Miracle-dz/UniFAR-FTUs huggingface dataset:
The Infection Hypothesis Revisited: Oral Infection and Cardiovascular Disease

Background. The pathophysiology of cardiovascular disease (CVD) includes inflammation in the development of atherosclerosis and thrombosis. Increasing evidence supports oral infections, and in particular the common periodontal disease, to be associated with CVD development. Periodontal infection is present in populations worldwide and in the moderate to mild form in about 35% of populations according to the World Health Organization. Objective. This review of the literature aims to present cross evidence from medical research disciplines that explore how oral infections can contribute to increase the risk for CVDs and how treatment of oral infections can reduce the risk for CVDs. Design. Review article. Results. Long-term exposure to active nontreated infections of the oral cavity presents an opportunity for bacteria, bacterial products, and viruses to enter the circulation. Toxic bacterial products enter the circulation, affecting atherosclerosis, causing platelet adhesiveness that results in clot formation, and establishing cardiac vegetation. Pathological observations have identified oral bacteria in heart valves, aortic aneurysms, and arterial walls. Clinical intervention studies on periodontal disease reduce the risk level of serological predictors for CVDs. Conclusions. This paper presents evidence across medical research disciplines for oral infections to be considered as one of the risk factors for CVDs.
The Impact of Autoimmune Hepatitis and Its Treatment on Health Utility

Patient reporting suggests that the physical and psychological effects of autoimmune hepatitis (AIH) can be substantial. However, health‐related quality of life (HRQOL) in patients with AIH remains incompletely characterized, and health utility remains to be explored. Treatment for AIH often includes the use of corticosteroids, which are agents that can be associated with significant adverse effects. Here we explore the impact of AIH and its treatments on patient‐reported HRQOL and health utility in a large cohort of prevalent cases from the United Kingdom Autoimmune Hepatitis (UK‐AIH) national study. Data were collected from 990 adult participants with a clinical diagnosis of AIH using validated HRQOL tools including the European Quality‐of‐Life 5‐Dimension 5‐Level (EQ‐5D‐5L) and clinical data forms. The EQ‐5D‐5L dimension scores were compared with UK population norms and with a disease control cohort with primary biliary cholangitis (PBC). Within the AIH cohort, regression analysis was used to explore associations between HRQOL and demographic and clinical variables with a particular focus on the impact of AIH therapies including corticosteroid use. HRQOL, measured by the EQ‐5D‐5L utility index, is shown to be significantly impaired in our cohort of AIH patients compared with population norms. Within the AIH cohort, corticosteroid use was found to be significantly associated with impaired HRQOL, even when controlling for biochemical disease activity status. Conclusion: Our data show evidence of HRQOL impairment in a large cohort of AIH patients compared with the general population. Furthermore, corticosteroid use is strongly associated with decreased HRQOL, independent of remission status. This highlights the need for better corticosteroid‐free therapy approaches and it emphasizes the need for future novel therapeutic trials in AIH. (Hepatology 2018; 00:000‐000).
Emerging concepts in cardiovascular disease risk assessment: Where do women fit in?

Purpose: To highlight the current limitations in the assessment of cardiovascular disease (CVD) risk for women. This article will offer the reader information on the current process for assessing CVD risk in women, the pitfalls associated with this current strategy, and the role of novel risk factors. Data sources: Extensive review of the medical literature in the area of women's cardiovascular health. Conclusions: The assessment of CVD risk for women is currently an evolving science. Limitations in the ability of the Framingham score to accurately estimate risk in women from diverse populations are increasingly recognized. Vastly different treatment goals between the genders for similar levels of risk factors have led to a re‐evaluation of this strategy in women. While the Framingham score is still useful for guiding cholesterol treatment goals, the current preventive guidelines for women emphasize assessing a woman's risk throughout her lifetime. The future development of tools for improved risk stratification that incorporate novel risk factors may in fact improve our ability to appropriately risk stratify women to evidence‐based therapies. Implications for practice: Utilizing the Framingham Risk Assessment Tool and further CVD risk stratification using novel markers such as high sensitivity C‐reactive protein, family history, and functional capacity may identify unique subsets of women at higher risk for CVD. Nurse practitioners can be instrumental in this assessment, education, and treatment of women at risk for CVD.
Tissue engineered vascular grafts: current state of the field

ABSTRACT Introduction: Conventional synthetic vascular grafts are limited by the inability to remodel, as well as issues of patency at smaller diameters. Tissue-engineered vascular grafts (TEVGs), constructed from biologically active cells and biodegradable scaffolds have the potential to overcome these limitations, and provide growth capacity and self-repair. Areas covered: This article outlines the TEVG design, biodegradable scaffolds, TEVG fabrication methods, cell seeding, drug delivery, strategies to reduce wait times, clinical trials, as well as a 5-year view with expert commentary. Expert commentary: TEVG technology has progressed significantly with advances in scaffold material and design, graft design, cell seeding and drug delivery. Strategies have been put in place to reduce wait times and improve ‘off-the-shelf’ capability of TEVGs. More recently, clinical trials have been conducted to investigate the clinical applications of TEVGs.
Cardiovascular imaging environment: will the future be cloud-based?

ABSTRACT Introduction: In cardiovascular CT and MR imaging large datasets have to be stored, post-processed, analyzed and distributed. Beside basic assessment of volume and function in cardiac magnetic resonance imaging e.g., more sophisticated quantitative analysis is requested requiring specific software. Several institutions cannot afford various types of software and provide expertise to perform sophisticated analysis. Areas covered: Various cloud services exist related to data storage and analysis specifically for cardiovascular CT and MR imaging. Instead of on-site data storage, cloud providers offer flexible storage services on a pay-per-use basis. To avoid purchase and maintenance of specialized software for cardiovascular image analysis, e.g. to assess myocardial iron overload, MR 4D flow and fractional flow reserve, evaluation can be performed with cloud based software by the consumer or complete analysis is performed by the cloud provider. However, challenges to widespread implementation of cloud services include regulatory issues regarding patient privacy and data security. Expert commentary: If patient privacy and data security is guaranteed cloud imaging is a valuable option to cope with storage of large image datasets and offer sophisticated cardiovascular image analysis for institutions of all sizes.
Safety and efficacy of the Tryton Side Branch Stent™ for the treatment of coronary bifurcation lesions: an update

ABSTRACT Introduction: Percutaneous coronary interventions (PCIs) involving coronary bifurcation lesions are associated with adverse outcomes compared with non-bifurcation lesions. The Tryton Side Branch Stent has been developed to improve clinical outcomes after bifurcation PCI. Areas covered: We will discuss observational data (clinical registries and intravascular imaging studies) and randomized data from the TRYTON trial (comparing Tryton [used in combination with a main branch drug-eluting stent (DES)] with side branch balloon angioplasty [in combination with a main branch DES; also referred to the provisional strategy]). Expert commentary: The published data showed that the use of Tryton was feasible (successful stent placement in ~95%) and safe (stent thrombosis rates ~0.5% at 9–12 months; no cardiac deaths in the TRYTON trial). Its use resulted in excellent acute angiographic results. However, the TRYTON trial also showed that due to neo-intimal tissue growth, luminal dimension at 9 months were similar between Tryton and the provisional strategy. Furthermore, the trial showed an increased risk of peri-procedural myocardial infarction when Tryton was used in small side branches. Based on all data available, the provisional strategy should still be considered as the default strategy in the majority of bifurcation cases, although the use of Tryton may be considered in complex bifurcation anatomies with extensive disease in large side branches, especially when the device will be further improved by a drug-coating.
Effects of aerobic versus resistance training on glycaemic control in men with type 2 diabetes

Abstract The aim of this study was to compare the effects of aerobic training and resistance training on glycaemic control factors in men with type 2 diabetes. We performed a randomized clinical trial in which 26 men (age 57±8 years) with type 2 diabetes were randomly assigned to an aerobic training group or a resistance training group. The participants exercised three times a week for 12 weeks. Metabolic factors (haemoglobin A1C; fasting glucose and C-peptide; total, LDL, and HDL cholesterol; triglycerides), blood pressure, body composition, maximum oxygen uptake, and muscular strength were measured before and after the intervention. Both training groups experienced significant improvements in haemoglobin A1C: the aerobic training group saw a decrease in absolute values from 7.10±0.97% to 6.55±0.74% (P=0.001) and the resistance training group from 7.21±1.8% to 6.85±0.66% (P=0.024). Both training groups had significant improvements in systolic and diastolic blood pressure (P<0.05) and in several of the measured body composition variables (P<0.05). In conclusion, the aerobic and resistance training groups saw similar improvements in glycaemic control. This suggests that both aerobic training and resistance training have beneficial effects for men with type 2 diabetes.
Schistosoma mansoni Egg–Secreted Antigens Activate Hepatocellular Carcinoma–Associated Transcription Factors c‐Jun and STAT3 in Hamster and Human Hepatocytes

Clinical data have provided evidence that schistosomiasis can promote hepatocellular carcinogenesis. c‐Jun and STAT3 are critical regulators of liver cancer development and progression. The aim of the present study was to investigate the hepatocellular activation of c‐Jun and STAT3 by Schistosoma mansoni infection. Expression and function of c‐Jun and STAT3 as well as proliferation and DNA repair were analyzed by western blotting, electrophoretic mobility‐shift assay, and immunohistochemistry in liver of S. mansoni–infected hamsters, Huh7 cells, primary hepatocytes, and human liver biopsies. Hepatocellular activation of c‐Jun was demonstrated by nuclear translocation of c‐Jun, enhanced phosphorylation (Ser73), and AP‐1/DNA‐binding in response to S. mansoni infection. Nuclear c‐Jun staining pattern around lodged eggs without ambient immune reaction, and directionally from granuloma to the central veins, suggested that substances released from schistosome eggs were responsible for the observed effects. In addition, hepatocytes with c‐Jun activation show cell activation and DNA double‐strand breaks. These findings from the hamster model were confirmed by analyses of human biopsies from patients with schistosomiasis. Cell culture experiments finally demonstrated that activation of c‐Jun and STAT3 as well as DNA repair were induced by an extract from schistosome eggs (soluble egg antigens) and culture supernatants of live schistosome egg (egg‐conditioned medium), and in particular by IPSE/alpha‐1, the major component secreted by live schistosome eggs. The permanent activation of hepatocellular carcinoma–associated proto‐oncogenes such as c‐Jun and associated transcription factors including STAT3 by substances released from tissue‐trapped schistosome eggs may be important factors contributing to the development of liver cancer in S. mansoni–infected patients. Therefore, identification and therapeutic targeting of the underlying pathways is a useful strategy to prevent schistosomiasis‐associated carcinogenesis.
In situ quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Abstract Although titanium dioxide nanoparticles (TiO2 NPs) have been extensively studied, their possible impact on health due to their specific properties supported by their size and geometry, remains to be fully characterized to support risk assessment. To further document NPs biological effects, we investigated the impact of TiO2 NPs morphology on biological outcomes. To this end, TiO2 NPs were synthesized as nanoneedles (NNs), titanate scrolled nanosheets (TNs), gel-sol-based isotropic nanoparticles (INPs) and tested for perturbation of cellular homeostasis (cellular ion content, cell proliferation, stress pathways) in three cell types and compared to the P25. We showed that TiO2 NPs were internalized at various degrees and their toxicity depended on both titanium content and NPs shape, which impacted on intracellular calcium homeostasis thereby leading to endoplasmic reticulum stress. Finally, we showed that a minimal intracellular content of TiO2 NPs was mandatory to induce toxicity enlightening once more the crucial notion of internalized dose threshold beside the well-recognized dose of exposure.
What can nanosafety learn from drug development? The feasibility of “safety by design”

Abstract “Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing and assessment practices in DDD. From this comparison, it is clear that “safety” is not obtained through DDD, and that SbD should be considered a starting point rather than an end, meaning that products will still need to progress through thorough safety evaluations and regulation. We conclude that although risk reduction is clearly desirable, the way SbD is currently communicated tends to treat safety as an inherent material property and that this is fundamentally problematic as it represents a recasting and reduction of societal issues into technical problems. SbD therefore faces a multitude of challenges, from practical implementation to unrealistic stakeholder expectations.
Coping behaviors used by Army wives during deployment separation and their perceived effectiveness

Purpose: The purpose of this descriptive correlational study was to describe the coping behaviors used by Army wives during deployment separation, the perceived effectiveness of the coping behaviors used, and the correlation between the two variables. Data sources: A secondary analysis was conducted to examine coping use and perceived effectiveness, measured by the Jalowiec Coping Scale (JCS), in a sample of 102 Army wives surveyed during deployment separation. Conclusions: The most used coping subscales from the JCS were the optimistic and supportant and the most effective were the supportant and confrontive. The strongest correlations between coping use and effectiveness were found in the supportant subscale, which measures use of support systems (r= 0.77, p < .00), and the confrontive subscale, which includes behaviors of constructive problem solving (r= 0.62, p < .00). The use and effectiveness of individual behaviors are also identified. Implications for practice: Identifying effective and ineffective coping behaviors of spouses of deployed troops can potentially reduce stress and improve well‐being. Primary care providers should encourage military spouses to engage in optimistic thinking, seek out spiritual support, talk to others in a similar situation, and participate in physical activity. Disclosure The views expressed are those of the authors and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of the Defense, or the United States government.
Bile Infarcts: New Insights Into the Pathogenesis of Obstructive Cholestasis

Bile infarcts were first accurately described in 1876 by Charcot and Gombault in studies in animals after bile duct ligation. Since that time, the cause of these infarcts known as "Charcot-Gombault necrosis" has been widely debated. Modern hypotheses first suggested that the accumulation of bile acids in hepatocytes is directly responsible for hepatocyte death due to their cytotoxic detergent properties. Subsequent studies suggested that bile acids cause hepatocyte apoptosis. Currently it is believed that bile acids injure hepatocytes not by their detergent properties but by triggering a cytokine-mediated inflammatory response. Although considerable evidence now supports this latter hypothesis (1-3), the sequence of events that lead to bile infarcts and hepatocyte necrosis after BDL remains to be elucidated. This article is protected by copyright. All rights reserved.
Self-directed interventions to promote weight loss: a systematic review and meta-analysis

ABSTRACT Many self-directed weight-loss interventions have been developed using a variety of delivery formats (e.g., internet and smartphone) and change techniques. Yet, little research has examined whether self-directed interventions can exclusively promote weight loss. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were systematically reviewed for randomised controlled trials evaluating self-directed interventions in relation to weight-loss outcomes in adults. Standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random effects model. Twenty-seven trials incorporating 36 comparisons met our inclusion criteria. Participants using self-directed interventions lost significantly more weight (MD = −1.56 kg, CI −2.25, −0.86 ranging from 0.6 to 5.3 kg) compared to those in the minimal intervention or no-treatment groups (3.1-month follow-up median). The majority of interventions were internet based (18 evaluations) and these were effective at 3 months (MD = −1.74 kg, CI −2.65, −0.82 ranging from 0.6 to 4.8 kg) (SMD = −0.48, 95% CI −0.72, −0.24, I2 = 82%; p < .0001; 16 evaluations) and 6 months follow-up (MD = −2.71 kg, CI −4.03, −1.39 ranging from 2.2 to 5.3 kg) (SMD = −0.59, 95% CI −0.99, −0.19, I2 = 76%; p = .004; 4 evaluations). Self-directed weight-loss interventions can generate modest weight loss for up to 6 months but may need to be supplemented by other interventions to achieve sustained and clinically meaningful weight loss.
Participant experiences and perceptions of physical activity-enhancing interventions for people with physical impairments and mobility limitations: a meta-synthesis of qualitative research evidence

ABSTRACT Disabled people face multiple personal, environmental and social barriers that interfere with leading a physically active lifestyle. Thus, there is an urgent need for behaviour change interventions to increase physical activity (PA) by specifically addressing the situations of disabled people, and barriers to participation. This original meta-synthesis of qualitative research was undertaken to explore participants’ experiences and perceptions of PA-enhancing interventions for adults with physical impairments resulting in mobility limitations. Published articles were identified through a rigorous systematic search. Based on the inclusion/exclusion criteria, 10 articles were included for review. Following a critical appraisal of the articles, methods of thematic synthesis were drawn upon to generate overarching concepts through interpretation and conceptual synthesis. Seven interrelated concepts were constructed representing both components and outcomes of the interventions. These were (i) Diversity of interventions; (ii) Importance of communication; (iii) Need for social support; (iv) Behavioural strategies; (v) Gaining knowledge; (vi) Re-framing thoughts about exercise and the self and (vii) Health and well-being. The results revealed that a combination of informational, social and behavioural interventions is perceived as crucial for PA initiation and maintenance. Furthermore, key elements of effective intervention design and implications for policies and practices to increase PA participation are proposed.
Unusual Fentanyl Patch Administration

Fentanyl is an extremely potent narcotic analgesic that is becoming more popular as a drug of abuse. Because of the unique way in which the drug is packaged and delivered, the potential for unusual methods of abuse exists. We report the first case of true fentanyl patch ingestion in the medical literature. Initially, though unusual, cases of fentanyl ingestion were thought to have been reported, but further investigation of the literature revealed that in other case reports the patches had been held in the mouth and chewed. Because no reports of swallowing the patch had been published, suicide was initially a strong consideration in this case; however, further investigation showed that the decedent and his brother enjoyed swallowing the patches for quick “highs. ” Cases such as these serve to remind medical examiners and law enforcement officials of the value of performing thorough death investigations by performing complete autopsies with toxicological testing and correlating with investigation information to form an opinion with regard to the cause and manner of death.
Prevention of Cholestatic Liver Disease and Reduced Tumorigenicity in a Murine Model of PFIC Type 3 Using Hybrid AAV‐piggyBac Gene Therapy

Recombinant adeno‐associated viral (rAAV) vectors are highly promising vehicles for liver‐targeted gene transfer, with therapeutic efficacy demonstrated in preclinical models and clinical trials. Progressive familial intrahepatic cholestasis type 3 (PFIC3), an inherited juvenile‐onset, cholestatic liver disease caused by homozygous mutation of the ABCB4 gene, may be a promising candidate for rAAV‐mediated liver‐targeted gene therapy. The Abcb4‐/‐ mice model of PFIC3, with juvenile mice developing progressive cholestatic liver injury due to impaired biliary phosphatidylcholine excretion, resulted in cirrhosis and liver malignancy. Using a conventional rAAV strategy, we observed markedly blunted rAAV transduction in adult Abcb4‐/‐ mice with established liver disease, but not in disease‐free, wild‐type adults or in homozygous juveniles prior to liver disease onset. However, delivery of predominantly nonintegrating rAAV vectors to juvenile mice results in loss of persistent transgene expression due to hepatocyte proliferation in the growing liver. Conclusion: A hybrid vector system, combining the high transduction efficiency of rAAV with piggyBac transposase‐mediated somatic integration, was developed to facilitate stable human ABCB4 expression in vivo and to correct juvenile‐onset chronic liver disease in a murine model of PFIC3. A single dose of hybrid vector at birth led to life‐long restoration of bile composition, prevention of biliary cirrhosis, and a substantial reduction in tumorigenesis. This powerful hybrid rAAV‐piggyBac transposon vector strategy has the capacity to mediate lifelong phenotype correction and reduce the tumorigenicity of progressive familial intrahepatic cholestasis type 3 and, with further refinement, the potential for human clinical translation.