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The official "Zeitschrift für Urologie" was not the only journal in the field of Urology in Germany at the beginning of the 20th century. The Berlin-based "Folia Urologica" was at least as influential and important and probably the better known journal. It relied on international exchange, disputes, and interdisciplinary work. With the outbreak of World War I in 1914, the international discourse ended. Die Zeitschrift für Urologie war in den ersten Jahren ihrer Existenz nicht konkurrenzlos. Auf internationaler Ebene war die in Berlin erscheinende Folia Urologica mindestens ebenbürtig, wenn nicht gar das bekanntere Journal. Auf internationalen Austausch und Interdisziplinarität ausgelegt, wurde ihr durch den Ersten Weltkrieg die Existenzgrundlage entzogen.
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease caused by pathogenic variants in SACS. ARSACS is characterized by mitochondrial abnormalities and disruptions of the neurofilament cytoskeleton. In other conditions, these features have been linked to activation of Sterile Alpha and TIR Motif Containing 1 (SARM1), an enzyme that can trigger axon degeneration and neuronal death. Inhibition of SARM1 is an attractive therapeutic strategy because SARM1 is inactive in healthy cells and knockout of SARM1 has little or no deleterious effects. We therefore asked whether SARM1 activity contributed to Purkinje cell degeneration and motor defects present in a Sacs -/- mouse model of ARSACS. We studied 4 cohorts of mice: (1) Sacs -/- ; Sarm1 +/+ ; (2) Sacs +/+ ; Sarm1 +/- ; (3) Sacs -/- ; Sarm1 +/- ; and (4) Sacs -/- ; Sarm1 -/- . In 9-month-old mice, we analyzed protein markers of Purkinje cells (n = 3-4 mice per genotype) and counted surviving Purkinje cells in folia III, IV, and VIII of cerebellar sections (n = 3 mice per genotype, 6 sections per mouse), and tested motor function at 3, 6, and 9 months by quantifying parameters of gait (Digigait) and coordination and balance (Rotarod) (8 male, 8 female mice of each genotype). Probing of cerebellar extracts showed that the Purkinje cell protein markers Calbindin-1, RGS8, and PCP2 were decreased in Sacs -/- mice but restored to normal levels in Sacs -/- ; Sarm1 -/- mice. Purkinje cell loss in Sacs -/- mice was most prominent in anterior folia, as previously noted. Sarm1 loss partially mitigated the Purkinje cell death in folium III of 9-month-old Sacs -/- mice. Similarly, longitudinal behavioral assessment of motor functions showed that disturbances in gait pattern (slower cadence, prolonged swing, and stance phases) were partially alleviated. Rotarod tests gave more ambivalent results, as the homozygous loss of Sarm1 was less effective than heterozygous loss in ameliorating the Sacs -/- phenotype. We conclude that SARM1 contributes to neurodegeneration in ARSACS, and its downregulation or inhibition could constitute a significant therapeutical strategy in the treatment of the disease.
Marsupials lack a corpus callosum; in its place Diprodontia have a fasciculus aberrans connecting the hemispheres. However, despite this uniqueness, the realm of marsupial brain anatomy remains largely unexplored, especially through the lens of modern imaging techniques. Currently, there is a glaring absence of publicly available reference materials to explore normal brain morphometry to aid in defining and investigating marsupial neurodegenerative brain diseases. This study segmented magnetic resonance images of a wombat brain with an overall size of 41,745.46 mm3 to create a three-dimensional atlas. The volume and ratio to the overall brain size of each segment were quantified. The common wombat has a moderate hippocampal formation (2464.34 mm3; 5.90%), thick hippocampal commissure (535.19 mm3; 1.28%), well-developed tectum (481.42 mm3; 1.15% and a large epithalamus; 53.96 mm3; 0.13%). The common wombat's moderately sized cerebellum (5181.99 mm3; 12.41%) with prominent folia and fissures but less folding may suggest the low need for complex motor movement when burrowing. The common wombat also has a large diencephalon (3104.70 mm3; 7.44%), large thalamus (2206.81 mm3; 5.29%), a moderately sized hypothalamus (530.71 mm3; 1.27%), moderately sized basal ganglia (caudoputamen) (1345.26 mm3; 3.22%) and moderately sized pons and medulla (2475.26 mm3; 5.93%).
Homozygous mutations in the AGTPBP1 gene are associated with childhood-onset neurodegeneration and cerebellar atrophy (CONDCA). These mutations disrupt neuronal maintenance, leading to progressive motor and cognitive deficits. This case highlights the pathological findings and systemic complications in a 4.5-month-old boy with this rare genetic disorder. A 4.5-month-old boy presented with global developmental delay and progressively worsening floppiness of the body for the past 2 months. There was a history of similar illness in his previous sibling, who died at 2.5 months of age. The serum creatine kinase of the index child was mildly elevated. Antemortem muscle biopsy had revealed the presence of neurogenic atrophy. Peripheral blood count revealed persistent lymphopenia (ALC range: 1,270/μL to 2,482/μL). The child developed severe respiratory distress and succumbed to his illness at 5 months of age. The autopsy revealed the atrophy of cerebellar folia with a striking reduction of Purkinje and granular cells and preserved molecular layer. There was thinning of the corpus callosum and anterior horn cell degeneration in the spinal cord. Lung examination demonstrated fibrinous bronchitis, bronchiolitis, and pneumonia; a result of adenovirus infection confirmed by electron microscopy and PCR. The thymus was absent. Genetic testing identified a homozygous mutation in the AGTPBP1 gene (c2833C>T), confirming the diagnosis of CONDCA. This is the first autopsy description of CONDCA with detailed neuropathological evaluation. Although cerebellar atrophy is well known, this case reveals a wider neuropathological change and thymic aplasia in such patients. This case highlights the structural consequences of the AGTPBP1 gene-associated enzyme deficiency crucial for post-translational modifications of tubulin, resulting in the degeneration of specific sets of neurons and immune deficiency secondary thymic involvement.
In the article "A Phenomenological Study Exploring the Perceptions of Parents and Children Participating in the Lidcombe Program for Early Stuttering in Turkiye" [Folia Phoniatr Logop. 2025; https://doi.org/10.1159/000548660] by Subasi et al., the copyright license has been changed to a CC BY-NC 4.0 license.The original online article has been updated to reflect this.
This study aimed to comparatively evaluate the morphological and morphometric characteristics of the right atrial appendage (RAA) and left atrial appendage (LAA) in the same individuals using multidetector computed tomography (CT) and to investigate age- and sex-related differences. Pulmonary multidetector CT angiography images of 300 patients (167 women, 133 men; mean age, 54.0 ± 15.9 years) without pathological findings were retrospectively evaluated to assess the morphological and morphometric characteristics of both atrial appendages. Detailed morphometric measurements, including appendage length, width, orifice dimensions, orifice area, and volume, were performed for the RAA and LAA in each individual. RAA and LAA measurements were compared, and age- and sex-based analyses were performed. Interobserver agreement was assessed using kappa statistics. The most common RAA morphologies were sailboat (triangular) (48.3%) and horsehead (quadrangular) (25%), whereas the most frequent LAA types were chicken wing (55.7%) and windsock (20%). All morphometric parameters, including length, width, orifice dimensions, orifice area, and volume, were significantly greater in the RAA than in the LAA (all p < 0.001). No significant sex-related differences were observed for any RAA or LAA measurements. Age-based analysis revealed no significant changes in RAA parameters; however, LAA width (p = 0.002), orifice length (p = 0.027), orifice area (p = 0.031), and volume (p = 0.036) increased significantly, particularly in individuals older than 65 years. Interobserver agreement was excellent for all measurements. The RAA has significantly larger morphometric dimensions than the LAA in the same individuals and does not appear to be affected by age or sex. In contrast, several LAA parameters show age-related increases. These distinct morphometric differences provide clinically relevant anatomical reference data and may have important implications for interventional planning and the assessment of atrial appendage-related pathologies.
Pregnancy and diabetes increase the risk of developing pathologies in the oral cavity. Saliva biomarkers can be used as diagnostic markers in the monitoring of dental diseases. The study aimed to evaluate hard dental tissue health in pregnant women with two forms of diabetes and salivary antioxidant activity to identify optimal non-invasive caries risk factors. The study involved 104 pregnant women: 35 patients with gestational diabetes mellitus (GDM), 30 patients with type 1 diabetes (T1D), and 39 pregnant patients without diabetes mellitus (control group). Physical examination included caries assessment using the dental DMFT index, caries frequency, SiC index, and dental treatment index. Oral hygiene was also assessed using the Approximal Plaque Index (API). The study of unstimulated saliva measured the total Ferric Reducing Ability of Plasma (FRAP), as well as the activity of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPX). In the analyzed patient population, caries frequency totalled 100%, with active tooth decay observed in 72.12% of patients, whereas caries intensity was similar in the studied groups. In all groups, oral hygiene (API) was average. In T1D group, higher values of the API index (p = 0.001) were observed vs. the control group. Antioxidant activity was similar in the study groups. The independent determinants of caries occurrence included API (p = 0.002) and FRAP concentration (p = 0.02). The health of dental hard tissues in the examined patients was unsatisfactory and similar in the studied groups. FRAP concentration and oral hygiene (API) functioned as determinants of caries.
Patients with psoriasis treated with biologic therapy are considered to have increased risk of developing skin neoplasms. The impact of novel therapies on the development and biology of melanocytic lesions is not completely known. The aim of the study was assess if the treatment with biologics exerts effects on the melanocytic nevi. Dermoscopy and videodermoscopic imaging of 276 melanocytic lesions were performed at the initial visit and after one year in 13 patients with psoriasis treated with IL-12/23 inhibitors, IL-23 inhibitors or IL-17 inhibitors. The nevi size significantly increased at the one-year follow-up in the whole study group and in patients treated either with IL-23 inhibitors or IL-12/23 inhibitor. 2% of melanocytic nevi showed an increase in any of the scores (ABCD score, 7-Point Checklist score, CASH score) or at least 1-mm change in the diameter at the one-year follow-up; however, these changes were not statistically significant between the different therapy groups. Although treatment with novel groups of biologics leads to an increase in nevi size, it does not contribute to significant structural or color changes in melanocytic nevi or to the development of dysplastic nevi or melanoma at the one-year follow-up.
Industrial effluent and common effluent treatment plant (CETP)-associated samples from Navi Mumbai, India, were screened for indigenous lead-tolerant bacteria. Among 32 isolates, EP-L-21 showed the highest Pb tolerance, with growth at the highest tested concentration (>2,000 mg/L) Pb, broad pH tolerance (pH 4-10), and robust growth across 20-37 [Formula: see text]C, with consistent optical density at 600 nm (OD[Formula: see text]) values indicating broad temperature tolerance under Pb stress. VITEK® 2 identification and whole-genome sequencing (WGS) assigned EP-L-21 to Klebsiella pneumoniae (K. pneumoniae) sequence type 86 (ST86). The draft genome (5.38 Mb; 57.3 mol% GC; 46 contigs) encoded metal-resistance and stress-response determinants, including resistance-nodulation-division (RND)-family efflux systems, P-type ATPases, oxidative stress-associated genes. In addition, enterobactin- and aerobactin-associated siderophore biosynthetic clusters were identified, which may contribute indirectly to metal-stress adaptation under iron-limited and metal-stressed conditions; no canonical czcCBA operon was detected. In Luria-Bertani (LB) broth containing a measured initial supernatant-associated Pb concentration of 88.40 ± 0.43 mg/L, residual supernatant-associated Pb decreased to 0.58 ± 0.43 mg/L after 72 h, corresponding to 99.34% removal, whereas abiotic controls showed negligible Pb loss. Pb reduction over time was statistically significant ([Formula: see text]). Mass-balance analysis indicated that >99% of removed Pb was associated with non-supernatant fractions, although surface-bound, intracellular, and precipitated pools were not independently resolved. EP-L-21 also exhibited tolerance to Ni, with intermediate resistance to Cr, Cd, and sensitivity to Hg at lower concentrations. Genome analysis predicted the presence of antimicrobial resistance (AMR) and virulence-associated determinants, therefore, the strain should be considered an environmental opportunist and is suitable only for contained bioreactor-based applications, with environmental release not recommended. These findings link high-level Pb tolerance with a predicted multimetal resistome and support further mechanistic validation in contained bioprocess systems.
Periodontitis, a chronic inflammatory disease that severely compromises oral health and is linked to systemic disorders, has attracted increasing research attention. Kangfuxin (KFX), an ethanol extract derived from Periplaneta americana (L.) with documented anti-inflammatory and tissue-regenerative properties, remains unexplored for localized periodontal therapy. This study investigated whether KFX extended-release gel (KFX-ERG) could inhibit the progression of periodontal disease and provide potential support for the treatment of periodontitis. We selected the optimal concentration from different component ratios of KFX-ERG for subsequent experiments. In vivo, a periodontitis model was established in rats, and pathological changes in periodontal tissue were examined using histological and micro-computed tomography (micro-CT) analyses. Micro-computed tomography revealed that KFX-ERG reduced alveolar bone resorption in experimental periodontitis in rats. Histopathological analysis further revealed markedly reduced inflammatory cell infiltration and concurrently elevated osteoblast density in periodontal tissues of the KFX-ERG group. This study establishes a theoretical foundation for the therapeutic application of KFX-ERG in mitigating periodontitis progression and demonstrates its significant potential to promote periodontal tissue regeneration, thereby offering promising translational prospects for clinical regenerative periodontal therapy.
Pregnancy and the postpartum period are associated with physiological, hormonal, and hemodynamic changes that may increase susceptibility to cervical artery dissection. Structural alterations of the arterial wall can result from a variety of factors, predisposing vessels to injury and subsequent neurovascular events. In the present study, we analysed the contribution of multiple factors to the development of cervical artery dissection in pregnant women, including advanced maternal age, hormonal status, hypertension, hyperlipidaemia, connective tissue disorders, arterial malformations, migraine, adverse or rapidly changing head and neck positions, neck trauma, chiropractic manipulation, the presence of an elongated styloid process, pressure-inducing activities, and physical exercise.
Episodic ataxias (EAs) are rare autosomal-dominant channelopathies presenting with recurrent attacks of ataxia and variable neurological features. While MRI studies suggest mild cerebellar atrophy in some patients, detailed neuropathological descriptions are lacking. We examined postmortem brains and spinal cords from two genetically confirmed patients: EA1 (KCNA1 Val174Phe mutation) and EA2 (CACNA1A A253Y mutation). Routine histology and immunohistochemistry were performed. In EA1, the cerebellar vermis and hemispheres showed narrowing of the folia, segmental Purkinje cell loss, Bergmann gliosis, and scattered torpedoes. The dentate nucleus contained focal lipofuscin-laden macrophages and Rosenthal fibers. Concurrently, α-synuclein pathology (Braak stage 3) was also present, along with sparse age-related tau tangles and minimal vascular amyloid. In EA2, only focal Purkinje cell loss was detected, but novel p62-positive axonal and dendritic inclusions were observed in the cerebellar cortex and inferior olive. No additional α-synuclein, tau, or amyloid pathology was found. A concurrent glioblastoma was identified as the immediate cause of death. These are the first detailed autopsy reports of EA1 and EA2. Both revealed cerebellar pathology, with EA1 showing more pronounced Purkinje cell degeneration, while EA2 demonstrated previously undescribed p62-positive inclusions. These findings expand the clinicopathological spectrum of EAs and highlight the value of postmortem studies in elucidating underlying disease mechanisms.
Congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease (HD) belong to neurocristopathies - autonomic nervous system defects caused by abnormal neural crest cells migration. Their co-occurrence defines Haddad Syndrome (HS) associated also with increased risk of neural crest origin tumors, mainly neuroblastoma (NBL), and PHOX2B gene mutation. This case concerns a male newborn presenting respiratory failure minutes after birth. Due to sleep apnea and increasing hypercapnia, he required intubation. Genetic testing revealed an anomaly in PHOX2B gene. In subsequent days, the patient did not pass the meconium, which, based on the imaging tests and biopsy, raised a suspicion of HD. The boy was diagnosed with HS and additional diagnostic measures, including cancer screening, were ordered, owing to the syndrome's characteristics. Awareness of such conditions enables clinicians to implement targeted management that may significantly improve long-term outcomes and quality of life for affected children.
Gnotobiology, from the Greek gnotos (meaning 'known') and bios (meaning 'life'), is a research discipline that uses organisms with a defined microbiological status to study the interaction between hosts and microbes. This review traces six decades of Czech gnotobiology, beginning with the launch of a dedicated gnotobiology programme at Nový Hrádek in 1962 by Jaroslav Šterzl, whose visionary aims anticipated by decades the current recognition of the microbiota as a central determinant of immune and broader physiological function. The site - originally established in 1953 as the Biological Station - was thereby transformed into one of only four gnotobiological laboratories worldwide at that time and the first in Central and Eastern Europe. The facility pioneered the rearing of germ-free piglets, rats, rabbits, and mice, establishing the experimental foundation for the laboratory's work on immune ontogeny, mucosal immunity and tolerance, and microbiota-host interactions in immune development and regulation. This review discusses the key discoveries made using these models. Among them, work at the Institute of Microbiology (Prague and Nový Hrádek) demonstrated that germ-free animals have underdeveloped lymphoid tissue and impaired adaptive immunity. The review also describes the subsequent development of gnotobiotic models of human metabolic, immune-mediated, neoplastic, and neuropsychiatric diseases. The completion of the Human Genome Project in 2001 and the emergence of microbial metagenomics in the early 2000s sparked renewed interest in host-microbe interactions and led to a rediscovery of gnotobiotic approaches as essential tools for establishing causation in microbiome research. We examine how integrating these approaches with high-throughput sequencing, metabolomics, and other omics technologies has shifted the focus from cataloguing the microbiome to mechanistically dissecting host-microbe interactions. Finally, we outline future directions, including humanized gnotobiotic models, microbiota-based therapeutics, and the convergence of gnotobiology with personalized medicine and synthetic biology.
The aim of this study was to demonstrate the application of preoperative three-dimensional (3D) computed tomography (CT) reconstruction in the surgical management of paranasal sinus (PNS) osteomas.Osteomas are the most common benign PNS tumors and can lead to significant symptoms, including chronic rhinosinusitis, frontal pressure, and orbital or intracranial complications. Surgical excision is recommended for symptomatic cases or those with potential complications, with endoscopic and external approaches being the primary techniques. A 74-year-old patient presented with symptoms of chronic rhinosinusitis, including nasal obstruction and anosmia. CT revealed osteomas in the left ethmoid and frontal sinuses, measuring 27 × 21 × 28 mm and 15 × 17 mm, respectively. The patient was qualified for surgical excision of lesions. Preoperative planning included 3D CT reconstruction to assess the osteomas' size, location, and surgical access, particularly for a planned osteoplastic flap (OPF). During surgery, an endoscopic approach was initially utilized, resulting in frontosphenoethmoidectomy and removal of ethmoid osteoma. The other osteoma extended from the anterior to the posterior wall of the frontal sinus and required conversion to an external approach using the preplanned OPF. The surgery was successfully completed, with intraoperative findings being consistent with imaging. Postoperative complications were limited to frontal sinus outflow stenosis, managed endoscopically during follow-up. PNS osteomas may require complex surgical planning, especially when endoscopic and external approaches are combined. Preoperative 3D CT reconstruction provides valuable insights into tumor characteristics and aids in precise surgical planning. This case highlights the utility of 3D imaging in safe and effective management of challenging PNS osteomas.
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The femoral artery (FA) is a key site for femoral vascular access, but the length of the arterial segment available for access may vary with the level of profunda femoris artery (PFA) origin. This study evaluated the morphometric variability of the FA access window in relation to the PFA origin and described arterial caliber at fixed measurement points. This descriptive cadaveric study included 20 lower limbs from 10 adult Caucasian formalin-fixed cadavers. The FA access window was defined as the segment of the femoral artery between the inguinal ligament (IL) and the proximal margin of the PFA origin. Three fixed points were analyzed: P1, P5 and P10, located 1 cm, 5 cm and 10 cm below the IL. Each point was classified as within the window or distal to the PFA origin. External arterial diameter was measured at each point. Mean femoral artery access window length was 4.48 ± 2.02 cm, ranging from 0.97 to 9.81 cm. A short access window was present in 4/20 limbs, an intermediate access window in 11/20, and a long access window in 5/20. P1 was within the window in 19/20 limbs, P5 in 5/20, and P10 in none. Mean arterial diameter was 10.25 ± 2.22 mm within the window and 8.46 ± 1.31 mm distal to the PFA origin. The FA access window showed marked variability. The 5-cm point was distal to the PFA origin in most specimens, indicating that fixed-distance assumptions do not reliably identify the FA access window.
Mycophenolate mofetil (MMF) is a cornerstone immunosuppressive agent used in combination with calcineurin inhibitors and corticosteroids to prevent acute allograft rejection in solid organ transplant recipients. Long-term transplant outcomes depend not only on the pharmacological efficacy of immunosuppressive regimens but also on individualized dosing strategies and sustained medication adherence. Owing to the complex and highly variable pharmacokinetics of MMF's active metabolite, mycophenolic acid (MPA), therapeutic drug monitoring (TDM) has become an important tool for optimizing treatment safety and efficacy. We report a case of a kidney transplant recipient with unexpectedly elevated MPA exposure in the absence of clinical toxicity. A detailed pharmacokinetic assessment combined with a comprehensive clinical pharmacist-led medication review indicated that the increased MPA concentrations and elevated AUC0-12h were most likely related to impaired renal elimination of mycophenolic acid glucuronide (MPAG). Reduced MPAG clearance may enhance enterohepatic recirculation (EHR) of MPA, resulting in increased systemic exposure. This case highlights the importance of interpreting elevated MPA concentrations within a broader clinical context and underscores the critical role of clinical pharmacists, as members of an interdisciplinary team, in integrating TDM with comprehensive pharmacokinetic assessment to ensure safe and effective long-term immunosuppressive therapy.
The right subclavian artery typically originates from the lateral wall of the brachiocephalic trunk without tortuosity. Its anatomical variations pose significant challenges during transradial access. Although variations of the right subclavian artery are well-documented, no study has reported a variation in its origin angle. We report an exceptionally rare dual variation identified during dissection and discuss the clinical significance of this novel variation, emphasizing the technical challenges it poses during transradial access. The right subclavian artery demonstrated a right-angled origin from the posterior wall of the brachiocephalic trunk, in contrast to the normal lateral wall origin, accompanied by severe tortuosity. To our knowledge, this is the first documented case of the right subclavian artery origin angle variation. This variation may reduce transradial access success rates and increase the risks of procedural complications and mortality. The finding expands the known spectrum of the right subclavian artery anatomical variations and identifies a previously unrecognized challenge in transradial access.
The Brief Version of the Unhelpful Thoughts and Beliefs About Stuttering Scales (UTBAS-6) is an efficient and reliable way to screen for unhelpful and negative thoughts, as well as negative beliefs and anxiety among people who stutter. It makes it easier to provide information about people who stutter by saving time for SLPs in clinics. The aim of this study was to construct an Arabic version of the Brief Version of the Unhelpful Thoughts and Beliefs About Stuttering Scales (A-UTBAS-6) and to evaluate its clinical validity, reliability, and internal consistency. The developed A-UTBAS-6 was administered to 53 adults who stuttered (AWS) and 112 adults who did not stutter (ANS). Both test-retest reliability and internal consistency were tested. The results for both groups were compared. The internal consistency of the A-UTBAS-6 total score was excellent (Cronbach's α = 0.957), and test-retest reliability was statistically significant (p < 0.001). The scores for the two groups in the A-UTBAS-6 were significantly different (p < 0.001). A-UTBAS-6 is a valid tool for the early detection of thoughts and beliefs that are unhelpful and which may accompany speech disorders among Arabic patients who stutter.