Diagnostic Accuracy of Leucine-Rich α-2-Glycoprotein 1 as a Non-Invasive Salivary Biomarker in Pediatric Appendicitis.

The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who presented with acute abdomen and suspected acute appendicitis were enrolled in this prospective study. The parameters documented included demographic and clinical information, as well as operative and postoperative data. Patients were divided into two groups: those with acute appendicitis who underwent laparoscopic appendectomy (n = 46) and those without appendicitis (n = 46). The total white blood cell (WBC) count, percent of neutrophils, C-reactive protein (CRP) level, and salivary LRG1 were compared between groups. A commercially available enzyme-linked immunosorbent assay (ELISA) LRG kit was used to measure the LRG levels. The median salivary LRG1 level was significantly higher in the group of children with pathohistologically confirmed acute appendicitis compared to the control group: 233.45 ng/mL (IQR 114.9, 531.2) vs. 55.95 ng/mL (IQR 51.5, 117.9), p < 0.001. LRG1 had an overall good receiver-operator characteristic area under the curve of 0.85 (95% CI 0.76-0.92; p < 0.001). The optimal LRG1 cutoff with best separation between acute appendicitis and the controls was >352.6 ng/mL (95% CI from >270.7 to >352.6). Although the specificity was 100% at this cutoff, the sensitivity for identifying appendicitis was 36%. In addition, a significant difference was found between groups in the laboratory values of all inflammatory markers tested: WBC, absolute neutrophil count, and CRP (p < 0.001 for all). Although LRG1 in saliva showed a good AUC parameter and significantly higher values in patients with acute appendicitis compared to the controls, its usefulness in the patient population who present at emergency departments with abdominal pain is debatable. Future studies should focus on investigating its diagnostic potential.

Synthesizing quantitative and qualitative information on multiple comparisons of health interventions to facilitate knowledge transfer: an example from an EUnetHTA multi-HTA.

OBJECTIVE: Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions. METHODS: Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence. RESULTS: The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables. CONCLUSION: Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers.

Cannabinoids for the treatment of dementia.

BACKGROUND: Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia. OBJECTIVES: To determine the efficacy and safety of cannabinoids for the treatment of dementia. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates. MAIN RESULTS: We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains.  The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants).  We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis.  There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness. AUTHORS' CONCLUSIONS: Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.

Comparison of new versus reused Harmonic scalpel performance in laparoscopic appendectomy in patients with acute appendicitis-a randomized clinical trial.

BACKGROUND: The aim of this study was to compare lateral thermal damage of the appendix and clinical outcomes after laparoscopic appendectomy using new versus reused Harmonic scalpels. METHODS: A total of 100 consecutive patients with acute appendicitis who underwent laparoscopic appendectomy were enrolled in the two-center, randomized clinical trial. Using a computer random number generator, patients were allocated to new or reused group. Histopathological measurement of lateral thermal damage of the appendiceal base and mesoappendix, speed of transection of the appendiceal base, duration of surgery, subjective rating of device functionality, length of hospital stay, and complications were compared within groups. RESULTS: The median lateral thermal damage on the appendiceal base in the new group (N = 49) was 0.2 mm (IQR 0.1-0.2) and 0.1 mm (IQR 0.1-0.3) in the reused group (N = 51) (P = 0.644), while on the mesoappendix for both groups, thermal damage was 0.1 mm (IQR 0.1-0.2) (P = 0.418). The median time required for base transection in both groups was 8 s (IQR 7-9) (P = 0.776). The median duration of surgery was also comparable between the groups (22 min, IQR 20-30 vs 25 min, IQR 21-35; P = 0.233). Two postoperative complications in the new group and one in the reused group were recorded (4% vs 2%; P = 0.536). Surgeons' subjective assessment of the instrument did not reveal significant difference between the groups in all of the investigated categories. CONCLUSIONS: The results of our study support the reuse of Harmonic scalpels especially in the settings where economic constraints might hamper access to minimally invasive surgery to a larger number of patients. The results obtained on laparoscopic appendectomy might not be reproducible to other more demanding surgical procedures. TRIAL REGISTRATION: ClinicalTrials.gov registry under identifier NCT04226482.

The global incidence of in-flight medical emergencies: A systematic review and meta-analysis of approximately 1.5 billion airline passengers.

BACKGROUND: Medical emergencies during short- or long-haul commercial airline flights have become more commonplace due to the aviation industry's contemporary growth, the popularization of commercial flights, and an increased aging of air travelers with significant comorbidities. However, the precise incidence of onboard medical events on commercial airlines and the most common medical conditions is unclear. METHODS: In this systematic review and meta-analysis, we explored the incidence of in-flight medical emergencies among airline passengers and estimated the incidence rate by physiological body system, or organ class/syndrome for emergencies that may be associated with different body systems. We limited our search to cohort studies published between 1945 to October 31, 2020 in MEDLINE, Embase, Cochrane Library and official reports from the Federal Aviation Administration/International Air Transport Association, regardless of the language of publication. Only studies that evaluated the overall frequency of onboard medical events on commercial air carriers (in which they also presented the total number of annual revenue passengers) and the frequency of events by physiological body systems or organ class/syndrome were included. We excluded case reports and case series, systematic or narrative reviews, and studies addressing specific health-related conditions. Two independent investigators performed first- and second-phase study screening, abstracted data, and appraised risk of bias. We rated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Using a quality effect model, we meta-analyzed data associated with the incidence of in-flight medical emergencies, all-cause fatality, incidence of medical events by medical condition category, frequency of en-route diversion, presence of medical personnel on board, and the use of an automatic external defibrillator. We also extracted data regarding the cost of flight diversion. RESULTS: Of 18 individual studies with approximately 1.5 billion passengers, 11 reported the overall incidence of in-flight medical emergencies. Low certainty of evidence suggested that the global incidence of in-flight medical emergencies was 18.2 events per million passengers (95% CI 0.5 to 53.4 per million; I2 = 100%, P < 0.001, very low certainty), and an all-cause mortality rate was 0.21 per million passengers (95% CI 0 to 0.76 per million; I2 = 99%, P < 0.001, low certainty). The four most common categories of medical conditions or syndromes during flight were syncope, gastrointestinal events, respiratory and neurological diagnostic groups. The diversion rate was 11.1 per 100,000 flights (95% CI 5.9 to17.6 per 100,000 flights; I2 = 97%, P < 0.001), with an average cost ranging from $15,000 to $893,000 per unplanned emergency landing across studies which examined this outcome. CONCLUSIONS: In-flight medical events on commercial travels are extremely low with a corresponding very low in-flight mortality rate. Associated costs derived from en-route diversion might significantly influence airlines' budgetary equilibrium. Novel and modern standardized reporting systems or platforms should be internationally provided and enforced by health and aviation authorities to obtain higher quality patient-passengers datasets. Onboard volunteer medical providers must be aware of everyday life-threatening events during commercial flights and should consider the establishment of a connection between the aircraft and ground-based medical advisory services while assisting in-flight medical events.

Comparison of inflammatory stress response between laparoscopic and open approach for pediatric inguinal hernia repair in children.

BACKGROUND: The aim of this study was to compare inflammatory stress response between laparoscopic percutaneous inguinal ring suturing (PIRS) and open modified Marcy technique for pediatric inguinal hernia repair. METHODS: From May 2017 to April 2018, 32 male children with median age of 4.5 years undergoing inguinal hernia repair were included in randomized controlled trial. The patients were divided in two groups, by using random number generator, depending on surgical approach. The blood was tested in three time frames for white blood cells count (WBC), C-reactive protein (CRP), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Significant increase in concentration for all inflammatory biomarkers, that occur over time, has been found (p < 0.001 for all). Additionally, it was also found that the type of surgery significantly influenced the level of WBC, CRP, and IL-6 with Marcy showing a higher level of inflammatory response (WBC 11.4 ± 3.1 × 109/L; CRP 11.5 mg/L; IL-6 11.0 pg/mL) than the PIRS (WBC 7.6 ± 1.6 × 109/L; CRP 0.8 mg/L; IL-6 2.0 pg/mL) (p < 0.001 for all). Similar pattern was also found for TNF-α (Marcy 16.8 pg/mL; PIRS 10.1 pg/mL), but correlation between surgery type and concentration of this biomarker was significant only at the 0.1 level (p = 0.055). The mean operation time was significantly shorter (9 ± 2 min) in PIRS group compared to Marcy group (25 ± 7 min) (p < 0.001). Significantly lower median of visual analog scale score (VAS) was found in PIRS group (VAS = 2) compared to Marcy group (VAS = 6) (p < 0.001). CONCLUSIONS: Use of laparoscopic (PIRS) technique in children shows significantly lower surgical stress in comparison to open hernia repair.

Fluoride toothpastes of different concentrations for preventing dental caries.

BACKGROUND: Caries (dental decay) is a disease of the hard tissues of the teeth caused by an imbalance, over time, in the interactions between cariogenic bacteria in dental plaque and fermentable carbohydrates (mainly sugars). Regular toothbrushing with fluoride toothpaste is the principal non-professional intervention to prevent caries, but the caries-preventive effect varies according to different concentrations of fluoride in toothpaste, with higher concentrations associated with increased caries control. Toothpastes with higher fluoride concentration increases the risk of fluorosis (enamel defects) in developing teeth. This is an update of the Cochrane Review first published in 2010. OBJECTIVES: To determine and compare the effects of toothpastes of different fluoride concentrations (parts per million (ppm)) in preventing dental caries in children, adolescents, and adults. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 15 August 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7) in the Cochrane Library (searched 15 August 2018); MEDLINE Ovid (1946 to 15 August 2018); and Embase Ovid (1980 to 15 August 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials (15 August 2018). No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials that compared toothbrushing with fluoride toothpaste with toothbrushing with a non-fluoride toothpaste or toothpaste of a different fluoride concentration, with a follow-up period of at least 1 year. The primary outcome was caries increment measured by the change from baseline in the decayed, (missing), and filled surfaces or teeth index in all permanent or primary teeth (D(M)FS/T or d(m)fs/t). DATA COLLECTION AND ANALYSIS: Two members of the review team, independently and in duplicate, undertook the selection of studies, data extraction, and risk of bias assessment. We graded the certainty of the evidence through discussion and consensus. The primary effect measure was the mean difference (MD) or standardised mean difference (SMD) caries increment. Where it was appropriate to pool data, we used random-effects pairwise or network meta-analysis. MAIN RESULTS: We included 96 studies published between 1955 and 2014 in this updated review. Seven studies with 11,356 randomised participants (7047 evaluated) reported the effects of fluoride toothpaste up to 1500 ppm on the primary dentition; one study with 2500 randomised participants (2008 evaluated) reported the effects of 1450 ppm fluoride toothpaste on the primary and permanent dentition; 85 studies with 48,804 randomised participants (40,066 evaluated) reported the effects of toothpaste up to 2400 ppm on the immature permanent dentition; and three studies with 2675 randomised participants (2162 evaluated) reported the effects of up to 1100 ppm fluoride toothpaste on the mature permanent dentition. Follow-up in most studies was 36 months.In the primary dentition of young children, 1500 ppm fluoride toothpaste reduces caries increment when compared with non-fluoride toothpaste (MD -1.86 dfs, 95% confidence interval (CI) -2.51 to -1.21; 998 participants, one study, moderate-certainty evidence); the caries-preventive effects for the head-to-head comparison of 1055 ppm versus 550 ppm fluoride toothpaste are similar (MD -0.05, dmfs, 95% CI -0.38 to 0.28; 1958 participants, two studies, moderate-certainty evidence), but toothbrushing with 1450 ppm fluoride toothpaste slightly reduces decayed, missing, filled teeth (dmft) increment when compared with 440 ppm fluoride toothpaste (MD -0.34, dmft, 95%CI -0.59 to -0.09; 2362 participants, one study, moderate-certainty evidence). The certainty of the remaining evidence for this comparison was judged to be low.We included 81 studies in the network meta-analysis of D(M)FS increment in the permanent dentition of children and adolescents. The network included 21 different comparisons of seven fluoride concentrations. The certainty of the evidence was judged to be low with the following exceptions: there was high- and moderate-certainty evidence that 1000 to 1250 ppm or 1450 to 1500 ppm fluoride toothpaste reduces caries increments when compared with non-fluoride toothpaste (SMD -0.28, 95% CI -0.32 to -0.25, 55 studies; and SMD -0.36, 95% CI -0.43 to -0.29, four studies); there was moderate-certainty evidence that 1450 to 1500 ppm fluoride toothpaste slightly reduces caries increments when compared to 1000 to 1250 ppm (SMD -0.08, 95% CI -0.14 to -0.01, 10 studies); and moderate-certainty evidence that the caries increments are similar for 1700 to 2200 ppm and 2400 to 2800 ppm fluoride toothpaste when compared to 1450 to 1500 ppm (SMD 0.04, 95% CI -0.07 to 0.15, indirect evidence only; SMD -0.05, 95% CI -0.14 to 0.05, two studies).In the adult permanent dentition, 1000 or 1100 ppm fluoride toothpaste reduces DMFS increment when compared with non-fluoride toothpaste in adults of all ages (MD -0.53, 95% CI -1.02 to -0.04; 2162 participants, three studies, moderate-certainty evidence). The evidence for DMFT was low certainty.Only a minority of studies assessed adverse effects of toothpaste. When reported, effects such as soft tissue damage and tooth staining were minimal. AUTHORS' CONCLUSIONS: This Cochrane Review supports the benefits of using fluoride toothpaste in preventing caries when compared to non-fluoride toothpaste. Evidence for the effects of different fluoride concentrations is more limited, but a dose-response effect was observed for D(M)FS in children and adolescents. For many comparisons of different concentrations the caries-preventive effects and our confidence in these effect estimates are uncertain and could be challenged by further research. The choice of fluoride toothpaste concentration for young children should be balanced against the risk of fluorosis.

How to choose an evidence-based medicine knowledge test for medical students? Comparison of three knowledge measures.

BACKGROUND: There are a few studies of alignment between different knowledge-indices for evidence-based medicine (EBM). The aim of this study was to investigate whether the type of test used to assess knowledge of EBM affects the estimation of this knowledge in medical students. METHODS: Medical students enrolled in 1-week EBM course were tested with the Fresno, Berlin, and ACE tests at the beginning and the end of the course. We evaluated the ability of these tests to detect a change in the acquired level of EBM knowledge and compared the estimates of change with those of the Control group that was tested with the ACE and Berlin tests before and after an unrelated non-EBM course. The distributions of test scores and average item difficulty indices were compared among the tests and the groups. RESULTS: Test scores improved on all three tests when compared with their pre-test results and the control. Students had on average a "good" performance on the ACE test, "sufficient" performance on the Berlin test, and "insufficient" performance or have "not passed" on the Fresno test. The post-test improvements in performance on the Fresno test (median 31% increase in percent scores, 95% confidence interval (CI) 25-42%) outperformed those on the ACE (13, 95% CI 13-20%) and Berlin tests (13, 95% CI 7-20%). Post-test score distributions demonstrated that the ACE test had less potential to discriminate between levels of EBM knowledge than other tests. CONCLUSION: The use of different EBM tests resulted in different assessment of general EBM knowledge in a sample of graduate medical students, with lowest results on the Fresno and highest on the ACE test. In the light of these findings, EBM knowledge assessment should be based on the course's content and learning objectives.

Lateral thermal damage of mesoappendix and appendiceal base during laparoscopic appendectomy in children: comparison of the harmonic scalpel (Ultracision), bipolar coagulation (LigaSure), and thermal fusion technology (MiSeal).

BACKGROUND: The aim of this study was to compare lateral thermal damage of mesoappendix and appendiceal base using three different instruments for sealing and cutting of mesoappendix. MATERIALS AND METHODS: A total number of 99 patients (54 males and 45 females) who underwent laparoscopic appendectomy because of suspected appendicitis between December 2013 and May 2015 were enrolled in the study. The patients were divided in three groups based on instrument used for sealing of mesoappendix: group 1 (Ultracision; n = 36), group 2 (LigaSure; n = 32), and group 3 (MiSeal; n = 31). Lateral thermal damage, intraoperative and postoperative complications, duration of surgery, hospital stay, and economic value were compared within groups. RESULTS: The median age of patients was 14 y (range 3-17). A histopathologic analysis revealed a positive diagnosis of appendicitis in 84 patients (85%). The median lateral thermal damage on appendiceal base using Ultracision, LigaSure, and MiSeal was 0.10 mm, 0.16 mm, and 0.10 mm respectively, and on mesoappendix, 0.08 mm, 0.13 mm, and 0.08 mm, respectively. Significantly higher thermal damage was found on mesoappendix (P = 0.015) and appendiceal base (P = 0.012) in patients treated with LigaSure than in patients from other groups. There were no statistical differences among the groups regarding intraoperative and postoperative complications (P = 0.098). No significant difference in thermal damage between appendicitis and nonappendicitis group was found (P = 0.266). CONCLUSIONS: Using of Ultracision, LigaSure, and MiSeal for sealing of mesoappendix in laparoscopic appendectomy in children is safe and useful. LigaSure produces significantly greater lateral thermal damage compared with other instruments.

Endoscopic placement of double-J ureteric stents in children as a treatment for primary hydronephrosis.

INTRODUCTION: The aim of this study was to determine the efficacy and potential complications of double-J ureteric stents in the treatment of primary hydronephrosis in pediatric patients. MATERIALS AND METHODS: A retrospective case-records review of 133 patients (45 girls and 88 boys) treated because of primary hydronephrosis with double-J ureteric stents, in Department of Pediatric Surgery, Split University Hospital, between December 1997 and December 2014, was performed. Success of treatment, results of follow up investigations and complications were recorded. Patients were followed up clinically and radiologically for a minimum of 2 years following stent insertion. RESULTS: In all, 133 endoscopic double-J ureteric stents insertions were performed. Of the total number of patients, left-sided hydronephrosis was found in 82 patients, right-sided in 38, and bilateral in 13 patients. The median age of children was 2 years (range 0-17 years). Mean hospital stay was 2 days (range 1-10 days). In primary hydronephrosis, double-J ureteric stenting alone was effective with resolution of hydronephrosis in 73% of cases (97/133 insertions). Regarding the age of the patients the highest success of 83.5% was achieved in age group 0-4 years. Success in groups 5-9 years; 10-14 years and 15-17 years were 47%; 33.5% and 0%, respectively. Several complications have been recorded: symptomatic infections, migration in the renal pelvis and bladder, progression of hydronephrosis, spontaneously prolapse of prosthesis, bleeding and perforation of the renal pelvis. A significant, decreasing trend in success rates by age of participants was observed (p < 0.001). CONCLUSIONS: Ureteric stenting is minimally invasive procedure that provides an alternative to open surgery in patients with primary hydronephrosis. Endoscopic placement of ureteric double-J stents should be considered as a first-line treatment in the management of primary hydronephrosis especially in children till 4 years of age, with success rate of 83.5% and without the need for conventional surgery. In a case of failure we are time-consuming to definitive surgery.

No difference in the intention to engage others in academic transgression among medical students from neighboring countries: a cross-national study on medical students from Bosnia and Herzegovina, Croatia, and Macedonia.

AIM: To asses if the level of intention to engage others in academic transgressions was comparable among medical students from five schools from neighboring Southern-European countries: Croatia, Bosnia and Herzegovina, and Macedonia; and medical students from western EU studying at Split, Croatia. METHODS: Five medical schools were surveyed in 2011, with ≥87% of the targeted population sampled and a response rate of ≥76%. Students' intention to engage a family member, friend, colleague, or a stranger in academic transgression was measured using a previously validated the Intention to Engage Others in Academic Transgression (IEOAT) questionnaire and compared with their intention to ask others for a non-academic, material favor. Data on students' motivation measured by Work Preference Inventory scale, and general data were also collected. Multiple linear regression models of the intention to engage others in a particular behavior were developed. RESULTS: The most important determinants of the intention to engage others in academic transgression were psychological factors, such as intention to ask others for a material favor, or students' motivation (median determinant's ß of 0.18, P≤0.045 for all), whereas social and cultural factors associated with the country of origin were either weak (median ß of 0.07, P≤0.031) or not relevant. A significant proportion of students were aware of the ethical violations in academic transgressions (P≤0.004 for all transgressions), but a large proportion of students also perceived academic cheating as a collective effort and were likely to engage people randomly (P≤0.001 for all, but the most severe transgression). This collective effort was more pronounced for academic than non-academic behavior. CONCLUSION: Culture differences among neighboring Southern-European countries were not an important determinant of the intention to engage others in academic cheating.

Genome-wide meta-analysis of common variant differences between men and women.

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

High NF-κB and STAT3 activity in human urothelial carcinoma: a pilot study.

PURPOSE: Given that the tumor-promoting inflammation has been previously established in squamous cell carcinoma of the bladder but its contribution to development of urothelial carcinoma (UC) still remains elusive, our aim was to study changes in expression and activity of inflammation-mediating NF-κB and STAT3 transcription factors in human urothelial bladder carcinoma as well as expression of their target genes cyclin D1, VEGFA and TGFß1. METHODS: Gene expression of STAT3, NF-κB, TGFß1, cyclin D1 and VEGFA was measured by quantitative real-time polymerase chain reaction in both tumor and healthy bladder tissue from 36 patients with UC of the bladder. Activation of STAT3 and NF-κB was assessed with immunohistochemistry and immunoblot. RESULTS: Urothelial bladder carcinoma displayed elevated expression as well as activation of NF-κB (P = 5.38e-10) and STAT3 (P = 0.002) transcription factors. Furthermore, elevated level of expression was observed for cyclin D1, VEGFA and TGFß1 (P = 9.71e-09, P = 9.71e-09, P = 5.38e-10). Preliminary statistical analysis indicated that the level of upregulation of STAT3 or NF-κB was probably not dependent upon the grade (P = 0.984 and 0.803, respectively) and invasiveness of the tumor (0.399 and 0.949), nor to the gender (0.780 and 0.536) and age (0.660 and 0.816) of the patients. CONCLUSIONS: NF-κB and STAT3 signaling pathways, as main inflammatory mediators, are found to be activated in urothelial bladder carcinoma indicating that chronic inflammatory processes are accompanying development of this tumor type. Future studies will have to determine possible causative role of inflammatory processes in development of urothelial bladder carcinomas.

Who would students ask for help in academic cheating? Cross-sectional study of medical students in Croatia.

BACKGROUND: Academic cheating does not happen as an isolated action of an individual but is most often a collaborative practice. As there are few studies that looked at who are collaborators in cheating, we investigated medical students' readiness to engage others in academic dishonest behaviours. METHODS: In a cross-sectional survey study in Zagreb, Croatia, 592 medical students from the first, 3rd and 6th (final) study year anonymously answered a survey of readiness to ask family, friends, colleagues or strangers for help in 4 different forms of academic cheating or for 2 personal material favours. Stepwise multiple linear regression models (MLR) were used to evaluate potential factors influencing propensity for engaging others in these two types of behaviour. RESULTS: Many students would ask another person for help in academic cheating, from 88.8% to 26.9% depending on a cheating behaviour. Students would most often ask a family member or friend for help in academic cheating. The same "helpers" were identified for non-academic related behaviour - asking for personal material favours. More respondents, however, would include three or four persons for asking help in academic cheating than for routine material favours. Score on material favours survey was the strongest positive predictor of readiness for asking help in academic cheating (stepwise MLR model; beta = 0.308, P < 0.0001) followed by extrinsic motivation (compensation) and male gender, whereas intrinsic motivation, year of study and grade point average were weak negative predictors. CONCLUSIONS: Our study indicates that medical students are willing to engage more than one person in either close or distant relationships in academic cheating. In order to develop effective preventive measures to deter cheating at medical academic institutions, factors surrounding students' preference towards academic cheating rather than routine favours should be further investigated.

Eicosapentaenoic acid in serum lipids could be inversely correlated with severity of clinical symptomatology in Croatian war veterans with posttraumatic stress disorder.

AIM: To explore the association between plasma fatty acids composition and the severity of clinical symptoms in Croatian war veterans with posttraumatic stress disorder (PTSD). METHODS: This cross-sectional study included 62 men diagnosed with PTSD caused by combat activities during the War in Croatia 1991-1995. Clinician-Administered PTSD Scale (CAPS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D-17) were used. Plasma fatty acids composition was determined by gas chromatography. Data about life-style habits were collected by a structured interview. To evaluate the association between plasma fatty acid levels and PTSD severity scales, multivariate general linear models (GLM) were applied while controlling for different confounders. RESULTS: Significant negative correlations were found between plasma eicosapentaenoic acid (EPA, 20:5n-3) level and the scores on psychological scales (τ = -0.326, P<0.001 for CAPS; τ-0.304, P =0 .001 for HAM-A; and τ = -0.345, P<0.001 for HAM-D-17). GLM confirmed that PTSD severity was affected by EPA (Wilks'Λ = 0.763-0.805, P = 0.006-0.018, ηp 0.195-0.237), arachidonic acid (AA)/EPA (Wilks'Λ = 0.699-0.757, P = 0.004, ηp 0.243-0.301), and dairy products consumption (Wilks'Λ = 0.760-0.791, P = 0.045-0.088, ηp 0.128-0.111). No other fatty acid or dietary/lifestyle variable was significant ( P = 0.362-0.633). CONCLUSION: The study suggests that lower EPA levels are associated with the severity of clinical symptoms in PTSD.

Medical device regulation in vascular ageing assessment: a VascAgeNet survey exploring knowledge and perception.

BACKGROUND: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field. RESEARCH DESIGN AND METHODS: A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform. RESULTS: Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department). CONCLUSIONS: Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices.

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

CD15s is a potential biomarker of serious bacterial infection in infants admitted to hospital.

Early recognition of serious bacterial infection (SBI) in children is essential for better treatment outcome. Flow cytometry analysis of neutrophil surface molecules has been more frequently utilized as a tool for diagnosis of infection. The infants (n = 105) under 6 months of age presenting to the pediatric emergency department with fever without apparent source who were hospitalized with suspicion of having SBI were enrolled in this prospective study. Sixty-nine infants were included into the training pool and were classified into bacterial or viral infection group. Validation pool consisted of 36 infants. The values of white blood cells counts, absolute neutrophil count (ANC), C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD11b, CD15s and CD64 expression, and the percentage (%CD15s+) and absolute count (AC-CD15s+) of CD15s+ neutrophils were determined. In infants with SBI, %CD15s+ was 10.5 times more likely to be higher than the cut-off value. ANC, CRP, PCT, CD64, and AC-CD15s+ were also found as useful biomarkers for differentiation between bacterial and viral infection. The best fit multivariate logistic regression model included CRP, PCT, and %CD15s+ as strong predictors of SBI. The model's sensitivity (87 %) and specificity (83 %) indicated high model's accuracy. After validation on independent dataset, model's accuracy maintained high: 86 % sensitivity and 93 % specificity, confirming its reliability and supporting CRP, PCT, and %CD15s+ as real predictors. The findings of this study support assumption made in the literature on significance of CD15s in inflammation processes. Also, this study demonstrated for the first time that CD15s is potentially valuable biomarker of SBI in infants.