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An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible and bench-stable difluoromethyltriphenylphosphonium bromide as the precursor of the -CF 2 H group has been developed to afford CF 2 H-substituted polycyclic imidazoles in moderate to good yields. This strategy, along with the construction of Csp 3 -CF 2 H/C-C bonds, is distinguished by mild conditions, no requirement of additives, simple operation, and wide substrate scope. In addition, the mechanistic experiments have indicated that the difluoromethyl radical pathway is essential for the methodology., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China., Methods: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed., Results: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits., Conclusions: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China., (© 2024. The Author(s).)

Objective: This study investigated the safety and efficacy of sclerotherapy with intralesional bleomycin injection (IBI) for retrobulbar orbital low-flow vascular lesions under multi-slice computed tomography (CT) guidance., Methods: Between January 2010 and September 2021, consecutive patients with retrobulbar orbital low-flow vascular lesions who underwent CT-guided IBI at a tertiary centre in Taiwan were enrolled. Their medical records and imaging data were retrospectively collected., Results: This study enrolled 13 patients (7 male and 6 female patients; age range: 1-57 years; mean age: 25.9 years) with lymphatic malformation (LM, n = 4), venolymphatic malformation (n = 1), and venous malformation (VM, n = 8). The overall radiological response rate was 76.9% (10 of 13); the radiological response rate was 75.0% in the VM group (6 of 8) and 75.0% in the LM group (3 of 4). Moreover, 3 patients (23.1%) had minor complications and 1 (7.7%) had a major complication. The mean clinical and radiological follow-up was 8.3 months and no recurrence or progression was reported., Conclusion: CT-guided IBI is an effective and relatively safe minimally invasive treatment for retrobulbar orbital low-flow vascular lesions, with an overall radiological response rate of 76.9% in a mean of 1.5 sessions and a low complication rate., Advances in Knowledge: CT-guided sclerotherapy with IBI is a relatively safe, effective, and feasible alternative treatment option for retrobulbar orbital low-flow vascular lesions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Acoustic force spectroscopy (AFS) is a single-molecule micromanipulation technique that uses sound waves to exert force on surface-tethered DNA molecules in a microfluidic chamber. As large numbers of individual protein-DNA complexes are tracked in parallel, AFS provides insight into the individual properties of such complexes as well as their population averages. In this chapter, we describe in detail how to perform AFS experiments specifically on bare DNA, protein-DNA complexes, and how to extract their (effective) persistence length and contour length from force-extension relations., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronavirus disease-2019 (COVID-19) remains a global public health concern, and remdesivir plus dexamethasone combination therapy is suggested for patients with severe disease. However, the factors associated with poor outcomes in these patients remain unclear. We identified the factors associated with poor outcomes in Taiwanese patients with severe COVID-19 treated with remdesivir plus dexamethasone., Methods: Adults with severe COVID-19 (oxygen saturation <94% on room air or requiring supplemental oxygen) treated with remdesivir and dexamethasone were identified between 1 May and 31 July 2021. The main outcomes were 14-day non-recovery, 28-day mortality, and progression to respiratory failure requiring invasive mechanical ventilation or death in initially non-ventilated patients. The prognostic factors associated with poor outcomes were analyzed by multivariate logistic regression and Cox regression., Results: Of the 110 patients treated with remdesivir and dexamethasone, 57 (51.8%) recovered within 14 days and 6 (5.5%) died within 28 days. Of the 89 initially non-ventilated patients, 12 (13.5%) progressed to respiratory failure or death. Charlson Comorbidity Index, SOFA score, and admission to remdesivir treatment interval were associated with 14-day non-recovery. C-reactive protein level was associated with 28-day mortality. Pneumonia Severity Index and admission to remdesivir treatment interval were associated with progression to respiratory failure requiring invasive mechanical ventilation or death in initially non-ventilated patients., Conclusion: High disease severity on admission and delayed initiation of remdesivir therapy were associated with poor outcomes in COVID-19 patients treated with remdesivir and dexamethasone., (Copyright © 2023. Published by Elsevier B.V.)

Background: The International Society of Urological Pathology (ISUP) grade and positive surgical margins (PSMs) after radical prostatectomy (RP) may reflect the prognosis of prostate cancer (PCa) patients. This study aimed to investigate whether DCE-MRI parameters (i.e., K trans , k ep , and IAUC) could predict ISUP grade and PSMs after RP., Method: Forty-five PCa patients underwent preoperative DCE-MRI. The clinical characteristics and DCE-MRI parameters of the 45 patients were compared between the low- and high-risk (i.e., ISUP grades III-V) groups and between patients with or without PSMs after RP. Multivariate logistic regression analysis was used to identify the significant predictors of placement in the high-risk group and PSMs., Results: The DCE parameter K trans-max was significantly higher in the high-risk group than in the low-risk group ( p = 0.028) and was also a significant predictor of placement in the high-risk group (odds ratio [OR] = 1.032, 95% confidence interval [CI] = 1.005-1.060, p = 0.021). Patients with PSMs had significantly higher prostate-specific antigen (PSA) titers, positive biopsy core percentages, K trans-max , k ep-median , and k ep-max than others (all p < 0.05). Of these, positive biopsy core percentage (OR = 1.035, 95% CI = 1.003-1.068, p = 0.032) and k ep-ma x (OR = 1.078, 95% CI = 1.012-1.148, p = 0.020) were significant predictors of PSMs., Conclusion: Preoperative DCE-MRI parameters, specifically K trans-max and k ep-max , could potentially serve as preoperative imaging biomarkers for postoperative PCa prognosis based on their predictability of PCa risk group and PSM on RP, respectively.

Numerous studies have found that repetitive transcranial magnetic stimulation (rTMS) modulates plasticity. rTMS has often been used to change neural networks underlying learning, often under the assumption that the mechanism of rTMS-induced plasticity should be highly similar to that associated with learning. The presence of visual perceptual learning (VPL) reveals the plasticity of early visual systems, which is formed through multiple phases. Hence, we tested how high-frequency (HF) rTMS and VPL modulate the effect of visual plasticity by investigating neurometabolic changes in early visual areas. We employed an excitatory-to-inhibitory (E/I) ratio, which refers to glutamate concentration divided by GABA+ concentration, as an index of the degree of plasticity. We compared neurotransmitter concentration changes after applying HF rTMS to the visual cortex with those after training in a visual task, in otherwise identical procedures. Both the time courses of the E/I ratios and neurotransmitter contributions to the E/I ratio significantly differed between HF rTMS and training conditions. The peak E/I ratio occurred 3.5 h after HF rTMS with decreased GABA+, whereas the peak E/I ratio occurred 0.5 h after visual training with increased glutamate. Furthermore, HF rTMS temporally decreased the thresholds for detecting phosphene and perceiving low-contrast stimuli, indicating increased visual plasticity. These results suggest that plasticity in early visual areas induced by HF rTMS is not as involved in the early phase of development of VPL that occurs during and immediately after training., (© 2023. The Author(s).)

Aim: The aim of this study was to evaluate depressive symptoms, emergency department visits, re-hospitalization and discharge to the same residence of comprehensive geriatric care in patients receiving hip-fracture surgery., Background: Hip fractures among older persons result in restricted activities of daily living, longer hospital stays, frequent emergency department visits and re-presentation to hospital, which may increase depressive symptoms and death risk. The benefits of comprehensive geriatric care have not been determined., Design: A five-step Cochrane collaboration meta-analysis was used., Data Sources: Randomized controlled trials published from 1980 to 2020 in which comprehensive geriatric care was provided following hip-fracture surgery were retrieved from the Cochrane Library, Clinical Key, Embase, MEDLINE, OVID and PubMed databases. Indicators were depressive symptoms, emergency department visits, re-hospitalization and discharge to the same residence., Review Methods: The Group Reading Assessment, Risk of Bias 2.0 tool, modified Jadad scale and Comprehensive Meta-Analysis Version 3 software were used., Results: Overall, 1291 patients from six randomised controlled trials were included. Comprehensive geriatric care improved depressive symptoms and lowered emergency department visits but did not improve re-hospitalization rates or discharge to the same residence., Conclusion: Comprehensive geriatric care should include depression management and individualized care plans. Further depression-related studies are required to verify their benefits., (© 2022 John Wiley & Sons Australia, Ltd.)

Genetic factors play an important role in early-onset Parkinson's disease (EOPD). The genetic spectrum of patients with EOPD varies widely among different ethnicities, with extensive investigations having been performed in Caucasian populations; however, research in Chinese populations remains limited. In this study, we performed multiplex ligation-dependent probe amplification assay and whole-exome sequencing in 15 unrelated Chinese EOPD patients with age of onset before 40 years. Among them, a patient carried compound heterozygous exon duplications in Parkin (exon 3 duplication and exon 4 duplication) (6.67 %) and two patients carried the homozygous pathogenic variant (p.D331Y) in PLA2G6 (13.33 %). Three novel variants in EIF4G1 (p.P1043S, p.R1505Q, and p.P266A) were identified and classified as uncertain significance. Additionally, a risk variant in GBA (p.L483P) was detected in one patient (6.67 %). PLA2G6 (13.33 %) was the most common causative gene among our EOPD patients. Furthermore, detailed clinical features were presented. Our results broaden the genetic spectrum and clinical phenotypic spectrum of EOPD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Inflammatory bowel diseases (IBD) cause chronic intestinal damage and extracellular matrix (ECM) remodeling. The ECM may play an active role in inflammation by modulating immune cell functions, including cell adhesion, but this hypothesis has not been tested in IBD., Design: Primary human intestinal myofibroblast (HIMF)-derived ECM from IBD and controls, 3D decellularized colon or ECM molecule-coated scaffolds were tested for their adhesiveness for T cells. Matrisome was analysed via proteomics. Functional integrin blockade was used to investigate the underlying mechanism. Analysis of the pediatric Crohn's disease (CD) RISK inception cohort was used to explore an altered ECM gene expression as a potential predictor for a future complicated disease course., Results: HIMF-derived ECM and 3D decellularized colonic ECM from IBD bound more T cells compared to control. Control HIMFs exposed to the pro-inflammatory cytokines Iinterleukin-1β (IL-1β) and tumor necrosis factor (TNF) increased, and to transforming growth factor-β1 (TGF-β1) decreased ECM adhesiveness to T cells. Matrisome analysis of the HIMF-derived ECM revealed collagen VI as a major culprit for differences in T cell adhesion. Collagen VI knockdown in HIMF reduced adhesion T cell as did the blockage of integrin αvβ1. Elevated gene expression of collagen VI in biopsies of pediatric CD patients was linked to risk for future stricturing disease., Conclusion: HIMF-derived ECM in IBD binds a remarkably enhanced number of T cells, which is dependent on Collagen VI and integrin αvβ1. Collagen VI expression is a risk factor for a future complicated CD course. Blocking immune cells retention may represent a novel approach to treatment in IBD., Competing Interests: Declaration of Competing Interest F.R. is consultant to Agomab, Allergan, AbbVie, Boehringer-Ingelheim, Celgene, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Jannsen, Koutif, Metacrine, Morphic, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Takeda, Techlab, Thetis, UCB, 89Bio. C.F. received speaker fees from UCB, Genentech, Sandoz, Janssen and he is consultant for Athos Therapeutics, Inc., (Copyright © 2022. Published by Elsevier B.V.)

Background: The cyclooxygenase-2 (COX-2) selective inhibitor parecoxib is widely used in the treatment of pain and inflammation. Parecoxib has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and dental surgery). Total knee or total hip arthroplasty (THA) surgery is mostly done in older patients, so postoperative analgesics need to be used more carefully, and the safety and efficacy of parecoxib in this type of surgery need to be further verified. The aim of this study was to investigate the effects of parecoxib on patient safety, cumulative morphine consumption and was at 24 and 48 hours in the analgesic treatment of total knee or THA for meta-analysis and systematic review, with few studies in this area so far., Methods: We searched the Online Database Cochrane Library, PubMed, Web of Science, EMBASE, and CBM (SinoMed), CNKI, VIP, WANFANG up to January 2021. According to the value of I2, the random-effect model or fixed-effect model was supposed to combine data from studies, respectively. Publication bias was assessed through funneling plot and Beggs test. Review Manager 5.3 and Stata 16.0 software were applied to perform the statistical analyses., Results: Eleven RCTs which involved 1690 participants were included in this study. The meta-analysis indicated parecoxib sodium could not significantly reduce the incidence of adverse events after total knee or THA compared with placebo. There was no statistical significance in incidence of nausea and vomiting. 24 hours resting VAS score was statistically significant between the group. The 48-hour resting VAS scores did not indicate a significant difference between the groups., Conclusion: Parecoxib can reduce the incidence of adverse events after total knee or total hip surgery to some extent but cannot reduce the incidence of nausea and vomiting. Twenty-four hour postoperative analgesia is better than placebo, but 48 hours after operation analgesia is the same as placebo., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: With the progress of urbanization, the mobility of people has gradually increased, which has led to the further spread of dengue fever. This study evaluated the transmissibility of dengue fever within districts and between different districts in Zhanjiang City to provide corresponding advice for cross-regional prevention and control. Methods: A mathematical model of transmission dynamics was developed to explore the transmissibility of the disease and to compare that between different regions. Results: A total of 467 DF cases (6.38 per 100,000 people) were reported in Zhanjiang City in 2018. In the model, without any intervention, the number of simulated cases in this epidemic reached about 950. The dengue fever transmissions between districts varied within and between regions. When the spread of dengue fever from Chikan Districts to other districts was cut off, the number of cases in other districts dropped significantly or even to zero. When the density of mosquitoes in Xiashan District was controlled, the dengue fever epidemic in Xiashan District was found to be significantly alleviated. Conclusions: When there is a dengue outbreak, timely measures can effectively control it from developing into an epidemic. Different prevention and control measures in different districts could efficiently reduce the risk of disease transmission.

Microbial carbon use efficiency (CUE) refers to the C transformation to microbial biomass from C uptake. The study of soil microbial CUE is very important for understanding the soil C cycle. Here, CUE, C growth , and C respiration were measured using the 18 O-H 2 O-DNA labeling method at six elevational sites (980-1765 m) in Daiyun Mountain, a subtropical montane forest, to understand the variation characteristics and influencing mechanisms. The results showed that:CUE varied from 0.1 to 0.4 and increased linearly with elevation; CUE was positively correlated with C growth , C respiration , and q growth but negatively correlated with q CO 2 , indicating that CUE increased with elevation by increasing microbial growth and inhibiting respiration; and temperature was the first controlling factor for the elevation variation in microbial CUE in the subtropical forest ecosystem.

Klebsiella pneumoniae is a common pathogen of nosocomial pneumonia worldwide and community-acquired pneumonia (CAP) in Asia. Previous studies have shown that K. pneumoniae bacteremic CAP is associated with high mortality. We aimed to revisit K. pneumoniae bacteremic pneumonia in the current era and determine the risk factors associated with 28-day mortality. Between January 2014 and August 2020, adult patients with K. pneumoniae bacteremic pneumonia in a medical center in Taiwan were identified. Clinical and microbiological characteristics were compared between CAP and nosocomial pneumonia. Risk factors for 28-day mortality were analyzed using multivariate logistic regression. Among 150 patients with K. pneumoniae bacteremic pneumonia, 52 had CAP and 98 had nosocomial pneumonia. The 28-day mortality was 52% for all patients, 36.5% for CAP, and 60.2% for nosocomial pneumonia. Hypervirulent K. pneumoniae was more prevalent in CAP (61.5%) than in nosocomial pneumonia (16.3%). Carbapenem-resistant K. pneumoniae was more prevalent in nosocomial pneumonia (58.2%) than in CAP (5.8%). Nosocomial pneumonia, a higher Severe Organ Failure Assessment score, and not receiving appropriate definitive therapy were independent risk factors for 28-day mortality. In conclusion, revisiting K. pneumoniae bacteremic pneumonia in the current era showed a high mortality rate. Host factors, disease severity, and timely effective therapy affect the treatment outcomes of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lin, Wu, Chou, Wang and Lin.)

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Lien, Lin, Kung, Huang, Lin and Chang.)

Intestinal fibrosis is considered an inevitable complication of Crohn's disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.

The cerebellum plays a critical role in acquiring visuomotor skills. Visuomotor task mastery requires improving both visuomotor accuracy and stability; however, the cerebellum's contribution to these processes remains unclear. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the cerebellum exerts frequency-dependent modulatory effects on both accuracy and stability in subjects performing a visuomotor coordination task (i.e., pursuit rotor task). We recruited 43 healthy volunteers and randomly assigned them to the high-frequency (HF), low-frequency (LF), and sham rTMS groups. We calculated changes in performance of the pursuit rotor task at the highest rotation speed and the minimum distance from target as indices of accuracy. We also calculated the intertrial variability (standard deviations) of time on target and distance from target as indices of stability. Visuomotor accuracy was significantly enhanced in the HF group and disrupted in the LF group compared to the sham group, indicating frequency-dependent effects of rTMS. In contrast, both HF and LF rTMS demonstrated no significant change in visuomotor stability. Surprisingly, our findings demonstrated that the accuracy and stability of visuomotor performance may be differentially influenced by cerebellar rTMS. This suggests that visuomotor accuracy and stability have different underlying neural mechanisms and revealed the possibility of training strategies based on cerebellar neuromodulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lien, Lin, Lin, Lin and Chang.)

Background: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China., Methods: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff ) was used to estimate the transmission interaction in different age groups., Results: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff  = 4.28), followed by group 2 to 3 (R eff  = 2.61), and group 2 to 4 (R eff  = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old., Conclusions: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China., (© 2021. The Author(s).)

Architectural DNA-binding proteins are involved in many important DNA transactions by virtue of their ability to change DNA conformation. Histone-like protein from E. coli strain U93, HU, is one of the most studied bacterial architectural DNA-binding proteins. Nevertheless, there is still a limited understanding of how the interactions between HU and DNA are affected by ionic conditions and the structure of DNA. Here, using optical tweezers in combination with fluorescent confocal imaging, we investigated how ionic conditions affect the interaction between HU and DNA. We directly visualized the binding and the diffusion of fluorescently labelled HU dimers on DNA. HU binds with high affinity and exhibits low mobility on the DNA in the absence of Mg 2+ ; it moves 30-times faster and stays shorter on the DNA with 8 mM Mg 2+ in solution. Additionally, we investigated the effect of DNA tension on HU-DNA complexes. On the one hand, our studies show that binding of HU enhances DNA helix stability. On the other hand, we note that the binding affinity of HU for DNA in the presence of Mg 2+ increases at tensions above 50 pN, which we attribute to force-induced structural changes in the DNA. The observation that HU diffuses faster along DNA in presence of Mg 2+ compared to without Mg 2+ suggests that the free energy barrier for rotational diffusion along DNA is reduced, which can be interpreted in terms of reduced electrostatic interaction between HU and DNA, possibly coinciding with reduced DNA bending., (© 2021. The Author(s).)

Purpose: To elucidate the usefulness of intravoxel incoherent motion (IVIM)/apparent diffusion coefficient (ADC) parameters in preoperative risk stratification using International Society of Urological Pathology (ISUP) grades., Materials and Methods: Forty-five prostate cancer (PCa) patients undergoing radical prostatectomy (RP) after prostate multiparametric magnetic resonance imaging (mpMRI) were included. The ISUP grades were categorized into low-risk (I-II) and high-risk (III-V) groups, and the concordance between the preoperative and postoperative grades was analyzed. The largest region of interest (ROI) of the dominant tumor on each IVIM/ADC image was delineated to obtain its histogram values (i.e., minimum, mean, and kurtosis) of diffusivity (D), pseudodiffusivity (D*), perfusion fraction (PF), and ADC. Multivariable logistic regression analysis of the IVIM/ADC parameters without and with preoperative ISUP grades were performed to identify predictors for the postoperative high-risk group., Results: Thirty-two (71.1%) of 45 patients had concordant preoperative and postoperative ISUP grades. D mean , D* kurtosis , PF kurtosis , ADC min , and ADC mean were significantly associated with the postoperative ISUP risk group (all p < 0.05). D mean and D* kurtosis (model I, both p < 0.05) could predict the postoperative ISUP high-risk group with an area under the curve (AUC) of 0.842 and a 95% confidence interval (CI) of 0.726-0.958. The addition of D* kurtosis to the preoperative ISUP grade (model II) may enhance prediction performance, with an AUC of 0.907 (95% CI 0.822-0.992)., Conclusions: The postoperative ISUP risk group could be predicted by D mean and D* kurtosis from mpMRI, especially D* kurtosis . Obtaining the biexponential IVIM parameters is important for better risk stratification for PCa., Competing Interests: Author C-YL was employed by General Electric (GE) Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chang, Lin, Wong, Lin, Lin, Lin, Sheng, Huang, Yang and Wang.)

Hip fractures decrease older adults' physical activity and quality of life (QoL). However, no current self-efficacy care programs are managed by clinical nurses, and thus no studies have measured their effects on self-care self-efficacy (SCSE). Hence, this quasi-experimental study determined the effectiveness of a self-efficacy care program (SECP) in 104 older adults receiving hip-fracture surgery who were divided into intervention and control groups. The Strategies Used by People to Promote Health and Short Form-36 were administered pre-surgery and at 1 and 3-month intervals post-surgery. The SCSE and QoL of the SECP group were significantly better than the control group at 1- and 3-month follow-ups post-surgery. Both groups' QoL decreased at one-month post-surgery but increased by 3-months post-surgery. The SECP group had higher psychological QoL than the control group post-surgery. This intervention increased the SCSE and QoL of older adults with hip fractures and improved post-operative care.

Background: Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province., Methods: We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness., Results: From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R 2  = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days)., Conclusions: HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-β/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding RNAs (ncRNAs) stands out in fibrotic diseases in that ncRNAs exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncRNAs, including the emerging long ncRNAs and circular RNAs, in intestinal fibrogenesis. Notably, the translational potential of ncRNAs as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: • Characteristics of ncRNAs and mechanisms of intestinal fibrogenesis • Wide participation of ncRNAs (especially the emerging long ncRNAs and circular RNAs) in intestinal fibrosis, including transforming growth factor-β signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling • Translational potential of ncRNAs in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy., Methods: We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0-0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1-3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (f c ) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15-44; 45-64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f)., Results: Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01-0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71-0.12%)., Conclusions: Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups.

Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients. Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed. Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders ( P < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate ( P < 0.0001) and mild ( P = 0.0002) histologically active disease. Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Qiu, Jeffery, Liu, Feng, He, Tan, Ye, Lin, Ghosh, Iacucci, Chen and Mao.)

HU is a nucleoid-associated protein expressed in most eubacteria at a high amount of copies (tens of thousands). The protein is believed to bind across the genome to organize and compact the DNA. Most of the studies on HU have been carried out in a simple in vitro system, and to what extent these observations can be extrapolated to a living cell is unclear. In this study, we investigate the DNA binding properties of HU under conditions approximating physiological ones. We report that these properties are influenced by both macromolecular crowding and salt conditions. We use three different crowding agents (blotting grade blocker (BGB), bovine serum albumin (BSA), and polyethylene glycol 8000 (PEG8000)) as well as two different MgCl 2 conditions to mimic the intracellular environment. Using tethered particle motion (TPM), we show that the transition between two binding regimes, compaction and extension of the HU protein, is strongly affected by crowding agents. Our observations suggest that magnesium ions enhance the compaction of HU-DNA and suppress filamentation, while BGB and BSA increase the local concentration of the HU protein by more than 4-fold. Moreover, BGB and BSA seem to suppress filament formation. On the other hand, PEG8000 is not a good crowding agent for concentrations above 9% ( w / v ), because it might interact with DNA, the protein, and/or surfaces. Together, these results reveal a complex interplay between the HU protein and the various crowding agents that should be taken into consideration when using crowding agents to mimic an in vivo system.

Background: A suitable disease classification is essential for individualized therapy in patients with Crohn's disease (CD). Although a potential mechanistic classification of colon-involving and non-colon-involving disease was suggested by recent genetic and microbiota studies, the clinical implication has seldom been investigated. We aimed to explore the association of this colonic-based classification with clinical outcomes in patients with CD compared with the Montreal classification., Methods: This was a retrospective study of CD patients from a tertiary referral center. Patients were categorized into colon-involving and non-colon-involving disease, and according to the Montreal classification. Clinico-demographic data, medications, and surgeries were compared between the two classifications. The primary outcome was the need for major abdominal surgery., Results: Of 934 patients, those with colonic involvement had an earlier median (interquartile range) age of onset [23.0 (17.0-30.0) versus 26.0 (19.0-35.0) years, p  = 0.001], higher frequency of perianal lesions (31.2% versus 14.5%, p  < 0.001) and extraintestinal manifestations (21.8% versus 14.5%, p  = 0.010), but lower frequency of stricture (B2) (16.3% versus 24.0%, p  = 0.005), than those with non-colon-involving disease. Colon-involving disease was a protective factor against major abdominal surgery [hazard ratio, 0.689; 95% confidence interval (CI), 0.481-0.985; p  = 0.041]. However, patients with colon-involving CD were more prone to steroids [odds ratio (OR), 1.793; 95% CI, 1.206-2.666; p  = 0.004] and azathioprine/6-mercaptopurine (AZA/6-MP) treatment (OR, 1.732; 95% CI, 1.103-2.719; p  = 0.017) than were patients with non-colon-involving disease. The Montreal classification was not predictive of surgery or steroids and AZA/6-MP treatment., Conclusion: This study supports the rationale for disease classification based on the involvement of colon. This new classification of CD is a better predictor of clinical outcomes than the Montreal classification., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background and Aims: The COVID-19 pandemic poses a great challenge to healthcare. We aimed to investigate the impact of COVID-19 on the healthcare of patients with inflammatory bowel disease (IBD) in epicenter and non-epicenter areas. Methods: Patients with IBD from Hubei province (the epicenter of COVID-19) and Guangdong province (a non-epicenter area), China were surveyed during the pandemic. The questionnaire included change of medications (steroids, immunomodulators, and biologics), procedures (lab tests, endoscopy, and elective surgery), and healthcare mode (standard healthcare vs. telemedicine) during 1 month before and after the outbreak of COVID-19. Results: In total, 324 IBD patients from Guangdong province (non-epicenter) and 149 from Hubei province (epicenter) completed the questionnaire with comparable demographic characteristics. Compared to patients in Guangdong province (non-epicenter), significantly more patients in Hubei (epicenter) had delayed lab tests/endoscopy procedures [61.1% (91/149) vs. 25.3% (82/324), p < 0.001], drug withdrawal [28.6% (43/149) vs. 9.3% (30/324), p < 0.001], delayed biologics infusions [60.4% (90/149) vs. 19.1% (62/324), p < 0.001], and postponed elective surgery [16.1% (24/149) vs. 3.7% (12/324), p < 0.001]. There was an increased use of telemedicine after the outbreak compared to before the outbreak in Hubei province [38.9% (58/149) vs. 15.4% (23/149), p < 0.001], while such a significant increase was not observed in Guangdong province [21.9% (71/324) vs. 18.8% (61/324), p = 0.38]. Approximately two-thirds of IBD patients from both sites agreed that telemedicine should be increasingly used in future medical care. Conclusions: Our patient-based survey study in a real-world setting showed that COVID-19 resulted in a great impact on the healthcare of patients with IBD, and such an impact was more obvious in the epicenter compared to the non-epicenter area of COVID-19. Telemedicine offers a good solution to counteract the challenges in an unprecedented situation such as COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Qiu, Zhang, Zhu, He, Tan, Tan, Lin, Lin, Ghosh, Chen and Mao.)

Background: Heart failure (HF) is associated with type 2 diabetes mellitus (T2DM). Antihyperglycemic drugs have interaction with heart failure among diabetic patients. To date, the data on real world use of diabetic medication in Malaysian heart failure patients with T2DM has not been elucidated. Objective: This study aims to identify the prescribing pattern of antihyperglycemic regimens in HF patients with T2DM, and to investigate the association between glycemic control and other factors such as demographic and clinical characteristics with left ventricular ejection fraction (LVEF) in these patients. Methods: This retrospective observational study involved patients diagnosed to have HF and T2DM who were seen in the outpatient clinic in a government tertiary hospital in Malaysia. Patients receiving at least one oral antidiabetic agent and/or insulin for at least 3 months prior were included. The differences and association between study outcomes were examined and analyzed using Pearson's Chi-square test, One-Way ANOVA, Binary Logistic Regression and multiple Multinomial Logistic Regression models. Results: From July to December 2019, 194 patients were included in this study. The majority (52.1%) of the patients had HF with preserved ejection fraction (HFpEF), 20.6% had HF with mid-range EF (HFmrEF), and 27.3% had HF with reduced EF (HFrEF). Overall, metformin (59.8%) was the commonest antihyperglycemic agent prescribed, followed by insulins (54.0%), and sulphonylureas (44.9%). The most prescribed agents for HFpEF, HFmrEF, and HFrEF patients were metformin (65.3%), insulins (62.5%), and sulphonylureas (60.4%), respectively. The prescribing trend of sulphonylureas was found to be significantly associated with patients' LVEF status ( p = 0.033). The odds for sulphonylurea prescription among the HFrEF patients were 2.42 times higher compared to the HFpEF patients [95% confidence interval [CI], 1.23-4.79]. There was no association found between glycemic control with patients' LVEF. Conclusion: Our findings reported metformin as the most commonly prescribed antihyperglycemic agent, sodium glucose linked transporter-2 (SGLT-2) inhibitor being under-prescribed, and detected poorly controlled diabetes in majority of patients with T2DM and HF. Understanding the prescribing pattern of antihyperglycemic agents supports the implementation of evidence-based treatment in HF patients with T2DM to improve patients' outcomes., (Copyright © 2020 Lin, Phang, Toh, Chee and Zaman Huri.)

Stroke is the most common cause of complex disability in Taiwan. After stroke onset, persistent physical practice or exercise in the rehabilitation procedure reorganizes neural assembly for reducing motor deficits, known as neuroplasticity. Neuroimaging literature showed rehabilitative effects specific to the brain networks of the sensorimotor network (SMN) and default-mode network (DMN). However, whether between-network interactions facilitate the neuroplasticity after stroke rehabilitation remains a mystery. Therefore, we conducted the longitudinal assessment protocol of stroke rehabilitation, including three types of clinical evaluations and two types of functional magnetic resonance imaging (fMRI) techniques (resting state and grasp task). Twelve chronic stroke patients completed the rehabilitation protocol for at least 24 h and finished the three-time assessments: before, after rehabilitation, and 1 month after the cessation of rehabilitation. For comparison, age-matched normal controls (NC) underwent the same fMRI evaluation once without repeated measure. Increasing scores of the Fugl-Meyer assessment (FMA) and upper extremity performance test reflected the enhanced motor performances after the stroke rehabilitation process. Analysis of covariance (ANCOVA) results showed that the connections between posterior cingulate cortex (PCC) and iM1 were persistently enhanced in contrast to the pre-rehabilitation condition. The interactions between PCC and SMN were positively associated with motor performances. The enhanced cross-network connectivity facilitates the motor recovery after stroke rehabilitation, but the cross-network interaction was low before the rehabilitation process, similar to the level of NCs. Our findings suggested that cross-network connectivity plays a facilitatory role following the stroke rehabilitation, which can serve as a neurorehabilitative biomarker for future intervention evaluations., (Copyright © 2020 Wu, Lin, Hsu, Yeh, Guu, Lee and Chen.)

Intestinal fibrosis and subsequent stricture formation are major clinical challenges in inflammatory bowel disease, resulting in an increased rate of operation and poor prognosis compared with those without. With the changing perception that intestinal fibrosis is irreversible to the point of view that it is reversible in recent years, various candidate serum biomarkers have been studied over the past decades, which may stratify patients based on their risks of developing stenosis and enable the detection of early stages of fibrosis. However, reliable and accurate biomarkers are still unavailable due to conflicting results and the lack of high-quality evidence. In this review we summarized the serum biomarkers that have been proposed for intestinal fibrosis in recent years, which includes gene polymorphisms or variants, epigenetic markers, extracellular matrix components, growth factors, and antibodies, aiming to provide clues for future research., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Hip fractures may increase mortality and decrease mobility in elderly patients. Effectiveness of comprehensive geriatric care (CGC) has not been verified. A systematic review and a meta-analysis were conducted by searching full-text databases (1988-2018) of Cochrane Library, Clinical Key, Embase, MEDLINE, CINAHL, and ProQuest for randomized controlled trials (RCTs) of CGC following hip fractures. Outcome measures were mortality, activities of daily living, hospital stay, and discharge to institutional setting. Cochrane RoB 2.0, Jadad Quality Score, and Group Reading Assessment were used for analysis. Of the 11 studies included, 8 examined mortality (effect size Z = 2.51, p = 0.01), 5 examined daily activities (effect size Z = 3.31, p = 0.0009), 7 examined length of hospital stay (effect size Z = 0.18, p = 0.85), and 5 examined discharged to an institutional setting (effect size Z = 0.81, p = 0.42). Results showed that CGC decreased mortality and improved daily living activities.

Many health promotion campaigns have incorporated multi-component nutrition interventions to promote healthy diet-related behaviours among Indigenous communities, particularly children and adolescents. However, these campaigns show mixed results and while research often describes outcomes of approaches and interventions, it does not extensively describe implementation processes and best practices for nutrition education for Indigenous youth. To enhance knowledge and understanding of best processes in nutritional education approaches with Indigenous youth, we conducted a search using multiple databases including PubMed, Google Scholar, the Australian Indigenous HealthInfoNet and Australian government research databases to identify relevant peer-reviewed and grey literature as well as educational resources, such as websites and handbooks for teachers, parents, and students. We list and describe common features of successful nutritional interventions in Indigenous settings, steps for nutrition education targeting youth, school-based nutrition education for different ages, and general guidelines for teaching Indigenous students. Current best practice and knowledge gaps for the delivery of nutrition education to Indigenous youth are described., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Two new diketopiperazine alkaloids, named protuboxepin C (1) and protuboxepin D (2), which contain D-Phe residue and oxepin ring, were isolated from EtOAc extract of sponge-derived fungus Aspergillus sp SCSIO XWS02F40. Their structures were elucidated by 1D, 2D NMR and HRESIMS dates, and their absolute configurations were confirmed by single crystal X-ray diffraction experiments and CD analyses. The in vitro cytotoxicity of these two new compounds was further evaluated using A549 and Hela cell lines.

Acoustic Force Spectroscopy (AFS) is a single-molecule micromanipulation technique that uses sound waves to exert force on surface-tethered DNA molecules in a microfluidic chamber. As large numbers of individual protein-DNA complexes are tracked in parallel, AFS provides insight into the individual properties of such complexes as well as their population averages. In this chapter, we describe in detail how to perform AFS experiments specifically on bare DNA, protein-DNA complexes, and how to extract their (effective) persistence length and contour length from force-extension relations.

Objective: To report the outcomes over 14 years of sustained systematic institutional focus on the care of women with major obstetric hemorrhage, defined as estimated blood loss greater than 1,500 mL., Methods: A retrospective cohort study of women with major obstetric hemorrhage at our hospital from 2000 to 2014 compares baseline conditions (age, multiparity, prior cesarean delivery, morbidly adherent placenta), morbidity (lowest mean temperature, lowest mean pH, coagulopathy, hysterectomy), and mortality among three time periods (period 1=January 2000 to December 2001, period 2=January 2002 to August 2005, period 3=September 2005 to December 2014). We also describe the systematic changes that helped to sustain our improved outcomes., Results: During the three time periods, there were 5,811, 12,912, and 38,971 births; the rate of major obstetric hemorrhage increased over these periods: 2.1, 3.8 and 5.3 cases per 1,000 births, respectively. Two deaths from hemorrhage occurred in period 1 and none thereafter. Among women who experienced massive hemorrhage, morbidity significantly improved in each successive period: median lowest pH increased from 7.23 to 7.34 to 7.35 (periods 2 and 3 significantly higher than period 1), median lowest maternal temperature (°C) improved, 35.2 to 36.1 to 36.4 (all difference significant), and the rate of coagulopathy decreased, 58.3% to 28.6% to 13.2% (period 3 significantly lower than periods 1 and 2) (all P values <.001). Peripartum hysterectomies were more frequent and more frequently planned over time rather than urgent in each successive period: 0 of 6 to 6 of 18 (33%) to 31 of 64 (48.4%) (P=.044). During period 3, we reorganized the obstetric rapid response team, instituted a massive transfusion protocol and use of uterine balloon tamponade, and promoted a culture of safety in two ways-through more intensive education regarding hemorrhage and escalation (encouraging all staff to contact senior leaders)., Conclusion: A sustained level of patient safety is achievable when treating major obstetric hemorrhage, as shown by a progressive decrease in morbidity despite increasing rates of hemorrhage.

DNA polymerase catalyzes the accurate transfer of genetic information from one generation to the next, and thus it is vitally important for replication to be faithful. DNA polymerase fulfills the strict requirements for fidelity by a combination of mechanisms: 1) high selectivity for correct nucleotide incorporation, 2) a slowing down of the replication rate after misincorporation, and 3) proofreading by excision of misincorporated bases. To elucidate the kinetic interplay between replication and proofreading, we used high-resolution optical tweezers to probe how DNA-duplex stability affects replication by bacteriophage T7 DNA polymerase. Our data show highly irregular replication dynamics, with frequent pauses and direction reversals as the polymerase cycles through the states that govern the mechanochemistry behind high-fidelity T7 DNA replication. We constructed a kinetic model that incorporates both existing biochemical data and the, to our knowledge, novel states we observed. We fit the model directly to the acquired pause-time and run-time distributions. Our findings indicate that the main pathway for error correction is DNA polymerase dissociation-mediated DNA transfer, followed by biased binding into the exonuclease active site. The number of bases removed by this proofreading mechanism is much larger than the number of erroneous bases that would be expected to be incorporated, ensuring a high-fidelity replication of the bacteriophage T7 genome., (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Sso10a proteins are small DNA-binding proteins expressed by the crenarchaeal model organism Sulfolobus solfataricus. Based on the structure of Sso10a1, which contains a winged helix-turn-helix motif, it is believed that Sso10a proteins function as sequence-specific transcription factors. Here we show that Sso10a1 and Sso10a2 exhibit different distinct DNA-binding modes. While the ability to bend DNA is shared between the two proteins, DNA bridging is observed only for Sso10a1 and only Sso10a2 exhibits filament formation along DNA. The architectural properties of Sso10a proteins suggest that these proteins fulfil generic roles in chromatin organization and compaction. As these proteins exhibit different binding behaviour depending on their DNA binding stoichiometry, altered levels of expression in the cell can be exploited to drive changes in local genome folding, which may operate to modulate transcription.

Background: Fontan failure (FF) occurs rarely. In patients with Fontan failure, heart transplantation is believed to be the most effective therapy. We review our experience in heart transplantations after the Fontan operation., Methods: From July 1987 to December 2014, 4 of 513 patients underwent orthotopic heart transplantation (OHT). Among them, 4 were due to FF. We reviewed these 4 cases via retrospective chart review. Clinical history, laboratory data, surgical technique, perioperative variables, and outcomes of long-term follow-up are presented herein. The primary outcomes were hospital mortality, 1-year-survival rate, and 4-year-survival rate. The secondary outcome is the improvement in patients with protein-losing enteropathy., Results: The hospital mortality rate was 0% in the 4 FF patients receiving OHT. No surgically related hemorrhage or infection was observed. The 1-year-survival rate was 100% (n = 4) and the 4-year-survival rate 50% (n = 2). One patient died of posttransplantation lymphoproliferative disorder. Hypoalbuminemia improved in 1 of 3 patients 4 months after OHT., Conclusions: Despite technical challenges, heart transplantation can be performed successfully in patients with Fontan operation. However, protein-losing enteropathy might not be resolved quickly after heart transplantation., (Copyright © 2016. Published by Elsevier Inc.)

Background: There is a paucity of data on the effect of vaginal lubricants on specimen adequacy in the era of liquid-based Papanicolaou (Pap) tests. Current manufacturer recommendations advise against the use of lubricants, especially those that contain carbomers or carbopol polymers. There is, however, no conclusive evidence to support this recommendation. Moreover, the data that does exist is conflicting., Methods: Retrospective review was performed of all liquid-based Pap tests collected between January 2010 and March 2012 by the Gynecologic Oncology division at a single hospital. Specimen adequacy was compared for vaginal and cervical specimens that were collected with and without a lubricant. Results were also compared for specimens collected with lubricants that did or did not contain carbomers., Results: There was no significant difference in specimen adequacy for cervical or vaginal Pap test specimens collected with a water-soluble lubricant not containing carbomers, compared to those collected without a lubricant. There was, however, a significantly higher rate of insufficient specimens when a water-soluble lubricant containing carbomers was used. This difference was most pronounced for vaginal Pap tests (26.9% versus 1.2%, OR = 30.3, 95% CI = 16.6-55.1, P < .0001)., Conclusions: Lubricants containing carbomers should be avoided when collecting liquid-based Pap tests because they can significantly decrease specimen adequacy. Lubricants that do not contain these substances do not significantly affect specimen adequacy. If there is an unusual increase in unsatisfactory Pap tests, the cytology laboratory should notify clinicians and work with them to determine the cause., (© 2013 American Cancer Society.)

Aim: The objective of this study was to assess the utilization of postpartum thromboprophylaxis with heparin in patients according to the Royal College of Obstetrics and Gynaecology Green-Top guidelines after change from an opt-in to an opt-out policy for health care providers ordering heparin thromboprophylaxis after cesarean delivery., Study Design: The present study is a retrospective review of 500 consecutive births at one academic institution before and after implementation of a uniform thromboprophylaxis policy with heparin for all cesarean deliveries. An "opt-out" policy for ordering physicians was implemented by automatically defaulting to order heparin in the electronic order set used after cesarean delivery., Results: Cesarean delivery rates were similar during both time periods. Heparin thromboprophylaxis was indicated in 99.6% of the cesarean delivery population before implementation and 94.5% after implementation. Prior to implementation only 5.7% received thromboprophylaxis compared to 96.1% after implementation, P<0.0001., Conclusion: An opt-out heparin thromboprophylaxis policy improves compliance with thromboprophylaxis guidelines compared to an opt-in policy. Institutions should consider opt-out heparin thromboprophylaxis policies after cesarean deliveries to improve compliance with recommendations.

Self-propelled particles (SPP) exhibit complex collective motions, mimicking autonomous behaviors that are often seen in the natural world, but essentially are generated by simple mutual interactions. Previous research on SPP systems focuses on collective behaviors of a uniform population. However, very little is known about the evolution of individual particles under the same global influence. Here we show self-organized rotating spiral coils in a two-dimensional (2D) active system. By using swarming bacteria Vibrio alginolyticus as an ideal experimental realization of a well-controlled 2D self-propelled system, we study the interaction between ultra-long cells and short background active cells. The self-propulsion of long cells and their interactions with neighboring short cells leads to a self-organized, stable spiral rotational state in 2D. We find four types of spiral coils with two main features: the rotating direction (clockwise or counter-clockwise) and the central structure (single or double spiral). The body length of the spiral coils falls between 32 and 296 μm and their rotational speed is within a range from 2.22 to 22.96 rad s(-1). The dynamics of these spiral coils involves folding and unfolding processes, which require local velocity changes of the long bacterium. This phenomenon can be qualitatively replicated by a Brownian dynamics simulation using a simple rule of the propulsion thrust, imitating the reorientation of bacterial flagella. Apart from the physical and biological interests in swarming cells, the formation of self-organized spiral coils could be useful for the next generation of microfabrication.

Objective: The objective of this study was to compare modified Shirodkar cerclage to bed rest for treatment of the midtrimester extremely short cervix., Methods: This study used a concurrent retrospective cohort design at two institutions over the same period, 2000-2010. Patients were included at both institutions when midtrimester endovaginal ultrasound cervical length was ≤ 15 mm and had modified Shirodkar cerclage (cerclage group) at New York Hospital Queens and bed rest (control group) at Weill Cornell Medical Center. Cerclage was placed as high on the cervix as possible. Indomethacin and antibiotics were used perioperatively., Results: The cerclage group included 112 patients and the control group included 55 patients. Median postoperative cervical length in the cerclage group was 3.3 cm (interquartile range 3.0-3.6). Cerclage patients were less likely to deliver preterm at 37, 35, 32, and 28 weeks (P=0.0066, 0.0004, 0.0023, and 0.03 respectively) and had longer latency (median 120 vs. 94 days P<0.0001). Kaplan-Meier survival curve showed a significant benefit in favor of cerclage (P=0.0043)., Conclusions: Our data suggest that modified Shirodkar cerclage as high as possible on the cervix with perioperative indomethacin and antibiotics is superior to bed rest for treatment of the midtrimester extremely short cervix (≤15 mm). We propose a randomized trial of this specific technique.

Objective: To describe the effects of hysterectomy on the anterior and posterior vaginal compartments and specific pelvic organ prolapsed quantification (POP-Q) data points., Methods: In a retrospective case-control study, data were analyzed from patients presenting at a urogynecologic center in Manhasset, USA, with urogenital prolapse between January 1, 2008, and December 31, 2010. Patients who underwent hysterectomy for indications not including prolapse were compared with age- and parity-matched women without prior hysterectomy. POP-Q points were measured and converted to stages for each vaginal compartment. The t test, Wilcoxon rank sum, and Fisher exact tests were used to compare normally distributed variables, nonparametric data, and categoric variables, respectively., Results: Seventy-one patients who underwent prior hysterectomy were matched to 71 patients with intact uteri. Women with prior hysterectomy had significantly greater prolapse at POP-Q point Bp and worse overall posterior compartment prolapse compared with those without prior hysterectomy. Women who underwent hysterectomy were more likely to have stage 2 or greater prolapse (OR 2.6, 95% CI, 1.3-5.2; P=0.01)., Conclusion: When matched for age and parity, women with prior hysterectomy had significantly greater posterior compartment prolapse compared with those without. Prior hysterectomy had no significant effect on the anterior vaginal compartment., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)