Relationship Between Gut Microbiota and the Clinical Course of COVID-19 Disease

Possible early detection of people at increased risk for severe COVID-19 clinical course is extremely important so that appropriate therapy can be initiated promptly to prevent numerous deaths. Our study included 45 patients treated for COVID-19 at Dubrava University Hospital, with clinical course analysed from medical records and stool samples collected for determination of the gut microbiota diversity using 16S rRNA analysis. Sequencing was successful for 41 samples belonging to four clinical course groups (WHO guidelines): 12 samples—critical, 12—severe, 9—moderate and 8—mild group. Microbial composition was assessed between groups using two approaches—ANCOM (QIIME2) and Kruskal–Wallis (MicrobiomeAnalyst). On the genus level, two taxa were found to be differentially abundant: archaeal Halococcus and Coprococcus (for both W = 37)—the two were most abundant in the critical group (10% and 0.94% of entire abundance, respectively). Coprococcus catus was the only species identified by both methods to be differentially abundant between groups and was most abundant in the critical group. Alpha diversity indicated greater evenness of features in the critical group. Beta diversity showed clustering of samples from the critical group. A relationship between gut microbiota composition and the clinical course of COVID-19 disease was indicated, pointing towards specific distinct features of the critical group. In a broader sense, our findings might be useful in combating potential future similar pandemics and emerging virus outbreaks

Myocardial deposition of aluminum, arsenic, cadmium, and lead accelerates heart failure and alters UPRmt in humans

In the myocardium of control subjects and patients undergoing heart transplantation or left ventricular assist device implantation (LVAD), we analyzed concentrations of Al, As, Cd, Pb, and Ni using inductively coupled plasma mass spectrometry. Myocardial generation of oxidative-stress-induced lipid peroxidation was analyzed by quantifying concentration of 4-Hydroxynonenal (4-HNE) with ELISA and pro-apoptotic DAPK2 gene expression was determined with quantitative RT-PCR. Compared to six control hearts, myocardial samples of 128 individuals undergoing heart transplantation or LVAD implantation exhibited a moderate increase in deposition of five tested non-essential elements, which was significantly increased only for Cd and cumulative deposition of Al, As, Cd, and Pb. Patients with higher cumulative deposition of Al, As, Cd, and Pb, underwent heart transplantation or LVAD implantation at a younger age than those with lower cumulative deposition, which was not observed in individual elements. Also, Al, As, and Ni exhibited a positive correlation with DAPK2 expression. Moreover, Al, As, Cd, and Ni showed positive correlations and Pb negative correlations with several mitochondrial quality control (MQC) genes. None of the elements showed correlation with 4-HNE generation in the myocardium. There was no difference in tested non-essential element deposition between dilated and ischemic cardiomyopathy. In conclusion, patients with higher cumulative deposition of Al, As, Cd, and Pb in the myocardium underwent heart transplantation or LVAD implantation at a younger age, indicating that they may accelerate heart failure, which is associated with induction of DAPK2 expression. Deposition of Al, As, Cd, Ni, and Pb also altered the expression of several MQC genes

Seawater quality and the presence of Staphylococcus aureus on selected Rijeka beaches

Kakvoća morske vode u Republici Hrvatskoj ima izniman javnozdravstveni značaj, osobito tijekom turističke sezone. Sustavno praćenje provodi se u skladu s Uredbom o kakvoći mora za kupanje (NN 73/2008), koja je usklađena s Direktivom 2006/7/EZ Europske unije. U okviru ovog diplomskog rada provedena je analiza mikrobioloških pokazatelja kvalitete morske vode na četiri riječke plaže (Kantrida, 3. maj, Nogometno igralište i Ploče) tijekom tri sezone kupanja (2021.–2023.), na ukupno 12 mjernih točaka. Uzorci su prikupljani tjedno te su analizirani fizikalno-kemijski parametri (temperatura zraka, temperatura mora, salinitet) i mikrobiološki pokazatelji (Escherichia coli, crijevni enterokoki, Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium perfringens, UBB22 i UBB37). Poseban naglasak stavljen je na prisutnost bakterije Staphylococcus aureus, koja nije uključena u važeću zakonsku regulativu, ali sve češće ulazi u znanstvenu raspravu kao potencijalni pokazatelj antropogenog onečišćenja. Ukupno je analizirano 900 uzoraka, pri čemu je S. aureus detektiran u 17 % slučajeva, s najvećom učestalošću na plaži Kantrida. Veća prisutnost zabilježena je u jutarnjim terminima, uključujući i uzorke ocijenjene kao „izvrsne“. Većina uzoraka (64 %) svrstana je u kategoriju izvrsne kakvoće, dok su preostali raspoređeni u kategorije dobra, zadovoljavajuća i nezadovoljavajuća. Statističkom obradom potvrđene su prostorne i vremenske razlike u prisutnosti mikroorganizama te su uočene korelacije između fizikalno-kemijskih i mikrobioloških parametara, osobito između saliniteta i prisutnosti fekalnih pokazatelja. Rezultati rada ukazuju na kompleksnost ocjene sanitarne ispravnosti morske vode te doprinose raspravi o mogućnosti proširenja skupa mikrobioloških parametara u sustavu monitoringa.Bathing water quality in the Republic of Croatia is of great public health importance, particularly during the summer tourist season. The monitoring system is implemented in accordance with the Regulation on Bathing Water Quality (NN 73/2008), which aligns with the Directive 2006/7/EC of the European Parliament and Council. This thesis presents an analysis of microbiological indicators of seawater quality at four urban beaches in the city of Rijeka (Kantrida, 3. maj, Nogometno igralište, and Ploče) over three consecutive bathing seasons (2021–2023), across a total of 12 sampling points. Samples were collected weekly and analyzed for physical-chemical parameters (air and sea temperature, salinity) and microbiological indicators: Escherichia coli, intestinal enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium perfringens, and total heterotrophic bacteria (UBB22 and UBB37). Special attention was given to Staphylococcus aureus, a bacterium not currently included in legal monitoring frameworks but increasingly discussed in the scientific community as a potential indicator of anthropogenic contamination. A total of 900 samples were analyzed, with S. aureus detected in 17 % of them, most frequently at the Kantrida beach. Higher detection rates were recorded in morning sampling sessions, even among samples rated as "excellent." Overall, 64 % of all samples were categorized as having excellent bathing water quality, while the remainder were classified as good, sufficient, or poor. Statistical analysis confirmed spatial and temporal variability in microbiological contamination, as well as correlations between physical-chemical and microbiological parameters-particularly a negative correlation between salinity and fecal indicators. The results highlight the complexity of assessing bathing water quality and support the ongoing discussion on expanding the set of microbiological indicators used in routine monitoring programs

ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication

Adenosine deaminase acting on dsRNA 1 (ADAR1) catalyzes the deamination of adenosines to inosines in double-stranded RNAs (dsRNA) and regulates innate immunity by preventing the hyperactivation of cytosolic dsRNA sensors such as MDA5, PKR or ZBP1. ADAR1 has been shown to exert pro- and antiviral, editing-dependent and editing-independent functions in viral infections, but little is known about its function in herpesvirus replication. We now demonstrate that herpes simplex virus 1 (HSV-1) hyperactivates PKR in the absence of ADAR1, resulting in eIF2α mediated translational arrest and reduced viral replication. Silencing of PKR or inhibition of its downstream effectors by viral (ICP34.5) or pharmacological (ISRIB) inhibitors rescues viral replication in ADAR1-deficient cells. Upon infection, ADAR1 p150 interacts with PKR and prevents its hyperactivation. Our findings demonstrate that ADAR1 is an important proviral factor that raises the activation threshold for sensors of innate immunity

Iodine and Selenium Status in Relation to Thyroid and Immune Functions—The Analysis of Their Dependencies in a Group of Women of Reproductive Age from the Southern Region of Poland

Objectives: Iodine and selenium are key elements for thyroid. There is also evidence of their immunoregulatory potential. However, the current state of knowledge of potential interactions among iodine—selenium—thyroid—immune system is not sufficient. The aim of the study was to evaluate iodine and selenium statuses and examine the relationship between them and the functioning of the thyroid and immune system in a group of women of reproductive age, without previously diagnosed disease. Methods: The study involved a group of 60 women aged 19–40 from southern Poland. The concentrations of iodine and selenium were determined in serum samples using the ICP-MS and AAS methods, respectively. Thyroid function was assessed by determining serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and anti-thyroid peroxidase antibodies (anti-TPO) by electrochemiluminescence methods. Glutathione peroxidase 3 (GPX3) and ferric ion reducing antioxidant power (FRAP) in serum were measured by spectrophotometric methods. Immune functions were evaluated by analyzing cytokine levels using ELISA tests, including interferon-γ, interleukin-4, interleukin-17, and transforming growth factor-β. Results: No significant correlations between selenium and thyroid or immunological parameters were observed. The level of iodine in serum positively correlated with free thyroxine, indicating its importance for maintaining normal thyroid function, as well as with FRAP in serum, suggesting a protective role of iodine-mediated antioxidant activity on thyroid function. Conclusions: Our results underline the complexity of the system of correlations between iodine–selenium–thyroid–immune function. Nevertheless, understanding them may turn out to be crucial for developing preventive and therapeutic strategies in the context of thyroid diseases

Occurrence of total coliform bacteria in a coastal sea loaded with inflows

Kakvoća mora za kupanje predstavlja važan javnozdravstveni pokazatelj koji može biti narušen fekalnim i sekundarnim onečišćenjem. Cilj ovog istraživanja bio je ispitati pojavnost ukupnih koliformnih bakterija (UKB) u priobalju Rijeke, s naglaskom na vrste koje nisu obuhvaćene standardnim monitoringom, ali mogu ukazivati na prisutnost oportunističkih patogena i bolničkog zagađenja. Istraživanje je provedeno u sklopu projekta EUROBATH na 12 lokacija, a obuhvatilo je ukupno 1119 uzoraka morske vode. Od toga je 117 uzoraka (10,5 %) bilo pozitivno na UKB. Najzastupljeniji je bio rod Citrobacter (79,5 %), a slijedili su rodovi Klebsiella, Enterobacter i Morganella. Identificirane su vrste poput Citrobacter freundii, Klebsiella pneumoniae i Enterobacter cloacae, poznate po višestrukoj antimikrobnoj rezistenciji i kliničkoj važnosti. Statistička analiza pokazala je značajnu povezanost roda Citrobacter s kategorijom kakvoće mora „dobar“ prema koncentraciji E. coli, dok takva povezanost nije utvrđena za crijevne enterokoke, što upućuje na potencijalni nesklad među fekalnim indikatorima. Salinitet je bio jedini okolišni čimbenik koji je pokazao značajan utjecaj na pojavnost UKB, dok temperatura mora i zraka nisu imale značajnu povezanost. Rezultati potvrđuju da se pojedine vrste UKB mogu pojavljivati i u odsutnosti izravnog fekalnog zagađenja, ali unatoč tome mogu imati važnu ulogu u dodatnim programima praćenja kakvoće obalnog mora, osobito u kontekstu praćenja antimikrobne rezistencije i sekundarnog onečišćenja bolničkog porijekla. Iako njihovo uvođenje u rutinski monitoring zasad nije opravdano zbog financijskih i dijagnostičkih ograničenja, praćenje vrsta poput Citrobacter spp. i Klebsiella spp. preporučljivo je u visokorizičnim i ciljanima istraživanjima.Bathing water quality is an important public health indicator that can be affected by both fecal and secondary contamination. The aim of this study was to examine the occurrence of total coliform bacteria (TCB) in the coastal waters of Rijeka, with a focus on species not included in standard monitoring but potentially indicative of opportunistic pathogens and hospital-related pollution. The research was conducted as part of the EUROBATH project at 12 locations, with a total of 1119 seawater samples analyzed. Of these, 117 samples (10.5%) tested positive for TCB. The most prevalent genus was Citrobacter (79.5%), followed by Klebsiella, Enterobacter, and Morganella. Identified species included Citrobacter freundii, Klebsiella pneumoniae, and Enterobacter cloacae, all known for their multidrug resistance and clinical relevance. Statistical analysis revealed a significant association between the presence of Citrobacter and the "good" bathing water quality category according to E. coli levels, but not according to intestinal enterococci, indicating a potential mismatch between standard fecal indicators. Salinity was the only environmental factor that showed a statistically significant influence on TCB occurrence, while sea and air temperature did not. The results confirm that certain TCB species can be present even in the absence of direct fecal contamination, yet may still play an important role in supplementary coastal water quality monitoring programs, especially in the context of antimicrobial resistance and secondary pollution of hospital origin. While their inclusion in routine monitoring is currently not justified due to financial and diagnostic constraints, tracking species such as Citrobacter spp. and Klebsiella spp. is recommended in high-risk and targeted investigation

Genetic Testing for Monogenic Forms of Male Infertility Contributes to the Clinical Diagnosis of Men with Severe Idiopathic Male Infertility

Purpose: In recent years, many genes have been associated with male infertility; however, testing of monogenic forms has not yet been clinically implemented in the diagnosis of severe forms of idiopathic male infertility, as the diagnostic utility has not been established yet. The aim of this study was therefore to answer if the implementation of genetic testing for monogenic forms of male infertility could contribute to the clinical diagnosis of men with severe forms of idiopathic male infertility. Materials and Methods: Based on the ClinGene curation protocol, we defined a panel of genes with sufficient evidence for the involvement with severe male infertility. We tested the 21-gene panel in a representative multicentric cohort of men with significantly impaired spermatogenesis. We performed whole exome sequencing on 191 infertile men with severe forms of idiopathic male infertility; non-obstructive azoospermia, and severe oligozoospermia (T, p.Arg926*; c.2817delG, p.Leu940fs), MSH4 (c.1392delG, p.Ile465fs; c.2261C>T, p.Ser754Leu), TEX15 (c.6848_6849delGA, p.Arg2283fs; c.6271dupA, p.Arg2091fs), and TEX14 (c.1021C>T, p.Arg341*) genes were found. Conclusions: In the present multicentric cohort study, a monogenic cause in 2.1% of infertile men was identified. These findings confirm the utility of monogenic testing and suggest the clinical use of monogenic testing for men with severe forms of idiopathic male infertility

Oxidative Stress and Down Syndrome: A Systematic Review

Down syndrome (DS), the most common human aneuploidy, is associated with oxidative stress, which contributes to morphological abnormalities, immune dysfunction, cognitive impairment and accelerated ageing. This article aims to provide an overview of the studies on oxidative stress in DS, in particular the investigation of endogenous and exogenous antioxidants, with a focus on endogenous systems. A literature search in MEDLINE and Scopus based on the PRISMA 2020 criteria revealed 41 relevant studies that mainly analysed blood samples (plasma or serum) and occasionally saliva or urine. The findings suggest that oxidative stress in DS is multifactorial and results from an imbalance of superoxide dismutase activity, overexpression of genes on chromosome 21, mitochondrial dysfunction and inflammation. Despite extensive studies over the decades, new sources and mechanisms for oxidative stress in DS continue to emerge, further highlighting the complexity of DS. The recognition that oxidative stress is a hallmark of DS emphasises the need to develop more sensitive and specific methods to detect it and to investigate the associated metabolic pathways in DS in more detail. The expansion of in vivo studies could facilitate the development of targeted interventions aimed at mitigating oxidative damage and ultimately improving outcomes for individuals with DS

Periarthritis Humeroscapularis – A Rare Radiological Case Report

Cilj: U ovome radu prikazujemo vrlo rijedak rendgenski i ultrazvučni nalaz u akutnoj egzacerbaciji periartritisa ramena. Prikaz slučaja: Temeljna lezija lokalizirana je tipično u tetivi m. supraspinatusa i inflamiranoj subakromijalnoj burzi u kojoj je radiološki dokazan izljev bogat otopljenim kalcijevim solima (engl. milk of calcium). Ovakav se rendgenski i ultrazvučni nalaz u kliničkom radu, a tako i u literaturi, rijetko zabilježi jer je vezan za tranzitornu, mehaničku fazu u evoluciji periartritisa tijekom koje solidni periartikularni vapneni depoziti prelaze u tekuću suspenziju. Zaključak: Radiološka dijagnostika, u prvom redu rendgenski i ultrazvučni pregled optimalne su metode za dijagnostiku, diferencijaciju i praćenje periartritisa.Aim: This paper presents a very rare X-ray and ultrasound finding in acute exacerbation of shoulder periarthritis. Case Report: The underlying lesion is typically localized in the tendon of the supraspinatus muscle and the inflamed subacromial bursa with calcium rich effusion – milk of calcium. Such X-ray and ultrasound findings are rarely recorded in clinical practice and in the literature, as they are associated with the transient, mechanical phase in the evolution of periarthritis during which solid periarticular calcium deposits transitions into a liquid phase. Conclusion: Radiological diagnostics, primarily X-ray and ultrasound examinations, are optimal methods for diagnosing, differentiating, and clinical monitoring of the shoulder periarthritis