NF‐κB signaling regulates the generation of intermediate progenitors in the developing neocortex

In addition to its well‐established role during immune system function, NF‐κB regulates cell survival and synaptic plasticity in the mature nervous system. Here, we show that during mouse brain development, NF‐κB activity is present in the neocortical ventricular and subventricular zones (VZ and SVZ), where it regulates proliferative pool maintenance. Activation of NF‐κB signaling, by expression of p65 or an activated form of the IκB kinase complex subunit IKK2, inhibited neuronal differentiation and promoted retention of progenitors in the VZ and SVZ. In contrast, blockade of the pathway with dominant negative forms of IKK2 and IκBα promoted neuronal differentiation both in vivo and in vitro. Furthermore, by modulating both the NF‐κB and Notch pathways, we show that in the absence of canonical Notch activity, after knockdown of the pathway effector CBF1, NF‐κB signaling promoted Tbr2 expression and intermediate neural progenitor fate. Interestingly, however, activation of NF‐κB in vivo, with canonical Notch signaling intact, promoted expression of the radial glial marker Pax6. This work identifies NF‐κB signaling as a regulator of neocortical neurogenesis and suggests that the pathway plays roles in both the VZ and SVZ.     

Steroidogenic gene expression following D-aspartate treatment in frog testis

Previous studies have provided evidence that D-Asp plays a role in steroid-mediated reproductive biology in amphibians, reptiles, birds and mammals. To examine the molecular involvement of D-Asp on steroidogenic pathway regulation, we analysed the expression of StAR, P450 aromatase and 5αRed2 mRNAs in Pelophylax esculentus testis, either in relation to the reproductive cycle or D-Asp treatment. Basal StAR mRNA levels, as well as D-Asp and testosterone concentrations, were higher in reproductive than in post-reproductive frogs. D-Asp treatment increased StAR mRNA expression and immunolocalisation in both the reproductive and post-reproductive periods. In control testis, aromatase mRNA levels were higher in the post-reproductive period, but following D-Asp administration, they increased only in the reproductive period. The level of 5αRed2 mRNA was higher in reproductive frogs than in post-reproductive frogs, and it increased after D-Asp treatment only in the post-reproductive phase. Our results suggest that, in P. esculentus testis, D-Asp increases StAR mRNA in both periods, and P450 aromatase and 5αRed2 mRNAs at different points during the reproductive cycle.     

An unusual case of fatty liver in a patient with desmoid tumor

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.     

Retroperitoneal hemorrhage after percutaneous coronary intervention in the current practice era: Clinical outcomes and prognostic value of abdominal/pelvic computed tomography

Background : Retroperitoneal hemorrhage (RPH) is a serious but infrequent complication of percutaneous coronary intervention (PCI). This study aimed to describe the clinical outcomes of patients who developed RPH following PCI in the current practice era, with particular focus on treatment strategies and the related prognostic value of abdominal/pelvic computed tomography (CT). Methods : Among 20,904 patients undergoing PCI, we identified 93 RPH (0.45%) confirmed by CT or by unequivocal surgical findings. We identified three groups with RPH for comparison: patients who developed refractory shock (systolic blood pressure <80 mm Hg for ≥30 min despite fluids and vasopressors, n = 16 [17.2%]); patients with transient hypotension (<30 min, n = 34 [36.6%]); and patients without hypotension (n = 43 [46.2%]). The primary endpoint was a composite of in‐hospital mortality, myocardial infarction, and cerebral vascular accident (CVA). Results : Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Patients who developed refractory shock had significantly more bleeding quantified by abdominal/pelvic CT (P < 0.001), had a higher rate and amount of red blood cell transfusion (P < 0.001), and were managed invasively more frequently (68.7%) than the rest of the population. The primary endpoint trended higher in patients presenting with refractory shock; however, this difference was not statistically significant. The volume of bleeding quantified by CT and the timing of imaging diagnosis did not correlate with the primary endpoint. Red blood cell transfusion, but not clopidogrel discontinuation, was associated with the primary endpoint. Conclusions : RPH remains as a serious complication of PCI and is associated with high rates of mortality and morbidity independently of the therapeutic strategy. In patients who were hemodynamically stable, RPH volume as quantified by non‐contrast abdominal/pelvic CT did not contribute to prognosis. © 2011 Wiley Periodicals, Inc.     

Low-Dose Acetazolamide in the Treatment of Premenstrual Dysphoric Disorder: A Case Series

The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.     

Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting

Clinical Rheumatology - Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to...     

Does Bone Resorption Stimulate Periosteal Expansion? A Cross‐Sectional Analysis of β‐C‐telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway,and Periosteal Circumference as Measured by pQCT

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β‐C‐telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMD_C). CTX and mid‐tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β = 0.19 [0.13, 0.24]) (coefficient = SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMD_C (β = –0.46 [–0.52,–0.40]) and cortical thickness [β = –0.11 (–0.18, –0.03)]. CTX was positively related to bone strength as reflected by the strength‐strain index (SSI) (β = 0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single‐nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF‐κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p < 0.05 cut‐off) (n = 2379). Subsequently, we performed a meta‐analysis of associations between these SNPs and PC in ALSPAC (n = 3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n = 938), and the Young Finns Study (YFS) (n = 1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p < 0.05 cut‐off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.