Describing our experience with the effects of multisystem inflammatory syndrome in children with COVID-19 on the cardiovascular system.

Cardiac involvement with multisystem inflammatory syndrome in children can include coronary artery abnormalities, ventricular dysfunction, conduction abnormalities, arrhythmias, pericarditis, and myocarditis. We report the cardiac findings in 34 patients with multisystem inflammatory syndrome in children admitted to a single institution. We looked at patient age, sex, brain natriuretic peptide levels, troponin levels, ejection fraction, presence of pericardial effusion, valvular changes, need for inotropic agents, and electrocardiogram findings. Our data showed that elevated brain natriuretic peptide did not predict troponin elevation and vice versa. Additionally, troponin rise was not a reliable marker for decreased left ventricular ejection fraction. All changes tracked were proven to be transient and resolved after initiating steroids, Intravenous immune globulin (IVIG), and occasionally anakinra.

Retrospective Analysis of Cataract Formation and Nutritional Etiology in a Managed Collection of Parakeet Auklets (Aethia psittacula).

The parakeet auklet (Aethia psittacula) is a piscivorous seabird with a natural diet of various invertebrate and teleost species, which is challenging to replicate in a managed collection. A high prevalence of early onset cataracts was observed in a managed collection of parakeet auklets at the North Carolina Zoo (Asheboro, NC, USA), which was hypothesized to be related to inappropriate vitamin A and E levels. From 1994 to 2002, these parakeet auklets were offered dietary supplementation comprising Vita-Zu small bird tablets. In June 2002, the birds were transitioned to only Thiamin-E paste (vitamin E and thiamin only). Plasma samples were collected from birds with and without cataracts from 1998 to 2005 and submitted for vitamin A (retinol) and vitamin E (α-tocopherol) analysis. Food items comprising the birds' diet were also evaluated for vitamin content. This information was combined with clinical and necropsy data from medical records from 1994 to 2015. A total of 78% of birds (39/50) developed cataracts, with a median age of onset of 7 years (range, 2-12 years). Cataracts ranged from incipient to hypermature during both routine ophthalmic examinations and postmortem evaluations. The median (range) of plasma retinol and α-tocopherol values were 1.99 µg/mL (0.20-6.68 µg/mL) and 15.39 µg/mL (3.40-96.27 µg/mL), respectively. There were no significant differences in plasma concentrations of vitamins based on the animals' sex, origin, presence of cataracts, or administered vitamin supplementation product. No other etiologies for cataract development were identified in the population. Further research in free-ranging parakeet auklet nutrition and cataract occurrence is warranted for continued species collection management.

The Relationship Between Patient Expectations and Functional Outcomes in Patients Undergoing Cartilage Repair of the Knee: A Mixed Methods Study.

CONTEXT: Patient expectations have been shown to be a major predictor of outcomes. Fulfilled expectations have been linked to increased patient satisfaction and rehabilitation adherence. Expectations may be influenced by a variety of factors, including patient characteristics, preoperative function, or disease characteristics. It is currently unknown what factors may influence patient expectations prior to cartilage repair of the knee, and to what degree. Furthermore, understanding the importance and values of those expectations for recovery using mixed methods has not previously been conducted in this patient population. The purpose of this mixed methods study is to examine and explore the relationships between patient expectations and functional outcome in patients undergoing cartilage repair of the knee. DESIGN: A mixed methods design was used. METHODS: Twenty-one patients scheduled to undergo cartilage repair of the knee were included. Participants completed the Hospital for Special Surgery Knee Surgery Expectations Survey and the Knee Injury and Osteoarthritis Outcome Score at their preoperative visit. Knee Injury and Osteoarthritis Outcome Scores were also obtained at 3 and 6 months postsurgery. A selected sample of 6 participants participated in semi-structured interviews 6 months postsurgery. Pearson correlation coefficients were used to determine relationships between expectations and functional outcome. RESULTS: Patients have moderate expectations for recovery, and these expectations were positively associated with preoperative pain, activities of daily living, and quality of life. Expectations also correlated with symptoms 3 months postsurgery, but there were no other significant correlations between preoperative expectations and postoperative function in the short term. Four qualitative themes emerged as participants described how previous recovery experiences shaped their expectations. CONCLUSIONS: Formalized patient and caregiver education, prehabilitation, and the use of psychological skills during rehabilitation may help to manage patient expectations and provide more focused and individualized care, thus improving outcomes.

Phenotypic characterization of complete CSNB in the inbred research beagle: how common is CSNB in research and companion dogs?

PURPOSE: Although congenital stationary night blindness (CSNB) has been described in a Japanese beagle dog research colony, certain clinical correlates with human CSNB have not yet been described, nor has an estimate of frequency of the condition been made in inbred and outbred beagle populations. METHODS: A beagle with CSNB obtained from a commercial research dog supplier in the USA and matched control dogs (n = 3) underwent examination, refraction, ocular imaging, assessment of visual navigation ability and detailed electroretinography (ERG). Retrospective review of ERGs in two independent groups of inbred (n = 15 and 537, respectively) and one group of outbred dogs (n = 36) was used to estimate CSNB frequency in these populations. RESULTS: In the affected dog, there were absent dark-adapted b-waves in response to dim-light flashes, severely reduced dark-adapted b-waves in response to bright-light flashes, and normal light-adapted b-waves with a-waves that had broadened troughs. Long-flash ERGs confirmed a markedly reduced b-wave with a preserved d-wave, consistent with cone ON-bipolar cell dysfunction. There was evidence of normal rod photoreceptor a-wave dark adaptation, and rapid light adaptation. In the wider beagle populations, five inbred beagles had a b/a wave ratio of < 1 in dark-adapted bright-flash ERG, whereas no outbred beagles had ERGs consistent with CSNB. CONCLUSIONS: The identified dog had clinical findings consistent with complete type CSNB, similar to that described in the Japanese colony. CSNB appears to be a rare disorder in the wider beagle population, although its detection could confound studies that use retinal function as an outcome measure in research dogs, necessitating careful baseline studies to be performed prior to experimentation.

The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye.

PURPOSE: To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). METHODS: Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. RESULTS: Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. CONCLUSION: Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted.

Fixed dynamometry is more sensitive than vital capacity or ALS rating scale.

INTRODUCTION: Improved outcome measures are essential to efficiently screen the growing number of potential amyotrophic lateral sclerosis (ALS) therapies. METHODS: This longitudinal study of 100 (70 male) participants with ALS compared Accurate Test of Limb Isometric Strength (ATLIS), using a fixed, wireless load cell, with ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC). RESULTS: Participants enrolled at 5 U.S. sites. Data were analyzed from 66 participants with complete ATLIS, ALSFRS-R, and VC data over at least 3 visits. Change in ATLIS was less variable both within- and among-person than change in ALSFRS-R or VC. Additionally, participants who had normal ALSFRS-R arm and leg function averaged 12 to 32% below expected strength values measured by ATLIS. CONCLUSIONS: ATLIS was more sensitive to change than ALSFRS-R or VC and could decrease sample size requirements by approximately one-third. The ability of ATLIS to detect prefunctional change has potential value in early trials. Muscle Nerve 56: 710-715, 2017.

Comparison of topically applied flurbiprofen or bromfenac ophthalmic solution on post-operative ocular hypertension in canine patients following cataract surgery.

OBJECTIVE: To compare the prevalence and kinetics of ocular hypertension after routine cataract extraction when using a predominately COX-2 inhibitor (bromfenac) versus a predominately COX-1 inhibitor (flurbiprofen) in combination with a topical corticosteroid. PROCEDURES: Patients undergoing unilateral or bilateral cataract surgery were randomly assigned to receive flurbiprofen or bromfenac at the day of surgery and continued for 6 weeks postoperatively, along with topical neo poly dexamethasone. No systemic nonsteroidal anti-inflammatory medications were administered before or after surgery. Intraocular pressure was monitored pre and postoperatively. When an IOP of >25 mmHg was detected, therapeutic intervention was performed. RESULTS: Eyes in both treatment groups showed a similar IOP profile with the highest mean IOP occurring two hours postsurgery and slowly declining during the next 6 weeks. However, eyes receiving bromfenac had a higher mean IOP at 2 h post-op (22.1 mmHg) than eyes receiving flurbiprofen (18.8 mmHg) and a slower decrease in IOP in the weeks after surgery. Over the course of the study, a higher percentage of eyes receiving bromfenac had therapy discontinued over concerns of elevated IOP compared to eyes receiving flurbiprofen (bromfenac 23.1% and flurbiprofen 9.8%). On average, the risk of having elevated intraocular pressure with bromfenac is 1.04 times higher than with flurbiprofen. CONCLUSION: Elevated postoperative IOP was observed in both treatment groups; however, bromfenac-treated eyes were more likely to require intervention for elevated IOP.

Causes of endogenous uveitis in cats presented to referral clinics in North Carolina.

OBJECTIVE: To investigate the causes of endogenous uveitis in cats presenting to referral ophthalmology clinics in North Carolina. PROCEDURE: Medical records of cats diagnosed with endogenous uveitis at North Carolina State University's College of Veterinary Medicine (NCSU-CVM) or Animal Eye Care Associates of Cary, NC between 2003 and 2015 were reviewed. Inclusion criteria were cats that had complete diagnostic workups, including clinical, clinicopathological, serological, and histopathological data, as well as imaging modalities. Serology was consistently completed for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), Toxoplasma gondii, and Bartonella spp. RESULTS: One hundred and twenty cats met the inclusion criteria. Seroprevalence of FeLV (2.7%), FIV (7.3%), FCoV (34.7%), T. gondii (23.7%), and Bartonella spp. (43.2%) was observed, with a combined seroprevalence of 59.2%. Nineteen cats (15.8%) were diagnosed with feline infectious peritonitis (FIP) based on clinical, hematological, serological, histopathological, and necropsy findings. The average age of all cases was 7.62 years, while the average age of cats diagnosed with FIP was 1.82 years. Neoplasia was diagnosed in six cats (5.0%). No underlying etiology was found in 49 cats (40.8%). CONCLUSIONS: Both idiopathic and neoplastic causes of uveitis were less prevalent than previously reported in studies, while seropositivity was higher than previously reported for the study area. This may be due to improved diagnostic capabilities or that cats with infectious disease were more likely to be referred. Because of the high prevalence of FIP, young cats with uveitis should be evaluated for hyperglobulinemia and FCoV serology should be performed as minimal diagnostics.

Efficacy of COX-2 inhibitors in controlling inflammation and capsular opacification after phacoemulsification cataract removal.

OBJECTIVE: To evaluate the efficacy of 0.9% bromfenac (Xibrom™) or a celecoxib-impregnated intraocular lens (celecoxib-IOL) compared with 1% prednisolone acetate (PA) in controlling postoperative inflammation and posterior capsule opacification (PCO). ANIMAL STUDIED: Fifty-nine dogs undergoing cataract extraction by phacoemulsification. PROCEDURE: Bilateral patients received bromfenac or celecoxib-IOL plus PA in one eye, and PA in the contralateral eye. Unilateral patients received bromfenac or PA. Complete ophthalmic examination including tonometry, slit-lamp grading of flare and PCO, and digital image acquisition for masked PCO evaluation was performed within 24 h and 1, 4, 12, 24, and 56 weeks following surgery. RESULTS: Celecoxib-IOL/PA-treated eyes had significantly less flare than PA-treated eyes, which had significantly less flare than bromfenac-treated eyes 24 h postoperatively. There was no significant difference in intraocular pressure (IOP) postoperatively, or at 1, 24, or 56 weeks. Celecoxib-IOL/PA-treated eyes had significantly lower IOP measurements than bromfenac and PA-treated eyes at 4 and 12 weeks. There was no significant difference in PCO level between groups using slit-lamp biomicroscopy at any time point. Masked evaluation of digital images revealed significantly less PCO in celecoxib-IOL/PA- vs. bromfenac-treated eyes at 4 weeks, and in bromfenac- vs. PA-treated eyes at 56 weeks. CONCLUSIONS: Eyes receiving celecoxib-IOL/PA had better initial control of inflammation. Bromfenac was equally effective compared with PA in controlling inflammation. There was no association between COX-2 inhibitor administration and ocular hypertension. Celecoxib-IOL/PA-treated eyes showed better initial control of PCO (up to 12 weeks), while eyes receiving bromfenac had better long-term control of PCO (56 weeks).

Influence of response shift on early patient-reported outcomes following autologous chondrocyte implantation.

PURPOSE: Response shift is the phenomenon by which an individual's standards for evaluation change over time. The purpose of this study was to determine whether patients undergoing autologous chondrocyte implantation (ACI) experience response shift. METHODS: Forty-eight patients undergoing ACI participated. The "then-test" method was used to evaluate response shift in commonly used patient-reported outcome measures (PROMs)-the SF-36 Physical Component Scale (SF-36 PCS), WOMAC, IKDC, and Lysholm. Each PROM was completed pre- and 6 and 12 months post-surgery. At 6 and 12 months, an additional "then" version of each form was also completed. The "then" version was identical to the original except that patients were instructed to assess how they were prior to ACI. Traditional change, response shift adjusted change, and response shift magnitude were calculated at 6 and 12 months. T tests (p < 0.05) were used to compare traditional change to response-shift-adjusted change, and response shift magnitude values to previously established minimal detectable change. RESULTS: There were no differences between traditional change and response-shift-adjusted change for any of the PROMs. The mean response shift magnitude value of the WOMAC at 6 months (15 ± 14, p = 0.047) was greater than the previously established minimal detectable change (10.9). The mean response shift magnitude value for the SF-36 PCS at 12 months (9.4 ± 6.8, p = 0.017) also exceeded the previously established minimal detectable change (6.6). CONCLUSIONS: There was no evidence of a group-level effect for response shift. These results support the validity of pre-test/post-test research designs in evaluating treatment effects. However, there is evidence that response shifts may occur on a patient-by-patient basis, and scores on the WOMAC and SF-36 in particular may be influenced by response shift. LEVEL OF EVIDENCE: II.

Proteomic identification of carbonylated proteins in the kidney of trichloroethene-exposed MRL+/+ mice.

Trichloroethene (TCE), a common environmental and occupational pollutant, is associated with multiorgan toxicity. Kidney is one of major target organs affected as a result of TCE exposure. Our previous studies have shown that exposure to TCE causes increased protein oxidation (protein carbonylation) in the kidneys of autoimmune-prone MRL+/+ mice, and suggested a potential role of protein oxidation in TCE-mediated nephrotoxicity. To assess the impact of chronic TCE exposure on protein oxidation, particularly to identify the carbonylated proteins in kidneys, female MRL+/+ mice were treated with TCE at the dose of 2 mg/ml via drinking water for 36 weeks and kidney protein extracts were analyzed for protein carbonyls and carbonylated proteins identified using proteomic approaches (2D gel, Western blot, MALDI TOF/TOF MS/MS, etc.). TCE treatment led to significantly increased protein carbonyls in the kidney protein extracts (20 000 g pellet fraction). Interestingly, among 18 identified carbonylated proteins, 10 were found only in the kidneys of TCE-treated mice, whereas other 8 were present in the kidneys of both control and TCE-treated mice. The identified carbonylated proteins represent skeletal proteins, chaperones, stress proteins, enzymes, plasma protein and proteins involved in signaling pathways. The findings provide a map for further exploring the role of carbonylated proteins in TCE-mediated nephrotoxicity.

Patient-oriented and performance-based outcomes after knee autologous chondrocyte implantation: a timeline for the first year of recovery.

CONTEXT: It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year after ACI. OBJECTIVE: To document the recovery of functional performance of activities of daily living after ACI. PATIENTS: ACI patients (n = 48, 29 male; 35.1 ± 8.0 y). INTERVENTION: All patients completed functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over, and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and completed patient-reported outcome measures (International Knee Documentation Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster Osteoarthritis Index [WOMAC], and 36-Item Short-Form Health Survey) preoperatively and 3, 6, and 12 mo postoperatively. MAIN OUTCOME MEASURES: A covariance pattern model was used to compare performance and self-reported outcome across time and provide a timeline for functional recovery after ACI. RESULTS: Participants demonstrated significant improvement in walk-across stride length from baseline (42.0% ± 8.9% height) at 6 (46.8% ± 8.1%) and 12 mo (46.6% ± 7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 mo than presurgery. Step-up/over time was significantly slower at 3 mo (1.67 ± 0.69 s) than at baseline (1.49 ± 0.33 s), 6 mo (1.51 ± 0.36 s), and 12 mo (1.40 ± 0.26 s). Step-up/over lift-up index was increased from baseline (41.0% ± 11.3% body weight [BW]) at 3 (45.0% ± 11.7% BW), 6 (47.0% ± 11.3% BW), and 12 mo (47.3% ± 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 ± 0.44 s) compared with baseline (1.39 ± 0.43 s), 6 mo (1.32 ± 0.05 s), and 12 mo (1.27 ± 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% ± 1.4% BW) compared with baseline (25.4% ± 1.5% BW). The WOMAC demonstrated significant improvements at 3 mo. All patient-reported outcomes were improved from baseline at 6 and 12 mo postsurgery. CONCLUSIONS: Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 mo after ACI should be anticipated, and improvement in performance of tasks requiring weight-bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or more after surgery.

Effect of a 2-week joint mobilization intervention on single-limb balance and ankle arthrokinematics in those with chronic ankle instability.

CONTEXT: A single talocrural joint-mobilization treatment has improved spatiotemporal measures of postural control but not ankle arthrokinematics in individuals with chronic ankle instability (CAI). However, the effects of multiple treatment sessions on these aspects of function have not been investigated. OBJECTIVE: To examine the effect of a 2-wk anterior-to-posterior joint-mobilization intervention on instrumented measures of single-limb-stance static postural control and ankle arthrokinematics in adults with CAI. DESIGN: Repeated measures. SETTING: Research laboratory. PARTICIPANTS: 12 individuals with CAI (6 male, 6 female; age 27.4 ± 4.3 y, height 175.4 ± 9.78 cm, mass 78.4 ± 11.0 kg). INTERVENTION: Subjects received 6 treatments sessions of talocrural grade II joint traction and grade III anterior-to-posterior joint mobilization over 2 wk. MAIN OUTCOME MEASURES: Instrumented measures of single-limb-stance static postural control (eyes open and closed) and anterior and posterior talar displacement and stiffness were assessed 1 wk before the intervention (baseline), before the first treatment (preintervention), 24-48 h after the final treatment (postintervention), and 1 wk later (1-wk follow-up). Postural control was analyzed as center-of-pressure velocity, center-of-pressure range, the mean of time-to-boundary minima, and standard deviation of time-to-boundary minima in the anteroposterior and mediolateral directions for each visual condition. RESULTS: No significant differences were identified in any measures of postural control (P > .08) or ankle arthrokinematics (P > .21). CONCLUSIONS: The 2-wk talocrural joint-mobilization intervention did not alter instrumented measures of single-limb-stance postural control or ankle arthrokinematics. Despite the absence of change in these measures, this study continues to clarify the role of talocrural joint mobilization as a rehabilitation strategy for patients with CAI.

Increasing femoral head size from 32 mm to 36 mm does not increase the revision risk for total hip replacement: a New Zealand joint registry study.

BACKGROUND: The use of larger femoral heads in total hip replacement (THR) has increased over the last decade. While the relationship between increasing head size and increased stability is well known, the risk of revision with increasing head size remains poorly understood. The aim of this study was to compare the outcome of total hip joint replacement with 32-mm and 36-mm heads. METHODS: We carried out a 20-year retrospective analysis of prospective data from the New Zealand Joint Registry (NZJR). All primary total hip replacements registered between January 1999 and December 2018 were included. We compared the rate of revision of 32-mm and 36-mm heads in THR. Sub-group analysis included comparisons of bearing type and all-cause revision. RESULTS: 60,051 primary THRs met our inclusion criteria. The revision rate per 100 component years was significantly higher with a 36-mm head than with a 32-mm head (0.649 vs. 0.534, p < 0.001). Subgroup analysis of bearing type showed no significant differences in revision rates for all combinations of 36-mm heads when compared to 32-mm (p = 0.074-0.92), with the exception of metal-on-metal (MoM); p = 0.038. When MoM was removed there was no significant difference in revision rates per 100 component years between 32-mm and 36-mm heads, 0.528 versus 0.578 (p = 0.099). CONCLUSIONS: Increasing head size from 32 mm to 36 mm results in no significant increase in revision in all bearing combinations except MoM.

Diode laser ablation of progressive pigmented iris lesions in 317 cats (356 eyes) appears overall safe and effective in decreasing progression of iris pigmentation.

OBJECTIVE: To describe a novel scoring system of feline pigmented iris lesions prior to utilization of diode laser ablation of progressive pigmented iris lesions and to retrospectively evaluate short- and long-term patient outcomes following transcorneal diode laser ablation. ANIMALS: 317 client-owned cats (356 eyes) were included. CLINICAL PRESENTATION: Records of cats undergoing diode laser ablation from January 2000 to December 2018 were retrospectively reviewed. A novel clinical grading system to describe severity of feline iris hyperpigmentation was developed. Recorded parameters included signalment, operated-upon eye, presurgical iris pigmentation score, intraocular pressure, visual status, postoperative complications, repeat laser surgery, patient status at last follow-up, time to death, and presumptive or known cause of death. RESULTS: Complications included corneal ulceration (25/356 [7%]), glaucoma (18/356 [5%]), uveitis (4/356 [1.1%]), and corneal edema (3/356 [0.8%]). Enucleation was performed in 12 eyes due to blindness and secondary glaucoma. Repeat laser due to continued progression of pigment was performed in 18.5% of eyes. Two study patients were euthanized due to presumptive metastatic disease. Of the 250 cats for whom confirmation was available via phone call or medical records, 240 (96%) were alive at 1 year. CLINICAL RELEVANCE: Diode laser ablation appears safe overall and may be effective in decreasing progression of feline iris pigmentation. Complication risks appear minimal.

Developing normalized strength scores for neuromuscular research.

INTRODUCTION: The Accurate Test of Limb Isometric Strength (ATLIS) device can reliably measure the strength of 12 muscle groups using a fixed load cell. The purpose of this study was to analyze ATLIS data from healthy adults to calculate an individual's predicted strength scores. METHODS: ATLIS data were collected from 432 healthy adults. Linear regression models were developed to predict each muscle group's strength. The R-squared statistic assessed variability accounted for by the models. RESULTS: Simple main effects models stratified by gender were used to establish regression equations for each muscle using factors of age, weight, and height. CONCLUSIONS: Normalizing raw strength scores controls for biometric factors, thus enabling meaningful comparisons between subjects and allowing each muscle to contribute equally to a summary score. Normalized scores are easily interpreted for broad clinical uses, and derived summary scores establish individuals' disease progression rates using a common scale, allowing for more efficient clinical trials.

The 'omics of obesity in B-cell acute lymphoblastic leukemia.

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, others have demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell-specific signature in patients associated with survival outcomes.

Model studies on iTRAQ modification of peptides: sequence-dependent reaction specificity.

A multiplexed peptide quantification strategy using the iTRAQ reagent has been described for relative measurements of peptides in digested protein mixtures. To validate the chemical specificity of the iTRAQ reaction, we have performed a detailed study of iTRAQ reactivity with two sets of synthetic peptides. The first set of peptides had sequences of Tyr-Xaa-Ser-Glu-Gly-Leu-Ser-Lys and Tyr-Xaa-Ser-Glu-Tyr-Leu-Ser-Lys where Xaa = Ala, Pro, Trp, Tyr, or Glu and was designed to study the extent of O-acylation by iTRAQ, especially hydroxyl-containing residues in different positions. The second set of peptides included Ala-Ser-Glu-His-Ala-Xaa-Tyr-Gly where Xaa = Ser, Thr, or Tyr and was selected to investigate the effect of histidyl residues separated by one amino acid residue from seryl, tyrosyl, or threonyl residues. Our findings indicated that, in addition to variable levels of O-acylation of nonsequence-specific hydroxyl-containing residues, significant sequence-specific O-acylation of seryl, threonyl, and tyrosyl hydroxyls occurred when separated one residue removed from a histidyl residue, that is, (Tyr/Ser)-Xaa-His or His-Xaa-(Tyr/Ser/Thr). This behavior was verified by a separate spiking experiment of one of the first set of peptides into Escherichia coli protein extracts, followed by retention time targeted LC-MS/MS to demonstrate the occurrence of modifications in a complex mixture. These sequence-dependent O-acylation modifications can be confounding factors to accurate MS quantification. Reversal of peptide O-acylation by the iTRAQ reagent can be accomplished by reaction with hydroxylamine with virtually no cleavage of N-acylation and is a recommended modification of the iTRAQ protocol for many applications.

Use of Botulinum Toxin for Androgenic Alopecia: A Systematic Review.

In this systematic review, we summarize the efficacy and safety of intradermal and intramuscular botulinum toxin injections for androgenic alopecia (AGA). Using PubMed, we conducted a literature search up to February 2021 using the following keyword combinations: "botulinum toxin" or "botox" and "androgenetic alopecia," "hair loss," or "alopecia." Five clinical studies met our inclusion criteria: 4 prospective cohorts and 1 randomized clinical trial (RCT). Study durations ranged from 24 to 60 weeks. No studies included control groups or compared botulinum toxin injections against approved treatments. A total of 165 participants were identified - all of whom were males with AGA. Of the 4 studies measuring response rates (i.e., subjects with >0% hair changes), response rates ranged from 75 to 79.1%. Within studies measuring hair count changes from intramuscular injections, changes ranged from 18 to 20.9%. No serious adverse events were reported. Studies on botulinum toxin injections have produced favorable outcomes for AGA subjects. However, results should be interpreted with caution due to the absence of control groups, small numbers of participants, and relatively low Jadad quality scores. Large RCTs are recommended to confirm efficacy and safety, explore the effects of botulinum toxin on females with pattern hair loss, and establish best practices for intradermal and intramuscular injection methodologies.

Microneedling and Its Use in Hair Loss Disorders: A Systematic Review.

INTRODUCTION: Microneedling (MN) is a minimally invasive procedure involving the induction of percutaneous wounds with medical-grade needles. In this literature review, we investigate clinical data on MN for the treatment of hair loss disorders. METHODS: A literature search was conducted through PubMed up to November 2021 to identify original articles evaluating the use of MN on hair loss disorders. The database was searched using the following keywords: "microneedling," "micro needling," "micro needle," "microneedle," "needle," "dermaroller" and "alopecia," "hair loss," "alopecia," "areata," "cicatricial," or "effluvium," RESULTS: A total of 22 clinical studies featuring 1127 subjects met our criteria for inclusion. Jadad scores ranged from 1 to 3, with a mean of 2. As an adjunct therapy, MN improved hair parameters across genders and a range of hair loss types, severities, needling devices, needling depths of 0.50-2.50 mm, and session frequencies from once weekly to monthly. Across 17 investigations totaling 911 androgenic alopecia (AGA) subjects, MN improved hair parameters when paired with 5% minoxidil, growth factor solutions, and/or platelet-rich plasma (PRP) topicals, or when introduced to subjects whose hair count changes had plateaued for ≥ 6 months on other treatments. Across four investigations on 201 alopecia areata (AA) subjects, MN improved hair parameters as a standalone therapy versus cryotherapy, as an adjunct to 5-aminolevulinic acid and photodynamic therapy, and equivalently when paired with topical PRP versus carbon dioxide laser therapy with topical PRP. Across 657 subjects receiving MN, no serious adverse events were reported. CONCLUSIONS: Clinical studies demonstrate generally favorable results for MN as an adjunct therapy for AGA and AA. However, data are of relatively low quality. Significant heterogeneity exists across interventions, comparators, and MN procedures. Large-scale randomized controlled trials are recommended to discern the effects of MN as a standalone and adjunct therapy, determine best practices, and establish long-term safety.