Objectives: To investigate possible associations between 25-hydroxyvitamin D₃(25(OH)D₃), oestradiol (E₂) and IFN-gamma (IFNγ) in female patients with inactive systemic lupus erythematosus (SLE).Methods: Female patients with inactive SLE and age-matched healthy controls were recruited into this cross-sectional study. Serum concentrations of 25(OH)D_3,E₂and IFNγ were measured by radioimmunoassay with gamma-counters and enzyme-linked immunosorbent assay.Results: 36 patients and 37 controls were enrolled. In patients with SLE, the concentration of 25(OH)D₃was lower and E₂was higher compared with controls. In vitamin D deficient (i.e., 25(OH)D₃≤20 ng/ml) patients, IFNγ was 150% higher compared with patients with 25(OH)D₃>20 ng/ml and controls. The concentration of E₂was higher in all patients compared with controls independently of the vitamin D level. A difference was found between patients and controls in the correlation of 25(OH)D₃with E₂and a positive correlation was found between E₂and IFNγ in all participants.Conclusions: Our results suggest that E₂may have a strong modulating effect on vitamin D function which is significant only at low concentration of E₂.

Background: Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient’s baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8–20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. Methods: The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed. Results: From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38). Conclusions: This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

Aims/Introduction: Prediabetes (PD) represents a transitional state where the glucose levels are higher than normal, but not enough for diabetes mellitus diagnosis. As there is a growing number of the population with PD, its early detection and treatment could prevent the development of diabetes mellitus and its complications. We aimed to assess the overall knowledge of PD among medical professionals of different varieties.Materials and Methods: A questionnaire‐based study addressing PD and type 2 diabetes mellitus knowledge among Southeastern European general practitioners, postgraduates, physicians and superior specialists was carried out.Results: A total of 397 physicians completed the questionnaire. The total rate of correct answers from diabetologists, non‐diabetologist internists, residents and general practitioners was 69, 56.1, 54 and 53%, respectively. Questions related to the PD definition achieved a total of 46.6% correct answers. Correct responses considering the numerical definition of impaired fasting glucose and impaired glucose tolerance were 46.3 and 46.8%, respectively. Younger physicians had better knowledge of numerical values regarding PD and type 2 diabetes mellitus criteria (P < 0.001).Conclusions: The present results show that overall knowledge of PD is poor among Southeastern European physicians, which necessitates adequate educational programs on PD in this region.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a group of drugs that are a staple in diabetes treatment. Its representatives dapagliflozin and empagliflozin are oftentimes used in combination with other antidiabetic drugs such as metformin. In this manuscript, we examine the interactions of dapagliflozin and empagliflozin in mixtures of metformin and water, varying the concentration of metformin to better reflect the drug ratios prescribed in therapy. We found that both SGLT2 inhibitors have a tendency to hydrogen bond with water rather than metformin, with more bonds formed simultaneously that have a lifetime in the picosecond range. These findings were corroborated with structural information, thus providing a backbone for future understanding of transport processes of SGLT2 inhibitors and metformin in highly complex environments.

Varicella je visoko zarazna infektivna bolest koja može uzrokovati brojne komplikacije. Jedna od rijeđih, epididimo-orhitis, je samim time i rijetko opisana u literaturi, rijetko dijagnosticirana te neadekvatno liječena. U ovom prikazu opisat ćemo slučaj 13-godišnjeg dječaka koji je inicijalno pregledan od strane infektologa i dječjeg kirurga pod dijagnozom skrotalne bakterijske superinfekcije tokom varicella infekcije. Pogrešno liječen antibioticima, dječak je potom pregledan od strane pedijatrijskog endokrinologa, dijagnosticiran mu je epididimo-orhitis te je liječen acetaminofenom, hladnim oblozima i skrotalnom suspenzijom, s obzirom da je 24-satni ‘prozor’ za uključivanje antiviralne terapije već bio prošao. U laboratorijski testovima nisu zabilježeni znakovi upale, a ultrazvučni pregled pokazao je uvećanje desnog testisa i epididimisa uz zadebljanje tunike albuginea i paratestikularni izljev. Pacijent je potom ultrazvučno praćen pri čemu je zabilježeno postupno poboljšanje uz potpuno normalan nalaz godinu nakon infekcije. Hormonski status bio je uredan tokom praćenja. Nakon 5 godina napravljen je spermatogram uz uredan broj spermija, ali i smanjenu mobilnost, te je pacijentu dijagnosticirana astenozoospermija. Na temelju ovog slučaja moramo naglasiti ulogu varicella infekcije u mogućem razvitku dugoročnih posljedica na reproduktivno zdravlje. S obzirom na smanjenu ulogu antiviralne terapije te još uvijek upitnu mogućnost prevencije komplikacija, moramo naglasiti važnost preventivnih mjera, uključujući cijepljenje, te pogled na razvitak novih antiviralnih metoda.