Notes

Genetic temporal lobe epilepsy because of key cortical dysplasia variety IIIa.
Breast cancer is the leading cause of cancer death among women worldwide. In solid tumors, the microenvironment plays a critical role in tumor development, and it has been described a communication between the different cell types that conform the stroma, including fibroblasts, pericytes, adipocytes, immune cells and cancer-associated fibroblasts. Intercellular communication is bidirectional, complex, multifactorial and is mediated by the secretion of molecules and extracellular vesicles. The extracellular vesicles are vesicles limited by two membranes that are secreted by normal and cancer cells into the extracellular space. Extracellular vesicle cargo is complex and includes proteins, miRNAs, DNA and lipids, and their composition is specific to their parent cells. Extracellular vesicles are taken up for neighboring or distant cells. Particularly, extracellular vesicles from breast cancer cells are taken up for fibroblasts and it induces the activation of fibroblasts into cancer-associated fibroblasts. Interestingly, cancer associated fibroblasts release extracellular vesicles that are taken up for breast cancer cells and promote migration, invasion, proliferation, epithelial-mesenchymal transition, changes in metabolism, chemoresistance, evasion of immune system and remodeling of extracellular matrix. In addition, the enrichment of specific cargos in extracellular vesicles of breast cancer patients has been suggested to be used as biomarkers of the disease. Here we review the current literature about the intercommunication between tumor cells and cancer associated fibroblasts through extracellular vesicles in breast cancer.Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti-inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds.Long noncoding RNAs (lncRNAs) are an ubiquitous feature of eukaryotic genomes and in recent decades have been shown to be highly abundant and varied. Many prominent examples have been described as having essential roles in regulating the expression of genes in different developmental and environmental contexts. As a result, much work has been done on elucidating the mechanisms by which they modulate the expression of protein coding genes. In this review, we focus on those which have been characterized in plants. We specifically examine common epigenetic mechanisms that regulate gene expression at the level of transcription. In this regard, we focus on the lncRNAs in plants that have primarily been associated with controlling the chromatin environment of genes at the level of modifications, RNA POLYMERASE II (RNAPII) processivity and efficiency of transcription, and mediating the formation of transcriptionally activating and repressive chromatin loops. We discuss open questions in plant lncRNA epigenetic regulation and opportunities for future study of functionally significant lncRNAs with yet-unknown epigenetic mechanisms.Despite the importance of accessible psychiatric care for the ultra-Orthodox Jewish community, prior research has characterized how stigma and suspicion of secular institutions limit mental healthcare utilization by this population. No study, however, has interviewed a cohort of psychiatrists to identify commonly encountered challenges or successfully employed strategies in the care of ultra-Orthodox Jewish psychiatric patients who have overcome these barriers to present for care. We recruited by snowball sampling from a sample of convenience 18 psychiatrists affiliated with the Weill Cornell Department of Psychiatry, experienced in the care of ultra-Orthodox Jewish patients. Each participant was engaged in a 20-45-min, semi-structured interview, which was subsequently transcribed, de-identified, and analyzed with combined deductive and inductive thematic analysis. Oxiglutatione clinical trial We identified 12 challenges and 11 strategies as particularly significant in psychiatric work with ultra-Orthodox Jewish patients at every phase of treatment, including rapport-building, history-taking, diagnostic formulation, and achieving concordance with patient and family. These challenges and strategies revolved around themes of community stigma, an extended family-patient-community team, cross-cultural communication, culture-related diagnostic complexity, transference/countertransference, and conflicts between Jewish law /community norms and treatment protocol. Psychiatrists caring for ultra-Orthodox Jewish patients face a range of complex challenges stemming from factors unique to ultra-Orthodox Jewish religion, culture, and family/community structure. However, they have also identified strategies to manage these challenges and provide culturally sensitive care. Further research is necessary to directly elicit perspectives from within the ultra-Orthodox Jewish community and validate our initial findings.
Sickle cell disease (SCD) is a lifelong burdensome disorder of heterogenic expression. This study investigated the longer-term economic burden of severe presentation of SCD. As SCD treatment landscapes evolve toward curative intent gene therapies, understanding how SCD-associated costs may change over the patient lifetime will be important for medical decision-making.

Patients with severe presentation of SCD (presence of acute vaso-occlusive events [VOEs] or history of stroke and/or other disease-related sequelae), were identified within the MarketScan Commercial and Medicare Supplemental and Multi-state Medicaid Databases from 1/1/2010 to 12/31/2018. The first SCD claim served as the index date and patients were followed over a 5-year post-period. Clinical characteristics and healthcare resource utilization and costs were assessed over follow-up for eligible cohorts of commercial and Medicaid patients with severe SCD presentation and age-based subgroups (<18, 18-30, and ≥31).

A total of 4,487 patienve intent therapies.
Results indicate high clinical need and economic burden among patients with severe presentation of SCD. These findings not only highlight the need for improved therapeutic options to limit or prevent disease progression, but also start to provide insight on lifetime costs of SCD that will be needed in the evaluation of emerging curative intent therapies.The tensile strength and corrosion behavior of dissimilar welded joints are currently a subject of concern. In this work, gas metal arc welding (GMAW) and distinct welding parameters (welding current, arc voltage, and welding speed) were used to join 304 stainless steel (SUS304) and SS400 low carbon steel, and the ultimate tensile strength (UTS) of the dissimilar welded joints was investigated. A corrosion test was conducted by immersion in 3.5 wt.% sodium chloride (NaCl) solution for 7, 14, and 21 days. Based on tensile strength and Tafel testing, the welding parameters "Item 4" (welding current 170 A, arc voltage 20 V, welding speed 40 cm/min) yielded good mechanical strength and low corrosion characteristics. The microstructure characterization showed that the area around the welded joints and SUS304 had more granular corrosion and corrosion tubercles with increasing immersion time. The chromium content gradually decreased. When exposed to the chloride environment, these welded joints easily underwent corrosion due to the loss of passivity. However, high-velocity oxygen-fuel (HVOF) spray used on the welded joints reduced the corrosion current density. Compared with the non-thermal spray sample (corrosion current density7.49e - 05 A/cm2) while the corrosion current density (7.89e - 10 A/cm2) is five orders of magnitude lower. This spray effectively slowed down the corrosion rate of the welded joints and gave the structural objects good protection in the sodium chloride solution.The Iowa Gambling Task (IGT) and the Hungry Donkey Task (HDT) are well-known tasks employed to assess decisions under ambiguity. Although the two tasks are equal in terms of wins and losses, they differ in terms of the recipient while in the IGT participants make decisions for themselves, in the HDT decisions are made to help a hungry donkey. Decisions for themselves versus another one in a situation of ambiguity are particularly important in the field of aging because of older adults' changes in motivational and other-oriented behavior. The present study aimed to test whether older adults make different decisions under ambiguity for themselves than for another one (i.e., the hungry donkey) as compared to younger adults. Forty-five young adults (M = 23.31; SD = 1.58) and 45 older adults (M = 72.47; SD = 5.49) performed the IGT and the HDT. In addition, participants performed tasks on working memory, set-shifting, and inhibition. Results showed age-related differences in the HDT but not in the IGT. Older adults, compared to younger adults, made disadvantageous decisions to help the hungry donkey as compared to themselves. Interestingly, this pattern of results is not explained by the age-related decline in cognitive functioning. The findings seem to suggest that older adults' decisions made under the condition of ambiguity are affected by motivational and emotional changes associated with aging.Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.
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