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In the myocardium of control subjects and patients undergoing heart transplantation or left ventricular assist device implantation (LVAD), we analyzed concentrations of Al, As, Cd, Pb, and Ni using inductively coupled plasma mass spectrometry. Myocardial generation of oxidative-stress-induced lipid peroxidation was analyzed by quantifying concentration of 4-Hydroxynonenal (4-HNE) with ELISA and pro-apoptotic DAPK2 gene expression was determined with quantitative RT-PCR. Compared to six control hearts, myocardial samples of 128 individuals undergoing heart transplantation or LVAD implantation exhibited a moderate increase in deposition of five tested non-essential elements, which was significantly increased only for Cd and cumulative deposition of Al, As, Cd, and Pb. Patients with higher cumulative deposition of Al, As, Cd, and Pb, underwent heart transplantation or LVAD implantation at a younger age than those with lower cumulative deposition, which was not observed in individual elements. Also, Al, As, and Ni exhibited a positive correlation with DAPK2 expression. Moreover, Al, As, Cd, and Ni showed positive correlations and Pb negative correlations with several mitochondrial quality control (MQC) genes. None of the elements showed correlation with 4-HNE generation in the myocardium. There was no difference in tested non-essential element deposition between dilated and ischemic cardiomyopathy. In conclusion, patients with higher cumulative deposition of Al, As, Cd, and Pb in the myocardium underwent heart transplantation or LVAD implantation at a younger age, indicating that they may accelerate heart failure, which is associated with induction of DAPK2 expression. Deposition of Al, As, Cd, Ni, and Pb also altered the expression of several MQC genes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Healthcare professionals (HCPs), including doctors of dental medicine (DMDs) and doctors of medicine (MDs), use social networking sites (SNSs) for personal and professional purposes. This study aims to: (i) explore DMDs and MDs awareness of their online presence, (ii) examine how frequently and for what reasons DMDs and MDs monitor their online images, (iii) determine the prevalence of finding inaccurate, incomplete, or unprofessional information about themselves, examine that experience, and investigate actions performed regarding unprofessional or embarrassing posted material, (iv) assess concerns about their own SNSs usage and the content they post., Methods: A cross-sectional study was conducted among DMDs and MDs in Croatia using a questionnaire., Results: Out of 1,013 participants, 753 were active SNS users. Facebook (91.6%) and Instagram (63.1%) were the predominant SNSs used. DMDs exhibited a significantly higher inclination to utilize SNSs for professional purposes than MDs. Both groups reported a high level of proficiency in using Facebook (M=3.2, SD=0.827) and Instagram (M=2.44, SD=1.162). Approximately 55.4% of the participants repored monitoring their online presence, typically once a year or less frequently. DMDs emphasized the completeness of posted information more than MDs (U=25,623.0, p=0.001). Their highest level of concern pertained to confidentiality breaches and inaccurate medical and dental information. There are similar results for MDs and DMDs for finding erroneous information posted on SNSs., Conclusions: This study offers insights into HCPs' online presence, and their concerns regarding SNS usage. It underscores the significance of e-professionalism, and provides recommendations for maintaining a positive online presence while mitigating potential risks., Competing Interests: Conflict of interest statement The authors attest that they have no financial or other conflict of interest that could influence the content of the article., (University of Zagreb School of Dental Medicine.)

This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.) doses (expressed as a total number of units (U) per animal or U/kg), possible systemic effects have not been conclusively excluded. Herein we assessed the effect of two pharmaceutical preparations, abobotulinumtoxinA (aboBoNT-A, 10, 20, and 40 U/kg corresponding to 0.05, 0.11, and 0.22 ng/kg neurotoxin) and onabotulinumtoxinA (onaBoNT-A, 10 and 20 U/kg corresponding to 0.09 and 0.18 ng/kg, respectively) injected into the rat knee, on safety-relevant readouts: digit abduction, motor performance and weight gain during 14 days post-treatment. The i. a. toxin produced dose-dependent impairment of the toe spreading reflex and rotarod performance, which was moderate and transient after 10 U/kg onaBoNT-A and ≤20 U/kg aboBoNT-A doses, and severe and long-lasting (examined up to 14 days) after ≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A. In addition, lower toxin doses prevented the normal weight gain compared to controls, while higher doses induced marked weight loss (≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A). Commonly employed BoNT-A formulations, depending on the doses, cause local relaxation of the surrounding muscles and systemic adverse effects in rats. Thus, to evade possible toxin unwanted local or systemic spread, careful dosing and motor testing should be mandatory in preclinical behavioral studies, irrespective of the sites and doses of toxin application., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by Ipsen, Croatian Science Foundation (Project ID: IP-2014-09-4503) and University of Zagreb Support project. Mikhail Kalinichev was an employee of Ipsen Innovation, France at the time the research was conducted. All other authors declare no conflicts of interest. The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication., (©2023PublishedbyElsevierLtd.)

Background: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors., Methods: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections., Results: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection., Conclusions: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors., Competing Interests: Potential conflicts of interest. C. M. C. reports the following grants or contracts unrelated to this work: Centers for Disease Control and Prevention (CDC) subaward from Johns Hopkins University to the Washington University in St. Louis (funding by the CDC grant number 1U54CK000617-01-00), vendor/individual agreement with Wayne State University for a case registry, and Associate Editor for Open Forum Infectious Diseases (1 May 2022 through 30 April 2023). D. F. P. reports payment or honoraria as a speaker for an antibiotic course for UMC Utrecht and as a teacher for Hospital Pharmacists in training for PAO; and participation on DSMB for the COBRA trial (Very short-course versus standard course antibiotic therapy in patients with acute Cholangitis after adequate endoscopic biliaRy drainage) in the Netherlands. M. J. M. reports consulting fees from Insmed and Biomerieux; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Microsoft Diagnostics (MSD), Insmed, and Teva; support for attending meetings and/or travel from MSD, Berlin Chemie; and participation on a Data Safety Monitoring Board or Advisory Board for Biomerieux, Insmed, MSD. J. T. S. reports payment or honoraria for manuscript writing for Gilead on subjects not related to this manuscript. M. B. reports support from Pfizer for attending a congress. N. K. reports royalties or licenses from Up To Date; consulting fees from Astellas, AstraZeneca, Biotest, ExeViR, Hansa, Merck Sharp and Dohme, Glasgow Smith Kline, Novartis Pharma, Takeda; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Astellas, Biotest, CSL Behring, Chiesi, Novartis Pharma, Sanofi, Sandoz, Takeda; and support for attending meetings and/or travel from Astellas, Novartis Pharma, Takeda. N. J. M. reports support for attending meetings and/or travel paid to author from Biotest; unpaid participation on a Data Safety Monitoring Board or Advisory Board for a CTX3 Study and paid participation on Advisory Boards for Takeda, MSD, and Pfizer. N. M. T. reports payment or honoraria for guest lecture for Boston Medical Center and Beth Israel Medical Center; payment for expert testimony for record review for Ficksman & Conley, LLP, in Boston, Massachusetts; participation on a Data Safety Monitoring Board or Advisory Board for United Network for Organ Sharing HIV Organ, Policy Equity (HOPE) Act Safety Review, and Workgroup (unpaid); role as Chair of the American Society of Transplantation and leadership or fiduciary role with Infectious Diseases Community of Practice (unpaid). O. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from MSD; and participation on a Data Safety Monitoring Board or Advisory Board for MSD. S. Be. reports grants or contracts unrelated to this work from Vancouver Costal Health Research Institute and Transplant Research Foundation of BC; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Merck; and participation on an Advisory Board for Evusheld (AstraZeneca). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Nickel allergy is the most common contact allergy, and a nickel salt is, therefore, included in most baseline patch test series. In the baseline series of the International Contact Dermatitis Research Group and the American Contact Dermatitis Society, nickel sulfate hexahydrate (NSH) in petrolatum at 2.5% is included, whereas NSH at 5.0% is included in many other baseline series, such as the European and Swedish ones., Objective: The aim of the study is to investigate whether NSH at 5.0% detects significantly more contact allergy than NSH 2.5% when both preparations are tested simultaneously in consecutive dermatitis patients., Patients and Methods: Two thousand two hundred eighty-seven consecutive dermatitis patients were patch tested simultaneously with NSH in petrolatum at 2.5% and 5.0%. The allergy rates were compared for all clinics individually and combined using McNemar test, 2-sided., Results: Contact allergy to NSH 5.0% and 2.5% was found in 20.3% and 16.8%, respectively ( P < 0.0001). In 6 of 11 clinics, significantly more patients tested positive to the higher NSH concentration. For the 2 clinics in North America combined, significantly more patients tested positive to NSH 5.0%., Conclusions: The NSH preparation in the International Contact Dermatitis Research Group baseline patch test series should be considered to be changed from NSH 2.5% (1 mg NSH/cm 2 ) to 5.0% (2 mg NSH/cm 2 )., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2022 American Contact Dermatitis Society. All Rights Reserved.)

Introduction: Reports showed that observing detrusor overactivity (DO) and maximum cystometric capacity (MCC) may guide rational pharmacotherapy. Since urodynamic studies (UDS) are challenging for both patients and the healthcare system, a non-invasive objective prognostic marker is preferable., Objectives: To investigate the value of the overactivity index (OI), a non-invasive measure calculated from the frequency-volume chart (FVC), for predicting the presence of symptoms and abnormal UDS in children with non-neurogenic OAB., Study Design: This was a prospective interventional study on a consecutive sample of 92 children with urgency treated with anticholinergics and standard urotherapy. Data from history, physical examination, bladder diaries, kidneys and bladder ultrasonography, uroflow, urinalysis, urine culture, and UDS was collected at baseline, and after 3 and 6 months. Binary logistic regression was used to evaluate noninvasive parameters as predictors of Overactive Bladder Symptom Score (OABSS) total score >2 and DO and/or small MCC defined as <65% of expected bladder capacity (EBC) for age. OI was calculated as (1 - (median (all voided volumes in FVC in ml))/(0.65 ∗ EBC in ml)) ∗ 100., Results: At baseline, 26 patients (36.1%) had DO and small MCC, while 21 patients (29.2%) only had DO. In 18 patients (25.0%) only small MCC was found. Seven patients had normal findings and 20 did not perform a urodynamic study. OI ≥ 23 returned as a single significant predictor of OABSS >2 (OR 7.97, 95% 1.97-32.22, p = 0.004) in multivariate regression (R 2  = 30.8%; AUC = 0.86). OI correlated with "urgency episodes over two weeks" and MCC/EBC with medium (r = 0.45) and large effect (r = -0.56), respectively, p = 0.001., Discussion: A strong correlation of OI and MCC/EBC ratio is useful, as rise in MCC is predictive of a positive outcome. Also, calculating the OI is more practical than performing UDS. This could contribute to the use of OI as a predictive marker for starting (or continuing) anticholinergic treatment (when OI ≥ 23) or for maintaining urotherapy alone (when OI < 23) in children with OAB. The limitations were lack of external validation of OI, a 37-49% drop-off rate for follow-up visits at 3 and 6 months, respectively, and not performing UDS on all participants at every follow-up visit., Conclusions: OI was found to be a significant predictor of the presence of OAB symptoms and correlated with the number of urgency episodes. It could estimate how much MCC differs from EBC., Competing Interests: Conflict of interest None., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Low-risk premature infants often develop visual deficits, even in the absence of ophthalmological complications and high-graded brain injury. These complications can be explained by the nature of subtle perinatal lesions and alterations of brain growth due to the prematurity. Subtle brain injuries and vulnerability of axonal pathways can be observed in spatiotemporal context of the white matter segments. The aim of this study was to examine the link between MRI quantitative (brain metrics data) and qualitative features (visibility of 2nd white matter segment - sagittal strata and periventricular crossroads C1-C6) and visual behavior in preterm neonates at term-equivalent age. Seventy-one very preterm infants without high-graded brain injury on MRI and no ocular pathologies were studies. The infants received MRI scans at term-equivalent age. MRI scans were analyzed using (a) simple brain metrics and (b) scoring the visibility of transient structural patterns (sagittal strata and periventricular crossroads). At the median age of 41 +5 PMA weeks infants completed the Neonatal Visual Assessment. Results indicated that visibility of temporal crossroad area C6 and frontal and occipital sagittal strata was positively correlated with visual tracking skills in neonatal period. Furthermore, the visibility of frontal and occipital sagittal strata were strong predictors of total Neonatal Visual Assessment score. The findings confirmed that sagittal strata and periventricular crossroads prominence is a valuable additional marker in perinatal neuroimaging at term-equivalent age. Thus, alteration in MRI appearance of temporal crossroad and sagittal strata may be useful in predicting of visual behavior for very premature born infants., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated the efficacy of a new laser-assisted irrigation system, the shock wave enhanced emission photo-acoustic streaming (SWEEPS) technique in removing pulp tissue from single-rooted premolars., Methods: Freshly extracted mandibular premolars with round root canals (n = 40), scanned using cone beam computed tomography, were randomly divided into control and four experimental (according to the irrigation technique used) groups (n = 8/group). Groups 1, 2, and 3 were instrumented using Reciproc Blue (RB25/0.06) followed by final irrigation protocol (FIP), activated by SWEEPS, ultrasonically activated irrigation (UAI), and conventional irrigation (CI), respectively. In these groups, 7 mL 3% NaOCl in total was used during instrumentation; for FIP, 3% NaOCl (60 s), ethylenediaminotetraacetic acid (60 s), and 3% NaOCl (30 s). In group 4, SWEEPS activation of 3% NaOCl for 6 × 30 s alone was performed. The untreated control group specimens were processed for histological evaluation of remaining pulp tissue (RPT) in each canal third. The results were analyzed using the Mann-Whitney U test (α = 0.05)., Results: Significant differences were observed between the control group and the experimental groups (p<0.05). In the middle third, the UIA and SWEEPS showed similar efficacy (p = 0.171), superior to CI and SWEEPS without instrumentation (p<0.05). In the apical third, SWEEPS was the most efficient (p = 0.002), and UIA and CI showed no difference (p = 0.643)., Conclusion: SWEEPS was superior to UIA and CI in removing RPT in the apical region of round canals after single instrument root canal preparation; SWEEPS without instrumentation was inefficient in removing pulp tissue., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As dyslipidemias remain one of the main risk factors for developing cardiovascular disease, the question of maintaining optimal lipid levels with pharmacotherapy remains a subject of interest worldwide. In contrast to conventional pharmacotherapy, human monoclonal antibodies directed against proprotein convertase subtilisin/kexin type 9 (PSCK9) and small interfering RNA- (siRNA-) based drug targeting PCSK9 represent a new strategy for managing lipid disorders and reducing cardiovascular risk. Inclisiran is a long-acting, synthetic siRNA that targets hepatic production of PCSK9 and consequently causes a reduction in LDL-C concentrations by approximately 50% compared to placebo. The structural modification of inclisiran has led to better stability and prolonged biological activity of the drug. The main advantage over conventional pharmacotherapy and anti-PCSK9 monoclonal antibodies is its favorable administration regimen (0-90-180 days), which should lead to much better compliance. Clinical trials conducted so far have confirmed the tolerability and efficacy of inclisiran in long-term PCSK9 and LDL-C level reductions. Moreover, a short-term follow-up on the safety of inclisiran showed a relatively good safety profile of the drug. However, it is still of great importance for ongoing and forthcoming clinical trials to be continued on a larger group of patients in order to assess long-term tolerability, efficacy, and safety of inclisiran., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Iveta Merćep et al.)

Background: Anorexia nervosa (AN) carries the risk of potentially irreversible medical complications, especially in children and adolescents. Constipation is frequent and difficult to manage. Due to the symptoms it causes, constipation can further compromise nutritional rehabilitation., Objective: To investigate the role of probiotics (Lactobacillus reuteri DSM 17938) in children and adolescent with AN., Design, Setting and Participants: Randomized, double blind, placebo controlled study in 31 female pediatric AN patients with constipation, referred to nutritional therapy in Pediatric Gastroenterology Department, Sestre milosrdnice University Hospital Centre in Zagreb., Methods: At hospitalization, patients were randomly assigned into two groups; one taking L. reuteri, and other placebo for 3 months, along with the conventional nutritional rehabilitation. Patients were followed 3 months after stopping the treatment. The primary outcome was relief of constipation, assessed after 3 months, while secondary outcomes were normalization of body weight, stool frequency and consistency, relief of dyspepsia, weight gain and recovery of malnutrition regarding bone density and vitamin D3 levels., Results: The study showed statistically significant difference between the two groups considering the stool frequency (6.4 vs. 4.2 stools/week; p < 0.05) and normalization of body weight (93 vs. 63%; p = 0.04) after 6 months, but no significant effect on the rate of relief of constipation (87 vs. 64%; p = 0.22) at 3 months. In the L. reuteri group, the normalization of BMD was achieved in 8/15, whereas in the placebo group, in 3/16 patients. However, there was no statistically significant difference compared to the placebo group regarding the BMD recovery as well as the normalization of D3 levels (p = 0.056)., Conclusions: Probiotics may serve as simple and safe adjuvant therapy of constipation in childhood AN and contribute to faster nutritional recovery. Although a statistically significant difference between the two group in relief of constipation could not be shown after 3 months, a benefit from probiotics could be in increasing stool frequency and nutritional recovery in childhood AN after six months. Registered under ClinicalTrials.gov Identifier no. NCT02004288., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: In the early 1980s, a preservative containing a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) in a ratio of 3:1 was introduced. This mixture (mix) has been patch tested at 100 ppm (0.01%) worldwide and at 200 ppm (0.02%) in Sweden since 1986 and also in the European baseline series since 2014., Objective: A new aqueous mix of MCI 0.015% and MI 0.2% was compared with patch testing with the 2 aqueous baseline preparations of MCI/MI 0.02% and MI 0.2%., Methods: Four thousand three hundred ninety-seven patients with dermatitis in 12 International Contact Dermatitis Research Group dermatology departments from 3 continents were patch tested simultaneously with the 3 preparations., Results: The frequency of positive patch tests to the allergens varied between 0% and 26.7% in the 12 test centers. The new mixture MCI/MI 0.215% in aqua (aq) detected significantly more patients with MCI/MI allergy than both MCI/MI 0.02% aq (P < 0.001) and MI 0.2% aq (P < 0.001) alone and combined., Conclusions: The results favor replacing the preparations MCI/MI 0.02% aq and MI 0.2% aq with the mixture MCI/MI 0.215% aq in the International Contact Dermatitis Research Group baseline series., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Background: Mercaptobenzothiazole compounds are associated with allergic contact dermatitis caused by rubber products. Several screening substances have been used for patch testing., Objective: To compare the frequency of positive test reactions to a mercapto mix containing a higher concentration of 2-mercaptobenzothiazole with reactions to the combination of 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0%., Methods: There were 7103 dermatitis patients in 12 International Contact Dermatitis Research Group dermatology departments who were patch tested with 2-mercaptobenzothiazole 2.0% petrolatum (pet.), mercapto mix 2.0% pet., and mercapto mix 3.5% pet., Results: Contact allergy to the 3 test preparations varied among the 12 centers: 2-mercaptobenzothiazole 2.0% pet. (0-2.4%), mercapto mix 2.0% pet. (0-4.9%), and mercapto mix 3.5% pet. (0-1.4%). 2-Mercaptobenzothiazole 2.0% and mercapto mix 2.0% detected a few more positive patients compared with mercapto mix 3.5%, but the difference was statistically insignificant (mercapto mix 2.0% pet., P = 1.0; 2-mercapto-benzothiazole 2.0% pet., P = 0.66)., Conclusions: Mercapto mix 3.5% pet. is not better than 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0% by a difference that is significant. By using only 1 test preparation (mercapto mix 3.5%), an additional hapten could be tested. No cases of suspected/proven patch test sensitization were registered., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Aim: To explore the relationships between transient structural brain patterns on MRI at preterm and at term-equivalent age (TEA) as a predictor of general movements (GMs) and motor development at 1-year corrected age (CA) in very preterm infants., Methods: In this prospective study, 30 very preterm infants (median = 28wks; 16 males) had structural magnetic resonance imaging (MRI) at preterm (median = 31wks + 6d) and at TEA (median = 40wks) and neuromotor assessments. The quality of GMs was assessed by Prechtl's general movements assessment and a detailed analysis of the motor repertoire was performed by calculating a motor optimality score (MOS), both at term age and at 3 months post-term. Motor development at 1-year CA was evaluated with the Infant Motor Profile (IMP). Associations between qualitative MRI findings and neuromotor scores were investigated., Results: Abnormal GMs and low motor performance at 1-year CA were associated with the poor visibility of transient structural pattern, that is with sagittal strata., Interpretation: Transient structural MRI pattern, sagittal strata, at preterm age is related to the quality of GMs and later motor development in preterm infants. This transient fetal brain compartment may be considered as a component of neurobiological basis for early neuromotor behavior, as expressed by GMs., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Development of novel antibodies to combat the novel SARS-CoV-2 virus is ongoing. Importantly, particular subgroups are more prone to severe disease, namely patients with poor immune responses. This includes cancer patients with solid and haematological disease, solid organ transplant (SOT) patients and those with congenital or acquired immunodeficiency. Outcomes for patients with poor immune responses receiving antibody therapy for underlying disease and SARS-CoV-2 severe infection are undergoing investigation. The objective of this study was to perform a search on patients with poor immune responses with severe SARS-CoV-2 infection, to assess if antibody therapy is beneficial in such populations. We performed searches using PubMED and medrXiv up to May 2021 of patients with solid and hematologic malignancy, SOT patients and acquired or congenital immunodeficiency. The primary outcome was to assess if antibody therapy was included during SARS-CoV-2 infection and the clinical outcomes of such treatment in this population. Here we find that there is a repurposing of monoclonal antibodies to target cytokine release syndrome, along with the use of convalescent plasma (CP). Despite CP demonstrating promising results, we reiterate evidence that CP forces mutational escape and subsequent variant development. Repurposing of antibody therapies (such as Tocilizumab) proved effective, especially in SOT patients. This also potentially opens an avenue for the use of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies; however, studies have yet to focus on patients with poor immune responses as a subpopulation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Introduction: The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries., Methods: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email., Results: In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine., Conclusions: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient-related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.

Aim of the Study: To collect and analyse data obtained from HCV opinion leaders/experts from central European countries, on factors which can affect the WHO target of HCV elimination by 2030., Material and Methods: Data were collected from opinion leaders/experts involved in management of HCV infections in Central European countries which participated in 9 th Conference of the Central European Hepatologic Collaboration (Warsaw, 10-11 October 2019). A dedicated questionnaire collected current information related to HCV elimination in Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland and Slovakia., Results: The HCV prevalence rate in particular countries varied from 0.2% to 1.7%. In most central European countries all the HCV infected population is eligible for reimbursement of treatment. However, in some countries there are still some limitations related to the stage of the disease and people who inject drugs. All countries have access to at least one pangenotypic regimen. The most common barrier to HCV elimination in all countries is insufficient political will to establish priority for HCV. None of the reporting countries has established a national screening programme., Conclusions: Access to therapy for HCV is similar and the majority of patients in Central Europe can be treated according to the current guidelines. Unfortunately there are still some limitations and a lack of political will to implement national screening programmes. According to collected data HCV elimination will not be possible in the region by 2030., Competing Interests: The authors report no conflict of interest., (Copyright: © 2020 Clinical and Experimental Hepatology.)

Background: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear., Methods: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded., Results: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS., Conclusions: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background & Aims: Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can progressively develop through various stages such as pre-cachexia; cachexia; and refractory cachexia. Therefore in year 2007 Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome were published. Aim of this study was to assess the awareness and implementation of Croatian guidelines for use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) into clinical practice among Croatian oncologists approximately 10 years after the publication, but also to point out the importance of adequate recognition and treatment of CC., Methods: Survey with questions was designed to assess the awareness and implementation of Croatian guidelines for use of EPA and MA into clinical practice and was distributed among all Croatian oncologists in secondary and tertiary hospital centers. Survey was conducted in January 2011 (40 months following release of the guidelines), February 2013 and June 2018, and were formed in a way of yes/no answers. Additional multiple choice questions that focus on the implementation of guidelines were added in June 2018., Results: A total of 128 oncologists completed a questionnaire. There was no statistically significant difference in follow up period (2011-2018) of percentage of oncologists that are familiar with Croatian guidelines for use of EPA and MA in CC, percentage of oncologists in which Croatian national guidelines changed their approach in treating patients with CC syndrome and proportion of oncologists that are using MA, enteral nutrition formulas with EPA or their combination. Most of the oncologists 38% (N = 44) are using >2.2 g of EPA per day. Nutritional support is prescribed in 25-50% of patients by 42% (N = 48) of oncologists and most of the oncologists (35%, N = 41) start with nutritional support when a body mass loss is >5%. Oncologists mostly recommend patients to use nutritional support during 1 year or more (43%, N = 49) or two months to 1 year (42%, N = 48). Compliance of patients with malignant diseases for using nutritional support was mostly evaluated as medium (69%, N = 60)., Conclusions: Results have shown that majority of oncologists who filled the questionnaire believe that the Croatian national guidelines for use of EPA and MA in CC syndrome changed their approach in treating patients with CC, but also that there are several targeted issues that can be significantly improved. The awareness of and adherence to national guidelines was maintained at high level even 11 years after the guidelines were published., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate the efficacy of fosfomycin in the treatment of complicated urinary tract infections (cUTIs) caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae., Methods: We retrospectively evaluated 42 ambulatory patients with cUTIs caused by ESBL-producing Enterobacteriaceae at the Outpatient Internal Medicine Clinic of the University Clinical Hospital Centre Zagreb in the period from June 2012 to June 2014. ESBL production was confirmed by double disk synergy test according to Jarlier. In vitro susceptibility to fosfomycin of ESBL-producing Escherichia coli, Klebsiella pneumoniae and Citrobacter freundii isolates was tested according to the European Committee on Antimicrobial Susceptibility Testing methodology., Results: In 42 patients with cUTIs, 43 urinary pathogens susceptible to fosfomycin were isolated in the urine cultures, including 34 E. coli ESBL, seven K. pneumoniae ESBL and two C. freundii ESBL isolates. On average, patients had 2.2 complicating factors (CFs) and received 3.6 fosfomycin doses per treatment course. The overall microbiological cure was 50%, clinical cure was 71% and ESBL eradication rate was 74%. Patients with between zero and one CFs received significantly fewer fosfomycin doses than patients with two or more CFs ( p  = 0.022). Three kidney transplant patients achieved microbiological cure following prolonged fosfomycin administration. No statistically significant correlation was found between the presence of individual CFs and treatment outcome., Conclusions: Fosfomycin may be a valid option for oral treatment of cUTIs caused by ESBL-producing pathogens. The optimal duration of fosfomycin treatment for cUTIs remains to be determined., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background: Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive effect of BT-A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT-A with endogenous opioid system within the trigeminal region., Methods: In orofacial formalin test we investigated the influence of centrally acting opioid antagonist naltrexone (2 mg/kg, s.c.) versus peripherally acting methylnaltrexone (2 mg/kg, s.c.) on BT-A's (5 U/kg, s.c. into whisker pad) or morphine's (6 mg/kg, s.c.) antinociceptive effect and the effect on dural neurogenic inflammation (DNI). DNI was assessed by Evans blue-plasma protein extravasation., Results: Naltrexone abolished the effect of BT-A on pain and dural plasma protein extravasation, whereas peripherally acting methylnaltrexone did not change either BT-A's effect on pain or its effect on dural extravasation. Naltrexone abolished the antinociceptive and anti-inflammatory effects of morphine, as well. However, methylnaltrexone decreased the antinociceptive effect of morphine only partially in the second phase of the test and had no significant effect on morphine-mediated reduction in DNI., Conclusions: Morphine acts on pain in trigeminal region both peripherally and centrally, whereas the effect on dural plasma protein extravasation seems to be only centrally mediated. However, the interaction of BT-A with endogenous opioid system, with consequent inhibition of nociceptive transmission as well as the DNI, occurs primarily centrally., Significance: Botulinum toxin type A (BT-A)'s axonal transport and potential transcytosis suggest that its antinociceptive effect might involve diverse neurotransmitters at different sites of trigeminal system. Here we discovered that the reduction in pain and accompanying DNI involves the interaction of BT-A with central endogenous opioid system (probably at the level of trigeminal nucleus caudalis)., (© 2017 European Pain Federation - EFIC®.)

Peripheral primitive neuroectodermal tumors (pPNET) are a group of extremely rare, aggressive, malignant tumors that are most often found in the thorax (Askin tumor), abdomen, pelvis, extremities and less frequently in the head and neck. The most important prognostic factor is the stage of the tumor. Significant progress both in surgery and in neoadjuvant and adjuvant chemotherapy and radiotherapy, as well as the improvement in diagnosis by cytogenetic and immunohistochemical analysis, should improve the survival rate. We report a case of a 14-year-old girl, with ataxic gait, cardiopulmonary compensated, without respiratory symptoms, who was referred to our hospital for further examination and treatment of newly discovered tumor of the left hemithorax. After a detailed radiological and laboratory investigation, next step was an extensive thoraco-neurosurgical surgery. After histopathological, cytological and molecular analysis, a diagnosis of Askin tumor was made.

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017. © 2016 Wiley Periodicals, Inc., Competing Interests: Authors declare no conflict of interest., (© 2016 Wiley Periodicals, Inc.)

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second-order neurons in the dorsal horn. The ultimate objective in the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, predifferentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of migration. Thus, bNCSCs migrated into the spinal cord, expressed glial markers and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone (DRTZ) area. In contrast, the ESC transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion. Copyright © 2014 John Wiley & Sons, Ltd., (Copyright © 2014 John Wiley & Sons, Ltd.)

Occlusion of cerebral arteries leads to ischemic stroke accompanied by subsequent brain edema. Bradykinin (BK) is involved in the formation of cerebral edema, and natriuretic peptides (NPs) potentially have beneficial effects on brain edema formation via a still unknown mechanism. The aim of this study was clarifying the mechanisms of action of NPs on BK signaling, and their interactive effects after ischemic brain injury. We used a mouse model for stroke, the middle cerebral artery (MCA) occlusion. Brain lesion and edema were measured by microcomputerized tomography volumetric measurements. To determine the effects of NPs on the BK signaling pathway in the MCAs we measured changes in vessel diameter and membrane potentials in endothelial cells. To determine the effects of NPs on BK signaling pathway in isolated astrocytes and neurons, membrane potentials and intercellular Ca 2+ concentrations were measured. Urodilatin inhibited and when applied together with BK, reduced the formation of the ischemic lesion via activation of G-Protein-Signaling Protein Type 4 at the cellular (atrocities, neurons) and blood vessel (endothelial cells and isolated MCA) level as well as in in vivo experiments. The results of this study show the existence of a natural antagonist of BK in the brain, and the possible use of NPs in the treatment of stroke., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Family medicine practices (FMPs) make the basis for the Croatian health care system. Use of electronic health record (EHR) software is mandatory and it plays an important role in running these practices, but important functional features still remain uneven and largely left to the will of the software developers., Objective: The objective of this study was to develop a novel and comprehensive model for functional evaluation of the EHR software in FMPs, based on current world standards, models and projects, as well as on actual user satisfaction and requirements., Methods: Based on previous theoretical and experimental research in this area, we made the initial framework model consisting of six basic categories as a base for online survey questionnaire. Family doctors assessed perceived software quality by using a five-point Likert-type scale. Using exploratory factor analysis and appropriate statistical methods over the collected data, the final optimal structure of the novel model was formed. Special attention was focused on the validity and quality of the novel model., Results: The online survey collected a total of 384 cases. The obtained results indicate both the quality of the assessed software and the quality in use of the novel model. The intense ergonomic orientation of the novel measurement model was particularly emphasised., Conclusions: The resulting novel model is multiple validated, comprehensive and universal. It could be used to assess the user-perceived quality of almost all forms of the ambulatory EHR software and therefore useful to all stakeholders in this area of the health care informatisation.

Background: Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in stroke patients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute stroke patients in Croatia., Methods: A total of 106 consented acute stroke patients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes., Results: We found that 83% of stroke patients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome., Conclusion: Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute stroke patients without increasing the risk of warfarin dosage complications in an elderly population., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Sclerosing polycystic adenosis (SPA) of salivary glands is a tumorous lesion of salivary glands, with clinical presentation of a slow-growing mass characterized by a combination of histological features, some of which are reminiscent of mammary fibrocystic disease. SPA is mostly unifocal, but rarely may be multifocal and/or bilateral. Recurrences have been reported in up to 19% of cases. Although originally considered pseudoneoplastic, the occurrence of "dysplasia" and carcinoma in situ of ductal epithelium, and recent evidence of clonality suggest a possible neoplastic nature. Herein we describe, for the first time, two cases of SPA in two sisters (7 and 33 years old). The younger patient experienced multiple recurrences. This is the first report of familial occurrence of SPA, suggesting a possible genetic background., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The aim of the paper is to provide an overview of HIV case reporting data for the year 2011 from the countries of the World Health Organization Eastern Mediterranean Region (WHO EMR). Fourteen countries provided data for the year 2011 and reported a total of 4263 HIV cases of which 66.8% were men. The highest number of reported HIV cases in men per 100,000 population was in Oman (5.8), Somalia (5.5) and Iran (3.3), while in women in Somalia (7.6), Oman (3.9) and Morocco (2.4). In the majority of the countries, the most common reported mode of transmission was heterosexual. This could be due to under-reporting of male-to-male transmission and more frequent testing of men than women.

Recent data suggests increased incidence of focal segmental glomerulosclerosis (FSGS) among children with idiopathic nephrotic syndrome (INS). To determine the causes and possible longitudinal changes in the etiology of INS, 282 Croatian children diagnosed with INS between 1990 and 2009 were evaluated. In total, 122 children were assessed as having minimal change nephrotic syndrome (MCNS) based on their initial presentation, laboratory findings and clinical course. Kidney biopsy was performed in the remaining 160 children. MCNS was present in 18.1% of all biopsies performed. Total incidence of MCNS (assessed + biopsy proven) was only 53.5%. In contrast, FSGS was found in 40.6% of all biopsies and accounted for 23.1% of all cases. Mesangial proliferative glomerulonephritis (MesPGN) was the third most common diagnosis, present in 26.9% of the biopsies, and accounted for 15.2% of all cases. There were no significant longitudinal differences in the incidence of different causes of INS. The overall response to steroids at presentation was 71.6%. A higher proportion of initial steroid responders among children with FSGS (43.1%) and MesPGN (67.4%) than previously reported was noted. A longitudinal tendency of increasing steroid resistance in FSGS and MesPGN groups was observed.

The aim of this study was to analyse patterns of metastatic spread from cutaneous head and neck melanoma, which are said to be highly variable. The medical records of 145 patients with pathologically proven metastatic melanoma were reviewed retrospectively. The location of pathologically positive lymph nodes was compared with clinically predicted spread, and patients with metastatic disease in areas outside of predicted drainage patterns were considered aberrant. There were 33 curative and 73 elective neck dissections. 21 of 77 patients undergoing parotidectomy had positive results for metastases. Clinical prediction proved to be correct in 33 of 45 cases (73.3%). Two patients with lateralized melanomas were initially seen with contralateral metastases. Six of 45 patients (13.3%) developed contralateral metastases after neck dissection. Patients with clinical involvement of the parotid gland were at high risk of occult neck disease (40%). Patients undergoing neck dissection for primaries originating in face, forehead, coronal scalp, periauricular area, and upper neck should be considered for parotidectomy. Patients with posterior scalp and posterior neck primaries should be considered for selective neck dissection in conjunction with posterior lymphadenectomy. In patients with coronal scalp and periauricular primaries, a complete neck dissection including parotidectomy is the recommended approach., (Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which is a member of the endosomal sorting complex required for transport (ESCRT-0) and is involved in the sorting process of the mono-ubiquitinated endosomal cargo for degradation in the lysosome. Analysis of gene trap mice carrying lacZ in frame with Stam2 revealed beta-galactosidase activity in the enteric nervous system (both in the myenteric and submucosal plexus) throughout the digestive tract. STAM2 immunostaining confirmed that the observed beta-galactosidase activity coincided with high Stam2 expression. To identify cell types with high Stam2 expression, STAM2 immunostaining was colocalized with the neuronal markers microtubule-associated protein 2 and protein gene product 9.5 and with c-kit as a marker for interstitial cells of Cajal (ICCs). STAM2 and c-kit positive cells comprised a subset of ICCs in the enteric nervous system. Qualitative and quantitative analysis of the morphology of the enteric nervous system in the homozygous mice carrying gene trap insertion in the Stam2 gene did not reveal phenotype changes; therefore, STAM2 function in the digestive tube remains elusive., (Copyright © 2011 Wiley Periodicals, Inc.)

In this article we present management of water resources in Croatia as a model of integral approach in public health interventions. The links between provision of clean water, sanitation and good health are so strong that today management and water protection are deeply integrated in primary health care. This article is a follow up on topics presented on 2nd Croatian congress on preventive medicine and health promotion which gave us "state of art" in Croatian public health. We strongly believe that every system has its own advantages and downsides, and only by knowing the system well and continuous improvement we can protect ourselves in time of health, social or economic crisis. The model of water protection showed that to prevent and overcome the variety of water-related health risks, implementation of various activities that include general environmental protection, development of water management system, permanent water quality monitoring and control, and improvement of standards and legislative is needed. On the other hand if there is no holistic approach, to the public health problems, all the efforts in just one field will not result in health indicators improvement. Constant monitoring and uniform analysis of data could help to identify possible risks of adverse effects of various environmental factors and possible burden of disease as a consequence. That information could be a point of arguing with local governments and communities for public health interventions. It is important that epidemiological and environmental data do not remain in the domain of academic discussion or statistics, and never reach primary health care which could use them in direct health care providing. Information exchange in real time is important for the real time public health intervention. Primary health care is the front line in communication with patients and diagnostics of disease as well as prevention, and they need to have access to all relevant data.

Perfect balance between maximal suture strength and minimal foreign-body reactivity guarantees success, using microsurgical techniques. The proposed initial locking knot allows optimal edge approximation. It has strength, it is simple to master, and is not too bulky. The knot is kept in its first position, without danger of slipping, before securing it with an additional knot of two loops. No additional knots are necessary, because the completed knot may fail by breaking, but never by slippage.

Cerebral acidic metabolites and penicillin are organic anions which can be carried by active transport into capillaries of the central nervous system (CNS). However, it is generally believed that these metabolites are mainly delivered from CNS to cerebrospinal fluid (CSF) and eliminated by CSF circulation over cortex and its absorption into dural venous sinuses. To test this hypothesis we studied fate of penicillin ([3H]benzylpenicillin) in the CSF under control conditions and when its active transport was blocked by probenecid. After application of penicillin into cisterna magna of control dogs, it is distributed only in traces to lumbar, ventricular and cortical CSF. However, when active transport of penicillin across capillary wall is blocked by probenecid, its disappearance from cisterna is slowed down and its distribution is greatly enhanced so that at 300 min penicillin concentrations in cisternal, lumbar and cortical CSF approach or equal each other. Disappearance of penicillin from cisternal CSF shows a single exponential course (half-time 30 min) in control, while in probenecid pretreated dogs this is a slow multiexponential process. The results indicate that the active transport across capillary wall in CNS, but not generally postulated unidirectional CSF circulation over cortex and its absorption into dural venous sinuses, is instrumental in elimination of cerebral acidic metabolites and in such a way homeostasis in brain and cerebrospinal fluid is maintained.

The article presents the investigation of histomorphological differentiation and growth of parathyroid glands in human fetus from the second to the ninth lunar month. The longer and the shorter diameter of these glands were measured. The obtained values are compared with the development and the growth intensity of the skeleton (biparietal head diameter and femoral length of a fetus from lunar months 3 to 9) and with the role of the placenta in the mentioned processes. The results of our investigation show the concordance of the skeletal growth with the development and histomorphological differentiation of these glands. The factors involved in these processes point out the complex relationship between the mother and fetus during osteogenesis, expressed on the hormonal level, in mineral metabolism and placental activity.

Eating attitudes and body image have been studied in a group of 109 girls, pupils of the fifth primary school grade (average age 10 years and 8 months). The Children's Eating Attitude Test (ChEAT) has been used in the study of eating attitudes. The mean questionnaire score is 11.38 +/- 8 with a range of 0 to 45. Fourteen girls (12.8%) had a total score higher than 20, making them an eating disorder risk group. A set of seven schematic figures showing silhouettes of girls ranging from very thin to very heavy has been used in the study of body image perception. The girls were supposed to indicate the figure having the highest resemblance to their own figure (self figure), and the figure they would like to have (ideal self figure). The mean value of the current figure was 4.28, and that of the ideal figure 3.95. Satisfaction with their figure was expressed by 46.79% of the girls; 39.45% wanted to be thinner, and 13.45% to be heavier. When these data were compared with BMI, 27.52% (of the total) of the girls wanting to be thinner were found to have a normal BMI, and 11.93% a > 95 centile BMI. Among the girls satisfied with their figure 2 had a low and 2 a high BMI, while 43.12% were within the normal BMI range. Out of the 13.45% of girls wanting to be heavier, 6.42% (of the total) had a low BMI, 6.42% a normal BMI, and 0.92% (one girl) a > 95 centile BMI. The girls were divided into two groups in terms of the ChEAT score: ChEAT+ (anorexia risk) and ChEAT-. The groups differed in terms of body weight and BMI (the ChEAT+ group was heavier); ChEAT+ girls tended to prefer a thinner figure and experienced themselves as being heavier.

This reported investigation was designed to determine the role of a new synthetic conduit-expanded polytetrafluoroethylene (ePTFE) tube--in clinical repair of median and ulnar nerves in the upper extremities. The main goals of this study were: to determine the effectiveness of the ePTFE conduit in clinical nerve reconstruction; to evaluate the potential of this technique in reconstruction of various nerve gaps (1.5 to 6 cm); and to analyze the results of repair with the ePTFE tube regarding different mechanisms of injury. Forty-three patients were evaluated. They had upper-extremity peripheral-nerve injuries (21 injuries to the median nerve, and 22 ulnar nerve injuries) located at the various levels of the upper extremities. All surgical procedures described in the study were secondary reconstructions, and the average delay from injury to repair was 4.2 months. With regard to the nerve-gap lengths, patients were categorized in two groups. Group 1 (gaps from 1.5 to 4 cm) included 28 patients (17 median nerve injuries and 11 ulnar nerve injuries), and Group 2 (gaps from 4.1 to 6 cm) comprised 15 patients (4 median nerve injuries and 11 ulnar nerve injuries). Results showed that 78.6 percent of patients from Group 1 demonstrated functional motor and sensory recovery, while reconstruction of only 13.3 percent of peripheral nerves from Group 2 resulted in useful reinnervation. According to published results, ePTFE conduit is a reliable and successful surgical procedure for nerve repair in reconstruction of nerve gaps up to 4 cm between the ends of median and ulnar nerves in various levels of the upper extremity. Because of its properties, ePTFE conduit has the advantages of promoting better nerve regeneration, compared to other synthetic tubes, especially in reconstruction of proximal nerve injuries, larger nerve gaps, and in cases with unfavorable mechanisms of nerve injury.

The aim of this study was to find out in what way adolescents assess their families and family functioning. An 34-item scale in self-report format was administered to 154 high school students and 34 patients in diagnostic procedure before entering psychotherapy in order to explore basic elements of family functioning (structure, affect, communication; behaviour control, ethic values transmission, intimacy and idealization, and elements of family dysfunction). The results showed that adolescents in general assessed their families as growth and individuation supportive. The adolescents in the clinical sample presented more dissatisfaction with their families and elements of family dysfunctions were more emphasized.

Population studies were carried out on unrelated individuals of Croatian ancestry. Genomic DNA was amplified by the polymerase chain reaction (PCR) at the polymorphic microsatellite loci HUMCD4 (n = 105 individuals) and HUMF13B (n = 108 individuals). After horizontal polyacrylamide gel electrophoresis followed by silver staining 6 alleles and 12 genotypes were observed for HUMCD4 and 6 alleles and 13 genotypes could be identified for HUMF13B. Data obtained were in concordance with the prediction of Hardy-Weinberg equilibrium. The allele frequency data were compared with Austrian and Italian population samples and no significant deviations between these populations were observed.

A rare anomaly of the vessels supplying the kidney of a 65 year-old male cadaver was found during a routine dissection. The right kidney received two renal arteries from the aorta that were similar in diameter, both entering through the hilus. The left kidney had three arteries originating from the aorta, one at its usual hilar position and two entering the renal cortex at its upper and lower poles. The upper pole of the left kidney also gave rise to an additional tributary of the renal vein.

Objectives: To determine the concentrations of hyaluronic acid, FSH, P, and E2 in the follicular fluid (FF) obtained from IVF-ET patients and to assess the value of these measurements in predicting the outcome of fertilization., Design: One hundred eleven samples were retrospectively analyzed for the hyaluronic acid and hormone contents., Setting: University-based tertiary care center., Patients: Preovulatory FF samples were collected from 67 women undergoing IVF-ET treatment because of tubal absence or obstruction., Main Outcome Measures: The FF hyaluronic acid and hormone concentrations were compared according to the type of ovulation induction, follicular development, and IVF outcome., Results: According to the type of ovulation induction, a significantly lower hyaluronic acid concentration was found in FF harvested from the patients treated with GnRH agonist-hMG. No significant correlation was found between FF hyaluronic acid and either morphological maturity of the oocyte-cumulus complex or fertilizability of oocytes. The level of FSH was significantly higher in FF, yielding a mature oocyte-cumulus complex and from which the oocyte obtained successfully fertilized and cleaved. A significant increase in the E2 concentration was found in FF in which mature cumuli oophori were present. The levels of hyaluronic acid significantly correlated with FSH in FF., Conclusions: Expansion of the human oocyte-cumulus cell complex is an FSH-dependent phenomenon. The data are in agreement with the hypothesis that intrafollicular FSH plays an important role in the secretion of hyaluronic acid by granulosa cells and may act synergistically with E2 to enhance cytoplasmic maturation, resulting in successful fertilization.