Computational Analysis of miR-140 and miR-135as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy

Background@#Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. @*Methods@#The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. @*Results@#Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. @*Conclusions@#In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.

Bilateral tension pneumothoraces in a preterm low-birthweight newborn: tube thoracostomy using four 7-French latex catheters performed by an emergency physician

Neonatal tension pneumothorax is life-threatening. A tension pneumothorax on the right side was detected on a newborn boy weighing 2,380 g, who was born at 35 weeks of gestation. Given the unavailability of an on-duty thoracic surgeon and appropriately sized chest tubes in the neonatal intensive care unit, an emergency physician performed closed thoracostomy using two 7-French latex catheters. Immediately after the re-expansion of the right lung, left tension pneumothorax was newly detected. Two more 7-French latex catheters were inserted, relieving the left lesion. We consider that the right pneumothorax occurred due to the mixture of spontaneous rupture of the subpleural blebs and barotrauma during the initial positive pressure ventilation, while the left lesion did due to the high-flow oscillatory ventilation. Despite the limited availability of devices in the present case, a favorable outcome was achieved by the use of alternative catheters, which were chosen by the emergency physician.

A single emergency center study for obstructive urinary tract infection with sepsis

Objective@#Unlike common acute urinary tract infections, obstructive urinary tract infections caused by urinary calculus can be fatal because they can progress to sepsis and cause shock or disseminated intravascular coagulation. The evidence of patients with obstructive urinary tract infections caused by urinary tract stones visiting the emergency center is still lacking. @*Methods@#Seventy-seven patients who visited the emergency room with obstructive urinary tract infections caused by urinary calculus from January 2016 to December 2018 were enrolled in this study and divided into two groups: sepsis group and non-sepsis group. @*Results@#The lymphocyte count, platelet count, neutrophil-lymphocyte ratio, serum creatinine, and C-reactive protein were significantly different in the sepsis-positive and negative groups. Percutaneous nephrostomy was also significantly higher in the sepsis-positive group. The area under the receiver operating characteristic curve was calculated to evaluate the ability of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to predict a septic urinary tract infection. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 0.659 and 0.550, respectively. Multivariate logistic regression analysis showed that diabetic patients, percutaneous nephrostomy, and serum creatinine were associated with septic obstructive urinary tract infection. @*Conclusion@#In patients with an obstructive urinary tract infection who were referred to the emergency center, diabetic patients and those with high blood urea nitrogen and creatinine levels are at high risk of sepsis. In such cases, rapid diagnosis and treatment, such as percutaneous nephrostomy, are necessary.

Relationship between emergency department crowding and initial management, mortality of severe trauma patients

OBJECTIVE: This study examined whether emergency department (ED) crowding influences the timing of the initial assessment and treatment in severe trauma patients, as well as their mortality rates. METHODS: This retrospective, observational study was conducted between January 2015 and October 2016, and included adult severe trauma patients who presented to the ED. The emergency department occupancy rate (EDOR) was used to measure ED crowding. The patients were divided into four groups using the EDOR quartile. The timeliness of the initial assessment and treatment in the four groups as well as the mortality rates were compared. RESULTS: This study investigated 307 patients. The timing of the first computed tomography (CT) and laboratory test order, CT and laboratory test result acquisition, first transfusion, and patient transfer from the ED to the operating room were similar in the four groups. Multivariable logistic regression analysis did not show a significant difference in mortality between the groups. CONCLUSION: ED crowding was not associated with delays in the initial assessment and treatment of severe trauma patients, or in their mortality rates.

Objective Clinical Evaluation of Ocular Optical Instrument According to the Type of Lens Opacity

PURPOSE: To investigate the results using the OQAS and the Pentacam in cataract patients classified according to the type of lens opacity. METHODS: The present study included 124 eyes of 92 patients who had cataract surgery at Seoul St. Mary's Hospital from December 2011 to January 2012 and were classified into nuclear, cortical, and posterior subcapsular cataract patients. The lens opacity was determined with OSI, MTF, Strehl ratio, width 10%, width 50% and the opacity of Scheimpflug image by the OQAS and the Pentacam. Additionally, the correlation between subjective cataract classification and objective opacity value was analyzed. RESULTS: The nuclear cataract group showed a 6.40 +/- 2.41 OSI value and had high opacity. The cortical cataract group showed the highest MTF cut-off value (12.02 +/- 6.19 C/deg). When evaluating Pentacam results, the posterior subcapsular cataract group had the lowest average level of lens opacity (9.12 +/- 1.08) followed by in increasing order, the cortical cataract group (9.79 +/- 1.67) and the nuclear cataract group (11.08 +/- 1.84). The results were statistically significant (p < 0.001). The OSI value of the OQAS was significantly correlated with nuclear and posterior opacity (p = 0.049, p = 0.039, respectively) except cortical opacity (p = 0.781). MTF and nuclear opacity showed statistically significant correlation and the lens opacity of Pentacam was correlated with nuclear and posterior opacities. In cortical cataract with severe peripheral opacity, the cortical opacity showed significant correlation with Maximum. CONCLUSIONS: The OQAS and Pentacam results showed high correlation with the nuclear and posterior opacities which can be useful for cataract surgery.

Clinical Outcomes of M-Plus Intraocular Lenses

PURPOSE: To evaluate the clinical outcomes of eyes implanted with a zonal refractive multifocal intraocular lens (IOL) with an inferior segmental near add (M-plus), and to compare the outcomes between M-plus and a diffractive-type multifocal IOL, AT LISA (366D, bifocal). METHODS: We reviewed 19 eyes from 10 patients who were implanted with M-plus and 52 eyes of 26 patients who were implanted with AT LISA. The clinical outcomes of these 2 intraocular lenses were evaluated at 1 day and 2 months postoperatively, and consisted of distant, intermediate, and near visual acuity, contrast sensitivity, degree of tilt, and decentration using anterior segment photography, depth of focus, and patient satisfaction. RESULTS: There were no statistical differences between the 2 groups with respect to distant vision, near vision, refractive error, contrast sensitivity, degree of tilt, decentration, or satisfaction score. The M-plus group demonstrated significantly better intermediate visual acuity. In the defocus curve, the M-plus group also demonstrated significantly better visual acuities for intermediate unfocused vision levels. CONCLUSIONS: The M-plus multifocal IOLs are able to provide satisfactory distant and near visual acuity and visual function. The M-plus multifocal IOLs provide better intermediate vision than the AT LISA.

Comparison of Intraocular Pressure Correction Programs in Pentacam after Corneal Refractive Surgery

PURPOSE: To evaluate the accuracy of Pentacam(R) built-in 5 intraocular pressure (IOP) correction programs used to measure the IOP of patients who received corneal refractive surgery. METHODS: IOP of 124 eyes from 62 patients who underwent epipolis laser in situ keratomileusis was measured with Goldmann applanation tonometry (GAT) at 6 months pre- and post-operatively. The collected data was input into Pentacam(R), calculated by 5 correction programs, Ehlers, Shah, Dresden, Orssengo / Pye, Kohlhaas, and compared. RESULTS: The GAT-based pre- and post-operative IOP was 15.75 +/- 2.24 mm Hg, and 10.72 +/- 2.31 mm Hg, respectively, revealing the post-operative IOP to be significantly lower than the pre-operative IOP (p < 0.001). Among the 5 correction programs within Pentacam(R), Ehlers program showed little difference between pre- and post-operative IOP values (p = 0.228) and the post-operative correction value showed no significant difference with the pre-operative GAT value (p = 0.413). CONCLUSIONS: The Ehlers program is the most accurate among the 5 Pentacam(R) correction programs evaluated in the present study, and can be a useful tool for correcting the true IOP of patients which tends to be higher after corneal refractive surgery.

Changes in Optical Quality of Cataract Patients' Corrected Visual Acuity before and after Phacoemulsification

PURPOSE: To evaluate objectively the improvement level of a patient's visual function using the NEI-VFQ-25 questionnaire pre- and post-operatively and the OQAS results from the patient group who had the same corrected visual acuity pre- and post-operatively. METHODS: We examined and compared the NEI-VFQ-25 test, OSI, MTF cut-off, strehl ratio, OQAS, and width at 50% and 10% in 24 eyes of 24 patients who had cataract surgery between December 2011 and February 2012. The patients' corrected visual acuity in both eyes had no change (0.8 and 0.8) pre-operatively and 2 months post-operatively (1.0 and 1.0). RESULTS: The satisfaction level regarding the patients' visual function increased. The NEI-VFQ-25 test was 71.54 +/- 14.88 points pre-operatively and 85.70 +/- 6.17 points post-operatively. OSI decreased to 3.13 +/- 1.66 (OSI value) and 1.53 +/- 0.58 (OSI value), and MTF cut off value improved from 14.51 +/- 6.97 (C/deg) to 27.63 +/- 8.98 (C/deg). Strehl ratio was improved to 0.09 +/- 0.03 and 0.14 +/- 0.03, width at 50% improved to 8.44 +/- 3.73 and 4.52 +/- 1.90 and width at 10% improved to 35.30 +/- 15.22 and 18.04 +/- 8.87 pre- and post-operatively, respectively. CONCLUSIONS: The NEI-VFQ-25 test reflected the vision improvement in patients where after cataract surgery, determination of the visual function improvement only through vision would not be possible. In addition, the OQAS showed the quality of vision improved through quantified values.