The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes’ distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

Purpose: Total elbow arthroplasty (TEA) is rarely performed compared to other arthroplasties. For many surgical procedures, literature shows better outcomes when they are performed by experienced surgeons and in so-called ‘high-volume’ hospitals. We systematically reviewed the literature on the relationship between surgical volume and outcomes following TEA. Methods: A literature search was performed using the MEDLINE, EMBASE and CINAHL databases. The literature was systematically reviewed for original studies comparing TEA outcomes among hospitals or surgeons with different annual or career volumes. For each study, data were collected on study design, indications for TEA, number of included patients, implant types, cut-off values for volume, number and types of complications, revision rate and functional outcome measures. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. Results: Two studies, which included a combined 2301 TEAs, found that higher surgeon volumes were associated with lower revision rates. The examined complication rates did not differ between high- and low-volume surgeons. In one study, low-hospital volume is associated with an increased risk of revision compared to high-volume hospitals, but for other complication types, no difference was found. Conclusions: Based on the results, the evidence suggests that high-volume centers have a lower revision rate in the long term. No minimum amount of procedures per year can be advised, as the included studies have different cut-off values between groups. As higher surgeon- and center-volume, (therefore presumably experience) appear to yield better outcomes, centralization of total elbow arthroplasty should be encouraged.

Artemisia annua L. has long been known for its medicinal properties and isolation of ingredients whose derivatives are used for therapeutic purposes. The CYP2B6 and CYP3A4 enzymes belong to a large family of cytochrome P450 enzymes. These enzymes are involved in the metabolism of drugs and other xeonobiotics. It is known that various compounds can induce or inhibit the activity of these enzymes. The aim of this study was to investigate the nature of the inhibitory effect of Artemisia annua extract on CYP2B6 and CYP3A4 enzymes, as well as the type of inhibition, the presence of reversible or pseudo-irreversible inhibition, and the possible heme destruction. The methanolic extract of Artemisia annua showed an inhibitory effect on CYP2B6 (by almost 90%) and CYP3A4 enzymes (by almost 70%). A significant decrease in heme concentration by 46.8% and 38.2% was observed in different assays. These results clearly indicate that the studied plant extracts significantly inhibited the activity of CYP2B6 and CYP3A4 enzymes. Moreover, they showed irreversible inhibition, which is even more important for possible interactions with drugs and dietary supplements.

With the goal of enhancing the quality of the environment, urban green infrastructure (UGI) is an essential element in sustainable cities, and nature-based solutions (NBS) are being carried out as new infrastructure solutions that increase the resilience of cities. In this research, the method of theoretical analysis and the content analysis as the basic fact-gathering technique was applied to answer to following questions: What are the hindrances and bottlenecks in implementing NBS? Are the current decision-making mechanisms helping NBS get in route to shape cities? Is there any binding policy in practice that promotes NBS? In Belgrade is planned Type 3 of the degree of intervention/level and engineering type—Creation and new ecosystem management in the classifications of intensive urban green space management; urban planning strategies; urban water management; ecological restoration of degraded terrestrial ecosystems; and restoration and creation of semi-natural water bodies and hydrographic networks. In the future, it is essential to implement policies and incentives on national, regional, and local scales that help encourage the usage of NBS in the development of urban infrastructure.

Purpose Paediatric Type 1 Diabetes (T1D) patients are at greater risk for developing severe hypo and hyperglycaemic events due to poor glycaemic control. To reduce the risk of adverse events, patients need to achieve the best possible glycaemic management through frequent blood glucose monitoring with finger prick or Continuous Glucose Monitoring (CGM) systems. However, several non-invasive techniques have been proposed aiming at exploiting changes in physiological parameters based on glucose levels. The overall objective of this study is to validate an artificial intelligence (AI) based algorithm to detect glycaemic events using ECG signals collected through non-invasive device. Methods This study will enrol T1D paediatric participants who already use CGM. Participants will wear an additional non-invasive wearable device for recording physiological data and respiratory rate. Glycaemic measurements driven through ECG variables are the main outcomes. Data collected will be used to design, develop and validate the personalised and generalized classifiers based on a deep learning (DL) AI algorithm, able to automatically detect hypoglycaemic events by using few ECG heartbeats recorded with wearable devices. Results Data collection is expected to be completed approximately by June 2023. It is expected that sufficient data will be collected to develop and validate the AI algorithm. Conclusion This is a validation study that will perform additional tests on a larger diabetes sample population to validate the previous pilot results that were based on four healthy adults, providing evidence on the reliability of the AI algorithm in detecting glycaemic events in paediatric diabetic patients in free-living conditions. Trial registration ClinicalTrials.gov identifier: NCT03936634. Registered on 11 March 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05278143?titles=AI+for+Glycemic+Events+Detection+Via+ECG+in+a+Pediatric+Population&draw=2&rank=1 .

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

Background Spontaneous sternal fracture is an extremely rare cause of chest pain during or after childbirth. To date, only three cases of sternal fracture during childbirth have been reported. This case report represents the first documented case of spontaneous sternal fracture among multiparous women. Case Description A 33-year-old multiparous woman with an uncomplicated medical history is described, who delivered a healthy fourth infant vaginally at 41 weeks of pregnancy. After the previous three deliveries, each child had been breastfed for more than a year, and the third delivery was eight months before conception, and she breastfed until 3 months of pregnancy. During the final stage of labor, while performing the Valsalva maneuver in the lithotomy position, she felt a sharp, severe chest pain. Postpartum work-up included cardioselective enzymes that were within reference values, and radiological work-up confirmed a non-displaced sternal fracture, which was treated conservatively with symptomatic therapy, with complete recovery after 6 weeks. Conclusions This case report suggests the need to consider sternal fracture as a differential diagnostic consideration in women who experience chest pain during or immediately after delivery. Changes in metabolism, especially calcium metabolism during pregnancy and lactation, can result in transient osteopenia and, with increased mechanical stress, cause bone fracture. Special attention should be paid to patients who breastfed immediately before conception or who breastfeed during pregnancy, to vitamin and mineral replacement therapy, adequate nutrition, and physical activity. Timely diagnosis of sternal fracture can significantly reduce the need for expensive and invasive diagnostic tests. Further research is needed on osteopenia in pregnant women, especially multiparous women who are breastfeeding immediately before conception or during pregnancy.

: The paper presents the chemical composition of the fruits of three apple cultivars (Jonagold Decosta, Red Idared and Gala Schnitzer Schniga) fertilized with three treatment: T 1 (control‒without fertilization); T 2 (300 kg/ha NPK (6:18:36) + 150 kg/ha N (calcium ammonium nitrate‒CAN)) and T 3 (foliar nutrition-mixture organic-mineral fertilizer commercially named ‘FitoFert Kristal’ (0.6%) (10:40:10) + ‘FitoFert Kristal’ (0.6%) (20:20:20) + ‘FoliFetril Ca’ (0.5%) (N:Ca) in Bosnia and Herzegovina during two years (2020‒2021). Significant differences of contents of soluble solids, total sugars, inverted sugars, sucrose, total phenolic content, content of flavonoids and antioxidant activity were found among cultivar/treatment combinations, cultivars, treatments and years. Differences in total acids content among treatments and years were not statistically significant, but significant differences among cultivars and cultivar/treatment combinations were found. The contents of soluble solids, total sugars and sucrose were the highest in fruits of cultivar Jonagold Decosta, while the highest contents of inverted sugars, total acids, total phenolics, flavonoids and antioxidant activity were found in fruits of Red Idared cultivar. The fertilization treatment T 2 significantly influenced the content of soluble solids, total sugars, inverted sugars, total acids, total phenolic, flavonoids and antioxidant activity in the apple fruits. According to the results obtained, we can say that fertilization treatment T 3 do not have much effect on bioactive ingredients, with the exception of the sucrose content. Among mineral elements, four were macroelements that were represented present in large amounts: potassium (K) (1266.15 mg kg –1 to 1652.89 mg kg –1 ), calcium (Ca) (122.76‒474.90 mg kg –1 ), phosphor (P) (86.14‒124.84 mg kg –1 ) and magnesium (Mg) (57.36‒70.68 mg kg –1 ). On the other hand, four microelements were determined: boron (B) (1.06‒14.25 mg kg –1 ); iron (Fe) (2.79‒4.62 mg kg –1 ); manganese (Mn) (0.27‒0.46 mg kg –1 ) and zinc (Zn) (0.15‒0.48 mg kg –1 ). Results showed that contents of macroelements and microelements have been strongly affected by cultivar/treatment combinations, cultivars, treatments and years.

Abstract Global brachial plexus injury (GBPI) mainly affects adults and causes severe life-changing consequences that lead to the deterioration of patients’ quality of life. Several surgical approaches have been described and reported in the literature to improve patients’ functional ability. A literature review is done on PubMed/MEDLINE and Embase using specific keywords to retrieve relevant articles assessing different surgical approaches for GBPI management. Inclusion and exclusion criteria were applied, and eligible articles were included in the review. The literature survey revealed that various surgical options had been used to manage GBPI patients. In this concise review, we discuss and compare the different surgical approaches related to GBPI and its outcome in terms of restoring elbow flexion and extension, shoulder abduction, and wrist and hand function. The primary surgical intervention relies mainly on transferring single or multiple nerves with/without nerve grafts to restore the function of the targeted muscle. Different techniques using a variety of nerve donors and recipients are compared to assess the functional outcomes of each option. Moreover, further options are addressed for delayed GBPI injuries or failed nerve transfer procedures, as in free functional muscle transfer techniques. In addition, information about brachial plexus injury cases faced in our center is presented along with our center’s approach to diagnosing and managing partial and GBPI cases.