Femoral Neck Shaft Angle Measurement for Differentiating Femoral Head Stress Fracture from Avascular Necrosis.

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.

Comparison of the Size Measurement of Gallbladder Polyps by Three Different Radiologists in Abdominal Ultrasonography.

BACKGROUND: There is little information regarding the size measurement differences in gallbladder (GB) polyps performed by different radiologists on abdominal ultrasonography (US). AIM: To reveal the differences in GB polyp size measurements performed by different radiologists on abdominal US. METHODS: From June to September 2022, the maximum diameter of 228 GB polyps was measured twice on abdominal US by one of three radiologists (a third-year radiology resident [reader A], a radiologist with 7 years of experience in abdominal US [reader B], and an abdominal radiologist with 8 years of experience in abdominal US [reader C]). Intra-reader agreements for polyp size measurements were assessed by intraclass correlation coefficient (ICC). A Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader. RESULTS: Reader A, reader B, and reader C evaluated 65, 77, and 86 polyps, respectively. The mean size of measured 228 GB polyps was 5.0 ± 1.9 mm. Except for the case where reader A showed moderate intra-reader agreement (0.726) for polyps with size ≤ 5 mm, all readers showed an overall high intra-reader reliability (reader A, ICC = 0.859; reader B, ICC = 0.947, reader C, ICC = 0.948), indicative of good and excellent intra-reader agreements. The 95% limit of agreement of reader A, B, and C was 1.9 mm of the mean in all three readers. CONCLUSIONS: GB polyp size measurement on abdominal US showed good or excellent intra-reader agreements. However, size changes of approximately less than 1.9 mm should be interpreted carefully because these may be within the measurement error.

Evaluating Aspirin's Efficacy for Primary Prevention in Cardiovascular and Cerebrovascular Disease: Insights from a Nationwide Cohort Study.

BACKGROUND: The effectiveness of aspirin for the primary prevention of cerebro-cardiovascular diseases in Koreans remains unclear. Therefore, we evaluated the preventive effects of low-dose aspirin (equal or less than 100 mg) on cerebro-cardiovascular events. METHOD: We conducted a retrospective cohort study using the National Sample Cohort dataset. From the 1,106,580 individuals eligible in 2004, we selected 200 individuals (47% male and 22.5% aged 65 or older) who consistently received low-dose aspirin from 2004 to 2013 for inclusion in the aspirin cohort. Participants for the control cohort, who did not use aspirin, were selected through propensity score matching based on variables. RESULT: We compared the incidences of endpoints (acute myocardial infarction, cerebral infarction, gastrointestinal hemorrhage, and cerebral hemorrhage) between the aspirin group and the non-aspirin group over the 9-year follow-up period. There was no significant difference in the incidence rates of acute myocardial infarction, cerebral infarction, gastrointestinal hemorrhage, or cerebral hemorrhage between the aspirin and non-aspirin groups. Low-dose aspirin for primary prevention in Koreans did not reduce myocardial or cerebral infarctions and did not increase the risk of gastrointestinal or cerebral hemorrhage. CONCLUSION: Therefore, we suggest that aspirin for primary prevention should be used cautiously and tailored to the individual's baseline cardiovascular risk.

Head and Neck Cancer: A Potential Risk Factor for Parkinson's Disease?

Head and neck cancers (HNC) are frequently associated with neurodegeneration. However, the association between HNC and Parkinson's disease (PD) remains unclear. This study aimed to clarify the relationship between HNC and subsequent PD. This retrospective study used data from a nationally representative cohort. Patients with HNC were identified based on the presence of corresponding diagnostic codes. Participants without cancer were selected using 4:1 propensity score matching based on sociodemographic factors and year of enrollment; 2296 individuals without HNC and 574 individuals with HNC were included in the study. Hazard ratios (HR) for the incidence of PD in patients with HNC were calculated using 95% confidence intervals (CI). The incidence of PD was 4.17 and 2.18 per 1000 person-years in the HNC and control groups, respectively (adjusted HR = 1.89, 95% CI = 1.08-3.33). The HNC group also showed an increased risk of subsequent PD development. The risk of PD was higher in middle-aged (55-69 years) patients with HNC and oral cavity cancer. Our findings suggest that middle-aged patients with HNC have an increased incidence of PD, specifically those with oral cavity cancer. Therefore, our findings provide new insights into the development of PD in patients with HNC.

FGFR3 drives Aß-induced tau uptake.

The amyloid cascade hypothesis suggests that amyloid beta (Aß) contributes to initiating subsequent tau pathology in Alzheimer's disease (AD). However, the underlying mechanisms through which Aß contributes to tau uptake and propagation remain poorly understood. Here, we show that preexisting amyloid pathology accelerates the uptake of extracellular tau into neurons. Using quantitative proteomic analysis of endocytic vesicles, we reveal that Aß induces the internalization of fibroblast growth factor receptor 3 (FGFR3). Extracellular tau binds to the extracellular domain of FGFR3 and is internalized by the FGFR3 ligand, fibroblast growth factor 2 (FGF2). Aß accelerates FGF2 secretion from neurons, thereby inducing the internalization of tau-attached FGFR3. Knockdown of FGFR3 in the hippocampus reduces tau aggregation by decreasing tau uptake and improving memory function in AD model mice. These data suggest FGFR3 in neurons as a novel tau receptor and a key mediator of Aß-induced tau uptake in AD.

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles.

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel-Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL's coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes.

Optimal methodology for percutaneous dilatational tracheostomy: a comparative analysis between conventional and multidisciplinary approaches utilizing ultrasound, flexible bronchoscopy, and microcatheter puncture in critically ill individuals of diminutive stature-a longitudinal single-institutional experience and retrospective analysis.

Background: Percutaneous dilatational tracheostomy (PDT), a bedside procedure in intensive care, enhances respiratory support for critically ill patients with benefits over traditional tracheostomy, such as improved safety, ease of use, cost-effectiveness, and operational efficiency by eliminating patient transfers to the operating room. It also minimizes complications including bleeding, infection, and inflammation. Despite decades of PDT evolution and device diversification, adaptations primarily cater to larger Western patients rather than smaller-statured Korean populations. This study assesses the efficacy and appropriateness of the Ciaglia Blue Rhino (Cook Critical Care, Bloomington, IN, USA), augmented with ultrasound, flexible bronchoscopy, and microcatheter techniques, for Korean patients with short stature. Methods: We conducted PDT on 183 intubated adults (128 male/55 female) with severe respiratory issues at a single medical center from January 2010 to December 2022. Patients were divided into two groups for retrospective analysis: a modified group (n=133) underwent PDT with ultrasound-guided flexible bronchoscopy and microcatheter puncture, and a conventional group (n=50) received PDT using only the Ciaglia Blue Rhino device. We assessed clinical and demographic characteristics, outcomes, and complications such as pneumothorax and emphysema. The study also evaluated the suitability and effectiveness of the devices for Korean patients with short stature. Results: Demographic characteristics including sex, body weight, height, body mass index, obesity status, and underlying diseases showed no significant differences between the two groups. However, the modified group was older (69.5±14.2 vs. 63.5±14.1 years; P=0.01). The sequential organ failure assessment (SOFA) and simplified acute physiology score (SAPS) II score was slightly higher in the modified groups, but no statistically significant differences were observed (7.1±2.3 vs. 6.7±2.3, P=0.31 and 46.7±9.0 vs. 44.0±9.1, P=0.08, respectively). The duration of hospital and ICU stays, as well as days post-PDT, were longer in the conventional group, yet these differences were not statistically significant (P=0.20, P=0.44, P=0.06). Total surgical time, including preparation, ultrasound, bronchoscopy, and microcatheter puncture, was significantly longer in the modified group (25.6±7.5 vs. 19.9±6.5 minutes; P<0.001), and the success rate of the first tracheal puncture was also higher (100.0% vs. 92.0%; P=0.006). Intra-operative bleeding was less frequent in the modified group (P=0.02 for tracheostomy site bleeding and P=0.002 for minor bleeding). Conclusions: PDT, performed at the bedside in intensive care settings, proves to be a swift and dependable method. Utilizing the Ciaglia Blue Rhino device, combined with ultrasound guidance, flexible bronchoscopy, and 4.0-Fr microcatheter puncture, PDT is especially effective for intubated patients who cannot be weaned from ventilation. This technique results in fewer complications than traditional tracheostomy and is particularly beneficial for patients with respiratory issues and smaller-statured Koreans, potentially reducing morbidity and mortality.

Mid- and Late-Life Chronic Kidney Disease Is Associated with Parkinson's Disease, Not with an Increased Risk of Alzheimer's Disease.

Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This study investigated the prospective association of patients with CKD aged ≥55 years with an increased risk of Alzheimer's or Parkinson's disease. We conducted a retrospective cohort analysis using a national cohort sample of approximately one million patients. Primary outcome indicators measured included incidence of all-cause dementia, Alzheimer's disease, and Parkinson's disease events using person-years at risk. The hazard ratio was adjusted using the Cox proportional hazards model. We included 952 patients without CKD and 476 with CKD over 55 years using propensity score matching. The CKD group exhibited higher incidences of all-cause dementia, Parkinson's disease, and Alzheimer's disease than the non-CKD group. Furthermore, the CKD group had an elevated risk of all-cause dementia and a significantly increased risk of Parkinson's disease, especially among older women. Notably, the risk of Parkinson's disease was higher within the first 3 years of CKD diagnosis. These findings emphasize the link between CKD in mid- and late-life individuals and a higher incidence of all-cause dementia and Parkinson's disease rather than Alzheimer's disease.

Virtual Golf, "Exergaming", Using Virtual Reality for Healthcare in Older Adults: Focusing on Leisure Constraints, Participation Benefits, and Continuous Participation Intention.

Exergaming, a new type of sport, combined with virtual reality, has provided new opportunities for the aging population. This study analyzed the differences in leisure constraints, participation benefits, and continuous participation intention in virtual golf (represented as an exergame) depending on the participants' ages. Data collection was conducted from August 2023 to November 2023. A quantitative research design and a convenience sampling method were employed, targeting 310 regular virtual golf participants aged 20 years or older in the Republic of Korea. For comparative analysis, the survey participants were segmented into three groups: Group 1, young adults (18-35 years); Group 2, middle-aged adults (36-55 years); and Group 3, older adults (56-69 years). To compare and analyze participation behaviors in virtual golf, the dependent variables were identified: (a) leisure constraints (four factors) to limit formation and participation in leisure; (b) participation benefits (four factors) to encourage participation in leisure; and (c) continuous participation intention (single factor) to show likelihood to participate in leisure in the future. The results revealed that the young adult group showed statistically high results for costs under leisure constraints (F = 14.949, p < 0.001, ηp2 = 0.089), and the older adult group reported statistically high results in physical (F = 9.346, p < 0.001, ηp2 = 0.057) and mental (F = 7.249, p < 0.001, ηp2 = 0.045) participation benefits and continuous participation intention (F = 6.486, p < 0.01, ηp2 = 0.041). This study confirmed that virtual golf using advanced technology brings physical and mental benefits to older people based on reasonable cost and enables continuous participation in physical activity.

Exploring the Link between Head and Neck Cancer and the Elevated Risk of Acute Myocardial Infarction: A National Population-Based Cohort Study.

Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50-1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer.

Microstructure-Based Modeling of Deformation and Damage Behavior of Extruded and Additively Manufactured 316L Stainless Steels.

In this study, we investigated the micromechanical deformation and damage behavior of commercially extruded and additively manufactured 316L stainless steels (AMed SS316L) by combining experimental examinations and crystal plasticity modeling. The AMed alloy was fabricated using the laser powder bed fusion (LPBF) technique with an orthogonal scanning strategy to control the directionality of the as-fabricated material. Optical microscopy and electron backscatter diffraction measurements revealed distinct grain morphologies and crystallographic textures in the two alloys. Uniaxial tensile test results suggested that the LPBFed alloy exhibited an increased yield strength, reduced elongation, and comparable ultimate tensile strength in comparison to those of the extruded alloy. A microstructure-based crystal plasticity model was developed to simulate the micromechanical deformation behavior of the alloys using representative volume elements based on realistic microstructures. A ductile fracture criterion based on the microscopically dissipated plastic energy on a slip system was adopted to predict the microscopic damage accumulation of the alloys during plastic deformation. The developed model could accurately predict the stress-strain behavior and evolution of the crystallographic textures in both the alloys. We reveal that the increased yield strength in the LPBFed alloy, compared to that in the extruded alloy, is attributed to the higher as-manufactured dislocation density and the cellular subgrain structure, resulting in a reduced elongation. The presence of annealing twins and favorable texture in the extruded alloy contributed to its excellent elongation, along with a higher hardening rate owing to twin-dislocation interactions during plastic deformation. Moreover, the grain morphology and defect state (e.g., dislocations and twins) in the initial state can significantly affect strain localization and damage accumulation in alloys.

Association between Head and Neck Cancer and Increased Risk of Ischemic Heart Disease: A Retrospective Cohort Study Using National Population Data.

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002-2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan-Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

The association of job training duration and risk of depression among wage workers: an analysis of the mediating factors.

Background: Research on job training and job satisfaction has been conducted from various perspectives. Job training is thought to be associated with job satisfaction, which is known as an important factor for depression among workers. We hypothesized that job training duration could influence depression through potential mediators (job satisfaction, motivation to work, and work engagement). Methods: This study encompassed participants from the sixth Korean Working Conditions Survey (KWCS), conducted between 2020 and 2021. To show the relationships between demographic or occupational characteristics and risk of depression, a χ2 test was conducted. The association between job training duration, potential mediators, and risk of depression was analyzed by constructing multiple logistic regression models. The mediating effects of potential mediators on job training duration and risk of depression was evaluated with flexible mediation analysis with weighting-based methods. Results: The final study population consisted of 25,294 participants. Longer job training duration significantly decreased risk of depression after adjusting for confounders. In the group that received the longest job training duration (≥ 10 days), compared with the group without job training, the odds ratio (OR) for high risk of depression was 0.46 (95% confidence interval [CI], 0.39-0.54). Each three potential mediators showed statistically significant indirect effects and direct effect. Although indirect effects were not strong compared to direct effect, motivation to work had the strongest mediating effect in this study, with an OR of 0.94 (95% CI, 0.92-0.95). Conclusions: Job training duration was found to have a statistically significant negative association on the risk of depression, and three mediators partially mediating this effect. Although the mechanism was unknown, our findings suggest that job training has a positive influence on workers' mental health. Furthermore, by suggesting the possibility of other pathways existing between job training and depression, we provide directions for future research.

Detection Rate of Small Pancreas Cysts and Intrareader Reliability of the Cysts Size Measurements on Transabdominal Ultrasonography.

ABSTRACT: This study aimed to assess the detection rate of small (<10 mm) pancreas cyst and intrareader reliability for cyst size measurements on transabdominal ultrasonography (US). From 2020 to 2022, 194 pancreas cysts in 173 patients, incidentally detected on computed tomography or magnetic resonance imaging, were evaluated on US by 1 of 2 radiologists (readers 1 and 2). Intrareader agreements of cyst size measurements on US were assessed by intraclass correlation coefficient (ICC). Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader. In this study, readers 1 and 2 evaluated 86 cysts in 76 patients and 108 cysts in 97 patients, respectively. Most of the cysts (191 of 194) were located in the nontail portion of the pancreas. Overall detection rate of pancreas cysts by US was 92.3% (179 of 194). The mean size of measured 179 pancreas cysts was 4.7 ± 1.5 mm. The readers showed excellent intrareader agreements (ICC = 0.925 and 0.960) for cyst size measurements, except for the cysts with size ≤5 mm, where both readers showed good intrareader agreements (ICC = 0.848 and 0.873). The 95% limits of agreement of readers 1 and 2 were 13.8% and 14.9% of the mean, respectively. Therefore, transabdominal US could be a reliable follow-up imaging modality for small (<10 mm) nontail pancreas cysts incidentally detected on computed tomography or magnetic resonance imaging, especially for the cysts with size between 5 and 10 mm. Size changes of the pancreas cysts approximately less than 15% may be within the measurement error.

Type-I-interferon-responsive microglia shape cortical development and behavior.

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.

Artificial intelligence-driven drug repositioning uncovers efavirenz as a modulator of α-synuclein propagation: Implications in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning. We used an artificial intelligence (AI)-based drug repositioning strategy to screen an extensive compound library and identify potential therapeutic agents for PD. Our AI-driven analysis revealed that efavirenz and nevirapine, approved for treating human immunodeficiency virus infection, had distinct profiles, suggesting their potential effects on PD pathophysiology. Among these, efavirenz attenuated α-synuclein (α-syn) propagation and associated neuroinflammation in the brain of preformed α-syn fibrils-injected A53T α-syn Tg mice and α-syn propagation and associated behavioral changes in the C. elegans BiFC model. Through in-depth molecular investigations, we found that efavirenz can modulate cholesterol metabolism and mitigate α-syn propagation, a key pathological feature implicated in PD progression by regulating CYP46A1. This study opens new avenues for further investigation into the mechanisms underlying PD pathology and the exploration of additional drug candidates using advanced computational methodologies.

Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (Ih) were recently identified in mature OLG and shown to play a role in regulating myelin length. Here we provide a biochemical and electrophysiological characterization of HCN channels in cells of the oligodendrocyte lineage. We observed that mice with a nonsense mutation in the Hcn2 gene (Hcn2ap/ap) have less white matter than their wild type counterparts with fewer OLG and fewer oligodendrocyte progenitor cells (OPCs). Hcn2ap/ap mice have severe motor impairments, although these deficits were not observed in mice with HCN2 conditionally eliminated only in oligodendrocytes (Cnpcre/+; Hcn2F/F). However, Cnpcre/+; Hcn2F/F mice develop motor impairments more rapidly in response to experimental autoimmune encephalomyelitis (EAE). We conclude that HCN2 channels in OLG may play a role in regulating metabolism.

Brain hypothyroidism silences the immune response of microglia in Alzheimer's disease animal model.

Thyroid hormone (TH) imbalance is linked to the pathophysiology of reversible dementia and Alzheimer's disease (AD). It is unclear whether tissue hypothyroidism occurs in the AD brain and how it affects on AD pathology. We find that decreased iodothyronine deiodinase 2 is correlated with hippocampal hypothyroidism in early AD model mice before TH alterations in the blood. TH deficiency leads to spontaneous activation of microglia in wild-type mice under nonstimulated conditions, resulting in lowered innate immune responses of microglia in response to inflammatory stimuli or amyloid-ß. In AD model mice, TH deficiency aggravates AD pathology by reducing the disease-associated microglia population and microglial phagocytosis. We find that TH deficiency reduces microglial ecto-5'-nucleotidase (CD73) and inhibition of CD73 leads to impaired innate immune responses in microglia. Our findings reveal that TH shapes microglial responses to inflammatory stimuli including amyloid-ß, and brain hypothyroidism in early AD model mice aggravates AD pathology by microglial dysfunction.