A Systematic Review of Sleep Disturbance in Idiopathic Intracranial Hypertension.

Purpose of Review: Sleep disturbances, particularly obstructive sleep apnea (OSA), may have a significant impact on the outcomes of patients with idiopathic intracranial hypertension (IIH). We conducted a PRISMA-compliant systematic literature review to study sleep disturbance in adult patients with IIH. Recent Findings: The current literature on the relationship between IIH and sleep is quite limited. Research has found that sleep disturbances are associated with lower quality of life and may worsen several symptoms associated with IIH, such as headache, cognitive deficits, and neuropsychiatric issues. Summary: OSA was more prevalent in patients with IIH than in healthy controls. Several studies found that OSA was associated with worse IIH symptoms and treatment of OSA helped improve these parameters. Limitations included available literature and heterogeneity in sleep metrics and OSA diagnostic criteria between studies. Overall, further study of sleep disturbances in patients with IIH may encourage earlier screening, improved treatment options, and long-term improvements in quality of life.

Optical scattering methods for the label-free analysis of single biomolecules.

Single-molecule techniques to analyze proteins and other biomolecules involving labels and tethers have allowed for new understanding of the underlying biophysics; however, the impact of perturbation from the labels and tethers has recently been shown to be significant in several cases. New approaches are emerging to measure single proteins through light scattering without the need for labels and ideally without tethers. Here, the approaches of interference scattering, plasmonic scattering, microcavity sensing, nanoaperture optical tweezing, and variants are described and compared. The application of these approaches to sizing, oligomerization, interactions, conformational dynamics, diffusion, and vibrational mode analysis is described. With early commercial successes, these approaches are poised to have an impact in the field of single-molecule biophysics.

Multiple recurrences of a left ventricular pseudoaneurysm: a case report.

Background: Takotsubo syndrome (TTS) is being diagnosed more often with its increased recognition over the past 2 decades and with the availability of imaging such as point-of-care echocardiography and tissue characterization by cardiovascular magnetic resonance (CMR). Case summary: A young man developed pericarditis and was treated with steroids. A few weeks later, he suffered classic TTS and then presented a week later with the rare complication of apical myocardial rupture and a left ventricular (LV) pseudoaneurysm. He subsequently sustained two recurrences, likely secondary to the poor tensile strength of the repair in the region of necrotic myocardium. Discussion: Various features of both syndromes are discussed herein (myopericarditis and TTS) as well as their classic imaging findings with an emphasis on the echocardiographic diagnosis of an LV pseudoaneurysm and differentiating it from an aneurysm. Furthermore, we elucidate the classic imaging findings of CMR in myocarditis, myocardial infarction with non-obstructive coronary arteries, and TTS. Lastly, we discuss treatment options for LV pseudoaneurysms and strategies to prevent recurrence.

A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).

 Alzheimer's disease (AD) is a leading cause of mortality and morbidity among aging populations worldwide. Despite arduous research efforts, treatment options for this devastating neurodegenerative disease are limited. Sleep disturbances, through their link to changes in neural excitability and impaired clearance of interstitial abnormal protein aggregates, are a key risk factor for the development of AD. Research also suggests that the neuroprotective effects of sleep are particularly active during slow wave sleep. Given the strong link between sleep disturbance and AD, targeting sleep in the prodromal stages of AD, such as in mild cognitive impairment (MCI), represents a promising avenue for slowing the onset of AD-related cognitive decline. In efforts to improve sleep in older individuals, several pharmacologic approaches have been employed, but many pose safety risks, concern for worsening cognitive function, and fail to effectively target slow wave sleep. Trazodone, a safe and widely used drug in the older adult population, has shown promise in inducing slow wave sleep in older adults, but requires more rigorous research to understand its effects on sleep and cognition in the prodromal stages of AD. In this review, we present the rationale and study design for our randomized, double-bind, placebo-controlled, crossover trial (NCT05282550) investigating the effects of trazodone on sleep and cognition in 100 older adults with amnestic MCI and sleep complaints.

Impact of motor dysfunction on neuropsychiatric symptom profile in patients with autopsy-confirmed Alzheimer's disease.

Motor dysfunction, which includes changes in gait, balance, and/or functional mobility, is a lesser-known feature of Alzheimer's Disease (AD), especially as it relates to the development of neuropsychiatric symptoms (NPS). This study (1) compared rates of NPS between autopsy-confirmed AD patients with and without early-onset motor dysfunction and (2) compared rates of non-AD dementia autopsy pathology (Lewy Body disease, Frontotemporal Lobar degeneration) between these groups. This retrospective longitudinal cohort study utilized National Alzheimer's Coordinating Center (NACC) data. Participants (N = 856) were required to have moderate-to-severe autopsy-confirmed AD, Clinical Dementia Rating-Global scores of ≤1 at their index visit, and NPS and clinician-rated motor data. Early motor dysfunction was associated with significantly higher NPI-Q total scores (T = 4.48, p < .001) and higher odds of delusions (OR [95%CI]: 1.73 [1.02-2.96]), hallucinations (2.45 [1.35-4.56]), depression (1.51 [1.11-2.06]), irritability (1.50 [1.09-2.08]), apathy (1.70 [1.24-2.36]), anxiety (1.38 [1.01-1.90]), nighttime behaviors (1.98 [1.40-2.81]), and appetite/eating problems (1.56 [1.09-2.25]). Early motor dysfunction was also associated with higher Lewy Body disease pathology (1.41 [1.03-1.93]), but not Frontotemporal Lobar degeneration (1.10 [0.71-1.69]), on autopsy. Our results suggest that motor symptoms in early AD are associated with a higher number and severity of NPS, which may be partially explained by comorbid non-AD neuropathology.

Sleepiness in retired male boxers: daytime sleepiness and its relationship with impulsiveness and depression symptomatology in retired professional male boxers.

BACKGROUND: Boxing exposes fighters to head impacts and potential traumatic brain injury (TBI). Though research has explored the neuropsychiatric consequences of contact sports, there is limited research into Excessive Daytime Sleepiness (EDS) and its relationship to other outcomes, such as impulsiveness and depression. Therefore, this study aimed to describe EDS in retired boxers using the Epworth Sleepiness Scale (ESS) and to examine how boxing and sleepiness relate to impulsiveness and depression symptomatology. METHODS: 86 male retired professional boxers from the Professional Fighters Brain Health Study (PFBHS) met the inclusion criteria. Adjusted multivariable models analyzed relationships between professional boxing bouts, EDS (ESS), impulsiveness (Barratt Impulsiveness Scale Version 11 (BIS-11)), and/or depression (Patient Health Questionnaire-9 (PHQ-9)). A causal mediation analysis was performed to assess whether boxing bouts and ESS scores predicted BIS-11 and PHQ-9 scores. RESULTS: Mean age was ∼51 years, fighters averaged ∼36 professional bouts, and ESS mean(SD) was 7.5(5.3). ESS scores were significantly associated with raw BIS-11 (Beta = 1.26, 95%CI = 0.77-1.75, p < 0.001) and ordinal PHQ-9 (OR = 1.20, 95%CI = 1.11-1.31, p < 0.001) scores in adjusted models, and the significant relationship between boxing bouts and BIS-11/PHQ-9 was mediated by ESS. CONCLUSIONS: EDS in retired male professional boxers may be strongly associated with other neuropsychiatric sequelae of TBI (impulsiveness and depression).Sleepiness; sleep; boxing; contact sports; impulsiveness; impulsivity; depression; Epworth sleepiness scale box.

Identifying Factors Predicting Margin Status After Mastectomy.

INTRODUCTION: A positive margin after mastectomy increases the risk of breast cancer recurrence and the morbidity associated with re-excision or chest wall irradiation. This study aimed to identify factors that may predict margin status after mastectomy. METHODS: Women with Tis-T3 breast cancers who underwent mastectomy from 2014 to 2020 were retrospectively analyzed. Comparisons of clinicopathologic data were made between patients with negative margins (> 1 mm) and close (≤ 1 mm) or positive margins. RESULTS: Of 938 women who underwent mastectomy, negative margins were reported for 794 (85%) women, while 144 (15%) women experienced close (97/144, 10%) or positive (47/144, 5%) margins. Re-excision of margins was performed in 37 (26%) of those patients, and 9 (24%) had residual cancer after re-excision. On multivariate analysis, increasing age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.99, p = 0.002), increased body mass index (BMI; OR 0.97, 95% CI 0.93-1.00, p = 0.049), and neoadjuvant chemotherapy (NAC; OR 0.44, 95% CI 0.25-0.79, p = 0.006) decreased the risk of close or positive margins. Tumors located in the lower inner quadrant (OR 3.83, 95% CI 1.90-7.72, p < 0.001), multifocal tumors (OR 1.78, 95% CI 1.19-2.66, p = 0.005), immediate reconstruction (OR 1.63, 95% CI 1.03-2.58, p = 0.039), and a preoperative tumor to breast volume ratio > 4.14 (OR 2.66, 95% CI 1.43-4.94, p = 0.002) significantly increased the risk of close or positive margins. CONCLUSIONS: Age, BMI, tumor location, multifocality, NAC, immediate reconstruction, and tumor to breast volume ratio independently predicted margin status after mastectomy. These data should be considered when counseling women considering mastectomy.

Mavacamten Safety and Efficacy in a Heart Transplant Patient Exhibiting Obstructive Hypertrophic Cardiomyopathy Phenotype.

Hypertrophic cardiomyopathy is the most common inherited cardiac disease, exhibiting diverse phenotypes. Obstructive hypertrophic cardiomyopathy occurs in about two-thirds of cases and carries a worse prognosis. Mavacamten use in heart transplant recipients is limited. This paper reports a recipient who developed severe symptomatic obstructive hypertrophic cardiomyopathy phenotype/phenocopy and was initiated on mavacamten.

A systematic review of pre-injury anxiety disorder and post-concussion outcomes in youth and young adult athletes.

Pre-injury anxiety disorder may be a risk factor for poor outcomes following sportsrelated concussion. A systematic review was performed to characterize the relationship between pre-injury anxiety disorder and post-concussion symptom presentation and recovery time after sports-related concussions among children, adolescents, and young adults. A PRISMA-compliant literature search was conducted in Ovid MEDLINE, PsycINFO, EMBASE, and Scopus for articles published up to 25 January 2024. The initial query yielded 1358 unique articles. Articles that analyzed the relationship between pre-injury anxiety disorder and post-concussion symptoms and recovery time were included. A final cohort of 11 articles was extracted, comprising a total of 8390 study participants, of whom 921 had a history of pre-injury anxiety disorder. Pre-injury anxiety disorder was associated with prolonged time to return to sports activity and an increased incidence of physical, emotional, cognitive, and sleep-related symptoms. While the results of this review suggest an association between pre-injury anxiety disorder and post-concussion symptoms and recovery time, future studies should be more stringent regarding standardized anxiety disorder definitions, longitudinal assessment of post-concussion symptoms, anxiety disorder subtypes, and anxiety treatment history.

Relationship Between Posttraumatic Headache and Depression After Mild Traumatic Brain Injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) can lead to psychiatric and somatic symptoms for some patients, including posttraumatic headache (PTH) and depression. This study attempted to further establish the relationship between PTH and depression following mTBI and investigate whether the presence of PTH immediately following injury can identify patients at risk for developing depressive symptoms up to 6 months later. METHODS: This study was a secondary analysis of data from Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART), a prospective study of adult patients in the emergency department with head injury. Participants included 265 patients who met criteria for mTBI and completed the Rivermead Post-Concussion Symptoms Questionnaire, to identify PTH within 24 hours after injury, and the Patient Health Questionnaire-9, to assess depressive symptoms during follow-up. Measures were completed at the initial visit immediately after the injury in the emergency department and at 1-, 3-, and 6-month follow-up visits. RESULTS: Patients with acute PTH (aPTH) at time of injury were more likely to report PTH at 1, 3, and 6 months. They also had more severe depressive symptoms and a greater likelihood of clinically significant depression at all time points. CONCLUSIONS: Patients with aPTH within 24 hours after injury were more likely to report continued symptoms of PTH and clinically significant depression at 1, 3, and 6 months. These findings provide support for using the presence of aPTH in the emergency department following mTBI as an indicator for monitoring persistent PTH and depressive symptoms in the postacute recovery period.

Prior football or rugby exposure and white matter signal abnormalities in professional male mixed martial arts fighters.

BACKGROUND: White matter signal abnormalities have been associated with traumatic brain injury (TBI) and repetitive head impacts (RHI) in contact sports (e.g. American football, rugby). However, previous studies of mixed martial arts (MMA) fighters from the Professional Fighters Brain Health Study have not found greater white matter signal abnormalities in fighters versus controls. OBJECTIVE: This study aims to explore the varying white matter effects of football/rugby and MMA by analyzing how football/rugby history in mixed martial arts fighters may relate to white matter signal abnormalities, helping to further our understanding of sport-specific brain health risks. METHODS: Baseline visits for 90 active, professional, male mixed martial arts fighters and 27 unexposed male controls were cross-sectionally analyzed. Wilcoxon and Kruskal-Wallis tests compared demographics and white matter signal abnormalities, and multivariable regression models examined the associations between football/rugby history and white matter signal abnormality burden in fighters, adjusting for age, education, race, fights, MRI scanner, and supratentorial volume. RESULTS: 37/90 fighters had football/rugby history (mean: 4 years; range: 1-12 years). White matter signal abnormalities were significantly greater in fighters with football/rugby history compared to fighters without football/rugby history (Wilcoxon, p = 0.0190). Football/rugby history was significantly associated with white matter signal abnormality burden >75th percentile (OR: 12, CI: 3.3-61, p < 0.001) and >50th percentile (OR: 3.2, CI: 1.2-9.4, p = 0.024) in fighters. Years of football/rugby were also significantly associated with white matter signal abnormalities. CONCLUSION: Our findings expand on previous literature by demonstrating a significant relationship between white matter signal abnormalities (WMSAs) and football/rugby history but not MMA. Furthermore, our study suggests an added risk for WMSAs in MMA fighters with a history of football/rugby. Future research should further evaluate WMSAs in contact sports, helping to inform athletes, regulatory bodies, and healthcare providers of the potential brain health risks of contact sports.

Bose-Einstein Condensation by Polarization Gradient Laser Cooling.

Attempts to create quantum degenerate gases without evaporative cooling have been pursued since the early days of laser cooling, with the consensus that polarization gradient cooling (PGC, also known as "optical molasses") alone cannot reach condensation. In the present work, we report that simple PGC can generate a small Bose-Einstein condensate (BEC) inside a corrugated micrometer-sized optical dipole trap. The experimental parameters enabling BEC creation were found by machine learning, which increased the atom number by a factor of 5 and decreased the temperature by a factor of 2.5, corresponding to almost 2 orders of magnitude gain in phase space density. When the trapping light is slightly misaligned through a microscopic objective lens, a BEC of ∼250 ^{87}Rb atoms is formed inside a local dimple within 40 ms of PGC after MOT loading.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Effect of a 4-Week Telerehabilitation Program for People With Post-COVID Syndrome on Physical Function and Symptoms: Protocol for a Randomized Controlled Trial.

OBJECTIVE: COVID-19 has led to significant morbidity and mortality globally. Post-COVID sequelae can persist beyond the acute and subacute phases of infection, often termed post-COVID syndrome (PCS). There is limited evidence on the appropriate rehabilitation for people with PCS. The aim of this study is to evaluate the effect on exercise capacity, symptoms, cognition, anxiety, depression, health-related quality of life, and fatigue of a 4-week, twice-weekly supervised pulmonary telerehabilitation program compared with usual medical care for people with PCS with persistent respiratory symptoms. METHODS: The study will be a multi-site randomized controlled trial with assessor blinding. Participants with confirmed previous COVID-19 infection and persistent respiratory symptoms who attend a post-COVID respiratory clinic will be randomized 1:1 to either an intervention group of 4 weeks, twice-weekly pulmonary telerehabilitation or a control group of usual medical care. Participants in the control group will be invited to cross-over into the intervention group after the week 4 assessment. Primary outcome: exercise capacity measured by the 1-minute sit-to-stand test. Secondary outcomes: 5 repetition sit-to-stand test; Montreal Cognitive Assessment; COVID-19 Yorkshire Rehabilitation Scale; Chronic Obstructive Pulmonary Disease Assessment Test; 36-Item Short-Form Health Survey; Hospital Anxiety and Depression Scale; Fatigue Severity Scale; and the Kessler Psychological Distress Scale. Outcomes will be collected at baseline, after 4-weeks intervention or control period, after intervention in the cross-over group, and at 12-month follow-up. IMPACT: Research into effective rehabilitation programs is crucial given the substantial morbidity associated with PCS and the lack of long-term data for COVID-19 recovery. A short-duration pulmonary telerehabilitation program, if effective compared with usual care, could inform practice guidelines and direct future clinical trials for the benefit of individuals with persistent respiratory symptoms post-COVID.

A population health approach to workplace mental health: rationale, implementation and engagement.

Objectives: To describe a population health-based program to support employee and dependent mental health and learn from engagement trends. Methods: Retrospective analysis of a program utilizing an assessment of mental health risk. For scoring "at risk," a Care Concierge is offered to connect users with resources. Results: Participation was offered to 56,442 employees and dependents. Eight thousand seven hundred thirty-one completed the assessment (15%). Of those, 4,644 (53%) scored moderate or higher. A total of 418 (9%) engaged the Care Concierge. Factors that negatively influenced the decision to engage care included bodily pain, financial concerns. Positive influences were younger age, high stress, anxiety, PTSD and low social support. Conclusion: Proactive assessment plus access to a Care Concierge facilitates mental healthcare utilization. Several factors influence likelihood to engage in care. A better understanding of these factors may allow for more targeted outreach and improved engagement.

Hydropneumopericardium Due to a Traumatic Esophageal-Pericardial Fistula.

Esophago-pericardial fistula is a rare, life-threatening condition, usually arising as a complication of benign esophageal disorders or iatrogenic causes. Prompt diagnosis via multimodality imaging is crucial, with computed tomography being the most sensitive. Management varies based on severity, with a growing trend toward early endoscopic interventions, which result in improved outcomes.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori-defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.