Communications Biophysics

Contains research objectives and reports on six research projects split into three sections.National Institutes of Health (Grant 5 P01 NS13126-07)National Institutes of Health (Training Grant 5 T32 NS07047-05)National Institutes of Health (Training Grant 2 T32 NS07047-06)National Science Foundation (Grant BNS 77-16861)National Institutes of Health (Grant 5 R01 NS1284606)National Institutes of Health (Grant 5 T32 NS07099)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 5 R01 NS14092-04)Gallaudet College SubcontractKarmazin Foundation through the Council for the Arts at M.I.T.National Institutes of Health (Grant 1 R01 NS1691701A1)National Institutes of Health (Grant 5 R01 NS11080-06)National Institutes of Health (Grant GM-21189

Communications Biophysics

Contains reports on eight research projects split into four sections.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 5 K04 NS00113)National Institutes of Health (Training Grant 5 T32 NS07047)National Science Foundation (Grant BNS80-06369)National Institutes of Health (Grant 5 ROl NS11153)National Institutes of Health (Fellowship 1 F32 NS06544)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 R01 NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 R01 NS14092)National Institutes of Health (Grant 2 R01 NS11680)National Institutes of Health (Grant 5 ROl1 NS11080)National Institutes of Health (Training Grant 5 T32 GM07301

Communications Biophysics

Contains reports on seven research projects split into three sections.National Institutes of Health (Grant 5 PO1 NS13126)National Institutes of Health (Grant 1 RO1 NS18682)National Institutes of Health (Training Grant 5 T32 NS07047)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 1 F33 NS07202-01)National Institutes of Health (Grant 5 RO1 NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Institutes of Health (Grant 1 RO1 NS16917)National Institutes of Health (Grant 1 RO1 NS14092-05)National Science Foundation (Grant BNS 77 21751)National Institutes of Health (Grant 5 R01 NS11080)National Institutes of Health (Grant GM-21189

Exercise and functional foods

Appropriate nutrition is an essential prerequisite for effective improvement of athletic performance, conditioning, recovery from fatigue after exercise, and avoidance of injury. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. In addition, several natural food components have been found to show physiological effects, and some of them are considered to be useful for promoting exercise performance or for prevention of injury. However, these foods should only be used when there is clear scientific evidence and with understanding of the physiological changes caused by exercise. This article describes various "functional foods" that have been reported to be effective for improving exercise performance or health promotion, along with the relevant physiological changes that occur during exercise

Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial

Summary: Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more eff ective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more eff ective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and effi cacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m², l-folinic acid 175 mg, fl uorouracil 400 mg/m² bolus, then 2400 mg/m² by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the fi rst 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratifi cation variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no signifi cant diff erences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had complications prolonging hospital stay (p=0·81). 98% (50 of 51) of postoperative chemotherapy patients had T3 or more advanced tumours confi rmed at post-resection pathology compared with 91% (90 of 99) of patients following preoperative chemotherapy (p=0·10). Preoperative therapy resulted in signifi cant downstaging of TNM5 compared with the postoperative group (p=0·04), including two pathological complete responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p<0·0001), resection margin involvement (4% [ four of 99] vs 20% [ten of 50], p=0·002), and blinded centrally scored tumour regression grading: 31% (29 of 94) vs 2% (one of 46) moderate or greater regression (p=0·0001). Interpretation Preoperative chemotherapy for radiologically staged, locally advanced operable primary colon cancer is feasible with acceptable toxicity and perioperative morbidity. Proceeding to the phase 3 trial, to establish whether the encouraging pathological responses seen with preoperative therapy translates into improved long-term oncological outcome, is appropriate

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

EDTA improves stability of whole blood C-peptide and insulin to over 24 hours at room temperature.

C-peptide and insulin measurements in blood provide useful information regarding endogenous insulin secretion. Conflicting evidence on sample stability and handling procedures continue to limit the widespread clinical use of these tests. We assessed the factors that altered the stability of insulin and C-peptide in blood.This article is freely available online via Open Access. Click on the 'Additional Link' above to access the full text

Beta-Ketothiolase Deficiency Presenting with Metabolic Stroke After a Normal Newborn Screen in Two Individuals

Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase) deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. It results from biallelic pathogenic variants in the ACAT1 gene, encoding mitochondrial beta-ketothiolase. We report two cases of beta-ketothiolase deficiency presenting with acute ketoacidosis and “metabolic stroke.” The first patient presented at 28 months of age with metabolic acidosis and pallidal stroke in the setting of a febrile gastrointestinal illness. Although 2-methyl-3-hydroxybutyric acid and trace quantities of tiglylglycine were present in urine, a diagnosis of glutaric acidemia type I was initially suspected due to the presence of glutaric and 3-hydroxyglutaric acids. A diagnosis of beta-ketothiolase deficiency was ultimately made through whole exome sequencing which revealed compound heterozygous variants in ACAT1. Fibroblast studies for beta-ketothiolase enzyme activity were confirmatory. The second patient presented at 6 months of age with ketoacidosis, and was found to have elevations of urinary 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, and tiglylglycine. Sequencing of ACAT1 demonstrated compound heterozygous presumed causative variants. The patient exhibited choreoathethosis 2 months after the acute metabolic decompensation. These cases highlight that, similar to a number of other organic acidemias and mitochondrial disorders, beta-ketothiolase deficiency can present with metabolic stroke. They also illustrate the variability in clinical presentation, imaging, and biochemical evaluation that make screening for and diagnosis of this rare disorder challenging, and further demonstrate the value of whole exome sequencing in the diagnosis of metabolic disorders

Flow diagram detailing the sample collection protocol for the preservative and stability study over 24 hours.

<p>At each time point the samples were centrifuged at 3000g for 10 minutes and the supernatant frozen at −80°C.</p