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1.
Nature ; 577(7791): 556-560, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942077

RESUMO

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.


Assuntos
Linfócitos B/imunologia , Imunoterapia , Sarcoma/tratamento farmacológico , Sarcoma/imunologia , Estruturas Linfoides Terciárias/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Células Dendríticas Foliculares/imunologia , Humanos , Mutação , Fenótipo , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Reprodutibilidade dos Testes , Sarcoma/classificação , Sarcoma/patologia , Taxa de Sobrevida , Microambiente Tumoral
2.
Antimicrob Agents Chemother ; 68(7): e0031924, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38757973

RESUMO

Treatment of Mycobacterium abscessus infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active in vitro. Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary Mycobacterium abscessus infection and was treated with a multi-drug regimen including two ß-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual ß-lactam therapy for the treatment of drug-resistant Mycobacterium abscessus infection.


Assuntos
Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , beta-Lactamas , Humanos , Mycobacterium abscessus/efeitos dos fármacos , Criança , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , beta-Lactamas/uso terapêutico , beta-Lactamas/farmacologia , Testes de Sensibilidade Microbiana , Masculino , Quimioterapia Combinada
3.
Am J Physiol Heart Circ Physiol ; 326(6): H1396-H1401, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578238

RESUMO

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.NEW & NOTEWORTHY This methods paper details dietary approaches to alter zinc homeostasis in rodents and qualitative and quantitative methods to ensure the zinc status of experimental animals. The outlined accessible and cost-effective protocol will elevate scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of a multitude of health conditions and diseases.


Assuntos
Zinco , Zinco/deficiência , Zinco/metabolismo , Zinco/urina , Zinco/sangue , Animais , Reprodutibilidade dos Testes , Camundongos , Camundongos Endogâmicos C57BL , Homeostase , Masculino
4.
New Phytol ; 242(4): 1448-1475, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581203

RESUMO

Research on mycorrhizal symbiosis has been slowed by a lack of established study systems. To address this challenge, we have been developing Suillus, a widespread ecologically and economically relevant fungal genus primarily associated with the plant family Pinaceae, into a model system for studying ectomycorrhizal (ECM) associations. Over the last decade, we have compiled extensive genomic resources, culture libraries, a phenotype database, and protocols for manipulating Suillus fungi with and without their tree partners. Our efforts have already resulted in a large number of publicly available genomes, transcriptomes, and respective annotations, as well as advances in our understanding of mycorrhizal partner specificity and host communication, fungal and plant nutrition, environmental adaptation, soil nutrient cycling, interspecific competition, and biological invasions. Here, we highlight the most significant recent findings enabled by Suillus, present a suite of protocols for working with the genus, and discuss how Suillus is emerging as an important model to elucidate the ecology and evolution of ECM interactions.


Assuntos
Evolução Biológica , Modelos Biológicos , Micorrizas , Micorrizas/fisiologia , Micorrizas/genética , Ecologia , Simbiose/genética , Basidiomycota/fisiologia , Basidiomycota/genética
5.
Opt Express ; 32(3): 3817-3825, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297594

RESUMO

Measuring the spectral phase of a pulse is key for performing wavelength resolved ultrafast measurements in the few femtosecond regime. However, accurate measurements in real experimental conditions can be challenging. We show that the reflectivity change induced by coherent phonons in a quantum material can be used to infer the spectral phase of an optical probe pulse with few-femtosecond accuracy.

6.
Cell Commun Signal ; 22(1): 2, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38169388

RESUMO

BACKGROUND: The B-cell lymphoma 2 (Bcl-2) protein regulates programmed cell death throughout the disease conditions by upholding apoptotic pathways. However, the mechanism by which it's expressed in chondrocytes still needs to be studied in chondrocyte-related disorders. Additionally, exploring the potential therapeutic role of Chlorogenic acid (CGA) in confluence with Bcl-2 modulation is of significant interest. METHODS: In vivo and in vitro studies were performed according to our previous methodologies. The chondrocytes were cultured in specific growth media under standard conditions after expression verification of different microRNAs through high-throughput sequencing and verification of Bcl-2 involvement in tibial growth plates. The effect of Bcl-2 expression was investigated by transfecting chondrocytes with miR-460a, siRNA, and their negative controls alone or in combination with CGA. The RNA was extracted and subjected to a reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blot analysis and immunofluorescence assays were performed to visualize the intracellular localization of Bcl-2 and associated proteins related to apoptotic and inflammasome pathways. Moreover, apoptosis through flow cytometry was also performed to understand the modulation of concerning pathways. RESULTS: The suppression of Bcl-2 induced higher apoptosis and mitochondrial dysfunction, leading to IL-1ß maturation and affecting the inflammasome during chondrocyte proliferation. Conversely, overexpression attenuated the activation, as evidenced by reduced caspase activity and IL-1ß maturation. In parallel, CGA successfully reduced siRNA-induced apoptosis by decreasing Cytochrome C (Cyto C) release from the mitochondria to the cytoplasm, which in turn decreased Caspase-3 and Caspase-7 cleavage with Bcl-2-associated X protein (Bax). Furthermore, siBcl-2 transfection and CGA therapy increased chondrocyte proliferation and survival. The CGA also showed a promising approach to maintaining chondrocyte viability by inhibiting siRNA-induced apoptosis. CONCLUSIONS: Targeting Bcl-2-mediated regulation might be a possible treatment for chondrocyte-related conditions. Moreover, these results add knowledge of the complicated processes underlying chondrocyte function and the pathophysiology of related diseases, highlighting the significance of target specific therapies. Video Abstract.


Assuntos
Condrócitos , MicroRNAs , Condrócitos/metabolismo , Inflamassomos/metabolismo , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismo , Apoptose , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/metabolismo , Interleucina-1beta/metabolismo
7.
Geochem Trans ; 25(1): 1, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206422

RESUMO

Bardawil Lake is a unique aquatic ecosystem that provides a habitat for various fish and other marine organisms. This study aimed to analyze the quality of fish species to prove that this lake is free of pollution, not other Egyptian lakes, due to the accumulation of some heavy metals (Cd, Pb, Cu, and Zn) in various tissues of fish species that were caught from this lake. Thirty-five fish samples were caught during the Spring of 2018 from seven different species: Mugil cephalus, Liza auratus, Sparus aurata, Dicentrarchus labrax, Siganus rivulatus, Anguilla angilla, and Solae solea. The Association of Official Analytical Chemists methods using a spectrophotometer determined the biochemical composition. In contrast, atomic absorption spectrometry (AAS) was employed to determine the heavy metals expressed by µg/g wet weight. Results exposed that the accumulation of essential micronutrient (Cu, Zn) content was higher than toxic elements (Cd & Pb) in muscles in order to Zn > Cu > Pb > Cd. Muscles < gills < liver in order of all metals except Pb with order muscles < liver < gills. The metals studied in the muscles were lower than those set by the WHO and the EU standards. The carcinogenic risk with lower allowable limits of 1 × 10-6 to 1 × 10-4 in both normal and high consumption groups; target and total target hazard quotients (THQ & HI) in muscles were < 1. The biochemical composition level was highest in the liver, except for protein, which was highest in muscle for all fish species. There is no evidence of harmful contaminants in the muscular tissue of the fish sampled from Bardawil Lake, although fishing activity. However, customers should know that health concerns may be associated with overeating fish.

8.
Ann Behav Med ; 58(9): 579-593, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-38985846

RESUMO

BACKGROUND: Considering the high rates of persistent tobacco use, effective cessation interventions are needed for cancer patients and caregivers. Despite the need, there is a significant lack of research on tobacco cessation, especially for non-respiratory cancers (breast, prostate, colorectal, cervical, and bladder cancer). PURPOSE: The objective was to evaluate tobacco use and tobacco cessation interventions among patients and caregivers for non-respiratory cancers. METHODS: Randomized controlled trials assessing tobacco cessation interventions were identified. Five electronic databases were searched in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines through July 2023. Studies exclusive to lung, oral, thoracic, and head and neck cancers were excluded. Effect sizes were estimated; risk of bias was assessed. RESULTS: Of 3,304 studies, 17 were included. Interventions included behavioral (n = 6), pharmacotherapy (n = 2), and a combination (n = 9) treatment. Eight studies included a health behavior model; mean behavioral change techniques were 5.57. Pooled magnitude of the odds of cessation was positive and significant (odds ratio = 1.24, 95% confidence interval [Lower Limit 1.02, Upper Limit 1.51]) relative to usual care/placebo. Cumulative meta-analysis examined the accumulation of results over-time and demonstrated that studies have been significant since 2020. Two studies included caregivers' who were involved in the provision of social support. CONCLUSIONS: Current interventions have the potential to reduce tobacco use in non-respiratory cancers. Results may be beneficial for promoting tobacco cessation among non-respiratory cancers. There is a considerable lack of dyadic interventions for cancer survivors and caregivers; researchers are encouraged to explore dyadic approaches.


We aimed to understand effective ways for cancer patients and caregivers to quit using tobacco. We focused on non-respiratory cancers (cancers not related to breathing issues) like breast, prostate, and colorectal cancer. We reviewed 17 randomized controlled trials designed to help people quit tobacco, which included behavioral therapies (e.g., education and counseling), pharmacotherapy (i.e., medicine), and combinations of both. We found that people in these studies quit using tobacco, especially when more than one approach was used. The studies also showed that these approaches have been more successful since 2020. The research highlighted a need for more studies that include both patients and their caregivers together in the quitting process. This approach, called dyadic intervention, could be more effective in supporting patients and their caregivers. Overall, while the current approaches are promising, more research is needed to develop better ways to help cancer patients and caregivers quit smoking for longer.


Assuntos
Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Abandono do Uso de Tabaco , Humanos , Neoplasias/terapia , Neoplasias/psicologia , Abandono do Uso de Tabaco/métodos , Cuidadores/psicologia
9.
Microb Cell Fact ; 23(1): 15, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183118

RESUMO

Attenuation of camptothecin (CPT) productivity by fungi with preservation and subculturing is the challenge that halts fungi to be an industrial platform of CPT production. Thus, screening for novel endophytic fungal isolates with metabolic stability for CPT production was the objective. Catharanthus roseus is one of the medicinal plants with diverse bioactive metabolites that could have a plethora of novel endophytes with unique metabolites. Among the endophytes of C. roseus, Aspergillus terreus EFBL-NV OR131583.1 had the most CPT producing potency (90.2 µg/l), the chemical identity of the putative CPT was verified by HPLC, FT-IR, NMR and LC-MS/MS. The putative A. terreus CPT had the same molecular mass (349 m/z), and molecular fragmentation patterns of the authentic one, as revealed from the MS/MS analyses. The purified CPT had a strong activity against MCF7 (5.27 µM) and UO-31 (2.2 µM), with a potential inhibition to Topo II (IC50 value 0.52 nM) than Topo 1 (IC50 value 6.9 nM). The CPT displayed a high wound healing activity to UO-31 cells, stopping their metastasis, matrix formation and cell immigration. The purified CPT had a potential inducing activity to the cellular apoptosis of UO-31 by ~ 17 folds, as well as, arresting their cellular division at the S-phase, compared to the control cells. Upon Plackett-Burman design, the yield of CPT by A. terreus was increased by ~ 2.6 folds, compared to control. The yield of CPT by A. terreus was sequentially suppressed with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by 3rd month and 5th generation. However, the productivity of the attenuated A. terreus culture was completely restored by adding 1% surface sterilized leaves of C. roseus, and the CPT yield was increased over-the-first culture by ~ 3.2 folds (315.2 µg/l). The restoring of CPT productivity of A. terreus in response to indigenous microbiome of C. roseus, ensures the A. terreus-microbiome interactions, releasing a chemical signal that triggers the CPT productivity of A. terreus. This is the first reports exploring the potency of A. terreus, endophyte of C. roseus" to be a platform for industrial production of CPT, with an affordable sustainability with addition of C. roseus microbiome.


Assuntos
Catharanthus , Cromatografia Líquida , Endófitos , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem , Isomerases , Camptotecina/farmacologia , Ciclo Celular
10.
Microb Cell Fact ; 23(1): 214, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060918

RESUMO

Suppression of fungal camptothecin (CPT) biosynthesis with the preservation and successive subculturing is the challenge that impedes fungi from the industrial application, so, screening for a novel fungal isolate with a conceivable stable producing potency of CPT was the main objective of this work. Catharanthus roseus with diverse contents of bioactive metabolites could have a plethora of novel endophytes with unique metabolic properties. Among the endophytes of C. roseus, Alternaria brassicicola EFBL-NV OR131587.1 was the highest CPT producer (96.5 µg/L). The structural identity of the putative CPT was verified by HPLC, FTIR, HNMR and LC-MS/MS, with a molecular mass 349 m/z, and molecular fragmentation patterns that typically identical to the authentic one. The purified A. brassicicola CPT has a strong antiproliferative activity towards UO-31 (0.75 µM) and MCF7 (3.2 µM), with selectivity index 30.8, and 7.1, respectively, in addition to resilient activity to inhibit Topo II (IC50 value 0.26 nM) than Topo 1 (IC50 value 3.2 nM). The purified CPT combat the wound healing of UO-31 cells by ~ 52%, stops their matrix formation, cell migration and metastasis. The purified CPT arrest the cellular division of the UO-31 at the S-phase, and inducing their cellular apoptosis by ~ 20.4 folds, compared to the control cells. Upon bioprocessing with the surface response methodology, the CPT yield by A. brassicicola was improved by ~ 3.3 folds, compared to control. The metabolic potency of synthesis of CPT by A. brassicicola was attenuated with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by the 6th month of storage and 6th generation. Practically, the CPT productivity of the attenuated A. brassicicola was restored by addition of 1% surface sterilized leaves of C. roseus, ensuring the eliciting of cryptic gene cluster of A. brassicicola CPT via the plant microbiome-A. brassicicola interactions. So, for the first time, a novel endophytic isolate A. brassicicola, from C. roseus, was explored to have a relatively stable CPT biosynthetic machinery, with an affordable feasibility to restore their CPT productivity using C. roseus microbiome, in addition to the unique affinity of the extracted CPT to inhibit Topoisomerase I and II.


Assuntos
Alternaria , Camptotecina , Catharanthus , Proliferação de Células , Endófitos , Camptotecina/farmacologia , Camptotecina/biossíntese , Camptotecina/metabolismo , Endófitos/metabolismo , Catharanthus/microbiologia , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Células MCF-7 , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos
11.
Eur J Clin Microbiol Infect Dis ; 43(7): 1383-1392, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38683272

RESUMO

INTRODUCTION: Bacterial meningitis poses significant medical challenges due to its acute inflammatory nature and potential for severe neurological complications, emphasizing the need for prompt diagnosis and treatment. Limited data exists on its epidemiology and antimicrobial resistance trends among hospitalized patients in Saudi Arabia. This study aimed to investigate these factors at a tertiary care hospital over six years. METHODS: A retrospective analysis was conducted on cerebrospinal fluid samples results from 222 bacterial meningitis cases among hospitalized patients between 2018 and 2023. Demographic, clinical, microbiological data, and antibiotic susceptibility patterns were collected and analyzed. RESULTS: Pseudomonas aeruginosa (43%) was the predominant pathogen isolated. Neonates (16%) and children (47%) were most affected population. Nosocomial meningitis accounted for 92% of cases, mainly in the intensive care settings (50.45%). Extended-spectrum beta-lactamase was the leading resistance pattern (12.2%). Seasonal variation was observed, with a peak incidence in October-November. CONCLUSION: The study highlights the substantial burden of bacterial meningitis among hospitalized patients, especially among high-risk groups. Emerging antimicrobial resistance emphasizes the need for optimized surveillance and stewardship. Future prospective research employing molecular techniques across multiple centers in the country is warranted to enhance understanding and guide public health strategies in Saudi Arabia.


Assuntos
Antibacterianos , Infecção Hospitalar , Meningites Bacterianas , Centros de Atenção Terciária , Humanos , Arábia Saudita/epidemiologia , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Meningites Bacterianas/tratamento farmacológico , Centros de Atenção Terciária/estatística & dados numéricos , Estudos Retrospectivos , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Recém-Nascido , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Hospitalização/estatística & dados numéricos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Idoso , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Incidência
12.
J Pediatr Gastroenterol Nutr ; 79(2): 278-289, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38828781

RESUMO

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.


Assuntos
Intestinos , Listas de Espera , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Pré-Escolar , Lactente , Intestinos/transplante , Adolescente , Insuficiência Intestinal , Síndrome do Intestino Curto/cirurgia , Hepatopatias/cirurgia
13.
Clin Radiol ; 79(10): 773-780, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39129105

RESUMO

AIM: The aim of this study was to determine whether biparametric magnetic resonance imaging (MRI) is effective in the diagnosis of clinically significant prostate cancer in prostate peripheral zone Prostate Imaging Reporting and Data System (PIRADS) 3 lesions without the use of dynamic contrast enhancement. MATERIALS AND METHODS: Patients who underwent biparametric MRI over a 12-month period from January 2022 to December 2022 and were diagnosed with PIRADS 3 lesion in the peripheral zone were included in the study. No patient received dynamic contrast enhancement. Histological analysis was done after performing local anesthetic transperineal biopsy to determine detection rate of clinically significant prostate cancer. Prostate-specific antigen density (PSAD) and biopsy complication rates were also reviewed. RESULTS: Sixty-one out of 688 MRIs (8.8%) performed over the study period had a PIRADS 3 lesion in the peripheral zone where contrast is supposed to add value. Fifty-eight of the 61 went ahead to biopsy, and csPCa (Gleason score: ≥3 + 4, with a max core length of ≥6 mm and above) was diagnosed in 17%. Among those diagnosed with csPCa, 80% had a PSAD of >0.15 ng/ml/cc. No postbiopsy complications were reported. CONCLUSION: Biparametric MRI without contrast offers a reliable alternative to multiparametric MRI with minimum or neglible impact on clinically significant prostate cancer (csPCa) diagnosis in peripheral zone PIRADS 3 lesions, especially when used in conjunction with other factors such as PSAD. There is potential to address health economics and patient burden in prostate cancer investigation.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/patologia , Prevalência , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos
14.
Med Sci Monit ; 30: e945089, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340141

RESUMO

BACKGROUND The aim of this study was to evaluate the time-dependent release of calcium (Ca⁺⁺) and hydroxyl (OH⁻) ions from 3 different pulp dressing materials used to cap root canal orifices in pulpotomized premolars. MATERIAL AND METHODS Freshly extracted (n=40) premolars were subjected to standardized pulpotomy procedure and finally restored in 5 groups using resin-modified glass ionmmer liner (RMGI) and bonded resin composite directly against the pulp chamber's floor (Control, G2) and over 3 different orifices' capping materials - Dycal (G3), Endo Sequence root repair material (ESRRM, G4), and mineral trioxide aggregate (MTA) Angelus (G5). Another 10 sound premolars served as the Reference group (G1). The restored teeth were incubated at 37±1°C in sealed containers filled with deionized water to assess Ca⁺⁺ and OH⁻ ions release after 24 h and at 1, 4, and 8 weeks. Two-way ANOVA and Tukey's comparisons at alpha=0.05 were used to statistically analyze the collected data. RESULTS Two-way ANOVA revealed significant differences in Ca⁺⁺ ions between test groups at different testing time intervals (P<0.05). Despite the constant (Tukey's, P<0.05) pH levels (OH⁻ release), Group 5 specimens exhibited higher Ca⁺⁺ ion release in comparison to Groups 4 and 3 at different testing timepoints (Tukey's, P<0.05). CONCLUSIONS Although all the assessed pulp dressing materials had equivalent and stable pH levels, ESRRM and MTA-Angelus had the highest Ca⁺⁺ ion release at the assessment intervals.


Assuntos
Compostos de Alumínio , Dente Pré-Molar , Compostos de Cálcio , Cálcio , Humanos , Compostos de Cálcio/química , Compostos de Alumínio/química , Silicatos/química , Combinação de Medicamentos , Íons , Óxidos/química , Materiais Restauradores do Canal Radicular/química , Polpa Dentária/metabolismo , Hidróxidos/química , Bandagens , Cavidade Pulpar , Capeamento da Polpa Dentária/métodos , Hidróxido de Cálcio , Minerais
15.
Eur Spine J ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292253

RESUMO

PURPOSE: Cauda equina syndrome (CES) may have significant individual consequences if diagnostic delays occur. Our aim was to evaluate the presenting subjective and objective features of patients with suspected CES in comparison to those with radiologically confirmed cauda equina compression (CEC).. METHODS: This was a retrospective analysis of all cases presenting with suspected CES to a tertiary emergency care unit over a two-year period. CEC was defined as radiological confirmation of CEC by Consultant Musculoskeletal (MSK) Radiologist report (MSK-CEC) and by measured canal occupancy due to an acute disc extrusion (> 75%)[measured by a Senior Spinal Surgeon (SP-CEC)]. Routine data collection was compared between categories. Chi square, multivariate regression analyses and ROC analysis of multiple predictors was performed. RESULTS: 530 patients were included in this analysis, 60 (11.3%) had MSK-CEC, and 470 had NO- CEC. Only 43/60 (71.7%) had emergent surgery. Those with MSK-CEC and SP-CEC were statistically more likely to present with bilateral leg pain [(MSK-CEC OR 2.6, 95%CI 1.2, 5.8; p = 0.02)(SP-CEC OR 4.7, 95%CI 1.7, 12.8; p = 0.003)]; and absent bilateral ankle reflexes [(MSK-CEC OR 4.3; 95% CI 2.0, 9.6; p < 0.001)(SP CEC OR 2.5; 95%CI 1.0, 6.19; p = 0.05)] on multivariate analysis. The ROC curve analysis acceptable diagnostic utility of having SP-CEC when both are present [Area under the curve 0.72 (95%CI 0.61, 0.83); p < 0.0001]. CONCLUSION: This study suggests that in those presenting with CES symptoms, the presence of both bilateral leg pain and absent ankle reflexes pose an acceptable diagnostic tool to predict a large acute disc herniation on MRI scan..

16.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34183396

RESUMO

The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism.


Assuntos
Reagentes de Ligações Cruzadas/química , Fator XIIIa/metabolismo , Fibrinogênio/metabolismo , Embolia Pulmonar/etiologia , Embolia Pulmonar/patologia , Veia Cava Inferior/patologia , Trombose Venosa/complicações , Animais , Coagulação Sanguínea , Plaquetas/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Imagem Óptica , Embolia Pulmonar/sangue , Trombose Venosa/sangue
17.
Luminescence ; 39(7): e4845, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39054772

RESUMO

A recently developed antipsychotic drug, lurasidone, was determined using a simple, sensitive, and eco-friendly spectrofluorimetric approach. The suggested approach was based on the quantifiable quenching impact of lurasidone on the inherent fluorescence of erythrosine B in an acidic environment employing a Teorell-Stenhagen buffer (pH 4). Following excitation at 530 nm, the quenching of erythrosine B fluorescence was monitored at 552 nm. The system variables were systematically optimized to enhance the formation of the lurasidone-erythrosine B ion pair for analytical purposes. A linear calibration graph was built in the range of 20-600 ng mL-1 with 0.9998 as a coefficient of correlation. The quantitation and detection limits were 13.5 and 4.5 ng/mL, respectively. The analytical validity of the designed approach was assessed with respect to International Council on Harmonization (ICH) guiding principles. The proposed methodology was employed with high recoveries for assessing lurasidone in bulk powder and its therapeutic tablet dosage form. Additionally, the uniformity of tablet formulations was tested using the developed approach. Finally, the established approach was assessed for its greenness using various tools.


Assuntos
Eritrosina , Cloridrato de Lurasidona , Espectrometria de Fluorescência , Cloridrato de Lurasidona/química , Cloridrato de Lurasidona/análise , Eritrosina/química , Eletricidade Estática , Concentração de Íons de Hidrogênio , Comprimidos/análise , Antipsicóticos/química , Corantes Fluorescentes/química , Limite de Detecção
18.
Luminescence ; 39(5): e4758, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38712530

RESUMO

The ability of heterogeneous photocatalysis to effectively remove organic pollutants from wastewater has shown great promise as a tool for environmental remediation. Pure zinc ferrites (ZnFe2O4) and magnesium-doped zinc ferrites (Mg@ZnFe2O4) with variable percentages of Mg (0.5, 1, 3, 5, 7, and 9 mol%) were synthesized via hydrothermal route and their photocatalytic activity was checked against methylene blue (MB) taken as a model dye. FTIR, XPS, BET, PL, XRD, TEM, and UV-Vis spectroscopy were used for the identification and morphological characterization of the prepared nanoparticles (NPs) and nanocomposites (NCs). The 7% Mg@ZnFe2O4 NPs demonstrated excellent degradation against MB under sunlight. The 7% Mg@ZnFe2O4 NPs were integrated with diverse contents (10, 50, 30, and 70 wt.%) of S@g-C3N4 to develop NCs with better activity. When the NCs were tested to degrade MB dye, it was revealed that the 7%Mg@ZnFe2O4/S@g-C3N4 NCs were more effective at utilizing solar energy than the other NPs and NCs. The synergistic effect of the interface formed between Mg@ZnFe2O4 and S@g-C3N4 was primarily responsible for the boosted photocatalytic capability of the NCs. The fabricated NCs may function as an effective new photocatalyst to remove organic dyes from wastewater.


Assuntos
Compostos Férricos , Azul de Metileno , Compostos de Nitrogênio , Energia Solar , Poluentes Químicos da Água , Zinco , Catálise , Poluentes Químicos da Água/química , Compostos Férricos/química , Azul de Metileno/química , Zinco/química , Magnésio/química , Fotólise , Processos Fotoquímicos , Corantes/química , Nanocompostos/química , Grafite/química , Águas Residuárias/química , Nitrilas/química
19.
Luminescence ; 39(6): e4799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858760

RESUMO

In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, Mn3O4, SnO2) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Telúrio , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Telúrio/química , Telúrio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Catálise , Nanopartículas Metálicas/química , Escherichia coli/efeitos dos fármacos , Processos Fotoquímicos , Azul de Metileno/química , Azul de Metileno/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Manganês/química , Manganês/farmacologia , Estanho/química , Estanho/farmacologia , Tamanho da Partícula , Óxidos/química , Óxidos/farmacologia
20.
Luminescence ; 39(3): e4724, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38523053

RESUMO

For white light-rendering research activities, interpretation by using colored emitting materials is an alternative approach. But there are issues in designing the white color emitting materials. Particularly, differences in thermal and decay properties of discrete red, green, and blue emitting materials led to the quest for the search of a single-phased material, able to emit primary colors for white light generation. The current study is an effort to design a simple, single-phase, and cost-effective material with the tunable emission of primary colors by a series of Mg1-xBaxAl2O4:Mn2+ nanopowders. Doping of manganese ion (Mn2+) in the presence of the larger barium cation (Ba2+) at tetrahedral-sites of the spinel magnesium aluminate (MgAl2O4) structure led to the creation of antisite defects. Doped samples were found to have lower bandgaps compared with MgAl2O4, and hybridization of 3d-orbitals of Mn2+ with O(2p), Mg(2s)/Al(2s3p) was found to be responsible for narrowing the bandgap. The distribution of cations at various sites at random results in a variety of electronic transitions between the valance band and oxygen vacancies as well as electron traps produced the antisite defects. The suggested compositions might be used in white light applications since they have three emission bands with centers at 516 nm (green), 464 nm (blue) and 622 nm (red) at an excitation wavelength of 380 nm. A detailed discussion to analyze the effects of the larger cationic radius of Ba2+ on the lattice strain, unit cell parameters, and cell volumes using X-ray diffraction analysis is presented.


Assuntos
Óxido de Alumínio , Óxido de Magnésio , Cristalografia por Raios X , Eletrônica
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