T-plastin contributes to epithelial-mesenchymal transition in human lung cancer cells through FAK/AKT/Slug axis signaling pathway.

T-plastin (PLST), a member of the actin-bundling protein family, plays crucial roles in cytoskeletal structure, regulation, and motility. Studies have shown that the plastin family is associated with the malignant characteristics of cancer, such as circulating tumor cells and metastasis, by inducing epithelialmesenchymal transition (EMT) in various cancer cells. However, the role of PLST in the EMT of human lung cancer cells remains unclear. In this study, we observed that PLST overexpression enhanced cell migratory and invasive abilities, whereas its downregulation resulted in their suppression. Moreover, PLST expression levels were associated with the expression patterns of EMT markers, including E-cadherin, vimentin, and Slug. Furthermore, the phosphorylation levels of focal adhesion kinase (FAK) and AKT serine/threonine kinase (AKT) were dependent on PLST expression levels. These findings indicate that PLST induces the migration and invasion of human lung cancer cells by promoting Slug-mediated EMT via the FAK/AKT signaling pathway. [BMB Reports 2024; 57(6): 305-310].

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

Pregnancy outcomes of cerclage in twin gestations: a multicenter retrospective cohort study.

OBJECTIVES: To determine the effects of cerclage on twin pregnancies. METHODS: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records. RESULTS: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group (n = 127) and the CL >2.5 cm group (n = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11-2.87; p = .016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30-0.82; p value = .006). CONCLUSIONS: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design.

Radiation dose during transarterial chemoembolization and associated factors.

PURPOSE: To provide detailed reports on radiation doses during transarterial chemoembolization (TACE) in the cone-beam computed tomography (CBCT) era and to identify the associated factors. METHODS: This retrospective study included 385 consecutive patients who underwent initial conventional TACE for hepatocellular carcinoma (HCC) between January 2016 and December 2017. In most cases, CBCT was performed at the common hepatic artery or celiac axis to confirm the location of the tumor and the three-dimensional hepatic artery anatomy. Superselective TACE was performed for all technically feasible cases. Information on total dose area product (DAP), total cumulative air kerma (CAK), fluoroscopy time, and DAP and CAK of each digital subtraction angiography (DSA) and CBCT scan was recorded. Multiple linear regression analysis was performed to identify the factors associated with increased DAP during TACE. RESULTS: The mean values of total DAP and CAK were 165.2 ± 81.2 (Gy·cm²) and 837.1 ± 571.0 (mGy), respectively. The mean fluoroscopy time was 19.1 ± 10.3 min. The mean DAP caused by fluoroscopy, DSA, and CBCT was 51.8 ± 43.9, 28.0 ± 24.1, and 83.9 ± 42.1 Gy·cm², respectively. Male sex, a high body mass index, largest tumor size > 3 cm, presence of aberrant right and left hepatic arteries, and superselective TACE were identified as independent predictors of increased total DAP during TACE. CONCLUSION: We were able to provide detailed reports on radiation doses during TACE and associated factors.

Computed tomographic evaluation of portal vein indices in cats with the extrahepatic portosystemic shunts.

IMPORTANCE: The portal vein to aorta (PV/Ao) ratio is used to assess the clinical significance of extrahepatic portosystemic shunt (EHPSS). Previous studies using computed tomography (CT) were conducted in dogs but not in cats. OBJECTIVE: This study aimed to establish normal reference values for PV indices (PV/Ao ratio and PV diameter) in cats and determine the usefulness of these for predicting symptomatic EHPSS. METHODS: This study included 95 dogs and 114 cats that underwent abdominal CT. The canine normal (CN) group included dogs without EHPSS. The cats were classified into feline normal (FN, 88/114), feline asymptomatic (FA, 16/114), and feline symptomatic (FS, 10/114) groups. The PV and Ao diameters were measured in axial cross-sections. RESULTS: The group FN had a higher PV/Ao ratio than the group CN (p < 0.001). Within the feline groups, the PV indices were in the order FN > FA > FS (both p < 0.001). The mean PV diameter and PV/Ao ratio for group FN were 5.23 ± 0.77 mm and 1.46 ± 0.19, respectively. The cutoff values between groups FN and FS were 4.115 mm for PV diameter (sensitivity, 100%; specificity, 97.7%) and 1.170 for PV/Ao ratio (90%, 92.1%). The cutoff values between group FA and FS were 3.835 mm (90%, 93.8%) and 1.010 (70%, 100%), respectively. CONCLUSIONS AND RELEVANCE: The results demonstrated significant differences in PV indices between dogs and cats. In cats, the PV/Ao ratio demonstrated high diagnostic performance for symptomatic EHPSS. The PV diameter also performed well, in contrast to dogs.

Assessment of TP53 and CDKN2A status as predictive markers of malignant transformation of sinonasal inverted papilloma.

The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status.

The Anti-Inflammatory Effect of SDF-1 Derived Peptide on Porphyromonas gingivalis Infection via Regulation of NLRP3 and AIM2 Inflammasome.

(1) Background: Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major etiologic agent of periodontitis and activates the NLR family pyrin domain containing 3 (NLRP3) but is absent in melanoma 2 (AIM2) inflammasomes, resulting in pro-inflammatory cytokine release. (2) Methods: We examined the anti-inflammatory effects of 18 peptides derived from human stromal cell-derived factor-1 (SDF-1) on THP-1 macrophages. Inflammation was induced by P. gingivalis, and the anti-inflammatory effects were analyzed using molecular biological techniques. In a mouse periodontitis model, alveolar bone resorption was assessed using micro-CT. (3) Results: Of the 18 SDF-1-derived peptides, S10 notably reduced IL-1ß and TNF-α secretion. S10 also diminished the P. gingivalis-induced expression of NLRP3, AIM2, ASC (apoptosis-associated speck-like protein), caspase-1, and IL-1ß. Furthermore, S10 attenuated the enhanced TLR (toll-like receptor) signaling pathway and decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). In addition, S10 mitigated alveolar bone loss in our P. gingivalis-induced mouse model of periodontitis. (4) Conclusions: S10 suppressed TLR/NF-κB/NLRP3 inflammasome signaling and the AIM2 inflammasome in our P. gingivalis-induced murine periodontitis model, which suggests that it has potential use as a therapeutic treatment for periodontitis.

Impact of fucosyltransferase 1-mediated epidermal blood group antigen H on anti-inflammatory response in atopic dermatitis.

The presence of the blood group H2 antigen on the membrane of red blood cells determines blood type O in individuals and this H2 antigen serves as a precursor to the A and B antigens expressed in blood types A and B, respectively. However, the specific involvement of ABH antigens in skin diseases is unknown. Therefore, we aim to investigate the expression of ABH antigens in skin tissue of patients with atopic dermatitis (AD) and MC903-induced AD-like mice. We demonstrated that the expression of ABH antigen is primarily located in the granular and horny layers of the skin in healthy control individuals. However, in patients with AD, the expression of the ABH antigen was absent or diminished in these layers, while the H2 antigen expression increased in the spinous layers of the affected skin lesions. Then, we investigated the biological function of blood group H antigen mediated by fucosyltransferase 1 (Fut1) in the skin, utilizing an AD mouse model induced by MC903 in wild-type (WT) and Fut1-knockout mice. After the application of MC903, Fut1-deficient mice, with no H2 antigen expression on their skin, exhibited more severe clinical signs, increased ear swelling, and elevated serum IgE levels compared with those of WT mice. Additionally, the MC903-induced thickening of both the epidermis and dermis was more pronounced in Fut1-deficient mice than that in WT mice. Furthermore, Fut1-deficient mice showed a significantly higher production of interleukin-4 (IL-4) and IL-6 in skin lesions compared with that of their WT counterparts. The expression of chemokines, particularly Ccl2 and Ccl8, was notably higher in Fut1-deficient mice compared with those of WT mice. The infiltration of CD4+ T cells, eosinophils, and mast cells into the lesional skin was significantly elevated in Fut1-deficient mice compared with that in WT mice. These findings demonstrate the protective role of H2 antigen expression against AD-like inflammation and highlight its potential therapeutic impact on AD through the regulation of blood group antigens.

Emergency cesarean section of a patient with refractory status epilepticus: A case report of challenges during anesthesia.

INTRODUCTION: Maternal epilepsy is a critical condition that can significantly affect mothers and fetuses. Notably, the admission of a laboring mother with uncontrolled refractory status epilepticus (RSE) to the operating room presents a challenging scenario for anesthesiologists. THE MAIN SYMPTOMS OF THE PATIENT AND THE IMPORTANT CLINICAL FINDINGS: A 30-year-old primigravida was transferred to the operating room for an emergency cesarean section. Cesarean section was performed after a provisional diagnosis of preeclampsia was made. THE MAIN DIAGNOSES, THERAPEUTIC INTERVENTIONS, AND OUTCOMES: Cesarean section was performed under general anesthesia. During the postoperative period, the patient exhibited no seizure activity in the brain; however, she experienced mild cognitive dysfunction for up to 6 months postdelivery. The neonate were discharged without any complications. CONCLUSION: Inducing anesthesia in pregnant women with ongoing seizure activity are challenging; however, anesthesiologists provide judgment based on the balance between the safety of the mother and fetus and the balance between patient monitoring and the progression of anesthesia. This challenge can be addressed through multidisciplinary collaboration.

Climate temperature and seasonal influences on the prevalence of temporomandibular disorders in South Korea.

This study aimed to explore seasonal variations in temporomandibular disorder (TMD) prevalence in South Korea, utilizing nationwide population-based big data. Data corresponding to the Korean Standard Classification of Diseases code of K07.6, which identifies TMD, were extracted from the Health Insurance Review and Assessment Service online platform for the period from 2010 to 2022. Additionally, we integrated these data with climate temperature records from the Korean Meteorological Administration. We subsequently conducted a statistical analysis of TMD patient data on a monthly and seasonal basis over the past 13 years to assess prevalence. Over the past 13 years, the number of TMD patients in Korea has steadily increased. The prevalence of TMD rose from 0.48% (224,708 out of a total population of 50,515,666) in 2010 to 0.94% (482,241 out of a total population of 51,439,038) in 2022, marking a 1.96-fold increase. Among children under 10 years of age, no significant differences were observed in TMD prevalence between boys and girls. However, a distinct female predominance emerged after the age of 10, with an average female-to-male ratio of 1.51:1. The peak prevalence of TMD occurred in individuals in their 20 s, followed by adolescents in their late 10 s. The majority of TMD patients were concentrated in Seoul and Gyeonggi province, with metropolitan areas accounting for 50% of the total patient count. Seasonally, TMD patient numbers showed no significant increase in winter compared with spring or summer. The temperature difference, defined as the absolute difference between the highest and lowest temperatures for each month, showed a positive correlation with TMD patient counts. A greater temperature difference was associated with higher patient counts. The strongest correlation between temperature differences and TMD patient numbers was observed in winter (r = 0.480, p < 0.01), followed by summer (r = 0.443, p < 0.01), and spring (r = 0.366, p < 0.05). Temperature differences demonstrated a significantly stronger correlation with the increase in the number of TMD patients than absolute climate temperatures. This aspect should be a key consideration when examining seasonal trends in TMD prevalence in South Korea.

Clinical Validation of Artificial Intelligence-Powered PD-L1 Tumor Proportion Score Interpretation for Immune Checkpoint Inhibitor Response Prediction in Non-Small Cell Lung Cancer.

PURPOSE: Evaluation of PD-L1 tumor proportion score (TPS) by pathologists has been very impactful but is limited by factors such as intraobserver/interobserver bias and intratumor heterogeneity. We developed an artificial intelligence (AI)-powered analyzer to assess TPS for the prediction of immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The AI analyzer was trained with 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSIs) stained by 22C3 pharmDx immunohistochemistry. The clinical performance of the analyzer was validated in an external cohort of 430 WSIs from patients with NSCLC. Three pathologists performed annotations of this external cohort, and their consensus TPS was compared with AI-based TPS. RESULTS: In comparing PD-L1 TPS assessed by AI analyzer and by pathologists, a significant positive correlation was observed (Spearman coefficient = 0.925; P < .001). The concordance of TPS between AI analyzer and pathologists according to TPS ≥50%, 1%-49%, and <1% was 85.7%, 89.3%, and 52.4%, respectively. In median progression-free survival (PFS), AI-based TPS predicted prognosis in the TPS 1%-49% or TPS <1% group better than the pathologist's reading, with the TPS ≥50% group as a reference (hazard ratio [HR], 1.49 [95% CI, 1.19 to 1.86] v HR, 1.36 [95% CI, 1.08 to 1.71] for TPS 1%-49% group, and HR, 2.38 [95% CI, 1.69 to 3.35] v HR, 1.62 [95% CI, 1.23 to 2.13] for TPS <1% group). CONCLUSION: PD-L1 TPS assessed by AI analyzer correlates with that of pathologists, with clinical performance also being comparable when referenced to PFS. The AI model can accurately predict tumor response and PFS of ICI in advanced NSCLC via assessment of PD-L1 TPS.

The hatred of all against all? Evidence from online community platforms in South Korea.

BACKGROUND: Over several years of recent efforts to make sense and detect online hate speech, we still know relatively little about how hateful expressions enter online platforms and whether there are patterns and features characterizing the corpus of hateful speech. OBJECTIVE: In this research, we introduce a new conceptual framework suitable for better capturing the overall scope and dynamics of the current forms of online hateful speech. METHODS: We adopt several Python-based crawlers to collect a comprehensive data set covering a variety of subjects from a multiplicity of online communities in South Korea. We apply the notions of marginalization and polarization in identifying patterns and dynamics of online hateful speech. RESULTS: Our analyses suggest that polarization driven by political orientation and age difference predominates in the hateful speech in most communities, while marginalization of social minority groups is also salient in other communities. Furthermore, we identify a temporal shift in the trends of online hate from gender to age based, reflecting the changing sociopolitical conditions within the polarization dynamics in South Korea. CONCLUSION: By expanding our understanding of how hatred shifts and evolves in online communities, our study provides theoretical and practical implications for both researchers and policy-makers.

Influence of Dietary Polyunsaturated Fatty Acid Intake on Potential Lipid Metabolite Diagnostic Markers in Renal Cell Carcinoma: A Case-Control Study.

Non-invasive diagnostics are crucial for the timely detection of renal cell carcinoma (RCC), significantly improving survival rates. Despite advancements, specific lipid markers for RCC remain unidentified. We aimed to discover and validate potent plasma markers and their association with dietary fats. Using lipid metabolite quantification, machine-learning algorithms, and marker validation, we identified RCC diagnostic markers in studies involving 60 RCC and 167 healthy controls (HC), as well as 27 RCC and 74 HC, by analyzing their correlation with dietary fats. RCC was associated with altered metabolism in amino acids, glycerophospholipids, and glutathione. We validated seven markers (l-tryptophan, various lysophosphatidylcholines [LysoPCs], decanoylcarnitine, and l-glutamic acid), achieving a 96.9% AUC, effectively distinguishing RCC from HC. Decreased decanoylcarnitine, due to reduced carnitine palmitoyltransferase 1 (CPT1) activity, was identified as affecting RCC risk. High intake of polyunsaturated fatty acids (PUFAs) was negatively correlated with LysoPC (18:1) and LysoPC (18:2), influencing RCC risk. We validated seven potential markers for RCC diagnosis, highlighting the influence of high PUFA intake on LysoPC levels and its impact on RCC occurrence via CPT1 downregulation. These insights support the efficient and accurate diagnosis of RCC, thereby facilitating risk mitigation and improving patient outcomes.

UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice.

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.

An exploratory clinical trial of preoperative non-invasive localization before breast-conserving surgery using augmented reality technology.

PURPOSE: This single-center, randomized, prospective, exploratory clinical trial was conducted to assess the clinical efficacy of an augmented reality (AR)-based breast cancer localization imaging solution for patients with breast cancer. METHODS: This clinical trial enrolled 20 women who were diagnosed with invasive breast cancer between the ages of 19 and 80, had a single lesion with a diameter ≥ 5 mm but ≤ 30 mm, had no metastases to other organs, and had not received prior chemotherapy. All patients underwent mammography, ultrasound, computed tomography, and magnetic resonance imaging for preoperative assessment. Patients were randomly assigned to ultrasound-guided skin marking localization (USL) and AR-based localization (ARL) groups (n = 10 in each group). Statistical comparisons between USL and ARL groups were made based on demographics, radiologic features, pathological outcomes, and surgical outcomes using chi-square and Student t-tests. RESULTS: Two surgeons performed breast-conserving surgery on 20 patients. Histopathologic evaluation of all patients confirmed negative margins. Two independent pathologists evaluated the marginal distances, and there were no intergroup differences in the readers' estimates (R1, 6.20 ± 4.37 vs. 5.04 ± 3.47, P = 0.519; R2, 5.10 ± 4.31 vs. 4.10 ± 2.38, P = 0.970) or the readers' average values (5.65 ± 4.19 vs. 4.57 ± 2.84, P = 0.509). In comparing the tumor plane area ratio, there was no statistically significant difference between the two groups in terms of either reader's mean values (R1, 15.90 ± 9.52 vs. 19.38 ± 14.05, P = 0.525; R2, 15.32 ± 9.48 vs. 20.83 ± 12.85, P = 0.290) or the overall mean values of two readers combined (15.56 ± 9.11 vs. 20.09 ± 13.38, P = 0.388). Convenience, safety, satisfaction, and reusability were all superior in the AR localization group (P < 0.001) based on the two surgeons' responses. CONCLUSION: AR localization is an acceptable alternative to ultrasound-guided skin marking with no significant differences in surgical outcomes.

Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes.

BACKGROUND/AIMS: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. METHODS: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. RESULTS: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the ß-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the ß-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05). CONCLUSION: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.

Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle-wasting disorder. Although many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential can be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations can identify treatments for clinical success. Here, we report the generation of a DMD mouse model with a CRISPR-induced deletion within exon 62 of the dystrophin gene (Dmd) and the first generated in BALB/c mice. Analysis of mice at 3, 6 and 12 months of age confirmed loss of expression of the dystrophin protein isoform Dp427 and resultant dystrophic pathology in limb muscles and the diaphragm, with evidence of centrally nucleated fibers, increased inflammatory markers and fibrosis, progressive decline in muscle function, and compromised trabecular bone development. The BALB/c.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, compared with those of existing models. It represents an important addition to the preclinical model toolbox for developing therapeutic strategies.

Comparison of the performance of MiSeq and NovaSeq in oral microbiome study.

Objective: Next generation sequencing is commonly used to characterize the microbiome structure. MiSeq is most commonly used to analyze the microbiome due to its relatively long read length. Illumina also introduced the 250 × 2 chip for NovaSeq. The purpose of this study was to compare the performance of MiSeq and NovaSeq in the context of oral microbiome study. Methods: Total read count, read quality score, relative bacterial abundance, community diversity, and correlation between two platforms were analyzed. Phylogenetic trees were analyzed for Streptococcus and periodontopathogens. Results: NovaSeq produced significantly more read counts and assigned more operational taxonomic units (OTUs) compared to MiSeq. Community diversity was similar between MiSeq and NovaSeq. NovaSeq were able to detect more unique OTUs compared to MiSeq. When phylogenetic trees were constructed for Streptococcus and periodontopathogens, both platforms detected OTUs for most of the clades. Conclusion: Taken together, while both MiSeq and NovaSeq platforms effectively characterize the oral microbiome, NovaSeq outperformed MiSeq in terms of read counts and detection of unique OTUs, highlighting its potential as a valuable tool for large scale oral microbiome studies.

Microbial Profiles in Oral Lichen Planus: Comparisons with Healthy Controls and Erosive vs. Non-Erosive Subtypes.

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.