[Normal Development and Variants in Pediatric Bone]. / 소아 뼈의 ì •ìƒ 발달과 변이.

Normal variants refer to imaging findings that are generally asymptomatic and discovered incidentally, yet may exhibit findings similar to those observed in pathological conditions. Recognizing normal variants in pediatric bone requires comprehension of the developmental process of long tubular bones and secondary ossification centers. Familiarity with various radiological findings of normal variants can prevent unnecessary follow-up imaging tests, as well as incorrect diagnosis and treatment. In this review, we will discuss the characteristic imaging findings of normal variants seen in growing pediatric bones, along with strategies for distinguishing them from pathologic conditions.

A derivative of 3-(1,3-diarylallylidene)oxindoles inhibits dextran sulfate sodium-induced colitis in mice.

BACKGROUND: IA-0130 is a derivative of 3-(1,3-diarylallylidene)oxindoles, which is a selective estrogen receptor modulator (SERM). A previous study demonstrated that SERM exhibits anti-inflammatory effects on colitis by promoting the anti-inflammatory phenotype of monocytes in murine colitis. However, the therapeutic effects of oxindole on colitis remain unknown. Therefore, we evaluated the efficacy of IA-0130 on dextran sulfate sodium (DSS)-induced mouse colitis. METHODS: The DSS-induced colitis mouse model was established by administration of 2.5% DSS for 5 days. Mice were orally administered with IA-0130 (0.01 mg/kg or 0.1 mg/kg) or cyclosporin A (CsA; 30 mg/kg). Body weight, disease activity index score and colon length of mice were calculated and histological features of mouse colonic tissues were analyzed using hematoxylin and eosin staining. The expression of inflammatory cytokines and tight junction (TJ) proteins were analyzed using quantitative real-time PCR and enzyme-linked immunosorbent assay. The expression of interleukin-6 (IL-6) signaling molecules in colonic tissues were investigated using Western blotting and immunohistochemistry (IHC). RESULTS: IA-0130 (0.1 mg/kg) and CsA (30 mg/kg) prevented colitis symptom, including weight loss, bleeding, colon shortening, and expression of pro-inflammatory cytokines in colon tissues. IA-0130 treatment regulated the mouse intestinal barrier permeability and inhibited abnormal TJ protein expression. IA-0130 down-regulated IL-6 expression and prevented the phosphorylation of signaling molecules in colonic tissues. CONCLUSIONS: This study demonstrated that IA-0130 suppressed colitis progression by inhibiting the gp130 signaling pathway and expression of pro-inflammatory cytokines, and maintaining TJ integrity.

A Tailored Intervention for Improving Diabetes Self-care Among Adults With Visual Impairment: A Pilot Study.

OBJECTIVES: Our aim in this study was to develop and evaluate a tailored intervention for improving diabetes self-care among people with visual impairment (TID-VI) in South Korea. METHODS: The TID-VI program was designed around the barriers, resources, and perceptual factors to promote diabetes self-care in those with visual impairment (VI). A single-arm pilot study was conducted to evaluate the feasibility and preliminary effects of the intervention. Diabetes self-efficacy, self-care behaviours, depression, health-related quality of life, and clinical outcomes (fasting blood glucose, glycated hemoglobin [A1C], lipids, and blood pressure) were measured before, and up to 2 months after the 12-week intervention. RESULTS: All 14 participants completed TID-VI. Diabetes self-efficacy, diabetes self-care behaviours, depression, and health-related quality of life showed improvement from baseline that was sustained at 2 months. Although high- and low-density lipoprotein also improved, there were no differences in blood glucose, A1C, total cholesterol, or blood pressure at 2 months. CONCLUSIONS: A theory-driven, tailored intervention specific to the needs of adults with VI can produce substantial improvements in patient-reported quality of life and health status outcomes, although the benefits are yet to be confirmed in a controlled study.

Improvement of Transfusion Practice in Cardiothoracic Surgery Through Implementing a Patient Blood Management Program.

Background: In this study, we examined the impact of a patient blood management (PBM) program on red blood cell (RBC) transfusion practices in cardiothoracic surgery. Methods: The PBM program had 3 components: monitoring transfusions through an order communication system checklist, educating the medical team about PBM, and providing feedback to ordering physicians on the appropriateness of transfusion. The retrospective analysis examined changes in the hemoglobin levels triggering transfusion and the proportions of appropriate RBC transfusions before, during, and after PBM implementation. Further analysis was focused on patients undergoing cardiac surgery, with outcomes including 30-day mortality, durations of intensive care unit and hospital stays, and rates of pneumonia, sepsis, and wound complications. Results: The study included 2,802 patients admitted for cardiothoracic surgery. After the implementation of PBM, a significant decrease was observed in the hemoglobin threshold for RBC transfusion. This threshold dropped from 8.7 g/dL before PBM to 8.3 g/dL during the PBM education phase and 8.0 g/dL during the PBM feedback period. Additionally, the proportion of appropriate RBC transfusions increased markedly, from 23.9% before PBM to 34.9% and 58.2% during the education and feedback phases, respectively. Among the 381 patients who underwent cardiac surgery, a significant reduction was noted in the length of hospitalization over time (p<0.001). However, other clinical outcomes displayed no significant differences. Conclusion: PBM implementation effectively reduced the hemoglobin threshold for RBC transfusion and increased the rate of appropriate transfusion in cardiothoracic surgery. Although transfusion practices improved, clinical outcomes were comparable to those observed before PBM implementation.

Influence of frailty status on the health-related quality of life in older patients with chronic low back pain: a retrospective observational study.

PURPOSE: Understanding the influence of frailty on health-related quality of life (HRQoL) in older individuals experiencing chronic low back pain can provide valuable insights into the impact of frailty. Therefore, the aim of our study is to assess how different frailty statuses among older outpatients with chronic low back pain affect their HRQoL. METHODS: Patients aged 60 and above with chronic low back pain were recruited from March 2022 to February 2023. Frailty was assessed via the frailty phenotype questionnaire, and HRQoL was evaluated using the EQ-5D-5L. Multiple regression models were used to explore the influence of frailty status on the EQ-5D-5L index and EQ-VAS. Logistic regression was used to determine odds ratios for the impact of frailty status on belonging to the lowest EQ-5D-5L index quartile. RESULTS: A total of 1,054 participants were classified into robust (29.8%), pre-frail (47.7%), and frail (22.5%) groups. Frailty was significantly associated with declining HRQoL. Pre-frail and frail statuses were inversely linked to the EQ-5D-5L index, with significantly higher odds of scoring in the lowest quartile compared to robust individuals. Stratification analysis identified sex as an effect modifier, emphasizing a more substantial association between frailty and the lowest EQ-5D-5L index quartile in female patients. CONCLUSIONS: A significant association exists between frailty and reduced HRQoL in patients with chronic low back pain. This association was predominant in female patients. Furthermore, considering the dynamic nature of frailty, early detection and effective interventions targeting pre-frailty are essential to delaying the transition to full frailty and improving HRQoL.

Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1ß.

IL-1ß is an important cytokine implicated in the progression of inflammatory bowel disease (IBD) and intestinal barrier dysfunction. The polyphenolic compound, geraniin, possesses bioactive properties, such as antitumor, antioxidant, anti-inflammatory, antihypertensive, and antiviral activities; however, its IL-1ß-targeted anticolitis activity remains unclear. Here, we evaluated the inhibitory effect of geraniin in IL-1ß-stimulated Caco-2 cells and a dextran sulfate sodium (DSS)-induced colitis mouse model. Geraniin blocked the interaction between IL-1ß and IL-1R by directly binding to IL-1ß and inhibited the IL-1ß activity. It suppressed IL-1ß-induced intestinal tight junction damage in human Caco-2 cells by inhibiting IL-1ß-mediated MAPK, NF-kB, and MLC activation. Moreover, geraniin administration effectively reduced colitis symptoms and attenuated intestinal barrier injury in mice by suppressing elevated intestinal permeability and restoring tight junction protein expression through the inhibition of MAPK, NF-kB, and MLC activation. Thus, geraniin exhibits anti-IL-1ß activity and anticolitis effect by hindering the IL-1ß and IL-1R interaction and may be a promising therapeutic anti-IL-1ß agent for IBD treatment.

Long-term results of atrial fibrillation surgery concomitant with mitral valve surgery: A propensity score-matched multicenter study.

OBJECTIVE: The aim of the study was to elucidate the long-term outcomes of atrial fibrillation surgery in patients with atrial fibrillation and mitral valve disease by comparing the patients who underwent mitral valve surgery with and without atrial fibrillation surgery. METHODS: Between 2005 and 2017, 2680 patients with atrial fibrillation who underwent mitral valve surgery (mitral valve surgery with atrial fibrillation surgery, n = 1841; mitral valve surgery without atrial fibrillation surgery, n = 839) at 5 centers were included. After propensity score matching, 1442 patients were extracted (atrial fibrillation surgery group, n = 721; non-atrial fibrillation surgery group, n = 721). All-cause mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, stroke or transient ischemic attack, and permanent pacemaker implantation were compared between the atrial fibrillation surgery and non-atrial fibrillation surgery groups. RESULTS: Overall survivals at 5 and 10 years postoperatively were 91.0% and 80.7% in the atrial fibrillation surgery group and 86.5% and 75.9% in the non-atrial fibrillation surgery group, respectively (P = .013). Cardiac mortality-free survivals at 5 and 10 years postoperatively were 96.9% and 91.7% in the atrial fibrillation surgery group and 90.9% and 83.7% in the non-atrial fibrillation surgery group, respectively (P < .001). Cumulative incidence of reoperation, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack was lower in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group up to 15 years postoperatively (P = .010, P < .001, and P = .012, respectively). Cumulative incidence of permanent pacemaker implantation was higher in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group (P < .001). CONCLUSIONS: In patients with atrial fibrillation and mitral valve disease, mitral valve surgery concomitant with atrial fibrillation surgery was associated with lower mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack up to 15 years after surgery when compared with mitral valve surgery without atrial fibrillation surgery.

Silent struggles to self-manage high blood pressure among deaf sign language users: a qualitative study.

AIMS: Tailored self-management support of hypertension, considering language and communication, is important for minorities, specifically in the deaf community. However, little is known about the experiences of hypertension self-management in deaf individuals who use sign language. This study aimed to explore the factors and processes of self-management in deaf sign language users with hypertension. METHODS AND RESULTS: Ten men and women who used sign language participated in this study. Data were collected using in-depth personal interviews conducted in the presence of a sign language interpreter between November 2022 and February 2023. All interviews were recorded and transcribed for conventional content analysis. Qualitative analyses identified four categories related to the self-management of hypertension among participants: personal factors (chronic hand pain, unique language and communication, and efforts to turn crisis into opportunities), family and socioeconomic factors (family support and financial burden of living), challenges (limited health literacy and alienation from health education), and desire for health education considering the deaf community. CONCLUSION: The results of this study suggest that family support, socioeconomic status, hand pain, and health literacy should be considered for the planning and development of health education on self-management of hypertension in deaf individuals. In addition, this health education requires cooperation with qualified sign language interpreters in healthcare settings.

Facet-Controlled Growth of Hydroxyapatite for Effectively Removing Pb from Aqueous Solutions.

To address the growing concerns regarding severe water pollution, effective and environmentally friendly adsorbents must be identified. In this study, we prepared hydroxyapatite (HAp, Ca10(PO4)6(OH)2) as an eco-friendly absorbent via simple precipitation and obtained rod- (r-HAp) and plate-shaped HAp (p-HAp). The approach to obtaining p-HAp involved a low pH titration rate, promoting growth along the c-axis due to the adsorption of OH- on the (110) facet. Conversely, r-HAp was obtained by maintaining a high concentration of OH- during the initial stage through rapid pH titration, leading to a stronger restrictive effect on the growth of positively charged a(b)-planes. p-HAp demonstrated superior adsorption capacity, removing Pb through dissolution and recrystallization, achieving an impressive 625 mg/g within a 60 min reaction time compared to r-HAp. Our findings afford insights into the Pb removal mechanisms of HAp with different morphologies and can aid in the development of water purification strategies against heavy metal contamination.

Use of Baclofen as a Treatment for Nocturnal Calf Cramps in Individuals With Lumbar Spinal Stenosis: A Prospective Randomized Study.

OBJECTIVE: This study aimed to compare the efficacy and safety of baclofen and gabapentin in reducing leg pain from nocturnal calf cramps in lumbar spinal stenosis patients. DESIGN: In a randomized clinical trial, the patients with lumbar spinal stenosis who commonly experienced nocturnal calf cramps were included. Patients were randomly assigned to either the baclofen or gabapentin group. Overall leg pain intensity, nocturnal calf cramp frequency and severity, sleep disturbances and functional disability were assessed at baseline and after 4 and 12 wks. RESULTS: Thirty-six patients completed the 3-mo study. Both gabapentin and baclofen groups showed a significant reduction in overall leg pain, calf cramp frequency and intensity, and insomnia severity index scores from baseline to the endpoint. However, there were no significant differences between the two groups in terms of symptom reduction at different time points. The baclofen group also demonstrated a significant decrease in Oswestry Disability Index scores ( P < 0.001), while the gabapentin group did not ( P = 0.344). No adverse effects were reported in either group. CONCLUSIONS: Baclofen seems to be as effective and as safe as gabapentin in treating nocturnal calf cramps in lumbar spinal stenosis patients and even shows superiority in enhancing functional outcomes.

Biomarker-driven phase 2 umbrella trial: Clinical efficacy of olaparib monotherapy and combination with ceralasertib (AZD6738) in small cell lung cancer.

BACKGROUND: Based on a high incidence of genomic alteration in the cell cycle and DNA damage and response (DDR)-related pathways in small cell lung cancer (SCLC), the clinical efficacy of the DDR-targeting agent olaparib (PARP inhibitor) as monotherapy and in combination with ceralasertib (ATR inhibitor) in relapsed or refractory SCLC was evaluated. METHODS: As part of a phase 2 biomarker driven umbrella study, patients with SCLC and predefined DDR gene alterations who failed to benefit from prior platinum-based regimens were allocated to the olaparib monotherapy arm and nonbiomarker-selected patients were allocated to the olaparib and ceralasertib combination arm. RESULTS: In the olaparib monotherapy arm (n = 15), the objective response rate was 6.7% (one partial response), and the disease control rate was 33.3%, including three patients with stable disease. The median progression-free survival was 1.3 months (95% CI, 1.2-NA). In the combination arm (n = 26), the objective response rate and disease control rate were 3.8% and 42.3%, respectively, with one partial response and 10 patients with stable disease. The median progression-free survival was 2.8 months (95% CI, 1.8-5.4). Treatment was generally well tolerated except for one fatal case of neutropenic fever in the combination arm. CONCLUSIONS: Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point. However, disease stabilization was more evident in the combination arm. Further investigation of the combination of olaparib in SCLC should be performed with diverse combinations and patient selection strategies to maximize efficacy.

Hydrogen-Bonded Organic Framework-Polyoxometalate-Based System for Electrochromic Devices.

A porous hydrogen-bonded organic framework (HOF) structure was explored for the first time in the design of high-performance electrochromic devices (ECDs) using polyoxometalate (POM)-based charge-balancing layers as counter electrodes (CEs). The novelty of this work lies in the facile construction of films using small molecule-based EC materials to form a porous HOF structure. A full-cell model of an ECD was constructed by utilizing a POM-based CE to optimize the voltage distribution on the HOF-coated working electrode (WE). The addition of PW12O403- (PW12) on CE significantly enhanced the voltage distribution on EC electrodes and decreased the overvoltage on the WE, further preventing the formation of non-EC species and resulting in a 3.3-fold increase in the lifetime of the ECD. The optical contrast was enhanced from 47% (TiO2 only) to 68%, and the coloration efficiency was enhanced from 185 (TiO2 only) to 373 cm2 C-1. The optimized voltage distribution on the WE, leading to the fast response time and high optical EC contrast, could be explained by the charge-balancing effect. Overall, this new finding provides a robust framework for designing high-performance ECDs, taking advantage of the porous morphology and potential matching of the HOF and PW12.

Understanding health literacy of deaf persons with hypertension in South Korea: A cross-sectional study.

BACKGROUND: Health literacy is strongly associated with health inequality among persons with deafness, and hypertension (HTN) is the most prevalent chronic disease among persons with deafness in South Korea. Despite its importance, research regarding the health literacy levels of persons with deafness with HTN in South Korea is lacking. This study aimed to comprehensively assess the health literacy levels of persons with deafness with HTN in South Korea, including linguistic, functional, and internet health literacy. METHODS: In this descriptive cross-sectional study, 95 persons with deafness with HTN were recruited through facilities associated with the deaf community. From August 2022 to February 2023, data were collected through face-to-face surveys attended by a sign language interpreter and online surveys. The data were analyzed using descriptive statistics and Spearman's correlation. RESULTS: Approximately 62.1% of the participants exhibited a linguistic health literacy level corresponding to less than that of middle school students, and the total percentage correct of functional health literacy was 17.9%. Each domain of internet health literacy was low. Significant correlations were found between some aspects of health literacy. CONCLUSIONS: The study's findings highlight the low health literacy levels across various facets among persons with deafness with HTN in South Korea. Based on these findings, several strategies are suggested for developing HTN self-management interventions for persons with deafness. This study contributes to the foundational understanding of health literacy among persons with deafness with HTN in South Korea and provides valuable insights and guidance for developing HTN self-management interventions.

Omics and Extreme Phenotyping Reveal Longitudinal Association Between Left Atrial Size and Pulmonary Vascular Resistance in Group 2 Pulmonary Hypertension.

BACKGROUND: Left heart disease is the most common cause of pulmonary hypertension (PH) and is frequently accompanied by increases in pulmonary vascular resistance. However, the distinction between phenotypes of PH due to left heart disease with a normal or elevated pulmonary vascular resistance-isolated postcapillary PH (IpcPH) and combined pre- and postcapillary PH (CpcPH), respectively-has been incompletely defined using unbiased methods. METHODS AND RESULTS: Patients with extremes of IpcPH versus CpcPH were identified from a single-center record of those who underwent right heart catheterization. Individuals with left ventricular ejection fraction <40% or with potential causes of PH beyond left heart disease were excluded. Medication usage in IpcPH and CpcPH was compared across Anatomical Therapeutic Chemical classes and identified vitamin K antagonists as the only medication with pharmacome-wide significance, being more commonly used in CpcPH and for an indication of atrial fibrillation in ≈90% of instances. Accordingly, atrial fibrillation prevalence was significantly higher in CpcPH in a phenome-wide analysis. Review of echocardiographic data most proximal to right heart catheterization revealed that left atrial diameter indexed to body surface area-known to be associated with atrial fibrillation-was increased in CpcPH regardless of the presence of atrial fibrillation. An independent cohort with serial right heart catheterizations and PH-left heart disease showed a significant positive correlation between change in left atrial diameter indexed to body surface area and change in pulmonary vascular resistance. CONCLUSIONS: Guided by pharmacomic and phenomic screens in a rigorously phenotyped cohort, we identify a longitudinal association between left atrial diameter indexed to body surface area and pulmonary vascular resistance with implications for the future development of diagnostic, prognostic, and therapeutic tools.

Patterns of genetic mutations explored by systematic screening of patients with aortopathy and their family members.

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P < .001). Mutated genes frequently identified were FBN1 (n = 199; Marfan), TGFBR1/2 or SMAD3 (n = 14; Loeys-Dietz), COL3A1/COL5A2 (n = 15; Ehlers-Danlos), and ACTA2 (n = 10). After enrollment, 123 aortic surgeries were performed in 117 patients (20.3%) including 15 family members, with resultant operative mortality of 0.8% (n = 1). In logistic regression analysis, systemic score in Ghent nosology was the only significant factor associated with positive gene mutation (odds ratio, 14.81; 95% confidence interval, 6.87-31.96), and its 3.5 point cutoff showed the best predictive value with 78.2% sensitivity and 87.2% specificity. Conclusions: Genetic aortopathy was identified in a considerable proportion of patients with aortopathy and their family members by systematic genetic testing. This strategy is recommended for timely diagnosis and proactive management of genetic aortopathy.

Alleviation of hippocampal necroptosis and neuroinflammation by NecroX-7 treatment after acute seizures.

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, but still one-third of patients cannot be properly treated by current medication. Thus, we investigated the therapeutic effects of a novel small molecule, NecroX-7, in TLE using both a low [Mg2+]o-induced epileptiform activity model and a mouse model of pilocarpine-induced status epilepticus (SE). NecroX-7 post-treatment enhanced the viability of primary hippocampal neurons exposed to low [Mg2+]o compared to controls in an MTT assay. Application of NecroX-7 after pilocarpine-induced SE also reduced the number of degenerating neurons labelled with Fluoro-Jade B. Immunocytochemistry and immunohistochemistry showed that NecroX-7 post-treatment significantly alleviated ionized calcium-binding adaptor molecule 1 (Iba1) intensity and immunoreactive area, while the attenuation of reactive astrocytosis by glial fibrillary acidic protein (GFAP) staining was observed in cultured hippocampal neurons. However, NecroX-7-mediated morphologic changes of astrocytes were seen in both in vitro and in vivo models of TLE. Finally, western blot analysis demonstrated that NecroX-7 post-treatment after acute seizures could decrease the expression of mixed lineage kinase domain-like pseudokinase (MLKL) and phosphorylated MLKL (p-MLKL), markers for necroptosis. Taken all together, NecroX-7 has potential as a novel medication for TLE with its neuroprotective, anti-inflammatory, and anti-necroptotic effects.

Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study.

Introduction: Mild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI. Methods: Near-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants. Results: Compared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance. Conclusion: Our results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.

Regeneration of taste through sonic hedgehog upregulation by photobiomodulation.

This study investigated photobiomodulation (PBM) effects in Sonic hedgehog (Shh) signaling as a potential approach to taste preservation and regeneration. Primary taste cell (TC) cultures were treated with Shh antagonist vismodegib and irradiated using a continuous wave type 630 nm light-emitting diode (10 mW/cm2 ) array, with single or multiple doses of 30 J/cm2 to determine dose inducing significant upregulation effect. Shh, Ptch, Smo, and Gli1 were significantly upregulated at 120 J/cm2 , used as the minimum dose in vivo. Vismodegib was administered via daily oral gavage for 21 days (30 mg/kg) to induce Shh inhibition in the tongue of rat animal models resulting in taste bud damage and taste dysfunction. PBM treatment using a 630 nm laser (3 W/cm2 ) at a radiant exposure of 120 J/cm2 (24 J/cm2 × 5) successfully upregulated the Shh protein expression, regenerated taste buds, and recovered taste function.