Enteral ß-hydroxy-ß-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs.

Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) µmol HMB·kg body wt(-1)·day(-1) Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E·eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2α and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation.

An evidence-informed rehabilitation management framework for posterior shoulder tightness: A scoping review.

Objective: To systematically scope the literature on posterior shoulder tightness (PST) and define a therapist-instructed and therapist-administered management framework. Design: Scoping review. Literature search: We searched MEDLINE, EMBASE, CINAHL, Scopus and Google Scholar from inception to December 2021. Study selection criteria: Peer-reviewed studies written in English, French, Greek, Japanese or Tamil, with extractable pre- and post-intervention data. Physiotherapy interventions amenable for posterior shoulder structural (muscle, capsule) causes of PST within an adult population. Data synthesis: Arksey and O'Malley's framework was implemented and the PRISMA extension for scoping reviews directed our data synthesis. The data charted from each study included authors, title, study year, location, study design; participant number, age, sex; PST intervention and parameters; patient-reported outcomes; and results. Themes were organized into therapist-instructed and therapist-administered rehabilitation strategies, as well as combined treatment methods. Results: Of 2777 articles identified from our search strategy, 21 articles were included. Therapist-instructed interventions included cross-body stretch (CBS), sleeper stretch (SS), a combination of the two and general stretching. Therapist-administered interventions included CBS, SS, instrument-assisted soft tissue mobilization (IASTM), muscle energy techniques, dry needling and Fauls protocol (12 therapist-assisted stretches). Combined interventions of tape with self-stretching and IASTM and stretching were also identified. Conclusion: Based on the current evidence, CBS and SS are the most researched treatments for PST and seem to be effective at improving PST. Furthermore, stabilization of the scapula while performing these stretches optimized the stretch targeted to the PST and ROM benefits for horizontal adduction.

Material evidence: interaction of well-learned priors and sensorimotor memory when lifting objects.

Skilled object lifting requires the prediction of object weight. When lifting new objects, such prediction is based on well-learned size-weight and material-density correlations, or priors. However, if the prediction is erroneous, people quickly learn the weight of the particular object and can use this knowledge, referred to as sensorimotor memory, when lifting the object again. In the present study, we explored how sensorimotor memory, gained when lifting a given object, interacts with well-learned material-density priors when predicting the weight of a larger but otherwise similar-looking object. Different groups of participants 1st lifted 1 of 4 small objects 10 times. These included a pair of wood-filled objects and a pair of brass-filled objects where 1 of each pair was covered in a wood veneer and the other was covered in a brass veneer. All groups then lifted a larger, brass-filled object with the same covering as the small object they had lifted. For each lift, we determined the initial peak rate of change of vertical load-force rate and the load-phase duration, which provide estimates of predicted object weight. Analysis of the 10th lift of the small cube revealed no effects of surface material, indicating participants learned the appropriate forces required to lift the small cube regardless of object appearance. However, both surface material and core material of the small cube affected the 1st lift of the large block. We conclude that sensorimotor memory related to object density can contribute to weight prediction when lifting novel objects but also that long-term priors related to material properties can influence the prediction.

Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease.

Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.

Serial bedside B-type natriuretic peptide strongly predicts prognosis in acute coronary syndrome independent of echocardiographic abnormalities.

BACKGROUND: Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH). METHODS: We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation. RESULTS: Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]). CONCLUSION: In ACS, bedside BNP levels predict CV events at 10 months, independent of many echocardiographic abnormalities including LVH. Furthermore, our study suggests that an additional 7 weeks post ACS BNP enhances risk stratification over and above a one-off high BNP at baseline.

The prognostic value of high sensitivity troponin T 7 weeks after an acute coronary syndrome.

OBJECTIVE: The role of high sensitivity troponin T (hs-TnT) in the convalescence phase after an acute coronary syndrome (ACS) is unknown. The authors aim to assess the prognostic utility of a single hs-TnT level at 7-week post-ACS. Second, the authors evaluated whether any serial changes in hs-TnT between the index admission and 7 weeks post-ACS had any link with the prognosis. Third, the authors assessed whether the prognostic utility of hs-TnT is independent of various echocardiographic abnormalities. METHODS: The authors measured hs-TnT levels in 326 consecutive patients at 7 weeks after an ACS event. The composite end point of death from any cause or acute myocardial infarction was evaluated over a median duration of 30 months. RESULTS: A high 7-week hs-TnT (>14 ng/l) predicted adverse clinical outcomes independent of conventional risk factors, left ventricular dysfunction and left ventricular hypertrophy on echocardiography (adjusted RR: 2.69 (95% CI 1.45 to 5.00)). Patients with persistent hs-TnT elevation at 7 weeks were also at an increased risk of cardiovascular events compared with those with an initial high hs-TnT which then normalised (unadjusted RR 3.39 (95% CI 2.02 to 5.68)). CONCLUSION: The authors have demonstrated the prognostic utility of a single 7-week hs-TnT measurement in routine ACS patients and that it could be used to assist medium term risk stratification in this patient cohort. In addition, the authors also showed that hs-TnT predicted long-term adverse prognosis independent of various echo parameters. Future studies should evaluate whether tailoring specific treatment interventions to higher risk individuals as identified by an elevated hs-TnT during the convalescence phase of ACS would improve clinical outcomes.

The prognostic significance of early and late anaemia in acute coronary syndrome.

BACKGROUND AND AIM: Anaemia in acute coronary syndrome (ACS) is a common and strong independent risk factor but it is unknown whether early anaemia is transient or whether it persists over the subsequent weeks. We also sought to evaluate whether late anaemia carries the similar prognostic significance as baseline anaemia. Another unknown is whether haemoglobin improves risk stratification over and above the GRACE score. DESIGN AND METHODS: Haemoglobin levels were prospectively measured in 448 consecutive patients presenting with ACS and at 7-weeks follow-up. Cardiovascular endpoints were defined as death or acute myocardial infarction (AMI) over a median duration of 30 months (range 1-50). RESULTS: The prevalence of anaemia on admission was 20% and this increased to 40% at 7-weeks follow-up. New anaemia occurred in 31% of patients. Baseline anaemia predicted CV endpoints independent of the admission GRACE (Global Registry of Acute Coronary Events) score [adjusted RR 2.54 (95% CI 1.73-3.71)]. Anaemia at 7-weeks follow-up was also a strong predictor of adverse outcomes [adjusted RR 1.67 (95% CI 1.04-2.69)]. Patients with persistent anaemia at 7 weeks were at an increased risk of death or AMI compared to those with persistently normal haemoglobin [unadjusted RR 3.58 (95% CI 2.04-6.29)]. CONCLUSION: In ACS, the prevalence of anaemia doubles from admission to 7-weeks follow-up (40%). Not only did baseline anaemia predict long-term prognosis independent of the admission GRACE score, but haemoglobin at 7-weeks post-ACS was also a simple independent predictor of adverse prognosis.