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An IFNγ-dependent immune–endocrine circuit lowers blood glucose to potentiate the innate antiviral immune response
No full textViral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal infection restricts systemic glucose availability, which promotes the antiviral type I interferon (IFN-I) response. Following viral infection, we find that IFNγ produced by γδ T cells stimulates pancreatic β cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune–endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral infection
Y Chromosome Story—Ancient Genetic Data as a Supplementary Tool for the Analysis of Modern Croatian Genetic Pool
No full textDue to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe’s population. SEE, including modern Croatian territory, was a crucial passage from the Near East and even more distant regions and human populations in this region, as almost any other European population represents a remarkable genetic mixture. Modern humans have continuously occupied this region since the Upper Paleolithic era, and different (pre)historical events have left a distinctive genetic signature on the historical narrative of this region. Our views of its history have been mostly renewed in the last few decades by extraordinary data obtained from Y-chromosome studies. In recent times, the international research community, bringing together geneticists and archaeologists, has steadily released a growing number of ancient genomes from this region, shedding more light on its complex past population dynamics and shaping the genetic pool in Croatia and this part of Europe
Estimated Pulse Wave Velocity and All-Cause and Cardiovascular Mortality in the General Population
No full textBackground: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10−3 × age2 − 2.621 × 10−5 × age2 × MBP + 3.176 × 10−3 × age × MBP − 1.832 × 10−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality
Assessment of Chitosan/Gelatin Blend Enriched with Natural Antioxidants for Antioxidant Packaging of Fish Oil
No full textIn this research, bio-based films were developed using polyelectrolyte complexes derived from chitosan and gelatin for packaging fish oil. To further enhance the antioxidant functionality, the films were enriched with gallic acid and orange essential oils, either individually or in combination. Initially, the films were characterized for their physico-chemical, optical, surface, and barrier properties. Subsequently, the phenolic compounds and antioxidant capacity of the films were assessed. Finally, the films were tested as antioxidant cover lids for packaging fish oil, which was then stored at ambient temperature for 30 days, with periodical monitoring of oil oxidation parameters. This study revealed that the inclusion of gallic acid-induced possible crosslinking effects, as evidenced by changes in moisture content, solubility, and liquid absorption. Additionally, shifts in the FTIR spectral bands suggested the binding of gallic acid and/or phenols in orange essential oils to CSGEL polymer chains, with noticeable alterations in film coloration. Notably, films containing gallic acid exhibited enhanced UV barrier properties crucial for preserving UV-degradable food compounds. Moreover, formulations with gallic acid demonstrated decreased water vapor permeability, while samples containing orange essential oils had lower CO2 permeability levels. Importantly, formulations containing both gallic acid and essential oils showed a synergistic effect and a significant antioxidant capacity, with remarkable DPPH inhibition rates of up to 88%. During the 30-day storage period, fish oil experienced progressive oxidation, as indicated by an increase in the K232 value in control samples. However, films incorporating gallic acid or orange essential oils as active antioxidants, even used as indirect food contact, effectively delayed the oxidation, highlighting their protective benefits. This study underscores the potential of sustainable bio-based films as natural antioxidant packaging for edible fish oil or fresh fish, offering a promising tool for enhancing food preservation while reducing its waste
Multimodal treatment of patients with prostate cancer
No full textRak prostate druga je po učestalosti maligna novotvorina među muškom populacijom u svijetu stoga predstavlja ozbiljan globalni zdravstveni problem. Godišnje se na globalnoj razini zabilježi 1,4 milijuna novootkrivenih i 397 000 umrlih, što ovu bolest svrstava na četvrto mjesto prema incidenciji, a na osmo mjesto prema smrtnosti među malignim neoplazmama kod muškaraca. Rak prostate najprije se odnosi na maligne promjene epitela stoga se klasificira kao karcinom. Periferno žljezdano tkivo prostate najčešće je zahvaćeno neoplastičnim promjenama. Klinička slika raka prostate može se kretati od asimptomatskog, mikroskopskog, dobro diferenciranog tumora pa sve do pregledom otkrivenog simptomatskog, agresivnog raka koji uzrokuje udaljene metastaze i izaziva smrt. U trenutku postavljanja dijagnoze 78% bolesnika ima lokalizirani karcinom, 12% zahvaćene regionalne limfne čvorove, a 6% ima udaljene metastaze. Multimodalno liječenje obuhvaća sinkroniziranu primjenu farmakoloških i nefarmakoloških postupaka uz integriranje pacijenta u proces samog liječenja. Početna procjena pacijenta mora uključivati digitorektalni pregled, serumski prostata specifični antigen (PSA) prije ikakvog liječenja, a također treba odrediti i Gleason zbroj u početnoj biopsiji. Aktivni nadzor definira se kao odgoda definitivne terapije s uvođenjem liječenja ako postoje klinički dokazi progresije bolesti i najčešće se primjenjuje kod lokalnih i niskorizičnih karcinoma. Radikalna prostatektomija je kirurški zahvat kojim se odstranjuje prostata u cijelosti zajedno sa svojom kapsulom i sjemenim mjehurićima, a provodi se u pacijenata koji su u grupi srednjeg rizika dok se kod pacijenata u grupi visokog rizika provodi u sklopu multimodalnog liječenja. Radioterapija i brahiterapija također se koriste u sklopu multimodalnog liječenja i kombiniraju se s drugim oblicima liječenja. Neoadjuvantne hormonske terapije koriste se za smanjenje volumena tumora i poboljšanje stope resekcije.Prostate cancer is the second most frequent malignant neoplasm among the male population in the world, therefore it represents a serious global health problem. Annually, 1.4 million new cases and 397,000 deaths are recorded globally, which ranks this disease in fourth place in terms of incidence, and in eighth place in terms of mortality among malignant neoplasms in men. Prostate cancer primarily refers to malignant changes in the epithelium, therefore it is classified as cancer. The peripheral glandular tissue of the prostate is most often affected by neoplastic changes. The clinical picture of prostate cancer can range from an asymptomatic, microscopic, well-differentiated tumor to a symptomatic, aggressive cancer that causes distant metastases and causes death. At the time of diagnosis, 78% of patients have localized cancer, 12% have affected regional lymph nodes, and 6% have distant metastases. Multimodal treatment includes the synchronized application of pharmacological and non-pharmacological procedures while integrating the patient into the treatment process itself. The initial assessment of the patient must include a digital rectal examination, serum prostate specific antigen (PSA) before any treatment, and the Gleason score should also be determined in the initial biopsy. Active surveillance is defined as the postponement of definitive therapy with the introduction of treatment if there is clinical evidence of disease progression and is most often applied in local and low-risk cancers. Radical prostatectomy is a surgical procedure that removes the entire prostate along with its capsule and seminal vesicles, and is performed in patients who are in the medium-risk group, while in patients in the high-risk group, it is performed as part of multimodal treatment. Radiotherapy and brachytherapy are also used as part of multimodality treatment and are combined with other forms of treatment. Neoadjuvant hormonal therapies are used to reduce tumor volume and improve resection rates
How does the presence of Gram-positive and Gram-negative bacteria in various clinical samples relate to levels of inflammation markers?
No full textThis study reveals that all four parameters of interest (fibrinogen, CRP, procalcitonin and leukocytes) cannot be used solely for distinguishing between a gram-negative and gram-positive infection. Analysing the data revealed some differences between both groups. However, they were not significant enough to conclude that one or more parameters could help determine the type of infection. The study shows limitations, especially a small sample size and no subcategorisation according to trauma and sepsis, which had a significant impact on the study result. Nevertheless, the increasing antimicrobial resistance and intrahospital infections worldwide emphasise the need for appropriate antimicrobial treatment. This shows the importance of further research in this field to improve patient outcomes by choosing appropriate antimicrobial therapy as early as possible
Monogenic forms of diabetes as a diagnostic and therapeutic challenge
No full textMonogenetski tipovi dijabetesa uzrokovani su mutacijom u jednom genu. Ovi su tipovi dijabetesa rijetki te obuhvaćaju tek 2-3% od ukupnog broja oboljelih od šećerne bolesti. Postoji nekoliko podtipova monogenetskog dijabetesa, a oni uključuju dijabetes zrele dobi kod mladih (MODY), neonatalni dijabetes melitus (NDM) te sindromske oblike dijabetesa. MODY je najčešći od ovih podtipova te se javlja kod adolescenata i u mlađoj odrasloj dobi. Razlikuje se 14 podtipova MODY-ja, a najčešći su HNF1A-MODY, GCK-MODY, HNF4A-MODY i HNF1B-MODY. Neonatalni dijabetes melitus je vrsta dijabetesa koja se javlja kod djece mlađe od 6 mjeseci, a etiologija bolesti je najčešće mutacija u ABCC8 i KCNJ11 genima. Monogenetski dijabetes može se javiti i u sklopu sindroma, od kojih su najčešći mitohondrijski dijabetes, Wolframov sindrom, NHF1B-MODY, lipodistrofije i sindromi teške inzulinske rezistencije. Nakon što se postavi dijagnoza šećerne bolesti, važno je odrediti o kojem se tipu dijabetesa radi kako bi se započelo adekvatno liječenje. Monogenetski dijabetes dijagnosticira se na temelju kliničkih obilježja, laboratorijskih nalaza i najvažnije, genetskog testiranja. Izbor pacijenata za genetsko testiranje provodi se na temelju nekoliko kriterija: dobi u kojoj se javlja dijabetes, obiteljske anamneze, odsutnosti značajki koje su karakteristične za dijabetes tipa 1 i dijabetes tipa 2, prisutnosti kliničkih obilježja sindroma povezanih s dijabetesom i biokemijskih parametara. Nakon postavljanja dijagnoze kod pacijenata, testirati se mogu i članovi njihovih obitelji. Liječenje je ovisno o zahvaćenom genu, a provodi se nefarmakološkim mjerama i lijekovima – najčešće inzulinom i derivatima sulfonilureje.Monogenic types of diabetes are caused by a mutation in a single gene. These types of diabetes are rare and comprise only 2-3% of total diabetes cases. There are several subtypes of monogenic diabetes, including maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM), and syndromic forms of diabetes. MODY is the most common of these subtypes and it occurs in adolescents and young adults. There are 14 subtypes of MODY, the most common of which are HNF1A-MODY, GCK-MODY, HNF4A-MODY and HNF1B-MODY. Neonatal diabetes mellitus is a type of diabetes that is diagnosed in children under 6 months of age, and the etiology of the disease is most often a mutation in the ABCC8 and KCNJ11 genes. Monogenic diabetes can also present as part of a syndrome, most common of which are mitochondrial diabetes, Wolfram syndrome, NHF1B-MODY, lipodystrophy and severe insulin resistance syndromes. After the diagnosis of diabetes is made, it is important to determine which type of diabetes the patient has and begin adequate treatment. Monogenic diabetes is diagnosed based on clinical features, laboratory findings and most importantly, genetic testing. Selection of patients that require genetic testing is based on several criteria: age of onset of diabetes, family history, absence of features characteristic of type 1 diabetes and type 2 diabetes, presence of clinical features of diabetes-related syndromes, and biochemical parameters. Once the patient's diagnosis is made, their family members can also be tested. Treatment is based on the affected gene and is carried out by non-pharmacological interventions and medications - most often insulin and sulfonylurea
FROM ORIGINS TO OUTCOMES: INVESTIGATING THE COMPLEXITY OF PORTAL HYPERTENSION IN ETIOLOGY, DIAGNOSIS, TREATMENT AND COMPLICATIONS
No full textPortal hypertension is defined as an increased pressure within the portal circulation and is defined as such by determining the pressure difference between the systemic and portal circulation. Under physiological conditions, this gradient is less than 5 mmHg, but higher values lead to worsening of the underlying disease and other complications. The most common causes are cirrhosis, NAFLD, schistosomiasis, intoxication and others, although these vary according to age and geographical location. Understanding the pathogenesis is key to treatment, as there are several therapeutic options to prevent and treat portal hypertension. The therapies of choice are the introduction of non-selective beta-blockers, endoscopic variceal ligation and implantation of a transjugular intrahepatic portosystemic shunt. They are aimed at the most serious complications such as variceal bleeding, ascites or hepatic encephalopathy
FRONTOTEMPORAL DEMENTIA : graduate thesis
No full textFrontotemporalna demencija (FTD) je neurodegenerativna bolest i treća po učestalosti demencija u svijetu. Prvi ju je opisao češki neurolog Albert Pick, 1892.godine. Postoje tri varijante FTD-a: bihevioralna varijanta FTD-a (bvFTD), semantička varijanta primarne progresivne afazije (svPPA) i nefluentna/agramatička varijanta PPA (nfvPPA). Glavni mehanizam nastanka FTD-a je frontotemporalna lobarna degeneracija (FTLD). To je neuropatološki proces u kojem dolazi do atrofije frontalnog i temporalnog režnja mozga. Pretpostavlja se da je 40% slučajeva FTD-a uzrokovano genskom mutacijom. Simptomi se obično ranije prezentiraju, nego kod ostalih oblika demencija. Bihevioralna varijanta može imati slične simptome kao i razna psihijatrijska oboljenja. To je i razlog zbog kojega pacijenti često odlaze na prvi pregled kod psihijatra. Međutim, postoje dijagnostički kriteriji iz 2011. godine, koji mogu pomoći pri dijagnosticiranju bvFTD-a. Primarna progresivna afazija se sastoji od dva oblika: svPPA i nfvPPA. Pacijenti sa semantičkom varijantom imaju poremećeno razumijevanje pojedinih riječi s očuvanom gramatikom, dok pacijenti s nefluentnom/agramatičkom varijantom, imaju poremećeno razumijevanje složenih riječi i otežan govor radi nerazumijevanja gramatike. Obije varijante PPA imaju zasebne dijagnostičke kriterije po Mesulamu. Trenutno FDA i EMA ne propisuju niti jedno specifično liječenje za FTD. Jedina mogućnost liječenja kod ovih pacijenata je farmakološka ili nefarmakološka simptomatska terapija. Provode se istraživanja, čija je zadaća pronaći specifične lijekove koji se mogu koristiti u obliku genske terapije, ali su ona još uvijek u ranim fazama pretkliničkih i kliničkih istraživanja.Frontotemporal dementia (FTD) is a neurodegenerative disease and the third most common form of dementia in the world. It was first described by the Czech neurologist Albert Pick in 1892. There are three variants of FTD: behavioral variant of FTD (bvFTD), semantic variant of primary progressive aphasia (svPPA), and non-fluent/agrammatic variant of PPA (nfvPPA). The main mechanism of FTD is frontotemporal lobar degeneration (FTLD). It is a neuropathological process in which the frontal and temporal lobes of the brain atrophy. It is thought that 40% of FTD cases are caused by a gene mutation. Symptom onset is usually earlier than in other forms of dementia. Behavioural variant can have similar symptoms as various psychiatric disorders. This is also the reason why these patients often go to a psychiatrist for their first examination. However, there are diagnostic criteria from 2011 that can help diagnose bvFTD. Primary progressive aphasia consists of two forms: svPPA and nfvPPA. Patients with the semantic variant have impaired understanding of individual words with preserved grammar, while patients with the non-fluent/agrammatic variant have impaired understanding of complex words and difficult speech due to lack of understanding of grammar. Both variants of PPA have separate diagnostic criteria based on Mesulam. Currently, the FDA and EMA do not prescribe any specific treatment for FTD. The only treatment option for these patients is pharmacological or non-pharmacological symptomatic therapy. Research is being conducted to find specific drugs that can be used in the form of gene therapy, but they are still in the early stages of preclinical and clinical research
Incidence of newly discovered nonvalvular atrial fibrillation in patients with ischemic stroke
No full textCILJ: Cilj istraživanja je utvrditi zastupljenost novootkrivenih nevalvularnih fibrilacija u
bolesnika s moždanim udarom, utvrditi distribuciju bolesnika prema dobi i spolu. Utvrditi udio
bolesnika koji su unatoč provedenoj tromboprofilaksi dobili moždani udar te analizirati propisanu
antikoagulacijsku terapiju pri prijemu i pri otpustu pacijenta.
ISPITANICI I METODE: Istraživanje analizira ukupno 140 pacijenata zaprimljenih na Kliniku
za neurologiju Kliničkog bolničkog centra Rijeka u razdoblju od 1.1.2023. do 31.2023.godine s
dijagnozom moždanog udara i fibrilacije atrija. Podatci prikupljeni analizom medicinske
dokumentacije uključuju dob i spol ispitanika, ima li pacijenta otprije dijagnosticiranu fibrilaciju
atrija i ako ima uzima li propisanu terapiju, također bilježimo prisustvo čimbenika rizika;
hipertenzija, diabetes mellitus, hiperlipidemija, prethodni MU/TIA, karotidnih stenoza te podatke
o tromboprofilaksi pri prijemu i pri otpustu pacijenta.
REZULTATI: Od 140 zaprimljenih pacijenata 54.3% su žene, a 45.7% muškarci, medijan dobi
iznosi 83 godine. Novootkrivena nevalvularna atrijska fibrilacija dijagnosticirana je u 42 (30%)
pacijenata, 80 (57%) pacijenta s fibrilacijom atrija unatoč antikoagulatornoj terapiji zadobivaju
moždani udar, 18 (12.9%) pacijenta unatoč poznatoj fibrilaciji nije uzimalo tromboprofilaksu.
98.6% moždanih udara ishemijskog je tipa, a kod 2 (1.4%) pacijenata javlja se hemoragijski tip
moždanog udara. Najzastupljeniji čimbenik rizika s 117 (83.6%) bolesnika je hipertenzija, a na
drugom mjestu u 38 bolesnika (27.1%) je šećerna bolest. Pri prijemu najzastupljeniji NOAK je bio
rivaroksabon koji je uzimalo 23 bolesnika (26.1%), dok pri otpustu najčešće prepisan NOAK bio
je edoksaban uveden kod 42 (35%) bolesnika.
ZAKLJUČAK: Istraživanje pokazuje zabrinjavajuću činjenicu gdje 30% ispitanika zaprimljenih
zbog moždanog udara imalo istodobno novootkrivenu nevalvularnu fibrilaciju atrija Unatoč
antikoagulantnoj terapiji 57% bolesnika doživjelo je moždani udar. Taj podatak ukazuje na
potrebu za boljom edukacijom kako medicinskog osoblja tako i samih pacijenta. Ključ uspješne
tromboprofilakse je suradnja pacijenta u vidu pravilnog uzimanja propisane terapije. Također
istraživanje ukazuje na visoku zastupljenost rizičnih čimbenika među kojima se posebno ističe
hipertenzija.AIM: The aim of the research is to determine the prevalence of newly discovered non-valvular
fibrillation in patients with stroke, to determine the distribution of patients according to age and
gender. To determine the proportion of patients who had a stroke despite thromboprophylaxis. we
also analyze the prescribed anticoagulation therapy at admission and at discharge of the patient.
PARTICIPANTS AND METHODS: The research analyzes a total of 140 patients admitted to
the Neurology Clinic of the Rijeka Clinical Hospital Center in the period from 1 January 2023.
until 31.2023 with a diagnosis of stroke and atrial fibrillation. The data collected through the
analysis of medical records include the age and gender of the subject, whether the patient has
previously been diagnosed with atrial fibrillation and, if so, whether he is taking the prescribed
therapy, we also record the presence of risk factors; hypertension, diabetes mellitus,
hyperlipidemia, previous stroke/TIA, stenosis, and data on thromboprophylaxis at admission and
discharge of the patient.
RESULTS: Of the 140 admitted patients, 54.3% were women and 45.7% were men, median age
was 83 years. Newly discovered nonvalvular atrial fibrillation was diagnosed in 42 (30%) patients,
80 (57%) patients with atrial fibrillation suffered a stroke despite anticoagulant therapy, 18
(12.9%) patients did not take thromboprophylaxis despite known fibrillation. 98.6% of strokes are
of the ischemic type, and 2 (1.4%) patients have a hemorrhagic type of stroke. The most frequently
described risk factor with 117 (83.6%) patients is hypertension, and in second place with 38
(27.1%) patients is diabetes mellitus. At admission, the most common anticoagulant prescribed
was rivaroxaban, which was prescribed in 23 (26.1%) patients, while at discharge, the most
frequently prescribed anticoagulant drug was edoxaban introduced in 42 (35%) patients.
CONCLUSION: The research shows a worrying fact where 30% of subjects admitted for stroke
have newly discovered non-valvular atrial fibrillation. Despite anticoagulation therapy, 57% of the
subjects had a stroke. This data points to the need for better education of both the medical staff
and the patients themselves. The key to successful thromboprophylaxis is the patient's cooperation
in the form of taking the prescribed therapy correctly. The research also indicates a high prevalence
of risk factors, among which hypertension stands out