Overuse Injury of the Epiphyseal Primary Physis.

Year-round participation in youth sport that involves high levels of repetitive movement fosters an environment in which overuse injuries are likely to occur. Epiphyseal primary physeal stress injuries (PSIs), unique to skeletally immature athletes, are a particular concern, given their potential for growth disturbance. Initially observed in Little League baseball players, these injuries are now known to affect the long bones around the shoulder, elbow, wrist, hand, knee, ankle, and foot of skeletally immature athletes involved in a variety of sport activities.This article offers an epidemiological and radiologic perspective on the extent and distribution of epiphyseal PSIs in youth sport. We also review a novel framework for understanding the pathophysiologic mechanisms causing these injuries. This information is essential for the early identification of epiphyseal PSIs and devising preventive measures that can reduce a delayed diagnosis and long-term morbidity. Preventing and reducing injury to the epiphyseal growth plates is essential because impairment and dysfunction can result in lifelong morbidity and a risk of premature osteoarthritis.

Imaging of the Pediatric Knee.

During normal development, imaging findings in the immature knee joint may mimic pathology or indicate transient sites of weakness, prone to injury. This article reviews the development of the knee joint, age- and maturation-dependent imaging considerations, and various developmental variants that can be encountered, subdivided into those that involve the tibiofemoral and patellofemoral compartments, soft tissues, and osseous components. The tibiofemoral compartment section reviews the focal periphyseal edema zone (FOPE), ossification variants of the femoral condyles, distal femoral metaphyseal cortical irregularity from periosteal traction, and the metaphyseal subperiosteal stripe, which should be distinguished from pathologic mimickers such as endochondral ossification dysfunction, osteochondritis dissecans (OCD), fibroosseous lesion, periosteal and subcortical pathologies. The patellofemoral compartment section includes a review of partite patella, dorsolateral defect, variant trochlear morphology, and maturation-dependent sites of transient weakness that are prone to injury from repetitive overuse (Sinding-Larsen-Johansson syndrome and Osgood-Schlatter disease) and avulsion fractures (patellar sleeve and tibial tubercle avulsions). Finally, soft tissue (discoid lateral meniscus, meniscal flounce, anterior cruciate ligament variants) and osseous components (meniscal ossicle, fabella, and cyamella) are reviewed.

Return to Play in Youth Athletes: Role of the Radiologist with Focus on the Upper Extremity.

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play.

Patellar osteochondritis dissecans: maturation-dependent patellofemoral joint characteristics.

BACKGROUND: The likelihood of healing of osteochondritis dissecans decreases with skeletal maturity and there are theories that abnormal biomechanical forces contribute to the development and progression of these lesions. OBJECTIVE: To characterize, according to regional skeletal maturity, the morphology and alignment indices of the patellofemoral joint on MRI in patients with patellar osteochondritis dissecans. MATERIALS AND METHODS: MRI examinations of patients with patellar osteochondritis dissecans obtained between January 2008 and May 2023 were retrospectively reviewed to determine regional skeletal maturity, osteochondritis dissecans lesion size and location, patellar and trochlear morphology (Wiberg/Dejour classifications), and to calculate trochlear sulcus angles, trochlear depth index, lateral trochlear inclination, Insall-Salvati index, Caton-Deschamps index, patellar tendon-lateral trochlear ridge, and tibial tubercle-trochlear groove distances. Values were compared between skeletally immature and mature groups. RESULTS: Sixty-eight children (22 girls, 46 boys, age: 14.0 ± 1.7 years) yielded 74 knees with patellar osteochondritis dissecans lesions, 14 (19%) of which were skeletally mature. The most common anatomic location was over the central patella [median ridge (34/74 - 46%) on the axial images and over the middle third (45/74 - 61%) on the sagittal images]. Overall, mean trochlear sulcus angle (high, 151 ± 11°), trochlear depth index (low, 2.8 ± 1.4 mm), and Insall-Salvati index (borderline, 1.3 ± 0.1) were abnormal for the entire sample. Skeletally mature knees were significantly more likely to have higher (more dysplastic) Dejour types when compared to skeletally immature knees (p < 0.01). Knees in the mature group, compared to immature, had significantly more abnormal mean lateral trochlear inclination (15 ± 8° vs. 19 ± 6°, p = 0.03) and patellar tendon-lateral trochlear ridge distance (5.55 ± 4.31 mm vs. 2.89 ± 4.69 mm, p = 0.04). Half of the knees had ≥ 4 abnormal features that predispose to patellofemoral maltracking; mature knees were significantly (p = 0.02) more likely to have a higher number of abnormal features (> 6 features, 7/14, 50.0%) versus immature knees (0-3 features, 33/60, 55.0%). CONCLUSION: In children with patellar osteochondritis dissecans, abnormal patellofemoral morphology and alignment indices were common in all patients and more severe in mature knees.

Pediatric thrower's elbow: maturation-dependent MRI findings in symptomatic baseball players.

BACKGROUND: Elbow pain is common among youth baseball players and elbow MRI is increasingly utilized to complement the clinical assessment. OBJECTIVE: To characterize, according to skeletal maturity, findings on elbow MRI from symptomatic youth baseball players. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant retrospective study included pediatric (<18 years of age) baseball players with elbow pain who underwent MRI examinations between 2010 and 2021. Two radiologists, blinded to the outcome, independently reviewed examinations to categorize skeletal maturity and to identify osseous and soft tissue findings with consensus used to resolve discrepancies. Findings were compared between skeletally immature and mature patients and logistic regression models identified predictors of surgery. RESULTS: This study included 130 children (115 boys, 15 girls): 85 skeletally immature and 45 mature (12.8±2.3 and 16.2±1.0 years, respectively, p<0.01). Kappa coefficient for interobserver agreement on MRI findings ranged from 0.64 to 0.96. Skeletally immature children, when compared to mature children, were more likely to have elbow effusion (27%, 23/85 vs 9%, 4/45; p=0.03), medial epicondyle marrow edema (53%, 45/85 vs 16%, 7/45; p<0.01), avulsion fracture (19%, 16/85 vs 2%, 1/45; p=0.02), and juvenile osteochondritis dissecans (OCD, 22%, 19/85 vs 7%, 3/45; p=0.04), whereas skeletally mature children were more likely to have sublime tubercle marrow edema (49%, 22/45 vs 11%, 9/85; p<0.01) and triceps tendinosis (40%, 18/45 vs 20%, 17/85; p=0.03). Intra-articular body (OR=4.2, 95% CI 1.5-47.8, p=0.02) and osteochondritis dissecans (OR=3.7, 95% CI 1.1-11.9, p=0.03) were independent predictors for surgery. CONCLUSION: Differential patterns of elbow MRI findings were observed among symptomatic pediatric baseball players based on regional skeletal maturity. Intra-articular body and osteochondritis dissecans were independent predictors of surgery.

Identification of fractures on pediatric foot radiographs: do localization cues improve diagnostic accuracy and reduce interpretation time?

OBJECTIVE: To investigate the diagnostic accuracy and time in the detection of fractures on pediatric foot radiographs marked without and with localization cues. METHOD: One-hundred randomly selected foot radiographic examinations that were performed on children (<18 years old) after injury and with at least 4 weeks of follow-up were included. Blinded to history and diagnosis, 4 readers (one each: medical student, pediatrician, pediatric orthopedic surgeon, and pediatric musculoskeletal radiologist) retrospectively and independently reviewed each examination twice (without and with cue, at least 1 month apart, and after randomization). Each reader recorded the presence or absence of a fracture, fracture location, diagnostic confidence, and the total (interpretation) time spent on each study. Diagnostic accuracy, reader confidence, and interpretation time were compared between examinations without and with cues. RESULTS: Our study included 59 examinations without and 41 with fractures (21 phalangeal, 18 metatarsal, and 2 tarsal fractures). Localization cues improved inter-reader agreement (κ=0.36 to 0.64), overall sensitivity (68 to 72%), specificity (66 to 73%), and diagnostic accuracy (67 to 73%); thus, overcalled and missed rates also improved from 34 to 27% and 32 to 28%, respectively. Reader confidence improved with cue (49 to 61%, p<0.01) with higher incremental improvement with younger children (30% for 1-6 years; 14% for 7-11 years; and 10% for 12-17 years). Interpretation time decreased by 40% per examination (40±22 s without to 24±13 s with cues, p<0.001). CONCLUSION: Localization cues improved diagnostic accuracy and reader confidence, reducing interpretation time in the detection of pediatric foot fractures.

Medial femoral condyle OCD (osteochondritis dissecans): correlation between imaging and arthroscopy.

Osteochondritis dissecans (OCD) describes a pathologic condition centered at the osteochondral junction that may result in an unstable subchondral fragment (progeny), disruption of the overlying cartilage, which may separate from the underlying parent bone. It is one of the causes of chronic knee pain in children and young adults. The current literature on OCD lesions focuses primarily on the medial femoral condyle (MFC), but inconsistent use of terminology, particularly in the distinction of OCD lesions between skeletally immature and mature patients has created uncertainty regarding imaging workup, treatment, and long-term prognosis. This article reviews the pathophysiology of MFC OCD lesions, highlighting the role of endochondral ossification at the secondary growth plate of the immature femoral condyles, the rationale behind the imaging work-up, and key imaging findings that can distinguish between stable lesions, unstable lesions, and physiologic variants. This overview also provides a case-based review to introduce imaging correlates with the ROCK (Research in Osteochondritis of the Knee) arthroscopic classification.

Pediatric foot fractures on radiographs: distribution and predictors of surgery.

PURPOSE: To examine the distribution and characteristics of pediatric foot fractures on radiographs with respect to age and skeletal maturation, and to identify predictors of surgery. METHODS: This retrospective study included children (≤ 18 years) with foot fractures, who underwent radiographic examinations (2020-2022). Electronic medical records were reviewed to obtain demographic and clinical data. Fracture characteristics, including anatomic location, presence of displacement, angulation, articular involvement, and, if skeletally immature, physeal involvement and Salter-Harris fracture pattern were collected. Logistic regression models were used to identify predictors of surgery. RESULTS: 1,090 (596-boys, 494-girls; mean age, 11.0 ± 4.0 years) patients with 1,325 (59.8% metatarsal, 33.8% phalangeal, and 6.4% tarsal) fractures were included. Fractures of 1st metatarsal were more common among younger children whereas fractures of 2nd-4th and 5th metatarsals were more common among older children (median ages: 5.9 years vs. 10.3 years and 12.4 years, p < 0.001). Intra-articular fractures were more common among maturing and mature than immature bones (25.3% and 20.4% vs. 9.9%, p < 0.001). Physeal involvement was uncommon (162/977, 16.6%) and the most common pattern was Salter-Harris type II (133/162, 82.1%). A minority (47/1090, 4.3%) of patients required surgery and independent predictors of surgery included physeal involvement (OR = 5.12, 95% CI: 2.48-10.39, p < 0.001), multiple fractures (OR = 3.85, 95% CI: 1.67-8.53, p = 0.001), fracture displacement (OR = 9.16, 95% CI:4.43-19.07, p < 0.001), and articular involvement (OR = 2.72, 95% CI:1.27-5.72, p = 0.008). Using these predictors, the likelihood for surgery ranged between 8.0% with 1 and 86.7% with 3 predictors. CONCLUSION: Pediatric foot fracture patterns differed based on age and regional skeletal maturation. Physeal involvement, multiple fractures, fracture displacement, and articular involvement were independent predictors of surgery in our study group.

Distribution of bacterial community structures and spread of antibiotic resistome at industrially polluted sites of Mini River, Vadodara, Gujarat, India.

The influence of anthropogenic pollution on the distribution of bacterial diversity, antibiotic-resistant bacteria (ARBs), and antibiotic resistance genes (ARGs) was mapped at various geo-tagged sites of Mini River, Vadodara, Gujarat, India. The high-throughput 16S rRNA gene amplicon sequencing analysis revealed a higher relative abundance of Planctomycetota at the polluted sites, compared to the pristine site. Moreover, the relative abundance of Actinobacteriota increased, whereas Chloroflexi decreased in the water samples of polluted sites than the pristine site. The annotation of functional genes in the metagenome samples of Mini River sites indicated the presence of genes involved in the defence mechanisms against bacitracin, aminoglycosides, cephalosporins, chloramphenicol, streptogramin, streptomycin, methicillin, and colicin. The analysis of antibiotic resistome at the polluted sites of Mini River revealed the abundance of sulfonamide, beta-lactam, and aminoglycoside resistance. The presence of pathogens and ARB was significantly higher in water and sediment samples of polluted sites compared to the pristine site. The highest resistance of bacterial populations in the Mini River was recorded against sulfonamide (≥ 7.943 × 103 CFU/mL) and ampicillin (≥ 8.128 × 103 CFU/mL). The real-time PCR-based quantification of ARGs revealed the highest abundance of sulfonamide resistance genes sul1 and sul2 at the polluted sites of the Mini River. Additionally, the antimicrobial resistance genes aac(6')-Ib-Cr and blaTEM were also found abundantly at polluted sites of the Mini River. The findings provide insights into how anthropogenic pollution drives the ARG and ARB distribution in the riverine ecosystem, which may help with the development of antimicrobial resistance mitigation strategies.

Diagnostic thresholds and optimal collection protocol of salivary pepsin for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD.

Pediatric hand fractures detection on radiographs: do localization cues improve diagnostic performance?

OBJECTIVE: To compare the diagnostic accuracy and interpretation time for detection of pediatric fractures on hand radiographs with and without localization cues. MATERIALS AND METHODS: Consecutive children, who underwent radiographic examinations after injury, over 2 years (2019-2021) and with > 2 weeks of follow-up to confirm the presence or absence of a fracture, were included. Four readers, blinded to history and diagnosis, retrospectively reviewed all images twice, without and with cue, at least 1 week apart and after randomization, to determine the presence or absence of a fracture, and if present, anatomic location and diagnostic confidence were recorded. Interpretation time for each study was also recorded and averaged across readers. Inter-reader agreement was calculated using Fleiss' kappa. Diagnostic accuracy and interpretation time were compared between examinations using sensitivity, specificity, and Mann-Whitney U correlation. RESULTS: Study group included 92 children (61 boys, 31 girls; 10.8 ± 3.4 years) with and 40 (31 boys, 9 girls; 10.9 ± 3.7 years) without fractures. Cue improved inter-reader agreement (κ = 0.47 to 0.62). While the specificity decreased (63 to 62%), sensitivity (75 to 78%), diagnostic accuracy (71 to 73%), and confidence improved (78 to 87%, p < 0.01), and interpretation time (median: 40 to 22 s, p < 0.001) reduced with examinations with localization cue. Specifically, examinations with fracture and cue had the shortest interpretation time (median: 16 s), whereas examinations without fracture and without cue had the longest interpretation time (median: 48 s). CONCLUSION: Localization cues increased inter-reader agreement and diagnostic confidence, reduced interpretation time in the detection of fractures on pediatric hand radiographs, while maintaining diagnostic accuracy.

Maturation-dependent patterns of knee injuries among symptomatic pediatric soccer players on MRI.

OBJECTIVE: To systematically investigate the prevalence of knee MRI findings among symptomatic pediatric soccer players with respect to skeletal maturity and to identify predictors of surgery. METHODS: This IRB-approved, HIPAA-compliant retrospective study included soccer players (< 18 years of age) who underwent MRI examinations in the past 5 years (2018-2023). Two radiologists retrospectively and independently reviewed all examinations to categorize skeletal maturity and to identify osseous and soft tissue findings. Findings were compared between maturation groups, and logistic regression models were used to identify predictors of surgery. RESULTS: Ninety-seven players (45 boys, 52 girls) included 39 skeletally immature, 21 maturing, and 37 mature knees. Kappa coefficient for interobserver reliability ranged between 0.65 and 1.00. Osgood-Schlatter disease (OSD) was more common among immature than maturing and mature knees (25% vs 14% and 5%, p = 0.04); anterior cruciate ligament (ACL) injury was more common among maturing and mature than immature knees (59% and 48%, vs 15%, p < 0.01); and meniscal tears were more common among mature than immature and maturing knees (medial, 41% vs 18% and 14%, p = 0.03; lateral, 43% vs 21% and 19%, p = 0.04). Players in the mature group were more likely to undergo surgery (p = 0.01). The presence of an effusion (OR = 19.5, 95% CI 2.8-240.9, p = 0.01), ACL injury (OR = 170.0, 95% CI 1.3-6996.9, p < 0.01), and lateral meniscal tears (OR = 10.8, 95% CI 1.8-106.1, p = 0.02) were independent predictors of surgery. CONCLUSION: Differential patterns of injury were found among symptomatic pediatric soccer players; the presence of an effusion, ACL injury, and lateral meniscal tears were independent predictors of surgery, likely contributing to the higher rates of surgery among skeletally mature players.

Distribution of pediatric hand fractures: age- and bone maturation-dependent differences.

PURPOSE: To investigate the distribution and characteristics of fractures of bones of the hand on radiographs with respect to age and skeletal maturity of the fractured bone, and to identify predictors of surgery. METHODS: This cross-sectional, retrospective study included children (≤ 18 years) with hand fractures who underwent radiographic examinations (2019-2021). Fracture location, presence of displacement (≥ 2 mm), angulation (≥ 10°), articular extension, and if skeletally immature, then physeal involvement and Salter-Harris grade were recorded. Mann-Whitney U, Kruskal-Wallis, Fisher's exact, and chi-square tests as well as logistic regression analyses were used. RESULTS: Study group of 508 (350 boys, 158 girls; median age, 11.9 years) included 575 (63% phalangeal, 37% metacarpal, and 0.3% carpal) fractures. Younger children were more likely to sustain phalangeal and older children carpal and metacarpal fractures (median ages: 10.8 vs 12.3 and 13.8 years, p < 0.001); and fractures of the small finger accounted for 50% of metacarpal and 43% of phalangeal fractures. Fracture displacement (12% vs 22%, p = 0.02) and angulation (25% vs 49%, p < 0.001) were more common with mature than immature bones. A third of immature bones had physeal involvement and the most common pattern was Salter-Harris type II (89%). Surgical intervention was uncommon (11%) and independent predictors were displacement (OR = 3.99, 95% CI 1.95-8.19, p < 0.001) and articular extension (OR = 5.11, 95% CI 2.00-13.07, p < 0.001). CONCLUSION: While younger children were more likely to sustain phalangeal than metacarpal fractures and less likely to have displacement and angulation when compared to older children; only displacement and articular extension were significant independent predictors of surgery.

Factors that Impact Day-to-Day Esophageal Acid Reflux Variability and Its Diagnostic Significance for Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disease affecting a significant number of adults both globally and in the USA. GERD is clinically diagnosed based on patient-reported symptoms, and the gold standard for diagnosis is ambulatory reflux monitoring, a tool particularly utilized in the common scenario of non-response to therapy or atypical features. Over the past 20 years, there has been a shift toward extending the duration of reflux monitoring, initially from 24 to 48 h and more recently to 96 h, primarily based on a demonstrated increase in diagnostic yield. Further, multiple studies demonstrate clinically relevant variability in day-to-day acid exposure levels in nearly 30% of ambulatory reflux monitoring studies. For these reasons, an ongoing clinical dilemma relates to the optimal activities patients should engage in during prolonged reflux monitoring. Thus, the aims of this review are to detail what is known about variability in daily acid exposure, discuss factors that are known to influence this day-to-day variability (i.e., sleep patterns, dietary/eating habits, stress, exercise, and medications), and finally provide suggestions for patient education and general GERD management to reduce variation in esophageal acid exposure levels.

Salivary biomarkers and esophageal disorders.

Saliva is a complex physiologic fluid that contains an abundance of biological analytes, or biomarkers. Recent research has shown that these biomarkers may be able to convey the physiologic health of a person. Work has been done linking derangements in these salivary biomarkers to a wide variety of pathologic disorders ranging from oncologic diseases to atopic conditions. The specific area of interest for this review paper is esophageal disorders. Particularly because the diagnosis and management of esophageal disorders often includes invasive testing such as esophagogastroduodenoscopy, prolonged pH monitoring, and biopsy. The aim of this review will be to explore salivary biomarkers (pepsin, bile, epidermal growth factor, and micro-RNA) that are being studied as they relate specifically to esophageal disorders. Finally, it will explore the benefits of salivary testing and identify areas of possible future research.

Age Dependency of Blood-Brain Barrier Penetration by cis- and trans-Permethrin in the Rat.

Permethrin (PER), a type I pyrethroid, is the most widely used insecticide in domestic settings in the United States. The overall objective of this study was to assess the efficiency of the blood-brain barrier (BBB) as an obstacle to the 14C-cis-permethrin (CIS) and 14C-trans-permethrin (TRANS) isomers of PER, and to determine whether its barrier function changes during maturation of the rat. Experiments were conducted to quantify brain uptake of CIS and TRANS in postnatal day 145, 21, and 90 Sprague-Dawley rats. The common carotid artery of anesthetized rats was perfused for 2 or 4 minutes with 1, 10, or 50 µM 14C-CIS or 14C-TRANS in 4% albumin. Brain deposition of each isomer was inversely related to age, with levels in the youngest animals >5 times those in adults. Brain uptake was linear over the 50-fold range of pyrethroid concentrations, indicative of passive, nonsaturable BBB permeation. The extent of uptake of toxicologically relevant concentrations of CIS and TRANS was quite similar. Thus, dissimilar BBB permeation does not contribute to the greater acute neurotoxic potency of CIS, but greater permeability of the immature BBB to CIS and TRANS may contribute to the increased susceptibility of preweanling rodents to the insecticides.

The human, F-actin-based cytoskeleton as a mutagen sensor.

BACKGROUND: Forty years ago the actin cytoskeleton was determined to be disrupted in fibroblasts from persons with DNA repair-defective, hereditary colon cancer, with no clear connection between the cytoskeleton and DNA repair defects at that time. Recently, the large number of sequenced genomes has indicated that mammalian mutagenesis has a large stochastic component. As a result, large coding regions are large mutagen targets. Cytoskeletal protein-related coding regions (CPCRs), including extra-cellular matrix proteins, are among the largest coding regions in the genome and are indeed very commonly mutated in cancer. METHODS: To determine whether mutagen sensitivity of the actin cytoskeleton could be assessed experimentally, we treated tissue culture cells with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and quantified overall cytoskeleton integrity with rhodamine-phalloidin stains for F-actin. RESULTS: The above approach indicated cytoskeletal degradation with increasing mutagen exposure, consistent with increased mutagenesis of CPCRs in TCGA, smoker samples, where overall mutation rates correlate with CPCR mutation rates (R2 = 0.8694; p < 0.00001). In addition, mutagen exposure correlated with a decreasing cell perimeter to area ratio, raising questions about potential decreasing, intracellular diffusion and concentrations of chemotherapy drugs, with increasing mutagenesis and decreasing cytoskeleton integrity. CONCLUSION: Determination of cytoskeletal integrity may provide the opportunity to assess mutation burdens in nonclonal cell populations, such as in intact tissues, where DNA sequencing for heterogeneous mutation burdens can be challenging.

Mammillary body volume abnormalities in anorexia nervosa.

OBJECTIVE: Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. METHOD: Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. RESULTS: We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. DISCUSSION: These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920-929).

Minimally Invasive Cheilectomy for Hallux Rigidus.

Hallux metatarsophalangeal joint cheilectomy is a joint-sparing technique that involves resection of the dorsal metatarsal head osteophytes; this may be achieved through minimally invasive and arthroscopic techniques. General indications for minimally invasive surgery (MIS) cheilectomy are mild-to-moderate hallux rigidus (Grades I-II) with symptomatic dorsal osteophytes causing dorsal impingement and/or shoe wear irritation in those who have failed extensive nonoperative management. The literature confirms equivalent outcomes to open cheilectomy; however, it is somewhat inconsistent regarding superiority. The theoretic benefits of MIS cheilectomy include better cosmesis, reduced wound complications, less soft tissue disruption, and faster recovery.

Mammalian RNAi represses pericentromeric lncRNAs to maintain genome stability.

Mammalian pericentromeric tandem repeats produce long noncoding RNAs (lncRNAs) that are dysregulated in cancer and linked to genomic instability. Identifying the basic molecular characteristics of these lncRNAs and their regulation is important to understanding their biological function. Here, we determine that the Argonaute (Ago) proteins of the RNA interference (RNAi) pathway directly and uniformly repress bidirectional pericentromeric lncRNAs in a Dicer-dependent manner in mouse embryonic and adult stem cells. Ago-dependent and Dicer-dependent autoregulatory small RNAs were identified within pericentromeric lncRNA degradation intermediates. We develop an RNase H cleavage assay to determine the relative proportions and lengths of the pericentromeric lncRNA targets. We find that 5'-phosphate and non-polyadenylated bidirectional pericentromeric lncRNAs are expressed at similar proportions. These lncRNAs can span up to 9 repeats, with transcription from the reverse strand template yielding the longer products. Using pericentromeric repeat RNA reporters, we determine that Ago represses pericentromeric lncRNAs after S phase transcription. Upon loss of Ago, pericentromeric lncRNA dysregulation results in delayed cell cycle progression, a defective mitotic spindle assembly checkpoint (SAC) and genomic instability. These results show that an evolutionarily conserved Ago activity at pericentromeres contributes to mammalian genome stability.