Ganaxolone: A Review in Epileptic Seizures Associated with Cyclin-Dependent Kinase-Like 5 Deficiency Disorder.

Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.

Facial Expression Perception and Psychological Changes During Space Analogs.

Introduction: Facial expression perception is the process by which someone can interpret the emotion of another individual using their facial cues. Below-average scores on tests designed to measure facial expression recognition (FER) accuracies are associated with inappropriate behavioral responses and are often linked to mental or neurological disorders. Head-down bed rest microgravity analog studies show changes in facial emotion processing that may indicate a behavioral health risk during spaceflight.

Seladelpar: First Approval.

Seladelpar (LIVDELZI) is an oral delpar [i.e. a selective peroxisome proliferator-activated receptor (PPAR)δ agonist] being developed by Gilead Sciences for the treatment of primary biliary cholangitis (PBC).

No thanks and not for me: A qualitative study of barriers to prehabilitation participation.

Background: Prehabilitation programs have been shown to improve functional status prior to surgery, postoperative recovery, and even long-term outcomes. However, these programs often lack participation, often by patients who seem to need it the most. This study aimed to identify the primary reasons for patients' declining enrollment or low adherence to a prehabilitation program.

Futibatinib: A Review in Locally Advanced and Metastatic Cholangiocarcinoma.

Futibatinib (LYTGOBI) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR)1-4. It is approved in the EU, Japan and the USA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma (CCA) harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy. In the phase II part (FOENIX-CCA2) of a multinational phase I/II study in this patient population, monotherapy with futibatinib 20 mg once daily was associated with clinically meaningful and durable responses, sustained health-related quality of life (HR-QOL), and a manageable safety profile with supportive care and as-needed dose modifications.

Gendered relations? Associations between Swedish parents, siblings, and adolescents' time spent sedentary and physically active.

Introduction: The family is assumed to be fundamental in youth socialization processes and development, connected to social and cultural practices such as healthy lifestyles and physical activity. However, gender patterns in physical activity among adolescents and the structural drivers of gender inequality (e.g.

Exagamglogene Autotemcel: First Approval.

Exagamglogene autotemcel (Casgevy™) is a genetically modified autologous CD34 cell enriched population. It contains human haematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 (a DNA double strand break-inducing nuclease system) to differentiate into erythroid cells that produce high levels of foetal hemoglobin. Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, exagamglogene autotemcel received its first approval on 16 November 2023 in the UK for the treatment of transfusion-dependent β-thalassemia (TDT) in patients aged ≥ 12 years for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available.

The difficulty of detecting inbreeding depression and its effect on conservation decisions.

Statistical inferences about inbreeding depression are often derived from analyses with low power and a high risk of failing to detect inbreeding depression. That risk is widely appreciated by scientists familiar with the relevant statistical and genetical theory, but may be overlooked and underappreciated by decision-makers. Consequently, there is value in demonstrating this risk using a real example.

Bosutinib: Pediatric First Approval.

Bosutinib (BOSULIF), an orally administered BCR-ABL tyrosine kinase inhibitor (TKI) developed by Pfizer Inc., is well established in the EU and the USA as a treatment for adults with newly diagnosed (ND) chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), and for CP, accelerated phase and blast phase Ph+ CML that is resistant or intolerant (R/I) to prior therapy. In September 2023, based on clinical data from patients aged ≥ 1 to < 18 years, bosutinib was approved in the USA for the treatment of pediatric patients aged ≥ 1 year with CP Ph+ CML that is ND or R/I to prior therapy.

Links between three chronic and age-related diseases, osteoarthritis, periodontitis, and osteoporosis, in a wild mammal (moose) population.

Objective: Osteoarthritis, periodontitis and osteoporosis are chronic, age-related diseases which adversely impact millions of people worldwide. Because these diseases pose a major global public health challenge, there is an urgent need to better understand how these diseases are interrelated. Our objective was to document the age and sex-specific prevalence of each disease and assess interrelationships among the three diseases in a wild mammal (moose, Alces alces) population.

Solriamfetol: A Review in Excessive Daytime Sleepiness Associated with Narcolepsy and Obstructive Sleep Apnoea.

Solriamfetol (SUNOSI) is an oral selective dopamine and norepinephrine reuptake inhibitor approved in the EU and the USA for improving wakefulness in adults with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnoea (OSA). In phase III studies, 12 weeks' therapy with solriamfetol within the recommended dosage range for narcolepsy (75 mg or 150 mg once daily) or OSA (37.5 mg, 75 mg or 150 mg once daily) provided early and sustained reductions in excessive sleepiness and improvements in wakefulness relative to placebo.

Solution-processable polytriazoles from spirocyclic monomers for membrane-based hydrocarbon separations.

The thermal distillation of crude oil mixtures is an energy-intensive process, accounting for nearly 1% of global energy consumption. Membrane-based separations are an appealing alternative or tandem process to distillation due to intrinsic energy efficiency advantages. We developed a family of spirocyclic polytriazoles from structurally diverse monomers for membrane applications.

The far-reaching effects of genetic process in a keystone predator species, grey wolves.

Although detrimental genetic processes are known to adversely affect the viability of populations, little is known about how detrimental genetic processes in a keystone species can affect the functioning of ecosystems. Here, we assessed how changes in the genetic characteristics of a keystone predator, grey wolves, affected the ecosystem of Isle Royale National Park over two decades. Changes in the genetic characteristic of the wolf population associated with a genetic rescue event, followed by high levels of inbreeding, led to a rise and then fall in predation rates on moose, the primary prey of wolves and dominant mammalian herbivore in this system.

Delandistrogene Moxeparvovec: First Approval.

Delandistrogene moxeparvovec (delandistrogene moxeparvovec-rokl; ELEVIDYS) is an adeno-associated virus (AAV) vector-based gene therapy designed to deliver a gene encoding a micro-dystrophin protein [i.e. a shortened (138 kDa) version of the dystrophin protein expressed in normal muscle cells (427 kDa)] to all muscles involved in the pathology of Duchenne muscular dystrophy (DMD).

Eftrenonacog Alfa: A Review in Haemophilia B.

Eftrenonacog alfa (Alprolix) is an extended half-life recombinant factor IX (rFIX)-Fc fusion protein (hereafter referred to as rFIXFc). Administered as an intravenous bolus, it is approved for prophylactic use and the treatment of bleeding in patients with haemophilia B in various countries worldwide, including those of the EU, as well as the USA. In multinational, phase III trials, rFIXFc was effective for the prophylaxis, perioperative management or on-demand treatment of bleeding in male patients with severe haemophilia B regardless of age and irrespective of whether or not they had been previously treated with FIX replacement products.

Effects of Yoga and Aerobic Exercise on Verbal Fluency in Physically Inactive Older Adults: Randomized Controlled Trial (FitForAge).

Purpose: To compare the effects on verbal fluency of a supported yoga-based exercise intervention to an aerobic exercise intervention and a wait-list control group.

Participants And Methods: Eighty-two physically-inactive but otherwise healthy adults (mean age 72.5 years, range 65-85, 77% female) were recruited into a 12-week, three-group, parallel randomized controlled trial.