Rapid Course Research Articles

Early-onset subacute sclerosing panencephalitis and its rapid clinical course of progression to vegetative state: An atypical presentation

Early-onset subacute sclerosing panencephalitis and its rapid clinical course of progression to vegetative state: An atypical presentation

Teaching "Usul-i Cedit" (The New Method) to Primary School Teachers in Ottoman Provinces

This research aims to uncover the activities undertaken to teach the new "usul-i cedit" teaching methods to sibyan (primary) school teachers who continued providing traditional education during the modernization period. Modernization of education encompasses various practices, from curricula of usul-i cedit to school management, teachers' personal rights, and health regulations in schools. Usul-i cedit focuses on teaching Turkish literacy and new methods developed for this purpose. Due to the failure of primary school reforms during the Tanzimat Period, the competence of school teachers was questioned. There was a push to gradually remove teachers unable to teach using usul-i cedit. However, training enough qualified teachers at Darülmuallimin-i Sıbyan would take time. Therefore, rapid courses were introduced to quickly train current primary school teachers in the new methods. Sample schools like iptidai, rüştiye, and provincial teacher training schools served as course centers. These courses primarily taught new methods for teaching Turkish literacy and included modern pedagogical methods for basic education subjects. The "usul-i tedris" (teaching method) lesson, central to teaching the new reading and writing methods, was a key component of all courses. The research employed document analysis, with data from Ottoman Archive documents forming the study's backbone. Historical data were analyzed using content analysis.

GIANT CELL MYOCARDITIS: AUTOPSY CONFIRMATION OF A DIAGNOSTIC DILEMMA - A RARE CASE REPORT

Abstract Introduction/Objective Giant cell myocarditis (GCM) is a rare and rapidly progressive form of myocarditis, commonly leading to fulminant heart failure (HF), refractory ventricular arrhythmias or conduction system abnormalities and carrying a high mortality rate without prompt treatment. Due to its rarity, there is limited data on its prevalence, although studies show an incidence of 0.007–0.053% among autopsied cases. This entity primarily affects the heart, exhibiting a rapid clinical course and a poor prognosis necessitating immunosuppressive therapy and, in most instances, heart transplantation to improve survival rates. Methods/Case Report We present a case of a 62-year-old male with a prior history of complete heart block status post permanent pacemaker placement, presenting with acute decompensated heart failure. Laboratory investigations revealed elevated cardiac troponin levels (>35000) with echocardiography showing a reduced ejection fraction of 25% and an initial diagnosis of non-ST elevation myocardial infarction (NSTEMI) was made. Endomyocardial biopsy revealed GCM. Despite aggressive management, including immunosuppressive therapy and mechanical circulatory support, his condition deteriorated rapidly, leading to multiorgan failure and eventual death. The diagnosis was confirmed on autopsy. The diagnostic challenge of GCM lies in its clinical or pathologic overlap with other myocardial disorders such as cardiac sarcoidosis, viral myocarditis, and cardiac amyloidosis. Endomyocardial biopsy (EMB) remains the gold standard for diagnosing this entity which is characterized by a widespread inflammatory cell infiltrate with multinucleated giant cells in association with myocyte damage. The etiology of GCM remains unclear, but it is believed to be immune-mediated, possibly triggered by an autoimmune response. Results (if a Case Study enter NA) NA Conclusion Pathologists should give importance to consider GCM in the differential diagnosis of patients presenting with acute heart failure refractory to standard therapy. Early recognition and prompt initiation of immunosuppressive therapy are crucial for improving outcomes in patients with GCM. Awareness of this entity is crucial to make a timely diagnosis.

A novel double antibody sandwich quantitative ELISA for detecting porcine epidemic diarrhea virus infection.

Porcine epidemic diarrhea (PED), a contagious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV), has caused significant economic losses to the global pig farming industry due to its rapid course and spread and its high mortality among piglets. In this study, we prepared rabbit polyclonal antibody and monoclonal antibody 6C12 against the PEDV nucleocapsid (N) protein using the conserved and antigenic PEDV N protein as an immunogen. A double-antibody sandwich quantitative enzyme-linked immunosorbent assay (DAS-qELISA) was established to detect PEDV using rabbit polyclonal antibodies as capture antibodies and horseradish peroxidase (HRP)-labeled 6C12 as the detection antibody. Using DAS-qELISA, recombinant PEDV N protein, and virus titer detection limits were approximately 0.05 ng/mL and 103.02 50% tissue culture infective dose per mL (TCID50/mL), respectively. There was no cross-reactivity with porcine reproductive and respiratory syndrome virus (PRRSV), porcine rotavirus (PoRV), porcine pseudorabies virus (PRV), porcine deltacoronavirus (PDCoV), or porcine circovirus (PCV). The reproducibility of DAS-qELISA was verified, and the coefficient of variation (CV) for intra- and inter-batch replicates was less than 10%, indicating good reproducibility. When testing anal swab samples from PEDV-infected piglets using DAS-qELISA, the coincidence rate was 92.55% with a kappa value of 0.85 when using reverse transcription-polymerase chain reaction (RT-PCR) and 94.29% with a kappa value of 0.88 when using PEDV antigen detection test strips, demonstrating the reliability of the method. These findings provide fundamental material support for both fundamental and practical studies on PEDV and offer a crucial diagnostic tool for clinical applications. KEY POINTS: • A new anti-PEDV N protein monoclonal antibody strain was prepared • Establishment of a more sensitive double antibody sandwich quantitative ELISA • DAS-qELISA was found to be useful for controlling the PEDV spread.

Implementing a rapid application development course in higher education and measuring its impact using Kirkpatrick’s model: a case study at Vilnius Gediminas Technical University

Nowadays, technological development and improvement in business is happening rapidly, so higher education (HE), and not only, studies should constantly provide and develop new up-to-date knowledge and skills to students, in order to train competitive specialists, address digital transformation by developing digital readiness of higher institutions, and increase employment opportunities of students. Consequently, this paper discusses the implementation of the newly developed courses for teaching Rapid Application Development (RAD) on the Oracle Application Express platform into the studies at Vilnius Gediminas Technical University (VILNIUS TECH) and presents the effectiveness of the implementation of this course measured using Kirkpatrick’s model. The obtained results show that students’ knowledge of RAD increased after attending the course. In addition, a 76% agreed that this course increased their knowledge of the subject matter.

Introducing rapid web application development with Oracle APEX to students of higher education

The rapid development of information and communication technologies (ICT), and enforcement of digital transformation have caused the need to develop and deliver software in even shorter time than previously, and has become crucial to businesses. Yet, this new need has caused a challenge of finding expert IT workforce able to deliver software applications due expected time. Moreover, in a rapidly changing business world, the traditional software development can no longer keep pace and provide solutions to businesses fast enough. Low-code development and inclusion of so-called citizen developers are seen as a solution for the problem. This paper explores the introduction of rapid application development courses on Oracle APEX technology to students of a European technological university. The paper discusses the implementation of the course and its design, and looks how the developed basic-level course was received by students. It is shown that the courses have been well-received by students, who based on provided feedback are satisfied with the online set up for self-regulated learning of rapid application development skills.

Proteome and Phosphoproteome Profiling Reveal the Toxic Mechanism of Clostridium perfringens Epsilon Toxin in MDCK Cells.

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein-protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.

P43: The pattern of social cognition impairment in young-onset and late-onset Alzheimer’s disease

Introduction: People with young-onset Alzheimer’s disease (YOAD) are diagnosed when the neurocognitive process begins before the age of 65 and often present with more global impairments and a more rapid course of the disease. In contrast, in late-onset Alzheimer’s disease (LOAD), the loss of short-term memory is most pronounced. Therefore, the age of onset may affect global functioning in different ways.Objectives: This study examines the relationship between Social Cognition, global cognition, and other clinical variables in young and late-onset people with Alzheimer’s disease and their caregivers.Methods: Using a cross-sectional design, we included 48 people with YOAD and 118 with LOAD and their carers. We assessed social cognition, global cognition, quality of life, dementia severity, mood, functionality, neuropsychiatric symptoms, and caregiver burden.Results: Our results showed that the YOAD group had more global cognitive impairment, lower MMSE scores (P = 0.018, d = 0.41), higher Adas cog (P = 0.002, d = 0.06), poorer quality of life (QoL- AD) (P = 0.036, d = 0.36), and more neuropsychiatric symptoms (NPI) (P = 0.044, d = 0.35). However, social cognition showed a stable pattern of impairments in YOAD that did not follow the global deficits. The multifactorial regression analyses further showed that in both groups functionality was significantly related to Social Cognition, YOAD (P = 0.035), and LOAD (P = 0.001).Conclusions: The significant findings of our study underscore that in YOAD, despite more pronounced global impairment compared to LOAD, social cognition remains stable. This finding is crucial for understanding the patterns of social cognition in YOAD and may potentially guide future interventions and care strategies.

Data-driven program adaptation and continuous improvement: A case study of the Adolescents 360 (A360) project in Ethiopia, Nigeria, and Tanzania

Interventions benefit from ongoing continuous quality improvement during implementation to refine and strengthen them in response to changing contexts and emerging opportunities. This article reflects on the experience from the Adolescents 360 (A360) project in implementing user-centered, adaptive programming across Tanzania, Ethiopia, and Nigeria from 2018 to 2020. During this implementation period, A360 progressed through three distinct phases: an ‘optimization’ of project interventions in pursuit of efficiency and preparation for scale; a re-focusing on user-centered programming to go beyond efficiency and pursue greater impact; and a rapid course correction in response to the emerging COVID-19 pandemic. A360’s approach to data-informed adaptation evolved throughout these phases. From a hyper focus on cost-efficiency during optimization to a more expansive use of mixed methods data for adaptation during its second phase and finally iteration in response to an extremely restrictive service delivery environment during the COVID-19 pandemic. In this article we reflect on how these periods of adaptation and course correction contributed to the evolution of the project’s interventions and provided significant lessons which the project has taken into its new investment phase. Balance is key – utilizing a range of mixed methods data instead of a singular focus on cost-efficiency, streamlining interventions while not compromising long-term impact, and retaining a user-focus even while considering sustainability.

Applications of nanostructured materials for severe acute respiratory syndrome-CoV-2 diagnostic

There is a growing concern that severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infections will continue to rise, and there is now no safe and effective vaccination available to prevent a pandemic. This has increased the need for rapid, sensitive, and highly selective diagnostic techniques for coronavirus disease (COVID-19) detection to levels never seen before. Researchers are now looking at other biosensing techniques that may be able to detect the COVID-19 infection and stop its spread. According to high sensitivity, and selectivity that could provide real-time results at a reasonable cost, nanomaterial show great promise for quick coronavirus detection. In order to better comprehend the rapid course of the infection and administer more effective treatments, these diagnostic methods can be used for widespread COVID-19 identification. This article summarises the current state of research into nanomaterial-based biosensors for quick SARS‑CoV‑2 diagnosis as well as the prospects for future advancement in this field. This research will be very useful during the COVID-19 epidemic in terms of establishing rules for designing nanostructure materials to deal with the outbreak. In order to predict the spread of the SARS-CoV-2 virus, we investigate the advantages of using nano-structure material and its biosensing applications.

Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, genetic counseling should be provided to the patient's relatives to extend multidisciplinary care to their first-degree family members. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric symptoms commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

#901 Natural history of idiopathic nephrotic syndrome: the UK National RaDaR Idiopathic Nephrotic Syndrome Cohort

Abstract Background and Aims Idiopathic nephrotic syndrome (INS) is an important class of proteinuric renal disease leading to kidney failure (KF). Here we describe the natural history of INS and congenital nephrotic syndrome (NS) using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4610 patients with NS not attributable to glomerulonephritis or systemic disorders recruited from 107 adult and paediatric kidney units across the UK since 2010. Method Participant eligibility of RaDaR-INS Cohort patients included ≥12 months observation from disease onset and no KF (CKD stage 5 or on renal replacement therapy) at or prior to disease onset. Disease onset date was defined as first database occurrence of kidney biopsy, primary diagnosis or protein-creatinine ratio (PCR) ≥1.5 g/g. Participants were sub-categorized into those with a genetic diagnosis (INS-genetic), biopsy-proven FSGS (FSGS-biopsy), biopsy–proven minimal change disease (MCD-biopsy) and those with no genetic or biopsy-proven diagnosis (INS-no genetic or biopsy diagnosis). Participants with a biopsy-proven MCD diagnosis and a subsequent biopsy proven FSGS diagnosis were included in both MCD-biopsy and FSGS-biopsy categories and formed a category of their own (MCD progressing to FSGS). Longitudinal proteinuria, assessed as time-average protein-to-creatinine ratio (TA-PCR), and eGFR slope were calculated over the full duration of follow-up or until KF. Kidney survival was calculated from disease onset to event (KF or death) and censored at last follow-up. Results Of the 4066 patients meeting eligibility, median age at disease onset was 28 years (IQR 6-51), with children (<18 yrs) representing 39% of the study population. Median proteinuria was 6.4 g/g (IQR 3.1-10.8; n = 923), while mean eGFR was 118 mL/min/1.73 m2 (SD 49; n = 240) and 69 mL/min/1.73 m2 (SD 34; n = 906) for children and adults, respectively. Median follow-up duration was 8.2 yrs (IQR 4.3-13.1) with KF/death events occurring in 30% of patients. Mean TA-PCR was greater in children than adults (5.0 g/g (SD 13.9) vs. 1.9 g/g (SD 2.5), as was annual rate of loss of eGFR (−7.4 mL/min/1.73 m2 (SD 21.8) vs. −3.1 mL/min/1.73 m2 (SD 10.2)). Characteristics at disease onset and clinical outcomes of the INS cohort sub-categories are presented in Fig. 1. Kaplan Meier survival plots of each sub-category, and further divided into children and adults, illustrate the poor survival probability for patients with FSGS, particularly INS-genetic patients who are predominantly diagnosed in childhood (Fig. 2). While INS with no genetic or biopsy diagnosis presenting in childhood exhibits disease course and outcomes similar to MCD-biopsy patients, those diagnosed in adulthood have a more rapid disease course similar to FSGS-biopsy patients. Conclusion The RaDaR-INS cohort represents a large study population with lengthy follow-up data. These analyses illustrate the difference in disease progression and survival rates for INS patients with different causes or histological descriptions, highlighting in particular an unmet need for effective treatments for patients with nephrotic syndrome and FSGS.

Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications.

Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets. ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS. Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.

Case of acute retinal necrosis with rapid progression to proliferative vitreoretinopathy: A case report.

Acute retinal necrosis (ARN) was first reported in 1971 by Urayama et al as an acute uveitis accompanied by retinal arteritis and white retinal lesions in the peripheral retina that can progress to a rhegmatogenous retinal detachment (RRD). We have experienced a case of ARN that, unlike the common developmental course to an RRD associated with ARN, progressed to proliferative vitreoretinopathy (PVR) involving the entire retina in 2 days. The purpose of this report is to present our findings in the case of ARN with an atypical rapid time course. The patient was a 56-year-old woman who was treated for uveitis of unknown origin by her primary care physician. She was referred to our hospital because of a worsening of the fundus findings. Fundus examination in our hospital revealed vitreous opacities in the right eye, yellowish-white lesions extending around the retina, and some retinal hemorrhages. Because the retinal changes suggested ARN, we performed a polymerase chain reaction of the anterior atrial fluid and detected varicella-zoster virus. Then, the diagnosis of ARN was confirmed, and treatment was begun. At 1 month and a half after beginning the treatment, focal retinal traction was observed in the right fundus. Two days later, a circumferential PVR and a total retinal detachment were detected. We then performed vitrectomy with an encircling buckle and a silicone oil tamponade. Our examination 6 months postoperatively showed that the retina was attached and the BCVA was 20/200. Our findings of a case of ARN showed that the progression from a local vitreous traction to a full circumferential PVR can develop in 2 days.

Characterisation of Lagovirus europaeus GI-RHDVs (Rabbit Haemorrhagic Disease Viruses) in Terms of Their Pathogenicity and Immunogenicity.

Rabbit haemorrhagic disease viruses (RHDV) belong to the family Caliciviridae, genus Lagovirus europaeus, genogroup GI, comprising four genotypes GI.1-GI.4, of which the genotypes GI.1 and GI.2 are pathogenic RHD viruses, while the genotypes GI.3 and GI.4 are non-pathogenic RCV (Rabbit calicivirus) viruses. Among the pathogenic genotypes GI.1 and GI.2 of RHD viruses, an antigenic variant of RHDV, named RHDVa-now GI.1a-RHDVa, was distinguished in 1996; and in 2010, a variant of RHDV-named RHDVb, later RHDV2 and now GI.2-RHDV2/b-was described; and recombinants of these viruses were registered. Pathogenic viruses of the genotype GI.1 were the cause of a disease described in 1984 in China in domestic (Oryctolagus (O.) cuniculus domesticus) and wild (O. cuniculus) rabbits, characterised by a very rapid course and a mortality rate of 90-100%, which spread in countries all over the world and which has been defined since 1989 as rabbit haemorrhagic disease. It is now accepted that GI.1-RHDV, including GI.1a-RHDVa, cause the predetermined primary haemorrhagic disease in domestic and wild rabbits, while GI.2-RHDV2/b cause it not only in rabbits, including domestic rabbits' young up to 4 weeks and rabbits immunised with rabbit haemorrhagic disease vaccine, but also in five various species of wild rabbits and seven different species of hares, as well as wild ruminants: mountain muskoxen and European badger. Among these viruses, haemagglutination-positive, doubtful and harmful viruses have been recorded and described and have been shown to form phylogenogroups, immunotypes, haematotypes and pathotypes, which, together with traits that alter and expand their infectious spectrum (rabbit, hare, wild ruminant, badger and various rabbit and hare species), are the determinants of their pathogenicity (infectivity) and immunogenicity and thus shape their virulence. These relationships are the aim of our consideration in this article.

A case of surgical treatment of neck phlegmon after gunshot wound complicated by total posterior mediastinitis using laparoscopic surgical techniques

The purpose of this article is to demonstrate the peculiarities of diagnosis and staged surgical treatment for neck phlegmon after gunshot wound complicated by total posterior mediastinitis using laparoscopic surgical techniques. Inflammatory complications in neck injuries are a serious complication with a rapid course. An important diagnostic method is multislice computed tomography. The use of multislice computed tomography in the dynamics of the postoperative period allows for timely detection of further spread of the mediastinal inflammatory process. In the surgical treatment of neck phlegmon, it is necessary to open all fascial spaces widely and perform drainage of the upper mediastinum. Laparoscopic access is a minimal trauma with good visualization of the posterior mediastinum (middle and lower), which allows for a complete revision, sanitation, and drainage of the posterior mediastinum. To prevent a leakage of purulent contents from the mediastinal cavity into the abdominal cavity, safety drains in both hypocostal areas are placed in subdiaphragmatic spaces to the oesophageal opening.

Evaluating Success and Challenges of a Primary Care Youth Mental Health Programme Using Complexity, Implementation Science, and Appreciative Inquiry.

Background Using an innovative framework of complexity and implementation science, with underpinning core values of appreciative inquiry (CIS-A), this paper describes the evaluation of a pilot service in New Zealand aiming to deliver integrated psychological therapy services within primary care, to young people (aged 18-24) experiencing mild to moderate mental distress. Method Using mixed quantitative and qualitative methods and multiple data sources,there was a strong focus on local innovation and co-design with service users, young people and multiple care providers. Data is drawn from service users, stakeholders and providers of the service in three areas of the lower North Island of New Zealand. Results The Piki pilot provided a significant and innovative enhancement of mental health care to this population. The service supported 5307 individuals with a range of therapy options, with the majority having between one and three therapy sessions. From 730 service users who completed a survey, 591 (81%) were 'very satisfied' with the service provided. The CIS-A framework was used successfully to provide rapid feedback and encourage adaptation to evolving issues. These included unexpected workload pressures, changes to therapy delivery, the integration of co-design and prioritising the needs of vulnerable groups. There was a successful incorporation of youth/service user input to co-design the programme, introduction of a peer-to-peer support service, and integration of a digital resource platform. The framework was also used to address challenges encountered and to support necessary adaptations in response to the COVID-19 pandemic. Conclusions We describe the use of an embedded evaluation to support and inform the implementation of a novel and innovative youth mental health programme. Complexity and implementation science, underpinned by the core values of appreciative inquiry (CIS-A), were successfully utilised providing potential learning that can be applied locally, nationally and internationally. This study has a focus on youth mental health but the principles and utility of applying a complexity and implementation science approach have application in many different health care settings. The use of a framework such as CIS-A can support complex innovation and implementation and can be used to enable rapid course correction and turn 'hindsight to foresight'.

Primary intracranial malignant melanoma in an adolescent female: a case report

BackgroundPrimary central nervous system melanoma is an extremely rare entity and even rarer in children and adolescents as compared to adults. It is often difficult to consider a diagnosis of intracranial melanoma pre-operatively without any clinical evidence of neurocutaneous melanosis.Case presentationHerein, a case of primary melanoma of the brain is reported in a 17-year-old female who presented with headache, vomiting, and focal neurological deficit in the form of left-sided facial palsy and limb weakness. A contrast-enhanced computed tomography of head was performed which revealed a heterogeneously hyperattenuating mass lesion at left gangliocapsular region showing peripheral enhancement with internal non-enhancing cystic component. The patient underwent left frontotemporal craniotomy. The diagnosis was made on histopathological examination, which showed an invasive tumor comprising of epithelioid to spindled cells arranged in sheets, nests, and singly scattered. The special stains and immunohistochemical markers proved very helpful in establishing the diagnosis.ConclusionsThe case highlights the uncommon occurrence of primary intracranial melanoma in the pediatric age group, the perplexing histological features, and the rapid and fatal course.

Retraction: Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Retraction: Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Exosome-transmitted podoplanin promotes tumor-associated macrophage-mediated immune tolerance in glioblastoma.

Glioblastoma is the most frequent and aggressive primary brain tumor, characterized by rapid disease course and poor treatment responsiveness. The abundance of immunosuppressive macrophages in glioblastoma challenges the efficacy of novel immunotherapy. Bulk RNA-seq and single-cell RNA-seq of glioma patients from public databases were comprehensively analyzed to illustrate macrophage infiltration patterns and molecular characteristics of podoplanin (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on macrophage immunosuppressive polarization was investigated using a co-culture system. Bone marrow-derived macrophages (BMDMs) and OT-II T cells isolated from BALB/c and OT-II mice respectively were co-cultured to determine T-cell adherence. Pathway alterations were probed through RNA sequencing and western blot analyses. Our findings demonstrated that PDPN is notably correlated with the expression of CD68 and CD163 in glioma tissues. Additionally, macrophages phagocytosing PDPN-containing EVs (EVsPDPN ) from GBM cells presented increased CD163 expression and augmented secretion of immunoregulatorycytokine (IL-6, IL-10, TNF-α, and TGF-β1). PDPN within EVs was also associated with enhanced phagocytic activity and reduced MHC II expression in macrophages, compromising CD4+ T-cell activation. This investigation underscores that EVsPDPN derived from glioblastoma cells contributes to M2 macrophage-mediated immunosuppression and is a potential prognostic marker and therapeutic target in glioblastoma.