ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients

ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction.     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Precommissural Fornix in the Human Brain: A Diffusion Tensor Tractography Study

Purpose

Other than a single case report, no diffusion tensor tractography (DTT) studies of the precommissural fornix in the human brain have been conducted. In the current study, we attempted to visualize the precommissural fornix in the human brain using DTT.

Materials and Methods

We recruited 36 healthy volunteers for this study. Diffusion tensor images were scanned using a 1.5-T scanner, and the precommissural fornix was analyzed using Functional Magnetic Resonance Imaging of the Brain (FMRIB) software. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the precommissural fornix were measured.

Results

The precommissural fornix originated from the hippocampal formation on each hemisphere as a crus; both crura were then joined to the body of the fornix. The body of the fornix continued anteriorly to the level just superior to the anterior commissure, where it divided into each column of the precommissural fornix. Each column descended anteriorly to the anterior commissure and terminated in the septal nuclei. Values of FA, MD, and tract volumes of the precommissural fornix did not differ between the right and left hemispheres (p>0.05).

Conclusion

We believe that the methodology and results of this study would be helpful to future research on the precommissural fornix and in the elucidation of the pathology of diseases involving the precommissural fornix.     

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

Purpose

The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood.

Materials and Methods

The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes.

Results

DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008).

Conclusion

DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.     

Wear of 3D printed and CAD/CAM milled interim resin materials after chewing simulation

PURPOSEThe purpose of this in vitro study was to investigate the wear resistance and surface roughness of three interim resin materials, which were subjected to chewing simulation.MATERIALS AND METHODSThree interim resin materials were evaluated: (1) three-dimensional (3D) printed (digital light processing type), (2) computer-aided design and computer-aided manufacturing (CAD/CAM) milled, and (3) conventional polymethyl methacrylate interim resin materials. A total of 48 substrate specimens were prepared. The specimens were divided into two subgroups and subjected to 30,000 or 60,000 cycles of chewing simulation (n = 8). The wear volume loss and surface roughness of the materials were compared. Statistical analysis was performed using one-way analysis of variance and Tukey''s post-hoc test (α=.05).RESULTSThe mean ± standard deviation values of wear volume loss (in mm³) against the metal abrader after 60,000 cycles were 0.10 ± 0.01 for the 3D printed resin, 0.21 ± 0.02 for the milled resin, and 0.44 ± 0.01 for the conventional resin. Statistically significant differences among volume losses were found in the order of 3D printed, milled, and conventional interim materials (P<.001). After 60,000 cycles of simulated chewing, the mean surface roughness (Ra; μm) values for 3D printed, milled, and conventional materials were 0.59 ± 0.06, 1.27 ± 0.49, and 1.64 ± 0.44, respectively. A significant difference was found in the Ra value between 3D printed and conventional materials (P=.01).CONCLUSIONThe interim restorative materials for additive and subtractive manufacturing digital technologies exhibited less wear volume loss than the conventional interim resin. The 3D printed interim restorative material showed a smoother surface than the conventional interim material after simulated chewing.     

Inertia sensor-based guidance system for upperlimb posture correction

Stroke rehabilitation is labor-intensive and time-consuming. To assist patients and therapists alike, we propose a wearable system that measures orientation and corrects arm posture using vibrotactile actuators. The system evaluates user posture with respect to a reference and gives feedback in the form of vibration patterns. Users correct their arm posture, one DOF at a time, by following a protocol starting from the shoulder up to the forearm. Five users evaluated the proposed system by replicating ten different postures. Experimental results demonstrated system robustness and showed that some postures were easier to mimic depending on their naturalness.     

Initial management and long‐term follow up after the rehabilitation of a patient with severe dentoalveolar trauma: A case report

Dental trauma is common and for patients who suffer significant oral injuries, rehabilitation can be challenging to the clinical team. This case report describes the successful prosthetic replacement of multiple missing teeth lost due to severe dentoalveolar trauma, using iliac crest bone grafting, an implant‐retained removable dental prosthesis and implant‐supported crowns. Good functionality and aesthetic outcome were achieved.     

Retroperitoneal Bronchogenic Cyst Presenting Paraadrenal Tumor Incidentally Detected by 18F-FDG PET/CT

A follow-up ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT scan of a 57-year-old asymptomatic male who had undergone total thyroidectomy for thyroid cancer revealed a 5.0 × 4.0-cm, well-defined, ovoid-shaped mass around the left adrenal gland without definite FDG uptake. On the adrenal CT scan, the left paraadrenal tumor showed high attenuation on the precontrast scan without enhancement. The average Hounsfield unit (HU) was 58.1 on the precontrast scan and 58.4 on the postcontrast scan. The patient underwent laparoscopic adrenalectomy for resection of the left paraadrenal tumor. The final histopathologic examination revealed a bronchogenic cyst. Although retroperitoneal bronchogenic cysts are rare, they should be considered in the differential diagnosis of retroperitoneal cystic tumors. The preoperative diagnosis is difficult, but a contrast-enhanced CT scan or ¹⁸F-FDG PET/CT scan may be useful for differentiating hyperattenuated cysts from other soft tissue masses.