Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.

Effectiveness of vancomycin powder for preventing postoperative spinal infection.

OBJECTIVE: This study aimed to assess the effectiveness of Vancomycin Power (VP) and the occurrence of resistant organisms after four-year of routine VP use. METHODS: The study included 1063 patients who underwent posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) between January 2010 and February 2020. Intrawound VP was applied to all instrumented fusions starting in January 2016. The patients were divided into two groups: those who did not apply VP (non-VP) (n = 605) between 2010 and 2015, and those who did apply VP (VP) (n = 458) between 2016 and 2020. The baseline characteristics, clinical symptoms, infection rate, and causative organisms were compared between the two groups. RESULTS: The rate of PSI was not significantly different between the non-VP group (1.32 %, n = 8) and the VP group (1.09 %, n = 5). Although adjusted by diabetes mellitus, VP still did not show statistical significance (OR = 0.757 (0.245-2.345), p = 0.630). There were no critical complications that were supposed to relation with vancomycin powder. In the 13 cases of PSI, seven pathogens were isolated, with a gram-negative organism identified in the non-VP group. However, the type of organism was not significantly different between the two groups. CONCLUSIONS: The use of intrawound VP may not affect the PSI and occurrence of resistant organism and may not cause critical complications. Therefore, clinicians may decide whether to use VP for preventing PSI not worrying about its safety.

A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

Improved prediction of protein-protein interactions by a modified strategy using three conventional docking software in combination.

Proteins play a crucial role in many biological processes, where their interaction with other proteins are integral. Abnormal protein-protein interactions (PPIs) have been linked to various diseases including cancer, and thus targeting PPIs holds promise for drug development. However, experimental confirmation of the peculiarities of PPIs is challenging due to their dynamic and transient nature. As a complement to experimental technologies, multiple computational molecular docking (MD) methods have been developed to predict the structures of protein-protein complexes and their dynamics, still requiring further improvements in several issues. Here, we report an improved MD method, namely three-software docking (3SD), by employing three popular protein-peptide docking software (CABS-dock, HPEPDOCK, and HADDOCK) in combination to ensure constant quality for most targets. We validated our 3SD performance in known protein-peptide interactions (PpIs). We also enhanced MD performance in proteins having intrinsically disordered regions (IDRs) by applying the modified 3SD strategy, the three-software docking after removing random coiled IDR (3SD-RR), to the comparable crystal PpI structures. At the end, we applied 3SD-RR to the AlphaFold2-predicted receptors, yielding an efficient prediction of PpI pose with high relevance to the experimental data regardless of the presence of IDRs or the availability of receptor structures. Our study provides an improved solution to the challenges in studying PPIs through computational docking and has the potential to contribute to PPIs-targeted drug discovery. SIGNIFICANCE STATEMENT: Protein-protein interactions (PPIs) are integral to life, and abnormal PPIs are associated with diseases such as cancer. Studying protein-peptide interactions (PpIs) is challenging due to their dynamic and transient nature. Here we developed improved docking methods (3SD and 3SD-RR) to predict the PpI poses, ensuring constant quality in most targets and also addressing issues like intrinsically disordered regions (IDRs) and artificial intelligence-predicted structures. Our study provides an improved solution to the challenges in studying PpIs through computational docking and has the potential to contribute to PPIs-targeted drug discovery.

Computed Tomography Evaluation of Percutaneous Pedicle Screws Inserted during Minimally Invasive Transforaminal Lumbar Interbody Fusion: Long-term Follow-up Results of Screw Violation.

Background: To evaluate the accuracy of percutaneous pedicle screw (PPS) insertion in degenerative lumbar disease treated with minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and to analyze risk factors and long-term clinical outcomes of screw violation. Methods: Sixty-two consecutive patients (262 screws) were included. Based on postoperative computed tomography (CT) axial images, a PPS that perforated out of the pedicle was classified into a violation group, while screws surrounded by pedicular cortical bone were classified into a correct group. A logistic regression model was used for risk factor analysis of violation. We also observed the long-term clinical outcomes using the Oswestry disability index and visual analog scale. Results: Of the 262 screws, 14 (5.3%) were considered to be violated (10 medial violations and 4 lateral violations). All violations of S1 and L5 were in the medial direction. In contrast, entire violations of L4 were always lateral and of the 2 violations of L3, one was lateral and the other was medial. There were no cases of superior or inferior violation. The mean pedicle convergence angle (CA) was significantly higher in the violation group (mean ± standard deviation, 27.0° ± 6.2°) than in the correct group (21.7° ± 5.4°). There were no significant differences according to vertebral rotational angle, body mass index, bone mineral density, and surgical timing (learning curve) between the two groups. Logistic regression analyses demonstrated that a high CA was a significant risk factor for pedicle wall violation (p = 0.002). There were no significant differences in clinical or radiographic results between the two groups in 60 patients who were followed up for more than 1 year and in 40 patients who were followed up for more than 5 years. There were 2 patients who required reoperation to replace a screw due to leg pain. Conclusions: With PPS insertion during MI-TLIF, the rate of pedicle violation was 5.3% (14/262). An understanding of the anatomical characteristics of each vertebra and the unique structures of the patient is essential to prevent pedicle violations. Even in the violation group, PPS fixation was found to be a safe and useful procedure with successful long-term radiographic and clinical outcomes.

SUMOylation-mediated PSME3-20S proteasomal degradation of transcription factor CP2c is crucial for cell cycle progression.

Transcription factor CP2c (also known as TFCP2, α-CP2, LSF, and LBP-1c) is involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies such as cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover an unprecedented mechanism of CP2c degradation via a previously unidentified SUMO1/PSME3/20S proteasome pathway and its biological meaning. CP2c is SUMOylated in a SUMO1-dependent way, and SUMOylated CP2c is degraded through the ubiquitin-independent PSME3 (also known as REGγ or PA28)/20S proteasome system. SUMOylated PSME3 could also interact with CP2c to degrade CP2c via the 20S proteasomal pathway. Moreover, precisely timed degradation of CP2c via the SUMO1/PSME3/20S proteasome axis is required for accurate progression of the cell cycle. Therefore, we reveal a unique SUMO1-mediated uncanonical 20S proteasome degradation mechanism via the SUMO1/PSME3 axis involving mutual SUMO-SIM interaction of CP2c and PSME3, providing previously unidentified mechanistic insights into the roles of dynamic degradation of CP2c in cell cycle progression.

Is Routine Use of Drain Really Necessary for Posterior Lumbar Interbody Fusion Surgery? A Retrospective Case Series with a Historical Control Group.

STUDY DESIGN: A retrospective case-control study. OBJECTIVES: The usefulness of a drain in spinal surgery has always been controversial. The purposes of this study were to determine the incidence of hematoma-related complications after posterior lumbar interbody fusion (PLIF) without a drain and to evaluate its usefulness. METHODS: We included 347 consecutive patients with degenerative lumbar disease who underwent single- or double-level PLIF. The participants were divided into 2 groups by the use of a drain or not; drain group and no-drain group. RESULTS: In 165 cases of PLIF without drain, there was neither a newly developed neurological deficit due to hematoma nor reoperation for hematoma evacuation. In the no-drain group, there were 5 (3.0%) patients who suffered from surgical site infection (SSI), all superficial, and 17 (10.3%) patients who complained of postoperative transient recurred leg pain, all treated conservatively. Days from surgery to ambulation and length of hospital stay (LOS) of the no-drain group were faster than those of the drain group (P < 0.001). In a multiple regression analysis, a drain insertion was found to have a significant effect on the delayed ambulation and increased LOS. No significant differences existed between the 2 groups in additional surgery for hematoma evacuation, or SSI. CONCLUSIONS: No hematoma-related neurological deficits or reoperations caused by epidural hematoma and SSI were observed in the no-drain group. The no-drain group did not show significantly more frequent postoperative complications than the drain use group, hence the routine insertion of a drain following PLIF should be reconsidered carefully.

Management of Osteoporotic Vertebral Fracture: Review Update 2022.

A vertebral fracture is the most common type of osteoporotic fracture. Osteoporotic vertebral fractures (OVFs) cause a variety of morbidities and deaths. There are currently few "gold standard treatments" outlined for the management of OVFs in terms of quantity and quality. Conservative treatment is the primary treatment option for OVFs. The treatment of pain includes short-term bed rest, analgesic medication, anti-osteoporotic medications, exercise, and a brace. Numerous reports have been made on studies for vertebral augmentation (VA), including vertebroplasty and kyphoplasty. There is still debate and controversy about the effectiveness of VA in comparison with conservative treatment. Until more robust data are available, current evidence does not support the routine use of VA for OVF. Despite the fact that the majority of OVFs heal without surgery, 15%-35% of patients with an unstable fracture, persistent intractable back pain, or severely collapsed vertebra that causes a neurologic deficit, kyphosis, or chronic pseudarthrosis frequently require surgery. Because no single approach can guarantee the best surgical outcomes, customized surgical techniques are required. Surgeons must stay current on developments in the osteoporotic spine field and be open to new treatment options. Osteoporosis management and prevention are critical to lowering the risk of future OVFs. Clinical studies on bisphosphonate's effects on fracture healing are lacking. Teriparatide was intermittently administered, which dramatically improved spinal fusion and fracture healing while lowering mortality risk. According to the available literature, there are no standard management methods for OVFs. More multimodal approaches, including conservative and surgical treatment, VA, and medications that treat osteoporosis and promote fracture healing, are required to improve the quality of the majority of guidelines.

Clinical differences between delayed and acute onset postoperative spinal infection.

ABSTRACT: Spine surgeons often encounter cases of delayed postoperative spinal infection (PSI). Delayed-onset PSI is a common clinical problem. However, since many studies have investigated acute PSIs, reports of delayed PSI are rare. The purpose of this study was to compare the clinical features, treatment course, and prognosis of delayed PSI with acute PSI.Ninety-six patients diagnosed with postoperative spinal infection were enrolled in this study. Patients were classified into 2 groups: acute onset (AO) within 90 days (n = 73) and delayed onset (DO) after 90 days (n = 23). The baseline data, clinical manifestations, specific treatments, and treatment outcomes were compared between the 2 groups.The history of diabetes mellitus (DM) and metallic instrumentation at index surgery were more DO than the AO group. The causative organisms did not differ between the 2 groups. Redness or heat sensation around the surgical wound was more frequent in the AO group (47.9%) than in the DO group (21.7%) (P = .02). The mean C-reactive protein levels during infection diagnosis was 8.9 mg/dL in the AO and 4.0 mg/dL in the DO group (P = .02). All patients in the DO group had deep-layer infection. In the DO group, revision surgery and additional instrumentation were required, and the duration of parenteral antibiotic use and total antibiotic use was significantly longer than that in the AO group. Screw loosening, disc space collapse, and instability were higher in the DO group (65.2%) than in the AO group (41.1%) (P = .04). However, the length of hospital stay did not differ between the groups.Delayed-onset PSI requires more extensive and longer treatment than acute-onset surgical site infection. Clinicians should try to detect the surgical site infection as early as possible.

Long-Term Clinical and Radiological Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion: 10-Year Follow-up Results.

BACKGROUND: Many studies have reported that minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) provides satisfactory treatment comparable to other fusion methods. However, in the case of MI-TLIF, there are concerns about the long-term outcome compared to conventional bilateral PLIF due to the small amount of disc removal and the lack of autogenous bone graft. Long-term follow-up studies are still lacking as most of the previous reports have follow-up periods of up to 5 years. METHODS: Thirty patients who underwent MI-TLIF were followed up for > 10 years (mean, 11.1 years). Interbody fusion rates were determined using a modified Bridwell grading system. Adjacent segment disease (ASD) was defined as radiological adjacent segment degeneration (R-ASDeg) as seen on plain X-rays; reoperated adjacent segment disease referred to the subsequent need for revision surgery. Clinical outcomes after surgery were assessed based on back and leg pain as well as the Oswestry disability index (ODI). RESULTS: The overall radiological fusion rate, at the 1-, 5-, and 10-year follow-up was 77.1%, 91.4%, and 94.3%, respectively. The incidence of R-ASDeg 1, 5, and 10 years after surgery was 6.7%, 16.7%, and 43.3% at the proximal adjacent segment and 4.8%, 14.3%, and 28.6% at the distal adjacent segment, respectively. R-ASDeg at either the proximal or distal segment was determined in 50.0% of the patients 10 years postoperatively. All clinical parameters improved significantly during follow-up, although the ODI and the visual analog scale (VAS) for leg pain at the 10-year follow-up were significantly worse in the R-ASDeg group than in the other patients (P = 0.009, P = 0.040). CONCLUSION: MI-TLIF improved both clinical and radiological outcomes, and the improvements were maintained for up to 10 years after surgery. However, R-ASDeg developed in up to 50% of the patients within 10 years, and both leg pain on the VAS and the ODI were worse in patients with R-ASDeg.

Comparative Study of Radiological and Clinical Outcomes in Patients Undergoing Minimally Invasive Lateral Lumbar Interbody Fusion Using Demineralized Bone Matrix Alone or with Low-Dose Escherichia coli-Derived rhBMP-2.

OBJECTIVE: To compare the results of interbody fusion in patients undergoing minimally invasive lateral lumbar interbody fusion (LLIF) using demineralized bone matrix (DBM) alone versus DBM+recombinant human bone morphogenetic protein-2 (rhBMP2). METHODS: This retrospective case-controlled study was conducted in patients undergoing minimally invasive LLIF (n = 54) for lumbar interbody fusion; they were divided into 2 groups: DBM-only group and DMB+rhBMP2 group. The improvements of segmental and lumbar lordosis and restoration of disc height were measured, and the interbody fusion rates were determined using a modified Bridwell grading system. Clinical outcomes after surgery, such as visual analog scale scores of back pain and leg pain, and Oswestry disability index were compared. RESULTS: There were no significant differences in disc height, lumbar and segmental lordosis, or interbody fusion rate between the 2 groups. However, the proportion of Bridwell grade 1 as complete interbody bridging was higher in the DBM+rhBMP2 group than in the DBM-only group at both 6 and 12 months (P < 0.001). Clinical parameters showed equally significant improvement during follow-up in both groups, with no significant differences between the groups. CONCLUSION: In minimally invasive LLIF, adding Escherichia coli-derived rhBMP2 to DBM did not affect clinical outcomes or radiation parameters, but increased the speed of fusion and interbody bony bridging rate.

Comparison of Minimally Invasive Lateral Lumbar Interbody Fusion, Minimally Invasive Lateral Lumbar Interbody Fusion, and Open Posterior Lumbar Interbody Fusion in the Treatment of Single-Level Spondylolisthesis of L4-L5.

OBJECTIVE: To compare the outcomes of minimally invasive lateral lumbar interbody fusion (LLIF) with minimally invasive transforaminal lumbar interbody fusion (TLIF) and conventional open posterior lumbar interbody fusion (PLIF) for treating single-level spondylolisthesis at L4-L5. METHODS: The patients underwent minimally invasive LLIF (n = 18), minimally invasive TLIF (n = 17), and conventional open PLIF (n = 20) for spondylolisthesis at L4-L5. Reduction of slippage, improvement in segmental lordosis, and restoration of foraminal height were measured. Perioperative parameters such as blood loss and operation time and clinical outcomes such as visual analog scale score and Oswestry Disability Index were compared. RESULTS: Compared with the open PLIF group, the minimally invasive LLIF group showed greater restoration of mean foraminal height, significantly smaller mean intraoperative estimated blood loss, and less mean hemoglobin reduction on the third day postoperatively. Compared with the minimally invasive TLIF group, the minimally invasive LLIF group showed greater restoration of mean segmental lordosis. The minimally invasive LLIF group showed a significantly shorter mean time to start walking after surgery compared with the conventional open PLIF and minimally invasive TLIF groups. However, compared with the minimally invasive TLIF group, the minimally invasive LLIF group showed a significantly longer mean operating time. Clinical outcomes were not statistically different among the 3 groups. CONCLUSIONS: In the treatment of spondylolisthesis of L4-L5, minimally invasive LLIF provided an effective surgical alternative to minimally invasive TLIF or conventional open PLIF, with the advantages of less blood loss, the faster start of postoperative walking, and comparable improvement in radiologic parameters.

Is it enough for COVID-19 screening test? Limitation of swab test and general characteristics of mild symptom patients.

The most common method for SARS-CoV-2 testing is throat or nasal swabbing by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. In South Korea, drive-through swab test is used for screening system and community treatment centers (CTCs), which admit and treat confirmed COVID-19 patients with mild symptoms, are being used. This retrospective study was conducted on patients admitted to a CTC on March 6, 2020. A total of 313 patients were admitted. The nasal and throat swabs were collected from the upper respiratory tract, and a sputum test was performed to obtain lower respiratory samples. The positive rate of the first set of test, sputum test was higher than that of the swab test (p = 0.011). In the second set of test, 1 week after the first ones, the rate of positive swab tests was relatively high (p = 0.026). In the first set of test, 66 of 152 (43.4%) patients showed 24-h consecutive negative swab test results, when the sputum test results were considered together, that number fell to 29 patients (19.1%) (p < 0.001). Also, in the second set of test, 63 of 164 (38.4%) patients met the discharge criteria only when the swab test was considered; that number fell to 30 (18.3%) when the sputum test results were also considered (p < 0.001). Using the swab test alone is insufficient for screening test and discharge decision. Patients who may have positive result in the sputum test can be missed.

Effects of smoking on delayed neuropsychiatric sequelae in acute carbon monoxide poisoning: A prospective observational study.

ABSTRACT: Smoking is a well-known risk factor for cardio-cerebrovascular disease. However, several studies have reported the "smoker's paradox" whereby smokers have a better prognosis for cardio-cerebrovascular diseases. Similar to cardio-cerebrovascular diseases, hypoxia is one of the major mechanisms of injury in carbon monoxide (CO) poisoning. This study investigated the association between smoking and delayed neuropsychiatric sequelae (DNS) in acute CO poisoning.This study involved patients with CO poisoning treated at a university hospital in Bucheon, Korea between September 2017 and March 2020. The exclusion criteria were age <18 years, discharge against medical advice, loss to follow-up, persistent neurological symptoms at discharge, transfer from another hospital 24 hours after exposure, and transfer from another hospital after hyperbaric oxygen therapy. Logistic regression analysis was performed to find factors associated with DNS.Two hundred sixty three patients visited the hospital due to CO poisoning and of these, 54 were excluded. DNS was evaluated up to 3 months after discharge, and until this time, DNS occurred in 35 (16.8%) patients. And the incidence rate of DNS was lower in smokers than non-smokers (15, 12% vs 20, 23.8%, P = .040). Multivariable logistic regression analysis revealed that CO exposure time (odds ratio [OR] 1.003; confidence interval [CI] 1.001-1.005; P = .003), the Glasgow coma scale (GCS) (OR 0.862; CI 0.778-0.956; P = .005), and pack-years (OR 0.947; CI 0.903-0.993; P = .023) were statistically significant for DNS development.These results indicate that more pack-years smoked were associated with reduced risk of the development of DNS in acute CO poisoning, and that CO exposure time and GCS is a predictive factor for DNS occurrence.

Current Concepts in the Management of Osteoporotic Vertebral Fractures: A Narrative Review.

Vertebral fractures are the most common type of osteoporotic fracture and can increase morbidity and mortality. To date, the guidelines for managing osteoporotic vertebral fractures (OVFs) are limited in quantity and quality, and there is no gold standard treatment for these fractures. Conservative treatment is considered the primary treatment option for OVFs and includes pain relief through shortterm bed rest, analgesics, antiosteoporotic drugs, exercise, and braces. Studies on vertebral augmentation (VA) including vertebroplasty and kyphoplasty have been widely reported, but there is still debate and controversy regarding the effectiveness of VA when compared with conservative treatment, and the routine use of VA for OVF is not supported by current evidence. Although most OVFs heal well, approximately 15%-35% of patients with unstable fractures, chronic intractable back pain, severely collapsed vertebra (leading to neurological deficits and kyphosis), or chronic pseudarthrosis frequently require surgery. Given that there is no single technique for optimizing surgical outcomes in OVFs, tailored surgical techniques are needed. Surgeons need to pay attention to advances in osteoporotic spinal surgery and should be open to novel thoughts and techniques. Prevention and management of osteoporosis is the key element in reducing the risk of subsequent OVFs. Bisphosphonates and teriparatide are mainstay drugs for improving fracture healing in OVF. The effects of bisphosphonates on fracture healing have not been clinically evaluated. The intermittent administration of teriparatide significantly enhanced spinal fusion and fracture healing and reduced mortality risk. Based on the current literature, there is still a lack of standard management strategies for OVF. There is a need for greater efforts through multimodal approaches including conservative treatment, surgery, osteoporosis treatment, and drugs that promote fracture healing to improve the quality of the guidelines.

Cellular dynamics of myogenic cell migration: molecular mechanisms and implications for skeletal muscle cell therapies.

Directional cell migration is a critical process underlying morphogenesis and post-natal tissue regeneration. During embryonic myogenesis, migration of skeletal myogenic progenitors is essential to generate the anlagen of limbs, diaphragm and tongue, whereas in post-natal skeletal muscles, migration of muscle satellite (stem) cells towards regions of injury is necessary for repair and regeneration of muscle fibres. Additionally, safe and efficient migration of transplanted cells is critical in cell therapies, both allogeneic and autologous. Although various myogenic cell types have been administered intramuscularly or intravascularly, functional restoration has not been achieved yet in patients with degenerative diseases affecting multiple large muscles. One of the key reasons for this negative outcome is the limited migration of donor cells, which hinders the overall cell engraftment potential. Here, we review mechanisms of myogenic stem/progenitor cell migration during skeletal muscle development and post-natal regeneration. Furthermore, strategies utilised to improve migratory capacity of myogenic cells are examined in order to identify potential treatments that may be applied to future transplantation protocols.

Drug Discovery Targeting the Disorder-To-Order Transition Regions through the Conformational Diversity Mimicking and Statistical Analysis.

Intrinsically disordered proteins exist as highly dynamic conformational ensembles of diverse forms. However, the majority of virtual screening only focuses on proteins with defined structures. This means that computer-aided drug discovery is restricted. As a breakthrough, understanding the structural characteristics of intrinsically disordered proteins and its application can open the gate for unrestricted drug discovery. First, we segmented the target disorder-to-order transition region into a series of overlapping 20-amino-acid-long peptides. Folding prediction generated diverse conformations of these peptides. Next, we applied molecular docking, new evaluation score function, and statistical analysis. This approach successfully distinguished known compounds and their corresponding binding regions. Especially, Myc proto-oncogene protein (MYC) inhibitor 10058F4 was well distinguished from others of the chemical compound library. We also studied differences between the two Methyl-CpG-binding domain protein 2 (MBD2) inhibitors (ABA (2-amino-N-[[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-acetamide) and APC ((R)-(3-(2-Amino-acetylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester))). Both compounds bind MBD2 through electrostatic interaction behind its p66α-binding site. ABA is also able to bind p66α through electrostatic interaction behind its MBD2-binding site while APC-p66α binding was nonspecific. Therefore, structural heterogeneity mimicking of the disorder-to-order transition region at the peptide level and utilization of the new docking score function represent a useful approach that can efficiently discriminate compounds for expanded virtual screening toward intrinsically disordered proteins.

Tracheal Irrigation Without Bronchoscopy as an Alternative Emergent Treatment of Blood Aspiration.

BACKGROUND: Tracheobronchial foreign body aspiration can cause mild symptoms but may also become dangerous enough to cause death. Bronchoscopy is the first choice for the diagnosis and the removal of aspirated foreign bodies. So, when bronchoscopy is not available, the situation might get challenging. CASE REPORT: A 62-year-old man was waiting for emergent surgery for traumatic epidural hematoma in the Emergency Department (ED). Endotracheal intubation was performed for surgery and airway maintenance. However, oxygen saturation dropped and respiratory arrest was expected. As emergent bronchoscopy could not be performed, the emergency physician decided to irrigate the trachea by using 0.9% normal saline in the ED. After three rounds of irrigation, vital signs including oxygen saturation improved and the patient could undergo neurosurgical surgery. The patient was subsequently discharged with improved health. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Bronchoscopy is the first choice for the treatment and diagnosis in cases of bronchial aspiration of blood, such as that caused by epistaxis. However, in emergency situations, such as deteriorating vital signs due to aspiration of life-threatening amounts of blood from epistaxis, using blind tracheal irrigation as an alternative tool when bronchoscopy is not available can help in achieving clinically acceptable results.