bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mycological and Molecular Epidemiologic Study on Onychomycosis and Determination In Vitro Susceptibilities of Isolated Fungal Strains to Conventional and New Antifungals
Authors: Halvaee Samaneh , Daie-Ghazvini Roshanak , Hashemi Seyed Jamal , Khodavaisy Sadegh , Rahimi-Foroushani Abbas , Bakhshi Heidar , Rafat Zahra , Ardi Pegah , Abastabar Mahdi , Zareei Mahdi , Borjian-Boroujeni Zeinab , Kamali Sarvestani Hasti
Published: July 2021

Background

Onychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated.

Methods

In this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts.

Results

594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi.

Conclusions

The prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis.
Virulence of Trypanosoma cruzi Strains Is Related to the Differential Expression of Innate Immune Receptors in the Heart
Authors: Queiroga Tamyres Bernadete Dantas , Pereira Nathalie de Sena , Silva Denis Dantas da , Andrade Cléber de Mesquita , Araújo Júnior Raimundo Fernandes de , Brito Carlos Ramon do Nascimento , Galvão Lúcia Maria da Cunha , Câmara Antônia Cláudia Jácome da , Nascimento Manuela Sales Lima , Guedes Paulo Marcos Matta
Published: July 2021

Resistance or susceptibility to T. cruzi infection is dependent on the host immunological profile. Innate immune receptors, such as Toll-like receptors (TLRs/TLR2, TLR4, TLR7, and TLR9) and Nod-like receptors (NLRs/NOD1 and NLRP3 inflammasome) are involved with the resistance against acute experimental T. cruzi infection. Here, we evaluated the impact of T. cruzi virulence on the expression of innate immune receptors and its products in mice. For that, we used six T. cruzi strains/isolates that showed low (AM64/TcIV and 3253/Tc-V), medium (PL1.10.14/TcIII and CL/TcVI), or high (Colombian/Tc-I and Y/TcII) virulence and pathogenicity to the vertebrate host and belonging to the six discrete typing units (DTUs)—TcI to TcVI. Parasitemia, mortality, and myocarditis were evaluated and correlated to the expression of TLRs, NLRs, adapter molecules, cytokines, and iNOS in myocardium by real time PCR. Cytokines (IL-1β, IL-12, TNF-α, and IFN-γ) were quantified in sera 15 days after infection. Our data indicate that high virulent strains of T. cruzi, which generate high parasitemia, severe myocarditis, and 100% mortality in infected mice, inhibit the expression of TLR2, TLR4, TLR9, TRIF, and Myd88 transcripts, leading to a low IL-12 production, when compared to medium and low virulent T. cruzi strains. On the other hand, the high virulent T. cruzi strains induce the upregulation of NLRP3, caspase-1, IL-1β, TNF-α, and iNOS mRNA in heart muscle, compared to low and medium virulent strains, which may contribute to myocarditis and death. Moreover, high virulent strains induce higher levels of IL-1β and TNF-α in sera compared to less virulent parasites. Altogether the data indicate that differential TLR and NLR expression in heart muscle is correlated with virulence and pathogenicity of T cruzi strains. A better knowledge of the immunological mechanisms involved in resistance to T. cruzi infection is important to understand the natural history of Chagas disease, can lead to identification of immunological markers and/or to serve as a basis for alternative therapies.
Proximate Causes of Forest Degradation in the Democratic Republic of the Congo Vary in Space and Time
Authors: Shapiro Aurélie C. , Bernhard Katie P. , Zenobi Stefano , Müller Daniel , Aguilar-Amuchastegui Naikoa , d'Annunzio Rémi
Published: July 2021

Forest degradation, generally defined as a reduction in the delivery of forest ecosystem services, can have long-term impacts on biodiversity, climate, and local livelihoods. The quantification of forest degradation, its dynamics and proximate causes can help prompt early action to mitigate carbon emissions and inform relevant land use policies. The Democratic Republic of the Congo is largely forested with a relatively low deforestation rate, but anthropogenic degradation has been increasing in recent years. We assess the impact of eight independent variables related to land cover, land use, infrastructure, armed conflicts, and accessibility on forest degradation, measured by the Forest Condition (FC) index, a measure of forest degradation based on biomass history and fragmentation that ranges from 0 (completely deforested) to 100 (intact). We employ spatial panel models with fixed effects using regular 25 × 25 km units over five 3-year intervals from 2002 to 2016. The regression results suggest that the presence of swamp ecosystems, low access (defined by high travel time), and forest concessions are associated with lower forest degradation, while built up area, fire frequency, armed conflicts result in greater forest degradation. The impact of neighboring units on FC shows that all variables within the 50 km spatial neighborhood have a greater effect on FC than the on-site spatial determinants, indicating the greater influence of drivers beyond the 25 km2unit. In the case of protected areas, we unexpectedly find that protection in neighboring locations leads to higher forest degradation, suggesting a potential leakage effect, while protected areas in the local vicinity have a positive influence on FC. The Mann-Kendall trend statistic of occurrences of fires and conflicts over the time period and until 2020 show that significant increases in conflicts and fires are spatially divergent. Overall, our results highlight how assessing the proximate causes of forest degradation with spatiotemporal analysis can support targeted interventions and policies to reduce forest degradation but spillover effects of proximal drivers in neighboring areas need to be considered.
Impact of Metabolic Syndrome and It's Components on Prognosis in Patients With Cardiovascular Diseases: A Meta-Analysis
Authors: Li Xiao , Zhai Yajing , Zhao Jiaguo , He Hairong , Li Yuanjie , Liu Yue , Feng Aozi , Li Li , Huang Tao , Xu Anding , Lyu Jun
Published: July 2021

Background: Patients with metabolic syndrome (MetS) have a higher risk of developing cardiovascular diseases (CVD). However, controversy exists about the impact of MetS on the prognosis of patients with CVD.

Methods: Pubmed, Cochrane library, and EMBASE databases were searched. Cohort Studies and randomized controlled trials post hoc analyses that evaluated the impact of MetS on prognosis in patients (≥18 years) with CVD were included. Relative risk (RR), hazard rate (HR) and 95% confidence intervals (CIs) were calculated for each individual study by random-effect model. Subgroup analysis and meta-regression analysis was performed to explore the heterogeneity.

Results: 55 studies with 16,2450 patients were included. Compared to patients without MetS, the MetS was associated with higher all-cause death [RR, 1.220, 95% CI (1.103 to 1.349), P, 0.000], CV death [RR, 1.360, 95% CI (1.152 to 1.606), P, 0.000], Myocardial Infarction [RR, 1.460, 95% CI (1.242 to 1.716), P, 0.000], stroke [RR, 1.435, 95% CI (1.131 to 1.820), P, 0.000]. Lower high-density lipoproteins (40/50) significantly increased the risk of all-cause death and CV death. Elevated fasting plasma glucose (FPG) (>100 mg/dl) was associated with an increased risk of all-cause death, while a higher body mass index (BMI>25 kg/m2) was related to a reduced risk of all-cause death.

Conclusions: MetS increased the risk of cardiovascular-related adverse events among patients with CVD. For MetS components, there was an increased risk in people with low HDL-C and FPG>100 mg/dl. Positive measures should be implemented timely for patients with CVD after the diagnosis of MetS, strengthen the prevention and treatment of hyperglycemia and hyperlipidemia.
Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study
Authors: Pivonello Rosario , Bancos Irina , Feelders Richard A. , Kargi Atil Y. , Kerr Janice M. , Gordon Murray B. , Mariash Cary N. , Terzolo Massimo , Ellison Noel , Moraitis Andreas G.
Published: July 2021

Introduction/Purpose

Relacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).

Materials and Methods

A single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).

Results

35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.

Conclusions

The SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.
Distribution Optimal Power Flow With Energy Sharing Via a Peer-To-Peer Transactive Market
Authors: Zheng Boshen , Fan Yue , Wei Wei , Xu Yourui , Huang Shaowei , Mei Shengwei
Published: July 2021

The technology advancement and cost decline of renewable and sustainable energy increase the penetration of distributed energy resources (DERs) in distribution systems. Transactive energy helps balance the local generation and demand. Peer-to-peer (P2P) energy trading is a promising business model for transactive energy. Such a market scheme can increase the revenue of DER owners and reduce the waste of renewable energy. This article proposes an equilibrium model of a P2P transactive energy market. Every participant seeks the maximum personal interest, with the options of importing or providing energy from/to any other peer across different buses of the distribution network. The market equilibrium condition is obtained by combining the Karush–Kuhn–Tucker conditions of all problems of individual participants together. The energy transaction price is endogenously determined from the market equilibrium condition, which is cast as a mixed-integer linear program and solved by a commercial solver. The transactive energy flow is further embedded in the optimal power flow problem to ensure operating constraints of the distribution network. We propose a remedy to recover a near optimal solution when the second-order cone relaxation is inexact. Finally, a case study demonstrates that the proposed P2P market benefits all participants.
Analysis of Decision Making of Energy Enterprises on Adaptive Behavior Amid COVID-19
Authors: Yang Xiurui , Li Jizu
Published: July 2021

There is no choice for energy businesses with ongoing epidemic prevention and control but to adapt themselves to the epidemic. Analyzing the decisions of energy enterprises on adaptive behaviors amid the Corona Virus disease 2019 (COVID-19) pandemic goes a long way toward economic and social stability and successful containment of the pandemic. With a phone-based or online (Tencent QQ and WeChat) survey on 500 energy companies in 17 prefecture-level cities and autonomous prefectures in Central China’s Hubei Province, we examined the types of adaptive behavior these businesses had chosen to respond to the virus. We utilized the entropy weight method (EWM) and identified key factors that impacted how these companies made decisions on adaptive behavior. On that basis, we compared the samples with state-owned enterprises and private businesses in terms of the criticality of factors affecting their decisions on adaptive behavior. The significant findings are as follows. First, the adaptive behaviors of Hubei-based energy companies were for philanthropic, economic, or technical purposes. Besides, concerning the confidence level, the central government’s general requirement for epidemic prevention and control, current economic realities, cost-benefit analysis of adaptive behavior, the awareness of corporate social responsibility, and energy policy support from governments were key factors that affect decisions of Hubei’s energy enterprises on adaptive behavior. Their criticality rates 0.999 6, 0.999 5, 0.999 0, 0.997 1, and 0.995 8, respectively. Moreover, the key affecting factors of these samples differed from those of energy enterprises of a different nature. The nature of energy businesses holds sway over the identification of those key factors. The criticality of which also varies with the distinctive nature of the enterprises. Finally, we presented the theoretical implications of the present work and policy-making recommendations.
Net Geochemical Release of Base Cations From 25 Forested Watersheds in the Catskill Region of New York
Authors: Nieman Sara C. , Johnson Chris E.
Published: July 2021

Chemical weathering of minerals is the principal mechanism by which base cations (Ca2+, Mg2+, K+, and Na+) are released and acidity is neutralized in soils, bedrock, and drainage waters. Quantifying the release of base cations from watershed soils is therefore crucial for the calculation of “critical loads” of atmospheric acidity to forest ecosystems. We used a mass-balance approach to estimate the rate of release of base cations in 25 headwater catchments in the Catskill region of New York, an area historically subject to high inputs of acid deposition. In 2010–2013, total net base cation release via geochemical processes averaged 1,704 eq ha–1 yr–1 (range: 928–2,622). Calcium accounted for 58% of this total, averaging 498 mol ha–1 yr–1 (range: 209–815). Mass balance estimates of net geochemical release of base cations were most strongly driven by stream export and biomass uptake fluxes, with only minor contributions from precipitation. Documented rates of base cation depletion from soil exchange sites in the region were also small relative to the net geochemical release rates. We observed a significant influence of bedrock type on net base cation release rates (P = 0.002), and a weak but significant negative correlation with watershed elevation (r = −0.51). Relationships with other geographic factors such as aspect and watershed size were not significant. Net base cation release was 4.5 times higher than precipitation inputs of SO42– and NO3–, suggesting that sources of acidity internal to the watershed are now more important drivers of weathering than acid deposition. Our data suggest that release of base cations from most Catskill forest soils is sufficient to neutralize existing inputs of acidity.
Exploring the Origin and Relatedness of Maternal Lineages Through Analysis of Mitochondrial DNA in the Holstein Horse
Authors: Engel Laura , Becker Doreen , Nissen Thomas , Russ Ingolf , Thaller Georg , Krattenmacher Nina
Published: July 2021

Maternal lineages are important for the breeding decision in the Holstein horse breed. To investigate the genetic diversity of the maternal lineages and the relationships between founder mares, the maternal inherited mitochondrial genome (except the repetitive part of the non-coding region) of 271 mares representing 75 lineages was sequenced. The sequencing predominantly revealed complete homology in the nucleotide sequences between mares from one lineage with exceptions in 13 lineages, where differences in one to three positions are probably caused by de novo mutations or alternate fixation of heteroplasmy. We found 78 distinct haplotypes that have not yet been described in other breeds. Six of these occurred in two or three different lineages indicating a common ancestry. Haplotypes can be divided into eight clusters with all mares from one lineage belonging to the same cluster. Within a cluster, the average number of pairwise differences ranged from zero to 16.49 suggesting close maternal relationships between these mares. The results showed that the current breeding population originated from at least eight ancestral founder mares.
Interaction of HLA Class II rs9272219 and TMPO rs17028450 (Arg690Cys) Variants Affects Neuromyelitis Optica Spectrum Disorder Susceptibility in an Admixed Mexican Population
Authors: Rosas-Madrigal Sandra , Villarreal-Molina María Teresa , Flores-Rivera José , Rivas-Alonso Verónica , Macias-Kauffer Luis Rodrigo , Ordoñez Graciela , Chima-Galán María del Carmen , Acuña-Alonzo Víctor , Macín-Pérez Gastón , Barquera Rodrigo , Granados Julio , Valle-Rios Ricardo , Corona Teresa , Carnevale Alessandra , Romero-Hidalgo Sandra
Published: July 2021

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating autoimmune disease of the central nervous system, more prevalent in individuals of non-European ancestry. Few studies have analyzed genetic risk factors in NMOSD, and HLA class II gene variation has been associated NMOSD risk in various populations including Mexicans. Thymopoietin (TMPO) has not been tested as a candidate gene for NMOSD or other autoimmune disease, however, experimental evidence suggests this gene may be involved in negative selection of autoreactive T cells and autoimmunity. We thus investigated whether the missense TMPO variant rs17028450 (Arg630Cys, frequent in Latin America) is associated with NMOSD, and whether this variant shows an interaction with HLA-class II rs9272219, previously associated with NMOSD risk. A total of 119 Mexican NMOSD patients, 1208 controls and 357 Native Mexican individuals were included. The HLA rs9272219 “T” risk allele frequency ranged from 21 to 68%, while the rs17028450 “T” minor allele frequency was as high as 18% in Native Mexican groups. Both rs9272219 and rs17028450 were significantly associated with NMOSD risk under additive models (OR = 2.48; p = 8 × 10–10 and OR = 1.59; p = 0.0075, respectively), and a significant interaction between both variants was identified with logistic regression models (p = 0.048). Individuals bearing both risk alleles had an estimated 3.9-fold increased risk of NMOSD. To our knowledge, this is the first study reporting an association of TMPO gene variation with an autoimmune disorder and the interaction of specific susceptibility gene variants, that may contribute to the genetic architecture of NMOSD in admixed Latin American populations.
IL-33 Drives Expansion of Type 2 Innate Lymphoid Cells and Regulatory T Cells and Protects Mice From Severe, Acute Colitis
Authors: Ngo Thi Phuong Nhi , Palmieri Vittoria , Adamczyk Alexandra , Klopfleisch Robert , Langhorst Jost , Hansen Wiebke , Westendorf Astrid M. , Pastille Eva
Published: July 2021

The hallmarks of inflammatory bowel disease are mucosal damage and ulceration, which are known to be high-risk conditions for the development of colorectal cancer. Recently, interleukin (IL)-33 and its receptor ST2 have emerged as critical modulators in inflammatory disorders. Even though several studies highlight the IL-33/ST2 pathway as a key factor in colitis, a detailed mode of action remains elusive. Therefore, we investigated the role of IL-33 during intestinal inflammation and its potential as a novel therapeutic target in colitis. Interestingly, the expression of IL-33, but not its receptor ST2, was significantly increased in biopsies from the inflamed colon of IBD patients compared to non-inflamed colonic tissue. Accordingly, in a mouse model of Dextran Sulfate Sodium (DSS) induced colitis, the secretion of IL-33 significantly accelerated in the colon. Induction of DSS colitis in ST2-/- mice displayed an aggravated colon pathology, which suggested a favorable role of the IL 33/ST2 pathway during colitis. Indeed, injecting rmIL-33 into mice suffering from acute DSS colitis, strongly abrogated epithelial damage, pro-inflammatory cytokine secretion, and loss of barrier integrity, while it induced a strong increase of Th2 associated cytokines (IL-13/IL-5) in the colon. This effect was accompanied by the accumulation of regulatory T cells (Tregs) and type 2 innate lymphoid cells (ILC2s) in the colon. Depletion of Foxp3+ Tregs during IL-33 treatment in DSS colitis ameliorated the positive effect on the intestinal pathology. Finally, IL-33 expanded ILC2s, which were adoptively transferred to DSS treated mice, significantly reduced colonic inflammation compared to DSS control mice. In summary, our results emphasize that the IL-33/ST2 pathway plays a crucial protective role in colitis by modulating ILC2 and Treg numbers.
SKI Expression Suppresses Pathogenic Th17 Cell Response and Mitigates Experimental Autoimmune Encephalomyelitis
Authors: Li Ping , Guo Zengli , Wan Yisong Y.
Published: July 2021

Pathogenic Th17 cells are critically involved in many autoimmune diseases, while non-pathogenic Th17 cells are more immune regulatory. Understanding the mechanisms of the induction and maintenance of pathogenic Th17 cells will benefit the development of therapeutic treatments of related diseases. We have shown that the transforming growth factor-β (TGFβ) induced SKI degradation and dissociation from Smad4 complex is a prerequisite for TGFβ-induced Th17 cell differentiation. However, it is unclear whether and how SKI regulates pathogenic Th17 differentiation, which does not require TGFβ cytokine. Here we showed that SKI expression was downregulated during pathogenic Th17 cell differentiation and the ectopic expression of SKI abrogated the differentiation of pathogenic Th17 cells. Functionally, using a knock-in mouse model, we found ectopic SKI expression specifically in T cells prevented myelin oligodendrocyte glycoprotein peptide (MOG33–55) induced experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis. We further revealed that induced SKI expression in already differentiated pathogenic Th17 cells reduced the maintenance of Th17 program and ameliorated EAE in an adoptive T cell transfer model. Therefore, our study provides valuable insights of targeting SKI to modulate pathogenic Th17 cell function and treat Th17-related diseases.
On the Circulation and Thermohaline Properties of the Eastern Mediterranean Sea
Authors: Menna Milena , Gerin Riccardo , Notarstefano Giulio , Mauri Elena , Bussani Antonio , Pacciaroni Massimo , Poulain Pierre-Marie
Published: July 2021

The circulation of the Eastern Mediterranean Sea is characterized by numerous recurrent or permanent anticyclonic structures, which modulate the pathway of the main currents and the exchange of the water masses in the basin. This work aims to describe the main circulation structures and thermohaline properties of the Eastern Mediterranean with particular focus on two anticyclones, the Pelops and the Cyprus gyres, using in-situ (drifters and Argo floats) and satellite (altimetry) data. The Pelops gyre is involved in the circulation and exchange of Levantine origin surface and intermediate waters and in their flow toward the Ionian and the Adriatic Sea. The Cyprus Gyre presents a marked interannual variability related to the presence/absence of waters of Atlantic origin in its interior. These anticyclones are characterized by double diffusive instability and winter mixing phenomena driven by salty surface waters of Levantine origin. Conditions for the salt finger regime occur steadily and dominantly within the Eastern Mediterranean anticyclones. The winter mixing is usually observed in December–January, characterized by instability conditions in the water column, a gradual deepening of the mixed layer depth and the consequent downward doming of the isohalines. The mixing generally involves the first 200 m of the water column (but occasionally can affect also the intermediate layer) forming a water mass with well-defined thermohaline characteristics. Conditions for salt fingers also occur during mixing events in the layer below the mixed layer.
Sequestration of Polystyrene Microplastics by Jellyfish Mucus
Authors: Lengar Živa , Klun Katja , Dogsa Iztok , Rotter Ana , Stopar David
Published: July 2021

The worldwide microplastics pollution is a serious environmental and health problem that is currently not effectively mitigated. In this work we tested jellyfish mucus as a new bioflocculent material capable of sequestration of polystyrene microplastics in aqueous environments. Mucus material was collected from different jellyfish species and was used to trap fluorescently tagged polystyrene microspheres. The efficiency of removal was tested using varying concentrations of microplastics and mucus. The interaction between the microplastics and mucus was determined by viscosity measurements and confocal laser scanning microscopy. Different mucus preparation methods were also tested: freshly prepared, mechanically sheared, freeze-thawed, freeze-dried, and hydrolyzed mucus. The results demonstrate that jellyfish mucus can efficiently sequester polystyrene microplastics particles from the suspension. The fraction of the removed microplastics was highest with freshly prepared mucus and decreased with freeze-thawing and freeze-drying. The mucus ability to sequester microplastics was completely lost in the hydrolyzed mucus. The results imply that the intact jellyfish mucus has the potential to be used as a biopolymer capable of removing microplastics material.
Rapid and Reliable Assessment of Fish Physiological Condition for Fisheries Research and Management Using Fourier Transform Near-Infrared Spectroscopy
Authors: Goldstein Esther D. , Helser Thomas E. , Vollenweider Johanna J. , Sreenivasan Ashwin , Sewall Fletcher F.
Published: July 2021

Measuring fish population responses to climate change requires timely ecological information, warranting innovative approaches to data collection in fisheries research and management. Fourier transform near-infrared (FT-NIR) spectroscopy is a promising tool to efficiently and cost-effectively obtain multiple types of fisheries data including fish physiological health and energetics that can provide indicators of stock status and environmental change. We tested the applicability of FT-NIR spectroscopy to determine fish physiological state and condition by developing calibration models for morphometric indices of body condition [Fulton’s K and hepatosomatic index (HSI)], biochemical measurements of tissue composition (lipid content and energy density), and a nucleic acid-based index of recent growth (RNA:DNA) of juvenile Pacific cod (Gadus macrocephalus). Calibration models had the best predictive ability for lipid content followed by HSI and energy density, whereas spectral data had weak relationships with Fulton’s K and RNA:DNA. For lipid content, energy density, and HSI, informative spectral regions were primarily associated with carbon-hydrogen bonds in lipid molecules. Additionally, FT-NIR spectroscopy calibration models better predicted lipid content than morphometric measurements that are often used as proxies for measuring energy reserves, indicating that FT-NIR spectroscopy might serve as a more informative index of body condition and energy stores than other rapid methods. Efficient sample analysis by FT-NIR spectroscopy can supplement traditional metrics of body condition and be especially useful for ensuring the availability of monitoring data in support of fisheries research and management.
Antibacterial Properties and Cytotoxicity of 100% Waste Derived Alkali Activated Materials: Slags and Stone Wool-Based Binders
Authors: Sgarlata Caterina , Dal Poggetto Giovanni , Piccolo Federica , Catauro Michelina , Traven Katja , Češnovar Mark , Nguyen Hoang , Yliniemi Juho , Barbieri Luisa , Ducman Vilma , Lancellotti Isabella , Leonelli Cristina
Published: July 2021

In this study we compare the leaching behavior and the antibacterial and cytotoxic properties of 100% slag or stone wool derived alkali activated materials. The antibacterial activity was measured as the inhibiting capacity against two Gram-negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa and one Gram-positive bacterial strain: Enterococcus faecalis. The cytotoxicity properties were tested on mouse embryonic fibroblast NIH-3T3 cell-line. It was proved that the high quality of the 3D aluminosilicate network of the consolidated materials obtained from powders of CaO or MgO-rich slags or stone wool, opportunely activated with NaO and/or Na-silicate, was capable of stabilizing heavy metal cations. The concentrations of leachate heavy cations were lower than the European law limit when tested in water. The effect of additives in the composites, basal fibers or nanocellulose, did not reduce the chemical stability and slightly influenced the compressive strength. Weight loss in water increased by 20% with basalt fibers addition, while it remained almost constant when nanocellulose was added. All the consolidated materials, cement-like in appearance, exhibited limited antibacterial properties (viability from 50 to 80% depending on the bacterial colony and the amount of sample) and absence of cytotoxicity, envisaging good acceptance from part of the final consumer and zero ecological impact. CaO-rich formulations can replace ordinary Portland cement (showing bacterial viability at 100%) with a certain capability for preventing the reproduction of the E. coli and S. aureus bacteria with health and environmental protection results.
Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights
Authors: Sahu Smrity , Sharma Keshav , Sharma Maryada , Narang Tarun , Dogra Sunil , Minz Ranjana Walker , Chhabra Seema
Published: July 2021

Erythema nodosum leprosum (ENL), also known as type 2 reaction (T2R) is an immune complex mediated (type III hypersensitivity) reactional state encountered in patients with borderline lepromatous and lepromatous leprosy (BL and LL) either before, during, or after the institution of anti-leprosy treatment (ALT). The consequences of ENL may be serious, leading to permanent nerve damage and deformities, constituting a major cause of leprosy-related morbidity. The incidence of ENL is increasing with the increasing number of multibacillary cases. Although the diagnosis of ENL is not difficult to make for physicians involved in the care of leprosy patients, its management continues to be a most challenging aspect of the leprosy eradication program: the chronic and recurrent painful skin lesions, neuritis, and organ involvement necessitates prolonged treatment with prednisolone, thalidomide, and anti-inflammatory and immunosuppressive drugs, which further adds to the existing morbidity. In addition, the use of immunosuppressants like methotrexate, azathioprine, cyclosporine, or biologics carries a risk of reactivation of persisters (Mycobacterium leprae), apart from their own end-organ toxicities. Most ENL therapeutic guidelines are primarily designed for acute episodes and there is scarcity of literature on management of patients with chronic and recurrent ENL. It is difficult to predict which patients will develop chronic or recurrent ENL and plan the treatment accordingly. We need simple point-of-care or ELISA-based tests from blood or skin biopsy samples, which can help us in identifying patients who are likely to require prolonged treatment and also inform us about the prognosis of reactions so that appropriate therapy may be started and continued for better ENL control in such patients. There is a significant unmet need for research for better understanding the immunopathogenesis of, and biomarkers for, ENL to improve clinical stratification and therapeutics. In this review we will discuss the potential of neutrophils (polymorphonuclear granulocytes) as putative diagnostic and prognostic biomarkers by virtue of their universal abundance in human blood, functional versatility, phenotypic heterogeneity, metabolic plasticity, differential hierarchical cytoplasmic granule mobilization, and their ability to form NETs (neutrophil extracellular traps). We will touch upon the various aspects of neutrophil biology relevant to ENL pathophysiology in a step-wise manner. We also hypothesize about an element of metabolic reprogramming of neutrophils by M. leprae that could be investigated and exploited for biomarker discovery. In the end, a potential role for neutrophil derived exosomes as a novel biomarker for ENL will also be explored.
National Early Warning Score Does Not Accurately Predict Mortality for Patients With Infection Outside the Intensive Care Unit: A Systematic Review and Meta-Analysis
Authors: Zhang Kai , Zhang Xing , Ding Wenyun , Xuan Nanxia , Tian Baoping , Huang Tiancha , Zhang Zhaocai , Cui Wei , Huang Huaqiong , Zhang Gensheng
Published: July 2021

Background: The prognostic value of the national early warning score (NEWS) in patients with infections remains controversial. We aimed to evaluate the prognostic accuracy of NEWS for prediction of in-hospital mortality in patients with infections outside the intensive care unit (ICU).

Methods: We searched PubMed, Embase, and Scopus for related articles from January 2012 to April 2021. Sensitivity, specificity, and likelihood ratios were pooled by using the bivariate random-effects model. Overall prognostic performance was summarized by using the area under the curve (AUC). We performed subgroup analyses to assess the prognostic accuracy of NEWS in selected populations.

Results: A total of 21 studies with 107,008 participants were included. The pooled sensitivity and specificity of NEWS were 0.71 and 0.60. The pooled AUC of NEWS was 0.70, which was similar to quick sequential organ failure assessment (qSOFA, AUC: 0.70) and better than systemic inflammatory response syndrome (SIRS, AUC: 0.60). However, the sensitivity (0.55) and AUC (0.63) of NEWS were poor in elder patients. The NEWS of 5 was more sensitive, which was a better threshold for activating urgent assessment and treatment.

Conclusions: The NEWS had good diagnostic accuracy for early prediction of mortality in patients with infections outside the ICU, and the sensitivity and specificity were more moderate when compared with qSOFA and SIRS. Insufficient sensitivity and poor performance in the elder population may have limitations as an early warning score for adverse outcomes. NEWS should be used for continuous monitoring rather than a single time point predictive tool.
Genetic Characteristics of Human Parainfluenza Virus Types 1–4 From Patients With Clinical Respiratory Tract Infection in China
Authors: Shao Nan , Liu Bo , Xiao Yan , Wang Xinming , Ren Lili , Dong Jie , Sun Lilian , Zhu Yafang , Zhang Ting , Yang Fan
Published: July 2021

Human parainfluenza viruses (HPIV1–4) cause acute respiratory tract infections, thereby impacting human health worldwide. However, there are no current effective antivirals or licensed vaccines for infection prevention. Moreover, sequence information for human parainfluenza viruses (HPIVs) circulating in China is inadequate. Therefore, to shed light on viral genetic diversity and evolution, we collected samples from patients infected with HPIV1–4 in China from 2012 to 2018 to sequence the viruses. We obtained 24 consensus sequences, comprising 1 for HPIV1, 2 for HPIV2, 19 for HPIV3, and 2 for HPIV4A. Phylogenetic analyses classified the 1 HPIV1 into clade 2, and the 2 HPIV4 sequences into cluster 4A. Based on the hemagglutinin-neuraminidase (HN) gene, a new sub-cluster was identified in one of the HPIV2, namely G1c, and the 19 HPIV3 sequences were classified into the genetic lineages of C3f and C3a. The results indicated that HPIV1–4 were co-circulated in China. Further, the lineages of sub-cluster C3 of HPIV3 were co-circulated in China. A recombination analysis indicated that a putative recombination event may have occurred in the HN gene of HPIV3. In the obtained sequences of HPIV3, we found that two amino acid substitution sites (R73K in the F protein of PUMCH14028/2014 and A281V in the HN protein of PUMCH13961/2014) and a negative selection site (amino acid position 398 in the F protein) corresponded to the previously reported neutralization-related sites. Moreover, amino acid substitution site (K108E) corresponded to the negative selection site (amino acid position 108) in the 10 F proteins of HPIV3. However, no amino acid substitution site corresponded to the glycosylation site in the obtained HPIV3 sequences. These results might help in studying virus evolution, developing vaccines, and monitoring HPIV-related respiratory diseases.
Aerobactin-Mediated Iron Acquisition Enhances Biofilm Formation, Oxidative Stress Resistance, and Virulence of Yersinia pseudotuberculosis
Authors: Li Changfu , Pan Damin , Li Mengyuan , Wang Yao , Song Luting , Yu Danyang , Zuo Yuxin , Wang Kenan , Liu Yuqi , Wei Zhiyan , Lu Zhiqiang , Zhu Lingfang , Shen Xihui
Published: July 2021

Aerobactin is a citrate-hydroxamate siderophore that is critical for the virulence of pathogenic enteric bacteria. However, although the aerobactin-producing iucABCD-iutA operon is distributed widely in the genomes of Yersinia species, none of the pathogenic Yersinia spp. was found to produce aerobactin. Here, we showed that the iucABCD-iutA operon in the food-borne enteric pathogen Yersinia pseudotuberculosis YPIII is a functional siderophore system involved in iron acquisition. The expression of the operon was found to be directly repressed by the ferric uptake regulator (Fur) in an iron concentration-dependent manner. In addition, we demonstrated that the aerobactin-mediated iron acquisition contributes to bacterial growth under iron-limited conditions. Moreover, we provided evidence that aerobactin plays important roles in biofilm formation, resistance to oxidative stress, ROS removal, and virulence of Y. pseudotuberculosis. Overall, our study not only uncovered a novel strategy of iron acquisition in Y. pseudotuberculosis but also highlighted the importance of aerobactin in the pathogenesis of Y. pseudotuberculosis.
Changes in Growth Performance and Ileal Microbiota Composition by Xylanase Supplementation in Broilers Fed Wheat-Based Diets
Authors: Wang Jian , Liu Sujie , Ma Jiayu , Piao Xiangshu
Published: July 2021

Xylanase exerts key roles in improving growth performance and intestinal health of broilers fed wheat-based diets. However, knowledge is limited regarding effects of xylanase supplementation on ileal microbiota in broilers. A total of 128 one-day-old broilers (initial BW 48.03 ± 0.33 g) were selected to investigate effects of xylanase (AT-xynA) on growth performance, ileal morphology, microbiota composition, immune response, antioxidant capacity, and endocrine peptide levels in broilers. Broilers were randomly allotted into two dietary treatments (n = 8), namely, a wheat-soybean basal diet and a basal diet with 4,000 U/kg AT-xynA (XY). On days 7, 14, 21, and 42, broilers were weighted and ileal tissues were sampled. Ileal digesta samples were collected for analyzing microbiota composition on days 21 and 42. The results showed that AT-xynA could improve average daily weight gain and average daily feed intake, and there were interactions between diet and age of broilers (p < 0.05). On days 21 and 42, xylanase supplementation decreased ileal microbiota α-diversity, and the relative abundance of potentially pathogenic microbiota, such as phylum Proteobacteria, family Moraxellaceae and Staphylococcaceae, genus Staphylococcus, Pseudomonas, Streptococcus, and Enterococcus, increased the abundance of Lactobacillus (p < 0.05). Moreover, the reduction in acetate concentration and abundance of short-chain fatty acid-producing bacteria was also observed in broilers from XY group (p < 0.05). AT-xynA increased ileal villus height, glucagon-like peptide-1, and insulin-like growth factor-1 concentrations and decreased interleukin-1β, interleukin-6, tumor necrosis factor-α, and malondialdehyde content in broilers, and these positive effects on intestinal health were greater in young broilers. In conclusion, xylanase supplementation to wheat-based diets could improve ileal intestinal morphology and immune function, and alleviate excess fermentation of bacteria, which may be related to changes of intestinal microbiota. In addition, the positive effects of xylanase on intestinal health were more pronounced in young broilers, thus contributing to subsequent improvement in growth performance of broilers.
Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat
Authors: Nogal Ana , Louca Panayiotis , Zhang Xinyuan , Wells Philippa M. , Steves Claire J. , Spector Tim D. , Falchi Mario , Valdes Ana M. , Menni Cristina
Published: July 2021

Background

Acetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort.

Results

Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18],P= 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations withCoprococcus,Barnesiella,Ruminococcus, andRuminococcaceae NK4A21and negative correlations were observed withLachnoclostridiumandBacteroides.We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = −0.07 [−0.11, −0.04],P= 2.8 × 10–4) and between visceral fat andLachnoclostridium(Beta [95%CI] = 0.076 [0.042, 0.11],P= 1.44 × 10–5). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect ofLachnoclostridiumon visceral fat. The taxonomic diversity showed thatLachnoclostridiumandCoprococcuscomprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found thatCoprococcusspp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol inLachnoclostridiumspp.

Conclusions

Our data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat.Coprococcusmay play an important role in host health by its production of vitamins B and SCFAs, whereasLachnoclostridiummight have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.
Regulation of Carbohydrate-Responsive Metabolic Genes by Histone Acetylation and the Acetylated Histone Reader BRD4 in the Gene Body Region
Authors: Mochizuki Kazuki , Ishiyama Shiori , Hariya Natsuyo , Goda Toshinao
Published: July 2021

Studies indicate that induction of metabolic gene expression by nutrient intake, and in response to subsequently secreted hormones, is regulated by transcription factors binding to cis-elements and associated changes of epigenetic memories (histone modifications and DNA methylation) located in promoter and enhancer regions. Carbohydrate intake-mediated induction of metabolic gene expression is regulated by histone acetylation and the histone acetylation reader bromodomain-containing protein 4 (BRD4) on the gene body region, which corresponds to the transcribed region of the gene. In this review, we introduce carbohydrate-responsive metabolic gene regulation by (i) transcription factors and epigenetic memory in promoter/enhancer regions (promoter/enhancer-based epigenetics), and (ii) histone acetylation and BRD4 in the gene body region (gene body-based epigenetics). Expression of carbohydrate-responsive metabolic genes related to nutrient digestion and absorption, fat synthesis, inflammation in the small intestine, liver and white adipose tissue, and in monocytic/macrophage-like cells are regulated by various transcription factors. The expression of these metabolic genes are also regulated by transcription elongation via histone acetylation and BRD4 in the gene body region. Additionally, the expression of genes related to fat synthesis, and the levels of acetylated histones and BRD4 in fat synthesis-related genes, are downregulated in white adipocytes under insulin resistant and/or diabetic conditions. In contrast, expression of carbohydrate-responsive metabolic genes and/or histone acetylation and BRD4 binding in the gene body region of these genes, are upregulated in the small intestine, liver, and peripheral leukocytes (innate leukocytes) under insulin resistant and/or diabetic conditions. In conclusion, histone acetylation and BRD4 binding in the gene body region as well as transcription factor binding in promoter/enhancer regions regulate the expression of carbohydrate-responsive metabolic genes in many metabolic organs. Insulin resistant and diabetic conditions induce the development of metabolic diseases, including type 2 diabetes, by reducing the expression of BRD4-targeted carbohydrate-responsive metabolic genes in white adipose tissue and by inducing the expression of BRD4-targeted carbohydrate-responsive metabolic genes in the liver, small intestine, and innate leukocytes including monocytes/macrophages and neutrophils.