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Wounds have become one of the causes of death worldwide. The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds that bring great pain to patients, and there is currently no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal dressing candidate because of its 3D structure, good permeability, excellent biocompatibility, and ability to provide a moist environment for wound repair, which overcomes the shortcomings of traditional dressings. This article first briefly introduces the skin wound healing process, then the preparation methods of hydrogel dressings and the characteristics of hydrogel wound dressings made of natural biomaterials and synthetic materials are introduced. Finally, the development prospects and challenges of hydrogel wound dressings are discussed. Full article

Mutations resulting in amino-acid substitutions of the SARS-CoV-2 spike protein receptor-binding domain (RBD) have been associated with enhanced transmissibility and immune escape of the respective variants, namely Alpha, Beta, Gamma or Delta. Rapid identification of the aforementioned variants of concern and their discrimination of other variants is thus of importance for public health interventions. For this reason, a one-step real-time RT-PCR assay employing four locked nucleic acid (LNA) modified TaqMan probes was developed, to target signature mutations associated with amino-acid substitutions at positions 478, 484 and 501 present in the receptor-binding motif (RBM) of the spike protein RBD. This region contains most contacting residues of SARS-CoV-2 that bind to ACE2. A novel strategy employing the use of non-extendable LNA oligonucleotide blockers that can reduce non-specific hybridization of probes increased the number of different mutated sites examined in a multiplex PCR. The combinatory analysis of the different fluorescence signals obtained enabled the preliminary differentiation of SARS-CoV-2 variants of concern. The assay is sensitive with a LOD of 263 copies/reaction for the Delta variant, 170 copies/reaction for the Beta variant, amplification efficiencies > 91% and a linear range of >5 log₁₀ copies/reaction against all targets. Validation of the assay using known SARS-CoV-2-positive and negative samples from humans and animals revealed its ability to correctly identify the targeted mutations and preliminary characterize the SARS-CoV-2 variants. The novel approach for mutation typing using LNA oligonucleotide blockers can be modified to target signature mutations at four different sites in the RBM and further expand the range of variants detected. Full article

The electrocardiogram (ECG) is widely used for cardiovascular disease diagnosis and daily health monitoring. Before ECG analysis, ECG quality screening is an essential but time-consuming and experience-dependent work for technicians. An automatic ECG quality assessment method can reduce unnecessary time loss to help cardiologists perform diagnosis. This study aims to develop an automatic quality assessment system to search qualified ECGs for interpretation. The proposed system consists of data augmentation and quality assessment parts. For data augmentation, we train a conditional generative adversarial networks model to get an ECG segment generator, and thus to increase the number of training data. Then, we pre-train a deep quality assessment model based on a training dataset composed of real and generated ECG. Finally, we fine-tune the proposed model using real ECG and validate it on two different datasets composed of real ECG. The proposed system has a generalized performance on the two validation datasets. The model’s accuracy is 97.1% and 96.4%, respectively for the two datasets. The proposed method outperforms a shallow neural network model, and also a deep neural network models without being pre-trained by generated ECG. The proposed system demonstrates improved performance in the ECG quality assessment, and it has the potential to be an initial ECG quality screening tool in clinical practice. Full article

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of life. The pathogenesis of VKC has not yet been completely understood, and it is still controversial. In fact, VKC is considered an ocular allergic disease due to the involvement of immunoglobulin E, eosinophils, and mast cells, and of a lymphocyte T-helper type 2 reaction. However, approximately half of VKC patients have negative allergological history and testing, suggesting that other pathogenic mechanisms participate in VKC development and severity. Specifically, evidence suggests that genetic, endocrine, neuronal factors and an imbalance of innate immunity are involved in the pathogenesis of VKC. The purpose of this review is to summarize evidence on the pathogenic role of innate immunity, neuroimmune reaction, and hormonal changes in VKC. Increasing understanding of the pathogenic mechanisms behind VKC may lead to the identification of novel biomarkers for diagnosis and/or potential therapeutic targets in order to improve the management of this challenging condition. Full article

An undetermined saprobic fungal taxon from Yunnan (China) is revealed as a new genus in Scortechiniaceae (Coronophorales). The novel taxon, Yuxiensis, is characterized by immersed to erumpent, semi-globose ascomata, which are not surrounded by any tomentum or conspicuous subiculum, a subcylindrical quellkörper in the centrum, clavate asci with long pedicels and allantoid hyaline ascospores with granular contents. Maximum likelihood and Bayesian posterior probability analyses based on LSU, ITS, tef1 and rpb2 sequence data depict a close phylogenetic relationship of the new genus to Pseudocatenomycopsis, hence, confirming its placement in Scortechiniaceae. Parasympodiellaceae, thus far belonging to Parasympodiellales, is transferred to Coronophorales based on multi-gene phylogenetic evidence. Additionally, the incertae sedis monotypic genus Arthrocristula is treated as a synonym of Parasympodiella, with Arthrocristula hyphenata recombined as Parasympodiella hyphenata comb. nov., as the type strain of Arthrocristula hyphenata clusters inside the Parasympodiellaceae clade along with other Parasympodiella taxa. Full article

Although many reports characterize the transcriptional response of Arabidopsis seedlings to microgravity, few investigate the effect of partial or fractional gravity on gene expression. Understanding plant responses to fractional gravity is relevant for plant growth on lunar and Martian surfaces. The plant signaling flight experiment utilized the European Modular Cultivation System (EMCS) onboard the International Space Station (ISS). The EMCS consisted of two rotors within a controlled chamber allowing for two experimental conditions, microgravity (stationary rotor) and simulated gravity in space. Seedlings were grown for 5 days under continuous light in seed cassettes. The arrangement of the seed cassettes within each experimental container results in a gradient of fractional g (in the spinning rotor). To investigate whether gene expression patterns are sensitive to fractional g, we carried out transcriptional profiling of root samples exposed to microgravity or partial g (ranging from 0.53 to 0.88 g). Data were analyzed using DESeq2 with fractional g as a continuous variable in the design model in order to query gene expression across the gravity continuum. We identified a subset of genes whose expression correlates with changes in fractional g. Interestingly, the most responsive genes include those encoding transcription factors, defense, and cell wall-related proteins and heat shock proteins. Full article

During the last decades, the number of lowland children exposed to high altitude (HA) has increased drastically. Several factors may influence the development of illness after acute HA exposure on children and adolescent populations, such as altitude reached, ascent velocity, time spent at altitude and, especially, their age. The main goal of this study was to evaluate the resting cardiorespiratory physiological and submaximal exercise responses under natural HA conditions by means of the six-minute walking test (six MWT). Secondly, we aimed to identify the signs and symptoms associated with acute mountain sickness (AMS) onset after acute HA exposure in children and adolescents. Forty-two children and adolescents, 18 boys and 24 girls aged from 11 to 15 years old, participated in this study, which was performed at sea level (SL) and during the first 42 hours at HA (3330 m). The Lake Louise score (LLS) was recorded in order to evaluate the evolution of AMS symptoms. Submaximal exercise tests (six MWT) were performed at SL and HA. Physiological parameters such as heart rate, systolic and diastolic blood pressure, respiratory rate and arterialized oxygen saturation were measured at rest and after ending exercise testing at the two altitudes. After acute HA exposure, the participants showed lower arterial oxygen saturation levels at rest and after the submaximal test compared to SL (p < 0.001). Resting heart rate, respiratory rate and diastolic blood pressure presented higher values at HA (p < 0.01). Moreover, heart rate, diastolic blood pressure and dyspnea values increased before, during and after exercise at HA (p < 0.01). Moreover, submaximal exercise performance decreased at HA (p < 0.001). The AMS incidence at HA ranged from 9.5% to 19%, with mild to moderate symptoms. In conclusion, acute HA exposure in children and adolescent individuals produces an increase in basal cardiorespiratory parameters and a decrement in arterial oxygen saturation. Moreover, cardiorespiratory parameters increase during submaximal exercise at HA. Mild to moderate symptoms of AMS at 3330 m and adequate cardiovascular responses to submaximal exercise do not contraindicate the ascension of children and adolescents to that altitude, at least for a limited period of time. Full article

Microgravity environments are known to cause a plethora of stressors to astronauts. Recently, it has become apparent that gut microbiome composition of astronauts is altered following space travel, and this is of significance given the important role of the gut microbiome in human health. Other changes observed in astronauts comprise reduced muscle strength and bone fragility, visual impairment, endothelial dysfunction, metabolic changes, behavior changes due to fatigue or stress and effects on mental well-being. However, the effects of microgravity on angiogenesis, as well as the connection with the gut microbiome are incompletely understood. Here, the potential association of angiogenesis with visual impairment, skeletal muscle and gut microbiome is proposed and explored. Furthermore, metabolites that are effectors of angiogenesis are deliberated upon along with their connection with gut bacterial metabolites. Targeting and modulating the gut microbiome may potentially have a profound influence on astronaut health, given its impact on overall human health, which is thus warranted given the likelihood of increased human activity in the solar system, and the determination to travel to Mars in future missions. Full article

Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder that occurs due to a deficiency of a β hexosaminidase A (HexA) enzyme, resulting in the accumulation of GM₂ gangliosides. In this work, we analyzed the effect of umbilical cord blood cell transplantation (UCBCT) and curcumin administration on the course of the disease in a patient with adult TSD. The patient’s serum cytokine profile was determined using multiplex analysis. The level of GM₂ gangliosides in plasma was determined using mass spectrometry. The enzymatic activity of HexA in the plasma of the patient was assessed using a fluorescent substrate assay. The HexA α-subunit (HexA) concentration was determined using ELISA. It was shown that both UCBCT and curcumin administration led to a change in the patient’s cytokine profile. The UCBCT resulted in an increase in the concentration of HexA in the patient’s serum and in an improvement in the patient’s neurological status. However, neither UCBCT nor curcumin were able to alter HexA activity and the level of GM₂ in patient’s plasma. The data obtained indicate that UCBCT and curcumin administration can alter the immunity of a patient with TSD, reduce the level of inflammatory cytokines and thereby improve the patient’s condition. Full article

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients. Full article

Coronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients´ outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization. Full article

The COVID-19 pandemic has had a major impact on cardiovascular emergencies. The aim of this study was to investigate the impact of the COVID-19 pandemic on a regional network for management of ST-segment elevation acute myocardial infarction (STEMI). Methods: We report a single center’s experience of patients hospitalized for ACS in a high-volume hub of a STEMI network during the lockdown (in the first pandemic trimester), compared with the same time interval of the previous year and including all consecutive patients referred for an AMI during the second trimester of 2020 (from April to June) or during the same time interval of the previous year, 2019. Results: The absolute number of hospital admissions for AMI decreased by 22.3%, while the non-AMI hospitalizations decreased by 77.14% in Q2-2020 compared to Q2-2019 (210 vs. 48, p < 0.0001). As a consequence, the percentage of AMI cases from the total number of hospital admission increased from 38% to 68% (p < 0.0001), AMI becoming the dominant pathology. In the STEMI group there was a significant reduction of 55% in the absolute number of late STEMI presentations. Functionality of the STEMI network at the hub level did not present a significant alteration with only a minor increase in the door-to-balloon time, from 34 min to 41 min. However, at the level of the network we recorded a lower number of critical cases transferred to the interventional center, with a dramatic reduction of 56.1% in the number of critical STEMI cases arriving in the acute cardiac care unit (17.0% vs. 7.3%, p-0.04 for KILLIP class III, and 21.17% vs. 11.11%, p = 0.08 for resuscitated out of hospital cardiac arrest). Conclusions: The COVID-19 outbreak did not have a major impact on the interventional center’s functionality, but it limited the capacity of the regional STEMI network to bring the critical patient with complicated STEMI to the cathlab in time during the first months of the lockdown. Even a very well-functioning STEMI network like the one in Central Romania had difficulties bringing the most critical STEMI cases to the cathlab in time. Full article

Raman stable isotope probing (Raman-SIP) is an excellent technique that can be used to access the overall metabolism of microorganisms. Recent studies have mainly used an excitation wavelength in the visible range to characterize isotopically labeled bacteria. In this work, we used UV resonance Raman spectroscopy (UVRR) to evaluate the spectral red-shifts caused by the uptake of isotopes (¹³C, ¹⁵N, ²H(D) and ¹⁸O) in E. coli cells. Moreover, we present a new approach based on the extraction of labeled DNA in combination with UVRR to identify metabolically active cells. The proof-of-principle study on E. coli revealed heterogeneities in the Raman features of both the bacterial cells and the extracted DNA after labeling with ¹³C, ¹⁵N, and D. The wavelength of choice for studying ¹⁸O- and deuterium-labeled cells is 532 nm is, while ¹³C-labeled cells can be investigated with visible and deep UV wavelengths. However, ¹⁵N-labeled cells are best studied at the excitation wavelength of 244 nm since nucleic acids are in resonance at this wavelength. These results highlight the potential of the presented approach to identify active bacterial cells. This work can serve as a basis for the development of new techniques for the rapid and efficient detection of active bacteria cells without the need for a cultivation step. Full article

Nosocomial fungal infections are an emerging global public health threat that requires urgent attention and proper management. With the limited availability of treatment options, it has become necessary to understand the emerging epidemiological trends, mechanisms, and risk factors. However, very limited surveillance reports are available in the Latvian and broader European context. We therefore conducted a retrospective analysis of laboratory data (2017–2020) from Pauls Stradinš Clinical University Hospital (PSCUH), Riga, Latvia, which is one of the largest public multispecialty hospitals in Latvia. A total of 2278 fungal isolates were analyzed during the study period, with Candida spp. comprising 95% of the isolates, followed by Aspergillus spp. and Geotrichum spp. Amongst the Candida spp., C. albicans and C. glabrata made up about 75% of the isolates. The Department of Lung Diseases and Thoracic Surgery had the highest caseload followed by Intensive Care Department. Majority of the fungal isolates were collected from the bronchoalveolar lavage (37%), followed by urine (19%) and sputum (18%) samples. A total of 34 cases of candidemia were noted during the study period with C. albicans being the most common candidemia pathogen. Proper surveillance of emerging epidemiological trends serve as the most reliable and powerful cornerstone towards tackling this emerging threat. Full article

Background: Telocytes (TCs) are a peculiar morphological type of stromal cells. They project long and moniliform telopodes, visible on various bidimensional sections. Originally regarded as “interstitial Cajal-like cells”, gastrointestinal TCs were CD34+. Further double-labelling studies found that colon TCs are negative for the expressions of the PDGFR-α and α-SMA. However, the TCs in colon were not distinguished specifically from endothelial cells (ECs), vascular or lymphatic. A combinational approach is important for accurate TC identification. Hence, we designed an immunohistochemical study of human colon to check whether ECs and CD34+ TCs express different markers. Methods: Immunohistochemistry was performed on archived paraffin-embedded samples of human colon (nine cases) for the following markers: CD31, CD34, CD117/c-kit and D2-40 (podoplanin). Results: A distinctive population of CD34+ TCs was found coating the myenteric ganglia. However, also perivascular cells and vascular ECs were CD34+. c-kit expression was equally found in interstitial Cajal cells (ICCs) and perivascular cells. The CD34 TCs did not express c-kit. As they were equally CD31- and D2-40- they were assessed as different from ECs. Conclusions: Testing specific markers of ECs, vascular and lymphatic, in the same tissues in which CD34+ TCs are found, is much more relevant than to identify TCs by transmission electron microscopy alone. Full article

Psoriasis is a chronic immunoinflammatory skin disease. Although its diagnosis is clinical, differences in the appearance and severity of lesions pose a challenge for clinicians worldwide. The use of accessible biomarkers for psoriasis could aid in the early diagnosis and treatment of the disease. To date, evidence on the analysis of gingival crevicular fluid (GCF) molecules as novel, accessible, and reliable biomarkers for psoriasis is limited. This cross-sectional study compared the GCF levels of IL-18, soluble (s)ICAM-1, and sE-selectin in psoriatic patients (n = 42) and healthy controls (n = 39). Individuals with psoriasis not undergoing treatment and healthy individuals were included independent of periodontal status. GCF samples were collected, and a multiplex bead immunoassay was performed to quantify the levels of the target molecules. Psoriatic patients presented higher concentrations of IL-18 and lower concentrations of sE-selectin compared to controls (p < 0.05). No differences were found in the levels of sICAM-1 between the two groups (p > 0.05). Psoriasis was associated with IL-18 and E-selectin levels regardless of periodontal status, age, and smoking habit (p < 0.05). The areas under the receiver operating characteristic curve (ROC) for IL-18 and sE-selectin were 0.77 and 0.68, respectively. In conclusion, IL-18 and sE-selectin levels in the GCF could be promising biomarker for psoriasis. Full article

A hallmark of Bacillus thuringiensis bacteria is the formation of one or more parasporal crystal (Cry) proteins during sporulation. The toxicity of these proteins is highly specific to insect larvae, exerting lethal effects in different insect species but not in humans or other mammals. The aim of this review is to summarize previous findings on Bacillus thuringiensis, including the characteristics of the bacterium, its subsequent contribution to biotechnology as a bioinsecticide due to the presence of Cry proteins, and its potential application as an adjuvant. In several studies, Cry proteins have been administered together with specific antigens to immunize experimental animal models. The results have shown that these proteins can enhance immunogenicity by generating an adequate immune response capable of protecting the model against an experimental infectious challenge, whereas protection is decreased when the specific antigen is administered without the Cry protein. Therefore, based on previous results and the structural homology between Cry proteins, these molecules have arisen as potential adjuvants in the development of vaccines for both animals and humans. Finally, a model of the interaction of Cry proteins with different components of the immune response is proposed. Full article

Seahorses are considered a flagship species for conservation efforts and due to their conservation status, improving knowledge on their dietary composition while applying a non-invasive approach, could be useful. Using Hippocampus guttulatus as a case study, the present study represents pioneering research into investigating the diet of seahorses by NGS-based DNA metabarcoding of fecal samples. The study developed and tested the protocol for fecal DNA metabarcoding during the feeding trials where captive seahorses were fed on a diet of known composition; the process was subsequently applied on fecal samples collected from wild individuals. The analysis of samples collected during the feeding trials indicated the reliability of the applied molecular approach by allowing the characterization of the effectively ingested prey. In the field study, among detected prey species, results revealed that the majority of the seahorse samples contained taxa such as Amphipoda, Decapoda, Isopoda, and Calanoida, while less common prey taxa were Gastropoda and Polyplacophora. As only a small amount of starting fecal material is needed and the sampling procedure is neither invasive nor lethal. The present study indicates DNA metabarcoding as useful for investigating seahorse diet and could help define management and conservation actions. Full article