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1.
Cureus ; 16(5): e61471, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38953060

RESUMO

BACKGROUND:  De Quervain tenosynovitis (DQT) is a condition that affects the first extensor compartment of the wrist, resulting in stenosing tenosynovitis. This work aimed to evaluate the effects of platelet-rich plasma (PRP) injection in the treatment of DQT in comparison with corticosteroid (CS) injections. METHODS:  This study was carried out on 40 DQT patients aged above 18 years old of both sexes, based on a combination of clinical symptoms and signs including persistent tenderness on the radial styloid, swelling on the radial styloid, positive provocative tests such as the Finkelstein test, and patients with failed medical treatment. Patients were divided into two equal groups: group I and group II. Group I was injected with PRP, and group II was injected with CS. Follow-ups were conducted at two weeks and six months. RESULTS:  There were statistically significant differences among both groups regarding the visual analog scale (VAS), and Disabilities of Arm, Shoulder, and Hand (QuickDASH-9) score. However, complications were statistically insignificant between both groups. After injection, CS was better than PRP after two weeks, but PRP was superior to CS after six months concerning QuickDASH-9 and VAS. These differences were statistically significant. CONCLUSIONS:  CS is more effective than PRP in the short term (two weeks) and PRP is more effective in the intermediate term (six months). Both modalities are safe; however, PRP is relatively safer than CS.

2.
Front Pharmacol ; 15: 1192659, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957387

RESUMO

Introduction: Emergence of drug resistant strains of Plasmodium species has necessitated the search for novel antimalarials with unique mechanisms of action. Synthesis of hybrid compounds has been one approach to tackling this challenge. In this study, the synthesis of artesunate-ellagic acid hybrid compound (EA31) from ellagic acid and artesunate and its evaluation for antimalarial and antioxidant activities using in vitro and in vivo models were carried out. Method: EA31 was synthesized from artesunate and ellagic acid. The activities of the hybrid compound against Plasmodium falciparum W2 and P. berghei NK65 were evaluated, and its antioxidant activities were also determined. Results: The results revealed that EA31 was more active against P. falciparum W2 (chloroquine resistant) clone and less cytotoxic to buffalo green monkey kidney cell line compared to artesunate. EA31 was also active against Plasmodium berghei NK65 in vivo. The results revealed inhibition of ß-hematin formation as one of the mechanisms of action of EA31. EA31 also exhibited antioxidant activities. Conclusion: The results revealed that EA31 may exert dual action of killing malaria parasite and mopping the reactive oxygen species that mediate the secondary complications of malaria.

3.
Drug Dev Ind Pharm ; : 1-40, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963406

RESUMO

BACKGROUND: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins as FDA approved anti-hyperlipidemic drugs, still poses some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. AIM: This work aimed to study the hypolipidemic effect of Lepidium Sativum Garden Cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. METHODS: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. RESULTS: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post treatment for one month. CONCLUSION: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

4.
Ann R Coll Surg Engl ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961733

RESUMO

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

5.
Sci Rep ; 14(1): 14992, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951540

RESUMO

This study investigates methane emissions from the livestock sector, representing by enteric fermentation and manure management, in Egypt from 1989 to 2021, focusing on spatial and temporal variations at the governorate level. Utilizing IPCC guidelines and emission factors, methane emissions were estimated for dairy and non-dairy cattle, buffalo, sheep and goat, poultry, and other livestock categories. Results reveal fluctuating emission patterns over the study period, with notable declines in certain governorates such as Kafr El-Sheikh and Red Sea, attributed to reductions in livestock populations. However, increasing trends were observed overall, driven by population growth in other regions. Hotspots of methane emissions were identified in delta governorates like Behera and Sharkia, as well as agriculturally rich regions including Menia and Suhag. While livestock populations varied between regions, factors such as water availability, climatic conditions, and farming practices influenced distribution. Notably, cluster analysis did not reveal regional clustering among governorates, suggesting emissions changes were not dependent on specific geographic or climatic boundaries. Manure management accounted for only 5-6% of total emissions, with emissions at their lowest in the last three years due to population declines. Despite the highest livestock populations being sheep and goats, emissions from enteric fermentation and manure management were highest from buffalo and cattle. This study underscores the importance of accurate data collection and adherence to IPCC recommendations for estimating GHG emissions, enabling the development of targeted mitigation strategies to address climate change challenges in the livestock sector.


Assuntos
Gases de Efeito Estufa , Gado , Metano , Animais , Egito , Metano/análise , Metano/metabolismo , Gases de Efeito Estufa/análise , Esterco/análise , Bovinos , Ovinos , Monitoramento Ambiental/métodos
6.
Gene ; : 148743, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964493

RESUMO

Fascin-1 (FSCN1) is recognized as an actin-binding protein, commonly exhibits up-regulation in breast cancer (BC) and is crucial for tumor invasion and metastasis. The existence of FSCN1 gene polymorphisms may raise the potential for developing BC, and there are still no studies focusing on the relationship between the FSCN1 rs2966447 variant and BC risk in Egyptian females. Thus, we investigated the serum fascin-1 levels in BC patients and the association between the FSCN1 rs2966447 variant with its serum levels and BC susceptibility. Genotyping was conducted in 153 treatment-naïve BC females with different stages and 144 apparent healthy females by TaqMan® allelic discrimination assay, whereas serum fascin-1 level quantification was employed by ELISA. The FSCN1 rs2966447 variant demonstrated a significant association with BC susceptibility under all utilized genetic models, cancer stages and estrogen receptor negativity. Also, BC females with AT and TT genotypes had higher serum fascin-1 levels and tumor size than those with the AA genotype. Moreover, serum fascin-1 levels were significantly elevated in the BC females, notably in those with advanced-stages. Furthermore, serum fascin-1 levels were markedly positively correlated with number of positive lymph nodes as well as tumor size. Collectively, these findings revealed that the FSCN1 rs2966447 variant may be regarded as a strong candidate for BC susceptibility. Also, this intronic variant is associated with increased serum fascin-1 levels and tumor size.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38967398

RESUMO

OBJECTIVE: Posterior left atrial wall isolation (PWI) plus traditional pulmonary vein isolation (PVI) has been proposed as a promising intervention to decrease atrial fibrillation (AF) recurrence. We aim to investigate the efficacy and safety of adding PWI to the traditional PVI in patients with AF. METHODS: A systematic review and meta-analysis was conducted using synthesizing randomized controlled trials (RCTs) retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane through June 14, 2023. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023446227). RESULTS: We included 11 RCTs with a total number of 1534 patients. Combined ablation with PWI + PVI was not associated with any significant difference over PVI only regarding the recurrence of clinical AF (RR: 0.86 with 95% CI [0.70-1.06]), all atrial arrhythmia (RR: 0.93 with 95% CI [0.82-1.07]), nonatrial fibrillation arrhythmia (RR: 1.22 with 95% CI [0.97-1.53]), early AF (RR: 0.89 with 95% CI [0.62-1.27]), and antiarrhythmic drugs at discharge (RR: 0.83 with 95% CI [0.67-1.04]). However, it was associated with increased total ablation duration (minutes) (MD: 12.58 with 95% CI [6.80-18.37]) and total procedure duration (minutes) (MD: 16.77 with 95% CI [9.63-23.91]), without any significant difference regarding adverse events (RR: 1.05 with 95% CI [0.63-1.74]). CONCLUSION: While the pooled data from PWI + PVI using point-by-point radiofrequency did not suggest a benefit in the recurrence of various atrial arrhythmias compared to PVI alone, PWI+PVI using direct posterior wall ablation, especially with cryoballoon, demonstrated a significant reduction in recurrence of AF/atrial arrhythmias. Also, PWI + PVI significantly increased the ablation and total procedure durations.

8.
Egypt Heart J ; 76(1): 89, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976090

RESUMO

BACKGROUND: Persistent Atrial Fibrillation (PeAF) is a challenging case for rhythm control modalities. Catheter ablation is the mainstay in PeAF management; however, data regarding the comparative safety and efficacy of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) for PeAF is still limited. We aim to compare the safety and efficacy of CBA versus RFA for PeAF ablation. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through October 2023. RevMan version 5.4 software was used to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023480314. RESULTS: Three RCTs with 400 patients were included. There was no significant difference between RFA and CBA regarding AF recurrence (RR: 0.77, 95% CI [0.50, 1.20], P = 0.25), atrial tachycardia or atrial flutter recurrence (RR: 0.54, 95% CI [0.11, 2.76], P = 0.46), and any arrhythmia recurrence (RR: 0.96, 95% CI [0.70, 1.31], P = 0.80). CBA was significantly associated with decreased total procedure duration (MD: - 45.34, 95% CI [- 62.68, - 28.00], P < 0.00001), with no significant difference in fluoroscopy duration (MD: 3.59, 95% CI [- 5.13, 12.31], P = 0.42). Safety parameters were similar in both groups, including the incidence of any complications, phrenic nerve palsy (RR: 2.91 with 95% CI [0.31, 27.54], P = 0.35), access site complications (RR: 0.33 with 95% CI [0.05, 2.03], P = 0.23), and pericardial effusion. CONCLUSIONS: In PeAF catheter ablation, CBA is comparable to RFA in terms of safety and efficacy. Also, CBA is associated with a shorter total procedure duration.

9.
Sci Rep ; 14(1): 15441, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965246

RESUMO

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.


Assuntos
Anti-Infecciosos , Antineoplásicos , Testes de Sensibilidade Microbiana , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Química Verde/métodos , Proliferação de Células/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Simulação de Acoplamento Molecular , Células MCF-7 , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos
10.
Geriatr Nurs ; 59: 1-6, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972259

RESUMO

In this longitudinal study, we investigated the effects of institutionalization on the sense-of-self in individuals with Alzheimer's Disease (AD). We recruited two groups of participants: one living in care facilities (i.e., institutionalized-group) and another group living in their own home (i.e., non-institutionalized-group). In the two groups, we assessed the "Who-am-I" task on which participants were invited to provide statements beginning with the phrase "I am" that they felt were essential in defining who they are. We assessed this task, in the two groups, at a baseline (approximately one-month before-institutionalization) and at a follow-up (approximately six months after institutionalization). We analyzed whether responses on the "Who-am-I" task reflected physical-, social-, or psychological-self. Unlike at the baseline, fewer statements describing physical-, social-, and psychological-self were observed in the institutionalization than in the non-institutionalized group at the follow up. These findings demonstrate negative effects of institutionalization on the sense of self in AD.

11.
BMC Cancer ; 24(1): 809, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973003

RESUMO

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.


Assuntos
Carcinoma Ductal Pancreático , Progressão da Doença , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/genética , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , África do Sul , Idoso , Adulto , Biomarcadores Tumorais/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Pancreatite Crônica/imunologia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Espécies Reativas de Oxigênio/metabolismo , Imunofenotipagem
12.
Diabetes Metab Syndr Obes ; 17: 2655-2670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974950

RESUMO

Purpose: Cognitive flexibility is a mental ability that aids in smoothly alternating between them tasks in the brain. Diabetes Mellitus (DM) is a, common disorder that has been associated with impairments in cognitive functions. This research is a retrospective case-control study aimed at establishing a clear relationship between cognitive flexibility and diabetes among Jordanians, considering demographic, anthropometric, and therapeutic variables. Patients and Methods: The Wisconsin Card Sorting Test (WCST)-64 item and the Trail Making Test (TMT) assessed cognitive flexibility in 268 people with diabetes and healthy control. Demographic, therapeutic data were collected. We also measured waist-to-hip ratio (WHR) and body mass index (BMI). As the variables were non-normally distributed, non-parametric statistical tests were used to examine differences (Kruskal-Wallis) and correlation (Spearman) between variables. Results: The patient group did worse on the WCST In contrast to the control group, patients exhibited more significant delays for both Part A and Part B of the TMT (p<0.05). Males had higher WCST conceptual level responses than females. In addition, participants with professional jobs showed less delay in TMT Part A (p<0.05). Age was positively correlated with WCST's total errors and TMT's Parts A and B (p<0.05). BMI was negatively correlated with the WCST's conceptual level of responses and positively correlated with TMT's Part B (p<0.05). In addition, urea and albumin levels were positively correlated with TMT's Part A (p<0.05). Furthermore, creatinine was positively correlated with WCST's total errors and TMT's Part A (p<0.05). Conclusion: Some measures of cognitive flexibility are associated with DM status in the studied sample of Jordanians and other variables (educational levels, occupation, lifestyle, average duration of illness, and age).

13.
Cardiovasc Diagn Ther ; 14(3): 340-351, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975005

RESUMO

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

14.
Drug Dev Res ; 85(5): e22228, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38952003

RESUMO

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA-MB-231, the triple-negative breast cancer cell line, was found to be the most sensitive, where the N-(2-furylmethylene) (15) and the α-methylated N-benzyl (17) derivatives demonstrated the highest growth inhibition with GI50 values of 14.8 and 17.1 µM, respectively. In vitro mechanistic studies confirmed the significant roles of compounds 15 and 17 in the induction of apoptosis and suppression of EGFR, FGFR3, and VEGF protein levels in MDA-MB-231 cancer cells. Moreover, compound 15 exerted cell cycle arrest at both the G0-G1 and G2-M phases. The in vivo efficacy of compound 15 as an antitumor agent was further investigated in female mice bearing Solid Ehrlich Carcinoma. Notably, administration of compound 15 resulted in a marked decrease in both tumor weight and volume, accompanied by improvements in biochemical, hematological, histological, and immunohistochemical parameters that verified the repression of both angiogenesis and inflammation as additional Anticancer mechanisms. Moreover, the binding interactions of compounds 15 and 17 within the binding sites of all three target receptors (EGFR, FGFR3, and VEGF) were clearly illustrated using molecular docking.


Assuntos
Antineoplásicos , Cromonas , Receptores ErbB , Simulação de Acoplamento Molecular , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Neoplasias de Mama Triplo Negativas , Fator A de Crescimento do Endotélio Vascular , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Camundongos , Cromonas/farmacologia , Cromonas/síntese química , Cromonas/química , Cromonas/uso terapêutico , Desenho de Fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
15.
Cureus ; 16(5): e61307, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38947653

RESUMO

INTRODUCTION: Despite the recognition of the importance of physician knowledge and physician-patient communication about the use of complementary and alternative medicine (CAM), few studies have explored this issue. Therefore, this study aims to assess physicians' knowledge and physician-patient communication regarding CAM. METHODS: A cross-sectional study was conducted among physicians working at governmental hospitals and primary healthcare centers in Madinah, Saudi Arabia. The data collection tool was a validated English language questionnaire distributed using social media platforms. The questionnaire included sections to assess physician knowledge and communication about CAM. RESULTS: Of the 373 completed questionnaires, around 151 (40.5%) of the respondents stated that they have a poor level of knowledge about CAM, and 272 (72.9%) need to gain additional knowledge to properly counsel patients on CAM. Medical journals were the main source of knowledge about CAM. There were 121 (32.4%) physicians who believed that <20% of their patients use some form of CAM, and 180 (48.3%) believed that <20% of their patients spontaneously reported their CAM use without prompting or direct questioning. Around 180 (48.3%) of physicians believed that they asked <20% of their patients about using CAM. Regarding barriers that limit communication with the patient about CAM, the highest percentage was insufficient knowledge about CAM (137, 36.7%). CONCLUSION: The study showed that a significant number of physicians lack the appropriate knowledge about CAM and most of them agreed to gain additional knowledge to properly counsel their patients. Further research is needed to evaluate physicians' knowledge about CAM using a more objective method.

16.
Cureus ; 16(5): e61320, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38947675

RESUMO

Coronary arteriovenous fistulas (CAVFs) are congenital or acquired communications between the coronary arteries and coronary venous system, and they can also include other cardiac structures or vasculature. We discuss a case of a large fistula between the left main coronary artery and the right atrium in a geriatric patient with a history of gastrointestinal arteriovenous malformations (AVM). The occurrence of CAVFs, an uncommon cardiac irregularity, is particularly infrequent among older adults. Typically, it is discovered by chance when investigating symptoms such as shortness of breath or chest pain, where coronary angiography is necessary to determine the most effective treatment strategy. This case highlights the possible utility of evaluating CAVFs in patients with a history of gastrointestinal AVM who similarly present with clinical symptoms of high-output heart failure. Once identified, this could simplify the treatment approach and improve communication between healthcare providers to minimize the risk of harm to the patient.

17.
Integr Pharm Res Pract ; 13: 81-89, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948431

RESUMO

Purpose: Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is challenging due to its narrow therapeutic range and variable dose. This study aimed to highlight polypharmacy and drug interactions in patients receiving warfarin therapy at Medani Heart Centre, Sudan. Methods: This retrospective hospital-based study was conducted from May 2017 to October 2018. Each concurrent medication prescribed for 104 patients was collected and checked for drug-drug interactions using Medscape Reference-Drug Interaction Checker. The data were analysed by using SPSS 20, and descriptive statistics were used. Results: The results revealed that 95.2% of patients had more than three medications in their profile, (3-5), (6-9) and more than 10 medications were prescribed for 40.4%, 44.2% and 10.6% of patients, respectively. A total of 93.3% of patients had drug-drug interactions, as follows: (1-5), (6-10), (11-15), (16-20) and more than 20 drug-drug interactions were found in 31.7%, 32.7%, 19.2%, 5.8% and 3.8% of patients, respectively. A total of 178 warfarin-drug interactions were identified in 88.5% of the patients. The INR ranged between 2 and 2.99 in 13.4% of patients, and INR values below 2 and above 5 were found in 44.2% and 21.2% of patients, respectively. Analgesics (n=54; 30.3%), cardiovascular drugs (n=51; 28.6%), and anticoagulants (n=46; 25.8%) were the most common drug classes that interact with warfarin. Significant and serious types of interactions with warfarin were found in 51% and 37.5% of patients, respectively. Conclusion: This study highlights the complexity of managing warfarin therapy amid prevalent polypharmacy. A substantial majority of patients experienced multiple drug interactions. The identification of significant and serious interactions emphasizes the need for vigilant management strategies, including improved communication among healthcare professionals and targeted education for both providers and patients, to enhance the safety and efficacy of warfarin therapy.

18.
Nat Commun ; 15(1): 5449, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937456

RESUMO

Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.


Assuntos
Envelhecimento , Bleomicina , Células Endoteliais , Lesão Pulmonar , Pulmão , Fibrose Pulmonar , Animais , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Envelhecimento/patologia , Bleomicina/toxicidade , Humanos , Camundongos , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/genética , Pulmão/patologia , Pulmão/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , Receptor trkB/metabolismo , Receptor trkB/genética , Camundongos Endogâmicos C57BL , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas de Sinalização YAP/metabolismo , Masculino , Análise de Célula Única , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Modelos Animais de Doenças
19.
Biomed Pharmacother ; 177: 117005, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38945084

RESUMO

Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.

20.
J Clin Immunol ; 44(7): 153, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896122

RESUMO

Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.


Assuntos
Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Linfo-Histiocitose Hemofagocítica , Humanos , Masculino , Proteínas de Transporte de Cátions , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/genética , Doença de Hodgkin/etiologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/genética , Recidiva
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