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1.
Eur Arch Otorhinolaryngol ; 281(4): 2087-2093, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37980605

RESUMO

PURPOSE: This study explores the potential of the Chat-Generative Pre-Trained Transformer (Chat-GPT), a Large Language Model (LLM), in assisting healthcare professionals in the diagnosis of obstructive sleep apnea (OSA). It aims to assess the agreement between Chat-GPT's responses and those of expert otolaryngologists, shedding light on the role of AI-generated content in medical decision-making. METHODS: A prospective, cross-sectional study was conducted, involving 350 otolaryngologists from 25 countries who responded to a specialized OSA survey. Chat-GPT was tasked with providing answers to the same survey questions. Responses were assessed by both super-experts and statistically analyzed for agreement. RESULTS: The study revealed that Chat-GPT and expert responses shared a common answer in over 75% of cases for individual questions. However, the overall consensus was achieved in only four questions. Super-expert assessments showed a moderate agreement level, with Chat-GPT scoring slightly lower than experts. Statistically, Chat-GPT's responses differed significantly from experts' opinions (p = 0.0009). Sub-analysis revealed areas of improvement for Chat-GPT, particularly in questions where super-experts rated its responses lower than expert consensus. CONCLUSIONS: Chat-GPT demonstrates potential as a valuable resource for OSA diagnosis, especially where access to specialists is limited. The study emphasizes the importance of AI-human collaboration, with Chat-GPT serving as a complementary tool rather than a replacement for medical professionals. This research contributes to the discourse in otolaryngology and encourages further exploration of AI-driven healthcare applications. While Chat-GPT exhibits a commendable level of consensus with expert responses, ongoing refinements in AI-based healthcare tools hold significant promise for the future of medicine, addressing the underdiagnosis and undertreatment of OSA and improving patient outcomes.


Assuntos
Tomada de Decisão Clínica , Apneia Obstrutiva do Sono , Humanos , Estudos Transversais , Estudos Prospectivos , Alanina Transaminase , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia
2.
J Infect Dis ; 226(4): 585-594, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-35413121

RESUMO

The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested rhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a seronegative macaque oral challenge model. Immunogens included a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing titers comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-specific cytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and was detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV evades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity superior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.


Assuntos
Infecções por Citomegalovirus , Vacinas contra Citomegalovirus , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Citomegalovirus , Humanos , Macaca mulatta , Proteínas do Envelope Viral
3.
Biotechnol Lett ; 43(4): 845-854, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33389270

RESUMO

The aim of this study was to characterize the growth of the fungus Leucoagaricus gongylophorus LEU18496, isolated from the fungus garden of the nest of leaf cutter ants Atta mexicana. The fungus garden was cultivated in an artificial laboratory nest and the fungus further grown in submerged (SmC) and solid state (SSC) cultures with sugarcane bagasse, grass or model substrates containing CM-cellulose, xylan or lignin. The CO2 production rate with grass in SmC (Vmax 34.76 mg CO2 Lgas-1 day- 1) was almost four times than SSC (Vmax 9.49 mg CO2 Lgas-1 day- 1), while the production rate obtained in sugarcane bagasse in SmC (Vmax 16.02 mg CO2 Lgas-1 day- 1) was almost three times than that for SSC (Vmax 5.42 mg CO2 Lgas-1 day- 1). In addition, the fungus grew with defined carbon substrates mixtures in SmC, but at different rates, first xylan, followed by CM-cellulose and lignin. Endoglucanase and xylanase activities (U mgprotein-1) were detected in all cultures, the specific activity was higher in the fungus-garden, 5.2 and 1.8; followed by SSC-grass, 1.5 and 0.8, and SSC-bagasse, 0.9 and 0.8, respectively. Laccase activity in the fungus-garden was 44.8 U L- 1 and 10.9 U L- 1 in the SSC-grass. The gongylidia structures observed by environmental scanning electron microscopy were ca. 40 µm and the hyphae width ca. 5 µm. The results show that L. gongylophorus from A. mexicana have promising applications for the treatment of plant residues to release fermentable sugars and the production of high value lignocellulolytic enzymes such as endoglucanase, xylanase or laccases.


Assuntos
Agaricales/crescimento & desenvolvimento , Formigas/microbiologia , Celulase/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Lignina/metabolismo , Agaricales/enzimologia , Agaricales/isolamento & purificação , Animais , Celulose/química , Cromatografia Gasosa , Fermentação , Proteínas Fúngicas/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Microscopia Eletrônica de Varredura , Folhas de Planta/parasitologia
4.
J Clin Microbiol ; 54(1): 25-34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26311858

RESUMO

Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis; however, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are now licensed for the prevention of MnB disease; a possible additional benefit of these vaccines could be to protect against disease indirectly by disrupting nasopharyngeal carriage (e.g., herd protection). To investigate this possibility, accurate diagnostic approaches to characterize MnB carriage isolates are required. In contrast to invasive meningococcal disease (IMD) isolates, which can be readily serogrouped, carriage isolates often lack capsule expression, making standard phenotypic assays unsuitable for strain characterization. Several antibody-based methods were evaluated for their abilities to serogroup isolates and were compared with two genotyping methods (real-time PCR [rt-PCR] and whole-genome sequencing [WGS]) to identify which approach would most accurately ascertain the polysaccharide groups associated with carriage isolates. WGS and rt-PCR were in agreement for 99% of IMD isolates, including those with coding sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly identified serogroups for 69 to 98% of IMD isolates. In contrast, only 47% of carriage isolates were groupable by genotypic methods, due to mutations within the capsule operon; of the isolates identified by genotypic methods, ≤43% were serogroupable with any of the phenotypic methods tested. These observations highlight the difficulties in the serogrouping and capsular genogrouping of meningococcal carriage isolates. Based on our findings, WGS is the most suitable approach for the characterization of meningococcal carriage isolates.


Assuntos
Cápsulas Bacterianas/classificação , Portador Sadio/microbiologia , Técnicas de Genotipagem/métodos , Neisseria meningitidis/classificação , Infecções por Neisseriaceae/microbiologia , Sorotipagem/métodos , Adolescente , Adulto , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/imunologia , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Adulto Jovem
5.
Phys Rev Lett ; 115(17): 171801, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26551101

RESUMO

We employ a continuum approach to the three valence-quark bound-state problem in relativistic quantum field theory to predict a range of properties of the proton's radial excitation and thereby unify them with those of numerous other hadrons. Our analysis indicates that the nucleon's first radial excitation is the Roper resonance. It consists of a core of three dressed quarks, which expresses its valence-quark content and whose charge radius is 80% larger than the proton analogue. That core is complemented by a meson cloud, which reduces the observed Roper mass by roughly 20%. The meson cloud materially affects long-wavelength characteristics of the Roper electroproduction amplitudes but the quark core is revealed to probes with Q(2)≳3m(N)(2).

6.
Opt Express ; 21(26): 32450-67, 2013 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-24514839

RESUMO

A supercontinuum laser based double integrating sphere setup in combination with an unscattered transmittance measurement setup was developed and carefully validated for optical characterization of turbid samples in the 500-2250 nm wavelength range. A set of 57 liquid optical phantoms, covering a wide range of absorption and scattering properties, were prepared and measured at two sample thicknesses. The estimated bulk optical properties matched well for both thicknesses, and with theory and literature, without significant crosstalk between absorption and scattering. Equations were derived for the bulk scattering properties µ(s), µ(s)' and g of Intralipid® 20% which can be used to calculate the bulk scattering properties of intralipid-dilutions in the 500-2250 nm range.


Assuntos
Algoritmos , Lasers , Nanopartículas/química , Nanopartículas/ultraestrutura , Nefelometria e Turbidimetria/métodos , Fosfolipídeos/química , Refratometria/métodos , Óleo de Soja/química , Emulsões/análise , Emulsões/química , Imagens de Fantasmas , Fosfolipídeos/análise , Óleo de Soja/análise
7.
Phys Rev E ; 108(6-1): 064904, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38243544

RESUMO

The triggering of avalanches is investigated using discrete element simulations for a process of random extraction of spheres. A monolayer, formed by identical spheres in a hexagonal configuration, is placed on a tilted plane surrounded by a small fence that sustains the spheres, mimicking the disposal of fruits in the market. Then, a random continuous extraction process of spheres is imposed until the collapse. For this simple numerical experiment, a phase diagram was obtained to visualize the occurrence of avalanches triggered by vacancies as a function of the tilting angle, system size, and friction coefficient. More importantly, a subzone was found where we can predict the critical number of extractions until the avalanche takes place. The prediction is made from an evolution model of the average coordination number based on statistical considerations. The theoretical prediction also gives a constant critical void fraction of spheres, which implies the system collapses at a critical packing fraction.

8.
Front Immunol ; 14: 1286750, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022679

RESUMO

The ability to expand and activate natural Killer (NK) cells ex vivo has dramatically changed the landscape in the development of novel adoptive cell therapies for treating cancer over the last decade. NK cells have become a key player for cancer immunotherapy due to their innate ability to kill malignant cells while not harming healthy cells, allowing their potential use as an "off-the-shelf" product. Furthermore, recent advancements in NK cell genetic engineering methods have enabled the efficient generation of chimeric antigen receptor (CAR)-expressing NK cells that can exert both CAR-dependent and antigen-independent killing. Clinically, CAR-NK cells have shown promising efficacy and safety for treating CD19-expressing hematologic malignancies. While the number of pre-clinical studies using CAR-NK cells continues to expand, it is evident that solid tumors pose a unique challenge to NK cell-based adoptive cell therapies. Major barriers for efficacy include low NK cell trafficking and infiltration into solid tumor sites, low persistence, and immunosuppression by the harsh solid tumor microenvironment (TME). In this review we discuss the barriers posed by the solid tumor that prevent immune cell trafficking and NK cell effector functions. We then discuss promising strategies to enhance NK cell infiltration into solid tumor sites and activation within the TME. This includes NK cell-intrinsic and -extrinsic mechanisms such as NK cell engineering to resist TME-mediated inhibition and use of tumor-targeted agents such as oncolytic viruses expressing chemoattracting and activating payloads. We then discuss opportunities and challenges for using combination therapies to extend NK cell therapies for the treatment of solid tumors.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Microambiente Tumoral , Células Matadoras Naturais , Imunoterapia Adotiva/métodos
9.
Cell Physiol Biochem ; 29(5-6): 697-704, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22613970

RESUMO

Insulin secretion from the pancreatic ß-cell is controlled by changes in membrane potential and intracellular Ca(2+). The contribution of intracellular Ca(2+) stores to this process is poorly understood. We have previously shown that ß-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express reduced levels of IP(3) receptors and defects in IP(3)-dependent Ca(2+) signaling. To further elucidate the effect of the Anx7(+/-) mutation on signaling related to intracellular Ca(2+) stores in the ß-cell, we measured the effects of Ca(2+) mobilizing agents on electrical activity, intracellular Ca(2+) and insulin secretion in control and mutant ß-cells. We found that the muscarinic agonist carbachol and the ryanodine receptor agonists caffeine and 4-chloro-m-cresol had more potent depolarizing effects on Anx7(+/-) ß-cells compared to controls. Accordingly, glucose-induced insulin secretion was augmented to a greater extent by caffeine in mutant islets. Surprisingly, ryanodine receptor-mediated Ca(2+) mobilization was not affected by the Anx7(+/-) mutation, suggesting that the mechanism underlying the observed differences in electrical and secretory responsiveness does not involve intracellular Ca(2+) stores. Our results provide evidence that both IP3 receptors and ryanodine receptors play important roles in regulating ß-cell membrane potential and insulin secretion, and that the Anx7(+/-) mutation is associated with alterations in the signaling pathways related to these receptors.


Assuntos
Anexina A7/fisiologia , Cálcio/metabolismo , Ilhotas Pancreáticas/fisiopatologia , Mutação , Animais , Anexina A7/genética , Glucose/farmacologia , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Potenciais da Membrana , Camundongos , Camundongos Knockout , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos
10.
Cureus ; 14(2): e21910, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35265431

RESUMO

Snake bites (ophidism) constitute a public health problem in tropical and subtropical countries, due to their lethality, and the lack of access to prompt treatment in these regions. Catastrophic consequences follow the injection of the venom due to its proteolytic, procoagulant, hemorrhagic, nephrotoxic, vasculotoxic, and myonecrotizing properties, which can lead to severe complications if not managed promptly and adequately. In this report, we present the case of a 26-year-old male patient who suffered a snake bite (Bothrops asper) on the back of his right foot. Initially, he received eight vials of antivenom and was transferred to a specialized center. However, a few hours after his arrival, a necrotic wound developed on the back of the foot along with compartment syndrome, and hence emergency fasciotomies had to be performed and the patient was admitted to the ICU for multidisciplinary management and continuous monitoring. After 14 days, fasciotomy closure and eschar incision on the dorsum of the foot were performed along with an aesthetic reconstruction with an advancement flap and full-thickness graft. The patient had a satisfactory outcome thanks to the prompt evaluation and access to a unit with experience in managing highly complex cases. Our case highlights the importance of prompt and meticulous assessment after a snake bite due to its potential for causing highly complex clinical scenarios, and early diagnosis, proper management, and continuous multidisciplinary monitoring are key for a favorable prognosis. In many cases, these bites can lead to significant tissue loss and may necessitate the amputation of the affected limb. In severe cases, compartment syndrome frequently ensues and further complicates the management and increases morbidity if not recognized and managed promptly.

11.
Cureus ; 13(9): e17884, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34660083

RESUMO

Pterygium is a common ocular disease caused by abnormal cellular proliferation leading to abnormal fibrovascular growth of the conjunctiva. The main treatment is surgical removal; however, despite the improvement of surgical techniques and development of adjuvant therapies, postoperative recurrence, which can be as high as 89%, remains a challenge. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique, although there is no gold standard technique to prevent pterygium recurrence. We have conducted a thorough and comprehensive review of the scientific literature regarding the use of PRF membranes in pterygium surgery. We aim to assess the safety, effectiveness, and applicability of platelet-rich fibrin membrane for primary pterygium surgery and assess its possible benefits in resource-limited settings.

12.
J Basic Clin Physiol Pharmacol ; 32(5): 935-942, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34018379

RESUMO

OBJECTIVES: The role of the environment and climate in the transmission and case fatality rates of SARS-CoV-2 is still being investigated a year into the pandemic. Elevation and air quality are believed to be significant factors in the development of the pandemic, but the influence of additional environmental factors remains unclear. METHODS: We explored the relationship between the cumulative number of infections and mortality cases with climate (temperature, precipitation, solar radiation, water vapor pressure, wind), environmental data (elevation, normalized difference vegetation index or NDVI, particulate matter at 2.5 µm or PM2.5 and NO2 concentration), and population density in Peru. We use confirmed cases of infection from 1,287 districts and mortality in 479 districts, we used Spearman's correlations to assess the bivariate correlation between environmental and climatic factors with cumulative infection cases, cumulative mortality and case-fatality rate. We explored district cases within the ecozones of coast, sierra, high montane forest and lowland rainforest. RESULTS: Multiple linear regression models indicate elevation, mean solar radiation, air quality, population density and green vegetation cover, as a socioeconomic proxy, are influential factors in the distribution of infection and mortality of SARS-CoV-2 in Peru. Case-fatality rate was weakly associated with elevation. CONCLUSIONS: Our results also strongly suggest that exposure to poor air quality is a significant factor in the mortality of individuals below the age of 30. We conclude that environmental and climatic factors do play a significant role in the transmission and case fatality rates in Peru, however further study is required to see if these relationships are maintained over time.


Assuntos
COVID-19/epidemiologia , Meio Ambiente , Poluição do Ar , COVID-19/mortalidade , COVID-19/transmissão , Clima , Humanos , Modelos Lineares , Peru/epidemiologia , SARS-CoV-2 , Fatores Socioeconômicos , Tempo (Meteorologia)
13.
Cureus ; 13(9): e18004, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667680

RESUMO

We present the case of an 18-year-old male patient with a penetrating lesion at zone II of the flexor compartment of the left hand. During surgery, complete reabsorption of the second deep and superficial flexor tendons was evidenced, prompting the decision to perform a two-stage procedure. First, a spacer was placed, and pulley reconstruction was performed. Six weeks later, we placed a cadaveric allograft and splint with the Kleinert-Duran technique for proper rehabilitation. Our case report highlights that a two-stage procedure with an allograft is a feasible technique resulting in good post-surgical functional status despite tendon reabsorption and six months between trauma and surgical intervention.

14.
J Immunother Cancer ; 9(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33479024

RESUMO

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1-blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients' tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1- patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.


Assuntos
Antígeno B7-H1/metabolismo , Técnicas de Cocultura/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Células Matadoras Naturais/citologia , Neoplasias Pulmonares/imunologia , Células A549 , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Células K562 , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral
15.
iScience ; 24(6): 102619, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34159300

RESUMO

Despite the remarkable success of chimeric antigen receptor (CAR)-T cells against hematologic malignancies, severe off-tumor effects have constrained their use against solid tumors. Recently, CAR-engineered natural killer (NK) cells have emerged as an effective and safe alternative. Here, we demonstrate that HER2 CAR-expression in NK cells from healthy donors and patients with breast cancer potently enhances their anti-tumor functions against various HER2-expressing cancer cells, regardless of MHC class I expression. Moreover, HER2 CAR-NK cells exert higher cytotoxicity than donor-matched HER2 CAR-T cells against tumor targets. Importantly, unlike CAR-T cells, HER2 CAR-NK cells do not elicit enhanced cytotoxicity or inflammatory cytokine production against non-malignant human lung epithelial cells with basal HER2 expression. Further, HER2 CAR-NK cells maintain high cytotoxic function in the presence of immunosuppressive factors enriched in solid tumors. These results show that CAR-NK cells may be a highly potent and safe source of immunotherapy in the context of solid tumors.

16.
Cell Metab ; 33(6): 1205-1220.e5, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852875

RESUMO

NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor microenvironment is due to suppression of glucose metabolism via lipid peroxidation-associated oxidative stress. Activation of the Nrf2 antioxidant pathway restored NK cell metabolism and function and resulted in greater anti-tumor activity in vivo. Strikingly, expanded NK cells reprogrammed with complete metabolic substrate flexibility not only sustained metabolic fitness but paradoxically augmented their tumor killing in the tumor microenvironment and in response to nutrient deprivation. Our results uncover that metabolic flexibility enables a cytotoxic immune cell to exploit the metabolic hostility of tumors for their advantage, addressing a critical hurdle for cancer immunotherapy.


Assuntos
Antineoplásicos/imunologia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Neoplasias/terapia , Microambiente Tumoral , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Células Matadoras Naturais/citologia , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto Jovem
17.
Rep Biochem Mol Biol ; 9(3): 297-308, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33649723

RESUMO

BACKGROUND: One of the major challenges in gene therapy is producing gene carriers that possess high transfection efficiency and low cytotoxicity (1). To achieve this purpose, crystal nanocellulose (CNC) -based nanoparticles grafted with polyethylenimine (PEI) have been developed as an alternative to traditional viral vectors to eliminate potential toxicity and immunogenicity. METHODS: In this study, CNC-PEI10kDa (CNCP) nanoparticles were synthetized and their transfection efficiency was evaluated and compared with linear cationic PEI10kDa (PEI) polymer in HEK293T (HEK) cells. Synthetized nanoparticles were characterized with AFM, FTIR, DLS, and gel retardation assays. In-vitro gene delivery efficiency by nano-complexes and their effects on cell viability were determined with fluorescent microscopy and flow cytometry. RESULTS: Prepared CNC was oxidized with sodium periodate and its surface cationized with linear PEI. The new CNCP nano-complex showed different transfection efficiencies at different nanoparticle/plasmid ratios, which were greater than those of PEI polymer. CNPC and Lipofectamine were similar in their transfection efficiencies and effect on cell viability after transfection. CONCLUSION: CNCP nanoparticles are appropriate candidates for gene delivery. This result highlights CNC as an attractive biomaterial and demonstrates how its different cationized forms may be applied in designing gene delivery systems.

18.
PLoS One ; 14(11): e0225367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31747419

RESUMO

We estimate the effects of Peru's oldest watershed payments for environmental services (PES) initiative in Moyobamba (Andes-Amazon transition zone) and disentangle the complex intervention into its two main forest conservation treatments. First, a state-managed protected area (PA) was established, allowing sustainable use but drastically limiting de facto land use and land rights of households in the upper watershed through command-and-control interventions. Second, a subset of those environmentally regulated households also received incentives: PES-like voluntary contracts with conditional in-kind rewards, combined with access to participation in sustainable income-generating activities of the integrated conservation and development project (ICDP) type. To evaluate impacts, we perform matching procedures and adjustment regressions to obtain the average treatment effect on the treated (ATT) of each intervention. We investigate impacts on plot-level forest cover and household welfare for the period 2010-2016. We find that both treatments-command-and-control restrictions and the incentive package-modestly but significantly mitigated primary forest loss. Incentive-induced conservation gains came at elevated per-hectare implementation costs. We also find positive effects on incentive-treated households' incomes and assets; however, their self-perceived wellbeing counterintuitively declined. We hypothesise that locally frustrated beneficiary expectations vis-a-vis the ambitiously designed PES-cum-ICDP intervention help explain this surprising finding. We finalise with some recommendations for watershed incentives and policy mix design in Moyobamba and beyond.


Assuntos
Conservação dos Recursos Naturais/economia , Florestas , Recompensa , Conservação dos Recursos Naturais/métodos , Características da Família , Modelos Teóricos , Peru
19.
PLoS One ; 14(1): e0208356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641545

RESUMO

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors under evaluation as vaccine antigens. Clinical S. aureus isolates have the biosynthetic capability to express either CP5 or CP8 and an understanding of the relationship between CP genotype/phenotype and S. aureus epidemiology is valuable. Using whole genome sequencing, the clonal relatedness and CP genotype were evaluated for disease-associated S. aureus isolates selected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) to represent different geographic regions in the United States (US) during 2004 and 2009-10. Thirteen prominent clonal complexes (CC) were identified, with CC5, 8, 30 and 45 representing >80% of disease isolates. CC5 and CC8 isolates were CP type 5 and, CC30 and CC45 isolates were CP type 8. Representative isolates from prevalent CC were susceptible to in vitro opsonophagocytic killing elicited by anti-CP antibodies, demonstrating that susceptibility to opsonic killing is not linked to the genetic lineage. However, as not all S. aureus isolates may express CP, isolates representing the diversity of disease isolates were assessed for CP production. While approximately 35% of isolates (primarily CC8) did not express CP in vitro, CP expression could be clearly demonstrated in vivo for 77% of a subset of these isolates (n = 20) despite the presence of mutations within the capsule operon. CP expression in vivo was also confirmed indirectly by measuring an increase in CP specific antibodies in mice infected with CP5 or CP8 isolates. Detection of antigen expression in vivo in relevant disease states is important to support the inclusion of these antigens in vaccines. Our findings confirm the validity of CP as vaccine targets and the potential of CP-based vaccines to contribute to S. aureus disease prevention.


Assuntos
Cápsulas Bacterianas/metabolismo , Epidemiologia Molecular , Polissacarídeos Bacterianos/metabolismo , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/metabolismo , Animais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Cápsulas Bacterianas/genética , Vias Biossintéticas/genética , Modelos Animais de Doenças , Feminino , Humanos , Mutação INDEL/genética , Soros Imunes/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Óperon/genética , Proteínas Opsonizantes/metabolismo , Fagocitose , Polimorfismo de Nucleotídeo Único/genética , Polissacarídeos Bacterianos/genética , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Estados Unidos/epidemiologia
20.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1430557

RESUMO

El retratamiento no quirúrgico es la primera opción ante el fracaso del tratamiento endodóntico, por lo que se vuelve importante asegurar el completo retiro del material de relleno del conducto radicular, para mejorar el pronóstico del procedimiento. Los cementos biocerámicos en base a silicatos cálcicos han aparecido en los últimos años, caracterizados principalmente por su bioactividad, lo que adicionalmente se puede traducir en una mayor dificultad para su retiro del conducto radicular. El objetivo de esta revisión es determinar qué técnica de retratamiento es más efectiva en la eliminación de cementos selladores biocerámicos, en base al volumen de material remanente en el conducto radicular, evaluado a través del análisis de imágenes con micro-CT. Se realizó una revisión sistemática mediante la búsqueda de publicaciones en las bases de datos Pubmed, ScienceDirect y SciELO, de los últimos 10 años, en idioma español e inglés. Se incluyeron sólo estudios in vitro de dientes obturados con cemento biocerámico y diferentes técnicas de retratamiento endodóntico, en los que se evalúe la limpieza del conducto post eliminación del relleno mediante micro-CT. De un total de 174 artículos encontrados, 7 fueron seleccionados, analizados y se incluyeron en esta revisión sistemática. Los resultados de los estudios seleccionados no encuentran diferencias significativas en la eliminación de material entre las diferentes técnicas de retratamiento evaluadas. A pesar de la heterogeneidad presente en las metodologías de los artículos analizados, ninguna técnica de retratamiento ni técnicas complementarias lograron dejar completamente limpios los conductos radiculares, por lo que se sugiere realizar nuevos estudios en el futuro que evalúen nuevas técnicas de desobturación radicular.


Non-surgical retreatment is the first option in the case of endodontic treatment failure, so it becomes important to ensure complete removal of the root canal filling material, to improve the prognosis of the procedure. Bioceramic cements based on calcium silicate have appeared in recent years, characterized mainly for their bioactivity, which can additionally translate into greater difficulty in their removal from the root canal. The aim of this review is to determine which retreatment technique is most effective in the removal of bioceramic sealer cements, evaluated through micro-CT image analysis. A systematic review was performed by searching for publications in Pubmed, ScienceDirect and SciELO databases, of the last 10 years in Spanish and English. Only in vitro studies of teeth filled with bioceramic cement and different endodontic retreatment techniques were included, in which the cleaning of the canal after removal of the filling was evaluated by micro- CT. From a total of 174 articles found, 7 were selected, analyzed and included in this systemic review. The results of the included studies did not find significant differences in the removal of material between the different retreatment techniques evaluated. Despite the heterogeneity in the methodologies of the studies, no retreatment technique or complementary techniques were able to completely clean the root canals, it is therefore suggested that new studies be carried out in the future to evaluate new techniques.

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