Cancer,hear my battle CRY

Circadian clocks are cell-autonomous self-sustaining oscillators that allow organisms to anticipate environmental changes throughout the solar day and persist in nearly every cell examined. Environmental or genetic disruption of circadian rhythms increases the risk of several types of cancer, but the underlying mechanisms are not well understood. Here, we discuss evidence connecting circadian rhythms—with emphasis on the cryptochrome proteins (CRY1/2)—to cancer through in vivo models, mechanisms involving known tumor suppressors and oncogenes, chemotherapeutic efficacy, and human cancer risk.     

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.     

Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels

Chemokine-induced stem cell recruitment is a promising strategy for post myocardial infarction treatment. Injection of stromal cell-derived factor 1 (SDF1) has been shown to attract bone marrow-derived progenitor cells (BMPCs) from the blood that have the potential to differentiate into cardiovascular cells, which support angiogenesis, enabling the improvement of myocardial function. SDF1-GPVI bi-specific protein contains a glycoprotein VI (GPVI)-domain that serves as an anchor for collagen type I (Col I) and III, which are exposed in the wall of injured vasculature. In this study, we generated a cytocompatible hydrogel via photo-crosslinking of poly(ethylene glycol) diacrylate that serves as a reservoir for SDF1-GPVI. Controlled and sustained release of SDF1-GPVI was demonstrated over a period of 7 days. Release features were modifiable depending on the degree of the crosslinking density. Functionality of the GPVI-domain was investigated using a GPVI-binding ELISA to Col I. Activity of the SDF1-domain was tested for its CXCR4 binding potential. Preserved functionality of SDF1-GPVI bi-specific protein after photo-crosslinking and controllable release was successfully demonstrated in vitro supporting the implementation of this drug delivery system as a powerful tool for therapeutic protein delivery in the treatment of cardiovascular ischemic disease.     

Hippocampal degeneration in patients with amyotrophic lateral sclerosis

There is increasing appreciation of non-motor system involvement in amyotrophic lateral sclerosis (ALS), although its full extent and clinical significance remains to be established. This study tested the hypothesis that memory impairment in patients with ALS is related to hippocampal degeneration. Consecutive patients with ALS (58) and 29 matched controls participated in standardized neuropsychological assessment and magnetic resonance imaging. Patients with ALS performed worse in global cognitive functioning and executive and verbal memory tests (p < 0.05). The hippocampus was manually segmented in each hemisphere, and volumes were calculated with correction for intracranial volume. Analysis of covariance, controlled for the effect of age and education years, showed significantly smaller hippocampal volume on the right (p = 0.004) in patients with ALS. Verbal memory test performance correlated with the left hippocampal volume in patients with ALS (p < 0.05), although there was no significant correlation with tests of executive function and clinical variables underscoring the specificity of the present findings. Hippocampal volume loss and its correlation with the severity of verbal memory impairment highlight significant hippocampal involvement which can occur as a non-motor deficit in patients with ALS.