A student-centered seminar course as a complementary approach to a traditional journal club.

Graduate physiology programs strive to provide students with in-depth expertise in a particular academic discipline, often facilitating this process in the form of a departmental seminar course. Within the Department of Physiology and Biophysics at the University of California Irvine (UCI), students are required to attend a seminar course, most often designed as a journal club, each quarter until they are ready to graduate. While this format may work well in departments where research topics are closely related, it has historically been less successful in UCI's Department of Physiology and Biophysics, where wide-ranging interests make for little overlap in foundational knowledge, limiting meaningful engagement with the material or with peers in the class. In this paper, we describe a complementary approach of developing a syllabus around student interests and covering topics that are critical for student success but often omitted from graduate curricula, such as interview skills, grant writing, and scientific communication. Results from our preclass survey motivated this approach to the class, and our retrospective survey demonstrated the substantial differences in student engagement, enthusiasm, and perceived benefits of this course relative to the journal club style course. We hope that the success of our course may serve as an exemplar for strategies to engage students more effectively and provide critical training in diverse skillsets that will help students after graduation.

The Costs of Interfacility Transfers for Nonurgent Pediatric Supracondylar Fractures.

BACKGROUND: Unnecessary transfers of nonemergent pediatric musculoskeletal injuries to regional trauma centers can be costly. The severity of fracture displacement in supracondylar humerus fractures dictates the risk of complications, the urgency of transfer and the need for surgical treatment. The purpose of this study is to examine the transfer patterns of Gartland type II pediatric supracondylar humerus fractures to identify strategies for improving patient care, improving health care system efficiency, and reducing costs. We hypothesize that there will be a high rate of unnecessary, emergent transfers resulting in increased cost. METHODS: We retrospectively identified all pediatric patients that underwent treatment for a supracondylar humerus fracture between 2013 and 2018. Patient demographics, injury characteristics, chronological data, and surgical data were collected and analyzed from ambulance run sheets, transferring hospital records, and electronic medical records. Transfer distances were estimated using Google-Maps, while transfer costs were estimated using Internal Revenue Service (IRS) standard mileage rates and the American Ambulance Association Medicare Rate Calculator. A student t test was used to evaluate different treatment groups. RESULTS: Sixty-two patients had available and complete transfer data, of which 44 (71%) patients were safely transferred via private vehicle an average distance of 51.8 miles, and 18 (29%) patients were transferred via ambulance on an average distance of 55.6 miles ( P =0.76). The average transfer time was 4.1 hours by private vehicle, compared with 3.9 hours by ambulance ( P =0.56). The average estimated cost of transportation was $28.23 by private vehicle, compared with $647.83 by ambulance ( P =0.0001). On average, it took 16.1 hours after injury to undergo surgery and 25.7 hours to be discharged from the hospital, without a significant difference in either of these times between groups. There were no preoperative or postoperative neurovascular deficits. CONCLUSION: Patients with isolated Gartland type II supracondylar humerus fractures that are transferred emergently via ambulance are subjected to a significantly greater financial burden with no demonstrable improvement in the quality of their care, since prior research has shown these injuries can safely be treated on an outpatient basis. Potential options to help limit costs could include greater provider education, telemedicine and improved coordination of care. LEVEL OF EVIDENCE: Level III (retrospective comparative study).

Do subcortical gray matter volumes and aerobic capacity account for cognitive-motor coupling in multiple sclerosis?

BACKGROUND: There is evidence of cognitive-motor coupling in multiple sclerosis (MS) such that the slowing of cognitive processing speed correlates with the worsening of walking speed and endurance. OBJECTIVE: The current study first established the presence of cognitive-motor coupling and second examined the possibility that volumes of subcortical gray matter (SGM) structures and aerobic capacity might explain the coupling of cognitive and motor functions in persons with MS. METHODS: We included data from 62 persons with clinically definite MS who underwent assessments of cognitive processing speed, walking performance, and aerobic capacity, and completed magnetic resonance imaging (MRI) within 7 days of the aforementioned assessments. RESULTS: The strong correlations between cognitive processing speed and walking performance were attenuated in magnitude and not statistically significant when controlling for aerobic capacity alone and aerobic capacity and SGM volumes together. The associations between cognitive processing speed and walking performance remained statistically significant when controlling for SGM volumes alone. CONCLUSION: Aerobic capacity may be an important target for neurorehabilitation-based approaches for managing co-occurring cognitive and motor dysfunction in MS.

Gradual Deformity Correction in Blount Disease.

BACKGROUND: Blount disease is a disorder of the posteromedial proximal tibial physis which causes a progressive varus, procurvatum, and internal rotation deformity of the tibia. Untreated, it can cause significant limb malalignment. The goal of this study is to evaluate the results of correction of Blount disease using types of external fixation. METHODS: We conducted a retrospective review of 41 patients (51 limbs) who underwent correction of Blount disease with an Ilizarov external fixator or a Taylor spatial frame (TSF) by a single surgeon. The medial proximal tibial angle (MPTA), mean axis deviation (MAD), posterior proximal tibial angle, and joint line congruence angle (JLCA) were measured on radiographs preoperatively, at frame removal and at final follow-up. RESULTS: The average age at treatment was 9.6 years old, with a mean follow-up time of 34 months. Mean preoperative MPTA, MAD, and JLCA were significantly improved at the time of frame removal as well as at final follow-up with no significant changes in correction between the time of frame removal and final follow-up. There was no difference in MPTA and MAD in patients treated with an Ilizarov frame versus a TSF. MPTA, MAD, and JLCA all significantly improved regardless of the underlying diagnosis (infantile vs. adolescent Blount disease) or history of prior surgical intervention. The most common complication was superficial pin-site infection. CONCLUSIONS: Both Iliazarov and TSF are viable treatment options for infantile and adolescent Blount disease, with the ability to significantly improve both the limb mechanical axis and the mechanical axis of the affected tibia. Correction can be attained regardless of whether patients have previously failed surgical intervention. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Retrograde Stainless Steel Flexible Nails Have Superior Resistance to Bending in Distal Third Femoral Shaft Fractures.

BACKGROUND: It has been shown that retrograde titanium flexible intramedullary nails (Ti FIN) provide superior resistance to bending compared to antegrade Ti FIN in distal femur fractures. The purpose of this study was to compare resistance to torsional and bending forces of stainless steel (SS) FIN, with or without a locking screw, and Ti FIN in distal third femoral shaft fractures. We hypothesize that locked retrograde SS FIN will demonstrate greater resistance to both bending and torsional forces. METHODS: Thirty adolescent synthetic femur models were used to simulate transverse distal femoral fractures at either 60 mm or 90 mm proximal to the distal femoral physis. The femurs were instrumented with antegrade Ti FIN, antegrade SS FIN, retrograde Ti FIN, retrograde SS FIN, or retrograde locked SS FIN. Three models for each construct at both osteotomy levels were tested. Models were analyzed to determine maximum resistance to bending and torsion. RESULTS: In fractures 60 mm from the physis, retrograde SS FIN demonstrated statistically superior resistance to bending when compared with both antegrade and retrograde Ti FIN (P=0.001 and 0.008, respectively) and antegrade SS FIN (P=0.0001). Locked SS constructs showed a trend towards greater resistance to bending forces when compared with unlocked constructs (P>0.05). No significant difference was seen in resistance to bending when fractures were 90 mm proximal to the distal femoral physis between the five groups. No significant differences were observed in resistance to torsion in either the proximal or distal fracture models, regardless of construct type. CONCLUSIONS: Retrograde SS FIN confer significantly greater resistance to bending forces for fractures 60 mm proximal to the distal femoral physis compared with Ti FIN or antegrade entry SS FIN. In fractures 90 mm from the physis, no differences were noted in our model. Our results support the use of retrograde SS nails in the pediatric patient with distal femoral shaft fractures. LEVEL OF EVIDENCE: Level II-comparative biomechanical study.

Adenoma detection rate metrics in colorectal cancer surveillance colonoscopy.

BACKGROUND: A target goal for screening adenoma detection rate (S-ADR) of ≥ 25% has been set to define high-quality colonoscopy performance. However, there is no current accepted target goal for ADR in colorectal cancer (CRC) surveillance. This makes quality assessment challenging when physicians perform cancer surveillance colonoscopy but minimal screening procedures. METHODS: In this cohort study, consecutive colonoscopies performed at either Rush University Medical Center or Rush Oak Park Hospital by a gastroenterologist or colorectal surgeon in average risk screening population and CRC surveillance population were reviewed retrospectively from 2006 to 2012 and prospectively from 2013 to 2016. ADR in first surveillance colonoscopy following surgical resection of CRC (CRC-ADR) was reported in high-quality detectors (HQD) or low-quality detectors (LQD) based on achievement of 25% ADR in consecutive screening colonoscopy in average risk patients. Pearson's correlation was used to describe the association between individual S-ADR and CRC-ADR for colonoscopists. RESULTS: There was a very strong positive correlation (r = 0.88, p = 0.002) between ADR in average risk screening and first time CRC surveillance. For HQD as defined by S-ADR ≥ 25% (n = 10 colonoscopists), the CRC-ADR was 37.7% (78/207, SD 8%) which was very similar to their respective S-ADR of 33.4% (816/2440, p = 0.22). For LQD (n = 5 colonoscopists), the CRC-ADR was 20.2% (40/198) which was similar to their respective S-ADR of 20.1% (119/591, p = 0.99). The CRC-ADR was significantly higher for HQD than for LQD (37.7 vs. 20.2%, p < 0.0001). CONCLUSIONS: The major finding of this study is a defined CRC-ADR for HQD based on the ability to achieve S-ADR ≥ 25%. S-ADR strongly correlates with CRC-ADR. CRC-ADR is quite similar to the colonoscopists' respective S-ADR for both HQD and LQD. For colonoscopists who perform limited screening colonoscopies but do perform CRC surveillance colonoscopies, ADR metrics similar to S-ADR to assess quality in colonoscopy could be considered.

Self-efficacy and Walking Performance in Persons With Multiple Sclerosis.

BACKGROUND AND PURPOSE: Impairment of walking function is a prevalent and burdensome feature of multiple sclerosis (MS), and represents a primary focus of rehabilitation research and clinical care. Research examining self-efficacy as a correlate of walking performance in MS is lacking; self-efficacy represents a theory-based, modifiable target of rehabilitation approaches for improving walking outcomes. This cross-sectional study examined the association between self-efficacy and walking performance in persons living with MS. METHODS: The sample included 69 persons with MS who completed the Multiple Sclerosis Self-Efficacy (MSSE) Scale and Exercise Self-Efficacy (EXSE) Scale and undertook the Timed 25-Foot Walk (T25FW) and the 6-Minute Walk (6MW) tests. The data were analyzed using the Pearson product moment correlation coefficients and linear regression. RESULTS: Correlation analysis indicated that function subscale scores on the MSSE correlated more strongly with T25FW (r = 0.55) than did the control subscale (r = 0.40) and EXSE (r = 0.38) scores, and both function (r = 0.67) and control (r = 0.53) subscale scores on the MSSE correlated more strongly with 6MW than did EXSE scores (r = 0.40). Linear regression analyses indicated that (1) function MSSE subscale, but not control subscale, explained significant variance in T25FW speed and 6MW distance and (2) function MSSE subscale, but not EXSE, explained significant variance in T25FW speed and 6MW distance. DISCUSSION AND CONCLUSIONS: We provide the first evidence of an association between self-efficacy, particularly for functioning with MS, and objective walking performance in MS. Future research to replicate and extend these results can inform rehabilitation efforts that target improvement of walking performance in persons with MS.Digital Abstract available for more insights from the authors (see Slides, Supplemental Digital Content 1, http://links.lww.com/JNPT/A171).

Reliability of Accelerometer Scores for Measuring Sedentary and Physical Activity Behaviors in Persons With Multiple Sclerosis.

This brief research note examined the reliability of scores from an accelerometer as measures of sedentary and physical activity behaviors in persons with multiple sclerosis (MS). The analysis was performed on a combined data set from 2 previous longitudinal investigations of physical activity in MS. We focused on the number of days required to reliably estimate sedentary behavior, based on time spent in sedentary behavior per day and number of sedentary breaks, number of long sedentary bouts, and average length of sedentary bouts per day. We further examined the number of days required to reliably estimate physical activity behavior, based on time spent in light and moderate-to-vigorous physical activity and average length of activity bouts per day. Between 4-6 days of monitoring and 3-7 days of monitoring were necessary for good reliability of scores from all sedentary outcomes and physical activity outcomes, respectively. These results should guide research and practice examining sedentary and physical activity behaviors using accelerometry in persons with MS.

Physical Fitness Assessment Across the Disability Spectrum in Persons With Multiple Sclerosis: A Comparison of Testing Modalities.

BACKGROUND AND PURPOSE: Appropriate assessment of physical fitness (ie, aerobic capacity and muscular strength) is necessary for the design and evaluation of exercise training in multiple sclerosis (MS). However, this is challenging in persons with substantial disability, because of physical inaccessibility and insensitivity of certain exercise testing modalities. This study compared different methods of measuring cardiorespiratory (arm ergometer vs recumbent stepper) and muscular (hand-held dynamometry vs computerized dynamometry) fitness across the MS disability spectrum. Associations between physical fitness and other measures that represented all domains of the International Classification of Functioning, Disability and Health (ICF) were also examined. METHODS: Sixty-four participants with MS completed 2 symptom-limited cardiorespiratory fitness and muscular strength tests. We also assessed disability, cognition, fatigue, walking speed and endurance, health-related quality of life, and activities of daily living. RESULTS: Across all levels of disability, peak aerobic capacity assessed by recumbent stepping was higher compared with arm ergometry (P < 0.001). Peak torque of the knee extensors and knee flexors was significantly higher assessed by computerized dynamometry compared with hand-held dynamometry (P < 0.001). Aerobic capacity and peak torque decreased as a function of increasing disability (P < 0.001). Significant, moderate to strong correlations were observed between the physical fitness measures and measures representing all domains of the ICF, irrespective of the fitness testing mode. DISCUSSION AND CONCLUSIONS: Overall, peak physical capacity was higher when assessed by recumbent stepping and computerized dynamometry. The assessment and prescription of exercise in MS should be based on these modalities to provide the most appropriate stimulus for exercise training adaptations. There continues to be an important association between physical fitness and other measures that represent all domains of the ICF, regardless of fitness assessment mode.Video Abstract available for additional insights from the authors (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/JNPT/A109).

Preliminary validation of the short physical performance battery in older adults with multiple sclerosis: secondary data analysis.

BACKGROUND: There are relatively few standard, objective measures for studying physical function among older adults with multiple sclerosis (MS), yet such measures are necessary considering the shift in prevalence and associated consequences of both MS and older age on physical function. We undertook a preliminary examination of the construct validity of Short Physical Performance Battery (SPPB) scores in older adults with MS based on an expected differential pattern of associations with measures of lower and upper extremity function. METHODS: The sample included 48 persons with MS aged 50 years and older who were enrolled in a pilot, randomized controlled trial of exercise training. Participants completed the SPPB and other objective and self-report measures of lower and upper extremity function as part of baseline testing. RESULTS: SPPB scores demonstrated strong associations with measures of lower extremity function (|r s| = .66-.79), and weak associations with measures of upper extremity function (|r s| = .03-.33). CONCLUSIONS: We provide preliminary evidence that supports the validity of scores from the SPPB as a measure of lower extremity function for inclusion in clinical research and practice involving older adults with MS.

An Unusual Cause of Longstanding Diarrhea.

Colchicine is an alkaloid drug used in multiple medical conditions. It has a narrow therapeutic index, and gastrointestinal symptoms can occur at the beginning or after long-term therapy. Unintentional toxicity is common and has a high mortality rate when missed. Histopathologic recognition is challenging, and timely identification is conducted to improve patients' outcomes. We describe the case of a 77-year-old female who presented to the emergency room for dehydration, longstanding diarrhea, and weight loss. Upper and lower endoscopies showed erythematous mucosa without bleeding in the gastric antrum and an unremarkable duodenum and colon. Duodenal biopsies demonstrated partial villous atrophy with elongated glands and numerous arrested ring mitoses, consistent with colchicine toxicity.

Neural circuit basis of adolescent THC-induced potentiation of opioid responses in adult mice.

Use of one drug of abuse typically influences the behavioral response to other drugs, either administered at the same time or a subsequent time point. The nature of the drugs being used, as well as the timing and dosing, also influence how these drugs interact. Here, we tested the effects of adolescent THC exposure on the development of morphine-induced behavioral adaptations following repeated morphine exposure during adulthood. We found that adolescent THC administration impacted morphine-induced behaviors across several dimensions, including potentiating reward and paradoxically impairing the development of morphine reward. We then mapped the whole-brain response to a reinstatement dose of morphine, finding that adolescent THC administration led to increased activity in the basal ganglia and increased functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells that has the potential to influence dopaminergic response to morphine administration during adulthood. Our study adds to the rich literature on the interaction between drugs of abuse and provides potential circuit substates by which adolescent THC exposure influences responses to morphine later in life.

Results of a feasibility and initial efficacy clinical trial of a high-intensity interval training program using adaptive equipment in persons with multiple sclerosis who have walking disability.

BACKGROUND: High intensity interval training (HIIT) has been identified as potential stimulus for eliciting health-promoting physical activity in an efficient manner among persons with multiple sclerosis (MS). The current study aimed to examine the feasibility and initial efficacy of a 12-week HIIT program using a recumbent stepper (RSTEP) in persons with MS who have walking disability. Feasibility outcomes of interest included process (i.e., recruitment, adherence, and retention rates), resource (i.e., time and monetary costs), management (i.e., data management and safety reporting assessment), and science (i.e., safety, burden, and treatment effect assessment). We hypothesized that 12-weeks of HIIT will be feasible via meeting a priori benchmarks in process, resource, management, and scientific outcomes. The efficacy outcomes of interest included changes in aerobic fitness, physical activity, walking, upper arm function, cognition, fatigue, and depressive symptoms. We hypothesized that 12 weeks of HIIT would result in improvements in aerobic capacity, walking, upper arm function, cognition, fatigue, and depression. METHODS: A pre-post clinical trial design was applied. Participants (N = 16) were recruited and enrolled in the 12-week RSTEP HIIT program who met the following inclusion criteria: age ≥18 years, self-reported diagnosis of MS, Patient Determined Disability Steps scale score 3.0-7.0, relapse free in past 30 days, willing to visit a University Laboratory for study protocol, asymptomatic status for maximal exercise testing, physician approval, and a self-reported ability to speak, read, and understand English. Measures of efficacy outcomes of interest included Six Minute Walk Test (6MW), Timed 25 Foot Walk Test (T25FW), the Brief International Cognitive Assessment in MS (BICAMS), 9-hole peg test (9-HPT), Expanded Disability Status Scale (EDSS), Fatigue Severity Survey (FSS), Hospital Anxiety and Depression Scale (HADS), Godin Leisure Time Exercise Questionnaire (GLTEQ), Multiple Sclerosis Walking Scale-12 (MSWS-12). Participants completed a graded maximal exercise test for measuring aerobic fitness (VO2peak) and prescription of exercise throughout the intervention. All outcomes were measured at baseline, mid-point (6-weeks), and post-intervention (12-weeks). The intervention involved 12 weeks of supervised, individualized HIIT sessions two times per week using RSTEP. The individual HIIT sessions included 10 cycles of 60 s intervals at the work rate associated with 90 % VO2peak followed by 60 s of active recovery intervals, totaling 20 minutes plus 5-minute warm-up and cool-down periods. Process, resources, management, and scientific feasibility outcomes were examined using descriptive statistics, percentage, and frequency analyses. The efficacy of the intervention was assessed using a 1-factor (Time), repeated measure analysis of variance to identify significant changes over time. RESULTS: Fourteen of 16 participants were retained throughout the full study period and adherence with prescribed exercise sessions was 97 %. Twenty-three staff were comprehensively trained across two sites. There was only one adverse event reported that did not impact participation in the study and overall mean satisfaction rating with the program among participants was 4.7/5. There were statistically significant changes in cognitive processing speed (p = 0.002), GLTEQ (p = 0.005), and MSWS-12 (p = 0.04), but not the other outcomes of fitness, arm function, and walking. Of note, there were large effect sizes noted for peak power output (d = 1.10) and FSS (d = 1.05) despite the lack of statistically significant changes CONCLUSION: Feasibility of a 12-week individualized RSTEP HIIT program was established and participants significantly improved on measures of cognition, physical activity, and walking.

"Bounded" empowerment: analyzing tensions in the practice of youth-led participatory research in urban public schools.

This multi-method study examines tensions in the practice of youth-led participatory research (YPAR) in urban high schools among 15 semester-cohorts. Student participants in the present study were 77 ethnically diverse youth from four high schools in a major metropolitan school district. Data were gathered using systematic classroom observations, interviews with teachers and students involved in the projects, and participant observation. The two most commonly-constrained phases of the YPAR project were issue selection and action steps. A central tension in the issue selection phase for projects enacted across multiple semester cohorts was the tension between original inquiry and "traction:" Sticking with the same topic enabled sustained building of strategic alliances and expertise for making change, but limited the incoming cohort's power to define the problem to be addressed. In further analyses, we identified processes that promoted student power despite continuity-related constraints-teachers' framing and buy-in strategies, "micro-power" compensation, and alignment of students' interests with the prior cohort-as well as constraints in other phases of the projects. This study's findings regarding the promotion of youth power in the face of constraints advance the integration of theory and practice in youth-led research and have implications for participatory research more broadly.

Early emergency department discharge for intermediate heart score patients presenting for chest pain.

Study Objective: The use of the HEART score to risk stratify patients for short-term major adverse cardiac events in the emergency department (ED) setting is well established. Although discharge to home for low-risk HEART score patients is widely accepted as safe practice, there are limited outcomes data on moderate-risk HEART score patients discharged to home. We investigated the safety of discharging moderate-risk HEART score patients to home from the ED with established early cardiology follow-up. Methods: We performed a retrospective cohort analysis of patients presenting to the ED with chest pain from April 2020 through December 2020. Patients were evaluated in the ED and underwent serial conventional troponin testing and electrocardiogram (ECG). Clinicians calculated a HEART score and employed shared decision-making with moderate-risk patients (score 4-6), offering hospital admission versus discharge home with a formalized process for rapid cardiology follow-up (within 2 business days). We assessed the frequency of acute myocardial infarction or death at 30 days and before cardiology follow-up. Results: During our study period, 2939 patient encounters were screened for chest pain. Of these, 333 of 547 eligible moderate-risk HEART score patients were referred for rapid follow-up. The median time to follow-up appointment was 2.9 business days (interquartile range 1.3, 6.5), and 264 (79%) of patients kept their follow-up appointment. One patient (0.3%) suffered death within 30 days, before cardiology follow-up. There were no myocardial infarctions. Conclusions: These results suggest that moderate-risk HEART score patients may be considered for discharge from the ED with rapid cardiology follow-up. Formalizing processes to facilitate these early evaluations may represent a viable alternative to hospital admission, without diminishing patient outcomes.

Predictors of appointment adherence following operative treatment of pediatric supracondylar humerus fractures: which patients are not following up?

This study aims to identify characteristics associated with poor appointment adherence after surgical stabilization of supracondylar humerus fractures (SCHFX) in children. A retrospective review of 560 consecutive, surgically managed patients with SCHFX from 2010 to 2015 was performed. One missed follow-up appointment was classified as 'low adherence', whereas missing two or more appointments was classified as 'very low adherence'. Demographics, insurance status, estimated family income and distance from clinic were analyzed to identify differences in variables between adherent and low-adherent groups. Of 560, 121 (21.8%) missed one follow-up visit and 39/560 (7.1%) missed more than two visits. Age, gender, distance traveled, insurance status and primary language were nonpredictive. Estimated income <$50 000 was associated with a >200% increase in low adherence vs patients with estimated income >$50 000 (9.3 vs 3.8%; P = 0.012). African American patients had significantly lower adherence vs patients of other races (47.5 vs 19.6%; P < 0.0001). Ethnicity remained the only significant factor correlated to adherence after multivariate analysis. African Americans were three times more likely demonstrate low adherence (P = 0.0014). Ethnicity and estimated income <$50 000 were predictors of missing two or more visits. African American patients were four times more likely to miss two or more visits [odds ratio (OR), 4.17; P = 0.0026] than others; estimated income <$50 000 was associated with a two-fold increase in missing two or more visits (OR, 2.33; P = 0.035). By identifying at-risk patient populations, healthcare systems can adopt strategies to remove barriers of accessing follow-up care.

An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.

Cytologic analysis of vitreous fluids: A retrospective review of our 24 years of experience.

BACKGROUND: Cytologic analysis of vitreous fluid is an important component in diagnosis of vitreitis. No standard reporting guidelines exist for these specimens. This study chronicles our 24 years experience and proposes a tentative diagnostic model. METHODS: Retrospective cytology reports review and database study. Clinical indications, cytologic patterns, ancillary studies performed, and diagnoses were recorded. RESULTS: 176 samples from 160 patients were included and main cytologic patterns are reflected in Table 1. Most fluids were negative for malignancy (88%) and patterns IIB (53%) and IIA (19%) were dominant. The non-diagnostic rate was 7%; atypical and suspicious categories represented <0.5% of fluids tested and only 2% were positive for malignancy (3 intraocular lymphoma and one melanoma). Clinical indications for fluid examination were infection/inflammation (59%), to rule out lymphoma (11%), amyloidosis (3%), melanoma (2%), or to investigate intraocular hemorrhage. Fungal elements were demonstrated in 7 cases. No viral inclusions were appreciated; however, one case was positive for HSV 2 by IHC and 2 were negative by PCR. One case had Gram + cocci. Flow cytometry studies were suboptimal in 6 fluids, negative for an aberrant lymphocyte population in 11, and positive for high grade lymphoma in 3 cases. Atypical, suspicious and positive for melanoma were reported in 3 samples. Amyloid was identified in 1 aspirate. CONCLUSIONS: Cytologic analysis of vitreous fluid is a useful tool. Modern techniques like flow cytometry and PCR testing further expand the diagnostic possibilities. Standardization of diagnostic terminology will aid clinicians caring for patients suffering from ocular disease.

A connectomic analysis of deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD. METHODS: We performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset. RESULTS: Probabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets. CONCLUSIONS: Our results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.

Feasibility and initial efficacy of a high-intensity interval training program using adaptive equipment in persons with multiple sclerosis who have walking disability: study protocol for a single-group, feasibility trial.

BACKGROUND: There is considerable evidence for the efficacy of moderate-intensity continuous exercise benefitting clinically relevant outcomes in persons with multiple sclerosis (MS). However, persons with MS who have walking disability (pwMS-wd) are severely deconditioned and may achieve superior benefits by engaging in high-intensity interval training (HIIT), especially while utilizing adaptive equipment, such as recumbent arm/leg stepping (RSTEP). The proposed study will assess the feasibility of a 12-week, RSTEP HIIT program in pwMS-wd. The secondary aim will examine changes in aerobic fitness, physical activity, ambulation, upper arm function, cognition, fatigue, and depression as clinically relevant efficacy outcomes following the 12-week, RSTEP HIIT intervention. METHODS: The study will recruit 15 pwMS-wd. Feasibility will be measured via process, resource, management, and scientific outcomes throughout the entirety of the research study. The secondary, clinically relevant outcomes will consist of a neurological exam, aerobic capacity, physical activity, ambulation, cognition, upper arm function, fatigue, and depression. Outcomes will be assessed at baseline (T1), midpoint (T2, following 6 weeks), and post-intervention (T3, following 12 weeks). The intervention will involve 12 weeks of supervised, individualized HIIT sessions two to three times per week. The individual HIIT sessions will each involve 10 cycles of 60-s intervals at the wattage associated with 90% VO2peak followed by 60 s of active recovery intervals at 15 W, totaling 20 min in length plus 5-min warm-up and cool-down periods. DISCUSSION: The feasibility design of the proposed study will provide experience and preliminary data for advancing towards a proof-of-concept study comparing HIIT to moderate-intensity continuous RSTEP for improving clinically relevant outcomes in a randomized control trial design. The results will be disseminated via manuscripts for publication and a report for distribution among the National Multiple Sclerosis Society. TRIAL REGISTRATION: ClinicalTrials.gov NCT04416243 . Retrospectively registered on June 4, 2020.