Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

AmelHap: Leveraging drone whole-genome sequence data to create a honey bee HapMap.

Honey bee, Apis mellifera, drones are typically haploid, developing from an unfertilized egg, inheriting only their queen's alleles and none from the many drones she mated with. Thus the ordered combination or 'phase' of alleles is known, making drones a valuable haplotype resource. We collated whole-genome sequence data for 1,407 drones, including 45 newly sequenced Scottish drones, collectively representing 19 countries, 8 subspecies and various hybrids. Following alignment to Amel_HAv3.1, variant calling and quality filtering, we retained 17.4 M high quality variants across 1,328 samples with a genotyping rate of 98.7%. We demonstrate the utility of this haplotype resource, AmelHap, for genotype imputation, returning >95% concordance when up to 61% of data is missing in haploids and up to 12% of data is missing in diploids. AmelHap will serve as a useful resource for the community for imputation from low-depth sequencing or SNP chip data, accurate phasing of diploids for association studies, and as a comprehensive reference panel for population genetic and evolutionary analyses.

Diffusion magnetic resonance imaging assessment of regional white matter maturation in preterm neonates.

PURPOSE: Diffusion magnetic resonance imaging (dMRI) studies report altered white matter (WM) development in preterm infants. Neurite orientation dispersion and density imaging (NODDI) metrics provide more realistic estimations of neurite architecture in vivo compared with standard diffusion tensor imaging (DTI) metrics. This study investigated microstructural maturation of WM in preterm neonates scanned between 25 and 45 weeks postmenstrual age (PMA) with normal neurodevelopmental outcomes at 2 years using DTI and NODDI metrics. METHODS: Thirty-one neonates (n = 17 male) with median (range) gestational age (GA) 32+1 weeks (24+2-36+4) underwent 3 T brain MRI at median (range) post menstrual age (PMA) 35+2 weeks (25+3-43+1). WM tracts (cingulum, fornix, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), optic radiations) were delineated using constrained spherical deconvolution and probabilistic tractography in MRtrix3. DTI and NODDI metrics were extracted for the whole tract and cross-sections along each tract to assess regional development. RESULTS: PMA at scan positively correlated with fractional anisotropy (FA) in the CST, fornix and optic radiations and neurite density index (NDI) in the cingulum, CST and fornix and negatively correlated with mean diffusivity (MD) in all tracts. A multilinear regression model demonstrated PMA at scan influenced all diffusion measures, GA and GAxPMA at scan influenced FA, MD and NDI and gender affected NDI. Cross-sectional analyses revealed asynchronous WM maturation within and between WM tracts.). CONCLUSION: We describe normal WM maturation in preterm neonates with normal neurodevelopmental outcomes. NODDI can enhance our understanding of WM maturation compared with standard DTI metrics alone.

The Research Centers in Minority Institutions (RCMI) Translational Research Network: Building and Sustaining Capacity for Multi-Site Basic Biomedical, Clinical and Behavioral Research.

The Research Centers in Minority Institutions (RCMI) program was established by the US Congress to support the development of biomedical research infrastructure at minority-serving institutions granting doctoral degrees in the health professions or in a health-related science. RCMI institutions also conduct research on diseases that disproportionately affect racial and ethnic minorities (ie, African Americans/Blacks, American Indians and Alaska Natives, Hispanics, Native Hawaiians and Other Pacific Islanders), those of low socioeconomic status, and rural persons. Quantitative metrics, including the numbers of doctoral science degrees granted to underrepresented students, NIH peer-reviewed research funding, peer-reviewed publications, and numbers of racial and ethnic minorities participating in sponsored research, demonstrate that RCMI grantee institutions have made substantial progress toward the intent of the Congressional legislation, as well as the NIH/NIMHD-linked goals of addressing workforce diversity and health disparities. Despite this progress, nationally, many challenges remain, including persistent disparities in research and career development awards to minority investigators. The continuing underrepresentation of minority investigators in NIH-sponsored research across multiple disease areas is of concern, in the face of unrelenting national health inequities. With the collaborative network support by the RCMI Translational Research Network (RTRN), the RCMI community is uniquely positioned to address these challenges through its community engagement and strategic partnerships with non-RCMI institutions. Funding agencies can play an important role by incentivizing such collaborations, and incorporating metrics for research funding that address underrepresented populations, workforce diversity and health equity.

Conduction block in immune-mediated neuropathy: paranodopathy versus axonopathy.

BACKGROUND AND PURPOSE: Conduction block is a pathognomonic feature of immune-mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). METHODS: A multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments. RESULTS: Of 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons. CONCLUSIONS: The underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody-mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.

Comparing longitudinal brain atrophy measurement techniques in a real-world multiple sclerosis clinical practice cohort: towards clinical integration?

BACKGROUND: Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients. METHODS: Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner. Three-dimensional (3D) T1-weighted and two-dimensional (2D)/3D fluid-attenuated inversion-recovery sequences were analysed. Percentage brain volume change (PBVC) measurements were calculated using SIENA and icobrain long. Statistical correlation, agreement and consistency between methods was evaluated; MRI brain volumetric and clinical data were compared. The proportion of the cohort with annualized brain volume loss (aBVL) rates ⩾ 0.4%, ⩾0.8% and ⩾0.94% were calculated. No evidence of disease activity (NEDA) 3 and NEDA 4 were also determined. RESULTS: Mean annualized PBVC was -0.59 (±0.65)% and -0.64 (±0.73)% as measured by icobrain long and SIENA. icobrain long and SIENA-measured annualized PBVC correlated strongly, r = 0.805 (p < 0.001), and the agreement [intraclass correlation coefficient (ICC) 0.800] and consistency (ICC 0.801) were excellent. Weak correlations were found between MRI metrics and Expanded Disability Status Scale scores. Over half the cohort had aBVL ⩾ 0.4%, approximately a third ⩾0.8%, and aBVL was ⩾0.94% in 28.43% and 23.53% using SIENA and icobrain long, respectively. NEDA 3 was achieved in 35.29%, and NEDA 4 in 15.69% and 16.67% of the cohort, using SIENA and icobrain long to derive PBVC, respectively. DISCUSSION: icobrain long quantified longitudinal WBA with a strong level of statistical agreement and consistency compared to SIENA in this real-world MS population. Utility of WBA measures in individuals remains challenging, but show promise as biomarkers of neurodegeneration in MS clinical practice. Optimization of MRI analysis algorithms/techniques are needed to allow reliable use in individuals. Increased levels of automation will enable more rapid clinical translation.

Therapist Reports of EBP Client Engagement Challenges in Sessions with Diverse Youth and Families in Community Mental Health Settings.

BACKGROUND: The implementation of evidence-based practices (EBPs) in community settings appears to result in reduced benefit relative to controlled trials. This difference in outcomes may be attributable in part to engagement challenges therapists encounter when delivering EBPs to low-income ethnic minority youth and families. OBJECTIVE: The current study sought to identify therapist, client, and session characteristics associated with therapist-reported engagement challenges in therapy sessions, as well the associations between two types of client engagement challenges and therapists' self-reported ability to deliver the EBP in sessions within a system-driven implementation in public children's mental health services. METHOD: One hundred and three therapists reported on two types of engagement challenges-Limited Client Engagement and Expressed Client Concerns-in 702 sessions with 274 clients. RESULTS: Results indicated that therapists reported a higher frequency of Limited Client Engagement in sessions with male clients and in sessions where the youth was present, and by therapists with smaller caseloads. No variables significantly predicted Expressed Client Concerns. Both types of engagement challenges were negatively associated with therapists' report of their ability to carry out intended activities in the same session. CONCLUSIONS: Findings suggest that therapists may benefit from learning strategies to address these two distinct types of engagement challenges encountered in implementation of EBPs with diverse families in community settings.

The Role of Vitamin D and Oxidative Stress in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested that low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence, or lack thereof, of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Jupiter's Mesoscale Waves Observed at 5 µm by Ground-based Observations and Juno JIRAM.

We characterize the origin and evolution of a mesoscale wave pattern in Jupiter's North Equatorial Belt (NEB), detected for the first time at 5 µm using a 2016-17 campaign of "lucky imaging" from the VISIR instrument on the Very Large Telescope and the NIRI instrument on the Gemini observatory, coupled with M-band imaging from Juno's JIRAM instrument during the first seven Juno orbits. The wave is compact, with a 1°.1-1°.4 longitude wavelength (wavelength 1300-1600 km, wavenumber 260-330) that is stable over time, with wave crests aligned largely north-south between 14°N and 17°N (planetographic). The waves were initially identified in small (10° longitude) packets immediately west of cyclones in the NEB at 16°N but extended to span wider longitude ranges over time. The waves exhibit a 7-10 K brightness temperature amplitude on top of an ∼210 K background at 5 µm. The thermal structure of the NEB allows for both inertio-gravity waves and gravity waves. Despite detection at 5 µm, this does not necessarily imply a deep location for the waves, and an upper tropospheric aerosol layer near 400-800 mbar could feature a gravity wave pattern modulating the visible-light reflectivity and attenuating the 5-µm radiance originating from deeper levels. Strong rifting activity appears to obliterate the pattern, which can change on timescales of weeks. The NEB underwent a new expansion and contraction episode in 2016-17 with associated cyclone-anticyclone formation, which could explain why the mesoscale wave pattern was more vivid in 2017 than ever before.

Rationale and design of a placebo controlled randomized trial to assess short term, high-dose oral cholecalciferol on select laboratory and genomic responses in African Americans with hypovitaminosis D.

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

The evolution of "No Evidence of Disease Activity" in multiple sclerosis.

The availability of effective therapies for patients with relapsing-remitting multiple sclerosis (RRMS) has prompted a re-evaluation of the most appropriate way to measure treatment response, both in clinical trials and clinical practice. Traditional parameters of treatment efficacy such as annualized relapse rate, magnetic resonance imaging (MRI) activity, and disability progression have an important place, but their relative merit is uncertain, and the role of other factors such as brain atrophy is still under study. More recently, composite measures such as "no evidence of disease activity" (NEDA) have emerged as new potential treatment targets, but NEDA itself has variable definitions, is not well validated, and may be hard to implement as a treatment goal in a clinical setting. We describe the development of NEDA as an outcome measure in MS, discuss definitions including NEDA-3 and NEDA-4, and review the strengths and limitations of NEDA, indicating where further research is needed.

Progression of retinal ganglion cell loss in multiple sclerosis is associated with new lesions in the optic radiations.

BACKGROUND AND PURPOSE: The mechanism of retinal ganglion cell and retinal nerve fiber layer loss in multiple sclerosis (MS) remains unknown. This study aimed to investigate the association between temporal retinal nerve fiber layer (tRNFL) thinning and disease activity in the brain determined by T2 lesions on magnetic resonance imaging (MRI). METHODS: Fifty-five consecutive patients with relapsing-remitting MS and 25 controls were enrolled. All patients underwent annual optical coherence tomography and high-resolution MRI scans for tRNFL thickness and brain lesion volume analysis, respectively. RESULTS: Significant tRNFL thickness reduction was observed over the 3-year follow-up period at a relatively constant rate (1.02 µm/year). Thinning of tRNFL fibers was more prominent in younger patients (P = 0.01). The tRNFL loss was associated with new MRI lesions in the optic radiations (ORs). There was significantly greater tRNFL thinning in patients with new lesional activity in the ORs compared with patients with new lesions outside the ORs (P = 0.009). CONCLUSIONS: This study supports the notion that retrograde transneuronal degeneration caused by OR lesions might play a role in progressive retinal nerve fiber layer loss. In addition, the results of the study also indicate that the disease-related neurodegenerative changes in the retina start much earlier than the clinical diagnosis of MS.

Autoantibody responses to nodal and paranodal antigens in chronic inflammatory neuropathies.

Autoantibodies to nodal/paranodal proteins have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). To determine the frequency of anti-paranodal antibodies in our cohort of CIDP patients and to validate the presence anti-nodal antibodies in MMN, sera were screened for IgG against human neurofascin 155, contactin-1, neurofascin 186 and gliomedin using ELISA. In CIDP patients, 7% were anti-NF155 IgG4 positive and 7% were anti-CNTN1 IgG4 positive. Positive results were confirmed using cell based assays and indirect immunofluorescence on teased nerve fibres. We did not detect IgG autoantibodies against these nodal/paranodal antigens in MMN patients.

Neurological deficit following stereotactic radiosurgery for trigeminal neuralgia.

We report a unique case of neurological deficit from late onset multiple sclerosis (MS), in a 65-year-old woman, after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). At 3.5months post-SRS for TN, the patient developed ataxia and left leg paraesthesiae and brain MRI showed altered signal and enhancement in the vicinity of the right trigeminal root entry zone (REZ). The symptoms remitted following treatment with intravenous methylprednisolone, however, 10months post-SRS, the patient developed gait ataxia and left lower limb weakness. MRI showed persistent T2 changes at the REZ and multiple new non-enhancing white matter lesions in the cerebrum and spinal cord; and oligoclonal bands were present in the cerebrospinal fluid but not serum. A diagnosis of multiple sclerosis (MS) was made. This report raises the issue of whether the risk of radiation-induced toxicity is increased in patients with MS treated with SRS. We hypothesise that breakdown in the blood brain barrier secondary to the radiosurgery may have triggered a vigorous local inflammatory response.

Automated brain volumetrics in multiple sclerosis: a step closer to clinical application.

BACKGROUND: Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. METHODS: MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. RESULTS: Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. CONCLUSIONS: In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon ß/glatiramer acetate (IFNß/GA) to oral therapy are unknown. OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNß/GA, relative to a propensity-matched comparator of patients remaining on IFNß/GA. METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNß/GA ('stayers') using a Cox marginal model. RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26). CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1ß concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.

User-Friendly Data-Sharing Practices for Fostering Collaboration within a Research Network: Roles of a Vanguard Center for a Community-Based Study.

Although various attempts have been made to build collaborative cultures for data sharing, their effectiveness is still questionable. The Jackson Heart Study (JHS) Vanguard Center (JHSVC) at the NIH-funded Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) Data Coordinating Center (DCC) may be a new concept in that the data are being shared with a research network where a plethora of scientists/researchers are working together to achieve their common goal. This study describes the current practices to share the JHS data through the mechanism of JHSVC. The JHS is the largest single-site cohort study to prospectively investigate the determinants of cardiovascular disease among African-Americans. It has adopted a formal screened access method through a formalized JHSVC mechanism, in which only a qualified scientist(s) can access the data. The role of the DCC was to help RTRN researchers explore hypothesis-driven ideas to enhance the output and impact of JHS data through customized services, such as feasibility tests, data querying, manuscript proposal development and data analyses for publication. DCC has implemented these various programs to facilitate data utility. A total of 300 investigators attended workshops and/or received training booklets. DCC provided two online and five onsite workshops and developed/distributed more than 250 copies of the booklet to help potential data users understand the structure of and access to the data. Information on data use was also provided through the RTRN website. The DCC efforts led to the production of five active manuscript proposals, seven completed publications, 11 presentations and four NIH grant proposals. These outcomes resulted from activities during the first four years; over the last couple of years, there were few new requests. Our study suggested that DCC-customized services enhanced the accessibility of JHS data and their utility by RTRN researchers and helped to achieve the principal goal of JHSVC of scientific productivity. In order to achieve long-term success, the following, but not limited to these, should be addressed in the current data sharing practices: preparation of new promotional strategies in response to changes in technology and users' needs, collaboration with the Network statisticians, harmonization of the JHS data with the other local-based heart datasets to meet the needs of the potential users from the broader geographical areas, adoption of the RTRN comprehensive data-sharing policy to broaden the variety of research topics and implementation of an ongoing monitoring program to evaluate its success.

Older Adults Have Delayed Amino Acid Absorption after a High Protein Mixed Breakfast Meal.

OBJECTIVES: To measure the postprandial plasma amino acid appearance in younger and older adults following a high protein mixed meal. DESIGN: Cross-sectional study. SETTING: Clinical research setting. PARTICIPANTS: Healthy men and women aged 60-75 (n=15) years, and young controls aged 20-25 years (n=15) matched for body mass index and insulin sensitivity based on the homeostatic model assessment of insulin resistance. INTERVENTION: High protein mixed meal of complete food products. MEASUREMENTS: Circulating amino acid concentrations were determined hourly before and for 5 hours after meal ingestion. RESULTS: There was no difference between cohorts in postprandial appearance of non-essential amino acids, or area under the curve of any individual amino acid or amino acid class. However, older adults had higher baseline concentrations of aspartic acid, glutamic acid, glycine, ornithine, threonine and tyrosine and lower baseline concentrations of hydroxyproline, isoleucine, leucine, methionine and valine compared to younger adults. Younger adults showed peak essential (EAA) and branched-chain amino acid (BCAA) concentrations at 1 hour post meal while older adults' peak EAA and BCAA concentration was at 3 hours. Similarly, peak total amino acid concentrations were at 3 hours in older adults. CONCLUSION: Older adults digested and absorbed the protein within a mixed meal more slowly than younger adults. Delayed absorption of AA following a mixed meal of complete food products may suppress or delay protein synthesis in senescent muscle.

Low ambient temperature elevates plasma triiodothyronine concentrations while reducing digesta mean retention time and methane yield in sheep.

Ruminant methane yield (MY) is positively correlated with mean retention time (MRT) of digesta. The hormone triiodothyronine (T3 ), which is negatively correlated with ambient temperature, is known to influence MRT. It was hypothesised that exposing sheep to low ambient temperatures would increase plasma T3 concentration and decrease MRT of digesta within the rumen of sheep, resulting in a reduction of MY. To test this hypothesis, six Merino sheep were exposed to two different ambient temperatures (cold treatment, 9 ± 1 °C; warm control 26 ± 1 °C). The effects on MY, digesta MRT, plasma T3 concentration, CO2 production, DM intake, DM digestibility, change in body weight (BW), rumen volatile fatty acid (VFA) concentrations, estimated microbial protein output, protozoa abundance, wool growth, water intake, urine output and rectal temperature were studied. Cold treatment resulted in a reduction in MY (p < 0.01); digesta MRT in rumen (p < 0.01), hindgut (p = 0.01) and total digestive tract (p < 0.01); protozoa abundance (p < 0.05); and water intake (p < 0.001). Exposure to cold temperature increased plasma T3 concentration (p < 0.05), CO2 production (p = 0.01), total VFA concentrations (p = 0.03) and estimated microbial output from the rumen (p = 0.03). The rate of wool growth increased (p < 0.01) due to cold treatment, but DM intake, DM digestibility and BW change were not affected. The results suggest that exposure of sheep to cold ambient temperatures reduces digesta retention time in the gastrointestinal tract, leading to a reduction in enteric methane yield. Further research is warranted to determine whether T3 could be used as an indirect selection tool for genetic selection of low enteric methane-producing ruminants.