A Case of a Tarlov Cyst in a Pediatric Patient With Ehlers-Danlos Syndrome.

Ehlers-Danlos Syndrome (EDS), a rare genetic disorder, causes hyperlaxity, skin bruising, vascular disruption, and organ rupture. It presents with numerous complications, ranging from delayed gastric emptying to spontaneous rupture of blood vessels. A rare complication involves the neurological system and causes Tarlov cysts in the spinal canal. This gives rise to several symptoms, ranging from urinary and bowel incontinence to numbness and paresthesia. We report a case of an 11-year-old male with a past medical history of Ehlers-Danlos Syndrome, who presented with continued urinary and bowel incontinence, which was eventually found to be due to a Tarlov cyst. Although a handful of reports of Tarlov cysts exist in the literature, a presentation in a pediatric patient with a history of Ehlers-Danlos Syndrome is unconventional and unforeseen.

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their proliferation. The purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies (both in vitro and in vivo). An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies, to further improve survival outcomes in patients with solid organ cancers.

Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer's and Parkinson's diseases.

Genome-wide association studies of neurological diseases have identified thousands of variants associated with disease phenotypes. However, most of these variants do not alter coding sequences, making it difficult to assign their function. Here, we present a multi-omic epigenetic atlas of the adult human brain through profiling of single-cell chromatin accessibility landscapes and three-dimensional chromatin interactions of diverse adult brain regions across a cohort of cognitively healthy individuals. We developed a machine-learning classifier to integrate this multi-omic framework and predict dozens of functional SNPs for Alzheimer's and Parkinson's diseases, nominating target genes and cell types for previously orphaned loci from genome-wide association studies. Moreover, we dissected the complex inverted haplotype of the MAPT (encoding tau) Parkinson's disease risk locus, identifying putative ectopic regulatory interactions in neurons that may mediate this disease association. This work expands understanding of inherited variation and provides a roadmap for the epigenomic dissection of causal regulatory variation in disease.

HiChIRP reveals RNA-associated chromosome conformation.

Modular domains of long non-coding RNAs can serve as scaffolds to bring distant regions of the linear genome into spatial proximity. Here, we present HiChIRP, a method leveraging bio-orthogonal chemistry and optimized chromosome conformation capture conditions, which enables interrogation of chromatin architecture focused around a specific RNA of interest down to approximately ten copies per cell. HiChIRP of three nuclear RNAs reveals insights into promoter interactions (7SK), telomere biology (telomerase RNA component) and inflammatory gene regulation (lincRNA-EPS).

The chromatin accessibility landscape of primary human cancers.

We present the genome-wide chromatin accessibility profiles of 410 tumor samples spanning 23 cancer types from The Cancer Genome Atlas (TCGA). We identify 562,709 transposase-accessible DNA elements that substantially extend the compendium of known cis-regulatory elements. Integration of ATAC-seq (the assay for transposase-accessible chromatin using sequencing) with TCGA multi-omic data identifies a large number of putative distal enhancers that distinguish molecular subtypes of cancers, uncovers specific driving transcription factors via protein-DNA footprints, and nominates long-range gene-regulatory interactions in cancer. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy.

Tracking yeast pheromone receptor Ste2 endocytosis using fluorogen-activating protein tagging.

To observe internalization of the yeast pheromone receptor Ste2 by fluorescence microscopy in live cells in real time, we visualized only those molecules present at the cell surface at the time of agonist engagement (rather than the total cellular pool) by tagging this receptor at its N-terminus with an exocellular fluorogen-activating protein (FAP). A FAP is a single-chain antibody engineered to bind tightly a nonfluorescent, cell-impermeable dye (fluorogen), thereby generating a fluorescent complex. The utility of FAP tagging to study trafficking of integral membrane proteins in yeast, which possesses a cell wall, had not been examined previously. A diverse set of signal peptides and propeptide sequences were explored to maximize expression. Maintenance of the optimal FAP-Ste2 chimera intact required deletion of two, paralogous, glycosylphosphatidylinositol (GPI)-anchored extracellular aspartyl proteases (Yps1 and Mkc7). FAP-Ste2 exhibited a much brighter and distinct plasma membrane signal than Ste2-GFP or Ste2-mCherry yet behaved quite similarly. Using FAP-Ste2, new information was obtained about the mechanism of its internalization, including novel insights about the roles of the cargo-selective endocytic adaptors Ldb19/Art1, Rod1/Art4, and Rog3/Art7.

A Comparison of Face to Face and Video-Based Self Care Education on Quality of Life of Hemodialysis Patients.

BACKGROUND: End stage renal disease negatively affects the patients' quality of life. There are different educational methods to help these patients. This study was performed to compare the effectiveness of self-care education in two methods, face to face and video educational, on the quality of life in patients under treatment by hemodialysis in education-medical centers in Urmia. METHODS: In this quasi-experimental study, 120 hemodialysis patients were selected randomly; they were then randomly allocated to three groups: the control, face to face education and video education. For face to face group, education was given individually in two sessions of 35 to 45 minutes. For video educational group, CD was shown. Kidney Disease Quality Of Life- Short Form (KDQOL-SF) questionnaire was filled out before and two months after the intervention. Data analysis was performed in SPSS software by using one-way ANOVA. RESULTS: ANOVA test showed a statistically significant difference in the quality of life scores among the three groups after the intervention (P=0.024). After the intervention, Tukey's post-hoc test showed a statistically significant difference between the two groups of video and face to face education regarding the quality of life (P>0.05). CONCLUSION: Implementation of the face to face and video education methods improves the quality of life in hemodialysis patients. So, it is suggested that video educational should be used along with face to face education.