Sirtuin 6 Overexpression Improves Rotator Cuff Tendon-to-Bone Healing in the Aged.

Aging is an independent risk factor for recurrent tearing after surgical repair of rotator cuff ruptures around the tendon-to-bone area. However, aging signature factors and related mechanisms involved in the healing of the rotator cuff are still unknown. We hypothesized that differences in proteins involved in the rotator cuff according to age may affect tendon-to-bone healing.

Comparison of Functional and Cosmetic Outcomes According to Fracture Level in Gartland Type III Pediatric Supracondylar Humerus Fractures.

Background: Supracondylar humerus (SCH) fractures in children have been traditionally categorized according to the Wilkins-modified Gartland classification scheme, which is solely based on the degree of displacement. As this classification does not consider fracture patterns in the coronal or sagittal plane, the relationship between the fracture pattern and prognosis in SCH fractures remains unclear. Therefore, the purpose of this study was to evaluate the relationship between the fracture level and prognosis of pediatric SCH fractures.

Sirt6 Activation Ameliorates Inflammatory Bone Loss in Ligature-Induced Periodontitis in Mice.

Periodontitis is an inflammatory disease caused by microorganisms that induce the destruction of periodontal tissue. Inflamed and damaged tissue produces various inflammatory cytokines, which activate osteoclasts and induce alveolar bone loss and, eventually, tooth loss. Sirt6 expression suppresses inflammation and bone resorption; however, its role in periodontitis remains unclear.

Locking Multi-Laser Frequencies to a Precision Wavelength Meter: Application to Cold Atoms.

We herein report a simultaneous frequency stabilization of two 780-nm external cavity diode lasers using a precision wavelength meter (WLM). The laser lock performance is characterized by the Allan deviation measurement in which we find σy=10-12 at an averaging time of 1000 s. We also obtain spectral profiles through a heterodyne spectroscopy, identifying the contribution of white and flicker noises to the laser linewidth.

CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway.

CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in resistance to conventional anti-cancer therapies. We evaluated the expression of CSNK2A1 and phosphorylated SIRT6 in the 37 osteosarcoma patients and investigated the effects of CSNK2A1 and the phosphorylation of SIRT6 on Ser338 on resistance to the anti-cancer effects of doxorubicin.

Expression of IL4Rα and IL13Rα1 are associated with poor prognosis of soft-tissue sarcoma of the extremities, superficial trunk, and retroperitoneum.

Background: IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited.

Translation step-cut osteotomy for posttraumatic Cubitus Varus in adults: a retrospective study.

Background: Cubitus varus is a complex three-dimensional deformity. Various osteotomies have been introduced to correct this complex deformity. The objective of the present study was to evaluate clinical and functional outcomes of adult cubitus varus deformity treated with translation step-cut osteotomy.

Inhibition of SIRT6 potentiates the anti-tumor effect of doxorubicin through suppression of the DNA damage repair pathway in osteosarcoma.

Background: SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy.

Methods: We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor.

Poly (ADP-Ribose) Polymerase Inhibitor Treatment as a Novel Therapy Attenuating Renal Ischemia-Reperfusion Injury.

Intrarenal robust inflammatory response following ischemia-reperfusion injury (IRI) is a major factor in the pathogenesis of renal injury in ischemic acute kidney injury (AKI). Although numerous studies have investigated various agents of immune modulation or suppression for ischemic AKI, few showed reproducible effects. We hypothesized that poly (ADP-ribose) polymerase (PARP) inhibitor may favorably change post-ischemic intrarenal immunologic micromilieu by reducing damage-associated molecular pattern (DAMP) signals and improve renal outcome in ischemic AKI.

Osteoblasts/Osteocytes sirtuin6 Is Vital to Preventing Ischemic Osteonecrosis Through Targeting VDR-RANKL Signaling.

Ischemic osteonecrosis (ION) can produce permanent deformity and osteoarthritis in the femoral head and other joints. No biologic treatment has been established, and the molecular mechanisms involved in the pathogenesis of ION have not been elucidated. In this work, we found that treatment with sirtuin6 (Sirt6) suppressed inflammatory cytokines, bone resorption, progression of osteoarthritis, and reduced bone deformity in an ION mouse model.

Myositis ossificans of the thigh causing external compression of the superficial femoral artery and vein: A case report.

Rationale: Myositis ossificans (MO) is a benign condition characterized by heterotopic bone formation in the skeletal muscle of extremities. Marked variation can occur in the incidence and location of the bone formed as well as resulting complications. Femoral vessel obstruction caused by MO is an extremely rare but disabling complication.

Treatment Outcomes at Skeletal Maturity after Calcaneo-Cuboid-Cuneiform Osteotomy for Symptomatic Flatfoot Deformity in Children.

Background: The purpose of this study was to evaluate clinical and radiological outcomes at skeletal maturity after a calcaneo-cuboid-cuneiform osteotomy (triple C osteotomy) for symptomatic flatfoot deformity compared with healthy young adult controls.

Methods: Nineteen patients (30 feet) who undergone a triple C osteotomy for idiopathic symptomatic flatfeet from July 2006 to April 2013 were compared with 19 controls (38 feet). Radiographic measurements at preoperative examination, 1-year postoperative follow-up, and follow-up at skeletal maturity were evaluated.

Non-compartmental data analysis using SimBiology and MATLAB.

MATLAB® is widely used for numerical analysis, modeling, and simulation. One of MATLAB's tools, SimBiology®, is often used for pharmacokinetic, pharmacodynamic model and dynamic systems; however, SimBiology seems to be rarely used for non-compartmental analysis (NCA), and the published official documentation provides a poor description of the analysis algorithm for NCA. Therefore, we conducted NCAs with a hypothetical dataset and some scenarios and compared the results.

Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.

In this study, we aimed to identify a candidate drug that can activate endogenous Angiopoietin 1 (Ang1) expression via drug repositioning as a pharmacological treatment for avascular osteonecrosis. After incubation with 821 drugs from the Food and Drug Administration (FDA)-approved drug library, Ang1 expression in U2OS cell culture media was examined by ELISA. Metformin, the first-line medication for treatment of type 2 diabetes, was selected as a candidate for in vitro and in vivo experimental evaluation.

Do All ASPECT Score Regions have the Same Predictive Power for Functional Outcomes?

Background And Purpose: ASPECTS (Alberta Stroke Program Early CT Score) is a 10-point topographic CT scan score that has been shown to be a strong prognostic factor in acute ischemic stroke. We investigated whether all ASPECTS regions have the same prognostic value.

Methods: Clinical characteristics, ASPECTS, and 3-month modified Rankin Scale (mRS) data were retrospectively collected in 350 patients who were diagnosed with middle cerebral artery (MCA) territory stroke.

Effects of Celecoxib on the QTc Interval: A Thorough QT/QTc Study.

Purpose: Celecoxib is a selective cyclooxygenase-2 inhibitor widely used in patients with osteoarthritis and rheumatoid arthritis. Recently, nonclinical data on the inhibition of human ether-à-go-go-related gene potassium channels by celecoxib were reported, but there is no compelling evidence for this finding in humans. The aim of this study was to assess the potential effects of celecoxib on cardiac repolarization by conducting a thorough QT study, which was designed in compliance with the related guidelines.

Squamous cell carcinoma of the renal pelvis presenting as an integumentary neoplasm of the flank: A case report.

Rationale: Although chronic pyelonephritis and urolithiasis are established risk factors for squamous cell carcinoma (SCC), only a minority of patients with chronic urolithiasis eventually develop SCC. It is believed that the chronic irritation leads to squamous cell metaplasia that may subsequently develop into SCC. Although studies show that SSC generally spreads locally with associated symptoms of lymphadenopathy, metastasis to the lungs and liver have also been reported.

Pharmacokinetic and Safety Profiles of a Fixed-Dose Combination of Amlodipine, Valsartan, and Atorvastatin: A 3-Period Replicate Crossover Study.

The objective of study was to compare the pharmacokinetic and safety profiles of a fixed-dose combination (FDC) formulation of 5/160/20 mg amlodipine/valsartan/atorvastatin with those of separate formulations of a 5/160-mg amlodipine/valsartan tablet and a 20-mg atorvastatin tablet. This was a randomized, open-label, single-dose, 3-sequence, 3-period replicate crossover study with 42 subjects. Serial blood samples for pharmacokinetic assessment were collected up to 72 hours postdose.

FAM83H is involved in stabilization of β-catenin and progression of osteosarcomas.

Background: FAM83H was initially identified as a protein essential for dental enamel formation. Recent reports have shown that FAM83H is also involved in the progression of human cancers in conjunction with tumor-associated molecules, such as MYC and β-catenin. However, the role of FAM83H in sarcoma has not yet been investigated.

Sirtuin 6 in preosteoclasts suppresses age- and estrogen deficiency-related bone loss by stabilizing estrogen receptor α.

Emerging evidence indicates that estrogen receptor (ER) α is an important modulator of bone homeostasis, which occurs partly by promoting osteoclast apoptosis. Sirtuin 6 (Sirt6) is an anti-aging molecule, and its deficiency in mice results in skeletal malformations associated with progeroid features. However, the effects of Sirt6 on ERα function in osteoclasts, and thus on aging- or estrogen deficiency-induced bone loss, have not been studied.

Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects.

Purpose: We evaluated potential drug-drug interactions between cilostazol and simvastatin, both CYP3A substrates, in healthy subjects.

Methods: An open-label, two-period, fixed-sequence clinical study was conducted. Seventeen subjects were given a single oral dose of simvastatin 40 mg on day 1 and multiple oral doses of cilostazol 100 mg twice daily on days 2 to 5 followed by a single dose of cilostazol and simvastatin on day 6.

Effect of surgical approach for contralateral side hip arthroplasty in below knee amputees: a retrospective cohort study.

Background: The gluteus medius muscle plays a very important role in the stability of the gait, especially in patients with amputation of the lower limbs. Therefore, choosing the appropriate type of approach for hip arthroplasty is very important. Hence, this study aimed to compare the outcomes and complications between the anterolateral approach (ALA) and posterior approach (PA) for hip arthroplasty in patients with contralateral below knee amputation.

Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

Objective: This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and safety properties of the test (CJ-40001) and reference (NESP) versions of darbepoetin alfa following a single subcutaneous (SC) or intravenous (IV) administration in healthy male subjects.

Methods: A single-blind, randomized, single-dose, two-period, two-intervention crossover study was conducted, with two separate parts consisting of SC or IV administration. In each period, either a test or reference product was administered via the SC or IV route.

No pharmacokinetic interactions between candesartan and amlodipine following multiple oral administrations in healthy subjects.

Purpose: To evaluate the pharmacokinetics and pharmacodynamics of candesartan and amlodipine in the absence and presence of each other in healthy subjects.

Methods: This study consisted of two parts: part 1, the effect of amlodipine on candesartan; part 2, the effect of candesartan on amlodipine. Each part was designed as a randomized, open-label, two-sequence, two-period, two-intervention crossover study with 20 subjects and performed separately in different populations.