Electrophysiological properties of dorsal root ganglion neurons cultured on 3D silicon micro-pillar substrates.

BACKGROUND: Silicon-based micro-pillar substrates (MPS), as three-dimensional cell culture platforms with vertically aligned micro-patterned scaffolding structures, are known to facilitate high-quality growth and morphology of dorsal root ganglion (DRG) sensory neurons, promote neurite outgrowth and enhance neurite alignment. However, the electrophysiological aspects of DRG neurons cultured on silicon MPSs have not been thoroughly investigated, which is of greatest importance to ensure that such substrates do not disrupt neuronal homeostasis and function before their widespread adoption in diverse biomedical applications. NEW METHOD: We conducted whole-cell patch-clamp recordings to explore the electrophysiological properties of DRG neurons cultured on MPS arrays, utilizing a custom-made upright patch-clamp setup. RESULTS: Our findings revealed that DRG neurons exhibited similar electrophysiological responses on patterned MPS samples when compared to the control planar glass surfaces. Notably, there were no significant differences observed in the action potential parameters or firing patterns of action potentials between neurons grown on either substrate. COMPARISON WITH EXISTING METHODS: In the current study we for the first time confirmed that successful electrophysiological recordings can be obtained from the cells grown on MPS. CONCLUSION: Our results imply that, despite the potential alterations caused by the cumulative trauma of tissue harvest and cell dissociation, essential functional cell properties of DRG neurons appear to be relatively maintained on MPS surfaces. Therefore, vertically aligned silicon MPSs could be considered as a potentially effective three-dimensional system for supporting a controlled cellular environment in culture.

Difficulties in Accessing the List and Full Text of the Defended PhD Theses from Medical Schools: a Retrospective Case Study from Croatia.

OBJECTIVE: To conduct scientometric studies on PhD ("Doctor of Philosophy") theses (i.e., doctoral theses), researchers should be able to access the theses. We aimed to explore how to obtain a list and full text of the defended PhD theses from medical schools in Croatia over 30 years (from the beginning of 1992 to the end of 2021). METHODS: We tried to obtain information from the Croatian Bureau of Statistics, the National and University Library in Zagreb (NSK), universities, medical schools and online repositories. RESULTS: We could not find a single list (source) of all PhD theses. Based on 4 different sources (website of the University of Zagreb and Medical School in Rijeka; school administrator from Split; library catalog from Osijek), we gathered information that from the beginning of 1992 to the end of 2021, there were 2955 PhD theses defended at medical schools in Croatia - 357 in Osijek, 550 in Rijeka, 337 in Split and 1711 in Zagreb. In May 2022, the online Croatian Digital Dissertations Repository contained 631 (22%) of full-text theses in Portable Document Format (PDF). University of Zagreb School of Medicine has its own repository that holds the full text of 834 (49%) of their PhD theses. One of the three PhD programs of the University of Split School of Medicine, namely Translational Research in Biomedicine (TRIBE), published full texts of all PhD theses defended at that program on its website. NSK held 2650 (90%) of the theses in a printed version. CONCLUSION: It was extremely challenging to access the list and full texts of doctoral theses defended in Croatia. Making PhD theses publicly available would ensure transparency and enable analyses that should improve scientific policy.

Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain.

Resident macrophages from dorsal root ganglia are important for the development of traumatic-induced neuropathic pain. In the first 5-7 days after a traumatic sciatic nerve injury (i.e., spinal nerve ligation (SNL), spared nerve injury (SNI), sciatic nerve transection or sciatic nerve ligation and transection), Ionized binding adapter protein 1 (Iba1) (+) resident macrophages cluster around dorsal root ganglia neurons, possibly contributing to nerve injury-induced hypersensitivity. Since infiltrating macrophages gradually recruited to the lesion site peak at about 7 days, the first few days post-lesion offer a window of opportunity when the contribution of Iba1 (+) resident macrophages to neuropathic pain pathogenesis could be investigated. Iba1 is an actin cross-linking cytoskeleton protein, specifically located only in macrophages and microglia. In this study, we explored the contribution of rat Iba1 (+) macrophages in SNL-induced neuropathic pain by using intra-ganglionic injections of naked Iba1-siRNA, delivered at the time the lesion occurred. The results show that 5 days after Iba1 silencing, Iba1 (+) resident macrophages are switched from an M1 (pro-inflammatory) phenotype to an M2 (anti-inflammatory) phenotype, which was confirmed by a significant decrease of M1 markers (CD32 and CD86), a significant increase of M2 markers (CD163 and Arginase-1), a reduced secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1ß) and an increased release of pro-regenerative factors (BDNF, NGF and NT-3) which initiated the regrowth of adult DRG neurites and reduced SNL-induced neuropathic pain. Our data show for the first time, that it is possible to induce macrophages towards an anti-inflammatory phenotype by interacting with their cytoskeleton.

Assessing the quality and completeness of reporting in health systems guidance for pandemics using the AGREE-HS tool.

Background: During health emergencies, leading healthcare organisations, such as the World Health Organization (WHO), the European Centre for Disease Control and Prevention (ECDC), and the United States Centers for Disease Control and Prevention (CDC), provide guidance for public health response. Previous studies have evaluated clinical practice guidelines (CPGs) produced in response to epidemics or pandemics, yet few have focused on public health guidelines and recommendations. To address this gap, we assessed health systems guidance (HSG) produced by the WHO, the ECDC, and the CDC for the 2009 H1N1 and COVID-19 pandemics. Methods: We extracted HSG for the H1N1 and COVID-19 pandemics from the organisations' dedicated repositories and websites. After screening the retrieved documents for eligibility, five assessors evaluated them using the Appraisal of Guidelines Research & Evaluation - Health Systems (AGREE-HS) tool to assess the completeness and transparency of reporting according to the five AGREE-HS domains: "Topic", "Participants", "Methods", "Recommendations", and "Implementability". Results: Following the screening process, we included 108 HSG in the analysis. We observed statistically significant differences between the H1N1 and COVID-19 pandemics, with HSG issued during COVID-19 receiving higher AGREE-HS scores. The HSG produced by the CDC had significantly lower overall scores and single-domain scores compared to the WHO and ECDC. However, all HSG scored relatively low, under the median of 40 total points (range = 10-70), indicating incomplete reporting. The HSG produced by all three organisations received a median score <4 (range = 1-7) for the "Participants", "Methods", and "Implementability" domains. Conclusions: There is still significant progress to be made in the quality and completeness of reporting in HSG issued during pandemics, especially regarding methodological approaches and the composition of the guidance development team. Due to their significant impact and importance for healthcare systems globally, HSG issued during future healthcare crises should adhere to best reporting practices to increase uptake by stakeholders and ensure public trust in healthcare organisations.

Changes in information-seeking patterns and perception of health crisis management in a year of COVID-19 pandemic: a repeated cross-sectional study.

AIM: To assess the changes in the health information search patterns related to the COVID-19 pandemic and the use of this information in Croatia. METHODS: This repeated cross-sectional study was based on an online survey among adults in Croatia from June 5 to July 5 2020 and from May 25 to June 15 2021. The survey inquired about demographic characteristics, health information search patterns, and emotional reactions to health information. The differences between the year 2020 and the year 2021 were assessed. RESULTS: The survey was completed by 569 respondents (median age 38.5 years) in 2020 and by 598 respondents (median age 40 years) in 2021. In 2020, institutional governmental bodies were perceived to be a reliable source of information, but this perception declined in 2021. Whereas in 2020 TV was the most used source of health-related information, online media prevailed in 2021. After one year of the pandemic, respondents attributed significantly greater importance to the reliability of the information obtained from different sources. CONCLUSION: Our results may be valuable in designing public health communication strategies and campaigns, in selecting communication channels and sources, and in tailoring health information according to the characteristics and habits of the studied population.

Creating an online educational intervention to improve knowledge about systematic reviews among healthcare workers: mixed-methods pilot study.

BACKGROUND: Lack of knowledge about systematic reviews (SRs) could prevent individual healthcare workers (HCWs) from using SRs as a source of information in their clinical practice or discourage them from participating in such research. In this study, we aimed to explore in-depth the opinion of a sample of HCWs about the newly created online educational intervention designed to improve knowledge about SRs. METHODS: We created a brief online educational intervention on SRs, consisting of 11 textual modules. We evaluated it among practicing HCWs who graduated from a university-level health sciences program using a mixed-methods pilot study that consisted of pre- and post-intervention questionnaires and qualitative evaluation via semi-structured interviews. We assessed participants' knowledge about SR methodology before and after the intervention, and compared the responses. We sought their opinions about the characteristics of SRs. Also, the participants were presented with four scientific abstracts, where they were asked to distinguish whether those abstracts presented summaries of a systematic or a non-systematic review. RESULTS: Twelve participants took part in the study. In the pilot study, the participants' knowledge about SRs was improved after the intervention compared to the baseline. Participants provided positive feedback regarding the educational intervention. Suggestions to improve the educational intervention were to provide more details about the forest plot, add more digital content or images, provide more details about the methodological steps of an SR, add descriptions about practical applications of SRs and provide links to additional educational materials. The participants suggested that HCWs could be motivated to take part in such an education if it is offered as continuing medical education (CME) course or credit for academic/career advancement. CONCLUSION: HCWs provided positive feedback about the newly designed online educational intervention on SRs; they considered it an appropriate tool for learning about SRs and resulted in increased knowledge about SRs. In addition, participants gave suggestions for improving education, which can be used to tailor the education for end-users. In future studies, it would be useful to examine the effectiveness of the modified educational intervention on increasing knowledge in a larger sample and in the form of a randomized controlled trial.

Web-Based Educational Intervention to Improve Knowledge of Systematic Reviews Among Health Science Professionals: Randomized Controlled Trial.

BACKGROUND: Lack of knowledge of systematic reviews (SRs) could prevent individual health care professionals from using SRs as a source of information in their clinical practice or discourage them from participating in such research. OBJECTIVE: In this randomized controlled trial, we evaluated the effect of a short web-based educational intervention on short-term knowledge of SRs. METHODS: Eligible participants were 871 Master's students of university health sciences studies in Croatia; 589 (67.6%) students who agreed to participate in the trial were randomized using a computer program into 2 groups. Intervention group A (294/589, 49.9%) received a short web-based educational intervention about SR methodology, and intervention group B (295/589, 50.1%) was presented with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The participants' knowledge of SRs was assessed before and after the intervention. The participants could not be blinded because of the nature of the intervention. The primary outcome was the difference in the percentage of correct answers about SR methodology per participant between the groups after the intervention, expressed as relative risk and 95% CI. RESULTS: Results from 162 and 165 participants in the educational intervention and PRISMA checklist groups, respectively, were available for analysis. Most of them (educational intervention group: 130/162, 80.2%; PRISMA checklist group: 131/165, 79.4%) were employed as health care professionals in addition to being health sciences students. After the intervention, the educational intervention group had 23% (relative risk percentage) more correct answers in the postintervention questionnaire than the PRISMA checklist group (relative risk=1.23, 95% CI 1.17-1.29). CONCLUSIONS: A short web-based educational intervention about SRs is an effective tool for short-term improvement of knowledge of SRs among health care studies students, most of whom were also employed as health care professionals. Further studies are needed to explore the long-term effects of the tested education. TRIAL REGISTRATION: OSF Registries 10.17605/OSF.IO/RYMVC; https://osf.io/rymvc.

Implantable, Programmable, and Wireless Device for Electrical Stimulation of the Dorsal Root Ganglion in Freely-Moving Rats: A Proof of Concept Study.

OBJECTIVE: This was a proof of concept study, based on systematic reviews of the efficacy and safety of the dorsal root ganglion (DRG) stimulation. The main objective was to develop an implantable, programmable, and wireless device for electrical stimulation of DRG and a methodology that can be used in translational research, especially to understand the mechanism of neuromodulation and to test new treatment modalities in animal models of pain. METHODS: We developed and tested a stimulator that uses a battery-powered microelectronic circuit, to generate constant current square biphasic or monophasic pulsed waveform of variable amplitudes and duration. It is controlled by software and an external controller that allows radio frequency communication with the stimulator. The stimulator was implanted in Sprague-Dawley (SD) rats. The lead was positioned at the L5 DRG level, while the stimulator was placed in the skin pocket at the ipsilateral side. Forty-five animals were used and divided into six groups: spinal nerve ligation (SNL), chronic compression injury of the DRG (CCD), SNL + active DRG stimulation, intact control group, group with the implanted sham stimulator, and sham lead. Behavioral testing was performed on the day preceding surgery and three times postoperatively (1st, 3rd, and 7th day). RESULTS: In animals with SNL, neurostimulation reduced pain-related behavior, tested with pinprick hyperalgesia, pinprick withdrawal test, and cold test, while the leads per se did not cause DRG compression. The rats well tolerated the stimulator. It did not hinder animal movement, and it enabled the animals to be housed under regular conditions. CONCLUSION: A proof-of-concept experiment with our stimulator verified the usability of the device. The stimulator enables a wide range of research applications from adjusting stimulation parameters for different pain conditions, studying new stimulation methods with different frequencies and waveforms to obtain knowledge about analgesic mechanisms of DRG stimulation.

Efficacy and Safety of Pulsed Radiofrequency as a Method of Dorsal Root Ganglia Stimulation in Patients with Neuropathic Pain: A Systematic Review.

OBJECTIVE: Pulsed radiofrequency (PRF) is a nonablative pain treatment that uses radiofrequency current in short high-voltage bursts, resulting in interruption of nociceptive afferent pathways. We conducted a systematic review with the aim to create a synthesis of evidence about the efficacy and safety of PRF applied to the dorsal root ganglion (DRG) for the treatment of neuropathic pain. METHODS: We searched MEDLINE, CINAHL, Embase, and PsycINFO through January 8, 2019, as well as ClinicalTrials.gov and the clinical trial register of the World Health Organization. All study designs were eligible. We assessed risk of bias using the Cochrane tool for randomized controlled trials and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). We assessed level of evidence using the Oxford tool and quality of evidence with GRADE. RESULTS: We included 28 studies with participants suffering from lumbosacral, cervical, or thoracic radicular pain, post-herpetic neuralgia, neuropathicbone pain in cancer patients, or carpal tunnel syndrome. Only five studies were randomized controlled trials (RCTs), while others were of nonrandomized designs, predominantly before and after comparisons. A total of 991 participants were included, with a median number (range) of 31 (1-101) participants. Only 204 participants were included in the RCTs, with a median number (range) of 38 (23-62) participants. The overall quality of evidence was low, as the majority of the included studies were rated as evidence level 4 or 5. The quality of evidence was very low. CONCLUSIONS: Evidence about the efficacy and safety of PRF of the DRG for the treatment of neuropathic pain is based mainly on results from very small studies with low evidence quality. Current research results about the benefits of PRF of the DRG for the treatment of neuropathic pain should be considered preliminary and confirmed in high-quality RCTs with sufficient numbers of participants.

Efficacy and safety of pulsed radiofrequency as a method of dorsal root ganglia stimulation for treatment of non-neuropathic pain: a systematic review.

BACKGROUND: We systematically reviewed the evidence on the efficacy and safety of dorsal root ganglion (DRG) targeted pulsed radiofrequency (PRF) versus any comparator for treatment of non-neuropathic pain. METHODS: We searched MEDLINE, CINAHL, Embase, PsycINFO, clinicaltrials.gov and WHO clinical trial register until January 8, 2019. All study designs were eligible. Two authors independently conducted literature screening. Primary outcomes were pain intensity and serious adverse events (SAEs). Secondary outcomes were any other pain-related outcome and any other safety outcome that was reported. We assessed the risk of bias using the Cochrane tool and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I). We conducted narrative evidence synthesis and assessed the conclusiveness of included studies regarding efficacy and safety. RESULTS: We included 17 studies with 599 participants, which analyzed various pain syndromes. Two studies were randomized controlled trials; both included participants with low back pain (LBP). Non-randomized studies included patients with the following indications: LBP, postsurgical pain, pain associated with herpes zoster, cervicogenic headache, complex regional pain syndrome type 1, intractable vertebral metastatic pain, chronic scrotal and inguinal pain, occipital radiating pain in rheumatoid arthritis and chronic migraine. In these studies, the PRF was usually initiated after other treatments have failed. Eleven studies had positive conclusive statements (11/17) about efficacy; the remaining had positive inconclusive statements. Only three studies provided conclusiveness of evidence statements regarding safety - two indicated that the evidence was positive conclusive, and one positive inconclusive. The risk of bias was predominantly unclear in randomized and serious in non-randomized studies. CONCLUSION: Poor quality and few participants characterize evidence about benefits and harms of DRG PRF in patients with non-neuropathic pain. Results from available studies should only be considered preliminary. Not all studies have reported data regarding the safety of the intervention, but those that did, indicate that the intervention is relatively safe. As the procedure is non-destructive and early results are promising, further comparative studies about PRF in non-neuropathic pain syndromes would be welcomed.

Overactive bladder symptoms in patients undergoing rigid and flexible cystoscopy.

PURPOSE: To evaluate overactive bladder (OAB) symptoms in patients undergoing diagnostic cystoscopy. Overall changes in the entire study population were assessed, as well as broken down by various subgroups. METHODS: A prospective multi-center study among consecutive 450 adults undergoing diagnostic cystoscopy was conducted. OAB-symptoms were evaluated with the validated eight-item OAB Screening Awareness Tool (OAB-V8) immediately before and on days 1, 4, and 7 after cystoscopy. Patients were distinguished between being OAB-negative and OAB-positive (< 8 and ≥ 8 sum-score, respectively). Average sum-scores and subdomains were evaluated. RESULTS: Before cystoscopy, 44.7% of patients were screened OAB-positive and 55.3% OAB-negative. Out of those being screened negative, development of de-novo OAB was noticed in 16.8%, declining to 8.1% on day 7 (p < 0.001). In patients being OAB-positive before cystoscopy, a decline of OAB-positivity was noted during follow-up (p < 0.001). No statistically significant differences were noted when broken down by gender (p = 0.92), age (p = 0.82) and type cystoscope (rigid vs. flexible, p = 0.38). Average sum-scores declined from 8.68 before cystoscopy to 6.9 during follow-up. Flexible cystoscopy was superior over rigid in four subdomains: uncomfortable urge to urinate (p = 0.04), sudden urge to urinate with little or no warning (p = 0.02), uncontrollable urge to urinate (p = 0.03), and urine loss associated with a strong desire to void (p = 0.009). CONCLUSION: OAB-symptoms are common in patients undergoing cystoscopy. Cystoscopy itself can cause de-novo OAB-symptoms. Controversially, a decline of OAB-symptoms was noted after cystoscopy when patients were screened OAB-positive before cystoscopy. Flexible scopes were superior in some subdomains.

Neuromodulation with electrical field stimulation of dorsal root ganglion in various pain syndromes: a systematic review with focus on participant selection.

OBJECTIVE: We conducted a systematic review about patient selection, efficacy, and safety of neuromodulation with electrical field stimulation (EFS) of dorsal root ganglion (DRG) in various painful conditions. We also analyzed conclusion statements as well as conflict of interest and financing of the included studies. METHODS: All study designs were eligible for inclusion. We searched MEDLINE, CINAHL, Embase, PsycINFO, and clinical trial registries until September 7, 2018. We assessed risk of bias by using Cochrane tool for randomized controlled trials (RCTs). RESULTS: Among the 29 included studies, only one was RCT, majority being case series and case reports. The evidence is based on studies with small number of participants (median: 6, range 1-152) with various painful conditions. Neuromodulation with EFS of DRG was mostly performed in participants who have failed other treatment modalities. Most of the authors of the included studies reported positive, but inconclusive, evidence regarding efficacy of neuro-modulation with EFS of DRG. Meta-analysis was not possible since only one RCT was included. CONCLUSION: Available evidence suggest that neuromodulation with EFS of DRG may help highly selected participants with various pain syndromes, who have failed to achieve adequate pain relief with other pharmacological and nonpharmacological interventions. However, these findings should be confirmed in high-quality RCTs with sufficient numbers of participants.

The Medical School of the Catholic University of Croatia: Principles, Goals, Standards and Organization.

The aim of the study was to present the concept on which the School of Medicine at the Catholic University of Croatia (CUC) will be established. The new School will alleviate the shortage of physicians in Croatia and introduce an innovative form of medical education focused on principles of patient-centered care and social accountability. At the same time, the students will acquire all relevant competencies and levels of knowledge, skills and attitudes that are required by current evidence in medical education, European standards and guidelines for quality assurance at higher education institutions. The four pillars of the CUC Medical School are: 1) distributed medical education that involves health institutions outside major medical centers, 2) the concept of transformative learning, 3) teaching and practicing evidence-based medicine, and 4) implementation of quality management principles supported by information technology solutions for effective management of learning, research and practice. The overall aim of the CUC School of Medicine is to educate and train physicians capable of using best available medical evidence to deliver economically sustainable healthcare that can improve equity and health outcomes in the communities they serve, particularly those that are currently underserved. CONCLUSION: The proposed programme is introducing an original system of modern medical education that insists on developing humanistic aspects of medicine, patient-centred care and social accountability, while maintaining all competencies and knowledge levels that a physician should have according to the current understanding of medical education.

Electrical Stimulation of Dorsal Root Ganglion in the Context of Pain: A Systematic Review of In Vitro and In Vivo Animal Model Studies.

OBJECTIVE: Dorsal root ganglion (DRG) has recently emerged as an attractive target for neuromodulation therapy since primary sensory neurons and their soma in DRGs are important sites for pathophysiologic changes that lead to neuropathic pain. Our aim was to create evidence synthesis about the effects of electrical stimulation of DRG in the context of pain from in vitro and in vivo animal models, analyze methodology and quality of studies in the field. METHODS: For conducting systematic review we searched three data bases: MEDLINE, Embase and Web of Science. The quality of included studies was assessed with the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool for animal studies. The study was registered in the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies data base. RESULTS: We included six in vitro and eight in vivo animal studies. All included in vitro studies combined neurostimulation with substances or drugs and reported an improvement in pain-related parameters due to neurostimulation. Among in vivo studies, six used pulsed radiofrequency, while two used electrical field stimulation. All in vivo studies reported improvement in pain-related behavior following stimulation. Meta-analysis was not possible because of heterogeneity and missing data. The quality of included studies was suboptimal since all had an unclear risk of bias in multiple domains. CONCLUSIONS: Limited data from in vitro and in vivo animal studies indicate that electrical stimulation of DRG has a positive therapeutic effect in the context of pain-related outcomes. Further studies with a standardized methodological approach and outcomes will provide useful information about electrical stimulation of DRG in animal models.

Acceptance of a systematic review as a thesis: survey of biomedical doctoral programs in Europe.

BACKGROUND: Systematic reviews (SRs) have been proposed as a type of research methodology that should be acceptable for a graduate research thesis. The aim of this study was to analyse whether PhD theses in European biomedical graduate programs can be partly or entirely based on SRs. METHODS: In 2016, we surveyed individuals in charge of European PhD programs from 105 institutions. The survey asked about acceptance of SRs as the partial or entire basis for a PhD thesis, their attitude towards such a model for PhD theses, and their knowledge about SR methodology. RESULTS: We received responses from 86 individuals running PhD programs in 68 institutions (institutional response rate of 65%). In 47% of the programs, SRs were an acceptable study design for a PhD thesis. However, only 20% of participants expressed a personal opinion that SRs meet the criteria for a PhD thesis. The most common reasons for not accepting SRs as the basis for PhD theses were that SRs are 'not a result of a PhD candidate's independent work, but more of a team effort' and that SRs 'do not produce enough new knowledge for a dissertation'. The majority of participants were not familiar with basic concepts related to SRs; questions about meta-analyses and the type of plots frequently used in SRs were correctly answered by only one third of the participants. CONCLUSIONS: Raising awareness about the importance of SRs and their methodology could contribute to higher acceptance of SRs as a type of research that forms the basis of a PhD thesis.

Improving completion rates of students in biomedical PhD programs: an interventional study.

BACKGROUND: Analysis of graduation success at the University of Split School of Medicine PhD programs conducted in 2011 revealed that only 11% of students who enrolled and completed their graduate coursework between 1999 and 2011 earned a doctoral degree. In this prospective cohort study we evaluated and compared three PhD programs within the same medical school, where the newest program, called Translational Research in Biomedicine (TRIBE), established in the academic year 2010/11, aimed to increase the graduation rate through an innovative approach. METHODS: The intervention in the new program was related to three domains: redefined recruitment strategy, strict study regulations, and changes to the curriculum. We compared performance of PhD students between the new and existing programs and analyzed their current status, time to obtain a degree (from enrolment to doctorate), age at doctorate, number of publications on which the thesis was based and the impact factor of journals in which these were published. RESULTS: These improvement strategies were associated with higher thesis completion rate and reduced time to degree for students enrolled in the TRIBE program. There was no change in the impact factor or number of publications that were the basis for the doctoral theses. CONCLUSION: Our study describes good practices which proved useful in the design or reform of the PhD training program.

Methodological and Reporting Quality of Systematic Reviews Published in the Highest Ranking Journals in the Field of Pain.

BACKGROUND: Systematic reviews (SRs) are important for making clinical recommendations and guidelines. We analyzed methodological and reporting quality of pain-related SRs published in the top-ranking anesthesiology journals. METHODS: This was a cross-sectional meta-epidemiological study. SRs published from 2005 to 2015 in the first quartile journals within the Journal Citation Reports category Anesthesiology were analyzed based on the Journal Citation Reports impact factor for year 2014. Each SR was assessed by 2 independent authors using Assessment of Multiple Systematic Reviews (AMSTAR) and Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) tools. Total score (median and interquartile range, IQR) on checklists, temporal trends in total score, correlation in total scores between the 2 checklists, and variability of those results between journals were analyzed. RESULTS: A total of 446 SRs were included. Median total score of AMSTAR was 6/11 (IQR: 4-7) and of PRISMA 18.5/27 (IQR: 15-22). High compliance (reported in over 90% SRs) was found in only 1 of 11 AMSTAR and 5 of 27 PRISMA items. Low compliance was found for the majority of AMSTAR and PRISMA individual items. Linear regression indicated that there was no improvement in the methodological and reporting quality of SRs before and after the publication of the 2 checklists (AMSTAR: F(1,8) = 0.22; P = .65, PRISMA: F(1,7) = 0.22; P = .47). Total scores of AMSTAR and PRISMA had positive association (R = 0.71; P < .0001). CONCLUSIONS: Endorsement of PRISMA in instructions for authors was not a guarantee of compliance. Methodological and reporting quality of pain-related SRs should be improved using relevant checklists. This can be remedied by a joint effort of authors, editors, and peer reviewers.

Characterization of dorsal root ganglion neurons cultured on silicon micro-pillar substrates.

Our study focuses on characterization of dorsal root ganglion (DRG) neurons cultured on silicon micro-pillar substrates (MPS) with the ultimate goal of designing micro-electrode arrays (MEAs) for successful electrophysiological recordings of DRG neurons. Adult and neonatal DRG neurons were cultured on MPS and glass coverslips for 7 days in vitro. DRG neuronal distribution and morphometric analysis, including neurite alignment and length, was performed on MPS areas with different pillar width and spacing. We showed that MPS provide an environment for growth of adult and neonatal DRG neurons as permissive as control glass surfaces. Neonatal DRG neurons were present on MPS areas with narrow pillar spacing, while adult neurons preferred wider pillar spacing. Compared to the control glass surfaces the neonatal and adult DRG neurons in regions with narrow pillar spacing range developed a smaller number of longer neurites. In the same area, neurites were preferentially oriented along three directional axes at 30°, 90° and 150°. MPS architecture influenced growth directionality of all main DRG neuronal subtypes. We can conclude that specific micro-pillar substrate topography affects the morphology of DRG neurons. This knowledge can enable development of MEAs with precisely defined physical features for various neuroscience applications.

The business process management software for successful quality management and organization: A case study from the University of Split School of Medicine.

OBJECTIVE: Our aim was to describe a comprehensive model of internal quality management (QM) at a medical school founded on the business process analysis (BPA) software tool. METHODS: BPA software tool was used as the core element for description of all working processes in our medical school, and subsequently the system served as the comprehensive model of internal QM. RESULTS: The quality management system at the University of Split School of Medicine included the documentation and analysis of all business processes within the School. The analysis revealed 80 weak points related to one or several business processes. CONCLUSION: A precise analysis of medical school business processes allows identification of unfinished, unclear and inadequate points in these processes, and subsequently the respective improvements and increase of the QM level and ultimately a rationalization of the institution's work. Our approach offers a potential reference model for development of common QM framework allowing a continuous quality control, i.e. the adjustments and adaptation to contemporary educational needs of medical students.

Management of teaching processes using the Share point platform: A case study from the University of Split School of Medicine.

OBJECTIVE: To develop a software tool that will combine teaching timetables with the generation of reports on teaching load. METHODS: The University of Split School of Medicine project team and the external experts from the company LAMA, LLC. determined necessary functionalities and developed the software platform as an extension of the existing software solutions already in use by the Croatian academic community. RESULTS: By combining comprehensive scheduling functionality with planned and performed teaching activities we determined the teaching load and realized automatic generation of payments for adjunct lecturers. The implementation required perfecting of the human resources services, brought about a manifold alleviation of the work of the entire school's administration and substantially increased the effectiveness of the quality management. The software is currently managing 54,676 teaching hours, 841 teaching staff member, 111 teaching rooms, 8 study programs, and 645 courses. CONCLUSION: The program resolved several administrative problems of the school and is an example of successful implementation of IT technology in medical school management.