Bronconeumol ; 60(3): 133-142, 2024 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38238188

RESUMO

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Irrigação Terapêutica , Citologia , Estadiamento de Neoplasias , Doença Crônica , Recidiva Local de Neoplasia/epidemiologia , Prognóstico
12.
Pediatr Infect Dis J ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916929

RESUMO

Central nervous system infections in children caused by group A Streptococcus are rare. This study, conducted across 52 hospitals in Spain from 2019 to 2023, identified 32 cases of central nervous system infections in children caused by group A Streptococcus, with a significant increase from October 2022 onward (1.1% vs. 5.9%, P = 0.002). Half required pediatric intensive care unit admission, 12.5% exhibited sequelae and the mortality rate was 6.2%. Mastoiditis was the predominant primary infection.

13.
Mol Ther Methods Clin Dev ; 32(1): 101193, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38352270

RESUMO

Friedreich's ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA is characterized by progressive neurodegeneration, with many patients developing cardiomyopathy that progresses to heart failure and death. The potential to reverse or prevent progression of the cardiac phenotype of FRDA was investigated in a mouse model of FRDA, using an adeno-associated viral vector (AAV8) containing the coding sequence of the FXN gene. The Fxnflox/null::MCK-Cre conditional knockout mouse (FXN-MCK) has an FXN gene ablation that prevents FXN expression in cardiac and skeletal muscle, leading to cardiac insufficiency, weight loss, and morbidity. FXN-MCK mice received a single intravenous injection of an AAV8 vector containing human (hFXN) or mouse (mFXN) FXN genes under the control of a phosphoglycerate kinase promoter. Compared to vehicle-treated FXN-MCK control mice, AAV-treated FXN-MCK mice displayed increases in body weight, reversal of cardiac deficits, and increases in survival without apparent toxicity in the heart or liver for up to 12 weeks postdose. FXN protein expression in heart tissue was detected in a dose-dependent manner, exhibiting wide distribution throughout the heart similar to wild type, but more speckled. These results support an AAV8-based approach to treat FRDA-associated cardiomyopathy.

14.
Virol J ; 10: 349, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24304565

RESUMO

BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.


Assuntos
Adenoviridae/genética , Portadores de Fármacos , Vetores Genéticos , Febre do Vale de Rift/prevenção & controle , Vírus da Febre do Vale do Rift/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Febre do Vale de Rift/imunologia , Vírus da Febre do Vale do Rift/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
15.
Arch Dis Child ; 108(6): 445-450, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37019466

RESUMO

OBJECTIVE: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae. DESIGN: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019. PATIENTS: A total of 688 patients were recruited. MAIN OUTCOME MEASURES: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI. RESULTS: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%). CONCLUSIONS: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.


Assuntos
Infecções Bacterianas , Exantema , Púrpura , Infecções Estreptocócicas , Humanos , Criança , Lactente , Pré-Escolar , Estudos Prospectivos , Infecções Bacterianas/epidemiologia , Febre/etiologia , Febre/microbiologia , Serviço Hospitalar de Emergência , Púrpura/diagnóstico , Púrpura/epidemiologia , Púrpura/etiologia , Exantema/epidemiologia , Exantema/etiologia
16.
Pediatr Infect Dis J ; 42(10): 837-843, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37410579

RESUMO

BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.


Assuntos
Tuberculose Pulmonar , Tuberculose , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Tuberculose Pulmonar/diagnóstico , Estudos Retrospectivos , Prevalência , Espanha/epidemiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
17.
ACS Appl Mater Interfaces ; 15(38): 44786-44795, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37699547

RESUMO

AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.


Assuntos
Antracenos , Imagem Óptica , Citoplasma , Membrana Celular , Polímeros , Água
18.
Science ; 379(6637): 1140-1149, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36927019

RESUMO

Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in cryptic splicing and polyadenylation of pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3' splice site in STMN2 pre-mRNA. Targeting dCasRx or antisense oligonucleotides (ASOs) suppressed cryptic splicing, which restored axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons. In mice that were gene-edited to contain human STMN2 cryptic splice-polyadenylation sequences, ASO injection into cerebral spinal fluid successfully corrected Stmn2 pre-mRNA misprocessing and restored stathmin-2 expression levels independently of TDP-43 binding.


Assuntos
Proteínas de Ligação a DNA , Edição de Genes , Poliadenilação , Splicing de RNA , Estatmina , Proteinopatias TDP-43 , Animais , Humanos , Camundongos , Proteínas de Ligação a DNA/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Estatmina/genética , Estatmina/metabolismo , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/terapia , Sítios de Splice de RNA , Oligonucleotídeos Antissenso/genética , Crescimento Neuronal
19.
Laryngoscope Investig Otolaryngol ; 7(2): 417-424, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434333

RESUMO

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

20.
Materials (Basel) ; 15(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36295320

RESUMO

In this study, functional nanocoatings for water-repellent footwear leather materials were investigated by chemical plasma polymerisation by implanting and depositing the organosilicon compound hexamethyldisiloxane (HMDSO) using a low-pressure plasma system. To this end, the effect of monomers on leather plasma deposition time was evaluated and both the resulting plasma polymers and the deposited leather samples were characterised using different experimental techniques, such as: Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). In addition, leather samples were tested by standard tests for color change, water resistance, surface wetting resistance and dynamic water contact angle (DWCA). The resulting polysiloxane polymers exhibited hydrophobic properties on leather. Furthermore, these chemical surface modifications created on the substrate can produce water repellent effects without altering the visual leather appearance and physical properties. Both plasma coating treatments and nanocoatings with developed water-repellency properties can be considered as a more sustainable, automated and less polluting alternative to chemical conventional processing that can be introduced into product-finishing processes in the footwear industry.

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