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1.
Cell ; 168(3): 473-486.e15, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-28129541

RESUMO

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.


Assuntos
Quimerismo , Edição de Genes , Mamíferos/embriologia , Animais , Blastocisto , Sistemas CRISPR-Cas , Bovinos , Embrião de Mamíferos/citologia , Feminino , Humanos , Masculino , Mamíferos/classificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Células-Tronco Pluripotentes , Ratos , Ratos Sprague-Dawley , Sus scrofa
3.
Nature ; 571(7765): E7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31263274

RESUMO

Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.

4.
Nature ; 568(7753): 487-492, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31019327

RESUMO

Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.


Assuntos
Dióxido de Carbono/análise , Sequestro de Carbono , Sedimentos Geológicos/química , Biomassa , Isótopos de Carbono , Costa Rica , Sedimentos Geológicos/microbiologia , Hélio
5.
Glob Chang Biol ; 30(1): e16997, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37937346

RESUMO

Mediterranean spring ecosystems are unique habitats at the interface between surface water and groundwater. These ecosystems support a remarkable array of biodiversity and provide important ecological functions and ecosystem services. Spring ecosystems are influenced by abiotic, biotic, and anthropogenic factors such as the lithology of their draining aquifers, their climate, and the land use of their recharge area, all of which affect the water chemistry of the aquifer and the spring discharges. One of the most relevant characteristics of spring ecosystems is the temporal stability of environmental conditions, including physicochemical features of the spring water, across seasons and years. This stability allows a wide range of species to benefit from these ecosystems (particularly during dry periods), fostering an unusually high number of endemic species. However, global change poses important threats to these freshwater ecosystems. Changes in temperature, evapotranspiration, and precipitation patterns can alter the water balance and chemistry of spring water. Eutrophication due to agricultural practices and emergent pollutants, such as pharmaceuticals, personal care products, and pesticides, is also a growing concern for the preservation of spring biodiversity. Here, we provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems. We then describe their ecological value and biodiversity patterns and highlight the main risks these ecosystems face. Moreover, we identify existing knowledge gaps to guide future research in order to fully uncover the hidden biodiversity within these habitats and understand the main drivers that govern them. Finally, we provide a brief summary of recommended actions that should be taken to effectively manage and preserve Mediterranean spring ecosystems for future generations. Even though studies on Mediterranean spring ecosystems are still scarce, our review shows there are sufficient data to conclude that their future viability as functional ecosystems is under severe threat.


Assuntos
Ecossistema , Nascentes Naturais , Refúgio de Vida Selvagem , Biodiversidade , Água
6.
J Org Chem ; 89(7): 4702-4711, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38502009

RESUMO

A new atom-economical synthesis of ß-alkenyl-substituted BODIPYs via indium(III)-catalyzed intermolecular alkyne hydroarylation with meso-substituted BODIPYs is described. While catalysis with InI3 allows the double ß-functionalization of BODIPY, resulting in regioselectively branched ß,ß'-disubstituted alkenyl BODIPYs, catalytic InCl3 enables the formation of linear ß-substituted alkenyl BODIPYs. Subsequent In(III)-catalyzed intermolecular alkyne hydroarylation allows the synthesis of unsymmetrical push-pull BODIPY derivatives. Therefore, indium catalysis offers complementary regioselectivity in good chemical yields and functional group tolerance. The resulting BODIPY dyes displayed bathochromically shifted absorption and emission according to the electron-nature of the substituents in the alkenyl moiety with high molar extinction coefficients (ε up to 88,200 M-1 cm-1) and quantum yields (0.14-0.96).

7.
Ultrasound Obstet Gynecol ; 63(3): 350-357, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37774112

RESUMO

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.


Assuntos
Pré-Eclâmpsia , Recém-Nascido , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Fator de Crescimento Placentário , Estudos Prospectivos , Biomarcadores , Primeiro Trimestre da Gravidez
8.
Environ Res ; 250: 118510, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387495

RESUMO

The literature rarely compiles studies devoted to the removal of pollutants in aqueous media comparing adsorption and photocatalytic degradation, and does not pay enough attention to the analysis of combined adsorption-photocatalytic oxidation processes. In the present manuscript, the removal of malachite green (MG) from aqueous solutions has been investigated in three different sustainable scenarios: i) adsorption on activated carbon (AC) derived from a residue, luffa cylindrica, ii) photocatalytic oxidation under simulated solar light using titanium dioxide (TP) and iii) combined adsorption-photocatalytic oxidation using TP-AC (70/30 wt./wt.) under simulated solar light. The study has revealed that in the three scenarios and studied conditions, the total removal of this endocrine-disrupting dye from the solution takes place in the assayed time, 2 h, in some cases just in a few minutes. MG adsorption in the AC is a very fast and efficient removal method. MG photocatalytic oxidation with TP also occurs efficiently, although the oxidized MG is not totally mineralized. MG removal using the TP-AC composite under simulated solar light occurs only slightly faster to the MG adsorption in the AC, being adsorption the dominating MG removal mechanism for TP-AC. Thus, more than 90% of the removed MG with TP-AC under simulated solar light is adsorbed in this carbon-containing composite. The obtained results highlight the interest in adsorption, being the selection of the most suitable removal method dependent on several factors (i.e., the cost of the AC regeneration, for adsorption, or the toxicity of the intermediate oxidation species, for photooxidation). Paying attention to MG photooxidation with TiO2, comparison of two working photodegradation schemes shows that the direct photodegradation of MG from solution, avoiding any initial dark equilibrium period, is more efficient from a time perspective. The use of scavengers has proved that MG photodegradation occurs via an oxidation mechanism dominated by superoxide anion radicals.


Assuntos
Oxirredução , Corantes de Rosanilina , Titânio , Poluentes Químicos da Água , Corantes de Rosanilina/química , Titânio/química , Adsorção , Poluentes Químicos da Água/química , Catálise , Carvão Vegetal/química , Purificação da Água/métodos , Fotólise , Processos Fotoquímicos
9.
BMC Pregnancy Childbirth ; 24(1): 335, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698309

RESUMO

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM. METHODS: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected. RESULTS: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI. CONCLUSIONS: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications.


Assuntos
Anormalidades Congênitas , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Gravidez em Diabéticas , Nascimento Prematuro , Humanos , Feminino , Gravidez , Gravidez em Diabéticas/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Estudos Prospectivos , Recém-Nascido , Anormalidades Congênitas/epidemiologia , Nascimento Prematuro/epidemiologia , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Peso ao Nascer , Índice de Massa Corporal , Hemoglobinas Glicadas/análise , Resultado da Gravidez/epidemiologia
10.
Arch Womens Ment Health ; 27(3): 405-415, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38150150

RESUMO

Early interventions may promote reductions in mothers' anxiety-depression (AD) symptoms and improvements in their offspring. This longitudinal randomized research was conducted to assess the effects of interdisciplinary online therapeutic groups (GIO) in at-risk mothers and babies during the COVID-19 pandemic in a disadvantaged neighborhood in Barcelona (Spain). A total of 135 babies were born from March 2020 to June 2021 in a primary healthcare center of Barcelona (Spain). Pregnant woman and new mothers were screened for AD symptomatology through EPDS and STAI questionnaires. Seventy-two of them met high-risk criteria for AD and were included in the study. They were randomly assigned into the two groups of the study: 40 participants were assigned to GIO, the therapeutic group (TG), while 32 of them were assigned to the control group (CG) and received treatment as usual. The course of the mothers' symptomatology was assessed, as well as the baby's development at 6 months old in a blind pediatric follow-up. No differences were found in AD between both groups before the intervention. However, we obtained a significant decrease in AD symptomatology (EPDS p < .001; STAI state p = .015 and STAI trait p < .001at 6 months of life) after the intervention in the TG compared to the CG. Pediatric follow-up at 6 months demonstrated significant differences between groups in babies' development assessment (manipulation p = .003; language p < .001; sociability p < .001). The GIO helped to ensure healthy development of the baby and reduction of the mothers' depressive-anxiety symptomatology.


Assuntos
Ansiedade , COVID-19 , Depressão , Humanos , Feminino , Gravidez , Adulto , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/terapia , Projetos Piloto , Depressão/terapia , Depressão/psicologia , Espanha/epidemiologia , Ansiedade/terapia , SARS-CoV-2 , Mães/psicologia , Intervenção Baseada em Internet , Lactente , Psicoterapia de Grupo/métodos , Complicações na Gravidez/terapia , Complicações na Gravidez/psicologia , Internet , Estudos Longitudinais , Recém-Nascido
11.
Public Health ; 226: 128-137, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056400

RESUMO

OBJECTIVE: The purpose was to analyze age-standardized trends in diabetes mortality rates (DMR) from 1998 to 2022, stratified by sex and Mexican state, and the effects attributable to age, period, and cohort by sex. STUDY DESIGN: Joinpoint regression and age-period-cohort effect analysis. METHODS: Based on the tenth revision of the International Classification of Diseases, E11, E12, E13, and E14 codes of the death certificate, a daily record of mortality was extracted from the death certificate attributable to diabetes as the main cause. From 1998 to 2022, sexes and ages (≥20 years) were used to calculate the crude mortality rates and standardized at the national and Mexican state levels. Additionally, the age-period-cohort model was used to examine age, period, and cohort effects. RESULTS: From 1998 to 2005, the age-adjusted DMR increased by 3.6% (95% confidence interval [CI]: 2.7, 4.5) for the total population, as shown by the joinpoint regression analysis at a national level; from 2017 to 2020, it increased by 7.4% (95% CI: 0.6, 14.8). The DMR with the highest increase during the study period came mainly from states in the country's southeastern region, 2.3% to 3.7% per year. The net age and period effects showed that mortality increased with advancing age and with going time, respectively; and the net cohort effect revealed that mortality increased in more recent birth cohorts, mainly in men Rate Ratio (RR) = 2.37 (95% CI: 2.29, 2.46) vs RR = 1.13 (95% CI: 1.09, 1.17). CONCLUSION: The DMR increased among older age groups. The period effect showed that mortality increased over time. Furthermore, the cohort effect showed that mortality increased in more recent birth cohorts, especially among men.


Assuntos
Diabetes Mellitus , Masculino , Humanos , Idoso , Efeito de Coortes , México/epidemiologia , Estudos de Coortes , Análise de Regressão , Mortalidade
12.
Public Health ; 229: 13-23, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382177

RESUMO

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.


Assuntos
Comparação Transcultural , Ideação Suicida , Humanos , Estudos Transversais , Psicometria , Reprodutibilidade dos Testes , Prevenção do Suicídio
13.
Int J Mol Sci ; 25(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542182

RESUMO

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients. It has also been shown that small extracellular vesicles (sEVs) carrying PD-L1 induce lymphocyte dysfunction. Thus, the aim of our study was to analyze the expression of PD-L1 on sEVs of OSA patients and to evaluate the role of sEVs on lymphocyte activation and cytotoxicity. Circulating sEVs were isolated from OSA patients and the control group. Lymphocytes were isolated from the control group. Circulating sEVs were characterized by western blot, nanotracking analysis, and flow cytometry and were incubated with lymphocytes. Our results show no differences in the quantity and composition of sEVs in OSA patients and no significant effects of sEVs in OSA patients on lymphocyte activation and cytotoxicity. These results suggest that OSA does not modify PD-L1 expression on sEVs, which does not contribute to dysregulation of cytotoxic lymphocytes.


Assuntos
Vesículas Extracelulares , Neoplasias , Apneia Obstrutiva do Sono , Humanos , Antígeno B7-H1 , Vesículas Extracelulares/metabolismo , Neoplasias/complicações , Apneia Obstrutiva do Sono/metabolismo
14.
Aten Primaria ; 56(7): 102922, 2024 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-38583414

RESUMO

The care of migrant patients includes initial screening and lifelong monitoring, highlighting the importance of preventing and tracking chronic, communicable and non-communicable diseases. The prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity varies by ethnicity, influenced by genetic factors, lifestyle, and socio-economic status. Preventive measures, health promotion, and risk factor identification are crucial. Chronic communicable diseases may manifest years after transmission, underscoring the necessity of primary care screening, especially for populations from endemic or high-risk areas. Imported skin lesions are a common reason for consultation among migrant and traveller patients. Their ethiology is varied, ranging from common conditions such as scabies, mycoses, and urticaria to tropical dermatoses like filariasis and leprosy.


Assuntos
Dermatopatias , Migrantes , Humanos , Doença Crônica , Dermatopatias/etiologia , Doenças não Transmissíveis/epidemiologia , Doenças Transmissíveis/epidemiologia
15.
Actas Dermosifiliogr ; 115(6): 547-554, 2024 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38395224

RESUMO

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.


Assuntos
Bexaroteno , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Tetra-Hidronaftalenos , Humanos , Bexaroteno/uso terapêutico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/efeitos adversos , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Espanha , Linfoma Cutâneo de Células T/tratamento farmacológico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
16.
Actas Dermosifiliogr ; 115(6): T547-T554, 2024 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38653368

RESUMO

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.


Assuntos
Bexaroteno , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Tetra-Hidronaftalenos , Humanos , Bexaroteno/uso terapêutico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/efeitos adversos , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Espanha , Linfoma Cutâneo de Células T/tratamento farmacológico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
17.
J Struct Biol ; 215(4): 108024, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37704013

RESUMO

Single particle analysis (SPA) in cryo-electron microscopy (cryo-EM) is highly used to obtain the near-atomic structure of biological macromolecules. The current methods allow users to produce high-resolution maps from many samples. However, there are still challenging cases that require extra processing to obtain high resolution. This is the case when the macromolecule of the sample is composed of different components and we want to focus just on one of them. For example, if the macromolecule is composed of several flexible subunits and we are interested in a specific one, if it is embedded in a viral capsid environment, or if it has additional components to stabilize it, such as nanodiscs. The signal from these components, which in principle we are not interested in, can be removed from the particles using a projection subtraction method. Currently, there are two projection subtraction methods used in practice and both have some limitations. In fact, after evaluating their results, we consider that the problem is still open to new solutions, as they do not fully remove the signal of the components that are not of interest. Our aim is to develop a new and more precise projection subtraction method, improving the performance of state-of-the-art methods. We tested our algorithm with data from public databases and an in-house data set. In this work, we show that the performance of our algorithm improves the results obtained by others, including the localization of small ligands, such as drugs, whose binding location is unknown a priori.


Assuntos
Algoritmos , Imagem Individual de Molécula , Microscopia Crioeletrônica/métodos , Substâncias Macromoleculares/química
18.
Phys Rev Lett ; 131(22): 222501, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101385

RESUMO

We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82 kg×yr of ^{82}Se. We identify with improved precision the background sources within the 3 MeV energy region, where neutrinoless double ß decay of ^{82}Se and ^{100}Mo is expected, making more solid the foundations for the background budget of the next-generation CUPID experiment. Relying on the excellent data reconstruction, we measure the two-neutrino double ß-decay half-life of ^{82}Se with unprecedented accuracy: T_{1/2}^{2ν}=[8.69±0.05(stat)_{-0.06}^{+0.09}(syst)]×10^{19} yr.

19.
Psychol Med ; 53(9): 4266-4274, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35534479

RESUMO

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Catatonia , Delírio , Discinesias , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Catatonia/etiologia , Estudos Prospectivos , N-Metilaspartato , Receptores de N-Metil-D-Aspartato , Convulsões/complicações , Delírio/complicações , Discinesias/complicações
20.
Curr Allergy Asthma Rep ; 23(10): 567-578, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561310

RESUMO

PURPOSE OF REVIEW: Mechanical nasal obstruction (MNO) is a prevalent condition with a high impact on patient's quality-of-life (QoL) and socio-economic burden. The aim of this study was to determine the usefulness of both subjective and objective criteria in the appropriate management of MNO, either alone or associated to upper airway inflammatory diseases such as allergic rhinitis (AR) or chronic rhinosinusitis with nasal polyps (CRSwNP). RECENT FINDINGS: A long debate persists about the usefulness of subjective and objective methods for making decisions on the management of patients with nasal obstruction. Establishing standards and ranges of symptom scales and questionnaires is essential to measure the success of an intervention and its impact on QoL. To our knowledge this is the first real-life study to describe the management of MNO using both subjective and objective criteria in MNO isolated or associated to upper airway inflammatory diseases (AR or CRSwNP). Medical treatment (intranasal corticosteroids) has a minor but significant improvement in MNO subjective outcomes (NO, NOSE, and CQ7) with no changes in loss of smell and objective outcomes. After surgery, all MNO patients reported a significant improvement in both subjective and objective outcomes, this improvement being higher in CRSwNP. We concluded that in daily clinical practice, the therapeutic recommendation for MNO should be based on both subjective and objective outcomes, nasal corrective surgery being the treatment of choice in MNO, either isolated or associated to upper airway inflammatory diseases, AR or CRSwNP.


Assuntos
Obstrução Nasal , Pólipos Nasais , Rinite Alérgica , Rinite , Humanos , Obstrução Nasal/terapia , Obstrução Nasal/cirurgia , Qualidade de Vida , Rinite/complicações , Rinite/diagnóstico , Rinite/terapia , Nariz , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/terapia , Doença Crônica
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