E2027 (irsenontrine), a phosphodiesterase 9 inhibitor, enhances cholinergic function when combined with donepezil hydrochloride.

Phosphodiesterase 9 (PDE9) is an enzyme that hydrolyzes cyclic guanosine monophosphate (cGMP)-a second messenger that regulates neuronal plasticity and memory function. PDE9 inhibition has been shown to enhance cognitive function in rodents, underlining the potential of PDE9 inhibitors (PDE9Is) as novel therapeutics for cognitive dysfunction. Considering the critical role of nitric oxide (NO)-cGMP signaling cascade in acetylcholine (ACh) release, the combination of PDE9Is and acetylcholinesterase inhibitors may synergistically elevate ACh levels in the brain.

An Anti-tau Therapeutic Antibody Etalanetug (E2814): A Phase 1, First-in-human (FIH) Study of Single and Multiple Ascending Doses in Healthy Subjects.

Background: Etalanetug (E2814), an anti-tau monoclonal antibody (mAb), is intended to inhibit spreading of pathologic tau species by binding to the microtubule binding region (MTBR). It is being developed as a potential disease-modifying therapy for Alzheimer disease.

Methods: This randomized, placebo-controlled study comprised of 2 parts: single ascending doses evaluating 5 etalanetug doses and multiple ascending doses evaluating 4 fixed doses in each cohort, 8 healthy subjects were randomized (3:1) to single etalanetug dose or placebo.

Associations between footwear fit and developmental milestones in toddlers: a cross-sectional study.

[Purpose] To investigate the relationship between footwear characteristics and motor development in toddlers walking independently. [Participants and Methods] A total of 13 toddlers (mean age: 26.5 ± 4.

Main complaints identified by parents of children with developmental delays during the initial consultation: a 10-year all-case study.

Background: In Japan, the child development support initiative is one of the government's daycare support programs for children with disabilities. Children, aged 0-6 years, who are not attending elementary school can participate in the initiative and receive various support. Reports on the approaches taken by private child development support centers and the guardians' perceptions are increasing.

Japanese translation and validation of the 12-item Multiple Sclerosis Walking Scale version 2.

Background: Disability in ambulation has a critical impact on activities of daily living in patients with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a self-reported instrument developed to assess the impact of MS on walking. The scale's 12 items assess various aspects of walking-related tasks during the past 2 weeks.

Differences in walking and running parameters in elementary school students with and without backpacks.

Background: Backpack syndrome (BS) is a term used to describe symptoms such as shoulder and back pain that are believed to be caused by carrying a backpack. Few studies have investigated the changes in walking and running parameters with and without backpacks.

Objective: The present study aimed to investigate the differences in walking and running parameters with and without backpacks in primary school children with and without BS.

Trabeculotomy Using the Kahook Dual Blade for Exfoliation Glaucoma and Primary Open Angle Glaucoma: Comparison of Outcomes According to Incision Range.

Prcis: Large amount of trabeculotomy with Kahook Dual Blade (KDB) confers better intraocular pressure (IOP) lowering.

Purpose: We compared the postoperative outcomes of trabeculotomy using the KDB in patients with exfoliation glaucoma (EXG) and primary open angle glaucoma between the 120-degree incision and the 210- to 240-degree incision groups.

Patients And Methods: We retrospectively analyzed the postoperative outcomes of trabeculotomy performed using the KDB in 101 eyes with EXG and primary open angle glaucoma, who received 120- and 210- to 240-degree incisions at Kumamoto University Hospital between April 25, 2018, and August 11, 2021.

Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration.

In animal species that have the capability of regenerating tissues and limbs, cell proliferation is enhanced after wound healing and is essential for the reconstruction of injured tissue. Although the ability to induce cell proliferation is a common feature of such species, the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Here, we show that upon injury, InhibinβA and JunB cooperatively function for this transition during Xenopus tadpole tail regeneration.

Silencing of ocular transthyretin, a gene responsible for hereditary transthyretin amyloidosis, by intravitreal injection of an siRNA conjugate into rabbit eyes.

The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes.

Exercise habits and perception of physical exercise among residents of an island in the Western Pacific Region.

[Purpose] The current study aimed to validate the exercise habits and perception of physical exercise among residents of an island in the Western Pacific Region, where the high prevalence of noncommunicable diseases is a serious health issue. [Participants and Methods] Semi-structured interviews were conducted with one doctor, three nurses, and six patients from a noncommunicable disease clinic on one island of the Kingdom of Tonga. The questions focused on the patients' exercise habits and perception of physical exercise.

Risk factors for Baerveldt glaucoma drainage implantation for uveitic glaucoma.

Uveitic glaucoma (UG) is sometimes intractable, including intricate interaction between intraocular pressure (IOP) elevation associated with inflammation and side effects of steroids. Based on the Tube Versus Trabeculectomy study in refractory glaucoma results in 2012, tube shunt surgeries have been performed for UG, but few reports have focused on UG. We retrospectively examined the surgical efficacy, complications, and risk factors in 62 eyes with UG that underwent Baerveldt glaucoma drainage device (BGD) implantation at Kumamoto University.

Smoking and younger age at onset in anti-acetylcholine receptor antibody-positive myasthenia gravis.

Smoking is a known risk factor for the development and progression of several autoimmune diseases. Previous studies have pointed out the association of smoking with the development and worsening of symptoms in myasthenia gravis (MG), but further investigation is necessary to confirm this association. Smoking history was investigated in a cross-sectional study of 139 patients with anti-acetylcholine receptor antibody-positive MG, and the association of smoking history with the age at the onset of MG was analyzed.

Health-related quality of life in Japanese patients with multiple sclerosis.

Objectives: Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related quality of life (HRQOL). On the other hand, physical and psychiatric symptoms are variable in people with MS, and QOL can be influenced by cultural and educational background. This study aimed to evaluate the association of HRQOL with disabilities, fatigue, and depression in Japanese subjects with MS.

Stages of brain volume loss and performance in the Brief International Cognitive Assessment for Multiple Sclerosis.

Background: Cognitive dysfunction occurs in a substantial proportion of patients with multiple sclerosis (MS), negatively affects their daily activities, and is associated with poor prognosis. Cognitive dysfunction in MS can extend across multiple cognitive domains, depending on the patterns and extent of the brain regions affected. Therefore, a combination of tests, including the Brief International Cognitive Assessment for MS (BICAMS), that assess different aspects of cognition is recommended to capture the full picture of cognitive impairment in each patient.

Correlation of the symbol digit modalities test with the quality of life and depression in Japanese patients with multiple sclerosis.

Background: This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS).

Methods: The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively.

Association of Smoking and Generalized Manifestations of Myasthenia Gravis.

Objective Smoking is a known risk factor for the development and progression of autoimmune diseases. Previous studies in ocular myasthenia gravis (MG) patients showed that smoking is associated with the severity of symptoms and progression to generalized MG. However, whether smoking affects MG symptoms in patients with a broader clinical spectrum of presentations is unknown.

Eleven new C-diterpenoid alkaloids from Delphinium elatum cv. Pacific Giant.

Diterpenoid alkaloids, the main components of plants of the genera Aconitum, Delphinium, and Garrya, are a group of natural products with notable chemical properties and biological activities. Several C-diterpenoid alkaloid components from Delphinium elatum cv. Pacific Giant, as well as their derivatives, exhibited cytotoxic activity against lung, prostate, cervical, and vincristine-resistant cervical cancer cell lines.

Relationships between Gross Motor Abilities and Sensory Processing in Children Aged 18 to 36 Months.

Objective: We investigated the relationship between gross motor abilities and sensory processing in typically developing children.

Method: Participants included children aged 18 to 36 months (N = 48). All participants were full-term infants.

Potential roles of the IL-6 family in conjunctival fibrosis.

Elevated intraocular pressure (IOP) is a significant risk factor for vision loss due to glaucoma, which is a major cause of blindness worldwide. Glaucoma filtration surgery (GFS) is an important method to reduce IOP by guidance of aqueous humor into a newly built filtration bleb in the conjunctiva; management of the wound healing mechanism is essential for the success of GFS. Here, we investigated the roles of interleukin (IL)-6 family members during the wound healing process after GFS.

Seasonal fluctuations in serum levels of vitamin D in Japanese patients with multiple sclerosis.

We explored the presence of seasonal fluctuations in serum vitamin D levels and potential relationship between vitamin D levels and disease severity or prognosis in patients with multiple sclerosis (MS) in northern Japan. Serum levels of 25(OH)D in spring were significantly lower than in summer and autumn, whereas no differences in 1,25(OH)D levels were demonstrated among four seasons. Seasonal fluctuations in 25(OH)D were demonstrated in patients with EDSS ≤3.

Correction: TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness.

[This corrects the article DOI: 10.1371/journal.pone.