5-Hydroxytryptamine Enhances the Pacemaker Activity of Interstitial Cells of Cajal in Mouse Colon.

We examined the localization of the 5-hydroxytryptamine (5-HT) receptor and its effects on mouse colonic interstitial cells of Cajal (ICCs) using electrophysiological techniques. Treatment with 5-HT increased the pacemaker activity in colonic ICCs with depolarization of membrane potentials in a dose-dependent manner. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers blocked pacemaker activity and 5-HT-induced effects. Moreover, an adenylate cyclase inhibitor inhibited 5-HT-induced effects, and cell-permeable 8-bromo-cAMP increased the pacemaker activity. Various agonists of the 5-HT receptor subtype were working in colonic ICCs, including the 5-HT4 receptor. In small intestinal ICCs, 5-HT depolarized the membrane potentials transiently. Adenylate cyclase inhibitors or HCN blockers did not show any influence on 5-HT-induced effects. Anoctamin-1 (ANO1) or T-type Ca2+ channel blockers inhibited the pacemaker activity of colonic ICCs and blocked 5-HT-induced effects. A tyrosine protein kinase inhibitor inhibited pacemaker activity in colonic ICCs under controlled conditions but did not show any influence on 5-HT-induced effects. Among mitogen-activated protein kinase (MAPK) inhibitors, a p38 MAPK inhibitor inhibited 5-HT-induced effects on colonic ICCs. Thus, 5-HT's effect on pacemaker activity in small intestinal and colonic ICCs has excitatory but variable patterns. ANO1, T-type Ca2+, and HCN channels are involved in 5-HT-induced effects, and MAPKs are involved in 5-HT effects in colonic ICCs.

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate.

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or ß--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.

Phase patterning of liquid crystal elastomers by laser-induced dynamic crosslinking.

Liquid crystal elastomers hold promise in various fields due to their reversible transition of mechanical and optical properties across distinct phases. However, the lack of local phase patterning techniques and irreversible phase programming has hindered their broad implementation. Here we introduce laser-induced dynamic crosslinking, which leverages the precision and control offered by laser technology to achieve high-resolution multilevel patterning and transmittance modulation. Incorporation of allyl sulfide groups enables adaptive liquid crystal elastomers that can be reconfigured into desired phases or complex patterns. Laser-induced dynamic crosslinking is compatible with existing processing methods and allows the generation of thermo- and strain-responsive patterns that include isotropic, polydomain and monodomain phases within a single liquid crystal elastomer film. We show temporary information encryption at body temperature, expanding the functionality of liquid crystal elastomer devices in wearable applications.

Prognosis of amyotrophic lateral sclerosis patients after tracheostomy invasive ventilation in Korea.

Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [≥80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.

A Gradient Stiffness-Programmed Circuit Board by Spatially Controlled Phase-Transition of Supercooled Hydrogel for Stretchable Electronics Integration.

Due to emerging demands in soft electronics, there is an increasing need for material architectures that support robust interfacing between soft substrates, stretchable electrical interconnects, and embedded rigid microelectronics chips. Though researchers have adopted rigid-island structures to solve the issue, this approach merely shifts stress concentrations from chip-conductor interfaces to rigid-island-soft region interfaces in the substrate. Here, a gradient stiffness-programmed circuit board (GS-PCB) that possesses high stretchability and stability with surface mounted chips is introduced. The board comprises a stiffness-programmed hydrogel substrate and a laser-patterned liquid metal conductor. The hydrogel simultaneously obtains a large stiffness disparity and robust interfaces between rigid-islands and soft regions. These seemingly contradictory conditions are accomplished by adopting a gradient stiffness structure at the interfaces, enabled by combining polymers with different interaction energies and a supercooled sodium acetate solution. By integrating the gel with laser-patterned liquid metal with exceptional properties, GS-PCB exhibits higher electromechanical stability than other rigid-island research. To highlight the practicality of this approach, a finger-sensor device that successfully distinguishes objects by direct physical contact is fabricated, demonstrating its stability under various mechanical disturbances.

Optimization and scale up of production of the PSMA imaging agent [18F]AlF-P16-093 on a custom automated radiosynthesis platform.

BACKGROUND: Recent advancements in positron emission tomograph (PET) using prostate specific membrane antigen (PSMA)-targeted radiopharmaceuticals have changed the standard of care for prostate cancer patients by providing more accurate information during staging of primary and recurrent disease. [68Ga]Ga-P16-093 is a new PSMA-PET radiopharmaceutical that demonstrated superior imaging performance in recent head-to-head studies with [68Ga]Ga-PSMA-11. To improve the availability of this new PSMA PET imaging agent, [18F]AlF-P16-093 was developed. The 18F-analog [18F]AlF-P16-093 has been synthesized manually at low activity levels using [18F]AlF2+ and validated in pre-clinical models. This work reports the optimization of the production of > 15 GBq of [18F]AlF-P16-093 using a custom automated synthesis platform. RESULTS: The sensitivity of the radiochemical yield of [18F]AlF-P16-093 to reaction parameters of time, temperature and reagent amounts was investigated using a custom automated system. The automated system is a low-cost, cassette-based system designed for 1-pot syntheses with flow-controlled solid phase extraction (SPE) workup and is based on the Raspberry Pi Zero 2 microcomputer/Python3 ecosystem. The optimized none-decay-corrected yield was 52 ± 4% (N = 3; 17.5 ± 2.2 GBq) with a molar activity of 109 ± 14 GBq/µmole and a radiochemical purity of 98.6 ± 0.6%. Run time was 30 min. A two-step sequence was used: SPE-purified [18F]F- was reacted with 80 nmoles of freeze-dried AlCl3·6H2O at 65 °C for 5 min followed by reaction with 160 nmoles of P16-093 ligand at 40 °C for 4 min in a 1:1 mixture of ethanol:0.5 M pH 4.5 NaOAc buffer. The mixture was purified by SPE (> 97% recovery). The final product formulation (5 mM pH 7 phosphate buffer with saline) exhibited a rate of decline in radiochemical purity of ~ 1.4%/h which was slowed to ~ 0.4%/h when stored at 4 °C. CONCLUSION: The optimized method using a custom automated system enabled the efficient (> 50% none-decay-corrected yield) production of [18F]AlF-P16-093 with high radiochemical purity (> 95%). The method and automation system are simple and robust, facilitating further clinical studies with [18F]AlF-P16-093.

Healthcare Utilization and Supportive Care Timing in South Korean People Living With Amyotrophic Lateral Sclerosis: A Single-Center Retrospective Study.

BACKGROUND AND PURPOSE: Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea. METHODS: A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit. RESULTS: Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period. The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively. CONCLUSIONS: During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportive-care program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions.

Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy: A Multicenter Cohort Study in South Korea.

BACKGROUND AND PURPOSE: Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. METHODS: This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. RESULTS: The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). CONCLUSIONS: Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

Varicella zoster virus glycoprotein E facilitates PINK1/Parkin-mediated mitophagy to evade STING and MAVS-mediated antiviral innate immunity.

Viruses have evolved to control mitochondrial quality and content to facilitate viral replication. Mitophagy is a selective autophagy, in which the damaged or unnecessary mitochondria are removed, and thus considered an essential mechanism for mitochondrial quality control. Although mitophagy manipulation by several RNA viruses has recently been reported, the effect of mitophagy regulation by varicella zoster virus (VZV) remains to be fully determined. In this study, we showed that dynamin-related protein-1 (DRP1)-mediated mitochondrial fission and subsequent PINK1/Parkin-dependent mitophagy were triggered during VZV infection, facilitating VZV replication. In addition, VZV glycoprotein E (gE) promoted PINK1/Parkin-mediated mitophagy by interacting with LC3 and upregulating mitochondrial reactive oxygen species. Importantly, VZV gE inhibited MAVS oligomerization and STING translocation to disrupt MAVS- and STING-mediated interferon (IFN) responses, and PINK1/Parkin-mediated mitophagy was required for VZV gE-mediated inhibition of IFN production. Similarly, carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-mediated mitophagy induction led to increased VZV replication but attenuated IFN production in a three-dimensional human skin organ culture model. Our results provide new insights into the immune evasion mechanism of VZV gE via PINK1/Parkin-dependent mitophagy.

Ordovician origin and subsequent diversification of the brown algae.

Brown algae are the only group of heterokont protists exhibiting complex multicellularity. Since their origin, brown algae have adapted to various marine habitats, evolving diverse thallus morphologies and gamete types. However, the evolutionary processes behind these transitions remain unclear due to a lack of a robust phylogenetic framework and problems with time estimation. To address these issues, we employed plastid genome data from 138 species, including heterokont algae, red algae, and other red-derived algae. Based on a robust phylogeny and new interpretations of algal fossils, we estimated the geological times for brown algal origin and diversification. The results reveal that brown algae first evolved true multicellularity, with plasmodesmata and reproductive cell differentiation, during the late Ordovician Period (ca. 450 Ma), coinciding with a major diversification of marine fauna (the Great Ordovician Biodiversification Event) and a proliferation of multicellular green algae. Despite its early Paleozoic origin, the diversification of major orders within this brown algal clade accelerated only during the Mesozoic Era, coincident with both Pangea rifting and the diversification of other heterokont algae (e.g., diatoms), coccolithophores, and dinoflagellates, with their red algal-derived plastids. The transition from ancestral isogamy to oogamy was followed by three simultaneous reappearances of isogamy during the Cretaceous Period. These are concordant with a positive character correlation between parthenogenesis and isogamy. Our new brown algal timeline, combined with a knowledge of past environmental conditions, shed new light on brown algal diversification and the intertwined evolution of multicellularity and sexual reproduction.

Morphologic differences between ruptured and unruptured choroidal anastomosis in adult moyamoya disease: a high-resolution vessel wall imaging study.

OBJECTIVE: Choroidal anastomosis (ChA) has been implicated as the main indicator of an increased hemorrhagic risk in adult moyamoya disease. In this retrospective study, the authors aimed to identify the potential risk factors that can influence the rupture of ChA. METHODS: The authors evaluated the clinical and radiological data on brain hemispheres positive for ChA from September 2019 to March 2023. The rupture status of the ChA was determined using previously described methods. Two independent raters quantitatively investigated the lumen diameter (LD) and lumen area (LA) of the ChA using high-resolution vessel wall imaging (VWI). Multivariate logistic regression analysis was conducted to identify the risk factors for ruptured ChA. RESULTS: Ruptured and unruptured ChAs were identified in 16 and 60 hemispheres, respectively. Univariate analysis showed that the mean values of the LD (1.251 ± 0.241 vs 0.967 ± 0.214 mm, p < 0.001) and LA (1.607 ± 0.445 vs 0.945 ± 0.372 mm2, p < 0.001) of ChAs were significantly greater in the ruptured group than in the unruptured group. A periventricular anastomosis (PA) score of 1, indicating the angiographic presence of ChA alone, was more prevalent in the ruptured group than in the unruptured group (43.8% vs 11.7%, p = 0.003). Multivariate analysis demonstrated that a larger LA of the ChA (OR 37.01, 95% CI 5.787-236.7, p < 0.001) and PA score 1 (OR 6.661, 95% CI 1.260-35.21, p = 0.026) were independently associated with ruptured ChA hemispheres. Receiver operating characteristic curve analysis revealed that the optimal cutoff point for the LA was 1.285 mm2 (sensitivity 81.3%, specificity 86.7%). CONCLUSIONS: A larger LA (> 1.285 mm2) of the ChA and the angiographic presence of ChA alone are independent risk factors for a ruptured ChA. Revascularization surgery for the prevention of future hemorrhage may be indicated for hemispheres with a high-risk unruptured ChA. These characteristics may help to determine treatment strategies for patients with an unruptured ChA.

Tunable Radiative Cooling by Mechanochromic Electrospun Micro-Nanofiber Matrix.

Radiative thermoregulation has been regarded as an energy-efficient method for thermal management. In this study, the development of a mechanoresponsive polydimethylsiloxane (PDMS) micro-nanofiber matrix capable of both sub-ambient radiative cooling and solar heating is presented, achieved through a core-shell electrospinning technique. The electrospun PDMS micro-nanofibers, with diameters comparable to the solar wavelengths, exhibit excellent solar reflectivity (≈93%) while preserving its pristine high infrared (IR) emissivity. As a result, the electrospun PDMS radiative cooler (EPRC) successfully demonstrated sub-ambient radiative cooling performance (≈3.8°C) during the daytime. Furthermore, the exceptional resilient property of PDMS facilitated the reversible alteration of the structural morphology created by the fiber-based matrix under mechanical force, resulting in the modulation of solar reflectivity (≈80%). The precise modulation of solar reflectivity enabled reversibly switchable multi-step radiative thermoregulation, offering enhanced flexibility in addressing varying thermal environments even in maintaining the desired temperature. The findings of this work offer a promising approach toward dynamic radiative thermoregulation, which holds significant potential for addressing global climate change concerns and energy shortage.

Are Veterinary Costs and Socioeconomic Status Risk Factors for Companion Animal Relinquishment in the Republic of Korea?

More than 110,000 companion animals are sent to shelters each year due to abandonment in Republic of Korea, and there is a need to analyze the causes of the relinquishment of animals and implement appropriate policies. Veterinary costs have been blamed for this issue in Republic of Korea above the reported leading causes of socioeconomic status of owners, cost and behavior issues of the animals, or housing restrictions. However, it is rare to find supporting evidence. In this study, we aimed to determine whether veterinary costs and socioeconomic factors are related to animal relinquishment in Republic of Korea. Multiple regression models were used to test if veterinary costs and socioeconomic indicators can account for relinquishment in 128 regions of Republic of Korea in 2020 and 2021. When five independent variables (two veterinary cost data and three socioeconomic indicators) were included, the regression model showed significance in explaining pet relinquishment in 2020, with an adjusted coefficient of determination of 0.3956. Pet relinquishment can also be explained by the same five variables for 2021, with an adjusted coefficient of determination of 0.391 with p < 0.0001. The findings suggest that intervention to reduce companion animal relinquishment in Republic of Korea should focus on lightening the financial burdens of owners as the socioeconomic status of a community worsens.

Massive Hyperostotic Meningioma En Plaque Mimicking Fibrous Dysplasia.

The authors report an extremely rare case of a massive hyperostotic meningioma en plaque, which had characteristics of unique bony growth. A 34-year-old man presented with a palpable solid mass in the left cranial region that had gradually grown in size with a broad base on the calvarium for 8 years. Radiologically, the area involved by the mass ranged from the sphenoid bone to the frontal, parietal, temporal, and occipital bones. Three-dimensional CT revealed multiple growing spiculate features on the inner and outer cranial surface. Even though the radiologic features resembled fibrous dysplasia, it was histologically found to be a type of meningioma.

Wedge resection combined with 3D-printed polycaprolactone mesh for caudal septal deviation.

BACKGROUND: Biocompatibility and stability of three-dimensional printed polycaprolactone mesh grafts for nasal surgery are proven in both animal and human models. However, their safety and durability as batten grafts for caudal septal deviation has not been documented. This study was designed to investigate the efficacy and safety of three-dimensional printed polycaprolactone mesh batten graft in septoplasty using the wedge resection technique for the correction of caudal septal deviation. METHODS: This retrospective study reviewed the medical records of 20 patients aged ≥ 18 years with caudal septal deviation who underwent septoplasty with wedge resection and three-dimensional printed polycaprolactone mesh graft from a tertiary medical center in South Korea, between December 1, 2019 and May 31, 2021. Those without nasal obstruction before surgery or with a short follow-up period (< 28 days) were excluded from the survey analysis. RESULTS: Of the 20 patients (mean age, 48.0 [range, 19-65] years), 17 (85.0%) were male, and three (15.0%) were female. A significant change was noted in the mean nasal obstruction symptom evaluation score (68.2 vs. 15.0, P < .001) in the 17 patients included in the analysis. Postoperative endoscopic evaluation revealed a straight septum in 19/20 (95.0%) patients, and no complications were noted in the postoperative follow-up period of up to 364 days. CONCLUSIONS: The three-dimensional printed polycaprolactone nasal mesh is safe and provides adequate support to resist the intrinsic memory of the cartilage of the caudal septum. In addition to nasal surgeries, it has great potential as a graft in other reconstructive surgeries. Trial registration Retrospectively registered.

Subclinical articulatory changes of vowel parameters in Korean amyotrophic lateral sclerosis patients with perceptually normal voices.

The available quantitative methods for evaluating bulbar dysfunction in patients with amyotrophic lateral sclerosis (ALS) are limited. We aimed to characterize vowel properties in Korean ALS patients, investigate associations between vowel parameters and clinical features of ALS, and analyze subclinical articulatory changes of vowel parameters in those with perceptually normal voices. Forty-three patients with ALS (27 with dysarthria and 16 without dysarthria) and 20 healthy controls were prospectively collected in the study. Dysarthria was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) speech subscores, with any loss of 4 points indicating the presence of dysarthria. The structured speech samples were recorded and analyzed using Praat software. For three corner vowels (/a/, /i/, and /u/), data on the vowel duration, fundamental frequency, frequencies of the first two formants (F1 and F2), harmonics-to-noise ratio, vowel space area (VSA), and vowel articulation index (VAI) were extracted from the speech samples. Corner vowel durations were significantly longer in ALS patients with dysarthria than in healthy controls. The F1 frequency of /a/, F2 frequencies of /i/ and /u/, the VSA, and the VAI showed significant differences between ALS patients with dysarthria and healthy controls. The area under the curve (AUC) was 0.912. The F1 frequency of /a/ and the VSA were the major determinants for differentiating ALS patients who had not yet developed apparent dysarthria from healthy controls (AUC 0.887). In linear regression analyses, as the ALSFRS-R speech subscore decreased, both the VSA and VAI were reduced. In contrast, vowel durations were found to be rather prolonged. The analyses of vowel parameters provided a useful metric correlated with disease severity for detecting subclinical bulbar dysfunction in ALS patients.

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy.

Prostate-specific membrane antigen (PSMA) is an excellent target for imaging and radionuclide therapy of prostate cancer. Recently, [177Lu]Lu-PSMA-617 (Pluvicto) was approved by the FDA for radionuclide therapy. To develop hetero-bivalent agents targeting both PSMA and bone metastasis, [177Lu]Lu-P17-079 ([177Lu]Lu-1) and [177Lu]Lu-P17-081 ([177Lu]Lu-2) were prepared. In vivo biodistribution studies of [177Lu]Lu-PSMA-617, [177Lu]Lu-1, and [177Lu]Lu-2 in mice bearing PC3-PIP (PSMA positive) tumor showed high uptake in PSMA-positive tumor (14.5, 14.7, and 11.3% ID/g at 1 h, respectively) and distinctively different bone uptakes (0.52, 6.52, and 5.82% ID/g at 1 h, respectively). PET imaging using [68Ga]Ga-P17-079 ([68Ga]Ga-1) in the same mouse model displayed excellent images confirming the expected dual-targeting to PSMA-positive tumor and bone. Results suggest that [177Lu]Lu-P17-079 ([177Lu]Lu-1) is a promising candidate for further development as a hetero-bivalent radionuclide therapy agent targeting both PSMA expression and bone metastases for the treatment of prostate cancer.

Suicide Attempts in Patients With Amyotrophic Lateral Sclerosis: An Analysis of the Korean National Health Insurance Database.

Objective: The knowledge of the common risk factors for suicide attempts may not be simply applicable to patients with amyotrophic lateral sclerosis (ALS). We aimed to identify risk factors associated with suicide attempts in patients with ALS and to determine the annual prevalence and periods of vulnerability associated with attempts.Methods: This nationwide cohort study was performed using the Korean National Health Insurance Database. All patients with ALS concomitantly registered for the Exempted Calculation of Health Insurance for rare, incurable diseases between 2011 and 2017 were identified. We used the Cox proportional hazards regression model and competing risk model to identify the risk factors for suicide attempts. The multivariable models were adjusted for potential risk factors from the univariate analysis.Results: Among 2,955 incident patients, 47 attempted suicide. After adjusting for sex, previous attempts, and previous psychiatric disorders, the hazard ratios for psychiatric hospitalization before ALS diagnosis were 3.17 (95% confidence interval [CI], 1.31-7.70; P = .01) and 3.02 (95% CI, 1.32-6.90; P = .01) in the Cox regression model and the competing risk model, respectively. The annual prevalence of suicide attempts was 0.29%-1.12%. Twenty (42.6%) and 9 (19.1%) attempts occurred within 3 months and 12-18 months after diagnosis, respectively.Conclusions: Psychiatric hospitalization increased the risk of suicide attempts, which clustered at the early stage or on losing autonomy. Those with a history of psychiatric hospitalization should receive an in-depth evaluation and be cautiously monitored.

High resolution vessel-wall imaging for peripheral aneurysms in adult moyamoya disease: a report of three cases.

Peripheral aneurysms in patients with moyamoya disease have been reported to be hazardous owing to their rupture-prone nature. High-resolution vessel wall imaging has recently emerged as a useful modality for evaluating intracranial aneurysmal status. We present the vessel-wall imaging of peripheral aneurysms in three patients with moyamoya disease. Strong circumferential wall enhancement was observed in ruptured peripheral aneurysms. Peripheral aneurysms were located at the connection point between the single main stem and the multiple medullary tributaries of the choroidal anastomosis. Using high-resolution vessel-wall imaging, we identified the characteristics of peripheral aneurysms in patients with moyamoya disease.