The effectiveness of cervical transforaminal epidural steroid injections for the treatment of cervical radicular pain: A prospective cohort study reporting 12-month outcomes.

Objectives: To evaluate the effectiveness of cervical transforaminal epidural steroid injection (CTFESI) for the treatment of unilateral cervical radicular pain. Design: Single-group prospective cohort study. Methods: Outcomes included ≥50% reductions in Numeric Rating Scale (NRS) for arm pain, ≥30% Neck Disability Index (NDI-5) improvement, health-related quality of life (EQ-5D), global improvement (PGIC), personal goal achievement (COMBI), Chronic Pain Sleep Index (CPSI), and healthcare utilization at one, three, six, and 12 months. Data analysis included descriptive statistics with the calculations of 95% confidence intervals (CIs), contingency table analysis, and multilevel logistic regression (LR) analysis, including a worst-case (WC) sensitivity analysis in which missing data were treated as treatment failure. Participants who were treated surgically were considered failures in the categorical analyses. Results: 33 consecutively enrolled participants (63.6% females, 51.2 ± 12.2 years of age, BMI 28.3 ± 4.5 kg/m2) were analyzed. Success rates for ≥50% reduction in NRS for arm pain at one, three, six and 12 months were 57.6% (95% CI 40.8-72.8%), 71.9% (95% CI 54.6-84.4%), 64.5% (95% CI 46.9-78.9%), and 64.5% (95% CI 46.9-78.9%). Success rates for ≥30% improvement in NDI-5 were 60.6% (95% CI 43.7-75.3%), 68.8% (95% CI 51.4-82.0%), 61.3% (95% CI 43.8-76.3%), and 71.0% (95% CI 53.4-83.9%). In WC analysis, success rates for ≥50% arm NRS and NDI-5 were 0-4.3% lower between 1 and 12 months. PGIC scores were at least "much improved" or "very much improved," in 48.4-65.6% of participants between 1 and 12 months. 6.1%, 6.1%, and 3.0% had one, two, or three repeat injections, respectively. 18.2% of participants underwent surgery by 12 months. Participants showed significant improvements in arm NRS and NDI-5 after treatment (p < 0.05), multilevel logistic regression models showed no significant decline in improvements across the follow-up time points (p > 0.05). Conclusion: Statistically significant and clinically meaningful improvements in pain and disability were observed after CTFESI for up to 12 months in individuals with unilateral cervical radicular pain.

Wireless In-Ear Communication for Total Joint Arthroplasty: A Simulated Operating Room Evaluation.

Effective communication is vital for patient safety, yet failures are common, often due to outdated methods. This study aimed to assess whether in-ear communication devices improve communication in orthopedic surgery simulations compared to traditional loud voice methods. Fifteen participants underwent simulations using both in-ear wireless devices and standard communication. Results showed significant improvements with in-ear devices in correctly identifying phrases (78.6% vs 44%), effectiveness (7.9/10 vs 4.9/10), and clarity (8/10 vs 4/10), all P < .001. Participants also favored in-ear devices in usability assessments. Sound levels recorded were comparable between groups. In conclusion, in-ear communication is safe and effective in orthopedic settings, potentially enhancing efficiency and safety. These devices can mitigate loud noises, benefiting surgeon well-being and patient outcomes.

Predictors and patterns of suicidal ideation disclosures among American adults.

INTRODUCTION: When experiencing suicidal thoughts, many individuals do not tell others, making it difficult to ensure suicide prevention resources reach those who need it. METHODS: The current study utilizes a large sample of US adults who have experienced suicidal ideation in their lifetime (n = 1074) to examine predictors of disclosures. We also explore who participants disclose to and how helpful these disclosures are rated. RESULTS: A majority (n = 812, 75.6%) reported disclosing. Black and Hispanic participants were less likely to disclose than White participants. Those who were never married were more likely to disclose, as were those who have attempted suicide. Mental healthcare utilization and favorable attitudes toward mental healthcare were also positive predictors of disclosure. More participants reported disclosing to a personal connection (n = 532, 65.5%) than a mental health professional (n = 282, 34.8%). On average, most sources were rated as neither helpful nor harmful. CONCLUSION: The study highlights those who may be at a higher risk of experiencing suicidal thoughts but going unidentified. To increase helpfulness of disclosures, suicide prevention programming should emphasize training for laypersons and professionals on how to effectively respond when someone reveals that they are thinking of suicide.

Enhancing Health Literacy: Evaluating the Readability of Patient Handouts Revised by ChatGPT's Large Language Model.

OBJECTIVE: To use an artificial intelligence (AI)-powered large language model (LLM) to improve readability of patient handouts. STUDY DESIGN: Review of online material modified by AI. SETTING: Academic center. METHODS: Five handout materials obtained from the American Rhinologic Society (ARS) and the American Academy of Facial Plastic and Reconstructive Surgery websites were assessed using validated readability metrics. The handouts were inputted into OpenAI's ChatGPT-4 after prompting: "Rewrite the following at a 6th-grade reading level." The understandability and actionability of both native and LLM-revised versions were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results were compared using Wilcoxon rank-sum tests. RESULTS: The mean readability scores of the standard (ARS, American Academy of Facial Plastic and Reconstructive Surgery) materials corresponded to "difficult," with reading categories ranging between high school and university grade levels. Conversely, the LLM-revised handouts had an average seventh-grade reading level. LLM-revised handouts had better readability in nearly all metrics tested: Flesch-Kincaid Reading Ease (70.8 vs 43.9; P < .05), Gunning Fog Score (10.2 vs 14.42; P < .05), Simple Measure of Gobbledygook (9.9 vs 13.1; P < .05), Coleman-Liau (8.8 vs 12.6; P < .05), and Automated Readability Index (8.2 vs 10.7; P = .06). PEMAT scores were significantly higher in the LLM-revised handouts for understandability (91 vs 74%; P < .05) with similar actionability (42 vs 34%; P = .15) when compared to the standard materials. CONCLUSION: Patient-facing handouts can be augmented by ChatGPT with simple prompting to tailor information with improved readability. This study demonstrates the utility of LLMs to aid in rewriting patient handouts and may serve as a tool to help optimize education materials. LEVEL OF EVIDENCE: Level VI.

Association of Auditory Interference and Ocular-Motor Response with Subconcussive Head Impacts in Adolescent Football Players.

The aim of this study was to examine whether neuro-ophthalmological function, as assessed by the King-Devick test (KDT), alters during a high school football season and to explore the role of auditory interference on the sensitivity of KDT. During the 2021 and 2022 high school football seasons, football players' neuro-ophthalmological function was assessed at five time points (preseason, three in-season, postseason), whereas control athletes were assessed at preseason and postseason. Two-hundred ten football players and 80 control athletes participated in the study. The year 1 cohort (n = 94 football, n = 10 control) was tested with a conventional KDT, whereas the year 2 cohort (n = 116 football, n = 70 control) was tested with KDT while listening to loud traffic sounds to induce auditory interference. There were improvements in KDT during a season among football players, regardless of conventional KDT (preseason 53.4 ± 9.3 vs. postseason 46.4 ± 8.5 sec; ß = -1.7, SE = 0.12, p < 0.01) or KDT with auditory interference (preseason 52.3 ± 11.5 vs. postseason 45.1 ± 9.5 sec; ß = -1.7, SE = 0.11, p < 0.001). The degree of improvement was similar between the tests, with no significant group-by-time interaction (ß = -0.08, SE = 0.17, p = 0.65). The control athletes also improved KDT performance at a similar degree as the football cohorts in both KDT conditions. Our data suggest that KDT performance improves during a season, regardless of auditory interference or head impact exposure. KDT performance was not impacted by a noisy environment, supporting its sideline utility for screening more severe forms of injury.

Balancing act: the complex role of artificial intelligence in addressing burnout and healthcare workforce dynamics.

Burnout and workforce attrition present pressing global challenges in healthcare, severely impacting the quality of patient care and the sustainability of health systems worldwide. Artificial intelligence (AI) has immense potential to reduce the administrative and cognitive burdens that contribute to burnout through innovative solutions such as digital scribes, automated billing and advanced data management systems. However, these innovations also carry significant risks, including potential job displacement, increased complexity of medical information and cases, and the danger of diminishing clinical skills. To fully leverage AI's potential in healthcare, it is essential to prioritise AI technologies that align with stakeholder values and emphasise efforts to re-humanise medical practice. By doing so, AI can contribute to restoring a sense of purpose, fulfilment and efficacy among healthcare workers, reinforcing their essential role as caregivers, rather than distancing them from these core professional attributes.

Permanent Indian ink tattoos for breast cancer radiotherapy: A United Kingdom study of the emotional impact on patients following radiotherapy.

INTRODUCTION: Post-operative radiotherapy for early breast cancer is recommended for over 30,000 people every year in the United Kingdom. The majority of these patients will be advised to have radiotherapy alignment tattoos; permanent skin marks applied with Indian ink and a lancing needle, black/green/blue in colour and approximately 2 mm in diameter. The tattoos assist the therapeutic radiographers to position the patient accurately and reproducibly for each treatment fraction. The aim of this study was to investigate the emotional impact of radiotherapy tattoos on people following breast cancer radiotherapy. METHODS: An electronic questionnaire was distributed by the charitable organisation, Breast Cancer Now, to their members who had undergone radiotherapy for early breast cancer. Based on the responses to the open and closed questions, an overall impact score was assigned to each respondent, and representative quotes extracted to contextualise the themes identified. Statistical tests were performed to evaluate the relationship between overall impact scores and several variables such as age at the time of radiotherapy, skin type, and age at the time of completing the questionnaire. RESULTS: 204 people responded to the questionnaire. 100% had permanent Indian ink tattoos during breast cancer radiotherapy. 95% could still see the midline tattoo. 22 subthemes were identified; 4 positive, 4 neutral and 14 negative. Radiotherapy tattoos served as a constant negative reminder for 27% and affected clothing choices in 14% of respondents. 11% described feelings of 'hating' them. 6% were assigned positive overall impact scores, 43% neutral, and 51% had negative overall impact scores. The black/green/blue ink pigment used was commonly described as unnatural; contributing strongly to the negative appearance of the tattoos. CONCLUSION: Permanent Indian ink tattoos have a negative impact on emotional well-being in the months and years following radiotherapy for early breast cancer for many people. In contrast, a very small minority feel positively about the tattoos. IMPLICATIONS FOR PRACTICE: Our findings are unlikely to be unique to this diagnostic cohort and supports the need to offer alternatives that are less-impactful to the recipient, accessible for people of all skin colours, and fit-for-purpose in terms of radiotherapy set-up. Acknowledgement of the significant negative impact and collaboration between industry, healthcare professionals and patient representatives is key to identifying and implementing suitable alternatives as standard of care.

Normative Modeling of Thalamic Nuclear Volumes and Characterization of Lateralized Volume Alterations in Alzheimer's Disease Versus Schizophrenia.

BACKGROUND: Thalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer's disease (AD) and schizophrenia. The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in schizophrenia and AD. METHODS: Volumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 MRI data using a state-of-the-art novel segmentation method in healthy control subjects (n=2374) and early mild cognitive impairment (MCI, n=211), late MCI (n=113), AD (n=88), and schizophrenia (n=168). Normative models for each nucleus were generated from healthy control subjects while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z|>1.96) and z-score distributions were compared across phenotypes. Z-scores were associated with clinical descriptors. RESULTS: Increased infranormal and decreased supranormal z-scores were observed in schizophrenia and AD. Z-score shifts representing reduced volumes were observed in most nuclei in schizophrenia and AD with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD with evidence of a left-sided preference in early MCI while a predilection for right thalamic nuclei was observed in schizophrenia. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations. CONCLUSION: In AD, thalamic nuclei are more severely and symmetrically affected while in schizophrenia, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of schizophrenia and is affected early in the disease course.

The Influence of Acute Oral Lactate Supplementation on Responses to Cycle Ergometer Exercise: A Randomized, Crossover Pilot Clinical Trial.

The purpose of this study was to investigate the potential ergogenic effects of an oral lactate supplement. For this double-blind, randomized, placebo-controlled crossover design, fifteen recreational exercisers (nine males, six females) ingested a placebo or a commercially available lactate supplement prior to cycle ergometer exercise. Primary outcomes included peak oxygen uptake (VO2peak; via indirect calorimetry), VO2 at the ventilatory threshold, and work rate at the lactate threshold (arterialized venous blood from a heated hand) determined during incremental exercise to fatigue, and power output during a 20-min cycling time trial. Compared with placebo, the oral lactate supplement (19 ± 1 mg/kg body mass) did not influence VO2peak (placebo: 44.3 ± 7.8 vs. oral lactate: 44.3 ± 7.1 mL/kg/min (mean ± SD); p = 0.87), VO2 at the ventilatory threshold (placebo: 1.63 ± 0.25 vs. oral lactate: 1.65 ± 0.23 L/min; p = 0.82), or work rate at the lactate threshold (placebo: 179 ± 69 vs. oral lactate: 179 ± 59 W; p = 0.41). Throughout the 20-min time trial, the work rate was slightly greater (4%) with oral lactate (204 ± 41 W) compared with placebo (197 ± 41 W; main effect of treatment p = 0.02). Collectively, these data suggest that this commercially available lactate supplement did not acutely influence the physiological responses to incremental cycle ergometer exercise but elicited a modest ergogenic effect during the short-duration time trial.

Total Ankle Arthroplasty Templating: Preoperative Computer Templating Correlates Highly with Intraoperative Component Selection.

Proper alignment and sizing are critical to the performance of a successful total ankle arthroplasty. While it is common practice in preoperative planning prior to total knee and total hip arthroplasty, preoperative computer templating has not been well established in the setting of total ankle arthroplasty. A retrospective review of all total ankle arthroplasties performed during a 10-year period by a single fellowship-trained orthopaedic surgeon was conducted. Computer templating was utilized for all preoperative AP and lateral standing radiographs, and templated component sizes were compared to the operative reports and postoperative radiographs to determine the precision of the available templates. Statistical analysis was performed with Interclass Correlation Coefficients (ICC) and descriptive statistical tests. Seventy patients with a mean age of 64.8 years (range, 48-87) and mean BMI of 30.34 (range, 19.1-55.6) were included. The Interclass Correlation Coefficient demonstrated that both the AP (ICC 0.80 - 95% CI 0.679-0.876) and lateral (ICC 0.786 - 95% CI 0.655-0.867) radiographs provided for accurate tibial total ankle arthroplasty component templating. Similarly, the AP (ICC 0.842 - 95% CI 0.745-0.902) and lateral (ICC 0.809 - 95% CI 0.692-0.881) radiographs provided for accurate talar templating. No differences were observed when comparing AP to lateral radiographs in percentage of correct component templating: tibial AP 61.4% vs lateral 58.6%, p=0.119 and talar component anterior-posterior 57.1% vs lateral 45.7%, p=0.176. These study findings demonstrate that preoperative templating for total ankle arthroplasties is accurate in determining appropriate implant sizing. Accurate templating is an absolute necessity for future templating studies. Level of clinical evidence: III.

Comorbid onset of cardiovascular diagnosis and long-term confirmed disability progression in multiple sclerosis: A 15-year follow-up study.

BACKGROUND: People with multiple sclerosis (pwMS) have greater prevalence of comorbid cardiovascular diseases (CVD) when compared to the general population despite similar frequency of CV risk factors. OBJECTIVE: Determine the impact of comorbid-onset of CVD diagnosis on long-term confirmed disability progression (CDP). METHODS: 276 pwMS (29 clinically isolated syndrome, 130 relapsing-remitting and 117 progressive) were clinically followed an average of 14.9 years, with a mean of 14.4 clinical visits. Retrospective electronic medical records (EMR) review determined CVD diagnoses (hypertension, hyperlipidemia, diabetes, and heart disease) at baseline and over the follow-up. CDP was determined with ≥1.0 point Expanded Disability Status Scale (EDSS) increase from EDSS <5.5, or ≥ 0.5-point increase from ≥5.5, and was sustained on next clinical visit. RESULTS: A significantly shorter time to overall CDP was detected in 213 pwMS who had an existing (28 pwMS) or developed new onset (185 pwMS) of CVD, compared to 63 CVD-healthy pwMS over the follow-up (13.4 vs 15.9 years, Mantel-Cox p < 0.001), independent of baseline age and EDSS score. The CVD diagnosis preceded the CDP in 103 pwMS (55.7%), occurred after CDP in 71 pwMS (38.4%) and was concurrent in 11 pwMS (5.9%). Using mixed-effect models adjusted for significant age (F = 56.5, p < 0.001) and time effects (F = 67.8, p < 0.001), the CVD-onset diagnosis was associated with greater accrual of disability, as measured by longitudinal increase in EDSS score (F = 4.207, p = 0.04). Sex was not significant predictor of future disability in our cohort. CONCLUSION: PwMS with an existing or new onset of comorbid CVD diagnosis showed accelerated disability worsening over long-term. There was no temporal relationship between the onset of CVD and CDP within the group that had CVD-onset diagnosis.

Accelerated Discovery of Carbamate Cbl-b Inhibitors Using Generative AI Models and Structure-Based Drug Design.

Casitas B-lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that has an important role in effector T cell function, acting as a negative regulator of T cell, natural killer (NK) cell, and B cell activation. A discovery effort toward Cbl-b inhibitors was pursued in which a generative AI design engine, REINVENT, was combined with a medicinal chemistry structure-based design to discover novel inhibitors of Cbl-b. Key to the success of this effort was the evolution of the "Design" phase of the Design-Make-Test-Analyze cycle to involve iterative rounds of an in silico structure-based drug design, strongly guided by physics-based affinity prediction and machine learning DMPK predictive models, prior to selection for synthesis. This led to the accelerated discovery of a potent series of carbamate Cbl-b inhibitors.

Racial, Ethnic, and Age-Related Disparities in Sedation and Restraint Use for Older Adults in the Emergency Department.

OBJECTIVES: Older adults may present to the emergency department (ED) with agitation, a symptom often resulting in chemical sedation and physical restraint use which carry significant risks and side effects for the geriatric population. To date, limited literature describes the patterns of differential restraint use in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This retrospective cross-sectional study used electronic health records data from ED visits by older adults (age ≥65 years) ranging 2015-2022 across nine hospital sites in a regional hospital network. Logistic regression models were estimated to determine the association between patient-level characteristics and the primary outcomes of chemical sedation and physical restraint. RESULTS: Among 872,587 ED visits during the study period, 11,875 (1.4%) and 32,658 (3.7%) encounters involved the use of chemical sedation and physical restraints respectively. The populations aged 75-84, 85-94, 95+ years had increasingly higher odds of chemical sedation [adjusted odds ratios (AORs) 1.35 (95% CI 1.29-1.42); 1.82 (1.73-1.91); 2.35 (2.15-2.57) respectively] as well as physical restraint compared to the 65-74 group [AOR 1.31 (1.27-1.34); 1.55 (1.50-1.60); 1.69 (1.59-1.79)]. Compared to the White Non-Hispanic group, the Black Non-Hispanic and Hispanic/Latinx groups had significantly higher odds of chemical sedation [AOR 1.26 (1.18-1.35); AOR 1.22 (1.15-1.29)] and physical restraint [AOR 1.12 (95% CI 1.07-1.16); 1.22 (1.18-1.26)]. CONCLUSION: Approximately one in 20 ED visits among older adults resulted in chemical sedation or physical restraint use. Minoritized group status was associated with increasing use of chemical sedation and physical restraint, particularly among the oldest old. These results may indicate the need for further research in agitation management for historically marginalized populations in older adults.

Avoidant/Restrictive Food Intake Disorder: Review and Recent Advances.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder recently codified in DSM-5 that affects individuals of all ages. A proliferation of ARFID research has emerged over the years, and this review provides a brief overview of the current understanding of ARFID epidemiology, symptoms, comorbid conditions, assessment, and treatment. The review highlights recent research updates regarding ARFID among adults, putative neurobiological mechanisms underlying ARFID, and new treatment trials. Findings from this review demonstrate that ARFID is as prevalent as other eating disorders, even among adults, and is associated with significant medical and psychiatric comorbid conditions. New, promising treatments for children, adolescents, and adults are in the early stages of development. Several assessments are now available to aid in the screening and diagnosis of ARFID and have demonstrated cross-cultural validity. Areas for future research and clinical guidance, including unresolved questions regarding ARFID categorization and differential diagnosis, are discussed.

Plasma exchange and intravenous immunoglobulin for the peri-operative management of type 2 heparin-induced thrombocytopaenia in a patient requiring urgent surgery for critical limb ischaemia.

We report the case of a 61-year-old female who developed heparin-induced thrombocytopaenia following treatment of a submassive pulmonary embolism, and who then required an above knee amputation for critical limb ischaemia. Heparin-induced thrombocytopaenia is a rare, immune-mediated complication associated with an in-hospital mortality rate of 10%. It is more common in surgical patients, with patients undergoing orthopaedic surgery more likely to develop it than patients undergoing cardiac surgery, but heparin-dependent immunoglobulin G antibodies are more likely to be formed in the latter. Peri-operative management remains a challenge. Ideally, it is preferable to wait for the platelet count to improve; but in certain cases, surgery cannot be delayed. Heparin-induced thrombocytopaenia is usually managed with direct thrombin inhibitors, such as argatroban and bivalirudin. Newer therapeutic modalities, such as plasmapheresis and intravenous immunoglobulin, as used in this case, can rapidly remove antibodies, but the certainty of evidence is low. Our case adds to the literature regarding the use of these modalities and highlights the multidisciplinary team approach required to manage such complex cases.

Communicating the science of suicide prevention: A call to action for psychologists.

INTRODUCTION: Suicide is a major public health concern within the United States, and prevention efforts are essential for decreasing the suicide rate. Researchers and clinicians have knowledge and effective treatments for preventing suicide; however, their impact is limited to those with access to services. Science Communication (SciComm) is an effective tool that can be integrated into the field of suicide prevention and can bridge the gap between scientific findings and the general population. SciComm can help disseminate evidence-based strategies for suicide prevention, dispel misinformation on suicide, and normalize help-seeking. PURPOSE: In this article, we propose specific, tangible ways that SciComm can be integrated into graduate school programs, mentorship, career advancement requirements and can help enact systemic change within the field of suicide prevention. Additionally, we discuss why it is important that the field of suicide prevention, specifically, adopts a SciComm framework. Embracing SciComm can help the field of suicide prevention to have a broader impact and can help to reduce rates of suicide.

The stem cell niche transcription factor ETHYLENE RESPONSE FACTOR 115 participates in aluminum-induced terminal differentiation in Arabidopsis roots.

Aluminum-dependent stoppage of root growth requires the DNA damage response (DDR) pathway including the p53-like transcription factor SUPPRESSOR OF GAMMA RADIATION 1 (SOG1), which promotes terminal differentiation of the root tip in response to Al dependent cell death. Transcriptomic analyses identified Al-induced SOG1-regulated targets as candidate mediators of this growth arrest. Analysis of these factors either as loss-of-function mutants or by overexpression in the als3-1 background shows ERF115, which is a key transcription factor that in other scenarios is rate-limiting for damaged stem cell replenishment, instead participates in transition from an actively growing root to one that has terminally differentiated in response to Al toxicity. This is supported by a loss-of-function erf115 mutant raising the threshold of Al required to promote terminal differentiation of Al hypersensitive als3-1. Consistent with its key role in stoppage of root growth, a putative ERF115 barley ortholog is also upregulated following Al exposure, suggesting a conserved role for this ATR-dependent pathway in Al response. In contrast to other DNA damage agents, these results show that ERF115 and likely related family members are important determinants of terminal differentiation of the root tip following Al exposure and central outputs of the SOG1-mediated pathway in Al response.

Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed. Also, we aimed to determine the relationship between cognitive performance and MRI-based outcomes in these matched cohorts. The Comprehensive Assessment of Severely Affected Multiple Sclerosis study was carried out at the University at Buffalo and the Boston Home, a skilled nursing facility in Dorchester, MA. Inclusion criteria were age 30-80 years and expanded disability status scale 3.0-6.5 for community-dwelling and 7.0-9.5 for skilled nursing facility people with multiple sclerosis. The cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis consisting of Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test-2nd edition along with Auditory Test of Processing Speed, Paced Auditory Serial Addition Test-3 second and Controlled Oral Word Association Test. MRI scans were retrospectively collected and analysed for lesion and volumetric brain measurements. The rate of completion and performance of the cognitive tests was compared between the groups, and the relationship with MRI measures was determined using sex, age and years of education-adjusted linear regression models. Significantly greater percentage of the severe multiple sclerosis group completed Auditory Test of Processing Speed when compared with the current gold standard of Symbol Digit Modalities Test (93.2% versus 65.9%). Severe progressive multiple sclerosis had worse cognitive performance in all cognitive domains with greatest differences for cognitive processing speed (Symbol Digit Modalities Test > Paced Auditory Serial Addition Test-3 second > Auditory Test of Processing Speed, Cohen's d < 2.13, P < 0.001), learning and memory (Cohen's d < 1.1, P < 0.001) and language (Controlled Oral Word Association Test with Cohen's d = 0.97, P < 0.001). Multiple cognitive domains were significantly associated with lower thalamic (standardized ß < 0.419, P < 0.006) and cortical (standardized ß < 0.26, P < 0.031) volumes. Specially designed (auditory) cognitive processing speed tests may provide more sensitive screening of cognitive function in severe progressive multiple sclerosis. The cognitive profile of severe multiple sclerosis is proportional to their physical outcomes and best explained by decreased grey matter volume.

Developmental and age-related synapse elimination is mediated by glial Croquemort.

Neurons and glia work together to dynamically regulate neural circuit assembly and maintenance. In this study, we show Drosophila exhibit large-scale synapse formation and elimination as part of normal CNS circuit maturation, and that glia use conserved molecules to regulate these processes. Using a high throughput ELISA-based in vivo screening assay, we identify new glial genes that regulate synapse numbers in Drosophila in vivo, including the scavenger receptor ortholog Croquemort (Crq). Crq acts as an essential regulator of glial-dependent synapse elimination during development, with glial Crq loss leading to excess CNS synapses and progressive seizure susceptibility in adults. Loss of Crq in glia also prevents age-related synaptic loss in the adult brain. This work provides new insights into the cellular and molecular mechanisms that underlie synapse development and maintenance across the lifespan, and identifies glial Crq as a key regulator of these processes.

Accelerated Chest Pain Treatment With Artificial Intelligence-Informed, Risk-Driven Triage.

This quality improvement study evaluates the use of artificial intelligence to accelerate triage of patients presenting to the emergency department with chest pain.