RESUMO
Sterile inflammation after injury is important for tissue restoration. In injured human and mouse tissues, macrophages were recently found to accumulate perivascularly. This study investigates if macrophages adopt a mural cell phenotype important for restoration after ischemic injury. Single-cell RNA sequencing of fate-mapped macrophages from ischemic mouse muscles demonstrates a macrophage-toward-mural cell switch of a subpopulation of macrophages with downregulated myeloid cell genes and upregulated mural cell genes, including PDGFRß. This observation was further strengthened when including unspliced transcripts in the analysis. The macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRß deficiency prevented their perivascular macrophage phenotype, impaired vessel maturation and increased vessel leakiness, which ultimately reduced limb function. In conclusion, macrophages in adult ischemic tissue were demonstrated to undergo a cellular program to morphologically, transcriptomically and functionally resemble mural cells while weakening their macrophage identity. The macrophage-to-mural cell-like phenotypic switch is crucial for restoring tissue function and warrants further exploration as a potential target for immunotherapies to enhance healing.
Assuntos
Modelos Animais de Doenças , Isquemia , Macrófagos , Animais , Macrófagos/metabolismo , Macrófagos/imunologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/genética , Fenótipo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/lesões , Cicatrização/genética , Cicatrização/fisiologia , Camundongos Endogâmicos C57BL , Camundongos , Masculino , Membro Posterior/irrigação sanguínea , Neovascularização Fisiológica/genética , Regulação para Cima , Transcriptoma , Análise de Célula Única , Biomarcadores/metabolismo , Recuperação de Função Fisiológica , Camundongos KnockoutRESUMO
PURPOSE: Relebactam is a novel ß-lactamase inhibitor, which, when combined with imipenem/cilastatin, is active against both class A and class C ß-lactamases. To evaluate in vitro antimicrobial activity of imipenem/relebactam against a collection of recent clinical isolates of carbapenem-non-susceptible P. aeruginosa and K. pneumoniae ST258 and ST512 KPC producers belonging to different lineages from hospitals in Southern Spain. METHODS: Six hundred and seventy-eight isolates were tested: 265 K. pneumoniae (230 ST512/KPC-3 and 35 ST258/KPC-3) and 413 carbapenem-non-susceptible P. aeruginosa. Imipenem, piperacillin/tazobactam, ceftazidime, cefepime, aztreonam, ceftolozane/tazobactam, meropenem, amikacin, ciprofloxacin, colistin, and ceftazidime/avibactam were used as comparators against P. aeruginosa. Against K. pneumoniae ceftazidime, cefepime, aztreonam, and ceftolozane/tazobactam were not tested, and tigecycline was studied instead. MICs were determined in duplicate by broth microdilution according to EUCAST guidelines. RESULTS: Imipenem/relebactam displayed potent in vitro activity against both sequence types of KPC-3-producing K. pneumoniae. MIC50 and MIC90 values were 0.25 mg/L and 1 mg/L, respectively, with percent of susceptible isolates >97%. Only three K. pneumoniae ST512/KPC-3 isolates and one ST258/KPC-3 were resistant to imipenem/relebactam. Relebactam sensitized 98.5% of K. pneumoniae isolates resistant to imipenem. The activity of imipenem/relebactam against P. aeruginosa was moderate (susceptibility rate: 62.7%). Analysis of the acquired and mutational resistome of isolates with high levels of resistance to imipenem/relebactam has not shown a clear association between them. CONCLUSION: Imipenem/relebactam showed excellent activity against K. pneumoniae KPC-3. The activity of imipenem/relebactam against imipenem-resistant P. aeruginosa was moderate.
Assuntos
Compostos Azabicíclicos , Cefalosporinas , Imipenem , Infecções por Pseudomonas , Humanos , Imipenem/farmacologia , Ceftazidima/farmacologia , Pseudomonas aeruginosa , Klebsiella pneumoniae , Cefepima , Aztreonam , Antibacterianos/farmacologia , Infecções por Pseudomonas/microbiologia , Tazobactam/farmacologia , beta-Lactamases , Combinação de Medicamentos , Testes de Sensibilidade MicrobianaRESUMO
An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.
Assuntos
Cartilagem Articular , Gelatina , Animais , Porosidade , Condrócitos/transplante , Engenharia Tecidual , Hidrogéis , Materiais Biocompatíveis , Regeneração , Alicerces Teciduais , MamíferosRESUMO
Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsin vivoformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,in vivosubcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.
Assuntos
Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Gelatina/química , Porosidade , Materiais Biocompatíveis/química , Hidrogéis/química , Impressão TridimensionalRESUMO
The increasing demand for tissue replacement has encouraged scientists worldwide to focus on developing new biofabrication technologies. Multimaterials/cells printed with stringent resolutions are necessary to address the high complexity of tissues. Advanced inkjet 3D printing can use multimaterials and attain high resolution and complexity of printed structures. However, a decisive yet limiting aspect of translational 3D bioprinting is selecting the befitting material to be used as bioink; there is a complete lack of cytoactive bioinks with adequate rheological, mechanical, and reactive properties. This work strives to achieve the right balance between resolution and cell support through methacrylamide functionalization of a psychrophilic gelatin and new fluorosurfactants used to engineer a photo-cross-linkable and immunoevasive bioink. The syntonized parameters following optimal formulation conditions allow proficient printability in a PolyJet 3D printer comparable in resolution to a commercial synthetic ink (â¼150 µm). The bioink formulation achieved the desired viability (â¼80%) and proliferation of co-printed cells while demonstrating in vivo immune tolerance of printed structures. The practical usage of existing high-resolution 3D printing systems using a novel bioink is shown here, allowing 3D bioprinted structures with potentially unprecedented complexity.
Assuntos
Bioimpressão , Bioimpressão/métodos , Impressão Tridimensional , Gelatina/química , Reologia , Alicerces Teciduais/química , Engenharia Tecidual/métodosRESUMO
Introduction: Incisional hernia (IH) is common after open abdominal aortic aneurysm (AAA) repair. Recent studies reported incidence rates higher than previously stated. The aim of this study was to quantify the IH incidence after open AAA surgery. The secondary outcome was to identify the risk factors associated with the development of an IH. Methods: Retrospective observational study of all consecutive patients who underwent an open repair of AAA, from January 2010 to June 2018, at our institution. Patients were free of abdominal wall hernias at the moment of inclusion in the study. Data were extracted from electronic records: baseline characteristics, surgical factors, and postoperative events. Computed tomography (CT) scans performed during follow-up were analyzed. Results: A total of 157 patients were analysed. The IH incidence after open repair of AAA was 46.5% (73 patients). The median time for IH development was 24.43 months (IQR: 10.4045.27), while the median follow-up time was 37.20 months (IQR: 20.5364.12). The risk factors linked to IH were: active (HR: 4.535; 95% CI: 1.36915.022) or previous smoking habit (HR: 4.652; 95% CI: 1.43015.131), chronic kidney disease (HR: 2.007; 95% CI: 1.1623.467) and previous abdominal surgery (HR: 1.653; 95% CI: 1.0142.695). Conclusion: The incisional hernia after open abdominal aortic aneurysm repair affected a high proportion of the intervened patients. Previous abdominal surgery, chronic kidney disease, and smoking habit were independent factors for the development of an incisional hernia. (AU)
Introducción: La hernia incisional (HI) tras la cirugía abierta del aneurisma de aorta abdominal (AAA) es común. Estudios recientes muestran incidencias superiores a las consideradas anteriormente. El objetivo es evaluar la incidencia de HI tras la cirugía abierta del AAA. El objetivo secundario fue evaluar los factores de riesgo de HI. Métodos: Estudio observacional retrospectivo de pacientes consecutivos sometidos a cirugía abierta del AAA de enero de 2010 a junio de 2018 en nuestro centro. Todos los pacientes estaban libres de hernias de pared abdominal en el momento de la cirugía. Se analizaron los datos de la historia clínica electrónica: características basales, factores quirúrgicos y eventos postoperatorios. Se analizaron también los estudios de tomografía computarizada durante el seguimiento. Resultados: Se analizaron 157 pacientes. La incidencia de HI tras la cirugía abierta del AAA fue del 46,5% (73 pacientes). La mediana de tiempo para el desarrollo de HI fue de 24,43 meses (RIC 10,40-45,27), con una mediana de seguimiento de 37,20 meses (RIC 20,53-64,12). Los factores de riesgo asociados fueron: tabaquismo activo (HR 4,535; IC 95% 1,369-15,022) o hábito tabáquico previo (HR 4,652; IC 95% 1,430-15,131), enfermedad renal crónica (HR 2,007; IC 95% 1,162-3,467) y cirugía abdominal previa (HR 1,653; IC 95% 1,014-2,695). Conclusiones: La HI tras la cirugía abierta del AAA afectó a un gran número de pacientes intervenidos. La cirugía abdominal previa, la enfermedad renal crónica y el hábito tabáquico fueron factores de riesgo independientes de HI. (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hérnia Incisional , Aneurisma da Aorta Abdominal/cirurgia , Fatores de Risco , Estudos Retrospectivos , Parede Abdominal , EspanhaRESUMO
INTRODUCTION: Incisional hernia (IH) is common after open abdominal aortic aneurysm (AAA) repair. Recent studies reported incidence rates higher than previously stated. The aim of this study was to quantify the IH incidence after open AAA surgery. The secondary outcome was to identify the risk factors associated with the development of an IH. METHODS: Retrospective observational study of all consecutive patients who underwent an open repair of AAA, from January 2010 to June 2018, at our institution. Patients were free of abdominal wall hernias at the moment of inclusion in the study. Data were extracted from electronic records: baseline characteristics, surgical factors, and postoperative events. Computed tomography (CT) scans performed during follow-up were analyzed. RESULTS: A total of 157 patients were analysed. The IH incidence after open repair of AAA was 46.5% (73 patients). The median time for IH development was 24.43 months (IQR: 10.40-45.27), while the median follow-up time was 37.20 months (IQR: 20.53-64.12). The risk factors linked to IH were: active (HR: 4.535; 95% CI: 1.369-15.022) or previous smoking habit (HR: 4.652; 95% CI: 1.430-15.131), chronic kidney disease (HR: 2.007; 95% CI: 1.162-3.467) and previous abdominal surgery (HR: 1.653; 95% CI: 1.014-2.695). CONCLUSION: The incisional hernia after open abdominal aortic aneurysm repair affected a high proportion of the intervened patients. Previous abdominal surgery, chronic kidney disease, and smoking habit were independent factors for the development of an incisional hernia.
Assuntos
Aneurisma da Aorta Abdominal , Hérnia Incisional , Insuficiência Renal Crônica , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Incidência , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/complicações , Fatores de Risco , Insuficiência Renal Crônica/complicaçõesRESUMO
Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.
Assuntos
Obesidade , Dióxido de Silício , Digestão , Humanos , Lipídeos , Obesidade/tratamento farmacológico , Dióxido de Silício/uso terapêuticoRESUMO
Aim: To investigate the effect of oral consumption of engineered mesoporous silica particles, SiPore15®, on long-term blood glucose levels and other metabolic parameters in individuals with prediabetes and newly diagnosed Type 2 diabetes. Method: An open-label, single-arm, multicenter trial was conducted in which SiPore15 was consumed three times daily for 12 weeks. Hemoglobin A1c (HbA1c, primary end point) and an array of metabolic parameters were measured at baseline and throughout the trial. Result: SiPore15 treatment significantly reduced HbA1c by a clinically meaningful degree and improved several disease-associated parameters with minimal side effects. Conclusion: The results from this study demonstrate the potential use of SiPore15 as a treatment for prediabetes that may also delay or prevent the onset of Type 2 diabetes.
Lay abstract Prediabetes is a health condition in which blood sugar levels are higher than normal but below diabetes diagnosis level. Without intervention, prediabetic adults and children are most likely to progress to Type 2 diabetes. To try and prevent this progression, the authors of this article are proposing an innovative solution with an engineered material called SiPore15®. SiPore15 is classified as a medical device, and is made up entirely of porous silica particles. It has been proven to be safe to take orally. The effects of SiPore15 were investigated in people with prediabetes and newly diagnosed Type 2 diabetes. SiPore15 was taken three times a day for 12 weeks. It significantly reduced long-term blood glucose levels and improved other factors related to the disease with minimal side effects. The results from this study show that SiPore15 has the potential to be used as a treatment for prediabetes. This may help to delay or prevent the onset of Type 2 diabetes. Clinical Trial Registration: NCT03823027 (ClinicalTrials.gov).
Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Glicemia/metabolismo , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico , Dióxido de SilícioRESUMO
INTRODUCTION: Incisional hernia (IH) is common after open abdominal aortic aneurysm (AAA) repair. Recent studies reported incidence rates higher than previously stated. The aim of this study was to quantify the IH incidence after open AAA surgery. The secondary outcome was to identify the risk factors associated with the development of an IH. METHODS: Retrospective observational study of all consecutive patients who underwent an open repair of AAA, from January 2010 to June 2018, at our institution. Patients were free of abdominal wall hernias at the moment of inclusion in the study. Data were extracted from electronic records: baseline characteristics, surgical factors, and postoperative events. Computed tomography (CT) scans performed during follow-up were analyzed. RESULTS: A total of 157 patients were analysed. The IH incidence after open repair of AAA was 46.5% (73 patients). The median time for IH development was 24.43 months (IQR: 10.40-45.27), while the median follow-up time was 37.20 months (IQR: 20.53-64.12). The risk factors linked to IH were: active (HR: 4.535; 95% CI: 1.369-15.022) or previous smoking habit (HR: 4.652; 95% CI: 1.430-15.131), chronic kidney disease (HR: 2.007; 95% CI: 1.162-3.467) and previous abdominal surgery (HR: 1.653; 95% CI: 1.014-2.695). CONCLUSION: The incisional hernia after open abdominal aortic aneurysm repair affected a high proportion of the intervened patients. Previous abdominal surgery, chronic kidney disease, and smoking habit were independent factors for the development of an incisional hernia.
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[Figure: see text].
Assuntos
Quimiocina CXCL12/metabolismo , Isquemia/terapia , Macrófagos/fisiologia , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico Sintase Tipo II/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Animais , Movimento Celular , Proliferação de Células , Quimiocina CCL2/metabolismo , Humanos , Isquemia/fisiopatologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/deficiência , Óxido Nítrico Sintase Tipo III/metabolismo , Plasmídeos/metabolismo , Receptores CCR2/metabolismo , Receptores CXCR4/metabolismoRESUMO
Introducción: Coccyzus ferrugineus es el ave endémica menos estudiada de la Isla del Coco se desconocen muchos aspectos sobre su historia natural y comportamiento, siendo de las especies menos conocidas en Costa Rica. Objetivo: Describir el comportamiento reproductivo, de forrajeo, y el uso de hábitat de C. ferrugineus para generar información para la toma de decisiones de conservación de la especie. Métodos: Se hicieron observaciones directas de comportamiento (forrajeo, cortejo, vocalización, alimentación y cópula) durante dos periodos de observación (mañana y tarde), en parcelas entre los 0-400 m de altitud, clasificando el estrato de vegetación (bajo-medio-alto) para estudiar el uso de hábitat. Se presenta una descripción del comportamiento de forrajeo y del ciclo reproductivo. Resultados: Se demuestra que C. ferrugineus utiliza todo el gradiente altitudinal de la Isla del Coco, desde el nivel del mar hasta los 400 m de altitud en el bosque nuboso, para reproducirse y su época reproductiva está marcada por el inicio de la época seca. No se encontraron diferencias significativas entre las categorías de comportamiento establecidas y la hora del día (Fisher, P > 0.05). Sin embargo sí se mostró diferencias significativas para las categorías de comportamiento y el estrato vertical (Fisher, P < 0.05) demostrando que utiliza todo el estrato vertical de la estructura vegetal. Conclusiones: Este estudio representa la base para el conocimiento de la biología reproductiva e historia natural de C. ferrugineus, es urgente realizar más estudios sobre esta especie para poder protegerla y conservar el ecosistema terrestre de la Isla del Coco.
Introducción: Coccyzus ferrugineus is the least studied endemic bird of Isla del Coco, many aspects of its natural history and behavior remain unknown, being one the least known species in Costa Rica. Objective: To describe the reproductive behavior, foraging and habitat use of C. ferrugineus to generate information for making conservation decisions for the species. Methods: Direct behavioral observations (foraging, courtship, vocalization, feeding and intercourse) were made in plots between 0-400 m above sea level, during two observation periods (morning and afternoon). A description of the foraging behavior and the reproductive cycle is presented. Results: C. ferrugineus uses the entire altitudinal gradient of the island to reproduce, from sea level to 400 m altitude in the cloud forest. Its reproductive season is marked by the beginning of the dry season. No significant differences were found between the established behavior categories and the time of day (Fisher, P> 0.05). However, significant differences were shown for the behavioral categories and the vertical stratum (Fisher, P <0.05) demonstrating that it uses the entire vertical stratum of the vegetation structure. Conclusions: This study represents the basis for the knowledge of the reproductive biology and natural history of C. ferrugineus, it is urgent to carry out more studies on this species to be able to protect it and conserve the terrestrial ecosystem of Isla del Coco.
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INTRODUCTION: The Clinical and Endothelial Function Assessment after Endothelin Receptor Antagonist (CLAU) trial demonstrated the effect of bosentan on the endothelial function, inflammatory status and claudication distance in Hispanic patients with incipient peripheral arterial disease (PAD). Our aim was to assess the protective effect on cardiovascular events of bosentan versus conventional anti-atherosclerosis therapy. METHODS: CLAU included 56 patients with intermittent claudication, randomized 1:1 to receive bosentan for 12 weeks (n = 27) or placebo (n = 29), associating the best medical treatment. Log-rank and hazard ratio (HR) analyses were performed to estimate the relative efficacy of bosentan in preventing incidence of major adverse events (MAE) including target limb revascularization (TLR), amputation, myocardial infarction (MI), and all-cause death; major cardiovascular adverse events (MACE) including TLR, amputation, MI, stroke, and cardiovascular-cause death; and major adverse limb events (MALE), which combines TLR and amputation. RESULTS: During the follow-up period (34 ± 5 months), five MAE occurred in the control group only (17.2%), including two TLR, one amputation, one stroke, and an MI. The ratio of event-free survival for MAE to 3 years follow-up was higher in the group treated with bosentan (100% vs 66%, p = 0.01, HR = 76; 95% confidence interval 0.05-104,677, p = 0.24). A similar trend was observed in incidence of MACE (100% vs 66%, p = 0.01) and MALE (100% vs 80%, p = 0.15). CONCLUSION: Treatment with bosentan in the early low-to-mild stages of PAD may prevent cardiovascular events and the need for lower limb revascularization in the Hispanic population. Trial Registration ClinicalTrials.gov identifier NCT25102012.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bosentana/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Seguimentos , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , Resultado do TratamentoRESUMO
Many patients previously using darunavir/ritonavir (DRV/r) (800/100mg) have switched to darunavir/cobicistat (DRV/C) (800/150 mg) either as part of triple therapy (ART) or as monotherapy with DRV (mDRV). The latter approach continues to be used in some countries for patients receiving long-term treatment. However, to date, the behaviour of DRV/C in the seminal compartment has not been analysed. This study explores how the combination behaves in monotherapy, with respect to the control of viral load and seminal quality. To this end, we studied 20 patients who were treated with mDRV/C after previous treatment with mDRV/r for at least 24 weeks. A viral load control in seminal plasma similar to that published in the literature was observed after 24 weeks of treatment with mDRV/C (viral load positivity in 20% of patients). Similarly, semen quality was confirmed (70% normozoospermic) in patients treated with this formulation, as has previously been reported for ART and mDRV/r. The DRV levels measured in seminal plasma were above EC50, regardless of whether the seminal viral load was positive or negative. We conclude that this mDRV/C co-formulation behaves like mDRV/r in seminal plasma in terms of viral load control and semen quality.
Assuntos
Cobicistat/administração & dosagem , Darunavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Sêmen/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cobicistat/efeitos adversos , Estudos de Coortes , Darunavir/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sêmen/virologia , Análise do SêmenRESUMO
NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD). We measure differential relative gene expression of NLRP1 and NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair compared to aortic biopsies from 30 patients undergoing surgery to treat AOD. Aortic wall samples from autopsy without aortic disease were used as controls. NLRP3 was overexpressed in patients with AAA and AOD (RQ 1.185 ± 0.15, and 1.098 ± 0.05, respectively) compared to donors (RQ 1.001 ± 0.08) (OR 2.8, 95% CI 1.2-4.3, p < 0.05 for AAA and OR 2.1, 95% CI 1.1-3.8, p < 0.05 for AOD). NLRP1 gene expression was significantly upregulated in patients with AOD (RQ 1.197 ± 0.09). Meanwhile, NLRP1 was normal expressed in AAA (RQ 1.003 ± 0.07) as well as in autopsy aortic specimens (RQ 1.005 ± 0.11). Enhanced NLRP1 expression in AOD was even significant when compared to AAA (OR 2.3, 95% CI 1.2-3.3, p < 0.05) or controls (OR 2.2, 95% CI 1.1-3.1, p < 0.05). According to our findings, NLRP3 could be involved in the common etiology of AAA and AOD, whereas NLRP1 appears to have a specific role in AOD development.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Aneurisma da Aorta Abdominal/genética , Doenças da Aorta/genética , Proteínas Reguladoras de Apoptose/genética , Arteriopatias Oclusivas/genética , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Idoso , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Doenças da Aorta/etiologia , Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/cirurgia , Estudos de Casos e Controles , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas NLR , Razão de Chances , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Regulação para CimaRESUMO
NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD). We measure differential relative gene expression of NLRP1 and NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair compared to aortic biopsies from 30 patients undergoing surgery to treat AOD. Aortic wall samples from autopsy without aortic disease were used as controls. NLRP3 was overexpressed in patients with AAA and AOD (RQ 1.185 ± 0.15, and 1.098 ± 0.05, respectively) compared to donors (RQ 1.001 ± 0.08) (OR 2.8, 95% CI 1.2-4.3, p < 0.05 for AAA and OR 2.1, 95% CI 1.1-3.8, p < 0.05 for AOD). NLRP1 gene expression was significantly upregulated in patients with AOD (RQ 1.197 ± 0.09). Meanwhile, NLRP1 was normal expressed in AAA (RQ 1.003 ± 0.07) as well as in autopsy aortic specimens (RQ 1.005 ± 0.11). Enhanced NLRP1 expression in AOD was even significant when compared to AAA (OR 2.3, 95% CI 1.2-3.3, p < 0.05) or controls (OR 2.2, 95% CI 1.1-3.1, p < 0.05). According to our findings, NLRP3 could be involved in the common etiology of AAA and AOD, whereas NLRP1 appears to have a specific role in AOD development.
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The objective of this review is to outline existing artificial mitochondria transfer techniques and to describe the future steps necessary to develop new therapeutic applications in medicine. Inspired by the symbiotic origin of mitochondria and by the cell's capacity to transfer these organelles to damaged neighbors, many researchers have developed procedures to artificially transfer mitochondria from one cell to another. The techniques currently in use today range from simple coincubations of isolated mitochondria and recipient cells to the use of physical approaches to induce integration. These methods mimic natural mitochondria transfer. In order to use mitochondrial transfer in medicine, we must answer key questions about how to replicate aspects of natural transport processes to improve current artificial transfer methods. Another priority is to determine the optimum quantity and cell/tissue source of the mitochondria in order to induce cell reprogramming or tissue repair, in both in vitro and in vivo applications. Additionally, it is important that the field explores how artificial mitochondria transfer techniques can be used to treat different diseases and how to navigate the ethical issues in such procedures. Without a doubt, mitochondria are more than mere cell power plants, as we continue to discover their potential to be used in medicine.
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Introducción: La alimentación es una necesidad básica del ser humano que debe estar satisfecha plenamente. El Proceso de Atención de Enfermería es un método científico que permite actuar usando un lenguaje estandarizado. Objetivo y metodología: Dada la relación entre la alimentación y salud y la gran influencia que tiene la enfermería en la salud de la población surge la motivación de realizar una revisión bibliográfica en diferentes Bases de Datos para conocer las intervenciones nutricionales que las enfermeras realizan. Resultados y discusión: En la actualidad se da escasa importancia a los cuidados nutricionales, según esta revisión. Además, la enfermería tiene un perfil profesional idóneo para participar en la consecución de un adecuado estado nutricional de la población sana y enferma. La Malnutrición es un grave problema que se encuentra en hospitales y en Atención Primaria. Existen numerosas patologías relacionadas con la alimentación, algunas intervenciones enfermeras pueden solucionar esto. Además, se puede realizar desde hospitales y centros educativos o de salud. Conclusión: La malnutrición está reconocida como un problema de salud, dicho problema debe ser solventado, la formación de los profesionales sanitarios en temas de alimentación y nutrición puede mejorar la situación, estos conocimientos les permitirían tomar conciencia sobre el problema. Además, les permitiría saber cómo actuar para prevenir y/o tratar la malnutrición en la población (AU)
Introduction: Nutrition is a basic necessity for human being, and it has to be plenty satisfy. The Assistance in Nursing Process is a scientific method which permits acting using an standardized language. Methodology and goal: Given the relation among the nutrition and health, and the huge influence that nursing has in the population's health, it appears the motivation of carrying out a bibliographic revision in different databases in order to know the nutritional interventions of nurses. Results and discussion: Nowadays, considering this revision, nutritional cares are not taken as important. Furthermore, nursing has a perfect professional profile to take part in the achievement of a suitable nutritional state in the healthy population, as well as in the sick one. Malnutrition is a serious problem that can be found in hospitals and primary services. It exists a great amount of pathologies associated with nutrition, and some nursing interventions can solve this problem. Besides, it can be carried out from hospitals and educative or health centers. Conclusion: Malnutrition is related with a health problem which must be solved. The sanitary professional's formation regarding nutrition can improve this situation because of the fact that this knowledge can help to take consequence concerning the problem. Also, it can be considered as a formation on how to act to prevent and/or treat malnutrition in the population (AU)
Assuntos
Humanos , Masculino , Feminino , Enfermagem de Atenção Primária/métodos , Cuidados de Enfermagem/organização & administração , Hospitalização , Comportamento Alimentar , Papel do Profissional de EnfermagemRESUMO
BACKGROUND: Cocaine users tend to have a higher frequency of risk behaviors. AIM: To compare risk behaviors of out -of -treatment Cocaine Base Paste (CBP) and Cocaine Hydrochloride (CH) users, by means of Privileged Access Interviewing in a one- year prospective study. MATERIAL AND METHODS: Twenty -eight interviewers were trained to recruit and administer a questionnaire on substance use patterns and related risk behaviors. Intentioned sampling was carried out in four municipalities of Santiago, Chile. Subjects who used CBP (group 1) or CH (group 2) at least once in the last month, with primary current use of CBP (group 1) or CH (group 2), and without treatment for substance abuse in the last six months were interviewed. Generalized Estimating Equations (GEE) were employed to compare risk behaviors during follow -up. RESULTS: Four hundred and two of 467 subjects (86.1%) were followed up for one year. CBP users (n = 204) reported greater frequency of self -inflicted injuries (Odds Ratio (OR): 1.97 [95% confidence intervals (CI): 1.07-3.66]) and suicide attempts (OR: 2.68 [95% CI: 1.19-6.01]) than CH users. CONCLUSIONS: CBP users had a greater frequency of self -inflicted injuries and suicide attempts, both life threatening risk behaviors, than CH users. This profile shows the high vulnerability of CBP users and should encourage further research and design of outreach interventions, particularly focused on this group.