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The current epidemic of a new coronavirus disease (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reopened the issue of the role and importance of coronaviruses in human pathology. This epidemic definitively confirms that this heretofore relatively harmless family of viruses, Coronaviridae, includes major pathogens of epidemic potential. The COVID-19 epidemic has clearly demonstrated the power of infectious diseases, which have been responsible for many devastating epidemics throughout history. Most coronaviruses are adapted to their hosts, whether animal or human, although cases of possible animal-to-human transmission and adaptation have been described in the past two decades, causing two epidemics. The first such outbreak originated in China in 2002. The disease was named severe acute respiratory syndrome (SARS). The cause was shown to be a novel coronavirus (SARS-CoV), an animal virus that had crossed the species barrier and infected humans. In the summer of 2012, another epidemic caused by a novel coronavirus broke out in the Middle East. The disease, often complicated with respiratory and renal failure, was called Middle East respiratory syndrome (MERS), while the novel coronavirus causing it was called Middle East respiratory syndrome coronavirus (MERS-CoV). In mid-December of 2019, a pneumonia outbreak erupted once again in China, and spread during the next two months throughout the country, with currently over 80 000 cases and more than 2400 fatal outcomes (CFR 2.5%). Exported cases have been reported in 30 countries throughout the world, with over 2400 registered cases, of which 276 are in Europe. On February 25, the first case of COVID-19 was confirmed in Zagreb, Croatia, and was linked to the current outbreak in the Lombardy and Veneto regions of northern Italy. This third coronavirus epidemic caused by SARS-CoV-2, underscores the need for the ongoing surveillance of infectious disease trends throughout the world. The examples of pandemic influenza, avian influenza, but also the three epidemics caused by the novel coronaviruses, indicate that respiratory infections are a major threat to humanity. Although Ebola virus disease and avian influenza are far more contagious and influenza currently has a greater epidemic potential, each of the three novel coronaviruses require urgent epidemiologic surveillance. It is hoped that developments in vaccinology and antiviral treatment, as well as new preventive measures, will ultimately vanquish this and other potential threats from infectious diseases in the future.

Three strains of laboratory rats (Lewis, Wistar and Sprague–Dawley) commonly used for the study of movement disorders differ in gait traits. Sialic acid containing glycosphingolipids, called gangliosides, are abundant in the nervous system, where they affect numerous neurochemical events. Cerebellum plays the key role in the integration of body movements. This study investigated glycosphingolipid phenotypes with the hypothesis that they differ in cerebella of the three rat strains. In addition, forebrain and brain stem glycosphingolipid phenotypes were determined. Total glycosphingolipid fractions (neutral and acidic) were analysed by high performance thin-layer chromatography (HPTLC). Complex gangliosides were detected with HPTLC immunostaining by using cholera toxin B subunit after the neuraminidase pretreatment. The most significant differences were found in the cerebellum glycosphingolipid content. Lewis rats showed three fold higher monohexaosylceramides (galactosylceramide + sulfatide)/gangliosides ratio compared to Wistar rats. On the other hand, the cerebellum of Wistar rats contained an increased content of complex gangliosides GD1b, GT1b and GQ1b, fourfold, twofold and tenfold, respectively, compared to Lewis rats. This study shows that Wistar and Lewis rat strains have pronounced differences in glycosphingolipid content and the composition of cerebellum.

Tick-borne diseases are a serious threat to both public and veterinary health. In this study, we used high-throughput sequencing to characterize the virome of three tick species implicated in the spread of vector-borne disease throughout Croatia. Ten viruses were identified, including seven potential novel species within the viral families

The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the Fc domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID- 19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased ; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.

Introduction: Ebstein Barr virus is the most common cause of infectious mononucleosis. It is so widespread that by the time we reach adulthood, 90 to 95% of us will be seropositive. Infectious mononucleosis is usually a benign, self- limiting disease with fever, sore throat and cervical lymphadenopathy being the most common symptoms. Rarely it can have a severe course associated with a wide range of complications involving almost any organ. Splenic infarction is a rare complication which mostly occurs in young individuals, without underlying comorbidities. Materials and methods: We present two cases of splenic infarction accompanying infectious mononucleosis caused by EBV in young adults without underlying comorbidities that were hospitalized in our department in May and September of 2021 respectively. Both patients had multiple subcapsular splenic infarctions on CT scan of the abdomen and pelvis and they both recovered completely. Conclusion: Our aim is to raise clinicians' awareness of splenic infarction in infectious mononucleosis due to Ebstein Barr virus. It is rare but potentially fatal complication with clinical presentation that can often be very subtle, and almost 30% of patients are asymptomatic. Because of that a high index of suspicion is needed

Background: The primary pathological event in multiple sclerosis (MS) is demyelination with degeneration and loss of axons, which correlates with a permanent functional deficit. Monocytes, together with Th1 and Th17 cells, play a key role in CNS inflammation in MS. Gjelstrup et al. [1] showed a decreased expression of CD40 and CD192 markers in the total monocyte population in people with MS compared to the control group. Further, recent findings suggest an association between the pathophysiological mechanisms of MS (demyelination and loss of axons) and TMS neurophysiological measures [2-4]. Objective: To investigate CD40+ and CD192+ blood monocyte subpopulations in relapsing-remitting MS subjects undergoing TMS assessment of corticospinal tract integrity by recording MEPs from upper and lower extremity muscles. The CD40+ and CD192+ blood monocyte subpopulations were compared to healthy controls and MS subjects having prolonged latency of MEPs and subjects having neat MEP findings. Methods: Blood samples needed for flow cytometry were collected from 23 MS subjects and 10 healthy controls and incubated with anti-human-CD14 FITC antibodies, of phycoerythrin-conjugated antibodies reactive to human CD16, mouse antibodies reactive to human CD192 conjugated with BB700 and Alexa Flour 647 conjugated antibodies reactive to human CD40. Results: All MS subjects and MS subjects with prolonged MEP latency differed from the healthy controls in the percentage of CD192 in non- classical anti-inflammatory CD14+CD16++ monocytes, expression of CD40 in CD14++CD16-, percentage of total monocytes positive for CD40, and expression of CD192 in classical CD14++CD16-. MS subjects with prolonged MEP latency differed from MS subjects with neat MEP finding in the expression of CD40 in CD14++CD16- and the percentage of total monocytes positive for CD40.The percentage of CD192 in anti-inflammatory CD14+CD16++ monocytes correlated with the intensity of stimulation used to elicit MEP responses from lower extremity muscles. Conclusions: Distinct results were found concerning the percentage of CD192+ non-classical monocytes and expression of CD192 in classical monocytes when comparing MS subjects with altered MEP latency and those with neat MEP findings. Study results point to the subclinical relevance of CD192+ monocyte subpopulations in MS. The study represents the first attempt to apply TMS in evaluating corticospinal tract integrity with the immunological investigation of MS. References [1] Gjelstrup MC, Stilund M, Petersen T, i sur. Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis. Immunology & Cell Biology 2018 ; 96(2):160-174. doi: 10.1111/imcb.1025 [2] Chalah MA, Palm U, Ayache SS. Editorial: Corticospinal Excitability in Patients With Multiple Sclerosis. Frontiers in Neurology 2021 ; 11: 635612. doi: 10.3389/fneur.2020.635612 [3] Neva JL, Lakhani B, Brown KE, i sur. Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis. Behavioral Brain Reserach 2016 ; 297:187-95. doi: 10.1016/j.bbr.2015.10.015 [4] Stampanoni Bassi M, Buttari F, Gilio L, i sur. Inflammation and Corticospinal Functioning in Multiple Sclerosis: A TMS Perspective. Front Neurol 2020 ; 11:566. doi: 10.3389/fneur.2020.00566

U razvijenim demokratskim društvima od kraja XIX stoljeća jezgru državne (javne) uprave čini deset područja djelatnosti, a jedno od područja je javna zdravstvena skrb. Javno zdravstvo pripada korpusu javnih službi, odnosno u širem obuhvatu javnom sektoru u državi te je posvećeno zadovoljavanju javnih interesa građana na području zdravstvene skrbi. Javna uprava u cjelini, a posebno javno zdravstvo koje po opsegu djelatnosti i broju djelatnika čini više od trećine javne uprave, suočena je s dva oprečna i međusobno suprotstavljena zahtjeva građana. Javnost od službi očekuje maksimalno zadovoljavanje javnih interesa i potreba, a istovremeno zahtijeva da službe budu što je više moguće ekonomične i racionalne. Primarna zadaća strateškog menadžmenta u javnom zdravstvu mora kumulativno udovoljiti ta dva zahtjeva. Javni zdravstveni sustavi u svim zemljama konstantno su suočeni s manjkom financijskih sredstava kako bi se namirili svi nastali troškovi pružanja zdravstvenih usluga. Povećanju troškova u javnom zdravstvu značajno pridonosi produljenje životnog vijeka i starost populacije, što je razvidno iz činjenice da je najbrojnija skupina stanovništva sa zastupljenošću većom od 10% u dobnoj skupini od 60 do 65 godina. S druge strane, na ekonomičnost i efikasnost, ne samo poslovnih organizacija, u značajnoj mjeri utječu inovacije u poslovnim procesima. Digitalizacija poslovnih procesa kao predstavnik inovacija zadnjih nekoliko godina pridonosi racionalizaciji poslovanja, smanjenju troškova i konkurentnosti na tržištu. Procese digitalne transformacije, a poglavito implementaciju umjetne inteligencije u javnom zdravstvu, možemo promatrati kao inovacije u procesima zdravstvenog sustava te inovacije u organizaciji koje zadiru u konceptualni aspekt funkcionalnosti zdravstvenog sustava. Unatoč tome što javni zdravstveni sustav djeluje na načelu neprofitnosti, digitalizacija i digitalne promjene u zdravstvenom sustavu stvaraju dodatne vrijednosti pa ih možemo označiti kao značajne inkrementalne profitne promjene.

Background: Examining the integrity of the corticospinal tract by navigated TMS could help in understanding the neurophysiological correlates of multiple sclerosis (MS) symptoms. Objective: To investigate MEP measures of corticospinal tract integrity with navigated TMS and its correspondence with neurological (EDSS) and neuro- radiological (MRI) classifications in people with relapsing-remitting MS (pwMS). Methods: In a cross-sectional study, MEP measures of corticospinal excitability (RMT, MEP latency, MEP amplitude), clinical disease-related (EDSS), and MRI lesion data were collected in 23 pwMS receiving teriflunomide and compared to non- clinical samples. Results: PwMS subjects differed from non-clinical samples in MEP latency for upper and lower extremity muscles. PwMS with altered TMS finding (prolonged MEP latency or absent MEP), compared to pwMS with neat TMS finding, had higher EDSS score [Median = 3.5(range 0-4) vs. 0.5(0- 2.5)] and EDSS functional pyramidal score [Median = 3.0(0-3.5) vs. 0.5(0-2)]. RMT intensity for mapping representations for lower extremity muscles was predictive for EDSS functional pyramidal scores. Overall, TMS findings classified pwMS as the same as EDSS in 70-83% of cases and were similar or more successful than MRI, which corresponded to EDSS in 57- 65% of cases. PwMS with altered TMS findings differed from those with neat TMS finding on the total number of lesions in the brain corticospinal and in cervical corticospinal tract. Conclusions: The correspondence of TMS with MRI, and EDSS classifications implies the clinical utility of navigated TMS in assessing corticospinal tract integrity in pwMS.

Multiple sclerosis (MS) is currently an incurable autoimmune demyelinating and inflammatory disease affecting more than two million people worldwide. The neurophysiologic studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) reported consistent and substantial impairments in CNS generally correlating with disability. Studies of CNS showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies, while resting motor threshold, MEP amplitude, and cortical silent periods showed conflicting results. Studies of peripheral nervous system (PNS) function comprising electroneuronography (ENG) reported impairments of the PNS in MS that were less pronounced and inconsistent. However, neurophysiological investigations applying both TMS and ENG are not frequently used in routine diagnostic procedures to elucidate neurophysiological changes in CNS and PNS in patients with MS. We describe a case of a patient with MS examined with TMS and ENG. The ENG findings did not show clinically meaningful deviations in the PNS of upper and lower extremity muscles. Simultaneously, TMS proved pathological findings in MEPs of upper and lower extremity muscles.

During the COVID-19 pandemic, much effort has been made to investigate SARS-CoV-2–specific antibodies as possible therapeutic agents. During that challenging time we are dealing with a new and insufficiently know pathogen, when reagents, standards and methodologies for antibody characterization are lacking, and are developed in parallel with therapy, making it difficult to properly asses and compare the results of convalescent plasma usage within the individual trials. At present, no conclusions can be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterization in emergent times which would, if followed, enable comparison of results from different studies. We established an assay of wild-type SARS-CoV-2 neutralization, as the most relevant for antibody protectivity. To ensure the maximal reproducibility, we used a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralizing antibodies (NAbs) among convalescents ranged from 4 to 2869 IUmL-1, being in significant positive correlation to the disease severity. NAbs decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation of sera samples resulted in a 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID- 19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IUmL-1 or higher. Results have been published in Ravlić, Hećimović et al. Front. Immun. 2022 ; 13:816159. https://doi.org/10.3389/fimmu.2022.816159

In 2020, a worldwide spread of SARS-CoV-2 caused the global COVID-19 pandemic. Experience from previous outbreaks with other coronaviruses showed that convalescent sera contained neutralizing antibodies (NAbs) against the virus and that their use was beneficial to the treated patients. Although convalescent plasma therapy was considered generally beneficial, the scientific medical community lacks definitive proof of its efficacy coming from carefully designed clinical trials. The reasons for this can be found in its short-term usage only during epidemics caused by a new and insufficiently know pathogen, in a period when pathogen specific therapy and vaccines are lacking. During this period, methods for plasma neutralization potency determination are usually lacking or if they exist, they are neither standardized nor validated. All this results in the variability within different individual trials. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. We established an assay of wild-type SARS-CoV-2 neutralisation, as the most relevant for antibody protectivity. To ensure the maximal reproducibility, we used a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IUmL-1, being in significant positive correlation to the disease severity. NAbs decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation of sera samples resulted in a 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IUmL-1 or higher.

Metabolic profiling of cancer cells has ever growing role in elucidation of molecular base of cancer development, progression and prognosis. In this study, we investigated the effect of a novel thieno[2, 3-b]pyridine derivative on the metabolic profile of two breast cancer lines with different hormonal status ; MDA-MB-231 (triple negative) and MCF-7 (ER, PR, HER2-). The thieno[2, 3-b]pyridines were initially discovered as potential inhibitors of phospholipase C (PLC) isoforms by virtual high throughput screen (vHTS). GC-MS coupled system was used for separation and identification of metabolites. The objective was to identify the compound effect on each metabolite and to find metabolites significantly different between treated and control cells in each line. Data processing, data normalization, statistical analysis and high-level functional interpretation was performed using MetaboAnlayst, a webbased platform for comprehensive analysis of quantitative metabolomics data. Test of statistical significance shows that results for MDA-MB-231 cells are more significant than for MCF-7 cells. PCA results show that drug treatment causes metabolic alternations in both cell lines. Quantitative enrichment analysis was employed to identify patterns of metabolite concentrations and to help elucidate possible biological mechanisms. The results of analysis reveal that treatment has a major impact in glucose/energy metabolism specifically in glycolysis/gluconeogenesis, pyruvate metabolism, Warburg effect, inositol metabolism for both lines. Metabolic profiling of cancer cells plays an increasingly important role for research on the mechanism of action of anticancer drug candidates.

COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete pro-tection against breakthrough infections. This could be due to suboptimal mucosal immu-nity at the site of virus entry, given that all currently approved vaccines are administeredvia the intramuscular route. In this study, we assessed humoral and cellular immuneresponses in BALB/c mice after intranasal and intramuscular immunization with adenovi-ral vector ChAdOx1-S expressing full- length Spike protein of SARS-CoV-2. We showed thatboth routes of vaccination induced a potent IgG antibody response, as well as robust neu- tralizing capacity, but intranasal vaccination elicited a superior IgA antibody titer in thesera and in the respiratory mucosa. Bronchoalveolar lavage from intranasally immunizedmice efficiently neutralized SARS-CoV-2, which has not been the case in intramuscularlyimmunized group. Moreover, substantially higher percentages of epitope- specific CD8 Tcells exhibiting a tissue resident phenotype were found in the lungs of intranasally immu-nized animals. Finally, both intranasal and intramuscular vaccination with ChAdOx1- Sefficiently protected the mice after the challenge with recombinant herpesvirus express-ing the Spike protein. Our results demonstrate that intranasal application of adenoviralvector ChAdOx1-S induces superior mucosal immunity and therefore could be a promis-ing strategy for putting the COVID-19 pandemic under control.

Measuring the peritraumatic distress may help understand the psychological consequences of the COVID-19 pandemic. For that cause, a self-report questionnaire called Peritraumatic Distress Index (CPDI) was designed to capture peritraumatic distress among the general population of China. Since then, CPDI was adapted for use in general population in Peru and Italy. Similar tool is not available for the Croatian setting. Present research aimed at adapting the tool to measure peritraumatic distress among staff in two hospitals in Croatia (N=177). Present research aimed to examine the internal consistency and validity of the Croatian version of the CPDI. Additionally, levels of peritraumatic distress caused by the pandemic were explored among medical and non-medical professionals. The Croatian CPDI showed an internal-consistency of Cronbach's α =0.92. The scale was relevant with good face and content validity, following the integrated method of adaptation. The associations between CPDI and DASS-21, IES-R and PCL-C were explored to analyze the validity of the scale. The results indicate that the Croatian version of the CPDI scale is a valid rapid screening instrument. Such instrument may allow quick detection of the professionals working in the health system with increased peritraumatic distress during the pandemic.

Cilj: Cilj ovog rada bio je ispitati klinička obilježja i ishode u bolesnika hospitaliziranih zbog bolesti COVID-19 u Klinici za infektivne bolesti „Dr. Fran Mihaljević“ (KZIB) u Zagrebu tijekom prvog vala epidemije. Metode: Provedena je retrospektivna analiza medicinske dokumentacije kohorte bolesnika hospitaliziranih u KZIB zbog COVID-19 u kojih je infekcija virusom SARS-CoV-2 bila etiološki potvrđena pozitivnim nalazom RT-PCR testa. U istraživanje su uključeni svi bolesnici hospitalizirani tijekom prvog vala epidemije, između 25. veljače i 18. lipnja 2020. godine. Rezultati: Tijekom promatranog razdoblja, u KZIB je zbog COVID-19 bilo hospitalizirano ukupno 175 bolesnika, od čega 110 (62,9 %) muškaraca. Svi su bolesnici bili stariji od 18 godina (medijan 59 godina, raspon dobi 22–99 godina). Ukupno 110 (62,9 %) bolesnika imalo je jedan ili više komorbiditeta od kojih su najčešći bili kardiovaskularna bolest, uključujući hipertenziju (49,1 %), dijabetes (16,6 %) i KOPB/astma (6,9 %). Najčešći simptomi bolesti bili su: febrilitet (89,7 %), kašalj (73,7 %), dispneja (45,7 %), proljev (45,3 %) i malaksalost (33,1 %). Blagi oblik bolesti imalo je 24 (13,7 %) bolesnika, srednje teški oblik 54 (30,9 %), teški oblik 64 (36,6 %), a kritični oblik 33 (18,9 %) bolesnika. Potrebu za liječenje kisikom imalo je 104 (59,4 %) bolesnika, a za liječenjem u jedinici intenzivnog liječenja (JIL) 33 (18,9 %) bolesnika. Mehanički je ventilirano 29 (16,6 %) dok je 11 (6,3 %) bolesnika zahtijevalo liječenje hemodijalizom. Među bolesnicima hospitaliziranima zbog COVID-19 veći izgled smrtnog ishoda imali su bolesnici u dobi > 65 godina, oni s više od jednog komorbiditeta ili s istovremenim kardiovaskularnim bolestima, oni koji su pri prijmu imali perifernu saturaciju kisikom (SpO2) ≤ 90 %, respiratornu frekvenciju ≥ 22/min, MEWS zbroj ≥ 3, patološke promjene na rendgenogramu pluća, oni s duljim trajanjem hospitalizacije te bolesnici s potrebom za nadomjesnim liječenjem kisikom, dijalizom ili liječenjem u JIL-u. Terapiju hidroksiklorokinom primilo je 59 (22,3 %) bolesnika, lopinavir/ritonavirom 12 (6,9 %), azitromicinom 8 (4,6 %), a glukokortikoidima svega 11 (6,3 %) bolesnika. Preminuo je 21 hospitalizirani bolesnik (12 %). Rasprava: Rezultati našeg istraživanja pokazuju da su tijekom prvog vala epidemije bolesti COVID-19 u KZIB u Zagrebu hospitalizirani isključivo odrasli bolesnici, češće muškarci, s jednim ili više komorbiditeta, nerijetko s blagim oblikom bolesti i bez respiratorne insufi cijencije te potrebe za liječenjem kisikom. Bivarijatnom analizom nađene su razlike u kliničkim obilježjima i laboratorijskim nalazima između preživjelih i umrlih bolesnika, a značajnim prediktorima smrtnog ishoda pokazali su se dob > 65 godina, prisutnost komorbiditeta (osobito kardiovaskularnih bolesti), odsutnost febriliteta, prisutnost dispneje, težina bolesti (viši MEWS i respiratorna frekvencija, niža periferna saturacija kisikom pri prijmu te potreba za nadomjesnim liječenjem kisikom, dijalizom i liječenjem u JIL-u) te povišene vrijednosti leukocita, limfocita, CRP, ureje, ALT, kreatinina, CK i LDH. Multivarijatna analiza pokazala je da skup prediktora koji najtočnije predviđa smrtni ishod bolesnika uključuje dob bolesnika, prisutnost kardiovaskularnih bolesti te vrijednosti CRP-a, ureje i AST-a, budući da su ove vrijednosti bile različite između skupina preživjelih i umrlih bolesnika neovisno o vrijednostima drugih prediktora. Zaključak: Bolest COVID-19 je postala velika opasnost tijekom 2020. godine s velikim brojem oboljelih i umrlih bolesnika uz letalitet od 12 % među našim hospitaliziranim bolesnicima. Nepovoljan ishod bolesti bio je povezan s više kliničkih i laboratorijskih parametara. U prvom valu epidemije zbog COVID-19 bili su hospitalizirani uglavnom odrasli bolesnici sa srednje teškim do kritičnim oblikom bolesti, a lošije ishode bolesti imali su bolesnici s jednim ili više čimbenika rizika. U budućnosti će biti potrebno uložiti dodatne napore u aktivno traženje i pravovremeno prepoznavanje bolesnika s potencijalnim rizičnim čimbenicima koji zahtijevaju pravovremeno antivirusno i imunomodulacijsko liječenje. U konačnici, bolest COVID-19 je multisistemska bolest s još puno nepoznanica, a koju još uvijek svakodnevno upoznajemo., Aim: The aim of this study was to examine the clinical characteristics and patient outcomes of patients hospitalized for COVID-19 in the University Hospital for Infectious Diseases „Dr. Fran Mihaljevic“ (UHID) in Zagreb during the fi rst wave of the epidemic. Methods: A retrospective analysis was conducted using medical records of a cohort of patients hospitalized due to COVID-19 in the UHID in which infection with the SARS-CoV-2 virus was etiologically confi rmed by a positive result of the RT-PCR test. Included were all the patients hospitalized during the fi rst wave of the epidemic, between February 25th and June 18th, 2020. Results: During the study period, 175 patients with COVID-19 were hospitalized in the UHID of which 110 (62.9%) were men. All patients were over 18 years old (median age 59, range 22–99 years). A total of 110 (62.9%) patients had one or more comorbidities, the most common of which were cardiovascular disease including hypertension (49.1%), diabetes (16.6%) and COPD/asthma (6.9%). The most common symptoms of the disease were: fever (89.7%), cough (73.7%), dyspnoea (45.7%), diarrhoea (45.3%) and fatigue (33.1%). Of the total number of patients, 24 (13.7%) had a mild disease, 54 (30.9%) moderate, 64 (36.6%) severe and 33 (18.9%) critical. 104 (59.4%) patients required oxygen therapy, while 33 (18.9%) patients required ICU care. 29 (16.6%) patients required mechanical ventilationand 11 (6.3%) patients required haemodialysis. Among patients hospitalized due to COVID-19, the higher chance of fatal outcomes had patients aged > 65 years, those with more than one comorbidity or with concurrent cardiovascular diseases, those with peripheral oxygen saturation (SpO2) ≤ 90% on admission, respiratory frequency ≥ 22/min, MEWS score ≥ 3, pathological changes on the chest X-ray, those with longer hospitalization duration and patients in need of oxygen replacement treatment, dialysis or ICU care. 59 (22.3%) patients were treated with hydroxychloroquine, 11 (6.3%) glucocorticoids, 12 (6.9%) lopinavir/ritonavir and 8 (4.6%) azithromycin. 21 (12%) of hospitalized patients died. Discussion: Results show that during the fi rst wave of the COVID-19 epidemic only adult patients were hospitalized in the UHID in Zagreb, more often men, with one or more comorbidities, often with mild disease, without respiratory insuffi ciency and need for oxygen treatment. The bivariate analysis found differences in clinical characteristics and laboratory fi ndings between surviving and deceased patients, while signifi cant predictors of fatal outcome proved to be age > 65 years, presence of comorbidities (especially cardiovascular diseases), absence of febrility, presence of dyspnoea, disease severity (higher MEWS and respiratory frequency, lower peripheral oxygen saturation on admission and need for oxygen replacement treatment, dialysis and treatment in ICU) and elevated values of leukocytes, lymphocytes, CRP, urea, ALT, creatinine, CK and LDH. Multivariate analysis showed that the set of predictors that most accurately predicts thefatal outcome includes the patient's age, presence of cardiovascular diseases, and values of CRP, urea and AST, since these differed between surviving and deceased patients regardless of the values of other predictors. Conclusion: The COVID-19 disease became a great danger during 2020 with many ill and deceased patients and a fatality rate of 12% among our hospitalized patients. Unfavourable disease outcome was associated with several clinical and laboratory parameters. In the fi rst wave of the epidemic, mainly adult patients with moderate to critical COVID-19 disease were hospitalized, and those with one or more risk factors had worse disease outcomes. In the future, it will be necessary to invest additional efforts in active search and timely recognition of patients with potential risk factors that require timely antiviral and immunomodulating treatment. Ultimately, the COVID-19 disease is a multisystem disease with many unknowns, which we are still getting to know each day.

CD44 expressed in monocytes and lymphocytes seems to play a crucial role in gastrointestinal inflammation, such as the one occurring in the context of inflammatory bowel diseases (IBD). Differentially methylated genes are distinctly expressed across monocyte subpopulations related to the state of Crohn's disease. Hence, the aim of this study was to detect CD44 expression at monocyte subpopulations, lymphocytes and granulocytes in relation to the type of IBD, therapy and disease duration. Monocyte subpopulations CD14++CD16−, CD14+CD16++ and CD14+CD16+, as well as other leukocytes, were analyzed for their CD44 expression using flow cytometry in 46 patients with IBD and 48 healthy controls. Patients with Crohn's disease treated with non-biological therapy (NBT) exhibited lower percentage of anti-inflammatory CD14+CD16++ monocytes, whereas NBT-treated patients with ulcerative colitis had lower expression of CD44 on CD14+CD44+ lymphocytes, in comparison to controls, respectively. Conversely, patients with Crohn's disease treated with biological therapy had higher percentage of CD44+ granulocytes, but lower expression of CD44 on anti-inflammatory monocytes compared to controls. Percentage of classical CD14++CD16- monocytes was lower in the

Radiologist workload had increased significantly within the past three decades. In 2006-2007, the average annual workload per FTE radiologist was 14,900 procedures, an increase of 7% since 2002-2003 and 34.0% since 1991-1992. Annual RVUs per FTE radiologist were 10 200, an increase of 10% since 2002-2003 and 70.3% since 1991-1992.The study included worksheets data of three radiology specialists in their first three years as specialists. Data were collected and analyzed retrospectively for the period frame January 1Average total number of imaging procedures per radiologist was 2785. Separately, there were: 850 bone X ray images, 550 chest X rays, 250 ultrasound examinations, 860 CTs and 256 MRIs. Daily average of analyzed imaging procedures per radiologist was as followed: 7.4 bone X ray images, 4.8 chest X rays, 2.2 ultrasounds, 7.5 CTs and 2.2 MRIs. Total working time per radiologist in the analyzed time period was 684 hours. Average time spent for analyzing per one imaging procedure was 14 minutes and 45 seconds spread in total 114 working days.The conclusion is that current workload for a radiology specialist obviously represents a necessity to be thoroughly explored. This case study and previous literature results indicate that a well constructed large scale study represents a potential in resolving the previous studies limitations and providing relevant data, so correct measures and guidelines could be developed.

Background: Although MRI is the most efficient method of detecting breast cancer, its standard protocol is time-consuming and expensive. The objective of this study was to compare the diagnostic accuracy of the modified innovative abbreviated MRI protocol (AMRP) and the standard magnetic resonance protocol (SMRP) when detecting breast cancer. Methods: The research involved 477 patients referred for breast MRI due to suspected lesions. They were randomly assigned to the AMRP group (N = 232) or the SMRP group (N = 245). The AMRP comprised one native (contrast-free) and four post-contrast dynamic sequences of T1-weighted volume imaging for breast assessment (VIBRANT) and 3d MIP (maximum intensity projection) lasting for eight minutes. All the patients underwent a core biopsy of their lesions and histopathological analysis. Results: The groups were comparable regarding the pre-screening and post-diagnostic characteristics and were of average (±SD) age at breast cancer diagnosis of 53.6 ± 12.7 years. There was no significant difference between the two protocols in terms of specificity or sensitivity of breast cancer diagnosis. The sensitivity (95% Cis) of the AMRP was 99.05% (96.6–99.9%), and its specificity was 59.09% (36.4–79.3%), whereas the sensitivity of the SMRP was 98.12% (95.3–99.5%) and its specificity was 68.75% (50.0–83.9%). Most of the tumors comprised one solid lesion in one of the breasts (77.3%), followed by multicentric tumors (16%), bilateral tumors (4.3%), and multifocal tumors (1.7%). The average size of tumors was approximately 14 mm (ranging from 3 mm to 72 mm). Conclusion: Our innovative AMR protocol showed comparable specificity and sensitivity for the diagnosis of breast cancer when compared to SMRP, which is the “gold standard” for histopathological diagnosis. This can lead to great savings in terms of the time and cost of imaging and interpretation.

Anksiozna osjetljivost često se naziva kao „strah od straha“ te su osobe s visokom razinom anksiozne osjetljivosti sklone pogrešnom tumačenju anksioznih simptoma kao prijetećima. To podrazumijeva i strah od tjelesnih promjena tijekom uzbuđenja. Prema modelu dvostruke kontrole (Bancroft i Janssen, 2000) seksualni odgovor osobe ovisi o ekscitacijskim i inhibicijskim mehanizmima. Cilj istraživanja je utvrditi prediktore seksualnog uzbuđenja te ispitati ulogu seksualne inhibicije (SIS-1) u odnosu između anksiozne osjetljivosti i seksualnog uzbuđenja kod žena. U istraživanju je sudjelovalo 1605 punoljetnih žena prosječne dobi 32 godine. Sudionice su ispunile upitnik o učestalosti njihovih seksualnih ponašanja, Indeks anksiozne osjetljivosti (ASI), Skraćenu verziju skale seksualne inhibicije i seksualne ekscitacije (SIS/SES-SF), Višestruke indikatore subjektivnog seksualnog uzbuđenja. Anksiozna osjetljivost nisko je pozitivno povezana sa seksualnom ekscitacijom i inhibicijom te nisko negativno povezana s genitalnim senzacijama. Značajni prediktori seksualnog uzbuđenja su obrazovanje, maštanje, učestalost odnosa, seksualna ekscitacija i seksualna inhibicija (SIS-1). Značajni prediktori afektivnog seksualnog uzbuđenja su maštanje, učestalost odnosa, seksualna ekscitacija i seksualna inhibicija (SIS-1). Značajni prediktori genitalnih senzacija su obrazovanje, masturbacija, maštanje, učestalost odnosa, seksualna inhibicija (SIS-1) i anksiozna osjetljivost. Analizom medijacijskog učinka seksualne inhibicije (SIS-1) na odnos između anksiozne osjetljivosti i genitalnih senzacija utvrđena je djelomična medijacija. Anxiety sensitivity is often referred to as “fear of fear” and people with high levels of anxiety sensitivity are prone to misinterpreting anxiety symptoms as threatening. That also implies fear of bodily changes during arousal. According to the Dual Control Model (Bancroft and Janssen, 2000), a person’s sexual response depends on excitatory and inhibitory mechanisms. The aim of the study was to determine significant predictors of sexual arousal, affective sexual arousal and genital sensations and to examine the role of sexual inhibition (SIS-1) in the relationship between anxiety sensitivity and three measures of sexual arousal in women. The study involved 1,605 adult women with an average age of 32 years. Participants completed a questionnaire on the frequency of their sexual behaviors, Anxiety Sensitivity Index (ASI), Sexual Inhibition Scales/Sexual Excitation Scales short form (SIS/SES-SF) and Multiple Indicators of Subjective Sexual Arousal. Anxiety sensitivity slightly positively correlates with sexual excitation and inhibition and slightly negatively correlates with genital sensations. Significant predictors of sexual arousal are education, fantasy, frequency of intercourse, sexual arousal, and sexual inhibition (SIS-1). Significant predictors of affective sexual arousal are fantasy, frequency of intercourse, sexual arousal, and sexual inhibition (SIS-1). Significant predictors of genital sensations are education, masturbation, sexual fantasies, frequency of intercourse, sexual inhibition (SIS-1) and anxiety sensitivity. Analysis of the mediating effect of sexual inhibition (SIS-1) on the relationship between anxiety sensitivity and genital sensations revealed partial mediation.

The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is a glycoconjugate sialyl Lewis x (CD15s), which may be expressed as an oligosaccharide branch of the CD44 glycoprotein, as well as a self-contained glycosphingolipid. It is also known that increased sialylation of glycoconjugates is a feature of malignant cells. The aim of the study was to analyse the effect of a novel thieno[2,3-b]pyridine, compound 1, in MDA-MB-231 triple-negative breast cancer cells (TNBCs) upon CD15s and CD44 expression in different cell subpopulations using flow cytometry. CD15s expression was compared between mesenchymal-like cancer stem cells (CSC, CD44+CD24−), epithelial cells without CD44 (CD44−CD24+ and CD44−CD24−), and CD44+CD24+ cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s+CSC and CD15s−CSC was determined. Compound 1 significantly decreased the percentage of CD15s+CSC, CD15s+CD44+CD24+, and CD15s+CD44− subpopulations, as well as the expression of CD15s in CD44+CD24+ and CD44− cells, and therefore shows potential as a treatment for TNBC.

Pandemija COVID-19 je zdravstven, ekonomska, korporativna i politička kriza koja se brzo razvija i razlikuje se od svih kriznih situacija s kojima smo se do sada suočavali. No, neki izazovi su nam ostali gotovo isti kao i u kriznim situacijama koje su nas ranije pogađale. Navedene izazove možemo grupirati u tri skupine: prvi izazov je krizna komunikacija koja je uvijek unutarnji problem pogođene organizacije, tako je i sada tijekom pandemije COVID-19 ; drugi izazov je interna komunikacija koju u kriznim situacijama trebaju voditi članovi kriznog komunikacijskog tima, jedino se na taj način ne gubi empatija koja je posebno važna u svim kriznim situacijama ; i treći izazov je poslovna i komunikacijska strategija bez kojih je nemoguće jasno i učinkovito komunicirati u kriznim situacijama. Krizno komuniciranje je vrlo kompleksno područje javnog komuniciranja općenito. Ono podrazumijeva komunikaciju pojedinca, organizacije i institucije s javnostima tijekom kriznih situacija. Glavni cilj kriznog komuniciranja je sprječavanje poteškoća za nesmetano djelovanje organizacije ili institucije. U kriznom komuniciranju važno je imati osobu koja će biti glavni nositelj komunikacije. Tijekom trajanja pandemije COVID – 19 javnost u Republici Hrvatskoj je uplašena, zbunjena, informirana, dezinformirana i zastrašena? Pitanje pandemije COVID – 19 je eminentno političko pitanje, koje po kompleksnosti nadilazi banalno isticanje gole moći, te zahtijeva smještanje države kao glavnog aktera njegovih motiva i interesa u širi kontekst. Pandemija COVID – 19 utjecala je na sve aspekte naših života, no mi pandemiju za sada promatramo3 primarno u njenom zdravstvenom aspektu. Situacija je, izrazito izazovna i problem je što cijelo vrijeme slušamo kako postoje potpuno oprečni stavovi struke. Dakle epidemiolozi, mikrobiolozi, infektolozi i sve uključene zdravstvene struke iznose često vrlo oprečne stavove o trenutnoj kriznoj situaciji. Krajnje je vrijeme da se u javnim službama i institucijama shvati važnost kriznog komuniciranja. Cilj rada je istražiti iz javno dostupnih izvora ima li Republika Hrvatska ozbiljnu strategiju kriznog komuniciranja tijekom trajanja pandemije COVID 19.

We investigated SNPs of PNPLA3, EGF and Notch3 as genetic risk factors for alcoholic liver disease (ALD) and its progression to hepatocellular carcinoma (HCC). DNA was isolated from 245 ALD patients (124 without HCC and 121 with HCC) and 70 control patients. SNPs were determined by PCR using TaqMan assays. PNPLA3 rs738409 was associated with higher risk for ALD in dominant (OR95%CI = 3.36 (1.94‐5.82) for GG/GC vs CC), recessive (OR95%CI = 3.71 (1.42‐9.69) for GG vs GC/CC) and log‐additive model (OR95%CI = 2.60 (1.69‐3.99) for G allele). This SNP was also associated with a risk for HCC in recessive (OR 95%CI = 2.72 (1.43‐ 5.17) for GG vs GC/CC) and log‐additive model (OR95%CI = 1.63 (1.14‐2.34) for G allele). EGF rs4444903 was not associated with a risk for fibrosis development. However, it was associated with a mildly increased risk for fibrosis progression to HCC in a dominant model (OR95%CI = 1.92 (1.11‐3.32), for GA/GG vs. AA). Notch3 rs1043996 was associated with lower risk for ALD in recessive model (OR95%CI = 0.32 (0.14‐ 0.72) for GG vs GA/AA). There was no association between the Notch3 genotype and risk for HCC (p>0.05). PNPLA3 rs738409 is a considerable risk factor for the ALD and its progression towards HCC, while EGF rs4444903 might be an additional risk factor for HCC development. Notch3 rs1043996 genotype is associated with a lower risk for the development of ALD.

Introduction: Radiologist workload had increased significantly within the past three decades. In 2006-2007, the average annual workload per FTE radiologist was 14,900 procedures, an increase of 7% since 2002-2003 and 34.0% since 1991-1992. Annual RVUs per FTE radiologist were 10 200, an increase of 10% since 2002-2003 and 70.3% since 1991-1992. Subjects and methods: The study included worksheets data of three radiology specialists in their first three years as specialists. Data were collected and analyzed retrospectively for the period frame January 1st to September 21st 2018. The total data of imaging procedures by one radiologist had been collected and then separated by different imaging procedures as followed. Results: Average total number of imaging procedures per radiologist was 2785. Separately, there were: 850 bone X ray images, 550 chest X rays, 250 ultrasound examinations, 860 CTs and 256 MRIs. Daily average of analyzed imaging procedures per radiologist was as followed: 7,4 bone X ray images, 4,8 chest X rays, 2,2 ultrasounds, 7,5 CTs and 2,2 MRIs. Total working time per radiologist in the analyzed time period was 684 hours. Average time spent for analyzing per one imaging procedure was 14 minutes and 45 seconds spread in total 114 working days. Conclusions: The conclusion is that current workload for a radiology specialist obviously represents a necessity to be thoroughly explored. This case study and previous literature results indicate that a well constructed large scale study represents a potential in resolving the previous studies limitations and providing relevant data, so correct measures and guidelines could be developed.