Mitochondrial bioenergetics plays a fundamental role in neuronal development and function. Prenatal exposure to corticosterone in rats (Corti.Pup) has previously been shown to cause delayed neurodevelopment and synaptic plasticity deficits, showing attention deficit hyperactivity disorder (ADHD) - like behaviors. However, the underlying mitochondrial metabolic adaptations remain unclear. This study investigated mitochondrial function and metabolic remodeling in prefrontal cortex neurons of Corti.Pups, focusing on oxidative phosphorylation, calcium handling, and redox balance. We assessed neuronal viability, reactive oxygen species (ROS) production, and oxygen consumption rate (OCR) through experiments conducted in both neuron-glia co-culture and neuron-only conditions. Furthermore, we evaluated electron transport chain (ETC) activity, mitochondrial membrane potential (MMP), and mitochondrial Ca2+ uptake in purified isolated mitochondria. In results, Corti.Pup neurons exhibited increased vulnerability to glutamate-induced excitotoxicity in the absence of glial support. Despite reduced ROS production, these neurons showed elevated mitochondrial OCR and proton leak, coupled with decreased non-mitochondrial OCR and ETC complex activity. Surprisingly, MMP remained elevated despite ETC dysfunction, and mitochondrial Ca2+ uptake was suppressed. These features indicate mitochondrial metabolic reprogramming, prioritizing MMP maintenance over ATP synthesis. The observed mitochondrial inefficiency and compensatory adaptations may impair energy production, contributing to delayed neuronal development in Corti.Pups. These findings suggest that mitochondrial dysfunction and metabolic remodeling play central roles in the pathogenesis of neurodevelopmental disorders such as ADHD.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Background and Objectives: This study introduced and evaluated the efficacy of an ultrasonic bony aspirator (UBA) in revision endoscopic sinus surgery and compared the outcomes to those of the traditional cold instrument approach. Methods: This retrospective study enrolled 57 patients who underwent revision endoscopic sinus surgery between June 2010 and December 2017, 17 patients with a UBA approach and 40 patients with traditional instruments. Results: Median Lund–Kennedy scores showed a statistically significant difference between the two groups at 3 months (p=0.004). Synechiae occurred in 17.6% and 35% of cases in the UBA and traditional groups, respectively. The mean operative time was significantly shorter in the traditional group (p=0.001). Conclusion The use of a UBA in revision endoscopic sinus surgery was safe and effective.

Determining blood loss [100% – RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1 , Hct2 ) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2 ) – 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague–Dawley rats by withdrawing 20.0%–60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct 2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2 ) – 1]. Seven rats losing 30.0%–60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2 ) – 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14–8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N.Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

Background: The importance of infection with COVID-19 is being emphasized in dentistry with high risks such as aerosols. The purpose of this study is to investigate the knowledge and practice of infection control, stress and coping, and turnover of dental hygienists. Methods: Questionnaire was conducted knowledge and practice of infection control, occupational stress and coping, turnover. Survey data was investigated about 149 dental hygienists from February to March 2021 Data were analyzed t-test, ANOVA, Pearson’s correlation using statistical programs of PASW Statistics ver. 21.0. Results: Regarding occupational stress, relationship conflict was higher in the group with less than 2 years of experience (p＜0.05). Job anxiety, organizational system, inadequate compensation, and workplace culture were highly surveyed in the 3 to 5 year of experience. The group with more than 6 years of experience had the highest perception of lack of job autonomy (p＜0.05). The group with higher knowledge of infection control had lower mean inappropriate rewards and stress (p＜0.05). The group with high infection control performance had a lower average in items such as job instability, organizational system, inadequate compensation, workplace culture, and stress. And problem-focused coping ability was found to be high (p＜0.05). Infection control knowledge and performance were positively correlated (r=0.251, p＜0.01), infection control practice and stress were negatively correlated (r=−0.264, p＜0.01), and stress and emotional coping were positively correlated (r=0.367, p＜0.01). Stress was positively correlated with turnover rate (r=0.549, p＜0.01). Conclusion Infection control training was required to reduce occupational stress. Occupational stress was highly correlated with turnover, a holistic and systemic organizational operation and improvement of the quality of medical care were required to reduce stress.

A substantial portion of gout patients have normal serum urate levels during an acute attack but data on the clinical characteristics and risk of recurrence compared with hyperuricemic patients are limited. Methods: In this retrospective cohort study, clinical features of normouricemic and hyperuricemic patients were compared. Multivariate analysis was performed to determine whether normouricemic patients were less likely to have a recurrent attack. Results: Among a total of 221 gout patients, 88 (39.8%) had normouricemia during an acute attack. Postsurgical gout (22.7% vs. 6.0%, p < 0.001), hemodialysis initiation (9.1% vs. 2.3%, p = 0.029) and inflammatory activity were higher in normouricemic patients than in hyperuricemic patients. The frequency of renal insufficiency was lower in normouricemic patients (25.0% vs. 53.4%, p < 0.001). However, the recurrence rate of gout attack was not different between the two groups (24.7% vs. 33.0%, p = 0.220). In multivariate analysis, female sex, history of urinary stone, presence of tophi, and use of thiazide were associated with increase of recurrent gout attack, but not with serum urate status during an acute attack (hazard ratio, 1.075; 95% confidence interval, 0.972 to 1.190; p = 0.159). Conclusions: Normouricemia during an acute gout attack was more frequently observed in postsurgical episodes, hemodialysis initiation and patients with preserved renal function. While higher inflammatory activity was observed in normouricemic patients, recurrent attack was not associated with serum urate levels during an acute attack. Thus, careful follow-up should be considered in gout patients regardless of serum urate levels during an acute attack.