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Kresimir Gabric,1,2,* Andrija Matetic,1,* Marino Vilovic,1 Tina Ticinovic Kurir,1 Doris Rusic,3 Tea Galic,4 Ivana Jonjic,2 Josko Bozic1 1Department of Pathophysiology, University of Split School of Medicine, Split, Croatia; 2University Eye Hospital Svjetlost, Zagreb, Croatia; 3Department of Pharmacy, University of Split School of Medicine, Split, Croatia; 4Study of Dental Medicine, University of Split School of Medicine, Split, Croatia *These authors contributed equally to the work Purpose: Our study primarily aimed to investigate health-related quality of life (HRQoL) in type 2 diabetes mellitus (T2DM) patients with different risk for obstructive sleep apnea (OSA).Patients and methods: This cross-sectional, questionnaire-based study included 466 adult patients with T2DM on regular visit to Center for Diabetes of University Hospital of Split from April to September 2017. All subjects underwent detailed anamnestical evaluation and physical examination with anthropometric measurements. Additionally, all subjects completed STOP (Snoring, Tiredness, Observed apnea, and high blood Pressure) questionnaire to assess risk for OSA, Epworth Sleepiness Scale to assess daytime sleepiness, and Medical Outcomes Study Short Form-36 (SF-36) instrument to evaluate HRQoL.Results: Most subjects (N=312, 67.0%) represented high-risk OSA group based on STOP questionnaire (STOP score ≥2). Statistically significantly lower HRQoL scores in all SF-36 dimensions were found in T2DM patients with high risk for OSA compared to low-risk group (P

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.

As accumulated evidence suggests that individuals with post-traumatic stress disorder (PTSD) encounter earlier and more frequent occurrences of cardiovascular diseases, the aim of this study was to ascertain the differences in lifestyle and cardiovascular risk between PTSD and complex PTSD patients. We enrolled 137 male war veterans with PTSD (89 had complex PTSD). The diagnosis was established based on 11th revision of International Classification of Diseases (ICD-11), and cardiovascular risk was estimated by the measurement of advanced glycation end products. Adherence to Mediterranean diet (MD) was lower in the complex PTSD group (2.2% vs. 12.5%, p = 0.015). Accordingly, patients with complex PTSD had lower healthy lifestyle scores in comparison to PTSD counterparts (50.6 ± 9.7 vs. 59.6 ± 10.1, p < 0.001), and a positive association was noted between MD adherence and a healthy lifestyle (r = 0.183, p = 0.022). On the other hand, differences were not noted in terms of physical activity ( p = 0.424), fat % ( p = 0.571) or cardiovascular risk ( p = 0.573). Although complex PTSD patients exhibit worse adherence to MD and lower healthy lifestyle scores, these differences do not seem to impact physical activity, body composition, or estimated cardiovascular risk. More research is needed to clarify if this lack of association accurately reflects the state of the PTSD population or results from insufficient statistical power.

Antimicrobial resistance is recognised as one of the top threats healthcare is bound to face in the future. There have been various attempts to preserve the efficacy of existing antimicrobials, develop new and efficient antimicrobials, manage infections with multi-drug resistant strains, and improve patient outcomes, resulting in a growing mass of routinely available data, including electronic health records and microbiological information that can be employed to develop individualised antimicrobial stewardship. Machine learning methods have been developed to predict antimicrobial resistance from whole-genome sequencing data, forecast medication susceptibility, recognise epidemic patterns for surveillance purposes, or propose new antibacterial treatments and accelerate scientific discovery. Unfortunately, there is an evident gap between the number of machine learning applications in science and the effective implementation of these systems. This narrative review highlights some of the outstanding opportunities that machine learning offers when applied in research related to antimicrobial resistance. In the future, machine learning tools may prove to be superbugs' kryptonite. This review aims to provide an overview of available publications to aid researchers that are looking to expand their work with new approaches and to acquaint them with the current application of machine learning techniques in this field.

Purpose: Primary aim of the study was to investigate the status of different health-related quality of life (HRQoL) domains in postmenopausal women with osteoporosis and osteopenia, and to explore possible associations with bone microarchitecture and nutritional status., Methods: This was a single-center cross-sectional study that included 232 postmenopausal women, from which they were divided into three groups-osteoporosis (OP, N = 63), osteopenia (OPIA, N = 123), and control group (N = 46). Detailed medical history data and anthropometric measurements were taken from all women. Bone structure parameters were taken with DXA device, with additional analysis of bone microarchitecture status with Trabecular Bone Score (TBS). Nutritional status was assessed with Mini Nutritional Assessment (MNA) questionnaire, and HRQoL with Medical Outcomes Study Short Form-36 (SF-36) questionnaire., Results: Nutrition evaluation analysis have shown that patients in OP group had significantly lower values of MNA score compared to the OPIA group and control group (P = 0.005). Furthermore, a significant positive correlation was found between all of the SF-36 domains and MNA scores, while significant positive correlation was found between TBS values and Physical functioning (P < 0.001), Bodily pain (P = 0.027), Social functioning (P = 0.029), and Vitality domains (P = 0.041) in total investigated population. Further analyses were performed only in OP and OPIA groups, and TBS score showed significant positive correlation with Physical functioning (r = 0.248, P < 0.001) and Bodily pain domains as well (r = 0.180, P = 0.014), while MNA score positively correlated with each of the SF-36 domains. Multiple regression models have shown that MNA score retained significant association with each SF-36 domains, and TBS value with Physical functioning (P = 0.003), Social functioning (P = 0.012), and Vitality domains (P = 0.014)., Conclusion: This study highlights the associations that TBS has with some domains of HRQoL in postmenopausal women with osteoporosis and osteopenia. Moreover, nutritional status could play a role in the complex interplay between TBS and HRQoL., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4-55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

Primarily a consequence of sedentary lifestyle, atherosclerosis has already reached pandemic proportions, and with every year the burden of it is only increasing. As low-density lipoprotein cholesterol (LDL-C) represents a crucial factor in atherosclerosis formation and progression, stringent lipid-lowering therapy could conceivably be the key to preventing the unfavorable outcomes that arise as a consequence of atherosclerosis. The use of statins in lipid-lowering is often burdened by adverse events or is insufficient to prevent cardiovascular events as a monotherapy. Therefore, in the present review, the authors aimed to discuss the underlying mechanisms of dyslipidemia and associated atherosclerotic cardiovascular disease (ASCVD) and preclinical and clinical trials of novel therapeutic approaches to its treatment, some of which are still in the early stages of development. Apart from novel therapies, a novel change in perspective is needed. Specifically, the critical objective in the future management of ASCVD is to embrace emerging evidence in the field of atherosclerosis, because clinicians are often burden by common practice and personal experience, both of which have so far been shown to be futile in the setting of atherosclerosis.

While surgical therapy for head and neck cancer (HNC) is showing improvement with the advancement of reconstruction techniques, the focus in these patients should also be shifting to supportive pre and aftercare. Due to the highly sensitive and anatomically complex region, these patients tend to exhibit malnutrition, which has a substantial impact on their recovery and quality of life. The complications and symptoms of both the disease and the therapy usually make these patients unable to orally intake food, hence, a strategy should be prepared for their nutritional management. Even though there are several possible nutritional modalities that can be administrated, these patients commonly have a functional gastrointestinal tract, and enteral nutrition is indicated over the parenteral option. However, after extensive research of the available literature, it seems that there is a limited number of studies that focus on this important issue. Furthermore, there are no recommendations or guidelines regarding the nutritional management of HNC patients, pre- or post-operatively. Henceforth, this narrative review summarizes the nutritional challenges and management modalities in this particular group of patients. Nonetheless, this issue should be addressed in future studies and an algorithm should be established for better nutritional care of these patients.

It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.

Advanced glycation end products (AGEs) represent an endogenously produced or exogenously derived group of compounds derived from nonenzymatic glycation. Recent experimental studies are suggesting that AGEs could play an important role in the skin's quality and its aging process. Hence, the aim of this study was to clinically evaluate the AGEs and skin quality parameters across different age groups in the general population. The study included 237 participants. Melanin, erythema, hydration, friction and transepidermal water loss (TEWL) were evaluated using noninvasive probes, while AGEs were evaluated using a skin autofluorescence reader. There was a significant positive correlation between AGEs and the amount of melanin ( p < 0.001), erythema ( p < 0.001) and TEWL ( p < 0.001), while there was a significant negative correlation between AGEs and hydration ( p < 0.001) and friction ( p < 0.001). After dividing the sample into three groups depending on their age, in all three groups, there was a significant positive correlation between AGEs and the melanin count ( p < 0.001) and TEWL ( p < 0.001), while there was a significant negative correlation between AGEs and skin hydration ( p < 0.001). Multiple linear regression analysis showed that the level of AGEs as a dependent variable retained a significant association with age ( p < 0.001), melanin ( p < 0.001), erythema ( p = 0.005) and TEWL ( p < 0.001) as positive predictors. Moreover, AGEs retained a significant association with skin hydration ( p < 0.001) and friction ( p = 0.017) as negative predictors. These outcomes imply that AGEs could be linked with the complex physiology of the skin and its aging process.

Background: The aim of this study was to explore community pharmacy service users' attitudes and opinions towards vaccination programs in pharmacy conducted by a doctor of medicine or a pharmacist., Methods: The questionnaire used in this study comprised 40 items about demographics, sources of information, attitudes about vaccination, attitudes about vaccination in community pharmacies, and willingness to pay for such a service., Results: A total of 385 people participated in this study. Injection was the preferred route of administration of vaccine for more than half of study participants (50.6%). Univariate analysis showed that those who had a healthcare worker as a family member and those familiar with the HPV vaccine had better attitudes; however, those results were no longer significant after factoring in other variables in multivariate analysis. More than half (59.2%) of the study population would consider vaccination service in community pharmacies only if it were free or covered by the national health insurance., Conclusions: More than half of the participants believed that providing vaccination services in community pharmacies would result in greater vaccination rates for seasonal illnesses. However, around half would prefer that it were conducted exclusively by a physician. Less than 10% of the study participants would pay out of their pocket for such a service.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated beneficial renoprotective effects, which culminated in the recent approval of their use for patients with chronic kidney disease (CKD), following a similar path to one they had already crossed due to their cardioprotective effects, meaning that SGLT2i represent a cornerstone of heart failure therapy. In the present review, we aimed to discuss the pathophysiological mechanisms operating in CKD that are targeted with SGLT2i, either directly or indirectly. Furthermore, we presented clinical evidence of SGLT2i in CKD with respect to the presence of diabetes mellitus. Despite initial safety concerns with regard to euglycemic diabetic ketoacidosis and transient decline in glomerular filtration rate, the accumulating clinical data are reassuring. In summary, although SGLT2i provide clinicians with an exciting new treatment option for patients with CKD, further research is needed to determine which subgroups of patients with CKD will benefit the most, and which the least, from this therapeutical option.

Catestatin is a pleiotropic peptide with a wide range of immunomodulatory effects. Considering that patients with a severe COVID-19 infection have a major immunological dysregulation, the aim of this study was to evaluate catestatin levels in patients with COVID-19 treated in the intensive care unit (ICU) and to compare them between the fatal and non-fatal outcomes. The study included 152 patients with severe COVID-19, out of which 105 had a non-fatal outcome and 47 had a fatal outcome. Serum catestatin levels were estimated by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. The results show that catestatin levels were significantly lower in the fatal group compared to the non-fatal group (16.6 ± 7.8 vs. 23.2 ± 9.2 ng/mL; p < 0.001). Furthermore, there was a significant positive correlation between serum catestatin levels and vitamin D levels (r = 0.338; p < 0.001) while there was also a significant positive correlation between serum catestatin levels and growth differentiation factor-15 (GDF-15) levels (r = −0.345; p < 0.001). Furthermore, multivariate logistic regression showed that catestatin, GDF-15 and leukocyte count were significant predictors for COVID-19 survival. These findings imply that catestatin could be playing a major immunomodulatory role in the complex pathophysiology of the COVID-19 infection and that serum catestatin could also be a predictor of a poor COVID-19 outcome.

Purpose: Orthorexia nervosa (ON) is an eating behavior where patients obsessively try to reach health through "purity" of food. Narcissism is a personality trait characterized with the self-belief of grandiosity, importance and need of appreciation. Both of these conditions are connected through self-image in way of reaching perfection through health and body image, whereas one of the ways for reaching it is exercising. This cross-sectional study aimed to investigate ON and its possible association with narcissism in fitness center users., Methods: The study included 1017 fitness center users and three questionnaires were used for the assessment: general information, ORTO-R and Narcissistic personality inventory-13 (NPI-13)., Results: There was a significant negative correlation (r = - 0.467, p < 0.001) between the ORTO-R score and the NPI-13 score. Comparison of the ORTO-R score between different durations of using a fitness center showed statistically significant differences (H = 134.72, p < 0.001). The subjects who are using the fitness center for less than 1 year have the highest ORTO-R score, while those who are using it 1-3 years have the lowest ORTO-R score. Moreover, multiple linear regression showed that ORTO-R score retained significant association with NPI-13 (β ± SE, - 0.416 ± 0.026, p < 0.001) and the duration of using a fitness center (0.576 ± 0.068, p < 0.001) after model adjustment for age and BMI., Conclusion: These results are implying that fitness center users could possibly be vulnerable of developing ON and that there is a strong association between ON and narcissism in this population. However, future larger-scale longitudinal studies are needed to address these findings., Level of Evidence: Level V, cross-sectional survey-based study., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Local random skin flaps and skin grafts are everyday surgical techniques used to reconstruct skin defects. Although their clinical advantages and disadvantages are well known, there are still uncertainties with respect to their long-term results. Hence, the aim of this study was to evaluate outcomes more than one-year post operatively using objective measurement devices. The study included 31 facial defects reconstructed with local random flap, 30 facial defects reconstructed with split-thickness skin grafts (STSGs) and 30 facial defects reconstructed with full-thickness skin grafts (FTSGs). Skin quality was objectively evaluated using MP6 noninvasive probes (Courage + Khazaka GmbH, Cologne, Germany), which measure melanin count, erythema, hydration, sebum, friction and transepidermal water loss. The results showed that there were no significant differences in melanin count, erythema, hydration, sebum level, friction value and transepidermal water loss (TEWL) between the site reconstructed with random local flaps and the same site on the healthy contralateral side of the face. However, both FTSGs and STSGs showed significantly higher levels in terms of TEWL and erythema, whereas the levels of hydration, sebum and friction were significantly lower compared to the healthy contralateral side. Moreover, STSGs resulted in a significant difference in melanin count. These findings imply that the complex pathophysiology of the wound-healing process possibly results in better skin-quality outcomes for random local flaps than skin autografts. Consequently, this suggests that random local flaps should be implemented whenever possible for the reconstruction of facial region defects.

With the rising global burden of inflammatory bowel disease (IBD) and the rising costs of novel biological drugs, there is an increasing need for dietary approaches and functional foods that could modulate the course of IBD. The Mediterranean diet has proven to be efficacious in managing chronic inflammatory diseases, and recent studies have also shown its benefits in the setting of IBD. Since olive oil and its compounds have been shown to provide a considerable anti-inflammatory effect, in this review, we aim to discuss the latest evidence concerning the impact of olive oil and its bioactive compounds on IBD. Numerous preclinical studies have exhibited solid evidence on the mechanisms by which polyphenol-rich extra-virgin olive oil (EVOO) or specific polyphenols like hydroxytyrosol (HT) provide their anti-inflammatory, antioxidative, antitumour, and microbiota-modulation effects. Accordingly, several human studies that explored the effects of olive oil on patients with IBD further confirmed the evidence brought forward by preclinical studies. Nevertheless, there is a need for larger-scale, multicentric, randomized control trials that would finally elucidate olive oil's level of efficacy in modulating the course of IBD.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia. Due to the high prevalence (around 1/3 of the world population) economic burden of MetS, there is a need for new dietary, lifestyle, and therapeutic options. Recently, fasting emerged as a dietary method proposed for controlling metabolic risk factors. Intermittent fasting (IF), or time-restricted feeding (TRF), describes an array of feeding patterns in which calorie intake is restricted to a specific time period. Hence, this review aimed to elucidate the latest data on MetS and explore the viability of simple management options, such as IF and TRF. Preclinical studies have shown how IF/TRF exerts beneficial effects on the gut microbiota, glucose and insulin metabolism, weight and visceral fat, and lipid metabolism. However, the results obtained from human studies are somewhat conflicting, as weight loss was achieved in all studies, whereas in some studies, there was no significant effect on insulin resistance, cholesterol/lipid metabolism, or blood pressure. Nevertheless, as only very few human studies were performed, there is a need for more randomized control trials on larger cohorts of patients with MetS to gather higher-yield evidence to clarify whether IF/TRF are suitable dietary patterns for this population.

Family physicians (FPs) are exposed to high amounts of stress, and could be susceptible to the development of mental health disorders (MHD), especially after the emergence of the COVID-19 pandemic. The aim of the current study was to assess MHD history, attitudes toward MHDs and stress-coping strategies in FPs. An additional goal was to estimate their comprehensive well-being and investigate connections with resilience and a healthy lifestyle. A total of 483 FPs submitted their responses via online survey. MHD attitudes were assessed with the according questionnaires, while burnout levels, healthy lifestyle, resilience, job and life satisfaction were estimated with validated scales. Results have shown that 32.5% of FPs disclosed positive MHD history, while 68.7% used professional help. Resilience and healthy lifestyle levels were significantly higher in MHD negative FPs ( p < 0.001), while burnout levels were lower ( p < 0.001). Moreover, healthy lifestyle (β = 0.03, p < 0.001) was an independent correlate of resilience, while healthy lifestyle (β = -0.35, p < 0.001, and resilience (β = -1.82, p < 0.001) were of burnout levels. Finally, resilience (OR = 0.387, p < 0.001) and healthy lifestyle (OR = 0.970, p = 0.021) were shown as independent predictors of positive MHD history status. Strong promotion and education of FP population regarding resilience and healthy lifestyle should be utilized in practice in order to alleviate the possibility of mental health disturbances and the according consequences.

Among many lifestyle components that professional athletes have to follow, nutrition is gradually growing to be one of the key factors for achieving and maintaining optimal sport performance. The Mediterranean diet (MD) is recognized as one of the healthiest dietary patterns worldwide; however, data regarding adherence to the MD among professional athletes are still scarce. Moreover, with the imposed need for a healthy diet among professional athletes, orthorexia nervosa (ON) could become a rising issue. This cross-sectional study included 150 professional athletes and 150 matched recreational athletes from Croatia. Four questionnaires were used for the assessment: general information, a test for the diagnosis of ON (ORTO-15), the International Physical Activity Questionnaire (IPAQ) and the Mediterranean Diet Serving Score (MDSS). Significantly more professional athletes were adherent to the MD ( p < 0.001) and had a tendency to ON ( p < 0.001). Moreover, there was a significant negative correlation between the ORTO-15 score and the total MET min/week score (r = -0.524, p < 0.001) and a significant positive correlation between the MDSS score and the total MET min/week score in the professional athlete group (r = 0.478, p < 0.001). All of these results imply that professional athletes are more concentrated on their dietary patterns than recreational athletes, and that due to this dedication, they possibly have a higher adherence to the MD but also possibly a higher risk for developing ON. However, the association between ON and the MD should be further addressed in the future.

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

The prevalence and incidence of gout doubled from 1990 to 2017. Therefore, we can expect that a number of doctors have come across a patient with gout in their daily practice. Hence, we wanted to investigate how familiar our medical students, as future medical professionals, are with gout. This cross-sectional survey included Medical Studies students from the two largest universities in Croatia: the University of Split School of Medicine, and the University of Zagreb School of Medicine, and included a total of 221 fifth or sixth year medical students. Most students gave correct answers to questions about treatment approach and non-pharmacological interventions in asymptomatic hyperuricemia (>80%). Less than 3% of all students agreed they knew enough about care for patients with asymptomatic hyperuricemia, whereas almost 15% thought they were well familiar with care for gout patients. Less than 8% of students considered their school education adequate on both topics, and less than 2% were aware of the existence of EULAR guidelines. Physicians lacking in the latest knowledge on the pathophysiology of gout, the influence of lifestyle, and genetic factors limits their ability to properly manage gout. With increasing prevalence, gout should be more represented in medical students' education.

Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future.

Background: In recent years, American Diabetes Association started to strongly advocate the Mediterranean diet (MD) over other diets in patients with diabetes mellitus (DM) because of its beneficial effects on glycemic control and cardiovascular (CV) risk factors. Tissue levels of advanced glycation endproducts (AGEs) emerged as an indicator of CV risk in DM. Skin biopsy being invasive, the use of AGE Reader has been shown to reflect tissue AGEs reliably., Aim: To examine the association between adherence to MD and AGEs in patients with DM type II., Methods: This cross-sectional study was conducted on 273 patients with DM type II. A survey questionnaire was composed of 3 separate sections. The first part of the questionnaire included general data and the habits of the participants. The second part aimed to assess the basic parameters of participants' diseases and associated conditions. The third part of the questionnaire was the Croatian version of the 14-item MD service score (MDSS). AGEs levels and associated CV risk were measured using AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands)., Results: A total of 27 (9.9%) patients fulfilled criteria for adherence to MD, with a median score of 8.0 (6.0-10.0). Patients with none/limited CV risk had significantly higher percentage of MD adherence in comparison to patients with increased/definite CV risk (15.2% vs 6.9%, P = 0.028), as well as better adherence to guidelines for nuts (23.2% vs 12.6%, P = 0.023) and legumes (40.4% vs 25.9%, P = 0.013) consumption. Higher number of patients with glycated hemoglobin (HbA1c) < 7% adhered to MD when compared to patients with HbA1c > 7% (14.9% vs 7.3%, P = 0.045). Moreover, those patients followed the MDSS guidelines for eggs (33.0% vs 46.8%, P = 0.025) and wine (15.6% vs 29.8%, P = 0.006) consumption more frequently. MDSS score had significant positive correlation with disease duration ( r = 0.179, P = 0.003) and negative correlation with body mass index (BMI) values ( r = -0.159, P = 0.008). In the multiple linear regression model, BMI (β ± SE, -0.09 ± 0.04, P = 0.037) and disease duration (β ± SE, 0.07 ± 0.02, P < 0.001) remained significant independent correlates of the MDSS score. Patients with HbA1c > 7% think that educational programs on nutrition would be useful for patients in significantly more cases than patients with HbA1c < 7% (98.9% vs 92.6%, P = 0.009)., Conclusion: Although adherence to MD was very low among people with diabetes, we demonstrated that adherence to MD is greater in patients with lower CV risk, longer disease duration, and well-controlled glycaemia., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Mediterranean diet (MD) is based on the traditional cuisine of south European countries, and it is considered one of the healthiest dietary patterns worldwide. The promotion of combined MD and physical activity has shown major benefits. However, the association between physical activity and the MD in regular fitness center users is still insufficiently investigated. This cross-sectional survey-based study was conducted on 1220 fitness center users in Croatia. The survey consisted of three parts: general information, the Mediterranean Diet Serving Score (MDSS) and the International Physical Activity Questionnaire Short Form (IPAQ-SF). The results showed that 18.6% of fitness center users were adherent to the MD, and there was a significant positive correlation between the level of physical activity and the MDSS score (r = 0.302, p < 0.001). Moreover, after dividing the sample into tertiles based on the IPAQ-SF score, the third tertile (MET > 3150 min/wk) had the most fitness center users (34.4%) adherent to the MD, while the first tertile (MET < 1750 min/wk) had the least (6.1%). These outcomes emphasize the importance of physical activity as they imply that, with higher levels of physical activity, people are also possibly more aware of the importance that a healthy and balanced diet has on their well-being.

Although a large amount of data supports the crucial role of endothelial dysfunction (ED) in cardiovascular diseases (CVDs), there is a large bench-to-bedside chasm between basic and clinical research of ED, limiting the implementation of these findings in everyday clinical settings. Hence, it is important to further investigate the pathophysiological mechanisms underlying ED and find modalities that will alleviate its clinical implementation. Adropin, a highly conserved peptide hormone secreted primarily by the liver, recently emerged as an important regulatory component of the vascular endothelium. Specifically, the vasoprotective role of adropin is achieved mainly by affecting endothelial NO synthesis. Thus, in this review, we aimed to summarize the current knowledge regarding the role of adropin in physiological processes and address the protective role of adropin in endothelium with consequent implications to CV pathologies. We focused on data regarding the role of adropin in the clinical setting, with concurrent implications to future clinical use of adropin. Studies suggest that plasma levels of adropin correlate with indices of ED in various pathologies and enhanced disease progression, implying that adropin may serve as a useful biomarker of ED in the upcoming future. On the other hand, despite notable results with respect to therapeutic potential of adropin in preliminary experiments, further well-designed studies are warranted in order to establish if adropin might be beneficial in this setting.

Background: Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII., Aim: To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters., Methods: This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn's disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn's Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer's instructions., Results: IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn's disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels ( r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins ( r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic ( r = 0.387, P = 0.005) and diastolic ( r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity ( r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn's Disease ( r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030)., Conclusion: It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies., Competing Interests: Conflict-of-interest statement: There are no conflict of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1-2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.

The literature indicates that the limited pharmacovigilance knowledge demonstrated by healthcare professionals is the main reason for the underreporting of adverse drug reactions. Therefore, the main objective of this study was to investigate pharmacy, dental and medical students' knowledge and attitudes to pharmacovigilance and pharmacovigilance education. The cross-sectional questionnaire study was conducted at the University of Split School of Medicine in November 2020. In total, 350 students participated in the study. The results have shown that pharmacy students showed a significantly higher knowledge score compared to dental and medical students ( P < 0.001). In total 92.2% of pharmacy, 21.8% of dental and 70.8% of medical students had knowledge of patients' involvement in adverse drug reactions, reporting ( P < 0.001). Interestingly, only 44.3% of all students knew that adverse drug reactions could be reported using a mobile application. Moreover, significantly more pharmacy students (74.4%) were aware of the adverse drug reactions monitoring center in Croatia, with 47.5% of dental and 39.2% of medical students correctly identifying it ( P < 0.001). The results showed that most students felt that pharmacovigilance was not adequately covered in curricula; therefore, there is a great need to increase the knowledge and awareness of pharmacovigilance among students aspiring to become future healthcare professionals, and improve their reporting practice in clinical future.

The "Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines" (CRUSADE) score emerged as a predictor of major bleeding in patients presenting with the acute coronary syndrome. On the other hand, previous studies established the association of dephosphorylated-uncarboxylated Matrix Gla protein (dp-ucMGP) and vitamin K, as well as their subsequent impact on coagulation cascade and bleeding tendency. Therefore, in the present study, we explored if dp-ucMGP plasma levels were associated with CRUSADE bleeding score. In this cross-sectional study, physical examination and clinical data, including plasma dp-ucMGP levels, were obtained from 80 consecutive patients with acute myocardial infarction (AMI). A significant positive correlation was found between CRUSADE bleeding score and both dp-ucMGP plasma levels (r = 0.442, p < 0.001) and risk score of in-hospital mortality (r = 0.520, p < 0.001), respectively. In comparing the three risk groups of risk for in-hospital bleeding, the high/very high-risk group had significantly higher dp-ucMGP levels from both very low/low group (1277 vs. 794 pmol/L, p < 0.001) and the moderate group (1277 vs. 941 pmol/L, p = 0.047). Overall, since higher dp-ucMGP levels were associated with elevated CRUSADE score and prolonged hemostasis parameters, this may suggest that there is a biological link between dp-ucMGP plasma levels and the risk of bleeding in patients who present with AMI.

Aims: The aim of this study was to evaluate pharmacists' and physicians' attitudes and knowledge about antimicrobial treatment and resistance and based on the results to identify possible gaps and suggest opportunities for collaboration between the two professions. Methods: The physician's questionnaire consisted of 47 items and the pharmacists' questionnaire consisted of 50 items. Participants were asked to identify situations in which they were more likely to prescribe/dispense an antimicrobial without a firm indication, to identify the greatest contributors to antimicrobial resistance (AMR) among health care workers, to rate statements related to AMR, how frequently they used different sources of information and to rate the possible causes of AMR. Furthermore, preparedness for specific actions in practice was self-rated and knowledge was evaluated. The questionnaires were anonymous and participation in the study was voluntary. Results: This research included 180 community pharmacists and 181 physicians. As many as 76 (42.0%) physicians stated they would prescribe an antimicrobial when unsure whether the infection was of viral or bacterial etiology. More than half of the participants considered family medicine doctors the greatest contributors to AMR ( N  = 216, 59.8%), followed by patients ( N  = 175, 48.5%). In questions focusing on knowledge, physicians scored significantly higher compared with pharmacists (4.06 ± 1.01 vs. 3.71 ± 1.08, p  = 0.001). Conclusion: This research revealed practices among pharmacists and physicians that should be improved and it highlighted gaps in knowledge by both professions. More attention should be given to patient consultation when dispensing and prescribing an antimicrobial as this may reduce their contribution to AMR.

Adropin is a novel pleotropic peptide involved in energy homeostasis, with possible contribution to cardiovascular protection through production of nitric oxide and subsequent blood pressure regulation. Given that patients undergoing hemodialysis (HD) are related with high cardiovascular risk, hyperlipidemia, chronic low-grade inflammation, and malnutrition the aim of our study was to investigate serum adropin levels in HD patients to evaluate possible associations with nutritional status and other relevant clinical and laboratory parameters. The study included 70 patients on HD and 60 healthy controls. Serum adropin levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. Serum adropin levels were significantly lower in the HD group compared to the control group (2.20 ± 0.72 vs. 4.05 ± 0.93 ng/mL, p < 0.001). Moreover, there was a significant negative correlation with malnutrition-inflammation score (r = -0.476, p < 0.001), dialysis malnutrition score (r = -0.350, p = 0.003), HD duration (r = -0.305, p = 0.010), and high sensitivity C-reactive protein (hsCRP) (r = -0.646, p < 0.001). Additionally, there was a significant negative correlation between adropin levels and pre-dialysis systolic (r = -0.301, p = 0.011) and diastolic blood pressure (r = -0.299, p = 0.011). These results are implying that adropin is potentially involved in the pathophysiological mechanisms of chronic kidney disease (CKD)/HD and its complications. However, future larger scale longitudinal studies need to further address it.

Catestatin (CST) is a pleiotropic peptide involved in cardiovascular protection with its antihypertensive and angiogenic effects. Considering that patients with end-stage renal disease (ESRD) who are undergoing hemodialysis (HD) are associated with higher cardiovascular risk, the aim of this study was to investigate plasma CST levels in HD patients, compare them to healthy controls and evaluate possible CST associations with advanced glycation end products (AGEs) and laboratory, anthropometric and clinical parameters. The study included 91 patients on HD and 70 healthy controls. Plasma CST levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit, while AGEs were determined using skin autofluorescence. Plasma CST levels were significantly higher in the HD group compared to the controls (32.85 ± 20.18 vs. 5.39 ± 1.24 ng/mL, p < 0.001) and there was a significant positive correlation between CST and AGEs (r = 0.492, p < 0.001). Furthermore, there was a significant positive correlation between plasma CST levels with both the Dialysis Malnutrition Score (r = 0.295, p = 0.004) and Malnutrition-Inflammation Score (r = 0.290, p = 0.005). These results suggest that CST could be playing a role in the complex pathophysiology of ESRD/HD and that it could affect the higher cardiovascular risk of patients on HD.

The net effect of the coronavirus disease 2019 (COVID-19) pandemic and the response to it on the emergence of antimicrobial resistance is yet unknown. Positive impacts on the spread of multiresistant pathogens and infections in general may be observed with the implementation of general preventative measures for the spread of infectious disease such as social distancing, reduced travel and increased personal hygiene. This pandemic has accelerated the development of novel technologies, such as mRNA vaccines, that may be used to fight other diseases. These should be capitalized upon to manage the ongoing antimicrobial resistance pandemic in the background. However, it is likely that the COVID-19 pandemic is fueling the emergence of antimicrobial resistance due to high rates of inappropriate antimicrobial prescribing, the high use of biocides and the interruption of treatment for other conditions. Clinical uncertainty driven by the lack of effective diagnostics and practice of telemedicine may have driven the inappropriate use of antimicrobials. As pathogens know no borders, increased focus is needed for infectious diseases still threatening low- and middle-income countries such as tuberculosis. Stewardship measures for future outbreaks should stress the importance of social distancing and hand washing but discourage the overuse of disinfectants and antimicrobials that are not proven effective.

During the coronavirus disease 2019 (COVID-19) outbreak, family physicians (FPs) are the backbone of the healthcare system with considerable impact on the general population, and their well-being is of great importance. The aim of this investigation was to assess FPs mental health, as well as knowledge, attitudes and practices (KAPs) regarding the pandemic, and opinions on non-communicable disease (NCD) health care provided to patients. A cross-sectional study was carried out with a sample of 613 FPs. Anxiety and depression levels were estimated with the Hospital Anxiety and Depression Scale, subjective perceived stress with the Perceived Stress Scale, while trauma-related symptoms were assessed using the Impact on Event Scale-COVID19. KAPs toward the pandemic and opinions regarding NCD patients were evaluated with questionnaires accordingly. Results have shown that age (β = -0.02, p = 0.013) and personal risk of COVID‑19 (β = 1.05, p < 0.001) were significant independent correlates of the knowledge score. A total of 87.7% FPs expressed moderate/high perceived stress, 45.2% moderate/severe trauma-related symptoms, 60.4% borderline/abnormal anxiety levels, and 52.4% borderline/abnormal depression levels. Knowledge score was an independent predictor of perceived stress (β = -0.33, p = 0.023) and anxiety (β = -0.31, p = 0.006) levels. Limited accessibility to healthcare services and decreased number of newly-diagnosed NCD cases were mostly agreed on. The pandemic puts a considerable strain on FPs mental health, as well as on public health measures, due to the decreased overall quality of NCD patient health care. Educational programs may bridge the gaps between FPs' knowledge. Thus lowering anxiety and improving patient care.

Biomedical students should have suitable knowledge about sport dietary supplements (SDS) usage as they are future medical professionals who will have SDS users in their care. The aim of this study was to assess the habits, opinions, and knowledge about SDS usage, along with the level of physical activity, in 386 biomedical students at the University of Split School of Medicine. A specialized questionnaire was developed by a group of experts for the assessment of habits, opinions, and knowledge about SDS and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) was used to evaluate the level of physical activity. The results showed that 49.2% of students used SDS and there was a significant positive correlation between the knowledge questionnaire score and the level of physical activity (r = 0.744, p < 0.001). Moreover, SDS users had a higher knowledge questionnaire score ( p < 0.001) and a higher level of physical activity ( p < 0.001) compared to non-users. These results suggest that more physically active students are better informed about SDS, but these results also imply that SDS should be implemented in the study program of future medical professionals to ensure that they are informed for their own personal consumption and will be confident in giving advice about SDS usage to their future patients.

Community pharmacists recognize the need to implement antimicrobial stewardship activities in community pharmacies. They are in a unique position to provide triage for common primary care indications and to lower the burden of patients at general practitioners' offices. However, research shows that, in some areas, dispensing of antimicrobials without valid prescription is still highly prevalent. Regardless of training, every community pharmacist can give his contribution to antimicrobial stewardship. One of the basic elements should be antimicrobial dispensing according to regulations, either prescription only, or according to guidelines where pharmacists have prescribing authority. Patient consultation supported with educational materials, such as leaflets, may reduce patients' expectations to receive antibiotics for self-limiting infections and reduce pressure on general practitioners to prescribe antibiotics on patients' demand. Treatment optimization may be achieved in collaboration with the prescribing general practitioners or by providing feedback. At last, pharmacists provided with additional training may be encouraged to provide consultation services to long-term care facilities, to introduce point-of-care testing for infectious diseases in their pharmacies or prescribe antimicrobials for uncomplicated infections. These services are welcomed by patients and communities. Expanding pharmacy services and pharmacists' prescribing autonomy have shown a positive impact by reducing antibiotics consumption, thus ensuring better compliance with treatment guidelines.

Background: Matrix Gla protein (MGP) is a vitamin K dependent peptide which has an established role in suppression of vascular calcification. Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease (IBD)., Aim: To compare plasma levels of dephosphorylated and uncarboxylated MGP (dp-ucMGP) between IBD patients and controls., Methods: This cross-sectional study was conducted on 70 patients with IBD (30 patients with ulcerative colitis and 40 patients with Crohn's disease) and 60 age and gender matching healthy controls. Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP (Immunodiagnostic Systems, Frankfurt, Germany) according to the manufacturer's instructions. fecal calprotectin (FC) levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay (Bühlmann Laboratories Aktiengesellschaft, Schonenbuch, Switzerland). Other parameters were analyzed according to the standard laboratory procedures., Results: Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group (629.83 ± 124.20 pmol/mL vs 546.7 ± 122.09 pmol/mL, P < 0.001), and there was no significant difference between patients with Crohn's disease and patients with ulcerative colitis (640.02 ± 131.88 pmol/mL vs 616.23 ± 113.92 pmol/mL, P = 0.432). Furthermore, a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels ( r = 0.396, P < 0.001) and high sensitivity C-reactive protein (hsCRP) levels ( r = 0.477, P < 0.001). Moreover, in the total study population a significant positive correlation was found between dp-ucMGP with age ( r = 0.210, P = 0.016) and waist circumference (r = 0.264, P = 0.002). Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC (β ± SE, 0.06 ± 0.02, P = 0.003)., Conclusion: Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease, and possibly extraintestinal manifestations., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: First choice of therapy for severe hypoglycemia outside hospital environment is glucagon injection, an undertaught and underused remedy. Aim of this study was to investigate knowledge about glucagon therapy, possession rate and usage rate in insulin-treated diabetic patients, with special emphasis on history of hypoglycemia and severe hypoglycemia episodes., Methods: In this cross-sectional study, 300 insulin-treated diabetic patients (146 males and 154 females, mean age 61.1±16.4 years) were recruited from comprehensive Diabetes Center in Croatia. Specialized self-administered, 13-item questionnaire regarding glucagon therapy and history of hypoglycemia was obtained from each patient, as well as data collected from medical history documentation., Results: Experience of hypoglycemic episode was reported by 233 (77.7%), and severe hypoglycemia by 73 (24.3%) patients. Participants with experience of hypoglycemia have significantly longer diabetes duration (17.2±11.2 vs. 11.9±8.5 years, P<0.001) and lower BMI values (26.38±3.97 vs. 31.11±7.17 kg/m 2 , P<0.001). Knowledge about glucagon therapy had 55.3% patients, 44.7% obtained it from the pharmacy, while glucagon was used in 35.6% cases of severe hypoglycemia. Glucagon knowledge was better in patients that attended at least one diabetes lecture (P=0.038), while educational level showed no statistical significance (P=0.286). Main significant positive predictor of glucagon knowledge was history of severe hypoglycemia (OR 4.71, 95% CI 1.38 - 16.02, P=0.013)., Conclusions: Glucagon therapy was underused in treating severe hypoglycemia. It is highly important to emphasize value of quality education as one of the fundamentals of good diabetes management., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn's disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = -0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = -0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251-0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.

Study Objectives: The aim of this study was to investigate differences in dual-energy X-ray absorptiometry (DXA) parameters, trabecular bone score (TBS), bone turnover markers and inactive matrix Gla protein (dp-ucMGP) between patients with obstructive sleep apnea (OSA) and healthy controls., Methods: This study enrolled 53 male patients diagnosed with OSA, and 50 age- and body mass index (BMI)-matched control subjects. All participants underwent DXA imaging, TBS assessment and blood sampling for biochemical analysis of bone metabolism markers., Results: Mean apnea-hypopnea index (AHI) score of OSA patients was 43.8 ± 18.8 events/h. OSA patients had significantly higher plasma dp-ucMGP levels in comparison to controls (512.7 ± 71.9 vs. 465.8 ± 50.9 pmol/L, p < 0.001). OSA and control group did not significantly differ regarding standard DXA results, while TBS values were significantly lower in the OSA group (1.24 ± 0.17 vs. 1.36 ± 0.15, p < 0.001). AHI score was a significant independent correlate of plasma dp-ucMGP levels (β ± SE, 1.461 ± 0.45, p = 0.002). In addition, TBS retained a significant relationship with dp-ucMGP values (β ± SE, -93.77 ± 38.1, p = 0.001)., Conclusions: dp-ucMGP levels are significantly higher in patients with OSA and correlate with disease severity. In addition, TBS values in OSA patients are lower in comparison with the control group and decrease with disease severity., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Catestatin (CST) is an important peptide in the pathophysiology of chronic inflammatory disorders. However, clinical studies on inflammatory bowel disease (IBD) patients are lacking. Our goal was to investigate CST concentrations in IBD patients compared to healthy subjects. Additionally, we aimed to determine arterial stiffness parameters in relation to CST. This cross-sectional study compared 80 IBD patients (45 Crohn's disease (CD) and 35 ulcerative colitis (UC) patients) with 75 control subjects. Serum CST levels were significantly higher in the IBD group compared to control subjects (11.29 ± 9.14 vs. 7.13 ± 6.08 ng/mL, p = 0.001) and in the UC group compared to CD patients (13.50 ± 9.58 vs. 9.03 ± 6.92 ng/mL, p = 0.021), irrespective of age and BMI. IBD patients exhibited significantly higher values of heart rate adjusted central augmentation index (cAIx-75) (14.88 ± 10.59 vs. 6.87 ± 9.50 %, p < 0.001) and pulse wave velocity (PWV) (8.06 ± 3.23 vs. 6.42 ± 1.47 m/s, p < 0.001) compared to control group. Furthermore, PWV was the only significant independent correlate of CST ( B = 1.20, t = 4.15, p < 0.001), while CST, PWV, cAIx-75, high-sensitivity C-reactive protein and BMI were significant predictors of positive IBD status (1.089 (1.022-1.161), 1.515 (1.166-1.968), 1.060 (1.024-1.097), 1.458 (1.116-1.906), 0.793 (0.683-0.920), respectively). Serum CST levels were significantly higher in IBD patients compared to controls and an independent positive correlation of CST with PWV existed. Therefore, it is possible that CST could have a role in the complex pathophysiology of IBD and its cardiovascular complications., Competing Interests: The authors declare no conflict of interest.

Limited evidence exists regarding cognitive and psychomotor function in patients with inflammatory bowel disease (IBD). Therefore, we aimed to compare the neurocognitive and psychomotor function of 60 IBD patients with 60 age/sex-matched controls. Computer-based instrument Complex Reactinometer Drenovac (CRD) was used for assessment of cognitive domains: convergent thinking (simple mathematical tasks; CRD-11), perceptive abilities (light signal position discrimination; CRD-311) and sophisticated operative thinking (complex psychomotor coordination; CRD-411). The most important analyzed parameters were total test solving time (T TTS ); minimal time of particular test solving (T MIN ) and total number of wrong reactions (N ER ). Performance in all three cognitive tests showed statistically significantly longer T TTS and T MIN in IBD patients (P < 0.05), while there was no significant difference in N ER . Aforementioned findings were adjusted for BMI, age and duration of education. Our study has shown impaired neurocognitive and psychomotor function in IBD patients compared to controls, especially in mental processing speed and mental endurance of perceptive abilities, convergent thinking and complex operative thinking.

Purpose: Future physicians and pharmacists have to be educated and prepared to rationally manage the use of antimicrobials. The aim of this study was to evaluate attitudes and knowledge regarding the use of antimicrobials and antimicrobial resistance of medical and pharmacy students. Methods: We conducted a survey-based cross-sectional study at the University of Split School of Medicine (USSM). The survey consisted of 50 items. A total of 161 students participated in the study across 3 study programs as follows: Medicine ( N  = 78), Medical Studies in English (MSE; N  = 37), and Pharmacy ( N  = 46). Results: Majority of students believe that antimicrobials are overused (90.7%). Keeping a stock of antibiotics at home is a practice more commonly seen among students who have a family member working in a health related field (58.5% vs. 25.0%, p  < 0.001). There was no difference in average knowledge score among medical, MSE, or pharmacy students ( p  = 0.416). Students who achieved higher knowledge score were more likely to rate their education about antimicrobial use and resistance as very useful ( p  < 0.001). Conclusion: This study reveals that medical and pharmacy students at the USSM have a relatively good understanding of antibiotic resistance. However, more education on the appropriate use of antimicrobials is needed.