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1.
J Chem Phys ; 159(17)2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37929867

ABSTRACT

In this work we implement a new methodology to study structural and mechanical properties of systems having spherical and planar symmetries throughout Molecular Dynamics simulations. This methodology is applied here to a drug delivery system based in polymersomes, as an example. The chosen model drug was the local anesthetic prilocaine due to previous parameterization within the used coarse grain scheme. In our approach, mass density profiles (MDPs) are used to obtain key structural parameters of the systems, and pressure profiles are used to estimate the curvature elastic parameters. The calculation of pressure profiles and radial MPDs required the development of specific methods, which were implemented in an in-house built version of the GROMACS 2018 code. The methodology presented in this work is applied to characterize poly(ethylene oxide)-poly(butadiene) polymersomes and bilayers loaded with the model drug prilocaine. Our results show that structural properties of the polymersome membrane could be obtained from bilayer simulations, with significantly lower computational cost compared to whole polymersome simulations, but the bilayer simulations are insufficient to get insights on their mechanical aspects, since the elastic parameters are canceled out for the complete bilayer (as consequence of the symmetry). The simulations of entire polymersomes, although more complex, offer a complementary approach to get insights on the mechanical behavior of the systems.


Subject(s)
Molecular Dynamics Simulation , Polyethylene Glycols , Pharmaceutical Preparations , Polyethylene Glycols/chemistry , Drug Delivery Systems , Prilocaine
2.
BMC Biol ; 21(1): 66, 2023 04 03.
Article in English | MEDLINE | ID: mdl-37013555

ABSTRACT

BACKGROUND: Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes. RESULTS: In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of ß anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation. CONCLUSIONS: Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.


Subject(s)
Fishes , Guanine , Animals , Guanine/chemistry , Skin , Bacteria
3.
Mol Pharm ; 20(6): 2814-2821, 2023 06 05.
Article in English | MEDLINE | ID: mdl-36625731

ABSTRACT

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound (R2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.


Subject(s)
Administration, Topical , Salicylic Acid , Sublimation, Chemical , Humans
4.
Biodegradation ; 34(2): 181-197, 2023 04.
Article in English | MEDLINE | ID: mdl-36596914

ABSTRACT

Polycyclic Aromatic Hydrocarbons (PAHs) impose adverse effects on the environment and human life. The use of synthetic microbial consortia is promising in bioremediation of contaminated sites with these pollutants. However, the design of consortia taking advantage of natural interactions has been poorly explored. In this study, a dual synthetic bacterial consortium (DSC_AB) was constructed with two key members (Sphingobium sp. AM and Burkholderia sp. Bk), of a natural PAH degrading consortium. DSC_AB showed significantly enhanced degradation of PAHs and toxic intermediary metabolites relative to the axenic cultures, indicating the existence of synergistic relationships. Metaproteomic and gene-expression analyses were applied to obtain a view of bacterial performance during phenanthrene removal. Overexpression of the Bk genes, naph, biph, tol and sal and the AM gene, ahdB, in DSC_AB relative to axenic cultures, demonstrated that both strains are actively participating in degradation, which gave evidence of cross-feeding. Several proteins related to stress response were under-expressed in DSC_AB relative to axenic cultures, indicating that the division of labour reduces cellular stress, increasing the efficiency of degradation. This is the one of the first works revealing bacterial relationships during PAH removal in a synthetic consortium applying an omics approach. Our findings could be used to develop criteria for evaluating the potential effectiveness of synthetic bacterial consortia in bioremediation.


Subject(s)
Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Sphingomonadaceae , Humans , Microbial Consortia/genetics , Soil Pollutants/metabolism , Polycyclic Aromatic Hydrocarbons/metabolism , Biodegradation, Environmental , Gene Expression Profiling , Sphingomonadaceae/metabolism , Soil Microbiology
5.
Nat Rev Nephrol ; 19(5): 337-350, 2023 05.
Article in English | MEDLINE | ID: mdl-36596918

ABSTRACT

Pyroptosis is a form of regulated cell death that is mediated by the membrane-targeting, pore-forming gasdermin family of proteins. Pyroptosis was initially described as a caspase 1- and inflammasome-dependent cell death pathway typified by the loss of membrane integrity and the secretion of cytokines such as IL-1ß. However, gasdermins are now recognized as the principal effectors of this form of regulated cell death; activated gasdermins insert into cell membranes, where they form pores that result in the secretion of cytokines, alarmins and damage-associated molecular patterns and cause cell membrane rupture. It is now evident that gasdermins can be activated by inflammasome- and caspase-independent mechanisms in multiple cell types and that crosstalk occurs between pyroptosis and other cell death pathways. Although they are important for host antimicrobial defence, a growing body of evidence supports the notion that pyroptosis and gasdermins have pathological roles in cancer and several non-microbial diseases involving the gut, liver and skin. The well-documented roles of inflammasome activity and apoptosis pathways in kidney diseases suggests that gasdermins and pyroptosis may also be involved to some extent. However, despite some evidence for involvement of pyroptosis in the context of acute kidney injury and chronic kidney disease, our understanding of gasdermin biology and pyroptosis in the kidney remains limited.


Subject(s)
Gasdermins , Pyroptosis , Humans , Pyroptosis/physiology , Inflammasomes , Cytokines/metabolism , Kidney/metabolism
6.
Clin Oncol (R Coll Radiol) ; 35(3): 163-176, 2023 03.
Article in English | MEDLINE | ID: mdl-36443137

ABSTRACT

The standard treatment for renal cell carcinoma (RCC) is surgery. However, a number of patients will not be candidates for surgical treatment or will reject this therapeutic approach. Therefore, alternative approaches are required. Historically, radiotherapy has been considered an ineffective treatment for RCC due to the radioresistance of renal tumour cells to conventional fractionation and the increased rate of toxicity. Stereotactic body radiotherapy (SBRT) is a radiotherapy technique that provides a non-invasive ablative treatment with remarkable rates of local control in both primary tumours and metastases in several locations, with a low associated morbidity due to the highly conformal dose and the use of image-guided techniques. Current evidence shows that a higher dose per fraction, achieving a higher biological effective dose, can overcome the radioresistance of RCC cells. Therefore, SBRT, as well as the combination of SBRT and new emerging immune therapies, has a potential role in the local treatment of primary RCC and oligometastatic RCC patients.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Radiosurgery , Humans , Carcinoma, Renal Cell/radiotherapy , Radiosurgery/methods , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Dose Fractionation, Radiation
7.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(10): 923-929, nov.- dic. 2022. ilus, tab, graf
Article in English | IBECS | ID: ibc-213026

ABSTRACT

Background The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. Patients and methods Case–control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. Results The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4–99.96%] and a positive predictive value (PPV) of 98.80% [92.54–99.94%] were estimated for NA and a specificity of 99.27% [95.4–99.96%] and a PPV of 92.86% [64.17–99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). Conclusions NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated (AU)


Antecedentes El diagnóstico de la neurofibromatosis tipo 1 (NF1) se demora normalmente en niños sin antecedentes familiares. Nuestro objetivo fue definir la prevalencia y características de las manifestaciones cutáneas prevalentes en NF1, en comparación con la población general, que siguen siendo excluidas de los criterios diagnósticos para NF1. Pacientes y métodos Estudio de casos y controles, pareado por grupos de edad, en el que se incluyeron 108 pacientes diagnosticados de NF1 y 137 controles sanos. Resultados La prevalencia de nevus anemicus (NA) (p < 0,001) y xantogranuloma juvenil (XJ) (p < 0,001) fue significativamente superior en la población afectada de NF1, en comparación con el grupo control. Se estimaron una especificidad del 99,27% [Intervalo de confianza (IC): 95,4-99,96%] y un valor predictivo positivo (VPP) del 98,80% [92,54-99,94%] para NA, y una especificidad del 99,27% [95,4-99,96%] y VPP del 92,86% [64,17-99,63%] para XJ en el diagnóstico de NF1 en niños que presentan 6 o más manchas café con leche. También se evidenciaron diferencias estadísticamente significativas en la distribución por fototipos (p 0,025), y con relación al prurito generalizado sin ninguna otra causa (p <,001). Conclusiones Los NA y los XJ son hallazgos clínicos relevantes para el diagnóstico de NF1, especialmente durante los primeros años de vida. Consideramos que debería evaluarse su inclusión en los criterios diagnósticos de la enfermedad (AU)


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Cafe-au-Lait Spots/diagnosis , Neurofibromatosis 1/diagnosis , Pigmentation Disorders/diagnosis , Xanthogranuloma, Juvenile/diagnosis , Case-Control Studies , Cross-Sectional Studies
8.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(10): t923-t929, nov.- dic. 2022. ilus, tab, graf
Article in Spanish | IBECS | ID: ibc-213027

ABSTRACT

Antecedentes El diagnóstico de la neurofibromatosis tipo 1 (NF1) se demora normalmente en niños sin antecedentes familiares. Nuestro objetivo fue definir la prevalencia y características de las manifestaciones cutáneas prevalentes en NF1, en comparación con la población general, que siguen siendo excluidas de los criterios diagnósticos para NF1. Pacientes y métodos Estudio de casos y controles, pareado por grupos de edad, en el que se incluyeron 108 pacientes diagnosticados de NF1 y 137 controles sanos. Resultados La prevalencia de nevus anemicus (NA) (p < 0,001) y xantogranuloma juvenil (XJ) (p < 0,001) fue significativamente superior en la población afectada de NF1, en comparación con el grupo control. Se estimaron una especificidad del 99,27% [Intervalo de confianza (IC): 95,4-99,96%] y un valor predictivo positivo (VPP) del 98,80% [92,54-99,94%] para NA, y una especificidad del 99,27% [95,4-99,96%] y VPP del 92,86% [64,17-99,63%] para XJ en el diagnóstico de NF1 en niños que presentan 6 o más manchas café con leche. También se evidenciaron diferencias estadísticamente significativas en la distribución por fototipos (p 0,025), y con relación al prurito generalizado sin ninguna otra causa (p <,001). Conclusiones Los NA y los XJ son hallazgos clínicos relevantes para el diagnóstico de NF1, especialmente durante los primeros años de vida. Consideramos que debería evaluarse su inclusión en los criterios diagnósticos de la enfermedad (AU)


Background The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. Patients and methods Case–control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. Results The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4–99.96%] and a positive predictive value (PPV) of 98.80% [92.54–99.94%] were estimated for NA and a specificity of 99.27% [95.4–99.96%] and a PPV of 92.86% [64.17–99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). Conclusions NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated (AU)


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Cafe-au-Lait Spots/diagnosis , Neurofibromatosis 1/diagnosis , Pigmentation Disorders/diagnosis , Xanthogranuloma, Juvenile/diagnosis , Case-Control Studies , Cross-Sectional Studies
9.
Materials (Basel) ; 15(19)2022 Sep 26.
Article in English | MEDLINE | ID: mdl-36234017

ABSTRACT

Chitin nanocrystals (ChNCs) and cellulose nanocrystals (CNCs) have been recently used to stabilize emulsions; however, they generally require significant amounts of salt, limiting their applicability in food products. In this study, we developed nanoconjugates by mixing positively charged ChNCs and negatively charged CNCs at various ChNC:CNC mass ratios (2:1, 1:1, and 1:2), and utilized them in stabilizing soybean oil-water Pickering emulsions with minimal use of NaCl salt (20 mM) and nanoparticle (NP) concentrations below 1 wt%. The nanoconjugates stabilized the emulsions better than individual CNC or ChNC in terms of a reduced drop growth and less creaming. Oppositely charged CNC and ChNC neutralized each other when their mass ratio was 1:1, leading to significant flocculation in the absence of salt at pH 6. Raman spectroscopy provided evidence for electrostatic interactions between the ChNCs and CNCs, and generated maps suggesting an assembly of ChNC bundles of micron-scale lengths intercalated by similar-size areas predominantly composed of CNC. The previous measurements, in combination with contact angles on nanoparticle films, suggested that the conjugates preferentially exposed the hydrophobic crystalline planes of CNCs and ChNCs at a 1:1 mass ratio, which was also the best ratio at stabilizing soybean oil-water Pickering emulsions.

10.
Actas Dermosifiliogr ; 113(10): T923-T929, 2022.
Article in English, Spanish | MEDLINE | ID: mdl-36162491

ABSTRACT

BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (P<.001) and juvenile xanthogranulomas (JXG) (P<.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% (confidence interval): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (P=.025) and in relation to generalized itching with no other cause (P<.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.


Subject(s)
Neurofibromatosis 1 , Pigmentation Disorders , Xanthogranuloma, Juvenile , Child , Humans , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/epidemiology , Case-Control Studies , Cafe-au-Lait Spots/diagnosis , Prevalence , Inflammation
11.
J Org Chem ; 87(20): 13480-13493, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36154121

ABSTRACT

The oxidative α-functionalization of 2-aryl-1,2,3,4-tetrahydroisoquinolines (THIQs) promoted by a versatile heterogeneous nanocatalyst consisting of copper nanoparticles immobilized on silica-coated maghemite (CuNPs/MagSilica) has been accomplished. The methodology was successfully applied in the cross-dehydrogenative coupling (CDC) reaction of N-aryl THIQs and other tertiary amines with nitromethane as a pro-nucleophile (aza-Henry reaction) and the α-oxidation of THIQs with O2 as a green oxidant. Phosphite, alkyne, or indole derivatives were also shown to be suitable candidates for their use as pro-nucleophiles in the CDC reaction with THIQs. The catalyst, with very low copper loading (0.4-1.0 mol % Cu), could be easily recovered by means of an external magnet and reused in four cycles without significant loss of activity.


Subject(s)
Phosphites , Tetrahydroisoquinolines , Copper , Catalysis , Alkynes , Silicon Dioxide , Oxidants , Amines , Oxidative Stress , Indoles
12.
BMC Psychiatry ; 22(1): 537, 2022 08 09.
Article in English | MEDLINE | ID: mdl-35941557

ABSTRACT

BACKGROUND: Emotional and stress-related disorders show high incidence, prevalence, morbidity, and comorbidity rates in Mexico. In recent decades, research findings indicate that cognitive behavioral interventions, from a disorder-specific perspective, are the effective front-line treatment for anxiety and depression care. However, these treatments are not often used. Reasons include limited access and low availability to effective interventions and comorbidity between mental disorders. Emotional deregulation of negative affectivity has been found to be a mediating factor in addressing emotional disorders from a transdiagnostic perspective, aimed at two or more specific disorders. In addition, technological advancement has created alternatives for psychological assistance, highlighting the possibilities offered by technologies since Internet-supported intervention programs have been empirically tested for effectiveness, efficiency and efficacy and can be key to ensuring access to those who are inaccessible. The aim of the study is to evaluate the efficacy, moderators of clinical change and acceptability of a transdiagnostic guided Internet-delivered intervention versus a transdiagnostic self-guided Internet-delivered intervention for emotional, trauma and stress-related disorders, and waiting list in community sample. METHODS: A three-armed, parallel group, superiority randomized controlled clinical trial with repeated measurements at four times: pretest, posttest, follow-up at 3, 6 and 12 months. Outcomes assessor, participant, care provider and investigator will be blinded. Participants aged 18 to 70 years will be randomly allocated 1:1:1 to one of three study arms: a) Transdiagnostic guided internet-delivered intervention with synchronous assistance, b) Transdiagnostic self-guided internet-delivered intervention, c) Waiting list group. Based on sample size estimation, a minimum of 207 participants (69 in each intervention group) will be included. DISCUSSION: The study could contribute to improving the efficacy of transdiagnostic internet-delivered interventions to promote the dissemination of evidence-based treatments and eventually, to decrease the high prevalence of emotional and trauma-related disorders in the Mexican population. TRIAL REGISTRATION: ClinicalTrial.gov: NCT05225701 . Registered February 4, 2022.


Subject(s)
Cognitive Behavioral Therapy , Therapy, Computer-Assisted , Anxiety Disorders/diagnosis , Anxiety Disorders/therapy , Cognitive Behavioral Therapy/methods , Humans , Internet , Mexico , Randomized Controlled Trials as Topic , Therapy, Computer-Assisted/methods , Treatment Outcome
13.
Evol Anthropol ; 31(5): 237-239, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35758530

ABSTRACT

In an Evolutionary Anthropology article Roksandic et al. (2022) propose a new middle Pleistocene hominin species H. bodoensis to replace a "poorly defined" Homo heidelbergenis. Homo bodoensis extends from the African Middle Pleistocene through the Levant to South-eastern Europe with all currently classified H. heidelbergensis fossils from western Europe subsumed into Homo neandertalensis. The authors claim their new species will be more clearly defined than H. heidelbergensis and will better describe hominin variation and evolution in the middle Pleistocene. Roksandic et al. are unable to account for some European fossils (i.e., Petralona and Arago) and provide no evidence as to how their new species meets their objectives. Fatally, they overlook the priority rule and fail to realize that H. bodoensis is both a junior synonym of Homo rhodesiensis and Homo saldanensis. Roksandic et al. conflate taxonomy with phylogeny, present hypotheses as facts, and harbor many systematic and evolutionary misconceptions.


Subject(s)
Hominidae , Animals , Fossils , Anthropology , Europe , Biological Evolution
14.
Actas Dermosifiliogr ; 113(10): 923-929, 2022.
Article in English, Spanish | MEDLINE | ID: mdl-35636506

ABSTRACT

BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.


Subject(s)
Neurofibromatosis 1 , Pigmentation Disorders , Xanthogranuloma, Juvenile , Child , Humans , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/epidemiology , Case-Control Studies , Cafe-au-Lait Spots/epidemiology , Cafe-au-Lait Spots/etiology , Cafe-au-Lait Spots/diagnosis , Prevalence , Inflammation
15.
ESMO Open ; 7(2): 100463, 2022 04.
Article in English | MEDLINE | ID: mdl-35405437

ABSTRACT

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Female , Humans , Indoles/adverse effects , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Male , Prospective Studies , Sunitinib/adverse effects
16.
Med. intensiva (Madr., Ed. impr.) ; 46(3): 123-131, Mar. 2022. tab
Article in Spanish | IBECS | ID: ibc-204233

ABSTRACT

Objective: To describe the transfusion practice in the ICUs in Spain, according to national and international recommendations (guidelines). Design: Prospective, cross-sectional, multi-centre study. Scope: Data collection was carried out by means of a questionnaire sent electronically to the Heads of Service of 111 ICUs in Spain. Participants: 1,448 patients were included, aged 61.8 (SD 15.7) years, 66.2% male, with an SOFA of 4.7 ± 3.8 and average stay of 10.62 ± 17.49 days. Variables: Demographic and clinical variables of the patients were collected, as well as variables related to the transfusion act. Results: Of the 1,448 patients, 9.9% received al least one transfusion of any blood product, 3.7% fresh plasma, 3.9% platelets and 8.9% red blood cell concentrate, mainly by analytical criteria (36.2%). Hemoglobin had a mean of 7.8 g/dL (95% CI: 6-9-8.5) and 9.8 g/dL (95% CI: 8.5–11.2) before and after the transfusion, respectively, p < 0.001. The transfusion units had a mean of 2.5 ± 2.4 per patient. The most commonly used blood product was red blood cell concentrate (CH) (90.2%). Patients admitted for surgery had a higher transfusion rate (14.4%) than those admitted for medical pathology (8.9%) (p = 0.006). 5.4% (7/129) of patients who received CH died compared to 2.4% (31/1302) who did not (p = 0.04). Mortality of transfused patients was higher. The transfusion rate in most of hospitals was 5% to 20%, with 18 hospitals (16.21%) having transfusion rates between 20% and 50%. Hospitals with PBM programs and mass transfusion programs had a lower transfusion rate, although not statistically significant. Conclusions: In this multicenter cross-sectional study, a transfusion prevalence of 9.9% was observed in Spanish Critical Care Units. The most frequent blood product transfused was red blood cells and the main reasons for transfusion were acute anemia with hemodynamic impact and analytical criteria. Mortality of transfused patients was higher (AU)


Objetivo: Describir la práctica transfusional en las UCIs de España, acorde con recomendaciones (guidelines) nacionales e internacionales. Diseño: Estudio prospectivo, transversal y multicéntrico. Ámbito: La recogida de datos se realizó mediante una encuesta enviada electrónicamente a los médicos intensivistas de 111 UCIs de España. Participantes: Se incluyeron 1.448 pacientes, de 61,8 (DE 15,7) años, el 66,2% varones, con un SOFA de 4,7 ± 3,8 y estancia media de 10,62 ± 17,49 días. Variables: Se recogieron variables demográficas y clínicas de los pacientes, así como variables relacionadas con el propio acto transfusional. Resultados: De los 1.448 pacientes, el 9,9% recibieron al menos una transfusión de cualquier hemocomponente, 3,7% de plasma fresco, 3,9% de plaquetas y 8,9% de concentrado de hematíes, siendo la causa principal el umbral transfusional basado en la hemoglobina (36,2%). La hemoglobina tuvo una media de 7,8 g/dL (IC 95%: 6,9–8,5), y de 9.8 g/dl (IC95%: 8,5–11,2) antes y después de la transfusión respectivamente (p < 0,001). Las unidades transfundas tuvo una media por paciente de 2,5 ± 2,4 por paciente. El hemoderivado más utilizado fue el concentrado de hematíes (CH) (90,2%). Los pacientes ingresados por motivos quirúrgicos tuvieron una tasa de transfusión mayor (14,4%) respecto a los ingresados por patología médica (8,9%) (p = 0,006). El 5,4% (7/129) de los pacientes que recibieron CH fallecieron respecto el 2,4% (31/1302) que no lo recibieron (p = 0,04). La tasa de transfusión en la mayor parte de hospitales fue de 5% al 20%, habiendo 18 hospitales (16.21%) con tasas de transfusión entre el 20% y el 50%. Los hospitales con programas PBM y programas de transfusión masiva tuvieron una menor tasa de transfusión, aunque sin ser significativa. Conclusiones: En este estudio multicéntrico de corte transversal se observó una prevalencia transfusional en las unidades de críticos españolas del 9,9% (AU)


Subject(s)
Humans , Male , Female , Pregnancy , Middle Aged , Aged , Blood Transfusion/statistics & numerical data , Erythrocyte Transfusion/statistics & numerical data , Intensive Care Units , Critical Care , Prospective Studies , Cross-Sectional Studies , Spain
17.
Med Intensiva (Engl Ed) ; 46(3): 123-131, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34996742

ABSTRACT

OBJECTIVE: To describe the transfusion practice in the ICUs in Spain, according to national and international recommendations (guidelines). DESIGN: Prospective, cross-sectional, multi-centre study. SCOPE: Data collection was carried out by means of a questionnaire sent electronically to the Heads of Service of 111 ICUs in Spain. PARTICIPANTS: 1,448 patients were included, aged 61.8 (SD 15.7) years, 66.2% male, with an SOFA of 4.7 ±â€¯3.8 and average stay of 10.62 ±â€¯17.49 days. VARIABLES: Demographic and clinical variables of the patients were collected, as well as variables related to the transfusion act. RESULTS: Of the 1,448 patients, 9.9% received al least one transfusion of any blood product, 3.7% fresh plasma, 3.9% platelets and 8.9% red blood cell concentrate, mainly by analytical criteria (36.2%). Hemoglobin had a mean of 7.8 g/dL (95% CI: 6-9-8.5) and 9.8 g/dL (95% CI: 8.5-11.2) before and after the transfusion, respectively, p < 0.001. The transfusion units had a mean of 2.5 ±â€¯2.4 per patient. The most commonly used blood product was red blood cell concentrate (CH) (90.2%). Patients admitted for surgery had a higher transfusion rate (14.4%) than those admitted for medical pathology (8.9%) (p = 0.006). 5.4% (7/129) of patients who received CH died compared to 2.4% (31/1302) who did not (p = 0.04). Mortality of transfused patients was higher. The transfusion rate in most of hospitals was 5% to 20%, with 18 hospitals (16.21%) having transfusion rates between 20% and 50%. Hospitals with PBM programs and mass transfusion programs had a lower transfusion rate, although not statistically significant. CONCLUSIONS: In this multicenter cross-sectional study, a transfusion prevalence of 9.9% was observed in Spanish Critical Care Units. The most frequent blood product transfused was red blood cells and the main reasons for transfusion were acute anemia with hemodynamic impact and analytical criteria. Mortality of transfused patients was higher.


Subject(s)
Blood Transfusion , Erythrocyte Transfusion , Critical Care , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prospective Studies
18.
Adv Colloid Interface Sci ; 299: 102530, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34610863

ABSTRACT

Nanocelluloses in recent years have garnered a lot of attention for their use as stabilizers of liquid-liquid and gas-liquid interfaces. Both cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs) have been used extensively in multiple studies to prepare emulsions and foams. However, there is limited literature available that systematically discusses the mechanisms that affect the ability of nanocelluloses (modified and unmodified) to stabilize different types of interfaces. This review briefly discusses key factors that affect the stability of Pickering emulsions and foams and provides a detailed and systematic analysis of the current state knowledge on factors affecting the stabilization of liquid-liquid and gas-liquid interfaces by nanocelluloses. The review also discusses the effect of nanocellulose surface modifications on mechanisms driving the Pickering stabilization of these interfaces.


Subject(s)
Cellulose , Nanoparticles , Aerosols , Emulsions
19.
Insects ; 12(8)2021 Jul 21.
Article in English | MEDLINE | ID: mdl-34442229

ABSTRACT

Aedes aegypti control programs require more sensitive tools in order to survey domestic and peridomestic larval habitats for dengue and other arbovirus prevention areas. As a consequence of the COVID-19 pandemic, field technicians have faced a new occupational hazard during their work activities in dengue surveillance and control. Safer strategies to monitor larval populations, in addition to minimum householder contact, are undoubtedly urgently needed. Drones can be part of the solution in urban and rural areas that are dengue-endemic. Throughout this study, the proportion of larvae breeding sites found in the roofs and backyards of houses were assessed using drone images. Concurrently, the traditional ground field technician's surveillance was utilized to sample the same house groups. The results were analyzed in order to compare the effectiveness of both field surveillance approaches. Aerial images of 216 houses from El Vergel village in Tapachula, Chiapas, Mexico, at a height of 30 m, were obtained using a drone. Each household was sampled indoors and outdoors by vector control personnel targeting all the containers that potentially served as Aedes aegypti breeding sites. The main results were that the drone could find 1 container per 2.8 found by ground surveillance; however, containers that were inaccessible by technicians in roofs and backyards, such as plastic buckets and tubs, disposable plastic containers and flowerpots were more often detected by drones than traditional ground surveillance. This new technological approach would undoubtedly improve the surveillance of Aedes aegypti in household environments, and better vector control activities would therefore be achieved in dengue-endemic countries.

20.
Med. intensiva (Madr., Ed. impr.) ; 45(5): 289-297, jun.-jul. 2021. tab, ilus
Article in Spanish | IBECS | ID: ibc-186896

ABSTRACT

Objetivo: Describir las características y la evolución de los pacientes con bronquiolitis ingresados en una unidad de cuidados intensivos pediátricos. Comparar el tratamiento administrado pre y pospublicación de la guía de práctica clínica de la Academia Americana de Pediatría. Diseño: Estudio descriptivo y observacional realizado entre septiembre de 2010 y septiembre de 2017. Configuración: Unidad de cuidados intensivos pediátricos. Pacientes: Menores de un año con bronquiolitis grave. Intervenciones: Se compararon 2 períodos (2010-14 y 2015-17), antes y después de la modificación del protocolo de manejo de la bronquiolitis en el hospital, según las guías de la Academia Americana de Pediatría. Principales variables: Sexo, edad, comorbilidades, gravedad, etiología, tratamiento administrado, infecciones bacterianas, soporte respiratorio e inotrópico, estancia y mortalidad. Resultados: Se recogieron 706 pacientes, 414 (58,6%) varones, con una mediana de edad de 47 días (RIC 25-100,25). Mediana de escala de gravedad de bronquiolitis (BROSJOD) al ingreso: 9 puntos (RIC 7-11). La etiología por virus respiratorio sincitial se dio en 460 (65,16%) pacientes. El primer período (2010-14) incluyó 340 pacientes y el segundo (2015-17), 366 pacientes. En el segundo período se administraron más nebulizaciones de adrenalina y suero salino hipertónico, y más tratamiento con corticoides. Se usó más ventilación no invasiva y menos ventilación mecánica convencional y precisaron menos soporte inotrópico, sin diferencias significativas. La tasa de antibioterapia disminuyó de forma estadísticamente significativa (p = 0,003). Conclusiones: Pese a la disminución en la antibioterapia, se debería limitar la utilización de nebulizaciones y corticoides en estos pacientes, como recomienda la guía


Objective: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. Design: A descriptive and observational study was carried out between September 2010 and September 2017. Setting: Pediatric intensive care unit. Patients: Infants under one year of age with severe bronchiolitis. Interventions: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. Main variables: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. Results: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (P = .003). Conclusions: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide


Subject(s)
Humans , Male , Female , Infant , Bronchiolitis/therapy , Practice Guidelines as Topic , Clinical Decision-Making , Acute Disease/therapy , Intensive Care Units, Pediatric/statistics & numerical data , Academies and Institutes/standards , Respiratory Syncytial Virus Infections/etiology , Respiratory Insufficiency/etiology , Retrospective Studies , Algorithms
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