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1.
J Taibah Univ Med Sci ; 19(4): 753-765, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39105209

RESUMO

Objective: This study assessed the prophylactic anti-HCC effects of a combined stem and root alkaloidal extract of Zanthoxylum zanthoxyloides (Z. zanthoxyloides) (SRAEZZ) in rats with a CCl4/olive oil-induced HCC-like phenotype. Methods: SRAEZZ was prepared from dried stems and roots of Z. zanthoxyloides in a 1:1 proportion and chemically characterized. A total of 30 healthy male Wistar rats (weighing 210-280 g) were randomly assigned to six groups (control, model, capecitabine, and SRAEZZ [50, 100, or 200 mg/kg]). All groups except the control received CCl4/olive oil (3 mL/kg, po) in the morning, whereas in the afternoon of the same dosing day, the model group received normal saline (5 mL/kg, po), the capecitabine group received capecitabine (50 mg/kg, po), and the SRAEZZ groups received SRAEZZ (50, 100, or 200 mg/kg, po, respectively) once per week for 36 days. Survival rate, serum α-fetoprotein (AFP), and C-reactive protein (CRP) were monitored. Gross liver anatomy, liver histology, liver enzymes (ALP, AST, and ALT), bilirubin, creatinine, urea, albumin, globulins, and hematological parameters were assessed. Results: SRAEZZ yield was 0.58% from the initial stem and root sample (520 g). Quaternary phenanthridin alkaloids were detected in SRAEZZ. Control rats had a 100% survival rate compared with rats in the model group. SRAEZZ treatment improved the survival rate with respect to that in the model group. Serum AFP, CRP, and bilirubin levels were greater in the model group than the control group. SRAEZZ decreased serum AFP, CRP, and bilirubin below the levels observed in the model group. ALP, AST, and AST were higher in the model group, but lower in SRAEZZ-treated group, than the control group. Conclusion: SRAEZZ demonstrated prophylactic anti-HCC effects against CCl4/olive oil-induced HCC-like phenotypes in rats. These findings highlight the potential of crude alkaloids from Z. zanthoxyloides as natural templates for semi-synthesis of anti-HCC pharmacotherapeutics.

2.
Polymers (Basel) ; 16(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39125178

RESUMO

With the rapid development of wireless communication technologies and the miniaturization trend in the electronics industry, the reduction of electromagnetic interference has become an important issue. To solve this problem, a lot of attention has been focused on polymer composites with combined functional fillers. In this paper, we report a method for creating an acrylonitrile butadiene styrene (ABS) plastic composite with a low amount of conductive carbon and magnetic fillers preparation. Also, we investigate the mechanical, thermophysical, and electrodynamic characteristics of the resulting composites. Increasing the combined filler amount in the ABS composite from 1 to 5 wt % leads to a composite conductivity growth of almost 50 times. It is necessary to underline the temperature decrease of 5 wt % mass loss and, accordingly, the composite heat resistance reduction with an increase in the combined filler from 1 to 5 wt %, while the thermal conductivity remains almost constant. It was established that electrodynamic and physical-mechanical characteristics depend on the agglomeration of fillers. This work is expected to reveal the potential of combining commercially available fillers to construct effective materials with good electromagnetic interference (EMI) protection using mass production methods (extrusion and injection molding).

3.
Commun Biol ; 7(1): 978, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134631

RESUMO

The evolutionary histories of adaptive radiations can be marked by dramatic demographic fluctuations. However, the demographic histories of ecologically-linked co-diversifying lineages remain understudied. The Laurentian Great Lakes provide a unique system of two such radiations that are dispersed across depth gradients with a predator-prey relationship. We show that the North American Coregonus species complex ("ciscoes") radiated rapidly prior to the Last Glacial Maximum (80-90 kya), a globally warm period, followed by rapid expansion in population size. Similar patterns of demographic expansion were observed in the predator species, Lake Charr (Salvelinus namaycush), following a brief time lag, which we hypothesize was driven by predator-prey dynamics. Diversification of prey into deep water created ecological opportunities for the predators, facilitating their demographic expansion, which is consistent with an upward adaptive radiation cascade. This study provides a new timeline and environmental context for the origin of the Laurentian Great Lakes fish fauna, and firmly establishes this system as drivers of ecological diversification and rapid speciation through cyclical glaciation.


Assuntos
Lagos , Animais , Great Lakes Region , Peixes/classificação , Peixes/fisiologia , Salmonidae/fisiologia , Salmonidae/genética , Evolução Biológica , Truta/fisiologia , Especiação Genética
4.
Ophthalmology ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39128550

RESUMO

OBJECTIVE: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DESIGN: Secondary analysis of four prospective population-based studies. PARTICIPANTS: We included four European-ancestry cohorts: the United States (US) based Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. METHODS: PRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. MAIN OUTCOME MEASURES: The relative risk for POAG and Harrell's C-statistic (the equivalent of an area-under-the-curve for longitudinal models). RESULTS: Among 1,046 cases and 38,809‬ controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). CONCLUSIONS: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

5.
J Clin Invest ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207859

RESUMO

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the Bvax (B-cell-based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aim to characterize the antigenic reactivity of BVax-derived antibodies and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and human GBM patient samples. Our investigations revealed that BVax distributes throughout the GBM tumor microenvironment (TME) and then differentiates into antibody-producing plasmablasts. Proteomic analyses indicate that the antibodies produced by BVax display unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these antibodies inhibit critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of BVax-derived antibodies for GBM patients, pointing towards a novel direction in GBM immunotherapy.

6.
ACS Appl Mater Interfaces ; 16(34): 45411-45421, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39158685

RESUMO

Physicochemical properties of polymers strongly depend on the arrangement and distribution of attached monomers. Templated polymerization using porous crystalline materials appears as a promising route to gain control on the process. Thus, we demonstrate here the potential of metal-organic frameworks as scaffolds with a versatile and very regular porosity, well adapted for the regioselective oxidative polymerization of pyrene. This photoresponsive monomer was first encapsulated within the one-dimensional (1D) microporosity of the robust zirconium(IV) carboxylate metal-organic framework (MOF) (MIL-140D) to, later, undergo in situ oxidative polymerization, enabling the growth of a highly selective polypyrene (PPyr) regioisomer over other potential polymer configurations. To confirm the polymerization and the geometry control of pyrene, the resulting composites were exhaustively characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), N2 sorption measurements, scanning transmission electron microscopy coupled with energy-dispersive X-ray (STEM-EDX) spectroscopy, and fluorescence spectroscopy. Among others, photoluminescence quenching and emission shift in the solid state demonstrated the presence of PPyr inside the MOF porosity. Furthermore, an in-depth joint analysis combining solid-state, magic-angle spinning (MAS) 1H and 13C NMR spectroscopy, Fourier transform infrared (FTIR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS), and molecular simulations (grand canonical Monte Carlo (GCMC) and density functional theory (DFT)) allowed the elucidation of the spatial, host-guest interactions driving the polymerization reaction.

7.
Cancer Invest ; : 1-11, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007916

RESUMO

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

8.
Diagnostics (Basel) ; 14(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39001281

RESUMO

This article examines two cases of odontogenic orbital cellulitis, highlighting the complexities and interdisciplinary approaches required for effective management. We present two cases and describe the clinical challenges and treatment strategies employed. We report the diagnosis, treatment, and follow-up of patients who developed orbital cellulitis as a complication of an odontogenic infection. Our objective is to report and discuss the clinical aspects and management of this pathology compared to those observed in the literature. This study underscores the necessity for collaboration among various specialties, including ophthalmology, otolaryngology, oral surgery, radiology, and infectious disease, to address the multifaceted challenges posed by this condition. Effective management of orbital abscesses of odontogenic origin requires a timely and multidisciplinary approach for successful outcomes. This article emphasizes the importance of early diagnosis and coordinated care to prevent serious complications, such as vision loss or intracranial infections.

9.
Wiad Lek ; 77(5): 1101-1105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008604

RESUMO

Eccrine acrospiroma is a rare benign tumor of the skin arising from the epithelial cells of eccrine sweat ducts. The clinical picture is characterized by its variability, so a detailed morphological study of the operative material is necessary to establish a diagnosis. Differential diagnosis must be carried out with hemangioma, melanoma, infected sebaceous cyst, metastatic skin lesion, and other tumors from elements of the sweat gland. In the article the authors presented the clinical and morphological analysis of own case from practice of large eccrine acrospiroma on the back surface of the left thigh which was diagnosed in a 56-year-old man.


Assuntos
Acrospiroma , Neoplasias das Glândulas Sudoríparas , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Diferencial , Neoplasias das Glândulas Sudoríparas/patologia , Acrospiroma/patologia , Acrospiroma/diagnóstico , Glândulas Écrinas/patologia , Coxa da Perna/patologia
11.
Cancer Med ; 13(14): e70000, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031958

RESUMO

BACKGROUND: In the last decade, technical innovations have resulted in the development of several minimally invasive diagnostic cancer tools. Within women at high risk of developing ovarian or endometrial cancer (EC) due to hereditary cancer syndrome, there is an urgent need for minimally invasive and patient-friendly methods to detect ovarian cancer and EC at an early stage. MATERIALS AND METHODS: We performed a systematic search of studies using DNA methylation or mutation analysis, microbiome, or proteomics performed on cervicovaginal specimens (smear, swab, or tampon) intended to detect ovarian and EC published until January 2024. RESULTS: Included studies (n = 36) showed high heterogeneity in terms of biomarkers used and outcomes, and only a few studies reported on the detection of biomarkers in high-risk subgroups. CONCLUSION: Based on the findings in this review, DNA methylation techniques seem to be the most promising for detecting ovarian and EC at early stages in the general population. Future validation of cervicovaginal DNA methylation techniques is needed to determine whether this technique might be beneficial in hereditary high-risk subgroups.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Detecção Precoce de Câncer , Neoplasias do Endométrio , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Detecção Precoce de Câncer/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/genética , Vagina/metabolismo , Vagina/microbiologia , Colo do Útero/metabolismo , Colo do Útero/patologia , Proteômica/métodos
12.
J Am Coll Cardiol ; 84(5): 417-429, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39048273

RESUMO

BACKGROUND: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction. OBJECTIVES: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers. METHODS: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery. RESULTS: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HRadjusted: 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%). CONCLUSIONS: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events.


Assuntos
Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio , Isquemia Miocárdica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Idoso , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/diagnóstico por imagem , Teste de Esforço/métodos , Estados Unidos/epidemiologia
13.
Neuro Oncol ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028616

RESUMO

BACKGROUND: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers. METHOD: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor associated macrophages/microglia (TAMs). RESULTS: FcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed in TAMs in human glioblastoma, most robustly at diagnosis. Notably, FcE-aCTLA-4 mediated selective depletion of intra-tumoral regulatory T cells (Tregs) via TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, a chemotherapeutic drug with immunomodulatory functions, was found to upregulate FcγRIIIA on TAMs in glioblastoma patients who received doxorubicin and anti-PD-1 with concomitant LIPU/MB. In murine models of immunotherapy-resistant gliomas, a combinatorial regimen of FcE-aCTLA-4, anti-PD-1, and doxorubicin with LIPU/MB, achieved a 90% cure rate, that was associated robust infiltration of activated CD8+ T cells and establishment of immunological memory as evidenced by rejection upon tumor rechallenge. CONCLUSION: Our findings demonstrate that FcE-aCTLA-4 promotes robust immunomodulatory and anti-tumor effects in murine gliomas and is significantly enhanced when combined with anti-PD-1, doxorubicin, and LIPU/MB. We are currently investigating this combinatory strategy in a clinical trial (clinicaltrials.gov NCT05864534).

14.
Nat Commun ; 15(1): 5336, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914549

RESUMO

Transition metal chalcogenides have been identified as low-cost and efficient electrocatalysts to promote the hydrogen evolution reaction in alkaline media. However, the identification of active sites and the underlying catalytic mechanism remain elusive. In this work, we employ operando X-ray absorption spectroscopy and near-ambient pressure X-ray photoelectron spectroscopy to elucidate that NiS undergoes an in-situ phase transition to an intimately mixed phase of Ni3S2 and NiO, generating highly active synergistic dual sites at the Ni3S2/NiO interface. The interfacial Ni is the active site for water dissociation and OH* adsorption while the interfacial S acts as the active site for H* adsorption and H2 evolution. Accordingly, the in-situ formation of Ni3S2/NiO interfaces enables NiS electrocatalysts to achieve an overpotential of only 95 ± 8 mV at a current density of 10 mA cm-2. Our work highlighted that the chemistry of transition metal chalcogenides is highly dynamic, and a careful control of the working conditions may lead to the in-situ formation of catalytic species that boost their catalytic performance.

15.
World Neurosurg ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906465

RESUMO

OBJECTIVE: Neurosurgery is one of the most competitive specialties, and navigating the match process is often challenging for aspiring applicants. Here, we analyze insights from the National Resident Matching Program Director Surveys, illustrating evolving trends in applicant selection for interviews and for the ranking process, and providing a comparison with other specialties. METHODS: We evaluated 7 surveys administered from 2012 to 2022. Six biennial surveys reported on factors influencing interview and ranking processes, while all 7 surveys included data about the program director (PD)'s attitude toward United States Medical Licensing Examination (USMLE) test scores. RESULTS: The response rate of PDs decreased over the years. The most cited factor for interviews included specialty-specific recommendation letters (95%), USMLE Step 1 scores (91%), and interest in research (78%). A recent decline in emphasis on USMLE Step 1 scores coincided with a growing reliance on USMLE Step 2 scores. Award in basic science held significant esteem to a subset of programs. Personal characteristics dominated for ranking, with faculty interaction (89%), interpersonal skills (89%), and house staff interaction (85%) being the most important. Yet, PDs reported a difficulty in assessing interpersonal skills through virtual interviews. CONCLUSIONS: Our analysis revealed the pervasive importance of specialized endorsements and academic achievements when screening applicants for the interview process. A shift in emphasis toward the USMLE Step 2 became apparent. Personal characteristics, on the other hand, seemed crucial to make a match and rank high among the pool of interviewed applicants. We uncovered difficulties in assessing these characteristics through virtual interviews.

16.
Nat Commun ; 15(1): 4698, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844770

RESUMO

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Doxorrubicina , Microbolhas , Receptor de Morte Celular Programada 1 , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/análogos & derivados , Animais , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Camundongos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/imunologia , Glioma/patologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Feminino , Sistemas de Liberação de Medicamentos , Ondas Ultrassônicas , Glioblastoma/tratamento farmacológico , Glioblastoma/imunologia , Glioblastoma/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Camundongos Endogâmicos C57BL , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Polietilenoglicóis
17.
J Endocrinol ; 262(2)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38861364

RESUMO

Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitation of GIP receptor (GIPR) pathways as a means of metabolic disease management. However, debate has long surrounded the use of the GIPR as a therapeutic target and whether agonism or antagonism is of most benefit in management of obesity/diabetes. This controversy appears to be partly resolved by the success of tirzepatide. However, emerging studies indicate that prolonged GIPR agonism may desensitise the GIPR to essentially induce receptor antagonism, with this phenomenon suggested to be more pronounced in the human than rodent setting. Thus, deliberation continues to rage in relation to benefits of GIPR agonism vs antagonism. That said, as with GIPR agonism, it is clear that the metabolic advantages of sustained GIPR antagonism in obesity and obesity-driven forms of diabetes can be enhanced by concurrent GLP-1 receptor (GLP-1R) activation. This narrative review discusses various approaches of pharmacological GIPR antagonism including small molecule, peptide, monoclonal antibody and peptide-antibody conjugates, indicating stage of development and significance to the field. Taken together, there is little doubt that interesting times lie ahead for GIPR agonism and antagonism, either alone or when combined with GLP-1R agonists, as a therapeutic intervention for the management of obesity and associated metabolic disease.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Obesidade , Receptores dos Hormônios Gastrointestinais , Humanos , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Receptores dos Hormônios Gastrointestinais/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Animais , Polipeptídeo Inibidor Gástrico/agonistas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 2
18.
Arch. cardiol. Méx ; 94(2): 219-239, Apr.-Jun. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1556919

RESUMO

resumen está disponible en el texto completo


Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

19.
MHSalud ; 21(1): 238-262, ene.-jun. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1569333

RESUMO

Resumen Introducción: Los juegos y deportes alternativos surgen con la intención de introducir nuevas alternativas que hagan posible una evolución más lógica del juego y del deporte, favoreciendo la motivación, la participación y el disfrute para evadirse de la monotonía de las metodologías tradicionales. Objetivo: Este trabajo tiene por objetivo realizar una revisión sistemática de la literatura en torno al juego y deporte alternativo Ringol. Metodología: Para ello, se llevó a cabo una búsqueda de documentos en las siguientes bases de datos: Google Académico, Web of Science, Scopus y Sportdiscus. Para la búsqueda de los documentos, se han utilizado las siguientes palabras clave: "Ringol", "Physical education", y "Primary education", obteniendo un número final de 6 documentos válidos, identificados hasta el mes de noviembre de 2022. Para limitar la búsqueda y conseguir los documentos más adecuados, se establecieron una serie de criterios de inclusión y exclusión elaborados por los investigadores. Resultados: Los resultados muestran que la mayoría de los documentos son proyectos académicos, escritos en español y encontrados en Google Académico, en los cuales predomina la temática de información deportiva. Conclusiones: Los documentos analizados revelan que los principales beneficios del Ringol son la práctica igualitaria, el desarrollo de habilidades motrices y acciones como la participación, la motivación, la cooperación y el respeto. El nivel educativo donde se realizan estos proyectos es tanto, educación primaria como, secundaria. Por último, esta revisión sirve de base y guía para investigaciones futuras sobre el Ringol.


Abstract Introduction: Alternative Games and Sports arise with the intention of introducing new alternatives that make possible a more logical evolution of the game and sport, favouring motivation, participation, and enjoyment to escape from the monotony of traditional methodologies. Objetive: Therefore, the aim of this paper is to carry out a systematic review of the literature on the game and alternative sport Ringol. Methodology: For this, a document search has been carried out in the following databases: Google Scholar, Web of Science, Scopus and Sportdiscus. For the search of the documents, the following keywords have been used: "Ringol", "Physical education", and "Primary education", obtaining a final number of 6 valid documents, identified until November 2022. To limit the search and obtain the most appropriate documents, a series of inclusion and exclusion were established. Results: The results show that most of the documents are Academic Projects, written in Spanish and found in Google Scholar, with a predominance of Sports Information. Conclusions: The documents analyzed show that the main benefits of Ringol are egalitarian practice, the development of motor skills and actions such as participation, motivation, cooperation, and respect. The educational level where these projects are carried out is both Primary Education and Secondary Education. Finally, this review serves as a basis and guide for future research on the Ringol.


Resumo Introdução: Os Jogos e Esportes Alternativos surgem com a intenção de introduzir novas alternativas que possibilitem uma evolução mais lógica do jogo e do esporte, favorecendo a motivação, participação e o desfrute para escapar da monotonia das metodologias tradicionais. Objetivo: Assim, o objetivo do presente trabalho é realizar uma revisão sistemática da literatura em torno do jogo e esporte alternativo Ringol. Metodologia: Para isso, foi realizada uma busca de documentos nas seguintes bases de dados: Google Acadêmico, Web of Science, Scopus e Sportdiscus. Para a busca dos documentos, foram utilizadas as seguintes palavras-chave: "Ringol", "Physical education", e "Primary education", obtendo um número final de 6 documentos válidos, identificados até o mês de novembro de 2022. Para limitar a busca e obter os documentos mais adequados, foram estabelecidos uma série de critérios de inclusão e exclusão elaborados pelos pesquisadores. Resultados: Os resultados mostram que a maioria dos documentos são Projetos acadêmicos, escritos em espanhol e encontrados no Google Acadêmico, predominando a temática de Informação esportiva. Conclusões: Os documentos analisados mostram que os principais benefícios do Ringol são a prática igualitária, o desenvolvimento de habilidades motoras e ações como participação, motivação, cooperação e respeito. O nível educativo onde esses projetos são realizados é tanto na Educação Primária quanto na Educação Secundária. Por fim, esta revisão serve como base e guia para pesquisas futuras sobre o Ringol.

20.
J Trauma Acute Care Surg ; 97(2S Suppl 1): S98-S104, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38745348

RESUMO

BACKGROUND: The Compensatory Reserve Metric (CRM) provides a time sensitive indicator of hemodynamic decompensation. However, its in-field utility is limited because of the size and cost-intensive nature of standard vital sign monitors or photoplethysmographic volume-clamp (PPG VC ) devices used to measure arterial waveforms. In this regard, photoplethysmographic measurements obtained from pulse oximetry may serve as a useful, portable alternative. This study aimed to validate CRM values obtained using pulse oximeter (PPG PO ). METHODS: Forty-nine healthy adults (25 females) underwent a graded lower body negative pressure (LBNP) protocol to simulate hemorrhage. Arterial waveforms were sampled using PPG PO and PPG VC . The CRM was calculated using a one-dimensional convolutional neural network. Cardiac output and stroke volume were measured using PPG VC . A brachial artery catheter was used to measure intra-arterial pressure. A three-lead electrocardiogram was used to measure heart rate. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. Log-rank analyses were used to examine differences in shock determination during LBNP between monitored hemodynamic parameters. RESULTS: The median LBNP stage reached was 70 mm Hg (range, 45-100 mm Hg). Relative to baseline, at tolerance, there was a 47% ± 12% reduction in stroke volume, 64% ± 27% increase in heart rate, and 21% ± 7% reduction in systolic blood pressure ( p < 0.001 for all). Compensatory Reserve Metric values obtained with both PPG PO and PPG VC were associated with changes in heart rate ( p < 0.001), stroke volume ( p < 0.001), and pulse pressure ( p < 0.001). Furthermore, they provided an earlier detection of hemodynamic shock relative to the traditional metrics of shock index ( p < 0.001 for both), systolic blood pressure ( p < 0.001 for both), and heart rate ( p = 0.001 for both). CONCLUSION: The CRM obtained from PPG PO provides a valid, time-sensitized prediction of hemodynamic decompensation, opening the door to provide military medical personnel noninvasive in-field advanced capability for early detection of hemorrhage and imminent onset of shock. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level III.


Assuntos
Pressão Negativa da Região Corporal Inferior , Oximetria , Fotopletismografia , Humanos , Masculino , Feminino , Adulto , Oximetria/métodos , Pressão Negativa da Região Corporal Inferior/métodos , Fotopletismografia/métodos , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Volume Sistólico/fisiologia , Frequência Cardíaca/fisiologia , Voluntários Saudáveis , Débito Cardíaco/fisiologia , Hemodinâmica/fisiologia , Adulto Jovem , Hemorragia/diagnóstico , Hemorragia/fisiopatologia , Eletrocardiografia/métodos
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