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1.
Cureus ; 15(9): e45355, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37849570

RESUMO

Background In the United States, homelessness is an issue that may affect a significant portion of the adolescent population. There is no consensus on the extent to which this population has been impacted by poor mental health and lack of resources. This study aimed to characterize trends among those who struggle with housing insecurity and mental illness to provide a clearer picture of mental health needs among this population. Methods Data from 641 adolescents who presented to a local adolescent homeless shelter between 2015 and 2021 were utilized to determine if there were significant associations between specific mental illness diagnoses and biopsychosocial characteristics. A chi-square test of independence was performed on demographic and psychosocial variables for categories with a frequency greater than five. For continuous variables, an unpaired t-test was utilized to assess significance (p<0.05). Results Among the study population, 61.3% (369) had at least one psychiatric diagnosis, which is higher than even the most conservative estimates of mental illness among the general public. Having one or more psychiatric diagnoses was significantly associated with suicide attempts, documented aggressive behavior, and tobacco use. Contrary to our initial hypothesis, there were no significant correlations between psychiatric diagnoses and demographic characteristics or drug use other than tobacco. Conclusions Our findings indicate that though the particular reasons for homelessness among adolescents may vary, the prevalence of mental illness among these young individuals was roughly uniformly distributed and vastly above normal levels. Future research must focus on developing interventions to mitigate the effects of mental illness among homeless adolescents, as they are at a vulnerable point in their formative years.

2.
Molecules ; 28(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37570892

RESUMO

Coffee pulp is an abundant residue from the coffee industry, but it still contains large amounts of valuable compounds such as polyphenols. The extraction of polyphenols from coffee pulp by the conventional method is accompanied by contaminated compounds. This study, therefore, applied an aqueous two-phase system consisting of different ratios of ethanol/ammonium sulfate to eliminate impurities from coffee-pulp crude extract. The purification efficiency was evaluated via total polyphenol content, antioxidant activity and two major polyphenols in coffee pulps including chlorogenic acid and caffeic acid. Results showed that phenolic compounds mostly predominated in the alcohol-rich phase in which the antioxidant activity was greatly increased after the purification process. Compared to un-purified crude-coffee extract, the antioxidant activity of the purified samples increased approximately 34%, which was assumed to occur due to the slight increase of chlorogenic acid and caffeic acid. Fourier-transform infrared spectroscopy supported the effectiveness of the purification process by eliminating some impurities.


Assuntos
Ácido Clorogênico , Polifenóis , Antioxidantes/farmacologia , Ácidos Cafeicos , Extratos Vegetais/química , Etanol
3.
Chem Sci ; 14(12): 3311-3325, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36970097

RESUMO

Radical ring-opening polymerization (rROP) has received renewed attention to incorporate cleavable linkages into the backbones of vinyl polymers, especially from cyclic ketene acetals (CKAs). Among the monomers that hardly copolymerize with CKAs are (1,3)-dienes such as isoprene (I). This is unfortunate since synthetic polyisoprene (PI) and its derivatives are the materials of choice for many applications, in particular as elastomers in the automotive, sport, footwear, and medical industries, but also in nanomedicine. Thionolactones have been recently proposed as a new class of rROP-compatible monomers for insertion of thioester units in the main chain. Herein, we report the synthesis of degradable PI by rROP via the copolymerization of I and dibenzo[c,e]oxepane-5-thione (DOT). Free-radical polymerization as well as two reversible deactivation radical polymerization techniques were successfully used for the synthesis of (well-defined) P(I-co-DOT) copolymers with adjustable molecular weights and DOT contents (2.7-9.7 mol%). Reactivity ratios of r DOT = 4.29 and r I = 0.14 were determined, suggesting preferential incorporation of DOT in comparison to I. The resulting P(I-co-DOT) copolymers were successfully degraded (from -47% to -84% decrease in M n) under basic conditions. As a proof of concept, the P(I-co-DOT) copolymers were formulated into stable and narrowly dispersed nanoparticles, showing similar cytocompatibility on J774.A1 and HUVEC cells compared to their PI counterparts. Furthermore, Gem-P(I-co-DOT) prodrug nanoparticles were synthesized by the "drug-initiated" method and exhibited significant cytotoxicity on A549 cancer cells. P(I-co-DOT) and Gem-P(I-co-DOT) nanoparticles were degraded under basic/oxidative conditions by bleach and under physiological conditions in the presence of cysteine or glutathione.

4.
Front Pediatr ; 10: 982614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081635

RESUMO

Objective: The purpose of this study was to establish a predictive model of postoperative fever in children with acute appendicitis through retrospective analysis, and the prediction ability of the model is demonstrated by model evaluation and external validation. Methods: Medical records information on children undergoing surgery for acute appendicitis within 2 years were retrospectively collected, prospective collection was performed for external validation in the next 3 months. The patients were divided into two groups according to whether the postoperative body temperature exceeded 38.5°C. Multivariate logistic regression analysis was used to determine independent risk factors and develop regression equations and nomogram. ROC curve, calibration curve and decision curve were made for model evaluation. Finally, the clinical implication of the prediction model was clarified by associating postoperative fever with prognosis. Results: High risk factors of postoperative fever included in the prediction model were onset time (X1), preoperative temperature (X2), leukocyte count (X3), C-reactive protein (X4) and operation time (X5). The regression equation is logit (P) = 0.005X1+0.166X2+0.056X3+0.004X4+0.005X5-9.042. ROC curve showed that the area under the curve (AUC) of the training set was 0.660 (0.621, 0.699), and the AUC of the verification set was 0.712 (0.639, 0.784). The calibration curve suggested that the prediction probability was close to the actual probability. Decision curve analysis (DCA) showed that patients could benefit from clinician's judgment. Furthermore, prognostic analysis showed children presenting with postoperative fever had the more duration of postoperative fever, hospitalization stays and cost, except for rehospitalization. Conclusion: All the results revealed that the model had good predictive ability. Pediatricians can calculate the probability of postoperative fever and make timely interventions to reduce pain for children and parents.

5.
Sci Adv ; 8(21): eabm8478, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35622910

RESUMO

Administering medicines to 0- to 5-year-old children in a resource-limited environment requires dosage forms that circumvent swallowing solids, avoid on-field reconstitution, and are thermostable, cheap, versatile, and taste masking. We present a strategy that stands to solve this multifaceted problem. As many drugs lack adequate water solubility, our formulations used oils, whose textures could be modified with gelling agents to form "oleogels." In a clinical study, we showed that the oleogels can be formulated to be as fluid as thickened beverages and as stiff as yogurt puddings. In swine, oleogels could deliver four drugs ranging three orders of magnitude in their water solubilities and two orders of magnitude in their partition coefficients. Oleogels could be stabilized at 40°C for prolonged durations and used without redispersion. Last, we developed a macrofluidic system enabling fixed and metered dosing. We anticipate that this platform could be adopted for pediatric dosing, palliative care, and gastrointestinal disease applications.


Assuntos
Alimentos , Óleos , Animais , Criança , Pré-Escolar , Sistemas de Liberação de Medicamentos , Géis , Humanos , Suínos , Água
6.
Int J Gynaecol Obstet ; 158(2): 325-329, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34735727

RESUMO

OBJECTIVE: To analyze a case of heavy uterine bleeding in adolescence caused by an arteriovenous malformation (AVM) in Hanoi Obstetrics and Gynecology Hospital, Vietnam. METHODS: We observed a case of a 14-year-old girl, without vaginal sexual intercourse experience, having heavy uterine bleeding caused by AVM. She underwent a laparoscopic operation at the hospital for vascular lesions in the uterine anterior wall, which caused an internal hemorrhage of 1500 ml blood loss into the peritoneal cavity. Three years later, this patient was hospitalized twice for massive vaginal bleeding. RESULTS: Results of ultrasound and magnetic resonance imaging indicated a uterine intramural mass with enlarged vessels connecting to the endometrial cavity. A pelvic digital subtraction angiography was performed and showed profuse bleeding from a ruptured branch of the left uterine artery. This artery was embolized at Bach Mai hospital and the bleeding was stopped. The patient had stable health and normal menstrual periods after 4 months of follow up. CONCLUSION: Abnormal mass with dilated vessels in the myometrium in a patient experiencing heavy uterine bleeding is an exclusive sign of uterine vascular malformation and can be treated by angioembolization.


Assuntos
Malformações Arteriovenosas , Útero , Adolescente , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/terapia , Feminino , Humanos , Gravidez , Anormalidades Urogenitais , Artéria Uterina/diagnóstico por imagem , Hemorragia Uterina/cirurgia , Útero/anormalidades
7.
Curr Probl Cancer ; 45(5): 100796, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34657748

RESUMO

The concept of personalized medicine has been steadily growing for the past decades. Monoclonal antibodies (mAbs) are undoubtedly playing an important role in the transition away from conventional medical practice to a more tailored approach to deliver the best therapy with the highest safety margin to a specific patient. In certain instances, mAbs and antibody drug conjugates (ADCs) may represent the preferred therapeutic option for several types of cancers due to their high specificity and affinity to the antigen. Monoclonal antibodies can be labeled with specific radionuclides well-suited for PET (Positron Emission Tomography) or gamma camera scintigraphy. The use of radiolabeled mAbs allows the interrogation of specific biomarkers and assessment of tumor heterogeneity in vivo by a single diagnostic imaging scan that includes the whole-body in the field-of-view. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of beta-minus radiation or alpha-particles as part of a radioimmunotherapy (RIT) approach. However, the path to develop, validate, and implement mAb-based radiopharmaceuticals from bench-to-bedside is complex due to the extensive pre-clinical experiments and toxicological studies required, and the necessity of labor-intensive clinical trials that often require multi-time-point imaging and blood draws for internal radiation dosimetry and pharmacokinetics. As more mAb-based radiopharmaceuticals have been developed and evaluated, the opportunities and limitations offered by mAbs have become better defined. Our aim with this manuscript is therefore to provide an overview of the recent advances in the development of mAb-based radiopharmaceuticals and their clinical applications in Oncology.


Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/farmacologia , Humanos , Medicina de Precisão/métodos
8.
Cancer Biother Radiopharm ; 36(3): 237-251, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32589458

RESUMO

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and ß-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications.


Assuntos
Glutamato Carboxipeptidase II/antagonistas & inibidores , Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia (Especialidade)/tendências , Compostos Radiofarmacêuticos/administração & dosagem , Antígenos de Superfície , Humanos , Masculino , Imagem Molecular/métodos , Imagem Molecular/tendências , Terapia de Alvo Molecular/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/tendências , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Radioterapia (Especialidade)/métodos , Sensibilidade e Especificidade
9.
Clin Cancer Res ; 26(22): 5830-5842, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32816889

RESUMO

PURPOSE: 90Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors. PATIENTS AND METHODS: The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5-25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months. RESULTS: 111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity. CONCLUSIONS: The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Caderinas/antagonistas & inibidores , Neoplasias/radioterapia , Radioimunoterapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Caderinas/genética , Caderinas/imunologia , Antígeno Carcinoembrionário/genética , Adesão Celular/efeitos dos fármacos , Fracionamento da Dose de Radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulinas/imunologia , Radioisótopos de Índio/administração & dosagem , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Baço/efeitos dos fármacos , Testículo/efeitos dos fármacos , Radioisótopos de Ítrio/administração & dosagem
10.
Appl Radiat Isot ; 155: 108936, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655351

RESUMO

68Ga-PSMA-11 is currently one of the most investigated PET agents for imaging both recurrent prostate cancer and relevant metastases; however, the production and distribution of 68Ga-PSMA-11 is limited to a supply of only a few daily doses when using a commercially available 68Ge/68Ga generator. 68Ge/68Ga generators deliver only a modest amount of activity, up to 1850 MBq (50 mCi), when new, but it decreases with time. Additionally, the production of 68Ga/68Ge generators has not been able to meet the increasing demand of 68Ga radiotracers. In response to the need for a more economically viable alternative, the focus of this study was to provide a simple and efficient method for producing 68Ga-PSMA-11, using cyclotron-produced 68Ga that is ready for routine clinical practice.


Assuntos
Ciclotrons , Glicoproteínas de Membrana/química , Compostos Organometálicos/química , Automação , Linhagem Celular Tumoral , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino
12.
Small ; 14(36): e1801571, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30079605

RESUMO

Recent advances in super-resolution microscopy and fluorescence bioimaging allow exploring previously inaccessible biological processes. To this end, there is a need for novel fluorescent probes with specific features in size, photophysical properties, colloidal and optical stabilities, as well as biocompatibility and ability to evade the reticuloendothelial system. Herein, novel fluorescent nanoparticles are introduced based on an inherently fluorescent polypyrazoline (PPy) core and a polyethylene glycol (PEG) shell, which address all aforementioned challenges. Synthesis of the PPy-PEG amphiphilic block copolymer by phototriggered step-growth polymerization is investigated by NMR spectroscopy, size-exclusion chromatography, and mass spectrometry. The corresponding nanoparticles are characterized for their luminescent properties and hydrodynamic size in various aqueous environments (e.g., cell culture media). PPy nanoparticles particularly exhibit a large Stokes shift (Δλ = 160 nm or Δν > 7000 cm-1 ) with visible light excitation and strong colloidal stability. While clearance by macrophages and endothelial cells is minimal, PPy displays good biocompatibility. Finally, PPy nanoparticles prove to be long circulating when injected in zebrafish embryos, as observed by in vivo time-lapse fluorescence microscopy. In summary, PPy nanoparticles are highly promising to be further developed as fluorescent nanodelivery systems with low toxicity and exquisite retention in the blood stream.


Assuntos
Diagnóstico por Imagem/métodos , Nanopartículas/química , Pirazóis/química , Animais , Materiais Biocompatíveis/química , Embrião não Mamífero/metabolismo , Fluorescência , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Hidrodinâmica , Nanopartículas/ultraestrutura , Polímeros/síntese química , Polímeros/química , Pirazóis/síntese química , Peixe-Zebra/embriologia
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