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Mucosal and systemic antibody responses to pneumococcal capsular polysaccharide were studied in 17 children with culture-verified pneumococcal acute otitis media. Serotype-specific antibody-secreting cells (ASCs) in peripheral blood and antibodies in acute and convalescent sera and nasopharyngeal aspirates were measured. A polysaccharide-specific ASC response was induced in all subjects. The response was age dependent, and the dominant antibody class was IgA. Three children > 24 months old had > 100 IgA-class ASCs/10(6) cells and serum and nasopharyngeal IgA responses; 2 had only a nasopharyngeal IgA response. None of 8 children < 24 months old showed a systemic response; however, a nasopharyngeal IgA response was detected in 1. Results suggest that whole pneumococci can induce a mucosal polysaccharide-specific antibody response independent of the systemic response. Results are also in accordance with earlier studies suggesting that the mucosal immune system matures earlier in life than does the systemic immune response. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate childhood bacterial meningitis (BM): incidence, clinical presentation, causative pathogens, diagnostics, and outcome (neurological sequelae, hearing loss, and death). A retrospective review of all children aged ≤ 16 years and 1 month diagnosed with BM at a tertiary children's centre in the period 2010-2020. The Glasgow Outcome Scale (GOS) was used to assess outcome, with a GOS score of 1-4 considered to be an unfavourable outcome. Logistic regression univariate analysis was used to determine predefined risk factors for death, unfavourable outcome, and long-term neurological sequelae. Seventy-four patients (44 males) with a median age of 8.0 months (range 1 day to 16 years and 1 month) and 77 BM episodes were included in the study. The average incidence rate of BM was 2.2/100,000/year, the majority (91%) being community-acquired BM. Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens 12/77 (16%) each. Neurological sequelae at discharge were present in 24 (34%) patients, unfavourable outcome in 19 (25%), and hearing loss (deafness) in two (3%) survivors of BM. Seven (9%) patients died. Long-term neurological sequelae were observed in 19/60 (32%), aphasia/dysphasia being the most common in 10 (17%) BM children. No independent risk factors were identified for long-term neurological sequelae in univariate analysis., Conclusion: The risk for a fatal course of BM is still remarkable. Neurological sequelae persisted in a substantial proportion of BM survivors in long-term follow-up, aphasia/dysphasia being the most common. Hearing loss (deafness) occurred in 3%. However, no specific risk factors predicting the long-term sequelae were found., What Is Known: • Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens causing bacterial meningitis. • Risk for fatal course of bacterial meningitis (BM) remains remarkable despite advances in modern medicine., What Is New: • In long-term follow-up, 1/3 of BM children suffered from neurological sequelae in the 2010s, aphasia and dysphasia being the most common sequelae. • Hearing loss was diagnosed in only two (3%) children, whom of both were deaf., (© 2024. The Author(s).)

Background: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas., Methods: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 10 6 /L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84)., Results: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association., Conclusions: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries., (© 2024. The Author(s).)

Introduction: Balloon Eustachian tuboplasty (BET) is used to treat obstructive Eustachian tube dysfunction (OETD) and recurrent otitis media with effusion (OME). However, there are no indisputable evidence of its efficacy. Here, we present a multicenter, double-blinded, randomized, placebo-controlled trial (MDRCT) design to evaluate the efficacy of BET, and the results of a pilot trial with 3- and 12-months' follow-up., Material and Methods: This was a prospective MDRCT. For a pilot study, OETD (n = 10) and OME (n = 5) patients were recruited and followed. Detailed inclusion and exclusion criteria were used. Participants were randomized at beginning of the operation to active or sham surgery. All procedures were performed under local anesthesia. Controls were performed in double-blinded manner (both patient and physician), at 3 and 12 months after the procedure., Results: Altogether, 20 ears were treated and followed for 12 months, including 14 active BETs and 6 sham surgeries. Both the active and sham surgery were performed under local anesthesia without problems or deviations from the protocol. There were no differences in the preoperative symptoms (ETDQ-7) or objective measures (tympanometry, Valsalva and Toynbee maneuvers, tubomanometry, Eustachian tube score) between active and sham surgery arms. During follow-up, we noticed largely similar reduction in subjective symptoms and improvement in Eustachian tube score both in active and sham surgery arms., Conclusions: The pilot study demonstrates that our MDRCT protocol is feasible, and that blinded RCTs are dearly needed to objectively measure the efficacy of BET., Level of Evidence: 2 Laryngoscope, 134:1874-1881, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: This study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM)., Methods: The medical records of patients under 16 years of age, treated by Turku University Hospital, Finland, from 2011 to 2018, were screened for meningitis using the International Classification of Diseases, Tenth Revision codes. Patients were included if bacteria were detected in cerebrospinal fluid (CSF) or other predefined laboratory variables indicated BM, despite CSF testing negative for bacteria. The Glasgow Outcome Scale (GOS) was used to determine outcomes., Results: We identified 37 children with BM: 22 infants aged 0-89 days and 15 children aged 90 days to 15 years. The overall incidence was approximately 5.7/100 000/year. Nosocomial meningitis was documented in 51%. Bacterial growth was detected in the CSF or blood cultures of the majority of patients (57%). Escherichia coli (14%), group B streptococcus (11%) and Streptococcus pneumoniae (8%) were the most common pathogens. There were 14% of patients with unfavourable outcomes, namely GOS scores of 1-4, but no deaths., Conclusion: The incidence of paediatric BM was low during the study period, but the proportion of nosocomial meningitis was substantial. The frequency of unfavourable long-term outcomes was relatively low., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Non-muscle myosin II activation by regulatory light chain (Rlc1 Sp ) phosphorylation at Ser35 is crucial for cytokinesis during respiration in the fission yeast Schizosaccharomyces pombe. We show that in the early divergent and dimorphic fission yeast S. japonicus non-phosphorylated Rlc1 Sj regulates the activity of Myo2 Sj and Myp2 Sj heavy chains during cytokinesis. Intriguingly, Rlc1 Sj -Myo2 Sj nodes delay yeast to hyphae onset but are essential for mycelial development. Structure-function analysis revealed that phosphorylation-induced folding of Rlc1 Sp α1 helix into an open conformation allows precise regulation of Myo2 Sp during cytokinesis. Consistently, inclusion of bulky tryptophan residues in the adjacent α5 helix triggered Rlc1 Sp shift and supported cytokinesis in absence of Ser35 phosphorylation. Remarkably, unphosphorylated Rlc1 Sj lacking the α1 helix was competent to regulate S. pombe cytokinesis during respiration. Hence, early diversification resulted in two efficient phosphorylation-independent and -dependent modes of Rlc1 regulation of myosin II activity in fission yeasts, the latter being conserved through evolution., Competing Interests: The authors declare no competing interests., (© 2023 Universidad de Murcia.)

Plastics are essential materials for modern societies, but their production contributes to significant environmental issues. Power-to-X processes could produce plastics from captured CO 2 and hydrogen with renewable electricity, but these technologies may also face challenges from environmental perspective. This paper focuses on environmental sustainability assessment of CO 2 -based low-density polyethylene (LDPE) compared to bio-based LDPE. Life cycle assessment has been applied to study climate impacts and land use related biodiversity impacts of different plastic production scenarios. According to the climate impact results, the carbon footprint of the produced plastic can be negative if the energy used is from wind, solar, or bioenergy and the carbon captured within the plastic is considered. In terms of biodiversity, land-use related biodiversity impacts seem to be lower from CO 2 -based polyethylene compared to sugarcane-based polyethylene. Forest biomass use for heat production in CO 2 -based polyethylene poses a risk to significantly increase biodiversity impacts. Taken together, these results suggest that CO 2 -based LDPE produced with renewable electricity could reduce biodiversity impacts over 96 % while carbon footprint seems to be 6.5 % higher when compared to sugarcane-based polyethylene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Macroautophagy/autophagy is an essential adaptive physiological response in eukaryotes induced during nutrient starvation, including glucose, the primary immediate carbon and energy source for most cells. Although the molecular mechanisms that induce autophagy during glucose starvation have been extensively explored in the budding yeast Saccharomyces cerevisiae , little is known about how this coping response is regulated in the evolutionary distant fission yeast Schizosaccharomyces pombe . Here, we show that S. pombe autophagy in response to glucose limitation relies on mitochondrial respiration and the electron transport chain (ETC), but, in contrast to S. cerevisiae , the AMP-activated protein kinase (AMPK) and DNA damage response pathway components do not modulate fission yeast autophagic flux under these conditions. In the presence of glucose, the cAMP-protein kinase A (PKA) signaling pathway constitutively represses S. pombe autophagy by downregulating the transcription factor Rst2, which promotes the expression of respiratory genes required for autophagy induction under limited glucose availability. Furthermore, the stress-activated protein kinase (SAPK) signaling pathway, and its central mitogen-activated protein kinase (MAPK) Sty1, positively modulate autophagy upon glucose limitation at the transcriptional level through its downstream effector Atf1 and by direct in vivo phosphorylation of Rst2 at S292. Thus, our data indicate that the signaling pathways that govern autophagy during glucose shortage or starvation have evolved differently in S. pombe and uncover the existence of sophisticated and multifaceted mechanisms that control this self-preservation and survival response.

Cytokinesis, the separation of daughter cells at the end of mitosis, relies in animal cells on a contractile actomyosin ring (CAR) composed of actin and class II myosins, whose activity is strongly influenced by regulatory light chain (RLC) phosphorylation. However, in simple eukaryotes such as the fission yeast Schizosaccharomyces pombe , RLC phosphorylation appears dispensable for regulating CAR dynamics. We found that redundant phosphorylation at Ser35 of the S. pombe RLC homolog Rlc1 by the p21-activated kinases Pak1 and Pak2, modulates myosin II Myo2 activity and becomes essential for cytokinesis and cell growth during respiration. Previously, we showed that the stress-activated protein kinase pathway (SAPK) MAPK Sty1 controls fission yeast CAR integrity by downregulating formin For3 levels (Gómez-Gil et al., 2020). Here, we report that the reduced availability of formin For3-nucleated actin filaments for the CAR is the main reason for the required control of myosin II contractile activity by RLC phosphorylation during respiration-induced oxidative stress. Thus, the restoration of For3 levels by antioxidants overrides the control of myosin II function regulated by RLC phosphorylation, allowing cytokinesis and cell proliferation during respiration. Therefore, fine-tuned interplay between myosin II function through Rlc1 phosphorylation and environmentally controlled actin filament availability is critical for a successful cytokinesis in response to a switch to a respiratory carbohydrate metabolism., Competing Interests: FP, EG, RM, AP, JV, AF, TS, PP, MM, JC No competing interests declared, (© 2023, Prieto-Ruiz et al.)

Background: Bacterial meningitis (BM) causes significant morbidity and mortality. We investigated predisposing factors, clinical characteristics, spectrum of etiological bacteria, and clinical outcome of community-acquired and nosocomial BM., Methods: In this retrospective study we analyzed data of 148 adults (age > 16 years) with BM treated in Turku University Hospital, Southwestern Finland, from 2011 to 2018. Besides culture- or polymerase chain reaction (PCR)-positive cases we also included culture-negative cases with laboratory parameters strongly suggestive of BM and those with meningitis-related findings in imaging. We used Glasgow Outcome Scale (GOS) score 1-4 to determine unfavorable outcome., Results: The median age of patients was 57 years and 48.6% were male. Cerebrospinal fluid (CSF) culture for bacteria showed positivity in 50 (33.8%) cases, although pre-diagnostic antibiotic use was frequent (85, 57.4%). The most common pathogens in CSF culture were Streptococcus pneumoniae (11, 7.4%), Staphylococcus epidermidis (7, 4.7%), Staphylococcus aureus (6, 4.1%) and Neisseria meningitidis (6, 4.1%). Thirty-nine patients (26.4%) presented with the triad of fever, headache, and neck stiffness. A neurosurgical procedure or an acute cerebral incident prior BM was recorded in 74 patients (50%). Most of the patients had nosocomial BM (82, 55.4%) and the rest (66, 44.6%) community-acquired BM. Ceftriaxone and vancomycin were the most used antibiotics. Causative pathogens had resistances against the following antibiotics: cefuroxime with a frequency of 6.8%, ampicillin (6.1%), and tetracycline (6.1%). The case fatality rate was 8.8% and the additional likelihood of unfavorable outcome 40.5%. Headache, decreased general condition, head computed tomography (CT) and magnetic resonance imaging (MRI), hypertension, altered mental status, confusion, operative treatment, neurological symptoms, pre-diagnostic antibiotic use and oral antibiotics on discharge were associated with unfavorable outcome., Conclusions: The number of cases with nosocomial BM was surprisingly high and should be further investigated. The usage of pre-diagnostic antibiotics was also quite high. Headache was associated with unfavorable outcome. The frequency of unfavorable outcome of BM was 40.5%, although mortality in our patients was lower than in most previous studies., (© 2023. The Author(s).)

Background: Medical databases normally contain large amounts of data in a variety of forms. Although they grant significant insights into diagnosis and treatment, implementing data exploration into current medical databases is challenging since these are often based on a relational schema and cannot be used to easily extract information for cohort analysis and visualization. As a consequence, valuable information regarding cohort distribution or patient similarity may be missed. With the rapid advancement of biomedical technologies, new forms of data from methods such as Next Generation Sequencing (NGS) or chromosome microarray (array CGH) are constantly being generated; hence it can be expected that the amount and complexity of medical data will rise and bring relational database systems to a limit., Description: We present Graph4Med, a web application that relies on a graph database obtained by transforming a relational database. Graph4Med provides a straightforward visualization and analysis of a selected patient cohort. Our use case is a database of pediatric Acute Lymphoblastic Leukemia (ALL). Along routine patients' health records it also contains results of latest technologies such as NGS data. We developed a suitable graph data schema to convert the relational data into a graph data structure and store it in Neo4j. We used NeoDash to build a dashboard for querying and displaying patients' cohort analysis. This way our tool (1) quickly displays the overview of patients' cohort information such as distributions of gender, age, mutations (fusions), diagnosis; (2) provides mutation (fusion) based similarity search and display in a maneuverable graph; (3) generates an interactive graph of any selected patient and facilitates the identification of interesting patterns among patients., Conclusion: We demonstrate the feasibility and advantages of a graph database for storing and querying medical databases. Our dashboard allows a fast and interactive analysis and visualization of complex medical data. It is especially useful for patients similarity search based on mutations (fusions), of which vast amounts of data have been generated by NGS in recent years. It can discover relationships and patterns in patients cohorts that are normally hard to grasp. Expanding Graph4Med to more medical databases will bring novel insights into diagnostic and research., (© 2022. The Author(s).)

Objectives: The aims of this national register-based study were to examine patient injury claims related to tonsil and adenoid surgery injuries and to compare the frequency of claims between tonsillectomies and tonsillotomies in Finland., Methods: We analyzed the complaints related to tonsil and adenoid surgery received by the Finnish Patient Insurance Center (PIC) between the years 2000 and 2019. One hundred seventy-two cases were included in the analysis. The annual surgery rates between the years 2000 and 2018 were acquired from the Finnish Institute for Health and Welfare., Results: During the years 2000 to 2018, a total of 292,679 patients had tonsil and/or adenoid surgery nationwide. For tonsil or adenoid surgeries, the national average was 5.3 cases and 1.8 cases per 10,000, respectively, resulting in patient injury claims and compensations. A total of 33.1% of the claims regarding tonsil or adenoid surgery processed by the PIC were compensated. Most of the claims were made after a tonsillectomy (87.8%), and few were made after a tonsillotomy (1.7%). Seven deaths were recorded., Conclusion: Patient injuries from tonsil and adenoid surgeries were mostly related to traditional extracapsular tonsillectomies. Most surgeries, along with most complications, involved specialists, who performed routine operations in high-volume centers. Surgeries for acute or recurrent infections resulted in more claims. Severe complications arising from tonsil and adenoid surgeries were rare., Level of Evidence: 4., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Introduction: The standard surgical treatment for recurrent or chronic tonsillitis is extracapsular tonsillectomy. Recent studies show that intracapsular tonsillectomy has the potential to reduce the postoperative morbidity of patients undergoing tonsil surgery. The Finnish Intracapsular Tonsillectomy (FINITE) trial aims to provide level I evidence to support the hypothesis that the recovery time from tonsil surgery can be reduced with intracapsular tonsillectomy. Additionally, from this trial, major benefits in quality of life, reduction of postoperative complications, treatment costs and throat symptoms might be gained., Methods and Analysis: The FINITE trial is a prospective, randomised, controlled, patient-blinded, three-arm clinical trial. It is designed to compare three different surgical methods being extracapsular monopolar tonsillectomy versus intracapsular microdebrider tonsillectomy versus intracapsular coblation tonsillectomy in the treatment of adult patients (16-65 years) suffering from recurrent or chronic tonsillitis. The study started in September 2019, and patients will be enrolled until a maximum of 200 patients are randomised. Currently, we are in the middle of the study with 125 patients enrolled as of 28 February 2022 and data collection is scheduled to be completed totally by December 2027. The primary endpoint of the study will be the recovery time from surgery. Secondary endpoints will be the postoperative pain scores and the use of analgesics during the first 3 weeks of recovery, postoperative haemorrhage, quality of life, tonsillar remnants, need for revision surgery, throat symptoms, treatment costs and sick leave. A follow-up by a questionnaire at 1-21 days and at 1, 6, 24 and 60 months will be conducted with a follow-up visit at the 6-month time point., Ethics and Dissemination: Ethical approval was obtained from the Medical Ethics Committee of the Hospital District of Southwest Finland (reference number 29/1801/2019). Results will be made publicly available in peer-reviewed scientific journals., Trial Registration Number: NCT03654742., Competing Interests: Competing interests: The authors declare that they have no competing interests. TU has participated in a hands-on course for coblation by the manufacturer., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)