Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. METHODS: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. RESULTS: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. CONCLUSIONS: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. TRIAL REGISTRATION: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Inflammatory pathway communication with skeletal muscle-Does aging play a role? A topical review of the current evidence.

Skeletal muscle plays an integral role in locomotion, but also as part of the integrative physiological system. Recent progress has identified crosstalk between skeletal muscle and various physiological systems, including the immune system. Both the musculoskeletal and immune systems are impacted by aging. Increased age is associated with decreased muscle mass and function, while the immune system undergoes "inflammaging" and immunosenescence. Exercise is identified as a preventative medicine that can mitigate loss of function for both systems. This review summarizes: (1) the inflammatory pathways active in skeletal muscle; and (2) the inflammatory and skeletal muscle response to unaccustomed exercise in younger and older adults. Compared to younger adults, it appears older individuals have a muted pro-inflammatory response and elevated anti-inflammatory response to exercise. This important difference could contribute to decreased regeneration and recovery following unaccustomed exercise in older adults, as well as in chronic disease. The current research provides specific information on the role inflammation plays in altering skeletal muscle form and function, and adaptation to exercise; however, the pursuit of more knowledge in this area will delineate specific interventions that may enhance skeletal muscle recovery and promote resiliency in this tissue particularly with aging.

The neurodevelopmental genes alan shepard and Neuroglian contribute to female mate preference in African Drosophila melanogaster.

Mate choice is a key trait that determines fitness for most sexually reproducing organisms, with females often being the choosy sex. Female preference often results in strong selection on male traits that can drive rapid divergence of traits and preferences between lineages, leading to reproductive isolation. Despite this fundamental property of female mate choice, very few loci have been identified that contribute to mate choice and reproductive isolation. We used a combination of population genetics, quantitative complementation tests, and behavioral assays to demonstrate that alan shepard and Neuroglian contribute to female mate choice, and could contribute to partial reproductive isolation between populations of Drosophila melanogaster. Our study is among the first to identify genes that contribute to female mate preference in this historically important system, where female preference is an active premating barrier to reproduction. The identification of loci that are primarily known for their roles in neurodevelopment provides intriguing questions of how female mate preference evolves in populations via changes in sensory system and higher learning brain centers.

Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial.

BACKGROUND: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. METHODS: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. INTERPRETATION: Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. FUNDING: MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

Associations Between Psychopathological Symptom Severity Amid the Pandemic and the Childhood Sociodemographic Environment.

It is well-documented that childhood socioeconomic status (SES) is associated with various health conditions in adulthood. Here, we examine the extent to which childhood SES is associated with COVID-19 pandemic anxiety and depression. Participants (n = 212), recruited from Amazon Mechanical Turk, were assessed for depression and anxiety in February 2022 for both the current context and retrospective self-perceived early pandemic depression and anxiety (April 2020). Participants also reported childhood SES and current demographics. Consistent with predated findings, we show a strong, positive correlation between depression and anxiety under both conditions. Paternal unemployment in childhood was associated with increased anxiety, while maternal occupation was not. High household education in childhood was generally associated with greater anxiety and depression, similar to past studies examining education levels and depression. However, the shift from high school to post-secondary degrees (trade school and associate's) was associated with decreased anxiety and depression, which may reflect "essential work" careers, therefore indicating a dualism. Growing up in crowded, de-individualized spaces was associated with lower anxiety and depression, suggesting better conditioning for the imposition of COVID-19 quarantines. Pandemic-related unemployment was associated with an increase in anxiety and depression. Strong political views, regardless of ideology, were associated with increased anxiety. Finally, participants in our cohort perceived their mental health to be worse in the early pandemic for anxiety and depression, up 6.6% and 7.9%, respectively. Our work suggests a complex relationship between SES, demographics, and anxiety and depression during the pandemic. These findings emphasize the importance of exploring the dynamics between early SES and mental health in adulthood, particularly during extended societal stressors.

Self-Assembly of Hierarchical High-χ Fluorinated Block Copolymers with an Orthogonal Smectic-within-Lamellae 3 nm Sublattice and Vertical Surface Orientation.

Hierarchical structure-within-structure assemblies offer a route toward increasingly complex and multifunctional materials while pushing the limits of block copolymer self-assembly. We present a detailed study of the self-assembly of a series of fluorinated high-χ block copolymers (BCPs) prepared via postmodification of a single poly(styrene)-block-poly(glycidyl methacrylate) (S-b-G) parent polymer with the fluorinated alkylthiol pendent groups containing 1, 6, or 8 fluorinated carbons (termed trifluoro-ethanethiol (TFET), perfluoro-octylthiol (PFOT), and perfluoro-decylthiol (PFDT), respectively). Bulk X-ray scattering of thermally annealed samples demonstrates hierarchical molecular assembly with phase separation between the two blocks and within the fluorinated block. The degree of ordering within the fluorinated block is highly sensitive to synthetic variation; a lamellar sublattice was formed for S-b-GPFOT and S-b-GPFDT. Thermal analyses of S-b-GPFOT reveal that the fluorinated block exhibits liquid crystal-like ordering. The complex thin-film self-assembly behavior of an S-b-GPFOT polymer was investigated using real-space (atomic force microscopy and scanning electron microscopy) and reciprocal-space (resonant soft X-ray scattering (RSoXS), grazing incidence small- and wide-angle scattering) measurements. After thermal annealing in nitrogen or vacuum, films thicker than 1.5 times the primary lattice spacing exhibit a 90-degree grain boundary, exposing a thin layer of vertical lamellae at the free interface, while exhibiting horizontal lamellae on the preferential (polystyrene brush) substrate. RSoXS measurements reveal the near-perfect orthogonality between the primary and sublattice orientations, demonstrating hierarchical patterning at the nanoscale.

Magnetically propagating Hund's exciton in van der Waals antiferromagnet NiPS3.

Magnetic van der Waals (vdW) materials have opened new frontiers for realizing novel many-body phenomena. Recently NiPS3 has received intense interest since it hosts an excitonic quasiparticle whose properties appear to be intimately linked to the magnetic state of the lattice. Despite extensive studies, the electronic character, mobility, and magnetic interactions of the exciton remain unresolved. Here we address these issues by measuring NiPS3 with ultra-high energy resolution resonant inelastic x-ray scattering (RIXS). We find that Hund's exchange interactions are primarily responsible for the energy of formation of the exciton. Measuring the dispersion of the Hund's exciton reveals that it propagates in a way that is analogous to a double-magnon. We trace this unique behavior to fundamental similarities between the NiPS3 exciton hopping and spin exchange processes, underlining the unique magnetic characteristics of this novel quasiparticle.

Evaluation of Postoperative Outcomes After Enterostomy Closure in Low Body Weight Infants: A Multi-Center Retrospective Analysis.

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.

Independent transitions to freshwater environments promote phenotypic divergence, not convergence, in stingrays.

Instances of convergent or parallel evolution provide a potent model system for exploring contingency and determinism in evolutionary biology. Likewise, the multiple, independent habitat transitions from saltwater to freshwater biomes offer opportunity for studying convergent evolution within and among different vertebrate lineages. For example, stingrays have invaded freshwater habitats multiple times across different continents, sometimes even several times within the same clade (e.g., Dasyatidae). We evaluated the frequency of saltwater-freshwater invasions in stingrays, compared ecological and phenotypic diversification among freshwater and saltwater lineages, and assessed the degree of convergence among freshwater species. Despite not being morphologically distinct from saltwater stingrays, freshwater stingrays do expand the margins of stingray morphological diversity. According to our data, trophic specialists occupied non-overlapping regions of morphospace, with piscivores and molluscivores being distinct from other diet guilds. Freshwater stingrays as a group did not strongly converge morphologically, neither did freshwater rays from different lineages which shared similar niches. These findings could be explained by there not being enough time for convergence to occur among more ancient and more recent freshwater lineages. Alternatively, the different ancestral bauplans of various freshwater ray lineages and weak selection on optimal phenotypes could promote contingency in the form of evolution along paths of least resistance.

Calcified left ventricular apical aneurysm with intramural thrombus: a case report.

Background: Left ventricular aneurysms (LVAs) are a well-appreciated complication of acute myocardial infarction. Ventricular aneurysms involving the left ventricle (LV) typically evolve as a result of anterior myocardial infarction and are associated with greater morbidity, complication rates, and hospital resource utilization. Incidence of LVA is decreasing with advent of modern reperfusion therapies; however, in the setting of excess morbidity, clinicians must maintain an appreciation for their appearance to allow timely diagnosis and individualized care. Case summary: This case report describes the clinical history, investigation, appearance, and management of a patient with calcified apical LVA with history of previous anterior ST-elevation myocardial infarction. The patient was initially admitted for elective coronary angiography in the setting of worsening exertional dyspnoea and subsequently underwent coronary artery bypass graft, aneurysm resection, and LV reconstruction. Discussion: Left ventricular aneurysms are an uncommon complication experienced in the modern era of acute myocardial infarction and current reperfusion therapies, but remain an important cause of excess morbidity and complication. Evidence-based guidelines for the diagnosis, workup, and subsequent management of LVAs are lacking. The imaging findings presented in this case serve as an important reminder of the appearance of LVAs so that timely diagnosis and individualized care considerations can be made.

Identifying the Cerebral Physiologic Response to Aerobic Exercise Following Concussion: A Scoping Review.

OBJECTIVE: The purpose of this study was to identify the cerebral physiologic response to aerobic exercise in individuals with a symptomatic concussion, highlighting available knowledge and knowledge gaps in the literature. DESIGN: A systematic scoping review was conducted and reported in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane libraries was conducted on June 15, 2023 (from database inception). An online systematic/scoping review management system was used to remove duplicates, and the remaining articles were screened for inclusion by 2 researchers. Inclusion criteria required articles to be original research published in peer-reviewed journals. Additionally, studies were required to have an aerobic exercise component, include a measure of cerebral physiology during a bout of aerobic exercise, exclude moderate and/or severe traumatic brain injury (TBI) populations, and be in the English language. Both human and animal studies were included, with participants of any age who were diagnosed with a mild TBI/concussion only (ie, Glasgow Coma Scale score ≥ 13). Studies could be of any design as long as a measure of cerebral physiologic response to a bout of aerobic exercise was included. RESULTS: The search resulted in 1773 articles to be screened and data from 3 eligible studies were extracted. CONCLUSIONS: There are currently too few studies investigating the cerebral physiologic response to aerobic exercise following concussion or mild TBI to draw definitive conclusions. Further research on this topic is necessary since understanding the cerebral physiologic response to aerobic exercise in the concussion and mild TBI populations could assist in optimizing exercise-based treatment prescription and identifying other targeted therapies.

First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation.

BACKGROUND AND OBJECTIVES: In spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by desired therapeutic plasma concentration, there is lack of equivalent means of determining dose delivery in SCS. In open-loop (OL) SCS, due to the dynamic nature of the epidural space, the activating electric field delivered is inconsistent at the level of the dorsal columns. Recent Food and Drug Administration guidance suggests accurate and consistent therapy delivered using physiologic closed-loop control (PCLC) devices can minimize underdosage or overdosage and enhance medical care. PCLC-based evoked compound action potential (ECAP)-controlled technology provides the ability to prescribe a precise stimulation dose unique to each patient, continuously measure neural activation, and objectively inform SCS therapy optimization. METHODS: Neurophysiological indicator metrics of therapy dose, usage above neural activation threshold, and accuracy of SCS therapy were assessed for relationship with pain reduction in over 600 SCS patients. RESULTS: Significant relationships between objective metrics and pain relief across the patient population are shown, including first evidence for a dose-response relationship in SCS. CONCLUSIONS: Higher dose, more time over ECAP threshold, and higher accuracy are associated with better outcomes across patients. There is potential to optimize individual patient outcomes based on unique objective measurable electrophysiological inputs.

SmartFSCV: An Artificial Intelligence Enabled Miniaturised FSCV Device Targeting Serotonin.

Goal: Dynamically monitoring serotonin in real-time within target brain regions would significantly improve the diagnostic and therapeutic approaches to a variety of neurological and psychiatric disorders. Current systems for measuring serotonin lack immediacy and portability and are bulky and expensive. Methods: We present a new miniaturised device, named SmartFSCV, designed to monitor dynamic changes of serotonin using fast-scan cyclic voltammetry (FSCV). This device outputs a precision voltage potential between -3 to +3 V, and measures current between -1.5 to +1.5 µA with nano-ampere accuracy. The device can output modifiable arbitrary waveforms for various measurements and uses an N-shaped waveform at a scan-rate of 1000 V/s for sensing serotonin. Results: Four experiments were conducted to validate SmartFSCV: static bench test, dynamic serotonin test and two artificial intelligence (AI) algorithm tests. Conclusions: These tests confirmed the ability of SmartFSCV to accurately sense and make informed decisions about the presence of serotonin using AI.

Long-Term Robustness and Failure Mechanisms of Electrochemical Stripping for Wastewater Ammonia Recovery.

Nitrogen in wastewater has negative environmental, human health, and economic impacts but can be recovered to reduce the costs and environmental impacts of wastewater treatment and chemical production. To recover ammonia/ammonium (total ammonia nitrogen, TAN) from urine, we operated electrochemical stripping (ECS) for over a month, achieving 83.4 ± 1.5% TAN removal and 73.0 ± 2.9% TAN recovery. With two reactors, we recovered sixteen 500-mL batches (8 L total) of ammonium sulfate (20.9 g/L TAN) approaching commercial fertilizer concentrations (28.4 g/L TAN) and often having >95% purity. While evaluating the operation and maintenance needs, we identified pH, full-cell voltage, product volume, and water flux into the product as informative process monitoring parameters that can be inexpensively and rapidly measured. Characterization of fouled cation exchange and omniphobic membranes informs cleaning and reactor modifications to reduce fouling with organics and calcium/magnesium salts. To evaluate the impact of urine collection and storage on ECS, we conducted experiments with urine at different levels of dilution with flush water, extents of divalent cation precipitation, and degrees of hydrolysis. ECS effectively treated urine under all conditions, but minimizing flush water and ensuring storage until complete hydrolysis would enable energy-efficient TAN recovery. Our experimental results and cost analysis motivate a multifaceted approach to improving ECS's technical and economic viability by extending component lifetimes, decreasing component costs, and reducing energy consumption through material, reactor, and process engineering. In summary, we demonstrated urine treatment as a foothold for electrochemical nutrient recovery from wastewater while supporting the applicability of ECS to seven other wastewaters with widely varying characteristics. Our findings will facilitate the scale-up and deployment of electrochemical nutrient recovery technologies, enabling a circular nitrogen economy that fosters sanitation provision, efficient chemical production, and water resource protection.

Severe epistaxis after posterior nasal nerve ablation requiring surgical intervention: A multi-center case series.

KEY POINTS: Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type. Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post-procedure.

Evolution of the Magnetic Excitations in Electron-Doped La_{2-x}Ce_{x}CuO_{4}.

We investigated the high energy spin excitations in electron-doped La_{2-x}Ce_{x}CuO_{4}, a cuprate superconductor, by resonant inelastic x-ray scattering (RIXS) measurements. Efforts were paid to disentangle the paramagnon signal from non-spin-flip spectral weight mixing in the RIXS spectrum at Q_{∥}=(0.6π,0) and (0.9π,0) along the (1 0) direction. Our results show that, for doping level x from 0.07 to 0.185, the variation of the paramagnon excitation energy is marginal. We discuss the implication of our results in connection with the evolution of the electron correlation strength in this system.

TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions  in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient cells, Rheb knockdown or Rapamycin treatment paradoxically increases TFEB phosphorylation at the mTORC1-sites and relocalizes TFEB from nucleus to cytoplasm. In mice, Rapamycin treatment normalizes lysosomal gene expression, similar to TFEB knockout, suggesting that Rapamycin's benefit in TSC is TFEB-dependent. These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.

The Association Between Sexual Initiation and Membership in Dyadic Profiles of Perceived Shared Power.

There is scarce empirical evidence examining whether sexual initiation and power are associated with each other. Utilizing latent profile analyses, we examined in a nationally representative sample of US newlywed heterosexual couples (N = 1,948 couples) whether wives' and husbands' sexual initiation patterns and satisfaction with these patterns were associated with membership in different profiles of wives' and husbands' perceptions of shared relational power while accounting for both partner's satisfaction with sexual frequency. We found four profiles of wives' and husbands' perceptions of power. The most common profile was when both wives and husbands perceived high levels of power compared to other profiles, but wives had significantly higher reports of perceived power than husbands (High Power, Wife Higher; 40.8%). Husbands' sexual initiation patterns were not associated with profile membership. Wives who reported equal sexual initiation patterns had a higher probability of being in the High Power, Wife Higher profile compared to the Wife Low Power, Husband Moderate Power profile. Both wives' and husbands' satisfaction with sexual initiation patterns were associated with profile membership. Wives and husbands that were satisfied with sexual initiation patterns had a higher probability of being in the High Power, Wife Higher profile compared to the profile where both wives and husbands had high perceptions of shared relational power compared to other profiles, but their scores were not significantly different from each other (High Power, Equal).