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f tesserae, creating a rich connectivity among cells. The network arrangement and the shape variation of chondrocytes in tesserae indicate that cells may interact within and between tesserae and manage mineralization differently from chondrocytes in other vertebrates, perhaps performing analogous roles to osteocytes in bone. BACKGROUND The diagnosis of renal osteodystrophy is challenging. Bone biopsy is the gold standard, but it is invasive and limited to one site of the skeleton. The ability of biomarkers to estimate the underlying bone pathology is limited. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging technique that allows assessment of regional bone turnover at clinically relevant sites. The hypothesis of this study was, that 18F-NaF PET correlates with bone histomorphometry in dialysis patients and could act as a noninvasive diagnostic tool in this patient group. METHODS This was a cross-sectional diagnostic test study. 26 dialysis patients with biochemical abnormalities indicating mineral and bone disorder were included. All the participants underwent a 18F-NaF PET scan and a bone biopsy. Fluoride activity in the PET scan was measured in the lumbar spine and at the anterior iliac crest. Dynamic and static histomorphometric parameters of the bone biopsy were assessed. As histomorphometric markers for bone turnover we used bone formation rate per bone surface (BFR/BS) and activation frequency per year (Ac.f). RESULTS There was a statistically significant correlation between fluoride activity in the 18F-NaF PET scan and histomorphometric parameters such as bone formation rate, activation frequency and osteoclast and osteoblast surfaces and mineralized surfaces. 18F-NaF PET's sensitivity to recognize low turnover in respect to non-low turnover was 76% and specificity 78%. ML792 cost Because of the small number of patients with high turnover, we were unable to demonstrate significant predictive value in this group. CONCLUSIONS A clear correlation between histomorphometric parameters and fluoride activity in the 18F-NaF PET scan was established. 18F-NaF PET may possibly be a noninvasive diagnostic tool in dialysis patients with low turnover bone disease, but further research is needed. The vitellogenin receptor (VgR) plays a critical role in egg development by mediating endocytosis of the major yolk protein precursor vitellogenin (Vg). Therefore, identifying the VgR of beneficial insects and its characterization could lead to the development of novel egg production strategies to enhance their commercial values. Here, we present the cloning, expression, and functional characterization of the VgR from an economically important eri silkworm, Samia ricini. The complete mRNA sequence was 6002 bp with an ORF of 5484 bp, encoding a protein of 1827 amino acids. Sequence analyses revealed that the SrVgR contained all of the conservative structural motifs characteristics of LDLR family members. The SrVgR was specifically expressed in the ovary, and the mRNA level increased steadily in pupal stages, reached its peak on day 9, and then declined to a bare minimum in adults. RNA interference (RNAi) clearly reduced the VgR transcript levels, disrupted the ovarian development resulting in malformed ovarioles and abnormal development of eggs. Taken together, these data provide conclusive evidence for the essential roles of VgR in insect reproduction. BACKGROUND Chronic obstructive respiratory disorders (ORD) are linked to increased rates of cancer related deaths. Little is known about the effects of hypercapnia (elevated CO2) on pancreatic ductal adenocarcinoma (PDAC) development and drug-resistance. STUDY DESIGN Two PDAC cell-lines were exposed to normocapnic (5% CO2) and hypercapnic (continuous/intermittent 10% CO2) conditions, physiologically similar to patients with active ORD. Cells were assessed for proliferation rate, colony formation, and chemo/radiotherapeutic efficacy. In a retrospective clinical study design, patients with PDAC who have undergone pancreatic resection between the years of 2002-2014 were reviewed. Active smokers were excluded in order to remove possible smoking-related pro-tumorigenic influences. Clinical data, pathological findings, and survival endpoints were recorded. Kaplan-Meier and Cox regression analyses were performed. RESULTS Exposure to hypercapnia resulted in an increased colony formation and proliferation rate, in-vitro in both cell lines (MIA-PaCa-2111% increase and Panc-1114% increase, P less then 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (P less then 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (P less then 0.05). Five hundred and seventy-eight patients were included [52% males, median age was 68.7 years (IQR 60.6-76.8 years)]. Cox regression analysis, assessing TNM-staging, age, gender and ORD status, identified ORD as an independent risk factor for both overall survival (HR 1.64, 95%CI 1.2-2.3, P less then 0.05) and disease-free survival (HR 1.68, 95%CI 1.06-2.67). CONCLUSIONS PDAC cells exposed to hypercapnic environments, common to patients with ORD, showed tumor proliferation, radioresistance and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care. BACKGROUND KCNE1 loss-of-function variants cause type 5 long QT syndrome (LQT5). However, most alleged LQT5-causative KCNE1 variants were identified before the true rate of background genetic variation was appreciated fully. OBJECTIVE The purpose of this study was to reassess the clinical and electrophysiological (EP) phenotypes associated with KCNE1 variants detected in a single-center LQTS cohort. METHODS Retrospective analysis of 1026 LQTS patients was used to identify those individuals with isolated KCNE1 ultra-rare variants (minor allele frequency [MAF] less then 0.0004 in the Genome Aggregation Database [gnomAD]). After classification according to American College of Medical Genetics (ACMG) guidelines, variants of uncertain significance (VUS) were characterized in vitro using whole-cell patch-clamp technique. Lastly, the clinical phenotype observed in ACMG pathogenic/likely pathogenic (P/LP) KCNE1-positive individuals was assessed. RESULTS Overall, 6 KCNE1 variants were identified in 38 of 1026 LQTS patients (3.
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