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1.
Mymensingh Med J ; 33(4): 980-988, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39351714

RESUMO

Traditionally, percutaneous nephrolithotomy (PCNL) includes placing a nephrostomy tube and a Double J (DJ) stent to drain the kidney and operative tract following the procedure. However, more recent techniques, such as tubeless or totally tubeless PCNL, eliminate these drainage methods. The objective was to assess the feasibility, safety and effectiveness of performing tubeless or totally tubeless PCNL in comparison to standard PCNL a retrospective analysis was performed on 156 patients who underwent PCNL treatment From September 2022 to September 2023. Of these, 78 patients received traditional nephrostomy PCNL, while 46 patients underwent the tubeless procedure and the remaining 32 received the totally tubeless procedure. The three groups showed no significant differences in preoperative patient characteristics. The operation time, analgesic requirements and hospital stay were lower in the tubeless and totally tubeless PCNL group than in the standard PCNL group (p<0.05). No significant differences were found in the mean stone size, stone-free status or the occurrence of major complications. The overall complications (Grade-1, 2 and 3) rate was 14.2% in the standard PCNL group, 8.7% in the tubeless PCNL and 9.4% in the totally tubeless PCNL group. The tubeless and totally tubeless PCNL techniques have proven to be safe and effective, even for patients with incomplete staghorn stones and a moderate pelvic stone burden. These approaches are associated with reduced pain, lower analgesic needs, shorter operative times, and decreased hospital stays, making them more cost- effective and less likely to result in complications, while also improving patient satisfaction. Further research is essential to validate the safety of these techniques, encouraging urologists to adopt them in clinical practice.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/instrumentação , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Cálculos Renais/cirurgia , Adulto , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia
2.
Mymensingh Med J ; 33(4): 1033-1036, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39351721

RESUMO

Umbilical granuloma may be defined as a small mass of granulation tissue which develops at the base of the umbilicus after separation of the cord. It consists of true granulation tissue with fibroblast and abundant capillaries. Treatment options are chemical cauterization, electro cauterization and sometimes need surgical excision. Aims of this study were to develop a simple and feasible method for the treatment of umbilical granuloma with table salt (NaCl). This was a multi-center prospective type of observational study and conducted from January 2023 to March 2024 in the department of Pediatrics Surgery, Mymensingh Medical College Hospital, Mymensingh and other Private Hospitals of Mymensingh, Bangladesh. Total 66 patients were included among them 59(89.09%) cured and 7(10.6%) patients need other options. No complications and recurrence was seen in 3 months follow up. Treatment of umbilical granuloma with table salt (NaCl) is a simple, effective, low cost and feasible method.


Assuntos
Granuloma , Umbigo , Humanos , Feminino , Masculino , Estudos Prospectivos , Granuloma/tratamento farmacológico , Cloreto de Sódio/uso terapêutico , Bangladesh , Lactente , Resultado do Tratamento , Pré-Escolar
3.
Mymensingh Med J ; 33(4): 1176-1183, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39351741

RESUMO

Treatment of relapsed or refractory diffuse large B-cell lymphoma is difficult. The de novo diffuse large B-cell lymphoma has better prognosis than the transformed diffuse large B-cell lymphoma. The response of CHOP or a similar regimen has an important role in determining response to salvage therapy, in relapse or refractory diffuse large B-cell lymphoma patients. Patients who are non-responder to initial treatment have a very poor chance of responding to therapy for relapse. This was a small scale observational study and was conducted from January 2017 to December 2020 in National Institute of Cancer Research and Hospital, Bangladesh. A total of 34 patients with relapsed or refractory diffuse large B-cell lymphoma were identified at hematology department in National Institute of Cancer Research and Hospital, 28 of them were treated with ICE chemotherapy and 6 with R-ICE chemotherapy as second line regimen. Overall response rate to 2nd line chemotherapy was 64.8%, with 32.4% (11 patients) complete remission and 32.4% (11 patients) partial remission. Median overall survival to second line regimen was 10 months, corresponding to a 4 year overall survival of 32.4% and a 4 year progression free survival was 17.6%. Patient with stable disease/progressive disease median overall survival was 7 months compared with 15 months for complete remission and 9 months for partial remission (p<0.001). Median overall survival was significantly better in patients with international prognostic index 0-2 compared in those with international prognostic index >2 (p=0.010). However improvement of salvage efficacy is an urgent need with new drugs. Further studies are necessary to determine whether this regimen will improve outcomes of relapsed or refractory diffuse large B-cell lymphoma patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Etoposídeo , Ifosfamida , Linfoma Difuso de Grandes Células B , Rituximab , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Masculino , Feminino , Ifosfamida/administração & dosagem , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Adulto , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Idoso
4.
Med Oncol ; 41(11): 271, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39400594

RESUMO

The most prevalent form of primary liver cancer, hepatocellular carcinoma (HCC) poses a significant global health challenge due to its limited therapeutic options. Researchers are currently focused on the complex molecular landscape that governs the initiation and progression of HCC in order to identify new avenues for diagnosis, prognosis, and treatment. In the context of HCC, the Kinesin Superfamily Proteins (KIFs) have become critical regulators of cellular processes, prompting a growing interest in their function among the diverse array of molecular actors implicated in cancer. The KIFs, a family of microtubule-based molecular motors, are renowned for their essential roles in the dynamics of mitotic spindles and intracellular transport. Beyond their well-established functions in normal cellular physiology, emerging evidence indicates that dysregulation of KIFs significantly contributes to the pathogenesis of HCC. Novel therapeutic targets and diagnostic markers are revealed through the unique opportunity to comprehend the complex interplay between KIFs and the molecular events that drive HCC.


Assuntos
Carcinoma Hepatocelular , Cinesinas , Neoplasias Hepáticas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Humanos , Cinesinas/metabolismo , Cinesinas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Biomarcadores Tumorais/metabolismo
5.
Cureus ; 16(9): e68715, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39371709

RESUMO

Background Interventional radiology (IR) utilizes minimally invasive procedures guided by imaging to diagnose and treat various conditions, offering less invasive alternatives to traditional surgery. Despite its importance, awareness among family medicine practitioners can vary, affecting patient care. While IR has advanced in Saudi Arabia, there are limited data on family medicine practitioners' understanding of IR. This study assesses awareness of IR procedures among family medicine doctors in Jazan and their perceived need for further education. Methods A cross-sectional interview-administered survey was conducted online among family medicine doctors in Jazan via social media. The survey assessed demographic data, awareness of IR procedures, self-rated knowledge, and attitudes towards IR. Participants' understanding of IR training, hospital privileges, outpatient clinics, and recognition by the Saudi Commission for Health Specialties (SCHS) was evaluated. Data were analyzed using descriptive statistics and chi-square tests. Results Out of 395 respondents, the age distribution was as follows: 20-29 years (44.3%), 30-39 years (32.9%), and 40 years or older (22.8%). Gender distribution was as follows: females (44.6%) and males (55.4%). Specialties included family medicine consultants (10.6%), residents (32.4%), specialists (22.8%), and general practitioners (34.2%). Awareness of IR procedures varied: uterine fibroid embolization (58.7%), coronary angiography (57.5%), vascular angioplasty (63.5%), radiofrequency ablation (61.3%), peripheral vascular bypass (61.8%), brain biopsy (56.2%), nephrostomy tube placement (59.5%), varicose veins treatment (63.0%), and cystoscopic tumor resection (54.7%). Self-rated knowledge was as follows: poor (46.8%), adequate (27.1%), good (15.7%), and excellent (10.4%). Most believed that interventional radiologists' training was in radiology (62.8%), with fewer attributing it to vascular surgery (20.5%) or a combination (16.7%). Regarding privileges and facilities, 248 (62.8%) reported hospital admitting privileges for IRs, 251 (63.5%) reported outpatient clinics, and 45 (11.4%) were unsure about admitting privileges. SCHS recognition was confirmed by 267 (67.6%). Referrals to IRs were made by 283 (71.6%), and 260 (65.8%) would increase referrals with more knowledge. The perceived benefit of additional education was as follows: no benefit (48.4%), some benefit (30.6%), and significant benefit (21.0%). Conclusion The study reveals gaps in awareness and knowledge of IR among family medicine doctors in Jazan. While there is recognition of IR's value and a willingness to refer patients, variations in knowledge highlight the need for targeted educational interventions. Improving education on IR could enhance integration into patient care and optimize outcomes.

6.
Chem Biodivers ; : e202401960, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367808

RESUMO

This study investigated the therapeutic effect of Conocarpus erectus leaves methanolic extract against AlCl3 -induced Alzheimer's disease (AD) in rats comparing with Donepezil-hydrochloride as a reference drug. The bioactive compounds of C. erectus leaves were isolated and identified by GC/MS and LC-ESI-MS analysis. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), amyloid-ß-peptide (Aß-peptide), tau protein, acetylcholinesterase (AChE), serotonin (5-HT), dopamine (DA) and nor-adrenaline (NE) levels were estimated. The neuromuscular strength, memory behavior and histopathological examination of cerebral cortex region were also conducted. Forty-three compounds were characterized from the non-polar fraction of C. erectus L. leaves extract and nineteen compounds were identified from the defatted extract. AlCl3- induction caused significant elevation of brain oxidative stress, Aß-peptide, tau protein, IL-6, TNF-α and AChE levels. A significant decrease in 5-HT, ND and DA levels were noticed. Additionally, AlCl3 reduced neuromuscular strength and compromised memory function. Treatment of AlCl3- induced rats with C. erectuse extract ameliorated these selected parameters by variable degrees. In conclusion, C. erectus protects against AlCl3- induced AD in rats through its antioxidant, anti-inflammatory, and antineutron damage. It could be considered as a new nutraceutical agent for attenuating symptoms associated with Alzheimer's disease.

7.
Cureus ; 16(8): e65960, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39221331

RESUMO

Systemic light chain amyloidosis is a rare and severe disorder characterized by amyloid fibril deposition in various tissues, often leading to organ failure. Early diagnosis is crucial but challenging due to diverse clinical manifestations. Our case report presents a complex case of systemic light chain amyloidosis in a 62-year-old patient with cardiac, renal, neurological, and gastrointestinal involvement. The patient's treatment with cyclophosphamide, bortezomib, dexamethasone, and intravenous daratumumab yielded significant improvement, aligning with recent studies. Following treatment, the patient improved from stage IV to stage II systemic light chain amyloidosis per the National Comprehensive Cancer Network (NCCN) guidelines, indicating a more favorable prognosis. Hence, the successful integration of daratumumab in our case underscores its potential as a valuable addition to the treatment regimen for advanced systemic light chain amyloidosis, showcasing significant improvements across multiple organ systems.

8.
Pathol Res Pract ; 263: 155569, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39236498

RESUMO

Breast cancer (BC) is the most common cancer among women, characterized by significant heterogeneity. Diagnosis of the disease in the early stages and appropriate treatment plays a crucial role for these patients. Despite the available treatments, many patients due to drug resistance do not receive proper treatments. Recently, circular RNAs (circRNAs), a type of non-coding RNAs (ncRNAs), have been discovered to be involved in the progression and resistance to drugs in BC. CircRNAs can promote or inhibit malignant cells by their function. Numerous circRNAs have been discovered to be involved in the proliferation, invasion, and migration of tumor cells, as well as the progression, pathogenesis, tumor metastasis, and drug resistance of BC. Circular RNAs can also serve as a biomarker for diagnosing, predicting prognosis, and targeting therapy. In this review, we present an outline of the variations in circRNAs expression in various BCs, the functional pathways, their impact on the condition, and their uses in clinical applications.

9.
J Neurointerv Surg ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304195

RESUMO

BACKGROUND: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes. METHODS: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique repeated. The primary outcome was successful recanalization at second attempt defined as Thrombolysis in Cerebral Ischemia (TICI) score of 2B or higher. Secondary outcomes were 90-day modified Rankin Score (mRS) and postprocedural hemorrhage. RESULTS: Among 2167 patients, converting to an alternative technique after a failed first pass was associated with higher odds of successful recanalization (adjusted OR (aOR)=1.5, p=0.041), and higher odds of mRS 0-2 at 90 days (aOR=1.6, p=0.005) without additional risk of symptomatic hemorrhage (p=0.379). Using a propensity score matched cohort of 490 patients, technique conversion at second attempt increased odds of successful recanalization at second attempt (aOR=1.32, p=0.006) and 90-day mRS 0-2 (aOR=1.38, p=0.008). CONCLUSIONS: Early conversion to an alternative EVT technique after a failed first pass recanalization in patients with AIS is associated with better technical success and clinical outcomes.

10.
Pathol Res Pract ; 262: 155520, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217771

RESUMO

Carcinoma of the colon and rectum, also known as colorectal cancer, ranks as the third most frequently diagnosed malignancy globally. Sorafenib exhibits broad-spectrum antitumor activity against Raf, VEGF, and PDGF pathways in hepatocellular, thyroid, and renal cancers, but faces resistance in colorectal malignancies. 6-Shogaol, a prominent natural compound found in Zingiberaceae, exhibits antioxidant, anti-inflammatory, anticancer, and antiemetic properties. We investigated the influence of 6-shogaol on sorafenib's cytotoxic profile against colorectal cancer cell lines (HT-29, HCT-116, CaCo-2, and LS174T) through its effects on cellular accumulation and metabolism. Cytotoxicity was assessed using the sulpharodamine B assay, caspase-3 and c-PARP cleavage, cell cycle distribution analysis, and P-gp efflux activity. 6-Shogoal showed considerable cytotoxicity with decreased IC50 in colorectal cancer cell lines. Combining sorafenib and 6-shogaol increased c-PARP and pro-caspase-3 concentrations in HCT-116 cells compared to sorafenib alone. In combination, pro-caspase-3 concentrations were decreased in CaCo-2 cells compared to alone. Sorafenib combinations with 6-shogaol showed a significant drop in cell cycle distribution from 16.96±1.10 % to 9.16±1.85 %, respectively. At 100 µM, sorafenib and 6-shogaol showed potent and significant activity with intra-cellular rhodamine concentration on P-gp efflux activity in CRC cell lines. In conclusion, 6-shogaol substantially improved the cytotoxic profile of sorafenib by affecting its cellular uptake and metabolism. Future research should focus on dosage optimization and formulation and evaluate the efficacy and safety of the combination in animal models with colorectal cancer.


Assuntos
Catecóis , Neoplasias Colorretais , Sorafenibe , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Sorafenibe/farmacologia , Catecóis/farmacologia , Antineoplásicos/farmacologia , Sinergismo Farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células CACO-2 , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
11.
World Neurosurg ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326665

RESUMO

BACKGROUND: Relationships between low socioeconomic status (SES) and surgical outcomes are well established for certain procedures. However, scant literature has focused on relationships between median household income and lumbar fusion outcomes. METHODS: Patients who underwent fusion procedures between January 1, 2009 and December 31, 2020 were identified from the National Inpatient Sample (NIS) database. They were categorized into 4 quartiles, from lowest to highest, based on median household incomes in respective zip codes. We applied univariable and multivariable linear and logistic regression models to analyze perioperative data according to income quartiles. RESULTS: We included 2,826,396 patients. In multivariable regression, patients in the 3 lowest income quartiles exhibited higher rates of in-hospital cardiac events perioperatively, with odds ratios (OR) of 1.19 (95% confidence interval[CI]1.13-1.26, p<0.001), 1.10 (95%CI 1.05-1.16, p<0.001), and 1.06 (95%CI 1.01-1.12, p=0.011) for the first, second, and third quartiles, respectively. Patients in the lowest income (first) quartile had a higher occurrence of perioperative urinary complications (OR=1.07, 95%CI 1.03-1.12, p=0.001), systemic infectious complications (OR=1.17, 95% CI 1.04-1.32, p=0.006), neurological deficit (OR=1.17, 95%CI 1.06-1.30, p=0.002), and wound infections (OR=1.22, 95%CI 1.12-1.34, p<0.001). Those in the 3 lowest income quartiles were less likely to experience respiratory, gastrointestinal, and venous thrombotic complications (p<0.05). The lowest income quartile had protective associations for dural tears (OR 0.93, 95%CI 0.89-0.99, p=0.038) and postprocedure anemia across all 3 lower quartiles, with OR<1 and p<0.001. CONCLUSION: Reduced household income significantly affected perioperative outcomes after lumbar fusion and should be taken into consideration during the perioperative period.

12.
Behav Brain Funct ; 20(1): 26, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350139

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. METHODS: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. RESULTS: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. CONCLUSIONS: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.


Assuntos
Atorvastatina , Modelos Animais de Doenças , NADPH Oxidase 2 , NF-kappa B , Risperidona , Receptor 4 Toll-Like , Ácido Valproico , Animais , Risperidona/farmacologia , Atorvastatina/farmacologia , Ácido Valproico/farmacologia , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Ratos , Feminino , NADPH Oxidase 2/metabolismo , Masculino , Gravidez , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Ratos Sprague-Dawley , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos
14.
Biomed Pharmacother ; 179: 117365, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217837

RESUMO

Mangosteen (Garcinia mangostana) is well-known for its nutritional value and health benefits. Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. Here we show that the prenylated xanthones, α-mangostin, γ-mangostin, 9-hydroxycalabaxanthone (9-HCX), and garcinone E from the mangosteen pericarp exhibit cytotoxicity against a panel of human cancer cell lines including lung adenocarcinoma (A549), cervical carcinoma (HeLa), prostatic carcinoma (DU 145), pancreatic carcinoma (MIA PaCa-2), hepatocellular carcinoma (Hep G2), bladder urothelial cancer (5637), as well as the triple-negative breast cancer cells MDA-MB-231. In line with its higher predicted bioactivity score compared to other prenylated xanthones, 9-HCX induced the strongest antiproliferative and proapoptotic effects in MDA-MB-231 breast cancer xenografts in vivo. In different in vitro models, we demonstrate that prenylated xanthones from G. mangostana target mitochondria in cancer cells by inhibition of the mitochondrial respiratory chain complex II (α-mangostin, γ-mangostin, and garcinone E) and complex III (9-HCX) as shown in isolated mitochondria. Accordingly, oxidative mitochondrial respiration (OXPHOS) was inhibited, mitochondrial proton leak increased, and adenosine triphosphate (ATP) synthesis decreased as analyzed by Seahorse assay in MDA-MB-231 cells. Hence, the prenylated xanthones increased mitochondrial superoxide levels, induced mitochondrial membrane permeabilization, and initiated caspase 3/7-mediated apoptosis in MDA-MB-231 triple-negative breast cancer cells. Thus, prenylated xanthones from Garcinia mangostana exhibit anticancer activity based on interference with the mitochondrial respiration.


Assuntos
Garcinia mangostana , Mitocôndrias , Xantonas , Xantonas/farmacologia , Xantonas/isolamento & purificação , Humanos , Garcinia mangostana/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Animais , Prenilação , Feminino , Camundongos , Apoptose/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo
15.
Chest ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299388

RESUMO

BACKGROUND: Sarcoidosis is a granulomatous disease with varying courses of disease progression. Environmental exposures are thought to be contributors to disease onset. Exposure to air pollutants such as fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been identified as contributors to health disparities in lung diseases; little is known about these environmental exposures' associations with disease outcomes in sarcoidosis. RESEARCH QUESTION: Is higher exposure to PM2.5 and NO2 associated with worse lung function in sarcoidosis? STUDY DESIGN AND METHODS: We conducted a retrospective, cross-sectional study of individuals with pulmonary sarcoidosis seen from 2005 to 2015. Home addresses at the year of enrollment were geocoded, and exposure to PM2.5 and NO2 was modeled using high-resolution 1 km × 1 km annual surface exposure data during the year of enrollment. Racial and sex differences in exposure were determined. Multivariable linear regression models were used to examine the associations between PM2.5 and NO2 and the pulmonary function test (PFT) measures FVC, FEV1, and Dlco. RESULTS: Among the 415 individuals in the analysis, Black individuals had significantly higher exposure to PM2.5 and NO2 compared with non-Hispanic White individuals, 12.2 µg/m3 (SD 2.4) vs 11 µg/m3 (SD 2.2) and 6.3 ppb (SD 1.9) vs 5.0 ppb (SD 2.0), respectively. Every 1 µg/m3 higher exposure to PM2.5 was associated with 1.12% lower Dlco% predicted (95% CI, -1.83 to -0.41; P < .05). Every 1 ppb higher exposure to NO2 was associated with 1.04% lower Dlco% predicted (95% CI, -1.91 to -0.18; P < .05) in fully adjusted models. There were no significant associations between these pollutants and either FVC or FEV1% predicted. INTERPRETATION: Higher exposure to PM2.5 and NO2 was associated with worse Dlco% predicted. Black individuals with sarcoidosis were exposed to higher PM2.5 and NO2 than non-Hispanic White individuals. Air pollution exposure may be a contributor to reported health disparities in sarcoidosis.

17.
Pharmaceuticals (Basel) ; 17(9)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39338317

RESUMO

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a-2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI50 range from 1.55 to 2.95 µΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC50 value of 7.78 µM compared to Combretastatin-A4 (CA-4), with an IC50 value of 4.93 µM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

18.
Cureus ; 16(8): e66453, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39247002

RESUMO

Gallstone disease is a common condition affecting a substantial number of individuals globally. The risk factors for gallstones include obesity, rapid weight loss, diabetes, and genetic predisposition. Gallstones can lead to serious complications such as calculous cholecystitis, cholangitis, biliary pancreatitis, and an increased risk for gallbladder (GB) cancer. Abdominal ultrasound (US) is the primary diagnostic method due to its affordability and high sensitivity, while computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) offer higher sensitivity and specificity. This review assesses the diagnostic accuracy of machine learning (ML) technologies in detecting gallstones. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews and meta-analyses. An electronic search was conducted in PubMed, Cochrane Library, Scopus, and Embase, covering literature up to April 2024, focusing on human studies, and including all relevant keywords. Various Boolean operators and Medical Subject Heading (MeSH) terms were used. Additionally, reference lists were manually screened. The review included all study designs and performance indicators but excluded studies not involving artificial intelligence (AI)/ML algorithms, non-imaging diagnostic modalities, microscopic images, other diseases, editorials, commentaries, reviews, and studies with incomplete data. Data extraction covered study characteristics, imaging modalities, ML architectures, training/testing/validation, performance metrics, reference standards, and reported advantages and drawbacks of the diagnostic models. The electronic search yielded 1,002 records, of which 34 underwent full-text screening, resulting in the inclusion of seven studies. An additional study identified through citation searching brought the total to eight articles. Most studies employed a retrospective cross-sectional design, except for one prospective study. Imaging modalities included ultrasonography (four studies), computed tomography (three studies), and magnetic resonance cholangiopancreatography (one study). Patient numbers ranged from 60 to 2,386, and image numbers ranged from 60 to 17,560 images included in the training, validation, and testing of the diagnostic models. All studies utilized neural networks, predominantly convolutional neural networks (CNNs). Expert radiologists served as the reference standard for image labelling, and model performances were compared against human doctors or other algorithms. Performance indicators such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were commonly used. In conclusion, while the reviewed machine learning models show promising performance in diagnosing gallstones, significant work remains to be done to ensure their reliability and generalizability across diverse clinical settings. The potential for these models to improve diagnostic accuracy and efficiency is evident, but the careful consideration of their limitations and rigorous validation are essential steps toward their successful integration into clinical practice.

19.
RSC Adv ; 14(39): 28608-28625, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39247506

RESUMO

A series of derivatives (5-14) were synthesized through the diazotization of sulfadiazine with active methylene compounds. The chemical structures of these newly designed compounds were validated through spectral and elemental analysis techniques. The antiproliferative potential of derivatives 5-14 was assessed against three distinct cancer cell lines (A431, A549, and H1975) using the MTT assay. The results revealed that compounds 8, 12, and 14 exhibited the most potent antiproliferative activity, with IC50 values ranging from 2.31 to 7.56 µM. Notably, these values were significantly lower than those of known EGFR inhibitors, including erlotinib, gefitinib, and osimertinib, suggesting the potential of these derivatives as novel antiproliferative agents. Furthermore, compound 12 was identified as the most potent inhibitor of both EGFRWT and EGFRT790M protein kinases, with IC50 values of 14.5 and 35.4 nM, respectively. These results outperformed those of gefitinib and osimertinib, which exhibited IC50 values of 18.2 and 368.2 nM, and 57.8 and 8.5 nM, respectively. Molecular docking studies of compounds 8, 12, and 14 within the ATP-binding sites of both EGFRWT and EGFRT790M corroborated the in vitro results when compared to erlotinib, gefitinib, and osimertinib. The docking results indicated that compound 8 exhibited a favorable binding affinity for both EGFRWT and EGFRT790M, with binding scores of -6.40 kcal mol-1 and -7.53 kcal mol-1, respectively, which were comparable to those of gefitinib and osimertinib, with binding scores of -8.01 and -8.72 kcal mol-1, respectively. Furthermore, an assessment of the most promising EGFR inhibitors (8, 12, and 14) using the egg-boiled method for their in silico ADME properties revealed significant lipophilicity, blood-brain barrier (BBB) penetration, and gastrointestinal (GIT) absorption. Collectively, our designed analogs, particularly compounds 8, 12, and 14, exhibit promising dual antiproliferative and EGFRWT and EGFRT790M kinase inhibitory properties, positioning them as efficient candidates for further therapeutic development.

20.
BMC Med Educ ; 24(1): 1006, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39278910

RESUMO

BACKGROUND: The quality of education and the learning environment significantly influence dental trainees' success and experiences. However, the impact of the educational environment on dental residents in Saudi Arabia remains unexplored. This study aimed to assess the educational environment among dental residents at King Abdulaziz Medical City (KAMC) using the Postgraduate Hospital Educational Environment Measure (PHEEM) instrument, shedding light on its influence and providing insights for improvement. METHODS: A cross-sectional survey was conducted among 85 dental residents from various specialties at King Abdulaziz Medical City in Riyadh, Saudi Arabia, using the PHEEM instrument to evaluate the educational environment. Data analysis involved descriptive statistics, the Shapiro-Wilk test for score normality, and comparative analyses to explore the relationships between PHEEM scores and sociodemographic characteristics, specialties, residency years, and health habits. RESULTS: A total of 85 dental residents completed the survey. The majority of participants were aged 25 years and older (96.5%), female (56.5%), and single (78.8%). Most of the participating dental residents were Saudi board orthodontic residents (18.8%), and they were at the R2 level of training (32.9%). 88.2% were non-smokers, and 78.8% of them practiced physical activity. The PHEEM assessment revealed an overall score of 117.12 out of 160, with subscale scores of 41.54 out of 56 for role autonomy, 44.66 out of 60 for teaching, and 30.92 out of 44 for social support. Factors like age, marital status, and smoking were associated with lower scores, while being female and physically active were linked to higher scores. Notably, R3 residents had significantly lower scores than R1 residents (p < 0.05). CONCLUSION: This study evaluated the educational environment in Saudi board dental programs at KAMC, revealing an overall positive atmosphere but highlighting the need for improvement in certain areas. Despite some limitations, this research represents a significant step toward assessing and enhancing the educational environment for dental residents in Saudi Arabia, ultimately ensuring a better learning environment for future dental professionals.


Assuntos
Internato e Residência , Humanos , Arábia Saudita , Estudos Transversais , Feminino , Masculino , Adulto , Inquéritos e Questionários
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