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1.
BMC Pediatr ; 24(1): 450, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997672

RESUMO

BACKGROUND: Neonatal and early-life gut microbiome changes are associated with altered cardiometabolic and immune development. In this study, we explored Cesarean delivery effects on the gut microbiome in our high-risk, under-resourced Bronx, NY population. RESULTS: Fecal samples from the Bronx MomBa Health Study (Bronx MomBa Health Study) were categorized by delivery mode (vaginal/Cesarean) and analyzed via 16 S rRNA gene sequencing at four timepoints over the first two years of life. Bacteroidota organisms, which have been linked to decreased risk for obesity and type 2 diabetes, were relatively reduced by Cesarean delivery, while Firmicutes organisms were increased. Organisms belonging to the Enterococcus genus, which have been tied to aberrant immune cell development, were relatively increased in the Cesarean delivery microbiomes. CONCLUSION: Due to their far-reaching impact on cardiometabolic and immune functions, Cesarean deliveries in high-risk patient populations should be carefully considered.


Assuntos
Cesárea , Fezes , Microbioma Gastrointestinal , Humanos , Cesárea/efeitos adversos , Feminino , Recém-Nascido , Fezes/microbiologia , Cidade de Nova Iorque/epidemiologia , Gravidez , Lactente , Masculino , RNA Ribossômico 16S/genética , Firmicutes/isolamento & purificação , Enterococcus/isolamento & purificação , Bacteroidetes/isolamento & purificação
2.
J Neurooncol ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963658

RESUMO

PURPOSE: Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome. METHODS: This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions). RESULTS: Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks. CONCLUSION: Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.

3.
Luminescence ; 39(7): e4826, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39004784

RESUMO

Biocompatible and highly fluorescent phosphorus, nitrogen and sulfur carbon quantum dots (P,N,S-CQDs) were synthesized using a quick and ecologically friendly process inspired from plant sources. Garlic and red lentils were utilized as natural and inexpensive sources for efficient synthesis of the carbon-based quantum dots using green microwave-irradiation, which provides an ultrafast route for carbonization of the organic biomass and subsequent fabrication of P,N,S-CQDs within only 3 min. The formed P,N,S-CQDs showed excellent blue fluorescence at λem = 412 nm when excited at 325 nm with a quantum yield up to 26.4%. These fluorescent dots were used as a nano-sensor for the determination of the commonly used antibacterial and antiprotozoal drug, metronidazole (MTR). As MTR lacked native fluorescence and prior published techniques had several limitations, the proposed methodology became increasingly relevant. This approach affords sensitive detection with a wide linear range of 0.5-100.0 µM and LOD and LOQ values of 0.14 µM and 0.42 µM, respectively. As well as, it is cost-effective and ecologically benign. The MTT test was used to evaluate the in-vitro cytotoxicity of the fabricated P,N,S-CQDs. The findings supported a minimally cytotoxic impact and good biocompatibility, which provide a future perspective for the applicability of these CQDs in biomedical applications.


Assuntos
Carbono , Corantes Fluorescentes , Alho , Metronidazol , Micro-Ondas , Pontos Quânticos , Pontos Quânticos/química , Alho/química , Carbono/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Metronidazol/análise , Metronidazol/química , Metronidazol/farmacologia , Humanos , Sobrevivência Celular/efeitos dos fármacos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38977470

RESUMO

PURPOSE: Playing wind instruments is a strenuous task on the larynx, predisposing players to voice disorders. This study aims to evaluate potential vocal symptoms and vocal tract alterations in professional wind instrumentalists. METHODS: In this cross-sectional study, 26 male military subjects were interviewed, completed the voice handicap index (VHI) -10 questionnaire, and subjected to auditory-perceptual assessment, neck examination, rigid laryngostroboscopy and flexible nasofiberoscopy both before and during instrument playing. RESULTS: All participants had vocal fatigue symptoms, around one-quarter complained of voice change, one-quarter complained of shortness of breath while or after performing, and one-third complained of neck symptoms. The average score of VHI-10 was 16.2 ± 6.5, and approximately three-quarters of participants scored above the cut-off point. There were no significant correlations between age, years of instrument playing, average hours of daily practice, and VHI-10. Participants with neck symptoms had significantly higher VHI-10 scores. Those (around one-fifth) with an external neck swelling during Valsalva maneuver had a significantly higher VHI-10 score. Dysphonia, mainly mild and of strained, leaky quality, was detected in almost one-third of participants. While the instrument was being played, the vocal folds were somewhat adducted, and the vocal tract became more compressed as the task became more demanding. The most frequent observations in the vocal tract examination were hyperemia of the vocal folds or all over the laryngeal and pharyngeal mucosa, excessive secretions over the vocal folds, signs of hyperadduction, arytenoid edema, and phonatory waste. CONCLUSION: Wind instrumentalists frequently experience voice disorders, which necessitate further care and investigation.

5.
Heart Fail Rev ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014135

RESUMO

Heart failure (HF) is considered one of a leading cause of cardiovascular morbidity and mortality worldwide. The association between HF and venous thromboembolism (VTE) has been reported in several studies owing to many physiological and thromboembolic risk factors. Thus, the need for extended thromboprophylaxis during the post-discharge period in HF patients has been evaluated. Most guidelines do not recommend extended thromboprophylaxis because of its uncertain benefits and increased risk of bleeding. However, recent evidence in HF patients revealed no increased risk of bleeding with extended thromboprophylaxis, which highlights the importance of identifying ideal candidates who might benefit from extended thromboprophylaxis. Several risk assessment models (RAMs) have been developed to identify patients at a high risk of VTE who would benefit from in-hospital and post-discharge prophylactic anticoagulation therapy based on the risk-benefit principle. However, their accuracy in predicting VTE is questionable, and none have a standardized approach for evaluating the risk of VTE in HF patients. In this review, we provided an overview of the incidence and pathophysiology of VTE in HF patients, a summary of guideline recommendations for VTE prevention, and a summary of studies evaluating the use of extended thromboprophylaxis, with a focus on subgroup or post-hoc analyses of HF patients. We also discussed the need to design an ideal RAM that can identify candidate patients for extended thromboprophylaxis by stratifying the risk of VTE and identifying the key risk factors for bleeding in medically ill patients, including those with HF.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38847060

RESUMO

BACKGROUND: The medical treatment of ulcerative colitis (UC) includes the use of biological agents such as vedolizumab, a gut-selective alpha4beta7 (ɑ4ß7) antagonist. The mechanism of action of vedolizumab involves interfering with leukocyte trafficking into the gut vasculature, which halts inflammation. Due to this mechanism of action, concerns have arisen regarding an increased risk of gut infections, specifically, clostridium difficile infection (CDI). The aim is to provide clarity regarding the association between the use of vedolizumab as a therapy for ulcerative colitis and the risk of developing CDI. METHODS: A systematic literature review was conducted, starting with the scoping search, followed by backward snowballing parallel with keyword-based search to identify related articles. A quality assessment was conducted on the initially selected articles and excluded low-quality papers. RESULTS: Pooled analyses indicated that there was no significant association between the use of vedolizumab and the risk of developing CDI (effect size = 0.03 [-0.02, 0.07]). CONCLUSIONS: Vedolizumab does not increase the risk of CDI in patients with UC. Further studies are needed to confirm these findings.

7.
Saudi J Biol Sci ; 31(6): 104002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38706719

RESUMO

American foulbrood (AFB) is a harmful honeybee disease primarily caused by Paenibacillus larvae. The study aims to isolate and identify the AFB causative agent P. larvae and their specific phages to use as a new biological method for AFB disease control. Eight apiaries were inspected for AFB infections. Symptoms of diseased brood comb, were odd brood cells with soft brown decayed brood amongst healthy brood, were identified in the field and demonstrated the prevalence of AFB in every apiary. Three P. larvae isolates were identified using traditional techniques using a 452-bp PCR amplicon specific to the bacterial 16SrRNA gene and was compared between Paenibacillus isolates. Additionally, specific phages of P. larvae strains were applied to examine their efficiency in reducing the infection rate under the apiary condition. The infection rate was reduced to approximately 94.6 to 100 % through the application of a phage mixture, as opposed to 20 to 85.7 % when each phage was administered individually or 78.6 to 88.9 % when antibiotic treatment was implemented. Histological studies on phage-treated bee larvae revealed some cells regaining normal shape, with prominent nuclei and microvilli. The gastrointestinal tract showed normal longitudinal and circular muscles, unlike bee larvae treated with bacterial strains with abnormal and destroyed tissues, as shown by the basement membrane surrounding the mid-gut epithelium. Phage techniques exhibited promise in resolving the issue of AFB in honeybees due to their ease of application, comparatively lower cost, and practicality for beekeepers in terms of laboratory preparation.

8.
Saudi J Gastroenterol ; 30(3): 126-137, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38597333

RESUMO

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease that affects the colon, leading to symptoms of bloody diarrhea, abdominal cramps, and urgency. The treatment of UC has evolved over the past few decades from locally active anti-inflammatory compounds to more selective therapies that target specific arrays of the immune system. The challenge of selecting the first advanced therapy became apparent in this rapidly expanding landscape of medications. No current investigational tools, such as genetic, immunologic, or biological markers, can guide the identification of the safest and most effective therapeutic option for each patient. Hence, physicians must carefully assess patient/disease characteristics and match them with the most suitable drug through a clinically driven assessment. In this paper, we outline patient and drug characteristics that play a role in selecting first-line advanced therapies for UC and propose an algorithm for selection.


Assuntos
Colite Ulcerativa , Medicina de Precisão , Humanos , Colite Ulcerativa/tratamento farmacológico , Medicina de Precisão/métodos , Algoritmos , Anti-Inflamatórios/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Seleção de Pacientes
9.
J Econ Entomol ; 117(3): 809-816, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568949

RESUMO

In this study, we investigated the biological aspects and predation efficiency of 3 aphidophagous ladybird beetles, Coccinella novemnotata, Hippodamia variegata, and Coccinella septempunctata, on the cotton aphid, Aphis gossypii, reared on cucumber plants (Cucumis sativus L. cultivar barracuda) under laboratory conditions. The developmental periods of C. novemnotata, H. variegata, and C. septempunctata were observed to be 16.00 ±â€…0.25, 16.00 ±â€…0.25, and 20.58 ±â€…0.40 days, respectively. The larvae of these ladybird beetles consumed an average of 218.93 ±â€…8.86, 254.77 ±â€…8.86, and 537.36 ±â€…10.49 aphids, respectively. Fourth-instar larvae were particularly efficient, consuming 53.68%, 52.68%, and 52.64% of total aphids for C. novemnotata, H. variegata, and C. septempunctata, respectively. Adult emergence rates were promising, with 91.67%, 100.00%, and 92.86%, accompanied by sex ratios of 63.64%, 53.84%, and 61.54%, respectively. Notably, a single female of C. novemnotata, H. variegata, and C. septempunctata consumed an average of 2,215.30, 2,232.00, and 3,364.50 aphids, respectively, over its lifespan. Coccinella septempunctata demonstrated the highest predation efficiency among the 3 species, suggesting its potential for biological control of A. gossypii in both open fields and greenhouses, promoting sustainable agricultural practices.


Assuntos
Afídeos , Besouros , Larva , Controle Biológico de Vetores , Comportamento Predatório , Animais , Afídeos/fisiologia , Besouros/fisiologia , Larva/crescimento & desenvolvimento , Larva/fisiologia , Cucumis sativus , Feminino , Masculino , Cadeia Alimentar , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia
10.
AJNR Am J Neuroradiol ; 45(4): 475-482, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453411

RESUMO

BACKGROUND AND PURPOSE: Response on imaging is widely used to evaluate treatment efficacy in clinical trials of pediatric gliomas. While conventional criteria rely on 2D measurements, volumetric analysis may provide a more comprehensive response assessment. There is sparse research on the role of volumetrics in pediatric gliomas. Our purpose was to compare 2D and volumetric analysis with the assessment of neuroradiologists using the Brain Tumor Reporting and Data System (BT-RADS) in BRAF V600E-mutant pediatric gliomas. MATERIALS AND METHODS: Manual volumetric segmentations of whole and solid tumors were compared with 2D measurements in 31 participants (292 follow-up studies) in the Pacific Pediatric Neuro-Oncology Consortium 002 trial (NCT01748149). Two neuroradiologists evaluated responses using BT-RADS. Receiver operating characteristic analysis compared classification performance of 2D and volumetrics for partial response. Agreement between volumetric and 2D mathematically modeled longitudinal trajectories for 25 participants was determined using the model-estimated time to best response. RESULTS: Of 31 participants, 20 had partial responses according to BT-RADS criteria. Receiver operating characteristic curves for the classification of partial responders at the time of first detection (median = 2 months) yielded an area under the curve of 0.84 (95% CI, 0.69-0.99) for 2D area, 0.91 (95% CI, 0.80-1.00) for whole-volume, and 0.92 (95% CI, 0.82-1.00) for solid volume change. There was no significant difference in the area under the curve between 2D and solid (P = .34) or whole volume (P = .39). There was no significant correlation in model-estimated time to best response (ρ = 0.39, P >.05) between 2D and whole-volume trajectories. Eight of the 25 participants had a difference of ≥90 days in transition from partial response to stable disease between their 2D and whole-volume modeled trajectories. CONCLUSIONS: Although there was no overall difference between volumetrics and 2D in classifying partial response assessment using BT-RADS, further prospective studies will be critical to elucidate how the observed differences in tumor 2D and volumetric trajectories affect clinical decision-making and outcomes in some individuals.


Assuntos
Neoplasias Encefálicas , Glioma , Criança , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf , Resultado do Tratamento
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 311: 124017, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354677

RESUMO

Nanoparticles are a boon for humanity because of their improved functionality and unlimited potential applications. Considering this significance, the proposed study introduced a simple, fast and eco-friendly method for synthesis of fluorescent silver nanoparticles (Ag-NPs) using Panax Ginseng root extract as a reducing and capping agent. Synthesis of Ag-NPs was performed in one step within three minutes utilizing microwave irradiation. The resulting Ag-NPs were characterized using various microscopic and spectroscopic techniques such as, Transmission Electron Microscope (TEM), UV/Visible spectroscopy, Fourier Transform Infrared Spectroscopy(FTIR) and Energy Dispersive X-ray analysis (EDX). The prepared Ag-NPs, which act as a fluorescent nano-probe with an emission band at 416 nm after excitation at 331 nm, were used to assay nilvadipine (NLV) spectrofluorimetrically in its pharmaceutical dosage form with good sensitivity and reproducibility. The proposed study is based on the ability of NLV to quantitatively quench the native Ag-NPs fluorescence, forming a ground state complex as a result of static quenching and an inner filter mechanism. The suggested approach displayed a satisfactory linear relationship throughout a concentration range of 5.0 µM - 100.0 µM, with LOD and LOQ values of 1.18 µM and 3.57 µM, respectively. Validation of the suggested approach was examined in accordance with ICH recommendations. In addition, the anti-bacterial and anti-fungal activities of the prepared nanoparticles were investigated, and they demonstrated effective anti-microbial activities and opened a future prospective to combat future antibiotic resistance. Finally, in-vitro cytotoxicity assay of Ag-NPs against normal and cancerous human cell lines was studied using MTT assay. The results proved the potential use of the produced Ag-NPs as an adjunct to anticancer treatment or for drug delivery without significantly harming healthy human cells.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Nifedipino/análogos & derivados , Panax , Humanos , Prata/farmacologia , Prata/química , Corantes Fluorescentes/farmacologia , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Bactérias , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Testes de Sensibilidade Microbiana
12.
Sci Data ; 11(1): 254, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424079

RESUMO

Resection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.


Assuntos
Neoplasias Encefálicas , Humanos , Inteligência Artificial , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Imageamento por Ressonância Magnética , Radiocirurgia
13.
Neurooncol Adv ; 6(1): vdad172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38221978

RESUMO

Background: Although response in pediatric low-grade glioma (pLGG) includes volumetric assessment, more simplified 2D-based methods are often used in clinical trials. The study's purpose was to compare volumetric to 2D methods. Methods: An expert neuroradiologist performed solid and whole tumor (including cyst and edema) volumetric measurements on MR images using a PACS-based manual segmentation tool in 43 pLGG participants (213 total follow-up images) from the Pacific Pediatric Neuro-Oncology Consortium (PNOC-001) trial. Classification based on changes in volumetric and 2D measurements of solid tumor were compared to neuroradiologist visual response assessment using the Brain Tumor Reporting and Data System (BT-RADS) criteria for a subset of 65 images using receiver operating characteristic (ROC) analysis. Longitudinal modeling of solid tumor volume was used to predict BT-RADS classification in 54 of the 65 images. Results: There was a significant difference in ROC area under the curve between 3D solid tumor volume and 2D area (0.96 vs 0.78, P = .005) and between 3D solid and 3D whole volume (0.96 vs 0.84, P = .006) when classifying BT-RADS progressive disease (PD). Thresholds of 15-25% increase in 3D solid tumor volume had an 80% sensitivity in classifying BT-RADS PD included in their 95% confidence intervals. The longitudinal model of solid volume response had a sensitivity of 82% and a positive predictive value of 67% for detecting BT-RADS PD. Conclusions: Volumetric analysis of solid tumor was significantly better than 2D measurements in classifying tumor progression as determined by BT-RADS criteria and will enable more comprehensive clinical management.

14.
J Clin Oncol ; 42(4): 441-451, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37978951

RESUMO

PURPOSE: The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers. PATIENTS AND METHODS: Patients, age 3-21 years, with progressive/recurrent pLGG received everolimus orally, 5 mg/m2 once daily. Frequency of driver gene alterations was compared among independent pLGG cohorts of newly diagnosed and progressive/recurrent patients. PFS at 6 months (primary end point) and median PFS (secondary end point) were estimated for association with everolimus therapy. RESULTS: Between 2012 and 2019, 65 subjects with progressive/recurrent pLGG (median age, 9.6 years; range, 3.0-19.9; 46% female) were enrolled, with a median follow-up of 57.5 months. The 6-month PFS was 67.4% (95% CI, 60.0 to 80.0) and median PFS was 11.1 months (95% CI, 7.6 to 19.8). Hypertriglyceridemia was the most common grade ≥3 adverse event. PI3K/AKT/mTOR pathway activation did not correlate with clinical outcomes (6-month PFS, active 68.4% v nonactive 63.3%; median PFS, active 11.2 months v nonactive 11.1 months; P = .80). Rare/novel KIAA1549::BRAF fusion breakpoints were most frequent in supratentorial midline pilocytic astrocytomas, in patients with progressive/recurrent disease, and correlated with poor clinical outcomes (median PFS, rare/novel KIAA1549::BRAF fusion breakpoints 6.1 months v common KIAA1549::BRAF fusion breakpoints 16.7 months; P < .05). Multivariate analysis confirmed their independent risk factor status for disease progression in PNOC001 and other, independent cohorts. Additionally, rare pathogenic germline variants in homologous recombination genes were identified in 6.8% of PNOC001 patients. CONCLUSION: Everolimus is a well-tolerated therapy for progressive/recurrent pLGGs. Rare/novel KIAA1549::BRAF fusion breakpoints may define biomarkers for progressive disease and should be assessed in future clinical trials.


Assuntos
Everolimo , Glioma , Humanos , Criança , Feminino , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Masculino , Everolimo/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Glioma/tratamento farmacológico , Glioma/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/uso terapêutico , Biomarcadores
15.
Pediatr Neurol ; 151: 104-110, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154236

RESUMO

BACKGROUND: Individuals with childhood apraxia of speech (CAS) were reported to have genetic variations related to gluten sensitivity and some neuroanatomic changes, which could be associated with alterations in neurotransmitters levels such as glutamate and gamma-aminobutyric acid (GABA). The aim was to measure the levels of antigliadin immunoglobulin A (IgA) antibody, glutamate, and GABA in the plasma of children with CAS compared with children with delayed language development (DLD) and neurotypical (NT) children. METHODS: The participants (N = 120) were in three groups: Group I for CAS (N = 30), Group II for DLD (N = 60), and Group III for NT (N = 30). The abilities of children in Groups I and II were evaluated. The plasma levels of antigliadin IgA, glutamate, and GABA were determined by enzyme-linked immunosorbent assay. RESULTS: The intelligence quotient and expressive language age in Group I were low compared with Group II (P = 0.001; 0.004). The levels of antigliadin IgA and glutamate in Group I were higher compared with the other two groups, whereas the level of GABA was lower (P < 0.0001). An imbalance between glutamate and GABA was found in Group I. In Group II, no measures differed from NTs except lower GABA levels (P = 0.0007). CONCLUSIONS: The elevated levels of antigliadin IgA antibody and glutamate demonstrated high sensitivity and specificity, differentiating children with CAS from children with DLD and NT children. The low levels of GABA contributed to the imbalance between the excitatory and inhibitory neurotransmitters' levels detected in children with CAS.


Assuntos
Apraxias , Síndromes de Malabsorção , Criança , Humanos , Fala , Ácido Glutâmico , Imunoglobulina A , Glutens , Ácido gama-Aminobutírico , Neurotransmissores
16.
Future Med Chem ; 15(22): 2113-2141, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37929337

RESUMO

Given that mitochondrial dysregulation is a biomarker of many cancers, cationic quaternary phosphonium salt (QPS) conjugation is a widely utilized strategy for anticancer drug design. QPS-conjugated compounds exhibit greater cell permeation and accumulation in negatively charged mitochondria, and thus, show enhanced activity. Phylogenetic similarities between mitochondria and bacteria have provided a rationale for exploring the antibacterial properties of mitochondria-targeted compounds. Additionally, due to the importance of mitochondria in the survival of pathogenic microbes, including fungi and parasites, this strategy can be extended to these organisms as well. This review examines recent literature on the antimicrobial activities of various QPS-conjugated compounds and provides future directions for exploring the medicinal chemistry of these compounds.


Assuntos
Anti-Infecciosos , Filogenia , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Mitocôndrias , Compostos de Amônio Quaternário/química
17.
Cureus ; 15(10): e46742, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022032

RESUMO

Background Dyslipidemia affects approximately one-third of Saudi Arabia's adult population. Dyslipidemia, hypertension, diabetes mellitus (DM), smoking, and a familial predisposition to cardiovascular disease (CVD) are significant risk factors for CVD. It can be prevented effectively through lifestyle changes and lifelong statin therapy; however, poor adherence limits its effectiveness. This study is designed to assess the level of adherence to statin prescription in patients with DM in diabetic centers in the Qassim region and to assess the factors associated with neglecting to take medication. Methodology A cross-sectional study was conducted among 226 diabetic patients who were prescribed statins. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8). Demographic and clinical data were collected, and multivariate logistic regression analysis was used to identify factors associated with medication adherence. Results Of the 226 patients, 29.7% had high adherence, 32.7% had medium adherence, and 37.6% had low adherence to statin medication. Patients diagnosed with diabetes for less than five years had the highest proportion of low adherence (41.2%). No significant associations were found between medication adherence and gender, nationality, or educational level. Conclusion The study found that medication adherence to statins in diabetic patients in the Al Qassim region of Saudi Arabia is suboptimal, with a significant proportion of patients having low adherence. Patients diagnosed with diabetes for less than five years had the highest proportion of low adherence, suggesting that patients with a shorter disease duration may require additional support or interventions to improve their medication adherence. Healthcare providers should emphasize the importance of medication adherence and work with patients to develop personalized treatment plans that include medication and lifestyle modifications to optimize lipid control and improve overall health outcomes in diabetic patients.

18.
Neurooncol Adv ; 5(1): vdad118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37860269

RESUMO

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice.

19.
Cureus ; 15(9): e45222, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37842476

RESUMO

Thyroid cancer ranks as the ninth most common cancer worldwide and third in Saudi Arabia. Given thyroid cancer's high incidence, thyroid cancer patients' quality of life (QoL) has been a concern for many years. However, no study has been dedicated to assessing thyroid cancer patients' QoL in Saudi Arabia. Thus, we aimed to fill this gap by assessing thyroid cancer patients' QoL in Saudi Arabia. This cross-sectional study was conducted among thyroid cancer patients attending outpatient clinics at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia, from 2017 to 2023. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) assessed the patients' QoL through an individual interviewer-administered technique. We used RStudio to perform statistical analysis. Statistical differences between groups based on QoL scores were assessed using the Wilcoxon and Kruskal-Wallis rank-sum tests. Our results showed that for QoL scores of functional domains, the lowest was in social functioning, and the highest was in cognitive functioning. Regarding the subscales of symptoms, the highest scores were fatigue and insomnia. In conclusion, numerous factors affect thyroid cancer patients' QoL. Recognition and appropriate management of these factors will improve the overall QoL; there is a need to understand what is driving these factors in further clinical studies.

20.
Drug Discov Today ; 28(12): 103799, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839776

RESUMO

The reactive functionalities of drugs that engage in covalent interactions with the enzyme/receptor residue in either a reversible or an irreversible manner are called 'warheads'. Covalent warheads that were previously neglected because of safety concerns have recently gained center stage as a result of their various advantages over noncovalent drugs, including increased selectivity, increased residence time, and higher potency. With the approval of several covalent inhibitors over the past decade, research in this area has accelerated. Various strategies are being continuously developed to tune the characteristics of warheads to improve their potency and mitigate toxicity. Here, we review research progress in warhead discovery over the past 5 years to provide valuable insights for future drug discovery.


Assuntos
Química Farmacêutica , Descoberta de Drogas
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