A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: A cross sectional study comparing Osgood Schlatter disease with controls.

BACKGROUND: Osgood-Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. PURPOSE: This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. STUDY DESIGN: Cross-sectional study. METHODS: Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). RESULTS: Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the  tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2).  Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, -0.05, 95% CI: -0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, -0.09, 95% CI: -0.4 to 0.2, p = 0.04; distal mean difference, -0.6, 95% CI: -0.9 to -0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = -2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. CONCLUSION: Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. CLINICAL RELEVANCE: Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD.

Subgrouping of facilitatory or inhibitory conditioned pain modulation responses in patients with chronic knee pain. Explorative analysis from a multicentre trial.

BACKGROUND: Facilitatory and inhibitory conditioned pain modulation (CPM) responses are observed in healthy volunteers and chronic pain patients, but the clinical implications for phenotyping are unknown. This study aimed to subgroup and compare chronic knee pain patients according to their CPM responses. METHODS: This explorative, cross-sectional study included 127 patients with chronic knee pain (osteoarthritis or following total knee arthroplasty). Individual CPM responses were categorized as facilitatory (test stimuli pain intensity increased when conditioning stimuli were applied), as inhibitory (test stimuli pain intensity decreased) or as no change (defined as less than 5.3% change in pain intensity). Outcomes were clinical pain intensities, temporal summation, widespread pain, self-reported physical function, PainDETECT questionnaire and Pain Quality Assessment Scale. Data were analysed as comparisons between the inhibitory and the facilitatory groups and using multivariate linear regression models. RESULTS: Fifty-four patients had facilitatory CPM responses, 49 had inhibitory CPM responses, and 24 showed no change in CPM response. A between-group difference was observed for self-reported physical function, with the facilitatory CPM group reporting better function (54.4 vs. 46.0, p = 0.028) and the facilitatory CPM group reported more deep pain sensations (3.2 vs. 2.0, p = 0.021). The remaining outcomes showed no between-group differences. Higher clinical pain intensity and facilitated temporal summation were associated in the facilitated CPM group but not in the inhibitory CPM group. CONCLUSION: These explorative findings indicated that quantitative clinical and experimental differences exist between facilitatory or inhibitory CPM responses in a chronic knee pain patient population. Differences in patients' CPM responses should be further investigated to unravel possible clinical importance. SIGNIFICANCE: Our findings confirm that conditioned pain modulation consist of inhibitory and facilitatory responders among a patient population with chronic knee pain. This explorative study indicates that patients with either facilitatory or inhibitory conditioned pain modulation could exhibit differences in pain outcomes. Subgrouping of chronic pain patients depending on individual conditioned pain modulation responses could be considered in phenotyping patients prior to inclusion in clinical trials or used for personalizing the management regime.

Differences in the effects of school meals on children's cognitive performance according to gender, household education and baseline reading skills.

BACKGROUND/OBJECTIVES: We previously found that the OPUS School Meal Study improved reading and increased errors related to inattention and impulsivity. This study explored whether the cognitive effects differed according to gender, household education and reading proficiency at baseline. SUBJECTS/METHODS: This is a cluster-randomised cross-over trial comparing Nordic school meals with packed lunch from home (control) for 3 months each among 834 children aged 8 to 11 years. At baseline and at the end of each dietary period, we assessed children's performance in reading, mathematics and the d2-test of attention. Interactions were evaluated using mixed models. Analyses included 739 children. RESULTS: At baseline, boys and children from households without academic education were poorer readers and had a higher d2-error%. Effects on dietary intake were similar in subgroups. However, the effect of the intervention on test outcomes was stronger in boys, in children from households with academic education and in children with normal/good baseline reading proficiency. Overall, this resulted in increased socioeconomic inequality in reading performance and reduced inequality in impulsivity. Contrary to this, the gender difference decreased in reading and increased in impulsivity. Finally, the gap between poor and normal/good readers was increased in reading and decreased for d2-error%. CONCLUSIONS: The effects of healthy school meals on reading, impulsivity and inattention were modified by gender, household education and baseline reading proficiency. The differential effects might be related to environmental aspects of the intervention and deserves to be investigated further in future school meal trials.

Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children.

UNLABELLED: We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. INTRODUCTION: Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height-adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. METHODS: Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6 months from OPUS School Meal Study. RESULTS: In both sexes: gain in BAheight was positively associated with baseline FM (≥2.05 cm(2)/kg, both p ≤ 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (≥0.02 cm/ng/ml, p = 0.001) and osteocalcin (≥0.13 cm/ng/ml, p ≤ 0.009); and gain in BAheight was positively associated with baseline osteocalcin (≥0.35 cm(2)/ng/ml, p ≤ 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF-1 (0.06 cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/µg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). CONCLUSIONS: This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat-independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize.

Eating dark and milk chocolate: a randomized crossover study of effects on appetite and energy intake.

OBJECTIVE: To compare the effect of dark and milk chocolate on appetite sensations and energy intake at an ad libitum test meal in healthy, normal-weight men. SUBJECTS/METHODS: A total of 16 young, healthy, normal-weight men participated in a randomized, crossover study. Test meals were 100 g of either milk (2285 kJ) or dark chocolate (2502 kJ). Visual-analogue scales were used to record appetite sensations before and after the test meal was consumed and subsequently every 30 min for 5 h. An ad libitum meal was served 2 h after the test meal had been consumed. RESULTS: The participants felt more satiated, less hungry, and had lower ratings of prospective food consumption after consumption of the dark chocolate than after the milk chocolate. Ratings of the desire to eat something sweet, fatty or savoury were all lower after consumption of the dark chocolate. Energy intake at the ad libitum meal was 17% lower after consumption of the dark chocolate than after the milk chocolate (P=0.002). If the energy provided by the chocolate is included in the calculation, the energy intake after consumption of the dark chocolate was still 8% lower than after the milk chocolate (P=0.01). The dark chocolate load resulted in an overall energy difference of -584 kJ (95% confidence interval (-1027;-141)) during the test period. CONCLUSION: In the present study, dark chocolate promotes satiety, lowers the desire to eat something sweet, and suppresses energy intake compared with milk chocolate.

High gamma mapping using EEG.

High gamma (HG) power changes during motor activity, especially at frequencies above 70 Hz, play an important role in functional cortical mapping and as control signals for BCI (brain-computer interface) applications. Most studies of HG activity have used ECoG (electrocorticography) which provides high-quality spatially localized signals, but is an invasive method. Recent studies have shown that non-invasive modalities such as EEG and MEG can also detect task-related HG power changes. We show here that a 27 channel EEG (electroencephalography) montage provides high-quality spatially localized signals non-invasively for HG frequencies ranging from 83 to 101 Hz. We used a generic head model, a weighted minimum norm least squares (MNLS) inverse method, and a self-paced finger movement paradigm. The use of an inverse method enables us to map the EEG onto a generic cortex model. We find the HG activity during the task to be well localized in the contralateral motor area. We find HG power increases prior to finger movement, with average latencies of 462 ms and 82 ms before EMG (electromyogram) onset. We also find significant phase-locking between contra- and ipsilateral motor areas over a similar HG frequency range; here the synchronization onset precedes the EMG by 400 ms. We also compare our results to ECoG data from a similar paradigm and find EEG mapping and ECoG in good agreement. Our findings demonstrate that mapped EEG provides information on two important parameters for functional mapping and BCI which are usually only found in HG of ECoG signals: spatially localized power increases and bihemispheric phase-locking.

Bi-phase locking - a tool for probing non-linear interaction in the human brain.

We present a novel method for detecting frequency-frequency coupling between the electrical output of cortical areas as measured by electrocorticography (ECoG), electroencephalography (EEG) and magnetoencephalography (MEG), the biphase-locking value (bPLV). Our method is an extension of the well known phase-locking value (PLV) and is specifically sensitive to non-linear interactions, i.e. quadratic phase coupling across frequencies. Due to its sensitivity to non-linear interactions, it is robust to spurious synchronization arising from linear crosstalk, which is an especially useful property when analyzing data recorded by EEG/MEG. We discuss the statistical properties of the bPLV, specifically the distribution of the bPLV under assumption of random phases between the signals of interest. We also compare the bPLV to the PLV for cortical interactions that are computed for simulated EEG/MEG data. These data were mapped to the cortex using an inverse solution. We demonstrate our method for event related ECoG data recorded from the motor cortex of an epileptic patient, who performed a cued finger movement task. We find highly significant, movement related increase of the bPLV between the alpha (12 Hz) and high gamma (77 Hz) band in a pre-motor area, coupling to high gamma at 89 Hz in the motor cortex.

Disorder-induced microscopic magnetic memory.

Using coherent x-ray speckle metrology, we have measured the influence of disorder on major loop return point memory (RPM) and complementary point memory (CPM) for a series of perpendicular anisotropy Co/Pt multilayer films. In the low disorder limit, the domain structures show no memory with field cycling--no RPM and no CPM. With increasing disorder, we observe the onset and the saturation of both the RPM and the CPM. These results provide the first direct ensemble-sensitive experimental study of the effects of varying disorder on microscopic magnetic memory and are compared against the predictions of existing theories.

Effect of sensory perception of foods on appetite and food intake: a review of studies on humans.

OBJECTIVE: How much do the sensory properties of food influence the way people select their food and how much they eat? The objective of this paper is to review results from studies investigating the link between the sensory perception of food and human appetite regulation. CONTENT OF THE REVIEW: The influence of palatability on appetite and food intake in humans has been investigated in several studies. All reviewed studies have shown increased intake as palatability increased, whereas assessments of the effect of palatability using measures of subjective appetite sensations have shown diverging results, for example, subjects either feel more hungry and less full after a palatable meal compared to a less palatable meal, or they feel the opposite, or there is no difference. Whether palatability has an effect on appetite in the period following consumption of a test meal is unclear. Several studies have investigated which sensory properties of food are involved in sensory-specific satiety. Taste, smell, texture and appearance-specific satieties have been identified, whereas studies on the role of macronutrients and the energy content of the food in sensory-specific satiety have given equivocal results. Different studies have shown that macronutrients and energy content play a role in sensory-specific satiety or that macronutrients and energy content are not a factor in sensory-specific satiety. Sensory-specific satiety may have an important influence on the amount of food eaten. Studies have shown that increasing the food variety can increase food and energy intake and in the short to medium term alter energy balance. Further knowledge about the importance of flavour in appetite regulation is needed, for example, which flavour combinations improve satiety most, the possible connection between flavour intensity and satiety, the effect of persistence of chemesthetic sensation on palatability and satiety, and to what extent genetic variation in taste sensitivity and perception influences dietary habits and weight control.

Polymorphic hydroxylation of perhexiline in vitro.

AIMS: The aims of this study were to examine the in vitro enzyme kinetics and CYP isoform selectivity of perhexiline monohydroxylation using human liver microsomes. METHODS: Conversion of rac-perhexiline to monohydroxyperhexiline by human liver microsomes was assessed using a high-performance liquid chromatography assay with precolumn derivatization to measure the formation rate of the product. Isoform selective inhibitors were used to define the CYP isoform profile of perhexiline monohydroxylation. RESULTS: The rate of perhexiline monohydroxylation with microsomes from 20 livers varied 50-fold. The activity in 18 phenotypic perhexiline extensive metabolizer (PEM) livers varied about five-fold. The apparent Km was 3.3 +/- 1.5 micro m, the Vmax was 9.1 +/- 3.1 pmol min-1 mg-1 microsomal protein and the in vitro intrinsic clearance (Vmax/Km) was 2.9 +/- 0.5 micro l min-1 mg-1 microsomal protein in the extensive metabolizer livers. The corresponding values in the poor metabolizer livers were: apparent Km 124 +/- 141 micro m; Vmax 1.4 +/- 0.6 pmol min-1 mg-1 microsomal protein; and intrinsic clearance 0.026 micro l min-1 mg-1 microsomal protein. Quinidine almost completely inhibited perhexiline monohydroxylation activity, but inhibitors selective for other CYP isoforms had little effect. CONCLUSIONS: Perhexiline monohydroxylation is almost exclusively catalysed by CYP2D6 with activities being about 100-fold lower in CYP2D6 poor metabolizers than in extensive metabolizers. The in vitro data predict the in vivo saturable metabolism and pharmacogenetics of perhexiline.

No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects.

OBJECTIVE: To examine the effect of a GLP-2 infusion on appetite sensations and ad libitum energy intake in healthy, normal weight humans. DESIGN: The experiment was performed in a randomised, blinded, and placebo-controlled crossover design. Placebo or GLP-2 was infused (infusion rate of 25 pmol/kg body wth) for 4.5 h. SUBJECTS: A total of 18 healthy, normal weight young subjects participated; eight women and 10 men. MEASUREMENTS: During the infusion, subjects recorded their appetite sensations every 30 min using visual analogue scales, and blood was sampled frequently. After 2 h of infusion, an ad libitum meal, consisting of sandwiches, was served. RESULTS: The concentration of GLP-2 was significantly higher during the GLP-2 infusion compared with placebo (P<0.0001) and increased further in both conditions in response to the meal. Neither appetite sensations, nor palatability of the test meals, or energy intake were different on the two occasions. Glucose, GLP-1, insulin, and GIP responses were also unaffected by the infusion, whereas glucagon levels were higher during the GLP-2 treatment (P<0.05). CONCLUSION: Circulating GLP-2 in physiological concentrations does not seem to play a significant role in human appetite regulation.

Sample-angle feedback for diffraction anomalous fine-structure spectroscopy.

Diffraction anomalous fine-structure (DAFS) experiments measure Bragg peak intensities as continuous functions of photon energy near a core-level excitation. Measuring the integrated intensity at each energy makes the experiments prohibitively slow; however, in many cases DAFS can be collected quickly by measuring only the peak intensity at the center of the rocking curve. A piezoelectric-actuator-driven stage has been designed and tested as part of a sample-angle feedback circuit for locking onto the maximum of the rocking curve while the energy is scanned. Although software peak-tracking requires only a simple calculation of diffractometer angles, it is found that the additional hardware feedback dramatically improves the reproducibility of the data.

Institutional change. Experiences in two departments.

Though the principle may seem simple or fundamental it has been our experience that the best way to develop clinician-educators in an academic setting is to value their contributions. This means that those contributions must lead to promotion, they should be valued by colleagues, they must be valued by the administration and the chairman, and they must be considered when determining faculty salary. As faculty members perceived that they were valued for teaching and clinical service. and would not be punished for the amount of time they were spending in these endeavors, there was a clear group of faculty who came forward to take on a primary teaching role. This group was not limited to general pediatricians or ambulatory pediatricians, but included some specialists who felt that their pediatric background was sufficient for them to teach in a primary care setting. Two of our leading teachers in the generalist curriculum are specialists in nephrology and hematology/oncology. Although this requires them to go back and increase their knowledge in general pediatrics, it is far less difficult according to these faculty members than they expected. Our specialists continue to maintain their specialty practices, but have oriented their didactic lectures and clinical teaching to specialty and general aspects of pediatrics. It is not difficult to teach about parenting and psychosocial skills when describing a complicated specialty patient and to orient the students and residents to the general care of such a patient. Although the majority of strategies described in this article deal with departmental and college initiatives, the reason that these strategies have become an integral part of the Department of Pediatrics is the changing health care environment in Nebraska. Managed care has mandated that physicians be more flexible and be willing to take on a primary care role within their specialty. This has made the transition for many faculty much easier and has been reinforced by financial reimbursement for their services. The transition would not have been as easy had there been no movement of the community toward primary care, or no shift in the university's interest in primary care as a mechanism for providing sufficient patient numbers to fulfill our teaching missions. Clinical research has become the area of focus for many of the primary care physicians and some specialists in the past few years, and the university is in the process of developing a clinical research center to allow for outpatient studies. Although the strategies summarized are specific to the University of Nebraska Medical Center, many of the principles could be adapted to other teaching programs. The most basic element is to tie reward and recognition to efforts in primary care.

The application of atomic force microscopy for the detection of microcrystals in synovial fluid from patients with recurrent synovitis.

Synovial fluid from 33 patients with inflammatory arthritis was examined with a polarized light microscope (PLM) and an atomic force microscope (AFM). Two samples were imaged with a transmission electron microscope (TEM) to determine calcium/phosphate ratios and identify microcrystals of calcium pyrophosphate dihydrate and octacalcium phosphate. Additional correlative x-ray diffraction studies were performed on several samples including purified hydroxyapatite and sodium chloride crystals. Monosodium urate, calcium pyrophosphate dihydrate, hydroxyapatite, octacalcium phosphate, and cholesterol crystals were identified with AFM. AFM images of these microcrystals revealed detailed surface topology, including lattice parameters and structural irregularities at the crystals' surface. These features were consistent with those obtained by TEM and x-ray diffraction studies. In addition, AFM images revealed that some specimens contained microcrystals that were undetected by PLM and/or TEM. These results suggest that AFM may provide a simple yet powerful technique for the detection of microcrystals in synovial fluid taken from patients with crystal-induced arthritis.

Prevalence of rheumatoid arthritis, osteoarthritis, chondrocalcinosis and gouty arthritis at age 79.

The prevalence of rheumatic diseases was studied in representative subsamples by interview (n = 134), and by physical (n = 89) and radiographic (n = 81) examination in a representative sample of 79-year-olds in Göteborg, Sweden. The prevalence of rheumatoid arthritis (3-8 ARA criteria) was 10%. Radiographic osteoarthritis (OA) was diagnosed in wrists and/or finger joints of 65% of the probands and in knee joints of 14%. The first metacarpophalangeal (MCP I) joint was more frequently involved in males than in females (p less than 0.05). In females palpable enlargement of distal (DIP) and proximal interphalangeal finger joints correlated (p less than 0.01) to radiographic OA. The degree of heavy work in previous occupations was correlated to radiographic OA of DIP II-V in females (p less than 0.05 and of MCP I in males (p less than 0.05) but not to radiographic or clinical OA in knee joints. Symptoms of OA were reported by 6.1% in the knee and in 4.5% in hip joints. The prevalence of chondrocalcinosis averaged 15% (23% of females and 6% of males). Chondrocalcinosis of the hands occurred in 21% of females but in no males. The prevalence of hyperuricemia was 15% (women 6%, men 29%), and gouty arthritis was found in one woman.

Prevalence of symptoms and signs of joint impairment at age 79.

The prevalence of back and joint impairments was studied in a representative subsample of 77 women and 57 men aged 79. Forty-six per cent of the subjects had no history of back or joint complaints. Thirty-two per cent reported current back pains while 50% stated they never experienced such pains. Back pains (past or present) were localized in the lumbar region predominantly (40%), and were almost constantly present in 8% of the subjects. The spinal mobility remained acceptable for function of the activities of daily living (ADL) in the majority of the subjects. Thirty-six per cent of the subjects had past or present complaints from the joints of the extremities, predominantly of the knee, shoulder or hip joints. Physical signs of joint disorders as deformities, swelling or tenderness were rare except for enlargement of distal interphalangeal joints (right hand: females 38%, males 14%). Restricted range of motion (ROM) in one or several joints was found in one fifth (i.e., knee joints) to two thirds (i.e., hip joints). No significant gender differences were observed with the exception of the thoracolumbar ROM that was more frequently restricted in males. Severe restriction of separate movements (to less than 50% of ROM) was, generally, infrequent (0-8% of the subjects) although advanced impairment of hip inward rotation was found in 14% of the subjects. Restricted ROM associated with joint complaints was found in 2-11% of the subjects (i.e., knee joints 2%, shoulder joints 9%, hip joints 11%). A considerable proportion of 79-year-olds, thus, had some--though usually limited--restriction of joint ROM.

Cutaneous immunofluorescence studies in adult rheumatoid arthritis in sun-exposed and non-sun-exposed areas.

The incidence and significance of positive cutaneous immunofluorescence findings were assessed in biopsy specimens of both sun-exposed and non-sun-exposed skin of 34 adult patients with rheumatoid arthritis (RA) who were not receiving systemic corticosteroids. The incidence of lupus erythematosus (LE)-band was low (8.6%) in both groups. Twenty-eight percent of the patients had perivascular IgM and/or C3 deposits, and 74% had cytoid bodies in the papillary dermis. These studies indicate that the incidence of LE band is low in RA and that the detection of such a band in normal skin warrants close follow-up of RA patients for possible development of LE.