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City eco-friendly space utilize during a period of anxiety: An incident study during the COVID-19 widespread inside The brisbane area, Sydney.

Specialized medical, research laboratory, along with innate guns for the development or perhaps presence of psoriatic joint disease in epidermis individuals: an organized evaluation.

76% and reducing mature biofilm up to 56.22% at 75 μg/mL the minimum inhibitory concentration value. Therapeutic possibilities of the ZnFe2O4 NPs in antimicrobial applications are discussed which are helpful to overcome the challenges associated with biofilm infectivity.Decreases in acute stroke presentations have been reported during the coronavirus disease 2019 (COVID-19) pandemic surges. A recent study by Bojti et al. (GeroScience. 2021;432231-2248) sought to understand the relationship of public health mandates in Hungary as they were implemented with acute ischemic stroke admissions and interventions during two separate COVID-19 waves. We sought to perform a similar analysis of changes in ischemic stroke care at two distinct medical institutions in the USA. Two separate institutions and systems of ischemic stroke care were evaluated through a regional comprehensive stroke center telestroke service and a Veterans Affairs (VA) inpatient stroke and neurorehabilitation service. Telestroke consultations in a single system in Chicago, IL, were significantly decreased during the first COVID-19 wave during severely restricted public health mandates (z-score  less then   - 2), and were less depressed during a subsequent wave with less severe restrictions (z-score approaching - 1oke, may prove valuable for designing effective policies in the future.High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR 1.79, 95% CI 1.17-2.75, P = 0.008) and OS in post-menopausal women (HR 1.35, 95% CI 1.04-1.74, P = 0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation ("L-shaped" and "U-shaped", respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a "U-shaped" relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.Immunoglobulin A (Chan in J Allergy Clin Immunol 1341394-14014e4, 2014), the second most abundant immunoglobulin in serum, plays an important role in mucosal homeostasis. In human serum, there are two subclasses of IgA, IgA1 (≅ 90%) and IgA2 (≅ 10%), transcribed from two distinct heavy chain constant regions. This study evaluated the serum concentrations of total IgA, IgA1, and IgA2, and total IgG, IgG1, IgG2, IgG3, and IgG4 in T2-high asthmatics compared to healthy controls and the presence of gender-related variations of immunoglobulins. Total IgA levels were increased in asthmatics compared to controls. Even more marked was the increase in total IgA in male asthmatics compared to healthy male donors. IgA1 were increased only in male, but not in female asthmatics, compared to controls. Concentrations of IgG2, but not IgG1, IgG3, and IgG4, were reduced in asthmatics compared to controls. IgG4 levels were reduced in female compared to male asthmatics. In female asthmatics, IgA and IgA1 levels were increased in postmenopause compared to premenopause. IgA concentrations were augmented in mild, but not severe asthmatics. A positive correlation was found between IgA levels and the age of patients and an inverse correlation between serum concentrations of IgA2 and IgE in asthmatics. A positive correlation between total IgA or IgA2 and IgG2 was found in asthmatics. These results highlight a gender dimorphism in IgA subclasses in male and female T2-high asthmatics. More adequate consideration of immunological gender disparity in asthma may open new opportunities in personalized medicine by optimizing diagnosis and targeted therapy.

The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke.

Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims)as the randomization was broken.

Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups.

DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

To assess the cost-effectiveness of evolocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, compared with ezetimibe, both added to background statin therapy in patients with recent acute coronary syndrome (ACS) events (in the past 12 months) and low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL in China.

A health economic evaluation was performed from a Chinese healthcare perspective, using a Markov model over a lifetime horizon based on a baseline cardiovascular (CV) event rate from claims database data and efficacy from the FOURIER trial. The health benefit was reflected in the decrease of LDL-C level, which led to a decrease of cardiovascular events. The costs of cardiovascular events and the utility value of each health state were derived from the published literature. Sensitivity analyses were conducted to evaluate the effects of uncertainty in parameters and the robustness of the model. The cost-effectiveness of evolocumab was also explored in patients with recenthreshold of 217,341 yuan (three times per capita GDP, 2020) in patients with recent ACS events in China.

There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD).

To describe characteristics of patients with CD with and without perianal fistulae.

In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none).

Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3years; difference 4.3years; 95% CI, 2.0, 6.6) and fewer had Harvey-Bradshaw Index scores indicative of remission (0-4, 56.8% vs 69.6%; difference - 12.9%; 95% CI, - 21.6, - 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vprove outcomes in CD.

Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes.

We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis 1-3days of antibiotics, 4-6days of antibiotics and 7days or more of antibiotics. Rates of infection diagnosis within 30days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independediagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection.

Short course of antibiotics for prophylaxis (3days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

The present study aimed to examine the effects of cDMARD and bDMARD therapy on both gene expressions and protein levels of TNF-α, IL-6, IL-10 and fatty acid levels in patients with RA.

Plasma TNF-α, IL-6, and IL-10 levels were examined by the ELISA method, while TNF-α, IL-6, and IL-10 gene expression levels were examined by RT-qPCR, and fatty acid levels were examined by GC/MS.

IL-10 gene expression levels significantly increased in RA patients receiving cDMARD treatment compared to those of the control group. Also, eicosadienoic acid, myristoleic acid and capric acid levels were significantly lower in the patient groups compared to those in the control group.

The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines.

The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines.The UJA Covid-19 Jewish Impact Study constitutes a random sample of 4403 adults in Jewish households in the New York area. Collected between February and May 2021, the data include symptoms of depression and anxiety and the use of professional help. Via respondents' zip code tabulation areas (ZCTAs), these data are linked to contextual measures of mental health care access from two data sources the SAMHSA Locator on specialty community treatment clinics, and the Zip Code Business Patterns database on solo and small group practices. Both treatment facilities and office practices are added to multilevel logistic regression models as density rates (per 10,000 people) and as binary indicators of presence. While we find no meaningful relationship between the general presence of mental health care services and help-seeking behavior, the ZCTA-level density of office practices is significantly associated with service utilization among the socially isolated, foreign-born and Hispanics or non-white respondents.

Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics.

Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article.

Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.

Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.Research in health professions education has often been portrayed as an applied field, one that draws on more basic forms of research in pursuing what are primarily practical ends. While there is an undeniable practical side to much of the work published in our field, and in this Journal in particular, this can be problematic when the necessary basic research is not extant. In this editorial, two of this Journal's editors consider some of the challenges in bridging these basic research gaps in an erstwhile applied field, and the implications for the kinds of research we undertake and for the identity of the field as a whole.Given gaps in both identifying and providing targeted interventions to struggling learners, the purpose of this study is to both improve rapid identification and to improve individualized academic advising for learners using this visual representation of performance. Across three graduating classes, individual growth curves were calculated for each student on National Board of Medical Examiners customized assessments during the pre-clerkship period using their deviation from the class average at each assessment point. These deviation scores were cumulatively summed over time and were regressed onto the sequence of exams. We analyzed the difference between the regression slopes of those students placed on Academic Probation (AP) versus not, as well as differences in slopes based on the timing of when a struggling learner was placed on AP to explore learner trajectory after identification. Students on AP had an average growth slope of - 6.06 compared to + 0.89 for those not on AP. Findings also suggested that students who were placed on AP early during pre-clerkship showed significant improvement (positive changes in trajectory) compared to students identified later in the curriculum. Our findings suggest that earlier academic probation and intervention with struggling learners may have a positive effect on academic trajectory. Future research can better explore how academic trajectory monitoring and performance review can be regularly used in advising sessions with students.Professional identity is believed to foster self-confidence and resilience in health care professionals. While literature exists describing professional identity in medicine, the relevance of this evidence to rehabilitation professionals (occupational therapy (OT), physical therapy (PT) and speech-language pathology (S-LP)) is limited due to differences between professions in decision-making authority (patient care), professional autonomy and understanding of their scope of practice. The objective was to determine the extent, range and nature of the literature on professional identity/professional identity formation in rehabilitation professionals. Findings from the scoping review based on Arksey and O'Malley's methodological framework are presented. A search was conducted on MEDLINE (Ovid), Embase (Ovid), AMED, CINAHL, and ProQuest Dissertations and Theses from 1996 to October 2020 for empirical and conceptual studies on OT, PT, and S-LP clinicians or students. Of 4983 retrieved records, 53 papers were selected for data extraction. Data were organised into themes for professional identity/professional identity formation conceptual descriptors (dynamic state, multiple identities); influences (person, professional education/environments, profession-at-large). Findings are consistent with the professional identity literature in medicine. However, they point to gaps for further empirical inquiry in the role of symbols and rituals in the professional identity/professional identity formation of rehabilitation professionals, profession-specific differences between OT, PT and S-LP, and influences related to the profession-at-large on the professional identity/professional identity formation of rehabilitation professionals. These findings may help to inform professional education programs and health care and professional systems in developing resources to support professional identity formation of rehabilitation professionals.

Irisin is a newly discovered myokine released from skeletal muscle during exercise. The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a key role in the metastatic process via degrading extracellular matrix. The aim of this study was to investigate the effect of irisin on expression of metastatic markers MMP2 and MMP9 and induced apoptosis in human prostate cancer cells.

In this study, we examined the effect of different concentrations of irisin on induced apoptosis and cell viability of two cell lines, LNCaP and DU-145, by using flow cytometry and MTT assay, respectively. The expression of MMP2 and MMP9 genes was also analyzed by real-time PCR after irisin treatment. Data were analyzed usingthecomparative cycle threshold2

method.

Cell viability was reduced in both LNCaP and DU-145 cell lines at different concentrations of irisin. However, this decreased cell viability was strongly significant (p < 0.05) only at 5 and 10nM concentrations of irisin in the LNCaP cell line. link= Vorinostat Furthermore, irisin could induce apoptosis in both cell lines at a concentration of 10nM compared to 5nM. Real-time PCR results also demonstrated a decreased expression in MMP2 and MMP9 genes in a concentration-dependent manner in both cell lines.

These results showed the anticancer effects of irisin on cell viability of both LNCaP and DU-145 cell lines and also on the expression of MMP2 and MMP9 genes occurred in a dose- and time-dependent manner.

These results showed the anticancer effects of irisin on cell viability of both LNCaP and DU-145 cell lines and also on the expression of MMP2 and MMP9 genes occurred in a dose- and time-dependent manner.A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton-proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 , at a center-of-mass energy s = 13 TeV . No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.

This study aims to investigate the effect of ω-3 fatty acid immunonutritional therapy on natural killer (NK) cell gene methylation and function in elderly patients with gastric cancer.

A total of 70 cases of elderly patients with gastric cancer were randomized into the ω-3 fatty acid group and placebo group, according to the type of nutritional support administered. The methylation status of the tumor necrosis factor (TNF)-α gene promoter in peripheral NK cells was detected by methylation specific polymerase chain reaction, and the TNF-α level in peripheral NK cells was detected by enzyme-linked immunosorbent assay.

After 14 days of immunonutritional therapy with ω-3 fatty acid or placebo, patients in the ω-3 group had significantly higher average NK cell activity (0.27 vs. 0.24, P=0.013) and lower percentages of TNF-α gene promoter methylation (25.7% vs. 60%, P<0.05) than the placebo group. However, there were no significant differences in the concentration of albumin, prealbumin and TNF-α in serum, and the NK cell count between the ω-3 group and placebo group.

The postoperative application of ω-3 fatty acid may improve the activity of NK cells, which is correlated to the methylation status of the TNF-α gene promoter.

The postoperative application of ω-3 fatty acid may improve the activity of NK cells, which is correlated to the methylation status of the TNF-α gene promoter.[This corrects the article DOI 10.1007/s13340-021-00542-1.].Nonalcoholic fatty liver disease includes a wide spectrum of manifestations from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and eventually cirrhosis or even hepatocellular carcinoma. This disorder is also associated with an increased cardiovascular risk, renal involvement, oncologic processes, metabolic disturbances, and an increased risk of all-cause mortality or hepatic mortality. For this reason, nonalcoholic fatty liver disease should be considered a disorder with high morbidity and mortality that must be diagnosed appropriately as soon as possible to establish adequate treatment. Noninvasive methods based on biochemical parameters should be used as a first step in the evaluation of any patient in whom this disease is suspected. However, serum/blood levels of liver enzymes are not a good indicator of liver damage and noninvasive methods, including biochemical tests and imaging, have suboptimal accuracy or are patented prototypes that show limitations in clinical practice. There are currently no drugs specifically approved for the treatment of these liver disorders, thus the most relevant intervention for nonalcoholic fatty liver disease is lifestyle modification.Alcohol-related liver disease (ALD) is a major healthcare/economic burden and one of the leading causes of liver transplantation. New epidemiological studies that detail the course of the disease are needed since, despite its high prevalence, it is still a stigmatised condition with underlying pathology. Alcoholic hepatitis, as the highest expression of ALD, has high morbidity. Current treatments have suboptimal results with the exception of liver transplantation. Epidemiological studies must also be developed to improve prevention and implement early diagnosis policies. It is essential to develop multidisciplinary health models that allow the liver transplantation candidate to be approached in a holistic way, both for indication and follow up. The implementation of alcohol consumption biomarkers (ethyl glucuronide, phosphatidylethanol) can assist in diagnosing and supporting recovery. There are several initiatives with new therapies that must be validated to establish their effectiveness and indication.Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS) that leads to axonal damage and accumulation of disability. Relapsing-remitting MS (RR-MS) is the most frequent presentation of MS and this form of MS is three times more prevalent in females than in males. This female bias in MS is apparent only after puberty, suggesting a role for sex hormones in this regulation; however, very little is known of the biological mechanisms that underpin the sex difference in MS onset. Experimental autoimmune encephalomyelitis (EAE) is an animal model of RR-MS that presents more severely in females in certain mouse strains and thus has been useful to study sex differences in CNS autoimmunity. Here, we overview the immunopathogenesis of MS and EAE and how immune mechanisms in these diseases differ between a male and female. We further describe how females exhibit more robust myelin-specific T helper (Th) 1 immunity in MS and EAE and how this sex bias in Th cells is conveyed by sex hormone effects on the T cells, antigen presenting cells, regulatory T cells, and innate lymphoid cell populations.Sex and gender differences are seen in cognitive disturbances in a variety of neurological and psychiatry diseases. Men are more likely to have cognitive symptoms in schizophrenia whereas women are more likely to have more severe cognitive symptoms with major depressive disorder and Alzheimer's disease. Thus, it is important to understand sex and gender differences in underlying cognitive abilities with and without disease. Sex differences are noted in performance across various cognitive domains - with males typically outperforming females in spatial tasks and females typically outperforming males in verbal tasks. Furthermore, there are striking sex differences in brain networks that are activated during cognitive tasks and in learning strategies. Although rarely studied, there are also sex differences in the trajectory of cognitive aging. It is important to pay attention to these sex differences as they inform researchers of potential differences in resilience to age-related cognitive decline and underlying mechanisms for both healthy and pathological cognitive aging, depending on sex. We review literature on the progressive neurodegenerative disorder, Alzheimer's disease, as an example of pathological cognitive aging in which human females show greater lifetime risk, neuropathology, and cognitive impairment, compared to human males. Not surprisingly, the relationships between sex and cognition, cognitive aging, and Alzheimer's disease are nuanced and multifaceted. As such, this chapter will end with a discussion of lifestyle factors, like education and diet, as modifiable factors that can alter cognitive aging by sex. Understanding how cognition changes across age and contributing factors, like sex differences, will be essential to improving care for older adults.Before 1990, the multiplicity of dopamine receptors beyond D1 and D2 had remained a controversial concept, despite its substantial clinical implications, at a time when it was widely accepted that dopamine interacted with only two receptor subtypes, termed D1 and D2, differing one from the other by their pharmacological specificity and opposite effects on adenylyl cyclase. It was also generally admitted that the therapeutic efficacy of antipsychotics resulted from blockade of D2 receptors. Thanks to molecular biology techniques, the D3 receptor could be characterized as a distinct molecular entity having a restricted anatomical gene expression and different signaling, which could imply peculiar functions in controlling cognitive and emotional behaviors. Due to the structural similarities of D2 and D3 receptors, the search for D3-selective compounds proved to be difficult, but nevertheless led to the identification of fairly potent and in vitro and in vivo selective compounds. Vorinostat The latter permitted to confirm a role of D3 receptors in motor functions, addiction, cognition, and schizophrenia, which paved the way for the development of new drugs for the treatment of psychiatric disorders.Atherosclerosis is the most common arterial disease and is closely related to vascular calcification. CircHIPK3 has been implicated in atherosclerosis development, but the possible downstream regulatory mechanisms remain unclear. The levels of circHIPK3, miR-106a and MFN2 in tissues and blood samples of patients with atherosclerosis were detected by RT-qPCR. The levels of circHIPK3, miR-106a and MFN2 were detected by RT-qPCR and the expression levels of MFN2, osteogenic and cartilage differentiation marker proteins were detected by western blot in vitro. link2 ALP staining, Alizarin Red staining, and calcium content detection evaluated the degree of osteogenic differentiation of cells. Alcian blue staining detected the level of cell cartilage differentiation. link2 Luciferase detected the targeting relationship between circHIPK3 and miR-106a-5p, as well as miR-106a-5p and MFN2. CircHIPK3 and MFN2 were low expressed and miR-106a-5p was highly expressed in tissues and blood samples of patients with atherosclerosis, as well as vascular smooth muscle cell (VSMC) with osteogenic and cartilage differentiation. Overexpression of circHIPK3 reduced the cell mineralization and calcium content. Overexpression of circHIPK3 inhibited osteogenic differentiation by decreasing ALP activity, RUNX2, and OPG expression, and increasing SM22α and SMA level. What's more, overexpression of circHIPK3 decreased the chondrogenic differentiation by inhibiting the protein level of SOX9, aggrecan, and collagen II. CircHIPK3 targeted miR-106a-5p and miR-106a-5p targeted MFN2. MiR-106a-5p overexpression or MFN2 depletion repressed the effect of circHIPK3 overexpression on VSMC calcification. CircHIPK3 regulated osteogenic and cartilage differentiation of VSMC via miR-106a-5p/MFN2 axis, indicating a target for treating vascular calcification.Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication and consequently have the potential to be potent therapeutic vectors. Beyond their endogenous function, EVs are also being harnessed as drug delivery vehicles with possible benefits over synthetic nanoparticle systems. Despite advances in loading exogenous molecules into extracellular vesicles, efficient incorporation of nucleic acids remains a challenge due to aggregation and degradation. In this chapter, we detail a method to load EVs with negatively charged cargo, in particular nucleic acids, by modifying the internal pH of the vesicles to be acidic. This approach demonstrates that pH modification of EVs enables efficient loading of nucleic acids with functional cargo.Extracellular vesicles (EVs) are a population of particles naturally released by cells to transport biological messages, including nucleic acids. Thus, EVs represent an ideal vehicle to deliver therapeutic miRNAs. The current challenge is the development of efficient protocols to load EVs with exogenous miRNAs. Human plasma is an abundant source of EVs which can be manipulated for therapeutic applications. Despite numerous techniques are currently available to load EVs, all of them present issues which limit their clinical application. Among all, electroporation was shown to be superior to other protocols and to efficiently load plasma-derived EVs with miRNAs. However, also the electroporation procedure presents issues that can reduce the miRNA delivery. In this chapter, we describe a protocol to isolate EVs from human plasma, to load synthetic miRNA mimics using electroporation, to evaluate EV integrity and miRNA loading into EVs. Finally, the analysis of EV functionality allows to investigate the ability of engineered EVs to transfer the miRNAs to target cells and to exploit their biological effects.Extracellular vesicles (EVs) are membranous particles released by all cells in the external milieu. Depending on their origin, they are given different names exosomes are nanovesicles that originate from the endosomal compartment, whereas microvesicles bud from plasma membrane. Both contain molecules that are crucial for the onset and spreading of different pathologies, from neurodegenerative diseases to cancer, and are considered promising disease markers. On the other hand, EVs are often used as therapeutic tools, and can be engineered to carry drugs and chemicals. This chapter describes a method to produce EVs, mainly exosomes, containing the green fluorescent protein (GFP) linked to an exosome anchoring protein (Nefmut). This enables counting and tracing of fluorescent EVs by different methods, including conventional flow cytometry.Extracellular vesicles (EVs), comprising exosomes, ectosomes, and apoptotic bodies, are an important component of molecular cell-to-cell communication, and are critically involved in the pathophysiology of various diseases, including tumors. In order to study the interaction of tumor cell-derived EVs with their target cells and to investigate their biological functions in comparison to other tumor cell-released factors, efficient isolation of EVs from cultured tumor cells, as well as fluorescent labeling of these EVs, is often necessary. In addition, EVs and EV-like particles are emerging as versatile vehicles for the delivery of therapeutic substances. Here, we describe an easy size exclusion chromatography-based method to isolate EVs from the mouse melanoma cell line B16F10 that yields highly enriched EV samples for subsequent applications such as molecular and functional studies. Our protocol also includes an optional labeling step with the lipophilic dye DiD, which allows tracking of EV uptake by recipient cells in vitro and in vivo.Healthy cells constitutively release lipid bilayered vesicles of different sizes and recognizing different biogenesis, collectively referred to as extracellular vesicles (EVs). EVs can be distinguished in exosomes and microvesicles. Biological and biomedical research on EVs is an emerging field that is rapidly growing. Many EV features including biogenesis, cell uptake, and functions still require unambiguous elucidation. Nevertheless, it has been well established that EVs are involved in communication among cells, tissues, and organs under both healthy and disease conditions by virtue of their ability to deliver macromolecules to target cells. Here, we summarize most recent findings regarding biogenesis, structure, and functions of both exosomes and microvesicles. In addition, the use of EVs as delivery tools to induce CD8+ T cell immunity is addressed compared to current designs exploiting enveloped viral vectors and virus-like particles. Vorinostat Finally, we describe a both safe and original approach conceived for the induction of strong CTL immunity against antigens uploaded in EVs constitutively released by muscle cells.Lipidomics is an omics approach to comprehensively study lipid profiles in biological samples, such as plasma, serum, urine, and tissue specimens. Moreover, lipidomic analyses are useful for identifying novel lipid biomarkers, especially for various metabolic and malignant diseases in humans. Extracellular vesicles (EVs) are lipid bilayer-encapsulated nanoparticles secreted from various cells into the extracellular space. In particular, circulating EVs in the blood stream have attracted considerable research interest as they are considered the fingerprint of the cells from which they are secreted and are a promising source for less-invasive biomarker screening. Here, we describe the entire workflow for the lipidomic analysis of circulating EVs, including the methods for their purification from human plasma and serum, liquid chromatography coupled with high-resolution mass spectrometry-based lipid measurement, and data analyses for profiling EV lipids. Using this methodological workflow, over 260 lipid molecules belonging to the glycerophospholipid and sphingolipid groups can be detected.A successful phosphoproteomics analysis of extracellular vesicles (EVs) requires a unique approach, fine-tuned to address the challenges that have plagued plasma-based biomarker discovery. Here, I detail a procedure, which combines EVtrap-based high-recovery EV isolation, phase-transfer surfactant method for protein extraction, and PolyMAC-based enrichment of phosphopeptides. The combination of these methods provides a highly effective strategy for EV-based phosphoproteome analysis and leads to the discovery of novel phospho-markers previously undetectable.Extracellular vesicles (EVs) are biological carriers, and EV-associated miRNAs (EV-miRNAs) are considered as a novel biomarker in multiple diseases. Currently, the column-based purification method is used to purify miRNAs from EVs. However, this method of purification is complex, time-consuming, and expensive. Therefore, a simple and cost-effective single-step quantitative reverse transcription-polymerase chain reaction (RT-qPCR) method is required to detect the expression of EV-miRNAs. This chapter describes a protocol for directly analyzing the EV-miRNAs expression from mouse bronchoalveolar lavage fluid (BALF) and serum without going for an RNA isolation and purification step from EVs. It is an efficient method in several terms such as cost-wise, time, low expertise, and accuracy in results. This method may be helpful in diagnostic blood tests used in medical centers or research laboratories.Urine bears high potential for serving as biomarker repository for renal and urinary tract associated disorders. Besides various metabolites and salts, urine carries extracellular vesicles (EVs)-a heterogeneous group of cell-derived mediators comprising proteins, lipids, and nucleic acids such as microRNAs (miRNAs). Particularly, EV-derived miRNA biomarkers have already been identified for numerous disorders such as sepsis, various blood and solid cancer entities, respiratory and renal diseases. However, study results are often incomparable due to poorly reported EV separation and miRNA isolation protocols and emphasize the need for standardization and reproducibility. To ensure valid EV-derived miRNA biomarker findings from urine, a step-by-step protocol compliant with the "Minimal Information for Studies of Extracellular Vesicles" (MISEV) is outlined in the following paragraphs. Actually, an immunoaffinity-based EV separation method followed by EV characterization, quantification, and normalization, as well as consecutive miRNA isolation and miRNA profiling by small RNA sequencing, are described.Exosomes are small extracellular vesicles secreted by cells and are known to play a key role in intercellular communication. Several studies have associated exosomes with various roles in tumorigenesis and explored their potential as a source of biomarkers for diagnosis and prognosis in cancer research. Exosomes can be isolated from several body fluids, including those that are noninvasively accessible, such as human saliva. This book chapter provides a step-by-step detailed description of techniques that are used for the isolation, quantification, and characterization of exosomes from saliva. These include ultracentrifugation for the isolation, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot (WB) for characterization of exosomes. The NTA approach explores the Brownian motion and light scattering of particles to predict size and concentration. TEM enables visualization of the exosomes which often present a cup-shaped morphology. Western blot is used to detect commonly expressed exosome-associated proteins. Finally, salivary exosomes isolated using these protocols can further be characterized for downstream analysis according to their cargo (proteins, DNA, RNA, miRNA) and utilized for cancer biomarker discovery.Extracellular vesicles (EVs) secreted by human pluripotent stem cells-derived cardiovascular progenitor cells (hPSC-CVPCs) can improve repair of infarcted hearts in mouse and nonhuman primate myocardial infarction models. To fully achieve their values, it is essential to establish an efficient method for the isolation of EVs from hPSC-CVPCs. Here we describe the protocols for efficient isolation and characterization of EVs from the conditioned medium of hPSC-CVPCs.Extracellular vesicles (EVs) carry a wide range of molecules, such as proteins, RNAs, and DNA. EVs are secreted from a wide range of cells, including placental cells. Interestingly, EVs secreted from placental cells have been identified in maternal circulation as early as 6 weeks of gestation, and their concentration increases with the gestational age. While there is growing interest in elucidating the role of exosomes during normal and complicated pregnancies, progress in the field has been delayed because of the inability to quantify placental EVs from the maternal circulation. Recent reports have demonstrated the presence of placental-type alkaline phosphatase (PLAP) EVs only in the blood of pregnant women, indicating that PLAP is a marker to identify EVs secreted from the placenta. Therefore, here we describe a workflow to quantify placental EVs from maternal circulation using a targeted proteomics approach based on selecting specific peptides identified in the PLAP protein.Extracellular vesicles (EVs) are lipid membrane enclosed particles that are released from cells into body fluids, such as blood. EVs offer potential new biomarkers of diseases, because the cellular origin, composition, concentration, and function of EVs change in health and disease. The concentration of EVs from specific cell types in blood can be determined with flow cytometry. A flow cytometer measures fluorescence and light scattering signals from single EVs, but only if these signals are sufficiently bright to be detected. Measured concentrations of EVs are therefore only reproducible and comparable if the detection ranges are known and reported in standard units, such as molecules of equivalent soluble fluorophore (MESF) for fluorescence signals and the diameter in nm for scatter signals. The goal of this protocol is to discuss all steps needed to derive the concentration of cell-type specific EVs within a known diameter range and fluorescence range. More specifically, this protocol describes how to determine the concentration of CD61+ (Integrin beta-3, platelet marker), CD235a+ (Glycophorin A, erythrocyte marker), and CD45+ (leukocyte common antigen) EVs in human blood plasma with an Apogee A60-Micro flow cytometer using scatter-based triggering. The principles behind this protocol could lay a firm basis for the design of a protocol suitable for other flow cytometers and body fluids.Proteomics characterization of blood and circulating material has been extensively explored for the study of pathological states. In particular, circulating small extracellular vesicles (sEV, diameter 30-150 nm) are known to play an important role in intercellular communication processes, and proteomics profiling has been explored to develop minimally invasive assays for disease monitoring and diagnosis. Due to the genetic and physiological similarities between the two species, and also on account of their shorter life span and rapid disease progression, rodent models are the most commonly used animal model for many human diseases. Such models have provided invaluable insight into the molecular mechanisms of disease progression, candidate drug efficacy, therapy monitoring, and biomarkers research.Longitudinal investigations, in which individuals are monitored over periods of time, are more able to resolve molecular changes during disease progression because they circumvent the inter-individual variation. Longitudinal investigations of rodent models are challenging because of the limited amount of blood that can be withdrawn at each time; the American Association of Veterinary Science stipulates that fortnightly sampling should be limited to a maximum of 10% of the total blood volume. For adult mice this corresponds to approximately 75 μL of serum. link3 We developed an approach for the isolation and characterization of serum sEV proteins from just 50 μL of serum, for longitudinal studies of disease mouse models. This chapter describes in detail the steps and considerations involved in the sEV isolation, morphological characterization, and proteome profiling by mass spectrometry.Circulating extracellular vesicles (EVs) are gaining increased attention as carriers of proteins, nucleic acids, and lipids. Blood contains EVs from different cell sources that constitute an attractive target for biomarker studies. However, there is no consensus on the best approach to isolate EVs from blood. Non-EV proteins and lipoproteins in plasma/serum tend to contaminate isolated EVs and confound functional experiments. Here we describe a single-step, high-performance size-exclusion chromatography procedure for separation of EVs from most lipoproteins and non-EV proteins, and compare it to ultracentrifugation, still the most commonly used method for EV isolation.Exosomes are a type of extracellular vesicles that contain constituents including proteins, DNAs, and RNAs of the cells that secrete them. Cancerous exosomes are potential biomarkers for cancer diagnosis. Biosensors are useful analytical tools for quantification of biomarkers and targeted molecules. An aptasensor uses the aptamer as the biorecognition element to bind to the target and is one main type of biosensors that is promising for exosomes analysis and clinical cancer detection. The assay described in this chapter allows for reliable, sensitive, and specific detection of cancer-derived exosomes using a colorimetric aptasensor that is promising for point-of-care testing.Cancerous exosomes that carry multiple biomarkers are attractive targets for the early diagnosis and therapy of cancer. link3 As one of the powerful molecular recognition tools, aptamers with excellent binding affinity and specificity toward biomarkers have been exploited to construct various aptamer-based biosensors (aptasensors) for exosome detection. Here, we review recent advances in aptasensors for the detection of cancerous exosomes. We first discuss the importance and potential of cancerous exosomes in cancer diagnosis and then summarize some conventional aptasensors from the perspective of biomarker recognition and signal collection strategies. Finally, we comment on the outlook for aptasensor research and new directions for cancerous exosome detection.

To review our institutional experience with thesurgical management of prolactinomas through the endoscopic endonasal approach with specific focus on cavernous sinus invasion.

Clinical and radiographic data were collected retrospectively from the electronic medical record of 78 consecutive patients with prolactinomas undergoing endoscopic endonasal resection from 2002 to 2019. Immediate and late post-operative remission were defined as prolactin < 20ng/mL within 14days and 1-year of surgery without adjuvant therapy, respectively. Cavernous sinus invasion was quantified by Knosp score.

A total of 78 patients with prolactinoma, 59% being male, underwent surgical resection with a mean age of 37 ± 13years. Indications for surgery were medication resistance in 38 patients (48.7%), medication intolerance in 11 (14.1%), and patient preference in 29 (37.2%). Patients with Knosp 0-2 achieved higher immediate remission rates (83.8%) compared to patients with Knosp 3 (58.8%) and Knosp 4 (41.7%) patients (p = 0.0ut invasion.

Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels.

Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models.

Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy.

Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.

Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.Many patients with schizophrenia (SCZ) discontinue antipsychotics, frequently due to dose-related multiple and severe adverse effects. We hypothesized that a low-dose ziprasidone plus sertraline would reduce serious side effects without affecting treatment efficacy. Therefore, this clinical trial was designed to investigate the efficacy, safety, and tolerability of adding sertraline to ziprasidone in order to substantially reduce ziprasidone dose and potential side effects in first-episode and drug-naive (FEDN) patients with SCZ. This 24-week randomized, double-blinded, controlled clinical trial randomly allocated 452 FEDN SCZ patients to receive a usual dose of ziprasidone (control group) or half the dose of ziprasidone in combination with sertraline (ZS group). Treatment outcome included the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and the Personal and Social Performance Scale (PSP) at baseline and weeks 2, 4, 8, 12, and 24. Repeated measures ANCOVA showed significant treatment by time interactions on the PANSS general psychopathology and total scores, as well as CGI-S, HAMD, and PSP scores (all p  less then  0.05). Furthermore, the ZS group had greater reductions in PANSS general psychopathology, total scores, HAMD, and CGI-S (all p  less then  0.05) and greater increases in the PSP total score (p  less then  0.01) than the control group. Importantly, adverse effects were lower in the ZS than control group. The reduction in PANSS, CGI-S, or HAMD scores was not correlated with the increase in PSP. Sex and duration of disease predicted PSP improvement from baseline to week 24 in the ZS group. Our FEDN patients with SCZ were effectively treated for their psychotic and depressive symptoms while experiencing significantly fewer adverse effects using half the usual ziprasidone dose when combined with sertraline. ClinicalTrials.gov, NCT04076371.