Richardsonfisker0343

Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of hawthorn (Crataegus oxyacantha) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 μg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signaling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets, and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency, and cancer growth inhibition at stem cell level can be expected.Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.Neurodegenerative diseases represent a growing healthcare problem, mainly related to an aging population worldwide and thus their increasing prevalence. In particular, Alzheimer's disease (AD) and Parkinson's disease (PD) are leading neurodegenerative diseases. To aid their diagnosis and optimize treatment, we have developed a classification algorithm for AD to manipulate magnetic resonance images (MRI) stored in a large database of patients, containing 1,200 images. The algorithm can predict whether a patient is healthy, has mild cognitive impairment, or already has AD. We then applied this classification algorithm to therapeutic outcomes in PD after treatment with deep brain stimulation (DBS), to assess which stereotactic variables were the most important to consider when performing surgery in this indication. Here, we describe the stereotactic system used for DBS procedures, and compare different planning methods with the gold standard normally used (i.e., neurophysiological coordinates recorded intraoperatively). We used information collected from database of 72 DBS electrodes implanted in PD patients, and assessed the potentially most beneficial ranges of deviation within planning and neurophysiological coordinates from the operating room, to provide neurosurgeons with additional landmarks that may help to optimize outcomes we observed that x coordinate deviation within CT scan and gold standard intra-operative neurophysiological coordinates is a robust matric to pre-assess positive therapy outcomes- "good therapy" prediction if deviation is higher than 2.5 mm. When being less than 2.5 mm, adding directly calculated variables deviation (on Y and Z axis) would lead to specific assessment of "very good therapy".

Anterior vertebral body tethering (VBT) is a non-fusion surgical treatment for Adolescent Idiopathic Scoliosis requiring chest tube(s) (CT). We sought to assess the efficacy of post-op intravenous tranexamic acid (IV TXA) in reducing CT drainage and retention.

35 VBT patients received 24h of post-op IV TXA (2mg/kg/h) were compared to 49 who did not. Group comparisons were performed using Wilcoxon rank-sum and chi-squared tests. Multivariate linear regression analysis was used to assess the relationships between TXA and both CT drainage and retention time.

There were no group differences at baseline (Table). CTs placed for thoracic (T) and thoracolumbar (TL) curves were assessed separately. For TH CT, there was less total CT drainage in the TXA group (TXA 569.4 ± 337.4mL vs. Non-TXA 782.5 ± 338.9mL; p = 0.003) and shorter CT retention time (TXA 3.0 ± 1.3 vs. Non-TXA 3.9 ± 1.4days; p = 0.003). For TL CT, there was less total CT drainage in the TXA group (TXA 206.8 ± 152.2mL vs. Non-TXA 395.7 ± 196.1mL; p = 0.003) and shorter CT retention time (TXA 1.7 ± 1.3 vs. Non-TXA 2.7 ± 1.0days; p = 0.001). Following multivariate analysis, use of TXA was the only significant predictor of both drainage in T and TL CTs (p = 0.012 and p = 0.002, respectively) as well as T and TL CT retention time (p = 0.008 and p = 0.009, respectively). There were no differences in LOS (p = 0.863) or ICU stay (p = 0.290).

IV TXA results in a significant decrease in CT drainage and retention time. CT retention is decreased by 1 day for those that receive TXA.

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Frailty has been associated with adverse postoperative outcomes. Recently, a novel frailty index for preoperative risk stratification in patients with adult spinal deformity was developed. Components of the ASD-FI utilize patient comorbidity, clinical symptoms, and patient-reported-outcome-measures (PROMS). Our purpose was to investigate components of the Adult Spinal Deformity Frailty Index (ASD-FI) responsive to surgery and drivers of overall frailty.

Operative ASD patients ≥ 18years, undergoing multilevel fusions, with complete baseline, 6W, 1Y and 2Y ASD-FI scores. Descriptive analysis assessed demographics, radiographic parameters, and surgical details. Pearson bivariate correlations, independent and paired t tests assessed postoperative changes to ASD-FI components, total score, and radiographic parameters. Linear regression models determined the effect of successful surgery (achieving lowest level SRS-Schwab classification modifiers) on change in ASD-FI total scores.

409 6-week, 696 1-year, and 253 2-year operative ASD patients were included. 6-week and 1-year baseline frailty scores were 0.34, 2years was 0.38. Following surgery, 6-week frailty was 0.36 (p = 0.033), 1year was 0.25 (p < 0.001), and 2years was 0.28 (p < 0.001). Butyzamide activator Of the ASD-FI variables, 17/40 improved at 6weeks, 21/40 at 1year, and 18/40 at 2years. Successful surgery significantly predicted decreases in 1-year frailty scores (R = 0.27, p < 0.001), SRS-Schwab SVA modifier was the greatest predictor (Adjusted Beta - 0.29, p < 0.001).

Improvement in sagittal realignment and functional status correlated with improved postoperative frailty. Additional research and deformity sub-group analyses are needed to describe associations between specific functional activities that correlated with frailty improvement as well as evaluation of modifiable and non-modifiable indices.

Onychomycosis is the most common nail disorder in adults, with high recurrence and relapse rates. Its diagnosis may be difficult by non-experts because the clinical signs may overlap with other dermatoses. The treatment may be challenging, as it should be patient-tailored.

An online survey was conducted among European Nail Society (ENS) members to provide recommendations on the diagnosis and assessment of distal lateral subungual onychomycosis (DLSO) in non-specialized clinical environments, as well as recommendations for patient referral.

DLSO diagnosis is predominantly based on clinical aspects, and microscopy and fungal culture are commonly employed to establish the diagnosis. Assessment of clinical features is the main method for DLSO follow-up, and the main criterion to define cure is a combination of mycologic cure and clinical cure. The most commonly selected treatments for onychomycosis include oral antifungals, topical antifungals, and nail debridement. According to the nail experts, predisposie is treatment failure, concomitant diseases/comorbidities, presence of a dermatophytoma or involvement of the nail matrix, or involvement of several/all nails, referral should be considered.

According to the surveyed nail experts, after evaluating clinical signs and predisposing factors for DLSO, the diagnosis should include subungual hyperkeratosis, nail color (yellow-orange), and onycholysis and thickening. In cases of severe DLSO, when there is treatment failure, concomitant diseases/comorbidities, presence of a dermatophytoma or involvement of the nail matrix, or involvement of several/all nails, referral should be considered.

Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs).

Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.

Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.