Size-dependent reactivity of Rh cationic clusters to reduce NO by CO in the gas phase at high temperatures.

The reactivity of the reduction of NO pre-adsorbed on Rh2-9+ clusters by CO was investigated using a combination of an alternate on-off gas injection method and thermal desorption spectrometry. The reduction of RhnNxOy+ clusters by CO was evaluated by varying the CO concentration at T = 903 K. Among the RhnNxOx+ clusters, the Rh3N2O2+ cluster exhibited the highest reduction activity, whereas the other clusters, Rh2,4-9NxOx+, showed lower reactivity. Density functional theory (DFT) calculations for Rh3+ and Rh6+ revealed that the rate-determining step for NO reduction in the presence of CO was NO bond dissociation through the kinetics analysis using the RRKM theory. The reduction of Rh3N2O2+ is kinetically preferable to that of Rh6N2O2+. The DFT results were in qualitative agreement with the experimental results.

Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial.

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Effect of Liver Dysfunction on S-1 Therapy Induced Adverse Effects: A Retrospective Cohort Study.

BACKGROUND/AIM: Renal dysfunction necessitates S-1 dose reduction. However, decreased dihydropyrimidine dehydrogenase (DPD) activity may lead to adverse events due to 5-FU. The guidelines provided by pharmaceutical companies state that total bilirubin (T-Bil) should be ≤upper limit of normal (ULN)×1.5 as a reference value for safely taking S-1. Nevertheless, the relationship between the degree of liver dysfunction and S-1 dose reduction has not been clearly established. PATIENTS AND METHODS: This study focused on patients who received S-1 monotherapy for various types of cancer. The primary outcome was defined as the variation between blood sampling results on the test day and the subsequent test. The variation data were categorized based on the difference in T-Bil: Low T-Bil group (≤2.25) and High T-Bil group (>2.25). RESULTS: The number of patients that underwent S-1 monotherapy was 883 and the running number was 7,511; Low T-Bil group included 7,245 and High T-Bil group included 266. Examination of the effect of the T-Bil Group on clinical outcomes revealed a correlation with red blood cell (RBC) count, platelet (PLT) count, and T-Bil level. When the impact of the interaction between the T-Bil Group and any of the clinical outcomes, such as the RBC count, PLT count, and T-Bil level, was determined, each outcome showed a significant decrease in the High T-Bil group compared with the Low T-Bil group. CONCLUSION: S-1 administration in patients with liver dysfunction accompanied by elevated T-Bil levels may cause thrombocytopenia.

Factors associated with physical activity following total knee arthroplasty for knee osteoarthritis: a longitudinal study.

BACKGROUND: After total knee arthroplasty (TKA), patients' physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data. METHODS: Eighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus. RESULTS: A higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (ß = 0.155, p = 0.028) as well as a higher preoperative average daily step count (ß = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (ß = 0.723, p < 0.001). CONCLUSION: These findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.

Phase Angle as a Nutritional Assessment Method in Patients with Hip Fractures: A Cross-Sectional Study.

BACKGROUND: Phase angle, which is associated with cellular health, has attracted attention as a noninvasive and objective method for nutritional assessment. However, the association between malnutrition and phase angle in older inpatients with hip fractures has not been reported. Therefore, this study investigated this association in older inpatients (aged ≥65 years) with hip fractures and determined the cutoff phase angle for determining malnutrition. METHODS: This cross-sectional study retrospectively analyzed the data of 96 inpatients with hip fractures who were hospitalized in rehabilitation units after surgery (male, 29.4%; mean age, 82.4±6.2 years). Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), with malnutrition defined as a GNRI ≥98. Bioelectrical impedance analysis was used to measure phase angles. RESULTS: The phase angle was associated with malnutrition (B=-1.173; odds ratio=0.310; 95% confidence interval 0.58-0.83; p=0.015). The area under the receiver operating characteristic curve was 0.71. The cutoff phase angle for malnutrition was 3.96° (sensitivity=0.85, specificity=0.63). CONCLUSION: Phase angle could be an indicator of malnutrition in older inpatients with hip fractures. Our findings will help formulate rehabilitation strategies for these patients.

Appetite and family and friends network among community-dwelling older adults: A cross-sectional study.

OBJECTIVES: The aim of this study was to investigate the stronger correlate of appetite-family or friend networks-in community-dwelling older adults, given that undernutrition can impair physical function, increase mortality, and be influenced by social networks. METHODS: A cross-sectional study was conducted in Kasugai City, Aichi Prefecture, and Nara City, Nara Prefecture, Japan, between August 2019 and March 2023. The analysis included 119 participants (women: 79%, mean age: 76.5 ± 5.6 y). A multiple regression analysis was performed, using the scores from the Japanese version of the Simplified Nutritional Appetite Questionnaire (SNAQ-J) as the dependent variable and family network and friend network as the independent variables. The analysis included social participation, living alone status, sex, age, body mass index, skeletal muscle mass index, grip strength, walking speed, and the Japanese version of the 15 Geriatric Depression Scale score as covariates to examine their relationship with appetite. RESULTS: The mean value of the SNAQ-J score of the participants was 15.4 ± 1.2. Seven participants (6%) had a loss of appetite. Family network was significantly associated with appetite (B = 0.121, ß = 0.266, P <0.05; 95% condidence interval [CI], 0.030-0.212). In the single regression analysis, the friend network was significantly associated with the total score of the SNAQ-J (B = 0.115, P <0.001; 95% CI, 0.052-0.177); however, this association was not observed in the multiple regression analysis (B = 0.002, ß = 0.006, P = 0.954; 95% CI, -0.074-0.078). CONCLUSION: Appetite was associated with family networks. Among social networks, focusing on family networks may help prevent the loss of appetite in older adults in Japan.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

Longitudinal association between oral function and underweight onset among community-dwelling older adults: Role of regular self-weighing.

AIMS: Regular self-weighing is effective in weight management and may help to mitigate the risk of underweight among older adults. We examined which factors of oral function are associated with a risk for underweight among community-dwelling older adults and whether regular self-weighing can mitigate that risk. METHODS: This was a cohort study. Self-administered questionnaires were mailed to 7665 older adults in March 2019 (response rate 74.3%) and 7591 in March 2020 (response rate 74.7%). Among those who responded to both surveys, 3594 older adults who were not underweight in March 2019 were included (follow-up rate: 59.2%). We examined the association between dysphagia, poor masticatory function, and dry mouth and the development of underweight, and whether regular self-weighing reduced the risk for underweight. RESULTS: The average age ± standard deviation of participants was 71.1 ± 3.4 years. There was a significant association between swallowing difficulty and the occurrence of underweight (odds ratio = 1.65, p = .012). However, this relationship did not differ significantly with regular self-weighing (p = .477). CONCLUSIONS: These study findings suggest that to prevent underweight among community-dwelling older adults, it is important to focus on those with poor swallowing function.

Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE. METHODS: Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records. RESULTS: One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils. CONCLUSION: The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

High-level phenol bioproduction by engineered Pichia pastoris in glycerol fed-batch fermentation using an efficient pertraction system.

This study aimed to establish a high-level phenol bioproduction system from glycerol through metabolic engineering of the yeast Pichia pastoris (Komagataella phaffii). Introducing tyrosine phenol-lyase to P. pastoris led to a production of 59 mg/L of phenol in flask culture. By employing a strain of P. pastoris that overproduces tyrosine-a precursor to phenol-we achieved a phenol production of 1052 mg/L in glycerol fed-batch fermentation. However, phenol concentrations exceeding 1000 mg/L inhibited P. pastoris growth. A phenol pertraction system utilizing a hollow fiber membrane contactor and tributyrin as the organic solvent was developed to reduce phenol concentration in the culture medium. Integrating this system with glycerol fed-batch fermentation resulted in a 214 % increase in phenol titer (3304 mg/L) compared to glycerol fed-batch fermentation alone. These approaches offer a significant framework for the microbial production of chemicals and materials that are highly toxic to microorganisms.

Difference in tissue temperature change between two cryoballoons.

BACKGROUND: Cryoballoon ablation, especially Arctic Front Advance Pro (AFA-Pro) (Medtronic, Minneapolis, Minnesota, USA), has been widely recognised as a standard approach to atrial fibrillation (AF). Recently, Boston Scientific has released a novel cryoballoon system (POLARx). Despite comparable acute clinical outcomes of these two cryoballoons, the recent study reported a higher complication rate, especially for phrenic nerve palsy, with POLARx. However, their impact on biological tissue remains unclear. OBJECTIVE: The purpose of our study is to evaluate temperature change of biological tissue during cryoablation of each cryoballoon using a porcine experimental model. METHOD: A tissue-based pulmonary vein model was constructed from porcine myocardial tissue and placed on a stage designed to simulate pulmonary vein anatomy and venous flow. Controlled cryoablations of AFA-Pro and POLARx were performed in this model to evaluate the tissue temperature. A temperature sensor was set behind the muscle and cryoballoon ablation was performed after confirming the occlusion of pulmonary vein with cryoballoon. RESULTS: The mean tissue nadir temperature during cryoablation with AFA-Pro was -41.5°C±4.9°C, while the mean tissue nadir temperature during cryoablation with POLARx was -58.4°C±5.9°C (p<0.001). The mean balloon nadir temperature during cryoablation with AFA-Pro was -54.6°C±2.6°C and the mean balloon nadir temperature during cryoablation with POLARx was -64.7°C±3.8°C (p<0.001). CONCLUSION: POLARx could freeze the biological tissue more strongly than AFA-Pro.

Arteries Around the Superior Limiting Sulcus: Motor Complication Avoidance in Insular and Insulo-Opercular Surgery.

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

Genetic alterations that deregulate RB and PDGFRA signaling pathways drive tumor progression in IDH2-mutant astrocytoma.

In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.

Influence of Brain Metastasis on Analgesia-Related Outcomes in Patients with Lung and Breast Cancers Treated with Naldemedine: A Propensity Score-Matched Analysis.

Naldemedine is structurally designed to prevent passage across the blood-brain barrier (BBB), resulting in the attenuation of opioid-induced constipation without interfering with the analgesic effects of opioids. However, the influence of brain metastasis (BM), as one indicator of BBB disruption, on the analgesic effects of opioids in patients treated with naldemedine remains unclear. To examine whether the analgesic effects of opioids following naldemedine treatment are lower in patients with BM than in those without BM, we surveyed inpatients with lung and breast cancers treated with naldemedine at Fujita Health University Hospital between April 2017 and March 2022. Changes in the numeric rating scale (NRS) scores, morphine milligram equivalents (MMEs), and the number of rescues were assessed as analgesia-related outcomes during the first 7 days of naldemedine treatment in patients with or without BM, matched by the propensity score. In total, 172 patients were enrolled. After propensity-score matching, 30 patients with BM and 60 patients without BM were included in the analysis. Changes in NRS scores, MMEs, and the number of rescues did not differ between patients with and without BM. In the linear mixed-effects model, the coefficient of interaction between patients with or without BM and the days for each outcome was not statistically significant. BM does not influence the analgesic effect of opioids in patients with lung and breast cancers treated with naldemedine. Naldemedine may be useful for treating BM.

The association between early rehabilitation and ambulatory ability at discharge in patients with hip fractures at acute-phase rehabilitation wards: a survey of the Japan Association of Rehabilitation Database.

This study aimed to examine the effectiveness of early rehabilitation in patients with femoral neck fractures admitted to acute care settings in Japan using the data registered with the Japan Association of Rehabilitation Databases (JARD). We included data for 401 patients (out of 3088 patients) aged ≥ 65 years (85 males, 316 females) from nine hospitals who sustained a femoral neck fracture between July 2005 and September 2015. Using the number of days until surgery or the number of days until the start of rehabilitation or both as the explanatory variables, and the indoor mobility at discharge as the outcome variable, we calculated the adjusted rate ratio (ARR) and 95% confidence interval (CI) using Poisson regression analysis (age, sex, cognitive impairment, concurrent symptoms, and previous history of fracture adjusted as covariates). The ARR for independent walking at the discharge of the early-rehabilitation group (starting rehabilitation within two days after the injury) was significantly higher (ARR: 2.01, 95% CI: 1.34-3.02) than that of the non-early rehabilitation group. These results suggest that early acute-phase rehabilitation after a femoral neck fracture in older patients allows for better ambulatory ability at discharge, regardless of the time to surgery.

Elucidation of binding mechanism, affinity, and complex structure between mWT1 tumor-associated antigen peptide and HLA-A*24:02.

We have applied our advanced computational and experimental methodologies to investigate the complex structure and binding mechanism of a modified Wilms' Tumor 1 (mWT1) protein epitope to the understudied Asian-dominant allele HLA-A*24:02 (HLA-A24) in aqueous solution. We have applied our developed multicanonical molecular dynamics (McMD)-based dynamic docking method to analyze the binding pathway and mechanism, which we verified by comparing the highest probability structures from simulation with our experimentally solved x-ray crystal structure. Subsequent path sampling MD simulations elucidated the atomic details of the binding process and indicated that first an encounter complex is formed between the N-terminal's positive charge of the 9-residue mWT1 fragment peptide and a cluster of negative residues on the surface of HLA-A24, with the major histocompatibility complex (MHC) molecule preferring a predominantly closed conformation. The peptide first binds to this closed MHC conformation, forming an encounter complex, after which the binding site opens due to increased entropy of the binding site, allowing the peptide to bind to form the native complex structure. Further sequence and structure analyses also suggest that although the peptide loading complex would help with stabilizing the MHC molecule, the binding depends in a large part on the intrinsic affinity between the MHC molecule and the antigen peptide. Finally, our computational tools and analyses can be of great benefit to study the binding mechanism of different MHC types to their antigens, where it could also be useful in the development of higher affinity variant peptides and for personalized medicine.

[Port Site Recurrence After Laparoscopic Nephrectomy for Renal Cell Carcinoma --Report of Two Cases and Literature review-].

CASE 1: A male in his 60s underwent a right transperitoneal laparoscopic partial nephrectomy procedure for a right renal tumor. Rupture of a renal cyst located close to the tumor occurred intraoperatively. The histopathological diagnosis was clear cell renal cell carcinoma (CCRCC), pT1aN0M0, G2, v0, with negative resection margins. At 84 months after surgery, computed tomography (CT) revealed a 10 mm mass in the rectus abdominis muscle at the camera port site used for the partial nephrectomy. An open lumpectomy was then performed and the histopathological diagnosis was CCRCC. One year later, a 40 mm sized mass was detected in the mesentery of the small intestine by CT, which was removed laparoscopically with part of the mesentery and diagnosed as CCRCC. Since that surgery, the patient has been free from recurrence for 8 years. CASE 2: A male in his 60s underwent a left retroperitoneal laparoscopic nephrectomy procedure for a left renal tumor. The histopathological diagnosis was CCRCC, pT1aN0M0, G1, v0, with negative resection margins. At 31 months after surgery, CT revealed a 32 mm mass in the retroperitoneal cavity at the right hand port site used for the laparoscopic nephrectomy. The mass was removed with part of the twelfth rib and erector spinae muscles in a lump, and the histopathological diagnosis was CCRCC. Since that surgery, the patient has been free from recurrence for 19 months. For the treatment of solitary port site recurrence of renal cell carcinoma after a laparoscopic radical/partial nephrectomy, we recommend surgical resection for a good prognosis.

Mapping the Initial Stages of a Protective Pathway that Enhances Catalytic Turnover by a Lytic Polysaccharide Monooxygenase.

Oxygenase and peroxygenase enzymes generate intermediates at their active sites which bring about the controlled functionalization of inert C-H bonds in substrates, such as in the enzymatic conversion of methane to methanol. To be viable catalysts, however, these enzymes must also prevent oxidative damage to essential active site residues, which can occur during both coupled and uncoupled turnover. Herein, we use a combination of stopped-flow spectroscopy, targeted mutagenesis, TD-DFT calculations, high-energy resolution fluorescence detection X-ray absorption spectroscopy, and electron paramagnetic resonance spectroscopy to study two transient intermediates that together form a protective pathway built into the active sites of copper-dependent lytic polysaccharide monooxygenases (LPMOs). First, a transient high-valent species is generated at the copper histidine brace active site following treatment of the LPMO with either hydrogen peroxide or peroxyacids in the absence of substrate. This intermediate, which we propose to be a CuII-(histidyl radical), then reacts with a nearby tyrosine residue in an intersystem-crossing reaction to give a ferromagnetically coupled (S = 1) CuII-tyrosyl radical pair, thereby restoring the histidine brace active site to its resting state and allowing it to re-enter the catalytic cycle through reduction. This process gives the enzyme the capacity to minimize damage to the active site histidine residues "on the fly" to increase the total turnover number prior to enzyme deactivation, highlighting how oxidative enzymes are evolved to protect themselves from deleterious side reactions during uncoupled turnover.

Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study.

AIM: The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2. BACKGROUND: The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important. DESIGN: A Retrospective Cohort Study was conducted. METHODS: When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis. RESULTS: Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission. CONCLUSION: If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.