Developing and transferring a children's surgical training program from India to Africa a south-to-south global initiative.

PURPOSE: The availability of children's surgical care in lower middle-income countries is lacking. The authors describe a hub and spoke global training initiative in children's surgery for adult teams from district hospitals (spokes) comprising general and orthopaedic surgeons, anaesthetists, and nurses and specialist children's surgical trainers from tertiary centres (hubs) in delivering the course. METHODS: The training course developed in Vellore, trained several sets of district hospital adult teams and trainer teams in India. Six specialist children's surgical trainer teams were invited from African countries to the course delivered in Vellore, India. The aim was to train them to deliver the course in their countries. RESULTS: Participants underwent a precourse 'train the trainer' program, observed and assessed the suitability of the district hospital training course. The program received positive feedback, government supported planning of similar courses in some of the countries and discussions in others. CONCLUSION: The availability of children's surgical care is similarly limited in the Asian and African continent, and the regions have shared challenges of disease burden, lack of access, poverty, deficient infrastructure, and trained human resources. They would benefit from this 'South to South' collaboration to impart training skills and modules to the children's surgical trainers.

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.

Implication of saturated fats in the aetiology of childhood attention deficit/hyperactivity disorder - A narrative review.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common mental health disorder in the paediatric population. ADHD is highly comorbid with obesity, and has also been associated with poor dietary patterns such as increased consumption of refined carbohydrates and saturated fats. Although ADHD in children was associated with high consumption of saturated fats, so far there has been no evidence-based attempt to integrate dietary strategies controlling for intake of saturated fats into the etiological framework of the disorder. Evidence from human studies and animal models has shown that diets high in saturated fats are detrimental for the development of dopaminergic neurocircuitries, synthesis of neurofactors (e.g. brain derived neurotrophic factor) and may promote brain inflammatory processes. Notably, animal models provide evidence that early life consumption of a high saturated fats diet may impair the development of central dopamine pathways. In the present paper, we review the impact of high saturated fats diets on neurobiological processes in human studies and animal models, and how these associations may be relevant to the neuropathophysiology of ADHD in children. The validation of this relationship and its underlying mechanisms through future investigative studies could have implications for the prevention or exacerbation of ADHD symptoms, improve the understanding of the pathogenesis of the disorder, and help design future dietary studies in patients with ADHD.

Association between self-reported signs and symptoms and SARS-CoV-2 antibody detection in UK key workers.

BACKGROUND: Screening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity. METHODS: Cross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN). RESULTS: Between 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Amongst those without previous positive PCR tests, 687/2,579 (26%) reported belief they had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals. CONCLUSION: Non-COVID-19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.

Pediatric Surgery during the COVID-19 Pandemic: An International Survey of Current Practice.

INTRODUCTION: Understanding the challenges experienced by pediatric surgeons in the early phases of the pandemic may help identify key issues and focus research. MATERIALS AND METHODS: Two pediatric surgeons from each of the 10 countries most affected by COVID-19 were surveyed over a 10-day period. Data were obtained regarding service provision, infection control, specific surgical conditions, and the surgical workforce. RESULTS: Twenty pediatric surgeons responded. All centers had postponed non-emergency surgery and clinics for nonurgent conditions with virtual consultations being undertaken in 90% of centers. A majority (65%) of centers had not yet knowingly operated on a positive patient. Minimal access surgery was performed in 75% centers but a further 75% had reduced or stopped upper gastrointestinal endoscopy. The management of simple appendicitis was unchanged in 70% centers, patients with intussusception were being referred for radiological reduction in all centers and definitive pull-through surgery for Hirschsprung patients was performed by 95% where washouts were successful. Timing of surgery for reducible neonatal inguinal hernias had changed in 55% of centers and the management of urgent feeding gastrostomy referrals and of inflammatory bowel disease patients failing with biological therapy varied considerably. CONCLUSION: Service provision has been severely affected by COVID-19 leading to an inevitable increase in untreated surgical pathology. Better understanding of extrapulmonary infectivity, the risk of asymptomatic carriage in children, and the reliability of testing for surgical scenarios may allow appropriate use of conventional surgery, including laparoscopy and endoscopy, and rational development of the novel care pathways needed during the pandemic.

Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy.

This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.

Integrating Healthcare Services for Indigenous Australian Students at Boarding Schools: A Mixed-Methods Sequential Explanatory Study.

INTRODUCTION: Many Aboriginal and Torres Strait Islander Australian adolescents from remote communities attend boarding schools, requiring integrated healthcare between home and schools. This study explored students' health status, healthcare service use and satisfaction. METHODOLOGY: A two-phased mixed-methods explanatory design was implemented. 32 Indigenous primary and 188 secondary boarding school students were asked their health status, psychological distress, use of healthcare services in community and boarding school, and service satisfaction. Results were fed back to students, parents and community members, and education and healthcare staff to elicit further explanation and interpretation. RESULTS: In the previous year, 75% of primary and 81% of secondary boarding school students had visited a doctor. More than 90% were satisfied with healthcare services used. Despite 27.1% reporting high psychological distress, students did not perceive distress as reducing their overall health, nor was distress associated with mental healthcare service use. DISCUSSION: Despite high levels of service use and satisfaction, this study highlighted the need for improved healthcare integration for Indigenous adolescents between school-based and remote community services. Further research is needed to identify students' expectations and models for healthcare integration. CONCLUSION: With resourcing, schools could play a greater role in facilitating access to healthcare.

The effect of general duty police ensemble on graded exercise and simulated work performance.

This 2-part study examined the impact of general duty police ensemble on selected cardiopulmonary responses during incremental treadmill exercise and on simulated work performance in 25 healthy young male and female participants. Part I comprised randomly ordered treadmill tests in 2 experimental conditions: physical training (PT; undergarments, shorts, t-shirt, and running shoes) and police duty ensemble (PDE; undergarments, body armour, patrol uniform, boots, duty belt with required equipment, radio, and weapons). The PDE added 10.3 kg (SD 0.4) or 14% (SD 2) body mass. Participants walked at 5.6 km·h-1, starting at 0% grade with 2% increases in grade every 2 min. The 4% stage was 6 min in duration to achieve physiological steady state. Subsequently, the 2-min increments continued to exhaustion. Part II evaluated performance time on a recognized job-related work simulation circuit, in 3 experimental conditions: (i) PT, (ii) weighted belt (WB; PT plus a 7.5 kg weighted belt), and (iii) PDE. In Part I, physiological responses (e.g., oxygen uptake, ventilation, heart rate) were elevated (p < 0.05) with PDE during submaximal exercise but peak values were unchanged. Test duration and peak power output were significantly reduced with PDE. In Part II, circuit completion time was increased in PDE but not WB when compared with PT (p < 0.05). Heart rate and perceived exertion were similar in all conditions and perceived dyspnea was higher in PDE. Novelty Police duty ensemble negatively affected exercise performance more than would be expected due to load mass alone. Specificity must be considered when simulating occupational load carriage.

Sodium-activated potassium channels moderate excitability in vascular smooth muscle.

KEY POINTS: We report that a sodium-activated potassium current, IKNa , has been inadvertently overlooked in both conduit and resistance arterial smooth muscle cells. IKNa is a major K+ resting conductance and is absent in cells of IKNa knockout (KO) mice. The phenotype of the IKNa KO is mild hypertension, although KO mice react more strongly than wild-type with raised blood pressure when challenged with vasoconstrictive agents. IKNa is negatively regulated by angiotensin II acting through Gαq protein-coupled receptors. In current clamp, KO arterial smooth muscle cells have easily evoked Ca2+ -dependent action potentials. ABSTRACT: Although several potassium currents have been reported to play a role in arterial smooth muscle (ASM), we find that one of the largest contributors to membrane conductance in both conduit and resistance ASMs has been inadvertently overlooked. In the present study, we show that IKNa , a sodium-activated potassium current, contributes a major portion of macroscopic outward current in a critical physiological voltage range that determines intrinsic cell excitability; IKNa is the largest contributor to ASM cell resting conductance. A genetic knockout (KO) mouse strain lacking KNa channels (KCNT1 and KCNT2) shows only a modest hypertensive phenotype. However, acute administration of vasoconstrictive agents such as angiotensin II (Ang II) and phenylephrine results in an abnormally large increase in blood pressure in the KO animals. In wild-type animals Ang II acting through Gαq protein-coupled receptors down-regulates IKNa , which increases the excitability of the ASMs. The complete genetic removal of IKNa in KO mice makes the mutant animal more vulnerable to vasoconstrictive agents, thus producing a paroxysmal-hypertensive phenotype. This may result from the lowering of cell resting K+ conductance allowing the cells to depolarize more readily to a variety of excitable stimuli. Thus, the sodium-activated potassium current may serve to moderate blood pressure in instances of heightened stress. IKNa may represent a new therapeutic target for hypertension and stroke.

Skin Transcriptome of Middle-Aged Women Supplemented With Natural Herbo-mineral Shilajit Shows Induction of Microvascular and Extracellular Matrix Mechanisms.

Objective: Shilajit is a pale-brown to blackish-brown organic mineral substance available from Himalayan rocks. We demonstrated that in type I obese humans, shilajit supplementation significantly upregulated extracellular matrix (ECM)-related genes in the skeletal muscle. Such an effect was highly synergistic with exercise. The present study (clinicaltrials.gov NCT02762032) aimed to evaluate the effects of shilajit supplementation on skin gene expression profile and microperfusion in healthy adult females. Methods: The study design comprised six total study visits including a baseline visit (V1) and a final 14-week visit (V6) following oral shilajit supplementation (125 or 250 mg bid). A skin biopsy of the left inner upper arm of each subject was collected at visit 2 and visit 6 for gene expression profiling using Affymetrix Clariom™ D Assay. Skin perfusion was determined by MATLAB processing of dermascopic images. Transcriptome data were normalized and subjected to statistical analysis. The differentially regulated genes were subjected to Ingenuity Pathway Analysis (IPA®). The expression of the differentially regulated genes identified by IPA® were verified using real-time polymerase chain reaction (RT-PCR). Results: Supplementation with shilajit for 14 weeks was not associated with any reported adverse effect within this period. At a higher dose (250 mg bid), shilajit improved skin perfusion when compared to baseline or the placebo. Pathway analysis identified shilajit-inducible genes relevant to endothelial cell migration, growth of blood vessels, and ECM which were validated by quantitative real-time polymerase chain reaction (RT-PCR) analysis. Conclusions: This work provides maiden evidence demonstrating that oral shilajit supplementation in adult healthy women induced genes relevant to endothelial cell migration and growth of blood vessels. Shilajit supplementation improved skin microperfusion.

Functional connectivity of the vigilant-attention network in children and adolescents with attention-deficit/hyperactivity disorder.

The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaired in attention-deficit/hyperactivity disorder (ADHD), but the underlying pathophysiological mechanisms at the brain network level are not clear yet. We therefore investigated ADHD-related differences in resting-state functional connectivity within a meta-analytically defined brain network of 14 distinct regions subserving VA (comprising 91 connections in total), as well as the association of connectivity with markers of behavioural dysfunction in 17 children (age range: 9-14 years) with a diagnosis of ADHD and 21 age-matched neurotypical controls. Our analyses revealed selective, rather than global, differences in the intrinsic coupling between nodes of the VA-related brain network in children with ADHD, relative to controls. In particular, ADHD patients showed substantially diminished intrinsic coupling for 7 connections and increased coupling for 4 connections, with many differences involving connectivity with the anterior insula. Moreover, connectivity strength of several aberrant connections was found to be associated with core aspects of ADHD symptomatology, such as poor attention, difficulties with social functioning, and impaired cognitive control, attesting to the behavioural relevance of specific connectivity differences observed in the resting state.

No detectable effects of acute tryptophan depletion on short-term immune system cytokine levels in healthy adults.

Objectives: Recent research suggested an influence of diminished central nervous serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in healthy adult females. However, studies assessing immunological parameters in combination with dietary challenge techniques that impact brain 5-HT synthesis in humans are lacking. Methods: In the present trial, a pilot analysis was conducted on data obtained in healthy adult humans receiving either different dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced control conditions (BAL) to study the effects of reduced central nervous 5-HT synthesis on serum tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 concentrations. The data of N = 35 healthy adults were analysed who were randomly subjected to one of the following two dietary conditions in a double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations for the assessment of relevant parameters (TNF-α, IL-1ß and IL-6) and relevant TRP-related characteristics after the respective challenge procedures were assessed at baseline (T0) and in hourly intervals after administration over a period of 6 h (T1-T6). Results: The ATD condition did not result in significant changes to cytokine concentrations for the entire study sample, or in male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion appears to have no statistically significant short-term impact on cytokine concentrations in healthy adults. Conclusions: Future research on immunological stressors in combination with challenge techniques will be of value in order to further disentangle the complex interplay between brain 5-HT synthesis and immunological pathways.

Acute Tryptophan Depletion Moja-De: A Method to Study Central Nervous Serotonin Function in Children and Adolescents.

Serotonin (5-HT) is widely implicated as a key neurotransmitter relevant to a range of psychiatric disorders and psychological processes. The role of central nervous 5-HT function underlying these processes can be examined through serotonergic challenge methodologies. Acute tryptophan depletion (ATD) is a key challenge method whereby a diminished dietary intake of tryptophan-the amino acid precursor to brain 5-HT synthesis-results in temporary diminished central nervous 5-HT synthesis. While this particular methodology has been used in adult populations, it was only recently that modifications were made to enable the use of ATD in child and adolescent populations. Additionally, the Moja-De modification of the ATD challenge methodology has demonstrated benefits over other ATD techniques used previously. The aim of this protocol paper is to describe the ATD Moja-De methodology in detail, its benefits, as well as studies that have been conducted to validate the procedure in child and adolescent samples. The ATD Moja-De protocol provides a potential methodology for investigating the role of central nervous 5-HT via manipulation of brain tryptophan availability in human psychopathology from a developmental viewpoint.

Oxytocin can regulate myometrial smooth muscle excitability by inhibiting the Na+ -activated K+ channel, Slo2.1.

KEY POINTS: At the end of pregnancy, the uterus transitions from a quiescent state to a highly contractile state. This transition requires that the uterine (myometrial) smooth muscle cells increase their excitability, although how this occurs is not fully understood. We identified SLO2.1, a potassium channel previously unknown in uterine smooth muscle, as a potential significant contributor to the electrical excitability of myometrial smooth muscle cells. We found that activity of the SLO2.1 channel is negatively regulated by oxytocin via Gαq-protein-coupled receptor activation of protein kinase C. This results in depolarization of the uterine smooth muscle cells and calcium entry, which may contribute to uterine contraction. These findings provide novel insights into a previously unknown mechanism by which oxytocin may act to modulate myometrial smooth muscle cell excitability. Our findings also reveal a new potential pharmacological target for modulating uterine excitability. ABSTRACT: During pregnancy, the uterus transitions from a quiescent state to a more excitable contractile state. This is considered to be at least partly a result of changes in the myometrial smooth muscle cell (MSMC) resting membrane potential. However, the ion channels controlling the myometrial resting membrane potential and the mechanism of transition to a more excitable state have not been fully clarified. In the present study, we show that the sodium-activated, high-conductance, potassium leak channel, SLO2.1, is expressed and active at the resting membrane potential in MSMCs. Additionally, we report that SLO2.1 is inhibited by oxytocin binding to the oxytocin receptor. Inhibition of SLO2.1 leads to membrane depolarization and activation of voltage-dependent calcium channels, resulting in calcium influx. The results of the present study reveal that oxytocin may modulate MSMC electrical activity by inhibiting SLO2.1 potassium channels.

Advancing Risk-Informed Decision Making in Managing Defense Nuclear Waste in the United States: Opportunities and Challenges for Risk Analysis.

An omnibus spending bill in 2014 directed the Department of Energy to analyze how effectively Department of Energy (DOE) identifies, programs, and executes its plans to address public health and safety risks that remain as part of DOE's remaining environmental cleanup liabilities. A committee identified two dozen issues and associated recommendations for the DOE, other federal agencies, and the U.S. Congress to consider, as well as other stakeholders such as states and tribal nations. In regard to risk assessment, the committee described a risk review process that uses available data, expert experience, identifies major data gaps, permits input from key stakeholders, and creates an ordered set of risks based on what is known. Probabilistic risk assessments could be a follow-up from these risk reviews. In regard to risk management, the states, in particular, have become major drivers of how resources are driven. States use different laws, different priorities, and challenge DOE's policies in different ways. Land use decisions vary, technology choices are different, and other notable variations are apparent. The cost differences associated with these differences are marked. The net result is that resources do not necessarily go to the most prominent human health and safety risks, as seen from the national level.

Concurrent developmental course of sleep problems and emotional/behavioral problems in childhood and adolescence as reflected by the dysregulation profile.

OBJECTIVES: Longitudinal data on the course and relationship of concurrent psychopathology in youth are scarce but are of need for better practical patient care and prevention. This study explores the course of (and relationships over time) between sleep problems and concurrent dimensional difficulties relating to anxiety/depression, attention deficiency, and aggressive behaviors in childhood and adolescence. The latter three may jointly form a broad syndrome, the dysregulation profile. METHODS: Young people from the Raine Study, a large community cohort sample (N = 1625) were followed from age 5 to 17 years. Developmental courses of sleep problems and its concurrent regulatory difficulties were estimated separately and jointly. RESULTS: The majority of adolescents reported low levels of problems and which appeared to be stable over time, while a small group (rates between 7.8% and 10.1%) reported enduring problematic developmental courses. Sleep problems and regulatory difficulties shared a strong association in their development over time (individual's probabilities of having the same courses, i.e. low-low and high-high, were between 89.8% and 92.3%). Furthermore, having persistent sleep problems over time was associated with an increased risk of having regulatory difficulties by approximately 10 times, and vice versa. CONCLUSION: Findings from this study provide empirical evidence for a strong mutual association in the development of sleep problems and difficulties of dysregulation with emotion, cognition, and aggression. It may be suggested that a positive screening of one such psychopathological dimension should lead to a careful assessment, not only to reduce the problem in question but also to prevent the youth from further problems.

A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow.

Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. The vectors of Orientia tsutsugamushi were once thought to be confined to an area designated as the Tsutsugamushi Triangle. However, recent reports of scrub typhus caused by Orientia species other than O. tsutsugamushi well beyond the limits of the Tsutsugamushi Triangle have triggered concerns about the worldwide presence of scrub typhus. It is not known whether the vectors of O. tsutsugamushi will be the same for the new Orientia species, and this should be a consideration during outbreak/surveillance investigations. Additionally, concerns surrounding the antibiotic resistance of O. tsutsugamushi have led to considerations for the amendment of treatment protocols, and the need for enhanced public health awareness in both the civilian and medical professional communities. In this review, we discuss the history, outbreaks, antibiotic resistance, and burgeoning genomic advances associated with one of the world's oldest recognized vector-borne pathogens, O. tsutsugamushi.

Using acute tryptophan depletion to investigate predictors of treatment response in adolescents with major depressive disorder: study protocol for a randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown. METHODS: To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period. DISCUSSION: ATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply-A Pilot Study.

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.