bluuebunny/crossref_metadata_2025 huggingface dataset:
D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: a pilot study
Authors: Monastra Giovanni , Vazquez-Levin Mónica , Bezerra Espinola Maria Salome , Bilotta Gabriele , Laganà Antonio Simone , Unfer Vittorio
Published: June 2021

Background

Androgen deficiency affects men in the adulthood, causing several harmful effects at the reproductive and behavioural levels. Since aromatase is an enzyme that catalyses the conversion of androgens to estrogens, and it is responsible for an adequate balance of both sex hormones in males and females, the administration of molecules acting as down modulators may contribute to restore an abnormal enzymatic activity. A prospective pilot study was carried out to investigate the effect of D-chiro-inositol, a putative aromatase down-modulator, on serum levels of testosterone, estradiol, estrone, dehydroepiandrosterone and epiandrosterone from a group of adult male volunteers. Glucose, insulin, follicle-stimulating hormone, luteinizing hormone, inhibin B, D-chiro-inositol and myo-inositol serum levels were also measured.

Results

Male volunteers were selected according to age and body mass index. Subjects with altered glycemia and/or hormonal status, due to advanced age or abnormal weight, were enrolled in the study. Each of the 10 volunteers enrolled took oral D-chiro-inositol (1 g/day) for 1 month. Serum assays of selected markers were performed at baseline (control) and after treatment. D-chiro-inositol administration was associated to reduced serum levels of estrone (− 85.0%) and estradiol (− 14.4%), and increased serum levels of testosterone (+ 23.4%) and dehydroepiandrosterone (+ 13.8%). In addition, epiandrosterone levels were higher (+39%) after treatment. On the other hand, follicle-stimulating hormone, luteinizing hormone and inhibin B did not change. A trend toward a decrease of glycemia, insulinemia and Homeostatic Model Assessment index was observed after D-chiro-inositol treatment, although differences did not reach statistical significance. D-chiro-inositol treatment did not cause any noticeable adverse effect.

Conclusions

Increased androgens and decreased estrogens seem to confirm that D-chiro-inositol acts as an aromatase down-modulator, but with a still unknown mechanism of action. This pilot study opens up new perspectives of research and therapeutic applications for D-chiro-inositol at different dosages and length of treatment.

Authorization number 005/2020 released by the Local Ethics Committee of Alma Res Fertility Center, Rome.

Trial registration number

NCT04615767 (registry: ClinicalTrials.gov)

Date of registration: November 3, 2020
Transcriptomic analysis of caecal tissue in inbred chicken lines that exhibit heritable differences in resistance to Campylobacter jejuni
Authors: Russell Kay M. , Smith Jacqueline , Bremner Abi , Chintoan-Uta Cosmin , Vervelde Lonneke , Psifidi Androniki , Stevens Mark P.
Published: June 2021

Background

Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans and the handling or consumption of contaminated poultry meat is a key source of infection. Selective breeding of poultry that exhibit elevated resistance to Campylobacter is an attractive control strategy. Here we studied the global transcriptional response of inbred chicken lines that differ in resistance to C. jejuni colonisation at a key site of bacterial persistence.

Results

Three-week-old chickens of line 61 and N were inoculated orally with C. jejuni strain M1 and caecal contents and tonsils were sampled at 1 and 5 days post-infection. Caecal colonisation was significantly lower in line 61 compared to line N at 1 day post-infection, but not 5 days post-infection. RNA-Seq analysis of caecal tonsils of both lines revealed a limited response to C. jejuni infection compared to age-matched uninfected controls. In line N at days 1 and 5 post-infection, just 8 and 3 differentially expressed genes (DEGs) were detected (fold-change > 2 and false-discovery rate of < 0.05) relative to uninfected controls, respectively. In the relatively resistant line 61, a broader response to C. jejuni was observed, with 69 DEGs relating to immune regulation, cell signalling and metabolism at 1 day post-infection. However, by day 5 post-infection, no DEGs were detected. By far, the greatest number of DEGs were between uninfected birds of the two lines implying that differential resistance to C. jejuni is intrinsic. Of these genes, several Major Histocompatibility Complex class I-related genes (MHCIA1, MHCBL2 and MHCIY) and antimicrobial peptides (MUC2, AvBD10 and GZMA) were expressed to a greater extent in line N. Two genes within quantitative trait loci associated with C. jejuni colonisation were also more highly expressed in line N (ASIC4 and BZFP2). Quantitative reverse-transcriptase PCR analysis of a subset of transcripts confirmed the RNA-Seq results.

Conclusions

Our data indicate a limited transcriptional response in the caecal tonsils of inbred chickens to intestinal colonisation by Campylobacter but identify a large number of differentially transcribed genes between lines 61 and N that may underlie variation in heritable resistance to C. jejuni.
Prevalence, species distribution and antifungal susceptibility of Candida albicans causing vaginal discharge among symptomatic non-pregnant women of reproductive age at a tertiary care hospital, Vietnam
Authors: Anh Do Ngoc , Hung Dao Nguyen , Tien Tran Viet , Dinh Vu Nhat , Son Vu Tung , Luong Nguyen Viet , Van Nguyen Thi , Quynh Nguyen Thi Nhu , Van Tuan Nguyen , Tuan Le Quoc , Bac Nguyen Duy , Luc Nguyen Khac , Anh Le Tran , Trung Do Minh
Published: June 2021

Background

Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age.

Methods

Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4).

Results

The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively.

Conclusions

The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.
Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates
Authors: Rostami Jinar , Mothes Tobias , Kolahdouzan Mahshad , Eriksson Olle , Moslem Mohsen , Bergström Joakim , Ingelsson Martin , O’Callaghan Paul , Healy Luke M. , Falk Anna , Erlandsson Anna
Published: June 2021

Background

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by brain accumulation of aggregated amyloid-beta (Aβ) and alpha-synuclein (αSYN), respectively. In order to develop effective therapies, it is crucial to understand how the Aβ/αSYN aggregates can be cleared. Compelling data indicate that neuroinflammatory cells, including astrocytes and microglia, play a central role in the pathogenesis of AD and PD. However, how the interplay between the two cell types affects their clearing capacity and consequently the disease progression remains unclear.

Methods

The aim of the present study was to investigate in which way glial crosstalk influences αSYN and Aβ pathology, focusing on accumulation and degradation. For this purpose, human-induced pluripotent cell (hiPSC)-derived astrocytes and microglia were exposed to sonicated fibrils of αSYN or Aβ and analyzed over time. The capacity of the two cell types to clear extracellular and intracellular protein aggregates when either cultured separately or in co-culture was studied using immunocytochemistry and ELISA. Moreover, the capacity of cells to interact with and process protein aggregates was tracked using time-lapse microscopy and a customized “close-culture” chamber, in which the apical surfaces of astrocyte and microglia monocultures were separated by a <1 mm space.

Results

Our data show that intracellular deposits of αSYN and Aβ are significantly reduced in co-cultures of astrocytes and microglia, compared to monocultures of either cell type. Analysis of conditioned medium and imaging data from the “close-culture” chamber experiments indicate that astrocytes secrete a high proportion of their internalized protein aggregates, while microglia do not. Moreover, co-cultured astrocytes and microglia are in constant contact with each other via tunneling nanotubes and other membrane structures. Notably, our live cell imaging data demonstrate that microglia, when attached to the cell membrane of an astrocyte, can attract and clear intracellular protein deposits from the astrocyte.

Conclusions

Taken together, our data demonstrate the importance of astrocyte and microglia interactions in Aβ/αSYN clearance, highlighting the relevance of glial cellular crosstalk in the progression of AD- and PD-related brain pathology.
Functional cure for chronic hepatitis B: accessibility, durability, and prognosis
Authors: Song Aixin , Lin Xiao , Chen Xinyue
Published: June 2021

Hepatitis B surface antigen (HBsAg) clearance is regarded as the ideal endpoint for antiviral treatment in terms of drug withdrawal safety and improvements in prognosis. However, the overall rate of HBsAg clearance is low and differs based on treatment method and course. The recent application of combined and extended treatment strategies have improved the HBsAg clearance rate, and several patients achieved HBsAg clearance in clinical treatment. In addition, the durability of and clinical outcomes after HBsAg clearance have become the focus of both researchers and clinicians. This article reviews HBsAg clearance in terms of accessibility, durability, improvements in prognosis and relevant advances.
Birth prevalence of phenylalanine hydroxylase deficiency: a systematic literature review and meta-analysis
Authors: Foreman Pamela K. , Margulis Andrea V. , Alexander Kimberly , Shediac Renee , Calingaert Brian , Harding Abenah , Pladevall-Vila Manel , Landis Sarah
Published: June 2021

Background

Phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disorder that results in elevated concentrations of phenylalanine (Phe) in the blood. If left untreated, the accumulation of Phe can result in profound neurocognitive disability. The objective of this systematic literature review and meta-analysis was to estimate the global birth prevalence of PAH deficiency from newborn screening studies and to estimate regional differences, overall and for various clinically relevant Phe cutoff values used in confirmatory testing.

Methods

The protocol for this literature review was registered with PROSPERO (International prospective register of systematic reviews). Pubmed and Embase database searches were used to identify studies that reported the birth prevalence of PAH deficiency. Only studies including numeric birth prevalence reports of confirmed PAH deficiency were included.

Results

From the 85 publications included in the review, 238 birth prevalence estimates were extracted. After excluding prevalence estimates that did not meet quality assessment criteria or because of temporal and regional overlap, estimates from 45 publications were included in the meta-analysis. The global birth prevalence of PAH deficiency, estimated by weighting regional birth prevalences relative to their share of the population of all regions included in the study, was 0.64 (95% confidence interval [CI] 0.53–0.75) per 10,000 births and ranged from 0.03 (95% CI 0.02–0.05) per 10,000 births in Southeast Asia to 1.18 (95% CI 0.64–1.87) per 10,000 births in the Middle East/North Africa. Regionally weighted global birth prevalences per 10,000 births by confirmatory test Phe cutoff values were 0.96 (95% CI 0.50–1.42) for the Phe cutoff value of 360 ± 100 µmol/L; 0.50 (95% CI 0.37–0.64) for the Phe cutoff value of 600 ± 100 µmol/L; and 0.30 (95% CI 0.20–0.40) for the Phe cutoff value of 1200 ± 200 µmol/L.

Conclusions

Substantial regional variation in the birth prevalence of PAH deficiency was observed in this systematic literature review and meta-analysis of published evidence from newborn screening. The precision of the prevalence estimates is limited by relatively small sample sizes, despite widespread and longstanding newborn screening in much of the world.
A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia
Authors: Monteiro Vaneisse C. L. , de Oliveira Bibiana M. , dos Santos Bruna B. , Sperb-Ludwig Fernanda , Refosco Lilia F. , Nalin Tatiele , Derks Terry G. J. , Moura de Souza Carolina F. , Schwartz Ida V. D.
Published: June 2021

Background

Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. In vitro analyses suggest a longer release of glucose when using sweet manioc starch (SMS).

Methods

We compared the efficacy and safety of the administration of SMS and UCCS during a short-fasting challenge in patients with GSD Ia in a randomized, triple-blind, phase I/II, cross-over study. GSD Ia patients aged ≥ 16 years and treated with UCCS were enrolled. Participants were hospitalized for two consecutive nights, receiving UCCS or SMS in each night. After the administration of the starches, glucose, lactate and insulin levels were measured in 1-h interval throughout the hospitalization period. The procedures were interrupted after 10 h of fasting or in a hypoglycemic episode (< 3.88 mmol/L).

Results

Eleven individuals (mean age: 21.6 ± 4.3 years; all presenting body mass index > 25 kg/m2) participated in the study. The average fasting period was 8.2 ± 2.0 h for SMS and 7.7 ± 2.3 h for UCCS (p = 0.04). SMS maintained euglycemia for a greater period over UCCS. Increased lactate concentrations were detected even in absence of hypoglycemia, not being influenced by the different starches investigated (p = 0.17). No significant difference was found in total cholesterol, HDL, triglycerides and uric acid levels in both arms. None of the patients showed severe adverse events.

Conclusions

SMS appears to be non-inferior to UCCS in the maintenance of euglycemia, thus emerging as a promising alternative to the treatment of GSD Ia.
Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization
Authors: Ray Upasana , Roy Debarshi , Jin Ling , Thirusangu Prabhu , Staub Julie , Xiao Yinan , Kalogera Eleftheria , Wahner Hendrickson Andrea E. , Cullen Grace D. , Goergen Krista , Oberg Ann L. , Shridhar Viji
Published: June 2021

Background

Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined.

Methods

CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis.

Results

Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy.

Conclusions

Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.
Maternal and neonatal risk factors for neonatal respiratory distress syndrome in term neonates in Cyprus: a prospective case–control study
Authors: Stylianou-Riga Paraskevi , Boutsikou Theodora , Kouis Panayiotis , Kinni Paraskevi , Krokou Marina , Ioannou Andriani , Siahanidou Tania , Iliodromiti Zoi , Papadouri Thalia , Yiallouros Panayiotis K. , Iacovidou Nicoletta
Published: June 2021

Background

Neonatal respiratory distress syndrome (NRDS) is strongly associated with premature birth, but it can also affect term neonates. Unlike the extent of research in preterm neonates, risk factors associated with incidence and severity of NRDS in term neonates are not well studied. In this study, we examined the association of maternal and neonatal risk factors with the incidence and severity of NRDS in term neonates admitted to Neonatal Intensive Care Unit (NICU) in Cyprus.

Methods

In a prospective, case-control design we recruited term neonates with NRDS and non-NRDS admitted to the NICU of Archbishop Makarios III hospital, the only neonatal tertiary centre in Cyprus, between April 2017–October 2018. Clinical data were obtained from patients’ files. We used univariate and multivariate logistic and linear regression models to analyse binary and continuous outcomes respectively.

Results

During the 18-month study period, 134 term neonates admitted to NICU were recruited, 55 (41%) with NRDS diagnosis and 79 with non-NRDS as controls. In multivariate adjusted analysis, male gender (OR: 4.35, 95% CI: 1.03–18.39, p = 0.045) and elective caesarean section (OR: 11.92, 95% CI: 1.80–78.95, p = 0.01) were identified as independent predictors of NRDS. Among neonates with NRDS, early-onset infection tended to be associated with increased administration of surfactant (β:0.75, 95% CI: − 0.02-1.52, p = 0.055). Incidence of pulmonary hypertension or systemic hypotension were associated with longer duration of parenteral nutrition (pulmonary hypertension: 11Vs 5 days, p < 0.001, systemic hypotension: 7 Vs 4 days, p = 0.01) and higher rate of blood transfusion (pulmonary hypertension: 100% Vs 67%, p = 0.045, systemic hypotension: 85% Vs 55%, p = 0.013).

Conclusions

This study highlights the role of elective caesarean section and male gender as independent risk factors for NRDS in term neonates. Certain therapeutic interventions are associated with complications during the course of disease. These findings can inform the development of evidence-based recommendations for improved perinatal care.
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
Authors: Vivori Claudia , Papasaikas Panagiotis , Stadhouders Ralph , Di Stefano Bruno , Rubio Anna Ribó , Balaguer Clara Berenguer , Generoso Serena , Mallol Anna , Sardina José Luis , Payer Bernhard , Graf Thomas , Valcárcel Juan
Published: June 2021

Background

Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts.

Results

We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes.

Conclusions

Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets.
Global trend of Plasmodium malariae and Plasmodium ovale spp. malaria infections in the last two decades (2000–2020): a systematic review and meta-analysis
Authors: Hawadak Joseph , Dongang Nana Rodrigue Roman , Singh Vineeta
Published: June 2021

Background

Recent studies indicate that the prevalence of non-falciparum malaria, including Plasmodium malariae and Plasmodium ovale spp., is increasing, with some complications in infected individuals. The aim of this review is to provide a better understanding of the malaria prevalence and disease burden due to P. malariae and P. ovale spp.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Joanna Briggs Institute prevalence study assessment tool were used to select and evaluate the studies, respectively. Six databases: PubMed, WHOLIS, Wiley Library, ScienceDirect, Web of Science and Google Scholar were used to screen articles published during the period January 2000–December 2020. The pooled prevalence estimates for P. malariae and P. ovale spp. were analysed using a random-effects model and the possible sources of heterogeneity were evaluated through subgroup analysis and meta-regression.

Results

Out of the 3297 studies screened, only 113 studies were included; among which 51.33% were from the African Region. The P. malariae and P. ovale spp. pooled prevalence were 2.01% (95% CI 1.31–2.85%) and 0.77% (95% CI 0.50–1.10%) respectively, with the highest prevalence in the African Region. P. malariae was equally distributed among adults (2.13%), children (2.90%) and pregnant women (2.77%) (p = 0.862), whereas P. ovale spp. was more prevalent in pregnant women (2.90%) than in children ≤ 15 years (0.97%) and in patients > 15 years old (0.39%) (p = 0.021). In this review, data analysis revealed that P. malariae and P. ovale spp. have decreased in the last 20 years, but not significantly, and these species were more commonly present with other Plasmodium species as co-infections. No difference in prevalence between symptomatic and asymptomatic patients was observed for either P. malariae or P. ovale spp.

Conclusion

Our analysis suggests that knowledge of the worldwide burden of P. malariae and P. ovale spp. is very important for malaria elimination programmes and a particular focus towards improved tools for monitoring transmission for these non-falciparum species should be stressed upon to deal with increased infections in the future.

Graphical Abstract
Atypical behavior of a black fly species connects cavity-nesting birds with generalist blood parasites in an arid area of Spain
Authors: Chakarov Nayden , Veiga Jesús , Ruiz-Arrondo Ignacio , Valera Francisco
Published: June 2021

Background

The feeding behavior of bloodsucking insects determines the transmission, distribution, host spectrum and evolution of blood parasites in the wild. Conventional wisdom suggests that some vector groups (e.g. black flies, family Simuliidae) are consistently exophagous daytime biters. We aimed to understand more about the exceptions to this pattern by combining targeted trapping and molecular identification of parasites in vectors.

Methods

In this study, we collected black flies in nest boxes used by European rollers Coracias garrulus in southeastern Spain. We molecularly analyzed 434 individual insects, identifying the black fly species caught in the nest boxes, their potential vertebrate blood meals, and the haemosporidian parasite lineages that they carried.

Results

Only one black fly species, Simulium rubzovianum, appeared to enter the nest boxes of rollers. Among the trapped specimens, 15% contained vertebrate DNA, which always belonged to rollers, even though only half of those specimens were visibly engorged. Furthermore, 15% of all black flies contained Leucocytozoon lineages, indicating previous feeding on avian hosts but probably not on infected adult rollers. The known vertebrate hosts of the recorded Leucocytozoon lineages suggested that large and/or abundant birds are their hosts. Particularly represented were cavity-nesting species breeding in the vicinity, such as pigeons, corvids and owls. Open-nesting species such as thrushes and birds of prey were also represented.

Conclusions

Our data strongly suggest that S. rubzovianum bites uninfected roller nestlings and infected individuals of other species, potentially incubating adults, inside nest boxes and natural cavities. This simuliid does not appear to have a strong preference for specific host clades. Contrary to the general pattern for the group, and possibly enhanced by the harsh environmental conditions in the study area, this black fly appeared to intensively use and may even have a preference for confined spaces such as cavities for feeding and resting. Preferences of vectors for atypical microhabitat niches where hosts are less mobile may enable social and within-family transmission and parasite speciation in the long term. At the same time, a lack of host preference in concentrated multispecies communities can lead to host switches. Both processes may be underappreciated driving forces in the evolution of avian blood parasites.

Graphical abstract
Integrated microRNA and mRNA gene expression in peripheral blood mononuclear cells in response to acute psychosocial stress: a repeated-measures within-subject pilot study
Authors: Jurkiewicz Magdalena Maria , Mueller-Alcazar Anett , Moser Dirk Alexander , Jayatilaka Indralatha , Mikhailik Anatoly , Ferri Jamie , Fogelman Nia , Canli Turhan
Published: June 2021

Objective

The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points.

Results

For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.
Access to the 340B Drug Pricing Program: is there evidence of strategic hospital behavior?
Authors: Mulligan Karen , Romley John A. , Myerson Rebecca
Published: June 2021

Objective

The 340B Drug Pricing Program allows hospitals to purchase covered drugs at a discount and potentially generate profit if they are reimbursed at rates that exceed 340B acquisition prices. Disproportionate share hospitals (DSH) are eligible to participate in 340B if their DSH adjustment–a measure that identifies hospitals that treat a disproportionate share of low income Medicare or Medicaid patients–is above 11.75%. To assess whether hospitals behave strategically to gain access to the program, we examined data on the number of hospitals just above versus below the DSH adjustment threshold for 340B eligibility and conducted McCrary density tests to assess statistical significance.

Results

In 2014–2016, the number of hospitals increases by 41% just above the 340B eligibility threshold. McCrary density tests found this increase to be statistically significant across a range of bandwidths in 2014–2016 (p < 0.01). From 2011–2013, the findings are sensitive to the bandwidth around the threshold, but insignificant in 2008–2010. We found no comparable change among hospitals ineligible for the 340B program. These data are consistent with the hypothesis that some hospitals adjust their DSH to gain 340B eligibility. Our findings support recent calls from the Government Accountability Office to improve oversight of the 340B program.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) moonlights as an adhesin in Mycoplasma hyorhinis adhesion to epithelial cells as well as a plasminogen receptor mediating extracellular matrix degradation
Authors: Wang Jia , Li Yao , Pan Longji , Li Jun , Yu Yanfei , Liu Beibei , Zubair Muhammad , Wei Yanna , Pillay Bala , Olaniran Ademola Olufolahan , Chiliza Thamsanqa E. , Shao Guoqing , Feng Zhixin , Xiong Qiyan
Published: June 2021

Mycoplasma hyorhinis infects pigs causing polyserositis and polyarthritis, and has also been reported in a variety of human tumor tissues. The occurrence of disease is often linked with the systemic invasion of the pathogen. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), one of the key enzymes of glycolysis, was reported as a surface multifunctional molecule in several bacteria. Here, we investigated whether GAPDH could manifest binary functions; as an adhesin to promote colonization as well as a plasminogen receptor functioning in extracellular matrix (ECM) degradation to promote systemic invasion. The surface localization of GAPDH was observed in M. hyorhinis with flow cytometry and colony blot analysis. Recombinant GAPDH (rGAPDH) was found to be able to bind porcine-derived PK-15 and human-derived NCI-H292 cells. The incubation with anti-GAPDH antibody significantly decreased the adherence of M. hyorhinis to both cell lines. To investigate its function in recruiting plasminogen, firstly, the interaction between rGAPDH and plasminogen was demonstrated by ELISA and Far-Western blot assay. The activation of the rGAPDH-bound plasminogen into plasmin was proved by using a chromogenic substrate, and furtherly confirmed to degrade extracellular matrix by using a reconstituted ECM. Finally, the ability of rGAPDH to bind different ECM components was demonstrated, including fibronectin, laminin, collagen type IV and vitronectin. Collectively, our data imply GAPDH as an important adhesion factor of M. hyrohinis and a receptor for hijacking host plasminogen to degrade ECM. The multifunction of GAPDH to bind both plasminogen and ECM components is believed to increase the targeting of proteolysis and facilitate the dissemination of M. hyorhinis.
A mathematical analysis of Hopf-bifurcation in a prey-predator model with nonlinear functional response
Authors: Savadogo Assane , Sangaré Boureima , Ouedraogo Hamidou
Published: June 2021

In this paper, our aim is mathematical analysis and numerical simulation of a prey-predator model to describe the effect of predation between prey and predator with nonlinear functional response. First, we develop results concerning the boundedness, the existence and uniqueness of the solution. Furthermore, the Lyapunov principle and the Routh–Hurwitz criterion are applied to study respectively the local and global stability results. We also establish the Hopf-bifurcation to show the existence of a branch of nontrivial periodic solutions. Finally, numerical simulations have been accomplished to validate our analytical findings.
Knowledge of infection prevention and control among healthcare workers and factors influencing compliance: a systematic review
Authors: Alhumaid Saad , Al Mutair Abbas , Al Alawi Zainab , Alsuliman Murtadha , Ahmed Gasmelseed Y. , Rabaan Ali A. , Al-Tawfiq Jaffar A. , Al-Omari Awad
Published: June 2021

Background

Knowledge of infection prevention and control (IPC) procedures among healthcare workers (HCWs) is crucial for effective IPC. Compliance with IPC measures has critical implications for HCWs safety, patient protection and the care environment.

Aims

To discuss the body of available literature regarding HCWs' knowledge of IPC and highlight potential factors that may influence compliance to IPC precautions.

Design

A systematic review. A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis [PRISMA] statement.

Data sources

Electronic databases (PubMed, CINAHL, Embase, Proquest, Wiley online library, Medline, and Nature) were searched from 1 January 2006 to 31 January 2021 in the English language using the following keywords alone or in combination:knowledge, awareness, healthcare workers, infection, compliance, comply, control, prevention, factors. 3417 papers were identified and 30 papers were included in the review.

Results

Overall, the level of HCW knowledge of IPC appears to be adequate, good, and/or high concerning standard precautions, hand hygiene, and care pertaining to urinary catheters. Acceptable levels of knowledge were also detected in regards to IPC measures for specific diseases including TB, MRSA, MERS-CoV, COVID-19 and Ebola. However, gaps were identified in several HCWs' knowledge concerning occupational vaccinations, the modes of transmission of infectious diseases, and the risk of infection from needle stick and sharps injuries. Several factors for noncompliance surrounding IPC guidelines are discussed, as are recommendations for improving adherence to those guidelines.

Conclusion

Embracing a multifaceted approach towards improving IPC-intervention strategies is highly suggested. The goal being to improve compliance among HCWs with IPC measures is necessary.
Low shifts in salinity determined assembly processes and network stability of microeukaryotic plankton communities in a subtropical urban reservoir
Authors: Mo Yuanyuan , Peng Feng , Gao Xiaofei , Xiao Peng , Logares Ramiro , Jeppesen Erik , Ren Kexin , Xue Yuanyuan , Yang Jun
Published: June 2021

Background

Freshwater salinization may result in significant changes of microbial community composition and diversity, with implications for ecosystem processes and function. Earlier research has revealed the importance of large shifts in salinity on microbial physiology and ecology, whereas studies on the effects of smaller or narrower shifts in salinity on the microeukaryotic community in inland waters are scarce. Our aim was to unveil community assembly mechanisms and the stability of microeukaryotic plankton networks at low shifts in salinity.

Results

Here, we analyzed a high-resolution time series of plankton data from an urban reservoir in subtropical China over 13 consecutive months following one periodic salinity change ranging from 0 to 6.1‰. We found that (1) salinity increase altered the community composition and led to a significant decrease of plankton diversity, (2) salinity change influenced microeukaryotic plankton community assembly primarily by regulating the deterministic-stochastic balance, with deterministic processes becoming more important with increased salinity, and (3) core plankton subnetwork robustness was higher at low-salinity levels, while the satellite subnetworks had greater robustness at the medium-/high-salinity levels. Our results suggest that the influence of salinity, rather than successional time, is an important driving force for shaping microeukaryotic plankton community dynamics.

Conclusions

Our findings demonstrate that at low salinities, even small increases in salinity are sufficient to exert a selective pressure to reduce the microeukaryotic plankton diversity and alter community assembly mechanism and network stability. Our results provide new insights into plankton ecology of inland urban waters and the impacts of salinity change in the assembly of microbiotas and network architecture.
The effect of metabolic syndrome on head and neck cancer incidence risk: a population-based prospective cohort study
Authors: Jiang Huaili , Zhou Lei , He Qiangsheng , Jiang Kanglun , Yuan Jinqiu , Huang Xinsheng
Published: June 2021

Background

There are limited evidences clarifying the impact of metabolic syndrome (MS) and its components on head and neck cancer (HNC) incidence risk. We explored the correlation between MS, MS components, and the combined effects of MS and C-reactive protein (CRP) and HNC risk.

Methods

This is a prospective analysis of 474,929 participants from the UK Biobank cohort. Cox proportional hazard regression was utilized to assess the hazard ratio (HR) and 95% confidence interval (CI) and to explore the non-linear correlation between an individual MS component and HNC risk.

Results

Individuals with MS (HR, 1.05; 95%CI, 0.90–1.22) had no higher HNC risk than those without MS. More MS components showed no higher HNC risk. Nevertheless, hyperglycemia (HR, 1.22; 95%CI, 1.02–1.45) was independently correlated with elevated HNC risk. In a non-linear manner, waist circumference and high-density lipoprotein cholesterol (HDL-C) showed a U-shaped association with HNC risk. Further, piecewise linear model analysis indicated that higher male waist circumference, female waist circumference (≥93.16 cm), blood glucose (≥4.70 mmol/L) and male HDL-C (≥1.26mmo/L), and lower male HDL-C (<1.26mmo/L) were correlated with higher HNC risk. Increased CRP (≥1.00mg/dL) elevated HNC risk and individuals with MS and CRP≥1.00mg/dL had the highest HNC risk (HR, 1.29; 95%CI, 1.05–1.58). But no joint effect between MS and CRP was detected (p-interaction=0.501).

Conclusions

MS are not correlated with elevated HNC risk. High waist circumference and blood glucose are independent risk factor of HNC incidence. Controlling HDL-C in an appropriate range can get the lowest risk of male HNC. No joint effect of MS and CRP exists in HNC tumorigenesis.
Patients’ adherence to smartphone apps in the management of bipolar disorder: a systematic review
Authors: Patoz Marie-Camille , Hidalgo-Mazzei Diego , Pereira Bruno , Blanc Olivier , de Chazeron Ingrid , Murru Andrea , Verdolini Norma , Pacchiarotti Isabella , Vieta Eduard , Llorca Pierre-Michel , Samalin Ludovic
Published: June 2021

Background

Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies.

Methods

A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or “bipolar” combined with “digital” or “mobile” or “phone” or “smartphone” or “mHealth” or “ehealth” or "mobile health" or “app” or “mobile-health”.

Results

Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%.

Conclusion

The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.
Individual and situational determinants of plastic waste sorting: an experience sampling method study protocol
Authors: Broers Valérie J. V. , Van Scharrenburg Melina , Fredrix Lily , Lataster Johan , Löhr Ansje J. , Jacobs Nele
Published: June 2021

Background

Plastic waste management is one of the most challenging problems of our time. Until now, only 9% of the produced plastics has been recycled. In order to increase recycling, a behavior change towards sorting of plastic waste is needed. Therefore, the main aim of the study is to gain insight in the individual and situational determinants associated with plastic waste sorting behavior. The Integrated Framework for Encouraging Pro-environmental Behaviour will be used as the theoretical framework. This framework assumes that individual egoistic and hedonic values are negatively related to pro-environmental behaviour, whereas individual biospheric and altruistic values are positively related to pro-environmental behaviour. Situational cues can activate these values, resulting in (non) pro-environmental behaviour. Taking the Integrated Framework for Encouraging Pro-environmental Behaviour into account, this study will test the hypothesized associations between individual and situational determinants and plastic waste sorting behavior, using an ecological momentary assessment approach (Experience Sampling Method, ESM).

Methods

A signal-contingent scheme with semi-random intervals will be used for the ESM questionnaire. Over a period of seven consecutive days, an ESM-based smartphone app will prompt participants ten times a day to fill in a short questionnaire containing questions about situational determinants and plastic waste sorting behaviour. Participants will also complete an online questionnaire before and after the study measuring the individual determinants and plastic waste sorting behaviour.

Discussion

ESM has many benefits over traditional surveys, such as improved ecological validity and the possibility to explore temporal relationships. The disadvantages of ESM are mainly related to the burden for the participants and the possibility of reactivity effects. The results will provide insight into the relationship between situational cues, individual values and plastic waste behaviour. The practical implications of the findings of this study can be of interest for policy makers in order to reach plastic waste reduction targets. Furthermore, the situational cues that activate values, which increase or decrease plastic waste sorting, can be targeted in interventions. The results of this study can also be relevant for further research studying and stimulating pro-environmental behaviour in general.
Pathology of the neurovascular unit in leukodystrophies
Authors: Zarekiani Parand , Breur Marjolein , Wolf Nicole I. , de Vries Helga E. , van der Knaap Marjo S. , Bugiani Marianna
Published: June 2021

The blood–brain barrier is a dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma. Specialized brain endothelial cells, astrocytes, neurons, microglia and pericytes together compose the neurovascular unit and interact to maintain blood–brain barrier function. A disturbed brain barrier function is reported in most common neurological disorders and may play a role in disease pathogenesis. However, a comprehensive overview of how the neurovascular unit is affected in a wide range of rare disorders is lacking. Our aim was to provide further insights into the neuropathology of the neurovascular unit in leukodystrophies to unravel its potential pathogenic role in these diseases. Leukodystrophies are monogenic disorders of the white matter due to defects in any of its structural components. Single leukodystrophies are exceedingly rare, and availability of human tissue is unique. Expression of selective neurovascular unit markers such as claudin-5, zona occludens 1, laminin, PDGFRβ, aquaporin-4 and α-dystroglycan was investigated in eight different leukodystrophies using immunohistochemistry. We observed tight junction rearrangements, indicative of endothelial dysfunction, in five out of eight assessed leukodystrophies of different origin and an altered aquaporin-4 distribution in all. Aquaporin-4 redistribution indicates a general astrocytic dysfunction in leukodystrophies, even in those not directly related to astrocytic pathology or without prominent reactive astrogliosis. These findings provide further evidence for dysfunction in the orchestration of the neurovascular unit in leukodystrophies and contribute to a better understanding of the underlying disease mechanism.