Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial and three sporadic cases), all exhibiting a mild form of disease. Detailed clinical characterization of these subjects and other eight affected relatives showed that all individuals had multiple cafè-au-lait spots, frequently associated with skinfold freckling, but absence of discrete cutaneous or plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or symptomatic optic gliomas. Facial features in half of the individuals were suggestive of Noonan syndrome. Our finding and revision of the literature consistently indicate that the c.5425C>T change is associated with a distinctive, mild form of NF1, providing new data with direct impact on genetic counseling and patient management. 相似文献
The assessment of nutritional intakes during hospitalization is crucial, as it is known that nutritional status tends to worsen during the hospital stay, and this can lead to the negative consequences of malnutrition. International guidelines recommend the use of parenteral nutrition (PN) in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. However, to date, there are no published data regarding either energy intake or objective measurements associated with it in this patient population. The aim of the present exploratory methodological study was to evaluate whether phase angle (PhA) and handgrip strength normalized for skeletal muscle mass (HG/SMM) are sensitive early markers of energy intake in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. We evaluated 30 eligible patients, who were treated with personalized dietary modifications and supplemental PN for at least one week during hospitalization. In a liner regression model adjusted for age, gender, basal protein intake and the basal value of each variable, a trend toward improvement of PhA and preservation of HG/SMM was observed in patients satisfying the estimated calorie requirements (N = 20), while a significant deterioration of these parameters occurred in those who were not able to reach the target (N = 10). The mean adjusted difference and 95% CI were +1.4° (0.5–2.3) (p = 0.005) for PhA and +0.23 (0.20–0.43) (p = 0.033) for HG/SMM. A significant correlation between PhA and HG/SMM variations was also observed (r = 0.56 (95% CI, 0.23–0.77); p = 0.0023). PhA and HG/SMM were able to distinguish between hypophagic, non-surgical patients at nutritional risk who satisfied their estimated caloric requirements and those who did not after a one-week personalized nutritional support. Clinical studies are warranted, in order to verify these preliminary observations and to validate the role of PhA variations as early markers of anabolic/catabolic fluctuations. 相似文献
Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.
The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus’ replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly. 相似文献
Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events. 相似文献
To determine the utility of transesophageal echocardiographic monitoring during percutaneous balloon mitral valvotomy, we analyzed data from 40 consecutive patients who had been randomly assigned to undergo balloon mitral valvotomy under transesophageal echocardiographic guidance or without echo. All procedures were carried out under general anaesthesia. The completion rate (100% vs 73%), the procedure time (108 +/- 28 min vs 65 +/- 18 min), the X-ray exposure time (62 +/- 13 vs 33 +/- 12 min), resulted significantly (P less than 0.001) more favorable in the echo-monitored patients. Moreover, a lower rate of major complications (cardiac tamponade, large residual atrial shunting, and severe mitral regurgitation) was noted in the echo-monitored patients. The achieved final area of the mitral valve did not differ significantly between the two groups. From an evaluation of results as a whole, 96% of the echo-monitored procedures were successful, whereas only 40% of the procedures conducted without echocardiographic control achieved a satisfactory final result in absence of major complications. We conclude that transesophageal echocardiography is a safe, effective, and valuable tool to monitor each step of balloon mitral valvotomy in order to shorten the time of the procedure, and to improve the results of this complex interventional catheterization technique. 相似文献
The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the metabolism of fibrinogen (FBG), by measuring the FBG, D-dimer, and fibrin(ogen) degradation product levels in the blood from pulmonary and radial arteries from 99 patients undergoing aortocoronary bypass. For comparison, protein C, protein S, and factor VII, were also measured. The results showed, with respect to the pulmonary arterial blood levels, significantly lower FBG levels (3.72 +/- 0.83 vs 3.66 +/- 0.81 g/L; P < .001) and higher fibrin(ogen) degradation product levels (7.36 +/- 1.53 vs 8.15 +/- 1.59 mg/L; P < .000 01) in the radial arterial blood. No difference was found for d -dimer, protein C, protein S, and factor VII. The study demonstrated that the pulmonary capillary endothelium contributes to the FBG catabolism for about a 0.02 fractional rate and support the view of an endothelial FBG catabolic pathway as the main catabolic pathway, owing to the fact that the pulmonary endothelial surface is about a 0.1 fraction of the peripheral vessel endothelial surface. 相似文献