Sensitivity of cognitive function tests to acute hypoxia in healthy subjects: a systematic literature review

Acute exposure to hypoxia can lead to cognitive impairment. Therefore, hypoxia may become a safety concern for occupational or recreational settings at altitude. Cognitive tests are used as a tool to assess the degree to which hypoxia affects cognitive performance. However, so many different cognitive tests are used that comparing studies is challenging. This structured literature evaluation provides an overview of the different cognitive tests used to assess the effects of acute hypoxia on cognitive performance in healthy volunteers. Less frequently used similar cognitive tests were clustered and classified into domains. Subsequently, the different cognitive test clusters were compared for sensitivity to different levels of oxygen saturation. A total of 38 articles complied with the selection criteria, covering 86 different cognitive tests. The tests and clusters showed that the most consistent effects of acute hypoxia were found with the Stroop test (where 42% of studies demonstrated significant abnormalities). The most sensitive clusters were auditory/verbal memory: delayed recognition (83%); evoked potentials (60%); visual/spatial delayed recognition (50%); and sustained attention (47%). Attention tasks were not particularly sensitive to acute hypoxia (impairments in 0%-47% of studies). A significant hypoxia level-response relationship was found for the Stroop test (p = 0.001), as well as three clusters in the executive domain: inhibition (p = 0.034), reasoning/association (p = 0.019), and working memory (p = 0.024). This relationship shows a higher test sensitivity at more severe levels of hypoxia, predominantly below 80% saturation. No significant influence of barometric pressure could be identified in the limited number of studies where this was varied. This review suggests that complex and executive functions are particularly sensitive to hypoxia. Moreover, this literature evaluation provides the first step towards standardization of cognitive testing, which is crucial for a better understanding of the effects of acute hypoxia on cognition

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Days off scheduling - A 2-phase approach to personnel rostering

We discuss Days off scheduling as intermediate phase to personnel rostering

Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency

Over the past 5 yr several inactivating mutations in the LH receptor gene have been demonstrated to cause Leydig cell hypoplasia, a rare autosomal recessive form of male pseudohermaphroditism. Here, we report the identification of two new LH receptor mutations in a compound heterozygous case of complete Leydig hypoplasia and determine the cause of the signaling deficiency at a molecular level. On the paternal allele of the patient we identified in codon 343 a T to A transversion that changes a conserved cysteine in the hinge region of the receptor to serine (C343S); on the maternal allele a T to C transition causes another conserved cysteine at codon 543 in trans-membrane segment 5 to be altered to arginine (C543R). Both of these mutant receptors are completely devoid of hormone-induced cAMP reporter gene activation. Using Western blotting of expressed LH receptor protein with a hemagglutinin tag, we further show that despite complete absence of total and cell surface hormone binding, protein levels of both mutant LH receptors are only moderately affected

Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti-doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double-blinded, placebo-controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin beta) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl-PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl-PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl-PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings.Nephrolog

Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti-doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double-blinded, placebo-controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin beta) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl-PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl-PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl-PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings.Nephrolog