Optimal management of high bleeding risk patients undergoing percutaneous coronary interventions: Where do we stand?

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient.

The Use of Isoflavones as Lung Cancer Chemoprevention Agents and their Implications in Treatment through Radio Sensitization.

Epidemiological trends in cancer research show that lung cancer can affect up to 1 in 15 men and 1 in 17 women. With incidence rates as high as these and significant associated mortality and morbidity, it is no wonder that lung cancer is one of the main areas of research focused on cancer. Advances in targeted treatments and specialized irradiation protocols have allowed the treatment of more advanced cases. However, as the patient numbers grow, so does the need for cancer-preventive strategies. The present narrative review focuses on soy isoflavones' role in the chemoprevention of lung cancer and their possible role in therapeutic adjuncts. Laboratory studies on lung cancer cell lines have shown that isoflavones can induce apoptosis, tamper with the expression of proliferative molecular pathways, and even reduce tumor angiogenesis. Additionally, population-level studies have emerged that correlate the consumption of isoflavonoids with reduced risk for the development of lung cancer. Interestingly enough, the literature also contains small-scale studies with evidence of isoflavones being effective chemotherapeutic adjuncts that are currently understudied. Our literature review underlines such findings and provides a call for the enhancement of research regarding naturally occurring dietary products with possible anticarcinogenic effects.

Metabolic Profiles of Cancer Stem Cells and Normal Stem Cells and Their Therapeutic Significance.

Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This subset of cancer cells with stemness and tumorigenic properties is organized in niches within the tumor microenvironment (TME) and presents altered regulation in a variety of metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), as well as lipid, amino acid, and iron metabolism. CSCs exhibit similarities as well as differences when comparedto normal stem cells, but also possess the ability of metabolic plasticity. In this review, we summarize the metabolic characteristics of normal, non-cancerous stem cells and CSCs. We also highlight the significance and implications of interventions targeting CSC metabolism to potentially achieve more robust clinical responses in the future.

B-Cell-Directed Therapies: A New Era in Multiple Sclerosis Treatment.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted the role of T cells in disease pathophysiology; however, the success of B-cell-targeted therapies has led to an increased interest in how B cells contribute to disease immunopathology. In this review, we summarize evidence of B-cell involvement in MS disease mechanisms, starting with pathology and moving on to review aspects of B cell immunobiology potentially relevant to MS. We describe current theories of critical B cell contributions to the inflammatory CNS milieu in MS, namely (i) production of autoantibodies, (ii) antigen presentation, (iii) production of proinflammatory cytokines (bystander activation), and (iv) EBV involvement. In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton's Tyrosine Kinase (BTK) (evobrutinib). We finally discuss the use of B-cell-targeted therapeutics in pregnancy.

Kernel color and fertilization as factors of enhanced maize quality.

Maize is an important staple crop and a significant source of various nutrients. We aimed to determine the macronutrients, antioxidants, and essential elements in maize genotypes (white, yellow, and red kernel) using three different fertilizers, which could be used as a basis to increase the nutrient density of maize. The fertilizer treatments used bio- and organic fertilizers as a sustainable approach, urea, as a commonly used mineral fertilizer, and the control (no fertilization). We evaluated the yield, concentration of macronutrient (protein, oil, and starch), nonenzymatic antioxidants (phenolics, yellow pigment, total glutathione (GSH), and phytic phosphorus), and reduction capacity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, as well as essential elements that are commonly deficient in the diet (Mg, Ca, Fe, Mn, Zn, Cu, and S) and their relationships with phytic acid. The genotype expressed the strongest effect on the variability of grain yield and the analyzed grain constituents. The red-kernel hybrid showed the greatest accumulation of protein, oil, phenolics, and essential elements (Ca, Fe, Cu, and S) than a yellow and white hybrid, especially in the biofertilizer treatment. The yellow kernel had the highest concentrations of yellow pigment, GSH, phytic phosphorous, Mg, Mn, and Zn (19.61 µg g-1, 1,134 nmol g-1, 2.63 mg g-1, 1,963 µg g-1, 11.7 µg g-1, and 33.9 µg g-1, respectively). The white kernel had a greater starch concentration (2.5% higher than that in the red hybrid) and the potential bioavailability of essential metals, particularly under no fertilization. This supports the significance of white maize as a staple food in many traditional diets across the world. Urea was important for the enhancement of the antioxidant status (with 88.0% reduction capacity for the DPPH radical) and increased potential Zn bioavailability in the maize kernels (13.3% higher than that in the biofertilizer treatment). This study underlines the differences in the yield potential and chemical composition of red, yellow, and white-kernel maize and their importance as a necessary part of a sustainable human diet. This information can help determine the most appropriate genotype based on the antioxidants and/or essential elements targeted for kernel improvement.

The Association Between the Risk of Breast Cancer and Epigallocatechin- 3-Gallate Intake: A Literature Review of a Potential Chemopreventive Agent.

According to the latest epidemiological data, breast cancer has recently been the most frequently diagnosed malignancy. To date, a body of evidence has established the involvement of multiple - and frequently interrelated - genetic and environmental factors in the pathogenesis of the disease. Emerging research on cancer prevention has highlighted the deterrence potential of interventions targeting environmental risk factors, particularly diet. In this aspect, the current review reveals the latest scientific results regarding epigallocatechin-3-gallate (EGCG) - a catechin most commonly found in green tea, as a potential chemopreventive dietary agent against breast cancer. in vitro studies on EGCG have demonstrated its effect on cell cycle progression and its potential to suppress several intracellular signaling pathways involved in breast cancer pathogenesis. In addition, EGCG possesses specific apoptosis-inducing characteristics that seem to enhance its role as a regulator of cell survival. Preclinical data seem to support using EGCG as an effective adjunct to EGFR-targeting treatments. The authors' appraisal of the literature suggests that although preclinical evidence has documented the anticarcinogenic features of EGCG, limited large-scale epidemiological studies are investigating the consumption of EGCG - containing nutrients in the prevention and management of breast cancer risk. This literature review aims to liaise between preclinical and epidemiological research, surveying the existing evidence and unraveling relevant knowledge gaps.

Early detection, herbicide resistance screening, and integrated management of invasive plant species: a review.

Invasive plant species (IPS) are often considered weeds that cause high yield losses in crops, negatively affect the environment, and disrupt certain ecosystem services. The negative impact of IPS on biodiversity is increasing and disturbing native vegetation. The management of plant invasions can be divided in two phases (before and after invasion). Prior to introduction it is crucial to develop the knowledge base (biology, ecology, distribution, impact, management) on IPS, prevention measures and risk assessment. After introduction if eradication fails, the monitoring and the integrated management of IPS are imperative to prevent the naturalization and further dispersal. This review uses two major invasive weed species (Amaranthus palmeri S. Wats. and Solanum elaeagnifolium Cav.) as case studies to propose a framework for early detection, rapid herbicide resistance screening, and integrated management. The holistic framework that is presented exploits recent: (i) novel detection tools, (ii) rapid tests and assays for herbicide resistance, and (iii) biology, ecology, distribution traits, and management tools for the IPS. Farmers, advisors, researchers, and policymakers need briefing on IPS growth dynamics, adaptability rates, and response to conventional and novel treatments to prevent new invasions, eradicate isolated stands, and mitigate the impact of invasive weed species in the long term. © 2022 Society of Chemical Industry.

Effect of Adjuvant on Glyphosate Effectiveness, Retention, Absorption and Translocation in Lolium rigidum and Conyza canadensis.

Glyphosate retention, absorption and translocation with and without adjuvant were examined in Lolium rigidum and Conyza canadensis in greenhouse and laboratory settings to develop an understanding of the influence of the selected adjuvant on glyphosate activity. Tests on whole plants show that the dose of herbicide needed to reduce dry weight by 50% (GR50) or plant survival (LD50) decreases by mixing glyphosate and adjuvant to 22%-24% and 42%-44% for both populations of L. rigidum and C. canadensis, respectively. This improvement in efficacy could be attributed to the higher herbicide retention and lower contact angle of the glyphosate + adjuvant drops on the leaf surface compared to the glyphosate solution alone. Plants of both species treated with 14C-glyphosate + adjuvant absorbed more glyphosate compared to non-adjuvant addition. Furthermore, the movement of the herbicide through the plant was faster and greater with the adjuvant. Our results reveal that the use of adjuvants improves the effectiveness of glyphosate in two of the most important weeds in agricultural crops in Mediterranean countries.

Early hospital admission and treatment onset may positively affect spontaneous passage of ureteral stones in patients with renal colic.

OBJECTIVE: To evaluate the impact of early hospital admission and onset of medical expulsive therapy (MET) in spontaneous passage of ureteral stones causing renal colic. METHODS: We recruited 392 patients referred to the emergency room with symptoms of renal colic. All patients received standard MET of oral tamsulosin 0.4 mg at the time of diagnosis. In group A, patients who received MET in <2 hours from the symptom onset were included, whereas group B consisted of patients treated in >2 hours. The association of MET onset and stone-free rates after 6 weeks of follow-up was evaluated. Early MET onset predictive impact on spontaneous stone passage was evaluated as well. RESULTS: The stone-free rate in group A and B patients was 71.2% and 59.7% (P=.018), respectively. A significant association was observed between spontaneous calculus elimination and stone size (P≤.001), location within the ureter (P=.007), and the interval between pain onset and pharmaceutical management (P=.018). Patients who received a late-onset MET had an increased risk to develop febrile upper urinary tract infection during the follow-up period (P=.040). In the multivariate analysis, size (P≤.001) and early therapy onset (P=.019) were statistically important predictors for stone-free status after the surveillance period. CONCLUSION: Patients with renal colic who admitted to the emergency department earlier since symptom onset may have increased potential to be stone free during the surveillance period.

An 82-year-old Caucasian man with a ductal prostate adenocarcinoma with unusual cystoscopic appearance: a case report.

INTRODUCTION: Ductal adenocarcinoma is a rare variety of the common acinar adenocarcinoma. It usually presents with refractory symptoms, and during cystoscopy, it is seen as an exophytic lesion at the area of the verumontanum. CASE PRESENTATION: An 82-year-old Caucasian man was diagnosed with ductal adenocarcinoma of the prostate after undergoing transurethral resection of the prostate for urinary retention. Immunohistochemistry confirmed the nature of the tumor. The patient was treated with triptorelin, 3.75 mg once/month, and bicalutamide, 50 mg 1 × 1. The serum prostate-specific antigen at three, six and 12 months after transurethral resection of the prostate was 0.1 ng/ml. The patient remains asymptomatic, and he entered a six-month follow-up protocol. CONCLUSION: Ductal adenocarcinoma often involves the central ducts of the gland and may present as an exophytic papillary lesion in the prostatic urethra. This is why it usually presents with refractory symptoms. The outcome for men with prostatic ductal adenocarcinoma is, in most studies, worse than the outcome for men with prostatic acinar adenocarcinoma. Aggressive management is indicated, even with low-volume metastatic disease.