Measures Of Function Research Articles

Focused Update on Clinical Testing of Otolith Organs

Sensing gravity through the otolith receptors is crucial for bipedal stability and gait. The overall contribution of the otolith organs to eye movements, postural control, and perceptual functions is the basis for clinical testing of otolith function. With such a wide range of contributions, it is important to recognize that the functional outcomes of these tests may vary depending on the specific method employed to stimulate the hair cells. In this article, we review common methods used for clinical evaluation of otolith function and discuss how different aspects of physiology may affect the functional measurements in these tests. We compare the properties and performance of various clinical tests with an emphasis on the newly developed video ocular counter roll (vOCR), measurement of ocular torsion on fundus photography, and subjective visual vertical or horizontal (SVV/SVH) testing.

The acute effects of nonsleep deep rest on perceptual responses, physical, and cognitive performance in physically active participants.

This study aimed to examine the effect of nonsleep deep rest (NSDR) on physical and cognitive performance, as well as sleepiness, acute readiness, recovery, stress, and mood state in physically active participants. A total of 65 physically active participants (42 male, 23 female) were randomly assigned into two groups: an experimental group (NSDR, n= 34), in which participants completed a 10-min NSDR intervention, and a control group (CON, n= 31), whereby participants sat passively for 10min. Testing measures were assessed immediately pre and 10min post each condition and comprised completing a hand grip strength dynamometer test and a countermovement jump test on force plates, cognitive function measures via a psychomotor vigilance task (PVT-B), and a Simon task test, along with four questionnaires to assess sleep, recovery, and mood state. A significant Group × Time interaction favored the NSDR condition for handgrip strength, median reaction time during the PVT-B, and accuracy percentage during the Simon task. Questionnaire responses demonstrated NSDR to be associated with significant benefits to physical readiness, emotional balance, overall recovery, negative emotional state, overall stress, and tension in comparison to CON (p< .05). The NSDR intervention could be a valuable strategy for acutely enhancing overall well-being and readiness.

What facets of physical function are most important to adults diagnosed with cancer?

Successful patient-focused drug development involves selecting and measuring outcomes in clinical trials that are important to patients. The U.S. Food & Drug Administration's definition of clinical benefit includes how patients feel, function, or survive. Patients are considered the experts in describing how they feel and function. In cancer trials, patient-reported measures of physical function provide insight into how patients function at baseline, benefit from the interventions being studied, and the impact of treatment side effects. We conducted a qualitative study with adults diagnosed with cancer to describe facets of physical function from their perspective and to identify which facets are most important to this patient population. Using concept elicitation and cognitive interviewing techniques, we conducted semi-structured interviews with 72 adults ≥ 22years of age with cancer who received treatment with an anticancer drug or biologic within six months of the interview. We selected participants using purposive sampling with the aim to elicit diverse experiences regarding how they may interpret and respond to questions related to physical function. Participants were presented with patient-reported outcome (PRO) items representative of PRO measures used in cancer and general populations. Five facets of how physical function relates to activities were defined from the patient perspective: ability, difficulty, limitation, satisfaction, and completion. More than half of the participants indicated that ability was the most important facet of physical function. The next most important were satisfaction (18.3%), limitation (14.1%), difficulty (5.6%), and completion (2.8%). This study demonstrates that we must be more specific about the facets of physical function that we set out to assess when we use PRO measures to describe the patient experience. These results have implications for the specificity of physical function facets when measured in cancer clinical trials.

Associations between pain, function and quality of life after total hip arthroplasty

ObjectivesThis study investigated patient reported outcomes, and associations with improvement in quality of life 12-months after total hip arthroplasty (THA). Materials and MethodsParticipants were adults (n = 433) undergoing THA for osteoarthritis between January 2017 and October 2020 in a large publicly funded tertiary hospital in [country]. Participants completed patient reported outcome measures of pain, function and quality of life (QOL) preoperatively, 6- and 12-months following THA. ResultsClinically significant changes in domains of pain and function were associated with improved QOL, even when pre-operation scores were controlled for. The largest gains in all three domains occurred in the pre- to 6-month post-operation period. Baseline demographic variables such as gender and comorbidities were not associated with change in QOL pre- to post-operation. However, although modest, age at surgery was negatively correlated with change in QOL. ConclusionsTHA contributes to substantial improvements in QOL, pain and function outcomes, and although possibly tempered by age, these relationships are likely to be inter-related and mutually reinforcing. Future QOL outcomes research should also consider the impacts on QOL improvement of other aspects of functioning such as psychological and social wellbeing.

Relationships Among Baseline Concussion Balance Test and Gaze Stability Test Scores in Division-I Collegiate Athletes.

Sports-related concussions are commonly occurring injuries as a result of sports and recreation that may cause alterations in brain functioning. It is important to be able to evaluate the impact of these injuries on function to manage the injury recovery and ensure recovery. Recent literature suggests the use of objective evaluation strategies in a multifaceted approach to evaluate and manage these injuries. It is important to understand the relationships between the assessments and how best to utilize each assessment. The purpose of this study was to investigate if relationships exist between measures of vestibular function at baseline in assessments that may be used following sports-related concussions. Additionally, a secondary purpose was to determine if self-reported symptoms were related to performance on the assessments. This study aimed to identify if these assessments measured independent functions of the vestibulo-ocular reflex or if some redundancy existed among the assessment strategies. A cross-sectional study design was used in a cohort of collegiate athletes ages 18-24. Participants completed demographics questionnaires, the Post-Concussion Symptom Scale, Gaze Stabilization Test, and Concussion Balance Test. Spearman rho correlations were used to examine the relationships between the measures. One hundred and thirty-five collegiate athletes (82 males and 53females) were included, representative of 3 sports (cheerleading, soccer, and football) with a mean age of 19.77 (1.42)years old. There were weak to moderate, significant relationships between measures of Gaze Stabilization Test and Concussion Balance Test errors (r = .20-.31, P = .001-.03). The direction of these relationships indicated that greater Concussion Balance Test errors were associated with greater Gaze Stabilization Test performance. These relationships may be attributed to the difficulty created by the foam conditions and the integration of more complex sensory tasks required to maintain balance during the more difficult conditions.

Using Semantic Verbal Fluency to estimate the relative and absolute vocabulary size of bilinguals: An exploratory study of children and adolescents.

Introduction: The full assessment of bilingual children often involves at least one language for which formal vocabulary tests are lacking and which the examiner does not speak. We examined, in a sample of children with typical development (TD), whether a semantic verbal fluency task, typically used in research as a measure of executive function, could be used in the place of a formal vocabulary test to estimate vocabulary knowledge when formal tests are not available. Method: 113 TD monolingual French speakers and TD bilinguals and with varying degrees of exposure to French, age 6 to 17 years, completed tests of vocabulary knowledge and semantic verbal fluency. A subset of 64 participants spoke French and English and were tested in both languages. Verbal fluency measures calculated using a traditional method which uses specific rules for superordinate categories and for animals of different sex and age and a simplified scoring method which simply counts all words produced, included the total number of words produced in each language, Total Vocabulary and Conceptual Vocabulary measures combining both languages, as well as analyses of lexical composition and word frequency within the study sample. Results: Linear regressions revealed that the number of words produced predicted vocabulary size in a language-specific way, with slightly stronger predictions made by the simplified scoring method. As expected, bilinguals produced more words and more unique words in their language of greater exposure, while different exposure groups were equivalent in measures combining both languages, including their Total vocabulary and Conceptual vocabulary. Producing unusual words (infrequently produced in the study sample) indicated higher vocabulary scores. Conclusions: This study supports the use of the verbal fluency task as a quick and simple tool to obtain a rough estimate of vocabulary size in TD monolinguals and bilinguals. This tool shows promise as well in clinical work with other populations, subject to further verification.

Validity and reliability of the chronic composite XA, an upper limb motor assessment using Active Range of Motion in patients with chronic stroke.

Upper limb (UL) spastic paresis has been classically evaluated with assessments of passive movements with limited functional validity. The aim of this study was to assess whether a composite measure of active range of motion (AROM, or X<inf>A</inf>) is valid and reliable in chronic post-stroke spastic paresis. The primary objective was to investigate the validity and reliability of a composite score, comprising multiple X<inf>A</inf> measurements, to assess UL spastic paresis in patients in chronic stages post-stroke. In addition to this, an exploratory analysis was conducted to identify which muscles should be optimally included in this composite score. A psychometric proprieties study. Physical and Rehabilitation Medicine Department. twenty-eight chronic post-stroke participants with spastic paresis. Composite UL X<inf>A</inf> measurement in twenty-eight chronic post-stroke participants (age=59±11 years; delay post-stroke=29±37 months) with spastic paresis was repeated twice about 40 days apart in a standardized body position. Concurrent and construct validity was evaluated exploring correlation with the Fugl-Meyer Assessment Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and grip strength (JAMAR™). Reliability was assessed by calculating intraclass correlation coefficients (ICC). Regarding the exploratory analysis, a linear regression analysis was performed to examine the value of including various muscles. Composite X<inf>A</inf> against the resistance of elbow, wrist and finger flexors showed strong correlation with FMA-UE and ARAT (r=0.88; P<0.001 and r=0.82; P<0.001 respectively) and a weak association with grip strength (r=0.43; P=0.03). Test-retest reliability was excellent (ICC=0.92). However, the most effective regression model also included X<inf>A</inf> against the resistance of shoulder adductors as well as forearm pronator (adjusted R2=0.85; AIC=170). The present study provided satisfactory psychometric data for the upper limb composite active movement (CX<inf>A</inf>), derived from the Five Step Assessment. For overall measurement of UL mobility after stroke, we strongly recommend including shoulder and forearm muscles to the score. Composite X<inf>A</inf> is a valid and reliable measure of upper limb motor function in chronic post-stroke patients and could be used in clinical practice and research.

A Novel Technique for Improving Cyclic Behavior of Steel Connections Equipped with Smart Memory Alloys.

Residual drifts are an important measure of post-earthquake functionality in bridges and buildings, and can determine whether the structure remains fit for its intended purpose or not. This study aims at investigating numerically, through finite element (FE) analysis in ABAQUS, the cyclic response of exterior steel I beam-hollow column connection using welded shape memory alloys (SMA) bolts and seat angles. This is followed by validating the numerical model using an accredited experimental data available in the literature through different techniques, (1) SMA bolts, (2) SMA angles, (3) SMA bolts and angles. The parameters investigated included: SMA type, SMA angle thickness, SMA bolt diameter, SMA angle stiffener and SMA angle direction. The cyclic performance of the steel connection was enhanced further by varying the bolt diameter, plate thickness, angle type and direction. The results revealed that the connections equipped with a combination of SMA plates and SMA angles reduced the residual drift by up to 94%, and doubled the self-centering capability compared to conventional steel connections. Moreover, the parametric analysis showed that Fe-based SMA members could be a good alternative to NiTi based SMA members for improving the self-centering capability and reducing the residual drifts of conventional steel connections.

Home and School Pollutant Exposure, Respiratory Outcomes, and Influence of Historical Redlining

BackgroundThe discriminatory and racist policy of historical redlining in the United States (U.S.) during the 1930s played a role in perpetuating contemporary environmental health disparities. ObjectiveOur objectives were to determine associations between home and school pollutant exposure (fine particulate matter (PM2.5), nitrogen dioxide (NO2)) and respiratory outcomes (Composite Asthma Severity Index (CASI), lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. MethodsChildren ages 6 to 17 with moderate-to-severe asthma (N=240) from 9 U.S. cities were included. Combined home and school exposure to PM2.5 and NO2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of CASI and lung function were collected. ResultsOverall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO2 (median: 15.4 vs 12.1 ppb) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (p<0.01). Overall, PM2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM2.5 was associated with worse asthma severity (p<0.005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (p>0.005). ConclusionsOur findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM2.5 exposure and its associations with respiratory health.

Increasing region of interest width reduces neonatal circumferential strain.

There is growing interest in speckle tracking echocardiography-derived strain as a measure of left ventricular function in neonates. However, knowledge gaps remain regarding the effect of image acquisition and processing parameters on circumferential strain measurements. The aim of this study was to evaluate the effect of using different region of interest (ROI) widths on speckle tracking derived circumferential strain in healthy neonates. Thirty healthy-term-born neonates were examined with speckle-tracking echocardiography in the short-axis view. Circumferential strain values were acquired and compared using two different ROI widths. Furthermore, strain values in the different vendor-defined wall layers were also compared. Increasing ROI width led to a decrease in global circumferential strain (GCS) in the midwall and epicardial layers, the respective decreases in strain being -23.4±.6% to -22.0±1.1%, p<.0001 and 18.5±1.7% to -15.6±2.0%, p<.0001. Segmental analyses were consistent with these results, apart from two segments in the midwall. There was no statistically significant effect on strain for the endocardial layer. A gradient was seen where strain increased from the epicardial to endocardial layers. Increasing ROI width led to a decrease in GCS in the midwall and epicardium. There is an increase in circumferential strain when moving from the epicardial toward the endocardial layer. Clinicians wishing to implement circumferential strain into their practice should consider ROI width variation as a potential confounder in their measurements.

Home and School Pollutant Exposure, Respiratory Outcomes, and Influence of Historical Redlining

BackgroundThe discriminatory and racist policy of historical redlining in the United States (U.S.) during the 1930s played a role in perpetuating contemporary environmental health disparities. ObjectiveOur objectives were to determine associations between home and school pollutant exposure (fine particulate matter (PM2.5), nitrogen dioxide (NO2)) and respiratory outcomes (Composite Asthma Severity Index (CASI), lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. MethodsChildren ages 6 to 17 with moderate-to-severe asthma (N=240) from 9 U.S. cities were included. Combined home and school exposure to PM2.5 and NO2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of CASI and lung function were collected. ResultsOverall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO2 (median: 15.4 vs 12.1 ppb) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (p<0.01). Overall, PM2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM2.5 was associated with worse asthma severity (p<0.005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (p>0.005). ConclusionsOur findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM2.5 exposure and its associations with respiratory health.

Provision of Inpatient Rehabilitation to Individuals with Lower-Limb Amputation in Canada: An Epidemiological Analysis

ABSTRACT Objective The aim of this study was to determine the proportion of individuals with major lower-limb amputation (LLA) who received inpatient rehabilitation in Canadian provinces, their rehabilitation length, and their functional independence level at admission and discharge. Methods Major LLA records from April 1, 2006, to March 31, 2012, were obtained from the Canadian Institute for Health Information and linked to National Rehabilitation Reporting System data (Quebec data were unavailable). The proportions of individuals who received inpatient rehabilitation, mean length of stay, and Functional Independence Measure (FIM) scores (admission and discharge) were calculated. Results A total of 16,114 new individuals had major LLAs in nine Canadian provinces over the study period; 18% received inpatient rehabilitation. The mean (SD) length of stay was 37.3 (25.2) days. Nova Scotia and Ontario had the highest provision of inpatient rehabilitation (n = 235, 28.6% and n = 1779, 23.4%, respectively). Newfoundland and Labrador had the longest mean (SD) inpatient rehabilitation stay, 62.6 (36.6) days. Prince Edward Island had the highest FIM scores at admission and discharge (mean = 105.3, SD = 12.8; mean = 111.3, SD = 12.9 days, respectively). Conclusions We found that 18% of individuals with major LLA received inpatient rehabilitation across nine Canadian provinces. Costs and resource demands may prevent inpatient rehabilitation provision. Novel, cost-effective strategies may facilitate the provision of rehabilitation services. Clinical Relevance Despite the benefits of rehabilitation for individuals with major LLA, especially those whose amputations resulted from a traumatic incident, only 18% of patients with major LLA received inpatient rehabilitation across nine provinces between 2006 and 2012. Provinces with longer durations of inpatient rehabilitation reported higher levels of functional independence when patients with LLA were discharged.

The Effectiveness of Strengthening Exercise on Improving Physical Function in Chronic Dialysis with Comorbidity: A Case Study

BACKGROUND: Individuals living with End stage renal disease (ESRD) on long term hemodialysis (HD) generally has a sedentary life style. This leads to reduction of physical function and poor quality of life. Exercise intervention improves muscular strength, physical fitness and Quality of life (QOL) in maintained hemodialysis Individuals. CASE SCENARIO: A 67-year-old female presented with chronic hemodialysis period was carried on wheelchair with the help of relative as she was referred to physiotherapy department with chief complain of weakness in both lower limb and difficulty in walking for 1 year. In this case along with chronic dialysis related dysfunction, patient had atherosclerosis had an acute coronary event and she was on AKT since last one year as she was having pott’s spine. METHODOLOGY: In our evaluation, she had full range of motion of lower limb with muscle weakness by manual muscle testing (MMT=3-4/5), Reduced balance and physical performance by short physical performance battery (SPPB=4/12), and partially dependent for functional activity by functional independent measure (FIM= 81/126). In Physiotherapy intervention: Exercise program started with active exercise, cycling, balance and gait training. Progressively in active exercise increased weight with weight cuff, increase cycling time and task specific balance activities with independent walking each week. RESULT: After four week of intervention improvement in muscle strength (MMT=4-5/5), balance (SPPB=7/12), minimal assistance in functional activities (FIM=109/126). CONCLUSION: Individualized strengthening exercise program improve physical function and muscle strength in chronic dialysis patient. Keywords: Hemodialysis, physical function, muscle strength.

Assessing Pain and Functional Outcomes of Percutaneous Stabilization of Metastatic Pelvic Lesions via Photodynamic Nails: A Bi-Institutional Investigation of Orthopaedic Outcomes.

Minimally invasive surgical interventions for metastatic invasion of the pelvis have become more prevalent and varied. Our group hypothesized that the use of percutaneous photodynamic nails (PDNs) would result in decreased pain, improved functional outcomes and level of ambulation, and decreased use of opioid pain medication. We performed a retrospective chart review of patients with metastatic pelvic bone disease undergoing stabilization with PDNs (IlluminOss Medical) at 2 institutions. Functional outcome measures assessed include the Combined Pain and Ambulatory Function (CPAF), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, and PROMIS Global Health-Physical. Pain was assessed using a visual analog scale (VAS). Outcomes were assessed preoperatively and at 6 weeks, 3 months, 6 months, and 1 year following surgery. A total of 39 patients treated with PDNs were included. No cases of surgical site infection or implant failure were identified. The median pain VAS score decreased from 8 preoperatively to 0 at the 6-week time point (p < 0.0001). The median CPAF score improved from 5.5 points preoperatively to 7 points at the 3-month mark (p = 0.0132). A significant improvement in physical function was seen at 6 months in the PROMIS Physical Function (p = 0.02) and at both 6 months (p = 0.01) and 1 year (p < 0.01) for the PROMIS Global Health-Physical. The rate of patients prescribed opioid analgesia dropped from 100% preoperatively to 20% at 6 months following surgery (p < 0.001). By 6 weeks, all patients were fully weight-bearing and able to walk independently with or without assistive devices. Percutaneous stabilization of metastatic periacetabular defects using PDNs is a safe and effective palliative procedure that has been shown to improve patient mobility and provide early pain relief. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline.

Although white matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether connectome gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. A total of 758 WMH individuals completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations among the spatial distribution of WMH, functional gradient measures, and specific cognitive domains were explored. As the WMH volume increased, the executive function (r = -0.135, p = 0.001) and information-processing speed (r = -0.224, p = 0.001) became poorer, the gradient range (r = -0.099, p = 0.006), and variance (r = -0.121, p < 0.001) of the primary-to-transmodal gradient reduced. A narrower gradient range (r = 0.131, p = 0.001) and a smaller gradient variance (r = 0.136, p = 0.001) corresponded to a poorer executive function. In particular, the relationship between the frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient. These findings indicated that WMH volume, the primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was partly mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.

Physiotherapy treatment for reverse total shoulder arthroplasty: Results of a patient-centred rehabilitation guideline using functional and patient-reported outcome measures.

Rehabilitation after primary reverse total shoulder arthroplasty (RTSA) is accepted to be an essential component to successful outcome achievement, but successful rehabilitation approaches have yet to be well described in the literature. This retrospective review documents the outcomes of a cohort of 29 patients undergoing RTSA surgery with rehabilitation following the Upper Limb Treatment and Rehabilitation Advice (ULTRA) guideline (Appendix 1). The Oxford Shoulder Score, Quick Disabilities of the Arm, Shoulder and Hand score, range of movement (degrees of flexion, abduction and external rotation) and numerical rating score for pain were prospectively collected pre-operatively and at one- and two-years post-operatively. Scores were then evaluated to establish whether or not there were any significant changes over time. Statistically significant improvements were seen in all outcome domains from pre-operative to one-year post-operative. All improvements met the threshold for achieving substantial clinical benefit as well as exceeding the minimum clinically important difference, and all improvements were maintained at the two-year post-operative time point. The present study showed that following the ULTRA guideline after elective RTSA can give statistically significant improvements in range of movement, pain score and patient-reported outcome at one-year post-operatively, which can be maintained up to two-years post-operatively.

Association of dual task gait performance with cognitive outcomes among older adults: Piloting an inexpensive, portable assessment platform

Motor assessment has emerged as complementary evidence for the detection of late life cognitive disorders. Clinicians lack inexpensive, accurate, and portable tools for this purpose. To fill this void, the current study piloted measures from the Mizzou Point-of-care Assessment System a multimodal sensor platform. We examined the ability of these motor function measures to distinguish neurocognitive status and assessed their associations with cognitive performance. Data came from 42 older adults, including 16 with mild cognitive impairment (MCI). Participants performed dual task gait, pairing walking with serial subtraction by sevens, along with aa neuropsychological test battery. T-tests revealed that individuals with MCI demonstrated slower stride times (d = .55) and shorter stride lengths (d = .98) compared to healthy older adults. Results from hierarchical regression showed that stride time and stride length predicted cognitive performance across several domains, after controlling for cognitive status and demographics. Cognitive status moderated this relationship for global cognition and attention, wherein gait measures were significantly related to these outcomes for the cognitively normal group, but not the MCI group. Evidence from the current study provided preliminary support that MPASS measures demonstrate expected associations with cognitive performance and can distinguish amongst those with and without cognitive impairment.

Repeated exposure to multiple concurrent stressors alters visual processing in the adult posterior parietal cortex

Chronic stress is well known to erode cognitive functions. Yet, our understanding of how repeated stress exposure impacts one of the fundamental bases of cognition: sensory processing, remains limited. The posterior parietal cortex (PPC) is a high order visual region, known for its role in visually guided decision making, multimodal integration, attention, and working memory. Here, we used functional measures to determine how repeated exposure to multiple concurrent stressors (RMS) affects sensory processing in the PPC in adult male mice. A longitudinal experimental design, repeatedly surveying the same population of neurons using in vivo two-photon imaging, revealed that RMS disrupts the balanced turnover of visually responsive cells in layer 2/3 of the PPC. Across the population, RMS-induced changes in visual responsiveness followed a bimodal distribution suggesting idiosyncratic stress effects. In cells that maintained their responsiveness across recording sessions, we found that stress reduced visual response magnitudes and feature selectivity. While we did not observe stress-induced elimination of excitatory synapses, noise correlation statistics indicated that RMS altered visual input to the neuronal population. The impact of RMS was restricted to visually evoked responses and was not evident in neuronal activity associated with locomotion onset. Together, our results indicate that despite no apparent synaptic reorganization, stress exposure in adulthood can disrupt sensory processing in the PPC, with the effects showing remarkable individual variation.

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel–Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL’s coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype–phenotype relationships across complete genes.

OUTER RETINAL MICROCAVITATIONS IN RETINITIS PIGMENTOSA : A Novel Optical Coherence Tomography Finding Common in RP1 -Related Retinopathy.

To describe a novel optical coherence tomography (OCT) finding of outer retina microcavitations in RP1 -related retinopathy and other retinal degenerations. Medical charts and OCT images of 28 patients with either autosomal dominant retinitis pigmentosa or autosomal recessive retinitis pigmentosa RP1 -related retinopathy were reviewed. Outer retina microcavitations were defined as hyporeflective OCT structures of at least 30 µ m in diameter between the ellipsoid zone and retinal pigment epithelium. Comparison was made based on the following metrics: (1) functional measures including best-corrected visual acuity and color discrimination errors on D-15 test; and (2) structural measures, including central subfield, average macular thickness, and preserved transfoveal ellipsoid zone width. Mann-Whitney tests were used for comparisons with significance set at P < 0.05. The specificity of microcavitations for RP1 -related retinopathy was estimated against 26 patients with non- RP1 retinitis pigmentosa. Among 15 included patients, microcavitations were found in at least one eye of all patients with arRP and 7/12 (58%) of patients with adRP. Patients with adRP and microcavitations were older at the time of examination (51 vs. 43 years of age; P = 0.04) and their eyes demonstrated worse best-corrected visual acuity (0.09 vs. 0 logMAR; P = 0.008), reduced central subfield (256 vs. 293 µ m; P = 0.01), average macular thickness (241 vs. 270 µ m; P = 0.02), and shorter transfoveal ellipsoid zone widths (1.67 vs. 4.98 mm; P < 0.0001). The finding of microcavitations showed a specificity of 0.92 for RP1 -related retinopathy. A novel OCT finding of outer retina microcavitations was commonly observed in patients with RP1 -related retinopathy. Eyes with outer retinal OCT microcavitations had worse visual function and more affected central retinal structure.