Vertebral compression fractures (VCFs) have various causes, including osteoporosis, neoplasms, and acute trauma. As painful VCFs may contribute to general physical deconditioning, management of ...painful VCFs has the potential for improving quality of life and preventing superimposed medical complications. Various imaging modalities can be used to evaluate a VCF to help determine the etiology and guide intervention. The first-line treatment of painful VCFs has been nonoperative or conservative management as most VCFs show gradual improvement in pain over 2 to 12 weeks, with variable return of function. There is evidence that vertebral augmentation (VA) is associated with better pain relief and improved functional outcomes compared to conservative therapy for osteoporotic VCFs. A multidisciplinary approach is necessary for the management of painful pathologic VCFs, with management strategies including medications to affect bone turnover, radiation therapy, and interventions such as VA and percutaneous thermal ablation to alleviate symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
A case of percutaneous discal cyst rupture in a 25-year-old professional American football player is reported. The patient presented with a 3-day history of severe left-sided back pain. Magnetic ...resonance imaging examination demonstrated a discal cyst effacing the left L4-L5 lateral recess, with interposed thecal sac. A sublaminar epidural injection was performed displacing the thecal sac, exposing the discal cyst, and allowing for percutaneous perforation. The patient had complete resolution of symptoms after discal cyst rupture and was able to compete in a professional football game 3 days later. Computed tomography-guided percutaneous rupture is a therapeutic modality that may be considered for treatment of a symptomatic discal cyst.
Background
Many research papers claim that patients with specific psychiatric disorders (major depressive disorder, posttraumatic stress disorder, borderline personality disorder, alcohol use ...disorder, and others) have smaller hippocampi, but most of those reports compared patients to healthy controls. We hypothesized that if psychiatrically matched controls (psychiatric control, matched for demographics and psychiatric comorbidities) were used, much of the biomarker literature in psychiatric research would not replicate. We used hippocampus and amygdala volume only as examples, as these are very commonly replicated results in psychiatry biomarker research. We propose that psychiatry biomarker research could benefit from using psychiatric controls, as the use of healthy controls results in data that are not disorder-specific.
Method
Hippocampus/amygdala volumes were compared between major depressive disorder, sex-/age-/race-matched healthy control, and psychiatric control (N = 126/group). Similar comparisons were performed for posttraumatic stress disorder (N = 67), borderline personality disorder (N = 111), and alcohol use disorder (N = 136).
Results
Major depressive disorder patients had smaller left (p = 8.79 × 10−3) and right (p = 3.13 × 10−3) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p = 0.018) and right (p = 8.64 × 10−4) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p = 7.90 × 10−3) and amygdala (p = 1.49 × 10−3) than healthy control. Alcohol use disorder had smaller right hippocampus (p = 0.034) and amygdala (p = .024) than healthy control. No differences were found between any of the four diagnostic groups and psychiatric control.
Conclusion
When psychiatric controls were used, there was no difference in hippocampal or amygdalar volume between any of the diagnoses studied and controls. This strategy (keeping all possible relevant variables matched between experimental groups) has been used to advance science for hundreds of years, and we propose should also be used in biomarker psychiatry research.
Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of ...patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of existing gene and variant-specific therapeutics at the time of diagnosis to avoid that treatment delays add up to the diagnostic odyssey of rare diseases' patients and their families.
This paper aims to provide guidance and give detailed instructions on how to write homogeneous systematic reviews of rare diseases' treatments in a manner that allows the capture of the results in a computer-accessible form. The published results need to comply with the FAIR guiding principles for scientific data management and stewardship to facilitate the extraction of datasets that are easily transposable into machine-actionable information. The ultimate purpose is the creation of a database of rare disease treatments ("Treatabolome") at gene and variant levels as part of the H2020 research project Solve-RD.
Each systematic review follows a written protocol to address one or more rare diseases in which the authors are experts. The bibliographic search strategy requires detailed documentation to allow its replication. Data capture forms should be built to facilitate the filling of a data capture spreadsheet and to record the application of the inclusion and exclusion criteria to each search result. A PRISMA flowchart is required to provide an overview of the processes of search and selection of papers. A separate table condenses the data collected during the Systematic Review, appraised according to their level of evidence.
This paper provides a template that includes the instructions for writing FAIR-compliant systematic reviews of rare diseases' treatments that enables the assembly of a Treatabolome database that complement existing diagnostic and management support tools with treatment awareness data.
Undesirable truncated recombinant protein products pose a special expression and purification challenge because such products often share similar chromatographic properties as the desired full length ...protein. We describe here our observation of both full length and a truncated form of a yeast protein (Gcn5) expressed in Escherichia coli, and the reduction or elimination of the truncated form by mutating a cryptic Shine-Dalgarno or START codon within the Gcn5 coding region. Unsuccessful attempts to engineer in a cryptic translation initiation site into other recombinant proteins suggest that cryptic Shine-Dalgarno or START codon sequences are necessary but not sufficient for cryptic translation in E. coli.
•We observed a truncated version of a yeast protein expressed in Escherichia coli.•The truncated protein resulted from cryptic initiation from a GTG codon.•Mutating the cryptic Shine Dalgarno site eliminated the truncated protein.•Introducing cryptic sites for other proteins did not produce truncated proteins.
While the detection of single-nucleotide variants (SNVs) is important for evaluating human health and disease, most genotyping methods require a nucleic acid extraction step and lengthy analytical ...times. Here, we present a protocol which utilizes the integration of locked nucleic acids (LNAs) into self-annealing loop primers for the allelic discrimination of five isocitrate dehydrogenase 1 R132 (
-R132) variants using loop-mediated isothermal amplification (LAMP). This genotyping panel was initially evaluated using purified synthetic DNA to show proof of specific SNV discrimination. Additional evaluation using glioma tumor lysates with known
-R132 mutational status demonstrated specificity in approximately 35 min without the need for a nucleic acid extraction purification step. This LNA-LAMP-based genotyping assay can detect single base differences in purified nucleic acids or tissue homogenates, including instances where the variant of interest is present in an excess of background wild-type DNA. The pH-based colorimetric indicator of LNA-LAMP facilitates convenient visual interpretation of reactions, and we demonstrate successful translation to an end-point format using absorbance ratio, allowing for an alternative and objective approach for differentiating between positive and negative reactions. Importantly, the LNA-LAMP genotyping panel is highly reproducible, with no false-positive or false-negative results observed.
Adverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their ...atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA.
We retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling >1.10 (PR).
79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mm3, LD-NCP 16.8 mm3, NCP 403.1 mm3, and CP 390.1 mm3. HRP was present in 81.0% patients. Patients with at least one >50% stenosis, or obstructive lesions, had significantly higher TPV, LD-NCP, NCP, and CP. Patients >65 years had more CP and higher PAV.
Our study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.
•Artificial intelligence augmented CCTA can accurately provide plaque analysis in ESRD patients, even with severe CAD.•ESRD patients have high plaque burden, frequent stenoses, and increasing calcified plaques with age.•Atherosclerotic plaque characteristics using artificial intelligence augmented CCTA may provide clinical risk prognostication.
In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey ...to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States.
Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA or TKA but canceled due to the COVID-19 elective surgery stoppage (3/2020-5/2020) were included in the study. Descriptive statistics along with subgroup analysis with Wilcoxon rank were performed.
In total, surveys were distributed to 2135 patients and completed by 848 patients (40%) from 15 institutions. Most patients (728/848, 86%) had their surgery postponed or canceled by the surgeon or hospital. Unknown length of surgical delay remained the highest source of anxiety among survey participants. Male patients were more likely to be willing to proceed with surgery in spite of COVID-19. There were minimal regional differences in responses. Only 61 patients (7%) stated they will continue to delay surgery for fear of contracting COVID-19 while in the hospital.
Similar to the previous study, the most anxiety-provoking thought was the uncertainty, over if and when the canceled joint replacement surgery could be rescheduled. Patients suffering from the daily pain of hip and knee arthritis who have been scheduled for elective arthroplasty remain eager to have their operation as soon as elective surgery is allowed to resume.
The purpose of this study was to investigate combat‐related post‐traumatic stress symptoms (PTSS) and couple relationships in Army couples. US Army combat veteran couples (N = 66 couples) completed ...self‐report questionnaires on couple functioning, coercion, resilience, and PTSS. In 23% of the couples (n = 15), both members had PTSS above the clinical cut‐off for suspected Post‐traumatic Stress Disorder (PTSD). Higher levels of PTSS were associated with lower couple functioning and resilience. Individuals with high resilience scores reported higher couple functioning scores, regardless of PTSS (p = .004). Future researchers should focus on the role of resilience in relation to couple functioning, and ways to amplify resilience in military couples. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. Res Nurs Health 35:164–177, 2012
The binding of RCC1 (regulator of chromosome condensation 1) to chromatin is critical for cellular processes such as mitosis, nucleocytoplasmic transport, and nuclear envelope formation because RCC1 ...recruits the small GTPase Ran (
Ras-related
nuclear protein) to chromatin and sets up a Ran-GTP gradient around the chromosomes. However, the molecular mechanism by which RCC1 binds to nucleosomes, the repeating unit of chromatin, is not known. We have used biochemical approaches to test structural models for how the RCC1 β-propeller protein could bind to the nucleosome. In contrast to the prevailing model, RCC1 does not appear to use the β-propeller face opposite to its Ran-binding face to interact with nucleosomes. Instead, we find that RCC1 uses a conformationally flexible loop region we have termed the switchback loop in addition to its N-terminal tail to bind to the nucleosome. The juxtaposition of the RCC1 switchback loop to its Ran binding surface suggests a novel mechanism for how nucleosome-bound RCC1 recruits Ran to chromatin. Furthermore, this model accounts for previously unexplained observations for how Ran can interact with the nucleosome both dependent and independent of RCC1 and how binding of the nucleosome can enhance RCC1's Ran nucleotide exchange activity.
PDF
