BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy. 相似文献
Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n?=?3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β?=?0.90, 95% CI 0.40–1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR?=?1.21), being Black (AOR?=?1.79) or Latinx (AOR?=?1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR?=?1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19.
Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases. 相似文献
The spin-echo procedure is the basic technique in a magnetic resonance (MR) study (the magnetization vector is flipped by 90° onto the ortogonal plane to the main magnetic field). Very soon after the MR procedure was developed, it was pointed out how important it is to achieve the needed contrast with shorter repetition times (TRs) to reduce the imaging time. Recently, fast imaging techniques have been introduced (partial flip angles, short TRs, and the lack of 180° radiofrequency pulses to refocus the spins are their main characteristics; the spins are refocused by the application of a gradient reversal technique). These techniques are particularly needed in pediatric neuroradiology, where the examination time must be as short as possible. At present, partial flip-angle techniques are almost completely replacing the conventional spin-echo procedure, but the variations in flip angle could result in a change in contrast. For these reasons, conventional spin-echo techniques may still be useful in a routine MR study.Presented at the 11th Meeting of the European Society for Paediatric Neurosurgery, Naples 1988 相似文献
In the human neuroblastoma cell line SK-N-BE(2), arachidonic acid (AA), supplied in the medium at micromolar concentrations, markedly ehnanced [14C]stearic acid (SA) (but not [14C]palmitic acid or [14C]oleic acid) incorporation into phosphatidylinositol (PtdIns). AA failed to stimulate [14C]SA incorporation into PtdIns precursors, namely phosphatidic acid and cytidinediphosphodiacylglycerol; furthermore, enhanced [14C]SA incorporation, brought about by exogenously administered AA, was not restricted to PtdIns tetraenoic species. When cells were pulsed for 1 h with [14C]SA (either in the presence or absence of AA) and then reincubated in AA- and [14C]SA-free medium, a marked loss of radioactivity from PtdIns was observed, that however was restricted to molecular species other than tetraenoic. These results are discussed in the light of possible mechanisms through which PtdIns achieves the 1-stearoyl-2-arachidonoyl configuration. 相似文献
Stimulation of SK-N-BE(2) cells with 1 mM carbachol (Cch) elicited phosphoinositide (PPI) hydrolysis and a rapid elevation of cytosolic Ca2+ concentration ([Ca2+]i) from 115 nM to about 500 nM, followed by a plateau around 200 nM. In myo [3H]inositol-labelled cells, Cch-evoked accumulation of [3H]inositol phosphates (IPs) was not affected when [Ca2+]i was clamped at resting by cell loading with 10 M BAPTA/AM; under these conditions, maximal 1,4,5-inositol trisphosphate accumulation was not reduced either. When [Ca2+]i was clamped around 700 nM by cell treatment with 600 nM ionomycin, Cch-evoked [3H]IPs accumulation was enhanced by less than 20%, but it was impaired by a 30% and a 55% after [Ca2+]i reduction to about 70 nM and 35—50 nM, by cell loading with 20 M or 40 M BAPTA/AM, respectively. These results show that, in SK-N-BE(2) cells, Cch-activated PPI-specific phospholipase C is sensitive to [Ca2+]i but it already operates under suboptimal conditions at resting [Ca2+]i. 相似文献
A focus group comprised of persons who use power wheelchairs and professionals working in the field were asked to participate in a brainstorming session to determine priorities for the development and application of power mobility input devices and control concepts. The group consensus was that durability and reliability are the most important criteria. Essentially, the expectation is that a power wheelchair must work everyday in the way a person needs it and wants it. At the same time, there is a desire to enhance and advance the features of input devices and control systems. Many would say these changes constitute designing "smarter" power wheelchairs, such as systems that can independently detect obstacles and can provide users with more feedback. This paper presents the rationale behind forming this focus group and details of the results of a brainstorming session where ideas were generated and prioritized. The five most important issues as determined by the group are discussed in depth. 相似文献
Potentials were measured with nonpolarizable salt electrodes (agar KCl-AgCl) during the estral cycle and pregnancy of the rat. The vaginal fundus is positive in regard to the external end of the vagina and does not present changes associated with the estral cycle. Vaginal-tongue potentials present biphasic cyclic changes associated with the estral cycle, the vagina being (-) during estro and (+) during diestro. Vaginal-abdominal skin potentials present monophasic modifications associated with the estral cycle. Vaginal-tongue potentials registered during pregnancy were (-) on the first day of pregnancy, (+) throughout pregnancy, and (-) on the first day postpartum. 相似文献
A renal tumor developing in a patient receiving cyclophosphamide (Cytoxan) therapy for Wegener granulomatosis is reported. The tumor was similar histologically to the "immunoblastic" sarcoma that develops in renal allograft recipients as a complication of immunosuppressive therapy. This case report strengthens the cause and effect relationship between immunosuppressive drug usage and the subsequent development of neoplasia. 相似文献