NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation.

NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5's role in response to infections, PAMPs, DAMPs, and cytokines. We identified that NLRC5 acts as an innate immune sensor to drive inflammatory cell death, PANoptosis, in response to specific ligands, including PAMP/heme and heme/cytokine combinations. NLRC5 interacted with NLRP12 and PANoptosome components to form a cell death complex, suggesting an NLR network forms similar to those in plants. Mechanistically, TLR signaling and NAD+ levels regulated NLRC5 expression and ROS production to control cell death. Furthermore, NLRC5-deficient mice were protected in hemolytic and inflammatory models, suggesting that NLRC5 could be a potential therapeutic target.

NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs.

Cytosolic innate immune sensors are critical for host defense and form complexes, such as inflammasomes and PANoptosomes, that induce inflammatory cell death. The sensor NLRP12 is associated with infectious and inflammatory diseases, but its activating triggers and roles in cell death and inflammation remain unclear. Here, we discovered that NLRP12 drives inflammasome and PANoptosome activation, cell death, and inflammation in response to heme plus PAMPs or TNF. TLR2/4-mediated signaling through IRF1 induced Nlrp12 expression, which led to inflammasome formation to induce maturation of IL-1ß and IL-18. The inflammasome also served as an integral component of a larger NLRP12-PANoptosome that drove inflammatory cell death through caspase-8/RIPK3. Deletion of Nlrp12 protected mice from acute kidney injury and lethality in a hemolytic model. Overall, we identified NLRP12 as an essential cytosolic sensor for heme plus PAMPs-mediated PANoptosis, inflammation, and pathology, suggesting that NLRP12 and molecules in this pathway are potential drug targets for hemolytic and inflammatory diseases.

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer's disease mice.

Alzheimer's disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.

BACKGROUND: Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency. METHODS: To design a human microglial cell model with PGRN haploinsufficiency, monocyte-derived microglia (iMGs) were generated from FTD-GRN patients carrying pathogenic or likely pathogenic variants (p.M1? and p.W147*) and three healthy controls. RESULTS: iMGs from FTD-GRN patients with PGRN deficiency exhibited severe neuroinflammation phenotype and failure to maintain their homeostatic molecular signatures, along with impaired phagocytosis. In FTD-GRN patients-derived iMGs, significant cytoplasmic TDP-43 aggregation and accumulation of lipid droplets with profound lysosomal abnormalities were observed. These pathomechanisms were mediated by complement C1q activation and upregulation of pro-inflammatory cytokines. CONCLUSIONS: Our study provides considerable cellular and molecular evidence that loss-of-function variants of GRN in human microglia can cause microglial dysfunction with abnormal TDP-43 aggregation induced by inflammatory milieu as well as the impaired lysosome. Elucidating the role of microglial TDP-43 pathology in intensifying neuroinflammation in individuals with FTD due to PGRN deficiency and examining consequential effects on microglial dysfunction might yield novel insights into the mechanisms underlying FTD and neurodegenerative disorders.

Volume and Permeability of White Matter Hyperintensity on Cognition: A DCE Imaging Study of an Older Cohort With and Without Cognitive Impairment.

BACKGROUND: The impact of blood-brain barrier (BBB) leakage on white matter hyperintensity (WMH) subtypes (location) and its association with clinical factors and cognition remains unclear. PURPOSE: To investigate the relationship between WMH volume, permeability, clinical factors, and cognition in older individuals across the cognitive spectrum. STUDY TYPE: Prospective, cross-sectional. SUBJECTS: A total of 193 older adults with/without cognitive impairment; 128 females; mean age 70.1 years (standard deviation 6.8). FIELD STRENGTH/SEQUENCE: 3 T, GE Dynamic contrast-enhanced, three-dimensional (3D) Magnetization-prepared rapid gradient-echo (MPRAGE T1WI), 3D fluid-attenuated inversion recovery (FLAIR). ASSESSMENT: Periventricular WMH (PWMH), deep WMH (DWMH), and normal-appearing white matter (NAWM) were segmented using FMRIB automatic segmentation tool algorithms on 3D FLAIR. Hippocampal volume and cortex volume were segmented on 3D T1WI. BBB permeability (Ktrans) and blood plasma volume (Vp) were determined using the Patlak model. Vascular risk factors and cognition were assessed. STATISTICAL TESTS: Univariate and multivariate analyses were performed to identify factors associated with WMH permeability. Logistic regression analysis assessed the association between WMH imaging features and cognition, adjusting for age, sex, apolipoprotein E4 status, education, and brain volumes. A P-value <0.05 was considered significant. RESULTS: PWMH exhibited higher Ktrans (0.598 ± 0.509 × 10-3 minute-1) compared to DWMH (0.496 ± 0.478 × 10-3 minute-1) and NAWM (0.476 ± 0.398 × 10-3 minute-1). Smaller PWMH volume and cardiovascular disease (CVD) history were significantly associated with higher Ktrans in PWMH. In DWMH, higher Ktrans were associated with CVD history and cortical volume. In NAWM, it was linked to CVD history and dyslipidemia. Larger PWMH volume (odds ratio [OR] 1.106, confidence interval [CI]: 1.021-1.197) and smaller hippocampal volume (OR 0.069; CI: 0.019-0.253) were independently linked to worse global cognition after covariate adjustment. DATA CONCLUSION: Elevated BBB leakage in PWMH was associated with lower PWMH volume and prior CVD history. Notably, PWMH volume, rather than permeability, was correlated with cognitive decline, suggesting that BBB leakage in WMH may be a consequence of CVD rather than indicate disease progression. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Difference in trajectories according to early amyloid accumulation in cognitively unimpaired elderly.

BACKGROUND AND PURPOSE: Amyloid ß (Aß), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aß accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aß are anticipated. The evolution of Aß levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aß changes in older CU individuals, and differences between the groups were compared. METHODS: A total of 297 CU participants were included from the Alzheimer's Disease Neuroimaging Initiative database, and these participants underwent apolipoprotein E (APOE) genotyping, neuropsychological testing, brain magnetic resonance imaging, and an average of 3.03 follow-up 18F-florbetapir positron emission tomography scans. Distinct Aß trajectory patterns were classified using latent class growth analysis, and longitudinal cognitive performances across these patterns were assessed with a linear mixed effects model. RESULTS: The optimal model consisted of three classes, with a high entropy value of 0.947. The classes were designated as follows: class 1, non-accumulation group (n = 197); class 2, late accumulation group (n = 70); and class 3, early accumulation group (n = 30). The late accumulation and early accumulation groups had more APOE ε4 carriers than the non-accumulation group. The longitudinal analysis of cognitive performance revealed that the early accumulation group showed the steepest decline (modified Preclinical Alzheimer's Cognitive Composite with digit symbol substitution [mPACCdigit], p < 0.001; modified Preclinical Alzheimer's Cognitive Composite with trails B [mPACCtrailsB], p < 0.001) and the late accumulation group showed a steeper decline (mPACCdigit, p = 0.014; mPACCtrailsB, p = 0.007) compared to the non-accumulation group. CONCLUSIONS: Our study showed the heterogeneity of Aß accumulation trajectories in CU older individuals. The prognoses for cognitive decline differ according to the Aß trajectory patterns.

Association Between Influenza Vaccination and Acute Kidney Injury Among the Elderly: A Self-Controlled Case Series.

BACKGROUND: Several cases of renal complications, including acute kidney injury (AKI), after influenza vaccination have been reported, but the association remains unproven. We evaluated the association between influenza vaccination and AKI occurrence among the Korean elderly in the 2018-2019 and 2019-2020 seasons. METHODS: We used a large database combining vaccination registration data from the Korea Disease Control and Prevention Agency and claims data from the National Health Insurance Service. The study subjects were patients hospitalized with AKI for the first-time following vaccination among those who received one influenza vaccine in the 2018-2019 or 2019-2020 season. Only those aged 65 or older at the date of vaccination were included. We performed a self-controlled case series study, designating the risk period as 1 to 28 days post-vaccination and the observation period as each influenza season. The adjusted incidence rate ratio (aIRR) was calculated by adjusting for nephrotoxic drug use and influenza infection that may influence AKI occurrence using a conditional Poisson regression model. RESULTS: A total of 16 713 and 16 272 AKI events were identified during the 2018-2019 and 2019-2020 seasons, respectively. The aIRR for AKI was 0.83 (95% confidence interval [CI] = 0.79-0.87) in the 2018-2019 season. The aIRR for the 2019-2020 influenza season was similar to the 2018-2019 season (aIRR = 0.86; 95% CI = 0.82-0.90). CONCLUSIONS: Influenza vaccination is associated with a lower risk of AKI in the elderly over 65. This evidence supports the recommendation of annual influenza vaccination for the elderly. Further studies are needed to determine the biological mechanisms linking the influenza vaccine and AKI.

Ameliorating effects of Acanthopanax koreanum extract and components on nicotine dependence and withdrawal symptoms.

Tobacco smoking is a serious health problem in society. While smoking rates are declining, smoking remains a serious risk to national health. Currently, there are several medications available to aid in smoking cessation. However, these medications have the disadvantages of low success rates in smoking cessation and various side effects. Therefore, natural-based smoking cessation aids are being suggested as a good alternative due to their accessibility and minimal side effects. The roots and stems of Acanthopanax koreanum (AK) Nakai, a plant that is native to Jeju Island, South Korea, have traditionally been used as tonic and sedatives. Moreover, eleutheroside B and chlorogenic acid are the main components of AK stem extract. In the present study, we investigated the effect of 70% ethanol AK extract and its components on ameliorating nicotine dependence and withdrawal symptoms by using behavioural tests in mice. In addition, alterations in the dopaminergic and DRD1-EPAC-ERK-CREB pathways were observed using dopamine ELISA and western blotting using mouse brains. Our findings demonstrate that the AK extract and its components effectively mitigated the effects of nicotine treatment in behavioural tests. Furthermore, it normalized the dopamine concentration and the expression level of nicotine acetylcholine receptor α7. Additionally, it was observed that AK extract and its components led to the normalization of DRD1, ERK and CREB expression levels. These results indicate that AK extract exhibits effects in ameliorating nicotine dependence behaviour and alleviating withdrawal symptoms. Moreover, EB and CGA are considered potential marker components of AK extract.

Extracts of Prunella vulgaris Enhanced Pentobarbital-Induced Sleeping Behavior in Mice Potentially via Adenosine A2A Receptor Activity.

The increasing prevalence of sleep dysregulation cases has prompted the search for effective and safe sleep-enhancing agents. Numerous medications used in the treatment of sleep disorders function by enhancing γ-aminobutyric acid neurotransmitter activity. Unfortunately, these substances may induce significant adverse effects in chronic users, such as dependence and motor behavior impairments. Consequently, there is a growing interest in exploring therapeutic sleep-enhancing agents derived from natural sources, with the anticipation of causing less severe side effects. Prunella vulgaris (PV), a perennial plant indigenous to South Korea, exhibits various pharmacological effects, likely attributed to its chemical composition. Rosmarinic acid, one of its components, has previously demonstrated sleep-potentiating properties, suggesting the potential for PV to exhibit similar pharmacological effects. This study aims to investigate the potential effects of repeated administration of PV extract on the sleep behavior, brainwave activity, sleep-wake cycle, and physiological behavior of mice. Findings indicate that PV extracts exhibit sleep-enhancing effects in mice, characterized by prolonged sleep duration and a reduced onset time of pentobarbital-induced sleep. However, PV extracts only reduced alpha wave powers, with minor alterations in wakefulness and rapid-eye-movement sleep duration. In contrast to diazepam, PV extracts lack adverse effects on locomotor activity, motor coordination, or anxiety in mice. Receptor-binding assay and caffeine treatment support the potential involvement of adenosine A2A receptors in the effects of PV, suggesting distinct mechanisms of action compared to diazepam, despite both exhibiting sleep-altering effects. Overall, our results suggest that PV holds promise as a potential source of sleep-aiding agents.

Ultrasonographic Study of the Submandibular Gland for Botulinum Neurotoxin Injection.

BACKGROUND: Hypertrophied submandibular glands provide a bulky contour to the lower face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, no studies have suggested injection points because of the lack of delicate anatomical information on the submandibular gland. OBJECTIVE: The aim of this study was to determine the optimal injection site for botulinum neurotoxin injections in the submandibular gland. MATERIALS AND METHODS: Anatomical considerations when injecting botulinum neurotoxin into the submandibular gland were determined using ultrasonography. The thickness of the submandibular gland, its depth from the skin surface, and the location of the vascular bundle were observed bilaterally in 42 participants. Two cadavers were dissected to measure the location of the submandibular gland corresponding to the ultrasonographic observation. RESULTS: The thickest part of the submandibular gland measured 11.12 ± 2.46 in width with a depth of 4.63 ± 0.76. At the point where it crosses the line of the lateral canthus, it measured 5.53 ± 1.83 in width and 8.73 ± 1.64 in depth. CONCLUSION: The authors suggest optimal injection sites based on external anatomical landmarks. These guidelines aim to maximize the effects of botulinum neurotoxin therapy by minimizing its deleterious effects, which can be useful in clinical settings.

Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family.

MicroRNAs (miRNAs) have recently emerged as important regulators of ion channel expression. We show here that select miR-106b family members repress the expression of the KCNQ2 K+ channel protein by binding to the 3'-untranslated region of KCNQ2 messenger RNA. During the first few weeks after birth, the expression of miR-106b family members rapidly decreases, whereas KCNQ2 protein level inversely increases. Overexpression of miR-106b mimics resulted in a reduction in KCNQ2 protein levels. Conversely, KCNQ2 levels were up-regulated in neurons transfected with antisense miRNA inhibitors. By constructing more specific and stable forms of miR-106b controlling systems, we further confirmed that overexpression of precursor-miR-106b-5p led to a decrease in KCNQ current density and an increase in firing frequency of hippocampal neurons, while tough decoy miR-106b-5p dramatically increased current density and decreased neuronal excitability. These results unmask a regulatory mechanism of KCNQ2 channel expression in early postnatal development and hint at a role for miR-106b up-regulation in the pathophysiology of epilepsy.

Fourier Transform Infrared (FT-IR) Spectroscopy and Simple Algorithm Analysis for Rapid and Non-Destructive Assessment of Cotton Fiber Maturity and Crystallinity for Plant Mapping.

Information on boll distribution within a cotton plant is critical to evaluate the adaptation and response of cotton plants to environmental and biotic stress in cotton production. Cotton researchers have applied available conventional fiber measurements, such as the high volume instrument (HVI) and advanced fiber information system (AFIS), to map the location and the timing of boll development and distribution within plants and further to determine within-plant variability of cotton fiber properties. Both HVI and AFIS require numerous cotton bolls combined for the measurement. As an alternative approach, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy was proposed to measure fiber maturity (MIR) and crystallinity (CIIR) of a sample as little as 0.5 mg lint. Extending fiber maturity and crystallinity measurement into a single boll for node-by-node mapping, FT-IR method might be advantageous due to less sampling amount compared with HVI and AFIS methods. Results showed that FT-IR technique enabled the evaluation of fiber MIR and CIIR at a boll level, which resulted in average MIR and CIIR values highly correlated with HVI micronaire (MIC) and AFIS maturity ratio (M). Hence, FT-IR technique possesses a good potential for a rapid and non-destructive node-by-node mapping of cotton boll maturity and crystallinity distribution.

Ultrasonographic assessment of the lateral pterygoid muscle for BoNT-A injection.

The upper head of the lateral pterygoid muscle (LPM) is known to insert into the capsule of the temporomandibular joint and articular disc, and therefore its relationship with temporomandibular disorders (TMD) has been consistently suggested. The aim of the study was to determine the anatomical features of the LPM using ultrasonographic (US) imaging. Around 120 hemifaces from 60 healthy Korean volunteers were included in this study. US images were taken with the subject's mouth 2 cm open. The transducer was placed at a position where the infratemporal fossa could be observed through the mandibular notch, and its position was recorded. The locations of the coronoid process (CorP), lateral margin of the condylar process (ConP), and midpoint of CorP and ConP (MP) were measured with reference to the ala-tragus line. The thicknesses of the skin and subcutaneous tissue, the masseter muscle, the temporalis muscle, and the depth of the LPM were measured at the MP. The masseter muscle, temporalis muscle, and LPM were observed in all cases and located in order from superficial to deep. The MP was located 39.6 ± 3.3 mm anterior and 7.8 ± 1.6 mm inferior to the tragus. The thicknesses of the skin and subcutaneous tissue, the masseter muscle, the temporalis muscle, and the depth of the LPM at the MP were 9.7 ± 1.0, 10.3 ± 1.3, 10.9 ± 1.6, and 30.9 ± 1.9 mm, respectively. The information reported in this study may be useful for determining the location of the LPM and adjacent anatomical structures in TMD patients and provide accurate and safe injection guidelines.

Anatomical consideration of ultrasonography-guided intraoral injection for temporal tendinitis.

Temporal tendinitis is characterized by acute inflammation often resulting from mechanical stress, such as repetitive jaw movements associated with jaw opening and closing and teeth clenching. Treatment for temporal tendinitis typically involves the administration of local anesthetic or corticosteroid injections. However, the complex anatomical structure of the coronoid process, to which the temporalis tendon attaches, located deep within the zygomatic arch, poses challenges for accurate injections. In this study, we aimed to establish guidelines for the safe and effective treatment of temporal tendinitis by using intraoral ultrasonography (US) to identify the anatomical structures surrounding the temporalis tendon and coronoid process. US was performed using an intraoral transducer on 58 volunteers without temporomandibular joint disease. The procedure involved placing the transducer below the occlusal plane of the maxillary second molar. Measurements were taken for the horizontal distance from the anterior border of the coronoid process, observed at the midpoint (MP) of the US images, and the depth of the coronoid process and temporalis muscle from the oral mucosa. The anterior border of the coronoid process was visualized on all US images and classified into three observed patterns at the MP: type A (anterior to the MP, 56.2%), type B (at the MP, 16.1%), and type C (posterior to the MP, 27.7%). The temporalis muscle was located at a mean depth of 3.12 ± 0.68 mm from the oral mucosa. The maxillary second molar is an intraoral landmark for visualizing the anterior border of the coronoid process. The new location information obtained using intraoral US could help identify the safest and most effective injection sites for the treatment of temporal tendinitis.

Sihler's staining technique: How to and guidance for botulinum neurotoxin injection in human muscles.

The Sihler's stain is a whole-mount nerve staining technique that allows visualization of the nerve distribution and permits mapping of the entire nerve supply patterns of the organs, skeletal muscles, mucosa, skin, and other structures that contain myelinated nerve fibers. Unlike conventional approaches, this technique does not require extensive dissection or slide preparation. To date, the Sihler's stain is the best tool for demonstrating the precise intramuscular branching and distribution patterns of skeletal muscles. The intramuscular neural distribution is used as a guidance tool for the application of botulinum neurotoxin injections. In this review, we have identified and summarized the ideal botulinum neurotoxin injection points for several human tissues.

De Novo Occurrence of Hb Chile [ß28(B10) Leu→Met] in a Korean Boy with Methemoglobinemia.

Hemoglobin (Hb) Chile, a variant of Hb M, is produced by a point mutation of CTG→ATG on codon 29 (legacy codon 28) of the Hb ß locus gene, which results in an amino acid substitution of Leu→Met. It has been identified in two families worldwide and is inherited in an autosomal dominant manner. Here, we report a case of Hb Chile in which a de novo mutation was detected in the proband. A 17-year-old male presented to the outpatient clinic with a pale appearance. There was cyanosis on his lips and fingers. Blood tests indicated the existence of hemolysis, but complete blood counts revealed no anemia. Peripheral arterial oxygen saturation on pulse oximetry was 80% on room air and did not improve with oxygen supplementation. The level of methemoglobin was 15.4%. Targeted next-generation sequencing identified a heterozygous NM_000518.4(HBB):c.85C > A mutation, indicating Hb Chile. The Hb Chile mutation, on the other hand, was not discovered in his parents, implying that it arose as a result of a de novo mutation. This case highlights the necessity of suspecting Hb gene mutations in patients with unexplained chronic methemoglobinemia, even if there is no family history.

Ethnic differences in the prevalence of amyloid positivity and cognitive trajectories.

INTRODUCTION: We investigated the prevalence of amyloid beta (Aß) positivity (+) and cognitive trajectories in Koreans and non-Hispanic Whites (NHWs). METHODS: We included 5121 Koreans from multiple centers across South Korea and 929 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent Aß positron emission tomography and were categorized into cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia stages. Age, sex, education, and apolipoprotein E. genotype were adjusted using multivariable logistic regression and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances in these variables. RESULTS: The prevalence of Aß+ was lower in CU Koreans than in CU NHWs (adjusted odds ratio 0.60). Aß+ Koreans showed a faster cognitive decline than Aß+ NHWs in the CU (B = -0.314, p = .004) and MCI stages (B = -0.385, p < .001). DISCUSSION: Ethnic characteristics of Aß biomarkers should be considered in research and clinical application of Aß-targeted therapies in diverse populations. HIGHLIGHTS: Koreans have a lower prevalence of Aß positivity compared to NHWs in the CU stage. The effects of Alzheimer's risk factors on Aß positivity differ between Koreans and NHWs. Aß-positive (Aß+) Koreans show faster cognitive decline than Aß+ NHWs in the CU and MCI stages.

Comparison between botulinum toxin type A injection on masseter muscle only and additional injection on anterior belly of digastric muscle in sleep bruxism patients: A clinical trial.

OBJECTIVE: This study aims to evaluate the effects on bite force and muscle thickness of the botulinum toxin (BoNT) injection for patients with sleep bruxism (SB) by comparing injections into the masseter muscle only and both the masseter and the anterior belly of the digastric muscle (ABDM) in a clinical trial. METHODS: Twelve SB patients received BoNT-A injections using US-guided techniques into the masseter muscle only (Group A), while the remaining 12 SB patients received injections into both the masseter and ABDM (Group B). Bite force and muscle thickness were measured before injection, as well as 1 and 2 months after injection. RESULTS: The bite force and masseter muscle thickness decreased in both Group A and Group B before injection, and at 1 and 2 months after injection. However, there was no significant difference (p > .05, repeated measures analysis of variance) between the two groups, and there was also no significant difference in ABDM thickness (p > .05, repeated measures analysis of variance). CONCLUSION: This study is the first to assess the short-term effects of BoNT injected into ABDM for SB control. Results show no influence on SB reduction, suggesting the need for further research on BoNT's effectiveness in controlling intense ABDM contractions during sleep and assessing suprahyoid muscle potential impact on rhythmic masticatory muscle activity occurrence.

Effect of Copper Antifouling Paint on Marine Degradation of Polypropylene: Uneven Distribution of Microdebris between Nagasaki Port and Goto Island, Japan.

Microplastics (MP) encompass not only plastic products but also paint particles. Marine microdebris, including MP, was retrieved from five sampling stations spanning Nagasaki-Goto island and was classified into six types, primarily consisting of MP (A), Si-based (B), and Cu-based (C) paint particles. Type-A particles, i.e., MP, were exceedingly small, with 74% of them having a long diameter of 25 µm or less. The vertical distribution of type C, containing cuprous oxide, exhibited no depth dependence, with its dominant size being less than 7 µm. It was considered that the presence of type C was associated with a natural phenomenon of MP loss. To clarify this, polypropylene (PP) samples containing cuprous oxide were prepared, and their accelerated degradation behavior was studied using a novel enhanced degradation method employing a sulfate ion radical as an initiator. Infrared spectroscopy revealed the formation of a copper soap compound in seawater. Scanning electron microscopy/energy-dispersive X-ray spectroscopy analysis indicated that the chemical reactions between Cl- and cuprous oxide produced Cu+ ions. The acceleration of degradation induced by the copper soap formed was studied through the changes in the number of PP chain scissions, revealing that the presence of type-C accelerated MP degradation.

Sihler's staining of the anterior belly of digastric muscle for botulinum toxin injection.

PURPOSE: The anterior belly of the digastric muscle (ABDM) is the target of botulinum toxin injection; however, anatomical considerations related to the injection point are absent. This study used Sihler's staining to analyze the intramuscular nerve distribution of ABDM to identify the most effective botulinum toxin injection points. METHODS: We used 12 specimens from 6 embalmed cadavers in this study. The specimens were manually dissected to preserve the mylohyoid nerve and subjected to Sihler's staining. From the gnathion to and hyoid bone, the ABDM was divided into three equal parts, distinguishing the anterior, middle, and posterior thirds. RESULTS: Only a branch of the mylohyoid nerve entered the ABDM, and its entry point was located in the middle-third region in all cases. The nerve endings were concentrated in the middle third (100%), followed by the anterior third (58.3%) and were not observed in the posterior third. CONCLUSION: The landmarks used in this study (gnathion and hyoid bone) are easily palpable on the skin surface, allowing clinicians to target the most effective injection site (middle third of ABDM). These results provide scientific and anatomic evidence for injection points, and will aid in the management of ABDM injection procedures in clinical practice.