Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

Prognostic factors of subacute comprehensive encephalitis: a retrospective study.

Purpose: The etiology of encephalitis is unknown in 40%-50% of cases, so a comprehensive examination of encephalitis would be significant and meaningful. The short-term outcomes in appropriately managed patients are also unknown. Short-term clinical outcomes following onset can provide clinicians with clues regarding the clinical course in the immediate future.

Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342).

Objective: FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12-74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS).

Methods: In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period.

New FDA drug approvals for 2024: Synthesis and clinical application.

In 2024, the U.S. Food and Drug Administration (FDA) has approved a range of new drugs, including both 32 new chemical entities (NCEs) and 18 biological entities (NBEs).

Enhanced prediction of partial nitrification-anammox process in wastewater treatment by developing an attention-based deep learning network.

In the process of partial nitrification and anaerobic ammonia oxidation (anammox) for nitrogen removal, the process offers simple metabolic pathways, low operating costs, and high nitrogenous loading rates. However, since the partial nitrification-anammox (PN-anammox) process combines partial nitrification and anammox reactions within the same reactor, strict control of dissolved oxygen (DO) is essential. Additionally, assessing treatment performance through chemical measurement involves time lag, making it challenging to recover the biological process when issue arise, especially in the PN-anammox process, where strict DO control and the sensitivity of anammox bacteria to conditions and substrates demand timely intervention.

Simultaneous quantitation of pentacyclic triterpenoids in fruit peels using liquid chromatography-single quadrupole mass spectrometry.

The simultaneous determination of pentacyclic triterpenoids, which are secondary metabolites in plants, is difficult because of the similarity in structure and minimal differences in polarity. In this study, we established a simple and sensitive method for the simultaneous determination of pentacyclic triterpenoids based on liquid chromatography-single-quadrupole mass spectrometry (LC-MS) using a C30 column. The established method completely separated 13 pentacyclic triterpenoids based on their different retention times.

Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review.

Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.

Prevention of chronic pneumonia in children with severe motor and intellectual disabilities by long-term tobramycin inhalation: Its benefits and limitations.

Aim: To determine the effect of long-term tobramycin (TOB) inhalation therapy on recurrent pneumonia among ventilator-dependent children with profound neurological disabilities.

Methods: TOB inhalation was performed in eight series of trials in seven ventilator-dependent children who had intratracheal Pseudomonas aeruginosa and suffered from recurrent pneumonia. Their age at the initiation of therapy was 68 ± 50 months (mean ± standard deviation), whereas the duration of treatment was 30 ± 22 months.

Relationship between nonserviceable hearing and auditory brainstem response in patients with vestibular schwannoma.

Objective: The interpretation of ABR results in patients with vestibular schwannoma is often unclear. We investigated the correlation between serviceable hearing in patients with vestibular schwannoma (VS) and factors including auditory brainstem response (ABR) at their initial presentation.

Methods: We retrospectively analyzed initial magnetic resonance imaging findings, Gardner-Robertson (G&R) classification, ABR, and related data from 72 patients with VS who visited our institution between February 2017 and January 2023.

Perilymphatic fistula caused by Eustachian tube air inflation.

We present a case of a perilymphatic fistula (PLF) caused by Eustachian tube air inflation (ETAI) that was diagnosed using cochlin-tomoprotein (CTP) testing and successfully treated using transcanal endoscopic ear surgery to seal the inner ear window. A 77-year-old woman developed hearing loss and dizziness after undergoing ETAI at a local ear, nose, and throat clinic. Despite initial bed rest and steroid pulse therapy, the hearing did not improve, and transcanal endoscopic ear surgery was performed to repair the PLF.

Analysing the influence of hydrodynamic and sedimentary factors on the microplastic distribution in the Ashtamudi estuary, India.

This study evaluates the influence of water current and suspended sediment concentration (SSC) on microplastic distribution in various mixing regimes of the Ashtamudi estuary, India. Microplastic abundance ranged from 3.2 to 53 items/L, with highest concentrations observed near the confluence of the river and the sea.

A simple LC-MS/MS assay for the quantification of E6011, a novel anti-fractalkine monoclonal antibody, in cynomolgus monkey serum - comparison with ligand binding assay.

E6011 is a monoclonal antibody that is currently under development for the treatment of rheumatoid arthritis. While ligand binding assays (LBAs) are typically employed for the determination of therapeutic antibodies, ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) represents an alternative platform. E6011 in monkey serum was treated with ammonium sulfate to obtain pellets for subsequent processing.

Self-assembled doxorubicin prodrug riding on the albumin express train enable tumor targeting and bio-activation.

Doxorubicin (DOX) is a vital anthracycline chemotherapeutic drug, yet presenting significant challenges due to its severe cardiotoxicity. While Doxil enhances the pharmacokinetics and reduces the cardiotoxicity of DOX solution (DOX sol), it shows limitations of low drug loading capacity and inadequate cellular uptake. To overcome these issues, this study developed a novel disulfide bond-linked DOX-maleimide prodrug (DSSM).

Itaconate drives pro-inflammatory responses through proteasomal degradation of GLO1.

Itaconate is a small-molecule metabolite generated by the enzyme aconitate decarboxylase 1 (ACOD1), which is upregulated during inflammation. Traditionally, itaconate has been recognized for its anti-inflammatory properties; however, this study reveals a pro-inflammatory mechanism of itaconate in macrophages. We demonstrate that itaconate promotes the proteasomal degradation of glyoxalase 1 (GLO1) via Cys139.

PFAS contamination in tap water: Target and suspect screening of zwitterionic, cationic, and anionic species across Canada and beyond.

This study investigated the occurrence of perfluoroalkyl and polyfluoroalkyl substances (PFAS), including anionic, cationic, and zwitterionic compounds, in drinking water. Between 2021-2023, an expanded list of 76 target PFAS was screened in tap water samples mainly from Canada, but also including tap water samples from the Eastern United States, Mexico, South America (Argentina), the Caribbean (Dominican Republic, Cuba), Africa (Algeria, Cameroon, Central African Republic, Morocco, Rwanda, Tunisia), Europe (France, Greece, Italy, Spain, and the United Kingdom) and Asia (Japan, Vietnam, Iran, and Türkiye). An additional ∼ 200 suspect-target PFAS were screened using high-resolution Orbitrap mass spectrometry.

Knee injury and osteoarthritis outcome score and knee society score for the minimal clinically important differences after cruciate-retaining total knee arthroplasty: Two-year follow up.

Background: This study investigated changes in the Knee Injury and Osteoarthritis Outcome Score (KOOS), 2011 Knee Society Score (KSS), and minimal clinically important differences (MCIDs) of these scores preoperatively to 2 years after total knee arthroplasty (TKA).

Methods: This single-center retrospective study included 168 patients who underwent primary cruciate-retaining (CR) TKA using the subvastus approach. The KOOS and KSS were assessed preoperatively and during the 3-month, 6-month, 1-year, and 2-year follow ups.

Accessible Halitosis Diagnosis: Validating the Accuracy of Novel AI-based Compact VSC Measuring Instrument.

Halitosis presents a significant global health concern, necessitating the development of precise and efficient testing methodologies owing to the high prevalence and the associated social and psychological effects. The measurement of volatile sulfur compounds (VSCs), recognized as primary contributors to halitosis, is particularly significant. While gas chromatography (GC-MS) offers accurate measurements, its bulky and expensive nature limits widespread accessibility.

Effect of Epstein-Barr Virus infection on gene regulation in immune cells of patients with Immune-Mediated Diseases.

It has been known that Epstein-Barr virus (EBV) can latently infect immune cells after the initial infection, and epidemiological studies have suggested its association with the onset of immune-mediated diseases (IMDs). However, the specific impact of EBV infection on IMDs pathology remains unclear. We quantified EBV load of B cell subsets (Naïve B cells, Unswitched memory B cells, Switched memory B cells, Double negative B cells, and Plasmablasts) in IMD patients as well as healthy control (HC) using bulk RNA sequencing data of 504 donors.

Identification of key gene signatures for predicting chemo-immunotherapy efficacy in extensive-stage small-cell lung cancer using machine learning.

Objectives: The lack of definitive biomarkers presents a significant challenge for chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). We aimed to identify key genes associated with chemo-immunotherapy efficacy in ES-SCLC through comprehensive gene expression analysis using machine learning (ML).

Methods: A prospective multicenter cohort of patients with ES-SCLC who received first-line chemo-immunotherapy was analyzed.

Population pharmacokinetics of blonanserin in Japanese adolescent and adult patients with schizophrenia.

The second-generation antipsychotic blonanserin is a highly selective, full antagonist of dopamine D and D and serotonin 5-HT receptors. It is currently prescribed for patients with schizophrenia in Japan. We aimed to develop a population pharmacokinetic model of oral blonanserin, including data from 12 to 77 years old patients, to assess the covariates that influence blonanserin pharmacokinetics and evaluate appropriate dosage regimens in adolescents versus adults.

Does using multiple strategies enhance preschoolers' persistence in a challenging task?

Persistence, characterized by continued efforts in the face of difficulties, is crucial for children's success. Many researchers have aimed to identify the factors that improve persistence. Previous research has found that children who use more strategies to solve a challenging task tend to exhibit greater persistence, suggesting that providing instructions for multiple strategies may enhance their persistence.

Evaluation of dose calculation method with a combination of Monte Carlo method and removal-diffusion equation in heterogeneous geometry for boron neutron capture therapy.

Clinical research in boron neutron capture therapy (BNCT) has been conducted worldwide. Currently, the Monte Carlo (MC) method is the only dose calculation algorithm implemented in the treatment planning system for the clinical treatment of BNCT. We previously developed the MC-RD calculation method, which combines the MC method and the removal-diffusion (RD) equation, for fast dose calculation in BNCT.

Mini-review: Occupational Health Topics Series on the Effects of Chemicals Occupational cholangiocarcinoma incident.

In 2012, a social issue arose concerning a high incidence of cholangiocarcinoma (bile duct cancer) among printing workers. The cause was prolonged exposure to high concentrations of 1,2-dichloropropane that was included in the ink cleaning agent. Until then, it was not known that this substance could cause cancer in humans.

Efficacy of Unsupervised YouTube Dance Exercise for Patients With Hypertension: Randomized Controlled Trial.

Background: High blood pressure (BP) is linked to unhealthy lifestyles, and its treatment includes medications and exercise therapy. Many previous studies have evaluated the effects of exercise on BP improvement; however, exercise requires securing a location, time, and staff, which can be challenging in clinical settings. The antihypertensive effects of dance exercise for patients with hypertension have already been verified, and it has been found that adherence and dropout rates are better compared to other forms of exercise.

Sleep Deprivation Elevates Resting and Exercise Blood Pressures and Augments Pressor Response at Exercise Onset.

Purpose: Sleep deprivation and elevated blood pressure (BP) increase the risk of cardiovascular diseases. However, the effects of sleep deprivation on BP response, especially at exercise onset remain unclear. We aimed to elucidate the effects of experimental sleep deprivation (ESD) on resting and exercise BPs, including that at exercise onset, and investigate whether a night-time nap during ESD changes the ESD-altered BP.