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Context: The Balance Error Scoring System (BESS) is a commonly used clinical tool to evaluate postural control that is traditionally performed through visual assessment and subjective evaluation of balance errors. The purpose of this study was to evaluate an automated computer-based scoring system using an instrumented pressure mat compared to the traditional human-based manual assessment. Design: A descriptive cross-sectional study design was used to evaluate the performance of the automated versus human BESS scoring methodology in healthy individuals. Methods: Fifty-one healthy active participants performed BESS trials following standard BESS procedures on an instrumented pressure mat (MobileMat, Tekscan Inc). Trained evaluators manually scored balance errors from frontal and sagittal plane video recordings for comparison to errors scored using center of force measurements and an automated scoring software (SportsAT, version 2.0.2, Tekscan Inc). A linear mixed model was used to determine measurement discrepancies across the 2 methods. Bland–Altman analyses were conducted to determine limit of agreement for the automated and manual scoring methods. Results: Significant differences between the automated and manual errors scored were observed across all conditions (P <.05), excluding bilateral firm stance. The greatest discrepancy between scoring methods was during the tandem foam stance, while the smallest discrepancy was during the tandem firm stance. Conclusion: The 2 methods of BESS scoring are different with wide limits of agreement. The benefits and risks of each approach to error scoring should be considered when selecting the most appropriate metric for clinical use or research studies. [ABSTRACT FROM AUTHOR]

Background: Burnout is a complex phenomenon and a major concern in graduate medical education as it directly impacts trainee well‐being. Identifying modifiable lifestyle factors over which trainees have immediate control could support timely, actionable, individual and programme‐level interventions to combat it. Objective: The objective of this pilot study is to describe modifiable lifestyle factors that may limit the development of burnout in medical residents and fellows. Methods: We performed a cross‐sectional survey of residents and fellows at academic medical centre from September 2017 to October 2017. Participants completed the Maslach Burnout Inventory and a questionnaire designed to identify factors hypothesised to be protective against burnout. Findings: A total of 205/805 (25%) trainees completed the survey with a mean (SD) age of 29.7 (2.6) years. 52% (n = 107) were female. Averaging at least 7 h of sleep per night was found to have a significant association with lower scores for the emotional exhaustion (24.8 [11, p = 0.04]) and depersonalisation (11.1 [6.4, p = 0.02]) dimensions of burnout. Additionally, self‐identifying as a healthy eater was found to have a significant association with lower scores for emotional exhaustion (25 [11.5, p = 0.03]) and depersonalisation (11.5 [6.6, p = 0.04]) as well. Workouts, hobbies, identifying with organised religion, praying, meditation and mindfulness activities were not associated with a difference. Conclusions: Adequate sleep (7 or more hours per night) and healthy eating are modifiable individual‐level lifestyle factors associated with lower burnout scores in trainees. These items could be a target for trainee education and programme level support initiatives. [ABSTRACT FROM AUTHOR]

Objective We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. Methods In this institutional review board–approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. Results One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). Conclusion Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography. [ABSTRACT FROM AUTHOR]

Objective This article assesses the effectiveness of a standardized local anesthetic (LA) technique designed to minimize the pain of local anesthesia administration in interventional radiology (IR). Materials and Methods A prospective study compared participants' experience in a control group (n = 63) of random LA administration techniques to a separate experimental group (n = 60) with a standardized technique based on known methods to minimize the pain of LA. Participants in each group were surveyed after LA administration to assess perceived pain and number of times a painful stick was felt. Participants were also asked to compare LA pain to prior experiences with LA, and to compare the overall pain experienced during the procedure to expected pain. Statistical Analysis Ordinal variable distribution analyses were performed using the Wilcoxon rank sum test. Categorical variable analyses were performed with the Pearson's global exact chi-square test. Results Pain of LA (mean 1.1 vs. 3.3 on a 0–10 scale, p < 0.001), number of times a painful stick was felt (mean 0.8 vs. 1.9 times, p < 0.001), and overall pain during the procedure (mean 1.5 vs. 3.4 on 0–10 scale, p < 0.001) were significantly less using the standardized versus random techniques. Compared with prior experiences of LA, pain using the standardized technique was less in 77.6%, the same in 22.4%, and more in 0% of patients while pain using the random technique was less in 46.4%, the same in 39.3%, and more in 14.3% of patients (p < 0.05). Conclusion Severity and frequency of pain from LA administration in IR procedures is minimized using a standardized anesthetic portal technique. This technique may also decrease overall pain experienced during IR procedures as well. [ABSTRACT FROM AUTHOR]

Purpose: To test the non-inferiority of a novel game platform for the treatment of pediatric amblyopia compared to standard eye patching. Methods: Forty participants (ages 4 to 18 years) across seven optometric clinics in the United States diagnosed as having amblyopia associated with anisometropia were randomly assigned to either 12 weeks of eye patching therapy (n = 19) or Barron Vision (Barron Associates, Inc) video game treatment (n = 21). Participants in the eye patching group with best corrected visual acuity (BCVA) worse than 20/200 in their amblyopic eye were prescribed 6 hours of patching daily, whereas those whose BCVA was 20/200 (1.00 logarithm of the minimum angle of resolution [logMAR]) or better were instructed to patch for 2 hours daily. Participants in the video game group, irrespective of the severity of their amblyopia, were instructed to play four different 5-minute mini-games five times a week for a total of 20 minutes a day. Results: A mixed linear modeling analysis of before and after BCVA differences after 12 weeks showed the non-inferiority of video game treatment to eye patching using a 0.10 logMAR threshold while adjusting for the participant's age, sex, and baseline BCVA. Conclusions: The results of the study suggest that a 12-week home-based video game vision therapy intervention can provide equivalent treatment outcomes to eye patching for amblyopia in children ages 5 to 18 years. Video game–based vision therapy may be a more acceptable and time-efficient alternative to existing approaches. By incorporating elements of perceptual learning, approaches such as Barron Vision video game treatment may have additional long-term therapeutic benefits and may improve treatment compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):20–29.] [ABSTRACT FROM AUTHOR]

The aims of this study were twofold. First, we examined the relationship between patient and caregiver ratings of neuropsychiatric symptoms in Parkinson's disease (PD). Second, we examined if the severity of depressive symptoms affects patient and caregiver perceptions of other neuropsychiatric symptoms and contributes to discrepancies between their perceptions. We examined data from a retrospective clinical cohort of 209 patients with PD and their caregivers. We used intra-class correlation coefficients and the Bland Altman method to assess intra-respondent (retrospective versus current) and inter-respondent (patient versus caregiver) agreement between Frontal Systems Behavior Scales (FrSBe) subscale scores. We then used generalized estimating equation models to examine FrSBe subscale scores and the magnitude of the intra- and inter-respondent discrepancies in FrSBe subscale scores, as a function of Beck Depression Inventory-2nd Edition scores, with patient demographic variable adjustments. There was low agreement between patient and caregiver ratings on all three subscales, at both time points, and high response variability within and between raters. Patients generally reported more severe neuropsychiatric symptoms than caregivers. Depression severity predicted patients' perceptions at both time points, but was more strongly associated with current perceptions. Depression severity predicted caregivers' current perceptions only. The inter-respondent discrepancy in perceived apathy and disinhibition, but not executive dysfunction, increased as a function of depression severity. There are differences in how patients with PD and caregivers perceive neuropsychiatric behaviors and the extent to which depressive symptoms influence their perceptions. Shared neuropathology and negative response biases likely contribute to these relationships. [ABSTRACT FROM AUTHOR]

Background: The effect of nighttime behaviors on cognition has not been studied independently from other neuropsychiatric symptoms. Objective: We evaluate the following hypotheses that sleep disturbances bring increased risk of earlier cognitive impairment, and more importantly that the effect of sleep disturbances is independent from other neuropsychiatric symptoms that may herald dementia. Methods: We used the National Alzheimer's Coordinating Center database to evaluate the relationship between Neuropsychiatric Inventory Questionnaire (NPI-Q) determined nighttime behaviors which served as surrogate for sleep disturbances and cognitive impairment. Montreal Cognitive Assessment scores defined two groups: conversion from 1) normal to mild cognitive impairment (MCI) and 2) MCI to dementia. The effect of nighttime behaviors at initial visit and covariates of age, sex, education, race, and other neuropsychiatric symptoms (NPI-Q), on conversion risk were analyzed using Cox regression. Results: Nighttime behaviors predicted earlier conversion time from normal cognition to MCI (hazard ratio (HR): 1.09; 95% CI: [1.00, 1.48], p = 0.048) but were not associated with MCI to dementia conversion (HR: 1.01; [0.92, 1.10], p = 0.856). In both groups, older age, female sex, lower education, and neuropsychiatric burden increased conversion risk. Conclusion: Our findings suggest that sleep disturbances predict earlier cognitive decline independently from other neuropsychiatric symptoms that may herald dementia. [ABSTRACT FROM AUTHOR]

Introduction: In concussion, clinical and physiological recovery are increasingly recognized as diverging definitions. This study investigated whether central microglial activation persisted in participants with concussion after receiving an unrestricted return-to-play (uRTP) designation using [18F]DPA-714 PET, an in vivo marker of microglia activation. Methods: Eight (5 M, 3 F) current athletes with concussion (Group 1) and 10 (5 M, 5 F) healthy collegiate students (Group 2) were enrolled. Group 1 completed a pre-injury (Visit1) screen, follow-up Visit2 within 24 h of a concussion diagnosis, and Visit3 at the time of uRTP. Healthy participants only completed assessments at Visit2 and Visit3. At Visit2, all participants completed a multidimensional battery of tests followed by a blood draw to determine genotype and study inclusion. At Visit3, participants completed a clinical battery of tests, brain MRI, and brain PET; no imaging tests were performed outside of Visit3. Results: For Group 1, significant differences were observed between Visits 1 and 2 (p < 0.05) in ImPACT, SCAT5 and SOT performance, but not between Visit1 and Visit3 for standard clinical measures (all p > 0.05), reflecting clinical recovery. Despite achieving clinical recovery, PET imaging at Visit3 revealed consistently higher [18F]DPA-714 tracer distribution volume (VT) of Group 1 compared to Group 2 in 10 brain regions (p < 0.001) analyzed from 164 regions of the whole brain, most notably within the limbic system, dorsal striatum, and medial temporal lobe. No notable differences were observed between clinical measures and VT between Group 1 and Group 2 at Visit3. Discussion: Our study is the first to demonstrate persisting microglial activation in active collegiate athletes who were diagnosed with a sport concussion and cleared for uRTP based on a clinical recovery. [ABSTRACT FROM AUTHOR]

Objective: We sought to identify patient factors associated with patient-reported screening behaviors in women with dense breasts. Methods: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography at an outpatient imaging center was previously conducted from March 2017 to February 2018. The survey included questions regarding mammographic screening frequency and recent participation in supplemental screening. These survey data were combined post hoc with clinical and demographic data and socioeconomic data imputed from census data. Logistic regression was used to identify patient factors associated with reported screening behaviors. Results: Surveys were completed by 508 women (median age, 59.0 years; range, 31.0-86.0 years) with dense breasts. Multivariable analysis demonstrated an independent association of undergoing mammographic screening annually with a history of discussing breast density with a doctor (adjusted odds ratio [AOR], 2.60; P = 0.019). Undergoing supplemental screening in the previous three years was independently associated with younger age (AOR, 1.59; P = 0.004), strong family history of breast cancer (AOR, 3.84; P = 0.027), higher perceived personal risk for breast cancer (AOR, 3.47; P = 0.004), and increased concern about radiation associated with screening examinations (AOR, 3.31; P = 0.006). Conclusion: Women with dense breasts who had discussed breast density with a doctor were more likely to report undergoing annual screening mammography, while younger women and women with a strong family history of breast cancer, higher perceived personal risk for breast cancer, or greater concern about radiation were more likely to report recently undergoing supplemental screening. [ABSTRACT FROM AUTHOR]

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients. Research question: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data. Study design and methods: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL. Results: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization. Interpretation: This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment. [ABSTRACT FROM AUTHOR]

Introduction: Anxiety symptoms are the most common neuropsychiatric manifestation of Parkinson's disease (PD), contributing to decreased quality of life. Few longitudinal studies in PD samples have examined correlates of anxiety symptoms over time. Understanding predictor variables may help to identify novel targets for reducing anxiety in PD. The aim of this study was to identify predictors of anxiety symptoms over 3 years in a clinic-based PD cohort. Methods: Our cohort included patients with PD at an academic medical center in the Southeastern United States (n = 105). Visits included assessment of motor, psychiatric, and cognitive features, including neuropsychological testing. For our multivariate model, we selected 11 predictor variables with the most existing evidence or theoretical support for an association with anxiety symptoms in PD. Multivariate linear mixed model regression was performed to determine which variables were significantly associated with anxiety symptoms over time. Results: Over half of participants (57%) met the screening threshold for an anxiety disorder at some point during the study. Independent predictors of anxiety symptoms over time included symptoms of REM sleep behavior disorder (RBD) and dysautonomia. Discussion: In this PD sample, RBD and dysautonomia symptoms were significantly associated with anxiety symptoms over time. Each of these relationships has been reported in one of two prior longitudinal studies. Unlike prior studies, cognitive impairment was not a significant predictor of anxiety symptoms in our sample. Future research should confirm the direction and mechanisms underlying these relationships, including the potential for anxiety symptom reduction through treatment for RBD and dysautonomia. [ABSTRACT FROM AUTHOR]

Purpose : Nearly all literature for predicting tumor grade in astrocytoma and oligodendroglioma pre-dates the molecular classification system. We investigated the association between contrast enhancement, ADC, and rCBV with tumor grade separately for IDH-mutant astrocytomas and molecularly-defined oligodendrogliomas. Methods: For this retrospective study, 44 patients with IDH-mutant astrocytomas (WHO grades II, III, or IV) and 39 patients with oligodendrogliomas (IDH-mutant and 1p/19q codeleted) (WHO grade II or III) were enrolled. Two readers independently assessed preoperative MRI for contrast enhancement, ADC, and rCBV. Inter-reader agreement was calculated, and statistical associations between MRI metrics and WHO grade were determined per reader. Results: For IDH-mutant astrocytomas, both readers found a stepwise positive association between contrast enhancement and WHO grade (Reader A: OR 7.79 [1.97, 30.80], p = 0.003; Reader B: OR 6.62 [1.70, 25.82], p = 0.006); both readers found that ADC was negatively associated with WHO grade (Reader A: OR 0.74 [0.61, 0.90], p = 0.002); Reader B: OR 0.80 [0.66, 0.96], p = 0.017), and both readers found that rCBV was positively associated with WHO grade (Reader A: OR 2.33 [1.35, 4.00], p = 0.002; Reader B: OR 2.13 [1.30, 3.57], p = 0.003). For oligodendrogliomas, both readers found a positive association between contrast enhancement and WHO grade (Reader A: OR 15.33 [2.56, 91.95], p = 0.003; Reader B: OR 20.00 [2.19, 182.45], p = 0.008), but neither reader found an association between ADC or rCBV and WHO grade. Conclusions: Contrast enhancement predicts WHO grade for IDH-mutant astrocytomas and oligodendrogliomas. ADC and rCBV predict WHO grade for IDH-mutant astrocytomas, but not for oligodendrogliomas. [ABSTRACT FROM AUTHOR]

Background: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. Methods/Design: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. Discussion: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice. [ABSTRACT FROM AUTHOR]

3D Single-breath Chemical Shift Imaging (3D-SBCSI) is a hybrid MR-spectroscopic imaging modality that uses hyperpolarized xenon-129 gas (Xe-129) to differentiate lung diseases by probing functional characteristics. This study tests the efficacy of 3D-SBCSI in differentiating physiology among pulmonary diseases. A total of 45 subjects—16 healthy, 11 idiopathic pulmonary fibrosis (IPF), 13 cystic fibrosis (CF), and 5 chronic obstructive pulmonary disease (COPD)—were given 1/3 forced vital capacity (FVC) of hyperpolarized Xe-129, inhaled for a ~7 s MRI acquisition. Proton, Xe-129 ventilation, and 3D-SBCSI images were acquired with separate breath-holds using a radiofrequency chest coil tuned to Xe-129. The Xe-129 spectrum was analyzed in each lung voxel for ratios of spectroscopic peaks, chemical shifts, and T2* relaxation. CF and COPD subjects had significantly more ventilation defects than IPF and healthy subjects, which correlated with FEV1 predicted (R = −0.74). FEV1 predicted correlated well with RBC/Gas ratio (R = 0.67). COPD and IPF had significantly higher Tissue/RBC ratios than other subjects, longer RBC T2* relaxation times, and greater RBC chemical shifts. CF subjects had more ventilation defects than healthy subjects, elevated Tissue/RBC ratio, shorter Tissue T2* relaxation, and greater RBC chemical shift. 3D-SBCSI may be helpful in the detection and characterization of pulmonary disease, following treatment efficacy, and predicting disease outcomes. [ABSTRACT FROM AUTHOR]

Women with polycystic ovary syndrome (PCOS) demonstrate gonadotropin‐releasing hormone (GnRH) pulse generator resistance to suppression with 7 days of progesterone and estradiol administration. It remains unknown whether such women demonstrate impairments in acute progesterone negative feedback on LH pulse frequency or progesterone positive feedback on gonadotropin release. This was a randomized, double‐blind, placebo‐controlled crossover study designed to test the hypothesis that acute, progesterone‐related suppression of LH pulse frequency and progesterone‐related augmentation of gonadotropin release are impaired in PCOS. Twelve normally cycling women and 12 women with PCOS completed study. Volunteers were pretreated with transdermal estradiol (0.2 mg/day) for 3 days and then underwent a frequent blood sampling study (20:00–20:00 h), during which they received micronized progesterone (100 mg) or placebo at 06:00 h. In a second study admission, volunteers received the intervention they did not receive during the first admission, but the protocol was otherwise identical. The primary outcome measures were LH secretory characteristics and circulating gonadotropin concentrations. Exogenous progesterone did not reduce LH pulse frequency in either group. Mean LH, pulsatile LH secretion, LH pulse mass, and mean FSH increased more with progesterone compared to placebo in both groups. Although trends toward less pronounced changes in LH pulse mass and pulsatile LH secretion were observed in the PCOS group, these differences were not statistically significant. In summary, exogenous progesterone did not suppress LH pulse frequency within 12 hours in estradiol‐pretreated women, and the positive feedback effect of progesterone on gonadotropin release was not demonstrably impaired in PCOS. New & Noteworthy: This study indicated that exogenous progesterone does not reduce LH pulse frequency within 12 h in women with PCOS, but progesterone acutely increased gonadotropin in these women. This study suggested that progesterone‐related augmentation of gonadotropin release may be impaired in PCOS compared to normally cycling women, but this finding was not statistically significant. [ABSTRACT FROM AUTHOR]

Background: Rhegmatogenous retinal detachment (RRD) is a common, potentially blinding ocular pathology that is considered a surgical emergency. Macular involvement has been identified as a major negative prognostic indicator for visual recovery after RRD correction. It is not currently clear whether early intervention improves visual outcomes, and in practice, there are potential disadvantages to performing early surgery for fovea-involving RRD. Such disadvantages include inadequate assessment of coexisting comorbidities, increased rate of complications related to poorly trained staff or tired surgeons, and anesthetic risk.Methods: A single-center, retrospective, cohort study of patients who underwent repair of macula-involving rhegmatogenous retinal detachment at the University of Virginia was performed. Variables collected included patient demographics, ocular history, clinical characteristics, and post-operative complications. Patients were excluded if they had a history of congenital or acquired pathology with an effect on visual function, bilateral or repeat rhegmatogenous detachment, age less than 18 years, follow up duration less than 6 months, or if they were repaired using scleral buckle, pneumatic retinopexy, 25- or 27-gauge pars plana vitrectomy, or any combination of these techniques. A multivariate regression model was used to compare overall outcomes such as post-operative visual acuity, intra-ocular pressure, retina attachment status, and complications among patients of differing timing of surgical repair. These analyses were adjusted for clinical factors known or considered to be associated with worse prognosis in rhegmatogenous retinal detachment.Results: A total of 104 patients undergoing 23-gauge vitrectomy for repair of macula involving rhegmatogenous retinal detachments were included in this study with mean follow up period 17.9 ± 14.1 months. Early surgical repair (< 48 h) was pursued in 26 patients, moderately delayed surgical repair (3-7 days), was performed in 29 patients and late surgical repair (> 7 days) in 49 patients. Our analysis showed no difference in post-operative visual acuity between patients with detachments undergoing early versus moderately delayed repair of RRD. However, mean visual acuity differed between patients undergoing early versus late repair at 3, 6, and 12 months. No significant difference was observed in post-operative complications between the three surgical timepoints including cataract formation, development of glaucoma and re-detachment rate. Use of 360 laser was found to be protective against re-detachment overall (OR 6.70 95% CI 1.93-23.2).Conclusions: These findings indicate that a moderate delay of 3-7 days from symptom onset for repair of macula-involving retinal detachment may be a safe approach as there are no differences in terms of visual acuity or post-operative complications compared to early repair within 48 h. Delaying surgery for > 7 days however is not recommended due to the loss of recovery of visual acuity observed in this study. Use of 360 laser may prevent risk of re-detachment after primary repair. [ABSTRACT FROM AUTHOR]

Key points: Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may themselves alter vascular function.No prior studies have examined the effect of acute hyperglycaemia on both macro‐ and microvascular function while controlling plasma insulin concentrations.Macrovascular and microvascular functional responses to euglycaemia and hyperglycaemia were compared. Octreotide was infused throughout both protocols to prevent endogenous insulin release.Acute hyperglycaemia (induced by intravenous glucose) enhanced brachial artery flow‐mediated dilatation, increased skeletal muscle microvascular blood volume and flow, and expanded cardiac muscle microvascular blood volume.Compared to other published findings, the results suggest that vascular responses to acute hyperglycaemia differ based on the study population (i.e. normal weight vs. overweight/obese) and/or glucose delivery method (i.e. intravenous vs. oral glucose). High glucose concentrations acutely provoke endothelial cell oxidative stress and are suggested to trigger diabetes‐related macro‐ and microvascular injury in humans. Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may each independently alter vascular function and obscure the effect of acute hyperglycaemia per se. Surprisingly, no studies have examined the acute effects of intravenous glucose‐induced hyperglycaemia on both macro‐ and microvascular function while controlling plasma insulin concentrations. In this randomized study of healthy young adults, we compared macrovascular (i.e. brachial artery flow‐mediated dilatation, carotid‐femoral pulse wave velocity and post‐ischaemic brachial artery flow velocity) and microvascular (heart and skeletal muscle perfusion by contrast‐enhanced ultrasound) functional responses to euglycaemia and hyperglycaemia. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute intravenous glucose‐induced hyperglycaemia enhanced brachial artery flow‐mediated dilatation (P = 0.004), increased skeletal muscle microvascular blood volume and flow (P = 0.001), and expanded cardiac muscle microvascular blood volume (P = 0.014). No measure of vascular function changed during octreotide‐maintained euglycaemia. Our findings suggest that unlike meal‐provoked acute hyperglycaemia, 4 h of intravenous glucose‐induced hyperglycaemia enhances brachial artery flow‐mediated dilatation, provokes cardiac and skeletal muscle microvascular function, and does not impair aortic stiffness. Previous findings of acute large artery vascular dysfunction during oral glucose or mixed meal ingestion may be due to differences in study populations and meal‐induced humoral or neural factors beyond hyperglycaemia per se. (ClinicalTrials.gov number NCT03520569.) [ABSTRACT FROM AUTHOR]

Objective: Some vendors have created algorithms that generate synthetic 2D (s2D) images from a digital breast tomosynthesis (DBT) dataset to reduce the radiation from obtaining a separate 2D digital mammography (DM). This study evaluated the visibility of amorphous calcifications on 2D DM versus s2D on screening mammography. Methods: This IRB-approved, retrospective, reader study included screening mammograms from 36 women who received screening DBT exams where both 2D DM and s2D images were obtained: 28 screening mammograms that were eventually given BI-RADS category 4 or 5 for amorphous calcifications and 8 BI-RADS category 1 or 2 screening exams. Two rounds of interpretation were conducted with a six-week washout period. Cases were randomized to display either the 2D DM or s2D images, which were then alternated in the second round. Four fellowship-trained breast radiologists determined whether a study merited recall for calcifications. If so, they rated calcification visibility on a scale of 1 to 5. McNemar chi-square tests were conducted to assess differences in recall rates and Wilcoxon signed rank tests were used to examine shifts in visibility. Results: There was no difference in detection rates of amorphous calcifications between 2D DM and s2D, which were 75.9% and 75.0%, respectively (P = 1.000). Collectively, amorphous calcifications were more visible on s2D than 2D DM, with mean visibility scores of 3.4 versus 3.0, respectively (P = 0.005). Conclusion: Synthetic 2D did not change identification of amorphous calcifications compared to 2D DM, and readers considered them more visible on average. [ABSTRACT FROM AUTHOR]

Objective: A local anesthetic is frequently administered as part of a lumbar epidural steroid injection (LESI); however, there is a rare potential for this to result in transient paralysis if administered incorrectly. The purpose of this retrospective study is to determine if the addition of bupivacaine significantly improves patient-reported pain scores. Materials and methods: This retrospective review includes patients undergoing LESI over an approximately 1 year time span. Pre-procedure, immediate post-procedure, and 1-week integer scaled pain scores were recorded. Ordinal regression was used to compare the distributions of the aggregated ordinal pain score categories between bupivacaine- and non-bupivacaine-injected patients. Results: Two hundred fifty-eight patients met the inclusion criteria (126F:132 M, mean age 64.7 years) with 164 receiving bupivacaine and steroids and 94 receiving steroids alone. The relative frequency distributions for pre-injection pain did not differ between the bupivacaine patients and the non-bupivacaine patients (p = 0.114). Similarly, the relative frequency distributions for immediate and 1-week post-procedure pain did not differ between the bupivacaine patients and the non-bupivacaine patients (p = 0.293 at immediate time point and p = 0.306 at 1-week time point). Odds ratios comparing pain severity change between the bupivacaine and non-bupivacaine patients also were not significantly different at either the immediate post-procedure (p = 0.769) or 1-week (p = 0.203) time points. Conclusion: The lack of a significant downward shift in the bupivacaine patients' post-procedure pain scores compared to the non-bupivacaine patients' post-procedure pain scores raises doubts about bupivacaine's utility as a standard component of a lumbar epidural injection. [ABSTRACT FROM AUTHOR]

Background The Endocrine Self-Assessment Program In-Training Examination (ESAP-ITE) has the novel formative approach of allowing open access to all questions and answers after secure examination administration is complete, resulting in the creation of an entirely new in-training examination annually. Objective To determine whether scores on the novel ESAP-ITE predict pass/fail outcomes on the American Board of Internal Medicine Endocrinology, Diabetes, and Metabolism Certification Examination (ABIM-ECE). Methods All endocrine fellows-in-training who took the ESAP-ITE between 2016 and 2019 and then subsequently attempted the ABIM-ECE within the same calendar year were included (n = 982). Primary analyses used the ESAP-ITE score from the final year of fellowship training. Covariates included sex, age on date of ABIM-ECE, medical school country, fellowship program region, pass/fail outcomes on the ABIM Internal Medicine Certification Examination, and ESAP-ITE score. All variables were analyzed using multivariable logistic regression. Results ESAP-ITE score (P  < 0.001), ABIM Internal Medicine Certification Examination outcome (P  < 0.001), and age (P  = 0.005) were each significant predictors of passing the ABIM-ECE on the first attempt. ESAP-ITE score was the strongest predictor of passing the ABIM-ECE, and this relationship was such that a score of 75% correct yielded a 97% probability of passing the ABIM-ECE, whereas a score of 50% correct generated only a 70% probability of doing so. Sex, fellowship program region, and medical school country were not significant predictors of ABIM-ECE outcomes. Conclusions In addition to serving as an important learning instrument for endocrine fellowship programs, ESAP-ITE is a robust predictive tool for pass/fail outcomes on the ABIM-ECE. [ABSTRACT FROM AUTHOR]

Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO2max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO2max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = − 0.48, p ≤ 0.0001), BF (r = − 0.54, p ≤ 0.001), VO2max (r = 0.5, p ≤ 0.001), BMI (r = − 0.40, p < 0.001), WT (r = − 0.33, p = 0.001), LDL-C (r = − 0.26, p = 0.009), TG (r = − 0.25, p = 0.012) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO2max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate the diagnostic performance of a 1-min contrast-enhanced 3D-FLASH pulse sequence for detecting intracranial enhancing lesions compared to standard contrast-enhanced 3D-MPRAGE pulse sequence. Methods: Contrast-enhanced 3D-FLASH (acquisition time 49 s) and contrast-enhanced 3D-MPRAGE (4 min 35 s) pulse sequences were performed consecutively in 110 inpatient/emergency department 3T MRI brain examinations and analyzed by two independent neuroradiologist readers. For each sequence, the readers recorded (1) number of enhancing intracranial lesions; (2) intracranial susceptibility artifact (presence or absence; mm depth of intracranial signal loss); and (3) motion artifact (none, mild, moderate, severe). Inter and intra-reader agreement and reader accuracy relative to a reference standard were determined, and sequence comparison with respect to susceptibility and motion artifacts was performed. Results: There was substantial intra-reader, inter-sequence agreement [reader 1, κ = 0.70 (95% CI: [0.60, 0.81]); reader 2, κ = 0.70 (95% CI: [0.59, 0.82])] and substantial intra-sequence, inter-reader agreement [3D-MPRAGE assessment, κ = 0.76 (95% CI: [0.66, 0.86]); 3D-FLASH assessment, κ = 0.86 (95% CI: [0.77, 0.94]) for detection of intracranial enhancing lesions. For both readers, the diagnostic accuracy of 3D-FLASH and 3D-MPRAGE was similar (3D-MPRAGE: 86.4 and 88.1%; 3D-FLASH: 88.2 and 84.5%), with no inter-sequence diagnostic accuracy discordancy between the sequences for either reader. 3D-FLASH was associated with less susceptibility artifact (p < 0.001 both readers) and less motion artifact (p < 0.001 both readers). Conclusion: On 3T brain MRI in the inpatient and emergency department setting, 1-min 3D-FLASH pulse sequence achieved comparable diagnostic performance to 4.5 min 3D-MPRAGE pulse sequence for detecting enhancing intracranial lesions, with reduced susceptibility and motion artifacts. [ABSTRACT FROM AUTHOR]

Purpose: The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma. Methods: This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined. Results: Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [− 0.11–1.00]), necrosis (ĸ = 0.55 [0.34–0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68–0.99]), multifocal disease (ĸ = 0.55 [0.39–0.70]), and primary lobe (ĸ = 0.85 [0.80–0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2–0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044). Conclusions: Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant. [ABSTRACT FROM AUTHOR]

Background: Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. Little is known about the effects of environmental factors on HD symptom onset and severity. Objective: To evaluate the relationship between education level and age of diagnosis, symptom onset, and symptom severity in HD. Methods: This study evaluated 4537 adult‐onset, motor‐manifest HD participants from the Enroll‐HD global registry. Education level was assessed using International Standard Classification of Education categories, stratified into three education groups corresponding to pre‐secondary, secondary, and post‐secondary educational attainment. Motor and behavioral symptoms of HD, cognition, and functional capacity were measured using baseline Unified Huntington's Disease Rating Scale (UHDRS), Mini‐Mental State Exam (MMSE), Symbol Digit Modalities Test (SDMT), verbal fluency, and Stroop assessments. Results: After adjusting for CAG repeats, higher level of education predicted lower age of onset of motor symptoms, depression, irritability, and cognitive impairment (all P‐values < 0.001). After adjusting for age of enrollment and CAG repeats, the highest education level predicted the lowest UHDRS motor scores, higher UHDRS total functional capacity and functional assessment scores, and higher SDMT, MMSE, verbal fluency, and Stroop assessment scores (all P‐values < 0.001). Conclusions: HD participants with higher education levels have earlier age of diagnosis and age of symptom onset, but lower motor exam scores and higher functional assessment scores. Earlier recognition of symptoms in more highly educated participants may explain earlier symptom onset and diagnosis. Better performance on motor and functional assessments may be explained by higher cognitive reserve in those with greater education. [ABSTRACT FROM AUTHOR]

Introduction: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear. Materials and methods: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults. Results: Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p = 0.032), while other markers of arterial stiffness did not change (all p > 0.05). Heart rate (+3.62 bpm; p = 0.009), mean arterial pressure (+4.14 mmHg; p = 0.033), central diastolic blood pressure (+4.16 mmHg; p = 0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p = 0.044) also significantly increased during hyperglycemic-hyperinsulinemia. Conclusions: Hyperglycemic-hyperinsulinemia acutely increased cfPWV, heart rate, mean arterial pressure, and diastolic blood pressure in healthy humans, perhaps reflecting enhanced sympathetic tone. Whether repeated bouts of hyperglycemia with hyperinsulinemia contribute to chronically-enhanced arterial stiffness remains unknown. [ABSTRACT FROM AUTHOR]

Hypoadiponectinemia is speculated to play a key role in the relationship between obesity and COVID‐19 respiratory failure. However, only one study has examined adiponectin levels in COVID‐19 patients, and none have investigated adiponectin levels strictly in patients with acute respiratory failure. In this study, we performed a retrospective case‐control study of adipokine levels in patients with acute respiratory failure caused by either COVID‐19 or other viral/bacterial source. All patients with COVID‐19 respiratory failure in the University of Virginia Biorepository and Tissue Research database were included. We also selected patients with non‐COVID‐19 infectious respiratory failure from the same biorepository to serve as a comparison cohort. Plasma adipokine levels were measured on three occasions during the first 72 hours of hospitalization. Twelve patients with COVID‐19 respiratory failure and 17 patients with other infectious respiratory failure were studied. Adiponectin levels were significantly lower in patients with COVID‐19 respiratory failure, even after adjustment for age, sex, BMI, and other covariates. In conclusion, adiponectin levels appear to be reduced in COVID‐19 respiratory failure. Larger studies are needed to confirm this report. [ABSTRACT FROM AUTHOR]

To investigate whether hyperpolarised xenon-129 MRI (HXeMRI) enables regional and physiological resolution of diffusing capacity limitations in chronic obstructive pulmonary disease (COPD), we evaluated 34 COPD subjects and 11 healthy volunteers. We report significant correlations between airflow abnormality quantified by HXeMRI and per cent predicted forced expiratory volume in 1 s; HXeMRI gas transfer capacity to red blood cells and carbon monoxide diffusion capacity (%DLCO); and HXeMRI gas transfer capacity to interstitium and per cent emphysema quantified by multidetector chest CT. We further demonstrate the capability of HXeMRI to distinguish varying pathology underlying COPD in subjects with low %DLCO and minimal emphysema. [ABSTRACT FROM AUTHOR]

Background: There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed. Objectives: The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients. Methods: We investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex. Results: Reduced Ch4 GMD was associated with reduced Fast Walking Speed in the "on" medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the "on" medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021). Conclusions: Reduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD. [ABSTRACT FROM AUTHOR]

Object: The purpose of this study was to assess whether fluoroscopically guided corticosteroid injections into the extrabursal tissues, trochanteric (subgluteus maximus) bursa, or subgluteus medius bursa provide better immediate and short-term pain relief.Materials and Methods: All fluoroscopically guided corticosteroid injections performed over a 67-month period for greater trochanteric pain syndrome were retrospectively reviewed. Procedural images were reviewed by two musculoskeletal radiologists to determine the dominant injection site based on final needle positioning and contrast spread pattern, with discrepancies resolved by consensus. Statistical analysis of the association between pain score reduction and dominant injection site was performed.Results: One hundred forty injections in 121 patients met the inclusion criteria. The immediate and 1-week post-injection pain reduction was statistically significant for trochanteric bursa, subgluteus medius bursa, and non-bursal injections. However, there was no statistically significant difference in the degree of pain reduction between the groups. There was statistically significant increase in the 1-week post-injection mean pain score compared with immediate post-injection mean pain score in the subgluteus medius bursa and non-bursal injection groups (p < 0.01) but not in the trochanteric bursa group.Conclusion: Fluoroscopy is frequently chosen over blind injection or ultrasound guidance for trochanteric steroid injections in patients with a high body mass index. Our results indicate that fluoroscopically guided steroid injections into the trochanteric bursa and subgluteus medius bursa significantly reduced immediate and 1-week post-injection pain scores, as do non-bursal injections. Steroid injection into the subgluteus medius bursa and non-bursal sites may be less effective in maintaining pain reduction at 1-week post-injection. [ABSTRACT FROM AUTHOR]

Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared with normoglycemic controls. Currently, there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiological factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulinmediated actions on both micro- and macrovascular function in the same subjects. In this randomized crossover trial, healthy young adults underwent two infusion protocols designed to compare the effects of insulin infusion during euglycemia and hyperglycemia on micro- and macrovascular function. Both euglycemic- and hyperglycemic- hyperinsulinemia increased skeletal (but not cardiac) muscle microvascular blood volume (each P < 0.02) and blood flow (each P < 0.04) significantly, and these increases did not differ between protocols. Hyperglycemic-hyperinsulinemia trended toward increased carotid-femoral pulse wave velocity (indicating increased aortic stiffness; P = 0.065 after Bonferroni adjustment), whereas euglycemic-hyperinsulinemia did not. There were no changes in postischemic flow velocity or brachial artery flowmediated dilation during either protocol. Plasma endothelin-1 levels significantly decreased during both protocols (each P < 0.02). In this study, acute hyperglycemia for 4 h did not inhibit insulin's ability to increase skeletal muscle microvascular perfusion but did provoke a slight increase in aortic stiffness. Hyperglycemia also did not adversely affect myocardial microvascular perfusion or endothelial function or prevent the decline of endothelin-1 during insulin infusion. [ABSTRACT FROM AUTHOR]

The clinical and pathological progression of Alzheimer's disease often proceeds rapidly, but little is understood about its structural characteristics over short intervals. This study evaluated the short temporal characteristics of the brain structure in Alzheimer's disease through the application of cytoarchitectonic probabilistic brain mapping to measurements of gray matter density, a technique which may provide advantages over standard volumetric MRI techniques. Gray matter density was calculated using voxel-based morphometry of T1-weighted MRI obtained from Alzheimer's disease patients and healthy controls evaluated at intervals of 0.5, 1.5, 3.5, 6.5, 9.5, 12, 18, and 24 months by the MIRIAD study. The Alzheimer's disease patients had 19.1% less gray matter at 1st MRI, and this declined 81.6% faster than in healthy controls. Atrophy in the hippocampus, amygdala, and basal forebrain distinguished the Alzheimer's disease patients. Notably, the CA2 of the hippocampus was found to have atrophied significantly within 1 month. Gray matter density measurements were reliable, with intraclass correlation coefficients exceeding 0.8. Comparative atrophy in the Alzheimer's disease group agreed with manual tracing MRI studies of Alzheimer's disease while identifying atrophy on a shorter time scale than has previously been reported. Cytoarchitectonic mapping of gray matter density is reliable and sensitive to small-scale neurodegeneration, indicating its use in the future study of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objective: Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.Research Design and Methods: Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined.Results: Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ∼30% and ∼40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ∼20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.Conclusions: In obese humans with microvascular insulin resistance, GLP-1's vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that there is a measureable upward motion of the diaphragm during prolonged breath-holds that could have a detrimental effect on image quality in liver MRI and to identify factor that potentially influence the magnitude of this motion. Methods: 15 healthy volunteers underwent MRI examination using prolonged breath-holds in the maximum inspiratory position and a moderate inspiratory position. Coronal T1 weighted three-dimensional gradient echo sequences of the entire thorax were acquired every 6 s during breath-holding allowing the calculation of total lung volume and the measurement of the absolute position of the dome of the liver. The potential impact of subject’s gender, body mass index, and total lung capacity on the change in lung volume/diaphragmatic motion was assessed using random coefficient regression. Results: All volunteers demonstrated a slow reduction of the total lung volume during prolonged breath-holding up to 123 ml. There was a measurable associated upward shift of the diaphragm, measuring up to 5.6 mm after 24 s. There was a positive correlation with female gender (p = 0.037) and total lung volume (p = 0.005) and a negative association with BMI (p = 0.012) for the maximum inspiratory position only. Conclusion: There is a measureable reduction of lung volumes with consecutive upward shift of the diaphragm during prolonged breath-holding which likely contributes to motion artifacts in liver MRI. Advances in knowledge: There is a measureable gas exchange-related reduction of lung volumes with consecutive upward shift of the diaphragm during prolonged breath-holding which likely contributes to motion artifacts in liver MRI. Correcting for this predictable upward shift has potential to improve image quality. The magnitude of this effect does not seem to be related to gender, BMI or total lung capacity if a moderate inspiratory position is used. [ABSTRACT FROM AUTHOR]

Models which assess the progression of Lewy pathology in Parkinson's disease have proposed ascending spread in a caudal-rostral pattern. In-vivo human evidence for this theory is limited, in part because there are no biomarkers that allow for direct assessment of Lewy pathology. Here, we measured neurodegeneration via MRI, an outcome which may serve as a proxy for a more direct assessment of ascending models using a combination of (1) MRI-based measures of gray matter density and (2) regions of interest (ROIs) corresponding to cortical and subcortical loci implicated in past MRI and stereological studies of Parkinson's disease. Gray matter density was measured using brain MRI voxel-based morphometry from three cohorts: (1) early Parkinson's disease, (2) more advanced Parkinson's disease and (3) healthy controls. Early Parkinson's disease patients (N = 228, mean age = 61.9 years, mean disease duration = 0.6 years) were newly diagnosed by the Parkinson's Progression Markers Initiative (PPMI). Advanced Parkinson's disease patients (N = 136, mean age = 63.5 years, mean disease duration = 8.0 years) were collected retrospectively from a local cohort undergoing evaluation for functional neurosurgery. Control subjects (N = 103, mean age = 60.2 years) were from PPMI. Comparative analyses focused on gray matter regions ranging from deep gray subcortical structures to the neocortex. ROIs were defined with existing probabilistic cytoarchitectonic brain maps. For subcortical regions of the basal forebrain, amygdala, and entorhinal cortex, advanced Parkinson's disease patients had significantly lower gray matter density when compared to both early Parkinson's disease and healthy controls. No differences were seen in neocortical regions that are "higher" in any proposed ascending pattern. Across early and advanced Parkinson's disease, gray matter density from nearly all subcortical regions significantly decreased with disease duration; no neocortical regions showed this effect. These results demonstrate that atrophy in advanced Parkinson's patients compared to early patients and healthy controls is largely confined to subcortical gray matter structures. The degree of atrophy in subcortical brain regions was linked to overall disease duration, suggesting an organized pattern of atrophy across severity. [ABSTRACT FROM AUTHOR]

Background: Studies comparing the efficacy and safety of conventional saline-assisted piecemeal endoscopic mucosal resection (EMR) to underwater EMR (UEMR) without submucosal lifting of colorectal polyps are lacking. The objective of this study was to compare the efficacy and safety of EMR to UEMR of large colorectal polyps.Methods: Two hundred eighty-nine colorectal polyps were removed by a single endoscopist from 7/2007 to 2/2015 using EMR or UEMR. 135 polyps (EMR: 62, UEMR: 73) that measured ≥15 mm and had not undergone prior attempted polypectomy were evaluated for rates of complete macroscopic resection and adverse events. 101 of these polyps (EMR: 46, UEMR: 55) had at least 1 follow-up colonoscopy and were studied for rates of recurrence and the number of procedures required to achieve curative resection.Results: The rate of complete macroscopic resection was higher following UEMR compared to EMR (98.6 vs. 87.1%, p = 0.012). UEMR had a lower recurrence rate at the first follow-up colonoscopy compared to EMR (7.3 vs. 28.3%, OR 5.0 for post-EMR recurrence, 95% CI: [1.5, 16.5], p = 0.008). UEMR required fewer procedures to reach curative resection than EMR (mean of 1.0 vs. 1.3, p = 0.002). There was no significant difference in rates of adverse events.Conclusions: UEMR appears superior to EMR for the removal of large colorectal polyps in terms of rates of complete macroscopic resection and recurrent (or residual) abnormal tissue. Compared to conventional EMR, UEMR may offer increased procedural effectiveness without compromising safety in the removal of large colorectal polyps without prior attempted resection. [ABSTRACT FROM AUTHOR]

Background and purpose: Medically at-risk adolescents differ in their perception of severity and are vulnerable to substance use because of effects on their medical regimen. The intent in comparing two cohorts, adolescent survivors of cancer and teens with asthma, is to provide clinical predictors to help in monitoring those needing help with substance use decision making. Methods: Baseline data were obtained from two randomized controlled trials for a decision-making program of research for medically at-risk adolescents. Multivariate analyses were used to identify clinical predictors for poor decision making as well as lifetime and current substance use (smoking, alcohol use, and marijuana use). Conclusions: Predictors for both cohorts for lifetime and current substance use were increasing age and risk motivation. A significant predictor for both cohorts for poor decision making related to substance use was risk motivation, measured as a more positive attitude for engaging in substance use. Negative modeling by peers and family members had an impact on teen survivors' decision making; but, this was not clear for teens with asthma. Implications for practice: Research is needed comparing other medically at-risk adolescents to determine which cohorts on the substance use spectrum are less resilient to peer and parent modeling, have unrealistic views of their decision-making skills, and need close monitoring and guidance. [ABSTRACT FROM AUTHOR]

Hand motor control deficits following stroke can diminish the ability of patients to participate in daily activities. This study investigated the criterion validity of upper extremity (UE) performance measures automatically derived from sensor data during manual practice of simulated instrumental activities of daily living (IADLs) within a virtual environment. A commercial glove orthosis was specially instrumented with motion tracking sensors to enable patients to interact, through functional UE movements, with a computer-generated virtual world using the SaeboVR software system. Fifteen stroke patients completed four virtual IADL practice sessions, as well as a battery of gold-standard assessments of UE motor and hand function. Statistical analysis using the nonparametric Spearman rank correlation reveals high and significant correlation between virtual world-derived measures and the gold-standard assessments. The results provide evidence that performance measures generated during manual interactions with a virtual environment can provide a valid indicator of UE motor status. [ABSTRACT FROM AUTHOR]

Motivation Colocalization of structures in biomedical images can lead to insights into biological behaviors. One class of colocalization problems is examining an annular structure (disk-shaped such as a cell, vesicle or molecule) interacting with a network structure (vascular, neuronal, cytoskeletal, organellar). Examining colocalization events across conditions is often complicated by changes in density of both structure types, confounding traditional statistical approaches since colocalization cannot be normalized to the density of both structure types simultaneously. We have developed a technique to measure colocalization independent of structure density and applied it to characterizing intercellular colocation with blood vessel networks. This technique could be used to analyze colocalization of any annular structure with an arbitrarily shaped network structure. Results We present the circular colocalization affinity with network structures test (CIRCOAST), a novel statistical hypothesis test to probe for enriched network colocalization in 2D z-projected multichannel images by using agent-based Monte Carlo modeling and image processing to generate the pseudo-null distribution of random cell placement unique to each image. This hypothesis test was validated by confirming that adipose-derived stem cells (ASCs) exhibit enriched colocalization with endothelial cells forming arborized networks in culture and then applied to show that locally delivered ASCs have enriched colocalization with murine retinal microvasculature in a model of diabetic retinopathy. We demonstrate that the CIRCOAST test provides superior power and type I error rates in characterizing intercellular colocalization compared to generic approaches that are confounded by changes in cell or vessel density. Availability and implementation CIRCOAST source code available at: https://github.com/uva-peirce-cottler-lab/ARCAS. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]