Urotensin-II immunoreactivity in children with chronic glomerulonephritis

BACKGROUND: Human urotensin-II (hU-II) is one of the most potent vasoconstrictors in mammals. To our knowledge, there is no study about the role of U-II in childhood glomerulonephritis.We first determined the expression of h U-II in kidneys of children with chronic glomerular diseases. METHODS: Normal human kidneys were obtained from postmortem biopsies and compared with the kidney biopsy specimens of 24 children with membranoproliferative glomerulonephritis (MPGN) and 6 children with membranous GN. Kidney needle biopsies in 10% neutral buffered-formalin prior to routine processing through to embedded blocking sections were cut, and immunohistochemical reactions were performed on paraffin-embedded tissue by an avidin-biotin peroxidase complex method. The antibodies used in the present study were hU-II. The positivities were revealed as weak (+), moderate (++), and severe (+++), according to the color intensity. RESULTS: In kidneys of children with MPGN, differently fom the normal kidneys, more dense U-II immunoreactivity was seen in the glomerular basement membrane (GBM), glomerular mesangium, Bowman capsule, and tubules. Interestingly, we also observed U-II immunoreactivity in crescents. In children with MGN, U-II was mostly seen in GBM and Bowman capsule. CONCLUSION: Our findings suggest that U-II may have a possible autocrine/paracrine function in the kidneys, and may be an important target molecule in studying renal pathophysiology.     

FZD6 is a novel gene for human neural tube defects

Neural tube defects (NTDs) are severe malformations of the central nervous system, affecting 1 of 1,000 live births. Mouse models were instrumental in defining the signaling pathways defective in NTDs, including the planar cell polarity (PCP), also called noncanonical Frizzled/Disheveled pathway. Based on the highly penetrant occurrence of NTDs in double Fzd3/Fzd6(-/-) mutant mice, we investigated the role of the human orthologues, FZD3 and FZD6, by resequencing a cohort of 473 NTDs patients and 639 ethnically matched controls. While we could not demonstrate a significant contribution of FZD3 gene, we identified five rare FZD6 variants that were absent in all controls and predicted to have a functional effect by computational analysis: one de novo frameshift mutation (c.1843_1844insA), three missense changes (p.Arg405Gln, p.Arg511Cys p.Arg511His), and one substitution (c.*20C>T) affecting the 3'-untranslated region (UTR) of the gene. The overall rate of predicted deleterious variants of FZD6 was 5.1-fold higher in cases compared to controls, resulting in a significantly increased NTDs mutation burden. This study demonstrates that rare nonsynonymous variants in FZD6 may contribute to NTDs in humans and enlarges the spectrum of mutations that link PCP pathway to NTDs.     

Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects

The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.     

Scalp Dermatoscopic Findings in Androgenetic Alopecia and Their Relations with Disease Severity

Background

Clinicians are searching for new methods to diagnose and predict the course of androgenetic alopecia noninvasively.

Objective

Our aim is to evaluate trichoscopic findings and their relations with disease severity in androgenetic alopecia.

Methods

The videodermatoscopic findings of 143 female and 63 male patients with androgenetic alopecia were compared with each other, with those of healthy subjects (n=100), and with those of patients with other nonscarring alopecias (n=208). Mann-Whitney U-test, χ² analyses, and logistic regression analysis were used for statistical analysis.

Results

No statistically significant relation was found between trichoscopic findings and severity in male androgenetic alopecia (MAGA) on the basis of the modified Hamilton Norwood scale (among 7 degrees); however, multihair follicular unit and perifollicular pigmentation were related to low severity whereas white dots, honeycomb pattern pigmentation, and brown dots were related to high severity. On the other hand, according to the Ludwig classification, arborizing red lines were related to low severity and brown dots were related to high severity, whereas there was no difference in stages between the Ebling and Olsen classifications in female androgenetic alopecia (FAGA). In the characteristic trichoscopic findings in this study, perifollicular pigmentation was found as a normal feature of the scalp, whereas multihair follicular unit and honeycomb pigment pattern, which were previously considered as normal features, were observed to be related to androgenetic alopecia.

Conclusion

No relation was found between MAGA severity and trichoscopic findings, as well as between FAGA severity according to different disease severity classifications and trichoscopic findings.     

Dermoscopic Findings in Scalp Psoriasis and Seborrheic Dermatitis; Two New Signs; Signet Ring Vessel and Hidden Hair

Background:

Psoriasis and seborrheic dermatitis are both chronic erythemato-squamous dermatoses that can involve the scalp. It may be difficult to differentiate these two diseases when there is isolated scalp involvement. Recently, trichoscopy is commonly used to differentiate noncicatricial alopecias including psoriasis and seborrheic dermatitis that can lead to telogen effluvium (TE).

Objectives:

The objective of this study is to evaluate the trichoscopic figures that may help to differentiate scalp psoriasis and seborrheic dermatitis.

Materials and Methods:

Thirty one with scalp psoriasis and 112 patients with seborrheic dermatitis were enrolled. Trichoscopic examinations were performed using a videodermatoscope (MoleMax 3^®). Trichoscopic findings of scalp psoriasis and seborrheic dermatitis were compared with each other, with 100 healthy individuals and with other noncicatricial alopecias including female androgenetic alopecia (FAGA) (n: 138), male androgenetic alopecia (n: 63), FAGA of male pattern (FAGA.M) (n: 5), alopecia areata (39), TE (n: 22) and trichotillomania (n: 4).

Results:

Atypical red vessels, red dots and globules (RDG), signet ring vessels (SRV), structureless red areas and hidden hairs (HH) were statistically more common in psoriasis while twisted red loops and comma vessels (CV) in seborrheic dermatitis. RDG were considered as the characteristic videodermatoscopic figure for psoriasis and arborizing red lines and CV for seborrheic dermatitis. In comparison with previous reports, our study yielded two new trichoscopic structures supporting the diagnosis of psoriasis; HH and SRV. Besides, according to our study, CV were described for the first time in seborrheic dermatitis and considered to be specific for seborrheic dermatitis.

Conclusion:

This study confirmed that trichoscopy might be useful in differentiating scalp psoriasis and seborrheic dermatitis from each other and from other noncicatricial alopecia with three trichoscopic structures as HH, SRV and CV.     

Contribution of VANGL2 mutations to isolated neural tube defects

Kibar Z, Salem S, Bosoi CM, Pauwels E, De Marco P, Merello E, Bassuk AG, Capra V, Gros P. Contribution of VANGL2 mutations to isolated neural tube defects. Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non‐canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi‐ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.     

Laparoscopic versus robotic-assisted Roux-en-Y gastric bypass: a retrospective,single-center study of early perioperative outcomes at a community hospital

Background

The purpose of this study was to compare the operative and early perioperative outcomes of laparoscopic versus robotic-assisted Roux-en-Y gastric bypass procedures performed in a community hospital setting.

Methods

The study was a chart review and analysis of the early perioperative outcomes of a total of 345 Roux-en-Y gastric bypass procedures performed by a single surgeon in a community hospital setting from January 2011 to October 2014. Of these, 173 procedures were performed laparoscopically and 172 were performed with robotic assistance utilizing the daVinci^® surgical platform. Factors such as baseline patient characteristics, operative time, estimated blood loss (EBL), conversions to open procedure, complication rates, adverse events, length of stay (LOS), and return to the operating room for the two groups were retrospectively analyzed from a prospectively maintained database. Student’s t test with unequal variances was used for statistical analysis, and a p value <0.05 was used for significance.

Results

There were no statistically significant differences in complication rates, EBL, or LOS between the two groups. There was a significant difference between the total operative times (135.30 ± 37.60 min for the laparoscopic procedure versus 154.84 ± 38.44 min for the robotic procedure, p < 0.05). There were no adverse intraoperative events, conversions to open procedures, leaks, strictures, returns to the operating room within 30 days, or mortalities in either group.

Conclusion

Our study, which is the first of its kind to analyze the operative and early perioperative outcomes between laparoscopic and robotic-assisted Roux-en-Y gastric bypass procedures in the US community hospital setting, indicates that both are comparable in terms of safety, efficacy, and operative and early perioperative outcomes.