Preventative treatment of tuberous sclerosis complex with sirolimus: Phase I safety and efficacy results.

Objective: Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.

[Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model.

Background: Deep brain stimulation (DBS) targeting globus pallidus internus (GPi) is a recognised therapy for drug-refractory dystonia. However, the mechanisms underlying this effect are not fully understood. This study explores how pallidal DBS alters spatiotemporal pattern formation of neuronal dynamics within the cerebellar cortex in a dystonic animal model, the dt hamster.

Selective and complementary antimicrobial and antiviral activity of silver, copper, and selenium nanoparticle suspensions in deep eutectic solvent.

Metallic and nonmetallic nanoparticles are bioactive compounds that exhibit broad resistance to bacteria, fungi, and even viruses. In this paper, a deep eutectic solvent (DES) based on betaine, glucose, and ethylene glycol was used to obtain suspensions of silver, copper, and selenium nanoparticles. Depending on the nanoparticle precursor used, Ag, Cu, and Se nanoparticles (NPs) with an average particle size of 50-100 nm were prepared, and the properties of the products were confirmed by the STEM, XPS, DLS, and UV-VIS methods.

Mammalian Target of Rapamycin Inhibitor Levels Decrease Under Cenobamate Treatment.

Background: Everolimus therapy has been approved in Tuberous Sclerosis Complex (TSC), for drug-resistant epilepsy as adjunctive therapy. A novel anti-seizure medication is cenobamate, which was approved for adults as adjunctive treatment for focal-onset seizures in drug-resistant epilepsy and is now commonly used in patients with TSC. Drug-drug interactions between cenobamate and mammalian target of rapamycin (mTORi) have not been prospectively evaluated, even though these agents are frequently administered together.

Adolescent child custody loss and substance use treatment as predictors of young adult substance use trajectories among females with foster care and juvenile justice involvement.

This study aimed to identify trajectories of substance use from adolescence to young adulthood among 166 females with dual child welfare and juvenile justice system involvement, and to explore the influence of adolescent child custody status and substance use treatment on substance use trajectories. Results identified four substance use trajectory groups (stable moderate substance use, decreasing substance use, increasing substance use, stable high substance use). Custody loss during adolescence predicted membership in the stable high substance use trajectory group (log odds estimate = 2.

Approaching psychology's current crises by exploring the vagueness of psychological concepts: Recommendations for advancing the discipline.

Psychology is currently facing a multilayered crisis stemming from the fact that the results of many psychological studies cannot be replicated (replication crisis), that psychological research has neglected cross-cultural and cross-temporal variation (universality crisis), and that many psychological theories are ill-developed and underspecified (theory crisis). In the present article, we use ideas derived from debates in theoretical and philosophical psychology as a basis for responding to all three crises. In short, we claim that psychological concepts are inherently vague in the sense that their meanings and the rules for their application are indeterminate.

Short-term stimulations of the entopeduncular nucleus induce cerebellar changes of c-Fos expression in an animal model of paroxysmal dystonia.

Deep brain stimulation (DBS) of the globus pallidus internus (entopeduncular nucleus, EPN, in rodents) is important for the treatment of drug-refractory dystonia. The pathophysiology of this movement disorder and the mechanisms of DBS are largely unknown. Insights into the mechanisms of DBS in animal models of dystonia can be helpful for optimization of DBS and add-on therapeutics.

Optimizing Education to Improve COVID-19 Vaccination Rates in a Federally Qualified Health Center.

Introduction: COVID-19 vaccination hesitancy is prevalent in underserved communities, and family medicine clinics can combat hesitancy with vaccine education. However, due to general misinformation, physicians hesitate to educate patients because doing so can create conflict.

Methods: A series of resident-run, team-based quality improvement projects were conducted at a federally qualified health center every 4 months between June 2021 and May 2022.

Electrophysiological insights into deep brain stimulation of the network disorder dystonia.

Deep brain stimulation (DBS), a treatment for modulating the abnormal central neuronal circuitry, has become the standard of care nowadays and is sometimes the only option to reduce symptoms of movement disorders such as dystonia. However, on the one hand, there are still open questions regarding the pathomechanisms of dystonia and, on the other hand, the mechanisms of DBS on neuronal circuitry. That lack of knowledge limits the therapeutic effect and makes it hard to predict the outcome of DBS for individual dystonia patients.

Anions featuring an aluminium-silicon core with alumanyl silanide and aluminata-silene characteristics.

Molecular species containing multiple bonds to aluminium have long been challenging synthetic targets. Despite recent landmark discoveries in this area, heterodinuclear Al-E multiple bonds (where E is a group-14 element) have remained rare and limited to highly polarized π-interactions (Al=E ↔ Al-E). Here we report the isolation of three alumanyl silanide anions that feature an Al-Si core stabilized by bulky substituents and a Si-Na interaction.

Combining Electrostimulation with Impedance Sensing to Promote and Track Osteogenesis within a Titanium Implant.

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient's fracture healing process.

Client Characteristics Associated with Desire for Additional Services at Syringe Exchange Programs.

Objectives: The objective of this study was to explore the relationship between client characteristics and desired services offered at syringe exchange program (SEP) sites among women who inject drugs (WWID). We investigated whether a desire for additional services varied as a function of these client characteristics.

Methods: A sample of 69 women who were syringe exchange clients participated in a survey about adding services to syringe exchange programs.

Multi-scale computational investigation of Ag-doped two-dimensional Zn-based MOFs for storage and release of small NO and CO bioactive molecules.

Nitric oxide (NO) and carbon monoxide (CO) are two important gasotransmitters with critical biological roles in the human body. Due to their short lifetime and dangerous side effects at high concentrations, it is essential to find safe storage and slow release methods of these two gases. Herein, we report the multi-scale simulations of two-dimensional (Zn)MOF-470 doped with antimicrobial Ag atoms to evaluate the degree of enhancement of adsorption and dynamics of NO and CO.

Room Temperature Intermolecular Dearomatization of Arenes by an Acyclic Iminosilylene.

A novel nontransient acyclic iminosilylene (), bearing a bulky super silyl group (-SiBu) and -heterocyclic imine ligand with a methylated backbone, was prepared and isolated. The methylated backbone is the feature of that distinguishes it from the previously reported nonisolable iminosilylenes, as it prevents the intramolecular silylene center insertion into an aromatic C-C bond of an aryl substituent. Instead, exhibits an intermolecular Büchner-ring-expansion-type reactivity; the silylene is capable of dearomatization of benzene and its derivatives, giving the corresponding silicon analogs of cycloheptatrienes, .

Stiripentol for Drug-Resistant Epilepsy Treatment in Tuberous Sclerosis Complex.

Background: Drug-resistant epilepsy (DRE) is common in tuberous sclerosis complex (TSC). The role of stiripentol (STP) in seizure treatment in this population is not well understood. This study evaluates the efficacy and tolerability of STP in patients with TSC with DRE.

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model.

Dopamine has emerged as an important regulator of immunity. Recent evidence has shown that signalling through low-affinity dopamine receptors exerts anti-inflammatory effects, whilst stimulation of high-affinity dopamine receptors potentiates immunity in different models. However, the dopaminergic regulation of CD8 T-cells in anti-tumour immunity remains poorly explored.

Cellular and molecular characterization of two novel asparagine synthetase gene mutations linked to asparagine synthetase deficiency.

Asparagine synthetase (ASNS) catalyzes synthesis of asparagine (Asn) and Glu from Asp and Gln in an ATP-dependent reaction. Asparagine synthetase deficiency (ASNSD) results from biallelic mutations in the ASNS gene. Affected children exhibit congenital microcephaly, continued brain atrophy, seizures, and often premature mortality.

Changing the outcome in genetic brain disorders.

This commentary is on the original articles by Wang et al. and Zhang et al. on pages 1230–1236 and 1237–1245 of this issue.

Ultrashort Pulsed Laser Drilling of Printed Circuit Board Materials.

We report on a comprehensive study of laser percussion microvia drilling of FR-4 printed circuit board material using ultrashort pulse lasers with emission in the green spectral region. Laser pulse durations in the pico- and femtosecond regime, laser pulse repetition rates up to 400 kHz and laser fluences up to 11.5 J/cm2 are applied to optimize the quality of microvias, as being evaluated by the generated taper, the extension of glass fiber protrusions and damage of inner lying copper layers using materialography.

Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of (Michx.) Elliot and L.

Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry.

Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex.

Background: Tuberous sclerosis complex (TSC) results in neurodevelopmental phenotypes, benign tumors, and cysts throughout the body. Recent studies show numerous rare findings in TSC. Guidelines suggest routine abdominal and chest imaging to monitor these thoracoabdominal findings, but imaging is not uniformly done across centers.

Using Virtual Reality to Examine the Association Between Respiratory Sinus Arrhythmia and Adolescent Substance Use.

Early substance use is associated with long-term negative health outcomes. Emotion regulation (ER) plays an important role in reducing risk, but detecting those vulnerable because of ER deficits is challenging. Respiratory sinus arrhythmia (RSA), a biomarker of ER, may be useful for early identification of substance use risk.

Symptom rates and profile clustering in tuberous sclerosis complex-associated neuropsychiatric disorders (TAND).

Background: Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric difficulties, appropriately termed TSC-Associated Neuropsychiatric Disorders (TAND). The objectives of the study were to analyze the rates of TAND symptoms in a cohort of patients seen at the TSC Center of Excellence at Cincinnati Children's Hospital and to identify clinically meaningful profiles based on TAND symptoms.

Methods: Data from the TAND Checklist was obtained from participants seen at the TSC Center of Excellence at Cincinnati Children's Hospital Medical Center from June 2015 to August 2018.