bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiating severe and non-severe lower respiratory tract illness in patients hospitalized with influenza: Development of the Influenza Disease Evaluation and Assessment of Severity (IDEAS) scale
Authors: Chow Eric J. , Tenforde Mark W. , Rolfes Melissa A. , Lee Benjamin , Chodisetty Shreya , Ramirez Julio A. , Fry Alicia M. , Patel Manish M.
Published: October 2021

Background

Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury.

Methods

We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010–2013 seasons.

Results

We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2–8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%).

Conclusion

We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.
Estimation of air temperature and the mountain-mass effect in the Yellow River Basin using multi-source data
Authors: Pan Ziwu , Zhu Jun , Liu Junjie , Gu Jiangyan , Liu Zhenzhen , Qin Fen , Pan Yu
Published: October 2021

Quantitative studies of the multiple factors influencing the mountain-mass effect, which causes higher temperatures in mountainous than non-mountainous regions, remain insufficient. This study estimated the air temperature in the Yellow River Basin, which spans three different elevation ranges, using multi-source data to address the uneven distribution of regional meteorological stations. The differences in mountain-mass effect for different geomorphic regions at the same altitude were then compared. The Manner–Kendall nonparametric test was used to analyse time series changes in temperature. Moreover, we employed the geographically weighted regression (GWR) model, with MODIS land-surface and air-temperature data, station-based meteorological data, vertical temperature gradients corresponding to the 2000–2015 period, and elevation data, to estimate the correlation between monthly mean surface temperature and air temperature in the Yellow River Basin. The following major results were obtained. (1) The GWR method and ground station-based observations enhanced the accuracy of air-temperature estimates with an error of only ± 0.74°C. (2) The estimated annual variations in the spatial distributions of 12-month average temperatures showed that the upper Tibetan Plateau is characterised by low annual air temperatures with a narrow spatial distribution, whereas north-eastern areas upstream of the Inner Mongolia Plateau are characterised by higher air temperatures. Changes in the average monthly air temperature were also high in the middle and lower reaches, with a narrow spatial distribution. (3) Considering the seasonal variation in the temperature lapse rate, the mountain-mass effect in the Yellow River Basin was very high. In the middle of each season, the variation of air temperature at a given altitude over the Tibetan Plateau was higher than that over the Loess Plateau and Jinji Mountain. The results of this study reveal the unique temperature characteristics of the Yellow River Basin according to its geomorphology. Furthermore, this research contributes to quantifying mountain-mass effects.
Newborn infant skin gene expression: Remarkable differences versus adults
Authors: Visscher Marty O. , Hu Ping , Carr Andrew N. , Bascom Charles C. , Isfort Robert J. , Creswell Kellen , Adams Rachel , Tiesman Jay P. , Lammers Karen , Narendran Vivek
Published: October 2021

At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.
Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia
Authors: Miller Christopher R. , Monk Jonathan M. , Szubin Richard , Berti Andrew D.
Published: October 2021

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.
Adverse event profile and associated factors following surgical voluntary medical male circumcision in two regions of Namibia, 2015–2018
Authors: O’Bryan Gillian , Feldacker Caryl , Ensminger Alison , Nghatanga Magdaleena , Brandt Laura , Shepard Mark , Billah Idel , Aupokolo Mekondjo , Mengistu Assegid Tassew , Forster Norbert , Zemburuka Brigitte , Sithole Edwin , Mutandi Gram , Barnhart Scott , O’Malley Gabrielle
Published: October 2021

Introduction

Monitoring clinical safety of voluntary medical male circumcision (VMMC) is critical to minimize risk as VMMC programs for HIV prevention are scaled. This cross-sectional analysis describes the adverse event (AE) profile of a large-scale, routine VMMC program and identifies factors associated with the development, severity, and timing of AEs to provide recommendations for program quality improvement.

Materials and methods

From 2015–2018 there were 28,990 circumcisions performed in International Training and Education Center for Health (I-TECH) supported regions of Namibia in collaboration with the Ministry of Health and Social Services. Two routine follow-up visits after VMMC were scheduled to identify clients with AEs. Summary statistics were used to describe characteristics of all VMMC clients and the subset who experienced an AE. We used chi-square tests to evaluate associations between AE timing, patient age, and other patient and AE characteristics. We used a logistic regression model to explore associations between patient characteristics and AE severity.

Results

Of the 498 clients with AEs (AE rate of 1.7%), 40 (8%) occurred ≤2 days, 262 (53%) occurred 3–7 days, 161 (32%) between day 8 and 14, and 35 (7%) were ≥15 days post-VMMC. Early AEs (on or before day 2) tended to be severe and categorized as bleeding, while infections were the most common AEs occurring later (p<0.001). Younger clients (aged 10–14 years) experienced more infections, whereas older clients experienced more bleeding (p<0.001).

Conclusions

Almost 40% of AEs occurred after the second follow-up visit, of which 179 (91%) were infections. Improvements in pre-surgical and post-surgical counselling and post-operative educational materials encouraging clients to seek care at any time, adoption of alternative follow-up methods, and the addition of a third follow-up visit may improve outcomes for patients. Enhancing post-surgical counselling and emphasizing wound care for younger VMMC clients and their caregivers could help mitigate elevated risk of infection.
Dietary inulin supplementation modulates the composition and activities of carbohydrate-metabolizing organisms in the cecal microbiota of broiler chickens
Authors: Xia Yun , Miao Jiarong , Zhang Yu , Zhang Hongbo , Kong Lingdong , Seviour Robert , Kong Yunhong
Published: October 2021

Inulin is a highly effective prebiotic and an attractive alternative to antibiotic growth promoters for increasing production and maintaining health in chickens. However, how inulin elicits its effects on members of the intestinal microbiota is unknown, even though their importance for energy metabolism and the health of chickens is well documented. A combination of 16S rRNA Illumina sequencing and transcriptomic analysis was used to investigate the effects of supplementing a corn-based basal diet with 1, 2, or 4% inulin or 400 ppm bacitracin on the composition, diversity and activities of carbohydrate-metabolizing organisms (CMOs) in the cecal microbiota of broiler chickens. We found that members of Bacteroides were the most abundant non-starch degrading CMOs, contributing 43.6–52.1% of total glycoside hydrolase genes and 34.6–47.1% activity to the meta-transcriptomes of chickens in the different dietary groups, although members of Parabacteroides, Prevotella, Alistipes, Clostridium, Barnesiella, Blastocystis, Faecalibacterium and others were also actively involved. Inulin and bacitracin inclusion in the basal diet did not change significantly the composition or diversity of these CMOs. Inulin supplementation at three levels promoted the activities of Bacteroides, Prevotella and Bifidobacterium, and 2% level appears to be the most optimal dosage for bifidobacterial activity.
Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease
Authors: Cremer Sebastian , Pilgram Lisa , Berkowitsch Alexander , Stecher Melanie , Rieg Siegbert , Shumliakivska Mariana , Bojkova Denisa , Wagner Julian Uwe Gabriel , Aslan Galip Servet , Spinner Christoph , Luxán Guillermo , Hanses Frank , Dolff Sebastian , Piepel Christiane , Ruppert Clemens , Guenther Andreas , Rüthrich Maria Madeleine , Vehreschild Jörg Janne , Wille Kai , Haselberger Martina , Heuzeroth Hanno , Hansen Arne , Eschenhagen Thomas , Cinatl Jindrich , Ciesek Sandra , Dimmeler Stefanie , Borgmann Stefan , Zeiher Andreas ,   on behalf of the LEOSS study group
Published: October 2021

Aims

Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.

Methods and results

We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.

Conclusion

These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
Quality of adolescent and youth-friendly health services in Dehana district public health facilities, northeast Ethiopia: Using the Donabedian quality framework
Authors: Gebrie Muluye , Asrade Geta , Tsehay Chalie Tadie , Yazachew Lake , Dellie Endalkachew
Published: October 2021

Introduction

Adolescents and youths who need exceptional healthcare are the shapers and leaders of our global future. However, many of them are died prematurely, while others suffer from diseases partly because of the poor quality of health services. Thus, this study aimed to assess the quality of Adolescent and Youth-friendly Health Services (AYFHS) and associated factors in the public health facilities of Dehana district, Northeast Ethiopia.

Methods

A facility-based quantitative cross-sectional study supported with a qualitative component was conducted from February 24 to March 30, 2020. The quality of AYFHS was measured using the Donbidean framework (structure, process and output component). Accordingly, a total of 431 adolescents and youths, five health facilities, twenty-five client-provider interaction observations, and nine key informant interviews were conducted. Binary logistic regression analysis was done, and variables with a p-value of < 0.05 and Adjusted Odds Ratio (AOR) with its 95% Confidence Interval (CI) were used to measure the association. The qualitative data were audio-recorded and transcribed verbatim. Then, Open Code 4.03 software was used to manage and analyze the data.

Results

The quality of adolescent and youth-friendly health services was 58.8, 46.4, and 47.2% for structural, process, and output quality dimensions, respectively. The predictor variables for output quality were, being a student (AOR: 2.07, 95%CI: 1.07–3.40), farmers (AOR: 2.59, 95%CI: 1.25–5.39), own income sources (AOR: 1.99, 95%CI: 1.03–3.85), exempted services (AOR: 2.30, 95%CI: 1.43–3.71) and long waiting time (AOR: 3.8495%CI: 1.80–8.23).

Conclusions

The overall quality of adolescent and youth-friendly health services was still lower than the WHO good quality standards. The structural quality dimension was affected by the unavailability of adequate and trained health service providers, poor engagement of adolescents and youths in the facility governance structure, unavailability of guidelines, protocols and procedures. In contrast, the process quality dimension was also compromised due to the provider’s poor compliance with the national AYFHS guidelines. Therefore, health facilities need to engage adolescents and youths in the health facility governance structure, and providers should comply with the national guideline.
Proximal-end bias from in-vitro reconstituted nucleosomes and the result on downstream data analysis
Authors: Bates David A. , Bates Charles E. , Earl Andrew S. , Skousen Colin , Fetbrandt Ashley N. , Ritchie Jordon , Bodily Paul M. , Johnson Steven M.
Published: October 2021

The most basic level of eukaryotic gene regulation is the presence or absence of nucleosomes on DNA regulatory elements. In an effort to elucidate in vivo nucleosome patterns, in vitro studies are frequently used. In vitro, short DNA fragments are more favorable for nucleosome formation, increasing the likelihood of nucleosome occupancy. This may in part result from the fact that nucleosomes prefer to form on the terminal ends of linear DNA. This phenomenon has the potential to bias in vitro reconstituted nucleosomes and skew results. If the ends of DNA fragments are known, the reads falling close to the ends are typically discarded. In this study we confirm the phenomenon of end bias of in vitro nucleosomes. We describe a method in which nearly identical libraries, with different known ends, are used to recover nucleosomes which form towards the terminal ends of fragmented DNA. Finally, we illustrate that although nucleosomes prefer to form on DNA ends, it does not appear to skew results or the interpretation thereof.
Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis
Authors: Charfeddine Cherine , Laroussi Nadia , Mkaouar Rahma , Jouini Raja , Khayat Olfa , Redissi Aladin , Mosbah Amor , Dallali Hamza , Chedly Debbiche Achraf , Zaouak Anissa , Fenniche Sami , Abdelhak Sonia , Hammami-Ghorbel Houda
Published: October 2021

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.
Quantitative evaluation of abnormal finger movements in myelopathy hand during the grip and release test using gyro sensors
Authors: Date Shota , Nakanishi Kazuyoshi , Fujiwara Yasushi , Yamada Kiyotaka , Kamei Naosuke , Kurumadani Hiroshi , Yoshimura Manabu , Ueda Akio , Ishii Yosuke , Ohta Ryo , Kotaka Shinji , Tsuchikawa Yuji , Nakamae Toshio , Ishikawa Masakazu , Hirao Ken , Fujimoto Yoshinori , Adachi Nobuo , Sunagawa Toru
Published: October 2021

Previous studies have reported qualitative characteristics of myelopathy hand, but few studies have reported quantitative kinematic parameters of this condition. Our purpose of this study was to quantitatively evaluate the abnormal finger movements in patients with cervical compressive myelopathy (CCM) (termed myelopathy hand) and to understand the characteristics of myelopathy hand during the grip and release test (GRT) using gyro sensors. Sixty patients with CCM (severe: n = 30; mild-to-moderate: n = 30) and sixty healthy adults (age-matched control: n = 30; young control: n = 30) were included in this study. All participants performed the GRT. The index and little fingers’ and the wrist’s movements during the GRT were recorded using three gyro sensors. The number of cycles, switching time-delay, time per cycle, and peak angular velocity were calculated and compared between groups. Patients with severe CCM had the lowest number of cycles and longest switching time-delays, followed by patients with mild-to-moderate CCM, the age-matched control group, and the young control group. The time per cycle and the peak angular velocities of fingers in participants with severe CCM were significantly lower than those in participants with mild-to-moderate CCM; however, there were no significant differences between the control groups. The peak angular velocities of fingers were significantly lower during extension motions than during flexion motions in participants with CCM. Participants with CCM have lower peak angular velocities during finger movement. Finger extension also is impaired in participants with CCM. Abnormal finger movements and the severity of myelopathy in participants with CCM can be assessed using gyro sensors.
The impact of the Th17:Treg axis on the IgA-Biome across the glycemic spectrum
Authors: Essigmann Heather T. , Hoffman Kristi L. , Petrosino Joseph F. , Jun Goo , Aguilar David , Hanis Craig L. , DuPont Herbert L. , Brown Eric L.
Published: October 2021

Secretory IgA (SIgA) is released into mucosal surfaces where its function extends beyond that of host defense to include the shaping of resident microbial communities by mediating exclusion/inclusion of respective microbes and regulating bacterial gene expression. In this capacity, SIgA acts as the fulcrum on which host immunity and the health of the microbiota are balanced. We recently completed an analysis of the gut and salivary IgA-Biomes (16S rDNA sequencing of SIgA-coated/uncoated bacteria) in Mexican-American adults that identified IgA-Biome differences across the glycemic spectrum. As Th17:Treg ratio imbalances are associated with gut microbiome dysbiosis and chronic inflammatory conditions such as type 2 diabetes, the present study extends our prior work by examining the impact of Th17:Treg ratios (pro-inflammatory:anti-inflammatory T-cell ratios) and the SIgA response (Th17:Treg-SIgA axis) in shaping microbial communities. Examining the impact of Th17:Treg ratios (determined by epigenetic qPCR lymphocyte subset quantification) on the IgA-Biome across diabetes phenotypes identified a proportional relationship between Th17:Treg ratios and alpha diversity in the stool IgA-Biome of those with dysglycemia, significant changes in community composition of the stool and salivary microbiomes across glycemic profiles, and genera preferentially abundant by T-cell inflammatory phenotype. This is the first study to associate epigenetically quantified Th17:Treg ratios with both the larger and SIgA-fractionated microbiome, assess these associations in the context of a chronic inflammatory disease, and offers a novel frame through which to evaluate mucosal microbiomes in the context of host responses and inflammation.
Common and distinct predictors of non-symbolic and symbolic ordinal number processing across the early primary school years
Authors: Finke Sabrina , Banfi Chiara , Freudenthaler H. Harald , Steiner Anna F. , Vogel Stephan E. , Göbel Silke M. , Landerl Karin
Published: October 2021

What are the cognitive mechanisms supporting non-symbolic and symbolic order processing? Preliminary evidence suggests that non-symbolic and symbolic order processing are partly distinct constructs. The precise mechanisms supporting these skills, however, are still unclear. Moreover, predictive patterns may undergo dynamic developmental changes during the first years of formal schooling. This study investigates the contribution of theoretically relevant constructs (non-symbolic and symbolic magnitude comparison, counting and storage and manipulation components of verbal and visuo-spatial working memory) to performance and developmental change in non-symbolic and symbolic numerical order processing. We followed 157 children longitudinally from Grade 1 to 3. In the order judgement tasks, children decided whether or not triplets of dots or digits were arranged in numerically ascending order. Non-symbolic magnitude comparison and visuo-spatial manipulation were significant predictors of initial performance in both non-symbolic and symbolic ordering. In line with our expectations, counting skills contributed additional variance to the prediction of symbolic, but not of non-symbolic ordering. Developmental change in ordering performance from Grade 1 to 2 was predicted by symbolic comparison skills and visuo-spatial manipulation. None of the predictors explained variance in developmental change from Grade 2 to 3. Taken together, the present results provide robust evidence for a general involvement of pair-wise magnitude comparison and visuo-spatial manipulation in numerical ordering, irrespective of the number format. Importantly, counting-based mechanisms appear to be a unique predictor of symbolic ordering. We thus conclude that there is only a partial overlap of the cognitive mechanisms underlying non-symbolic and symbolic order processing.
Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys
Authors: Urabe Asako , Doi Shigehiro , Nakashima Ayumu , Ike Takeshi , Morii Kenichi , Sasaki Kensuke , Doi Toshiki , Arihiro Koji , Masaki Takao
Published: October 2021

Hypoxia is a common pathway to the progression of end-stage kidney disease. Retinoic acid-inducible gene I (RIG-I) encodes an RNA helicase that recognizes viruses including SARS-CoV2, which is responsible for the production of interferon (IFN)-α/β to prevent the spread of viral infection. Recently, RIG-I activation was found under hypoxic conditions, and klotho deficiency was shown to intensify the activation of RIG-I in mouse brains. However, the roles of these functions in renal inflammation remain elusive. Here, for in vitro study, the expression of RIG-I and IFN-α/β was examined in normal rat kidney (NRK)-52E cells incubated under hypoxic conditions (1% O2). Next, siRNA targeting RIG-I or scramble siRNA was transfected into NRK52E cells to examine the expression of RIG-I and IFN-α/β under hypoxic conditions. We also investigated the expression levels of RIG-I and IFN-α/β in 33 human kidney biopsy samples diagnosed with IgA nephropathy. For in vivo study, we induced renal hypoxia by clamping the renal artery for 10 min in wild-type mice (WT mice) and Klotho-knockout mice (Kl−/− mice). Incubation under hypoxic conditions increased the expression of RIG-I and IFN-α/β in NRK52E cells. Their upregulation was inhibited in NRK52E cells transfected with siRNA targeting RIG-I. In patients with IgA nephropathy, immunohistochemical staining of renal biopsy samples revealed that the expression of RIG-I was correlated with that of IFN-α/β (r = 0.57, P<0.001, and r = 0.81, P<0.001, respectively). The expression levels of RIG-I and IFN-α/β were upregulated in kidneys of hypoxic WT mice and further upregulation was observed in hypoxic Kl−/− mice. These findings suggest that hypoxia induces the expression of IFN-α/β through the upregulation of RIG-I, and that klotho deficiency intensifies this hypoxia-induced expression in kidneys.
The cariogenic effect of starch on oral microcosm grown within the dual constant depth film fermenter
Authors: Roberts Jonathan M. , Bradshaw David J. , Lynch Richard J. M. , Higham Susan M. , Valappil Sabeel P.
Published: October 2021

Evidence on the link between starch intake and caries incidence is conflicting, therefore the cariogenicity of starch compared with sucrose was explored using a dual Constant Depth Film Fermenter (dCDFF) biotic model system. Bovine enamel discs were used as a substrate and the dCDFF was inoculated using human saliva. CDFF units were supplemented with artificial saliva growth media at a constant rate to mimic resting salivary flow rate over 14 days. The CDFF units were exposed to different conditions, 2% sucrose or 2% starch 8 times daily and either no additional fluoride or 1450 ppm F- twice daily. Bovine enamel discs were removed at intervals (days 3, 7, 10 and 14) for bacterial enumeration and enamel analysis using Quantitative Light Induced Fluorescence (QLF) and Transverse Microradiography (TMR). Results showed that in the absence of fluoride there was generally no difference in mineral loss between enamel exposed to either sucrose or starch when analysed using TMR and QLF (P > 0.05). In the presence of fluoride by day 14 there was significantly more mineral loss under starch than sucrose when analysed with TMR (P < 0.05). It was confirmed that starch and sucrose are similarly cariogenic within the dCDFF in the absence of fluoride. With the aid of salivary amylase, the bacteria utilise starch to produce an acidic environment similar to that of bacteria exposed to sucrose only. In the presence of fluoride, starch was more cariogenic which may be due to the bacteria producing a more hydrophobic intercellular matrix lowering the penetration of fluoride through the biofilm. This is significant as it indicates that the focus on sugars being the primary cause of caries may need re-evaluating and an increase in focus on carbohydrates is needed as they may be similarly cariogenic as sugars if not more so.
Increase in rear-end collision risk by acute stress-induced fatigue in on-road truck driving
Authors: Minusa Shunsuke , Mizuno Kei , Ojiro Daichi , Tanaka Takeshi , Kuriyama Hiroyuki , Yamano Emi , Kuratsune Hirohiko , Watanabe Yasuyoshi
Published: October 2021

Increasing road crashes related to occupational drivers’ deteriorating health has become a social problem. To prevent road crashes, warnings and predictions of increased crash risk based on drivers’ conditions are important. However, in on-road driving, the relationship between drivers’ physiological condition and crash risk remains unclear due to difficulties in the simultaneous measurement of both. This study aimed to elucidate the relationship between drivers’ physiological condition assessed by autonomic nerve function (ANF) and an indicator of rear-end collision risk in on-road driving. Data from 20 male truck drivers (mean ± SD, 49.0±8.2 years; range, 35–63 years) were analyzed. Over a period of approximately three months, drivers’ working behavior data, such as automotive sensor data, and their ANF data were collected during their working shift. Using the gradient boosting decision tree method, a rear-end collision risk index was developed based on the working behavior data, which enabled continuous risk quantification. Using the developed risk index and drivers’ ANF data, effects of their physiological condition on risk were analyzed employing a logistic quantile regression method, which provides wider information on the effects of the explanatory variables, after hierarchical model selection. Our results revealed that in on-road driving, activation of sympathetic nerve activity and inhibition of parasympathetic nerve activity increased each quantile of the rear-end collision risk index. The findings suggest that acute stress-induced drivers’ fatigue increases rear-end collision risk. Hence, in on-road driving, drivers’ physiological condition monitoring and ANF-based stress warning and relief system can contribute to promoting the prevention of rear-end truck collisions.
TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure
Authors: Uchida Takatoshi , Shimizu Shota , Yamagishi Reiko , Tokuoka Suzumi M. , Kita Yoshihiro , Sakata Rei , Honjo Megumi , Aihara Makoto
Published: October 2021

Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how transient receptor potential cation channel subfamily V member 4 (TRPV4) functions in human trabecular meshwork cells (HTMC) and affects intraocular pressure (IOP). HTMC were treated with TRPV4 siRNA, followed by incubation for 24 hours. We confirmed the suppression of TRPV4 mRNA expression and the reduction of Ca2+ influx by the TRPV4 agonist GSK1016790A in TRPV4 siRNA-treated HTMC. TRPV4 siRNA-treated HTMC exhibited a significant reduction in Ca2+ influx and production of arachidonic acid and prostaglandin (PG) E2 induced by mechanical stretch, and direct activation of TRPV4 by GSK1016790A increased production of arachidonic acid, PGE2, and PGD2 and inhibited gel contraction. Furthermore, TRPV4-deficient mice had higher IOP than wild-type mice, and GSK1016790A administration lowered IOP. These results suggest that TRPV4 mediates the cellular response induced by trabecular meshwork stretch, leading to IOP reduction through the production of prostaglandins and inhibition of cell contraction. Targeting TRPV4 may have therapeutic benefits that lead to lowering IOP in glaucoma patients.
Inter-species cortical registration between macaques and humans using a functional network property under a spherical demons framework
Authors: Nam Haewon , Pae Chongwon , Eo Jinseok , Oh Maeng-Keun , Park Hae-Jeong
Published: October 2021

Systematic evaluation of cortical differences between humans and macaques calls for inter-species registration of the cortex that matches homologous regions across species. For establishing homology across brains, structural landmarks and biological features have been used without paying sufficient attention to functional homology. The present study aimed to determine functional homology between the human and macaque cortices, defined in terms of functional network properties, by proposing an iterative functional network-based registration scheme using surface-based spherical demons. The functional connectivity matrix of resting-state functional magnetic resonance imaging (rs-fMRI) among cortical parcellations was iteratively calculated for humans and macaques. From the functional connectivity matrix, the functional network properties such as principal network components were derived to estimate a deformation field between the human and macaque cortices. The iterative registration procedure updates the parcellation map of macaques, corresponding to the human connectome project’s multimodal parcellation atlas, which was used to derive the macaque’s functional connectivity matrix. To test the plausibility of the functional network-based registration, we compared cortical registration using structural versus functional features in terms of cortical regional areal change. We also evaluated the interhemispheric asymmetry of regional area and its inter-subject variability in humans and macaques as an indirect validation of the proposed method. Higher inter-subject variability and interhemispheric asymmetry were found in functional homology than in structural homology, and the assessed asymmetry and variations were higher in humans than in macaques. The results emphasize the significance of functional network-based cortical registration across individuals within a species and across species.
The importance of formal versus informal mindfulness practice for enhancing psychological wellbeing and study engagement in a medical student cohort with a 5-week mindfulness-based lifestyle program
Authors: Kakoschke Naomi , Hassed Craig , Chambers Richard , Lee Kevin
Published: October 2021

Purpose

Medical students commonly experience elevated psychological stress and poor mental health. To improve psychological wellbeing, a 5-week mindfulness-based lifestyle course was delivered to a first-year undergraduate medical student cohort as part of the core curriculum. This study investigated the effects of the program on mental health, perceived stress, study engagement, dispositional mindfulness, and whether any improvements were related to amount of formal and/or informal mindfulness practice.

Methods

Participants were first year undergraduate medical students (N = 310, 60% female, M = 18.60 years) with N = 205 individuals completing pre and post course questionnaires in a 5-week mindfulness-based lifestyle intervention. At pre- and post-intervention, participants completed the Mental Health Continuum-Short Form, the Perceived Stress Scale, the Utrecht Work Engagement Scale for Students, the Freiburg Mindfulness Inventory, and the Mindfulness Adherence Questionnaire.

Results

Mental health, perceived stress, study engagement, and mindfulness all improved from pre- to post-intervention (all p values < .001). Improvements on these outcome measures were inter-related such that PSS change scores were negatively correlated with all other change scores, FMI change scores were positively correlated with MHC-SF and UWES-S change scores, the latter of which was positively correlated with MHC-SF change scores (all p values < .01). Finally, observed improvements in all of these outcomes were positively related to informal practice quality while improved FMI scores were related to formal practice (all p values < .05).

Conclusions

A 5-week mindfulness-based program correlates with improving psychological wellbeing and study engagement in medical students. These improvements particularly occur when students engage in informal mindfulness practice compared to formal practice.
Association between hepatic oxygenation on near-infrared spectroscopy and clinical factors in patients undergoing hemodialysis
Authors: Ueda Yuichiro , Ookawara Susumu , Ito Kiyonori , Sasabuchi Yusuke , Hayasaka Hideyuki , Kofuji Masaya , Uchida Takayuki , Imai Sojiro , Kiryu Satoshi , Minato Saori , Miyazawa Haruhisa , Sanayama Hidenori , Hirai Keiji , Tabei Kaoru , Morishita Yoshiyuki
Published: October 2021

The hepato-splanchnic circulation directly influences oxygenation of the abdominal organs and plays an important role in compensating for the blood volume reduction that occurs in the central circulation during hemodialysis (HD) with ultrafiltration. However, the hepato-splanchnic circulation and oxygenation cannot be easily evaluated in the clinical setting of HD therapy. We included 185 HD patients and 15 healthy volunteers as the control group in this study. Before HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting the hepato-splanchnic circulation and oxygenation, was monitored using an INVOS 5100c oxygen saturation monitor. Hepatic rSO2 was significantly lower in patients undergoing HD than in healthy controls (56.4 ± 14.9% vs. 76.2 ± 9.6%, p < 0.001). Multivariable regression analysis showed that hepatic rSO2 was independently associated with body mass index (BMI; standardized coefficient: 0.294), hemoglobin (Hb) level (standardized coefficient: 0.294), a history of cardiovascular disease (standardized coefficient: -0.157), mean blood pressure (BP; standardized coefficient: 0.154), and serum albumin concentration (standardized coefficient: 0.150) in Model 1 via a simple linear regression analysis. In Model 2 using the colloid osmotic pressure (COP) in place of serum albumin concentration, the COP (standardized coefficient: 0.134) was also identified as affecting hepatic rSO2. Basal hepatic oxygenation before HD might be affected by BMI, Hb levels, a history of cardiovascular disease, mean BP, serum albumin concentration, and the COP. Further prospective studies are needed to clarify whether changes in these parameters, including during HD, affect the hepato-splanchnic circulation and oxygenation in HD patients.
Marek’s disease virus prolongs survival of primary chicken B-cells by inducing a senescence-like phenotype
Authors: Trapp-Fragnet Laëtitia , Schermuly Julia , Kohn Marina , Bertzbach Luca D. , Pfaff Florian , Denesvre Caroline , Kaufer Benedikt B. , Härtle Sonja
Published: October 2021

Marek’s disease virus (MDV) is an alphaherpesvirus that causes immunosuppression and deadly lymphoma in chickens. Lymphoid organs play a central role in MDV infection in animals. B-cells in the bursa of Fabricius facilitate high levels of MDV replication and contribute to dissemination at early stages of infection. Several studies investigated host responses in bursal tissue of MDV-infected chickens; however, the cellular responses specifically in bursal B-cells has never been investigated. We took advantage of our recently established in vitro infection system to decipher the cellular responses of bursal B-cells to infection with a very virulent MDV strain. Here, we demonstrate that MDV infection extends the survival of bursal B-cells in culture. Microarray analyses revealed that most cytokine/cytokine-receptor-, cell cycle- and apoptosis-associated genes are significantly down-regulated in these cells. Further functional assays validated these strong effects of MDV infections on cell cycle progression and thus, B-cell proliferation. In addition, we confirmed that MDV infections protect B-cells from apoptosis and trigger an accumulation of the autophagy marker Lc3-II. Taken together, our data indicate that MDV-infected bursal B-cells show hallmarks of a senescence-like phenotype, leading to a prolonged B-cell survival. This study provides an in-depth analysis of bursal B-cell responses to MDV infection and important insights into how the virus extends the survival of these cells.
Themes from literature on drama therapy with people living with Alzheimer’s disease and related dementias
Authors: Fleming Lesley
Published: October 2021

Dementia continues to be a global health issue with increasing numbers of people diagnosed each year. While ongoing research into pharmaceutical and medical treatments continues to yield hopeful results, complementary services and interventions seeking to improve the health and quality of life for those living with dementia are being investigated and implemented. This article presents a review of literature pertaining to the use of drama therapy with people living with Alzheimer’s disease and related dementias (ADRD). Seven themes emerged that offer insight into how drama and drama therapy may benefit people living with ADRD: quality of life; self-expression; psycho-education; communication in relationships; social engagement; sensory experiences; and physical exercise. A discussion of implications and recommendations for further research are included.
GIH-Pobreziari aurre egiteko, oinarrizko errenta behar da
Authors: ORTEGA Ángel ELÍAS
Published: October 2021

2030eko Garapen Iraunkorrerako 1. Helburua, pobreziari aurre egiteari dagokiona, zer den gogorarazi ondoren, helburu horren egungo bilakaera eta zer neurritan betetzen den aztertu da, bai mundu mailan, bai Espainian eta Euskadin, eta bereziki aipatu dira langile pobreen kolektiboa eta gizarte-babeserako sistemak. Jarraian, ikusi da oinarrizko errenta unibertsala, baldintzarik gabea eta banakakoa eskatzea, pobreziaren atalasetik gorako zenbatekoa izango duena. Nazioarteko hainbat forotan aztertu eta planteatu den neurri bat da, bai Nazio Batuetan, bai Europako Kontseiluko Parlamentu Batzarrean, bai finantza- eta lan-munduko esparruetan. Espainian ere eskatu izan da, gizarte-lanaren, kulturaren eta osasunaren esparru profesionaletan, bai eta feminismoan, ekologismoan eta LGBTI kolektiboetan ere. Azkenik, ondorio eta gogoeta labur batzuk atera dira, non berresten baita iritsi dela unea oinarrizko errentak neurri utopikoaren kategoria alde batera utzi eta behingoz abian jartzeko, horrela pobrezia materiala desagerrarazi eta Garapen Iraunkorraren 1. Helburua bete dadin.