Miracle-dz/UniFAR-FTUs huggingface dataset:
Totally thoracoscopic ablation for atrial fibrillation: a systematic safety analysis

Abstract Aims Thoracoscopic surgical ablation has evolved into a successful strategy for symptomatic atrial fibrillation (AF) refractory to other therapy. More widespread referral is limited by the lack of information on potential complications. Our aim was to systematically evaluate 30-day complications of totally thoracoscopic surgical ablation. Methods and results We retrospectively studied consecutive patients undergoing totally thoracoscopic surgical ablation at a referral centre in the Netherlands (2007–2016). Patients received pulmonary vein isolation, with additional lesion lines as needed, and left atrial appendage exclusion. The primary outcomes were freedom from any complications and freedom from irreversible complications at 30-days. Secondary outcomes included intra- and post-operative complications according to severity. Included were 558 patients with median age 62 years (interquartile range 56–68 years), 70% male and 53% with a previous failed catheter ablation. The cohort consisted of 43% paroxysmal AF, 47% persistent AF, and 10% long-standing persistent AF. Freedom from any 30-day complication was 88.2%, and from complications with life-long affecting consequences 97.5%. The intra-operative complication rate was 2.3% with no strokes or death observed. The median hospital length of stay was 4 days. The percentage of patients with major and minor complications at 30-days was 3.2% and 8.1%, respectively, with one patient dying of an ischaemic stroke. The only patient groups with excess complications were women aged ≥70 years and patients with a history of congestive heart failure. Conclusions Totally thoracoscopic ablation is associated with a low complication rate in a referral centre and may be a useful alternative to other rhythm control strategies.
Community based kangaroo mother care for low birth weight babies: A pilot study

Background & objectives: Kangaroo mother care (KMC - early continuous skin-to-skin contact between mother and infants) has been recommended as an alternative care for low birth weight infants. There is limited evidence in our country on KMC initiated at home. The present study was undertaken to study acceptability of KMC in different community settings. Methods: A community-based pilot study was carried out at three sites in the States of Odisha, Gujarat and Maharashtra covering rural, urban and rural tribal population, respectively. Trained health workers provided IEC (information, education and communication) on KMC during antenatal period along with essential newborn care messages. These messages were reinforced during the postnatal period. Outcome measures were the proportion of women accepting KMC, duration of KMC/day and total number of days continuing KMC. Focus group discussions and in-depth interviews were also carried out. Results: KMC was provided to 101 infants weighing 1500-2000 g; 57.4 per cent were preterm. Overall, 80.2 per cent mothers received health education on KMC during antenatal period, family members (68.3%) also attended KMC sessions along with pregnant women and 55.4 per cent of the women initiated KMC within 72 h of birth. KMC was provided on an average for five hours per day. Qualitative survey data indicated that the method was acceptable to mothers and family members; living in nuclear family, household work, twin pregnancy, hot weather, etc., were cited as reasons for not being able to practice KMC for a longer duration. Interpretation & conclusions: It was feasible to provide KMC using existing infrastructure, and the method was acceptable to most mothers of low birth infants.
Developing a novel international undergraduate surgical masterclass during a financial crisis: our 4-year experience

Background Essential Skills in the Management of Surgical Cases (ESMSC) is a novel 3-day international undergraduate surgical masterclass. Its current curriculum (Cores integrated for Research—Ci4R) is built on a tetracore, multiclustered architecture combining high-fidelity and low-fidelity simulation-based learning (SBL), with applied and basic science case-based workshops, and non-technical skills modules. We aimed to report our experience in setting up ESMSC during the global financial crisis. Methods We report the evolution of our curriculum’s methodology and summarised the research outcomes related to the objective performance improvement of delegates, the educational environment of the course and the use of mixed-fidelity SBL. Feedback from the last three series of the course was prospectively collected and analysed using univariate statistics on IBM SPSS V.23. Results 311 medical students across the European Union (EU) were selected from a competitive pool of 1280 applicants during seven series of the course between 2014 and 2017. During this period, curriculum 14 s evolved to the final Ci4R version, which integrates a tetracore structure combining 32 stations of in vivo, ex vivo and dry lab SBL with small group teaching workshops. Ci4R was positively perceived across different educational background students (p>0.05 for any comparison). Conclusions ESMSC is considered an innovative and effective multidisciplinary teaching model by delegates, where it improves delegates objective performance in basic surgical skills. Our experience demonstrates provision of high-quality and free surgical education during a financial crisis, which evolved through a dynamic feedback mechanism. The prospective recording and subsequent analysis of curriculum evolution provides a blueprint to direct development of effective surgical education courses that can be adapted to local needs.
Accelerated High Fidelity Prion Amplification Within and Across Prion Species Barriers

Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains.
Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na+-channel blocker (5 μM) ranolazine or the intracellular Ca2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.
Anticancer activity of biogenerated silver nanoparticles: an integrated proteomic investigation

Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS), were biogenerated by Klebsiella oxytoca DSM 29614 under aerobic (AgNPs-EPSaer) and anaerobic conditions (AgNPs-EPSanaer). Both AgNPs-EPS matrices were tested by MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) and colon (HT-29, HCT 116 and Caco-2) cancer cell lines, revealing AgNPs-EPSaer as the most active, in terms of IC50, with a more pronounced efficacy against breast cancer cell lines. Therefore, colony forming capability, morphological changes, generation of reactive oxygen species (ROS), induction of apoptosis and autophagy, inhibition of migratory and invasive capabilities and proteomic changes were investigated using SKBR3 breast cancer cells with the aim to elucidate AgNPs-EPSaer mode of action. In particular, AgNPs-EPSaer induced a significant decrease of cell motility and MMP-2 and MMP-9 activity and a significant increase of ROS generation, which, in turn, supported cell death mainly through autophagy and in a minor extend through apoptosis. Consistently, TEM micrographs and the determination of total silver in subcellular fractions indicated that the Ag+ accumulated preferentially in mitochondria and in smaller concentrations in nucleus, where interact with DNA. Interestingly, these evidences were confirmed by a differential proteomic analysis that highlighted important pathways involved in AgNPs-EPSaer toxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment triggering cell death trough apoptosis and/or autophagy activation.
Estimation of Foot Plantar Center of Pressure Trajectories with Low-Cost Instrumented Insoles Using an Individual-Specific Nonlinear Model

Postural control is a complex skill based on the interaction of dynamic sensorimotor processes, and can be challenging for people with deficits in sensory functions. The foot plantar center of pressure (COP) has often been used for quantitative assessment of postural control. Previously, the foot plantar COP was mainly measured by force plates or complicated and expensive insole-based measurement systems. Although some low-cost instrumented insoles have been developed, their ability to accurately estimate the foot plantar COP trajectory was not robust. In this study, a novel individual-specific nonlinear model was proposed to estimate the foot plantar COP trajectories with an instrumented insole based on low-cost force sensitive resistors (FSRs). The model coefficients were determined by a least square error approximation algorithm. Model validation was carried out by comparing the estimated COP data with the reference data in a variety of postural control assessment tasks. We also compared our data with the COP trajectories estimated by the previously well accepted weighted mean approach. Comparing with the reference measurements, the average root mean square errors of the COP trajectories of both feet were 2.23 mm (±0.64) (left foot) and 2.72 mm (±0.83) (right foot) along the medial–lateral direction, and 9.17 mm (±1.98) (left foot) and 11.19 mm (±2.98) (right foot) along the anterior–posterior direction. The results are superior to those reported in previous relevant studies, and demonstrate that our proposed approach can be used for accurate foot plantar COP trajectory estimation. This study could provide an inexpensive solution to fall risk assessment in home settings or community healthcare center for the elderly. It has the potential to help prevent future falls in the elderly.
Brain-Derived Neurotropic Factor Val66Met Polymorphism and Posttraumatic Stress Disorder among Survivors of the 1998 Dongting Lake Flood in China

Objective This study mainly aimed to explore the association between brain-derived neurotropic factor (BDNF) Val66Met polymorphism and posttraumatic stress disorder (PTSD) among flood survivors in China. Methods Individuals who experienced the 1998 Dongting Lake flood in Southeast Huarong, China, were enrolled in this study. Qualified health personnel carried out face-to-face interviews with participants. PTSD was identified using PTSD Checklist-Civilian version (PCL-C). Blood samples were collected from the participants to extract DNA for genotyping. Results A total of 175 participants were enrolled in this study. The prevalence of PTSD among flood survivors at 17-year follow-up was 16.0% (28/175). Individuals with PTSD were more likely to be female, experience at least three flood-related stressors, experience at least three postflood stressors, and carry the Met than those without PTSD. Compared with Val/Val homozygotes, Met carriers had higher scores of PCL-C (mean ± standard error: 23.60 ± 7.23 versus 27.19 ± 9.48, P < 0.05). Multivariable logistic regression analysis indicated that Met carriers (aOR = 4.76, 95% CI = 1.02–22.15, P < 0.05) were more likely to develop PTSD than Val/Val homozygotes. Conclusions Met carriers for BDNF rs6265 are at higher risk of developing PTSD and also exhibit more severe PTSD symptoms than Val/Val homozygotes among flood survivors in China.
The Signal Sequence of the Abundant Extracellular Metalloprotease PPEP-1 Can Be Used to Secrete Synthetic Reporter Proteins in Clostridium difficile.

Clostridium difficile is an opportunistic pathogen and the main cause of antibiotic-associated diarrhea. Adherence of C. difficile to host cells is modulated by proteins present on the bacterial cell surface or secreted into the environment. Cleavage of collagen-binding proteins is mediated by the zinc metalloprotease PPEP-1, which was identified as one of the most abundant secreted proteins of C. difficile. Here, we exploit the PPEP-1 signal sequence to produce novel secreted enzymes. We have constructed two functional secreted reporters, AmyEopt and sLucopt for gene expression analysis in C. difficile. AmyEopt extracellular activity results in starch degradation and can be exploited to demonstrate promoter activity in liquid or plate-based assays. sLucopt activity could reliably be detected in culture supernatant when produced from an inducible or native promoter. The secreted reporters can be easily assessed under aerobic conditions, without the need of complex sample processing.
Factors Affecting ISNT Rule Satisfaction in Normal and Glaucomatous Eyes

Purpose To determine the factors that influence the satisfaction of the ‘ISNT rule’ (neural rim width: inferior ≥ superior ≥ nasal ≥ temporal) in normal and glaucomatous eyes. Methods The medical records of patients that visited Boramae Medical Center, Seoul, Korea, were reviewed. Each group of normal and glaucomatous eyes was divided into subgroups based on whether or not they satisfied the ISNT rule. ISNT rule assessment was performed by measuring the rim width with stereoscopic optic disc photographs using ImageJ software. Logistic regression analysis was performed to determine the factors that affect ISNT rule satisfaction. Results Seventy-seven normal eyes and 97 glaucomatous eyes were included in the study. The ISNT rule was intact in 59 (76.6%) of the normal eyes and was violated in 71 (73.2%) of the glaucomatous eyes. Logistic regression analysis revealed a significant influence of axial length in violation of the ISNT rule in the normal eye group, while the mean deviation value was a significant factor for violation of the ISNT rule in the glaucomatous eye group. Conclusions The ISNT rule should be cautiously applied when evaluating normal eyes with long axial lengths. In addition, the ISNT rule might not be as effective for detecting early glaucoma.
Enumeration of Functional T-Cell Subsets by Fluorescence-Immunospot Defines Signatures of Pathogen Burden in Tuberculosis

Background IFN-γ and IL-2 cytokine-profiles define three functional T-cell subsets which may correlate with pathogen load in chronic intracellular infections. We therefore investigated the feasibility of the immunospot platform to rapidly enumerate T-cell subsets by single-cell IFN-γ/IL-2 cytokine-profiling and establish whether immunospot-based T-cell signatures distinguish different clinical stages of human tuberculosis infection. Methods We used fluorophore-labelled anti-IFN-γ and anti-IL-2 antibodies with digital overlay of spatially-mapped colour-filtered images to enumerate dual and single cytokine-secreting M. tuberculosis antigen-specific T-cells in tuberculosis patients and in latent tuberculosis infection (LTBI). We validated results against established measures of cytokine-secreting T-cells. Results Fluorescence-immunospot correlated closely with single-cytokine enzyme-linked-immunospot for IFN-γ-secreting T-cells and IL-2-secreting T-cells and flow-cytometry-based detection of dual IFN-γ/IL-2-secreting T-cells. The untreated tuberculosis signature was dominated by IFN-γ-only-secreting T-cells which shifted consistently in longitudinally-followed patients during treatment to a signature dominated by dual IFN-γ/IL-2-secreting T-cells in treated patients. The LTBI signature differed from active tuberculosis, with higher proportions of IL-2-only and IFN-γ/IL-2-secreting T-cells and lower proportions of IFN-γ-only-secreting T-cells. Conclusions Fluorescence-immunospot is a quantitative, accurate measure of functional T-cell subsets; identification of cytokine-signatures of pathogen burden, distinct clinical stages of M. tuberculosis infection and long-term immune containment suggests application for treatment monitoring and vaccine evaluation.
The Use of Motion-Based Technology for People Living With Dementia or Mild Cognitive Impairment: A Literature Review

Background The number of people living with dementia and mild cognitive impairment (MCI) is increasing substantially. Although there are many research efforts directed toward the prevention and treatment of dementia and MCI, it is also important to learn more about supporting people to live well with dementia or MCI through cognitive, physical, and leisure means. While past research suggests that technology can be used to support positive aging for people with dementia or MCI, the use of motion-based technology has not been thoroughly explored with this population. Objective The aim of this study was to identify and synthesize the current literature involving the use of motion-based technology for people living with dementia or MCI by identifying themes while noting areas requiring further research. Methods A systematic review of studies involving the use of motion-based technology for human participants living with dementia or MCI was conducted. Results A total of 31 articles met the inclusion criteria. Five questions are addressed concerning (1) context of use; (2) population included (ie, dementia, MCI, or both); (3) hardware and software selection; (4) use of motion-based technology in a group or individual setting; and (5) details about the introduction, teaching, and support methods applied when using the motion-based technology with people living with dementia or MCI. Conclusions The findings of this review confirm the potential of motion-based technology to improve the lives of people living with dementia or MCI. The use of this technology also spans across several contexts including cognitive, physical, and leisure; all of which support multidimensional well-being. The literature provides evidence that people living with dementia or MCI can learn how to use this technology and that they enjoy doing so. However, there is a lack of information provided in the literature regarding the introduction, training, and support methods applied when using this form of technology with this population. Future research should address the appropriate introduction, teaching, and support required for people living with dementia or MCI to use the motion-based technology. In addition, it is recommended that the diverse needs of these specific end-users be considered in the design and development of this technology.
Microbiome perturbation by oral vancomycin reduces plasma concentration of two gut-derived uremic solutes, indoxyl sulfate and p-cresyl sulfate, in end-stage renal disease

Background Observational studies have suggested a relationship between the plasma concentration of indoxyl sulfate (IS) and p-cresyl sulfate (PCS), small gut-derived 'uremic solutes', and the high incidence of uremic cardiomyopathy in patients with end-stage renal disease (ESRD). IS and PCS are derived from the metabolism of dietary components (tryptophan and tyrosine) by gut bacteria. This pilot study was designed to examine the effects of a poorly absorbable antibiotic (vancomycin) on the plasma concentration of two gut-derived 'uremic solutes', IS and PCS, and on the composition of the gut microbiome. Methods Plasma concentrations of IS and PCS were measured by MS-HPLC. The gut microbiome was assessed in stool specimens sequenced for the 16S rRNA gene targeting the V4 region. Results The pre-dialysis mean plasma concentrations of both IS and PCS were markedly elevated. Following the administration of vancomycin (Day 0), the IS and PCS concentrations decreased at Day 2 or Day 5 and returned to baseline by Day 28. Following vancomycin administration, several changes in the gut microbiome were observed. Most striking was the decrease in diversity, a finding that was evident on Day 7 and was still evident at Day 28. There was little change at the phylum level but at the genus level, broad population changes were noted. Changes in the abundance of several genera appeared to parallel the concentration of IS and PCS. Conclusions These findings suggest that alteration of the gut microbiome, by an antibiotic, might provide an important strategy in reducing the levels of IS and PCS in ESRD.