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The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group. Key words antioxidant; aged; cognition; oxidative stress; Pycnogenol, Introduction In both clinical neurodegenerative diseases and normal ageing, the brain is an organ that is particularly susceptible to oxidative injury from free radicals and reactive oxygen species (ROS). These [...]

Cleaning of conveyor belts in the food industry is imperative for preventing the buildup of microorganisms that can contaminate food. New technologies for decreasing water and energy consumption of cleaning systems are desired. Ultrasound can be used for cleaning a wide range of materials. Most commonly, baths containing fairly large amounts of water are used. One possibility to reduce water consumption is to use ultrasonic cavitation in a thin water film on a flat surface, like a conveyor belt. In order to test this possibility, a model system was set up, consisting of an ultrasound transducer/probe with a 70-mm-diameter flat bottom, operating at 19.8 kHz, and contaminated conveyor belt materials in the form of coupons covered with a thin layer of water or water with detergent. Ultrasound was then applied on the water surface at different power levels (from 46 to 260 W), exposure times (10 and 20 s), and distances (2 to 20 mm). The model was used to test two different belt materials with various contamination types, such as biofilms formed by bacteria in carbohydrate- or protein-fat-based soils, dried microorganisms (bacteria, yeasts, and mold spores), and allergens. Ultrasound treatment increased the reduction of bacteria and yeast by 1 to 2 log CFU under the most favorable conditions compared with water or water-detergent controls. The effect was dependent on the type of belt material, the power applied, the exposure time, and the distance between the probe and the belt coupon. Generally, dried microorganisms were more easily removed than biofilms. The effect on mold spores was variable and appeared to be species and material dependent. Spiked allergens were also efficiently removed by using ultrasound. The results in this study pave the way for new cleaning designs for flat conveyor belts, with possibilities for savings of water, detergent, and energy consumption. [ABSTRACT FROM AUTHOR]

Penicillium commune and Penicillium palitans isolates previously isolated from cheese samples and the indoor environment in four cheese factories were investigated using Polymerase Chain Reaction (PCR) fingerprinting with the core sequence of the phage M13 as primer. In total, 55 isolates of P. commune and 49 isolates of P. palitans were investigated. Four and seven different M13 fingerprinting profiles were found among the P. commune andP. palitans isolates, respectively. Three fingerprinting profiles dominated for each species, comprising 98% and 86% of the P. commune and P. palitans isolates, respectively. Each of the dominating profiles was found in at least three factories and was thus not factory-specific. For each species, one of the fingerprinting profiles was found only once. In addition, one profile of P. palitans was found twice and in one factory only. The M13 fingerprinting grouped theP. commune and P. palitans isolates and gave useful information with respect to identifying whether isolates of the same species could originate from the same contaminating strain. [Copyright &y& Elsevier]

Despite improvements in circulatory support options, heart transplantation remains the gold-standard treatment for appropriate patients with advanced heart failure. Expansion of the heart pool has occurred with the use of donation after circulatory death and extended marginal criteria such as prolonged ischemic time. Longer ischemic time is associated with adverse impact on allograft function and on early renal function. Recent studies suggest that HMP may favorably influence early graft function despite prolonged ischemic time but renal outcomes are not known. The purpose of this study was to compare early renal outcomes in HMP vs conventional heart transplant (C-HTx) recipients. Renal function and need for dialysis were compared at 24, 48 and 72 hours in participants (n=32) of the Australia and New Zealand Trial of HMP (XVIVO, Sweden) compared to a cohort of conventional single center HTx patients (n=62). Despite the prolonged ischemic time (377±15 vs 185±15 mins, p<0.001) in HMP patients the use of renal replacement therapy (RRT) at 72 hours tended to be less than C-HTx (22% vs 37%). The post-operative increase in creatinine in non-RRT was attenuated in HMP vs C-HTx patients at 24 hrs (26±10 vs 49±7 umol/L, p=0.06), 48 hrs (23±12 vs 69±12 umol/L, p=0.008) and 72 hrs (14±13 vs 60±13 umol/L, p=0.03). Despite the use of donor hearts with prolonged ischemic times, renal outcomes in recipients of cardiac allografts preserved using HMP were comparable or better than those in patients with shorter ischemic times. [ABSTRACT FROM AUTHOR]

Introduction: Rib fixation for ventilator dependent flail chest patients has become a mainstay of management in major trauma centres. However, the expansion of rib fixation for fractured ribs beyond this remains largely in the hands of enthusiasts with the benefits in non ventilator dependent groups largely unproven. Previous meta-analyses have largely included non-randomised and retrospective data, much of which is now more than two decades out of date. We wanted to perform an updated meta-analysis including only rigorous prospective trials which were randomised. Further we wanted to include quality of life outcomes which have not been previously examined in published meta-analyses., Methods: This meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomised controlled trials only, of rib fixation compared to non-operative management in adult patients., Results: Eight studies comprising 752 patients of whom 372 had been randomised to receive rib fixation were included. Benefits of rib fixation were identified with significant reductions in mechanical ventilation and lengths of stay (both ICU and hospital) as well as rates of pneumonia and tracheostomy. No significant benefit in quality of life at 6 months was identified., Conclusion: Operative intervention for rib fractures leads to significantly lower rates of pneumonia, lengths of intensive care stay and time on mechanical ventilation compared to non-operative intervention. Further study is needed to investigate quality of life improvements after rib fractures as operative rib fixation expands to non-ventilator dependent groups., Competing Interests: Declaration of competing interest SM has received honorariums for lectures given by Johnson and Johnson and Zimmer Biomet. VS, RS, YW and CK declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths in the world. More than half of patients with HCC present with advanced stage, and highly active systemic therapies are crucial for improving outcomes. Immune checkpoint inhibitor (ICI)-based therapies have emerged as novel therapy options for advanced HCC. Only one third of patients achieve an objective response with ICI-based therapies due to primary resistance or acquired resistance. The liver tumor microenvironment is naturally immunosuppressive, and specific mutations in cell signaling pathways allow the tumor to evade the immune response. Next, gene sequencing of the tumor tissue or circulating tumor DNA may delineate resistance mechanisms to ICI-based therapy and provide a rationale for novel combination therapies. In this review, we discuss the results of key clinical trials that have led to approval of ICI-based therapy options in advanced HCC and summarize the ongoing clinical trials. We review resistance mechanisms to ICIs and discuss how immunotherapies may be optimized based on the emerging research of tumor biomarkers and genomic alterations.

Purpose: Bilateral lung transplantation for end-stage pulmonary arterial hypertension (PAH) is traditionally associated with higher early post-transplant mortality when compared with other indications. Changes in perioperative management, including the growing use of perioperative extracorporeal membrane oxygenation (ECMO) and an increased awareness of postoperative left ventricular dysfunction (LVD), have resulted in outcomes that are uncertain., Materials and Methods: We conducted a single-center, retrospective observational study at a lung transplantation center in Melbourne, Australia, from 2006 to 2019. ECMO use was categorized as preoperative, prophylactic, or rescue. Postoperative LVD was defined as a reduction in left ventricular function on echocardiography or using strict clinical criteria., Results: 50 patients underwent lung transplantation for PAH. 12-month survival was 48/50 (96%). ECMO was used in 26 (52%) patients, and the use of prophylactic VA-ECMO increased over the study period. Postoperative LVD was diagnosed in 21 (42%) patients. 12-month survival and left ventricular function was no different between LVD and non-LVD groups., Conclusions: This study showed that high survival rates can be achieved following lung transplantation for PAH. We found that ECMO utilization was common, and indications have changed over time. LVD was common but did not impact 12-month survival., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: BiVACOR is a novel total artificial heart (TAH) utilizing a single centrifugal magnetically levitated rotor with the ability to modulate pulsatile flow. The device has been successfully tested in a bovine model. We undertook a multicenter anatomical and virtual fitting study of the BiVACOR in patients undergoing heart transplantation., Methods: 10 patients were recruited across two heart transplant centers. A sterilized 1:1 titanium model of the device was inserted into the patient's chest post heart explant, prior to implantation of the donor heart. Measurements were recorded in situ. The device was then removed. Following this, retrospective 3D reconstructions were created from computed tomography chest scans to simulate a virtual fitting., Results: Mean age was 53 years (range 38-67). Mean BMI was 28 (range 20-37). Heart failure etiology was varied-with ischemic cardiomyopathy being the most common. Mean spine-to-sternum distance at the tenth thoracic vertebrae (T10) was 14 cm (range 11-18). Mean aorta to aortic Port distance was 0.2 cm (range 0-0.5). Mean pulmonary artery to pulmonary artery port distance was 4.2 cm (range 1-7). The device fitted suitably in all patients without gross distortion to the geometry between native vessel/chamber and port., Conclusions: This study described the anatomical and virtual fitting of the BiVACOR TAH. The device fit well within the chest cavities of all 10 patients, who represented a variety of body morphologies and heart failure etiology., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Aims: The aim of the study was to apply Fourier Transform Infrared spectroscopy (FTIR) as a rapid screening method for moulds in a specific food production environment (cured meat) and to evaluate whether the method was sufficiently accurate to distinguish Penicillium species that constitute a hazard for the food quality and safety (Penicillium solitum and Penicillium nordicum) from closely related species., Methods and Results: FTIR was applied to classify the indigenous mycobiota of two production sites for dried and cured meat products in Norway. Results showed that FTIR was suitable to analyse large amounts of data. While correct classification rates varied depending on the species, overall results indicated that FTIR was able to distinguish the undesired mould species P. solitum and P. nordicum from other species and may hence present an option for rapid screening of large numbers of samples to identify changes in mould composition on site., Conclusions: FTIR presents a potential method for detecting changes in levels of undesired fungi in meat-processing environments., Significance and Impact of the Study: This is the first study that applies FTIR to a specific food production environment and it increases the knowledge on both possibilities and limitations of the method in classification of fungi., (© 2021 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Background: Right ventricular (RV) failure after left ventricular assist device (VAD) implantation is a difficult problem. One solution is the implantation of continuous-flow VADs in a biventricular configuration. Disappointing survival and a concerning incidence of right-sided pump thrombosis have been previously reported., Methods: From May 2017 to April 2020, a total of 12 patients underwent implantation of HeartMate 3 (HM3) biventricular VADs (BiVADs) as a bridge to cardiac transplantation. The right-sided pump was implanted in the right atrium in all cases. Adverse events and patient outcomes were determined., Results: Patients were male, and the mean age was 44 years. The etiology was dilated cardiomyopathy (6 patients), sarcoid heart disease (2 patients), ischemic cardiomyopathy (1 patient), anthracycline cardiomyopathy (1 patient), non-compaction cardiomyopathy (1 patient), and arrhythmogenic RV cardiomyopathy with biventricular involvement (1 patient). There was 1 death from multisystem failure. There were 3 episodes of right VAD thrombus (thrombosis or clot ingestion); 1 managed medically, 1 recognized intraoperatively treated with clot retrieval, and 1 requiring pump exchange. There were 3 driveline infections. At 18 months after the procedure, 5 patients (41.7%) had undergone cardiac transplantation, 5 patients (41.7%) were alive and on biventricular support, 1 patient had died (8.3%), and 1 patient had VAD explantation for myocardial recovery (8.3%). Actuarial survival at 18 months was 91.7%., Conclusions: In this small study, HM3 BiVAD in these critically ill patients was used with low mortality. This suggests that the timely deployment of biventricular support with HM3 can be associated with favorable outcomes., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: In adult ventricular assist device (VAD) programs in Australian hospitals, Medihoney Antibacterial Wound Gel (MAWG) is routinely used at the skin exit-site of VAD drivelines to prevent infections; however, its effectiveness remains unclear. Our aim was to assess antimicrobial activity of Medihoney wound gel, using in vitro models that mimic clinical biofilms grown at the driveline exit-site. Methods: Antimicrobial susceptibility testing of MAWG was performed for 24 clinical isolates grown under planktonic conditions, and four representative strains grown as biofilms. Different antimicrobial mechanisms of MAWG were assessed respectively for their relative contribution to its anti-biofilm activity. A colony biofilm assay and a drip-flow biofilm reactor assay mimicking the driveline exit-site environment were used to evaluate the activity of MAWG against biofilm growth at the driveline exit-site. Results: MAWG demonstrated species-specific activity against planktonic cultures [minimum inhibitory concentrations (MICs), 5-20% weight/volume (W/V) for Staphylococcus species, 20->40% (W/V) for Pseudomonas aeruginosa and Candida species]. Higher concentrations [MICs, 30->80% (W/V)] were able to inhibit biofilm growth, but failed to eradicate pre-established biofilms. The anti-biofilm properties of MAWG were multi-faceted, with the often-advertised "active" ingredient methylglyoxal (MGO) playing a less important role. The colony biofilm assay and the drip-flow biofilm reactor assay suggested that MAWG was unable to kill biofilms pre-established in a driveline exit-site environment, or effectively prevent planktonic cells from forming adherent monolayers and further developing mature biofilms. Conclusion: Our work suggests a suboptimal effectiveness of MAWG in preventing driveline infections due to biofilm development., (Copyright © 2020 Qu, McGiffin, Kure, McLean, Duncan and Peleg.)

Background: Driveline infections remain a major complication of ventricular assist device (VAD) implantation. This study aimed to characterize in vivo microbial biofilms associated with driveline infections and host tissue integration of implanted drivelines., Methods: A total of 9 infected and 13 uninfected drivelines were obtained from patients with VAD undergoing heart transplantation in Australia between 2016 and 2018. Each driveline was sectioned into 11 pieces of 1.5 cm in length, and each section was examined by scanning electron microscopy (SEM) and viable counts for microbial biofilms. Microorganisms were cultured and identified. Host tissue integration of clinical drivelines was assessed with micro-computed tomography (CT) and SEM. An in vitro interstitial biofilm assay was used to simulate biofilm migration in the driveline tunnel, and time-lapse microscopy was performed., Results: Of the 9 explanted, infected drivelines, all had organisms isolated from varying depths along the velour section of the drivelines, and all were consistent with the swab culture results of the clinically infected exit site. SEM and micro-CT suggested insufficient tissue integration throughout the driveline velour, with microgaps observed. Clinical biofilms presented as microcolonies within the driveline tunnel, with human tissue as the sub-stratum, and were resistant to anti-microbial treatment. Biofilm migration mediated by a dispersal-seeding mechanism was observed., Conclusions: This study of explanted infected drivelines showed extensive anti-microbial-resistant biofilms along the velour, associated with microgaps between the driveline and the surrounding tissue. These data support the enhancement of tissue integration into the velour as a potential preventive strategy against driveline infections by preventing biofilm migration that may use microgaps as mediators., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: Driveline infections remain an important complication of ventricular assist device therapy, with biofilm formation being a major contributor. This study aimed to elucidate factors that govern biofilm formation and migration on clinically relevant ventricular assist device drivelines., Methods: Experimental analyses were performed on HeartWare HVAD (HeartWare International Inc, Framingham, Mass) drivelines to assess surface chemistry and biofilm formation. To mimic the driveline exit site, a drip-flow biofilm reactor assay was used. To mimic a subcutaneous tissue environment, a tunnel-based interstitial biofilm assay was developed. Clinical HVAD drivelines explanted at the time of cardiac transplantation were also examined by scanning electron microscopy., Results: Common causative pathogens of driveline infections were able to adhere to the smooth and velour sections of the HVAD driveline and formed robust biofilms in the drip-flow biofilm reactor; however, Pseudomonas aeruginosa and Candida albicans had greater biomass. Biofilm migration within the interstitial driveline tunnel was evident for Staphylococcus epidermidis, Staphylococcus aureus, and C albicans, but not P aeruginosa. Biofilm formation by staphylococci was 500 to 10,000 times higher in the tunnel-based model compared with our exit site model. The 3-dimensional structure of the driveline velour and the use of silicone adhesive in driveline manufacturing were found to promote biofilm growth, and explanted patient drivelines demonstrated inadequate tissue in-growth along the entire velour with micro-gaps between velour fibers., Conclusions: This work highlights the predilection of pathogens to different parts of the driveline, the importance of the subcutaneous tunnel to biofilm formation and migration, and the presence of micro-gaps in clinical drivelines that could facilitate invasive driveline infections., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The HeartMate III (HM3) left ventricular assist device (LVAD) is the most recent LVAD to receive CE Mark and the Food and Drug Administration approval. It is a fully magnetically levitated pump with no reported haemolysis, pump thrombosis or pump failure in the first in-man study (a previous stody). It has now received market approval in the European Union, United States of America, and Australia. We reviewed our real-life experience with the device, to assess outcomes over the medium term., Methods: We conducted a retrospective review of prospectively collected data for 33 consecutive patients implanted with a HM3 LVAD between November 2014 and October 2018 at The Alfred Hospital, Melbourne, Australia., Results: Of the 33 patients, 31 remained alive at the census date, with only two early deaths and 11 patients transplanted. There were no pump thromboses, but there were three cases of clot ingestion (two on the right and one on the left). Seven patients required permanent biventricular assist device support. The duration of HM3 support at the time of census was a median of 196 (interquartile range, 118-386) days., Conclusion: This series demonstrates excellent results of the HM3 LVAD in an uncensored, real-life, consecutive group of patients in a single institution., (© 2019 Wiley Periodicals, Inc.)

Brain aging is a complex and multifactorial process broadly involving changes in the brain's structure, neuronal activity, and biochemical profile. These changes in brain function have also been linked to age-associated variations in cognitive function. Recent research has suggested a role of increased oxidative stress and reduced cognition in older people. Therefore, studies that examine the effects of antioxidants on cognitive performance are important, particularly in the context of an increase in elderly populations in most Western countries. One such antioxidant, Pycnogenol, is a standardized plant-based extract obtained from the bark of the French maritime pine and has a long historical use to treat inflammation and improve health. More recently, Pycnogenol has been subjected to more than 100 research trials. In vitro and animal studies using the standardized extract have indicated a multimodal action of Pycnogenol, and several human studies have shown improvements in cognitive function after chronic administration. In this paper, we review these studies in the context of understanding both biological and cognitive changes due to Pycnogenol and evaluate possibilities of Pycnogenol to improve neurocognitive function.

Background: The aim of this study was to define the status of preoperative zinc levels in patients with heart disease presenting for cardiac surgery and to identify any predictors for and any clinical consequences of low zinc levels., Methods: Adult patients presenting for elective surgery, either coronary artery bypass graft surgery and/or valve replacement, provided a fasting blood sample on the day of admission for surgery. Plasma and erythrocyte zinc levels were analysed and the levels correlated with the patient's characteristics and clinical outcomes., Results: Of 56 patients 53% (n=30) had abnormally low plasma zinc levels (<12μmol/L) and 5.5% (n=3) had abnormally low erythrocyte zinc levels (<160μmol/L), indicative of deficiency. There were significant associations between lower plasma zinc levels and the presence of hypertension (p=0.02), hypercholesteraemia (p=0.02) and higher body mass index (BMI) (p=0.034) but no effect on major postoperative clinical outcomes., Conclusions: This small study shows that zinc deficiency is common in cardiac surgery patients, especially in the presence of hypertension, hypercholesterolaemia or obesity. The effects of zinc deficiency in cardiac surgery need to be further investigated., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Advances in healthcare have considerably improved the life expectancy of the human population over the last century and this has brought about new challenges. As we live longer the capacity for cognitive aging increases. Consequently, it has been noted that decline in cognitive performance in the elderly in domains of reasoning, problem solving skills, attention, processing speed, working memory and episodic memory is a significant societal problem. Despite the enormity of this issue there are relatively few interventions for cognitive aging. This may be due to our current state of knowledge on biological factors that underpin cognitive aging. One of the biological contributors to cognitive aging is chronic neuroinflammation. This review will provide an overview of the peripheral and central mechanisms involved in chronic neuroinflammation and how neuroinflammation may be related to age-associated cognitive decline. Plant based extracts including herbal and nutritional supplements with anti-inflammatory properties will be examined in relation to their utility in treating age-related cognitive decline. Plant based extracts in particular offer interesting pharmacological properties that may be quickly utilized to prevent cognitive aging.

Reactive oxygen species (ROS) play an important role in the regulation of normal cellular function. When ROS are produced in excess they can have detrimental effects, a state known as oxidative stress. Thus ROS play both physiological and pathophysiological roles in the body. In clinical practice oxidative stress and its counterpart, antioxidant capacity can be measured and can guide remedial therapy. Oxidative stress can have a negative impact in all forms of major surgery including cardiac surgery, general surgery, trauma surgery, orthopedic surgery and plastic surgery; this is particularly marked in an ageing population. Many different therapies to reduce oxidative stress in surgery have been tried with variable results. We conclude that in surgical patients the assessment of oxidative stress, improvement of the understanding of its role, both positive and negative, and devising appropriate therapies represent fruitful fields for future research., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The omega-3 fatty acid docosahexaenoic acid (DHA) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging. A triple-blind placebo-controlled randomized repeated-measures trial was conducted with 74 healthy participants, aged 45-77 years. Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA(®) (Clover Corp., Sydney, NSW, Australia: 1000 mg of tuna oil; comprising 252 mg DHA, 60 mg EPA and 10 mg vitamin E) or placebo (1000 mg soybean oil). Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group, as well as significantly lower total ω-6 levels. However, no significant effects of DHA supplementation on cognitive functioning were found. For participants with corrected vision, the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group (F(1,22) = 7.651; p = 0.011; partial η(2) = 0.258)., (Copyright © 2012 Elsevier Inc. All rights reserved.)