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1.
Nat Commun ; 15(1): 2667, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531839

RESUMO

Mutual conversion of various kinds of magnetohydrodynamic (MHD) waves can have profound impacts on wave propagation, energy transfer, and heating of the solar chromosphere and corona. Mode conversion occurs when an MHD wave travels through a region where the Alfvén and sound speeds are equal (e.g., a 3D magnetic null point). Here we report the direct extreme ultraviolet (EUV) imaging of mode conversion from a fast-mode to a slow-mode MHD wave near a 3D null point using Solar Dynamics Observatory/Atmospheric Imaging Assembly (SDO/AIA) observations. An incident fast EUV wavefront associated with an adjacent eruptive flare propagates laterally through a neighboring pseudostreamer. Shortly after the passage of the fast EUV wave through the null point, a slow-mode wave appears near the null that propagates upward along the open structures and simultaneously downward along the separatrix encompassing the fan loops of the pseudostreamer base. These observations suggest the existence of mode conversion near 3D nulls in the solar corona, as predicted by theory and MHD simulations. Moreover, we observe decaying transverse oscillations in both the open and closed structures of the pseudostreamer, along with quasiperiodic type III radio bursts indicative of repetitive episodes of electron acceleration.

2.
BMC Cancer ; 24(1): 272, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408958

RESUMO

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Gencitabina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Cloridrato de Erlotinib/uso terapêutico , Adenocarcinoma/patologia , Desoxicitidina , Fluoruracila , Leucovorina/uso terapêutico , Paclitaxel , Albuminas
4.
Materials (Basel) ; 16(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38068057

RESUMO

The article reveals for the first time the features of nanoparticle morphology, phase compositions, and their changes when heating FePt and CoPt nanoalloys. Nanoparticles were obtained by co-reduction of precursor solution mixtures with hydrazine hydrate. The features were found by a complex of methods of X-ray diffraction (in situ XRD and X-ray scattering), TEM HR, and cyclic voltammetry. In addition, adsorbometry results were obtained, and the stability of different nanocluster structures was calculated by the molecular dynamics method. There were only FCC solid solutions in the X-ray patterns of the FePt and CoPt nanoalloys. According to XRD, in the case of nanoparticle synthesis with Fe and Co content less than 10 at. %, the composition of solid solutions was close to or practically equal to the composition of the as-synthesized nanoparticles quantified by inductively coupled plasma optical emission spectrometry. For systems synthesis with Fe and Co content greater than the above, the solubility limits (SLs) of Fe and Co in Pt were set 11.4 ± 0.7 at. % and 17.5 ± 0.6 at. %, respectively. Therefore, there were non-registered XRD extra-phases (XRNDPh-1) in the systems when CFe,Co ≥ SL. This statement was supported by the results of TEM HR and X-ray scattering: the smallest nanocrystals (1-2 nm) and amorphous particles were found, which qualitatively agreed with the sorbometry and SAXS results. Molecular dynamics calculations of stability for FePt and CoPt alloys claimed the structures of the most stable phase corresponded to phase diagrams (A1 and L12). Specific peculiarities of the morphology and compositions of the solid solutions of nanoalloys were established: structural blockiness (domain) and composition heterogeneity, namely, platinum enrichment of internal (deep) layers and homogenization of the nanoalloy compositions at relatively low temperatures (130-200 °C). The suggested model of the formation of nanoalloys during the synthesis, qualitatively, was compliant with the results of electrochemical deposition of FePt films on the surface of various electrodes. When nanocrystals of solid solutions (C(Fe, Co) < SL) were heated above specific temperatures, there were phase transformations with the formation of two-phase regions, with solid solutions enriched with platinum or iron (non-registered XRD phase XRNDPh-2). The newly formed phase was most likely intermetallic compounds, FePt3, CoPt3. As a result of the study, the model was developed, taking into account the nanoscale of the particles: XRDPh (A1, FeaPt1-a) → XRDPh (A1, Fem×a-xPtm-m×a+x) + XRNDPh-2 (Fen×a+yPtn-n×a-y) (here, m + n = 1, m ≤ 1, n ≤ 1).

5.
Biomedicines ; 11(10)2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37893072

RESUMO

Heteroatom steroids, a diverse class of organic compounds, have attracted significant attention in the field of medicinal chemistry and drug discovery. The biological profiles of heteroatom steroids are of considerable interest to chemists, biologists, pharmacologists, and the pharmaceutical industry. These compounds have shown promise as potential therapeutic agents in the treatment of various diseases, such as cancer, infectious diseases, cardiovascular disorders, and neurodegenerative conditions. Moreover, the incorporation of heteroatoms has led to the development of targeted drug delivery systems, prodrugs, and other innovative pharmaceutical approaches. Heteroatom steroids represent a fascinating area of research, bridging the fields of organic chemistry, medicinal chemistry, and pharmacology. The exploration of their chemical diversity and biological activities holds promise for the discovery of novel drug candidates and the development of more effective and targeted treatments.

6.
Biomedicines ; 11(10)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37893228

RESUMO

A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure-function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3's ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC50 = 0.42 µM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague-Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.

7.
Molecules ; 28(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37894502

RESUMO

This study investigated the effects of aseptic inflammation and heavy metal exposure on immune responses, as well as the potential immunomodulatory properties of the newly synthesized 1-[1-(2,5-dimethoxyphenyl)-4-(naphthalene-1-yloxy)but-2-ynyl]-4-methylpiperazine complexed with ß-cyclodextrin (ß-CD). Aseptic inflammation was induced by a subcutaneous injection of turpentine in rats, while heavy metal exposure was achieved through a daily administration of cadmium chloride and lead acetate. The levels of immune cell populations, including cytotoxic T lymphocytes (CTL), monocytes, and granulocytes, were assessed in the spleen. The results showed that aseptic inflammation led to decreased levels of CTL, monocytes, and granulocytes on the 14th day, indicating an inflammatory response accompanied by a migration of effector cells to the inflamed tissues. The exposure to cadmium chloride and lead acetate resulted in systemic immunotoxic effects, with reduced levels of B cells, CD4+ Th cells, monocytes, and granulocytes in the spleen. Notably, piperazine complexed with ß-CD (the complex) exhibited significant stimulatory effects on CD4+, CD8+, and myeloid cell populations during aseptic inflammation, even in the presence of heavy metal exposure. These findings suggest the potential immunomodulatory properties of the complex in the context of aseptic inflammation and heavy metal exposure.


Assuntos
Cádmio , Metais Pesados , Ratos , Animais , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Inflamação/induzido quimicamente , Piperazinas/farmacologia
8.
Mar Drugs ; 21(10)2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37888474

RESUMO

Reef-building corals, recognized as cornerstone species in marine ecosystems, captivate with their unique duality as both symbiotic partners and autotrophic entities. Beyond their ecological prominence, these corals produce a diverse array of secondary metabolites, many of which are poised to revolutionize the domains of pharmacology and medicine. This exhaustive review delves deeply into the multifaceted world of coral-derived lipids, highlighting both ubiquitous and rare forms. Within this spectrum, we navigate through a myriad of fatty acids and their acyl derivatives, encompassing waxes, sterol esters, triacylglycerols, mono-akyl-diacylglycerols, and an array of polar lipids such as betaine lipids, glycolipids, sphingolipids, phospholipids, and phosphonolipids. We offer a comprehensive exploration of the intricate biochemical variety of these lipids, related fatty acids, prostaglandins, and both cyclic and acyclic oxilipins. Additionally, the review provides insights into the chemotaxonomy of these compounds, illuminating the fatty acid synthesis routes inherent in corals. Of particular interest is the symbiotic bond many coral species nurture with dinoflagellates from the Symbiodinium group; their lipid and fatty acid profiles are also detailed in this discourse. This exploration accentuates the vast potential and intricacy of coral lipids and underscores their profound relevance in scientific endeavors.


Assuntos
Antozoários , Dinoflagelados , Animais , Antozoários/química , Ecossistema , Ácidos Graxos/metabolismo , Prostaglandinas/metabolismo , Recifes de Corais , Dinoflagelados/metabolismo , Simbiose
9.
Nat Commun ; 14(1): 5298, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699884

RESUMO

Decayless kink oscillations of plasma loops in the solar corona may contain an answer to the enigmatic problem of solar and stellar coronal heating. The polarisation of the oscillations gives us a unique information about their excitation mechanisms and energy supply. However, unambiguous determination of the polarisation has remained elusive. Here, we show simultaneous detection of a 4-min decayless kink oscillation from two non-parallel lines-of-sights, separated by about 104∘, provided by unique combination of the High Resolution Imager on Solar Orbiter and the Atmospheric Imaging Assembly on Solar Dynamics Observatory. The observations reveal a horizontal or weakly oblique linear polarisation of the oscillation. This conclusion is based on the comparison of observational results with forward modelling of the observational manifestation of various kinds of polarisation of kink oscillations. The revealed polarisation favours the sustainability of these oscillations by quasi-steady flows which may hence supply the energy for coronal heating.

10.
Molecules ; 28(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37570639

RESUMO

This review article delves into the realm of furanosteroids and related isoprenoid lipids derived from diverse terrestrial and marine sources, exploring their wide array of biological activities and potential pharmacological applications. Fungi, fungal endophytes, plants, and various marine organisms, including sponges, corals, molluscs, and other invertebrates, have proven to be abundant reservoirs of these compounds. The biological activities exhibited by furanosteroids and related lipids encompass anticancer, cytotoxic effects against various cancer cell lines, antiviral, and antifungal effects. Notably, the discovery of exceptional compounds such as nakiterpiosin, malabaricol, dysideasterols, and cortistatins has revealed their potent anti-tuberculosis, antibacterial, and anti-hepatitis C attributes. These compounds also exhibit activity in inhibiting protein kinase C, phospholipase A2, and eliciting cytotoxicity against cancer cells. This comprehensive study emphasizes the significance of furanosteroids and related lipids as valuable natural products with promising therapeutic potential. The remarkable biodiversity found in both terrestrial and marine ecosystems offers an extensive resource for unearthing novel biologically active compounds, paving the way for future drug development and advancements in biomedical research. This review presents a compilation of data obtained from various studies conducted by different authors who employed the PASS software 9.1 to evaluate the biological activity of natural furanosteroids and compounds closely related to them. The utilization of the PASS software in this context offers valuable advantages, such as screening large chemical libraries, identifying compounds for subsequent experimental investigations, and gaining insights into potential biological activities based on their structural features. Nevertheless, it is crucial to emphasize that experimental validation remains indispensable for confirming the predicted activities.


Assuntos
Produtos Biológicos , Ecossistema , Animais , Invertebrados/metabolismo , Organismos Aquáticos/química , Fungos/química , Produtos Biológicos/química , Lipídeos
11.
Biomedicines ; 11(8)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37626733

RESUMO

This review explores the biological activity and structural diversity of steroids and related isoprenoid lipids, with a particular focus on compounds containing an oxirane ring. These natural compounds are derived from fungi, fungal endophytes, as well as extracts of plants, algae, and marine invertebrates. To evaluate their biological activity, an extensive examination of refereed literature sources was conducted, including in vivo and in vitro studies and the utilization of the QSAR method. Notable properties observed among these compounds include strong anti-inflammatory, antineoplastic, antiproliferative, anti-hypercholesterolemic, antiparkinsonian, diuretic, anti-eczematic, anti-psoriatic, and various other activities. Throughout this review, 3D graphs illustrating the activity of individual steroids are presented, accompanied by images of selected terrestrial or marine organisms. Furthermore, this review provides explanations for specific types of biological activity associated with these compounds. The data presented in this review are of scientific interest to the academic community and carry practical implications in the fields of pharmacology and medicine. By analyzing the biological activity and structural diversity of steroids and related isoprenoid lipids, this review offers valuable insights that contribute to both theoretical understanding and applied research. This review draws upon data from various authors to compile information on the biological activity of natural steroids containing an oxirane ring.

12.
Sci Rep ; 13(1): 12963, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563258

RESUMO

The energy balance in the corona of the Sun is the key to the long-standing coronal heating dilemma, which could be potentially revealed by observational studies of decayless kink oscillations of coronal plasma loops. A bundle of very long off-limb coronal loops with the length of [Formula: see text] Mm and a lifetime of about 2 days are found to exhibit decayless kink oscillations. The oscillations are observed for several hours. The oscillation amplitude is measured at 0.3-0.5 Mm, and the period at 28-33 min. The existence of 30-min periodicity of decayless kink oscillations indicates that the mechanism compensating the wave damping is still valid in such a massive plasma structure. It provides important evidence for the non-resonant origin of decayless kink oscillations with 2-6 min periods, i.e., the lack of their link with the leakage of photospheric and chromospheric oscillations into the corona and the likely role of the broadband energy sources. Magnetohydrodynamic seismology based on the reported detection of the kink oscillation, with the assistance of the differential emission measure analysis and a background coronal model provides us with a comprehensive set of plasma and magnetic field diagnostics, which is of interest as input parameters of space weather models.

13.
Molecules ; 28(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37513423

RESUMO

This review delves into the investigation of the biological activity and structural diversity of steroids and related isoprenoid lipids. The study encompasses various natural compounds, such as steroids with aromatic ring(s), steroid phosphate esters derived from marine invertebrates, and steroids incorporating halogen atoms (I, Br, or Cl). These compounds are either produced by fungi or fungal endophytes or found in extracts of plants, algae, or marine invertebrates. To assess the biological activity of these natural compounds, an extensive examination of referenced literature sources was conducted. The evaluation encompassed in vivo and in vitro studies, as well as the utilization of the QSAR method. Numerous compounds exhibited notable properties such as strong anti-inflammatory, anti-neoplastic, anti-proliferative, anti-hypercholesterolemic, anti-Parkinsonian, diuretic, anti-eczematic, anti-psoriatic, and various other activities. Throughout the review, 3D graphs illustrating the activity of individual steroids are presented alongside images of selected terrestrial or marine organisms. Additionally, the review provides explanations for specific types of biological activity associated with these compounds. The data presented in this review hold scientific interest for academic science as well as practical implications in the fields of pharmacology and practical medicine. The analysis of the biological activity and structural diversity of steroids and related isoprenoid lipids provides valuable insights that can contribute to advancements in both theoretical understanding and applied research.


Assuntos
Produtos Biológicos , Fosfatos , Esteroides/farmacologia , Terpenos/farmacologia , Fungos , Plantas/química , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Lipídeos/farmacologia
14.
Cancer Chemother Pharmacol ; 92(3): 229-233, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37354233

RESUMO

BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.


Assuntos
Anticorpos Biespecíficos , Linfoma Difuso de Grandes Células B , Humanos , Síndrome da Liberação de Citocina/induzido quimicamente , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico
15.
Zookeys ; 1148: 1-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235139

RESUMO

This study contains an analysis of basal metabolic rate (BMR) in 1817 endothermic species. The aim was to establish how metabolic scaling varies between the main groups of endotherms during evolution. The data for all the considered groups were combined and the common exponent in the allometric relationship between the BMR and body weight was established as b = 0.7248. Reduced to the common slope, the relative metabolic rate forms the following series: Neognathae - Passeriformes - 1.00, Neognathae - Non-Passeriformes - 0.75, Palaeognathae - 0.53, Eutheria - 0.57, Marsupialia - 0.44, and Monotremata - 0.26. The main finding is that the metabolic rate in the six main groups of mammals and birds consistently increases as the geological time of the group's divergence approaches the present. In parallel, the average body temperature in the group rises, the duration of sleep decreases and the duration of activity increases. BMR in a taxon correlates with its evolutionary age: the later a clade diverged, the higher is its metabolic rate and the longer is its activity period; group exponents decrease as group divergence nears present times while with increase metabolic rate during activity, they not only do not decrease but can increase. Sleep duration in mammals was on average 40% longer than in birds while BMR, in contrast, was 40% higher in birds. The evolution of metabolic scaling, body temperature, sleep duration, and activity during the development of endothermic life forms is demonstrated, allowing for a better understanding of the underlying principles of endothermy formation.

16.
Sci Rep ; 13(1): 5829, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37037899

RESUMO

This study announces the anomalous phase separation in CoNiP alloy electroplating. The observed phenomenon of the formation of magnetic bubbles was described for the first time for this triple CoNiP system. This study briefly covers all stages of magnetic bubble formation, starting from the formation of an amorphous phosphor-rich sublayer, followed by nucleation centers, and finally cobalt-rich bubbles. An explanation for the anomalous mechanism of bubble formation was found in the effects of additives and the phenomena of depolarization and superpolarization.

17.
Front Endocrinol (Lausanne) ; 14: 1121002, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777337

RESUMO

Corticosteroids are critical for development and for mediating stress responses across diverse vertebrate taxa. Study of frog metamorphosis has made significant breakthroughs in our understanding of corticosteroid signaling during development in non-mammalian vertebrate species. However, lack of adequate corticosterone (CORT) response genes in tadpoles make identification and quantification of CORT responses challenging. Here, we characterized a CORT-response gene frzb (frizzled related protein) previously identified in Xenopus tropicalis tadpole tail skin by an RNA-seq study. We validated the RNA-seq results that CORT and not thyroid hormone induces frzb in the tails using quantitative PCR. Further, maximum frzb expression was achieved by 100-250 nM CORT within 12-24 hours. frzb is not significantly induced in the liver and brain in response to 100 nM CORT. We also found no change in frzb expression across natural metamorphosis when endogenous CORT levels peak. Surprisingly, frzb is only induced by CORT in X. tropicalis tails and not in Xenopus laevis tails. The exact downstream function of increased frzb expression in tails in response to CORT is not known, but the specificity of hormone response and its high mRNA expression levels in the tail render frzb a useful marker of exogenous CORT-response independent of thyroid hormone for exogenous hormone treatments and in-vivo endocrine disruption studies.


Assuntos
Corticosterona , Regulação da Expressão Gênica no Desenvolvimento , Animais , Xenopus/genética , Xenopus/metabolismo , Corticosterona/farmacologia , Corticosterona/metabolismo , Larva , Xenopus laevis/genética , Xenopus laevis/metabolismo , Hormônios Tireóideos/farmacologia , Hormônios Tireóideos/metabolismo
18.
Dig Liver Dis ; 55(3): 407-411, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36088220

RESUMO

BACKGROUND: Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there is little data and no consensus regarding subsequent lines [1-5]. In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy. METHOD: A retrospective analysis of patients with metastatic SCAC (mSCAC), who failed on at least one prior line of treatment, before being treated with the combination FOLFIRI and cetuximab between March 2015 and February 2022 at Gustave Roussy cancer center, was performed. RESULTS: A total of 33 patients with a pre-treated mSCAC were analyzed. The combination of FOLFIRI and cetuximab provided a disease control rate (DCR) of 73%, and response rate of 30%. With a median follow-up of 38 months, the median progression free survival was 5.5 months, and the median overall survival was 13.7 months. Fourteen patients (42%) experienced grade III/IV adverse events that remained manageable. CONCLUSION: Our study suggests that FOLFIRI and cetuximab is a promising combination in the management of mSCAC with a very good DCR and a manageable toxicity profile. Further prospective trials would be needed to confirm our results.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Cetuximab , Irinotecano/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Canal Anal , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Fluoruracila , Células Epiteliais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
19.
J Pediatr ; 257: 113304, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36528053

RESUMO

OBJECTIVE: Determine the clinical safety and feasibility of implementing a telemedicine and medication delivery service (TMDS) to address gaps in nighttime access to health care for children in low-resource settings. STUDY DESIGN: We implemented a TMDS called 'MotoMeds' in Haiti as a prospective cohort study. A parent/guardian of a sick child ≤ 10 years contacted the call center (6 PM-5 AM). A nurse provider used decision support tools to triage cases (mild, moderate, or severe). Severe cases were referred to emergency care. For nonsevere cases, providers gathered clinical findings to generate an assessment and plan. For cases within the delivery zone, a provider and driver were dispatched and the provider performed a paired in-person exam as a reference standard for the virtual call center exam. Families received a follow-up call at 10 days. Data were analyzed for clinical safety and feasibility. RESULTS: A total of 391 cases were enrolled from September 9, 2019, to January 19, 2021. Most cases were nonsevere (92%; 361); household visits were completed for 89% (347) of these cases. Among the 30 severe cases, 67% (20) sought referred care. Among all cases, respiratory problems were the most common complaint (63%; 246). At 10 days, 95% (329) of parents reported their child had "improved" or "recovered". Overall, 99% (344) rated the TMDS as "good" or "great". The median phone consultation time was 20 minutes, time to household arrival was 73 minutes, and total case time was 114 minutes. CONCLUSION: The TMDS was a feasible health care delivery model. Although many cases were likely self-limiting, the TMDS was associated with high rates of reported improvement in clinical status at 10 days. TRIAL REGISTRATION: clinicaltrials.gov: NCT03943654.


Assuntos
Telemedicina , Criança , Humanos , Estudos de Viabilidade , Projetos Piloto , Estudos Prospectivos , Encaminhamento e Consulta
20.
Zootaxa ; 5352(3): 426-432, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38221439

RESUMO

Paleogenia waichertae Loktionov, Lelej et Perkovsky, sp. nov. is a new species of extinct spider wasps. This new species is a second record of Pompilidae from Rovno amber, third yet known species of the extinct genus Paleogenia Waichert et Pitts, 2016 and 26th known extinct species of spider wasps. Sex of the holotype of the species Paleogenia indomini Colombo et Waichert, 2023 is clarified (male not female). A key to males of Paleogenia is provided.


Assuntos
Himenópteros , Vespas , Masculino , Animais , Âmbar , Fósseis
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