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Introduction The role of the pineal gland in psychiatric disorders is poorly investigated. There are studies, primarily on adult patients, that indicate a higher presence of pineal gland abnormalities in patients suffering from depression, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). When it comes to ADHD, there is speculation about the role of melatonin and the influence of the pineal gland on the dopaminergic system. Data on the association between pineal gland cysts and ADHD in juvenile patients are particularly scarce. Objectives Due to all of the above, our goal is to present the case of a nine-year-old male patient who has a confirmed cyst of the pineal gland and is being treated for ADHD. Methods The patient was examined by a neuropediatrician, EEG and brain MRI were performed. He was also examined by a psychologist and by a psychiatrist. Endocrinological, hematological, rheumatological, pulmonological treatment and karyotyping were performed. Results MRI of the brain revealed a cyst of the pineal gland with an anteroposterior diameter of 1 cm without significant compression. The EEG was mildly slowed and paroxysmally dysrhythmic for the age, ie. paroxysms of high-voltage delta waves were described. The EEG findings after sleep deprivation were paroxysmally altered with rare focal changes in the right temporoparietal region. Through psychological analysis, it was determined that specific deficits persist in the area of verbal understanding, perceptual organization and visual processing, information processing speed, numerical reasoning, attention and short-term memory. On the level of visuomotor perception and coordination, deviations are observed by organic type. He is motorically more active, impulsive, emotionally immature, easily distractible. Conclusions The etiology of ADHD is poorly researched, and so is the role of the pineal gland, its cyst and melatonin. There is scant knowledge for other psychiatric disorders, but primarily from researches on adult psychiatric patients. Additional researches are definitely needed on this topic, especially in the field of child and adolescent psychiatry. Disclosure of Interest None Declared

Introduction People with severe mental disorder (SMD) determine the goals and paths of recovery with professional and nonformal supporters such as family and friends. It is crucial that these people, as well as everyone who participates in the recovery process, are familiar with all the elements that contribute to the recovery of mental health in order to help people with SMD identify goals and assess their achievement. We have therefore created a Recovery Helm to assess the functioning in the various areas necessary for recovery to help us assess the needs and monitor the recovery process of people with mental health problems. Objectives The goal is to assess the initial state of mental health and monitor the effects of the mobile rehabilitation team program on the recovery of people with SMI through the use of the Recovery Helm. Methods We used the Recovery Helm: http://shorturl.at/gyCDQ as an instrument for the initial assessment of all areas crucial for recovery to determine the goals of recovery and interventions needed to achieve these goals of rehabilitation in 30 patients included in the program of the mobile rehabilitation team applying different psychosocial interventions according to the individual recovery plan made as a mutual agreement between patients and rehabilitation team. The status of recovery is evaluated after 3 and 6 months. Results The results indicate significant improvements in most areas of the recovery assessed at the Recovery Helm selected as individually important goal for a person included in the rehabilitation program Conclusions The Recovery Helm is an excellent clinical assessment instrument that helps determine recovery goals and rehabilitation interventions that promote recovery and monitor the achieved results. Disclosure of Interest None Declared

Introduction: Skin cancer, a significant global health issue, requires prompt detection and management, particularly among the elderly. Primary care physicians play a critical role in early diagnosis because they are often the first to evaluate patients with skin lesions. Accurate diagnosis by family physicians is essential for effective treatment and improved patient outcomes., Methods: Over a 12-year period, this study analyzed 125 samples from 89 patients that presented with visible skin changes or suspicious lesions identified during routine examinations. Initial working diagnoses made by family physicians were compared to final pathohistological diagnoses (PHD)., Results: The study found a significant difference between working diagnoses and final PHDs for malignant versus benign cases, with an accuracy of 83.3% and statistical significance (p = 0.04). A difference of 12.9% was observed, indicating areas for improvement. The diagnostic effectiveness for premalignant versus benign cases is high (accuracy of 88.2%), but without statistical significance (p = 0.50), and it suggests that these differences are not clinically relevant., Conclusions: Primary care physicians demonstrate high accuracy in identifying malignant skin conditions, which is crucial for effective skin cancer management. However, improving diagnostic accuracy, particularly to reduce the misclassification of benign conditions as malignant, remains necessary. Continued training and development are essential to further enhance diagnostic precision for all skin conditions.

Most developed societies managed, due to their prosperity and resource abundance, to structure relationships among free individuals in such a way to leave them fundamentally unstructured, according to the free market principle. As the pandemic illustrated well, this lack of structure when facing collective threats makes it impossible to collectively and proportionately assess and manage its implications and consequences. This may be particularly precarious when introducing comprehensive, monitoring and tracking, surveillance systems dependent on the vaccination status of the individual. If our previously shared aims were successfully and collectively enacted with the greatest of costs, is it permissible that the degree of personal freedom is a commodity, and everyone is a compulsory participant? The need to control one's COVID-19 status allows the individual to become legally free from excessive enactment of sovereignty of the state. Should these rights be regulated by the free market?, Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Košec, Hergešić, Zdilar, Svetina and Ćurković.)

Background: The pandemic of COVID-19 had a profound impact on our community and healthcare system. This study aims to assess the impact of COVID-19 on psychiatric care in Croatia by comparing the number of acute psychiatric cases before coronavirus disease (2017-2019) and during the pandemic (2020-2022)., Materials and Methods: The paper is a retrospective, comparative analyzes of the hospital admission rate in Diagnosis Related Group (DRG) classes related to mental diseases, and organic mental disorders caused by alcohol and drug use. This study used DRG data from all acute hospitals in Croatia accredited to provide mental health care services and relevant publicly available data from the Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF). All hospital admissions for acute psychiatric patients in Croatia were tracked during both periods under study., Results: During the pandemic, the average number of all such cases decreased by 28% in secondary and tertiary hospitals, and by 11% in specialist psychiatric hospitals. It was also found that during COVID-19, there was a decrease in case numbers in DRG classes related to major affective disorders and anxiety, alcohol, and drug intoxication (31, 48, 34 and 45%, respectively). However, the same period saw an increase in hospital activity for eating disorders and for involuntary admissions related to schizophrenia and paranoia (30, 34 and 39% respectively). There were no changes in the admission rate for cases related to opioid use., Conclusion: The COVID-19 pandemic resulted in both a steep decrease in the overall number of psychiatric cases inpatient treatment at mental health facilities and their DRG casemix. Increasing our understanding of how pandemics and isolation affect demand for psychiatric care will help us better plan for future crises and provide more targeted care to this vulnerable group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalanj, Ćurković, Peček, Orešković, Orbanić and Marshall.)

Introduction: Forest ecosystems are highly threatened by the simultaneous effects of climate change and invasive pathogens. Chestnut blight, caused by the invasive phytopathogenic fungus Cryphonectria parasitica , has caused severe damage to European chestnut groves and catastrophic dieback of American chestnut in North America. Within Europe, the impacts of the fungus are widely mitigated through biological control that utilizes the RNA mycovirus: Cryphonectria hypovirus 1 (CHV1). Viral infections, similarly to abiotic factors, can cause oxidative stress in their hosts leading to physiological attrition through stimulating ROS (reactive oxygen species) and NOx production., Methods: To fully understand the interactions leading to the biocontrol of chestnut blight, it is vital to determine oxidative stress damage arising during CHV1 infection, especially considering that other abiotic factors, like long-term cultivation of model fungal strains, can also impact oxidative stress. Our study compared CHV1-infected C. parasitica isolates from two Croatian wild populations with CHV1-infected model strains (EP713, Euro7 and CR23) that have experienced long-term laboratory cultivation., Results and Discussion: We determined the level of oxidative stress in the samples by measuring stress enzymes' activity and oxidative stress biomarkers. Furthermore, for the wild populations, we studied the activity of fungal laccases, expression of the laccase gene lac1 , and a possible effect of CHV1 intra-host diversity on the observed biochemical responses. Relative to the wild isolates, the long-term model strains had lower enzymatic activities of superoxide dismutase (SOD) and glutathione S-transferase (GST), and higher content of malondialdehyde (MDA) and total non-protein thiols. This indicated generally higher oxidative stress, likely arising from their decades-long history of subculturing and freeze-thaw cycles. When comparing the two wild populations, differences between them in stress resilience and levels of oxidative stress were also observed, as evident from the different MDA content. The intra-host genetic diversity of the CHV1 had no discernible effect on the stress levels of the virus-infected fungal cultures. Our research indicated that an important determinant modulating both lac1 expression and laccase enzyme activity is intrinsic to the fungus itself, possibly related to the vc type of the fungus, i.e., vegetative incompatibility genotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Popović, Nuskern, Peranić, Vuković, Katanić, Krstin, Ćurković-Perica, Leigh, Poljak, Idžojtić, Rigling and Ježić.)

Understanding the attitudes of a particular society on a "good death" is important when it comes to end-of-life decision-making and palliative care. In the Republic of Croatia no systematic research has been done on the attitudes of the general population about the concept of a "good death". This cross sectional survey was conducted on a three-stage random sample, stratified by regions, counties and locations within those counties (N = 1203) during November and December, 2019. ANOVA, to determine differences, factor analysis and multiple regression analysis were used. The most important characteristics of a good death outlined by the respondents were: the absence of pain, the presence and unencumberedness of family and loved ones, the importance of a sense of fulfilment and meaning in life in this regard, reconciliation with God, the presence of awareness and sobriety, and the possibility of treatment.

Background: Health information and patient education on lifestyle changes may have a positive effect on the prevention of many chronic conditions, especially cardiovascular diseases (CVDs). We performed a parallel, three-arm randomized controlled trial (RCT) of 6-month educational intervention in a form of letters containing a reminder of the participant's CVD risk with or without Cochrane blogshots to reduce CVD risk among women aged 45-65 with one or more known CVD risk factors., Methods: The control group received a letter about their CVD risk at the beginning of the trial. The intervention groups received the initial letter about their CVD risk and remainder letters about their CVD risk every 2 months, with or without Cochrane blogshots: (1) effect of calcium in the prevention of high blood pressure, (2) effect of reducing saturated fat acids in eating habits, and (3) effects of green and black tea in CVD prevention. The primary outcome was CVD risk reduction calculated as the difference between the baseline and 6-month score for a 10-year risk of fatal CVD according to the ACC/AHA guidelines., Results: After both interventions, CVD risk reduction was significantly higher compared to the control group (P < 0.001, Kruskal-Wallis H test). The number of participants who decreased their CV risk was 29% (20/70) in the control group, 69% (48/70) in the group receiving the reminder letters, and 70% (49/70) in the group receiving the reminder letters and blogshots. The number needed to treat to achieve risk reduction was 2.41 (95% CI = 1.77 to 3.78) for letters with a CVD risk reminder and 2.50 (1.81 to 4.03) for letters with a reminder and a blogshot. The group receiving reminder letters with Cochrane blogshots had a significant change in the category of CVD risk, mainly from high to moderate and from moderate to low CVD risk category., Conclusions: A simple and inexpensive intervention method in a form of letters reminding women about their CVD risk with or without providing additional health information in the form of Cochrane blogshots about interventions for important CVD risk factors may be effective in CVD management and could be considered by primary care providers., Trial Registration: ClinicalTrials.gov, NCT04601558. Retrospectively registered on October 19, 2020., (© 2022. The Author(s).)

Gene flow between cultivated and wild gene pools is common in the contact zone between agricultural lands and natural habitats and can be used to study the development of adaptations and selection of novel varieties. This is likely the case in the northern Adriatic region, where centuries-old cultivated orchards of sweet chestnut (Castanea sativa Mill.) are planted within the natural distribution area of the species. Thus, we investigated the population structure of several orchards of sweet chestnuts. Furthermore, the genetic background of three toponymous clonal varieties was explored. Six genomic simple sequence repeat (gSSR) and nine EST-derived SSR (EST-SSR) loci were utilized in this research, and both grafted and non-grafted individuals were included in this study. Five closely related clones were identified, which represent a singular, polyclonal marron variety, found in all three cultivation areas. Furthermore, many hybrids, a result of breeding between cultivated and wild chestnuts, have been found. Analyzed semi-wild orchards defined by a diverse genetic structure, represent a hotspot for further selection and could result in creation of locally adapted, high-yielding varieties., (© 2022. The Author(s).)

Background: Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally., Methods: We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age- and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation., Findings: We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well., Interpretation: Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue., Funding: None., Competing Interests: JP is funded by a National Health and Medical Research Council Investigator Grant (GNT1173126). DG receives funding support from the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust. He is an unpaid member of the UK Government's Department of Health and Social Care National Suicide Prevention Strategy Advisory Group, England and the COVID-19 response sub-group, an unpaid member of the Samaritan's Policy, Partnerships and Research Committee, and an unpaid member of the Movember Global Advisory Committee. LA has a research grant to Manchester University from Health Quality Improvement Partnership, on behalf of NHS England and devolved UK governments. He is also Chair, National Suicide Prevention Strategy Advisory Group, Department of Health and Social Care. SF was Special Advisor to a Coroner for a specific investigation and is Chairperson, New Zealand Mortality Review Committee. AB is supported by the EU Erasmus+ Strategic Partnership Programme (2019-1-SE01-KA203-060571). LFC is Primary Investigator for pesticide suicide research in Malaysia funded by the Centre of Pesticide Suicide Prevention Malaysia, University of Edinburgh (Oct 2020-31 March 2022). NK is Member, National Suicide Prevention Strategy Advisory Group (England) and Topic Advisor for NICE self-harm guidelines. NK also declares research grants paid to his institution by NIHR, HQIP and DHSC for work related to the treatment and prevention of suicidal behaviour (but not directly related to the current work). OJK is supported by a Senior Postdoctoral Fellowship from Research Foundation Flanders (FWO 1257821N); payment made to institution (KU Leuven). OJK reports grants from UCB Community Health Fund, outside the submitted work. The UCB Community Health funds in this case are managed and disbursed by the King Baudouin Foundation (Belgium). Selection is by an independent jury and UCB is not involved. Payment is to the institution (KU Leuven). OJK received a waived registration fee for the 2021 International Academy of Suicide Research (IASR) Summit in Barcelona (held online), as an invited speaker (unrelated to the current work). No payment was received directly. Fee was automatically waived at registration. OJK is a member of the Samaritans Research Ethics Board (SREB); this is an unpaid role. OJK is co-chair of the Early Career Group of the International Association for Suicide Prevention (IASP). This role is unpaid, but yearly IASP membership fee is covered in return for this service role. No funds are exchanged, but membership fee is covered directly by IASP. DK reports that the Wellcome Trust has supported the Elizabeth Blackwell Institute with a ISSF grant. DK also declares a grant from the Centre for Pesticide Suicide Prevention to conduct COVID-19 related work on self-harm in Sri Lanka, and panel fees from the Department of Health and Social Care for assessing grants. She also declares a leadership or fiduciary role with Migration Health and Development Research Initiative; no fees received. SL declares a $75,000 grant from Queensland Health; payment will be made to institution when payment occurs. SL also declares project funding from the Queensland Government for the Queensland Suicide Register; made to his institution. SL is also on the Technical Advisory Group (unfunded role), NSW Suicide Monitoring System. HO declares registration for the online congress DGPPN (2020 and 2021) and for the DGPPN congress (2019). He also declares registration for the congress OGPP (2019). SP declares a personal consultancy for support and advice to the National Office for Suicide Prevention (Health Service Executive, Dublin, Ireland) and a personal consultancy for support and advice to the National Suicide Prevention Leadership Group and the Scottish Government. SP also declares support from the World Health Organization for attending a workshop on National Suicide Prevention Implementation and Evaluation, Geneva, November 2019. SP also holds unpaid roles as adviser and committee chairmanships with the International Association for Suicide Prevention. GP is supported by the Flemish Government – Department of Health, Wellbeing and Family. AR and CR-L declare support by the Federal Health Ministry of Germany (BMG), grant number ZMVI1-2517FSB136. CR-L also declares payment or honoraria and participation on a Data Safety Monitoring Board or Advisory Board with Janssen and LivaNova. NR-V declares she is the designated representative of the Puerto Rico Department of Health in the Puerto Rico Administration of Mental Health and Anti-Addiction Services’ Mental Health and Addiction Council. It is not a paid position; she attends meetings as part of her responsibilities at the Puerto Rico Department of Health and is the Coordinator of the Public Policy Committee within this advisory council. The aforementioned council is a requisite with which the Puerto Rico Administration of Mental Health and Anti-Addiction Services must comply with because this Administration receives federal funding from the Substance Abuse and Mental Health Services Administration of the United States of America., (© 2022 The Authors.)

Cryphonectria parasitica is an invasive fungal pathogen that causes blight disease on chestnut trees. Its destructive effect can be controlled with naturally occurring mycovirus Cryphonectria hypovirus 1 (CHV1). To date, the spread of C. parasitica and CHV1 in Europe is fairly well documented, but there are still several unexplored regions. Thus, we sampled blight cankers from four sweet chestnut populations in Bay of Kotor and Lake Skadar regions in Montenegro. We determined vegetative compatibility (vc) type and mating-type diversity using molecular vic and MAT1 genotyping, as well as confirming the presence of CHV1 by RT-PCR. We identified 11 vc types, with EU-12 being the dominant one represented by 58.2% of all fungal isolates. The Shannon diversity index ranged from 0.93 to 1.47. Both mating types of C. parasitica were found in all four populations. The prevalence of CHV1 ranged from 15% to 40%. All CHV1 isolates belonged to Italian subtype I of CHV1 and were closely related, with relatively recent common ancestors. Our results indicate a longer presence of C. parasitica and CHV1 in Montenegro than previously thought. Natural biocontrol with CHV1 seems to be well established. However, it has the potential for deterioration; thus, close monitoring is required.

The link between chronic urticaria and accompanying thyroid disease is still not understood, with current treatment focusing on antihistamines and levothyroxine. A 35-year-old female patient presented with chronic idiopathic urticaria and facial angioedema for 9 months prior to evaluation. Oral corticosteroid therapy, antihistamines, leukotriene-antagonists, selenium, and omalizumab were all administered, with the disease relapsing within several days, accompanied with facial angioedema of varying severity. Laboratory results were negative for antinuclear antibodies (ANA) and cytoplasmic antineutrophil antibodies (ANCA). Immunoglobulins and complement levels were normal. Autologous serum testing, and skin-prick test for common inhalatory allergens were all normal. Levothyroxine was then administered with no effect on the symptoms. After considering all of the available treatment options, the patient decided to undergo total thyroidectomy. Urticaria and angioedema subsided on the third postoperative day, and she remains free of symptom recurrence during 10 months of postoperative follow-up. Her antiTPO titer decreased from > 1300 to 31.1 kIU/L and antiTG decreased from 272 to 4.9 kIU/L three months after the surgery. The most important element in this case report is an unexpected extra-thyroid presentation of an autoimmune thyroid disease, with a newly described association with facial angioedema. Additional important evidence may confirm the hypothesis that both conditions are indeed caused by a common immunological patohogenetic pathway that should be routinely evaluated in patients presenting with chronic idiopathic urticaria., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Background: Burnout is a common mental problem in medical students. For those who are following medical studies abroad there is a higher risk of suffering this syndrome, due to the combination of academic stress and the stress derived from their new living situation. This study was performed with the purpose of testing the following hypothesis: in medical students enrolled in medical programs abroad, abilities associated with professionalism and family support play a protective role in the prevention of suffering burnout., Methods: A cross-sectional study was performed in the Faculty of Medicine of the University of Zagreb, where a fully English medical program is offered. The general version of the Maslach Burnout Inventory (MBI-GS) was used as a dependent variable, while Jefferson Scales of empathy, teamwork, and physician lifelong learning and the Social and Emotional Loneliness Scale for Adults were used as predictive variables. In addition, information related to sex, country of birth, native language, age, academic achievement, and living situation were collected in a socio-demographic form. Linear regression models were applied to identify predictors of burnout., Results: In a sample composed of 188 medical students (38 Croatians and 144 foreigners from 28 countries), 18% of the global score in the MBI-GS was explained by lifelong learning and family loneliness. A separate analysis for each domain of the MBI-GS allowed the creation of three models: the first model explained 19% of the variance of the "exhaustion" domain by "country of birth", "living with parents", "academic year", and "cynicism"; a second model explained 24% of the variance of the "cynicism" domain by "academic year", "empathy", "lifelong learning", and "exhaustion"; and finally, a third model explained 24% of the variance of the "professional efficacy" domain by "lifelong learning", "family loneliness", and "cynicism". All obtained models presented an effect size between medium and large, as well as matching the required conditions for statistical inference., Conclusions: These findings confirm the important role that family plays as a source of support for medical students. Empathy and lifelong learning, two specific elements of medical professionalism, appear as protective factors in the prevention of burnout in international students.

Trust in healthcare systems and physicians is considered important for the delivery of good healthcare. A cross-sectional survey was conducted on a random three-stage sample of the general population of Croatia (N = 1230), stratified by regions. Of respondents, 58.7% displayed a high or very high level of trust in the healthcare system, 65.6% in physicians, and 78.3% in their family physician. Respondents' views regarding patients' roles in the discussion of treatment options, confidence in physicians' expertise, and underlying motives of physicians were mixed. Respondents with a lower level of education, those with low monthly incomes, and those from smaller settlements had lower levels of trust in physicians and the healthcare system. Trust in other institutions, religiosity and religious beliefs, tolerance of personal choice, and experience of caring for the seriously ill and dying were predictors of trust in healthcare and physicians. Our findings suggest that levels of healthcare-related trust in Croatia are increasing in comparison with previous research, but need improvement. Levels of trust are lowest in populations that are most vulnerable and most in need of care and protection.

Healthcare professionals working in intensive care units (ICUs) are often involved in end-of-life decision-making. No research has been done so far about these processes taking place in Croatian ICUs. The aim of this study was to investigate the perceptions, experiences, and challenges healthcare professionals face when dealing with end-of-life decisions in ICUs in Croatia. A qualitative study was performed using professionally homogenous focus groups of ICU nurses and physicians (45 in total) of diverse professional and clinical backgrounds at three research sites (Zagreb, Rijeka, Split). In total, six institutions at the tertiary level of healthcare were included. The constant comparative analysis method was used in the analysis of the data. Differences were found between the perceptions and experiences of nurses and physicians in relation to end-of-life decisions. Nurses' perceptions were more focused on the context and features of immediate care, while physicians' perceptions also included the wider sociocultural context. However, the critical issues these specific professional groups face when dealing with end-of-life decisions seem to overlap. A high variability of practices, both between individual practitioners and between different organizational units, was omnipresent. The lack of adequate legal, professional, and clinical guidelines was commonly expressed as one of the most critical source of difficulties., (© 2021. Journal of Bioethical Inquiry Pty Ltd.)

Intra-host dynamics are a core component of virus evolution but most intra-host data come from a narrow range of hosts or experimental infections. Gaining broader information on the intra-host diversity and dynamics of naturally occurring virus infections is essential to our understanding of evolution across the virosphere. Here we used PacBio long-read HiFi sequencing to characterize the intra-host populations of natural infections of the RNA mycovirus Cryphonectria hypovirus 1 (CHV1). CHV1 is a biocontrol agent for the chestnut blight fungus ( Cryphonectria parasitica ), which co-invaded Europe alongside the fungus. We characterized the mutational and haplotypic intra-host virus diversity of thirty-eight natural CHV1 infections spread across four locations in Croatia and Switzerland. Intra-host CHV1 diversity values were shaped by purifying selection and accumulation of mutations over time as well as epistatic interactions within the host genome at defense loci. Geographical landscape features impacted CHV1 inter-host relationships through restricting dispersal and causing founder effects. Interestingly, a small number of intra-host viral haplotypes showed high sequence similarity across large geographical distances unlikely to be linked by dispersal., (© The Author(s) 2021. Published by Oxford University Press.)

This paper showcases the development of plant virology in Croatia at the University of Zagreb, Faculty of Science, from its beginning in the 1950s until today, more than 70 years later. The main achievements of the previous and current group members are highlighted according to various research topics and fields. Expectedly, some of those accomplishments remained within the field of plant virology, but others make part of a much-extended research spectrum exploring subviral pathogens, prokaryotic plant pathogens, fungi and their viruses, as well as their interactions within ecosystems. Thus, the legacy of plant virology in Croatia continues to contribute to the state of the art of microbiology far beyond virology. Research problems pertinent for directing the future research endeavors are also proposed in this review.

Laccase activity reduction in the chestnut blight fungus Cryphonectria parasitica usually accompanies the hypovirulence caused by the infection of fungus with Cryphonectria hypovirus 1 (CHV1). However, the different methods utilized for assessing this phenomenon has produced varied and often conflicting results. Furthermore, the majority of experimental setups included only one prototypic system, further confounding the results. Considering the diversity of fungal isolates, viral strains, and variability of their effects on the phytopathogenic process observed in nature, our goal was to ascertain if laccase activity variability is affected by (1) different C. parasitica isolates infected with several CHV1 strains, and (2) growth conditions. We have demonstrated that some CHV1 strains, contrary to previous assumptions, increase the activity of C. parasitica laccases. The specific fungal isolates used in the experiments and culture conditions also affected the results. Furthermore, we showed that two commonly used laccase substrates, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,4-dimethoxyphenol, cannot be used interchangeably in C. parasitica laccase activity measurements. Our results illustrate the importance of conducting this type of study in experimental systems and culture conditions that resemble natural conditions as much as possible to be able to infer the most relevant conclusions applicable to natural populations.

Humans define well-being on predefined assumptions, based on inner and outer criteria as references. As illustrated, these criteria are subject to constant change, even in a situation when one is acting freely and is in control of all possible external influences. Even in scenarios that seemingly allow autonomy with one variable to analyse, underlying "irrationality" affects our ability to define and operationalize any desirable trait or state, such as well-being, euthymia or health. Before eating a bowl full of cherries, one creates an idea of how much cherries he/she will eat. However, as one starts eating, perception and following assumptions change. As cherries labeled as most desirable disappear, other cherries start to appear more alluring. The cherry effect could be of relevance in defining the terms such as well-being, euthymia and basically any other term encompassing a complex category of the human condition dependent on our perceived reality., (© 2021. Marta Olivetti Belardinelli and Springer-Verlag GmbH Germany, part of Springer Nature.)

This cross-sectional study evaluates the knowledge, attitudes, experiences, and behavior of final year medical students, PhD students, and supervisors at the School of Medicine of the University of Zagreb in relation to research misconduct, questionable research practices, and the research environment. The overall response rate was 36.4% (68%-100% for the paper survey and 8%-15% for the online surveys). The analysis reveals statistically significant differences in attitude scores between PhD students and supervisors, the latter having attitudes more in concordance with accepted norms. The results overall show a nonnegligible incidence of self-reported misconduct and questionable research practices, as well as some problematic attitudes towards misconduct and questionable research practices. The incidence of problematic authorship practices was particularly high. The research environment was evaluated as being mostly supportive of research integrity.

Chestnut blight has spread throughout Europe since the introduction of its causal agent, Cryphonectria parasitica , >70 years ago. In our study, we analyzed the diversity of vegetative compatibility (vc) and microsatellite genotypes of C. parasitica , as well as sequence diversity of Cryphonectria hypovirus 1 (CHV1) in six populations from Switzerland, Croatia, and North Macedonia. Resampling of local populations that were already investigated more than a decade ago allowed us to analyze the spatial and temporal population structure across an invasive range of the pathogen in Europe. Regardless of which genetic marker was used, the >60-year-old Swiss and Croatian populations had high population diversity, whereas more recent North Macedonian populations were mostly clonal. These diversity differences between the investigated populations remained stable over time. A high diversity of CHV1 was observed in all three countries, with North Macedonian strains forming a separate cluster from strains obtained in other countries. No correlation between vc diversity and CHV1 prevalence was observed, suggesting a well-established and maintained natural hypovirulence in all countries, further corroborated by an observed increase in genetic diversity of Croatian C. parasitica populations over time, without collapse of CHV1 prevalence.

Cutaneous head and neck melanoma is a separate subgroup of cutaneous melanoma that has a worse prognosis than other primary sites. The aim of this article is to examine the significance of sex and site of primary lesion as additional risk factors. Primary localization distribution and metastatic disease in the neck in a retrospective cohort of 159 patients with cutaneous head and neck malignant melanoma were analyzed. Men develop primary melanoma more frequently than women in the left peripheral head and neck regions ( P = .0364), as well as clinically visible and occult metastatic disease in the left side of the neck ( P = .0138). Patients with clinically occult regional metastatic disease showed a significantly poorer survival rate than the rest of the group that underwent elective neck dissections ( P = .0270). Left-sided disease in male patients may be an additional risk factor in cutaneous head and neck melanoma. Performing elective neck dissections in high-risk patients might identify patients with occult metastatic disease and worse prognosis but does not offer any significant therapeutic benefit.

Digital technologies have a significant role in collecting, filtering and disseminating information, allowing for social, healthcare and economic activities even in the context of highly restrictive public health measures in the current COVID-19 pandemic. As personal contact is greatly reduced, they also create a shared informational landscape, allowing for a shared threat response. This is a difficult task, since truthfulness of content that leads to actionable knowledge is impossible to consistently validate. So, not only that curation of information is rarely congruent with pressing health issues, but digital spaces may also become fertile ground for misinformation and disinformation, contributing to the devastating effects of an infodemic. Digital intermediaries are useful exactly because their representation of reality is not a true construct, but a result of purposely curated information. However, they are active, dynamic epistemological agents with their own logic and aim. In dealing with a pandemic, we should reconsider the ways how our digital informational landscapes are created and sustained. This urges us to consider ethical governance of digital data curation and dissemination, alongside forms of control of the truthfulness and reach of its content. Some of the most fundamental issues in dealing with the COVID-19 pandemic, including the newly available vaccines are reliant on digital information and data sharing among experts, and the role of informing the general public. The need to create a reproducible, valid and truthful informational landscape is paramount, while allowing for free and rational, behavioral individual choices oriented toward preserving and promoting healthy behavior. These are issues at the heart of dealing with any pandemic, as well as a well-organized health care policy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A crisis is an immediate threat to the functioning of society, while disaster is an actual manifestation of a crisis. Both are now even more critically socially constructed. In the middle of battle with the COVID-19 pandemic, the Republic of Croatia's capital of Zagreb was afflicted with another disaster - two severe earthquakes. Restrictive public health measures were already in place, including restriction on public transport, travel between regions, closure of educational and other public institutions, alongside measures of physical distancing. Most previous cases of COVID-19 were centered in Zagreb, leading to concern of spreading the disease into disease-free communities. It seems that earthquakes did not have an effect on disease transmission - the number of COVID-19 cases remained stable through the 14-day incubation period, with a linear pandemic curve in Croatia in April, and flattened in May. This leads to a conclusion that the earthquake did not have a direct effect on disease spread. Despite the fact that the current pandemic and its responses are unique, this paradox can have interesting repercussions on how we conceptualize and approach notions as vulnerability and resilience., Competing Interests: Declaration of competing interest MC have received lecture honoraria from Lundbeck, Sandoz, Janssen, Pliva (Teva) and Alkaloid. DC, AK, and LS have no conflicts of interest to declare, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Schizophrenia is a multifactorial neurodevelopmental disorder associated with cognitive dysfunction and changes in primary sensory processing. This article aims to explore the current insights into the relationship between schizophrenia and different visual disturbances., Methods: To provide a literature review of visual impairments in schizophrenia, we performed a PubMed/MEDLINE and Scopus search to identify all articles in English on the topic up to the end of 2018., Results: Multiple retinal functional and structural abnormalities are found in patients with schizophrenia. Wider retinal venules suggest chronically insufficient brain supply of oxygen and this could contribute to the occurrence of psychotic symptoms. Optical coherence tomography studies showed that retinal nerve fiber layer, macular thickness, and macular volume were significantly lowered in the chronic phase of schizophrenia. Results from electroretinogram recordings have demonstrated different declinations such as abnormalities of a - wave activity in the photoreceptors or b - wave activity in the bipolar and Muller cells. Abnormalities in eye movements, such as a notable decrease in saccades and smooth pursuit eye movements, are one of the most reliable and reproducible impairments associated with schizophrenia. Disrupted visual processing of the magnocellular pathway may result in a decrease of contrast sensitivity, sensory processing, orientation discrimination, visual integration, trajectory and spatial localization, backward masking and motion tracking. Visual perceptual abnormalities occur in more than 60% of schizophrenic patients and these are visual hallucinations, perceptual distortion of colors, shapes and light intensity, decrease in contour integration and surround suppression. Other, frequently present eye disorders include impaired visual acuity, strabismus and nystagmus., Conclusion: Visual impairments are one of the most important features of schizophrenia, which could help in defining the disease state and assigning appropriate treatment.

Transmissible hypovirulence associated with Cryphonectria hypovirus 1 (CHV1) has been used for biological control of chestnut blight, devastating disease of chestnut caused by the fungus Cryphonectria parasitica. The main aims of this study were to provide molecular characterization of CHV1 from Croatia and Slovenia and to reveal its genetic variability, phylogeny, and diversification of populations. Fifty-one CHV1 haplotypes were detected among 54 partially sequenced CHV1 isolates, all belonging to Italian subtype (I). Diversity was mainly generated by point mutations while evidence of recombination was not found. The level of conservation over analyzed parts of ORF-A proteins p29 and p40 varied, but functional sites were highly conserved. Phylogenetic analysis revealed close relatedness and intermixing of Croatian and Slovenian CHV1 populations. Our CHV1 isolates were also related to Swiss and Bosnian hypoviruses supporting previously suggested course of CHV1 invasion in Europe. Overall, this study indicates that phylogeny of CHV1 subtype I in Europe is complex and characterized with frequent point mutations resulting in many closely related variants of the virus. Possible association between variations within CHV1 ORF-A and growth of the hypovirulent fungal isolates is tested and presented.

Epigenetic modifications may play an important role in invasion and adaptation of clonal and invasive populations to different environments. The aim of this study was to analyse epigenetic diversity and structure within and among populations of invasive pathogenic fungus Cryphonectria parasitica from south-eastern Europe, where one haplotype S12 dominates. The highest level of epigenetic diversity was found in haplotype S1, followed by S2, while the lowest level of epigenetic diversity was found in haplotype S12. Similar pattern of epigenetic diversity was detected in the control, genetically diverse Croatian population where S1 haplotype dominates. In four south-eastern European populations, the highest level of epigenetic diversity was observed in the Italian population, the oldest population in the studied area, while the lowest diversity was found in most recently established Bulgarian population. This relationship between epigenetic diversity and population age implies the important role of epigenetic modifications on the process of invasion. Our data suggest that epigenetic differences might affect the success of expansion of certain haplotype into new regions. Understanding the role of epigenetic processes in expansion and (pre)adaptation of fungal plant pathogens, besides fundamental knowledge, can contribute to development of strategies for control of fungal spread and pathogenesis., (© 2019 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Using internet search engines (such as Google search) in systematic literature reviews is increasingly becoming a ubiquitous part of search methodology. In order to integrate the vast quantity of available knowledge, literature mostly focuses on systematic reviews, considered to be principal sources of scientific evidence at all practical levels. Any possible individual methodological flaws present in these systematic reviews have the potential to become systemic., Main Text: This particular bias, that could be referred to as (re)search bubble effect, is introduced because of inherent, personalized nature of internet search engines that tailors results according to derived user preferences based on unreproducible criteria. In other words, internet search engines adjust their user's beliefs and attitudes, leading to the creation of a personalized (re)search bubble, including entries that have not been subjected to rigorous peer review process. The internet search engine algorithms are in a state of constant flux, producing differing results at any given moment, even if the query remains identical. There are many more subtle ways of introducing unwanted variations and synonyms of search queries that are used autonomously, detached from user insight and intent. Even the most well-known and respected systematic literature reviews do not seem immune to the negative implications of the search bubble effect, affecting reproducibility., Conclusion: Although immensely useful and justified by the need for encompassing the entirety of knowledge, the practice of including internet search engines in systematic literature reviews is fundamentally irreconcilable with recent emphasis on scientific reproducibility and rigor, having a profound impact on the discussion of the limits of scientific epistemology. Scientific research that is not reproducible, may still be called science, but represents one that should be avoided. Our recommendation is to use internet search engines as an additional literature source, primarily in order to validate initial search strategies centered on bibliographic databases.

Invasive species, especially plant pathogens, have a potential to completely eradicate native plant species and remodel landscapes. Tripartite interactions among sweet chestnut (Castanea sativa), chestnut blight-causing invasive fungus Cryphonectria parasitica, and hyperparasitic virus Cryphonectria hypovirus 1 (CHV1) were studied in two populations. The number of different vegetative compatibility (vc) types of C. parasitica more than doubled over the 10 years, while the hypovirulence incidence dropped in one population and slightly increased in the other one. Over the course of our 3-year monitoring experiment, the prevalence of hypovirulent isolates obtained from monitored cankers increased slowly (i.e., more hypovirulent isolates were being obtained from the same cankers over time). Within studied cankers, considerable changes in vc type and CHV1 presence were observed, indicating a highly dynamic system in which virulent and hypovirulent mycelia, sometimes of discordant vc types, often appeared together. The increase in hypovirulence prevalence did not have any observable curative effect on the cankers and, occasionally, reactivation of healed cankers by new, virulent C. parasitica isolates was observed. Both short- and long-term observations and revalidation of the infected plant populations are necessary to accurately estimate disease progress and formulate an adequate disease management strategy.

Background: Charles Bonnet syndrome (CBS) refers to visual hallucinations that occur in individuals with preserved cognitive functions associated with visual impairment., Methods: This article reviews occurence of visual hallucinations in subjects with CBS by journals published in English in the Pubmed database in the period 1992-2018. Criteria for selection of appropriate papers were sufficient information and perspicuous view on pathogenesis, epidemiology, clinical presentation and treatment possibilities of CBS., Results: Most commonly, visual hallucinations in patients with CBS are complex, repetitive and stereotyped. Such individuals have preserved insight that those percepts are not real, and there is an absence of secondary explanatory delusions and hallucinations within other modalities. Seeing as the aforementioned percepts do not share all the characteristics of hallucinations, it remains unresolved how they should be referred to. Terms as release hallucinations, one that is reflecting its underlying pathogenesis, or confabulatory hallucinatory experiences have been proposed. Moreover, CBS has also been referred to as phantom vision syndrome and may occur in any ophthalmological disease. It is not particularly connected with loss of function along any level of the visual pathway. Although this syndrome is mostly associated with age-related macular degeneration, glaucoma and cataract, it could be related to almost any other ophthalmological conditions. The incidence of CBS alongside with mostly other ocular pathology is rising as population is ageing., Conclusions: Nonetheless, CBS remains commonly underreported, under recognized and/or misrecognized. Albeit the treatment recommendations and guidelines are not yet fully established, it is important to raise awareness of this specific and distinct condition, which inevitably implicates many differential diagnostic deliberations.

Biotic stress caused by virus infections induces epigenetic changes in infected plants and animals, but this is the first report on methylation pattern changes in a fungus after mycovirus infection. As a model pathosystem for mycovirus-host interactions, we used Cryphonectria hypovirus 1 (CHV1) and its host fungus Cryphonectria parasitica, in which deregulation of methylation cycle enzymes upon virus infection was observed previously. Six CHV1 strains of different subtypes were transferred into three different C. parasitica isolates in order to assess the effect of different CHV1 strains and/or subtypes on global cytosine methylation level in infected fungus, using methylation-sensitive amplification polymorphism (MSAP). Infection with CHV1 affected the methylation pattern of the C. parasitica genome; it increased the number and diversity of methylated, hemi-methylated, and total MSAP markers found in infected fungal isolates compared to virus-free controls. The increase in methylation levels correlated well with the CHV1-induced reduction of fungal growth in vitro, indicating that C. parasitica genome methylation upon CHV1 infection, rather than being the defensive mechanism of the fungus, is more likely to be the virulence determinant of the virus. Furthermore, the severity of CHV1 effect on methylation levels of infected C. parasitica isolates depended mostly on individual CHV1 strains and on the combination of host and virus genomes, rather than on the virus subtype. These novel findings broaden our knowledge about CHV1 strains which could potentially be used in human-aided biocontrol of chestnut blight, a disease caused by C. parasitica in chestnut forest ecosystems and orchards.

Understanding virus evolution is a fundamental goal of virology, evolutionary biology, and disease epidemiology. We provide a detailed analysis of evolution and origin of Cryphonectria hypovirus 1 (CHV1) populations in Europe, based on the complete genome sequence of all European subtypes. Phylogenetic analyses divided European strains into two closely related clades. Strains of the subtype I belong to the first, while strains of the subtypes F1, D and E belong to the second clade suggesting that the subtypes F1, D and E are more closely related than previously thought. Strains of the subtype F2 appeared to be recombinant; subtypes F1/D/E contributed a larger fraction of sequence while subtype I contributed a smaller fraction. The p29 was the most variable domain, while the replication-associated large ORF B protein was the most conserved domain within the CHV1. Low sequence similarity, predominant negative selection and frequent recombination characterise the evolution of CHV1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To examine primary care patients' knowledge and attitudes on off-label treatment., Methods: In 47 primary care offices in Osijek-Baranja County, 1300 patients were given questionnaires about their knowledge and attitudes on off-label treatment. Questionnaires were completed voluntarily and anonymously., Results: Majority of patients (96.3%) had no knowledge about off-label treatment, and upon having it explained, 42.3% would not accept such treatment under any circumstances, while 54.5% would never accept such treatment for their children. Patients place more trust in primary care doctors than in hospital doctors; 69.6% of patients strongly believe that primary care doctors would not expose them to off-label treatment while only 41.2% of them think the same in relation to hospital doctors. In case of serious consequences following off-label therapy 49.9% of patients would sue doctors who prescribed it., Conclusion: Patients in primary care possess limited knowledge about off-label treatment. Most patients do not wish to be exposed to such treatment, and are particularly reluctant to have their children exposed to it. In case of serious side effects, half of the patients would sue doctors who had prescribed the off-label therapy.

Cryphonectria parasitica is a phytopathogenic fungus introduced from Eastern Asia to North America and to Europe, where it causes chestnut blight, a devastating disease of chestnut trees. The disease can be biologically controlled utilising the mycovirus Cryphonectria hypovirus 1 (CHV1), which changes the physiology of the host, reducing its virulence towards chestnut. We measured fungal growth in vitro and activities of glutathione S-transferase, catalase and superoxide dismutase, enzymes involved in oxidative stress response, to elucidate the effects of CHV1 infection on the host. Six CHV1 strains of different subtypes and three fungal isolates were used in different combinations to better represent natural conditions, where higher genetic diversity of both fungus and virus is expected. The infection with different CHV1 strains decreased in vitro growth rate of infected fungal isolates and increased activity of their stress enzymes in most of the studied fungus/virus combinations, indicating increased oxidative stress following CHV1 infection. All our field CHV1 strains belong to the Italian subtype, but while strain M56-1 had equal or even stronger effect on its fungal host than prototypic strain EP713 of French subtype F1, strain B11 had no effect. Thus, the severity of the observed effects depended on a particular virus strain, fungal isolate, and the combination of the two, rather than solely on the virus subtype. Since previous research showed discordance between accumulation of mRNA and stress-related proteins in CHV1 infected C. parasitica, our results emphasise the importance of enzymes' activity measurements as an invaluable extension of transcriptomic and proteomic analyses.