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Purpose The measurement of fetal cardiovascular function parameters is not yet established in prenatal diagnostics. Now that the research field of fetal programming is becoming increasingly important, this might change. Fetal cardiovascular changes have been described above all in early/severe fetal growth restriction (FGR). The aim of this study was to investigate functional echocardiographic parameters in fetuses with late-onset small for gestational age (SGA)/FGR. Materials and methods A prospective cohort of SGA fetuses (including FGR) and a control group with similar distribution of gestational age were studied. Parameters of systolic, diastolic and global cardiac function, morphometry and measurements of the fetal abdominal aorta were collected. Results A total of 149 SGA fetuses and 143 control fetuses were included from 32 weeks until term. The total SGA group was further divided into SGA 3rd-10th (fetuses between the 3rd and 10th weight percentile) and FGR subgroups. In the total SGA group, relative right and left ventricular wall thickness, left E/A ratio, isovolumetric contraction time and left myocardial performance index were significantly increased compared to controls after adjustment for gestational age. MAPSE, TAPSE, ejection time, left cardiac output and abdominal aortic distensibility were significantly lower. The changes were more pronounced in the FGR subgroup. Conclusion Even in a group of late-onset SGA/FGR situation, echocardiographic parameters are already altered in utero. Zusammenfassung Ziel Die Messung fetaler kardiovaskulärer Funktionsparameter ist in der Pränataldiagnostik noch nicht etabliert. Nachdem das Forschungsgebiet der fetalen Programmierung einen immer höheren Stellenwert hat, könnte sich das bald ändern. Vor allem bei früher fetaler Wachstumsrestriktion (FGR) sind kardiovaskuläre Veränderungen beschrieben. Ziel dieser Studie war es dies bei Feten mit spät einsetzender FGR zu untersuchen. Material und Methode Eine prospektive Kohorte von Feten, die zu klein für das Gestationsalter (SGA) sind (einschließlich FGR) sowie eine Kontrollgruppe ähnlichen Gestionsalters wurden untersucht. Es wurden Parameter der systolischen, diastolischen sowie globalen Herzfunktion, der Morphometrie sowie Messungen der fetalen Aorta abdominalis erhoben. Ergebnisse Insgesamt wurden 149 SGA Feten sowie 143 Kontrollfeten ab 32 Schwangerschaftswochen eingeschlossen. Die Gesamt-SGA Gruppe wurde für eine Subgruppenanalyse weiterhin in eine SGA (SGA 3-10: Feten zwischen der 3. und 10. Gewichtsperzentile) sowie eine FGR Subgruppe unterteilt. In der Gesamt-SGA Gruppe zeigten sich im Vergleich zu den Kontrollen nach Adjustierung an das Gestationsalter die relative rechte sowie linke Ventrikelwanddicke, das linke E/A-Verhältnis, die isovolumetrische Kontraktionszeit und der linke myokardiale Performanceindex signifikant erhöht. MAPSE, TAPSE, die Ejektionszeit, das linke Herzzeitvolumen und die Beweglichkeit der Aorta abdominalis waren signifikant geringer. Die Ergebnisse waren im Subgruppenvergleich in der FGR Subgruppe ausgeprägter. Schlussfolgerung Auch in einer Gruppe spät einsetzender SGA/FGR Situation sind echokardiographische Parameter bereits intrauterin verändert.
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Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.
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Antineoplásicos , Indoles , Isoindoles , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Indoles/química , Indoles/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Iridio/química , Iridio/farmacología , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Compuestos de Zinc/química , Especies Reactivas de Oxígeno/metabolismo , Nanocápsulas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacosRESUMEN
Background: Most previous studies evaluated outcomes of twin-twin transfusion syndrome (TTTS) without considering the coexistence of selective fetal growth restriction (sFGR). The objectives of this study were to compare twin survival and pregnancy complications after laser therapy of TTTS with and without sFGR. Methods: For this purpose, a retrospective cohort study including 98 monochorionic diamniotic twins and three dichorionic triamniotic triplets treated in a single tertiary center was conducted. Results: Overall, 46 twins had selective fetal growth restriction (26 type I, 13 type II, 7 type III). At birth, donor survival (61% vs. 91%), double survival (57% vs. 82%), and overall survival (75% vs. 88%) were significantly lower in the group with coexistent sFGR. Recipient survival (89% vs. 86%), miscarriage (7% vs. 2%), PPROM < 32 weeks (48% vs. 29%), and preterm delivery < 32 weeks (52% vs. 45%) were not significantly higher in the group with coexistent sFGR. Donor twins with sFGR type I (69% vs. 91%) and types II-III (50% vs. 91%) showed significantly lower survival than those without sFGR. Multivariate regression analysis identified sFGR and its subtypes as independent predictors of donor demise. Conclusions: the coexistence of sFGR in TTTS pregnancies was associated with poor donor outcomes and is probably the most important predictor of donor survival.
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Place-based accessibility measures communicate the potential interaction with opportunities at a zone that populations can access. Recent research has explored the implications of how opportunities are counted by different accessibility methods. In conventional measures, opportunities are multiply counted if more than one zone offers access to the same opportunity. This multi-count of opportunities leads to values of accessibility that are difficult to interpret. A possible solution to enhance the meaning-making of accessibility results is by constraining the calculations to match a known quantity. This ensures all zonal values sum up to a predetermined quantity (i.e., the total number of opportunities). In this way, each value can be meaningfully related to this total. A recent effort that implements this solution is spatial availability, a singly-constrained accessibility measure. In this paper, we extend spatial availability for use in the case of multiple modes or more generally, heterogeneous population segments with distinct travel behaviors. After deriving a multimodal version of spatial availability, we proceed to illustrate its features using a synthetic example. We then apply it to an empirical example of low emission zones in Madrid, Spain. We conclude with suggestions for future research and its use in evaluating policy interventions.
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Accesibilidad a los Servicios de Salud , Viaje , EspañaRESUMEN
The present study explores the potential of rhizobacteria isolated from Baccharis linearis and Solidago chilensis in metal(loid)-contaminated soil for producing N-acyl-homoserine lactones (AHLs)-type signal molecules and promoting plant growth. A total of 42 strains were isolated, four demonstrating the production of AHL-type signal molecules. Based on 16S rRNA gene sequencing analyses and MALDI-TOF analyses, these four isolates were identified as belonging to the Pseudomonas genus, specifically P. brassicacearum, P. frederickberguensis, P. koreensis, and P. orientalis. The four AHL-producing strains were evaluated for metal(loid)s tolerance, their plant growth promotion traits, AHL quantification, and their impact on in vitro Lactuca sativa plant growth. The study found that four strains exhibited high tolerance to metal(loid)s, particularly As, Cu, and Zn. Additionally, plant growth-promoting traits were detected in AHL-producing bacteria, such as siderophore production, ammonia production, ACC deaminase activity, and P solubilization. Notably, AHL production varied among strains isolated from B. linearis, where C7-HSL and C9-HSL signal molecules were detected, and S. chilensis, where only C7-HSL signal molecules were observed. In the presence of copper, the production of C7-HSL and C9-HSL significantly decreased in B. linearis isolates, while in S. chilensis isolates, C7-HSL production was inhibited. Further, when these strains were inoculated on lettuce seeds and in vitro plants, a significant increase in germination and plant growth was observed. Mainly, the inoculation of P. brassicacearum and P. frederickberguensis led to extensive root hair development, significantly increasing length and root dry weight. Our results demonstrate that rhizospheric strains produce AHL molecules and stimulate plant growth, primarily through root development. However, the presence of copper reduces the production of these molecules, potentially affecting the root development of non-metalloid tolerant plants such as S. chilensis, which would explain its low population in this hostile environment.
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Acil-Butirolactonas , Percepción de Quorum , Percepción de Quorum/genética , Cobre , ARN Ribosómico 16S/genética , Plantas/genética , SueloRESUMEN
This study aimed to evaluate the in silico and in vitro inhibitory effect of the combined use of galantamine (GAL) and donepezil (DON) against acetylcholinesterase and butyrylcholinesterase (BuChE) enzymes. In silico and in vitro cholinesterase analysis were carried out for GAL and DON alone and combined. Molecular modeling studies were carried out (docking analysis, molecular dynamics simulation, and quantum theory of atoms in molecules). Cholinesterase's inhibitory activities by modified Ellman's method and the drug combination effect using the Chou-Talalay method were assayed. GAL/DON combination showed the co-occupancy of the ligands in both enzymes through in silico studies. Regarding in vitro BuChE inhibition analyses, three of five combinations showed an interaction between GAL and DON at the threshold of additive affect (0.9 < CI < 1.1), with a tendency toward a synergistic effect for higher concentrations. This is the first report showing the efficacy of the GAL/DON combinations inhibiting BuChE, showing the importance of analyzing the behavior of different ligands when co-occupancy into the active site is possible. These combinations might be a possible therapy to improved efficacy, reduced doses, minor side effects, and high levels of the neurotransmitter in the synaptic space for Alzheimer's disease.
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Enfermedad de Alzheimer , Galantamina , Humanos , Galantamina/farmacología , Butirilcolinesterasa/metabolismo , Donepezilo/farmacología , Inhibidores de la Colinesterasa/farmacología , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad , Enfermedad de Alzheimer/tratamiento farmacológico , Simulación del Acoplamiento MolecularRESUMEN
Fetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated female probands in whom de novo heterozygous missense variants in the planar cell polarity gene CELSR1 were detected using exome sequencing. Using several in vitro assays, we show that the CELSR1 p.(Cys1318Tyr) variant disrupted the subcellular localisation, affected cell-cell junction, impaired planar cell polarity signalling and lowered proliferation rate. These observations suggest that deleterious rare CELSR1 variants could be a possible cause of fetal hydrops.
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Heterocigoto , Hidropesía Fetal , Mutación Missense , Humanos , Femenino , Mutación Missense/genética , Hidropesía Fetal/genética , Hidropesía Fetal/patología , Embarazo , Derrame Pleural/genética , Derrame Pleural/patología , Cadherinas/genética , Secuenciación del Exoma , Polaridad Celular/genéticaRESUMEN
A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.
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Diversos estudios han informado que la calidad de vida relacionada con la salud (CVRS) en adolescentes ha disminuido durante la pandemia por COVID-19. En este trabajo se analizó la CVRS en jóvenes de 13 a 17 años una vez finalizada la pandemia. Para ello se hizo un seguimiento en tres momentos diferentes: antes de la pandemia (2019), durante las restricciones de la pandemia (2021) y tras las restricciones de la misma (2022). Se utilizó un diseño de retardo temporal (time-lag design) en tres fases, con un total de 2027 adolescentes que cumplimentaron el cuestionario Kidscreen-10 de CVRS. Mediante modelos ANOVA y de regresión logística se analizó la influencia del género, la práctica deportiva y estar en tratamiento en salud mental. Los resultados obtenidos mostraron un empeoramiento de la CVRS en 2021, cuando los jóvenes volvían a los centros educativos en régimen de semipresencialidad. Este descenso fue independiente del género. En 2022, una vez eliminadas todas las restricciones, la CVRS se recuperó a niveles prepandemia en los chicos, pero no en las chicas. Lo mismo ocurrió con los jóvenes en tratamiento de salud mental. En todos los casos, la práctica deportiva se mostró como un factor protector de la CVRS.(AU)
Several studies have reported that health-related quality of life (HRQoL) in adolescents has decreased during the COVID-19 pandemic. In this study, HRQoL was analyzed in young people aged 13 to 17 years after the end of the pandemic. For this purpose, we followed up at three different points in time: before the pandemic (2019), during (2021) and af-ter the pandemic restrictions (2022).A time-lag design in three phases was used, with a total of 2027 adolescents completing the Kidscreen-10 HRQoL questionnaire. ANOVA and logistic regression models were used to analyze the influence of gender, playing sports and mental health treat-ment.The results obtained showed a worsening of HRQoL in 2021, when young people returned to school on a blended learning basis.This worsen-ing occurred regardless of gender. In 2022, once all restrictions were re-moved, boys recovered health-related quality of life to pre-pandemic levels, but this did not occur in girls. The same happened with young people in mental health treatment. In all cases, doing sports was shown to be a pro-tective factor for HRQoL.(AU)
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Humanos , Calidad de Vida , Salud del Adolescente , Conducta del Adolescente , Pandemias , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/psicología , Psicología del Adolescente , Estudios Longitudinales , Encuestas y Cuestionarios , Salud Mental , Deportes , Conducta Alimentaria , Dieta SaludableRESUMEN
OBJECTIVES: To characterize the COVID-19 disease profile in Chilean children hospitalized in pediatric intensive care units (PICU) and to evaluate risk factors associated with severe COVID-19. PATIENTS AND METHOD: A multicenter prospective cohort study with patients 0-18 years of age with confirmed SARS-CoV-2 hospitalized in PICU. Clinical, laboratory, imaging, and therapeutic variables were recorded. We compared "mild/moderate COVID-19" with ''severe COVID-19" using median with interquartile range (IQR), Mann-Whitney U test, two-tailed Fisher's test, and forward binary multivariate analysis to adjust variables for "severe COVID-19". A p < 0.05 was considered significant. RESULTS: From 16 PICUs, 219 patients were recruited, 55.3% were male, with a median age of 86 months (IQR: 13.5-156). The most frequent comorbidities were obesity and respiratory diseases. Overall mortality was 3.6%. "Severe COVID-19" (26.5%) showed more leukopenia, lymphopenia, increased inflammatory parameters, and altered organ function (p < 0.05). It also developed more sepsis/shock, ARDS, and organ dysfunction, requiring more hemodynamic, anti-inflammatory, anticoagulation, and antibiotic therapy, with a longer stay in the PICU/hospital (p < 0.05), and 13.8% of mortality. Risk factors associated with "severe COVID-19" were shock on admission to the PICU [aOR 28.44 (95%CI 10.45-77.4)], obesity [aOR 3.55 (95%CI 1.3-9.6)], consolidation [aOR 3.1 (95%CI 1.1 -8.7)], atelectasis [aOR: 8.7 (95%CI 1.17-64.3)], stress dose of corticosteroids [aOR 7.7 (95%CI 1.9-30.6)], early antibiotic therapy [aOR: 12.02 (95%CI 1.11-130.02)], acquired/congenital immunodeficiency [aOR: 19.2 (95%CI: 1.19-321)], and oncological pathology [aOR 10.7 (95%CI 2.14-47.8)]. CONCLUSION: In this Chilean pediatric cohort, most patients with COVID-19 admitted to de PICU were male, of school age, with associated comorbidity. Risk factors for developing severe COVID-19 were the presence of comorbidities such as acquired/congenital immunodeficiency, oncological pathology, and obesity, in addition to shock on admission and consolidations on X-rays.
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COVID-19 , Trombocitopenia , Humanos , Niño , Masculino , Femenino , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Estudios Prospectivos , Obesidad , Antibacterianos/uso terapéuticoRESUMEN
Introduction: Proteolytic processing of amyloid protein precursor by ß-site secretase enzyme (BACE1) is dependent on the cellular lipid composition and is affected by endomembrane trafficking in dementia and Alzheimer's disease (AD). Stearoyl-CoA desaturase 1 (SCD1) is responsible for the synthesis of fatty acid monounsaturation (MUFAs), whose accumulation is strongly associated with cognitive dysfunction. Methods: In this study, we analyzed the relationship between BACE1 and SCD1 in vivo and in vitro neurodegenerative models and their association in familial AD (FAD), sporadic AD (SAD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using microscopy, biochemical, and mass SPECT approach. Results: Our findings showed that BACE1 and SCD1 immunoreactivities were increased and colocalized in astrocytes of the hippocampus in a rat model of global cerebral ischemia (2-VO). A synergistic effect of double BACE1/SCD1 silencing on the recovery of motor and cognitive functions was obtained. This neuroprotective regulation involved the segregation of phospholipids (PLs) associated with polyunsaturated fatty acids in the hippocampus, cerebrospinal fluid, and serum. The double silencing in the sham and ischemic groups was stronger in the serum, inducing an inverse ratio between total phosphatydilcholine (PC) and lysophosphatidylcholine (LPC), represented mainly by the reduction of PC 38:4 and PC 36:4 and an increase in LPC 16:0 and LPC 18:0. Furthermore, PC 38:4 and PC:36:4 levels augmented in pathological conditions in in vitro AD models. BACE1 and SCD1 increases were confirmed in the hippocampus of FAD, SAD, and CADASIL. Conclusion: Therefore, the findings suggest a novel convergence of BACE-1 and SCD1 in neurodegeneration, related to pro-inflammatory phospholipids.
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Metallo-phthalocyanines (MPc) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (ZnPc) or nickel (NiPc) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV-Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers. NiPc shows a high G4 binding but negligible photosensitizing ability while ZnPc exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.
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Antineoplásicos , G-Cuádruplex , Compuestos Organometálicos , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Oxígeno Singlete/química , Níquel , Antineoplásicos/química , Compuestos Organometálicos/química , Zinc/química , Compuestos de ZincRESUMEN
The synthesis and characterization of two new water soluble 2,6-bis(imidazolylmethyl)-4-methylphenoxy-containing perylenediimides, PDI-1 and PDI-2, are described. These compounds demonstrate a high fluorescence quantum yield in water and were investigated as potential photosensitizers for generating reactive oxygen species with applications in anticancer activities. The HeLa cell line (VPH18) was used to evaluate their efficacy. Fluorescence microscopy was employed to confirm the successful internalization of PDI-1 and PDI-2, while confocal microscopy revealed the specific locations of both PDIs within the lysosomes and mitochondria. In vitro studies were conducted to evaluate the anticancer activity of PDI-1 and PDI-2. Remarkably, these photosensitizers demonstrated a significant ability to selectively eliminate cancer cells when exposed to a specific light wavelength. The water solubility, high fluorescence quantum yield, and selective cytotoxicity of these PDIs toward cancer cells highlight their potential as effective agents for targeted photodynamic therapy. In conclusion, the findings presented here provide a strong foundation for the future exploration and optimization of PDI-1 and PDI-2 as effective photosensitizers in photodynamic therapy, potentially leading to improved treatment strategies for cancer patients.
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BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, represents a health threat to around 20 million people worldwide. Side effects of benznidazole (Bzn) cause 15-20% of patients to discontinue their treatment. Evidence has increased in favor of the use of drug combinations to improve the efficacy and tolerance of the treatment. Natural products are well known to provide structures that could serve as new drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family of Amaryllidaceae family are known by their bioactives alkaloids, which have been reported by their antiparasitic activities. PURPOSE: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine (Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combination effect between Cnd and Bzn against different life stages of T. cruzi parasites. METHODS: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense), including quantitation of Cnd was performed through GC/MS and UPLC-MS/MS techniques. Subsequently, Cnd was isolated using Shephadex LH-20. Then, the AE-H. escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, and amastigotes) by in vitro proliferation and viability assays. The cytotoxicity was evaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis was perform by transmission electron microscopy (TEM) and mitochondrial activity was carried out by MTT assay. Drug combination assay between Cnd and Bzn was evaluated using the Chou-Talalay method. RESULTS: The AE-H. escoipense and Cnd showed high and specific anti-T. cruzi activity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such as vacuolization, membrane blebs, and increased mitochondrial activity. Regarding the interaction between Cnd and Bzn, it generates synergism in the combinations of 0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and 4×IC50 in amastigotes. CONCLUSION: The synergism between Cnd and Bzn indicates that the combination at the concentration of 4×IC50 could be useful as an effective new therapy against CD in the chronic stage. Thus, Cnd isolated from the leaves of H. escoipense emerges as potential candidate for the development of a new drug for the treatment of CD.
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Alcaloides , Amaryllidaceae , Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Animales , Humanos , Cromatografía Liquida , Espectrometría de Masas en Tándem , Enfermedad de Chagas/tratamiento farmacológico , Alcaloides/farmacología , Tripanocidas/farmacología , MamíferosRESUMEN
Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.
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Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Aberraciones Cromosómicas , MonosomíaRESUMEN
BACKGROUND: Hippeastrum species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species. PURPOSE: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean Hippeastrum species and determine the synergism between the major isolated alkaloid-montanine-and benznidazole in anti-Trypanosoma cruzi activity. METHODS: The antiparasitic activity was evaluated through antiproliferative and viability assays against T. cruzi epimastigotes. Synergism assays were performed using the Chou-Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis. RESULTS: All extracts showed strong growth inhibition of T. cruzi epimastigote proliferation. The extracts from H. aglaiae, H. aulicum, and H. hybrid stand out for their potent and total growth inhibition, which was comparable to benznidazole. The H. reticulatum extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole. CONCLUSION: Hippeastrum species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.
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PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41â+â0 and 41â+â6 weeks and were delivered before 42â+â0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH <â7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH <â7.20, Apgar score <â7âat 5 minutes, and admission to the neonatal intensive care unit for >â24 hours. RESULTS: The study included 314 women with 32 (10â%) IVDs and 49 (16â%) CSs due to IFC and 85 (27â%) APO cases. Fetuses with CPR <â10th percentile showed a significantly higher rate of operative delivery for IFC (40â% (21/52) vs. 23â% (60/262); pâ=â0.008) yet not a significantly higher rate of APO (31â% (16/52) vs. 26â% (69/262); pâ=â0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26â% and 19â%, specificities of 87â% and 84â%, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.
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Cesárea , Resultado del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Pronóstico , Estudios Retrospectivos , Sufrimiento Fetal , Estudios Prospectivos , Feto , Arterias Umbilicales/diagnóstico por imagen , Ultrasonografía Prenatal , Flujo Pulsátil , Trabajo de Parto InducidoRESUMEN
PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup.âThe following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤â7.15 and/or 5-minute Apgar ≤â7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29â%, SGA: 28â%), especially the cesarean delivery rate after the onset of labor (11â% vs. 10â%). Most SGA cases ended up in induction of labor (61â% vs. 31â%, pâ<â0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUCâ=â0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.
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Enfermedades del Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Femenino , Humanos , Recién Nacido , Embarazo , Retardo del Crecimiento Fetal/diagnóstico por imagen , Feto/diagnóstico por imagen , Estudios de Seguimiento , Edad Gestacional , Placenta , Tercer Trimestre del Embarazo , Estudios Prospectivos , Ultrasonografía Doppler/métodos , Ultrasonografía Prenatal/métodos , Arterias Umbilicales/diagnóstico por imagen , Estudios de Casos y ControlesRESUMEN
Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.