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Blender is an open-source three-dimensional animation software, which can be used as a simulation tool in metrology, to build numerical models that can be used in the design and optimisation of camera-based measurement systems. In this work, the relevance of using Blender to model camera-based measurement systems was explored. Two experiments were conducted in real-world and Blender modelled environments, one using individual cameras for a simple measurement task, the other considering multi-camera position optimisation. The objective was to verify whether the virtual cameras created in Blender can perceive and measure objects in the same manner as the real cameras in an equivalent environment. The results demonstrate that in its native modelling format Blender satisfies the optical metrology characteristics of measurement, but the correlation between Blender output and real-world results is highly sensitive to initial modelling parameters such as illumination intensity, camera definitions and object surface texture. [ABSTRACT FROM AUTHOR]

Aims Graft materials used for pelvic floor reinforcement should still be considered as investigational and, therefore, evaluated experimentally and within clinical trials. The present report describes our biomechanical findings in rats implanted with selected novel implant materials, which in recent years have been suggested as alternatives to plain polypropylene (PP) meshes. Methods Full thickness abdominal wall defects were primarily repaired by the implant of interest. Experiments involved eight different implant materials: two partly degradable synthetic implants, that is, a hybrid of polyglactin 910 with PP (Vypro II) and collagen coated PP (Pelvitex); two non-cross linked (Surgisis, InteXēn LP) and two cross-linked materials (Pelvicol, Pelvisoft) and two porous modifications of InteXēn LP and Pelvicol implants. At different time points (7, 14, 30, and 90 days), the implants and surrounding host tissue (explant) were harvested and tensiometry was performed. Tensile strength and location of breakage were recorded. Results In general resorbable non-cross linked collagen matrices and porous materials were weaker after 90 days; similar behavior was seen for implant materials alone and their construction with the surrounding native tissue. Both non-porous and porous modification of InteXēn LP appeared at 90 days as a very thin layer of collagen that was two-thirds, respectively one-third of the initial thickness. Conclusions In experimental conditions, sufficient strength was obtained only after 3 months, and PP containing constructs appeared as the strongest though reconstruction with Pelvicol showed comparable outcomes. Lower values for strength of non-cross linked and porous collagen materials are questioning their efficacy for pelvic floor reconstruction. Neurourol. Urodynam. 29:488-493, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

An abstract of the article "Molecular diagnosis of inheritable neuromuscular disorders," by C. Pottier is presented.

Abstract: Pelvic organ prolapse is an increasingly frequent problem and surgical repair remains the mainstay of therapy. Failure rates are as high as 30%, probably because the connective tissue used for repair is by definition qualitatively insufficient. There is therefore a lot of interest for augmentation of fascial repairs with implants. Experimental studies play an important role in the evaluation of such materials, documenting in vivo tensile strength, the host response to these foreign materials, particularly over longer periods. Non-reabsorbable synthetic implants lead to a permanent repair but the host usually develops a chronic inflammatory reaction which can be associated with bothersome side effects. Biological materials on the other hand have been much less studied and little is known about their long-term tissue response. They may, however, have their role as they may lead to less local side effects which may be mastered conservatively. The ultimate test for any material is obviously the clinical trial, defining its role in practice. [Copyright &y& Elsevier]

We conducted an in-depth longitudinal study on an individual carrying the presenilin 2 p.Asn141Ile mutation, traditionally associated with dominantly inherited Alzheimer's disease (AD), who has remarkably remained asymptomatic past the expected age of clinical onset. This study combines genetic, neuroimaging and biomarker analyses to explore the underpinnings of this resilience. Unlike typical progression in dominantly inherited AD, tau pathology in this case was confined to the occipital region without evidence of spread, potentially explaining the preservation of cognitive functions. Genetic analysis revealed several variants that, although not previously associated with protection against AD, suggest new avenues for understanding disease resistance. Notably, environmental factors such as significant heat exposure and a unique proteomic profile rich in heat shock proteins might indicate adaptive mechanisms contributing to the observed phenotype. This case underscores the complexity of Alzheimer's pathology and suggests that blocking tau deposition could be a promising target for therapeutic intervention. The study highlights the need for further research to identify and validate the mechanisms that could inhibit or localize tau pathology as a strategy to mitigate or delay the onset of Alzheimer's dementia., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Amyloid-PET imaging tracks the accumulation of amyloid beta (Aβ) deposits in the brain. Amyloid plaques accumulation may begin 10 to 20 years before the individual experiences clinical symptoms associated with Alzheimer's diseases (ad). Recent large-scale genome-wide association studies reported common risk factors associated with brain amyloidosis, suggesting that this endophenotype is driven by genetic variants. However, these loci pinpoint to large genomic regions and the functional variants remain to be identified. To identify new risk factors associated with brain amyloid deposition, we performed whole-genome sequencing on a large cohort of European descent individuals with amyloid PET imaging data (n = 1,888). Gene-based analysis for coding variants was performed using SKAT-O for amyloid PET as a quantitative endophenotype that identified genome-wide significant association for APOE (P = 2.45 × 10-10), and 26 new candidate genes with suggestive significance association (P < 5. 0 × 10-03) including SCN7A (P = 7.31 × 10-05), SH3GL1 (P = 7.56 × 10-04), and MFSD12 (P = 8.51 × 10-04). Enrichment analysis highlighted the lipid binding pathways as associated with Aβ deposition in brain driven by PITPNM3 (P = 4.27 × 10-03), APOE (P = 2.45 × 10-10), AP2A2 (P = 1.06 × 10-03), and SH3GL1 (P = 7.56 × 10-04). Overall, our data strongly support a connection between lipid metabolism and the deposition of Aβ in the brain. Our study illuminates promising avenues for therapeutic interventions targeting lipid metabolism to address brain amyloidosis., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g. protective). Classifying novel variants in APP, PSEN1, or PSEN2 as pathogenic, risk, benign, or protective is a critical step in evaluating disease risk profiles which further impacts eligibility for clinical trials focused on the ADAD population. Here, we classify 53 novel variants in APP, PSEN1, and PSEN2 based on bioinformatic data and cell-based assays. We identified 6 benign variants, 2 risk variants, and 32 likely pathogenic variants. Thirteen variants were associated with reduced Aβ levels in cell-based assays, consistent with a potential protective effect. Together, this study highlights the complexities associated with classification of rare variants in ADAD genes., 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 © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Older studies reported an increased risk of relapse after in vitro fertilization (IVF) in women with multiple sclerosis (MS), which has not been confirmed by more recent works. All these studies had several limitations, such as small sample sizes, absence of a control population, or lack of neurologic validation of the relapses. The aim of this study was to determine the risk of relapse after IVF in women with MS., Methods: This retrospective cohort study included all women with MS who underwent IVF between 2009 and 2019 and a control group of women with MS who did not undergo IVF matched on age, MS duration, number of relapses, and MS-specific treatments in the previous year. Data on MS (disease duration, treatments, and relapses) were from the French MS Registry (OFSEP), whereas data on IVF (number of procedures, stimulation protocol type, and outcomes) were from the French national health insurance database. For this, the 2 databases were linked by indirect matching., Results: In total, 115 women with MS underwent 199 IVF procedures (mean age at first IVF: 33.9 ± 4.0 years; 45.2% had ≥2 IVF procedures), and 175 IVFs (88.0%) could be matched to specific patients. The risk of relapse in the 3 months after index date was the same in both IVF group and control group (0.06 relapse per patient-year), as confirmed also by the before-after analysis in the IVF group (0.06 vs 0.08)., Discussion: This study, using a 10-year clinical and administrative dataset, did not find any increased risk of relapse after IVF. The maintenance of disease-modifying therapies until IVF was a determining factor in reducing the risk of relapse.

There is growing evidence suggesting that the lysosome or lysosome dysfunction is associated with Alzheimer's disease (AD). Pathway analysis of post mortem brain-derived proteomic data from AD patients shows that the lysosomal system is perturbed relative to similarly aged unaffected controls. However, it is unclear if these changes contributed to the pathogenesis or are a response to the disease. Consistent with the hypothesis that lysosome dysfunction contributes to AD pathogenesis, whole genome sequencing data indicate that heterozygous pathogenic mutations and predicted protein-damaging variants in multiple lysosomal enzyme genes are enriched in AD patients compared to matched controls. Heterozygous loss-of-function mutations in the palmitoyl protein thioesterase-1 ( PPT1 ), α-L-iduronidase ( IDUA ), β-glucuronidase ( GUSB ), N-acetylglucosaminidase ( NAGLU ), and galactocerebrosidase ( GALC ) genes have a gene-dosage effect on Aβ 40 levels in brain interstitial fluid in C57BL/6 mice and significantly increase Aβ plaque formation in the 5xFAD mouse model of AD, thus providing in vivo validation of the human genetic data. A more detailed analysis of PPT1 heterozygosity in 18-month-old mice revealed changes in α-, β-, and γ-secretases that favor an amyloidogenic pathway. Proteomic changes in brain tissue from aged PPT1 heterozygous sheep are consistent with both the mouse data and the potential activation of AD pathways. Finally, CNS-directed, AAV-mediated gene therapy significantly decreased Aβ plaques, increased life span, and improved behavioral performance in 5xFAD/PPT1+/- mice. Collectively, these data strongly suggest that heterozygosity of multiple lysosomal enzyme genes represent risk factors for AD and may identify precise therapeutic targets for a subset of genetically-defined AD patients.

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development., Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI)., Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection., Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise., Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated., Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs., Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyses, we further identify for the first time genome-wide significant loci specific to each of the three main FTLD-TDP pathological subtypes (A, B and C), as well as enrichment of risk loci in distinct tissues, brain regions, and neuronal subtypes, suggesting distinct disease aetiologies in each of the subtypes. Rare variant analysis confirmed TBK1 and identified VIPR1 , RBPJL , and L3MBTL1 as novel subtype specific FTLD-TDP risk genes, further highlighting the role of innate and adaptive immunity and notch signalling pathway in FTLD-TDP, with potential diagnostic and novel therapeutic implications.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement., Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy., Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses., Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET)., Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02)., Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

Aim: To evaluate the knowledge, practices and self-confidence of community pharmacists, pharmacy technicians and pharmacy students about infantile haemangioma (IH) and propranolol treatment., Methods: A national survey was conducted in France from May 2022 to October 2022. A 42-item online questionnaire was used to assess pharmacists' knowledge of the epidemiology, clinical features and management of IH and propranolol treatment., Results: The survey included 255 participants. The mean age was 34.9 years (±9.0); 225 (88%) were women. In all, 193 (76%) practised in urban pharmacies. Altogether, 83 participants (33%) had delivered oral propranolol solution for IH in the last 6 months. Participants' median score for self-confidence regarding propranolol dispensing was five (interquartile range, 2.5-6) on a scale of 1 to 10. Overall, 96 (38%) had more than 50% correct answers on the questionnaire. Multinomial regression models showed high scores on the questionnaire associated with high self-confidence when delivering oral propranolol solution, low number of years since graduation and having already delivered propranolol treatment., Conclusion: This study highlights a lack of knowledge of IH and modalities of propranolol treatment by community pharmacists and slight self-confidence when delivering propranolol. Greater cooperation between healthcare professionals could improve the proper use of medicine., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Importance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity., Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET., Design, Setting, and Participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022., Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab., Main Outcomes and Measures: Time to first relapse., Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy., Conclusion and Relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion. We focused on the cerebellum, since key C9orf72-related pathologies are abundant in this neuroanatomical region, yet TDP-43 pathology and neuronal loss are minimal. Consistent with previous work, we showed a reduction in the expression of the C9orf72 gene and an elevation in homeobox genes, when comparing patients with the expansion to both patients without the C9orf72 repeat expansion and control subjects. Interestingly, we identified more than 1000 alternative splicing events, including 4 in genes previously associated with ALS and/or FTLD. We also found an increase of cryptic splicing in C9orf72 patients compared to patients without the expansion and controls. Furthermore, we demonstrated that the expression level of select RNA-binding proteins is associated with cryptic splice junction inclusion. Overall, this study explores the presence of widespread transcriptomic changes in the cerebellum, a region not confounded by severe neurodegeneration, in post-mortem tissue from C9orf72 patients., (© 2024. The Author(s).)

Photometric stereo uses images of objects illuminated from various directions to calculate surface normals which can be used to generate 3D meshes of the object. Such meshes can be used by engineers to estimate damage of a concrete surface, or track damage progression over time to inform maintenance decisions. This dataset [1] was collected to quantify the uncertainty in a photometric stereo test rig through both the comparison with a well characterised method (coordinate measurement machine) and experiment virtualisation. Data was collected for 9 real objects using both the test rig and the coordinate measurement machine. These objects range from clay statues to damaged concrete slabs. Furthermore, synthetic data for 12 objects was created via virtual renders generated using Blender (3D software) [2]. The two methods of data generation allowed the decoupling of the physical rig (used to light and photograph objects) and the photometric stereo algorithm (used to convert images and lighting information into 3D meshes). This data can allow users to: test their own photometric stereo algorithms, with specialised data created for structural health monitoring applications; provide an industrially relevant case study to develop and test uncertainty quantification methods on test rigs for structural health monitoring of concrete; or develop data processing methodologies for the alignment of scaled, translated, and rotated data., (© 2024 The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Aims: The rare yeast species Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus are increasingly implicated in severe mycoses in immunocompromised patients. This study aimed to assess the prevalence of uncommon yeast species in Côte d'Ivoire., Methods: The yeast isolates from superficial samples, mainly vaginal swabs, were collected at the Pasteur Institute of Abidjan in a study on the molecular epidemiology of clinical yeast species. Identification relied on MALDI-TOF MS and ITS sequence analysis. Antifungal susceptibility testing was performed using the CLSI method., Results: Of the 315 strains analysed from 227 outpatients, 14 belonged to 4 uncommon species: Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus. None exhibited elevated fluconazole, amphotericin B, caspofungin, ketoconazole, or flucytosin MIC., Conclusions: The presence of these rare yeasts represents a risk in immunocompromised people. Their adequate and timely identification is a priority. Overall, enhancing the mycoses diagnostic capacities in Côte d'Ivoire, and more generally in African clinical laboratories with limited resources is a critical aim., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

We previously demonstrated that increased expression of the SERPINA5 gene is associated with hippocampal vulnerability in Alzheimer's disease (AD) brains. SERPINA5 was further demonstrated to be a novel tau-binding partner that colocalizes within neurofibrillary tangles. Our goal was to determine whether genetic variants in the SERPINA5 gene contributed to clinicopathologic phenotypes in AD. To screen for SERPINA5 variants, we sequenced 103 autopsy-confirmed young-onset AD cases with a positive family history of cognitive decline. To further assess the frequency of a rare missense variant, SERPINA5 p.E228Q, we screened an additional 1114 neuropathologically diagnosed AD cases. To provide neuropathologic context in AD, we immunohistochemically evaluated SERPINA5 and tau in a SERPINA5 p.E228Q variant carrier and a matched noncarrier. In the initial SERPINA5 screen, we observed 1 individual with a rare missense variant (rs140138746) that resulted in an amino acid change (p.E228Q). In our AD validation cohort, we identified an additional 5 carriers of this variant, resulting in an allelic frequency of 0.0021. There was no significant difference between SERPINA5 p.E228Q carriers and noncarriers in terms of demographic or clinicopathologic characteristics. Although not significant, on average SERPINA5 p.E228Q carriers were 5 years younger at age of disease onset than noncarriers (median: 66 [60-73] vs 71 [63-77] years, P = .351). In addition, SERPINA5 p.E228Q carriers exhibited a longer disease duration than noncarriers that approached significance (median: 12 [10-15]) vs 9 [6-12] years, P = .079). More severe neuronal loss was observed in the locus coeruleus, hippocampus, and amygdala of the SERPINA5 p.E228Q carrier compared to noncarrier, although no significant difference in SERPINA5-immunopositive lesions was observed. Throughout the AD brain in either carrier or noncarrier, areas with early pretangle pathology or burnt-out ghost tangle accumulation did not reveal SERPINA5-immunopositive neurons. Mature tangles and newly formed ghost tangles appeared to correspond well with SERPINA5-immunopositive tangle-bearing neurons. SERPINA5 gene expression was previously associated with disease phenotype; however, our findings suggest that SERPINA5 genetic variants may not be a contributing factor to clinicopathologic differences in AD. SERPINA5-immunopositive neurons appear to undergo a pathologic process that corresponded with specific levels of tangle maturity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cross-resistance to medical azoles by exposure to azole pesticides is well documented for Aspergillus family fungi but is poorly evaluated for other environmental pathogen fungi, particularly for yeasts belonging to the Cryptococcus neoformans / Cryptococcus gattii species complexes., Methods: One thousand C. neoformans yeast were exposed to various concentrations of seven different commonly used azole pesticides. Clones surviving exposure were picked randomly, and their minimal inhibitory concentrations (MICs) of fluconazole, voriconazole, posaconazole, itraconazole and isavuconazole were assessed., Results: Depending on the pesticide used for exposure, up to 13.3% of selected Cryptococcus colonies showed a phenotype of resistance to fluconazole, and among them, several showed cross-resistance to another or several other medical azoles. Molecular mechanisms involved in the resistance setups seem to be dependent on ERG11 and AFR1 gene overexpression., Conclusion: Exposure to any of the seven azole pesticides tested is capable of increasing the MIC of fluconazole in C. neoformans , including up to the level of the fluconazole-resistant phenotype, as well as generating cross-resistance to other medical azoles in some cases.