Dietary Tyrosine Intake (FFQ) Is Associated with Locus Coeruleus, Attention and Grey Matter Maintenance: An MRI Structural Study on 398 Healthy Individuals of the Berlin Aging Study-II.

BACKGROUND AND OBJECTIVE: It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus-Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer's disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC signal intensity 2) whether LC mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test - TMT), and 3) whether LC signal intensity relates to an objective measure of brain maintenance (BrainPAD). METHODS: The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC signal intensity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA - measured with Food Frequency Questionnaire - FFQ). As a control procedure, the same analyses were repeated on other main seeds of the neuromodulators' subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. RESULTS: Results show that HD-Tyr-IDA is positively associated with LC signal intensity. Similarly, LC disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. CONCLUSIONS: These findings provide the first evidence linking tyrosine intake with LC-NA system signal intensity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Results of an American College of Radiology-Society of Interventional Radiology Membership Survey on Exclusive Contracts and the Attitudes of Interventional Radiologists.

PURPOSE: To assess the attitudes of interventional radiologists (IRs) and diagnostic radiologists (DRs) toward exclusive contracts and independently practicing IRs who may request privileges at a hospital where an exclusive contract exists with a different group of radiologists. MATERIALS AND METHODS: A total of 22,400 survey instruments were distributed to 4,490 IRs and 17,910 DRs in the United States. Statistical evaluation included multivariate ordinal logistic regression analysis with calculation of the odds ratios and forest plots. RESULTS: Completed surveys were received from 525 (11.69%) IRs and 401 (2.23%) DRs. Given the low response rate of DRs, data analysis was focused on IRs. Early-career IRs and those in outpatient practices had a more positive attitude toward independent IRs who requested admitting and/or procedural privileges. A supermajority of both IRs and DRs who responded to the survey agreed that the importance of IR to hospital and health system contracts will increase. CONCLUSIONS: This survey identified many interrelated and complex variables that significantly affected the attitudes of IRs in various practice settings toward independent IRs requesting hospital admitting and/or procedural privileges. It will benefit independent IRs seeking admitting privileges to better understand some of the factors that impact the potential willingness of the radiology groups and other IRs with exclusive hospital contracts to work toward mutually beneficial practice paradigms, especially as more clinically oriented IRs complete their training in the new, integrated residency programs.

Alternate Cervical Venous Access Sites for Implantable Port Catheters: Experience at a Single Quaternary Care Institution.

INTRODUCTION: Clinical outcomes of implantable port catheters (IPCs) placed via alternative veins such as the external jugular and cervical collaterals have not been well established. This investigation evaluates the short- and long-term outcomes of IPCs inserted via alternate cervical veins (ACV) compared to traditionally inserted IPCs via the internal jugular vein (IJV). MATERIALS AND METHODS: A total of 24 patients who received an IPC between 2010 and 2020 via an ACV-defined as the external jugular vein, superficial cervical vein, or unnamed collateral veins-were identified. Based on power analysis, a matched control group of 72 patients who received IPCs via the IJV was identified. Non-inferiority analysis for port complications was performed between the two groups based on the selected non-inferiority margin of 20%. Secondary end points included complication-free survival and comparison of complications by the time at which they occurred. RESULTS: ACV access was non-inferior to traditional access for overall complications. Alternate access resulted in fewer complications than traditional access with an estimated reduction of - 7.0% [95% CI - 23.6%, 39.7%]. There was no significant difference in peri-procedural and post-procedural complications between the two groups. Complication-free survival was also equivalent between the two groups. CONCLUSION: IPC placement via ACVs was non-inferior to IPCs placed via traditional access through the IJV. When abnormal pathology obviates the use of IJV access, other cervical veins may be considered prior to seeking alternate locations such as femoral, translumbar, inferior vena cava, and hepatic veins.

Embolic Pneumonectomy for the Treatment of Proximal Pulmonary Artery Pseudoaneurysm.

Pulmonary artery pseudoaneurysm is an uncommon and potentially fatal abnormality. It has been described from a wide variety of etiologies, including infectious, iatrogenic, neoplastic, congenital, and traumatic causes. There are currently no published consensus guidelines for the diagnostic testing and management of pulmonary artery pseudoaneurysm. This case report presents an uncommon case of pulmonary artery pseudoaneurysm emerging from a non-small cell lung cancer that was successfully managed using coil embolization.

Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for blaCTX-M-15, blaNDM, blaKPC and blaOXA-48-like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates' rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers' rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae/E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes.

Molecular identification of trematode parasites infecting the freshwater snail Bithynia siamensis goniomphalos in Thailand.

Digenetic trematodes are important parasites of humans and animals. They have complex life cycles and typically infect a gastropod as the first intermediate host. Bithynia siamensis goniomphalos, the first intermediate host of the liver fluke, Opisthorchis viverrini, harbours a wide variety of other trematode species. Morphological details of cercariae of 20 trematode taxa from B. s. goniomphalos, collected mainly in Thailand from 2009 to 2014, were provided in an earlier paper. Correct identification to the species or genus level based on morphology of these cercariae is generally not possible. Therefore, we used molecular data to improve identification and to investigate the diversity of the species of trematodes infecting B. s. goniomphalos. We were successful in extracting, amplifying and sequencing portions of the 28S ribosomal RNA (rRNA) gene for 19 of these 20 types of cercaria, and the internal transcribed spacer 2 region for 18 types. BLAST searches in GenBank and phylogenetic trees inferred from the 28S rRNA sequences identified members of at least nine superfamilies and 12 families. Only a few cercariae could be assigned confidently to genus or species on the basis of the sequence data. Matching sequence data from named adult trematodes will be required for definitive identification. There is clearly a great diversity of trematode species utilizing B. s. goniomphalos in Thailand.

Is glycaemic control associated with dietary patterns independent of weight change in people newly diagnosed with type 2 diabetes? Prospective analysis of the Early-ACTivity-In-Diabetes trial.

BACKGROUND: It is unclear whether diet affects glycaemic control in type 2 diabetes (T2D), over and above its effects on bodyweight. We aimed to assess whether changes in dietary patterns altered glycaemic control independently of effects on bodyweight in newly diagnosed T2D. METHODS: We used data from 4-day food diaries, HbA1c and potential confounders in participants of the Early-ACTivity-In-Diabetes trial measured at 0, 6 and 12 months. At baseline, a 'carb/fat balance' dietary pattern and an 'obesogenic' dietary pattern were derived using reduced-rank regression, based on hypothesised nutrient-mediated mechanisms linking dietary intake to glycaemia directly or via obesity. Relationships between 0 and 6 month change in dietary pattern scores and baseline-adjusted HbA1c at 6 months (n = 242; primary outcome) were assessed using multivariable linear regression. Models were repeated for periods 6-12 months and 0-12 months (n = 194 and n = 214 respectively; secondary outcomes). RESULTS: Reductions over 0-6 months were observed in mean bodyweight (- 2.3 (95% CI: - 2.7, - 1.8) kg), body mass index (- 0.8 (- 0.9, - 0.6) kg/m2), energy intake (- 788 (- 953, - 624) kJ/day), and HbA1c (- 1.6 (- 2.6, -0.6) mmol/mol). Weight loss strongly associated with lower HbA1c at 0-6 months (ß = - 0.70 [95% CI - 0.95, - 0.45] mmol/mol/kg lost). Average fat and carbohydrate intakes changed to be more in-line with UK healthy eating guidelines between 0 and 6 months. Dietary patterns shifting carbohydrate intakes higher and fat intakes lower were characterised by greater consumption of fresh fruit, low-fat milk and boiled/baked potatoes and eating less of higher-fat processed meats, butter/animal fats and red meat. Increases in standardised 'carb/fat balance' dietary pattern score associated with improvements in HbA1c at 6 months independent of weight loss (ß = - 1.54 [- 2.96, - 0.13] mmol/mol/SD). No evidence of association with HbA1c was found for this dietary pattern at other time-periods. Decreases in 'obesogenic' dietary pattern score were associated with weight loss (ß = - 0.77 [- 1.31, - 0.23] kg/SD) but not independently with HbA1c during any period. CONCLUSIONS: Promoting weight loss should remain the primary nutritional strategy for improving glycaemic control in early T2D. However, improving dietary patterns to bring carbohydrate and fat intakes closer to UK guidelines may provide small, additional improvements in glycaemic control. TRIAL REGISTRATION: ISRCTN92162869 . Retrospectively registered on 25 July 2005.

A Survey of Interventional Radiologists Regarding the Use of Morbidity and Mortality Conferencing in Departmental Quality Improvement Programs.

PURPOSE: To investigate the degree to which morbidity and mortality (M&M) conferencing is utilized in interventional radiology (IR), identify impediments to its adoption, and assess the experience of those using this tool. MATERIALS AND METHODS: Members of the Society of Interventional Radiology (SIR) were offered a 9-question survey of practices and experiences regarding M&M conferencing within their quality assessment (QA) programs. RESULTS: Among 604 respondents, 37.8% were university-based practitioners and 60% were from outside of university practices. Of all respondents, 43% reported practicing 100% IR, with 28.5% practicing IR 75%-99% and 11% practicing IR <50% of the time. The use of M&M conferencing was significantly greater in university practices (90.7%) than in nonuniversity practices (37.1%) and among practitioners performing at least 75% IR (71.2%) than among those practicing <75% (28.8%). The conferences were held monthly (66.6%) or more often, and the majority (56%) of the events identified were scored using the SIR severity score. Approximately 20% of M&M conferences were multidisciplinary, shared most commonly with vascular surgery. The reasons cited for not using M&M included the lack of time and the logistical challenges of the process. However, among those who participate in M&M conferences, the QA goals of the conference were met at very high rates. CONCLUSIONS: M&M conferencing is well established in university IR programs and among full-time practitioners but much less so elsewhere. For those sites that do not utilize M&M conferencing, there may be a considerable benefit to addressing the obstacles that are limiting their implementation of this tool.

Ambulatory Phlebectomy and Sclerotherapy as Tools for the Treatment of Varicose Veins and Telangiectasias.

Treatment of chronic venous disease is a fascinating and rewarding undertaking. Once the truncal reflux is addressed, several options are available that can be used to treat the associated ulcers, varicosities, reticular veins, and telangiectasias. This review will focus on two widely employed procedures: ambulatory phlebectomy and sclerotherapy.

CT-guided cryoablation of mediastinal parathyroid adenoma: an alternative to surgery.

Primary hyperparathyroidism is most commonly caused by adenoma formation in one of the 4 parathyroid glands. The presence of ectopic parathyroid tissue is relatively common and can lead to difficulties in identification and treatment if affected by adenoma. This report describes the case of a 45-year-old female who presented 10 years status post thyroidectomy with symptomatic hyperparathyroidism and found to have ectopic parathyroid adenoma in the anterior mediastinum. Parathyroid scintigraphy with 99m-Technetium sestamibi and computed tomography were used for localization of the adenoma to a 1.9-centimeter para-aortic nodule. Computed tomography-guided transsternal cryoablation was subsequently performed for treatment, with intraoperative evaluation of serum parathyroid and calcium levels for confirmation. This case highlights that a sharp increase in parathyroid hormone immediately after cryoablation is not necessary for successful confirmation of the procedure. It additionally contributes to the growing literature on computed tomography-guided cryoablation as a legitimate alternative to surgery for treatment of ectopic parathyroid adenoma.

Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK's 2019 remission workshop.

AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.

Matrix metalloproteinases regulate ECM accumulation but not larval heart growth in Drosophila melanogaster.

The Drosophila heart provides a simple model to examine the remodelling of muscle insertions with growth, extracellular matrix (ECM) turnover, and fibrosis. Between hatching and pupation, the Drosophila heart increases in length five-fold. If major cardiac ECM components are secreted remotely, how is ECM "self assembly" regulated? We explored whether ECM proteases were required to maintain the morphology of a growing heart while the cardiac ECM expanded. An increase in expression of Drosophila's single tissue inhibitor of metalloproteinase (TIMP), or reduced function of metalloproteinase MMP2, resulted in fibrosis and ectopic deposition of two ECM Collagens; type-IV and fibrillar Pericardin. Significant accumulations of Collagen-IV (Viking) developed on the pericardium and in the lumen of the heart. Congenital defects in Pericardin deposition misdirected further assembly in the larva. Reduced metalloproteinase activity during growth also increased Pericardin fibre accumulation in ECM suspending the heart. Although MMP2 expression was required to remodel and position cardiomyocyte cell junctions, reduced MMP function did not impair expansion of the heart. A previous study revealed that MMP2 negatively regulates the size of the luminal cell surface in the embryonic heart. Cardiomyocytes align at the midline, but do not adhere to enclose a heart lumen in MMP2 mutant embryos. Nevertheless, these embryos hatch and produce viable larvae with bifurcated hearts, indicating a secondary pathway to lumen formation between ipsilateral cardiomyocytes. MMP-mediated remodelling of the ECM is required for organogenesis, and to prevent assembly of excess or ectopic ECM protein during growth. MMPs are not essential for normal growth of the Drosophila heart.

Development of a group structured education programme to support safe exercise in people with Type 1 diabetes: the EXTOD education programme.

AIM: To develop a structured education programme for individuals with Type 1 diabetes who are engaging in regular exercise. METHOD: A multidisciplinary team of experts in supporting exercise and physical activity for people with Type 1 diabetes, alongside researchers with experience of developing self-management education, developed an exercise programme using the Medical Research Council framework. The programme was informed by a review of the evidence relating to Type 1 diabetes and exercise, the behaviour change literature (including the behaviour change taxonomy), and qualitative interviews with stakeholders. The programme and supporting resources were refined using an iterative process of testing, delivery and collecting feedback from participants and the wider development team. RESULTS: The outcome of the intervention development was the design of a feasible and acceptable intervention for people with Type 1 diabetes to support safe exercise. The pilot allowed refinement of the intervention prior to testing in a two-site feasibility randomized controlled trial. Key findings from the pilot informed minor restructuring of the timetable (timings and order) and adaptation of supporting educational materials (participant handbook and teaching materials). CONCLUSION: The 'EXercise in people with Type One Diabetes' (EXTOD) education programme has been developed using robust methodology for the generation of educational interventions. It now needs testing in a randomized controlled trial.

Exercise-induced hypoglycaemia in type 1 diabetes.

NEW FINDINGS: What is the topic of this review? Hypoglycaemia is a commonly cited barrier to exercise in type 1 diabetes mellitus (T1D). Knowledge of approaches to prevent or manage exercise-induced hypoglycaemia can support patients to exercise and help clinicians to give advice. This review presents evidence-based strategies to prevent exercise-induced hypoglycaemia in T1D. What advances does it highlight? This review highlights approaches that can be used before, during and after exercise to mitigate the risk of hypoglycaemia. The approaches include the timing of exercise, the type of exercise, adjustments to insulin and carbohydrate, use of novel technology and education. ABSTRACT: Exercise is a key component for the management of type 1 diabetes mellitus (T1D) and is associated with reduced risk of cardiovascular disease, decreased daily insulin requirements and improved quality of life. Owing to these benefits, people with T1D are recommended to undertake regular physical activity, 150 min per week for adults and 60 min per day for children and adolescents. Despite the recommendations, many people do not meet these targets. One of the commonly cited barriers to exercise is fear of hypoglycaemia along with limited knowledge of effective preventative strategies. Hypoglycaemia can be difficult to predict, and symptoms are often masked during exercise or stress of competition. For athletes with T1D, hypoglycaemia can also limit sporting success. Hypoglycaemia before an event increases the risks of hypoglycaemia during competition and can reduce performance. To avoid hypoglycaemia, people with T1D may avoid exercise altogether or consume excessive amounts of carbohydrates, which mitigates many of the health benefits of exercise. Increased understanding of approaches to prevent or manage hypoglycaemia is therefore important to help increase levels of physical activity in people with T1D and to support athletes with T1D to compete at the highest level. This review outlines the prevalence of exercise-related hypoglycaemia, its underlying physiology and the strategies that can be used to prevent and manage exercise-induced hypoglycaemia in T1D. Our hope is that this knowledge will be used by people with T1D and their clinicians to find individual approaches to manage exercise-related hypoglycaemia.

James Lind Alliance research priorities: should diet and exercise be used as an alternative to drugs for the management of type 2 diabetes or alongside them?

AIM: To review evidence on whether diet and exercise should be used as an alternative to drug therapy for the management of type 2 diabetes or alongside. METHOD: We present a narrative review that draws on evidence from other systematic reviews and meta-analyses, narrative reviews, trials and cohort studies. We focused mainly on glycaemic control rather than control of blood pressure or cholesterol. RESULTS: Good-quality dietary advice that results in weight loss of >5% and physical activity interventions of >150 min/week of moderate to vigorous physical activity, combined with resistance exercise, can produce improvements in HbA1c similar to those produced by the addition of glucose-lowering drugs. These improvements can be seen at all stages of the disease. There are recognized interactions between glucose-lowering drugs and physical activity which may not be synergistic, but these are not well understood, and it is not clear if they are considered in clinical practice. Studies that explicitly compare drugs with diet or physical activity or control for drug use found that lifestyle could delay or reduce medication use, but most people eventually needed to progress to drug treatment. There are few studies, however, that provide strategies for the long-term maintenance of weight loss or physical activity. CONCLUSION: Diet and physical activity are of key importance in type 2 diabetes management, and attention to them improves glycaemic control and cardiovascular disease risk, but it is not yet known whether maintained lifestyle changes provide an alternative to drug therapy in the long term.

Measurement of Motion beyond the Quantum Limit by Transient Amplification.

Through simultaneous but unequal electromechanical amplification and cooling processes, we create a method for a nearly noiseless pulsed measurement of mechanical motion. We use transient electromechanical amplification (TEA) to monitor a single motional quadrature with a total added noise -8.5±2.0 dB relative to the zero-point motion of the oscillator, or equivalently the quantum limit for simultaneous measurement of both mechanical quadratures. We demonstrate that TEA can be used to resolve fine structure in the phase space of a mechanical oscillator by tomographically reconstructing the density matrix of a squeezed state of motion. Without any inference or subtraction of noise, we directly observe a squeezed variance 2.8±0.3 dB below the oscillator's zero-point motion.