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The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via Visium spatial transcriptomics, eight distinct tissue clusters were revealed from aggregated transcriptomes of aging and young AAP mice: five acinar, two stromal, and one islet, which were then merged into three clusters: acinar, stromal, and islet for the comparative analysis. Compared to young AAP mice, > 1300 differentially expressed genes (DEGs) and approximately 3000 differentially regulated pathways were identified in aging AAP mice. The top five DEGs upregulated in aging AAP mice include Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp with heterogeneous distributions among the clusters. Taken together, this study demonstrates spatial heterogeneity of inflammatory processes in aging AAP mice, offering novel insights into the mechanisms and potential drivers for AAP development. KEY MESSAGES: Mechanisms regarding high mortality of AAP in aging remain undefined. An aging AAP mouse model was developed recapturing clinical exhibition in humans. Spatial transcriptomics identified contrasted DEGs in aging vs. young AAP mice. Top five DEGs were Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp in aging vs. young AAP mice. Our findings shed insights for identification of molecular drivers in aging AAP.
Subject(s)
Aging , Pancreatitis , Transcriptome , Animals , Aging/genetics , Mice , Pancreatitis/genetics , Pancreatitis/chemically induced , Pancreatitis/metabolism , Pancreatitis/pathology , Gene Expression Profiling , Disease Models, Animal , Male , Inflammation/genetics , Mice, Inbred C57BL , Ethanol/adverse effects , Pancreatitis, Alcoholic/genetics , Pancreatitis, Alcoholic/metabolism , Pancreatitis, Alcoholic/pathology , Acute Disease , Pancreas/metabolism , Pancreas/pathologyABSTRACT
OBJECTIVE: The pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts (CAFs) and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not adequately defined. METHODS: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas (TCGA) RNA-sequencing data and characterized the expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies. RESULTS: Grem1 expression is associated with an activated stroma and increased M1 and M2 macrophages. Only full length Grem1 variant 1 and isoform 1 were detectable in human pancreatic cells, and remarkably high levels of Grem1 were observed in pancreatic fibroblasts (P < 0.05). Immunohistochemistry detected Grem1 protein in PDAC tumor cells and stromal cells, which correlated with infiltrating macrophages in PDAC tumors. Grem1 knockdown in CAFs suppressed transforming growth factor (TGF)-ß-induced extracellular matrix proteins (P < 0.05). Grem1 recombinant protein treatment in vitro increased M1 and M2 macrophages (P < 0.05). CONCLUSIONS: Grem1 acts as a profibrogenic factor in the PDAC microenvironment via modulation of fibroblasts and macrophages. Grem1 may have the potential to be developed as a therapeutic target for PDAC.
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The transforming growth factor (TGF)-ß superfamily has important physiologic roles and is dysregulated in many pathologic processes, including pancreatic cancer. Pancreatic cancer is one of the most lethal cancer diagnoses, and current therapies are largely ineffective due to tumor resistance and late-stage diagnosis with poor prognosis. Recent efforts are focused on the potential of immunotherapies in improving therapeutic results for patients with pancreatic cancer, among which TGF-ß has been identified as a promising target. This review focuses on the role of TGF-ß in the diseased pancreas and pancreatic cancer. It also aims to summarize the current status of therapies targeting the TGF-ß superfamily and postulate potential future directions in targeting the TGF-ß signaling pathways.
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Large-area metamorphic stretchable sensor networks are desirable in haptic sensing and next-generation electronics. Triboelectric nanogenerator-based self-powered tactile sensors in single-electrode mode constitute one of the best solutions with ideal attributes. However, their large-area multiplexing utilizations are restricted by severe misrecognition between sensing nodes and high-density internal circuits. Here, we provide an electrical signal shielding strategy delivering a large-area multiplexing self-powered untethered triboelectric electronic skin (UTE-skin) with an ultralow misrecognition rate (0.20%). An omnidirectionally stretchable carbon black-Ecoflex composite-based shielding layer is developed to effectively attenuate electrostatic interference from wirings, guaranteeing low-level noise in sensing matrices. UTE-skin operates reliably under 100% uniaxial, 100% biaxial, and 400% isotropic strains, achieving high-quality pressure imaging and multi-touch real-time visualization. Smart gloves for tactile recognition, intelligent insoles for gait analysis, and deformable human-machine interfaces are demonstrated. This work signifies a substantial breakthrough in haptic sensing, offering solutions for the previously challenging issue of large-area multiplexing sensing arrays.
Subject(s)
Touch Perception , Wearable Electronic Devices , Humans , Touch , ElectricityABSTRACT
OBJECTIVE: One of the most serious complications of Crohn's disease is intestinal strictures that may lead to bowel obstruction. Understanding the underlying mechanisms of stricture formation is essential in order to develop more effective nonsurgical prevention and treatment modalities. The aim of this pilot study was to determine whether Gremlin1, a protein implicated in fibrogenesis and smooth muscle proliferation, is overexpressed in Crohn's-associated bowel strictures. METHODS: Paired sections from three strictured and non-strictured surgically resected bowel from patients with Crohn's disease were evaluated for Gremlin1 expression by immunohistochemistry. RESULTS: Strictured areas from all three specimens showed strong Gremlin1 staining in the hypertrophic muscularis mucosae area compared to no staining in the mucosa or muscularis propria in the same sections and in contrast to sections from non-strictured areas which were negative. CONCLUSIONS: This short report is the first to describe the overexpression of Gremlin1 in the hypertrophied muscularis mucosae of strictured small intestine from patients with Crohn's disease. Additional studies are needed to elucidate the potential role of Gremlin1 in the etiopathogenesis of Crohn's disease strictures, and to investigate whether targeting Gremlin1 may be an option for preventing or treating strictures in patients with Crohn's disease.
Subject(s)
Crohn Disease , Intercellular Signaling Peptides and Proteins , Humans , Constriction, Pathologic , Crohn Disease/complications , Pilot Projects , Staining and Labeling , Intercellular Signaling Peptides and Proteins/geneticsABSTRACT
OBJECTIVE: To systematically review the published literature on the use of prophylactic mesh reinforcement of midline laparotomy closures for prevention of VIH. SUMMARY OF BACKGROUND DATA: VIH are common complications of abdominal surgery. Prophylactic mesh has been proposed as an adjunct to prevent their occurrence. METHODS: PubMed, Embase, Scopus, and Cochrane were reviewed for RCTs that compared prophylactic mesh reinforcement versus conventional suture closure of midline abdominal surgery. Primary outcome was the incidence of VIH at postoperative follow-up ≥24 months. Secondary outcomes included surgical site infection and surgical site occurrence (SSO). Pooled risk ratios were obtained through random effect meta-analyses and adjusted for publication bias. Network meta-analyses were performed to compare mesh types and locations. RESULTS: Of 1969 screened articles, 12 RCTs were included. On meta-analysis there was a lower incidence of VIH with prophylactic mesh [11.1% vs 21.3%, Relative risk (RR) = 0.32; 95% confidence interval (CI) = 0.19-0.55, P < 0.001), however, publication bias was highly likely. When adjusted for this bias, prophylactic mesh had a more conservative effect (RR = 0.52; 95% CI = 0.39-0.70). There was no difference in risk of surgical site infection (9.1% vs 8.9%, RR = 1.08, 95% CI = 0.82-1.43; P = 0.118), however, prophylactic mesh increased the risk of SSO (14.2% vs 8.9%, RR = 1.57, 95% CI = 1.19-2.05; P < 0.001). CONCLUSION: Current RCTs suggest that in mid-term follow-up prophylactic mesh prevents VIH with increased risk for SSO. There is limited long-term data and substantial publication bias.
Subject(s)
Incisional Hernia , Humans , Incisional Hernia/epidemiology , Surgical Wound Infection/etiology , Surgical Mesh/adverse effects , Publication Bias , Laparotomy/adverse effectsABSTRACT
Electrochromic devices (ECDs) are a promising material for smart windows that are capable of transmittance variation. However, ECDs are still too expensive to achieve a wide market reach. Reducing fabrication cost remains a challenge. In this study, we inserted an IrO2 buffer layer on Ti-doped V2O5 (Ti:V2O5) as a counter electrode using various Ar/O2 gas flow ratios (1/2, 1/2.5, 1/3 and 1/3.5) in the fabrication process. The buffered-ECD resulted in a larger cyclic voltammetry (CV) area and the best surface average roughness (Ra = 3.91 nm) to promote electrochromic performance. It was fabricated using the low-cost, fast deposition process of vacuum cathodic arc plasma (CAP). This study investigates the influence of the IrO2 buffer/Ti:V2O5 electrode on ECD electrochemical and optical properties, in terms of color efficiency (CE) and cycle durability. The buffered ECD (glass/ITO/WO3/liquid electrolyte/IrO2 buffer/Ti:V2O5/ITO/glass) demonstrated excellent optical transmittance modulation; ∆T = 57% (from Tbleaching (67%) to Tcoloring (10%)) at 633 nm, which was higher than without the buffer (ITO/WO3/liquid electrolyte/Ti:V2O5/ITO) (∆T = 36%). In addition, by means of an IrO2 buffer, the ECD exhibited high coloration efficiency of 96.1 cm2/mC and good durability, which decayed by only 2% after 1000 cycles.
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INTRODUCTION: In response to the COVID-19 pandemic, hospitals reported decreased admissions for acute surgical diagnoses, but scant data was available to quantify the decrease and its consequences. The objective of this study was to examine the incidence of acute care surgery encounters before and during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective cohort study was performed at a single, urban, United States safety-net hospital. Emergency room encounters, admissions, non-elective surgical procedures, patient acuity, and surgical complications were compared before and after the start of the COVID-19 pandemic. The primary outcome of the study was the incidence rate (IR) and incidence rate ratios (IRR) for surgical admissions, laparoscopic appendectomy, and urgent laparoscopic cholecystectomy. RESULTS: During the COVID-19 (exposure) time period, the number of nonelective procedures was 143 (IR 4.76) which was significantly lower than the control periods (n = 431, IR 7.2), P < 0.001. During the COVID-19 exposure period, there were significantly fewer urgent cholecystectomies performed (1.37 per day versus 2.80-2.93 per day, P < 0.001). There was a trend toward fewer appendectomies performed, but not significant. There was little difference in patient acuity between the exposure and control periods. A higher proportion of patients that underwent urgent cholecystectomy during the COVID time period had been seen in the ED in the prior 30 d (22% versus 5.6%). CONCLUSIONS: Surgical volume significantly decreased during the COVID-19 pandemic. Management of acute cholecystitis may require re-evaluation as nonsurgical management appears to increase repeat presentations.
Subject(s)
COVID-19 , Appendectomy/adverse effects , Appendectomy/methods , COVID-19/epidemiology , Humans , Pandemics , Retrospective Studies , Safety-net Providers , United States/epidemiologyABSTRACT
BACKGROUND: Our aim was to report the natural history of operative versus expectant management of patients with ventral hernias and co-morbidities at five years. METHODS: This was a prospective observational study. Patients were managed with elective repair or expectantly, based on co-morbidities and patient/surgeon choice. Primary outcome was functional status. Patients were matched using optimal matching. Outcomes were compared using multivariable regression. RESULTS: A total of 197 patients were included (78 operative, 119 expectant) with median follow-up of 5.1 (3.2-5.5) years. In the matched-cohort (n = 80), 58 vs 68% were obese, and 88% vs 95% had a major comorbidity. Both groups had similar baseline functional status (p = 0.788), but only those repaired initially had significantly improved scores at five years (p < 0.050). Half (20) of patients managed expectantly crossed over to repair, and 15% (3) were emergent/urgent. CONCLUSION: Initial repair improves long-term functional status significantly compared to expectant management. Repair by hernia experts should be considered for high-risk patients.
Subject(s)
Hernia, Ventral , Herniorrhaphy , Comorbidity , Follow-Up Studies , Hernia, Ventral/surgery , Humans , Morbidity , Patient-Centered Care , Prospective Studies , Watchful WaitingABSTRACT
Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in situ hybridization, we detected GREM1 mRNA expression within α-smooth muscle actin (SMA)-positive fibroblasts of the pancreatic stroma. These designated FibroblastsGrem1+ marginally increased from CP to pancreatic intraepithelial neoplasia (PanIN) and PDAC. Within PDAC, FibroblastsGrem1+ increased with higher pathological tumor stages and in a majority of PDAC subtypes screened. Additionally, FibroblastsGrem1+ positively correlated with total macrophages (MacCD68+) and M2 macrophages (M2CD163+) in PDAC. To begin exploring potential molecular links between FibroblastsGrem1+ and macrophages in PDAC, we examined the expression of macrophage migration inhibitory factor (MIF), an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor. By IHC staining of MIF, we found MIF to be expressed by tumor cells, positively correlated with GREM1; by IHC co-staining, we found MIF to be negatively correlated with M2CD163+ expression. Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development, and GREM1/MIF may play an important role in macrophage phenotype.
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OBJECTIVE: To determine if preoperative nutritional counseling and exercise (prehabilitation) improve outcomes in obese patients seeking ventral hernia repair (VHR)? SUMMARY BACKGROUND DATA: Obesity and poor fitness are associated with complications following VHR. It is unknown if preoperative prehabilitation improves outcomes of obese patients seeking VHR. METHODS: This is the 2-year follow-up of a blinded randomized controlled trial from 2015 to 2017 at a safety-net academic institution. Obese patients (BMI 30-40) seeking VHR were randomized to prehabilitation versus standard counseling. Elective VHR was performed once preoperative requirements were met: 7% total body weight loss or 6 months of counseling and no weight gain. Primary outcome was percentage of hernia-free and complication-free patients at 2 years. Complications included recurrence, reoperation, and mesh complications. Primary outcome was compared using chi-square. We hypothesize that prehabilitation in obese patients with VHR results in more hernia- and complication-free patients at 2-years. RESULTS: Of the 118 randomized patients, 108 (91.5%) completed a median (range) follow-up of 27.3 (6.2-37.4) months. Baseline BMI (mean±SD) was similar between groups (36.8â±â2.6 vs 37.0â±â2.6). More patients in the prehabilitation group underwent emergency surgery (5 vs 1) or dropped out of the program (3 vs 1) compared to standard counseling (13.6% vs 3.4%, P = 0.094). Among patients who underwent surgery, there was no difference in major complications (10.2% vs 9.1%, P = 0.438). At 2-years, there was no difference in percentage of hernia-free and complication-free patients (72.9% vs 66.1%, P = 0.424, 1.14, 0.88-1.47). CONCLUSION: There is no difference in 2-year outcomes of obese patients seeking VHR who undergo prehabilitation versus standard care. Prehabilitation may not be warranted in obese patients undergoing elective VHR.Clinical Trial Registration: This trial was registered with clinicaltrials.gov (NCT02365194).
Subject(s)
Directive Counseling , Hernia, Ventral/surgery , Preoperative Exercise , Adult , Female , Follow-Up Studies , Hernia, Ventral/complications , Humans , Male , Middle Aged , Obesity/complications , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: To validate the adapted Clavien-Dindo in trauma (ACDiT) tool as a novel outcome measure for patients with acute diverticulitis managed both operatively and nonoperatively. BACKGROUND: Complications following diverticulitis are difficult to classify because no traditional tools address patients managed both operatively and nonoperatively. The ACDiT grading system-graded from 0 to 5b-is applied in this manner but has not yet been validated for this patient group. METHODS: We performed a 5-year observational study of patients with acute diverticulitis at a safety-net hospital. Baseline demographics and hospitalization data were collected. ACDiT scores were assigned, and validation was undertaken by comparing scores with hospital-free days, and verifying that higher scores were associated with known risk factors for poor outcomes. Inverse probability weighted propensity scores were assigned for surgical management, and inverse probability weighted regression analysis was used to determine factors associated with ACDiT ≥ grade 2. RESULTS: Of 260 patients, 188 (72%) were managed nonoperatively. Eighty (31%) developed a complication; 73 (91%) were grades 1 to 3b. Higher grades correlated inversely with hospital-free days (rsâ=â-0.67, P < 0.0001) for all patients and for nonoperative (rsâ=â-0.63, P < 0.0001) and operative (rsâ=â-0.62, P < 0.0001) patients. Hinchey 2 to 3 and initial operative management had higher odds of having a complication of ACDiT ≥ grade 2. CONCLUSION: The ACDiT tool was successfully applied to acute diverticulitis patients managed operatively and nonoperatively, is associated with known risk factors for adverse outcomes. ACDiT may be considered a meaningful outcome measure for comparing strategies for acute diverticulitis.
Subject(s)
Diverticulitis/therapy , Outcome Assessment, Health Care , Postoperative Complications/classification , Postoperative Complications/epidemiology , Acute Disease , Adult , Cohort Studies , Diverticulitis/surgery , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
INTRODUCTION: Vacuum erectile device (VED) therapy is commonly used for penile rehabilitation after radical prostatectomy, however, the underlying mechanism of this effect is not fully understood. AIM: To evaluate the presence of label-retaining cells (LRCs), cells with long-term retention of 5-ethynyl-2-deoxyuridine (EdU) labeling and recognized as adult stem cells or progenitor-like cells, in cavernous tissue after VED treatment using a BCNC rat model. METHODS: Postnatal pups (1 day old) of Sprague Dawley (SD) rats were intraperitoneally injected with EdU (50 ug/g, BID for 3 days) and BCNC surgery was conducted at 6 weeks old (designated as natal-labeled rats). Adult SD rats underwent BCNC surgery and EdU injection (50 ug/g, once) after surgery (designated as adult-labeled rats). One week after surgery, both natal- and adult-labeled rats received daily VED treatment for 4 weeks. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured for all rats and then the penile tissue was harvested. The ratio of ICP/MAP was calculated to represent erectile function. Penile tissue was examined by immunofluorescence staining to detect EdU positive cells. MAIN OUTCOME MEASURES: The ratio of Intracavernous pressure (ICP) /MAP and the percentage of EdU positive cells were measured. RESULTS: The erectile function was impaired after BCNC and partially restored after VED treatment in both natal- and adult-labeled rats (P < .05). There was no difference in the percentage of EdU positive cells in natal-labeled rat cavernous tissue in BCNC group compared with VED group. Among the adult-labeled rats, the percentage of EdU positive cells increased in BCNC group (P < .05) but didn't change significantly after VED treatment (P = .35). CONCLUSION: LRCs may play a limited role in the restoration of erectile dysfunction through VED treatment after BCNC. Yang B, Luse D, Cao Y, et al. The Role of Long Term Label-Retaining Cells in the Treatment of Erectile Dysfunction by Vacuum Erectile Device. Sex Med 2021;9:100442.
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BACKGROUND: The Gallstone Pancreatitis: Admission vs Normal Cholecystectomy (Gallstone PANC) Trial demonstrated that cholecystectomy within 24 hours of admission (early) compared with after clinical resolution (control) for mild gallstone pancreatitis, significantly reduced 30-day length-of-stay (LOS) without increasing major postoperative complications. We assessed whether early cholecystectomy decreased 90-day healthcare use and costs. STUDY DESIGN: A secondary economic evaluation of the Gallstone PANC Trial was performed from the healthcare system perspective. Costs for index admissions and all gallstone pancreatitis-related care 90 days post-discharge were obtained from the hospital accounting system and inflated to 2020 USD. Negative binomial regression models and generalized linear models with log-link and gamma distribution, adjusting for randomization strata, were used. Bayesian analysis with neutral prior was used to estimate the probability of cost reduction with early cholecystectomy. RESULTS: Of 98 randomized patients, 97 were included in the analyses. Baseline characteristics were similar in early (n = 49) and control (n = 48) groups. Early cholecystectomy resulted in a mean absolute difference in LOS of -0.96 days (95% CI, -1.91 to 0.00, p = 0.05). Ninety-day mean total costs were $14,974 (early) vs $16,190 (control) (cost ratio [CR], 0.92; 95% CI, 0.73-1.15, p = 0.47), with a mean absolute difference of $1,216 less (95% CI, -$4,782 to $2,349, p = 0.50) per patient in the early group. On Bayesian analysis, there was an 81% posterior probability that early cholecystectomy reduced 90-day total costs. CONCLUSION: In this single-center trial, early cholecystectomy for mild gallstone pancreatitis reduced 90-day LOS and had an 81% probability of reducing 90-day healthcare system costs.
Subject(s)
Cholecystectomy/statistics & numerical data , Gallstones/surgery , Pancreatitis/surgery , Postoperative Complications/epidemiology , Time-to-Treatment/statistics & numerical data , Adult , Cholecystectomy/adverse effects , Cholecystectomy/economics , Cost-Benefit Analysis , Female , Gallstones/complications , Gallstones/diagnosis , Gallstones/economics , Health Care Costs/statistics & numerical data , Humans , Length of Stay/economics , Length of Stay/statistics & numerical data , Male , Middle Aged , Pancreatitis/diagnosis , Pancreatitis/economics , Pancreatitis/etiology , Postoperative Complications/economics , Postoperative Complications/etiology , Severity of Illness Index , Time Factors , Time-to-Treatment/economicsABSTRACT
We have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery. CP was induced by intraperitoneally injecting cerulein in C57BL/6 mice. Time-matched controls (CON) were given normal saline. Pancreata were harvested from mice 4 days after the final injections (designated as CP and CON) or 4 weeks after the final injections (designated as CP recovery (CPR) and control recovery (CONR)). Pancreatic RNAs were extracted for RNA-seq and quantitative (q) PCR validation. Using RNA-seq, we identified a total of 3,600 differentially expressed genes (DEGs) in CP versus CON and 166 DEGs in CPR versus CONR. There are 132 DEGs overlapped between CP and CPR and 34 DEGs unique to CPR. A number of selected pancreatic fibrosis-relevant DEGs were validated by qPCR. The top 20 gene sets enriched from DEGs shared between CP and CPR are relevant to extracellular matrix and cancer biology, whereas the top 10 gene sets enriched from DEGs specific to CPR are pertinent to DNA methylation and specific signaling pathways. In conclusion, we identified a distinct set of DEGs in association with extracellular matrix and cancer cell activities to contrast CP and CPR. Once during ongoing CP recovery, DEGs relevant to DNA methylation and specific signaling pathways were induced to express. The DEGs shared between CP and CPR and the DEGs specific to CPR may serve as the unique transcriptomic signatures and biomarkers for determining CP recovery and monitoring potential therapeutic responses at the molecular level to reflect pancreatic histological resolution.
Subject(s)
Gene Expression Regulation , Pancreas/metabolism , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/therapy , Transcriptome , Animals , Ceruletide/metabolism , Cholecystokinin/metabolism , Disease Models, Animal , Extracellular Matrix/metabolism , Female , Gene Expression Profiling , Male , Mice , Mice, Inbred C57BL , RNA-Seq , Signal TransductionABSTRACT
In complementary electrochromic devices (ECDs), nickel oxide (NiO) is generally used as a counter electrode material for enhancing the coloration efficiency. However, an NiO film as a counter electrode in ECDs is susceptible to degradation upon prolonged electrochemical cycling, which leads to an insufficient device lifetime. In this study, a type of counter electrode iridium oxide (IrO2) layer was fabricated using vacuum cathodic arc plasma (CAP). We focused on the comparison of IrO2 and NiO deposited on a 5 × 5 cm2 indium tin oxide (ITO) glass substrate with various Ar/O2 gas-flow ratios (1/2, 1/2.5, and 1/3) in series. The optical performance of IrO2-ECD (glass/ITO/WO3/liquid electrolyte/IrO2/ITO/glass) was determined by optical transmittance modulation; ∆T = 50% (from Tbleaching (75%) to Tcoloring (25%)) at 633 nm was higher than that of NiO-ECD (ITO/NiO/liquid electrolyte/WO3/ITO) (∆T = 32%). Apart from this, the ECD device demonstrated a fast coloring time of 4.8 s, a bleaching time of 1.5 s, and good cycling durability, which remained at 50% transmittance modulation even after 1000 cycles. The fast time was associated with the IrO2 electrode and provided higher diffusion coefficients and a filamentary shape as an interface that facilitated the transfer of the Li ions into/out of the interface electrodes and the electrolyte. In our result of IrO2-ECD analyses, the higher optical transmittance modulation was useful for promoting electrochromic application to a cycle durability test as an alternative to NiO-ECD.
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BACKGROUND: A systemic evaluation of immune cell infiltration patterns in experimental acute pancreatitis (AP) is lacking. Using multi-dimensional flow cytometry, this study profiled infiltrating immune cell types in multiple AP mouse models. METHODS: Three AP models were generated in C57BL/6 mice via cerulein (CAE) injection, alcohol and palmitoleic acid (EtOH + POA) injection, and alcohol diet feeding and cerulein (EtOH + CAE) injection. Primary pancreatic cells and splenocytes were prepared, and multi-dimensional flow cytometry was performed and analyzed by manual gating and computerized PhenoGraph, followed by visualization with t-distributed stochastic neighbor embedding (t-SNE). RESULTS: CAE treatment induced a time-dependent increase of major innate immune cells and a decrease of follicular B cells, and TCD4+ cells and the subtypes in the pancreas, whereas elicited a reversed pattern in the spleen. EtOH + POA treatment resulted in weaker effects than CAE treatment. EtOH feeding enhanced CAE-induced amylase secretion, but unexpectedly attenuated CAE-induced immune cell regulation. In comparison with manual gating analysis, computerized analysis demonstrated a remarkable time efficiency and reproducibility on the innate immune cells and B cells. CONCLUSIONS: The reverse pattern of increased innate and decreased adaptive immune cells was consistent in the pancreas in CAE and EtOH + POA treatments. Alcohol feeding opposed the CAE effect on immune cell regulation. Together, the immune profiling approach utilized in this study provides a better understanding of overall immune responses in AP, which may facilitate the identification of intervention windows and new therapeutic strategies. Computerized analysis is superior to manual gating by dramatically reducing analysis time.
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OBJECTIVE: The aim of this study was to compare clinical and patient-reported outcomes of robotic versus laparoscopic ventral hernia repair (LVHR) at 1-year postoperative. SUMMARY OF BACKGROUND DATA: Despite a relative lack of research at low risk for bias assessing robotic ventral hernia repair (RVHR), the growth of RVHR has been rapid. We previously reported short-term results of the first randomized control trial comparing RVHR versus LVHR; there was no clear difference in clinical outcomes but increased operative time and cost with robotic repair. METHODS: Patients from a multicenter, blinded randomized control trial comparing RVHR versus LVHR were followed at 1 year. Outcomes included wound complication (surgical site infection, surgical site occurrence, wound dehiscence), hernia occurrence including recurrence and port site hernia, readmission, reoperation, and patient-reported outcomes (functional status, pain, and satisfaction with repair and cosmesis). RESULTS: A total of 124 patients were randomized and 113 patients (91%; 60 robot, 53 laparoscopic) completed 1-year follow-up. Baseline demographics were similar in both groups. No differences were seen in wound complication (15% vs 15%; P = 0.899), hernia recurrence (7% vs 9%; P = 0.576), or readmission (2% vs 6%; P = 0.251). No patients underwent reoperation in the robotic arm, whereas 5 (9%) did in the laparoscopic arm (P = 0.020). No differences were seen in patient-reported outcomes. Both arms reported clinically significant improvements in functional status, low pain scores, and high satisfaction scores at 1-year post repair. CONCLUSION: This study confirms that robotic ventral hernia repair is safe when compared to laparoscopy. Further studies are needed to confirm these findings.
Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy/methods , Laparoscopy , Robotic Surgical Procedures , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
The incidence of acute and chronic pancreatitis is increasing in the United States. Rates of acute pancreatitis (AP) are similar in both sexes, but chronic pancreatitis (CP) is more common in males. When stratified by etiology, women have higher rates of gallstone AP, while men have higher rates of alcohol- and tobacco-related AP and CP, hypercalcemic AP, hypertriglyceridemic AP, malignancy-related AP, and type 1 autoimmune pancreatitis (AIP). No significant sex-related differences have been reported in medication-induced AP or type 2 AIP. Whether post-endoscopic retrograde cholangiopancreatography pancreatitis is sex-associated remains controversial. Animal models have demonstrated sex-related differences in the rates of induction and severity of AP, CP, and AIP. Animal and human studies have suggested that a combination of risk factor profiles, as well as genes, may be responsible for the observed differences. More investigation into the sex-related differences of AP and CP is desired in order to improve clinical management by developing effective prevention strategies, diagnostics, and therapeutics.
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BACKGROUND: Multiple strategies exist to improve the timeliness and efficiency of surgical care at safety-net hospitals (SNH), such as acute care surgery models and nighttime surgery. However, the patient-centeredness of such approaches is unknown. METHODS: Adults ( ≥18 years) with acute cholecystitis were interviewed upon admission to a SNH. Interviews were semi-structured and designed to obtain both exploratory qualitative data and ratings of patient-centered outcomes, ranked by importance to the patient. Outcomes included for rating were general health, symptom status, quality of life, and return to prior functional status. Latent content analysis applying inductive coding methods were used to code and condense raw qualitative data from interview transcripts. RESULTS: Thematic saturation was reached with a sample size of 15 patients. Most participants were female (87%), Hispanic (87%), and had prior diagnosis of benign biliary disease (60%). Patients identified symptom resolution as the highest-ranked outcome in their treatment. Themes expressed by patients during the exploratory segments of the interview included: desire for pain alleviation, frustration with delays to both symptom resolution and surgical intervention, lack of perceived control over their health care, and reticence in discussing preferences with physicians. All patients preferred to have surgical treatment as soon as possible, even if that meant having nighttime surgery. CONCLUSIONS: Effective and timely resolution of symptoms is of utmost importance to patients with acute cholecystitis at a SNH. Efforts to improve timeliness of surgical care are also perceived as patient-centered.