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.

Ancient Roman concretes have survived millennia, but mechanistic insights into their durability remain an enigma. Here, we use a multiscale correlative elemental and chemical mapping approach to investigating relict lime clasts, a ubiquitous and conspicuous mineral component associated with ancient Roman mortars. Together, these analyses provide new insights into mortar preparation methodologies and provide evidence that the Romans employed hot mixing, using quicklime in conjunction with, or instead of, slaked lime, to create an environment where high surface area aggregate-scale lime clasts are retained within the mortar matrix. Inspired by these findings, we propose that these macroscopic inclusions might serve as critical sources of reactive calcium for long-term pore and crack-filling or post-pozzolanic reactivity within the cementitious constructs. The subsequent development and testing of modern lime clast–containing cementitious mixtures demonstrate their self-healing potential, thus paving the way for the development of more durable, resilient, and sustainable concrete formulations.

Background Clinical guidelines recommend the identification of asthma comorbidities, especially treatable problems such as parental behaviours and child and parent anxiety. Purpose We aimed to (1) explore associations of asthma severity with child and parent state anxiety, trait anxiety, and asthma-related anxiety as well as with caregiver behaviours around physical activity and (2) explore if caregiver behaviours around physical activity were associated with use of inhaled β-Agonists when symptomatic, and with child and parent anxiety. Patients and methods Patients ages 3–17 years with asthma (n = 72) and their parents were recruited from the Pulmonology-Allergology Pediatric clinic University Hospital Centre Split in Split, Croatia during 2021. During a clinical visit, the pharmacological regimen was assessed and spirometry was performed. Children completed the State-Trait Anxiety Inventory for Children (STAI-C) and the Youth Asthma-Related Anxiety Scale (YASS). Parents completed the State-Trait Anxiety Inventory (STAI), the Parent Asthma-Related Anxiety Scale (PASS), and the Physical Activity Parenting Practices – Short Form (PAPP). Results Most patients had mild asthma (69.4%). Children with moderate to severe asthma had increased asthma-related anxiety (mean = 11.94 ± 6.1) compared with children with mild asthma (mean = 5.97 ± 6.39, p = 0.003). Parents of children with mild asthma reported behaviours allowing unsupervised physical activity outside more often when compared to parents of children with moderate or severe asthma. Physical activity facilitation parenting behaviour reduced the odds of a child's need for quick-reliever medication when symptomatic (OR = 0.376,95% CI = −1.885 to −0.072; p = 0.034); more coercive parenting increased the odds of a child's additional use of such medications (OR = 2.602; 95% CI = 0.005 to 1.908; p = 0.049). Parents of children in the highest quartile of trait anxiety showed less non-directive support (1.97 ± 1.01 vs. 2.89 ± 1.19, p = 0.031) and less autonomy support (3.14 ± 1.32 vs. 4.11 ± 1.23, p = 0.037) of physical activity in their children than those with less trait anxiety. Conclusion Asthma-related anxiety was an important construct in this sample of children, associated with their disease severity as well as their parent's behaviours around the child's physical activities. Current research, conducted during the COVID-19 pandemic, recognised the tangible ways that parents support or avoid the asthmatic children's physical activity participation. Child anxiety and recognised parental physical activity behaviours are potentially important factors to assess and target for intervention.

Abstract Orevactaene yellow pigment was produced by solid-state fermentation of broken rice using Epicoccum nigrum. The pigment was extracted using water as a solvent and subjected to stability studies at different temperatures (30, 40, 60, and 80°C), pH (4, 6, and 8), sterilization, and sunlight exposure treatment. The observed data were fitted in the first-order kinetic model. Yellow pigment stability was found to vary at different temperatures studied. At 30°C, only a 4% decrease in color intensity was observed after 2 h; at 40°C, an 8% decrease was observed, and at 80°C and pH 6.0, 17% of color intensity was lost. These results showed that the orevactaene pigment produced by E. nigrum is heat-sensitive and changes in color intensity should be expected in heat-processed products. After 180 min at 80°C, yellow pigments maintained 82 and 76% of the initial color at pH 6 and 8, while a 65% decrease in color intensity was observed at 80°C, pH 4. Autoclaving resulted in 69% decay and exposure of pigment to sunlight for 2 h showed 1% decay. The half-life period of the pigment at different temperatures varied from 82.5 to 5.25 h. The decimal reduction time decreased from 275 to 17.5 h with an increase in the temperature. Thermodynamic parameters for pigment decay at pH 6.0 were represented in terms of enthalpy ∆H, activation energy E a, free energy ∆G, and entropy ∆S. The values observed were 44.52–44.93, 48.48, 96.60–105.18 kJ/mol, and −170.50 to −171.85 J/mol/K, respectively. All these parameters help in predicting the quality changes in terms of appearance during thermal processing and optimizing the process.

In this study, the authors summarize the current knowledge on epidemiology, demographics, risk factors, and prognostic factors that influence outcomes in patients with adult Chiari malformation type I (CM-I) who underwent posterior fossa decompression surgery with duraplasty. Furthermore, they describe the contribution of their research group to the field of adult CM-I treatment, including association of increased body mass index with severity of CM-I and syringomyelia, relevant surgical anatomy, and surgical technique of 270° microsurgical decompression of foramen magnum. The authors also report on common complications in the literature and describe techniques for prevention of complications.

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.

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.

High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation identification, variant calling, and phasing within each pharmacogene copy present in the sample. Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that uses combinatorial optimization for accurate star-allele calling across different sequencing technologies. Aldy 4 adds support for long reads and uses a novel phasing model and improved copy number and variant calling models. We compare Aldy 4 against the current state-of-the-art star-allele callers on a large and diverse set of samples and genes sequenced by various sequencing technologies, such as whole-genome and targeted Illumina sequencing, barcoded 10x Genomics, and Pacific Biosciences (PacBio) HiFi. We show that Aldy 4 is the most accurate star-allele caller with near-perfect accuracy in all evaluated contexts, and hope that Aldy remains an invaluable tool in the clinical toolbox even with the advent of long-read sequencing technologies.

Background: Response to the outbreak of poliomyelitis in mid-1950 led to recognition and consequent development of critical care. Seventy years later the humankind was struck by COVID-19, another major challenge for critical care medicine which was especially big in Low-Resources-Settings where more than two thirds of the world population live, including the population of the Republic of Srpska (RS). Design and methods: The main aim was to show an overview of all interventions in order to boost hospitals’ capacities to the level which is sufficient to manage high amount of critically ill COVID-19 patients in the RS. A before-after cohort study design was conducted to evaluate the effects of interventions for increase in preparedness and capacity of ICUs for admission and treatment of COVID-19 critically ill patients in nine hospitals in the RS. Results: Following interventions, the biggest and university affiliated hospital in the RS has increased ICU capacities: total number of ICU beds increased by 38% and number of ventilators by 114%. Availability of machines for veno-venous extracorporeal membrane oxygenation (vvECMO) increased by 100%. Number of doctors who were involved in treatment of critically ill patients increased by 47% and nurse/patient’s ratio reached 1:2.5. Similarly, all other hospitals experienced boosting of ICU beds by 189% and ventilators by 373% while number of doctors increased by 108% and nurse/patient’s ratio reached 1:4. Conclusion: All interventions implemented during COVID-19 pandemic outbreak in the RS resulted in increasing capacity for treatment of critically ill patients, but the education of health care professionals was identified as the most important conducted intervention.

With no expected vaccine for HIV in the near future, we aimed to define the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE). The Euroguidelines CEE Network Group members were invited to respond to a 27-item survey including questions on PrEP (response rate 91.6%). PrEP was licensed in 68.2%; 95 centers offered PrEP and the estimated number on PrEP was around 9000. It was available in daily (40.1%), on-demand (13.3%), or both forms (33.3%). The access rate was <1–80%. Three major barriers for access were lack of knowledge/awareness among people who are in need (59.1%), not being reimbursed (50.0%), and low perception of HIV risk (45.5%). Non-occupational PEP was available in 86.4% and was recommended in the guidelines in 54.5%. It was fully reimbursed in 36.4%, only for accidental exposures in 40.9%, and was not reimbursed in 22.72%. Occupational PEP was available in 95.5% and was reimbursed fully. Although PrEP scale-up in the region has gained momentum, a huge gap exists between those who are in need of and those who can access PrEP. Prompt action is required to address the urgent need for PrEP scale-up in the CEE region.