Interleukin 10 (IL-10) is an immunosuppressive cytokine and its genetic variants could have an indirect impact on viral biology and human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) expression as well. This study evaluates the association between IL-10-592 C/A (rs1800872) single-nucleotide polymorphism and HPV E6/E7 mRNA expression in a group of women from the Republic of North Macedonia. Using a commercial test, 272 women's cervical samples were analyzed for HPV E6/E7 mRNA and HPV DNA presence. The cases were stratified into three groups: double-positive (n = 108, positive for both tests), negative (n = 51, negative for HPV E6/E7 mRNA and HPV DNA positive), and the control group (n = 113, negative for both tests). The IL-10-592 C/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The results showed the CC genotype and the C allele frequencies of IL-10-592C/A were significantly higher in double-positive (59.3% and 78.2%) compared to negative group (39.2% and 65.7%), (p = 0.018, confidence interval [CI] = 2.25; 1.14-4.45 and p = 0.016, CI = 1.88; 1.11-3.16, respectively). The CC genotype and C allele of rs1800872 polymorphism were shown to be associated with HPV E6/E7 mRNA but not with HPV DNA positivity, which implies a possible role of this polymorphism in the course of the infection only after HPV onset, and lack of association with the susceptibility to HPV.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
The Impact of COVID-19 on Prison Conditions and Penal Policy presents the results of a worldwide exchange of information on the impact of COVID-19 in prisons. It also focuses on the human rights questions that have been raised during the pandemic, relating to the treatment of prisoners in institutions for both juveniles and adults worldwide.
To be a pediatrician means that one encounters many serious childhood health problems and one finds many ways to help families cope with these problems. Symptoms in children can be discrete, and the responsibility of the pediatrician to distinguish normal development from pathological. We are facing a new era in the developmental assessment of children. A cluster of neurodevelopmental disorders includes ASD (autism spectrum disorder) and ADHD (attention deficit hyperactivity disorder). Parents often do not recognize the problem on time. Generally, their first concern is speech delay, leading to the suspicion of hearing problems. Therefore, it is very important to obtain objective anamnestic information and for the child to undergo a careful physical examination, a neurophysiological assessment, and metabolic and genetic testing. The etiology usually is multifactorial: genetic, epigenetic, and non-genetic factors act in combination through various paths. Most children seem to have typical neurodevelopment during first their year. It was found that approximately one-third of children with ASD lose some skills during the preschool period, usually speech related, but sometimes also non-verbal communication, social or play skills. In conclusion we must say that it is very important to recognize the early signs of ASD and any kind of other developmental delay and to start with early intervention. Clinical pediatricians tend to correlate clinical manifestations and biological underpinnings related to neurodevelopmental disorder, especially ASD. Therefore, better treatment possibilities are needed.
Communicating safety information to patients and healthcare professionals is a public health responsibility and is essential for achieving the objectives of pharmacovigilance in terms of promoting the rational, safe and effective use of medicines, preventing harm from adverse reactions, minimising risks and contributing to the protection of patients and public health. The main emphasis of this article is on direct healthcare professional communication (DHPC). Countries of interest are Macedonia, Serbia, Bosnia & Herzegovina, Montenegro, Albania and Kosovo. Safety communication should deliver relevant, clear, accurate and consistent messages and reach the right audiences at the right time for them to take appropriate action. Readers will get an indepth look at regulation compliance from the emerging markets within country-specific environments.
SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1 % of individuals aged 20–70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7–24.7] for individuals under 70 years old and 5.8[4.5–7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8–774.4] and 7.2[5.0–10.3], respectively. IFRs increased with age, from 0.17%[0.12–0.31] for individuals <40 years old to 26.7%[20.3–35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31–8.28] to 40.5%[27.82–61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
This study addresses the potential of combining multiple electroless plating reactions for homogeneous decoration of three-dimensional carbon fibers (CFs) with shape-controlled AgNi and AgCu bimetallic nanostructures. Morphology, crystal structure, and composition of the obtained bimetallic nanostructures were systemically examined by various spectroscopic and microscopic techniques including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrocatalytic performance of the synthesized materials was investigated for the oxygen evolution reaction (OER). AgCu and AgNi bimetallic surfaces showed superior activity and stability compared to pristine Ag, Ni, or Cu. These observed enhancements on the bimetallic nanostructures are attributed to the synergistic effect between the elements present. AgNi nanoplate-decorated CFs exhibited the highest activity toward OER, which is attributed to the key role of Ag in stabilizing and increasing the number of β-NiOOH surface sites, which are the most relevant OER-active Ni species.
With the development of technology and the overwhelming expansion of the social networks in people’s daily life nowadays, a completely new branch in the direct marketing has emerged, and that is the influencer marketing. Influencer - marketing is emerging as a new and successful tool for promoting products, with more and more people appearing on social media. Over the years, the rate of influencers in digital marketing has been increasing, and it is believed that they can influence consumers’ decision to buy products directly. The emergence of influencers and their engagement is relatively new, hence the question of the status of influencers and their commercial activity in the legal system becomes an issue worth considering and regulating. How do influencers make money? Is there regulation for their actions? Are their actions in the internet space limited? What is their status? Do they pay taxes? These questions are the subject for analysis and elaboration in this text. The legal scope of this influencer – marketing is entering in many aspects of the Macedonian legal system, thus providing space for legal analysis, interpretation and regulation. This text in particular aims to make an analysis of the legal aspects of the contracts between the influencers and the brands, as well as the legal impact of the influencers’ actions on the consumers’ rights.
ife-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
Идејата на овој труд е да се утврди на кој начин се обезбедува правната заштита на компјутерските програми. Законодавството на ЕУ го има во предвид зголеменото значење на овој тип на технологија, а се повеќе внимание се посветува на законската регулатива за заштита на компјутерските програми, со цел да се обезбеди соодветна безбедност и да се поттикнат поединците се повеќе да придонесуваат во оваа област. Различни правни системи се стремат да ја уредат оваа област преку збир на акти и прописи кои начелно се разликуваат во зависност од правната традиција во која припаѓаат. Засега не може да се каже дека европската, а уште помалку домашната судска пракса е богата со предмети поврзани со прекршување на авторските права на компјутерските програми. Но, неколку предмети, поради нивната специфичност, имаат особено влијание врз понатамошното постапување на судовите. Оттука, овој труд анализира како се применува релевантната законска регулатива низ праксата на Европскиот суд за човекови права во предметот SAS Institute Inc. vs. World Programming Ltd (WPL). Главните правни прашања кои се провлекуваат низ овој труд се, што е предмет на заштита кај компјутерските програми и кои елементи на компјутерската програма се штитат со авторските права.
To sustainably exist within planetary boundaries, we must greatly curtail our extraction of fuels and materials from the Earth. This requires new technologies based on reuse and repurposing of material already available. Electrochemical conversion of CO2 into valuable chemicals and fuels is a promising alternative to deriving them from fossil fuels. But most metals used for electrocatalysis are either endangered or at serious risk of limitation to their future supply. Here, we demonstrate a combined strategy for repurposing of a waste industrial Cu–Sn bronze as a catalyst material precursor and its application toward CO2 reuse. By a simple electrochemical transfer method, waste bronzes with composition Cu14Sn were anodically dissolved and cathodically redeposited under dynamic hydrogen bubble template conditions to yield mesoporous foams with Cu10Sn surface composition. The bimetal foam electrodes exhibited high CO2 electroreduction selectivity toward CO, achieving greater than 85% faradaic efficiency accompanied by a considerable suppression of the competing H2 evolution reaction. The Cu–Sn foam electrodes showed good durability over several hours of continuous electrolysis without any significant change in the composition, morphology, and selectivity for CO as a target product.
Mass activity and long-term stability are two major issues in current fuel cell catalyst designs. While supported catalysts normally suffer from poor long-term stability but show high mass activity, unsupported catalysts tend to perform better in the first point while showing deficits in the latter one. In this study, a facile synthesis route towards self-supported metallic electrocatalyst nanoarchitectures with both aspects in mind is outlined. This procedure consists of a palladium seeding step of ion track-etched polymer templates followed by a nickel electrodeposition and template dissolution. With this strategy, free-standing nickel nanowire networks which contain palladium nanoparticles only in their outer surface are obtained. These networks are tested in anodic half-cell measurements for demonstrating their capability of oxidising methanol in alkaline electrolytes. The results from the electrochemical experiments show that this new catalyst is more tolerant towards high methanol concentrations (up to 5molL−1">) than a commercial carbon supported palladium nanoparticle catalyst and provides a much better long-term stability during potential cycling.
Introduction. COVID-19 pandemic threatens global human health. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is a reference test for identification of acute SARS-CoV-2 infection, but it is associated with results delay. There is a need of fast and reliable tests which can improve the efforts of controlling the transmission of SARS-CoV-2. Aim. The aim of this study was to determine the analytical value of the rapid SARS-CoV-2 Ag-test in relation to the Ct values of the RT-qPCR. Methods. The study group comprised outpatients suspected for COVID-19, sampled twice, first for the routine RT-qPCR, and second for SARS-CoV-2 antigen testing. The results obtained by the rapid antigen test (Panbio™ COVID-19) were evaluated in relation to Ct values of the SARS-CoV-2 E-gene, obtained by RTqPCR Allplex 19-nCoV multiplex assay platform. Results. SARS-CoV-2 prevalence, based on RT-qPCR, was 50.8% (186/366). Specificity of the PanbioTM COVID- 19 Ag Rapid Test was 100%. Test sensitivity was 73.8%. Restricting RT-qPCR to Ct-values<30 increased test sensitivity to 91.2%. Conclusion. The findings underscored the epidemiological value of the rapid Ag-test since it reliably identifies contagious SARS-CoV-2 infected individuals who actively spread the virus in the community.
This book covers the complexity of diabetes and related complications and presents the socio-economic burden of the disease, taking into account the rising prevalence reaching pandemic proportions and the associated costs. Factors causing high diabetes prevalence and the influence of the pharmaceutical industry are evaluated and solutions for sustainable diabetes care with limited resources are provided, including national focus on providing cost-effective diabetes treatment, nutrition and physical activity, structured diabetes education and centralized National e-Health System. Moreover, elaboration of long-term efforts to curb the diabetes burden through prevention activities are presented in this book.Managing Diabetes in Low Income Countries represents an essential guide for diabetes care clinicians and researchers, medical students and clinicians in training, diabetes policy makers, regulatory authorities, international diabetes and patient organisations all of whom are involved in current clinical practice for diabetes management.