TOLLIP acts as a cargo adaptor to promote lysosomal degradation of aberrant ER membrane proteins.

Endoplasmic reticulum (ER) proteostasis is maintained by various catabolic pathways. Lysosomes clear entire ER portions by ER-phagy, while proteasomes selectively clear misfolded or surplus aberrant proteins by ER-associated degradation (ERAD). Recently, lysosomes have also been implicated in the selective clearance of aberrant ER proteins, but the molecular basis remains unclear. Here, we show that the phosphatidylinositol-3-phosphate (PI3P)-binding protein TOLLIP promotes selective lysosomal degradation of aberrant membrane proteins, including an artificial substrate and motoneuron disease-causing mutants of VAPB and Seipin. These cargos are recognized by TOLLIP through its misfolding-sensing intrinsically disordered region (IDR) and ubiquitin-binding CUE domain. In contrast to ER-phagy receptors, which clear both native and aberrant proteins by ER-phagy, TOLLIP selectively clears aberrant cargos by coupling them with the PI3P-dependent lysosomal trafficking without promoting bulk ER turnover. Moreover, TOLLIP depletion augments ER stress after ERAD inhibition, indicating that TOLLIP and ERAD cooperatively safeguard ER proteostasis. Our study identifies TOLLIP as a unique type of cargo-specific adaptor dedicated to the clearance of aberrant ER cargos and provides insights into molecular mechanisms underlying lysosome-mediated quality control of membrane proteins.

Genetically encoded multimeric tags for subcellular protein localization in cryo-EM.

Cryo-electron tomography (cryo-ET) allows for label-free high-resolution imaging of macromolecular assemblies in their native cellular context. However, the localization of macromolecules of interest in tomographic volumes can be challenging. Here we present a ligand-inducible labeling strategy for intracellular proteins based on fluorescent, 25-nm-sized, genetically encoded multimeric particles (GEMs). The particles exhibit recognizable structural signatures, enabling their automated detection in cryo-ET data by convolutional neural networks. The coupling of GEMs to green fluorescent protein-tagged macromolecules of interest is triggered by addition of a small-molecule ligand, allowing for time-controlled labeling to minimize disturbance to native protein function. We demonstrate the applicability of GEMs for subcellular-level localization of endogenous and overexpressed proteins across different organelles in human cells using cryo-correlative fluorescence and cryo-ET imaging. We describe means for quantifying labeling specificity and efficiency, and for systematic optimization for rare and abundant protein targets, with emphasis on assessing the potential effects of labeling on protein function.

Association between motor symptoms of Parkinson's disease and swallowing disorders.

BACKGROUND: Parkinson's disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores. METHODS: This study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2-4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores. RESULTS: Twenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035-1.617; p = 0.024). CONCLUSION: This study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures. TRIAL REGISTRATION NUMBER: jRCTs062220013.

Dibenzotropylium-Capped Orthogonal Geometry Enabling Isolation and Examination of a Series of Hydrocarbons with Multiple 14π-Aromatic Units.

A series of six dications composed of pure hydrocarbons with one to six non-substituted 9,10-anthrylene units end-capped with two dibenzotropyliums were designed and synthesized to elucidate the electronic properties of huge oligo(9,10-anthrylene) backbones. Their structures were successfully determined by X-ray analyses even in the case of eight planar 14π-electron units, revealing that all dications adopt almost orthogonally twisted structures between neighboring units. Spectroscopic and voltammetric analyses show that neither the significant overlap of orbitals nor the delocalization of electrons between 14π-electron units occurs due to the orthogonally twisted geometry even in solution. As a result, sequential oxidation processes were observed with the reversible formation of multivalent cations with the release of the same number of electrons as the number of anthrylene units. Upon two-electron reduction, a closed-shell butterfly-shaped form was obtained from the dication containing one anthrylene unit, whereas open-shell twisted biradicals were isolated as stable entities in the cases of derivatives containing three to six anthrylene units. Notably, from the derivative with two anthrylene units, a metastable open-shell isomer was obtained quantitatively and underwent slow thermal conversion to the most stable closed-shell isomer (Ea = 23.1 kcal mol-1). There is a drastic change in oxidation potentials between two neutral species (ΔE = 1.32 V in CH2Cl2). Since the present dications were regenerated upon oxidation of the isolated reduction products, these systems may contribute to the development of advanced response systems capable of switching color, magnetic properties, and oxidative properties by using a "cation-capped orthogonal geometry".

Image-Based Quantification of Arabidopsis thaliana Stomatal Aperture from Leaf Images.

The quantification of stomatal pore size has long been a fundamental approach to understand the physiological response of plants in the context of environmental adaptation. Automation of such methodologies not only alleviates human labor and bias but also realizes new experimental research methods through massive analysis. Here, we present an image analysis pipeline that automatically quantifies stomatal aperture of Arabidopsis thaliana leaves from bright-field microscopy images containing mesophyll tissue as noisy backgrounds. By combining a You Only Look Once X-based stomatal detection submodule and a U-Net-based pore segmentation submodule, we achieved a mean average precision with an intersection of union (IoU) threshold of 50% value of 0.875 (stomata detection performance) and an IoU of 0.745 (pore segmentation performance) against images of leaf discs taken with a bright-field microscope. Moreover, we designed a portable imaging device that allows easy acquisition of stomatal images from detached/undetached intact leaves on-site. We demonstrated that this device in combination with fine-tuned models of the pipeline we generated here provides robust measurements that can substitute for manual measurement of stomatal responses against pathogen inoculation. Utilization of our hardware and pipeline for automated stomatal aperture measurements is expected to accelerate research on stomatal biology of model dicots.

Type 2C protein phosphatase clade D family members dephosphorylate guard cell plasma membrane H+-ATPase.

Plasma membrane (PM) H+-ATPase in guard cells is activated by phosphorylation of the penultimate residue, threonine (Thr), in response to blue and red light, promoting stomatal opening. Previous in vitro biochemical investigation suggested that Mg2+- and Mn2+-dependent membrane-localized type 2C protein phosphatase (PP2C)-like activity mediates the dephosphorylation of PM H+-ATPase in guard cells. PP2C clade D (PP2C.D) was later demonstrated to be involved in PM H+-ATPase dephosphorylation during auxin-induced cell expansion in Arabidopsis (Arabidopsis thaliana). However, it is unclear whether PP2C.D phosphatases are involved in PM H+-ATPase dephosphorylation in guard cells. Transient expression experiments using Arabidopsis mesophyll cell protoplasts revealed that all PP2C.D isoforms dephosphorylate the endogenous PM H+-ATPase. We further analyzed PP2C.D6/8/9, which display higher expression levels than other isoforms in guard cells, observing that pp2c.d6, pp2c.d8, and pp2c.d9 single mutants showed similar light-induced stomatal opening and phosphorylation status of PM H+-ATPase in guard cells as Col-0. In contrast, the pp2c.d6/9 double mutant displayed wider stomatal apertures and greater PM H+-ATPase phosphorylation in response to blue light, but delayed dephosphorylation of PM H+-ATPase in guard cells; the pp2c.d6/8/9 triple mutant showed similar phenotypes to those of the pp2c.d6/9 double mutant. Taken together, these results indicate that PP2C.D6 and PP2C.D9 redundantly mediate PM H+-ATPase dephosphorylation in guard cells. Curiously, unlike auxin-induced cell expansion in seedlings, auxin had no effect on the phosphorylation status of PM H+-ATPase in guard cells.

Suppressive effects of violet light transmission on myopia progression in a mouse model of lens-induced myopia.

The prevalence of myopia has been steadily increasing for several decades, and this condition can cause extensive medical and economic issues in society. Exposure to violet light (VL), a short wavelength (360-400 nm) of visible light from sunlight, has been suggested as an effective preventive and suppressive treatments for the development and progression of myopia. However, the clinical application of VL remains unclear. In this study, we aimed to investigate the preventive and suppressive effects of VL on myopia progression. Various transmittances of VL (40%, 70%, and 100%) were tested in C57BL/6J mice with lens-induced myopia (LIM). Changes in the refractive error, axial length, and choroid thickness during the 3-week LIM were measured. The myopic shift in refractive error and difference in axial length between the 0 and -30 diopter lens was lessened in a transmission-dependent manner. Choroidal thinning, which was observed in myopic conditions, was suppressed by VL exposure and affected by its transmission. The results suggest that myopia progression can be managed using VL transmittance. Therefore, these factors should be considered for the prevention and treatment of myopia.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.

OBJECTIVE: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. METHODS: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. RESULTS: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. CONCLUSIONS: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Preoperative Sarcopenia Assessment Using Pectoralis Muscle Mass Indicated Poor Mid-term Cardiac Surgery Prognosis.

BACKGROUND: Many studies have defined sarcopenia based on psoas muscle mass using abdominal computed tomography (CT). We hypothesized that sarcopenia can be assessed by measuring pectoralis muscle mass on chest CT and aimed to examine its relationship with the postoperative prognosis of cardiac surgery. METHODS: This retrospective study included 189 patients who underwent cardiac surgery via median sternotomy between July 2020 and June 2022. We excluded patients <70 years old, urgent/emergent cases, no chest CT within 90 days before surgery, and cases in which evaluation of the pectoralis muscle was impossible with CT. The pectoralis muscle area (PMA) was measured using a preoperative chest CT. The sarcopenia cut-off value was defined as the lowest sex-specific tertile in PMA at the level of the 4th thoracic vertebrae. RESULTS: Eighty patients were included. The lower tertile were classified as the sarcopenia group (SG) (n = 26) and the rest as the non-sarcopenia group (NSG) (n = 54). In the SG, 1-year survival was significantly worse than that in NSG (NSG: 92.7% vs. SG: 54.9%, p < 0.0001). In the multivariate model, sarcopenia was an independent risk factor for mid-term all-cause death (hazard ratio, 4.89; 95% confidence interval: 1.14-21.0, p = 0.033). CONCLUSION: Preoperative sarcopenia defined using PMA was associated with poor mid-term survival after elective cardiac surgery via median sternotomy. The pectoralis muscle mass observed through a chest CT could be used for preoperative risk scoring in older patients undergoing cardiac surgery.

[Sixteen Cases of Appendiceal Mucinous Neoplasm].

Appendiceal mucinous neoplasm is a relatively rare disease. It is classified as mucinous adenocarcinoma(MACA)and low- grade appendiceal mucinous neoplasm(LAMN). We retrospectively evaluated 16 cases of appendiceal mucinous neoplasm (LAMN: 13 cases, MACA: 3 cases)that were surgically resected in our hospital between January 2010 and July 2021. There were 7 men and 9 women, with a median age of 61 years(27-85 years). The most common chief complaint was abdominal pain(12 patients), while 3 cases were incidental findings following medical checkups for other diseases and without a chief complaint. Colonoscopy was performed for 9 cases. Of these, 5 revealed abnormal findings. The preoperative diagnosis was appendicitis in 7 patients and appendiceal tumor in 8 patients. The surgical procedures were planned for 8 cases and performed as emergencies in 8 cases. The procedures included laparoscopic surgery(n=6)and laparotomy(n=10). The resection range included appendectomy(n=9), partial cecal resection(n=4), and ileocecal resection(n=3). Surgical margins were negative in all cases. Metastases were not observed in patients who underwent lymph node dissections (2 patients with MACA and 1 patient with LAMN). The median follow-up was 17 months(1-43 months). Recurrence including peritoneal pseudomyxoma was not detected in any of the patients.

SF3B14 is involved in the centrosome regulation through splicing of TUBGCP6 pre-mRNA.

Splicing precursor messenger RNA (pre-mRNA) is a critical step to produce physiologically functional protein. Splicing failure not only gives rise to dysfunctional proteins but also generates abnormal protein function, which causes several diseases. Several pre-mRNA splicing factors are reported to regulate mitosis directly at mitotic structures and/or indirectly through controlling the pre-mRNA splicing for mitotic proteins. In this study, we described the mitotic functions of SF3B14, a component of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), which we identified as a candidate involved in mitosis based on the large-scale RNA interference (RNAi) screen of the nucleolar proteome database. We observed that SF3B14 depletion caused prolonged mitosis and several mitotic defects, such as monopolar spindle and chromosome misalignment during metaphase. Although SF3B14 was found in the nucleolar proteome database, our immunofluorescent stainings demonstrated that SF3B14 was predominantly localized in the nucleoplasm and excluded from the nucleolus during interphase. In addition, SF3B14 did not colocalize with specific mitotic structures during mitosis, which is not in line with its direct mitotic function. Notably, we found that the SF3B14 depletion reduced protein levels of TUBGCP6, required for centrosome regulation, and increased the unspliced/spliced ratio of its mRNA. Taken together, we propose that the pre-mRNA of TUBGCP6 is one of the targets for SF3B14 splicing through which SF3B14 controls mitotic chromosome behavior.

Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B.

The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.

A new deep-learning model using YOLOv3 to support sperm selection during intracytoplasmic sperm injection procedure.

Purpose: To create and evaluate a machine-learning model for YOLOv3 that can simultaneously perform morphological evaluation and tracking in a short time, which can be adapted to video data under an inverted microscope. Methods: Japanese patients who underwent intracytoplasmic sperm injection at the Jikei University School of Medicine and Keiai Reproductive and Endosurgical Clinic from January 2019 to March 2020 were included. An AI model that simultaneously performs morphological assessment and tracking was created and its performance was evaluated. Results: For morphological assessment, the sensitivity and positive predictive value (PPV) of this model for abnormal sperm were 0.881 and 0.853, respectively. The sensitivity and PPV for normal sperm were 0.794 and 0.689, respectively. For tracking performance, among the 51 objects, 40 (78.4%) were mostly tracked, 11 (21.6%) were partially tracked, and 0 (0%) were mostly lost. Conclusions: This study showed that evaluating sperm morphology while tracking in a single model is possible by training YOLO v3. This model could acquire time-series data of one sperm, which will assist in acquiring and annotating sperm image data.

[Report on a new remote collaborative medical care system -construction and operation of a remote collaborative medical care network for inflammatory bowel disease using information and communication technology in Hokkaido].

Inflammatory bowel disease (IBD) comprises 2 major types-ulcerative colitis (UC) and Crohn's disease (CD). A remote collaborative medical care fee has been established for patients with suspected intractable diseases since 2020. Remote collaborative medical care is a type of telemedicine wherein a hospital specialist for intractable diseases, the patient, and an attending physician at a community hospital communicate via video calls. In IBD cases, however, treating patients who have already been diagnosed with severe or intractable diseases is difficult. As a part of the Hokkaido Intractable Disease Medical Care System Development Project, we have started providing free remote collaborative medical care services for all IBD patients, including those with a confirmed diagnosis and attending regional hospitals. We set up the telemedicine system using Microsoft365, a commercial cloud, and Nextcloud, a PaaS, to ensure robust security and enable rapid and massive sharing of medical details by information and communication technology. Since April 2021, we have examined 27 patients (36 times). Among these patients, 5 patients from regional hospitals were undiagnosed (1 patient of suspected CD, 3 patients of suspected IBD unclassified (IBD-U), and 1 patient of undiagnosed enteritis). Twenty-two patients from regional hospitals had a confirmed diagnosis (17 UC and 5 CD patients). Eight patients required a second time remote collaborative medical care, and 1 patient required a third time remote collaborative medical care. There was no equipment failure such as communication failure or system trouble, and all patients could be examined smoothly. The maintenance cost of the telemedicine system was 2500yen/month per hospital. Among all cases receiving remote collaborative medical care, 86% were consultations for refractory or severe active cases with a confirmed diagnosis of IBD. At present, the remote collaborative medical care fee for diagnosed patients is not permitted. Since remote collaborative medical care has the potential to correct regional disparities in medical standards, there is an urgent need to review the criteria for remote collaborative medical care fees.

cnm-Positive Streptococcus mutans and diffusion-weighted imaging hyperintensities in acute intracerebral hemorrhage.

BACKGROUND: Strains of Streptococcus mutans expressing the cell surface collagen-binding protein, Cnm, encoded by cnm (cnm-positive S. mutans), are associated with hypertensive intracerebral hemorrhage (ICH) and the occurrence of cerebral microbleeds (CMBs). Small diffusion-weighted imaging (DWI) hyperintensities in patients with acute ICH are also associated with CMBs. However, the association between cnm-positive S. mutans and DWI hyperintensities is unclear. Hence, this study aimed to investigate the association between cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH. METHODS: Patients with acute ICH were prospectively registered at three hospitals. Dental plaque specimens were collected within 4 days after admission, and cnm-positive S. mutans was detected using the polymerase chain reaction. Magnetic resonance imaging at 14 ± 5 days after admission was used to evaluate DWI hyperintensities and CMBs. RESULTS: A total of 197 patients were enrolled in this study. cnm-positive S. mutans was detected in 30 patients (15.2%), and DWI hyperintensities were observed in 56 patients (28.4%). Patients with cnm-positive S. mutans had a higher frequency of DWI hyperintensities (50.0% vs 24.6%; p = 0.008) and a higher number of CMBs (5.5 vs 1.5; p < 0.001) than those without cnm-positive S. mutans. Multivariable logistic analysis revealed that the presence of cnm-positive S. mutans was independently associated with DWI hyperintensities (OR 2.38; 95% CI 1.01-5.61; p = 0.047) after adjusting for several confounding factors. CONCLUSION: This study found an association between the presence of cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.

Effects of CYP2D6 Genotypes on Venlafaxine Metabolism in Japanese Psychiatric Patients With Depression.

BACKGROUND: Venlafaxine (VEN) is primarily metabolized by CYP2D6. Although several studies have reported the significant effects of CYP2D6 on VEN and O-desmethylvenlafaxine (ODV) pharmacokinetics in Whites, limited data are available regarding the effects of the Asian-specific CYP2D6 genotype on VEN metabolism. This study evaluated the effects of the CYP2D6*10 and CYP2D6*5 genotypes on the steady-state plasma concentrations of VEN and ODV in Japanese patients. METHODS: This study included 75 Japanese patients with depression who were treated with VEN. Steady-state plasma concentrations of VEN and ODV were measured using liquid chromatography. Polymerase chain reaction was used to determine CYP2D6 genotypes. A stepwise multiple regression analysis was performed to analyze the relationship between independent variables (sex, age, smoking habit, and number of mutated alleles, CYP2D6*10 and CYP2D6*5), subject-dependent variables (plasma concentrations of VEN and ODV [all corrected for dose and body weight]), and the ODV/VEN ratio. RESULTS: Significant correlations were observed between the daily dose of VEN (corrected for body weight) and plasma concentrations of VEN (r = 0.498, P < 0.001) and ODV (r = 0.380, P = 0.001); ODV plasma concentrations were approximately 3.2 times higher than VEN plasma concentrations (VEN versus ODV = 18.60 ng/mL versus 59.10 ng/mL). VEN plasma concentrations (corrected for dose and body weight) did not differ with differing numbers of CYP2D6-mutated alleles. However, the ODV/VEN ratio decreased as the number of mutated CYP2D6 alleles increased (P = 0.001). CONCLUSIONS: This is the first study to examine the effects of CYP2D6*10 in a clinical setting. Although no effects on the plasma concentrations of VEN or ODV were observed, CYP2D6 polymorphism affects the ODV/VEN ratio. Further studies are needed to confirm the clinical relevance of these findings.

Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis.

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".

Characteristics and Prognostic Factors of Swallowing Dysfunction in Patients with Lateral Medullary Infarction.

OBJECTIVES: Lateral medullary infarction mainly impairs the pharyngeal phase of swallowing. We aimed to investigate the utility of the assessment tools of swallowing function in patients with lateral medullary infarction and to determine the factors that could predict the outcomes of swallowing function. MATERIALS AND METHODS: 15 patients with lateral medullary infarction who were admitted to Suiseikai Kajikawa Hospital between August 1, 2016, and March 31, 2020 (age 62.7 ± 14.8 years, 5 women) were enrolled in this prospective study. The diagnosis was made using brain magnetic resonance imaging. We analyzed the factors associated with severe swallowing dysfunction, which was defined as the necessity for tube feeding on the 90th day from admission, with multiple logistic regression analysis. RESULTS: Multivariate analyses identified the repetitive saliva swallowing test, modified water swallowing test, and vertical spread of stroke lesions as independent significant factors affecting severe swallowing dysfunction (p = 0.002, 0.016, and 0.011, respectively). The sub-scores of the pharyngeal phase of the Mann Assessment of Swallowing Ability were also significantly associated with severe swallowing dysfunction (p < 0.001). However, tongue pressure, severe passage pattern abnormality on videofluoroscopic examination, and vertebral artery dissection were not significantly associated with swallowing dysfunction. CONCLUSIONS: Since lateral medullary infarction presents with swallowing dysfunction mainly in the pharyngeal phase, tools that can be used to evaluate the pharyngeal phase of swallowing, such as repetitive saliva swallowing test and modified water swallowing test, are moreuseful than tongue pressure measurement.

Utility of Magnetic Resonance Spectroscopy for the Progression of Neurological Symptoms in Lenticulostriate Artery Territory Infarction.

OBJECTIVES: The present study aimed to examine the effectiveness of proton magnetic resonance spectroscopy (1HMRS) in determining the progression of neurological symptoms resulting in acute ischemic stroke in patients with lenticulostriate artery (LSA) infarction. MATERIALS AND METHODS: 1HMRS was performed within 72 h after neurological symptom onset. Voxel of interest was placed in tissue that included the pyramidal tract and identified diffusion weighted echo planar spin-echo sequence (DWI) coronal images. Infarct volume in DWI was calculated using the ABC/2 method. 1HMRS data (tNAA, tCr, Glx, tCho, and Ins) were analyzed using LCModel. Progressive neurological symptoms were defined as an increase of 1 or more in the NIHSS score. Patients who underwent 1HMRS after progressive neurological symptoms were excluded. RESULTS: In total, 77 patients were enrolled. Of these, 19 patients had progressive neurological symptoms. The patients with progressive neurological symptoms were significantly more likely to be female and had higher tCho/tCr values, higher rates of axial slices ≥ 3 slices on DWI, higher infarct volume on DWI, higher maximum diameter of infarction of axial slice on DWI, and higher SBP on admission compared to those without. Multivariable logistic analysis revealed that higher tCho/tCr values were independently associated with progressive neurological symptoms after adjusting for age, sex, and initial DWI infarct volume (tCho/tCr per 0.01 increase, OR 1.26, 95% CI 1.03-1.52, P = 0.022). CONCLUSIONS: Increased tCho/tCr score were associated with progressive neurological symptoms in patients with LSA ischemic stroke. Quantitative evaluation of 1HMRS parameters may be useful for predicting the progression of neurological symptoms.

Autophagy and Autophagy-Related Diseases: A Review.

Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.