Interplay between Inter-Subunit Rotation of the Ribosome and Binding of Translational GTPases.

Translational G proteins, whose release from the ribosome is triggered by GTP hydrolysis, regulate protein synthesis. Concomitantly with binding and dissociation of protein factors, translation is accompanied by forward and reverse rotation between ribosomal subunits. Using single-molecule measurements, we explore the ways in which the binding of translational GTPases affects inter-subunit rotation of the ribosome. We demonstrate that the highly conserved translation factor LepA, whose function remains debated, shifts the equilibrium toward the non-rotated conformation of the ribosome. By contrast, the catalyst of ribosome translocation, elongation factor G (EF-G), favors the rotated conformation of the ribosome. Nevertheless, the presence of P-site peptidyl-tRNA and antibiotics, which stabilize the non-rotated conformation of the ribosome, only moderately reduces EF-G binding. These results support the model suggesting that EF-G interacts with both the non-rotated and rotated conformations of the ribosome during mRNA translocation. Our results provide new insights into the molecular mechanisms of LepA and EF-G action and underscore the role of ribosome structural dynamics in translation.

Understanding the immunological aspects of SARS-CoV-2 causing COVID-19 pandemic: A therapeutic approach.

In December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a novel variant of coronavirus has emerged from Wuhan in China and has created havoc impulses across the world with a larger number of fatalities. At the same time, studies are on roll to discover potent vaccine against it or repurposing of approved drugs which are widely adopted are under trial to eradicate the SARS-CoV-2 causing COVID-19 pandemic. Reports have also shown that there are asymptomatic carriers of COVID-19 disease who can transmit the disease to others too. However, the first line defense of the viral attack is body's strong and well-coordinated immune response producing excessive inflammatory innate reaction, thus impaired adaptive host immune defense which lead to death upon the malfunctioning. Considerable works are going on to establish the relation between immune parameters and viral replication that, might alter both the innate and adaptive immune system of COVID-19 patient by up riding a massive cytokines and chemokines secretion. This review mainly gives an account on how SARS-CoV-2 interacts with our immune system and how does our immune system responds to it, along with that drugs which are being used or can be used in fighting COVID-19 disease. The curative therapies as treatment for it have also been addressed in the perspective of adaptive immunity of the patients.

Impact of the COVID-19 pandemic on the workflow of an ambulatory endoscopy center: an assessment by discrete event simulation.

BACKGROUND AND AIMS: As community-based ambulatory endoscopy centers (AECs) across the nation are trying to reopen and safely resume outpatient endoscopic procedures after the unprecedented lockdown related to the coronavirus disease 2019 (COVID-19) pandemic, guidelines recommend pretesting and screening for COVID-19 along with other mitigation measures for the safety of patients and staff. The impact of such changes in the workflow of AECs on throughput and other performance indicators is largely unknown, although a significant reduction in revenue stream is expected. METHODS: A discrete event simulation-based model was developed in the setting of a small to medium community-based single-specialty AEC to quantify the impact of COVID-19-related workflow changes on performance indicators and cost per case compared with the pre-COVID-19 baseline. RESULTS: In the simulation model, post-COVID-19 recommended workflow changes significantly impacted the operational and productivity metrics and, in turn, adversely affected financial metrics. Overall, there was a significant decrease in staff utilization and consequent increase in total facility time, waiting time for patients, and cost per case because of a bottleneck at the time of preprocedure COVID-19 screening and testing while practicing social distancing. Strategies to minimize this adverse impact on productivity were assessed. CONCLUSIONS: Pretesting and screening for COVID-19 as recommended by current guidelines will significantly impact the productivity and revenue stream of AECs. Urgent measures by payors are needed to adjust the facility reimbursement of endoscopy centers to ensure successful reopening and ramping up outpatient endoscopy services in these facilities already hit hard by the pandemic.

Diagnostic Yield From Screening Asymptomatic Individuals at High Risk for Pancreatic Cancer: A Meta-analysis of Cohort Studies.

BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk. METHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years. RESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI. CONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.

Reply to the 'Comment on ""Where does the fluorescing moiety reside in a carbon dot?"- Investigations based on fluorescence anisotropy decay and resonance energy transfer dynamics"' by H. C. Joshi, Phys. Chem. Chem. Phys., 2019, 21, DOI: 10.1039/c9cp00136k.

The claim that the analysis regarding resonance energy transfer should have been made using different equations than those that we have used is negated based on the following points: (1) we are well aware of the equations the author has provided in his comment. The equation (eqn (3) mentioned below) that the author has written is undoubtedly too simple to describe the complex system delineated in our original paper. This particular equation is perhaps OK for simple dye (donor and acceptor) systems; however, such a simple equation is never enough for nanoparticle/quantum dot systems. (2) Another equation suggested by the author in his comment (eqn (2)) contains a parameter called donor concentration in excited state. We have categorically described in page 6-7 of our original paper why it is difficult to measure the donor concentration accurately even in the ground state. When the donor concentration can't be known accurately it can't be used in the suggested equation. (3) Donor-acceptor distance calculated by eqn (3)/Table 1 provided by the author deviates more than 100% from the distance that is physically feasible. Such kinds of problems are well documented in the literature. (4) One of the papers cited by the author in his comment and many other published papers clearly mention that in the case when all donor molecules/particles do not take part in the resonance energy transfer process or the stoichiometry of a donor-acceptor complex is not known or deviates strongly from 1 : 1, especially in quantum dots or any other nanomaterial system, it is not possible to extract accurate dynamical information related to RET from donor decay. Instead risetime of acceptor yields much more accurate information. Such situations do arise in our system as well.

Cost effectiveness of endoscopic gallbladder drainage to treat acute cholecystitis in poor surgical candidates.

BACKGROUND: Endoscopic gallbladder drainage (GBD) is an alternative to percutaneous GBD (PGBD) to treat acute cholecystitis, yielding similar success rates and fewer adverse events. To our knowledge, no cost-effectiveness analysis has compared these procedures. We performed an economic analysis to identify clinical and cost determinants of three treatment options for acute cholecystitis in poor surgical candidates. METHODS: We compared three treatment strategies: PGBD, endoscopic retrograde cholangiographic transpapillary drainage (ERC-GBD), and endosonographic GBD (EUS-GBD). A decision tree was created over a 3-month period. Effectiveness was measured using hospital length of stay, including adverse events and readmissions. Costs of care were calculated from the National Inpatient Sample. Technical and clinical success estimates were obtained from the published literature. Cost effectiveness was measured as incremental cost effectiveness and compared to the national average cost of one hospital bed per diem. RESULTS: Analysis of a hypothetical cohort of poor candidates for cholecystectomy showed that, compared to PGBD, ERC-GBD was a cost-saving strategy and EUS-GBD was cost effective, requiring $1312 per hospitalization day averted. Additional costs of endoscopic interventions were less than the average cost of one hospital bed per diem. Compared to ERC-GBD, EUS-GBD required expending an additional $8950 to prevent one additional day of hospitalization. Our model was considerably affected by lumen-apposing metal stent cost and hospital length of stay for patients managed conservatively and those requiring delayed surgery. CONCLUSIONS: Endoscopic GBD is cost effective compared to PGBD, favoring ERC-GBD over EUS-GBD. Further efforts are needed to make endoscopic GBD available in more medical centers, reduce equipment costs, and shorten inpatient stay.

Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Unresectable malignant biliary strictures are generally managed by palliative stent placement for drainage of biliary tree. Recently, radiofrequency ablation (RFA) has been used to improve the patency of biliary stents in these patients. Several studies have evaluated the effectiveness of biliary stent placement with RFA on stent patency and patient survival with variable results. We performed this meta-analysis to evaluate the efficacy and safety of biliary stent placement with RFA compared with stent placement alone in patients with malignant biliary strictures. METHODS: We performed a comprehensive search of electronic databases for all studies comparing RFA with biliary stent placement versus stent placement only. Measured outcomes included patient survival, stent patency, and procedure-related adverse events. An inverse variance method was used to pool data on stent patency into a random-effects model. Cox-regression analysis was used to calculate hazard ratio for survival analysis. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to interpret our findings. RESULTS: Nine studies (including 2 abstracts) with a total of 505 patients were included in the meta-analysis. The pooled weighted mean difference in stent patency was 50.6 days (95% confidence interval [CI], 32.83-68.48), favoring patients receiving RFA. Pooled survival analysis of the reconstructed Kaplan-Meier data showed improved survival in patients treated with RFA (hazard ratio, 1.395; 95% CI, 1.145-1.7; P < .001). However, RFA was associated with a higher risk of postprocedural abdominal pain (31% vs 20%, P = .003). Our analysis did not show significant difference between the RFA and stent placement-only groups with regard to the risk of cholangitis, acute cholecystitis, pancreatitis, and hemobilia. CONCLUSIONS: In the light of this limited data based on observational studies, RFA was found to be safe and was associated with improved stent patency in patients with malignant biliary strictures. In addition, RFA may be associated with improved survival in these patients.

"Where does the fluorescing moiety reside in a carbon dot?" - Investigations based on fluorescence anisotropy decay and resonance energy transfer dynamics.

It has been shown recently that aggregated dyes are responsible for very high fluorescence in a carbon dot (CD). However, what is the location of the fluorescing moiety in CD? Is it inside the CD or attached to the CD's surface? In order to answer these intriguing questions regarding the location of the fluorescing moiety in a CD, we performed rotational anisotropy decay dynamics and resonance energy transfer (RET) dynamics. Rotational correlation time of ∼120 picoseconds nullifies the fact that the whole CD is fluorescing. Instead, we can say that the fluorescing moiety is either embedded inside the CD or attached to the surface of the CD or linked to the CD through covalent bonds. From the fluorescence anisotropy decay dynamics in solvents of different viscosities, we could show that the fluorescing moiety is not attached to the surface of the CD or for that matter, the fluorescing moiety is not in a rigid environment inside the CD. RET dynamical analysis has shown that the time for RET (from CD to acceptor Rh123) is about 5.4 ns and the RET dynamics are independent of the acceptor concentration. Using RET dynamics, we could prove that the fluorescing moiety is not outside the CD; rather, it is inside the CD, but not in a rigid environment. The geometric distance between the fluorescing moiety of the CD and the acceptor (Rh123) has been obtained to be 4.55 nm. Using Förster formulation, the distance between the fluorescing moiety inside the CD and the acceptor Rh123 has been calculated to be 4.24 nm. Thus, we could not only reveal the exact location of the fluorescing moiety in a CD, but we could also demonstrate that unlike for many other nanomaterials, Förster formulation could explain the experimental observables regarding RET involving CD reasonably well.

Increasing Number of Passes Beyond 4 Does Not Increase Sensitivity of Detection of Pancreatic Malignancy by Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND & AIMS: It is not clear exactly how many passes are required to determine whether pancreatic masses are malignant using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We aimed to define the per-pass diagnostic yield of EUS-FNA for establishing the malignancy of a pancreatic mass, and identify factors associated with detection of malignancies. METHODS: In a prospective study, 239 patients with solid pancreatic masses were randomly assigned to groups that underwent EUS-FNA, with the number of passes determined by an on-site cytopathology evaluation or set at 7 passes, at 3 tertiary referral centers. A final diagnosis of pancreatic malignancy was made based on findings from cytology, surgery, or a follow-up evaluation at least 1 year after EUS-FNA. The cumulative sensitivity of detection of malignancy by EUS-FNA was calculated after each pass; in the primary analysis, lesions categorized as malignant or suspicious were considered as positive findings. RESULTS: Pancreatic malignancies were found in 202 patients (84.5% of the study population). EUS-FNA detected malignancies with 96% sensitivity (95% confidence interval [CI], 92%-98%); 4 passes of EUS-FNA detected malignancies with 92% sensitivity (95% CI, 87%-95%). Tumor size greater than 2 cm was the only variable associated with positive results from cytology analysis (odds ratio, 7.8; 95% CI, 1.9-31.6). In masses larger than 2 cm, 4 passes of EUS-FNA detected malignancies with 93% sensitivity (95% CI, 89%-96%) and in masses ≤2 cm, 6 passes was associated with 82% sensitivity (95% CI, 61%-93%). Sensitivity of detection did not increase with increasing number of passes. CONCLUSIONS: In a prospective study, we found 4 passes of EUS-FNA to be sufficient to detect malignant pancreatic masses; increasing the number of passes did not increase the sensitivity of detection. Tumor size greater than 2 cm was associated with malignancy, and a greater number of passes may be required to evaluate masses 2 cm or less. ClinicalTrials.gov number, NCT01386931.

Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort.

BACKGROUND AND AIMS: Rates of progression to esophageal adenocarcinoma in subjects with Barrett's esophagus (BE) are lower than previously estimated. Identification of predictors of progression will enable risk stratification of BE subjects, potentially making current surveillance programs more efficient. We aimed to assess the potential of demographic and lifestyle factors, obesity, and medications in predicting progression in BE. METHODS: BE subjects were identified from the General Practice Research Database using validated diagnostic codes. BE subjects developing esophageal cancer (EC) 12 months after their index BE diagnosis were defined as progressors. Time-to-event analysis was used to assess the overall risk of progression to EC. Cox proportional hazards models and time-varying marginal structural models were used to assess predictors of progression. RESULTS: Included in the analysis were 9660 BE patients. The mean age (SD) of the study subjects was 63 (13.5) years; 62.6% were men. One hundred three subjects (1.1%) progressed to EC. The mean (SD) follow-up since initial diagnosis was 4.8 (3.3) years. The incidence of EC was 2.23 per 1000 person-years of follow-up. Increasing age, male gender, and being overweight (body mass index, 25-29.9) were found to be independent predictors of progression. When time-varying models were used, proton pump inhibitor (PPI) and statin use were protective against progression. CONCLUSIONS: In this large population-based cohort of patients with BE, increasing age, male gender, and being overweight predicted progression to EC, whereas PPI and statin use were protective against EC development. These factors may aid in developing a risk score to predict the risk of progression and chemopreventive strategies in patients with BE.

Endoscopic resection is cost-effective compared with laparoscopic resection in the management of complex colon polyps: an economic analysis.

BACKGROUND AND AIMS: Endoscopic resection (ER) is an efficacious treatment for complex colon polyps (CCPs). Many patients are referred for surgical resection because of concerns over procedural safety, incomplete polyp resection, and adenoma recurrence after ER. Efficacy data for both resection strategies are widely available, but a paucity of data exist on the cost-effectiveness of each modality. The aim of this study was to perform an economic analysis comparing ER and laparoscopic resection (LR) strategies in patients with CCP. METHODS: A decision analysis tree was constructed using decision analysis software. The 2 strategies (ER vs LR) were evaluated in a hypothetical cohort of patients with CCPs. A hybrid Markov model with a 10-year time horizon was used. Patients entered the model after colonoscopic diagnosis at age 50. Under Strategy I, patients underwent ER followed by surveillance colonoscopy at 3 to 6 months and 12 months. Patients with failed ER and residual adenoma at 12 months were referred for LR. Under Strategy II, patients underwent LR as primary treatment. Patients with invasive cancer were excluded. Estimates regarding ER performance characteristics were obtained from a systematic review of published literature. The Centers for Medicare & Medicaid Services (2012-2013) and the 2012 Healthcare Cost and Utilization Project databases were used to determine the costs and loss of utility. We assumed that all procedures were performed with anesthesia support, and patients with adverse events in both strategies required inpatient hospitalization. Baseline estimates and costs were varied by using a sensitivity analysis through the ranges. RESULTS: LR was found to be more costly and yielded fewer quality-adjusted life-years (QALYs) compared with ER. The cost of ER of a CCP was $5570 per patient and yielded 9.640 QALYs. LR of a CCP cost $18,717 per patient and yielded fewer QALYs (9.577). For LR to be more cost-effective, the thresholds of 1-way sensitivity analyses were (1) technical success of ER for complete resection in <75.8% of cases, (2) adverse event rates for ER > 12%, and (3) LR cost of <$14,000. CONCLUSIONS: Our data suggest that ER is a cost-effective strategy for removal of CCPs. The effectiveness is driven by high technical success and low adverse event rates associated with ER, in addition to the increased cost of LR.

Molecular origin of photoluminescence of carbon dots: aggregation-induced orange-red emission.

The molecular origin of the photoluminescence of carbon dots (CDs) is not known. This restricts the design of CDs with desired optical properties. We have synthesized CDs starting from carbohydrates by employing a simple synthesis method. We were able to demonstrate that the CDs are composed of aggregated hydroxymethylfurfural (HMF) derivatives. The optical properties of these CDs are quite unique. These CDs exhibit an excitation-independent PL emission maximum in the orange-red region (λ ∼ 590 nm). These CDs also exhibit excitation as well as monitoring wavelength-independent single exponential PL decay. These observations indicate that only one type of chromophore (HMF derivative) is present within the CDs. Several HMF derivatives are aggregated within the CDs; therefore, the aggregated structure cause a large Stokes shift (∼150 nm). By several control experiments, we showed that the same aggregated chromophore unit (HMF derivative), and not the individual fluorophores, is the fluorescing unit. The emission maximum and the single exponential PL lifetime are independent of the polarity of the medium. The existence of a low-lying trap state could be reduced quite significantly. A model has been proposed to explain the interesting steady state and dynamical photoluminescence behaviour of the CDs. As the molecular origin of their photoluminescence is known, CDs with desired optical properties can be designed.

Endoscopic ultrasonography in esophageal cancer leads to improved survival rates: results from a population-based study.

BACKGROUND: The advantages of endoscopic ultrasound (EUS) and computed tomography (CT)-positron emission tomography (PET) with respect to survival for esophageal cancer patients are unclear. This study aimed to assess the effects of EUS, CT-PET, and their combination on overall survival with respect to cases not receiving these procedures. METHODS: Patients who were ≥66 years old when diagnosed with esophageal cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into 4 analytic groups: EUS only (n = 318), CT-PET only (n = 853), EUS+CT-PET (n = 189), and no EUS or CT-PET (n = 2439). Survival times were estimated with the Kaplan-Meier method and were compared with the log-rank test for each group versus the no EUS or CT-PET group. Multivariate Cox proportional hazards models were used to compare 1-, 3-, and 5-year survival rates. RESULTS: Kaplan-Meier analyses showed that EUS, CT-PET, and EUS+CT-PET patients had improved survival for all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy, and chemoradiation. Multivariate Cox proportional hazards models showed that receipt of EUS was a significant predictor of improved 1- (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39-0.59; P < .0001), 3- (HR, 0.57; 95% CI, 0.48-0.66; P < .0001), and 5-year survival (HR, 0.59; 95% CI, 0.50-0.68). Similar results were noted when the results were stratified on the basis of histology and for the CT-PET and EUS+CT-PET groups. CONCLUSIONS: Receipt of either EUS or CT-PET alone in esophageal cancer patients was associated with improved 1-, 3-, and 5-year survival. Future studies should identify barriers to the dissemination of these staging modalities.

The clinical impact of immediate on-site cytopathology evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: a prospective multicenter randomized controlled trial.

OBJECTIVES: Observational data on the impact of on-site cytopathology evaluation (OCE) during endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic masses have reported conflicting results. We aimed to compare the diagnostic yield of malignancy and proportion of inadequate specimens between patients undergoing EUS-FNA of pancreatic masses with and without OCE. METHODS: In this multicenter randomized controlled trial, consecutive patients with solid pancreatic mass underwent randomization for EUS-FNA with or without OCE. The number of FNA passes in the OCE+ arm was dictated by the on-site cytopathologist, whereas seven passes were performed in OCE- arm. EUS-FNA protocol was standardized, and slides were reviewed by cytopathologists using standardized criteria for cytologic characteristics and diagnosis. RESULTS: A total of 241 patients (121 OCE+, 120 OCE-) were included. There was no difference between the two groups in diagnostic yield of malignancy (OCE+ 75.2% vs. OCE- 71.6%, P=0.45) and proportion of inadequate specimens (9.8 vs. 13.3%, P=0.31). Procedures in OCE+ group required fewer EUS-FNA passes (median, OCE+ 4 vs. OCE- 7, P<0.0001). There was no significant difference between the two groups with regard to overall procedure time, adverse events, number of repeat procedures, costs (based on baseline cost-minimization analysis), and accuracy (using predefined criteria for final diagnosis of malignancy). There was no difference between the two groups with respect to cytologic characteristics of cellularity, bloodiness, number of cells/slide, and contamination. CONCLUSIONS: Results of this study demonstrated no significant difference in the diagnostic yield of malignancy, proportion of inadequate specimens, and accuracy in patients with pancreatic mass undergoing EUS-FNA with or without OCE.

Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study.

BACKGROUND: Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. OBJECTIVE: To compare colorectal cancer (CRC)-specific survival with ET and surgery. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. INTERVENTIONS: ET and surgery. MAIN OUTCOME MEASUREMENTS: Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. RESULTS: Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). LIMITATIONS: Comorbidity index not available, selection bias. CONCLUSIONS: ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion.

Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates.

OBJECTIVE: Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. STUDY DESIGN: A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. RESULTS: Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1ß, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. CONCLUSION: Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension.

Comparison of endoscopic therapies and surgical resection in patients with early esophageal cancer: a population-based study.

BACKGROUND: Outcome data comparing endoscopic eradication therapy (EET) and esophagectomy are limited in patients with early esophageal cancer (EC). OBJECTIVE: To compare overall survival and EC-related mortality in patients with early EC treated with EET and esophagectomy. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with early EC (stages T0 and T1) were identified from the Surveillance, Epidemiology, and End Results database (1998-2009). Demographics, tumor specific data, and survival were compared. Cox proportional hazards regression models were used to evaluate the association between treatment and EC-specific mortality. INTERVENTION: EET and esophagectomy. MAIN OUTCOME MEASUREMENTS: Mid- (2 years) and long- (5 years) term overall survival and EC-specific mortality, outcomes based on histology and stage, treatment patterns, and predictors of cancer-specific mortality. RESULTS: A total of 430 (21%) and 1586 (79%) patients underwent EET and esophagectomy, respectively. There was no difference in the 2-year (EET: 10.5% vs esophagectomy: 12.7%, P = .27).and 5-year (EET: 36.7% vs esophagectomy: 42.8%, P = .16) EC-related mortality rates between the 2 groups. EET patients had higher mortality rates attributed to non-EC causes (5 years: 46.6% vs 20.6%, P < .001). Similar results were noted when comparisons were limited to patients with stage T0 and T1a disease and esophageal adenocarcinoma. There was no difference in EC-specific mortality in the EET compared with the surgery group (hazard ratio 1.4; 95% confidence interval, 0.9-2.03). Variables associated with mortality were older age, year of diagnosis, radiation therapy, higher stage, and esophageal squamous cell carcinoma. LIMITATIONS: Comorbidities and recurrence rates were not available. CONCLUSIONS: This population-based study demonstrates comparable mid- and long-term EC-related mortality in patients with early EC undergoing EET and surgical resection.

Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

Mitochondria act as a key regulatory factor in cancer progression: Current concepts on mutations, mitochondrial dynamics, and therapeutic approach.

The diversified impacts of mitochondrial function vs. dysfunction have been observed in almost all disease conditions including cancers. Mitochondria play crucial roles in cellular homeostasis and integrity, however, mitochondrial dysfunctions influenced by alterations in the mtDNA can disrupt cellular balance. Many external stimuli or cellular defects that cause cellular integrity abnormalities, also impact mitochondrial functions. Imbalances in mitochondrial activity can initiate and lead to accumulations of genetic mutations and can promote the processes of tumorigenesis, progression, and survival. This comprehensive review summarizes epigenetic and genetic alterations that affect the functionality of the mitochondria, with considerations of cellular metabolism, and as influenced by ethnicity. We have also reviewed recent insights regarding mitochondrial dynamics, miRNAs, exosomes that play pivotal roles in cancer promotion, and the impact of mitochondrial dynamics on immune cell mechanisms. The review also summarizes recent therapeutic approaches targeting mitochondria in anti-cancer treatment strategies.