PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Flexible and Stretchable Light-Emitting Diodes and Photodetectors for Human-Centric Optoelectronics.

Optoelectronic devices with unconventional form factors, such as flexible and stretchable light-emitting or photoresponsive devices, are core elements for the next-generation human-centric optoelectronics. For instance, these deformable devices can be utilized as closely fitted wearable sensors to acquire precise biosignals that are subsequently uploaded to the cloud for immediate examination and diagnosis, and also can be used for vision systems for human-interactive robotics. Their inception was propelled by breakthroughs in novel optoelectronic material technologies and device blueprinting methodologies, endowing flexibility and mechanical resilience to conventional rigid optoelectronic devices. This paper reviews the advancements in such soft optoelectronic device technologies, honing in on various materials, manufacturing techniques, and device design strategies. We will first highlight the general approaches for flexible and stretchable device fabrication, including the appropriate material selection for the substrate, electrodes, and insulation layers. We will then focus on the materials for flexible and stretchable light-emitting diodes, their device integration strategies, and representative application examples. Next, we will move on to the materials for flexible and stretchable photodetectors, highlighting the state-of-the-art materials and device fabrication methods, followed by their representative application examples. At the end, a brief summary will be given, and the potential challenges for further development of functional devices will be discussed as a conclusion.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Stress Granules in Cancer.

The capacity of cells to organize complex biochemical reactions in intracellular space is a fundamental organizational principle of life. Key to this organization is the compartmentalization of the cytoplasm into distinct organelles, which is frequently achieved through intracellular membranes. Recent evidence, however, has added a new layer of flexibility to cellular compartmentalization. As such, in response to specific stimuli, liquid-liquid phase separations can lead to the rapid rearrangements of the cytoplasm to form membraneless organelles. Stress granules (SGs) are one such type of organelle that form specifically when cells are faced with stress stimuli, to aid cells in coping with stress. Inherently, altered SG formation has been linked to the pathogenesis of diseases associated with stress and inflammatory conditions, including cancer. Exciting discoveries have indicated an intimate link between SGs and tumorigenesis. Several pro-tumorigenic signaling molecules including the RAS oncogene, mTOR, and histone deacetylase 6 (HDAC6) have been shown to upregulate SG formation. Based on these studies, SGs have emerged as structures that can integrate oncogenic signaling and tumor-associated stress stimuli to enhance cancer cell fitness. In addition, growing evidence over the past decade suggests that SGs function not only to regulate the switch between survival and cell death, but also contribute to cancer cell proliferation, invasion, metastasis, and drug resistance. Although much remains to be learned about the role of SGs in tumorigenesis, these studies highlight SGs as a key regulatory hub in cancer and a promising therapeutic target.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

A multi-layered network model identifies Akt1 as a common modulator of neurodegeneration.

The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Feasibility of intraoperative pathologic examination for sentinel lymph nodes during sentinel node navigation surgery in early gastric cancer: results of pathologic protocol for SENORITA trial.

BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.

IFN-γ Induces IL-15 Trans-Presentation by Epithelial Cells via IRF1.

IL-15 exhibits pleiotropic effects on NK and CD8+ T cells and contributes to host protection or immunopathology during infection. Although both type I IFNs and IFN-γ upregulate IL-15 expression, their effects on IL-15 upregulation and underlying mechanisms have not been compared comprehensively. In addition, little is known about trans-presentation of IL-15 by epithelial cells to lymphocytes. In this study, we analyzed the expression of IL-15 and IL-15Rα in the human hepatocyte-derived Huh-7 cell line after stimulation with IFN-α, IFN-ß, or IFN-γ using RT-PCR, flow cytometry, and confocal microscopy. We also performed knockdown experiments to investigate the signaling pathway involved in IL-15 upregulation. IFN-γ more potently upregulated IL-15 expression in Huh-7 cells than IFN-α and IFN-ß. Knockdown experiments revealed that IFN-γ- and IFN-ß-induced IL-15 expression relied on IFN regulatory factor 1 (IRF1), which is upregulated by STAT1 and IFN-stimulated gene factor 3, respectively. Inhibitor of κB kinase α/ß was also involved in IFN-γ-induced upregulation of IL-15. Furthermore, human NK cells were activated by coculture with IFN-γ-treated Huh-7 cells, which was abrogated by knocking down IL-15Rα in IFN-γ-treated Huh-7 cells, indicating that IFN-γ-induced IL-15 on Huh-7 cells activates NK cells via trans-presentation. In summary, our data demonstrate that IFN-γ potently elicits IL-15 trans-presentation by epithelial cells via IRF1. These data also suggest that the IFN-γ-IRF1-IL-15 axis may be a regulatory target for the treatment of diseases with IL-15 dysregulation.

Association between temporary employment and current smoking and change in smoking behaviors: A prospective cohort study from South Korea (2009-2018).

Background Previous studies have suggested that employment insecurity is associated with adverse health outcomes. We explored the association between temporary employment and smoking behaviors.Methods We analyzed 11,795 workers (51,867 observations) from the Korea Health Panel Study (2009-2018). Employment types were categorized as regular, fixed-term, or daily, based on the duration of labor contract. The outcomes were current smoking status and changes in smoking behavior (initiation or cessation) in the following year. Generalized estimating equations were used to estimate odds ratio (OR) and 95% confidence interval (CI).Results The proportions of fixed-term and daily workers were 41.2% and 16.4% for women and 23.6% and 12.4% for men, respectively. Temporary employment was associated with increased odds of current smoking, while also demonstrating prospective associations with changes in smoking behaviors. For instance, in prospective analyses, male workers with fixed-term and daily employments were associated with a decreased likelihood of smoking cessation (OR:0.77; 95% CI:0.65-0.91 for fixed-term employment and OR:0.66; 95% CI:0.52-0.83 for daily employment) in the following year compared to those with regular employment. Moreover, those experiencing consecutive temporary employment was most inversely associated with smoking cessation in both men (OR:0.56; 95% CI:0.44-0.71) and women (OR:0.37; 95% CI:0.16-0.85) compared to those experiencing consecutive regular employment. However, no clear association between temporary employment and smoking initiation was observed in both men and women.Conclusions Temporary employment is directly associated with current smoking and inversely associated with smoking cessation. Policies are needed to improve job insecurity among temporary employees.

ADDITIONAL PNEUMATIC RETINOPEXY IN PATIENTS WITH PERSISTENT RETINAL DETACHMENT AFTER SCLERAL BUCKLING.

PURPOSE: To investigate the efficacy, safety, and indications for additional pneumatic retinopexy (PR) in patients with persistent retinal detachment after scleral buckling. METHODS: This retrospective study included patients who underwent additional PR after scleral buckling for primary rhegmatogenous retinal detachment (n = 78). We defined "inadequate buckle" as retinal detachment persistence because of low buckle height despite accurate buckle placement and "buckle misplacement" as an uncovered tear because of incorrect buckle placement. RESULTS: The anatomical success rate after additional PR was 52.6%. Development of proliferative vitreoretinopathy Grade B (hazard ratio, 5.73; P < 0.001) and inferior retinal tears (hazard ratio, 2.12; P = 0.040) were significant risk factors for anatomical failure. The most common cause of anatomical failure was proliferative vitreoretinopathy (19 of 37; 51.4%), and epiretinal membrane formation was a common complication after additional PR (22 of 78; 28.2%). The anatomical success rate with additional PR was significantly higher in the inadequate buckle group than in the misplacement group (8 of 9 [88.9%] vs. 1228 [42.9%]; P = 0.023). CONCLUSION: Development of proliferative vitreoretinopathy Grade B and inferior retinal tears were significantly associated with anatomical failure after additional PR. Additional PR may benefit patients with superior retinal tears or low buckle height and those without proliferative vitreoretinopathy.

Association between sickness presenteeism and depressive symptoms: a cross-sectional study using the 6th Korean working conditions survey.

PURPOSE: This study aimed to reveal the relationship of the days of experiencing sickness presentism and depressive symptoms among Korean workers. Sickness presenteeism which defined as the act of going to work despite being feeling unhealthy triggers various adverse effects on mental health, including increased risks of depression. Furthermore, Sickness presenteeism is a major social issue causing substantial socioeconomic costs. METHODS: The data of 25120 participants from sixth Korean Working Condition Survey was utilized in this cross-sectional study. Sickness presenteeism was defined using a self-reported questionnaire and depressive symptoms were assessed by WHO well-being index. Multivariate logistic regression analysis was conducted to calculate the odd ratios for depressive symptoms regarding the number of days experiencing sickness presenteeism. We calculated odds ratios (ORs) and 95% confidence interval (95% CI) for depressive symptoms after categorizing participants into three groups based on the duration of experiencing sickness presenteeism, using cut-off values of 3 and 5 days. RESULTS: Workers who have experienced sickness presenteeism for more than 5 days were at highest risk for depressive symptoms than referent group (OR 2.87; 95% CI 2.17-3.76 in male, OR 3.86; 95% CI 3.02-4.91 in female). Furthermore, there was a trend of increasing risk for depressive symptom as the duration of experiencing sickness presenteeism extended. CONCLUSION: This study presents the association between experiencing sickness presenteeism in the previous 12 months and depressive symptoms. Based on the results, we provide individual and organizational strategies of reducing sickness presenteeism. Also, screening for workers who have experienced sickness presenteeism are needed to ensure good mental health.

Impact of inhalation exposure to cigarette smoke on the pathogenesis of pulmonary hypertension primed by monocrotaline in rats.

Extensive, long-term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)-induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100-300 µg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin-1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short-term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.

Trends and Barriers in Diabetic Retinopathy Screening: Korea National Health and Nutritional Examination Survey 2016-2021.

BACKGROUND: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey. METHODS: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression. RESULTS: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 (P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05). CONCLUSION: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Musculoskeletal Injuries in Table Tennis during Competition: A Systematic Review.

The study aimed to investigate the incidence of musculoskeletal injuries among table tennis players and identify their associated risk factors. We conducted a literature search in online databases using relevant search terms related to "table tennis" and "injury". To compare the rate of injuries according to player-related variables, we extracted information on sex, level of games, circumstances of injury, and duration of sport absence after injury. Furthermore, we calculated the odds ratios based on the number of injuries according to variables. Eight articles included 873 professional table tennis players, revealing an overall musculoskeletal injury rate of 3.6% (31 musculoskeletal injuries). The incidence was 10.0 injuries per 1,000 playing hours (range, 0-27.0). The rate of musculoskeletal injuries for female and male players were 3.2% and 3.8%, respectively, and those for Summer Olympic Games, Asian Games, and domestic national games was 4.8%, 15.4%, and 0%, respectively. More than half (52%) of injuries occurred during training, and most injuries (64%) were of a nature that did not cause time loss. This review provides valuable information about the incidence of musculoskeletal injuries in table tennis competitions. However, owing to the limitations of this study in identifying injury-related risk factors, future studies analyzing comprehensive variables are required.

Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

Repeated intratracheal instillation of whole-cigarette smoke condensate to assess lung damage in a rat model.

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.

Transoral Endoscopy-Assisted Tongue-Lip Adhesion With Modified Tongue Base Suspension in a Pierre-Robin Sequence: A Safe and Effective Technique.

Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS.

Extension of Operating Range in Hybrid Cascaded H-Bridge Inverters with Capacitor Voltage Balancing Capability.

In this article, a generalized control scheme is proposed to extend the operating range of three-phase hybrid cascaded H-bridge (HCHB) inverters into various voltage levels without necessitating alterations to the core structure or the integration of additional H-bridge submodules. This study addresses a critical challenge related to capacitor voltage drift at various modulation indices and power factors, which is a serious impediment to various applications. To overcome this challenge, a novel balancing control scheme has been developed based on the injection of two independent offset voltages to simultaneously control the DC-link and flying capacitors. A distinctive aspect of the proposed technique involves adjusting the common reference voltage to attain the nearest level in the same cluster, thereby mitigating the insufficiency of redundant switching states. The effectiveness of the proposed technique to regulate the capacitor voltages at various operating conditions has been verified through simulation and experimental results.