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Purpose In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia.Materials and methods Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions – ‘70/26’, and ‘Do you know what is your number?’ aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and ‘School of Communication in Hypertension’. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies.Conclusion We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy.

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5'-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5'-ssDNA, ensuring the correct ssDNA bubble size before cleavage.

Kardiovaskularne bolesti (KVB) su vodeći uzrok pobola i smrtnosti diljem svijeta pa tako i u Hrvatskoj. Budući da je u većine bolesnika prisutno više poremećaja i bolesti kojima su u podlozi u najvećem dijelu isti čimbenici rizika, te kako je nužno svakom bolesniku pristupati kao osobi sa svim poremećajima, danas se govori o novoj paradigmi – kardio-reno-metaboličkom (KRM) sindromu i kardio-reno-metaboličkom zdravlju, u što je neizostavno uključeno i zdravlje mozga. Povišen sistolički arterijski tlak, LDL-kolesterol, pušenje, debljina, šećerna bolest, oštećena bubrežna funkcija, tj. kronična bubrežna bolest, u podlozi kojih je nedovoljno tjelesne aktivnosti, nezdrava prehrana s prekomjernim unosom kuhinjske soli zajedno s onečišćenjem zraka vodeći su uzroci ukupnoga pobola i smrtnosti od KRM bolesti, a napose smrtnosti od KVB. Stručnjaci iz raznih područja ključnih za KRM zdravlje napisali su ovaj dokument s ciljem da bude sastavni dio nacionalnog plana za prevenciju kroničnih nezaraznih bolesti s fokusom na KVB koji treba postati obvezujući, a utemeljen na postojećim smjernicama stručnih društava. Naglašena je važnost pravovremenog probira i postavljanja dijagnoze, no težište je stavljeno i na nužnost organiziranja i provođenja mjera primordijalne i primarne prevencije. Istaknuta je važnost multidisciplinarnoga pristupa i trajnog obrazovanja opće populacije i bolesnika kako bi se promijenile loše životne navike i povećala ustrajnost uzimanja lijekova, ali isto tako podizanje zdravstvene pismenosti zdravstvenih radnika, napose liječnika kako bi se smanjila klinička inercija.

It is well known that beer is more than 90% water, and therefore, water can be one of the main sources of fluoride in beers. With this in mind, the goal of the present study was to determine the mass concentration of fluoride in 53 beer samples. Using the recently published standard addition method in potentiometry, the fluoride content of 28 samples of the most consumed beers in the Republic of Croatia was determined. The remaining 25 beer samples tested came from so-called microbreweries, which together account for less than 10% of the Croatian market. Fluoride concentrations in light beers ranged from 49 to 180 μg L−1, with a mean value of 95 ± 34 μg L−1, and from 52 to 164 μg L−1, with a mean value of 89 ± 29 μg L−1 in dark beers. The mean value of fluoride content in beers from large producers was 100 ± 38 μg L−1 and 89 ± 38 μg L−1 in beers from small producers. All values are within the recommended range and thus do not pose a risk to human health. The statistical analysis showed no correlation between the mass concentration of fluoride and pH, i.e., alcohol content in beers.

ObjectiveTo evaluate the impact of research design on the perceived medical treatment effectiveness among researchers, healthcare workers (HCWs) and consumers in Croatia.MethodsA cross-sectional study was conducted from November 2021 to February 2022 using an online survey. The participants were researchers, HCWs and consumers from Croatia. The survey had six scenarios about the same medical treatment presented within different study designs and in random order. Participants were asked to assess on a scale from 1 to 10 if the descriptions presented a sufficient level of evidence to conclude that the treatment was effective.ResultsFor researchers (n = 97), as the number of participants and degree of variable control in the study design increased, the perceived level of sufficient evidence also increased significantly. Among consumers (n = 286) and HCWs (n = 201), no significant differences in scores were observed between the cross-sectional study, cohort study, RCT, and systematic review.ConclusionThere is a need to implement educational courses on basic research methodology in lower levels of education and as part of Continuing Medical Education for all stakeholders in the healthcare system. Trial registration: this study has been registered on the Open Science Framework prior to study commencement (https://osf.io/t7xmf).

All tumors have DNA mutations, and a predictive understanding of those mutations could inform clinical treatments. However, 40% of the mutations are variants of unknown significance (VUS), with the challenge being to objectively predict whether a VUS is pathogenic and supports the tumor or whether it is benign. To objectively decode VUS, we mapped cancer sequence data and evolutionary trace (ET) scores onto crystallography and cryo-electron microscopy structures with variant impacts quantitated by evolutionary action (EA) measures. As tumors depend on helicases and nucleases to deal with transcription/replication stress, we targeted helicase-nuclease-RPA complexes: (1) XPB-XPD (within TFIIH), XPF-ERCC1, XPG, and RPA for transcription and nucleotide excision repair pathways and (2) BLM, EXO5, and RPA plus DNA2 for stalled replication fork restart. As validation, EA scoring predicts severe effects for most disease mutations, but disease mutants with low ET scores not only are likely destabilizing but also disrupt sophisticated allosteric mechanisms. For sites of disease mutations and VUS predicted to be severe, we found strong co-localization to ordered regions. Rare discrepancies highlighted the different survival requirements between disease and tumor mutations, as well as the value of examining proteins within complexes. In a genome-wide analysis of 33 cancer types, we found correlation between the number of mutations in each tumor and which pathways or functional processes in which the mutations occur, revealing different mutagenic routes to tumorigenesis. We also found upregulation of ancient genes including BLM, which supports a non-random and concerted cancer process: reversion to a unicellular, proliferation-uncontrolled, status by breaking multicellular constraints on cell division. Together, these genes and global analyses challenge the binary "driver" and "passenger" mutation paradigm, support a gradient impact as revealed by EA scoring from moderate to severe at a single gene level, and indicate reduced regulation as well as activity. The objective quantitative assessment of VUS scoring and gene overexpression in the context of functional interactions and pathways provides insights for biology, oncology, and precision medicine.

Critical for transcription initiation and bulky lesion DNA repair, TFIIH provides an exemplary system to connect molecular mechanisms to biological outcomes due to its strong genetic links to different specific human diseases. Recent advances in structural and computational biology provide a unique opportunity to re-examine biologically relevant molecular structures and develop possible mechanistic insights for the large dynamic TFIIH complex. TFIIH presents many puzzles involving how its two SF2 helicase family enzymes, XPB and XPD, function in transcription initiation and repair: how do they initiate transcription, detect and verify DNA damage, select the damaged strand for incision, coordinate repair with transcription and cell cycle through Cdk-activating-kinase (CAK) signaling, and result in very different specific human diseases associated with cancer, aging, and development from single missense mutations? By joining analyses of breakthrough cryo-electron microscopy (cryo-EM) structures and advanced computation with data from biochemistry and human genetics, we develop unified concepts and molecular level understanding for TFIIH functions with a focus on structural mechanisms. We provocatively consider that TFIIH may have first evolved from evolutionary pressure for TCR to resolve arrested transcription blocks to DNA replication and later added its key roles in transcription initiation and global DNA repair. We anticipate that this level of mechanistic information will have significant impact on thinking about TFIIH, laying a robust foundation suitable to develop new paradigms for DNA transcription initiation and repair along with insights into disease prevention, susceptibility, diagnosis and interventions.

Razvoj elektroda s ugljikovom pastom (CPE, engl. carbon paste electrode) sedamdesetih godina prošlog stoljeća privukao je velik interes znanstvene zajednice budući da je otkriveno da one nude nekoliko prednosti u odnosu na konvencionalne membranske elektrode. Početkom novog tisućljeća dodatni impuls njihovom razvoju dala je primjena ugljikovih nanomaterijala kao novog trenda u njihovu razvoju. Nakon što su uspješno razvijene CPE za potenciometrijsko određivanje više od 70 kemijskih elemenata, te su elektrode privukle dodatno zanimanje za primjenu u farmaciji i medicini. Ovim radom dat je pregled znanstvene literature u posljednjih desetak godina vezan za razvoj CPE za kvantitativno određivanje djelatnih tvari farmaceutika i njihovu primjenu u realnim uzorcima.

Pretilost je kompleksna bolest uzrokovana interakcijom genetskih i okolišnih čimbenika. Kliničku i javnozdravstvenu pozornost pedijatara privlači zbog učestalosti, direktnih i indirektnih učinaka na morbiditet u dječjoj i adolescbetnoj dobi te dugoročno i na mortalitet u odrasloj dobi. Roditelji biraju pedijatre primarne zdravstvene zaštite i često ne percipiraju pretilost djece kao zdravstveni problem. Pedijatri primarne zdravstvene zaštite imaju povjerenje roditelja, što im, uz znanje i alate kontinuiranog nadzora rasta i razvoja djece, daje mogućnost koordinirane pravodobne intervencije, informiranja i savjetovanja. U preglednom se radu iznosi značenje objektivne dijagnostike pretilosti, razumijevanja nastanka jednostavne pretilosti, kao i pojavu pretilosti u sklopu sindroma i endokrinoloških bolesti. Analiziraju se mogućnosti racionalnog personaliziranog pristupa pretilom djetetu u odnosu na etiološku podlogu i potencijalni razvoj komorbiditeta. Poseban je istaknuta praktična primjena personaliziranih intervencija u pretilog djeteta na razini primarne pedijatrijske zdravstvene zaštite.

The aim of this study was to investigate 30 different types of Dalmatian wines as a potential source of fluoride. A fluoride ion selective electrode was used to measure the fluoride concentration in each sample. The direct potentiometric method and the standard addition method were evaluated, the latter being suggested as more accurate and precise. Measurements were performed in two buffers, acetate buffer and total ionic strength adjustment buffer (TISAB), to compare their influence on fluoride determination. The obtained results show that TISAB is a better choice than acetate buffer as a medium for fluoride determination. According to the proposed method, mass concentrations of fluoride of 0.19 and 0.18 mg/L were found in the studied red and white wines, with standard deviations of 0.04 and 0.03 mg/L, respectively. All determined fluorine levels in the tested wines were within the recommended limits and do not pose a risk to human health. No significant difference was found between the fluorine content in white and red wines, but there was a difference depending on the place of origin of the wine. The measured pH values for all the wines studied (except one sample) are very similar and show no significant correlation with the fluoride content.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today, we are talking about a new paradigm—cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, an unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies. [ABSTRACT FROM AUTHOR]

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14++CD16−), intermediate CD14++CD16+ and non-classical (CD14+CD16++) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing–remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40’s pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

Probing the cortic ospinal tract integrity by transcranial magnetic stimulation (TMS) could help to understand the neurophysiological correlations of multiple sclerosis (MS) symptoms. Therefore, the study objective was, first, to investigate TMS measures (resting motor threshold-RMT, motor evoked potential (MEP) latency, and amplitude) of corticospinal tract integrity in people with relapsing-remitting MS (pwMS). Then, the study examined the conformity of TMS measures with clinical disease-related (Expanded Disability Status Scale—EDSS) and magnetic resonance imaging (MRI) results (lesion count) in pwMS. The e-field navigated TMS, MRI, and EDSS data were collected in 23 pwMS and compared to non-clinical samples. The results show that pwMS differed from non-clinical samples in MEP latency for upper and lower extremity muscles. Also, pwMS with altered MEP latency (prolonged or absent MEP response) had higher EDSS, general and pyramidal, functional scores than pwMS with normal MEP latency finding. Furthermore, the RMT intensity for lower extremity muscles was predictive of EDSS functional pyramidal scores. TMS/MEP latency findings classified pwMS as the same as EDSS functional pyramidal scores in 70–83% of cases and were similar to the MRI results, corresponding to EDSS functional pyramidal scores in 57–65% of cases. PwMS with altered MEP latency differed from pwMS with normal MEP latency in the total number of lesions in the brain corticospinal and cervical corticospinal tract. The study provides preliminary results on the correspondence of MRI and TMS corticospinal tract evaluation results with EDSS functional pyramidal score results in MS.

Community-acquired pneumonia is potentially serious infection in children. The diagnosis can be based on the history and clinical signs and symptoms. Additional diagnostic tests (laboratory, imaging, and microbiology) may be helpful when diagnosis is unclear. The most likely etiology depends on a number of factors such as seasonality, geographic location, the age of child, and the severity of disease. Treatment involves symptomatic measures, and in most children antibiotic therapy. This paper presents the clinical guidelines of the Croatian Society of Pediatric Pulmonology to standardize the procedures for the diagnosis and treatment of children with community-acquired pneumonia.

Our aim was to determine the frequency and characteristics of neurological post-COVID-19 syndrome and the diagnostic and therapeutic measures that were used for the treatment of these patients. Data were collected for 243 patients examined during the period of 11 May 2021 to 22 June 2022. The inclusion criteria were COVID-19 illness and neurological symptoms associated with COVID-19. The exclusion criteria were non-neurological symptoms, patients who did not suffer from COVID-19, and symptoms that occurred after vaccination against the SARS-CoV-2 virus. Data for 227 patients with neurological post-COVID-19 symptoms were analyzed. Most patients presented with multiple symptoms, most often headache, cognitive impairment, loss of smell, paresthesia, fatigue, dizziness, and insomnia. Patients were most often referred for consultative examinations, neuroradiological imaging, and EEG. The therapy was mostly symptomatic. Most patients had no change in their symptoms on follow-up visits (53.21%), while positive outcome was found in 44.95% of patients. This study found that neurological post-COVID-19 syndrome appears to be more common in women, and generally, the most common symptoms are headache and cognitive impairment. The gender distribution of symptoms was clearly visible and should be further investigated. There is a need for longitudinal follow-up studies to better understand the disease dynamic.

Obesity is a pandemic of the 21st century. Increasing trends in the frequency of obesity is a worrying public health, psycho-social and clinical problem and consequently also an economic problem. Appearance of childhood obesity contributes to the adolescent and adult obesity and it is accompanied by a series of complications and comorbidities. Obesity is a risk factor for the development of chronic non-communicable diseases. Cardiovascular diseases, hypertension, dyslipidemia, insulin resistance, type 2 diabetes, fertility disorder, weaker mobility, psychosocial deprivation affect the quality and length of an individual’s life and indirectly have an impact on society as a whole. The primary health care pediatrician is at the source of the problem, often the first specialist in contact with the obese child and parents who first need to recognize the problem, and then get involved in its systematic solution. Education and motivation of the parents and then of the child himself, members of the extended family as well as all non-health workers who encounter obesity problems through the upbringing and education system are crucial for successful prevention. Prevention of obesity must be approached in a complex, multidisciplinary, expertly coordinated manner, in which the primary health care pediatrician plays a key role. The paper analyzes the importance of primary health care pediatricians starting with recognition of family and personal risk factors, objective diagnostics, education of parents and children, and non-health workers as well as sensitizing the entire social community about the far-reaching effects of childhood obesity on the health of population. [ABSTRACT FROM AUTHOR]

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Background: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. Aim: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs’ prescribing confidence. Design & setting: Prospective audit in 18 European countries. Method: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. Results: Antibiotic prescribing proportions varied considerably: 40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. Conclusion: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.

Background Healthcare professionals (HCPs) in family medicine (FM) in Croatia work in a demanding environment caused by the SARS-CoV-2 pandemic. Besides particular circumstances in healthcare, an unknown virus, social distancing, and homeschooling, the capital was hit with the earthquake during the lockdown. Objectives To assess the prevalence of stress, anxiety, depression, posttraumatic stress disorder (PTSD) and the influence of demographic characteristics, professional differences, medical history, and specific stressors on the psychological outcomes. Methods A cross-sectional study with the online questionnaire containing the Depression, Anxiety and Stress Scale (DASS-21) and the Impact of Event Scale-Revised (IES-R) was conducted from 1st to 15 May 2020 in FM. Results HCPs (534, 35% response rate), predominantly female (84.5%), participated in the research. High prevalence of stress (30.9%), anxiety (33.1%), depression (30.7%), and PTSD (33.0%) were found. Female participants had higher results in the anxiety subscale of DASS-21 and IES-R scores. Pre-existing conditions were associated with higher levels of stress, anxiety, depression, and PTSD. The IES-R score for PTSD showed borderline correlation (p = 0.053) with working in regions with the highest incidence of COVID-19. Having schoolchildren made a difference on a stress subscale in DASS-21 (p

Industrial heritage plays an important role in the economical, historical, and cultural identity of contemporary European society. A significant part of the industrial heritage consists of historical buildings which have remained after mining and petroleum exploitation. Moreover, industrial heritage can be also nurtured in countries in which mining and petroleum activities are not fully developed. It is inevitably associated with geological heritage. Furthermore, geological heritage is essential for a better understanding of nature, its wider appreciation and better protection. Mining has always played a significant industrial role, but it has recently lost its significance due to increasing environmental requirements regarding the European green deal and transforming the economy for a sustainable future. However, old mining and petroleum heritage sites can become attractions and they can contribute to the development of tourism and the community itself. A new term “geotechnological heritage”, presented in this paper, is related to mining, geological and petroleum heritage due to their significant interaction. This paper presents the used and unused touristic potential of heritage on selected sites in the Republic of Croatia. In addition, an analysis of the Croatian undervalued geotechnological heritage has been performed after the exploitation of stone and other nonmetallics, coal, metals, and petroleum. Unlike Croatia, the potential of geotechnological heritage has been recognized and exploited in most European countries. Therefore, Croatia has a great opportunity to develop heritage based on the experience of more successful members of the European Union.

The island Goli otok (north Adriatic, Croatia) cultural landscape is a complex system of interactions between people and nature, which has arisen through the anthropogenic use of this unique natural space with the aim of implementing ideas of the ideological re-education of political prisoners between 1949 and 1956, and the punishment of criminals and some political prisoners between 1956 and 1988. The most significant elements of the cultural landscape of the island are comprised of the anthropogenic structures of the political prison camp which deliberately used the natural features of the landscape in such a way as to enable methods of coercion of prisoners, which finally resulted in the unique identity of the space as a unit.

Abstract Background Evidence-based medicine (EBM) aims to assist physicians in making medical decisions based on the integration of the current best evidence, clinical expertise, and patients’ values. Extensive research has been conducted regarding physicians’ awareness, attitudes, barriers, and knowledge about EBM. In Croatia, there is a lack of research on this topic, especially among family physicians (FP). The aim of this study was to assess the awareness, attitudes, barriers, and knowledge about EBM among FPs in Croatia after six years of educational activities organized and provided by Cochrane Croatia. Methods In a cross-sectional study, conducted in 2016, we offered to FPs in Croatia a printed or online validated questionnaire to assess attitudes toward and barriers when considering the use of EBM, awareness about sources of evidence, and their level of understanding of evidence-based medicine terminology. The physicians were approached during mandatory continuing medical education courses and through their professional associations. We compared results from two groups of physicians, one with family medicine specialization and the other without. Results 295 (14%) of all officially registered FPs responded to the questionnaire. Respondents were very positive toward the promotion and usage of EBM. 160 (67%) indicated that they did not have access to the Cochrane Library. The majority reported lack of time available for finding evidence (80%), and patients’ unrealistic expectations that influence doctors’ choice of treatment (72%). Between the two groups of physicians, more family medicine specialists reported time restrictions for finding evidence. The highest level of EBM terminology understanding was reported for study design terms, and the lowest for statistical terms. Conclusions This study demonstrated that FPs in Croatia had very positive attitudes toward the use of EBM, they agreed that EBM improves patient care, and they estimated that more than two thirds of their practice is EBM-based. Compared to the results of the first assessment of physicians in 2010, there was some increase in the level of EBM awareness among FPs. However, to further increase the quality of EBM practice in Croatia better access to EBM sources and further educational activities are needed.

Abstract Background Hypoglycemia in type 2 diabetes mellitus (T2DM) is still unsolved issue. The aim of this study was to investigate hypoglycemia in T2DM in participants treated with oral antihyperglycemic agents using different glucose cut-off values and to explore influence of different therapies. Methods This multi-center prospective observational study included participant with T2DM from primary care offices across Croatia treated with antihyperglycemic agents who were monitored using professional continuous glucose monitoring (CGM) device (iPro™2). Hypoglycemia was defined as at least 1% of the monitored period spent in the hypoglycemic range and/or area under the curve of glycemia registered ever under the defined cut-off value. The higher upper limit of blood glucose cut-off value was 3.9 mmol/L (70 mg/dL) and the lower one 3.0 mmol/L (54 mg/dL). Results Study included 94 participants. Median hemoglobin A1C levels, age, T2DM duration, body mass index, and CGM use duration were 7 (5.8–11.5) %, 65 (40–86) years, 7 (1–36) years, 30.4 (21.3–41.5) kg/m2 and 6 (1–7) days, respectively. Fifty participants were treated with sulfonylurea, primarily gliclazide (84%). The percentage of participant with hypoglycemia based on the higher cut-off value was 42.6% vs. 16% based on the higher cut-off value. The percentage of participant with nocturnal hypoglycemia (23 PM to 06 AM) was significantly lower among participant with hypoglycemia based on the higher cut-off value compared to lower one (7.8% vs. 22.9%). Sulfonylurea treatment did not influence the occurrence of hypoglycemia. Analysis of the data from participants having hypoglycemia based on the lower cut-off value pointed to other possible risk factors for hypoglycemia like prolonged overnight fasting, physical activity, alcohol consumption, and concomitant therapy with angiotensin-converting enzyme inhibitors. Conclusions In participant with T2DM treated with oral antihyperglycemic agents hypoglycemia based on the blood glucose cut-off value of 3.9 mmol/L was more prevalent, but with less nocturnal hypoglycemia. Sulfonylurea therapy was not risk factor for hypoglycemia regardless of cut-off value. In participants having hypoglycemia based on the blood glucose cut-off value of 3.0 mmol/L some other possible factors were identified related to concomitant therapy, nutrition and daily habits. Trial registration ClinicalTrials.gov Identifier: NCT03253237.

Background: Pulse wave velocity (PWV) is a known predictor of target organ damage, cardiovascular disease and overall mortality. The aim of this study was to compare the PWV values in subjects with prediabetes, a non-dipper profile and arterial hypertension with their values in healthy subjects. Methods: A total of 301 subjects, aged 40–70 years, without diabetes mellitus were included in this cross-sectional study (150 with prediabetes). They underwent a 24 h ambulatory blood pressure monitoring (ABPM). Subjects were divided into three hypertension groups (A = healthy, B = controlled hypertension, C = uncontrolled hypertension). Dipping status was determined according to ABPM results, and PWV was measured by an oscillometric device. Prediabetes was defined as having 2 separate fasting plasma glucose (FPG) measurements between 5.6 and 6.9 mmol/L. Results: The highest PWV values were found in group C (9.60 ± 1.34 vs. 8.46 ± 1.01 in group B vs. 7.79 ± 1.10 in group A; p < 0.001), in subjects with prediabetes (8.98 ± 1.31 m/s vs. 8.26 ± 1.22 m/s; p < 0.001) and in prediabetic non-dippers among age groups (p = 0.05). In the multivariate regression model age, blood pressure, nocturnal indices and FPG were shown as independent predictors of PWV values. Conclusion: Significantly higher PWV values were found in subjects with prediabetes and non-dipping profiles in all three examined hypertension groups.

Up to 80% of antibiotics are prescribed in the community. An assessment of prescribing by indication will help to identify areas where improvement can be made. A point prevalence audit study (PPAS) of consecutive respiratory tract infection (RTI) consultations in general practices in 13 European countries was conducted in January–February 2020 (PPAS-1) and again in 2022 (PPAS-4). The European Surveillance of Antibiotic Consumption quality indicators (ESAC-QI) were calculated to identify where improvements can be made. A total of 3618 consultations were recorded for PPAS-1 and 2655 in PPAS-4. Bacterial aetiology was suspected in 26% (PPAS-1) and 12% (PPAS-4), and an antibiotic was prescribed in 30% (PPAS-1) and 16% (PPAS-4) of consultations. The percentage of adult patients with bronchitis who receive an antibiotic should, according to the ESAC-QI, not exceed 30%, which was not met by participating practices in any country except Denmark and Spain. For patients (≥1) with acute upper RTI, less than 20% should be prescribed an antibiotic, which was achieved by general practices in most countries, except Ireland (both PPAS), Croatia (PPAS-1), and Greece (PPAS-4) where prescribing for acute or chronic sinusitis (0–20%) was also exceeded. For pneumonia in adults, prescribing is acceptable for 90–100%, and this is lower in most countries. Prescribing for tonsillitis (≥1) exceeded the ESAC-QI (0–20%) in all countries and was 69% (PPAS-1) and 75% (PPAS-4). In conclusion, ESAC-QI applied to PPAS outcomes allows us to evaluate appropriate antibiotic prescribing by indication and benchmark general practices and countries.

All tumors have DNA mutations, and a predictive understanding of those mutations could inform clinical treatments. However, 40% of the mutations are variants of unknown significance (VUS), with the challenge being to objectively predict whether a VUS is pathogenic and supports the tumor or whether it is benign. To objectively decode VUS, we mapped cancer sequence data and evolutionary trace (ET) scores onto crystallography and cryo-electron microscopy structures with variant impacts quantitated by evolutionary action (EA) measures. As tumors depend on helicases and nucleases to deal with transcription/replication stress, we targeted helicase–nuclease–RPA complexes: (1) XPB-XPD (within TFIIH), XPF-ERCC1, XPG, and RPA for transcription and nucleotide excision repair pathways and (2) BLM, EXO5, and RPA plus DNA2 for stalled replication fork restart. As validation, EA scoring predicts severe effects for most disease mutations, but disease mutants with low ET scores not only are likely destabilizing but also disrupt sophisticated allosteric mechanisms. For sites of disease mutations and VUS predicted to be severe, we found strong co-localization to ordered regions. Rare discrepancies highlighted the different survival requirements between disease and tumor mutations, as well as the value of examining proteins within complexes. In a genome-wide analysis of 33 cancer types, we found correlation between the number of mutations in each tumor and which pathways or functional processes in which the mutations occur, revealing different mutagenic routes to tumorigenesis. We also found upregulation of ancient genes including BLM, which supports a non-random and concerted cancer process: reversion to a unicellular, proliferation-uncontrolled, status by breaking multicellular constraints on cell division. Together, these genes and global analyses challenge the binary “driver” and “passenger” mutation paradigm, support a gradient impact as revealed by EA scoring from moderate to severe at a single gene level, and indicate reduced regulation as well as activity. The objective quantitative assessment of VUS scoring and gene overexpression in the context of functional interactions and pathways provides insights for biology, oncology, and precision medicine.

Ancient Sparta is generally recognized as a Greek polis with specific and non-typical state system determined by firmly established set of laws, commonly considered (by Spartans and other Greeks of the time) as a constitution of lawgiver Lykourgos. Spartan constitution was the essence of the state, and this work reviews some of the main institutions established by the constitution. Principal section of the text is dedicated to the basic element and the major purpose of the state and the constitution itself - namely, to the spartan education. It is the peculiar Spartan education and training system called agōgē that particularly enabled ancient Spartans to maintain their durable military might and decisive influence in classical period. Lawgiver of Sparta dedicated primary function in the arrangement of the state itself to the educational system, principally focused on physical and moral education. Capital purpose of educational system was character forming of young Spartans who were expected, mainly on a battlefield in a hoplite phalanx formation, to materialize Spartan ideal of a paramount skilled combatant and fearless warrior.

Purpose: In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia. Materials and methods: Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions – '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies. Conclusion: We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy. Hypertension is the most compelling cause of death in Croatia with increasing prevalence. Still 50.1% of treated hypertensive patients and more than 70% of patients with dyslipidaemia in Croatia are uncontrolled. Programs 70/26 and Do you know your number aimed to achieve 70% and 50% control of hypertensive and dyslipidaemia patients, respectively, by 2026. To accomplish these goals, health literacy of healthcare workers, patients, and general population we will try to improve mostly using digital education and by organising schools of communication. [ABSTRACT FROM AUTHOR]

This article discusses how Venice, in its political representation, valued the relation with the sacred as one of the main strategies for strengthening its political power in Istrian communities. Through associations with the cults of local saints, the Republic participated in the (co)creation of local memory and identity as evinced in the cases of St. Nazarius, the patron saint of Koper, and St. Euphemia, the patron saint of Rovinj. A new impetus was given to their cults in the 15th century after the restitution of their relics as attested by commissions of several liturgical objects made in the Venetian botteghe. The restitution of the relics of St. Euphemia in 1401, here confirmed by the archival research, is a rare documented case in Venetian political and religious practices. The growth of devotion to the saint was prompted by the return of the body, but also by the Venetian custom of developing cults in a coordinated manner, encompassing liturgical celebrations, legends and their visual expressions. This article sheds new light on the role of Venetian officials in the promotion of the cult of St. Euphemia and the authorship of the key illuminations in the Rovinj Illuminated Codex.

In this paper an analysis is made of the influence of the changed political situation on the workings of secondary schools in Zadar in which the language of instruction was Croatian. At the end of the World War I in 1918, the political situation on the Croatian side of the Adriatic had not calmed down. From November 4th, 1918, the Italian army progressively occupied northern Dalmatia and a part of central, while at the same time putting both institutional and non-institutional pressure on the operations of Croatian schools. Italian public and official communication are imposed, and the occupied areas of Dalmatia are kept separate from the hinterland. In such circumstances, the functioning of the school system is made more difficult, as a portion of Croatian and Serbian teachers leave Zadar, and Italian teachers take their place. Occasionally the teaching process is disturbed due to physical attacks and the occupation of the school space by the Italian army. With the signing of the Treaty of Rapallo from November of 1920, the fate of previous Croatian scholastic institutions is sealed, and they cease operations at the end of the 1920/1921 school year.

U radu se razmatra primjena FIDIC-ovih općih uvjeta ugovora u izvođenju radova na izgradnji željezničke infrastrukture. Analiziraju se ugovorna ograničenja kao što su: minimalni iznos situacije, predujam i dinamika vraćanja predujma, garancije i zadržana sredstva, ugovaranje izvođenja radova prema FIDIC-ovoj crvenoj knjizi, uvjeti ugovora za radove prema projektu naručitelja, bez izvedbene dokumentacije u doba ugovaranja, izvedba radova uz odvijanje prometa, priprema, zatvori pruge, problematika situiranja dodatnih radova, ugovorne procedure.

Introducción: Evaluar la precisión de la cirugía artroscópica de Latarjet–Bankart, mediante tomografía computada post operatoria. Describir resultados y complicaciones en la primera serie prospectiva de esta técnica en Chile. Material y Método: Quince pacientes fueron sometidos a cirugía de estabilización mediante la técnica artroscópica de Latarjet–Bankart. Se realizó una evaluación de la posición del injerto de coracoides mediante tomografía computada considerando los índices: ángulo tornillo - superficie articular, tornillo excesivamente largo, distancia línea articular - borde injerto en plano axial (método tangente), distancia borde injerto – superficie articular (método del círculo) en planos axial y coronal y relación posición injerto – diámetro glenoideo. Resultados: Se obtuvo un ángulo tornillo – superficie promedio de 32.9°. En un paciente se objetivó un tornillo de largo excesivo (+ 4 mm). De acuerdo al método tangente axial la distancia fue de 0 mm [0 mm – 2,5 mm], método circulo axial 0 mm [-0,8 mm – 1 mm], circulo coronal 0 mm [-1 mm – 2 mm]. En el 100% de los casos la posición injerto – diámetro glenoideo, fue bajo el 50% o subecuatorial. El injerto se encontró en posición “flush” en todos los pacientes. En un paciente fue necesario convertir a cirugía abierta. En un paciente ocurrió una factura parcial del injerto y un paciente presento una fractura de glenoides y una plexitis transitoria de 5 semanas. Un 13% de los pacientes presentó recurrencia al seguimiento a los 2 años. Conclusión: Es factible realizar esta técnica quirúrgica de manera artroscópica, con una baja necesidad de conversión y complicaciones, logrando una posición óptima del injerto. Tipo de estudio: Serie de Casos Nivel de Evidencia: IV