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Binge-like eating behavior (BLE) has been characterized as an eating disorder in which subjects have an enhanced intake of food, mainly fats. However, intake of fats and carbohydrates may have differential effects on motivation. Previously it was shown that BLE produces an increase in operant responding for vegetable shortening, but others were unable to replicate the finding using sucrose as the reinforcer. Our aim was to determine if BLE behavior induced with a cafeteria-like diet (CaLD) with several options with fat content would produce an increment in performance. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE using CaLD options. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. Rats with intermittent access to CaLD options showed a clear BLE with an escalation in their intake; however they showed compensatory decrements of chow intake that rendered a similar body weight gain to a continuous access group. Although we were unable to observe an increase in BPs after BLE we were able to observe a protection against the decrements of BP previously observed with sugar. Different mechanisms for processing high fat and high carbohydrate reinforcers are variables worth exploring to gain a better understanding of BLE behavior in rodent models.Hh signaling has been shown to be activated in intact and injured peripheral nerve. However, the role of Hh signaling in peripheral nerve is not fully understood. In the present study, we observed that Hh signaling responsive cells [Gli1(+) cells] in both the perineurium and endoneurium. In the endoneurium, Gli1(+) cells were classified as blood vessel associated or non-associated. After injury, Gli1(+) cells around blood vessels mainly proliferated to then accumulate into the injury site along with endothelial cells. Hh signaling activity was retained in Gli1(+) cells during nerve regeneration. To understand the role of Hedgehog signaling in Gli1(+) cells during nerve regeneration, we examined mice with Gli1(+) cells-specific inactivation of Hh signaling (Smo cKO). After injury, Smo cKO mice showed significantly reduced numbers of accumulated Gli1(+) cells along with disorganized vascularization at an early stage of nerve regeneration, which subsequently led to an abnormal extension of the axon. Thus, Hh signaling in Gli1(+) cells appears to be involved in nerve regeneration through controlling new blood vessel formation at an early stage.Fracture healing is a complicated process affected by many factors, such as inflammatory responses and angiogenesis. Omentin-1 is an adipokine with anti-inflammatory properties, but whether omentin-1 affects the fracture healing process is still unknown. Here, by using global omentin-1 knockout (omentin-1-/-) mice, we demonstrated that omentin-1 deficiency resulted in delayed fracture healing in mice, accompanied by increased inflammation and osteoclast formation, and decreased production of platelet-derived growth factor-BB (PDGF-BB) and osteogenesis-promoting vessels that are strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in the fracture area. In vitro, omentin-1 treatment suppressed the ability of the tumor necrosis factor-α (TNF-α)-activated macrophages to stimulate multi-nuclear osteoclast formation, resulting in a significant increase in the generation of mono-nuclear preosteoclasts and PDGF-BB, a pro-angiogenic protein that is abundantly secreted by preosteoclasts. PDGF-BB significantly augmented endothelial cell proliferation, tube formation and migration, whereas direct treatment with omentin-1 did not induce obvious effects on angiogenesis activities of endothelial cells. Our study suggests a positive role of omentin-1 in fracture healing, which may be associated with the inhibition of inflammation and stimulation of preosteoclast PDGF-BB-mediated promotion of CD31hiEmcnhi vessel formation.Assessing male reproductive toxicity of environmental and therapeutic agents relies on the histopathology of the testis and epididymis in a pre-clinical setting. Animal histopathology poorly correlates with human sperm parameters, and none of these current methods are strong indicators of sperm health or reproductive potential. Therefore, there is an urgent need to identify a translatable, non-invasive and reliable approach to monitor environmental and therapeutic agents' effects on male reproductive health. mRNA sequences were analyzed in mouse, rat and human sperm samples to identify sperm transcriptomic similarities across species that could be used as biomarkers to predict male reproductive toxicity in animal models. Semen specimens were collected from men aged 18 to 55 years with proven fertility. Rat and mouse semen specimens were collected via needle punctures of the cauda epididymides. Sperm RNAs were extracted using an optimized sperm RNA isolation protocol and subjected to polyA-purified mRNA-sequencing. Bioinformatics analyses, including differential abundance and gene set enrichment analysis, were used to investigate the biological and molecular functions of all shared and differentially abundant transcripts across species. Transcriptome profiling identified 6,684 similarly expressed transcripts within the three species of which 1,579 transcripts were found to be involved in spermatogenic functions. Tazemetostat molecular weight Our findings have shown that sperm transcriptome is highly species dependent, however, there are some key similarities among transcripts that are required for fertility. Based on these similarities, sperm mRNA biomarker may be developed to monitor male reproductive toxicity where rodent models would make suitable laboratory substitutes for human.
B cell depletion with rituximab has emerged as a first line therapy for primary membranous nephropathy (PMN). However, most patients do not achieve complete remission with rituximab monotherapy. In this case series, we report longer-term remission and relapse rates, anti-phospholipase A2 receptor (PLA2R) antibody levels, B cell levels, and serious adverse events in patients with PMN who received rituximab combined with an initial short course of low-dose oral cyclophosphamide and a course of rapidly tapered prednisone (RCP).
Single-center retrospective case series.
60 consecutive patients with PMN treated with RCP at the Vasculitis and Glomerulonephritis Center at the Massachusetts General Hospital.
After treatment initiation, median follow-up was 38 months (IQR, 25 - 62); 100% of patients achieved partial remission, defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline, at a median of 3.4 months. By 2 years after treatment initiation, 83% achieved complete remission, defined as a UPCR < 0.
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