Rise, and pronounced regional variation, in methylphenidate, amphetamine, and lisdexamfetamine distribution in the United States
Background The prescription stimulants methylphenidate, amphetamine, and lisdexamfetamine are sympathomimetic drugs with therapeutic use. They are designated in the United States as Schedule II substances, defined by the 1970 Controlled Substances Act as having a “high potential for abuse”. Changing criteria for the diagnosis of Attention Deficit Hyperactivity Disorder in 2013 and the approval of lisdexamfetamine for binge eating disorder in 2015 may have impacted usage patterns. This report compared the pharmacoepidemiology of these stimulants in the United States from 2010–2017. Methods Distribution of amphetamine, methylphenidate, lisdexamfetamine were examined via weights extracted from the Drug Enforcement Administration’s (DEA) Automated Reports and Consolidated Ordering System (ARCOS). Median stimulant Daily Dosage per patient was determined for a regional analysis. The percent of cost and prescriptions attributable to each stimulant and atomoxetine in Medicaid from the “Drug Utilization 2018 - National Total” from the Centers for Medicare and Medicaid was determined. Results There was a rise in amphetamine (+67.5%) and lisdexamfetamine (+76.7%) from 2010–2017. The change in methylphenidate (−3.0%) was modest. Persons/day stimulant usage was lower in the West than in other US regions from 2014-2017. There was a negative correlation (r(48) = −0.43 to −0.65, p < .05) between the percent Hispanic population per state and the Daily Dosage/population per stimulant. Methylphenidate formulations accounted for over half (51.7%) of the $3.8 billion reimbursed by Medicaid and the plurality (45.4%) of the 22.0 million prescriptions. Amphetamine was responsible for less than one-fifth (18.4%) of cost but one-third of prescriptions (33.6%). Lisdexamfetamine’s cost (26.0%) exceeded prescriptions (16.3%). Conclusion The rising amphetamine and lisdexamfetamine distribution may correspond with a rise in adult ADHD diagnoses. Regional analysis indicates that stimulant distribution in the West may be distinct from that in other regions. The lower stimulant distribution in areas with greater Hispanic populations may warrant further study.
Vaddadi et al. (2021) Rise, and pronounced regional variation, in methylphenidate, amphetamine, and lisdexamfetamine distribution in the United States. PeerJ 9:e12619 https://doi.org/10.7717/peerj.12619
The relationship between numerosity perception and mathematics ability in adults: the moderating role of dots number
Background It has been proposed that numerosity perception is the cognitive underpinning of mathematics ability. However, the existence of the association between numerosity perception and mathematics ability is still under debate, especially in adults. The present study examined the relationship between numerosity perception and mathematics ability and the moderating role of dots number (i.e., the numerosity of items in dot set) in adults. Methods Sixty-four adult participants from Anshun University completed behavioral measures that tested numerosity perception of small numbers and large numbers, mathematics ability, inhibition ability, visual-spatial memory, and set-switching ability. Results We found that numerosity perception of small numbers correlated significantly with mathematics ability after controlling the influence of inhibition ability, visual-spatial memory, and set-switching ability, but numerosity perception of large numbers was not related to mathematics ability in adults. Conclusions These findings suggest that the dots number moderates the relationship between numerosity perception and mathematics ability in adults and may contribute to explaining the contradictory findings in the previous literature about the link between numerosity perception and mathematics ability.
Sun et al. (2021) The relationship between numerosity perception and mathematics ability in adults: the moderating role of dots number. PeerJ 9:e12660 https://doi.org/10.7717/peerj.12660
Interpopulational differences in the nutritional condition of Aequiyoldia eightsii (Protobranchia: Nuculanidae) from the Western Antarctic Peninsula during austral summer
The Western Antarctic Peninsula (WAP) is a hotspot for environmental change and has a strong environmental gradient from North to South. Here, for the first time we used adult individuals of the bivalve Aequiyoldia eightsii to evaluate large-scale spatial variation in the biochemical composition (measured as lipid, protein and fatty acids) and energy content, as a proxy for nutritional condition, of three populations along the WAP: O’Higgins Research Station in the north (63.3°S), Yelcho Research Station in mid-WAP (64.9°S) and Rothera Research Station further south (67.6°S). The results reveal significantly higher quantities of lipids (L), proteins (P), energy (E) and total fatty acids (FA) in the northern population (O’Higgins) (L: 8.33 ± 1.32%; P: 22.34 ± 3.16%; E: 171.53 ± 17.70 Joules; FA: 16.33 ± 0.98 mg g) than in the mid-WAP population (Yelcho) (L: 6.23 ± 0.84%; P: 18.63 ± 1.17%; E: 136.67 ± 7.08 Joules; FA: 10.93 ± 0.63 mg g) and southern population (Rothera) (L: 4.60 ± 0.51%; P: 13.11 ± 0.98%; E: 98.37 ± 5.67 Joules; FA: 7.58 ± 0.48 mg g). We hypothesize these differences in the nutritional condition could be related to a number of biological and environmental characteristics. Our results can be interpreted as a consequence of differences in phenology at each location; differences in somatic and gametogenic growth rhythms. Contrasting environmental conditions throughout the WAP such as seawater temperature, quantity and quality of food from both planktonic and sediment sources, likely have an effect on the metabolism and nutritional intake of this species.
Bascur et al. (2021) Interpopulational differences in the nutritional condition of Aequiyoldia eightsii (Protobranchia: Nuculanidae) from the Western Antarctic Peninsula during austral summer. PeerJ 9:e12679 https://doi.org/10.7717/peerj.12679
Sequence characteristics and phylogenetic analysis of H9N2 subtype avian influenza A viruses detected from poultry and the environment in China, 2018
H9N2 subtype avian influenza A virus (AIV) is a causative agent that poses serious threats to both the poultry industry and global public health. In this study, we performed active surveillance to identify H9N2 AIVs from poultry (chicken, duck, and goose) and the environment of different regions in China, and we phylogenetically characterized the sequences. AIV subtype-specific reverse transcription polymerase chain reaction (RT-PCR) showed that 5.43% (83/1529) samples were AIV positive, and 87.02% (67/77) of which were H9N2 AIVs. Phylogenetic analysis revealed that all H9N2 field viruses belonged to the Y280-like lineage, exhibiting 93.9–100% and 94.6–100% of homology in the hemagglutinin (HA) gene and 94.4–100% and 96.3–100% in the neuraminidase (NA) gene, at the nucleotide (nt) and amino acid (aa) levels, respectively. All field viruses shared relatively lower identities with vaccine strains, ranging from 89.4% to 97.7%. The aa sequence at the cleavage site (aa 333–340) in HA of all the isolated H9N2 AIVs was PSRSSRG/L, which is a characteristic of low pathogenic avian influenza virus (LPAIV). Notably, all the H9N2 field viruses harbored eight glycosylation sites, whereas a glycosylation site 218 NRT was missing and a new site 313 NCS was inserted. All field viruses had NGLMR as their receptor binding sites (RBS) at aa position 224–229, showing high conservation with many recently-isolated H9N2 strains. All H9N2 field isolates at position 226 had the aa Leucine (L), indicating their ability to bind to sialic acid (SA) α, a 2–6 receptor of mammals that poses the potential risk of transmission to humans. Our results suggest that H9N2 AIVs circulating in poultry populations that have genetic variation and the potential of infecting mammalian species are of great significance when monitoring H9N2 AIVs in China.
Gao et al. (2021) Sequence characteristics and phylogenetic analysis of H9N2 subtype avian influenza A viruses detected from poultry and the environment in China, 2018. PeerJ 9:e12512 https://doi.org/10.7717/peerj.12512
Understanding the transmission dynamics of Escherichia coli O157:H7 super-shedding infections in feedlot cattle
Background The presence of Escherichia coli O157:H7 (E. coli O157:H7) super-shedding cattle in feedlots has the potential to increase the overall number (bio-burden) of E. coli O157:H7 in the environment. It is important to identify factors to reduce the bio-burden of E. coli O157 in feedlots by clarifying practices associated with the occurrence of super-shedders in feedlot cattle. Methods The objective of this study is to (1) identify host, pathogen, and management risk factors associated with naturally infected feedlot cattle excreting high concentrations of E. coli O157:H7 in their feces and (2) to determine whether the ingested dose or the specific strain of E. coli O157:H7 influences a super-shedder infection within experimentally inoculated feedlot cattle. To address this, (1) pen floor fecal samples and herd parameters were collected from four feedlots over a 9-month period, then (2) 6 strains of E. coli O157:H7, 3 strains isolated from normal shedder steers and 3 strains isolated from super-shedder steers, were inoculated into 30 one-year-old feedlot steers. Five steers were assigned to each E. coli O157:H7 strain group and inoculated with targeted numbers of 102, 104, 106, 108, and 1010 CFU of bacteria respectively. Results In the feedlots, prevalence of infection with E. coli O157:H7 for the 890 fecal samples collected was 22.4%, with individual pen prevalence ranging from 0% to 90% and individual feedlot prevalence ranging from 8.4% to 30.2%. Three samples had E. coli O157:H7 levels greater than 104 MPN/g feces, thereby meeting the definition of super-shedder. Lower body weight at entry to the feedlot and higher daily maximum ambient temperature were associated with increased odds of a sample testing positive for E. coli O157:H7. In the experimental inoculation trial, the duration and total environmental shedding load of E. coli O157:H7 suggests that the time post-inoculation and the dose of inoculated E. coli O157:H7 are important while the E. coli O157:H7 strain and shedding characteristic (normal or super-shedder) are not. Discussion Under the conditions of this experiment, super-shedding appears to be the result of cattle ingesting a high dose of any strain of E. coli O157:H7. Therefore strategies that minimize exposure to large numbers of E. coli O157:H7 should be beneficial against the super-shedding of E. coli O157:H7 in feedlots.
Antaki-Zukoski et al. (2021) Understanding the transmission dynamics of Escherichia coli O157:H7 super-shedding infections in feedlot cattle. PeerJ 9:e12524 https://doi.org/10.7717/peerj.12524
A novel machine learning derived RNA-binding protein gene–based score system predicts prognosis of hepatocellular carcinoma patients
Background Although the expression of RNA-binding protein (RBP) genes in hepatocellular carcinoma (HCC) varies and is associated with tumor progression, there has been no overview study with multiple cohorts and large samples. The HCC-associated RBP genes need to be more accurately identified, and their clinical application value needs to be further explored. Methods First, we used the robust rank aggregation (RRA) algorithm to extract HCC-associated RBP genes from nine HCC microarray datasets and verified them in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and International Cancer Genome Consortium (ICGC) Japanese liver cancer (ICGC-LIRI-JP) cohort. In addition, the copy number variation (CNV), single-nucleotide variant (SNV), and promoter-region methylation data of HCC-associated RBP genes were analyzed. Using the random forest algorithm, we constructed an RBP gene–based prognostic score system (RBP-score). We then evaluated the ability of RBP-score to predict the prognosis of patients. The relationships between RBP-score and other clinical characteristics of patients were analyzed. Results The RRA algorithm identified 30 RBP mRNAs with consistent expression patterns across the nine HCC microarray datasets. These 30 RBP genes were defined as HCC-associated RBP genes. Their mRNA expression patterns were further verified in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Among these 30 RBP genes, some showed significant copy number gain or loss, while others showed differences in the methylation levels of their promoter regions. Some RBP genes were risk factors or protective factors for the prognosis of patients. We extracted 10 key HCC-associated RBP genes using the random forest algorithm and constructed an RBP-score system. RBP-score effectively predicted the overall survival (OS) and disease-free survival (DFS) of HCC patients and was associated with the tumor, node, metastasis (TNM) stage, α-fetoprotein (AFP), and metastasis risk. The clinical value of RBP-score was validated in datasets from different platforms. Cox analysis suggested that a high RBP-score was an independent risk factor for poor prognosis in HCC patients. We also successfully established a combined RBP-score+TNM LASSO-Cox model that more accurately predicted the prognosis. Conclusion The RBP-score system constructed based on HCC-associated RBP genes is a simple and highly effective prognostic evaluation tool. It is suitable for different subgroups of HCC patients and has cross-platform characteristics. Combining RBP-score with the TNM staging system or other clinical parameters can lead to an even greater clinical benefit. In addition, the identified HCC-associated RBP genes may serve as novel targets for HCC treatment.
Zhang et al. (2021) A novel machine learning derived RNA-binding protein gene–based score system predicts prognosis of hepatocellular carcinoma patients. PeerJ 9:e12572 https://doi.org/10.7717/peerj.12572
Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating
SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes’ integrity may abrogate its therapeutic potential against COVID and should be carefully considered.
Salerno et al. (2021) Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating. PeerJ 9:e12595 https://doi.org/10.7717/peerj.12595
Ability to detect antibodies to beak and feather disease virus in blood on filter paper decreases with duration of storage
Background Beak and feather disease virus (BFDV) is a circovirus that infects captive and wild psittacine birds, and is of conservation concern. The haemagglutination inhibition (HI) assay is used to determine antibody titres against BFDV, and the use of dried blood spots (DBS) on filter paper stored at room temperature has been suggested to be an equally valid technique to the use of frozen serum. However, research on other pathogens has found variable results when investigating the longevity of antibodies stored on DBS at room temperature. Consequently, we aimed to test the temporal stability of antibodies to BFDV in DBS samples stored long-term at room temperature. A further goal was to add to the current knowledge of antibody response to naturally acquired BFDV infection in crimson rosellas (Platycercus elegans). Methods Blood was collected from wild P. elegans in Victoria, Australia, that had been live-trapped (n = 9) or necropsied (n = 11). BFDV virus load data were obtained from blood stored in ethanol by real-time quantitative PCR (qPCR); antibody titres were obtained by HI assay from either DBS or serum samples, which had been collected concurrently. All HI assays were performed commercially by the Veterinary Diagnostic Laboratory (VDL) in Charles Sturt University, Australia, who were blind to BFDV blood status. Results HI titres from DBS stored at room temperature declined significantly over time (~80 weeks). By contrast, frozen serum samples assayed after 80 weeks in storage all had high HI titres, only varying up to one dilution step from the initial HI titres obtained from DBS at 3–6 weeks after sampling. Weak HI titres from DBS samples all came back negative when the test was repeated only nine weeks later. Novel high HI titres were reported in P. elegans, and while most birds with high antibody titres had corresponding negative qPCR results, a single subadult presented with high HI titres and virus load simultaneously. Conclusion Detection of antibodies on filter paper stored at room temperature decreases over time, increasing the chances of false negatives in these samples, and in repeated testing of samples with weak HI titres. Consequently, serum should be the preferred sample type to use for seroepidemiological studies on BFDV in parrots and other bird species. When not possible, it may help to store DBS on filter paper at −20 °C or lower. However, prompt testing of DBS samples (e.g., <6 weeks in storage) is recommended pending further research on antibody temporal stability. We also show that P. elegans, especially adults, can produce high antibody titres against BFDV, which may help them resist infection.
Blanch-Lázaro et al. (2021) Ability to detect antibodies to beak and feather disease virus in blood on filter paper decreases with duration of storage. PeerJ 9:e12642 https://doi.org/10.7717/peerj.12642
Utility of olfactory identification test for screening of cognitive dysfunction in community-dwelling older adults
Background There is a need for a large-scale screening test that can be used to detect dementia in older individuals at an early stage. Olfactory identification deficits have been shown to occur in the early stages of dementia, indicating their usefulness in screening tests. This study investigated the utility of an olfactory identification test as a screening test for mild cognitive dysfunction in community-dwelling older people. Methods The subjects were city-dwelling individuals aged over 65 years but under 85 years who had not been diagnosed with dementia or mild cognitive impairment. The Japanese version of the Mild Cognitive Impairment Screen was used to evaluate cognitive function. Based on the results, the subjects were divided into two groups: healthy group and cognitively impaired group. Olfactory identification abilities based on the Japanese version of the University of Pennsylvania Smell Identification Test were compared between the groups. Results There were 182 participants in total: 77 in the healthy group and 105 in the cognitively impaired group. The mean olfactory identification test score of the cognitively impaired group was significantly lower than that of the healthy group. The cognitive impairment test score was significantly correlated with the olfactory identification test score. Conclusions Cross-sectional olfactory identification deficits at baseline in community-dwelling older adults reflected cognitive dysfunction. Assessing olfactory identification ability might be useful as a screening test for mild cognitive dysfunction in community-dwelling older people.
Nogi et al. (2021) Utility of olfactory identification test for screening of cognitive dysfunction in community-dwelling older adults. PeerJ 9:e12656 https://doi.org/10.7717/peerj.12656
Sagittal spine disposition and pelvic tilt during outdoor fitness equipment use and their associations with kinanthropometry proportions in middle-aged and older adults
Background Outdoor fitness training has become popular as a tool for improving the health, especially middle-aged and older adults. For this purpose, outdoor fitness equipment (OFE) have been installed in public areas. However, their safety and effectiveness are still unknown. The aim of the present research was to analyze the sagittal disposition of the spine and pelvic tilt during the use of OFE, and to determine the influence of anthropometric variables on these factors in middle-aged and older adults. Methods Seventy healthy volunteers, 56 women and 14 men (age: 63.14 ± 8.19 years) participated in the study. Sagittal spine disposition and pelvic tilt were measured using a Spinal Mouse®, in the relaxed standing position, and during the use of the OFE. In addition, kinanthropometry variables were also measured according to the guidelines of the International Society for the Advancement of Kinanthropometry. Results Regarding thoracic kyphosis, a significant decrease was found in thoracic kyphosis in the initial position (IP) in single bonny rider (SBR) (p = 0.006) and row (p = 0.046), and a significant increase in the final position (FP) in the row (p = 0.011), surfboard (p < 0.001) and air walker (p = 0.027) machines. In relation to the lumbar curvature and pelvic tilt, a significant decrease in lumbar lordosis and a decrease in pelvic anteversion were observed in the IP and FP in SBR and row; and in the bike (p < 0.001) machine. In the surfboard machine, a significant decrease in lumbar lordosis was found (p = 0.002), with no changes in pelvic tilt. According to the multiple linear regression analysis, the subjects with a higher cormic index and height were more at risk of increasing their thoracic kyphosis, decreasing lumbar lordosis and/or decreasing pelvic anteversion towards pelvic retroversion. Conclusions Middle-aged and older adults show spinal misalignments when using the OFE with respect to the standing position, showing a decrease in the thoracic kyphosis in IP of SBR and ROW, and a significant increase in the surfboard and air walker, and in the FP of Row, in the lumbar lordosis in all the OFE in sitting and some in standing, and in the pelvic anteversion in all the OFE in sitting. The variables height and the cormic index explained most of the changes in sagittal spine disposition.
Abelleira-Lamela et al. (2021) Sagittal spine disposition and pelvic tilt during outdoor fitness equipment use and their associations with kinanthropometry proportions in middle-aged and older adults. PeerJ 9:e12657 https://doi.org/10.7717/peerj.12657