Expanding Complex Morpholines Using Systematic Chemical Diversity.

The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute). These diverse C-substituted morpholines can be directly applied in fragment screening or incorporated as building blocks in medicinal chemistry and library synthesis.

MRI findings of peroneal tendon tears do not necessarily correlate to clinical findings in paediatric and adolescent patients.

PURPOSE: Pathologic abnormality of the peroneal tendons are thought to be an under-appreciated source of vague ankle and hindfoot pain in paediatric patients, partly because they can be difficult to diagnose and differentiate from lateral ankle ligament injuries. While magnetic resonance imaging (MRI) is the primary imaging modality used to detect peroneal tendon pathology, previous studies in adults have found that positive MRIs demonstrate a positive predictive value (PPV) of associated clinical findings around 48%. There are no similar known published studies in the paediatric population. Our objective was to determine the positive predictive value of peroneal tendon pathology as diagnosed by MRI as related to positive clinical exam findings in the paediatric and adolescent population. METHODS: This IRB approved retrospective study was conducted at a tertiary children's hospital. Inclusion criteria included patients under 18 years from our tertiary care institution with (a) ankle MRI findings indicating pathology of the peroneus brevis/longus tendons confirmed by a board certified paediatric musculoskeletal radiologist and (b) formal review of the clinical examination by a fellowship trained paediatric orthopaedic surgeon. Patients with congenital deformities or previous surgical intervention of the lateral ankle were excluded. RESULTS: Forty-seven patients (with 48 MRIs) met inclusion criteria over a ten year period. The majority of the positive MRI scans (70%) demonstrated a peroneus brevis split tear. Of the patients with positive findings on MRI, 17 patients had an associated positive clinical exam. The positive predictive value of MRI for peroneal tendon tears with positive clinical findings was 35.41% (95% confidence interval = 31.1% to 41.6%). There were 31 patients with MRI positive findings with a negative clinical exam. CONCLUSION: Despite having a negative clinical exam, a high percentage of patients had positive MRI findings suggestive of peroneal tendon pathology which confirms findings of adult populations demonstrating a high rate of incidental finding of peroneal tendon pathology on MRI in paediatric patients.

Variations in Trochlear Morphology of Contemporary and Legacy Total Knee Arthroplasty Prostheses: A Review of 22 Designs.

BACKGROUND: The morphology of the trochlear compartment of total knee arthroplasty (TKA) prostheses is a major determinant of postoperative patello-femoral kinematics, particularly with unresurfaced patellae. The objective of this study was to quantify and compare the trochlear morphology of a large series of contemporary and legacy TKA designs. METHODS: The 3-dimensional surface models of 22 femoral components (13 contemporary and 9 legacy) were created using high-resolution laser scanning. The trochlear profile of each component was analyzed from proximal to distal in 15° increments around the trochlear axis. In each profile, the following variables were measured: sulcus angle, medio-lateral deviation of the sulcus, the height and width of the facets, and the trochlear groove orientation. RESULTS: In the contemporary group, the sulcus angle decreased progressively along the trochlear arc to varying degrees, except for 2 symmetrical designs, whereas the sulcus angle of the legacy designs showed considerable variability. The height of the medial facet was very strongly correlated with that of the lateral facet in the contemporary group (R2 = 0.89), whereas the correlation was weak for the legacy designs (R2 = 0.36). Moreover, the trochlear sulcus deviated laterally from distal to proximal in 10 contemporary designs and 7 legacy designs, resulting in a trochlear groove orientation of 4.2 to 11.1° and 4.3 to 10.5°, respectively. In the remaining 5 designs (3 contemporary and 2 legacy), the sulcus was vertical. CONCLUSIONS: There is more consistency in trochlear morphology of contemporary TKA designs compared to that of legacy designs, yet there are still large variations between different designs.

Pediatric Hand and Wrist Fractures in Osteogenesis Imperfecta: An Analysis of Incidence, Patient-specific Risk Factors, and Fracture-specific Characteristics.

BACKGROUND: Children with osteogenesis imperfecta (OI) frequently present with fractures; however, hand and wrist fractures (HWFs), those distal to the radial and ulnar diaphysis, are seldom observed. Yet, HWFs remain among the most common fractures in children with non-OI. The objective of this study was to identify the incidence of OI HWFs. Secondary objectives aimed at identifying patient-specific risk factors for HWFs in OI and comparing clinical courses to non-OI HWFs. METHODS: A retrospective cohort study was conducted. Database query by ICD-10 codes identified 18 patients with OI HWF, 451 patients with OI without HWFs, and 26,183 patients with non-OI HWF. Power analysis estimated appropriate sample sizes and random sampling was utilized to collect patients. Patient demographics, OI-specific variables, fracture morphology, and fracture clinical courses were recorded. Data were analyzed for patient-specific and fracture-specific factors affecting OI HWF incidence. RESULTS: Of patients with OI, 3.8% (18/469) sustained HWFs. Patients with OI HWF were significantly older than patients with OI without HWFs ( P = 0.002) with no differences in height, weight, ethnicity, sex, or ambulatory status. Compared with non-OI HWFs, patients with OI HWF were significantly shorter ( P < 0.001), weighed less ( P = 0.002), and were less likely to be ambulatory ( P < 0.001). OI HWFs were more commonly on the side of hand dominance ( P < 0.001) with transverse patterns ( P = 0.001). OI HWFs were less frequent in the thumb ( P = 0.048) and trended towards significance in the metacarpals ( P = 0.054). All OI HWFs were treated nonoperatively with similar union rates and refracture rates to non-OI HWFs. Multivariate regression showed that older patient age (odds ratio: 1.079, 95% CI: 1.005,1.159, P = 0.037) and OI type I (odds ratio: 5.535, 95% CI: 1.069, 26.795, P = 0.041) were significant prognosticators for HWFs in patients with OI. CONCLUSION: OI HWFs are uncommon (3.8%, 18/469) but specific HWF morphologies and locations are more common in patients with OI; however, these are not pathognomonic. Older patients with mild penetrance of type I OI are at the highest risk for HWFs. OI HWFs do well when managed nonoperatively with noninferior clinical courses compared with non-OI HWFs. LEVEL OF EVIDENCE: Level III.

Health-Related Physical Fitness and Activity in Homeschool: A Systematic Review With Implications for Return to Public School.

BACKGROUND: The purpose of this systematic review is to summarize what is known about health-related physical fitness (cardiovascular endurance, muscular strength and endurance, flexibility, and body composition) and physical activity among homeschool youth. Findings from this study have implications for all American youth as they return to public school from mandated schooling at home during the COVID-19 pandemic. METHODS: Database engines identified over 22,000 articles with 82 abstracts screened for further review. Of these, 18 full-text articles were additionally screened with 10 cross-sectional articles included in the final review. Articles were condensed into a standard review template and findings were summarized by topic. RESULTS: Cardiovascular endurance findings were inconsistent. Abdominal, but not upper body, muscular strength and endurance were significantly lower in homeschool students. There were no reports on flexibility. Body composition was generally healthy in homeschool students and no differences in physical activity were seen. CONCLUSIONS: Research on health-related physical fitness in homeschool youth is limited and descriptive. Further testing and potential remediation may be needed for cardiovascular endurance, muscular strength and endurance, and flexibility in homeschool youth and their public school counterparts as they return to campus. However, existing literature supports healthy body composition and physical activity in this population.