RESUMO
Several pulsar timing array collaborations recently reported evidence of a stochastic gravitational wave background (SGWB) at nHz frequencies. While the SGWB could originate from the merger of supermassive black holes, it could be a signature of new physics near the 100 MeV scale. Supercooled first-order phase transitions (FOPTs) that end at the 100 MeV scale are intriguing explanations, because they could connect the nHz signal to new physics at the electroweak scale or beyond. Here, however, we provide a clear demonstration that it is not simple to create a nHz signal from a supercooled phase transition, due to two crucial issues that could rule out many proposed supercooled explanations and should be checked. As an example, we use a model based on nonlinearly realized electroweak symmetry that has been cited as evidence for a supercooled explanation. First, we show that a FOPT cannot complete for the required transition temperature of around 100 MeV. Such supercooling implies a period of vacuum domination that hinders bubble percolation and transition completion. Second, we show that even if completion is not required or if this constraint is evaded, the Universe typically reheats to the scale of any physics driving the FOPT. The hierarchy between the transition and reheating temperature makes it challenging to compute the spectrum of the SGWB.
RESUMO
OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus corticosteroid as initial monotherapy in adult-onset minimal change disease (MCD) patients. METHODS: Databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to March 20, 2021. Eligible studies comparing TAC monotherapy and corticosteroid as initial monotherapy for adult-onset MCD patients were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Four randomized controlled trials (RCTs) involving 196 patients were included in the meta-analysis. For initial monotherapy for adult-onset MCD, TAC and corticosteroid had similar complete remission (OR 1.06, 95% CI 0.47-2.41, P = 0.89), total remission (OR 1.30, 95% CI 0.39-4.35, P = 0.67), relapse rate (OR 0.63, 95% CI 0.28-1.42, P = 0.26). Main drug-related adverse effects of two therapeutic regimens had no difference concerning infection (OR 0.54, 95% CI 0.23-1.27, P = 0.15), glucose intolerance (OR 0.55, 95% CI 0.16-1.84, P = 0.33) and acute renal failure (OR 1.37, 95% CI 0.36-7.31, P = 0.71). CONCLUSION: TAC monotherapy is comparable with corticosteroid monotherapy in initial therapy of MCD. To further confirm the conclusion, more large multicenter RCTs are necessary.
Assuntos
Corticosteroides , Nefrose Lipoide , Tacrolimo , Corticosteroides/efeitos adversos , Adulto , Humanos , Nefrose Lipoide/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Tacrolimo/efeitos adversosRESUMO
To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-ß-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.