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Aim To investigate the serum value of brain derived neurotrophic factor (BDNF), proteins S-100, NSE, IL-6 in normal pressure patients (NPH) compared to control (healthy) group and also a possible correlation with radiological findings in NPH patients. Methods Study patients were included during the period of 2020- 2022. All NPH patients met the diagnostic criteria for probability of NPH. Control patients group included patients without known brain disorder, without clinical symptoms of NPH. Blood samples were taken before planned surgery for NPH. BDNF serum concentrations were assessed by a sensitive ELISA kit, and serum concentrations of S-100, NSE and IL-6 were assessed by using ECLIA technology for immunoassay detection. Results Among 15 patients who were included, seven NPH patients were compared to eight control patients. Non-significant decrease in BDNF serum concentrations, an increase of protein S-100 serum concentrations, a decrease of NSE serum concentrations, as well as an increase of IL-6 serum concentrations in NPH patients compared to healthy controls was found. Strong positive correlation between BNDF and Evans index was observed (p=0.0295). Conclusion We did not find a significant difference of BDNF, protein S-100, IL-6 and NSE between serum concentration in NPH and healthy patients. More future research is needed to find the role of BDNF in NPH patients.

F. Spagnolo, A. Depeursinge, Sabine Schädelin, Aysenur Akbulut, H. Müller, M. Barakovic, L. Melie-García, M. Bach Cuadra et al.

Mirsad Serdarević, M. Cvitanovich, Brooke R. MacDonald, J. D'Etienne, Dustin S DeMoss, R. Ojha

STUDY OBJECTIVES Little is known about the effectiveness of bridge clinics as transitional care programs for people with opioid use disorder in emergency departments (EDs). We assessed the effect of bridge clinic referral on health services use among patients with opioid use disorder identified in the ED. METHODS We used data for individuals aged 18 years and over with active opioid use disorder and no history of medication for opioid use disorder who were administered medication for opioid use disorder while in the ED between January 2013 and August 2022. Bridge clinic referrals started in January 2021. Eligible patients after this date comprised the intervention group. The usual care group included eligible patients before bridge clinic implementation, who were a 1:1 propensity score matched to intervention patients. We estimated risk differences and 95% confidence limits for linkage to long-term care, ED use, and inpatient admission within 120 days of the index ED visit. RESULTS Our study population comprised 928 observations after matching. Patients referred to the bridge clinic had a higher risk of linkage to long-term care (risk differences=25%; 95% confidence limits: 20%, 30%), higher risk of ED use (risk differences=7.5%, 95% confidence limits: 1.6%, 13%), and lower risk of inpatient admission (risk differences= -1.9%, 95% confidence limits: -5.9%, 2.1%). Inpatient admission increased among patients with serious mental illness but decreased among patients without serious mental illness. CONCLUSION Our overall results suggest that bridge clinic referral increases linkage to long-term care. Nevertheless, qualitatively different effects on inpatient admission between patients with and without serious mental illness warrant consideration of unmet needs among patients with serious mental illness.

Aim The two most commonly used implants for treatment of trochanteric fractures are the dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA). The aim of this study was to evaluate blood loss in patients with trochanteric fracture treated with DHS or PFNA. Methods This retrospective comparative study included 61 patients with trochanteric fracture, who were divided according to a surgical method into DHS and PFNA groups. In the PFNA group, a short third generation gamma-nail was used for osteosynthesis (Supernail GT, Lima Corporate, Italy), and in the DHS group a dynamic hip screw was used (Synthes, Oberdorf, Switzerland). Complete blood count with haemoglobin and haematocrit values was taken preoperatively and on the first day postoperatively and a number of red blood cell transfusions (RBC) were evaluated. Electronic medical records from 2022 were used to collect patient data. Results There were no significant differences in terms of gender and age between the groups (p=0.510 and p=0.087, respectively), as well as in the fracture type distribution (p=0.886). The duration of postoperative hospitalisation was similar between the groups (p=0.643). There was no statistically significant association between the number of RBC transfusions and fixation method (p=0.091), as well as in postoperative haemoglobin and haematocrit levels between the groups (p=0.180 and p=0.225, respectively). Conclusion Both DHS and PFNA implants are safe surgical techniques for the treatment of trochanteric fractures, with similar blood loss, number of blood transfusions and hospital stay.

D. Dujak, A. Karac, Z. Jakšić, S. Vrhovac, L. Budinski-Petković

Percolation properties of an adsorbed polydisperse mixture of extended objects on a triangular lattice are studied by Monte Carlo simulations. The depositing objects of various shapes are formed by self-avoiding walks on the lattice. We study polydisperse mixtures in which the size ℓ of the shape making the mixture increases gradually with the number of components. This study examines the influence of the shape of the primary object defining a polydisperse mixture on its percolation and jamming properties. The dependence of the jamming density and percolation threshold on the number of components n making the mixture is analyzed. Determining the contribution of the individual components in the lattice covering allowed a better insight into the deposit structure of the n-component mixture at the percolation threshold. In addition, we studied mixtures of objects of various shapes but the same size.

M. F. Basso, F. Contaldi, F. Celso, E. Karalija, L. Paz-Carrasco, G. Barone, António Ferrante, F. Martinelli

Carotenoid cleavage dioxygenase (CCD) gene family is organized in two subfamilies: (i) 9-cis epoxycarotenoid dioxygenase (NCED) genes and (ii) CCD genes. NCED genes are essential for catalyzing the first step of the abscisic-acid (ABA) biosynthesis, while CCD genes produce precursors of the strigolactones hormone. The functional characterization of these gene subfamilies has not been yet performed in chickpea and lentil. Herein, were identified and systematically characterized two NCED and five CCD genes in the chickpea and two NCED and six CCD genes in lentil. After in silico sequence analysis and phylogeny, the expression profile of the NCED/CCD genes was determined by meta-analysis and real-time PCR in plants under different stress conditions. Sequence data revealed that NCED/CCD genes are highly conserved between chickpea and lentil. This conservation was observed both at gene and protein sequence levels and phylogenetic relationships. Analysis of the promoter sequences revealed that all NCED/CCD genes have a considerable number of cis-regulatory elements responsive to biotic and abiotic stress. Protein sequence analysis evidenced that NCED/CCD genes share several conserved motifs and that they have a highly interconnected interaction network. Furthermore, the three-dimensional structure of these proteins was determined and indicated that some proteins have structures with considerable similarity. The meta-analysis revealed that NCED/CCD genes are dynamically modulated in different organs and under different stress conditions, but they have a positive correlation with plant tolerance. In accordance, real-time PCR data showed that both NCED and CCD genes are differentially modulated in plants under drought stress. Particularly, CaNCED2, CaCCD5, LcNCED2, LcCCD1, and LcCCD2 genes have a positive correlation with improved plant tolerance to drought stress. Therefore, this study presented a detailed characterization of the chickpea and lentil NCED/CCD genes and provided new insights to improve abiotic stress tolerance in these two important crops.

Danique J. I. Heuvelings, A. Wintjens, L. Moonen, S. Engelen, I. D. de Hingh, L. V. Valkenburg-van Iersel, M. den Dulk, Jan Beckervordersandforth et al.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.

Objective. This study aimed to analyze the crown and root morphology of maxillary and mandibular third molars, and assess their position in relation to adjacent anatomical structures using clinical examination and radiographic images. Materials and Methods. A total of 176 extracted impacted or partially impacted third molars were included in this study. Orthopantomogram images (OPG) were used to evaluate the number of roots, position, depth of impaction relative to the occlusal plane of the second molar, and angulation of maxillary and mandibular third molars. The extracted teeth were examined to determine the actual number of roots. The root morphology was classified using the Alavi classification system for maxillary third molars and the Machado classification for mandibular third molars. Additionally, the number of cusps, crown dimensions, and morphology were analyzed using digital and dental calipers. Results. The extracted samples exhibited a significantly higher number of roots compared to the number assessed on OPG images (P<0.001). The majority of mandibular third molars had two fused roots (37.39%) and a five-cuspid crown (48.70%), while maxillary third molars had three fused roots (26.23%) and four cusps (42.62%). Both maxillary (60.66%) and mandibular third molars (61.74%) were predominantly vertically positioned. Regarding the depth of impaction, maxillary third molars were primarily classified as Class C (65.57%), while mandibular third molars were classified as Class B (47.83%). Differences in crown shape were observed, with maxillary crowns being mostly triangular (36.07%) and mandibular crowns being oval (38.26%). Maxillary third molars had shorter crowns compared to mandibular third molars (P<0.05). Conclusion. The root morphology of maxillary and mandibular third molars in the population of Bosnia and Herzegovina displays variability. Orthopantomogram imaging was found to be inadequate for accurate determination of the number of roots in third molars. The number of cusps on third molars cannot be relied upon as a predictor of the number of roots. The study’s findings will have implications for dental practice, particularly for oral surgeons and restorative dentists.

H. Y. Wunrow, Rose G. Bender, Avina Vongpradith, Sarah Brooke Sirota, Lucien R. Swetschinski, Amanda Novotney, Authia Gray, K. Ikuta et al.

Summary Background Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories. Methods We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category. Findings In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000–277 000) and 2·51 million (2·11–2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400–145 000) and 1·28 million incident cases (0·947–1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6–8·4) per 100 000 population in 1990 to 3·3 (2·8–3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1–19·2]), followed by N meningitidis (13·6% [12·7–14·4]) and K pneumoniae (12·2% [10·2–14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5–81·8]), followed by N meningitidis (72·3% [64·4–78·5]) and viruses (58·2% [47·1–67·3]). Interpretation Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment. Funding Bill & Melinda Gates Foundation.

Fatima Efendic, S. Krohn, H. M. Escobar, S. Venkateswaran, S. Bennett, Andreas Hermann, M. Frech

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a hereditary neurodegenerative disease caused by mutations in the FA2H gene. Patients show a wide range of neurological symptoms and an abnormal myelination. Here we describe the generation of the human induced pluripotent stem cell (hiPSC) lines AKOSi011-A and AKOSi012-A, derived from FAHN-patient fibroblasts, carrying the compound heterozygous mutation p.Pro65Ser/p.Asp35Tyr and the homozygous mutation p.Tyr231His, respectively. The hiPSC lines were generated using a non-integrating Sendai virus. The obtained hiPSCs show an unobtrusive karyotype, carry the mutations of the original fibroblasts, express pluripotency markers and can differentiate into cells of the three germ layers.

The constant worsening of antimicrobial resistance (AMR) imposes the need for an urgent response. Use of antibiotics (AB), both due to irrational prescribing by doctors and irrational use by patients, is recognized as one of the leading causes of this problem. This study aimed to identify knowledge, attitudes, and practices about AB use and AMR within the general population, stratified by age, gender, and urban/rural areas during the COVID-19 pandemic. This questionnaire-based cross-sectional study was conducted in April 2022 among patients who visited three health centers in the eastern region of Bosnia and Herzegovina. A high frequency of AB use was observed during the COVID-19 pandemic (64.2% of respondents were treated with AB). Age and place of residence have not been shown to be factors associated with AB use practices that pose a risk for AMR. However, female gender (β = 0.063; p = 0.041), better knowledge (β = 0.226; p < 0.001), and positive attitudes (β = 0.170; p < 0.001) about use of AB and towards to AMR proved to be factors associated with better practice by respondents. Women, younger respondents, and respondents from urban areas showed better knowledge, attitudes, and behavior about the use of AB and AMR during the COVID-19 pandemic.

O. A. Nicholson, Cornelia G. F. van Lanschot, B. N. van den Besselaar, Y. Aaboubout, T. Iseli, J. Hardillo, H. Mast, L. McDowell et al.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

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