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1.
PLoS Biol ; 22(5): e3002594, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38754362

RESUMO

The standard genetic code defines the rules of translation for nearly every life form on Earth. It also determines the amino acid changes accessible via single-nucleotide mutations, thus influencing protein evolvability-the ability of mutation to bring forth adaptive variation in protein function. One of the most striking features of the standard genetic code is its robustness to mutation, yet it remains an open question whether such robustness facilitates or frustrates protein evolvability. To answer this question, we use data from massively parallel sequence-to-function assays to construct and analyze 6 empirical adaptive landscapes under hundreds of thousands of rewired genetic codes, including those of codon compression schemes relevant to protein engineering and synthetic biology. We find that robust genetic codes tend to enhance protein evolvability by rendering smooth adaptive landscapes with few peaks, which are readily accessible from throughout sequence space. However, the standard genetic code is rarely exceptional in this regard, because many alternative codes render smoother landscapes than the standard code. By constructing low-dimensional visualizations of these landscapes, which each comprise more than 16 million mRNA sequences, we show that such alternative codes radically alter the topological features of the network of high-fitness genotypes. Whereas the genetic codes that optimize evolvability depend to some extent on the detailed relationship between amino acid sequence and protein function, we also uncover general design principles for engineering nonstandard genetic codes for enhanced and diminished evolvability, which may facilitate directed protein evolution experiments and the bio-containment of synthetic organisms, respectively.


Assuntos
Evolução Molecular , Código Genético , Proteínas , Proteínas/genética , Proteínas/metabolismo , Mutação/genética , Códon/genética , Modelos Genéticos , Biologia Sintética/métodos , Biossíntese de Proteínas , Engenharia de Proteínas/métodos
2.
Chem Soc Rev ; 53(8): 3714-3773, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38456490

RESUMO

Self-assembled monolayers (SAMs) represent highly ordered molecular materials with versatile biochemical features and multidisciplinary applications. Research on SAMs has made much progress since the early begginings of Au substrates and alkanethiols, and numerous examples of peptide-displaying SAMs can be found in the literature. Peptides, presenting increasing structural complexity, stimuli-responsiveness, and biological relevance, represent versatile functional components in SAMs-based platforms. This review examines the major findings and progress made on the use of peptide building blocks displayed as part of SAMs with specific functions, such as selective cell adhesion, migration and differentiation, biomolecular binding, advanced biosensing, molecular electronics, antimicrobial, osteointegrative and antifouling surfaces, among others. Peptide selection and design, functionalisation strategies, as well as structural and functional characteristics from selected examples are discussed. Additionally, advanced fabrication methods for dynamic peptide spatiotemporal presentation are presented, as well as a number of characterisation techniques. All together, these features and approaches enable the preparation and use of increasingly complex peptide-based SAMs to mimic and study biological processes, and provide convergent platforms for high throughput screening discovery and validation of promising therapeutics and technologies.


Assuntos
Peptídeos , Propriedades de Superfície , Peptídeos/química , Humanos , Técnicas Biossensoriais , Adesão Celular/efeitos dos fármacos
3.
J Infect Dis ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842497

RESUMO

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

4.
Antimicrob Agents Chemother ; 68(5): e0168623, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38534103

RESUMO

Nocardiosis typically requires a prolonged treatment duration of ≥6 months and initial combination therapy with 2-3 antibiotics. First-line regimens for nocardiosis are associated with considerable toxicity; therefore, alternative therapies are needed. Omadacycline is an aminomethylcycline with broad antimicrobial activity whose in vitro activity against Nocardia species has not been formally assessed. The in vitro potency of omadacycline was evaluated against 300 Nocardia clinical isolates by broth microdilution. The most common Nocardia species tested were N. cyriacigeorgica (21%), N. nova (20%), and N. farcinica (12%). The most common specimens were respiratory (178 isolates, 59%) and wound (57 isolates, 19%). Omadacycline minimum inhibitory concentrations (MICs) across all Nocardia species ranged from 0.06 µg/mL to 8 µg/mL, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL. The lowest MICs were found among N. paucivorans (MIC50 = 0.25 µg/mL, MIC90 = 0.25 µg/mL), N. asiatica (MIC50 = 0.25 µg/mL, MIC90 = 1 µg/mL), N. abscessus complex (MIC50 = 0.5 µg/mL, MIC90 = 1 µg/mL), N. beijingensis (MIC50 = 0.5 µg/mL, MIC90 = 2 µg/mL), and N. otitidiscaviarum (MIC50 = 1 µg/mL, MIC90 = 2 µg/mL). The highest MICs were found among N. farcinica (MIC50 = 4 µg/mL, MIC90 = 8 µg/mL). In vitro potency differed by species among Nocardia clinical isolates. Further studies are warranted to evaluate the potential clinical utility of omadacycline for nocardiosis.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Nocardiose , Nocardia , Tetraciclinas , Nocardia/efeitos dos fármacos , Tetraciclinas/farmacologia , Antibacterianos/farmacologia , Humanos , Nocardiose/microbiologia , Nocardiose/tratamento farmacológico
5.
Small ; 20(33): e2308534, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38573943

RESUMO

Thermal control at small scales is critical for studying temperature-dependent biological systems and microfluidic processes. Concerning this, optical trapping provides a contactless method to remotely study microsized heating sources. This work introduces a birefringent luminescent microparticle of NaLuF4:Nd3+ as a local heater in a liquid system. When optically trapped with a circularly polarized laser beam, the microparticle rotates and heating is induced through multiphonon relaxation of the Nd3+ ions. The temperature increment in the surrounding medium is investigated, reaching a maximum heating of ≈5 °C within a 30 µm radius around the static particle under 51 mW laser excitation at 790 nm. Surprisingly, this study reveals that the particle's rotation minimally affects the temperature distribution, contrary to the intuitive expectation of liquid stirring. The influence of the microparticle rotation on the reduction of heating transfer is analyzed. Numerical simulations confirm that the thermal distribution remains consistent regardless of spinning. Instead, the orientation-dependence of the luminescence process emerges as a key factor responsible for the reduction in heating. The anisotropy in particle absorption and the lag between the orientation of the particle and the laser polarization angle contribute to this effect. Therefore, caution must be exercised when employing spinning polarization-dependent luminescent particles for microscale thermal analysis using rotation dynamics.

6.
Arch Microbiol ; 206(9): 385, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177836

RESUMO

Hydrophobins (HFBs) and cerato-platanins (CPs) are surface-active extracellular proteins produced by filamentous fungi. This study identified two HFB genes (pshyd1 and pshyd2) and one CP gene (pscp) in the marine fungus Paradendryphiella salina. The proteins PsCP, PsHYD2, and PsHYD1 had molecular weights of 12.70, 6.62, and 5.98 kDa, respectively, with isoelectric points below 7. PsHYD1 and PsHYD2 showed hydrophobicity (GRAVY score 0.462), while PsCP was hydrophilic (GRAVY score - 0.202). Stability indices indicated in-solution stability. Mass spectrometry identified 2,922 proteins, including CP but not HFB proteins. qPCR revealed differential gene expression influenced by developmental stage and substrate, with pshyd1 consistently expressed. These findings suggest P. salina's adaptation to marine ecosystems with fewer hydrophobin genes than other fungi but capable of producing surface-active proteins from seaweed carbohydrates. These proteins have potential applications in medical biocoatings, food industry foam stabilizers, and environmental bioremediation.


Assuntos
Proteínas Fúngicas , Interações Hidrofóbicas e Hidrofílicas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Ascomicetos/genética , Ascomicetos/metabolismo , Ascomicetos/química , Alga Marinha/microbiologia , Alga Marinha/química , Organismos Aquáticos/genética , Organismos Aquáticos/metabolismo , Regulação Fúngica da Expressão Gênica , Água do Mar/microbiologia
7.
Curr Opin Crit Care ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39034915

RESUMO

PURPOSE OF THIS REVIEW: This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS: Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY: Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

8.
Psychophysiology ; 61(6): e14544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38351668

RESUMO

Predictive coding framework posits that our brain continuously monitors changes in the environment and updates its predictive models, minimizing prediction errors to efficiently adapt to environmental demands. However, the underlying neurophysiological mechanisms of these predictive phenomena remain unclear. The present study aimed to explore the systemic neurophysiological correlates of predictive coding processes during passive and active auditory processing. Electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and autonomic nervous system (ANS) measures were analyzed using an auditory pattern-based novelty oddball paradigm. A sample of 32 healthy subjects was recruited. The results showed shared slow evoked potentials between passive and active conditions that could be interpreted as automatic predictive processes of anticipation and updating, independent of conscious attentional effort. A dissociated topography of the cortical hemodynamic activity and distinctive evoked potentials upon auditory pattern violation were also found between both conditions, whereas only conscious perception leading to imperative responses was accompanied by phasic ANS responses. These results suggest a systemic-level hierarchical reallocation of predictive coding neural resources as a function of contextual demands in the face of sensory stimulation. Principal component analysis permitted to associate the variability of some of the recorded signals.


Assuntos
Percepção Auditiva , Eletroencefalografia , Potenciais Evocados Auditivos , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Sistema Nervoso Autônomo/fisiologia , Córtex Cerebral/fisiologia , Antecipação Psicológica/fisiologia , Atenção/fisiologia
9.
J Strength Cond Res ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39178063

RESUMO

ABSTRACT: Cardiel-Sánchez, S, Rubio-Peirotén, A, Molina-Molina, A, García-Cebadera Gómez, C, Almenar-Arasanz, A, Ráfales-Perucha, A, Roche-Seruendo, LE, and Cartón-Llorente, A. Effects of plyometric training on running biomechanics and jumping ability of U14 athletes. J Strength Cond Res XX(X): 000-000, 2024-Children under the age of 14 years (U14) are particularly susceptible to musculoskeletal disorders because of growth spurts. Plyometric training has been shown to be beneficial for both injury reduction and performance enhancement. The aim of this study was to evaluate the effects of plyometric training on the jumping ability and running biomechanics of U14 track-and-field athletes. A single-blind randomized controlled trial was conducted. Thirty-five (18 female and 17 male) U14 athletes (age: 12.5 ± 1.2 years; height: 152.3 ± 7.7 cm; body mass: 47.3 ± 6.9 kg) were randomized into experimental and control groups. All subjects completed their usual training for 4 weeks, and those in the intervention group added a low-volume plyometric program twice a week. Preintervention and postintervention assessments included a countermovement jump (CMJ) to determine maximum jump height, 10-second repeated jumps to assess reactive strength index (RSI), and a 3-minute run at 12 km·h-1 to analyze running kinematics contact time, flight time, step length (SL), step frequency (SF), mean power output, vertical spring stiffness, and leg spring stiffness (LSS). The results revealed no main effect of time for any of the variables. A group-by-time interaction was found for RSI (p = 0.045) in the intervention group, whereas a significant increase in LSS was also found after the intervention (p = 0.031). However, no changes in CMJ height or other running parameters were observed. The significance level for the study was set at ρ ≤ 0.05. Plyometric-jump training may improve the stretch-shortening cycle in U14 athletes by increasing RSI and LSS. Athletes and coaches in running-related sports should be aware of these short-term effects when aiming to optimize the energy storage and release mechanism.

10.
Rev Esp Enferm Dig ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38685898

RESUMO

33-year-old woman, previously hospitalized for self-limited migratory bile duct strictures, presented with jaundice three months after giving birth. Blood analysis revealed elevated levels of aspartate aminotransaminase 1064U/L, alanine aminotransaminase 1097U/L, gamma-glutamyl transferase 194U/L, alkaline phosphatase 284U/L, bilirubin 27mg/dL and prothrombin time of 19.3s. Magnetic resonance-cholangiopancreatography revealed intrahepatic bile duct dilation with a stenosis in the common hepatic duct, not detected on endoscopic retrograde cholangiopancreatography. Additionally, diffuse signal abnormalities were observed in the liver parenchyma on T2 sequences. An early liver biopsy showed moderate-severe interface hepatitis with IgG4-positive plasma cell infiltration (IgG4-PPC) of 8-20cells/HPF, hepatocellular ballooning and focal rosette formation, yielding 6 points of the simplified-score for autoimmune hepatitis and treatment with methylprednisolone was initiated. Despite treatment, there was no improvement after two weeks and the patient received rituximab as a rescue treatment, but three days later, developed candida sepsis with rapid progression to multiorgan failure, ultimately resulting in death.

11.
Aten Primaria ; 56(2): 102782, 2024 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-37924621

RESUMO

OBJECTIVE: The objective was to develop a screening for heart disease detection in primary care, to identify pathological electrocardiographic changes and underlying heart disease in adolescents. DESIGN: The study was carried out for one year using multistage sampling. SITE: Primary care centers in a health area that had digital ECG equipment (12 centers) were selected. PARTICIPANTS: Initially, 718 (16.6%) 14-year-old adolescents were recruited and those with a previous diagnosis of heart disease were excluded. INTERVENTIONS: Screening consisted of including a health questionnaire in the mandatory 14-year-old check-up. MAIN MEASUREMENTS: Screening included a questionnaire, cardiac auscultation, ECG and echocardiography. Abnormality criteria were established to refer for a second evaluation by a cardiologist. RESULTS: Finally, the sample was made up of 698 adolescents, with a mean age of 13.7±0.5 years, and 354 (50.7%) were boys. A total of 149 (21.3%) were selected for a second review by cardiology: 88 (12.6%) due to a positive questionnaire, 11 (2.2%) due to abnormal cardiac auscultation, and 66 (9.5%) due to ECG findings. Adolescents with evidence of heart disease were 24 (3.4%). Of these, 14 (2.0%) had suggestive alterations and follow-up was recommended, 6 (0.9%) had a definitive diagnosis of heart disease, and 4 (0.6%) had other pathological findings related to the cardiovascular system. CONCLUSIONS: The screening allowed us to identify 1% of adolescents with heart disease and another 2% will remain in follow-up. The ECG detected more pathological cases than the questionnaire.


Assuntos
Morte Súbita Cardíaca , Cardiopatias , Masculino , Humanos , Adolescente , Feminino , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Cardiopatias/diagnóstico , Ecocardiografia , Programas de Rastreamento
12.
Foot Ankle Surg ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39164136

RESUMO

BACKGROUND: Various fixation methods have been described for Akin osteotomy, based on using metal implants or transosseous sutures. The aim of this study was to evaluate radiological outcomes and complications of closing wedge Akin osteotomy based on a crossed suture configuration of the joint capsule rather than using implants. The null hypothesis is that a crossed suture has comparable radiological results to other techniques, with no additional complications. METHODS: It's a retrospective study. Patients who underwent Akin osteotomy fixed either with implant or joint capsule suture between 2015 and 2018 were included. Distal articular set angle corrections in pre- and postoperative anteroposterior foot x-rays were calculated by 2 observers. Complications, such as pain, infection, non-union and need of surgery revision, was compared at 1 year follow-up. RESULTS: 89 patients, 30 in the implant group and 59 in the suture group. Mean distal articular set angle corrections were 6.43 (SD 5.54) and 7.36 (SD 5.48) degrees in the implant and suture groups, respectively, without statistically significant differences (p 0454). Complications were 2 local pain and 1 wound infection cases in the suture and implant groups, respectively (p 0138, p 0197). CONCLUSION: Akin osteotomy with suture fixation yields comparable radiological results to metal implant fixation methods without increasing the associated complications.

13.
Clin Infect Dis ; 77(Suppl 1): S53-S61, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37406044

RESUMO

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Humanos , Antibacterianos/uso terapêutico , América Latina , Gestão de Antimicrobianos/métodos , Hospitais , Inquéritos e Questionários
14.
Neuroimage ; 280: 120332, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619796

RESUMO

The majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as "canonical" frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the "Connectivity-based Meta-Bands" (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation are partially aligned with the underlying network topologies at group level for the MEG signals, but they are missing individual idiosyncrasies that may be biasing previous studies, as revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited, revealing a simpler frequency parcellation, not aligned with that defined by the "canonical" frequency bands. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.


Assuntos
Eletroencefalografia , Magnetoencefalografia , Humanos , Algoritmos , Encéfalo , Bases de Dados Factuais
15.
Emerg Infect Dis ; 29(9): 1882-1885, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37610186

RESUMO

We report an acute Chagas disease outbreak among soldiers in Colombia. Trypanosoma cruzi infection was confirmed through parasitology, serology, and molecular methods. Among 9 affected soldiers, 2 died; 7 were hospitalized and received benznidazole treatment, which produced favorable outcomes. Personnel patrolling rural areas in Colombia could be at increased risk for Chagas disease.


Assuntos
Doença de Chagas , Militares , Humanos , Colômbia/epidemiologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Surtos de Doenças
16.
Ann Hematol ; 102(7): 1837-1843, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37246975

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.


Assuntos
COVID-19 , Linfoma de Células B , Receptores de Antígenos Quiméricos , Humanos , Idoso , Vacinas contra COVID-19 , SARS-CoV-2 , Linfoma de Células B/terapia , Terapia Baseada em Transplante de Células e Tecidos , Antígenos CD19
17.
Gynecol Oncol ; 170: 108-113, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36681011

RESUMO

INTRODUCTION: The aim of this study was to evaluate the indications and management of grade III-IV postoperative complications in patients requiring vacuum-assisted open abdomen after debulking surgery for ovarian carcinomatosis. METHODS: Retrospective study of prospectively collected data from patients who underwent a cytoreductive surgery by laparotomy for an epithelial ovarian cancer that required postoperative management of an open abdomen. An abdominal vacuum-assisted wound closure (VAWC) was applied in cases of abdominal compartmental syndrome (ACS) or intra-abdominal hypertension, to prevent ACS. The fascia was closed with a suture or a biologic mesh. The primary aim was to achieve primary fascial closure. Secondary outcomes considered included complications of cytoreductive surgery (CRS) and open abdominal wounds (hernia, fistula). RESULTS: Two percent of patients who underwent CRS required VAWC during the study's patient inclusion period. VAWC indications included: (i) seven cases of gastro-intestinal perforation, (ii) three necrotic enterocolitis, (iii) two intestinal ischemia, (iv) three anastomotic leakages and (v) four intra-abdominal hemorrhages. VAWC was used to treat indications (i) to (iv) (which represented 73.7% of cases), to prevent compartmental syndrome. Primary fascia closure was achieved in 100% of cases, in four cases (21.0%) a biologic mesh was used. Median hospital stay was 65 days (range: 18-153). Four patients died during hospitalization, three of these within 30 days of VAWC completion. CONCLUSION: VAWC for managing open abdominal wounds is a reliable technique to treat surgical post-CRS complications in advanced ovarian cancer and reduces the early post-operative mortality in cases presenting with severe complications.


Assuntos
Traumatismos Abdominais , Técnicas de Fechamento de Ferimentos Abdominais , Produtos Biológicos , Tratamento de Ferimentos com Pressão Negativa , Neoplasias Ovarianas , Humanos , Feminino , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Abdome/cirurgia , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias Ovarianas/etiologia , Carcinoma Epitelial do Ovário/etiologia , Tratamento de Ferimentos com Pressão Negativa/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/métodos
19.
Biomacromolecules ; 24(10): 4419-4429, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-36696687

RESUMO

Multicomponent self-assembly offers opportunities for the design of complex and functional biomaterials with tunable properties. Here, we demonstrate how minor modifications in the molecular structures of peptide amphiphiles (PAs) and elastin-like recombinamers (ELs) can be used to generate coassembling tubular membranes with distinct structures, properties, and bioactivity. First, by introducing minor modifications in the charge density of PA molecules (PAK2, PAK3, PAK4), different diffusion-reaction processes can be triggered, resulting in distinct membrane microstructures. Second, by combining different types of these PAs prior to their coassembly with ELs, further modifications can be achieved, tuning the structures and properties of the tubular membranes. Finally, by introducing the cell adhesive peptide RGDS in either the PA or EL molecules, it is possible to harness the different diffusion-reaction processes to generate tubular membranes with distinct bioactivities. The study demonstrates the possibility to trigger and achieve minor but crucial differences in coassembling processes and tune material structure and bioactivity. The study demonstrates the possibility to use minor, yet crucial, differences in coassembling processes to tune material structure and bioactivity.


Assuntos
Materiais Biocompatíveis , Peptídeos , Peptídeos/química , Estrutura Molecular
20.
Pharmacol Res ; 187: 106579, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435269

RESUMO

The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.


Assuntos
Ritmo Circadiano , Gordura Intra-Abdominal , Obesidade Mórbida , Ácido Oleico , Gordura Subcutânea , Humanos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Obesidade Mórbida/fisiopatologia , Ácido Oleico/farmacologia , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/fisiologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/fisiologia
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