Reliability of fitness trackers at different prices for measuring steps and heart rate: a pilot study

The purpose of this pilot study was to assess the accuracy of steps and heart rate measurement of wrist fitness trackers at different prices. Four healthy college students voluntarily tested three wrist fitness bands and a sports watch (Xiaomi Mi Band, Fitbit Charge HRm, Fitbit Surge, and sports watch Polar M400). Subjects performed two sets of 10 series of 100 steps wearing the fitness trackers on an indoor track in two situations: walking and jogging. In the walking situation, the subjects wore a winter coat and gloves. The variables measured were the number of steps, the heart rate, and the level of error. The steps error percentage for all four devices was lower than 8%. The Fitbit Surge registered significantly more steps in the walking situation (p < 0.001). No significant differences were found in the steps measurements in the jogging situation (p = 0.138). In the jogging situation, significantly lower values in the heart rate measurements for the Xiaomi Mi Band, Fitbit Charger HR, and Fitbit Surge were found (p < 0.001). The results showed that the wearable fitness trackers were relatively accurate for tracking steps (on average, there was a level of error of 2–6%). The assessment of the steps was more accurate in the jogging situation (higher and faster arm swing) than in the walking situation, which involved wearing coats and gloves. The results showed that the wearable fitness trackers that were tested underestimate the heart rate with a level of error of approximately 6–11%. The step error was lower in the walking situation (less mobility of the devices). The price of the devices that were tested did not affect the accuracy of the steps and heart rate assessment. Further studies with a larger sample and more type of devices are needed to confirm these results

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression

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

Identification and functional analysis of glycemic trait loci in the China Health and Nutrition Survey

<div><p>To identify genetic contributions to type 2 diabetes (T2D) and related glycemic traits (fasting glucose, fasting insulin, and HbA1c), we conducted genome-wide association analyses (GWAS) in up to 7,178 Chinese subjects from nine provinces in the China Health and Nutrition Survey (CHNS). We examined patterns of population structure within CHNS and found that allele frequencies differed across provinces, consistent with genetic drift and population substructure. We further validated 32 previously described T2D- and glycemic trait-loci, including <i>G6PC2</i> and <i>SIX3-SIX2</i> associated with fasting glucose. At <i>G6PC2</i>, we replicated a known fasting glucose-associated variant (rs34177044) and identified a second signal (rs2232326), a low-frequency (4%), probably damaging missense variant (S324P). A variant within the lead fasting glucose-associated signal at <i>SIX3-SIX2</i> co-localized with pancreatic islet expression quantitative trait loci (eQTL) for <i>SIX3</i>, <i>SIX2</i>, and three noncoding transcripts. To identify variants functionally responsible for the fasting glucose association at <i>SIX3-SIX2</i>, we tested five candidate variants for allelic differences in regulatory function. The rs12712928-C allele, associated with higher fasting glucose and lower transcript expression level, showed lower transcriptional activity in reporter assays and increased binding to GABP compared to the rs12712928-G, suggesting that rs12712928-C contributes to elevated fasting glucose levels by disrupting an islet enhancer, resulting in reduced gene expression. Taken together, these analyses identified multiple loci associated with glycemic traits across China, and suggest a regulatory mechanism at the <i>SIX3-SIX2</i> fasting glucose GWAS locus.</p></div

Signals associated with levels of quantitative glycemic traits among non-diabetic subjects in CHNS.

<p>Signals associated with levels of quantitative glycemic traits among non-diabetic subjects in CHNS.</p

Fasting glucose locus near <i>G6PC2</i> exhibits two association signals in the CHNS.

<p>The first association signal, rs34177044 (red diamond) shows the strongest association in the initial unconditioned analysis of fasting glucose. Coding variant rs2232326 (S324P; blue diamond), remained locus-wide significant after conditioning on rs34177044. The diamonds indicate the lead variants, which exhibited the strongest evidence of association at the locus among 1000 Genomes Project Phase 3-imputed variants. Variants are colored based on LD with the lead variants, rs34177044 (red) and rs2232326 (blue) within 8,403 CHNS subjects.</p

Comparison by province of genome-wide significant signals for fasting glucose.

<p>Comparison by province of genome-wide significant signals for fasting glucose.</p

Pancreatic islet eQTL colocalizes with the fasting glucose GWAS locus.

<p>(A) rs895636 (purple diamond) shows the strongest association with fasting glucose in the CHNS. Variants are colored based on East Asian LD from 1000 Genomes Project Phase 3. (B) rs12712929 (purple diamond) shows the strongest association with expression of <i>SIX3</i> in pancreatic islets in European ancestry individuals. Variants are colored based on European LD from 1000 Genomes Project Phase 3. (C) Although the LD r² between rs895636 and rs12712929 is moderate in both European and East Asian populations (1000G Phase 3), one variant, rs12712928, exhibits high LD (r²>0.80) with rs895636 in East Asians and rs12712929 in Europeans (arrow). Red font indicates variants above r² of 0.80. Vertical bars indicate the genomic regions examined for allelic differences in regulatory function.</p