Somatic Gene Therapy: Ethics and Access.

Manipulation of a patient's genome for therapeutic ends is being attempted through numerous methods, some of which have resulted in disease-modifying interventions. The much anticipated promise of somatic gene therapy is starting to pay off; however, there remain many scientific unknowns, including concerns about safety and durability. A significant ethical concern is that of access to these novel interventions, an issue that is normally framed in terms of the high costs of approved products. I describe how access issues permeate gene therapy long before there is any commercial product and how even upstream decisions-such as choices of indication to pursue, viral vector, and where to site a trial-have significant implications for access to resultant products in both the developmental and commercial stages.

Ubiquitin and Legionella: From bench to bedside.

Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires' disease, a specific type of atypical pneumonia. Despite intensive research efforts that elucidated many relevant structural, molecular and medical insights into Legionella's pathogenicity, Legionnaires' disease continues to present an ongoing public health concern. Legionella's virulence is based on its ability to simultaneously hijack multiple molecular pathways of the host cell to ensure its fast replication and dissemination. Legionella usurps the host ubiquitin system through multiple effector proteins, using the advantage of both conventional and unconventional (phosphoribosyl-linked) ubiquitination, thus providing optimal conditions for its replication. In this review, we summarize the current understanding of L. pneumophila from medical, biochemical and molecular perspectives. We describe the clinical disease presentation, its diagnostics and treatment, as well as host-pathogen interactions, with the emphasis on the ability of Legionella to target the host ubiquitin system upon infection. Furthermore, the interdisciplinary use of innovative technologies enables better insights into the pathogenesis of Legionnaires' disease and provides new opportunities for its treatment and prevention.

Structure-activity relationships and activity enhancement techniques of marine bioactive peptides (MBPs).

Marine bioactive peptides (MBPs) are a type of natural compound with a variety of bioactivities, such as anticancer, antimicrobial, antioxidant, and antihypertensive. Due to a wide range of sources, low toxicity, and high specificity, MBPs have now received extensive attention in the fields of food, medicine, and cosmetics. The structure of MBPs determines their biological activities. Therefore, it is essential to analyze the relationship between the structure and bioactivity of MBPs. Because of the advantages of mild conditions, high specificity, safety, and environmental friendliness, enzymatic hydrolysis has become the most commonly used method to produce MBPs. However, the high cost and low yield of enzymatic methods have motivated researchers to search for alternative technologies. Novel pretreatments like ultrasound, microwave, high hydrostatic pressure, and pulsed electric fields have been employed in the production of MBPs. By inducing protein unfolding and increasing enzymatic cleavage sites, these techniques have been demonstrated to accelerate protein hydrolysis and enhance the biological activity of MBPs. This article reviews recent research advances on marine-derived protein hydrolysates and peptides, discusses the relationship between their biological activity and structure, and compares the mechanisms of action of different novel technologies used to promote protein hydrolysis and enhance the biological activity of MBPs. In addition, the current challenges facing the development and application of MBPs are outlined and possible future work in tackling these challenges is also suggested in the current review. It is hoped that this review can promote further development and application of marine active substances.

Quality Assessment of Fish Oil Obtained after Enzymatic Hydrolysis of a Mixture of Rainbow Trout (Oncorhynchus mykiss) and Atlantic Salmon (Salmo salar) Rest Raw Material Pretreated by High Pressure.

Utilization of fish rest raw material for fish oil extraction has received interest with the increasing demand for sustainable food sources. Enzymatic hydrolysis is an efficient method for the extraction of value-added compounds, but its effectiveness may be enhanced by high-pressure processing (HPP). However, HPP can induce lipid oxidation, affecting the quality of the oil. This study aimed to evaluate the quality of fish oil obtained after enzymatic hydrolysis of a mixture of rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) rest raw material pretreated by HPP. Six pretreatments were tested prior to enzymatic hydrolysis; 200 MPa × 4 min, 200 MPa × 8 min, 400 MPa × 4 min, 400 MPa × 8 min, 600 MPa × 4 min, and 600 MPa × 8 min. The oil samples were analyzed for lipid oxidation parameters, free fatty acid content, fatty acid composition, and color changes over 8 weeks. The results confirmed that HPP may induce lipid oxidation and revealed significant influence of HPP parameters on lipid oxidation, with higher pressures leading to increased oxidation. Fatty acid composition varied among samples, but it was not substantially affected by HPP.

Fast and Fun: A Pilot Feasibility Study Using Dual Joystick-Operated Ride-on Toys for Upper Extremity Rehabilitation in Children with Hemiplegia.

AIM: Our study investigates the feasibility and utility of implementing a dual joystick-operated ride-on-toy navigation training (RNT) program within a 3-week intensive camp based on principles of modified constraint-induced movement therapy and bimanual training, to improve upper extremity (UE) function in children with unilateral cerebral palsy (UCP). METHODS: We employed a single-group pretest posttest, mixed methods study design. Eleven 4-to-10-year-old children with UCP received RNT as part of camp activities. Sessions required children to use both arms together for navigation and completing gross and fine motor UE challenges. We collected exit questionnaires from children, caregivers, and clinicians to assess the feasibility, acceptance, enjoyment, and perceived efficacy of RNT. Videos of training sessions were coded using Datavyu behavioral coding software to assess children's facial expressions and affective states, indicative of their level of engagement during intervention sessions. RESULTS: We found high levels of child engagement during RNT sessions based on video data and stakeholder feedback. The RNT program was smoothly integrated into the camp. Stakeholders acknowledged the highly motivating nature of RNT. When combined with other camp activities, the program led to stakeholder-reported improvements in bimanual skills and spontaneous daily use of the affected UE. CONCLUSIONS: Our pilot study provides promising evidence for using joystick-operated ride-on toys as engaging therapy adjuncts. Our findings call for future studies to systematically assess the efficacy of these devices in improving UE function among children with UCP.

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs.

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.

Recent progress in food processing applications of air impingement technology: A review.

Air impingement method has been widely used in a variety of industrial applications, such as textile and paper drying, turbine cooling, and glass quenching, because it is an efficient technology with high heat and mass transfer rates. This technology has received increasing interest in the field of food processing over the last two decades, such as drying, baking, blanching, freezing, and thawing. In a food processing equipment using air impingement, jets of high-velocity air (with speeds of 10-50 m/s) are directed at a food product. The performance of the system is influenced by several critical elements, including jet velocity, nozzle array diameter and layout, jet distance, and boundary layer characteristics. The use of computational fluid dynamics, an emerging tool, has been shown to be valuable in the analysis of fluid flow and heat and mass transfer in jet impingement systems. The physical properties of impinging jets, such as turbulent mixing in the free jet zone, stagnation, boundary layer formation, recirculation, and their interactions with food products in terms of heat and mass transfer, have been discussed in this article. The benefits and disadvantages of air jet impingement technology in different food processing applications together with potential trends for improving impingement technology performance were identified and discussed. This review not only contributes to a better understanding of the research status of impingement technology on food processing but also triggers new research opportunities in this field in order to provide more healthy and nutritious food in a more sustainable way to the world's growing population.

Direct comparison of two 50 W high power short duration approaches-Temperature- versus ablation index-guided radiofrequency ablation for atrial fibrillation.

INTRODUCTION: Approaches applying higher energy levels for shorter periods (high power short duration, HPSD) to improve lesion formation for atrial fibrillation (AF) ablation have been introduced. This single-center study aimed to compare the efficacy, safety, and lesion formation using the novel DiamondTemp (DT) catheter or an ablation index (AI)-guided HPSD ablation protocol using a force-sensing catheter with surround-flow irrigation. METHODS: One hundred thirteen consecutive patients undergoing radiofrequency-guided catheter ablation (RFCA) for AF were included. Forty-five patients treated with the DT catheter (50 W, 9 s), were compared to 68 consecutive patients undergoing AI-guided ablation (AI anterior 550; AI posterior 400) adherent to a 50 W HPSD protocol. Procedural data and AF recurrence were evaluated. RESULTS: Acute procedural success was achieved in all patients (n = 113, 100%). DT-guided AF ablation was associated with a longer mean procedure duration (99.10 ± 28.30 min vs. 78.24 ± 25.55, p < .001) and more RF applications (75.24 ± 30.76 min vs. 61.27 ± 14.06, p = .019). RF duration (792.13 ± 311.23 s vs. 1035.54 ± 287.24 s, p < .001) and fluoroscopy dose (183.81 ± 178.13 vs. 295.80 ± 247.54 yGym2 , p = .013) were lower in the DT group. AI-guided HPSD was associated with a higher AF-free survival rate without reaching statistical significance (p = .088). Especially patients with PERS AF (p = .009) as well as patients with additional atrial arrhythmia substrate (p = .002) benefited from an AI-guided ablation strategy. CONCLUSION: Temperature- and AI- controlled HPSD RFCA using 50 W was safe and effective. AI-guided HPSD ablation seems to be associated with shorter procedure durations and fewer RF applications. Particularly in advanced AF, freedom from AF-recurrence may be improved using an AI-guided HPSD approach.

Feasibility of a novel algorithm for automated reconstruction of the left atrial anatomy based on intracardiac echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) is frequently used to guide electrophysiology procedures. The novel automated algorithm Cartosoundfam is a model-based algorithm which reconstructs a 3D anatomy of the left atrium (LA) based on a set of 2D intracardiac echocardiography (ICE) frames, without the need to manually annotate ultrasound (US) contours. OBJECTIVE: The aim of this study was to determine the feasibility of the Cartosoundfam module in routine clinical setting. METHODS: We included 16 patients undergoing LA mapping/catheter ablation. Two-dimensional US frames were acquired from the right atrium (RA) and the right ventricular outflow tract. The Cartosoundfam map was validated in two steps: (1) identification of anatomical structures (pulmonary veins [PV] and LA body and appendage) by alignment of the ablation catheter to the automated map; and (2) analysis of the automated lesion tags (Visitag) location in relation to the PV antrum of the Cartosoundfam map in nine patients with paroxysmal atrial fibrillation (AF) undergoing first time pulmonary vein isolation (PVI). RESULTS: Mean 2D US frames per patient were 29 ± 6 and acquisition time was 16 ± 4 min. All anatomical structures were correctly identified in all patients (step 1). In the step 2 validation, the median distance to the map was 2.0 (IQR: 2.4) mm and the majority of the Visitags were classified as satisfactory (69%) but all PV segments had some Visitags classified as unsatisfactory. CONCLUSION: The automated ICE-based algorithm correctly identified the LA anatomical structures in all patients with a 69% anatomical accuracy of the Visitags alignments to the PV antrum segments.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Current view on novel vaccine technologies to combat human infectious diseases.

Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these vaccines have faults, such as reactivity or suboptimal efficacy and expensive and time-consuming development and production. Additionally, despite the enormous efforts to develop vaccines against some infectious diseases, the traditional technologies have not been successful in achieving this. At the same time, the concerns about emerging and re-emerging diseases urge the need to develop technologies that can be rapidly applied to combat the new challenges. Within the last two decades, the research of vaccine technologies has taken several directions to achieve safe, efficient, and economic platforms or technologies for novel vaccines. This review will give a brief overview of the current state of the novel vaccine technologies, new vaccine candidates in clinical trial phases 1-3 (listed by European Medicines Agency (EMA) and Food and Drug Administration (FDA)), and vaccines based on the novel technologies which have already been commercially available (approved by EMA and FDA) with the special reference to pandemic COVID-19 vaccines. KEY POINTS: • Vaccines of the new generation follow the minimalist strategy. • Some infectious diseases remain a challenge for the vaccine development. • The number of new vaccine candidates in the late phase clinical trials remains low.

Long non-coding RNAs as possible therapeutic targets in protozoa, and in Schistosoma and other helminths.

Long non-coding RNAs (lncRNAs) emerged in the past 20 years due to massive amounts of scientific data regarding transcriptomic analyses. They have been implicated in a plethora of cellular processes in higher eukaryotes. However, little is known about lncRNA possible involvement in parasitic diseases, with most studies only detecting their presence in parasites of human medical importance. Here, we review the progress on lncRNA studies and their functions in protozoans and helminths. In addition, we show an example of knockdown of one lncRNA in Schistosoma mansoni, SmLINC156349, which led to in vitro parasite adhesion, motility, and pairing impairment, with a 20% decrease in parasite viability and 33% reduction in female oviposition. Other observed phenotypes were a decrease in the proliferation rate of both male and female worms and their gonads, and reduced female lipid and vitelline droplets that are markers for well-developed vitellaria. Impairment of female worms' vitellaria in SmLINC156349-silenced worms led to egg development deficiency. All those results demonstrate the great potential of the tools and methods to characterize lncRNAs as potential new therapeutic targets. Further, we discuss the challenges and limitations of current methods for studying lncRNAs in parasites and possible solutions to overcome them, and we highlight the future directions of this exciting field.

Use of a novel 4D intracardiac echocardiography catheter to guide interventional electrophysiology procedures.

INTRODUCTION: Standard two-dimensional (2D), phased-array intracardiac echocardiography (ICE) is routinely used to guide interventional electrophysiology (EP) procedures. A novel four-dimensional (4D) ICE catheter (VeriSight Pro, Philips) can obtain 2D and three-dimensional (3D) volumetric images and cine-videos in real-time (4D). The purpose of this study was to determine the early feasibility and safety of this 4D ICE catheter during EP procedures. METHODS: The 4D ICE catheter was placed from the femoral vein in ten patients into various cardiac chambers to guide EP procedures requiring transseptal catheterization, including ablation for atrial fibrillation and left atrial appendage closure. 2D- and 3D-ICE images were acquired in real-time by the electrophysiologist. A dedicated imaging expert performed digital steering to optimize and postprocess 4D images. RESULTS: Eight patients underwent pulmonary vein isolation (cryoballoon in seven patients, pulsed field ablation in one, additional radiofrequency left atrial ablation in one). Two patients underwent left atrial appendage closure. High quality images of cardiac structures, transseptal catheterization equipment, guide sheaths, ablation tools, and closure devices were acquired with the ICE catheter tip positioned in the right atrium, left atrium, pulmonary vein, coronary sinus, right ventricle, and pulmonary artery. There were no complications. CONCLUSION: This is the first experience of a novel deflectable 4D ICE catheter used to guide EP procedures. 4D ICE imaging is safe and allows for acquisition of high-quality 2D and 3D images in real-time. Further use of 4D ICE will be needed to determine its added value for each EP procedure type.

Strategies and novel technologies to control Campylobacter in the poultry chain: A review.

Campylobacteriosis is one of the most common bacterial infections worldwide causing economic costs. The high prevalence of Campylobacter spp. in poultry meat is a result of several contamination and cross-contamination sources through the production chain. Moreover, survival mechanisms, such as biofilm formation, viable but nonculturable state, and antimicrobial resistance, enable its persistence during food processing. Therefore, mitigation strategies are necessary in order to avoid and/or inactivate Campylobacter at farm, abattoir, industry, and retail level. In this review, a number of potential strategies and novel technologies that could reduce the prevalence of Campylobacter in poultry meat have been identified and evaluated to provide a useful overview. At farm level for instance, biosecurity, bacteriocins, probiotics, feed and water additives, bacteriophages, and vaccination could potentially reduce colonization in chicken flocks. However, current technologies used in the chicken slaughter and processing industry may be less effective against this foodborne pathogen. Novel technologies and strategies such as cold plasma, ultraviolet light, high-intensity light pulses, pulsed electric fields, antimicrobials, and modified atmosphere packaging are discussed in this review for reducing Campylobacter contamination. Although these measures have achieved promising results, most have not been integrated within processing operations due to a lack of knowledge or an unwillingness to implement these into existing processing systems. Furthermore, a combination of existing and novel strategies might be required to decrease the prevalence of this pathogen in poultry meat and enhance food safety. Therefore, further research will be essential to assess the effectiveness of all these strategies.

Effects of thermal and non-thermal processing of cruciferous vegetables on glucosinolates and its derived forms.

Brassica vegetables, which include broccoli, kale, cauliflower, and Brussel sprouts, are known for their high glucosinolate content. Glucosinolates and their derived forms namely isothiocyanates are of special interest in the pharmaceutical and food industries due to their antimicrobial, neuroprotective, and anticarcinogenic properties. These compounds are water soluble and heat-sensitive and have been proved to be heavily lost during thermal processing. In addition, previous studies suggested that novel non-thermal technologies such as high pressure processing, pulsed electric fields, or ultraviolet irradiation can affect the glucosinolate content of cruciferous vegetables. The objective of this paper was to review current knowledge about the effects of both thermal and non-thermal processing technologies on the content of glucosinolates and their derived forms in brassica vegetables. This paper also highlights the importance of the incorporation of brassica vegetables into our diet for their health-promoting properties beyond their anticarcinogenic activities.

Focal Impulse and Rotor Modulation for the Treatment of Atrial Fibrillation: Locations and 1 Year Outcomes of Human Rotors Identified Using a 64-Electrode Basket Catheter.

INTRODUCTION: Pulmonary vein isolation (PVI) is currently the gold standard for catheter ablation of atrial fibrillation (AF). The mechanism for AF-maintenance is still controversial. The concept of rapidly activating spiral rotors perpetuating AF has led to the development of several rotor-mapping systems. We present our experience with focal impulse and rotor modulation (FIRM) using a 64-electrode basket catheter and computational system and evaluate its feasibility in conjunction with PVI to treat AF. METHODS AND RESULTS: Twenty-five patients underwent FIRM mapping and ablation to treat AF (paroxysmal = 10, 40%). A basket catheter was used for rotor identification within the right atrium (RA) then left atrium (LA). Radiofrequency energy was applied at and around each rotor core for 300 seconds and rotor-mapping and ablation was repeated until all rotors were eliminated before circumferential PVI was performed. Three (1.0, 4.0) rotors were identified per patient, predominantly in the LA (LA = 59). Note that 7/59 left-sided rotors were located 8/59 at the PV antrum. Twelve (48%) patients had either AF termination (termination = 6/12) or conversion to another rhythm, or cycle length (CL) prolongation ≥10% after rotor ablation. After a single procedure, 13 (52%) patients were free of atrial tachyarrhythmia after a follow-up period of 13 ± 1 months. CONCLUSION: Early results suggest that FIRM-ablation can terminate AF in a significant number of patients. Rotors were frequently identified in the PVs and PV antrum, supporting PVI as the cornerstone of AF ablation.

Novel technologies combined with traditional metabolic engineering strategies facilitate the construction of shikimate-producing Escherichia coli.

Shikimate is an important intermediate in the aromatic amino acid pathway, which can be used as a promising building block for the synthesis of biological compounds, such as neuraminidase inhibitor Oseltamivir (Tamiflu®). Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability, and product selectivity and diversity, thus receiving more and more attentions. The development of metabolic engineering allows for high-efficiency production of shikimate of Escherichia coli by improving the intracellular level of precursors, blocking downstream pathway, releasing negative regulation factors, and overexpressing rate-limiting enzymes. In addition, novel technologies derived from systems and synthetic biology have opened a new avenue towards construction of shikimate-producing strains. This review summarized successful and applicable strategies derived from traditional metabolic engineering and novel technologies for increasing accumulation of shikimate in E. coli.

Novel technologies provide more engineering strategies for amino acid-producing microorganisms.

Traditionally, amino acid-producing strains were obtained by random mutagenesis and subsequent selection. With the development of genetic and metabolic engineering techniques, various microorganisms with high amino acid production yields are now constructed by rational design of targeted biosynthetic pathways. Recently, novel technologies derived from systems and synthetic biology have emerged and open a new promising avenue towards the engineering of amino acid production microorganisms. In this review, these approaches, including rational engineering of rate-limiting enzymes, real-time sensing of end-products, pathway optimization on the chromosome, transcription factor-mediated strain improvement, and metabolic modeling and flux analysis, were summarized with regard to their application in microbial amino acid production.

Novel Technologies in Urologic Surgery: a Rapidly Changing Scenario.

The introduction of laparoscopy and robotic surgery revolutionized the surgical management of urologic patients. Nonetheless, we live in an era of rapid changes, and we are probably still in the infancy of technology applied to surgery. When considering currently available technologies, there are several unmet needs to be addressed. These include the application of augmented reality, haptic feedback, tissue recognition, distant remote control, miniaturization of surgical instruments, the learning curve typical of the introduction of novel techniques, and excessive costs. In the next few years, evolution in imaging modalities in pre- and intraoperative surgical planning, as well as the introduction of novel minimally invasive platforms, would in part address these issues, substantially improving surgical outcomes. In addition, validated training programs would allow for the safe implementation of novel techniques in the clinical practice. Finally, a reduction in costs would be necessary to make technology affordable and to optimize healthcare resources.

Novel trends in engineered milk products.

Food engineering within the dairy sector is an ever developing field of study purely based on the application of engineering principles and concepts to any aspect of dairy product manufacturing and operations. The last 25 years of science and technology devoted to milk and milk products have led to major advances. The purpose of this paper is to review the history and current status of some engineered milk products and to speculate regarding future trends. Much of the advancement has been directed towards production capacity, mechanisation, automation, hygiene within the processing plant, safety, extensions in shelf life, and new product introductions that bring variety and convenience for the consumer. Significant advancements in product quality have been made, many of these arising from improved knowledge of the functional properties of ingredients and their impact on structure and texture. In addition, further improvements focused on energy efficiency and environmental sustainability have been made and will be needed in the future.