Prevalence of cortical superficial siderosis in patients with cognitive impairment

Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group.     

Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis

Background

The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model.

Methods

Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used.

Results

In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls.

Conclusions

Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.     

The rectovaginal septum: visible on magnetic resonance images of women with Mayer-Rokitansky-Küster-Hauser syndrome (Müllerian agenesis)

Introduction and hypothesis

Ongoing debate exists about whether the rectovaginal septum (Denonvilliers’ fascia) is myth or reality. This study evaluates magnetic resonance images (MRI) of women with Müllerian agenesis for the presence of fascial layers between the rectum and the bladder to test the hypothesis that this layer exists in the absence of the vagina.

Methods

This is a secondary analysis of a study describing MRI aspects in women with vaginal agenesis before and after laparoscopic Vecchietti procedure. Study participants (n?=?16) had a multiplanar pelvic MR scan. Images were evaluated independently by two investigators (MH, JOLD) for the appearance of layers separate from the bladder and rectum in the area of interest, with characteristic anatomical features of the septum.

Results

Participants’ mean age was 19.4?±?2.6 years ± standard deviation (SD). In 12 of 16 patients (75 %) a distinct layer between rectum and bladder was identified in either the axial (4/16; 25 %) or sagittal (12/16; 75 %) scan or both. Characteristic anatomical features included lateral attachment to the levator ani muscle, cranial fusion to the cul-de-sac peritoneum, and caudal insertion into the perineal body.

Conclusions

Three quarters of women with Müllerian agenesis have a visible layer between bladder and rectum. As none of the participants had a vagina, these results support the existence of a rectovaginal septum, separate from a vaginal adventitia.     

Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.     

Sex differences in symptomatology of psychosis-risk patients and in prediction of psychosis

Archives of Women's Mental Health - Sex differences may be important for understanding underlying pathophysiological mechanisms and developing effective preventions and treatments of mental...     

Allorecognition of HLA-DP by CD4+ T cells is affected by polymorphism in its alpha chain

Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic alpha and a polymorphic beta chain, is increasingly being studied due to its relevance in clinical transplantation. We hypothesized that not only polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but also in other regions of the molecule and the alpha chain, could play a role in CD4+ T cell allorecognition. To test this possibility, we comparatively investigated CD4+ T cell allorecognition, measured by upregulation of the activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon 2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA-DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in CD4+ T cell allorecognition levels could be demonstrated for any of the beyond exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in CD4+ CD137+ cells was significantly higher when the target shared at least one DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1 background (1.65 vs 0.23, P < 0.005). Structural homology modeling suggested specific amino acid residues in the alpha chain, in particular position 31, to impact CD4+ T cell allorecognition of HLA-DP. Our data argue against a significant role of beyond exon 2 DPB1 polymorphisms for T cell alloreactivity, but show relevance of DPA1 polymorphism in this mechanism. These new findings impact HLA matching strategies in unrelated stem cell transplantation.     

Is there a need for orthodontic plaque indices?—diagnostic accuracy of four plaque indices

Objectives

The aim of this study was to assess the diagnostic performance and accuracy of four plaque indices for orthodontic patients.

Materials and methods

The plaque accumulation of 140 maxillary incisors with bonded brackets was recorded using intra-oral photographs and assessed using four different plaque indices: the orthodontic plaque (OP) index, the modified orthodontic plaque (MOP) index, the Quigley and Hein (QHP) index and the modified Navy plaque (MNP) index. The assessment was performed twice within a time interval of 4 weeks by four different examiner groups: orthodontists, dentists, students and orthodontic assistants.

Results

No significant differences were detected for the OP and MOP indices among the examiner groups. A significant difference was found for the QHP and MNP indices. The inter- and intra-examiner reliability of the OP and MOP indices was good. In contrast, the reliability for the QHP and MNP indices was moderate to poor with few exceptions. The discrimination performance of the OP and MOP indices was excellent. The sum of the sensitivity and specificity was generally lower for the QHP and MNP indices compared with the OP and MOP indices.

Conclusion

OP and MOP indices showed good performance. The QHP and MNP indices are not appropriate for orthodontic purposes.

Clinical relevance

Traditional plaque indices reflect the typical pattern of plaque accumulation for patients without multi-bracket appliances. The performance of these indices for orthodontic patients has never been investigated. Orthodontic plaque indices that focus on the surface along the gingival margin and areas around the bracket exhibit higher diagnostic performance and accuracy compared with traditional indices.