ARV1 deficiency induces lipid bilayer stress and enhances rDNA stability by activating the unfolded protein response in Saccharomyces cerevisiae.

The stability of ribosomal DNA (rDNA) is maintained through transcriptional silencing by the NAD+-dependent histone deacetylase Sir2 in Saccharomyces cerevisiae. Alongside proteostasis, rDNA stability is a crucial factor regulating the replicative lifespan of S. cerevisiae. The unfolded protein response (UPR) is induced by misfolding of proteins or an imbalance of membrane lipid composition and is responsible for degrading misfolded proteins and restoring endoplasmic reticulum (ER) membrane homeostasis. Recent investigations have suggested that the UPR can extend the replicative lifespan of yeast by enhancing protein quality control mechanisms, but the relationship between the UPR and rDNA stability remains unknown. In this study, we found that the deletion of ARV1, which encodes an ER protein of unknown molecular function, activates the UPR by inducing lipid bilayer stress. In arv1Δ cells, the UPR and the cell wall integrity pathway are activated independently of each other, and the high osmolarity glycerol (HOG) pathway is activated in a manner dependent on Ire1, which mediates the UPR. Activated Hog1 translocates the stress response transcription factor Msn2 to the nucleus, where it promotes the expression of nicotinamidase Pnc1, a well-known Sir2 activator. Following Sir2 activation, rDNA silencing and rDNA stability are promoted. Furthermore, the loss of other ER proteins, such as Pmt1 or Bst1, and ER stress induced by tunicamycin or inositol depletion also enhance rDNA stability in a Hog1-dependent manner. Collectively, these findings suggest that the induction of the UPR enhances rDNA stability in S. cerevisiae by promoting the Msn2-Pnc1-Sir2 pathway in a Hog1-dependent manner.

Comparing the clinical application of strain elastography and shear wave elastography for the evaluation of lateral epicondylitis.

PURPOSE: This study aimed to compare the diagnostic performance of gray-scale ultrasound (GSU), strain elastography (SE), and shear wave elastography (SWE) for lateral epicondylitis (LE). METHODS: From November 2018 to March 2021, 87 common extensor tendons (CETs) of 70 patients were evaluated using elbow ultrasound. Patients were divided into two groups: patients with LE and those without lateral elbow pain. GSU, SE, and SWE findings from the two groups were compared, and the diagnostic performance was compared for significant variables. RESULTS: Among the 70 patients, 41 with 44 CETs were clinically diagnosed with LE, and 29 with 43 CETs had no lateral elbow pain. Hypoechogenicity, calcification, and hyperemia were significantly different. Strain ratio (SR), stiffness, and shear wave velocity (SWV) were also significantly different. The diagnostic accuracy of stiffness and SWV was better than that of other significant findings. Furthermore, there were no superiorities in SR, stiffness, or SWV. CONCLUSION: Both SE and SWE can be valuable diagnostic tools for diagnosing LE. The diagnostic performances of both SE and SWE were similar in the detection of LE.

Loss of Smi1, a protein involved in cell wall synthesis, extends replicative lifespan by enhancing rDNA stability in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, replicative lifespan (RLS) is primarily affected by the stability of ribosomal DNA (rDNA). The stability of the highly repetitive rDNA array is maintained through transcriptional silencing by the NAD+-dependent histone deacetylase Sir2. Recently, the loss of Smi1, a protein of unknown molecular function that has been proposed to be involved in cell wall synthesis, has been demonstrated to extend RLS in S. cerevisiae, but the mechanism by which Smi1 regulates RLS has not been elucidated. In this study, we determined that the loss of Smi1 extends RLS in a Sir2-dependent manner. We observed that the smi1D mutation enhances transcriptional silencing at the rDNA locus and promotes rDNA stability. In the absence of Smi1, the stress-responsive transcription factor Msn2 translocates from the cytoplasm to the nucleus, and nuclear-accumulated Msn2 stimulates the expression of nicotinamidase Pnc1, which serves as an activator of Sir2. In addition, we observed that the MAP kinase Hog1 is activated in smi1D cells and that the activation of Hog1 induces the translocation of Msn2 into the nucleus. Taken together, our findings suggest that the loss of Smi1 leads to the nuclear accumulation of Msn2 and stimulates the expression of Pnc1, thereby enhancing Sir2-mediated rDNA stability and extending RLS in S. cerevisiae.

Loss of Smi1, a protein involved in cell wall synthesis, extends replicative life span by enhancing rDNA stability in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, replicative life span (RLS) is primarily affected by the stability of ribosomal DNA (rDNA). The stability of the highly repetitive rDNA array is maintained through transcriptional silencing by the NAD+-dependent histone deacetylase Sir2. Recently, the loss of Smi1, a protein of unknown molecular function that has been proposed to be involved in cell wall synthesis, has been demonstrated to extend RLS in S. cerevisiae, but the mechanism by which Smi1 regulates RLS has not been elucidated. In this study, we determined that the loss of Smi1 extends RLS in a Sir2-dependent manner. We observed that the smi1Δ mutation enhances transcriptional silencing at the rDNA locus and promotes rDNA stability. In the absence of Smi1, the stress-responsive transcription factor Msn2 translocates from the cytoplasm to the nucleus, and nuclear-accumulated Msn2 stimulates the expression of nicotinamidase Pnc1, which serves as an activator of Sir2. In addition, we observed that the MAP kinase Hog1 is activated in smi1Δ cells and that the activation of Hog1 induces the translocation of Msn2 into the nucleus. Taken together, our findings suggest that the loss of Smi1 leads to the nuclear accumulation of Msn2 and stimulates the expression of Pnc1, thereby enhancing Sir2-mediated rDNA stability and extending RLS in S. cerevisiae.

Probe-Free Identification of RNA Virus Variants with Point Mutations by Surface-Enhanced Raman Spectroscopy.

As observed in the COVID-19 pandemic, RNA viruses continue to rapidly evolve through mutations. In the absence of effective therapeutics, early detection of new severely pathogenic viruses and quarantine of infected people are critical for reducing the spread of the viral infections. However, conventional detection methods require a substantial amount of time to develop probes specific to new viruses, thereby impeding immediate response to the emergence of viral pathogens. In this study, we identified multiple types of viruses by obtaining the spectral fingerprint of their surface proteins with probe-free surface-enhanced Raman scattering (SERS). In addition, the SERS-based method can remarkably distinguish influenza virus variants with several surface protein point mutations from their parental strain. Principal component analysis (PCA) of the SERS spectra systematically captured the key Raman bands to distinguish the variants. Our results show that the combination of SERS and PCA can be a promising tool for rapid detection of newly emerging mutant viruses without a virus-specific probe.

SARS-CoV-2 Delta Variant Breakthrough Infection and Onward Secondary Transmission in Household.

BACKGROUND: Despite the extraordinary speed of mass vaccination efforts, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant in a vaccinee with coronavirus disease 2019 (COVID-19) mRNA vaccine was identified in an adult day service center (ADSC) of Jeju, South Korea. The primary objective of this study was to investigate the epidemiologic features in infection-vulnerable facilities with a high vaccination rate of BNT162b2 mRNA COVID-19 vaccine. The second was to estimate the secondary transmission prevention effect of the vaccine in the household members by vaccination status. METHODS: We included all ADSC participants, staff and their household members. All COVID-19 infected cases were confirmed by reverse transcriptase polymerase chain reaction. We calculated attack rate in ADSC and the secondary attack rate (SAR) in household members by vaccination status. RESULTS: Among a total of 42 participants and 16 staff, of which 96.6% were fully vaccinated with BNT162b2 mRNA COVID-19 vaccine, 12 symptomatic cases and 13 asymptomatic confirmed cases of COVID-19 were found. The attack rate was 43.1%, with 13 isolates identified as SARS-CoV-2 virus, delta variant. The SAR in unvaccinated and partially vaccinated household members were 27.8% (5/18) and 25.0% (5/20), respectively, while the SAR in fully vaccinated household members was 12.5% (1/8). CONCLUSION: We describe a SARS-CoV-2 delta variant outbreak in ADSC with high vaccine coverage rate, characterized by high infection rate, high transmissibility, and low clinical severity. The outbreak proceeded to unvaccinated or partially vaccinated household members, emphasizing the need for immunizing close contacts of high-risk groups.

Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.

Medicarpin and Homopterocarpin Isolated from Canavalia lineata as Potent and Competitive Reversible Inhibitors of Human Monoamine Oxidase-B.

Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.

Radiation resistance and injury in starved Escherichia coli O157:H7 treated with electron-beam irradiation in 0.85% saline and in apple juice.

This study evaluated the influence of starvation on the radiation resistance and injury in Escherichia coli O157:H7, following electron beam irradiation in 0.85% (wt/vol) saline and in apple juice. Washed exponential-phase cells of E. coli O157:H7 that were grown in tryptic soy broth (TSB) at 35°C were starved in 0.85% saline (25°C) for 10 days. Exponential- or stationary-phase cells grown in TSB (35°C) served as controls. Samples of 0.85% saline or pasteurized apple juice, inoculated with control cells or cells starved for 8 days, were exposed to electron beam irradiation at doses ranging from 0.0 (control) to 0.70 kGy. The E. coli survivors were enumerated by plating diluted samples on tryptic soy agar or on Sorbitol McConkey agar and counting bacterial colonies after incubation (35°C) for 24 h. Starved cells consistently exhibited higher irradiation D-values than controls (p<0.05). The D-values for control and starved E. coli O157:H7 in 0.85% saline were 0.11 and 0.26 kGy, respectively; D-values in apple juice were 0.16, 0.19, and 0.33 kGy for exponential, stationary, and starved cells, respectively. Irradiation (0.70 kGy) of E. coli O157:H7 in apple juice reduced numbers of exponential- and stationary-phase cells by ∼4.32 and 3.74 logs, respectively, whereas starved cells were reduced by only 2.20 logs. Exponential-phase cells exhibited the lowest resistance to irradiation, and sublethal injury in survivors of this group was higher than that of stationary-phase or starved cells irradiated at 0.50 or 0.70 kGy (p<0.05). The results of this study indicate that starvation-induced stress cross-protects E. coli O157:H7 from ionizing radiation and should be considered an important factor when determining irradiation D-values for this pathogen.

Evaluation of Extra-Prostatic Extension on Deep Learning-Reconstructed High-Resolution Thin-Slice T2-Weighted Images in Patients with Prostate Cancer.

The aim of this study was to compare diagnostic performance for extra-prostatic extension (EPE) and image quality among three image datasets: conventional T2-weighted images (T2WIconv, slice thickness, 3 mm) and high-resolution thin-slice T2WI (T2WIHR, 2 mm), with and without deep learning reconstruction (DLR) in patients with prostatic cancer (PCa). A total of 88 consecutive patients (28 EPE-positive and 60 negative) diagnosed with PCa via radical prostatectomy who had undergone 3T-MRI were included. Two independent reviewers performed a crossover review in three sessions, in which each reviewer recorded five-point confidence scores for the presence of EPE and image quality using a five-point Likert scale. Pathologic topographic maps served as the reference standard. For both reviewers, T2WIconv showed better diagnostic performance than T2WIHR with and without DLR (AUCs, in order, for reviewer 1, 0.883, 0.806, and 0.772, p = 0.0006; for reviewer 2, 0.803, 0.762, and 0.745, p = 0.022). The image quality was also the best in T2WIconv, followed by T2WIHR with DLR and T2WIHR without DLR for both reviewers (median, in order, 3, 4, and 5, p < 0.0001). In conclusion, T2WIconv was optimal in regard to image quality and diagnostic performance for the evaluation of EPE in patients with PCa.

Deep Learning Algorithm for Tumor Segmentation and Discrimination of Clinically Significant Cancer in Patients with Prostate Cancer.

BACKGROUND: We investigated the feasibility of a deep learning algorithm (DLA) based on apparent diffusion coefficient (ADC) maps for the segmentation and discrimination of clinically significant cancer (CSC, Gleason score ≥ 7) from non-CSC in patients with prostate cancer (PCa). METHODS: Data from a total of 149 consecutive patients who had undergone 3T-MRI and been pathologically diagnosed with PCa were initially collected. The labelled data (148 images for GS6, 580 images for GS7) were applied for tumor segmentation using a convolutional neural network (CNN). For classification, 93 images for GS6 and 372 images for GS7 were used. For external validation, 22 consecutive patients from five different institutions (25 images for GS6, 70 images for GS7) representing different MR machines were recruited. RESULTS: Regarding segmentation and classification, U-Net and DenseNet were used, respectively. The tumor Dice scores for internal and external validation were 0.822 and 0.7776, respectively. As for classification, the accuracies of internal and external validation were 73 and 75%, respectively. For external validation, diagnostic predictive values for CSC (sensitivity, specificity, positive predictive value and negative predictive value) were 84, 48, 82 and 52%, respectively. CONCLUSIONS: Tumor segmentation and discrimination of CSC from non-CSC is feasible using a DLA developed based on ADC maps (b2000) alone.

Study on the Nanopore Deformation Mechanisms in Shale Oil Reservoir: Insights from the Molecular Simulation.

The stress and adsorption motivation deformation during shale oil production directly affect its development dynamics. First, a mathematical simulation of pore deformation in shale oil under stress motivation is established. We analyzed the impact of factors including the reservoir pressure, Biot coefficient, bulk modulus, and tortuosity on the deformation characteristics of nanopores. Second, a pore deformation model under multifactor synergistic effect is derived by combining the molecular dynamics, which takes into account the influence of adsorption deformation on the total adsorption of shale oil reservoir. Finally, a shale oil pore deformation model under multifactor synergistic effect is obtained. The results show that the current pore diameter shows a trend of decreasing with the decrease of current formation pressure and the difference with original reservoir pressure increases. The pore shows a trend of less deformation with a decrease in the effective stress coefficient. When the Biot coefficient is 0.8, the pore diameter under 5 MPa is 4.01 nm. When the Biot coefficient decreases to 0.3, the pore diameter under 5 MPa becomes 9.12 nm, an increase of 127.43% compared to 4.01 nm. The bulk modulus affects the magnitude of pore deformation under the same pressure, which means that the pore diameter shows a tendency to deform more easily as the bulk modulus increases. Meanwhile, the pore diameter decreases with increasing tortuosity. In addition, the pore deformation is subject to both stress and adsorption motivation deformation synergistically. The stress motivation deformation leads to a decrease of pore diameter with pressure decrease, while, in contrast, the adsorption motivation leads to an increase of pore diameter. The pore diameter under synergy is influenced by the coupling effect, and the deformation under synergy tends to decrease as the pore diameter decreases. When the rock mechanical parameters are changed so that the pores are not easily deformed by stress, the adsorption motivation deformation plays a dominant role in synergy. The amount of synergistic deformation decreases with increasing temperature, while the change in the component ratio of multicomponent fluid mainly affects the corresponding adsorption and the amount of synergistic deformation. Interestingly, when the proportion of CO2 is the largest, the corresponding maximum deformation is higher than the other proportions (43.77%). It not only enhances the recovery rate of shale oil reservoirs by utilizing CO2 but also provides the possibility of geological CO2 burial.

Counting DNA molecules on a microchannel surface for quantitative analysis.

Microscopic visualization of DNA molecules is a simple, intuitive, and powerful method. Nonetheless, DNA-molecule quantification methods that employ microscopic visualization have not been reported so far. In this study, a new quantitative approach is presented that enables the counting of individual DNA molecules that have been rendered visible by fluorescence microscopy. Toward this, a microfluidic device was employed that directed DNA molecules into microchannels and deposited the molecules onto a positively charged surface. This microfluidic device had a vertically tapered channel inlet structure that prevented the accumulation of excess DNA molecules in the channel inlet while creating a tapering flow, thereby ensuring the even distribution of the DNA molecules in the microchannels. The channel heights and the density of positive charges on the surface were optimized for analysis. The linearity of this method with respect to the determination of the concentration of DNA in solutions was subsequently determined. The limit of detection was 0.48 fg/µL, which corresponds to 64 molecules of 7.25 kbp DNA in 1 µL of sample. This quantitative approach was finally used to count two types of plasmids co-transformed in an E. coli cell; a measurement that is typically considered challenging with gel electrophoresis.

Expression level of Sec62 modulates membrane insertion of marginally hydrophobic segments.

In the endoplasmic reticulum (ER) membrane, transmembrane (TM) domain insertion occurs through the Sec61 channel with its auxiliary components, including Sec62. Sec62 interacts with the Sec61 channel and is located on the front side of the Sec61 lateral gate, an entry site for TM domains to the lipid bilayer. Overexpression of Sec62 led to a growth defect in yeast, and we investigated its effects on protein translocation and membrane insertion by pulse labeling of Sec62 client proteins. Our data show that the insertion efficiency of marginally hydrophobic TM segments is reduced upon Sec62 overexpression. This result suggests a potential regulatory role of Sec62 as a gatekeeper of the lateral gate, thereby modulating the insertion threshold of TM segments.

Trust in information, political identity and the brain: an interdisciplinary fMRI study.

Misinformation has triggered government inquiries and threatens the perceived legitimacy of campaign processes and electoral outcomes. A new identity polarization has arisen between Remain and Leave sympathizers in the UK Brexit debate, with associated accusations of misinformation use. Competing psychological accounts of how people come to accept and defend misinformation pit self-reinforcing motivated cognition against lack of systematic reasoning as possible explanations. We harness insights from political science, cognitive neuroscience and psychology to examine the impact of trust and identity on information processing regarding Brexit in a group of Remain identifiers. Behaviourally, participants' affective responses to Brexit-related information are affected by whether the emotional valence of the message is compatible with their beliefs on Brexit (positive/negative) but not by their trust in the source of information. However, belief in the information is significantly affected by both (dis)trust in information source and by belief compatibility with the valence of the information. Neuroimaging results confirm this pattern, identifying areas involved in judgements of the self, others and automatic processing of affectively threatening stimuli, ultimately supporting motivated cognition accounts of misinformation endorsement. This article is part of the theme issue 'The political brain: neurocognitive and computational mechanisms'.

Increased representation of the non-dominant hand in pianists demonstrated by measurement of 3D morphology of the central sulcus.

Background: Post-mortem and magnetic resonance imaging (MRI) studies of the central sulcus, as an indicator of motor cortex, have shown that in the general population there is greater representation of the dominant compared to the non-dominant hand. Studies of musicians, who are highly skilled in performing complex finger movements, have suggested this dominance is affected by musical training, but methods and findings have been mixed. Objective: In the present study, an automated image analysis pipeline using a 3D mesh approach was applied to measure central sulcus (CS) asymmetry on MR images obtained for a cohort of right-handed pianists and matched controls. Methods: The depth, length, and surface area (SA) of the CS and thickness of the cortical mantle adjacent to the CS were measured in each cerebral hemisphere by applying the BrainVISA Morphologist 2012 software pipeline to 3D T1-weighted MR images of the brain obtained for 15 right-handed pianists and 14 controls, matched with respect to age, sex, and handedness. Asymmetry indices (AIs) were calculated for each parameter and multivariate analysis of covariance (MANCOVA), and post hoc tests were performed to compare differences between the pianist and control groups. Results: A one-way MANCOVA across the four AIs, controlling for age and sex, revealed a significant main effect of group (P = 0.04), and post hoc analysis revealed that while SA was significantly greater in the left than the right cerebral hemisphere in controls (P < 0.001), there was no significant difference between left and right SA in the pianists (P = 0.634). Independent samples t-tests revealed that the SA of right CS was significantly larger in pianists compared to controls (P = 0.015), with no between-group differences in left CS. Conclusions: Application of an image analysis pipeline to 3D MR images has provided robust evidence of significantly increased representation of the non-dominant hand in the brain of pianists compared to age-, sex-, and handedness-matched controls. This finding supports prior research showing structural differences in the central sulcus in musicians and is interpreted to reflect the long-term motor training and high skill level of right-handed pianists in using their left hand.

Low relative muscle volume: Correlation with prevalence of venous thromboembolism following total knee arthroplasty.

BACKGROUND: There have been many efforts to find modifiable risk factors for venous thromboembolism (VTE) in the perioperative period of total knee arthroplasty (TKA), while no study has investigated the relationship between the muscle mass and deep vein thrombosis (DVT) or pulmonary embolism frequency following TKA. This study aimed to evaluate the relationship between muscle volume and the prevalence of symptomatic and radiologically confirmed venous thromboembolism (VTE) after total knee arthroplasty (TKA). METHODS: A total of 261 consecutive patients who underwent primary TKA between 2013 and 2015 were enrolled. Computed tomographic venography with pulmonary angiography (CTVPA) was performed between the 5th and 7th postoperative days to assess the presence of VTE. Four parameters of muscle volume at three levels were evaluated on CTVPA: (i) the cross-sectional area of all skeletal muscles (skeletal muscle index) and total psoas area at the level of the third lumbar vertebrae; (ii) the vastus lateralis muscle at the thigh level; and (iii) the posterior crural muscle at the lower leg level. The relationship between the muscle volume at each level and the prevalence of VTE after TKA was evaluated with multivariate adjusted logistic regression models. RESULTS: The CTVPA scan showed no proximal DVT, and all thrombi were located in muscular, peroneal, and posterior tibial veins. In unilateral TKA, patients with lower muscle volume of the vastus lateralis at the thigh level in the nonoperated limb had significantly higher prevalence of distal DVT in the operated limb (adjusted OR: 2.97 at subclinical DVT revealed by CTVPA and adjusted OR: 2.68 at symptomatic DVT). This finding was also discovered in patients who underwent simultaneous bilateral TKA (adjusted OR: 1.73-2.97 at subclinical DVT and adjusted OR:1.76-1.86 at symptomatic DVT). CONCLUSIONS: The relative muscle volume of the vastus lateralis at the thigh level was negatively associated with the prevalence of symptomatic and radiologically confirmed DVT, suggesting that low thigh muscle mass is an independent risk factor for VTE in the postoperative period of TKA.

A novel device for endoscopic submucosal dissection, the Fork knife.

AIM: To introduce and evaluate the efficacy and technical aspects of endoscopic submucosal dissection (ESD) using a novel device, the Fork knife. METHODS: From March 2004 to April 2008, ESD was performed on 265 gastric lesions using a Fork knife (Endo FS) (group A) and on 72 gastric lesions using a Flexknife (group B) at a single tertiary referral center. We retrospectively compared the endoscopic characteristics of the tumors, pathological findings, and sizes of the resected specimens. We also compared the en bloc resection rate, complete resection rate, complications, and procedure time between the two groups. RESULTS: The mean size of the resected specimens was 4.27 +/- 1.26 cm in group A and 4.29 +/- 1.48 cm in group B. The en bloc resection rate was 95.8% (254/265 lesions) in group A and 93.1% (67/72) in group B. Complete ESD without tumor cell invasion of the resected margin was obtained in 81.1% (215/265) of group A and in 73.6% (53/72) of group B. The perforation rate was 0.8% (2/265) in group A and 1.4% (1/72) in group B. The mean procedure time was 59.63 +/- 56.12 min in group A and 76.65 +/- 70.75 min in group B (P < 0.05). CONCLUSION: The Fork knife (Endo FS) is useful for clinical practice and has the advantage of reducing the procedure time.

Food Elimination Diet and Nutritional Deficiency in Patients with Inflammatory Bowel Disease.

Certain types of foods are common trigger for bowel symptoms such as abdominal discomfort or pain in patients with inflammatory bowel disease (IBD). But indiscriminate food exclusions from their diet can lead extensive nutritional deficiencies. The aim of this study was to investigate nutritional status, food restriction and nutrient intake status in IBD patients. A total 104 patients (food exclusion group: n = 49; food non-exclusion group: n = 55) participated in the survey. The contents were examined by 3 categories: 1) anthropometric and nutritional status; 2) diet beliefs and food restriction; and 3) nutrient intake. The malnutrition rate was significantly higher in the food exclusion group (p = 0.007) compared to food non-exclusion group. Fifty-nine percent of patients in the food exclusion group held dietary beliefs and reported modifying their intake according to their dietary belief. The most common restricted food was milk, dairy products (32.7%), raw fish (24.5%), deep-spicy foods (22.4%), and ramen (18.4%). The mean daily intake of calcium (p = 0.002), vitamin A (p < 0.001), and zinc (p = 0.001) were significantly lower in the food exclusion group. Considering malnutrition in IBD patients, nutrition education by trained dietitians is necessary for the patients to acquire disease-related knowledge and overall balanced nutrition as part of strategies in treating and preventing nutrition deficiencies.

Mitochondrial dysfunction reduces yeast replicative lifespan by elevating RAS-dependent ROS production by the ER-localized NADPH oxidase Yno1.

Mitochondrial dysfunction leads to the accumulation of reactive oxygen species (ROS) which is associated with cellular dysfunction, disease etiology, and senescence. Here, we used the eukaryotic model Saccharomyces cerevisiae, commonly studied for cellular aging, to demonstrate how defective mitochondrial function affects yeast replicative lifespan (RLS). We show that RLS of respiratory-deficient cells decreases significantly, indicating that the maintenance of RLS requires active respiration. The shortening of RLS due to mitochondrial dysfunction was not related to the accumulation of extrachromosomal ribosomal DNA circles, a well-known cause of aging in yeast. Instead, intracellular ROS and oxidatively damaged proteins increased in respiratory-deficient mutants. We show that, while the protein kinase A activity is not elevated, ROS generation in respiratory-deficient cells depends on RAS signaling pathway. The ER-localized NADPH oxidase Yno1 also played a role in producing ROS. Our data suggest that a severe defect in mitochondrial respiration accelerates cellular aging by disturbing protein homeostasis in yeast.