Long noncoding RNAs (lncRNAs) influence cellular function through binding events that often depend on the lncRNA secondary structure. One such lncRNA, metastasis-associated lung adenocarcinoma ...transcript 1 (MALAT1), is upregulated in many cancer types and has a myriad of protein- and miRNA-binding sites. Recently, a secondary structural model of MALAT1 in noncancerous cells was proposed to form 194 hairpins and 13 pseudoknots. That study postulated that, in cancer cells, the MALAT1 structure likely varies, thereby influencing cancer progression. This work analyzes how that structural model is expected to change in K562 cells, which originated from a patient with chronic myeloid leukemia (CML), and in HeLa cells, which originated from a patient with cervical cancer. Dimethyl sulfate-sequencing (DMS-Seq) data from K562 cells and psoralen analysis of RNA interactions and structure (PARIS) data from HeLa cells were compared to the working structural model of MALAT1 in noncancerous cells to identify sites that likely undergo structural alterations. MALAT1 in K562 cells is predicted to become more unstructured, with almost 60% of examined hairpins in noncancerous cells losing at least half of their base pairings. Conversely, MALAT1 in HeLa cells is predicted to largely maintain its structure, undergoing 18 novel structural rearrangements. Moreover, 50 validated miRNA-binding sites are affected by putative secondary structural changes in both cancer types, such as miR-217 in K562 cells and miR-20a in HeLa cells. Structural changes unique to K562 cells and HeLa cells provide new mechanistic leads into how the structure of MALAT1 may mediate cancer in a cell-type specific manner.
Congenital pseudoarthrosis of the tibia (CPT) remains a challenge for physicians. Several treatment options have been proposed, but the standard of care remains inconclusive. In this study, we ...present three patients for whom the failure of prior treatments was managed with a contralateral vascularized fibular bone graft (VFG) and an anatomic distal tibial locking plate.
Between 2017 and 2021, three patients were referred for failed treatment of CPT. All patients had undergone multiple prior surgeries, including tumor excision and fixation with ring external fixators, plates, and screws. We performed radical tumor resection and reconstruction of bone defects with a VFG. The construct was fixed with an anatomic locking plate, and the patients were followed up for a mean of 45.7 months.
All three patients were able to obtain graft union at 19.3 weeks. At the final follow-up, all grafts achieved bony hypertrophy without evidence of bone resorption or local tumor recurrence. There was a mean leg length difference of 8.5 cm preoperatively, compared with 6.3 cm postoperatively. The average lower leg angulation was 7.4 degrees and the average ankle range of motion was 58.3 degrees. The mean VAS score was 0 and the mean AOFAS score was 88.3. No significant complications were noted.
Implantation of a VFG and an anatomic distal tibia locking plate can be considered an option for treatment-refractory CPT. Patients can expect to achieve bone consolidation, ambulate as tolerated, and have a low complication rate.
Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbilical cord blood (UCB)-derived myeloid progenitor cells have been shown to decrease neuronal damage ...associated with ischemia in the central nervous system. In this study we show that UCB-derived CD14(+) progenitor cells provide rescue effects in a mouse model of ischemic retinopathy by promoting physiological angiogenesis and reducing associated inflammation. We use confocal microscopy to trace the fate of injected human UCB-derived CD14(+) cells and PCR with species-specific probes to investigate their gene expression profile before and after injection. Metabolomic analysis measures changes induced by CD14(+) cells. Our results demonstrate that human cells differentiate in vivo into M2 macrophages and induce the polarization of resident M2 macrophages. This leads to stabilization of the ischemia-injured retinal vasculature by modulating the inflammatory response, reducing oxidative stress and apoptosis and promoting tissue repair.
Abstract
Dinoflagellates are a group of unicellular protists with immense ecological and evolutionary significance and cell biological diversity. Of the photosynthetic dinoflagellates, the majority ...possess a plastid containing the pigment peridinin, whereas some lineages have replaced this plastid by serial endosymbiosis with plastids of distinct evolutionary affiliations, including a fucoxanthin pigment-containing plastid of haptophyte origin. Previous studies have described the presence of widespread substitutional RNA editing in peridinin and fucoxanthin plastid genes. Because reports of this process have been limited to manual assessment of individual lineages, global trends concerning this RNA editing and its effect on the biological function of the plastid are largely unknown. Using novel bioinformatic methods, we examine the dynamics and evolution of RNA editing over a large multispecies data set of dinoflagellates, including novel sequence data from the peridinin dinoflagellate Pyrocystis lunula and the fucoxanthin dinoflagellate Karenia mikimotoi. We demonstrate that while most individual RNA editing events in dinoflagellate plastids are restricted to single species, global patterns, and functional consequences of editing are broadly conserved. We find that editing is biased toward specific codon positions and regions of genes, and generally corrects otherwise deleterious changes in the genome prior to translation, though this effect is more prevalent in peridinin than fucoxanthin lineages. Our results support a model for promiscuous editing application subsequently shaped by purifying selection, and suggest the presence of an underlying editing mechanism transferred from the peridinin-containing ancestor into fucoxanthin plastids postendosymbiosis, with remarkably conserved functional consequences in the new lineage.
To report the results of open reduction, ulnar osteotomy, and annular ligament reconstruction all through a Boyd incision for chronic radial head dislocations in children.
Retrospective review.
...Tertiary pediatric orthopaedic care unit at a general hospital in Taichung, Taiwan.
From 1986 to 2003, 13 children, aged 4 to 13 (mean, 8.3) years, who had a chronic traumatic anterior dislocation of the radial head were treated at our institute. These patients were seen at our hospital 2 to 36 (mean, 8.2) months after injury.
Open reduction of the radial head, ulnar osteotomy, then rigid fixation with plate/screws, and annular ligament reconstruction with forearm fascia, all performed through a Boyd incision.
Forearm radiographs for reduction and osteotomy site union, physical examinations for elbow mobility, and Kim's elbow performance scores for overall elbow function. Evaluations were done at a special follow-up clinic for this study by a pediatric orthopaedic surgeon who was not involved in the patients' previous care.
Patient follow-up averaged 7.8 (range, 1-16.9) years after surgery. Twelve of our cases had successful radial head reductions, satisfactory elbow mobility, and excellent functional outcome. One case had a redislocation, was retreated, and had a fair result. Other complications included 1 patient with transient posterior interosseous nerve palsy, and 1 delayed union of an ulnar osteotomy site, which healed without further intervention at 1 year with an excellent result.
This surgical procedure provides a high success rate with a low level of complications for chronic radial head dislocations in children.
Describes an extrinsic-point-based, interactive image-guided neurosurgical system designed at Vanderbilt University, Nashville, TN, as part of a collaborative effort among the Departments of ...Neurological Surgery, Computer Science, and Biomedical Engineering. Multimodal image-to-image (II) and image-to-physical (IP) registration is accomplished using implantable markers. Physical space tracking is accomplished with optical triangulation. The authors investigate the theoretical accuracy of point-based registration using numerical simulations, the experimental accuracy of their system using data obtained with a phantom, and the clinical accuracy of their system using data acquired in a prospective clinical trial by 6 neurosurgeons at 4 medical centers from 158 patients undergoing craniotomies to respect cerebral lesions. The authors can determine the position of their markers with an error of approximately 0.4 mm in X-ray computed tomography (CT) and magnetic resonance (MR) images and 0.3 mm in physical space. The theoretical registration error using 4 such markers distributed around the head in a configuration that is clinically practical is approximately 0.5-0.6 mm. The mean CT-physical registration error for the: phantom experiments is 0.5 mm and for the clinical data obtained with rigid head fixation during scanning is 0.7 mm. The mean CT-MR registration error for the clinical data obtained without rigid head fixation during scanning is 1.4 mm, which is the highest mean error that the authors observed. These theoretical and experimental findings indicate that this system is an accurate navigational aid that can provide real-time feedback to the surgeon about anatomical structures encountered in the surgical field.
To propose a new fracture classification according to the direction of epiphysis displacement and to compare clinical findings and surgical outcomes between these subtypes.
Retrospective study.
A ...tertiary referral hospital.
Twelve adolescents (mean age, 13.4 ± 1.3 years) who experienced separation of the distal ulnar physis were identified from the pediatric trauma database.
Closed reduction was attempted for all injuries. If a satisfactory alignment could not be achieved, an open reduction was performed.
The clinical outcome was evaluated with Mikic's criteria (union, alignment, length, distal radioulnar joint subluxation, limitations of elbow/wrist function, and degree of supination/pronation). The impacts of fracture patterns and locations of wrist abrasions on treatment decisions and clinical outcomes were tested with Fisher exact tests (unadjusted) and logistic regression analyses (adjusted for age and gender) with the bootstrap method. Five orthopedic surgeons used the new classification, and the reproducibility was tested with multirater kappa.
The injury patterns included 6 dorsally-tilted distal ulnas (type 1) and 6 volarly-tilted distal ulnas type 2-A (n = 1), type 2-B (n = 3), and type 2-C (n = 2). All type 1 fractures were successfully treated with closed reduction. Five of 6 cases with type 2 injuries failed closed reduction because of entrapment of the extensor carpi ulnaris tendon in the fracture site. Eleven of the patients' outcomes were excellent. One patient with a type 2-C injury experienced ulnar growth arrest. The multirater kappa for the new classification equals to 0.94, and P < 0.001.
A majority of volar-flexion injuries require surgery to reduce the entrapped soft tissue. This new classification is easy to understand with a good interrater reproducibility. It is useful in identifying the injury mechanism and correlated with the likelihood of open reduction.
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
To delineate signals by which the vascular abnormalities inherent to ocular rosacea arise and to correlate these signals with elements of the innate immune system.
Experimental study. ...Immunohistochemical staining was performed for a variety of vascular markers and for toll-like receptor-4 on eyelid biopsies taken from patients with ocular rosacea and normal controls. Statistical comparisons were then performed between the 2 groups.
Immunohistochemical staining for CD31 and integrin-β-3 did not demonstrate any statistically significant differences between eyelids from patients with ocular rosacea and normal controls. Cutaneous biopsies from ocular rosacea patients demonstrated statistically significant enrichments of intercellular adhesion molecule-1 and CD105 among arterioles, whereas there were no statistically significant differences in the venules between normal controls and ocular rosacea patients. The correlation between the number of toll-like receptor-4-positive cells and each vascular marker was statistically significant.
Cutaneous biopsies of the eyelid did not demonstrate an increase in the total number of blood vessels. However, the vascular abnormalities that are typical of ocular rosacea represent activated, inflamed vessels, and these phenomena may be mediated by intercellular adhesion molecule and CD105. Furthermore, the strong correlations between toll-like receptor-4 and each vascular marker suggest that the innate immune system may govern the cutaneous effects of ocular rosacea. Intercellular adhesion molecule, CD105, and toll-like receptor-4 may represent important therapeutic targets in the management of this disease.
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