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Background: A rodent model of gastroduodenal-esophageal reflux can result in replacement of squamous esophageal mucosa with intestinal-type columnar mucosa and carcinoma. The validity of this model is debated, as it is unproven whether this mucosa is intestinal metaplasia due to reflux or represents migration of adjacent jejunal mucosa above the anastomosis. The aim of this study was to evaluate the esophageal intestinal-type mucosa in these animals by measuring expression of trefoil factor genes (TFF-1, -2, -3) and comparing it with adjacent jejunum in order to determine its etiology.Methods: Twenty-five rats underwent esophagojejunostomy at the ligament of Treitz to induce reflux of gastric and duodenal contents. The animals were sacrificed at 16 weeks (n = 14) and 30 weeks (n = 11). After sacrifice, the distal esophagus, jejunum, and colon were obtained. RNA was isolated, reverse transcribed, and messenger RNA (mRNA) expression of TFF-1, -2, and -3 was measured with real-time polymerase chain reaction (PCR). Linear discriminant analysis classified samples based on gene expression.Results: Esophageal intestinal-type mucosa was present at sacrifice in 18 animals. Compared to jejunum, the expression of TFF-1 and TFF-2 mRNA in the intestinal mucosa of the distal esophagus was increased (p = 0.0007 and p < 0.0001, respectively). Expression of TFF-3 was also increased in esophageal intestinal mucosa compared with jejunum (p = 0.0002), but there was significant overlap in expression between these tissues for this gene. Linear discriminant analysis misclassified esophageal intestinal-type mucosa as jejunum in only one case. In no cases was jejunum misclassified as esophageal intestinal-type mucosa.Conclusion: The gene expression profile of esophageal intestinal-type mucosa following surgically induced reflux in a rodent model indicates that this represents intestinal metaplasia, not proximal migration of jejunum. This validates this model for studying the pathogenesis of Barrett's esophagus. Use of this model has potential for assessment of the impact of various therapies on the natural history of reflux disease. [ABSTRACT FROM AUTHOR]

Background: The unique setup of robotic surgery challenges the traditional instructional dynamic between surgical learners and teachers. Previous studies have posited difficulties such as reliance on observational learning and ease of takeover. However, we lack understanding of how these instructional challenges manifest and are perceived by learners. Improving instruction has the potential to optimize education and performance in robotic surgery., Methods: In this qualitative study, we conducted robotic case observations and learner interviews focusing on instruction in robotic surgery. We deductively generated codes in a theory-informed manner after review of the instructional literature in surgery, medicine, and other fields. We applied these codes in a rigorous directed content analysis of field notes and transcripts to identify themes., Results: Thirty-eight faculty, fellows, and residents participated in 10 robotic cases and 20 semistructured interviews. Observed practices on the basis of case observations differed substantially from preferred practices on the basis of interview data. Using 37 codes, we identified 4 main themes related to instruction in robotic surgery: contextualization, individualization, autonomy, and multimodality. We contrasted observed and preferred instruction in each of these areas to generate instructional considerations that may better align preferences and practices., Conclusions: We observed several suboptimal instructional practices that contradicted preferred ways of learning. We suggested robotic-specific instructional considerations such as using multimodality to promote active learning and to reduce ambiguity. We also provided considerations applicable to all types of surgery, such as to include rationale to promote learning consolidation and to frame operative steps to allow trainees to plan their participation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Objective: Randomized control trials are considered the highest level of evidence, yet the scalability and practicality of implementing randomized control trials in the thoracic surgical oncology space are not well described. The aim of this study is to understand what types of randomized control trials have been conducted in thoracic surgical oncology and ascertain their success rate in completing them as originally planned., Methods: The ClinicalTrials.gov database was queried in April 2023 to identify registered randomized control trials performed in patients with lung cancer who underwent surgery (by any technique) as part of their treatment., Results: There were 68 eligible randomized control trials; 33 (48.5%) were intended to examine different perioperative patient management strategies (eg, analgesia, ventilation, drainage) or to examine different intraoperative technical aspects (eg, stapling, number of ports, port placement, ligation). The number of randomized control trials was relatively stable over time until a large increase in randomized control trials starting in 2016. Forty-four of the randomized control trials (64.7%) were open-label studies, 43 (63.2%) were conducted in a single facility, 66 (97.1%) had 2 arms, and the mean number of patients enrolled per randomized control trial was 236 (SD, 187). Of 21 completed randomized control trials (31%), the average time to complete accrual was 1605 days (4.4 years) and average time to complete primary/secondary outcomes and adverse events collection was 2125 days (5.82 years)., Conclusions: Given the immense investment of resources that randomized control trials require, these findings suggest the need to scrutinize future randomized control trial proposals to assess the likelihood of successful completion. Future study is needed to understand the various contributing factors to randomized control trial success or failure., Competing Interests: Y.L. is a full-time employee at Intuitive Surgical. D.S.O. is a part-time medical advisor at Intuitive Surgical. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Background: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy., Methods: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores., Results: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55)., Conclusion: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The forkhead domain genes are important for development and morphogenesis in fungi. Six forkhead genes fkhA - fkhF have been found in the genome of the model filamentous Ascomycete Aspergillus nidulans . To identify the fkh gene(s) associated with fungal development, we examined mRNA levels of these six genes and found that the level of fkhB and fkhD mRNA was significantly elevated during asexual development and in conidia. To investigate the roles of FkhB and FkhD, we generated fkhB and fkhD deletion mutants and complemented strains and investigated their phenotypes. The deletion of fkhB , but not fkhD , affected fungal growth and both sexual and asexual development. The fkhB deletion mutant exhibited decreased colony size with distinctly pigmented (reddish) asexual spores and a significantly lower number of conidia compared with these features in the wild type (WT), although the level of sterigmatocystin was unaffected by the absence of fkhB . Furthermore, the fkhB deletion mutant produced sexual fruiting bodies (cleistothecia) smaller than those of WT, implying that the fkhB gene is involved in both asexual and sexual development. In addition, fkhB deletion reduced fungal tolerance to heat stress and decreased trehalose accumulation in conidia. Overall, these results suggest that fkhB plays a key role in proper fungal growth, development, and conidial stress tolerance in A. nidulans .

Surgical training relies on subjective feedback on resident technical performance by attending surgeons. A novel data recorder connected to a robotic-assisted surgical platform captures synchronized kinematic and video data during an operation to calculate quantitative, objective performance indicators (OPIs). The aim of this study was to determine if OPIs during initial task of a resident's robotic-assisted lobectomy (RL) correlated with bleeding during the procedure. Forty-six residents from the 2019 Thoracic Surgery Directors Association Resident Boot Camp completed RL on an ex vivo perfused porcine model while continuous video and kinematic data were recorded. For this pilot study, RL was segmented into 12 tasks and OPIs were calculated for the initial major task. Cases were reviewed for major bleeding events and OPIs of bleeding cases were compared to those who did not. Data from 42 residents were complete and included in the analysis. 10/42 residents (23.8%) encountered bleeding: 10/40 residents who started with superior pulmonary vein exposure and 0/2 residents who started with pulmonary artery exposure. Twenty OPIs for both hands were assessed during the initial task. Six OPIs related to instrument usage or smoothness of motion were significant for bleeding. Differences were statistically significant for both hands (p < 0.05). OPIs showing bimanual asymmetry indicated lower proficiency. This study demonstrates that kinematic and video analytics can establish a correlation between objective performance metrics and bleeding events in an ex vivo perfused lobectomy. Further study could assist in the development of focused exercises and simulation on objective domains to help improve overall performance and reducing complications during RL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/β-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair., Competing Interests: Declaration of interests J.-H.S. is a scientific co-founder of AAVAA Therapeutics and holds equity in this company. G.G. is a scientific co-founder of AAVAA Therapeutics, Voyager Therapeutics, and Aspa Therapeutics and holds equity in these companies. G.G. is an inventor on patents with potential royalties licensed to Voyager Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies. D.S.O. is a chief scientific officer of Osteogene Tech. These pose no conflicts for this study. The other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the anti-osteoporosis effects of Osmanthus fragrans leaf ethanol extract (OFLEE) in bone marrow-derived macrophages (BMM) and animals with osteoporosis. OFLEE not only suppressed tartrate-resistant acid phosphatase (TRAP)-positive cells with multiple nuclei but also decreased TRAP activity in BMM treated with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). The formation of F-actin rings and the expression and activation of matrix metalloproteinases were decreased by OFLEE in BMM treated with M-CSF and RANKL. OFLEE suppressed M-CSF- and RANKL-induced osteoclastogenesis by inhibiting NF-κB phosphorylation, tumor necrosis factor receptor-associated factor 6, c-fos, the nuclear factor of activated T-cells, cytoplasmic 1, and cathepsin K in BMM. OFLEE downregulated reactive oxygen species, cyclooxygenase-2, inducible nitric oxide synthase, prostaglandin E 2 , tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-17, and RANKL in BMM treated with M-CSF and RANKL. Oral administration of OFLEE suppressed osteoporotic bone loss without hepatotoxicity in ovariectomy-induced osteoporosis animals. Our findings suggest that OFLEE, with anti-inflammatory effects, prevents osteoporotic bone loss through the suppression of osteoclastic differentiation in BMM and animals with osteoporosis.

Background: There is no randomized controlled study about the effects of end-effector robot-assisted gait training (RAGT) in patients with spinal cord injury (SCI)., Objective: To examine the effects of end-effector RAGT on gait and balance abilities in SCI., Methods: Thirty-one patients were randomly assigned to the RAGT (Morning Walk®, Curexo, Seoul, South Korea) or conventional therapy (CT) group. Patients were assessed using the 10-meter walk test (10MWT), 6-minute walk test (6mWT), lower extremity motor score (LEMS) and proprioception, Berg Balance Scale (BBS), Walking Index for Spinal Cord Injury-II (WISCI-II), and mobility category of Spinal Cord Independence Measure-III., Results: All clinical outcome measures significantly improved in both groups. The BBS and WISCI-II were significantly improved in the RAGT group compared to the CT group. In the RAGT group, pre-LEMS and pre-WISCI-II of the 10MWT improved group and pre-BBS of the 6mWT improved group were higher than those of the 10MWT non-improved and 6mWT non-improved group, respectively., Conclusion: End-effector RAGT and CT in patients with incomplete SCI could lead to improvements in gait ability, lower extremity muscle strength, balance, proprioception, and mobility. Additionally, end-effector RAGT could improve balance and gait abilities substantially better than CT.

Fourteen maxillary sinuses were reconstructed in 12 patients who presented with a previous sinus elevation failure. In all cases, large perforations of the sinus membrane occurred during removal of the failed graft from the sinus; the perforations were sealed with fibrin glue, then the site was grafted using homologous fibrin glue (HFG) mixed with a calcium phosphate scaffold (CPS). Histologic analyses revealed that the CPS-HFG graft was followed by an ossification process, with the formation of spongy bone similar to that of the normal skeleton. Twenty-four endosseous implants were successfully placed into the newly regenerated bone. All implants were successfully restored with ceramic crowns 6 months after placement. At the 3-year follow-up, no infections or implant failures were reported. The described technique offers several clinical advantages, as the removal of the failed graft, the sinus perforation repair, and the sinus elevation can be achieved in the same surgery without needing to postpone the regenerative surgery phase.

Background: Conversion rates during minimally invasive surgery are generally examined in the limited scope of a particular procedure. However, for a hospital or payor, the cumulative impact of conversions during commonly performed procedures could have a much larger negative effect than what is appreciated by individual surgeons. The aim of this study is to assess open conversion rates during minimally invasive surgery (MIS) across common procedures using laparoscopic/thoracoscopic (LAP/VATS) and robotic-assisted (RAS) approaches., Study Design: Retrospective cohort study using the Premier Database on patients who underwent common operations (hysterectomy, lobectomy, right colectomy, benign sigmoidectomy, low anterior resection, inguinal and ventral hernia repair, and partial nephrectomy) between January 2013 and September 2015. ICD-9 and CPT codes were used to define procedures, modality, and conversion. Propensity scores were calculated using patient, hospital, and surgeon characteristics. Propensity-score matched analysis was used to compare conversions between LAP/VATS and RAS for each procedure., Results: A total of 278,520 patients had MIS approaches of the ten operations. Conversion occurred in 5% of patients and was associated with a 1.77 day incremental increase in length of stay and $3441 incremental increase in cost. RAS was associated with a 58.5% lower rate of conversion to open surgery compared to LAP/VATS., Conclusion: At a health system or payer level, conversion to open is detrimental not just for the patient and surgeon but also puts a significant strain on hospital resources. Use of RAS was associated with less than half of the conversion rate observed for LAP/VATS., (© 2022. The Author(s).)

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.

Sustainable substitutes for leather can be made from mushroom mycelium, which is an environmentally friendly alternative to animal and synthetic leather. Mycelium-based leather is derived from Polyporales, in which lignocellulosic material is used as the substrate. The plasticizing and crosslinking of mycelial mats with various reagents might affect the leather properties and mycelial architecture. This study investigated the physicochemical and mechanical properties of mycelium-based leather (MBL) samples, including the hygroscopic nature, thermal stability, cell wall chemistry, density, micromorphology, tensile strength, elongation rate, and Young's modulus. Micromorphological observations confirmed the mycelial networks and their binding performance, verifying their efficacy as a substitute leather. The most significant effects were observed after treatment with 20% polyethylene glycol, which resulted in an increase in Young's modulus and tensile strength. Furthermore, the samples generally exhibited a high density (1.35, 1.46 g/cm 3 ) and tensile strength (7.21 ± 0.93, 8.49 ± 0.90 MPa), resembling leather. The tear strength reached as low as 0.5-0.8 N/mm. However, the tensile and tear strength may be affected by leather processing and the tuning of mycelial growth. Nevertheless, high-density mycelia are shown to be suitable for the production of MBL, while mycofabrication and strain selection are sustainable for novel industrial applications of MBL.

One major issue facing the health care system in the United States is the disparity in health care management of diseases that affect minority patient populations. Pseudofolliculitis barbae (PFB) is very common in Black men. It presents as skin-colored to erythematous, follicular or perifollicular papules and pustules predominantly on the neck and chin. The most definitive treatment for PFB is cessation of close shaving. However, many Black men are forced to comply with "clean-shaven" policies in the workforce. For those who are able to obtain medical waivers, there is significant time and costs associated with this, especially if they must wait to receive this waiver from a dermatologist. If primary care providers are able to identify the disease and spread awareness of its legitimacy, it may be easier for patients to receive the necessary waivers and may encourage employers to reflect on the ethnic equity of this practice. Our professional support can help reduce stigma and lead to improvements in the physical and psychological health of this historically mistreated population., Competing Interests: Conflict of interest: none reported., (© Copyright 2022 by the American Board of Family Medicine.)

The primary aim of this study was to reveal the effects of end-effector robot-assisted gait training (RAGT) on motor function, proprioception, balance, and gait ability in patients with incomplete spinal cord injury (SCI). The secondary aim was to determine the correlation between clinical outcomes. This study was a prospective and multi-center study. A total of 13 incomplete SCI patients who met inclusion criteria received 30 min of RAGT with Morning Walk ® (Curexo, Seoul, South Korea), and 1 h of conventional physiotherapy 5 times per week for 4 weeks. Clinical outcome measures were 10 m walk test (10MWT), 6 min walk test (6mWT), lower extremity motor score (LEMS), proprioception, Berg Balance Scale (BBS), and Walking Index for Spinal Cord Injury (WISCI)-II. All participants were assessed within 48 h before and after the intervention.&nbsp;All clinical outcomes were statistically improved after RAGT. Subgroup analysis according to the initial proprioception, WISCI-II in the normal group showed a statistically significant improvement compared to the abnormal group. Initial BBS and WISCI-II had a positive correlation with most of the final clinical outcomes. The final BBS had a strong positive correlation with the final 10MWT, 6mWT, and WISCI-II. Initial proprioception had a positive correlation with the final WISCI-II. The final proprioception also had a moderate positive correlation with 6mWT and BBS. This study's results suggest that the end-effector RAGT could promote proprioception, balance ability and walking ability. Postural control ability and proprioception also had a positive relationship with gait ability.

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections in infants. Macroautophagy/autophagy is a catalytic metabolic process required for cellular homeostasis. Although intracellular metabolism is important for immune responses in dendritic cells, the link between autophagy and immunometabolism remains unknown. Here, we show that the autophagy-related protein ATG5 regulates immunometabolism. Atg5 -deficient mouse dendritic cells showed increased CD8A + T-cell response and increased secretion of proinflammatory cytokines upon RSV infection. Transcriptome analysis showed that Atg5 deficiency alters the expression of metabolism-related genes. Atg5 -deficient dendritic cells also showed increased activation of glycolysis and the AKT-MTOR-RPS6KB1 pathway and decreased mitochondrial activity, all of which are cellular signatures for metabolic activation. These cells also showed elevated CD8A + T-cell priming and surface major histocompatibility complex (MHC) class I expression. Our results suggested that ATG5 regulated host immune responses by modulating dendritic cell metabolism. These findings may help develop potential antiviral therapies that alter host immunity by regulating autophagy and immunometabolism. Abbreviations : 2-DG: 2-deoxyglucose; AAK1: AP2 associated kinase 1; AKT: AKT serine/threonine kinase; AM: alveolar macrophage; ATG: autophagy; ATP: adenosine triphosphate; BAL: bronchoalveolar lavage; BMDC: bone marrow dendritic cell; CSF2/GM-CSF: colony-stimulating factor 2 (granulocyte-macrophage); CTL: cytotoxic T lymphocyte; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; GSEA: gene-set enrichment analysis; H-2D b : H-2 class I histocompatibility antigen, D-B alpha chain; H-2K b : MHC class I H2-K-b; HIF1A: hypoxia-inducible factor 1 alpha; IFNG: interferon-gamma; IL: interleukin; ITGAX: integrin alpha X; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MHC: major histocompatibility complex; MTORC1: mammalian target of rapamycin kinase complex 1; PBS: phosphate-buffered saline; PFU: plaque-forming unit; RLR: retinoic acid-inducible-I-like receptor; ROS: reactive oxygen species; RPMI: Roswell Park Memorial Institute; RPS6KB1/S6K: ribosomal protein S6 kinase, polypeptide 1; RSV: respiratory syncytial virus; Th: T helper; TLR: toll-like receptor; Treg: regulatory T cells; UMAP: uniform manifold approximation and projection.

Objective: During robotic lobectomy (RL), the surgeon can elect to use either robotic staplers or hand-held laparoscopic staplers. It is assumed that either will result in similar outcomes, while robotic staplers increase cost. We sought to compare perioperative outcomes and costs between RL cases that utilized robotic staplers versus hand-held staplers in real-world clinical practice., Methods: Patients who underwent an elective RL between October 2015 and December 2017 were identified in the Premier Hospital Perspective Database. Propensity score matching (PSM) analysis was performed to compare perioperative outcomes, healthcare resource utilization, and costs between cases using robotic staplers and hand-held staplers during RL., Results: In the PSM analysis, RL cases that fully utilized robotic staplers compared to hand-held staplers were associated with significantly lower risks of developing bleeding (5.6% vs 9.8%, P = 0.03) and conversion to open surgery (0.3% vs 5.9%, P = 0.004). Additionally, in a multivariable regression analysis, robotic stapler was associated with reduced risk for air leak (OR 0.70, 95% CI 0.50-0.98) and overall complications (OR 0.76, 95% CI 0.58-0.99). The total index hospitalization costs were comparable between the 2 groups (median [IQR], $21,667 [$16,860-$29,033] in robotic stapler vs $21,398 [$17,258-$29,406] in hand-held stapler, P = 0.22)., Conclusions: Among RL cases, utilization of robotic staplers was associated with significantly lower risks of perioperative bleeding, conversion, and possibly air leak and overall complications compared to RL cases utilizing hand-held staplers. The choice of stapler may have an impact on outcomes and robotic staplers do not increase total costs.

A new category of commercial bulk fill composite resins (CRs) enables the placement of 4-mm-thick layers as an alternative to the traditional time-consuming incremental technique. The purpose of the present study was to compare the efficiency of the polymerization, adaptation and porosity of two high-viscosity 'sculptable' bulk fill CRs (Filtek™ Bulk Fill (3M™ ESPE, St. Paul, MN, USA) and Tetric EvoCeram ® Bulk Fill (Ivoclar Vivadent AG, Schwan, Liechtenstein)) and two low-viscosity 'flowable' bulk fill CRs (SureFil ® SDR™ flow (Dentsply Sirona, Charlotte, NC, USA) and Tetric EvoFlow ® Bulk Fill (Ivoclar Vivadent AG, Schaan, Liechtenstein)). Cylindrical samples of the bulk fill CRs (4 mm height × 10 mm diameter) were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Additionally, occlusal cavities were prepared in twelve extracted human molars and restored with the bulk fill CRs ( n = 3 for each CR). The adaptation and porosity of the bulk fill CRs were evaluated by X-ray microcomputed tomography (µCT) with a 3D morphometric analysis, and the adaptation was also analyzed by scanning electron microscopy (SEM) on longitudinal vestibulo-oral sections of the restored teeth. The AFM analysis demonstrated that the surface roughness of the SureFil ® SDR™ flow was higher than that of the Tetric EvoFlow ® Bulk Fill and that the surface roughness of Filtek™ Bulk Fill was higher than that of Tetric EvoCeram ® Bulk Fill. µCT and SEM confirmed that the flowable bulk fill CRs had excellent adaptation to the cavity walls. The 3D morphometric analysis showed the highest and lowest degrees of porosity in Filtek™ Bulk Fill and Tetric EvoFlow ® Bulk Fill, respectively. In general, the flowable bulk fill CRs exhibited better adaptation, a higher efficiency of polymerization and lower porosity than the sculptable materials.

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children. However, little is known about the contribution of monocytes to antiviral responses against RSV infection. We identified the IFN-β production of monocytes using IFN-β/YFP reporter mice. The kinetic analysis of IFN-β-producing cells in in vivo RSV-infected lung cells indicated that monocytes are recruited to the inflamed lung during the early phase of infection. These cells produced IFN-β via the myeloid differentiation factor 88-mediated pathway, rather than the TLR7- or mitochondrial antiviral signaling protein-mediated pathway. In addition, monocyte-ablated mice exhibited decreased numbers of IFN-γ-producing and RSV Ag-specific CD8 + T cells. Collectively, these data indicate that monocytes play pivotal roles in cytotoxic T-cell responses and act as type I IFN producers during RSV infection., Competing Interests: Conflicts of Interest: The authors declare no potential conflicts of interest., (Copyright © 2021. The Korean Association of Immunologists.)

Objective: To evaluate opioid administration after robotic lobectomy (RL) compared with video-assisted thoracic surgery (VATS) and open lobectomy in patients with lung cancer., Methods: Patients undergoing lobectomy for primary lung cancer between January 1, 2013, and September 30, 2015, were identified from the US Premier Hospital Perspective Database. The primary outcome was the average daily dose of opioids received from postoperative day (POD) 1 until discharge. Opioid doses were converted to morphine equivalent daily doses (MEDDs). Propensity score matching was performed to balance patient, hospital, and surgeon characteristics when comparing opioid administration by surgical approach., Results: The open versus RL cohort included 2061 matched pairs, and the VATS versus RL cohort included 2142 matched pairs. From POD 1 until discharge, the patients undergoing open lobectomy had a higher rate of opioid use compared with those undergoing RL (94.8% vs 87.2%; P < .001), with a higher total dose (median MEDD, 225.0 vs 100.0; P < .001) and average daily dose (median MEDD, 41.3 vs 30.0; P < .001). Similarly, from POD 1 until discharge, patients undergoing VATS lobectomy had a slightly higher rate of opioid use compared with those undergoing RL (89.6% vs 87.0%; P = .008), with a higher total dose (median MEDD, 130.0 vs 100.0; P < .001) and average daily dose (median MEDD, 33.8 vs 28.8; P < .001)., Conclusions: Patients undergoing RL for primary lung cancer received opioids less frequently, and with lower total and average daily doses, compared with those undergoing VATS and open lobectomy. Studies are needed to determine whether early opioid dosage reductions translate into less chronic opioid use., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Esophagogastroduodenoscopy (EGD) is commonly performed in patients with gastroesophageal reflux disease (GERD). An EGD report should document pertinent findings such as esophagitis, a columnar-lined esophagus (CLE), the location of the squamo-columnar and gastroesophageal junctions, the size and type of a hiatal hernia and the number and location of any biopsies. The aim of this study was to evaluate how commonly these findings were noted in the EGD reports of patients referred for antireflux surgery., Methods: A retrospective review was performed of patient charts from 2012 to 2015 to identify 100 consecutive EGD reports from different endoscopists in different patients. Each EGD report was reviewed for pertinent findings and the use of a classification system for esophagitis (Savory-Miller or Los Angeles) and for reporting a CLE (Prague)., Results: In 100 EGD reports, esophagitis was noted in 33 patients, but was graded in only 14 (42%). A CLE was noted in 28 patients, but the length was reported in only 16 (57%) and no report used the Prague classification system. A hiatal hernia was noted in 61 patients, measured in 31 (51%) and the type classified in 26%. A biopsy was taken in 93 patients and the location noted in 86 patients (93%). The number of biopsies was recorded in only 20 patients (22%). In 12 patients the EGD was for Barrett's surveillance, yet a Seattle biopsy protocol was reported to be used in only 3 patients., Conclusion: Endoscopy reports frequently do not include the use of a grading system for esophagitis or the Prague system for CLE. This hampers the assessment of change with therapy or over time. The size of a hiatal hernia was typically reported in a subjective fashion and only infrequently was the type specified. Lack of clarity about the presence of a paraesophageal hernia can impede evaluation of acute symptoms. In patients with Barrett's esophagus a standard biopsy protocol was infrequently reported to be used. These findings raise concern about the quality of upper endoscopy, both in the performance of the procedure and the documentation of findings. A consistent reporting system is recommended for routine use with upper endoscopy.

Extracellular basic pH regulates cellular processes in wounds, and consequently influenced wound healing. Oxidative defence system modulation in the skin helps heal wounds, inhibits skin ageing and improves the skin condition. Moreover, the role of keratinocyte growth factor (KGF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in antioxidant systems has been reported in various skin models. However, the effects of extracellular basic pH on wound- or skin ageing-related skin damage have not been examined. Thus, we investigated the antioxidant systems affected by extracellular basic pH in a 3D human skin equivalent system (3HSE). Extracellular basic pH decreased KGF expression and enhanced the oxidative defence system, and thus activated Nrf2 in the 3HSE. Additionally, extracellular basic pH and KGF treatment up-regulated Nrf2 activation and its regulation of the oxidative defence system in the 3HSE. This indicates that Nrf2 up-regulation is enhanced by reactive oxygen species production, rather than KGF, and by extracellular basic pH of the skin. The inhibition of skin damage through pH imbalance and KGF regulation suggests that the development of pH-regulating or pH-maintaining materials may provide effective therapeutic strategies for maintaining a healthy skin., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Osteoarthritis (OA) is the most common degenerative joint disease with chronic joint pain caused by progressive degeneration of articular cartilage at synovial joints. Acteoside, a caffeoylphenylethanoid glycoside, has various biological activities such as antimicrobial, anti-inflammatory, anticancer, antioxidative, cytoprotective, and neuroprotective effect. Further, oral administration of acteoside at high dosage does not cause genotoxicity. Therefore, the aim of present study is to verify the anticatabolic effects of acteoside against osteoarthritis and its anticatabolic signaling pathway. Acteoside did not decrease the viabilities of mouse fibroblast L929 cells used as normal cells and primary rat chondrocytes. Acteoside counteracted the IL-1 β -induced proteoglycan loss in the chondrocytes and articular cartilage through suppressing the expression and activation of cartilage-degrading enzyme such as matrix metalloproteinase- (MMP-) 13, MMP-1, and MMP-3. Furthermore, acteoside suppressed the expression of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E 2 in the primary rat chondrocytes treated with IL-1 β . Subsequently, the expression of proinflammatory cytokines was decreased by acteoside in the primary rat chondrocytes treated with IL-1 β . Moreover, acteoside suppressed not only the phosphorylation of mitogen-activated protein kinases in primary rat chondrocytes treated with IL-1 β but also the translocation of NF κ B from the cytosol to the nucleus through suppression of its phosphorylation. Oral administration of 5 and 10 mg/kg acteoside attenuated the progressive degeneration of articular cartilage in the osteoarthritic mouse model generated by destabilization of the medial meniscus. Our findings indicate that acteoside is a promising potential anticatabolic agent or supplement to attenuate or prevent progressive degeneration of articular cartilage., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 HyangI Lim et al.)

The aim of this study was to demonstrate the effects of motor imagery training on balance and gait abilities in older adults and to investigate the possible application of the training as an effective intervention against fall prevention. Subjects (n = 34) aged 65 years and over who had experienced falls were randomly allocated to three groups: (1) motor imagery training group (MITG, n = 11), (2) task-oriented training group (TOTG, n = 11), and (3) control group (CG, n = 12). Each group performed an exercise three times a week for 6 weeks. The dependent variables included Path Length of center of pressure (COP)-based static balance, Berg Balance Scale (BBS) score, Timed Up and Go Test (TUG) score, which assesses a person's mobility based on changes in both static and dynamic balance, Falls Efficacy Scale (FES) score, which evaluates changes in fear of falls, and gait parameters (velocity, cadence, step length, stride length, and H-H base support) to evaluate gait. After the intervention, Path Length, BBS, TUG, velocity, cadence, step length, and stride length showed significant increases in MITG and TOTG compared to CG ( p < 0.05). Post hoc test results showed a significantly greater increase in BBS, TUG, and FES in MITG compared with TOTG and CG ( p < 0.05). Our results suggest that motor imagery training combined with functional training has positive effects on balance, gait, and fall efficacy for fall prevention in the elderly.

Background: Sarcopenia progresses in chronic kidney disease (CKD) and is positively correlated with mortality in end-stage kidney disease patients. Circulating irisin, an exercise-induced myokine, gradually decreases during CKD stage progression. Irisin inhibits the progression of kidney fibrosis, which is the final common outcome of CKD. Our preliminary study with C2C12 cells showed that Dojuksan, a herbal decoction, increases the expression of PGC1α (a regulator of irisin) and FNDC5 (a precursor of irisin)., Hypothesis: Dojuksan may increase circulating irisin and prevent the progression of kidney fibrosis., Study Design and Methods: Unilateral ureteral obstruction (UUO) was performed on seven-week-old male C57BL/6 mice to induce kidney tubulointerstitial fibrosis. Dojuksan (50, 100, or 200 mg/kg/day) or losartan (1.5 mg/kg/day), a standard clinical treatment for CKD, was administered orally one day prior to surgery and continued for seven days thereafter. To determine the role of irisin released from muscles, TGFβ-stimulated murine proximal tubular epithelial cells (mProx24 cells) were treated with conditioned media (CM) from Dojuksan-treated C2C12 muscle cells transfected with FNDC5 siRNA., Results: UUO mice exhibited muscle wasting along with progressive kidney injury. Similar to losartan, Dojuksan ameliorated kidney inflammation and fibrosis in UUO mice. Dojuksan, but not losartan, increased plasma irisin concentration in UUO mice. Dojuksan significantly increased basal FNDC5 expression and inhibited TNFα-induced and indoxyl sulfate-induced FNDC5 down-regulation in C2C12 cells. The TGFβ-induced collagen I (COL1) up-regulation in mProx24 cells was effectively inhibited by CM from C2C12 cells after Dojuksan treatment. Moreover, irisin inhibited TGFβ-induced COL1 in mProx24 cells, which was not affected by CM from C2C12 cells transfected with FNDC5 siRNA., Conclusion: Dojuksan ameliorates kidney fibrosis through irisin-mediated muscle-kidney crosstalk, suggesting that Dojuksan may be used as an alternative therapeutic agent against CKD., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background/aim: Accumulating evidence has shown therapeutic effects of herbals on breast cancer, a commonly diagnosed malignancy in women worldwide. However, their underlying mechanisms remain unclear. We aimed to explore the mode of action of a recently developed herbal combination at system-level., Materials and Methods: We employed network pharmacological approaches to study the mechanism of a combination of three herbals, Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii by investigating active compounds and performing functional enrichment analysis for the interacting targets., Results: For in silico pharmacokinetic evaluation, ten active ingredients interacted with fifty-six breast cancer-associated therapeutic targets. Functional enrichment analysis revealed that TNF, estrogen, PI3K-Akt and MAPK signaling pathways were involved in tumorigenesis and development of breast cancer. The pharmacological mechanisms might be associated with cellular effects on proliferation, cell cycle process and apoptosis., Conclusion: The present study provides novel insights into the system-level pharmacological mechanisms underlying a herbal combination used for breast cancer therapies., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Genital herpes is one of the most common sexually transmitted infections (STIs), and it is mainly caused by the neurotropic herpes simplex virus (HSV-2). Not only does this infection cause ulcers, but HSV-2 can also stay in a latent state in the nervous system of the host throughout their lifespan. As a result, many people do not know that they harbor this infection. Moreover, HSV-2 serves as a major risk factor for human immunodeficiency virus (HIV) infection and can be transmitted to the fetus. Despite the high risk of infection and adverse effects, attempts at development of an effective vaccine for HSV-2 have not yet been successful. In this study, we developed a DNA vaccine for HSV-2 (SL-V20). This multivalent DNA vaccine effectively reduced the pathological symptoms of infection and induced efficient elimination of the virus in a mouse model. Intramuscular injection of SL-V20 led to induction of an HSV-2-specific T-cell response in the vagina, the major infection site, and in draining lymph organs. Dendritic cells (DCs), especially basic leucine zipper ATF-like transcription factor 3 (Baft3) + DCs and partially interferon regulatory factor 4 (Irf4) + DCs, were involved in this T-cell-mediated protective response, while B cells were dispensable for these prophylactic effects. This study demonstrates that SL-V20 offers a novel and effective vaccine against vaginal HSV-2 infection and may be applicable to patients, pending validation in clinical studies., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Elderly patients with femoral fractures are anticipated to endure the most pain caused by positional changes required for spinal anesthesia. To improve pain relief, we compared the analgesic effects of intravenous dexmedetomidine-ketamine and dexmedetomidine-fentanyl combinations to facilitate patient positioning for spinal anesthesia in elderly patients with proximal femoral fractures. Forty-six patients were randomly assigned to two groups and received either 1 mg/kg of intravenous ketamine (group K) or 1 μg/kg of intravenous fentanyl (group F) concomitant with a loading dose of dexmedetomidine 1 μg/kg over 10 minutes, then dexmedetomidine infusion only was continued at 0.6 μg/kg/h for following 20 minutes, and titrated at a rate of 0.2 to 0.6 μg/kg/h until the end of surgery. After completion of the infusion of either ketamine or fentanyl, the patients were placed in the lateral position with the fracture site up. The pain score (0 = calm, 1 = facial grimacing, 2 = moaning, 3 = screaming, and 4 = unable to proceed because of restlessness or agitation) was used to describe the pain intensity in each step during the procedure (lateral positioning, hip flexion, and lumbar puncture), and quality score (0 = poor hip flexion, 1 = satisfactory hip flexion, 2 = good hip flexion, and 3 = optimal hip flexion) was used to describe the quality of posture. Group K showed a median pain score of 0 (0-1), 0 (0-0) and 0 (0-0) in lateral positioning, hip flexion and lumbar puncture, respectively, while group F showed a score of 3 (2.75-3), 3 (2-3) and 0 (0-1), respectively. The pain score in lateral positioning (P < .0001) and hip flexion (P < .0001) was significantly lower in group K than group F. Group K showed the significantly higher quality scores of spinal anesthesia positioning (P = .0044) than group F. Hemodynamic adverse effects, such as bradycardia, hypotension, and desaturation, were not significantly different between the groups. The administration of dexmedetomidine-ketamine showed a greater advantage in reducing pain intensity and increasing the quality with patient positioning during spinal anesthesia in elderly patients with proximal femoral fractures, without any serious adverse effects.

Background: We sought to evaluate trends and clinical and economic outcomes between robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VL), and open pulmonary lobectomy (OL)., Methods: Patients who underwent a lobectomy for malignancy from January 1, 2008, to September 30, 2015, were identified in the Premier Healthcare Database. Propensity score matched (PSM) comparisons were performed between RL versus VL and RL versus OL. Patient characteristics were applied to generate propensity scores. In-hospital and perioperative 30-day outcomes and costs were compared within matched cohorts., Results: From 2008 to 2015, there was a marked decline for OL (71% to 43%, P<0.0001) with a significant increase in RL (1% to 17%, P<0.0001) and VL (28% to 41%, P<0.0001). In the early period (January 2008 to December 2012), total operating room time was longer (P<0.0001) and admission to ICU was more common for RL compared to VL or OL (P<0.0001) although the total length of ICU stay was shorter for RL compared to VL or OL (P<0.0001). In the late period (January 2013 to September 2015), RL was associated with significantly lower rates of complications (P<0.05), conversions, and shorter length of stay than VL and OL. When hospital volume was not considered, costs were higher for RL than VL and OL. In hospitals where >25 lobectomies were performed annually, the total cost of RL was comparable to VL (P=0.09) and OL (P=0.11)., Conclusions: During the study period, the utilization of RL increased substantially and was associated with improved perioperative outcomes compared with VL and OL. When annual hospital volume was >25 cases, these clinical advantages persisted and there was no significant cost difference between RL, VL, or OL. RL is an effective and cost-comparable approach for lobectomy in patients with lung malignancy., Competing Interests: Conflicts of Interest: IS Sarkaria serves as the unpaid editorial board member of Journal of Thoracic Disease from Sep 2018 to Aug 2020 and he is consultant and teacher for Intuitive. IS Sarkaria: consultant and teacher for Intuitive. DS Oh is a part-time employee of Intuitive as a medical advisor and C Song and E Liu are full-time employees of Intuitive, during the conduct of the study. L Shi serves as a consultant to Intuitive. The other authors have no conflicts of interest to declare. All authors had full access to all of the data in the study and accept responsibility for the integrity of the data and the accuracy of the data analysis., (2020 Journal of Thoracic Disease. All rights reserved.)

This work demonstrates a high-performance and hysteresis-free field-effect transistor based on two-dimensional (2D) semiconductors featuring a van der Waals heterostructure, MoS 2 channel, and GaS gate insulator. The transistor exhibits a subthreshold swing of 63 mV/dec, an on/off ratio over 10 6 within a gate voltage of 0.4 V, and peak mobility of 83 cm 2 /(V s) at room temperature. The low-frequency noise characteristics were investigated and described by the Hooge mobility fluctuation model. The results suggest that the van der Waals heterostructure of 2D semiconductors can produce a high-performing interface without dangling bonds and defects caused by lattice mismatch. Furthermore, a logic inverter and a NAND gate are demonstrated, with an inverter voltage gain of 14.5, which is higher than previously reported by MoS 2 -based transistors with oxide dielectrics. Therefore, this transistor based on van der Waals heterostructure exhibits considerable potential in digital logic applications with low-power integrated circuits.

Two-dimensional (2D) materials have attracted significant attention because of their outstanding electrical, mechanical, and optical characteristics. Because all of the conducting (graphene), semiconducting (molybdenum disulfide, MoS 2 ), and insulating (hexagonal boron nitride, h-BN) components can be constructed from 2D materials, thin-film transistors based on 2D materials (2D TFTs) have been developed. However, scaling-up is necessary for these technologies to go beyond their initial implementation using the mechanical exfoliation method. Furthermore, it would be beneficial to find a method to realize high flexibility and/or transparency to their full potential. In this study, large-scale, flexible, and transparent 2D TFTs are developed and demonstrated as a backplane in active-matrix organic light-emitting diodes (AMOLEDs). With the optical chemical vapor deposition of the 2D materials, flexible (bending radius < 1 mm) and transparent (transmittance > 70%) TFTs with high electrical performances (mobility ≈ 10 cm 2 V -1 s -1 , on/off current ratio > 10 6 ) can be achieved. Furthermore, 2D TFTs are integrated into OLEDs by connecting the source electrode of the TFT to the anode of the OLED via a single graphene film, thus demonstrating pixel-by-pixel driving through a 2D TFT array in an active-matrix configuration.

Macroautophagy/autophagy has been implicated in cytoplasmic and viral antigen presentation on major histocompatibility complex (MHC) class II molecules. However, the role of autophagy in the presentation of phagocytized tumor-associated antigens in vivo remains unclear. Following the administration of apoptotic tumor cells and in vivo chemotherapy, mice with a dendritic cell-specific deletion of Atg5 , a key autophagy gene, exhibit reduced CD4 + T-cell priming but not CD8 + cytotoxic T-cell priming. Interestingly, Atg5 -deficient dendritic cells have an elevated expression of scavenger receptor CD36 and show excessive lipid accumulation. Atg5 -deficient dendritic cells increased CD36-dependent phagocytosis of apoptotic tumor cells. CD36 blockade ameliorates elevated phagocytosis and increases CD4 + T-cell priming in dendritic cells; intratumoral CD36 blockade inhibits tumor growth. Our results demonstrate that Atg5 is required for proper antigen phagocytosis and presentation to MHC class II via modulation of CD36 in dendritic cells and may be a future therapeutic target for anti-tumor therapy. Abbreviations : APC: antigen-presenting cell; ATG: autophagy-related; BMDC: bone marrow-derived dendritic cell; BODIPY: 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene; CSFE: carboxyfluorescein diacetate succinimidyl ester; DAPI: 4',6-diamidino-2-phenylindole; IFNG/IFN-γ: interferon gamma; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MHC: major histocompatibility complex; NLDC: neonatal liver-derived dendritic cell; PDCD1/PD-1: programmed cell death 1; PI: propidium iodide; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate; SERPINB/OVA: serine (or cysteine) peptidase inhibitor, clade B; TIMD4/TIM-4: T cell immunoglobulin and mucin domain containing 4.

Objective: Robot-assisted lobectomy is the fastest growing technique for pulmonary lobectomy, but the diversity of approaches has led to apprehension about port placement among learning surgeons. The aim of this study was to survey high-volume thoracic surgeons who perform robot-assisted lobectomy to understand and consolidate common themes of port placement., Methods: An electronic online survey was created, and the link was emailed to the 100 highest volume robotic thoracic surgeons in the United States. The survey included an interactive graphical interface, which allowed each respondent to mark the preferential robotic port placement in the chest wall for each of the 5 pulmonary lobectomies. Results were analyzed individually and in aggregate. A heat map was generated to show trends., Results: One hundred surgeons were surveyed (response rate: 62%). Most (90%) respondents utilized a 4-arm approach and 79% used a completely 4-arm portal approach with CO 2 insufflation. Exact locations for each robotic port were reported by 60% of the surveyed surgeons and the results varied; however, most surgeons generally used the seventh to ninth interspaces for the camera and instruments. The use of multiple different interspace levels was common. Ninety-four percent of respondents used an additional nonrobotic assistant port., Conclusions: There is not a universal port strategy for robot-assisted lobectomy. However, placement of the camera and robotic ports low in the seventh to ninth interspaces is the most common approach. There are some nuances of stapling port strategies and sequence of port placement, which are identified.

In the present study, various extracts of C . tricuspidata fruit were prepared with varying ethanol contents and evaluated for their biomarker and biological properties. The 80% ethanolic extract showed the best tyrosinase inhibitory activity, while the 100% ethanolic extract showed the best total phenolics and flavonoids contents. The HPLC method was applied to analyze the chlorogenic acid in C . tricuspidata fruit extracts. The results suggest that the observed antioxidant and tyrosinase inhibitory activity of C . tricuspidata fruit extract could partially be attributed to the presence of marker compounds in the extract. In this study, we present an analytical method for standardization and optimization of C. tricuspidata fruit preparations. Further investigations are warranted to confirm the in vivo pharmacological activity of C . tricuspidata fruit extract and its active constituents and assess the safe use of the plant for the potential development of the extract as a skin depigmentation agent., Competing Interests: The authors declare no conflict of interest.

The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)- α , interferon (IFN)- γ , interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF- α , IFN- γ , IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to <1.0 μm through physical stress (micronization), promoted NK cell cytotoxicity to a greater extent than LM1004 subjected to heat treatment alone. These findings indicate that HT-LM1004 without or with micronization can reverse CTX-induced immunosuppression without adverse side effects by potentiating NK cell function.

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8 + T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection.

Background: The proportion of the elderly (≥80 years old) patient population in the United States is increasing. Consequently, surgeons are more involved in the care of these patients than they had been in the past. Therefore, surgeons must re-evaluate their prior assumptions about their surgical management of octogenarian patients. Although open thoracotomy is a popular approach for pulmonary lobectomy, minimally invasive techniques are associated with improved outcomes in this frail patient population. Our goal was to evaluate perioperative outcomes of standard open lobectomy to both video-assisted thoracoscopic and robotic-assisted lobectomy in patients ≥80 years old., Methods: Octogenarian patients, who underwent elective pulmonary lobectomy from January 1, 2011 through September 30, 2015, were identified from the National Premier Healthcare Database. One-to-one propensity score matching (PSM) was performed between robotic-assisted and open lobectomy populations and between video-assisted thoracoscopic and open lobectomy populations. Rates of perioperative outcomes from each comparison were analyzed., Results: Of the 1,849 octogenarian patients who satisfied the inclusion criteria, propensity-score matched (1:1) comparative analyses of robotic-assisted lobectomy (n=232) and open lobectomy (n=232) patients as well as video-assisted thoracoscopic lobectomy (n=562) and open lobectomy (n=562) patients were made. Both robotic-assisted and video-assisted thoracoscopic lobectomy cohorts were associated with shorter lengths of stay (both P<0.001) and higher rates of discharge to home compared to open lobectomy (P=0.0435 and P=0.0037, respectively). Robotic-assisted lobectomy was associated with fewer postoperative complications compared to open lobectomy (P=0.0249)., Conclusions: Minimally invasive lobectomy is a viable surgical option in octogenarians and provides improved outcomes compared to open thoracotomy in a retrospective cohort. Carefully selected patients can achieve excellent outcomes., Competing Interests: Conflicts of Interest: Dr. Sarkaria receives speaking and education honoraria from Intuitive Surgical; Dr. Oh was a past consultant for Ethicon and Covidien and is a part-time medical advisor for Intuitive Surgical; Dr. Gorrepati and Ms. Mehendale are employees of Intuitive Surgical.

The fruits, leaves, and roots of Cudrania tricuspidata have been reported to contain large amounts of vitamin B, vitamin C, and flavonoids. They exhibit various physiological activities such as antitumor and anti-inflammatory effects. However, the hepatoprotective effects of C. tricuspidata extracts against oxidative stress-mediated liver injury have not yet been investigated. We thus examined whether C. tricuspidata leaf extracts (CTEs) protect against oxidative stress-mediated liver injury in vitro and in vivo and elucidated the underlying mechanism. The cytoprotective effects of CTE through the NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation were presented and measured by biochemical analysis in HepG2 cells. To assess the protective effects of CTE in vivo , mice were administered with CTE (250 and 500 mg/kg; 5 days; p.o.) before a single dose of acetaminophen (APAP) (300 mg/kg; 24 h; i.p.). CTE increased ARE luciferase activity when compared with extracts of other parts of C. tricuspidata. CTE upregulated nuclear translocation of Nrf2 and its target gene expression. In addition, CTE inhibited the generation of reactive oxygen species (ROS) and cell death induced by arachidonic acid (AA) and iron (Fe) treatment in primary hepatocytes or HepG2 cells. The cytoprotective effects of CTE against oxidative stress might be due to kaempferol, the major flavonoid present in CTE. Kaempferol pretreatment blocked AA+Fe-induced ROS production and reversed glutathione depletion, which in turn led to decreased cell death. Furthermore, the protective effects of CTE against liver injury induced by excess APAP in mice or primary hepatocytes were observed. CTE could be a promising therapeutic candidate against oxidative stress-induced liver injury.

Background: People with a wide forehead often look older. Hairline lowering surgery is a good treatment option, which is generally performed utilizing Endotine., Objectives: We describe our hairline lowering surgical technique involving bone tunneling without Endotine, a method designed to produce comparable outcomes with fewer side effects. We evaluated the effectiveness and safety of our technique., Methods: Charts of 91 patients who underwent hairline lowering surgery without Endotine were reviewed retrospectively. We utilized standardized preoperative and postoperative photographs to measure the proportions of 3 face parts and the length of the forehead. We also determined changes in forehead length at various times after surgery, occurrence of postoperative complications, and overall patient satisfaction with their surgical results., Results: Of the 91 patients, 80 were female and the mean age was 28.67 ± 7.15 years. Preoperatively, the mean forehead length was 8.09 ± 0.69 cm and ratio of facial part lengths was 1.08:1:0.99 (cranial to caudal). The hairline was advanced 18.37 ± 2.90 mm. One month postoperatively, the mean forehead length was 6.57 ± 0.52 cm and facial parts ratio was 1:1:0.99. Compared with preoperatively, forehead length was significantly reduced at 1, 3, 6, and 12 months postoperatively. Forehead length was not significantly different at 1 and 12 months postoperatively. All patients were satisfied or very satisfied with their overall surgical results., Conclusions: Hairline lowering surgery with bone tunneling was effective and safe, and patients were satisfied with the results. The effects appeared immediately following surgery and were sustained over time., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: In December 2016, WHO released a report stating that in 2015 there were 383,000 deaths caused by asthma and 235 million people suffering from asthma. As there are many adverse effects associated with the currently-used asthma drugs, new anti-asthmatic drugs need to be developed., Purpose: In order to find new drug candidates with safe and low side effects, the anti-asthmatic function and mechanism of C. japonica oil were evaluated, and its active ingredients were analyzed for use in an ovalbumin asthma murine model., Study Design and Methods: The study consisted of six groups: control; ovalbumin group; and dexamethasone group as a positive control; and 10, 100, and 500 mg/kg C. japonica oil treatment groups. In order to measure the anti-asthmatic effect of C. japonica oil, WBC and differential cell count in BALF, IgE in serum, morphological changes in pulmonary system, and gene and protein levels such as IFN-γ, IL-12p40, IL-4, IL-5, IL-6, TNF-α, and IL-6 were all evaluated., Results: C. japonica oil had an anti-asthmatic effect and significantly controlled eosinophil in BALF, Th2-related factors such as GATA-3 that is Th2 cell transcription factor, IL-4, IL-5, and IL-13, and TNF-α in the lung. It also dose-dependently modulated inflammatory cells, T-bet, IL-12p40, and IL-6. Oleci acid was the major gradient (52.89%) in C. japonica oil and also had anti-asthmatic effects such as the downregulation of inflammatory cells, WBC, and eosinophil in BALF, IgE in serum, and morphological changes in the lung., Conclusion: We concluded that C. japonica oil is a new anti-asthmatic drug candidate and that oleic acid is the major anti-asthmatic ingredient in C. japonica oil., (Copyright © 2018. Published by Elsevier GmbH.)

Background: Prolonged hyperuricemia is associated with kidney disease or gouty arthritis. Whether Yokuininto, a commercially available Kampo medicine that has been used for osteoarthritis or rheumatoid arthritis, can exhibit anti-hyperuricemic and inflammatory effects remains elusive. In the present study, Yokuininto exerts multiple homeostatic action on serum uric acid (sUA) levels by blocking pro-inflammatory cytokine activities and inducing uricosuric function with anti-renal injury functions., Methods: The sUA was measured in potassium oxonate (PO)-administered mice. Renal transporter uptake assays were performed using HEK293 cells overexpressing OAT1, OCT2 or OAT3, MDCKII cells overexpressing BCRP, and Xenopus oocytes overexpressing OAT3 or URAT1. Immunoblot and ELISA assays were performed to detect the molecules (OAT3, GLUT9, XO, NGAL, KIM-1 and IL-1α) in various human kidney cell lines. Cell viability analysis was performed to evaluate the cytotoxicity of Yokuininto [Ephedrine + pseudoephedrine 21.94%; Paeoniflorin 35.40% and Liquiritin 16.21% relatively measured by the ratios (HR-MS2 intensity / HR-MS1 intensity)]., Results: Yokuininto (300 mg/kg) significantly reduced sUA by approximately 44% compared to that of PO-induced mice. The OAT3 levels were decreased in PO-induced hyperuricemic condition, whereas the GLUT9 transporter levels were markedly increased. However, PO did not alter the levels of URAT1. Yokuininto significantly inhibited the lipopolysaccharide (LPS)-induced secretion of IL-1α by approximately 63.2% compared to the LPS-treated macrophages. In addition, Yokuininto inhibited nitric oxide synthesis by approximately 33.7 (500 µg/mL) and 64.6% (1000 µg/mL), compared to that of LPS-treated macrophages. Yokuininto markedly increased xanthine oxidase inhibition activity. Furthermore, interleukin-1α (IL-1α), a pro-inflammatory cytokine, elevated neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) activities in LLC-PK1 cells. Expression of renal inflammatory biomarkers, NGAL and KIM-1, was reduced under the Yokuininto treatment by 36.9 and 72.1%, respectively., Conclusions: Those results suggest that Yokuininto may suppress inflammation and protect against kidney dysfunction in hyperuricemia. The present findings demonstrated that Yokuininto lowered sUA through both increased uric acid excretion and decreased uric acid production. Our results may provide a basis for the protection of prolonged hyperuricemia-associated kidney injury with uric acid-lowering agents such as Yokuininto.