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1.
JDS Commun ; 5(2): 91-95, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38482114

RESUMEN

The purpose of this study was to investigate the potential of using ruminal pH measurements to track time-series ruminal volatile fatty acid (VFA) concentrations occurring in response to short-term dietary disruption. Four ruminally cannulated dry Holstein dairy cows were individually housed and assigned to 4 treatments in a Latin square design. Treatments differing in forage-to-concentrate (F:C) ratio (100:0 to 55:45) were used because they were expected to result in large differences in VFA concentration, over which the relationships between pH and VFA could be robustly evaluated. Each sampling period lasted 36 h. Animals were removed from pasture and fasted for 24 h, after which time they were fed their treatment ration for 2 h and sampled for rumen fluid hourly for 12 h. Rumen fluid samples were analyzed immediately for pH, frozen, and subsequently analyzed for VFA concentrations using gas chromatography. Animals were returned to pasture for 7 d between sampling periods. To confirm that the short-term dietary disruptions resulted in expected variation in VFA concentrations, mean VFA concentrations during each animal period (n = 16) were analyzed using a linear mixed effects model with fixed (linear and quadratic) effects for F:C ratio and random effects for animal and period. Results indicated significant changes in VFA concentration across F:C ratio, but no significant shifts in VFA molar proportions, perhaps due to the short-term nature of the feeding protocol. To explore opportunity to use pH measurements to explain variability in VFA concentrations in real time across dietary conditions, a linear mixed-effect model was used to link the time-series measurements (n = 207). The VFA concentrations were analyzed with linear mixed effect models using linear and quadratic terms for pH, and random effects for animal and period. These models had poor accuracy, with residual error variance ranging from 21% to 38%, and residuals patterning significantly with F:C ratio. The data suggest that pH may lack reliability for VFA prediction in short-term feeding scenarios differing considerably in F:C ratio.

2.
Public Health ; 228: 200-205, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38412759

RESUMEN

OBJECTIVES: State-level abortion bans in the United States have created a complex legal landscape that forces many prospective patients to travel long distances to access abortion care. The financial strain and logistical difficulties associated with travelling out of state for abortion care may present an insurmountable barrier to some individuals, especially to those with limited resources. Tracking the impact of these abortion bans on travel and housing is crucial for understanding abortion access and economic changes following the Dobbs U.S. Supreme Court decision. STUDY DESIGN: This study used occupancy data from an average of 2,349,635 (standard deviation = 111,578) U.S. Airbnb listings each month from October 1st, 2020, through April 30th, 2023, to measure the impact of abortion bans on travel for abortion care and the resulting economic effects on regional economies. METHODS: The study used a synthetic difference-in-differences design to compare monthly-level occupancy rate data from 1-bedroom entire-place Airbnb rentals within a 30-min driving distance of abortion clinics in states with and without abortion bans. RESULTS: The study found a 1.4 percentage point decrease in occupancy rates of Airbnbs around abortion clinics in states where abortion bans were in effect, demonstrating reductions in Airbnb use in states with bans. In the 6-month period post Dobbs, this decrease translates to 16,548 fewer renters and a $1.87 million loss in revenue for 1-bedroom entire-place Airbnbs within a 30-min catchment area of abortion facilities in states with abortion restrictions. CONCLUSION: This novel use of Airbnb data provides a unique perspective on measuring demand for abortion and healthcare services and demonstrates the value of this data stream as a tool for understanding economic impacts of health policies.


Asunto(s)
Aborto Inducido , Vivienda , Embarazo , Femenino , Estados Unidos , Humanos , Estudios Prospectivos , Decisiones de la Corte Suprema , Viaje , Aborto Legal
4.
Int J Oral Maxillofac Surg ; 52(6): 691-695, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36115779

RESUMEN

The aim of this technical note is to describe a protocol for three-dimensional virtual simulation of orthognathic surgery that has been designed to be easily implemented, without the need for any special clinical apparatus, software brand, or computed tomography sequence. The protocol comprises innovative concepts and simplified steps for image segmentation, creation of a composite skull, control of the condylar position, and sequencing of bimaxillary surgery. This protocol was applied by the developers in about 2000 cases performed between 2015 and 2022, and has become quite popular among local surgeons. Previous preliminary studies have shown that it meets the accuracy standards for clinical use, although further studies with larger numbers of patients are desirable for additional validation.


Asunto(s)
Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Cirugía Asistida por Computador , Humanos , Procedimientos Quirúrgicos Ortognáticos/métodos , Imagenología Tridimensional/métodos , Cráneo , Simulación por Computador , Cirugía Asistida por Computador/métodos
5.
Braz. j. otorhinolaryngol. (Impr.) ; 88(supl.5): 126-132, Nov.-Dec. 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1420892

RESUMEN

Abstract Objective: To evaluate the surgical rehabilitation of cleft lip and/or palate by the Brazilian public health system. Methods: Retrospective, analytical and comparative ecological study, with information on hospital procedures performed on individuals with cleft lip and/or palate in Centers authorized by the Brazilian public health system, between the years 2008 and 2020. The information was collected in databases Ministry of Health data. Results: Between 2008 and 2020, there was an increase of 8 (36.4%) qualified Centers in Brazil, currently having 30 Centers in 100% of the geographic regions. The surgical procedures performed totaled 68,716; with multiple surgeries being the most frequent. Complete cleft lip and palate was the most frequent type in hospital admissions. The public financial resources invested in the surgical rehabilitation of cleft lip and palate in the qualified Lip and Palate Malformation Treatment Centers were US$ 39,693 million, making an average value per procedure of US$ 577.64. Conclusions: In Brazil, public health system performed and financed, over the years 2008 and 2020, an important volume of surgical procedures for cleft lip and/or palate, which presented a polarization in the Southeast region but with a slight tendency expansion to other regions of the country. The most performed surgical procedures were multiple surgeries and mostly for individuals with cleft lip and palate. The amounts paid showed a heretogeneous distribution in the national territory. Level of evidence: Level 5: Report containing program evaluation data.

6.
Braz J Otorhinolaryngol ; 88 Suppl 5: S126-S132, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35717308

RESUMEN

OBJECTIVE: To evaluate the surgical rehabilitation of cleft lip and/or palate by the Brazilian public health system. METHODS: Retrospective, analytical and comparative ecological study, with information on hospital procedures performed on individuals with cleft lip and/or palate in Centers authorized by the Brazilian public health system, between the years 2008 and 2020. The information was collected in databases Ministry of Health data. RESULTS: Between 2008 and 2020, there was an increase of 8 (36.4%) qualified Centers in Brazil, currently having 30 Centers in 100% of the geographic regions. The surgical procedures performed totaled 68,716; with multiple surgeries being the most frequent. Complete cleft lip and palate was the most frequent type in hospital admissions. The public financial resources invested in the surgical rehabilitation of cleft lip and palate in the qualified Lip and Palate Malformation Treatment Centers were US$ 39,693 million, making an average value per procedure of US$ 577.64. CONCLUSIONS: In Brazil, public health system performed and financed, over the years 2008 and 2020, an important volume of surgical procedures for cleft lip and/or palate, which presented a polarization in the Southeast region but with a slight tendency expansion to other regions of the country. The most performed surgical procedures were multiple surgeries and mostly for individuals with cleft lip and palate. The amounts paid showed a heretogeneous distribution in the national territory. LEVEL OF EVIDENCE: Level 5: Report containing program evaluation data.


Asunto(s)
Labio Leporino , Fisura del Paladar , Humanos , Brasil , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Salud Pública , Estudios Retrospectivos
7.
J Neonatal Perinatal Med ; 15(2): 351-356, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34974440

RESUMEN

BACKGROUND: There is little published data on how to prepare probiotic supplements for enteral delivery in the NICU. The objective of this study was to determine how a three-strain probiotic blend (Bb-02, TH-4® and BB-12®) would behave when mixed and held for 4 hours with saline water, sterile water, dextrose 5% in water (D5W), 24 kcal preterm formula, and human milk. METHODS: A packet of a three-strain probiotic supplement was mixed with 3 mL of saline water, sterile water, D5W, 24 kcal preterm formula, and human milk (tested at 3 mL and 2 mL). Samples were stored at room temperature for 60 minutes then refrigerated for 180 minutes. Probiotic survival, using quantitative enumeration, and pH were monitored over 4 hours. Samples were passed through a 5 French (Fr) feeding tube at the end of the study to evaluate viscosity. RESULTS: The largest variation in total cell count from 0-time was sterile water with a + 0.26 log(CFU)/mL change at 90 minutes and typical variation is considered±0.50 log units indicating no significant change between samples in 4 hours. Saline water had the lowest final pH at 4.88. All samples easily passed through a 5 Fr feeding tube. CONCLUSION: The study showed minimal change in cell counts across solutions for 4 hours of storage, indicating health care facilities may be able to prepare probiotic supplements with a variety of solutions in pharmacies or milk rooms. This allows greater flexibility for probiotic delivery to preterm infants.


Asunto(s)
Nutrición Enteral , Probióticos , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Leche Humana
9.
Indian J Nephrol ; 31(1): 1-8, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33994680

RESUMEN

The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the FAM20A gene. The syndrome is characterized by impaired amelogenesis of the hypoplastic type and nephrocalcinosis, presenting with presence of thin or absence of enamel, late dental eruption, intrapulpal calcifications, bilateral nephrocalcinosis, and normal plasma calcium level. The objective is to characterize ERS by systematically literature reviewing, highlighting the main findings of the syndrome to increase knowledge about this condition in the health professionals. The study is a systematic review of the scientific literature, whose research was developed in the PubMed database in March 2018. A total of 69 articles were found. Two authors analyzed their abstracts and selected, according to the language and main subject, 30 articles to write this study. A total of 69 patients were cited in the studies and their data were analysed. There was gender equivalence and the ages ranged from 1 to 64 years old. There is a clear hereditary relation of the syndrome, since there was consanguinity in 18 cases, indicating a percentage of 26.08% and family history in 30 cases (43.47%). Laboratory changes vary greatly from patient to patient and may even remain unchanged. The relationship between the syndrome and the mutation in the FAM20A gene can be proven from the data, since all patients with ERS screened by the mutation were positive. With the advancement of the ERS studies, some associations with the syndrome are suspected, such as the presence of gingival fibromatosis, hearing loss, and hypertrichosis. Thus, it is noticed that the syndrome does not show a predilection for gender or age and there is a strong hereditary character, marked by the consanguinity and family history of the patients. The association with the FAM20A gene is reinforced, since the mutation was identified in all patients analyzed.

10.
Transl Anim Sci ; 5(2): txab010, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34041440

RESUMEN

Precision technologies for confinement animal agricultural systems have increased rapidly over the past decade, though precision technology solutions for pastured livestock remain limited. There are a number of reasons for this limited expansion of technologies for pastured animals, including networking availability and reliability, power requirements, and expense, among others. The objective of this work was to demonstrate a rapidly deployable long-range radio (LoRa) based, low-cost sensor suite that can be used to track location and activity of pastured livestock. The sensor is comprised of an inexpensive Arduino-compatible microprocessor, a generic MPU-9250 motion sensor which contains a 3-axis accelerometer, 3-axis magnetometer, and a 3-axis gyroscope, a generic GPS receiver, and a RFM95W generic LoRa radio. The microprocessor can be programmed flexibly using the open source Arduino IDE software to adjust the frequency of sampling, the data packet to send, and what conditions are needed to operate. The LoRa radio transmits to a Dragino LoRa gateway which can also be flexibly programmed through the Arduino IDE software to send data to local storage or, in cases where a web or cellular connection is available, to cloud storage. The sensor was powered using a USB cord connected to a 3,350 mAh lithium-ion battery pack. The Dragino gateway was programmed to upload data to the ThingSpeak IoT application programming interface for data storage, handling, and visualization. Evaluations showed minimal benefit associated with reducing sampling frequency as a strategy to preserve battery life. Packet loss ranged from 40% to 60%. In a 3 d evaluation on pastured sheep, the sensor suite was able to report GPS locations, inertial sensor readings, and temperature. Preliminary demonstrations of our system are satisfactory to detect animal location based on GPS data in real-time. This system has clear utility as a lower-cost strategy to deploy flexible, useful precision technologies for pasture-based livestock species.

11.
Mater Sci Eng C Mater Biol Appl ; 121: 111815, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33579459

RESUMEN

This work deals with two new molecule-based materials, namely NiII-complexes of general formulae [Ni(L1)2] (Ni1) and [Ni(L2)2] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 21/c, also the asymmetric unit comprises of one NiII ion located on an inversion centre and one anionic ligand, which acts as a κ2N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 - 41.37 µM and 1.06 - 14.91 µM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 µM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (Kb values ~104 mol L--1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (Kb values ⁓103 mol L-1).


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Tiosemicarbazonas , Antineoplásicos/farmacología , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Estructura Molecular
13.
Sci Immunol ; 5(49)2020 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-32737068

RESUMEN

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.


Asunto(s)
Linfocitos B/inmunología , Microbioma Gastrointestinal , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Inmunoglobulina A/inmunología , Proteína Activadora Transmembrana y Interactiva del CAML/inmunología , Animales , Bacterias/genética , Inmunidad Mucosa , Inmunoglobulina A/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Ribosómico 16S/genética , Linfocitos T
14.
Neurourol Urodyn ; 39(3): 1002-1011, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32106344

RESUMEN

INTRODUCTION: The aim of this study was to compare long-term outcomes in patients who underwent either native tissue repair or monofilament macroporous polypropylene mesh. METHODS: This multicenter, randomized trial included-at the end of 5 years follow-up-122 women with severe pelvic organ prolapse, who were randomly assigned to undergo surgical treatment using native tissue repair (native tissue group, n = 59) or synthetic mesh repair (mesh group, n = 63). Cure criterion was when pelvic organ prolapse-quantification (POP-Q) point was ≤0. Quality of life was assessed using the prolapse quality-of-life questionnaire and sexual function with the quality of sexual function. RESULTS: Groups were homogeneous preoperatively with the exception of the previous pelvic surgery variable, which was higher in mesh (P = .019). Cure rate was significantly better for mesh group in the anterior compartment (P = .002) and in the combination of all compartments (P = .001). Native tissue group was significantly better when there was prolapse in the posterior and apical compartment (P = .031). In the quality of life analysis, mesh group showed a significant improvement compared with native tissue group (P = .004). Complications were significantly higher in mesh and recurrence in native tissue. Regarding the reoperation rate, there was no difference between groups, but native tissue had a higher reoperation rate due to recurrence (P = .031). CONCLUSIONS: Outcomes in women with severe POP were better with mesh use than native tissue repair, both in the anterior compartment and in the multicompartmental prolapse after 5-year follow-up. Complications were more common in the mesh group and recurrences were more frequent in the native tissue group.


Asunto(s)
Mallas Quirúrgicas , Prolapso Uterino/cirugía , Vagina/cirugía , Anciano , Fascia , Femenino , Estudios de Seguimiento , Humanos , Histerectomía , Persona de Mediana Edad , Prolapso de Órgano Pélvico/cirugía , Polipropilenos , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Procedimientos de Cirugía Plástica , Recurrencia , Reoperación/estadística & datos numéricos , Encuestas y Cuestionarios , Técnicas de Sutura , Resultado del Tratamiento
15.
Eur J Prosthodont Restor Dent ; 28(2): 65-74, 2020 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-32031764

RESUMEN

This in vitro study evaluated the effect of the application and previous photoactivation of bonding adhesives in lithium disilicate ceramics. This was achieved by analyzing the bond strength of the cement-ceramic interface, nanohardness and elastic modulus of bonding adhesives and resin cements. The bonding adhesives used were Scotchbond Multi-Purpose (SBMP); Scotchbond Multi-Purpose light-cured (SBMP+LC); Single Bond 2 (SB2); Single Bond 2 light-cured (SB2+LC); Single Bond Universal (SBU) and Single Bond Universal light-cured (SBU+LC). After luting the ceramic in composite resin blocks, all specimens were subjected to 10,000 thermocycles. Sticks were obtained for the microtensile bonding strength test and the nanohardness and elastic modulus of the bonding adhesive and resin cements. Data were submitted to one-way ANOVA and Fishers tests (α =0.05). The results indicated that the bonding strength and mechanical properties were influenced by the interaction of the bonding adhesive and resin cement. For the mechanical properties analyzed, no statistically significant differences were observed between the groups. Single Bond Universal was the only system that was effective with or without previous light activation. For the other adhesive systems, Scotchbond Multi- Purpose and Single Bond 2, the previous light activation was necessary to optimize the bonding strength of the adhesive interface.


Asunto(s)
Recubrimiento Dental Adhesivo , Cerámica , Coronas , Luces de Curación Dental , Cementos Dentales , Porcelana Dental , Ensayo de Materiales , Cementos de Resina , Resistencia a la Tracción
16.
J Mech Behav Biomed Mater ; 100: 103408, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31476552

RESUMEN

The aim of this study was to evaluate the color change of composite resin restorations in Class I cavity preparation with different depths, submitted to challenge of thermocycling in coffee, after the use of green tea extract (EGCG) as treatment on the dentin surface. Forty-eight human molars were divided into 6 groups according to dentin treatment and depth of restoration (n = 8): Group C3- Control/3 mm; Group C4- Control/4 mm; Group C5- Control/5 mm; Group EGCG3- EGCG/3 mm; Group EGCG4- EGCG/4 mm; and Group EGCG5- EGCG/5 mm. The teeth of the control groups were restored by the bulk fill technique (Filtek Bulk Fill), conditioning the dentin surface only with universal bonding system (Single Bond Universal). The teeth of the EGCG groups were also restored by the bulk filling technique, but conditioning the dentin surface with 0.5% EGCG for 30 s prior to the application of the adhesive system. Initial and final color readings were performed according to the CIE L*a*b* scale in UV-2450 spectroscope, before and after challenge of thermal cycling in coffee. The color change (ΔE) was then calculated based on the formula ΔE = [(ΔL*)2+(Δa*)2+(Δb*)2]½. The ΔE data were submitted to statistical tests of normality, two-way ANOVA and Tukey test to compare the means (p < 0.05). There was no statistically difference for both study factors analyzed (EGCG application and restoration depth), as well as the interaction between both, after aging in coffee (p > 0.05). It was concluded that the previous application of EGCG did not cause a significant color change at the dentin-resin interface.


Asunto(s)
Catequina/análogos & derivados , Color , Resinas Compuestas/química , Restauración Dental Permanente , Diente Molar/efectos de los fármacos , , Adhesivos , Bisfenol A Glicidil Metacrilato , Catequina/química , Café , Caries Dental/patología , Fracaso de la Restauración Dental , Dentina/química , Recubrimientos Dentinarios/química , Humanos , Ensayo de Materiales , Cementos de Resina , Propiedades de Superficie
17.
Phys Rev E ; 100(1-1): 012217, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31499878

RESUMEN

Solar systems complexity, multiscale, and nonlinearity are governed by numerous and continuous changes where the sun magnetic fields can successfully represent many of these phenomena. Thus, nonlinear tools to study these challenging systems are required. The dynamic system recurrence approach has been successfully used to deal with this kind challenge in many scientific areas, objectively improving the recognition of state changes, randomness, and degrees of complexity that are not easily identified by traditional techniques. In this work we introduce the use of these techniques in photospheric magnetogram series. We employ a combination of recurrence quantification analysis with a preprocessing denoising wavelet analysis to characterize the complexity of the magnetic flux emergence in the solar photosphere. In particular, with the developed approach, we identify regions of evolving magnetic flux and where they present a large degree of complexity, i.e., where predictability is low, intermittence is high, and low organization is present.

18.
Ann Oncol ; 30(8): 1381-1392, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31114846

RESUMEN

BACKGROUND: Emactuzumab is a monoclonal antibody against the colony-stimulating factor-1 receptor and targets tumor-associated macrophages (TAMs). This study assessed the safety, clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD) of emactuzumab, as monotherapy and in combination with paclitaxel, in patients with advanced solid tumors. PATIENTS AND METHODS: This open-label, phase Ia/b study comprised two parts (dose escalation and dose expansion), each containing two arms (emactuzumab, every 2 or 3 weeks, as monotherapy or in combination with paclitaxel 80 mg/m2 weekly). The dose-escalation part explored the maximum tolerated dose and optimal biological dose (OBD). The dose-expansion part extended the safety assessment and investigated the objective response rate. A PK/PD analysis of serial blood, skin and tumor biopsies was used to explore proof of mechanism and confirm the OBD. RESULTS: No maximum tolerated dose was reached in either study arm, and the safety profile of emactuzumab alone and in combination does not appear to preclude its use. No patients receiving emactuzumab monotherapy showed an objective response; the objective response rate for emactuzumab in combination with paclitaxel was 7% across all doses. Skin macrophages rather than peripheral blood monocytes or circulating colony-stimulating factor-1 were identified as an optimal surrogate PD marker to select the OBD. Emactuzumab treatment alone and in combination with paclitaxel resulted in a plateau of immunosuppressive TAM reduction at the OBD of 1000 mg administered every 2 weeks. CONCLUSIONS: Emactuzumab showed specific reduction of immunosuppressive TAMs at the OBD in both treatment arms but did not result in clinically relevant antitumor activity alone or in combination with paclitaxel. (ClinicalTrials.gov Identifier: NCT01494688).


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Macrófagos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Paclitaxel/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Factor Estimulante de Colonias de Macrófagos/sangre , Factor Estimulante de Colonias de Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/inmunología , Neoplasias/patología , Paclitaxel/uso terapéutico , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Piel/citología , Piel/inmunología , Resultado del Tratamiento , Adulto Joven
19.
J Mech Behav Biomed Mater ; 97: 1-6, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31082714

RESUMEN

The aim of this study was to evaluate influence of protease inhibitors on degradation of sound, sclerotic and caries-affected dentin. Thirty-nine molars were used, thirteen for each dentin condition. Three slices were obtained from each tooth, each one immersed in the following different solutions for 1 h: 1) artificial saliva; 2) 2% chlorhexidine; 3) 0.5% epigallocatechin-gallate (EGCG). After immersion, samples were subjected to enzymatic degradation challenge (collagenase from Clostridium histolyticum). Nanohardness (HIT) and elastic modulus (Er) were measured before and after enzymatic challenge, as well as the ultimate tensile strength (UTS). Results of UTS, HIT and Er tests were submitted to repeated measurements ANOVA and Tukey post-test (α = 0.05). Higher values of UTS were found for sound dentin in control (40.30 ±â€¯21.38 MPa) and 0.5% EGCG (30.05 ±â€¯19.67 MPa) groups. Before degradation, higher values of HIT (0.237 ±â€¯0.062 GPa) and Er (5.58 ±â€¯1.75 GPa) were found for 0.5% EGCG group in caries-affected dentin. After degradation, 2% chlorhexidine group had higher values of HIT and Er for sound (0.134 ±â€¯0.020 GPa and 3.57 ±â€¯0.40 GPa) and sclerotic (0.201 ±â€¯0.048 GPa and 4.30 ±â€¯0.56 GPa) dentin. The 2% chlorhexidine showed best effect increasing HIT and Er, mainly for sclerotic dentin, before/after enzymatic degradation. The 0.5% EGCG showed better effect on HIT and Er in caries-affected dentin, before enzymatic degradation.


Asunto(s)
Caries Dental , Dentina/efectos de los fármacos , Dentina/efectos de la radiación , Inhibidores de Proteasas/farmacología , Adolescente , Adulto , Catequina/análogos & derivados , Catequina/farmacología , Clorhexidina/farmacología , Clostridium histolyticum , Dureza , Humanos , Ensayo de Materiales , Persona de Mediana Edad , Diente Molar/efectos de los fármacos , Diente Molar/efectos de la radiación , Presión , Esclerosis , Sonido , Resistencia a la Tracción , Adulto Joven
20.
J Intern Med ; 285(2): 215-222, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30222212

RESUMEN

BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case-control study in a cohort of Brazilian women infected with ZIKV during pregnancy. METHODS: A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. RESULTS: From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION: These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.


Asunto(s)
Adenilil Ciclasas/genética , Mutación , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/genética , Adenilil Ciclasas/metabolismo , Brasil/epidemiología , Análisis Mutacional de ADN , ADN Viral/análisis , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Embarazo , Estudios Retrospectivos , Virus Zika/genética , Virus Zika/patogenicidad , Infección por el Virus Zika/enzimología , Infección por el Virus Zika/epidemiología
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