Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets.

Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms. Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets. Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063). Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

Lithiophilic Reduced Graphene Oxide/Carbonized Zeolite Imidazolate Framework-8 Composite Host for Stable Li Metal Anodes.

Lithium (Li) metal is regarded as a next-generation anode material owing to its high energy density. However, issues such as dendritic growth and volume changes during charging and discharging pose significant challenges for commercialization. We propose using lithiophilic reduced graphene oxide (rGO) and carbonized zeolite imidazolate framework-8 (C-ZIF-8) composites as host materials for Li to address these problems. The rGO/C-ZIF-8 composites are synthesized through a simple redox reaction followed by carbonization and are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The roles of chemical composition, characteristics, and morphology are demonstrated. As a result of these favorable structural and functional properties, the Li symmetric cell with rGO/C-ZIF-8 exhibits a stable voltage profile for more than 100 h at 1 mA cm-2 without short-circuiting. A relatively low Li plating/stripping overpotential of ~101.5 mV at a high current density of 10 mA cm-2 is confirmed. Moreover, a rGO/C-ZIF-8-Li full cell paired with a LiFePO4 cathode demonstrates good cyclability and rate capability.

Structural analysis, anti-inflammatory activity of the main water-soluble acidic polysaccharides (AGBP-A3) from Panax quinquefolius L berry.

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and ß-D-Galp, while the branch consisted mainly of α-L-Araf, ß-D-Glcp, α-D-GalAp, ß-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1ß secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

The Role of Predeployment Retraction in Biopsy Marker Migration During Stereotactic Breast Biopsies: A Randomized Controlled Trial.

OBJECTIVE: Inaccurate breast biopsy marker placement and marker migration during stereotactic biopsy procedures compromise their reliability for lesion localization and precise surgical excision. This trial evaluated the impact of 5-mm predeployment retraction of the marker introducer on marker migration, investigating other potential factors that influence the outcome. METHODS: This parallel, randomized controlled trial enrolled women aged ≥18 years undergoing stereotactic breast biopsy at a single institution from May 2020 through August 2022. The study was approved by the institutional review board at the University of Alabama at Birmingham (UAB). Patients were randomized to intervention (5-mm introducer retraction before marker deployment) or control (standard marker placement) by drawing a labeled paper. The primary outcome was the distance of marker migration on immediate postprocedure mammogram. RESULTS: Of 251 patients enrolled, 223 were analyzed; 104 received the intervention, and 119 received control. Mean (SD) marker migration was 12.1 (14.9) mm in the intervention group vs 9.8 (14.9) mm, with differences between groups estimated at 2.3 mm (SE = 1.9, P = .2312) (d = 0.16; 95% CI, 1.5-6.0). Effects of age, breast density, thickness, and biopsy approach showed no statistical significance. In exploratory models, central lesions exhibited 5.7 mm less migration than proximal lesions (95% CI, 0.7-10.6; P = .025), and each body mass index (BMI) unit increase was associated with 0.3 mm greater migration (95% CI, 0-0.6; P = .044). CONCLUSION: Retracting the marker introducer 5 mm before deployment did not reduce migration. Higher BMI and certain lesion locations were all associated with marker migration, highlighting the need to investigate biomechanical factors and techniques to optimize breast marker placement.Clinical Trials Registration: NCT04398537.

Evaluating the accuracy of CEREC intraoral scanners for inlay restorations: impact of adjacent tooth materials.

BACKGROUND: The accuracy of intraoral scanning is critical for computer-aided design/computer-aided manufacturing workflows in dentistry. However, data regarding the scanning accuracy of various adjacent restorative materials and intraoral scanners are lacking. This in vitro study aimed to evaluate the effect of adjacent restorative material type and CEREC's intraoral scanners on the accuracy of intraoral digital impressions for inlay cavities. METHODS: The artificial tooth was prepared with an occlusal cavity depth of 2 mm, a proximal box width at the gingival floor of 1.5 mm, and an equi-gingival margin extended disto-occlusally at the transition line angle on both the lingual and buccal sides for an inlay restoration. The adjacent teeth were veneered with crowns made of gold and zirconia, and an artificial tooth (resin) was utilized as the control group. The inlay cavity and adjacent teeth (Gold, Zirconia, and resin) were scanned 10 times using Chairside Economical Restoration of Esthetic Ceramics (CEREC) Primescan (PS), Omnicam (OC), and Bluecam (BC). A reference scan was obtained using a laboratory scanner (3-shape E3). Scanning was performed according to the manufacturer's instructions, including powder application for the BC group. Standard tesselation language files were analyzed using a three-dimensional analysis software program. Experimental data were analyzed using a two-way analysis of variance and the Tukey's post-hoc comparison test. RESULTS: The restorative materials of the adjacent teeth significantly affected the accuracy of the intraoral digital impressions (p < .05). The zirconia group exhibited the highest trueness deviation, followed by the resin and gold groups, with each demonstrating a statistically significant difference (p < .05). The resin group demonstrated the highest maximum positive deviation and deviation in precision. Gold exhibited the lowest average deviation value for trueness compared with those of the other adjacent restorative materials. Intraoral scanner type significantly influenced the trueness and precision of the scan data (p < .05). The average deviation of trueness according to the intraoral scanner type increased in the following order: BC > PS > OC. The average deviation in precision increased in the following order: PS>OC>BC (p < .05). CONCLUSION: The restorative materials of the adjacent tooth and the type of intraoral scanner affect the accuracy of the intraoral digital impression. The trueness of the digital images of the BC group, obtained by spraying the powder, was comparable to that of the PS group. Among the adjacent restorative materials, zirconia exhibited the lowest trueness. In contrast, PS demonstrated the highest precision among the intraoral scanners, while resin displayed the lowest precision among the adjacent restorative materials.

The Skin Histopathology of Pro- and Parabiotics in a Mouse Model of Atopic Dermatitis.

As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics.

Resilience of Family Caregivers of People With Dementia in South Korea: A Scoping Review.

BACKGROUND: Due to rapid increases in the number of Korean people with dementia, dementia has become a priority health issue in South Korea. Likewise, the well-being of family caregivers of people with dementia has also become an issue of concern. However, little is known about the resilience of Korean family caregivers because there is a lack of review studies from a Korean cultural perspective about the resilience of family caregivers of people with dementia. OBJECTIVES: The purpose of this scoping review was to investigate quantitative studies related to resilience theories, measurement instruments, correlates and resilience interventions for family caregivers of people with dementia. METHOD: This review was conducted according to the Joanna Briggs Institute based on Arksey and O'Malley. Nine databases were searched to retrieve evidence published in English or Korean between January 2000 and September 2022. Studies with a quantitative research design reporting the resilience of family caregivers of people with dementia based on a resilience theory framework were included. RESULTS: A total of 13 studies were included in this review. All studies used either a modified McCubbin and McCubbin's family stress, adjustment and adaptation model or Walsh's family resilience model. All resilience instruments were used without cross-cultural adaptation. Family adaptation, social support, life satisfaction, family (di)stress and caregiver burden were associated with resilience among family caregivers. A few family resilience-enhancing programmes showed a positive effect on caregiver resilience. CONCLUSION: This review noted that all the resilience measures documented in this study need to test for cultural adaptation in a Korean context. Further research is required to develop and implement family-based, culturally tailored interventions to effectively enhance Korean resilience for family caregivers of people with dementia. IMPLICATIONS FOR PRACTICE: Gerontological nurses should include Korean family caregivers in their nursing care and assess whether family caregivers have depression or suicidal thoughts to promote better health outcomes for caregivers and their family members.

SARS-CoV-2 detection in COVID-19 patients' sample using Wooden quoit conformation structural aptamer (WQCSA)-Based electronic bio-sensing system.

The COVID-19 epidemic and its continuous spread pose a serious threat to public health. Coronavirus strains known as SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) variants have undergone genomic changes. The severity of the symptoms, the efficiency of vaccinations, and the transmission capacity of the virus can be impacted by these alterations. Point-of-care diagnostic assays can identify particular genetic or protein sequences that are exclusive to each variety. Currently, ultrafast, responsive, and accurate antibody detection faces several challenges. Here, we outline the fabrication, implementation, and sensing performance benchmarking of an ultrafast (5 s) and inexpensive (0.15 USD) assay with label-free sensing of SARS-CoV-2 S (Spike)/N (Nucleocapsid) protein and other variants in real patient samples. A label-free DNA aptameric capacitive bio-sensing device was used to detect SARS-CoV-2 variants. Our novel, cutting-edge bio-sensing device contains a Wooden quoits conformation structural aptamer (WQCSA)-based inter-digitated capacitor electronic (WQCSA-IDCE) system. WQCSA-aptamer was used as a switch-turn on response to achieve ultrasensitivity in the variable area of the SARS-CoV-2. The molecular beacon (MB) method was also used to measure the fluorescently colored SARS-CoV-2 S/N protein. These sensors can be used with several types of label-free DNA aptamers to act as rapid, affordable, and label-free biosensors for a variety of critical acute respiratory virus syndrome disorders.

Evaluation of simplified ester-linked fatty acid analysis (ELFA) for phospholipid fatty acid (PLFA) analysis of bacterial population.

Phospholipid fatty acid (PLFA) analysis is used for characterizing microbial communities based on their lipid profiles. This method avoids biases from PCR or culture, allowing data collection in a natural state. However, PLFA is labor-intensive due to lipid fractionation. Simplified ester-linked fatty acid analysis (ELFA), which skips lipid fractionation, offers an alternative. It utilizes base-catalyzed methylation to derivatize only lipids, not free fatty acids, and found glycolipid and neutral lipid fractions are scarcely present in most bacteria, allowing lipid fractionation to be skipped. ELFA method showed a high correlation to PLFA data (r = 0.99) and higher sensitivity than the PLFA method by 1.5-2.57-fold, mainly due to the higher recovery of lipids, which was 1.5-1.9 times higher than with PLFA. The theoretical limit of detection (LOD) and limit of quantification (LOQ) for the ELFA method indicated that 1.54-fold less sample was needed for analysis than with the PLFA method. Our analysis of three bacterial cultures and a simulated consortium revealed the effectiveness of the ELFA method by its simple procedure and enhanced sensitivity for detecting strain-specific markers, which were not detected in PLFA analysis. Overall, this method could be easily used for the population analysis of synthetic consortia.

Assessing the abundance, sources, and potential ecological risk assessment of microplastics using their particle and mass units in Uiam Lake, South Korea.

Microplastics (MPs) enter lakes through various pathways, including effluents from wastewater treatment plants (WWTPs), surface runoff, and improperly disposed of plastic waste. In this study, the extent of MPs pollution in Uiam Lake in fall of 2022 and spring of 2023 was assessed by determining both the number (n/m3) and mass concentrations (µg/m3) of MPs. Moreover, the correlation between water quality parameters and MP properties was analyzed, and an ecological risk assessment was conducted. MPs abundance was higher in spring than in fall, probably due to the lifting of coronavirus disease-19 restrictions, melting of ice, higher rainfall, and faster wind speed. Fragment was the dominant shape of the MPs collected, while polyvinyl chloride (PVC) and polyester/polyethylene terephthalate were the frequently detected polymer types of MPs in fall and spring, respectively. There was a moderate positive correlation between the number concentration of MPs and the total nitrogen, total phosphorus (T-P), and total organic carbon levels; in contrast, there was no significant relationship between the mass concentration of MPs and all water quality parameters. However, the abundance (µg/m3) of PVC and polymethyl methacrylate MPs were positively correlated with T-P and electrical conductivity. The pollution load index, polymer hazard index, and potential ecological risk index (PERI) were generally higher when the mass unit of MPs was used due to the presence of large-sized MPs composed of highly hazardous polymers (e.g., polyurethane, PVC, and alkyd). For instance, the PERI value of the WWTP effluent was at the very high level (>1200) in both seasons, regardless of the abundance unit of MPs. Therefore, WWTP effluents may have increased the ecological toxicity of MPs pollution in Uiam Lake.

Prospective comparative analysis of three types of decompressive surgery for lumbar central stenosis: conventional, full-endoscopic, and biportal endoscopic laminectomy.

Conventional open laminectomy has long been considered one of the important surgical options for lumbar central stenosis owing to its positive outcomes. However, newer approaches have emerged as alternatives, including full-endoscopic and biportal endoscopic laminectomy. Therefore, a comparison of the outcomes that are associated with each of these surgical methods is warranted. This prospective multicenter trial, initiated in February 2019, compared the outcomes of three lumbar central stenosis surgical approaches: open laminectomy (OPEN), uniportal endoscopy (UNIPORT), and biportal endoscopy (BIPORT). Among 115 participants from seven centers, one-year follow-ups assessed laboratory, radiological, and clinical outcomes. Despite all groups showing adequate decompression and clinical improvement, the OPEN group exhibited less improvement in Visual analog scale (VAS) for back pain scores (p < 0.05) and significant postoperative increases in most laboratory markers. Furthermore, the OPEN group experienced a significant decrease in multifidus muscle cross-sectional area compared to endoscopic groups (p < 0.001). Each surgical techniques produced similar clinical outcomes and dural space expansion. However, endoscopic surgery was associated with better muscle preservation and better relief of back pain. Endoscopic surgery is a reasonable alternative to conventional laminectomy for treating lumbar central stenosis.This trial was registered on CRIS (Clinical Research Information Service, KCT0004355).

Joint Preservation Surgery Using Supramalleolar Osteotomy Combined with Posterior Tibial Tendon Release and Lateral Ligament Augmentation in Advanced Varus Ankle Arthritis.

Background: Recent studies utilizing weight-bearing computed tomography have identified abnormal internal rotation of the talus in advanced varus ankle arthritis (VAA) with a large talar tilt (TT), influenced by the posterior tibial tendon (PTT). This study aimed to evaluate the clinical and radiographic results of supramalleolar osteotomy (SMO) combined with PTT release and lateral ligament augmentation for VAA with a large TT. Methods: From January 2015 to September 2018, 15 patients with VAA and a large TT (greater than 5°) underwent SMO combined with PTT release. Clinical results, including visual analog scale (VAS) for pain, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle osteoarthritis scale (AOS), were assessed. Radiographic results were assessed with various parameters, including medial distal tibial angle (MDTA), anterior distal tibial angle (ADTA), talar tilt (TT), talus center migration (TCM), Meary angle, hindfoot alignment angle (HAA), and hindfoot moment arm (HMA) on foot and ankle weight-bearing radiographs. Clinical and radiographic results were evaluated preoperatively and at the last follow-up. Results: VAS, AOFAS ankle-hindfoot score, and AOS improved significantly from 7.5, 54.4, and 72.6 preoperatively to 3.1, 82.5, and 34.5 postoperatively, respectively. All radiographic parameters exhibited significant changes postoperatively, with the exception of the Meary angle, which demonstrated no significant change. Four patients exhibited improvement in radiographic stage postoperatively; however, average radiographic stage did not significantly improve postoperatively in all patients. One patient progressed to end-stage arthritis postoperatively, necessitating additional ankle arthrodesis. Conclusions: In conclusion, lengthening and lateral ligament augmentation combined with bony realignment procedures may be a reasonable option for treating VAA with a large TT greater that 5°.

Clinical Impact of Self-Recognition of Recurrent Acute Myocardial Infarction: From KRMI-RCC.

Background/Objectives: Self-recognition of recurrent myocardial infarction (re-MI) may be essential for reducing prehospital time contrast to awareness of re-MI symptoms. However, data on the current status and clinical impact of self-recognition of re-MI are limited in the contemporary period. Thus, this study aimed to increase this body of knowledge. Methods: We enrolled 1018 patients with re-MI using data from the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centres. The patients were classified into self-recognised MI and unrecognised MI groups, and the differences between them were compared. Results: The rate of self-recognition among the patients with previous experience of MI was only 52.4%. Among the patients with re-MI, factors associated with self-recognition included recent first MI within 3 years, prior dyslipidaemia, two or more MI symptoms, and the male gender (p < 0.05). Factors associated with a lack of recognition were older age (≥70 years), prior stroke, and cancer history (p < 0.05). The proportion of symptoms-to-emergency room arrival time within 90 min among the patients with ST-elevation MI was significantly higher in the self-recognised group than in the unrecognised group (52.6% vs. 31.6%, p < 0.001). The self-recognised group showed a lower in-hospital mortality rate (1.5% vs. 6.2%, p < 0.001), and this benefit was maintained even after 1 year (hazard ratio: 0.53; p < 0.001). Conclusions: Only half of the patients who previously experienced a MI recognised a re-MI when it occurred. This recognition reduced prehospital delay and led to higher survival rates, which highlights the importance of patient education as well as objective monitoring devices, irrespective of individual recognition ability for immediate response.

Lateral Spinal Artery Aneurysm Causing Subarachnoid Hemorrhage: Literature Review and Case Report.

Ruptured aneurysms of the lateral spinal artery (LSA) causing subarachnoid hemorrhage (SAH) are exceptionally rare. Unlike common aneurysms in the circle of Willis, LSA aneurysms present unique diagnostic and therapeutic challenges due to their complex anatomy. We reviewed the literature, examining case reports detailing LSA aneurysm occurrences, diagnoses, treatments, and complications, and our subsequent analysis highlights the clinical presentations, imaging findings, treatment methods, and anatomical features of the LSA. We identified 10 patients from 7 case reports of LSA aneurysm presenting with SAH, and combined with the present case, this comprised a total of 11 patients. An initial CT angiography identified LSA aneurysm in only 2 of 11 patients, while 5 cases were detected in transfemoral cerebral angiography. Seven patients had stenosis or occlusion of nearby arteries. Among the 10 patients treated, 7 underwent microsurgical clipping, and 3 had endovascular treatment; complications included PICA infarction and subdural hematoma. LSA aneurysms, though rare, should be considered in differential diagnoses of posterior fossa SAH. An accurate diagnosis often requires repeated imaging. It is proposed to individualize treatment strategies based on the unique anatomical structure and hemodynamic conditions of each patient, utilizing both endovascular and surgical approaches. Understanding the vascular anatomy and collateral pathways of the LSA is crucial for improving diagnostic accuracy and treatment outcomes.

Clinical data on treatment regimen and use of medication among patients with hemophilia B in Korea.

BACKGROUND: To investigate the clinical treatment status, such as treatment regimen, bleeding events, and drug dose, in patients with hemophilia B in South Korea. METHODS: In this retrospective chart review, data of patients with hemophilia B from eight university hospitals were collected. Demographic and clinical data, treatment data, such as regimen and number of injections, dose of factor IX concentrate, and bleeding data were reviewed. Descriptive analyses were performed with annual data for 2019, 2020, and 2021, as well as the three years consecutively. RESULTS: The medical records of 150 patients with hemophilia B between January 1, 2019, and December 31, 2021, were collected. Among these, 72 (48.0%) were severe, 47 (31.3%) were moderate, and 28 (18.7%) were mild. The results showed approximately two times more patients receiving prophylaxis as those receiving on-demand therapy, with 66.1% of patients receiving prophylaxis in 2019, 64.9% in 2020, and 72.1% in 2021. Annualized bleeding rates were 2.2% (± 3.1) in 2019, 1.8% (± 3.0) in 2020, and 1.8% (± 2.9) in 2021 among patients receiving prophylaxis. For the doses of factor IX concentrate, patients receiving prophylaxis received an average of 41.6 (± 11.9) IU/Kg/Injection in 2019, 45.7 (± 12.9) IU/Kg/Injection in 2020, and 60.1 (± 24.0) IU/Kg/Injection in 2021. CONCLUSIONS: Clinically, prophylaxis is more prevalent than reported. Based on insights gained from current clinical evidence, it is expected that the unmet medical needs of patients can be identified, and physicians can evaluate the status of patients and actively manage hemophilia B using more effective treatment strategies.

B cell senescence promotes age-related changes in oral microbiota.

In recent years, there has been increasing attention towards understanding the relationship between age-related alterations in the oral microbiota and age-associated diseases, with reports emphasizing the significance of maintaining a balanced oral microbiota for host health. However, the precise mechanisms underlying age-related changes in the oral microbiota remain elusive. We recently reported that cellular senescence of ileal germinal center (GC) B cells, triggered by the persistent presence of commensal bacteria, results in diminished IgA production with aging and subsequent alterations in the gut microbiota. Consequently, we hypothesize that a similar phenomenon may occur in the oral cavity, potentially contributing to age-related changes in the oral microbiota. Examination of p16-luc mice, wherein the expression of the senescent cell marker p16INK4a can be visualized, raised under specific pathogen-free (SPF) or germ-free (GF) conditions, indicated that, unlike ileal GC B cells, the accumulation of senescent cells in GC B cells of cervical lymph nodes increases with age regardless of the presence of commensal bacteria. Furthermore, longitudinal studies utilizing the same individual mice throughout their lifespan revealed concurrent age-related alterations in the composition of the oral microbiota and a decline in salivary IgA secretion. Further investigation involving Rag1-/- mice transplanted with B cells from wild-type or p16INK4a and p21Waf1/Cip1 -double knockout mice unveiled that B cell senescence leads to reduced IgA secretion and alteration of the oral microbiota. These findings advance our understanding of the mechanism of age-associated changes in the oral microbiota and open up possibilities of their control.

A Development of a Sound Recognition-Based Cardiopulmonary Resuscitation Training System.

The objective of this study was to develop a sound recognition-based cardiopulmonary resuscitation (CPR) training system that is accessible, cost-effective, easy-to-maintain and provides accurate CPR feedback. Beep-CPR, a novel device with accordion squeakers that emit high-pitched sounds during compression, was developed. The sounds emitted by Beep-CPR were recorded using a smartphone, segmented into 2-second audio fragments, and then transformed into spectrograms. A total of 6,065 spectrograms were generated from approximately 40 minutes of audio data, which were then randomly split into training, validation, and test datasets. Each spectrogram was matched with the depth, rate, and release velocity of the compression measured at the same time interval by the ZOLL X Series monitor/defibrillator. Deep learning models utilizing spectrograms as input were trained using transfer learning based on EfficientNet to predict the depth (Depth model), rate (Rate model), and release velocity (Recoil model) of compressions. Results: The mean absolute error (MAE) for the Depth model was 0.30 cm (95% confidence interval [CI]: 0.27-0.33). The MAE of the Rate model was 3.6/min (95% CI: 3.2-3.9). For the Recoil model, the MAE was 2.3 cm/s (95% CI: 2.1-2.5). External validation of the models demonstrated acceptable performance across multiple conditions, including the utilization of a newly-manufactured device, a fatigued device, and evaluation in an environment with altered spatial dimensions. We have developed a novel sound recognition-based CPR training system, that accurately measures compression quality during training. Significance: Beep-CPR is a cost-effective and easy-to-maintain solution that can improve the efficacy of CPR training by facilitating decentralized at-home training with performance feedback.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.

Mechanical Thrombectomy for Hyperacute Vertebrobasilar Ischemic Stroke via Nondominant Vertebral Artery : Clinical Experience and Considerations.

Objective: The dominant vertebral artery (VA) approach is primarily considered in mechanical thrombectomy (MT) for acute occlusion of the vertebrobasilar (VB) artery. As accessing the dominant artery is sometimes difficult, we present our experience treating acute VB stroke via a nondominant VA approach through a comparison with the dominant VA approach. Methods: Among 2,785 patients diagnosed with hyperacute ischemic stroke between January 2014 and December 2022, 50 patients with VB ischemic stroke underwent recanalization therapy through either dominant, nondominant, or bilateral VA approach. We evaluated patient characteristics and clinical course, highlighting the pros and cons of the access routes. Results: The patients with hyperacute VB ischemic stroke were predominantly male (72%), with a mean age of 68.12 years and an initial National Institutes of Health Stroke Scale (NIHSS) score mean of 17.1. Large-artery atherosclerosis (LAA, 48%) and cardio-embolism (CE, 36%) were the main etiologic factors in the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. After thrombectomy, 45 (90%) cases had final modified thrombolysis in cerebral infarction (mTICI) score of 2b or higher. In summary, 41 patients were treated through the dominant VA, and 8 patients underwent the nondominant VA approach. However, there was no statistically significant difference in functional outcome or mortality between the two approaches. Conclusion: In MT for VB occlusions, nondominant VA approach may be an option in situations when the vessel is accessible, stable, or less risky, as recanalization can be achieved without rescue balloon angioplasty and/or stenting.