• Richard Mattingly ha publicado una actualización hace 3 dias, 3 horas

    Cells can communicate through extracellular vesicle (EV) secretion and uptake. Exosomes are lipid bilayer-enclosed EVs of 30-150 nm in diameter, which can transfer RNA, functional proteins, lipids, and metabolites to recipient cells in vivo. Most cell types, including immune cells, can secrete and uptake exosomes. Biogenesis, secretion, and uptake of immune cell-derived exosomes are regulated by intracellular proteins and extracellular stimuli. Immune cell-derived exosomes can mediate crosstalk between innate and adaptive immunity and regulate cancer progression and metastasis. The dichotomous roles of immune cell-derived exosomes towards tumor cells can induce suppressive or active immune responses. Hence, immune cell-secreted exosomes may have applications in cancer diagnosis and immunotherapy and could potentially be developed for vaccination and chemotherapy drug transportation.In recent years immunotherapy has provided new hope for cancer patients. However, some patients eventually relapse. Immunological responses are thought to underlie the long-term effects of conventional or targeted therapies. Whether this influence emerges from direct effects on cancer cells through immunogenic cell death (ICD) or by modulating the immune environment requires further clarification. ICD-related molecular mechanisms are also shared by cell-intrinsic defense responses that combat foreign intrusions. Indeed, we could potentially mimic and harness these processes to improve cancer immunogenicity. In addition, the microbiome is materializing as a missing factor in the cancer-immune therapy axis. The emerging idea of manipulating the gut microbiota to improve responses to anticancer therapy is becoming increasingly popular, but further clinical authentication is needed.A biomarker, such as protein accumulation as an indicator of disease, can be used to predict disease manifestation, determine intervention, and monitor treatment efficacy. Biomarker development frequently focuses on early detection of disease as this is typically considered the only or most pressing need. However, the ideal time point for biomarker use may not always be early in disease but instead, as we will discuss, could be when enough information is available to predict the association between biomarker (protein accumulation) and disease manifestation (symptom severity, progression, prognosis). This Viewpoint highlights the importance of clearly defining the notion of «time» when discussing the development and utility of biomarkers. Using two disease examples, one with a clearly defined starting point (traumatic brain injury) and one with an indistinct starting point (Alzheimer’s disease), we explore the concept of timing in biomarker development and utility.Objective To perform a systematic review to identify the clinical, fiscal and environmental evidence on the use of urological telehealth and/or virtual clinic strategies. Our secondary aim was to highlight research gaps in this rapidly evolving field. Methods Our PROSPERO registered (CRD42019151946) systematic search of Embase, Medline and Cochrane Review Database was performed for original research articles pertaining to adult urology telehealth or virtual clinic strategies. Risk of bias (RoB) assessment performed according to Cochrane 2.0 RoB or Joanna Briggs Institute Checklist for non-randomised studies. Results 5,813 participants met inclusion from 18 original articles (2 randomised controlled trials; 10 prospective; 6 retrospective). Urology sub-specialities Uro-oncology (n=6), General urology (n=8), Endo-urology (n=2), and Lower urinary tract symptoms and/or incontinence (n=2). Across all sub-specialties, prospective studies utilising VC reported primary median VC discharge rate of 16.6% (IQR 14.7%-29.8%) and primary median face-to-face (FTF) clinic referral rate of 32.4% (IQR 15.5%-53.3%). Further, direct cost analysis demonstrated a median annual cost-savings of £56,232 (IQR £46,260-£61,116). Grade II and IIIb complications were reported in two acute ureteric colic studies, with a rate of 0.20% (3/1,534) and 0.13% (2/1,534), respectively. Annual carbon footprint avoided ranged from 0.7 to 4.35 metric tonnes of CO2 emissions, depending on mode of transport utilised. Patient satisfaction was inconsistently reported, and assessments lacked prospective evaluation using validated questionnaires. Conclusion Virtual urology clinics are a promising new platform which can offer clinical, financial and environmental benefits to support an increasing urological referral burden. Further prospective evidence is required across urological subspecialties to confirm equivalency and safety against traditional face-to-face assessment.Sam Foster, Chief Nurse, Oxford University Hospitals, considers how leaders can help their staff in times of stress, grief and bereavement during the current pandemic.Primary adrenal insufficiency is a defect in glucocorticoid, mineralocorticoid and sexual androgens production. Patients with this disorder have low cortisol levels and aldosterone deficiency with concomitant hyponatremia and hyperkalemia. The most common etiology of this disease is the production of antibodies against the enzyme 21 hydroxylase. Another common cause, particularly in low income countries, are infectious diseases. Several micro-organisms have been reported as a causal agent in adrenal insufficiency including Mycobacterium tuberculosis, Mycobacterium avium complex, Neisseria meningitidis, Pseudomonas aeruginosa, Haemophilus influenzae, cytomegalovirus, Pneumocystis jirovecii, Histoplasma capsulatum, Blastomyces dermatiditis, Cryptococcus neoformans, Cocciodiodes immitis, Nocardia spp. and Paracoccidioides brasiliensis. In this article, we present the computerized tomography and the adrenal biopsy of a patient with adrenal insufficiency. The final diagnosis was paracoccidioidomycosis.Dermatologists must be familiar with the safety, utility, and tolerability of a range of over-the-counter (OTC) products. In this article, the role of the US Food and Drug Administration in regulating safety of OTC products is discussed. Durvalumab Additionally, resources to help guide clinicians to learn about the pharmacology and tolerability of OTC products are reviewed.