Therapeutic ultrasound has been studied for over seven decades for different medical applications. The versatility of ultrasound applications are highly dependent on the frequency, intensity, duration, duty cycle, power, wavelength, and form. In this review article, we will focus on low-intensity continuous ultrasound (LICUS). LICUS has been well-studied for numerous clinical disorders, including tissue regeneration, pain management, neuromodulation, thrombosis, and cancer treatment. PubMed and Google Scholar databases were used to conduct a comprehensive review of all research studying the application of LICUS in pre-clinical and clinical studies. The review includes articles that specify intensity and duty cycle (continuous). Any studies that did not identify these parameters or used high-intensity and pulsed ultrasound were not included in the review. The literature review shows the vast implication of LICUS in many medical fields at the pre-clinical and clinical levels. Its applications depend on variables such as frequency, intensity, duration, and type of medical disorder. Overall, these studies show that LICUS has significant promise, but conflicting data remain regarding the parameters used, and further studies are required to fully realize the potential benefits of LICUS.

Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene. Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs). Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily. Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets. To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles. Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development. The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS. In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function. Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.

Previously, we created an 8-h limited-access dual bottle drinking paradigm to deliver methylphenidate (MP) to rats at two dosages that result in a pharmacokinetic profile similar to patients treated for attention deficit hyperactivity disorder. Chronic treatment resulted in altered behavior, with some effects persisting beyond treatment. In the current study, adolescent male Sprague–Dawley rats were split into three groups at four weeks of age: control (water), low-dose MP (LD), and high-dose MP (HD). Briefly, 4 mg/kg (low dose; LD) or 30 mg/kg (high dose; HD) MP was consumed during the first hour, and 10 mg/kg (LD) or 60 mg/kg (HD) MP during hours two through eight. Following three months of treatment, half of the rats in each group (n = 8–9/group) were euthanized, and remaining rats went through a 1-month abstinence period, then euthanized. In vitro receptor autoradiography was performed to quantify binding levels of dopamine transporter (DAT), dopamine type 1 (D1R)-like receptors, and dopamine type 2 (D2R)-like receptors using [³H] WIN35,428, [³H] SCH23390, and [³H] Spiperone, respectively. Immediately following treatment, HD MP-treated rats had increased DAT and D1R-like binding in several subregions of the basal ganglia, particularly more caudal portions of the caudate putamen, which correlated with some previously reported behavioral changes. There were no differences between treatment groups in any measure following abstinence. These findings suggest that chronic treatment with a clinically relevant high dose of MP results in reversible changes in dopamine neurochemistry, which may underlie some effects on behavior.

With the increasing elderly population and obesity epidemic, diabetes is an important factor in arthroplasty planning. Although research suggests diabetes is associated with increased postoperative morbidity after hip and knee replacement, the effect of diabetes and varying management with insulin versus non-insulin agents on total shoulder arthroplasty (TSA) is not established. All TSAs from 2015 to 2016 were queried from the American College of Surgeons National Surgical Quality Improvement Program database. Age, gender, BMI, steroid, ASA, operative time, and smoking status were compared between all diabetics, diabetics on insulin, diabetics on non-insulin agents, and non-diabetics to account for confounding variables. Thirty-day postoperative complications, readmission rate, surgical site infection (SSI), and non-routine discharge to rehabilitation were compared using bivariate and multivariate binary logistic regression. Postoperative time to discharge between diabetic groups was analyzed using univariate ANOVA with Tukey’s test. The analysis included 7246 patients (insulin in 5% (n = 380), non-insulin in 13% (n = 922), and non-diabetics in 82% (n = 5944)). Diabetics were more likely to have an ASA ≥ 3 compared to non-diabetics (89.5% vs 50.1%; p < 0.001). Bivariate logistic regression showed statistical significance in readmission and non-routine discharge between all diabetics and non-diabetics (OR 1.7, 1.4; p = 0.001, 0.001), but there was no significance between SSI rate (0.3% vs 0.4%; p = 0.924). Multivariate logistic regression between groups showed significance in readmission between non-insulin diabetics vs non-diabetics (OR 1.5; p = 0.027), readmission and non-routine discharge in insulin vs non-diabetics (OR 2.1, 1.7; p = 0.003, < 0.001), and no significance between insulin and non-insulin diabetics. Postoperative days to discharge were 2.4, 2.0, and 1.8 days in insulin, non-insulin, and non-diabetics respectively. Mean differences were significant between all groups. Diabetic patients are at a higher risk for readmission and non-routine discharge compared to non-diabetics. Despite no increased risk in SSI, longer postoperative discharge time in diabetics should be considered in TSA planning. Not applicable Level III, case-control study

Methylphenidate (MP) is the most prescribed psychostimulant for ADHD patients, with clinically demonstrated detrimental effects on bone quality, potentially leading to early onset osteoporosis and higher fracture risk. The underlying mechanism for the effects of MP on bone remains elusive. This study demonstrates that sex- and dose-dependent effects of MP on bone quality and quantity are mediated by osteoclast activity. Four-week-old male and female rats were treated with low and high dose MP for 13 weeks. Bone quality and quantity were analyzed using microCT, mechanical testing, histomorphometry, and TRAP staining. Male and female rat bone marrow-derived osteoclasts were treated in a dose-dependent manner (0–1000 ng/ml) and osteoclast activity was determined at days 5, 7, and 14 using TRAP staining, as well as a pit formation assay at day 18. Animal studies showed a dose- and a sex-dependent decrease in mechanical integrity in femora and increased TRAP staining in MP-treated rats. Primary cultures revealed that MP had direct dose- and sex-dependent effects on osteoclast activity, as seen by increased differentiation, activity, and resorption. This study demonstrates for the first time that osteoclasts are differentially regulated by MP in adolescent male and female rats, resulting in sex-dependent effects on the skeleton.