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BACKGROUND AIMS: Gene-silencing by small interfering RNA (siRNA) is an attractive therapy to regulate cancer death, tumor recurrence or metastasis. Because siRNAs are easily degraded, it is necessary to develop transport and delivery systems to achieve efficient tumor targeting. Self-nanoemulsifying systems (SNEDDS) have been successfully used for pDNA transport and delivery, so they may be useful for siRNA. The aim of this work is to introduce siRNA-RAD51 into a SNEDDS prepared with Phospholipon-90G, Labrafil-M1944-CS and Cremophor-RH40 and evaluate its efficacy in preventing homologous recombination of DNA double-strand breaks caused by photodynamic therapy (PDT) and ionizing radiation (IR). METHODS: The siRNA-RAD51 was loaded into SNEDDS using chitosan. Transfection capacity was estimated by comparison with Lipofectamine-2000. RESULTS: SNEDDS(siRNA-RAD51) induced gene silencing effect on the therapies evaluated by cell viability and clonogenic assays using T47D breast cancer cells. CONCLUSIONS: SNEDDS(siRNA-RAD51) shown to be an effective siRNA-delivery system to decrease cellular resistance in PDT or IR.
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Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs. While therapeutics exist that can help mitigate the detrimental effects of antibodies, they act broadly potentially dampening beneficial immunity. Identifying additional xenoantigens may enable more targeted approaches, such as gene editing, to overcome these challenges by further eliminating antibody targets on donor tissue. Because we have found that classical class I swine leukocyte antigens are targets of human antibodies, we now examine whether related pig proteins may also be targeted by human antibodies. We show here that non-classical class I swine leukocyte proteins (SLA-6, -7, -8) can be expressed at the surface of mammalian cells and act as antibody targets.
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Antígenos Heterófilos , Antígenos de Histocompatibilidad Clase I , Trasplante Heterólogo , Animales , Porcinos , Trasplante Heterólogo/métodos , Antígenos Heterófilos/inmunología , Humanos , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Rechazo de Injerto/inmunología , Animales Modificados GenéticamenteRESUMEN
Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes.
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Rechazo de Injerto , Xenoinjertos , Antígenos de Histocompatibilidad Clase I , Trasplante de Riñón , Macaca mulatta , Trasplante Heterólogo , Animales , Trasplante Heterólogo/métodos , Rechazo de Injerto/inmunología , Trasplante de Riñón/métodos , Antígenos de Histocompatibilidad Clase I/inmunología , Porcinos , Xenoinjertos/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Supervivencia de Injerto/inmunología , Isoanticuerpos/inmunología , HumanosAsunto(s)
Humanos , Masculino , Anciano de 80 o más Años , Carcinoma Medular , Hepatitis C , Sofosbuvir , Anemia Ferropénica , Gastroscopía , BiopsiaRESUMEN
Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α-granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.
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Células Endoteliales , Trombocitopenia , Porcinos , Animales , Humanos , Trasplante Heterólogo/métodos , Hígado , Plaquetas , Trombocitopenia/etiología , Antígenos Heterófilos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression. AIM: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG. METHOD: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot. RESULT: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined. CONCLUSION: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.
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Organ supply remains inadequate to meet the needs of many patients who could benefit from allotransplantation. Xenotransplantation, the use of animals as organ donors, provides an opportunity to alleviate this challenge. Pigs are widely accepted as the ideal organ donor, but humans and nonhuman primates have strong humoral immune responses to porcine tissue. Although carbohydrate xenoantigens have been studied intensively, the primate Ab response also targets class I and class II swine leukocyte Ags (SLAs). Human Abs that recognize HLAs can cross-react with SLA molecules because epitopes can be shared across species. However, â¼15% of people may also exhibit Abs toward class II SLAs despite lacking Abs that also recognize class II HLAs. Here, we extend these studies to better understand human Ab responses toward class I SLAs. When tested against a panel of 18 unique class I SLA proteins, 14 of 52 sera samples collected from patients in need of an organ transplant contained Abs that bound class I SLAs. Class I SLA-reactive sera may contain IgM only, IgG, only, or IgM and IgG capable of recognizing the pig proteins. The presence of class I HLA-reactive Abs was not essential to generating anti-class I SLA Ig. Last, anti-class I SLA reactivity varied by serum; some recognized a single SLA allele, whereas others recognized multiple class I SLA proteins.
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Leucocitos , Listas de Espera , Humanos , Animales , Porcinos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
OBJECTIVE: To follow the impact of the SARS-CoV-2 pandemic on the practice of assisted reproductive technology in centers reporting to the Latin American Registry during 2020. METHODS: An internally validated online survey designed on the Survey Monkey platform with a maximum of 20 closed questions was sent via e-mail or WhatsApp to the clinical director of each center reporting to the Latin American Registry of Assisted Reproduction between July and December 2020. RESULTS: The number of centers responding to the survey varied during the six months. The relative contribution of Brazil to all responses was 41.4% to 45%, followed by México (16.2% to 23.8%), Argentina (8.1% to 12.6%), Colombia (7.1% to 8.2%), Chile (3.6% to 6.1%) and Peru (4.0% to 4.9%). Most centers reported stopping activities before July 2020 (81%). COVID-19 related symptoms were a criterion on their own to postpone ovarian stimulation (80.1% to 87.7% of centers). Although in July only 76 of 166 centers (45.8%) performed embryo transfers, by October 104 of 109 centers (95.4%) performed them. In survey 6 (December), 78 of 79 centers (98.7%) that had initially closed had already reopened, although 62.3% (61 of 98 centers) still performed 80% or less of their usual number of ART cycles. CONCLUSIONS: Most centers modified their clinical practice and applied specific protocols to screen their staff and patients. Suspicion of COVID-19 delayed treatments. Despite a peak of the pandemic, by December most centers were performing all ART treatments, although the number of cycles remained low compared to pre-pandemic numbers.
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COVID-19 , Humanos , América Latina/epidemiología , COVID-19/epidemiología , SARS-CoV-2 , Reproducción , Transferencia de EmbriónRESUMEN
Introduction: Sleep-related problems are common in children with attention-deficit/hyperactivity disorder (ADHD). Sleep disorders are also side effects of all stimulant ADHD medications. Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is a once-daily treatment approved for patients age 6 years and older with ADHD. In this analysis, sleep behavior was assessed during SDX/d-MPH treatment in children with ADHD. Methods: In a 12-month, dose-optimized, open-label safety study in 6- to 12-year-old participants (NCT03460652), a secondary endpoint was assessment of sleep behavior based on the Children's Sleep Habits Questionnaire (CSHQ) consisting of 8 sleep domains (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness). This post hoc analysis examined the individual sleep domains in the 12-month safety study. Results: Of 282 participants enrolled, 238 were included in the sleep analysis. At baseline, mean (SD) CSHQ total sleep disturbance score was 53.4 (5.9). After 1 month of treatment, the mean (SD) CSHQ total score significantly decreased to 50.5 (5.4); least-squares mean change from baseline was -2.9 (95% CI: -3.5 to -2.4; p < 0.0001) and remained decreased up to 12 months. Mean sleep-score improvements from baseline to 12 months were statistically significant (p < 0.0001) for 5 of 8 sleep domains, including bedtime resistance, sleep anxiety, night wakings, parasomnias, and daytime sleepiness. Parasomnias and daytime sleepiness sleep domains showed the greatest mean improvement from baseline to 12 months. Sleep onset delay and sleep duration scores increased from baseline to 12 months. No statistically significant worsening occurred from baseline in sleep duration and sleep-disordered breathing domains; however, worsening of sleep onset delay was statistically significant. Conclusion: In this analysis of children taking SDX/d-MPH for ADHD, sleep problems did not worsen based on the mean CSHQ total sleep disturbance score. Statistically significant improvements in most CSHQ sleep domains were observed after 1 month and lasted for up to 12 months of treatment.
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Objetivos: Describir las características clínicas y el tratamiento del embarazo ectópico implantado en la cicatriz de cesárea, así como las complicaciones y el pronóstico obstétrico. Materiales y métodos: Estudio de cohorte retrospectivo de gestantes con diagnóstico de embarazo ectópico implantado en la cicatriz de cesárea según los criterios de la Sociedad de Medicina Materno-Fetal, atendidas entre enero de 2018 y marzo de 2022 en dos instituciones de alta complejidad, pertenecientes a la seguridad social, ubicadas en Lima, Perú. Se hizo un muestreo consecutivo. Se midieron variables sociodemográficas y clínicas de ingreso, diagnóstico, tipo de tratamiento, complicaciones y pronóstico obstétrico. Se hace un análisis descriptivo. Resultados: Se incluyeron 17 pacientes, de 29.919 partos. De estas, el 41,2 % recibió tratamiento médico y el resto recibió tratamiento quirúrgico. Se realizó un manejo local exitoso con metotrexato en el saco gestacional en dos pacientes con ectópico tipo 2. Cuatro de las pacientes requirieron histerectomía total. Seis pacientes experimentaron una gestación después del tratamiento, y 4 de ellas culminaron el embarazo con una madre y un neonato saludables. Conclusiones: El embarazo ectópico implantado en la cicatriz de una cesárea es una entidad poco frecuente, para la cual se cuenta con alternativas de manejo médico y quirúrgico con aparentes buenos resultados. Se requieren más estudios con mayor calidad metodológica de asignación aleatoria que ayuden a caracterizar la seguridad y la efectividad de las diferentes alternativas terapéuticas para las mujeres con sospecha de esta patología.
Objectives: To describe the clinical characteristics and treatment of ectopic pregnancy arising in the cesarean section scar, as well as its complications and obstetric prognosis. Material and methods: Retrospective cohort study of pregnant women with the diagnosis of a scar pregnancy in accordance with Maternal-Fetal Medicine Society criteria, seen between January 2018 and March 2022 in two high complexity institutions of the social security system, located in Lima, Peru. Consecutive sampling was used. Baseline sociodemographic and clinical variables were measured, including diagnosis, type of treatment, complications and obstetric prognosis. A descriptive analysis was performed. Results: Out of 29,919 deliveries, 17 patients were included. Of these, 41.2 % received medical management and the rest were treated surgically. Successful management with intra-gestational sac methotrexate was performed in two patients with ectopic pregnancy type 2. Four patients required total hysterectomy. Six patients became pregnant after the treatment and 4 completed their pregnancy with healthy mother and neonate pairs. Conclusions: Ectopic pregnancy implanted in a cesarean section scar is an infrequent occurrence for which medical and surgical management options are available with apparently good outcomes. Further studies of better methodological quality and random assignment are needed in order to help characterize the safety and effectiveness of the various therapeutic options for women with suspected scar pregnancy.
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Humanos , Femenino , EmbarazoRESUMEN
Objectives: To describe the clinical characteristics and treatment of ectopic pregnancy arising in the cesarean section scar, as well as its complications and obstetric prognosis. Material and methods: Retrospective cohort study of pregnant women with the diagnosis of a scar pregnancy in accordance with Maternal-Fetal Medicine Society criteria, seen between January 2018 and March 2022 in two high complexity institutions of the social security system, located in Lima, Peru. Consecutive sampling was used. Baseline sociodemographic and clinical variables were measured, including diagnosis, type of treatment, complications and obstetric prognosis. A descriptive analysis was performed. Results: Out of 29,919 deliveries, 17 patients were included. Of these, 41.2 % received medical management and the rest were treated surgically. Successful management with intra-gestational sac methotrexate was performed in two patients with ectopic pregnancy type 2. Four patients required total hysterectomy. Six patients became pregnant after the treatment and 4 completed their pregnancy with healthy mother and neonate pairs. Conclusions: Ectopic pregnancy implanted in a cesarean section scar is an infrequent occurrence for which medical and surgical management options are available with apparently good outcomes. Further studies of better methodological quality and random assignment are needed in order to help characterize the safety and effectiveness of the various therapeutic options for women with suspected scar pregnancy.
Objetivos: describir las características clínicas y el tratamiento del embarazo ectópico implantado en la cicatriz de cesárea, así como las complicaciones y el pronóstico obstétrico. Materiales y métodos: estudio de cohorte retrospectivo de gestantes con diagnóstico de embarazo ectópico implantado en la cicatriz de cesárea según los criterios de la Sociedad de Medicina Materno-Fetal, atendidas entre enero de 2018 y marzo de 2022 en dos instituciones de alta complejidad, pertenecientes a la seguridad social, ubicadas en Lima, Perú. Se hizo un muestreo consecutivo. Se midieron variables sociodemográficas y clínicas de ingreso, diagnóstico, tipo de tratamiento, complicaciones y pronóstico obstétrico. Se hace un análisis descriptivo. Resultados: se incluyeron 17 pacientes, de 29.919 partos. De estas, el 41,2 % recibió tratamiento médico y el resto recibió tratamiento quirúrgico. Se realizó un manejo local exitoso con metotrexato en el saco gestacional en dos pacientes con ectópico tipo 2. Cuatro de las pacientes requirieron histerectomía total. Seis pacientes experimentaron una gestación después del tratamiento, y 4 de ellas culminaron el embarazo con una madre y un neonato saludables. Conclusiones: el embarazo ectópico implantado en la cicatriz de una cesárea es una entidad poco frecuente, para la cual se cuenta con alternativas de manejo médico y quirúrgico con aparentes buenos resultados. Se requieren más estudios con mayor calidad metodológica de asignación aleatoria que ayuden a caracterizar la seguridad y la efectividad de las diferentes alternativas terapéuticas para las mujeres con sospecha de esta patología.
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Cesárea , Cicatriz , Embarazo Ectópico , Femenino , Humanos , Embarazo , Estudios de Cohortes , Perú , Placenta AccretaRESUMEN
BACKGROUND: Previous studies show contradictory results regarding the bidirectional association between physical activity and nighttime sleep. The objective of the present study was to add knowledge to these possible relationships using autoregressive models. METHOD: 214 adolescents (117 boys and 97 girls), with a mean age of 13.31 years agreed to participate. The study variables were measured with accelerometers for 7 full days over three consecutive years. The mlVAR package was used to compute estimates from multivariate vector autoregression models. RESULTS: The 5-delay models showed a better fit. Autoregressive effects were observed in sleep onset, sleep offset and sedentary behavior, which could explain the relationships found in previous studies between physical activity and sleep. Sleep onset, total sleep time, and sleep efficiency had direct effects on sedentary behavior. Moderate-to-vigorous physical activity was not related to any of the sleep variables. CONCLUSIONS: The hypothesis that there are bidirectional/reciprocal relationships between physical activity and sleep cannot be accepted.
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Duración del Sueño , Sueño , Masculino , Femenino , Humanos , Adolescente , Conducta SedentariaRESUMEN
Chemiluminescence (CL) reactions are widely used for the detection and quantification of many types of analytes. Laccase has previously been proposed in CL reactions; however, its light emission behaviour has not been characterized. This study was conducted to characterize the laccase-luminol system, determine its kinetic parameters, and analyze the effects of protein and OH- concentration on the CL signal. Laccase from Coriolopsis gallica was combined with different concentrations of luminol (125 nM to 4 mM), and the enzyme kinetics were evaluated using diverse kinetic models. The laccase-luminol system was able to produce CL without an intermediate molecule, but it exhibited substrate-inhibition behaviour. A two-site random model was used and suggested that when the first luminol molecule was bound to the active site, laccase affinity for the second luminol molecule was increased. This inhibition effect could be avoided using a low luminol concentration. At 5 µM luminol concentration, 1 mg/ml (0.13 U) laccase is needed to achieve nearly 90% of the maximum CL signal, suggesting that the available luminol could not bind to all active sites. Furthermore, the concentration of NaOH negatively affected the CL signal. The laccase-luminol system represents an alternative to existing CL systems, with potential uses in molecular detection and quantification.
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Lacasa , Luminol , Luminol/química , Lacasa/química , Luminiscencia , Mediciones LuminiscentesRESUMEN
Background: Previous studies show contradictory results regarding the bidirectional association between physicalactivity and nighttime sleep. The objective of the present study was to add knowledge to these possible relationshipsusing autoregressive models. Method: 214 adolescents (117 boys and 97 girls), with a mean age of 13.31 years agreedto participate. The study variables were measured with accelerometers for 7 full days over three consecutive years. ThemlVAR package was used to compute estimates from multivariate vector autoregression models. Results: The 5-delaymodels showed a better fit. Autoregressive effects were observed in sleep onset, sleep offset and sedentary behavior,which could explain the relationships found in previous studies between physical activity and sleep. Sleep onset,total sleep time, and sleep efficiency had direct effects on sedentary behavior. Moderate-to-vigorous physical activitywas not related to any of the sleep variables. Conclusions: The hypothesis that there are bidirectional/reciprocalrelationships between physical activity and sleep cannot be accepted.(AU)
Antecedentes: Los resultados de estudios previos sobre la asociación bidireccional entre actividad física y sueñonocturno son contradictorios. El objetivo del presente estudio es intentar dar una mejor explicación a estas posiblesrelaciones utilizando modelos autorregresivos. Método: Participaron 214 jóvenes (117 varones y 97 mujeres), con unamedia de edad de 13,31 años. Las variables del estudio se midieron con acelerómetros durante 7 días completos, en tresaños consecutivos. Se utilizó el paquete mlVAR para calcular las estimaciones de modelos vectoriales de autorregresiónmultivariables. Resultados: Los modelos de 5 retrasos fueron los que mostraron un mejor ajuste. Se observaron efectosautorregresivos en el inicio del sueño nocturno, el final del sueño nocturno y los comportamientos sedentarios, quepodrían explicar las relaciones encontradas en estudios previos entre actividad física y sueño. Se observaron efectosdirectos entre el inicio, la duración y la eficiencia del sueño nocturno sobre los comportamientos sedentarios. Laactividad física moderada-vigorosa no se relacionó con ninguna variable de sueño nocturno. Conclusiones: No se puedeaceptar la hipótesis de que existen relaciones bidireccionales/recíprocas, entre la actividad física y el sueño.(AU)
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Humanos , Masculino , Femenino , Adolescente , Actividad Motora , Sueño , Conducta Sedentaria , Trastornos del Inicio y del Mantenimiento del Sueño , Psicología , Psicología del AdolescenteRESUMEN
Reconstituted high-density lipoproteins (rHDLs) can transport and specifically release drugs and imaging agents, mediated by the Scavenger Receptor Type B1 (SR-B1) present in a wide variety of tumor cells, providing convenient platforms for developing theranostic systems. Usually, phospholipids or Apo-A1 lipoproteins on the particle surfaces are the motifs used to conjugate molecules for the multifunctional purposes of the rHDL nanoparticles. Cholesterol has been less addressed as a region to bind molecules or functional groups to the rHDL surface. To maximize the efficacy and improve the radiolabeling of rHDL theranostic systems, we synthesized compounds with bifunctional agents covalently linked to cholesterol. This strategy means that the radionuclide was bound to the surface, while the therapeutic agent was encapsulated in the lipophilic core. In this research, HYNIC-S-(CH2)3-S-Cholesterol and DOTA-benzene-p-SC-NH-(CH2)2-NH-Cholesterol derivatives were synthesized to prepare nanoparticles (NPs) of HYNIC-rHDL and DOTA-rHDL, which can subsequently be linked to radionuclides for SPECT/PET imaging or targeted radiotherapy. HYNIC is used to complexing 99mTc and DOTA for labeling molecules with 111, 113mIn, 67, 68Ga, 177Lu, 161Tb, 225Ac, and 64Cu, among others. In vitro studies showed that the NPs of HYNIC-rHDL and DOTA-rHDL maintain specific recognition by SR-B1 and the ability to internalize and release, in the cytosol of cancer cells, the molecules carried in their core. The biodistribution in mice showed a similar behavior between rHDL (without surface modification) and HYNIC-rHDL, while DOTA-rHDL exhibited a different biodistribution pattern due to the significant reduction in the lipophilicity of the modified cholesterol molecule. Both systems demonstrated characteristics for the development of suitable theranostic platforms for personalized cancer treatment.
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Nanopartículas , Medicina de Precisión , Animales , Ratones , Distribución Tisular , Benceno , Lipoproteínas HDL/metabolismo , Nanopartículas/uso terapéutico , Colesterol/metabolismo , Lipoproteínas/metabolismo , Radioisótopos , Fosfolípidos , Receptores Depuradores/metabolismoRESUMEN
Cerenkov radiation (CR) can be used as an internal light source in photodynamic therapy (PDT). Methotrexate (MTX) and paclitaxel (PTX), chemotherapeutic agents with wide clinical use, have characteristics of photosensitizers (PS). This work evaluates the possibility of photoexciting MTX and PTX with CR from 18F-FDG to produce reactive oxygen species (ROS) capable of inducing cytotoxicity. PTX did not produce ROS when excited by CR from 18F-FDG, so it is not useful for PDT. In contrast, MTX produces 1O2 (detected by ABMA) in amounts sufficient to significantly decrease the viability of the T47D cells. MTX solutions of 100 nM combined with 18F-FDG activities of 50 (1.85 MBq) and 100 µCi (3.7 MBq) produced a significant decrease in cell viability to (50.09 ± 4.95) and (47.96 ± 11.19)%, respectively, compared to MTX (66.29 ± 5.92)% and 18F-FDG (91.35 ± 7.00% for 50 µCi and 99.43 ± 11.03% for 100 µCi) alone. Using the CellRox Green reagent, the intracellular production of ROS was confirmed as the main mechanism of cytotoxicity. The results confirm the therapeutic potential of photoactivation with CR and the synergy of the combined treatment with chemotherapy + photodynamic therapy (CMT + PDT). The combination of chemotherapeutic agents with PS properties and ß-emitting radiopharmaceuticals, previously approved for clinical use, will make it possible to shorten the evaluation stages of new CMT + PDT systems.
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Background: Diagnosing periprosthetic joint infection (PJI) is challenging and usually requires the evaluation of several biomarkers. Our main aim was to evaluate the usefulness of D-dimer levels as well as the platelet count (PC) to mean platelet volume (MPV) ratio serum as biomarkers to rule out chronic knee and hip infection. Methods: The study enrolled a prospective cohort of 93 patients undergoing hip or knee revision. D-dimer values, PC to MPV ratio, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were preoperatively determined and evaluated as a predictor of PJI. The definitive diagnosis of PJI was established according to the 2018 International Consensus Meeting criteria. Results: A total of 24 (25.8â¯%) cases were postoperatively diagnosed with PJI. The median D-dimer value was significantly higher ( p ⯠< â¯0.001) for patients with PJI (1950â¯ngâ¯mL - 1 ) than for patients with aseptic failure (700â¯ngâ¯mL - 1 ). The area under the receiver operating characteristic curves for D-dimer, CRP and ESR was 0.820, 0.793 and 0.791 respectively. D-dimer⯠≥ â¯950â¯ngâ¯mL - 1 (91â¯% sensitivity, 64â¯% specificity), CRP⯠≥ â¯1.95â¯mgâ¯dL - 1 (61â¯% sensitivity, 90â¯% specificity) and ESR⯠> â¯20 (74â¯% sensitivity, 82â¯% specificity) were identified as the values with the best balance between sensitivity and specificity. The mean PC to MPV ratio was 37.0 for PJI patients and 29.8 for patients in the aseptic revision cohort ( p = 0 .067). Conclusions: Serum D-dimer levels appear very unlikely to remain normal in the presence of chronic PJI. The 91â¯% sensitivity when considering 950â¯ngâ¯mL - 1 as the threshold highlights D-dimer as the most accurate initial test to rule out chronic PJI. Conversely, the PC to MPV ratio may be of limited value for accurately diagnosing PJI.
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Abstract The COVID-19 pandemic elicited important changes in community habits and behaviors, including a distancing of people from the healthcare system. The objective of this work was to understand the causes that gave rise to changes in behavior from an individual perspective in the Argentine Republic. We performed a cross-sectional, web-based survey using an online questionnaire. The survey was distributed via the WhatsApp application for smartphones among subjects across the Argentine territory using a combination of convenience and snowball sampling. We received 6176 responses. Almost 70% of respondents manifested fear of visiting a physician. One third of respondents manifested having a desire or need in at least one occasion of visiting a physician but, of these, 48% avoided it. The main reasons for avoiding visits were: 1) a recommenda tion of staying home (40%); 2) lack of access to the physician (35%); and 3) fear of contagion (26%). The most common form of consultation was through unconventional means (e-mail, telephone, or WhatsApp). One of 5 respondents had difficulties to obtain a medication prescription and 5% stopped the use of at least one medica tion. Regarding healthy habits, almost 2/3 of those surveyed stated that they became more sedentary; 11% of hypertensive patients increased their consumption of salt and 15% saw their blood pressure values increase, while 16% of dyslipidemic patients showed increased consumption of fats.
Resumen La pandemia de COVID-19 determinó un importante cambio de los hábitos y comportamientos comu nitarios, entre ellos se observó un distanciamiento de la gente del sistema de salud y el abandono de hábitos saludables. El objetivo de este trabajo fue comprender las causas que dieron lugar a dichos cambios de com portamiento desde una perspectiva individual y evaluar el impacto en el control de los factores de riesgo car diovasculares. Realizamos una encuesta utilizando un cuestionario en línea y distribuida mediante la aplicación WhatsApp entre personas de la Argentina utilizando una combinación de muestreo por conveniencia y en "bola de nieve". Recibimos 6176 respuestas, casi el 70% de los encuestados manifestaron temor de realizar una con sulta médica. Un tercio de los encuestados manifestó haber tenido necesidad de ir al médico en al menos una oportunidad desde el inicio de la pandemia, pero de éstos, el 48% evitó la visita. Las principales razones para evitarla: 1) la recomendación de quedarse en casa (40%); 2) dificultad para acceder al sistema de salud (35%); y 3) miedo al contagio (26%). La forma de consulta más común fue a través de medios no convencionales (correo electrónico, teléfono o WhatsApp). Uno de cada 5 encuestados tuvo dificultades para obtener una receta y el 5% dejó de tomar al menos un medicamento. En cuanto a los hábitos saludables, casi 2/3 de los encuestados afirmaron volverse más sedentarios, el 11% de los hipertensos aumentó su consumo de sal y el 15% aumentó sus valores de presión arterial, mientras que el 16% de los dislipidémicos mostró un mayor consumo de grasas.
RESUMEN
The COVID-19 pandemic elicited important changes in community habits and behaviors, including a distancing of people from the healthcare system. The objective of this work was to understand the causes that gave rise to changes in behavior from an individual perspective in the Argentine Republic. We performed a cross-sectional, web-based survey using an online questionnaire. The survey was distributed via the WhatsApp application for smartphones among subjects across the Argentine territory using a combination of convenience and snowball sampling. We received 6176 responses. Almost 70% of respondents manifested fear of visiting a physician. One third of respondents manifested having a desire or need in at least one occasion of visiting a physician but, of these, 48% avoided it. The main reasons for avoiding visits were: 1) a recommendation of staying home (40%); 2) lack of access to the physician (35%); and 3) fear of contagion (26%). The most common form of consultation was through unconventional means (e-mail, telephone, or WhatsApp). One of 5 respondents had difficulties to obtain a medication prescription and 5% stopped the use of at least one medication. Regarding healthy habits, almost 2/3 of those surveyed stated that they became more sedentary; 11% of hypertensive patients increased their consumption of salt and 15% saw their blood pressure values increase, while 16% of dyslipidemic patients showed increased consumption of fats.
La pandemia de COVID-19 determinó un importante cambio de los hábitos y comportamientos comunitarios, entre ellos se observó un distanciamiento de la gente del sistema de salud y el abandono de hábitos saludables. El objetivo de este trabajo fue comprender las causas que dieron lugar a dichos cambios de comportamiento desde una perspectiva individual y evaluar el impacto en el control de los factores de riesgo cardiovasculares. Realizamos una encuesta utilizando un cuestionario en línea y distribuida mediante la aplicación WhatsApp entre personas de la Argentina utilizando una combinación de muestreo por conveniencia y en "bola de nieve". Recibimos 6176 respuestas, casi el 70% de los encuestados manifestaron temor de realizar una consulta médica. Un tercio de los encuestados manifestó haber tenido necesidad de ir al médico en al menos una oportunidad desde el inicio de la pandemia, pero de éstos, el 48% evitó la visita. Las principales razones para evitarla: 1) la recomendación de quedarse en casa (40%); 2) difi cultad para acceder al sistema de salud (35%); y 3) miedo al contagio (26%). La forma de consulta más común fue a través de medios no convencionales (correo electrónico, teléfono o WhatsApp). Uno de cada 5 encuestados tuvo dificultades para obtener una receta y el 5% dejó de tomar al menos un medicamento. En cuanto a los hábitos saludables, casi 2/3 de los encuestados afirmaron volverse más sedentarios, el 11% de los hipertensos aumentó su consumo de sal y el 15% aumentó sus valores de presión arterial, mientras que el 16% de los dislipidémicos mostró un mayor consumo de grasas.