Notes

Single-molecule, full-length records isoform sequencing shows disease-associated RNA isoforms throughout cardiomyocytes.
Impaired energy metabolism in proximal tubular epithelial cells (PTECs) is strongly associated with various kidney diseases. Here, we characterized proximal tubular phenotype alternations during kidney injury and repair in a mouse model of folic acid nephropathy, in parallel, identified carnitine palmitoyltransferase 1α (CPT1α) as an energy stress response accompanied by renal tubular dedifferentiation. Genetic ablation of Cpt1α aggravated the tubular injury and interstitial fibrosis and hampered kidney repair indicate that CPT1α is vital for the preservation and recovery of tubular phenotype. Our data showed that the lipid accumulation and mitochondrial mass reduction induced by folic acid were persistent and became progressively more severe in PTECs without CPT1α. Interference of CPT1α reduced capacities of mitochondrial respiration and ATP production in PTECs, and further sensitized cells to folic acid-induced phenotypic changes. On the contrary, overexpression of CPT1α protected mitochondrial respiration and prevented against folic acid-induced tubular cell damage. These findings link CPT1α to intrinsic mechanisms regulating the mitochondrial respiration and phenotype of kidney tubules that may contribute to renal pathology during injury and repair.BACKGROUND A predictable consequence of long-term injection drug use is the destruction of the native venous system; as a consequence, people who inject drugs may eventually move to injection into skin and subcutaneous tissue, wounds, muscles, and arteries. These practices put people who inject drugs at risk for injection-related soft-tissue infection, vascular damage, ischemia, and compartment syndrome, all of which have overlapping presenting symptoms. CASE REPORT A 35-year-old man who injects drugs presented with foot swelling and discoloration initially concerning for necrotizing fasciitis or compartment syndrome. After progression despite appropriate antimicrobial and surgical treatment for soft-tissue infection, he was diagnosed with arterial insufficiency and resultant distal ischemia. This diagnosis was discovered only after obtaining additional history of the patient's drug use practices. Just prior to his symptoms, he had unintentionally injected a formed thrombus into his dorsalis pedis artery. CONCLUSIONS Intra-arterial injection of drugs can cause ischemia through a variety of mechanisms, including direct vessel trauma, arterial spasm, toxicity from the drug of abuse or an adulterant, embolism of particulate matter, and as proposed here, direct injection of preformed thrombus. Medical providers should be aware of the steps of injection drug use and their associated risks so that they can ask appropriate questions to focus their differential diagnosis, increase their understanding of common or current local injection practices, and develop rapport with the patient. Patient education on safe injection techniques may also reduce the risk of serious complications.BACKGROUND The aim of this study was to compare the outcomes following anterior cervical discectomy and fusion with zero-profile anchored spacer-ROI-C-fixation (ROI-C) vs combined intervertebral cage and anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS We retrospectively analyzed 87 patients who underwent operations between January 2015 and January 2019, including 42 patients that underwent ROI-C treatment (group A) and 45 that were treated by the ACDF approach (group B). Operative duration, blood loss, dysphagia, Neck Disability Index scores (NDI), Japanese Orthopaedic Association scores (JOA), and other complications were compared between these groups. In addition, implant settlement, fusion, and cervical Cobb angle were assessed via imaging analyses. GSK-3 beta pathway RESULTS Patients in group A and group B were followed for 22.6±3.3 months and 27.1±3.5 months, respectively (range 13-30 months). Relative to preoperative values, JOA scores were increased and NDI scores were reduced in both groups following treatment (P0.05). However, operative duration, intraoperative blood loss, and postoperative complications did differ significantly between these groups (P less then 0.05). Specifically, rates of short-term dysphagia were lower and recovery time was faster in group A relative to group B (P less then 0.05). CONCLUSIONS The findings from this study showed that ROI-C fixation achieved satisfactory outcomes, improved cervical curvature, restored intervertebral height, and was associated with shorter operative duration, reduced blood loss, and less dysphagia.
Pure autonomic failure (PAF) is a peripheral autonomic neurodegenerative disease caused by alpha-synuclein deposition that is predominantly confined to peripheral autonomic neurons. Patients present with insidious features of autonomic failure that have a chronic course.In this review, we highlight the features of PAF, the differentiating features from other autonomic neuropathies, the diagnostic tests, and the predictors for conversion to a central synucleinopathy.

Natural history studies have defined the predictors for and rate of conversion to a central alpha-synucleinopathy. Skin immunohistochemistry techniques and demonstration of length-dependent neuronal loss of both somatic and autonomic small fiber nerves, and intraneural phosphorylated synuclein deposition provide diagnostic biomarkers. In the future, diagnosis maybe supported by measuring cerebrospinal fluid alpha-synuclein oligomers using techniques, such as protein misfolding cyclic amplification assay and real-time quaking-induced conversionor alpha-synuclein, and protein amplification techniques are being investigated to provide an earlier and more specific diagnosis. A substantial number of PAF patients' phenoconvert to a central alpha-synucleinopathy.
An intronic G4C2 expansion mutation in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Although there are currently no treatments for this insidious, fatal disease, intense research has led to promising therapeutic strategies, which will be discussed here.

Therapeutic strategies for C9-ALS/FTD have primarily focused on reducing the toxic effects of mutant expansion RNAs or the dipeptide repeat proteins (DPRs). The pathogenic effects of G4C2 expansion transcripts have been targeted using approaches aimed at promoting their degradation, inhibiting nuclear export or silencing transcription. Other promising strategies include immunotherapy to reduce the DPRs themselves, reducing RAN translation, removing the repeats using DNA or RNA editing and manipulation of downstream disease-altered stress granule pathways. Finally, understanding the molecular triggers that lead to pheno-conversion may lead to opportunities that can delay symptomatic disease onset.

A large body of evidence implicates RAN-translated DPRs as a main driver of C9-ALS/FTD. Promising therapeutic strategies for these devastating diseases are being rapidly developed with several approaches already in or approaching clinical trials.
A large body of evidence implicates RAN-translated DPRs as a main driver of C9-ALS/FTD. Promising therapeutic strategies for these devastating diseases are being rapidly developed with several approaches already in or approaching clinical trials.
Typical clinical dosimetry models for trans-arterial radioembolization (TARE) assume uniform dose distribution in each tissue compartment. We performed simple voxel-based dosimetry using post-treatment 90Y PET following TARE with 90Y-resin microspheres and investigated its prognostic value in a pilot cohort.

Ten patients with 14 hepatocellular carcinoma lesions who underwent TARE with 90Y-resin microspheres were retrospectively included. The partition model-based expected target tumor dose (TDp) was calculated using a pretreatment 99mTc-macroaggregated albumin scan. From post-treatment 90Y-microsphere PET and voxel-wise S-value kernels, voxel-based dose maps were produced and the absorbed dose of each lesion (TDv) was calculated. Heterogeneity of intratumoral absorbed doses was assessed using the SD and coefficient of variation of voxel doses. The response of each lesion was determined based on contrast-enhanced MRI or CT, or both. Lesion responses were classified as local control success or failure. ProgPET using a simple method. TDv was a more effective prognostic factor for TARE than TDp and clinicopathologic factors in this pilot study. Further studies are warranted on the role of voxel-based dose and dose distribution in TARE.
Role of texture parameters on the basis of Ga-68 PSMA PET/CT in prostate cancer (Pca) is largely unexplored. Present work done is a preliminary study that aims to evaluate the role of Haralick texture features on the basis of Ga-68 PSMA PET/CT in Pca in which texture features were used to differentiate between normal prostate and Pca tissue.

The study retrospectively enrolled patients in two groups group 1 included 30 patients with biopsy-proven adenocarcinoma prostate and median age 64 years (range 50-82 years) who underwent baseline Ga-68 PSMA PET/CT prior to therapy; group 2 included 24 patients with pathologies other than Pca and median age 53.5 years (range 18-80 years) who underwent Ga-68 PSMA PET/CT as part of another study in our department. Patients in group 2 did not have any prostate pathology and served as controls for the study. The segmented images of prostate (3-D image) were used to calculate 11 Haralick texture features in MATLAB. SUVmax was also evaluated. All parameters were compared among the two groups using appropriate statistical analysis and P value <0.05 was considered significant.

All 11 Haralick texture features, as well as SUVmax, were significantly different among Pca and controls (P < 0.05). Among the texture features, contrast was most significant (P value of Mann-Whitney U <0.001) in differentiating Pca from normal prostate with AUROC curve of 82.9% with sensitivity and specificity 83.30% and 73.30%, respectively at cut-off 0.640. SUVmax was also significant with AUROC curve 94.0% and sensitivity and specificity 62.5% and 90%, respectively at cut-off 5.7. A significant negative correlation of SUVmax was observed with contrast.

Haralick texture features have a significant role in differentiating Pca and normal prostate.
Haralick texture features have a significant role in differentiating Pca and normal prostate.
Post Z0011 trial, axillary lymph node dissections (ALNDs) can be performed in patients with ≥3 positive axillary lymph nodes (ALNs). We investigated the diagnostic performance of 18F-fluorodeoxyglucose PET/computed tomography (FDG PET/CT) to predict ≥3 metastasis [high nodal burden (HNB)].

We retrospectively analyzed preoperative FDG PET/CT from January 2010 to June 2012. Patients had clinical T1-2N0 primary invasive breast cancer and underwent breast-conserving surgery with sentinel lymph node biopsy ± ALND. All suspicious ALNs were counted considering FDG-avidity with morphologic changes. Images were considered positive if the axillary basin took up more FDG than the surrounding tissue. On CT, abnormal ALNs were round/ovoid or had cortical thickening with contrast enhancement. PET/CT results were compared with the histology and follow-up findings.

In total, 221 females with 224 axillae were enrolled; 161 had negative, 53 had 1-2 metastasis [low nodal burden (LNB)] and 10 had HNB. The sensitivity, specificity, negative predictive value and positive predictive value of PET/CT for HNB were 70, 100, 98.
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