Visualization of sheep kidney vasculature by modified corrosion cast technique

This Letter to the Editor correlates with the article: Aycan K, Köse F, Kamaşak Arpaçay B, et al. A new corrosion method (Aycan’s method). Folia Morphol. 2025; 84(1): 249–255, doi: 10.5603/fm.100364, indexed in Pubmed: 38895752

A Call for a Modern Satyagraha Against Metabolic Syndrome

Objective: In 1923, while India was engaged in the Flag Satyagraha movement for independence, the medical community witnessed the discovery of insulin and the early recognition of metabolic syndrome (MetS) by Swedish physician Eskil Kylin. This article draws parallels between the historical Satyagraha movement and the current fight against MetS, advocating for a comprehensive and integrated approach to managing this syndrome. We explore the multifaceted role of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in managing MetS, emphasizing their cardioprotective and renoprotective benefits. Materials and methods: A detailed review of existing literature on MetS, its definitions, prevalence, and management strategies was conducted. The therapeutic potential of SGLT2i was examined through a meta-analysis of randomized controlled trials (RCTs) to assess their impact on key components of MetS, including fasting plasma glucose, waist circumference (WC), blood pressure, body weight, and uric acid levels. Results and conclusions: SGLT2is, including empagliflozin, dapagliflozin, and canagliflozin, demonstrated significant efficacy in improving several components of MetS. Notably, these agents reduced fasting plasma glucose by up to 30.02 mg/dL and WC by 1.28 cm, while also providing modest reductions in systolic blood pressure and body weight. Additionally, SGLT2is were associated with significant reductions in uric acid levels, contributing to their renoprotective effects. Despite the minimal impact on high-density lipoprotein (HDL) cholesterol levels, SGLT2is showed broad cardiometabolic benefits, including anti-inflammatory effects and modulation of sympathetic nervous system activity. Public health initiatives must also prioritize lifestyle modifications and early detection to curb the rising prevalence of this condition

Antibodies against the receptor for insulin-like growth factor 1 (IGF-1RAb), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) in the serum of patients with Graves’ and Basedow’s disease with and without orbitopathy

Introduction: Proven risk factors for thyroid orbitopathy (TO) are thyroid dysfunction, smoking, and high levels of thyrotropin receptor antibodies (TRAb), and the role of insulin-like growth factor 1 (IGF-1), the receptor for IGF-1 (IGF-1R), and antibodies to the receptor for IGF-1 (IGF-1RAb) are also debated. IGF-1R is overexpressed in fibroblasts and orbital lymphocytes in TO patients. It forms a functional complex and mediates signal transduction through thyroid stimulating hormone receptor (TSHR). The study aimed to evaluate the levels of IGF-1RAb, IGF-1, and IGFBP-3 in a group of Graves’ and Basedow’s disease (GBD) patients with or without TO. Material and methods: Sixty-seven patients were included in the study, including 47 GBD and 20 control patients. In the GBD group, 31 patients were diagnosed with active TO and were treated with immunosuppressive therapy according to the standard of European Group on Graves’ Orbitopathy (EUGOGO) guidelines. In this group, 10 patients were in the sight-threatening stage of TO severity according to EUGOGO classification. IGF-1 and IGFBP-3 levels were determined with the use of chemiluminescence immunoassay (CLIA) methods. IGF-1RAb was measured by the “in-house” constructed enzyme-linked immunosorbent assay (ELISA) method. Results: Including our cut-off value (Q75 — 232.48 ng/mL), positive serum IGF-1RAb was found in 25% of patients in the control group (5 out of 20 patients), in 38.3 % (18 out of 47 patients) of patients with GBD, and in 22.5% of GBD patients with active TO (7 out of 31 patients). In GBD patients with active TO, there were no differences in IGF-1RAb when compared to the control group but with a significantly lower level when compared to the GBD patients without active TO. The group of patients with active TO in the sight-threatening stage had significantly lower values of IGF-1RAb compared to the group of patients with GBD without the presence of TO (p = 0.004). There was also a difference in IGF-1RAb concentration between the groups in moderate-to-severe and sight-threatening stages of TO before starting immunosuppressive treatment (p = 0.014). There was no difference in IGF-1 levels between the control group and GBD patients with active TO before starting immunosuppressive treatment and GBD patients without active TO. The was a significant difference in IGF-1 concentration between the group with moderate-to-severe and sight-threatening stages of TO before starting immunosuppressive treatment (p = 0.009). We found significantly lower IGFBP-3 concentrations in GBD patients regardless of the presence of TO compared to the control group (p = 0.016). There was no difference in IGFBP-3 concentrations between patients with moderate-to-severe and sight-threatening stages of TO (p = 0.203). Conclusion: It seems that high IGF-1RAb levels may have a protective effect against the onset or severe course of TO, and patients with low IGF-1RAb levels are at risk for severe TO. Our results suggest that anti-receptor antibodies to IGF-1 are inhibitory antibodies

Assessment of fracture risk based on FRAX score and Polish guidelines in patients with newly diagnosed osteoporosis

Introduction: The authors of the latest recommendations state that osteoporosis diagnosis should not rely solely on densitometric (DXA) criteria. Fracture risk assessment is crucial for determining diagnosis and intervention thresholds. Comprehensive assessment of fracture risk requires consideration of bone mineral density (BMD) results, use of risk calculators like Fracture Risk Assessment Tool (FRAXTM), and analysisof clinical and lifestyle factors. Experts highlight the need to identify patients at very high fracture risk to justify starting anabolic therapy. This retrospective study assessed fracture risk in newly diagnosed osteoporosis patients, identifying those at high and very high risk. Material and methods: The study included 159 postmenopausal women with newly diagnosed osteoporosis, identified by a T-score of ≤ –2.5 standard deviations (SD) from DXA scans of the femoral neck and/or lumbar spine. Demographic data and laboratory tests were collected, and the 10-year fracture risk for major osteoporotic fractures (FRAX MOF) and hip fractures (FRAX HF) was calculated using the FRAX-PL calculator, which included femoral neck BMD. Each patient was then classified into a risk group based on modified fracture risk assessment criteria. Results: The study found that the most common risk factor for osteoporosis was a previous fracture (56.6%). Other common risk factors included smoking (21.38%), parental hip fracture (13.21%), and glucocorticoid use (10.70%). The FRAX calculator showed that 47.80% of patients were at very high risk for HF and 23.90% for MOF. A high HF risk was present in 10.06% of patients, and high MOF risk in 34.59%, whereas a medium and low MOF risk concerned 25.79% and 15.72% of the subjects, respectively. With expanded criteria, 72.33% of patients were classified at very high risk, compared to 23.90% for MOF and 47.80% for HF based solely on FRAX. Most patients met the T-score ≤ –3.0 SD criterion (52.20%) and FRAX > 15% for MOF or FRAX > 4.5% for HF (52.20%). Women aged 65–70 and 70–75 years are at the highest risk and qualify for anabolic therapy. Conclusions: Our study highlights the importance of stratifying patients by fracture risk, showing that more individuals are identified at very high risk when using the expanded assessment criteria from the latest Polish guidelines

Genetic and functional analysis of TUBB1 variants in congenital hypothyroidism

Background: Congenital hypothyroidism (CH) is the most common neonatal disorder, primarily caused by thyroid dysgenesis (TD). While the genetic cause has been identified in less than 5% of TD cases, there is an urgent need to investigate additional gene mutations that may be responsible. In 2018, TUBB1 was identified as a novel candidate gene associated with TD. Nevertheless, further research is required to confirm the role of TUBB1 in TD pathogenesis and the association between TUBB1 mutations and TD in humans. Based on the previous genetic analysis of TUBB1 in 289 Chinese TD patients, this study aimed to further validate the association between TUBB1 and TD, and to explore the pathogenic mechanisms of TUBB1 c.952C>T at the cellular level. Material and methods: We performed real-time polymerase chain reaction (RT-PCR), western blot, Cell Counting Kit 8 (CCK8), and wound healing assay to evaluate the effect of TUBB1 c.952C>T on gene expression, cell proliferation, and migration. Results: The c.952C>T mutant decreased the expression of TUBB1 in both mRNA and protein level, and inhibited the proliferation of thyroid cells significantly. Also, c.952C>T mutant showed restrain effects on the migration, although there was no stistical significance. Notably, pathogenic TUBB1 variants were not detected in patients with dyshormonogenesis (DH). Conclusions: TUBB1 variants confer genetic susceptibility to TD but not DH. The pathogenic variant in TUBB1 was identified in 1.38% (4/289) of our Chinese TD patient cohort, and burden test analysis revealed an association between TUBB1 variants and TD. Functional experimental results indicated that the c.952C>T mutant dominantly affects gene expression and proliferation of thyroid cells

Root anatomy and canal configuration of human permanent maxillary third molar — a systematic review

Knowledge of the configuration of root canals is essential for the success of endodontic treatment. The main aim of this systematic review was to determine the number of roots and the number of root canals in maxillary third molars, as well as where possible to determine the Vertucci classification. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. The study protocol was registered and approved on PROSPERO, the International Prospective Register of Systematic Reviews (Reg. No: CRD42022366444), before the start of the study. 12 studies were included in the analysis, differing in sample origin and methodology. The combined studies were analysed based on the number of roots, the number of canals, and the root canal configurations, and the findings were compared to those of other international studies. Analysing the available research results regarding the root anatomy and canal configuration of the third maxillary molar, most commonly maxillary third molars had three roots (59.0%). Single-rooted teeth (24.2%) or double-rooted teeth (13.8%) were less common. In addition, we observed that maxillary third molars typically possessed three root canals (47.28%) and the MB (mesiobuccal), DB (distobuccal), and P (palatal) canals most often showed Vertucci Type I (59.53%, 95.83% and 98.61%, respectively) in three-rooted form. Due to the small number of available studies, it is necessary to conduct further analyses taking into account demographic and ethnic differences that may affect the anatomical and morphological structure of the teeth

Please be very careful, when describing variant muscle

This Letter to the Editor correlates with the article: Kowalczyk A, Topuzov N. Three in one — unusual palmaris longus muscle anatomical variation. Folia Morphol. 2024; 84(4): 925–929, doi: 10.5603/fm.98076, indexed in Pubmed: 38757504

Thyroid ima artery (the artery of Neubauer) — how much do we know?

The blood supply of the thyroid gland has been the subject of numerous original studies, case reports and meta-analyses. The number of surgical procedures carried out on the thyroid gland has significantly increased over the last few decades. The cadaveric report discusses the case of a thyroidea ima artery (TIA) which originated from the brachiocephalic artery before its terminal subdivision, giving off numerous branches to the infrahyoid muscles, trachea, and thyroid gland. Based on the current literature, we discuss the prevalence of TIA, its embryology, and possible clinical aspects of this variation, with special attention paid to the postoperative complications

Higher neoantigen load correlates with better overall survival in Chinese lung adenocarcinoma patients

Introduction. Neoantigen load (NAL) has been extensively studied as a promising biomarker for immunotherapy. Recently it was also reported that NAL is associated with lung cancer patient survival, but the results were not consistent. Material and methods. To further evaluate the prognostic value of NAL in lung cancer, we analyzed NAL in a cohort of 96 lung adenocarcinoma (AD) and 83 lung squamous cell carcinoma (SQ) patients from the Cancer Genome Atlas (TCGA). We found that high NAL correlates with better overall survival (OS) of AD patients but with worse OS of SQ patients. Next, we collected a total of 25 NSCLC patient samples and explored whole exome sequencing (WES) and a large targeted gene panel (Med1CDx panel containing 579 genes) for NAL and tumor mutation burden (TMB) analysis. Results. We found that patients with both higher NAL and TMB, who underwent chemotherapy combined with immunotherapy, showed better OS and progression-free survival (PFS) in both AD and SQ subgroups. We also compared the concordance of NAL and TMB between WES and the Med1CDx panel. The R2 for concordance of NAL and TMB prediction by WES and our Med1CDx panel was 0.81 and 0.86, respectively. Conclusions. In this study, we showed that NAL is a useful biomarker for lung cancer OS prediction at least in the AD cohort. Furthermore, considering the high cost ofWES, large targeted gene-panel-based NAL and TMB analysis could be a good alternative in clinical practical settings

Malignant peripheral nerve sheath tumor—from genetics to multidisciplinary treatment

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma (STS); it originates from nervous tissue and typically develops in proximity to nerve trunks in the limbs and trunk. These tumors, constituting approximately 5% of soft tissue sarcomas, can either form spontaneously or arise frompre-existing neurofibromas. The majority (90%) of cases occur in individuals between the 2nd and 5th decades of life. Themain risk factor for MPNST is von Recklinghausen disease (type 1 neurofibromatosis). The cornerstone of MPNST management involves radical surgicalmeasures, specifically tumor excision within healthy tissue boundaries (wide local excision), which is complemented by adjuvant radiotherapy. In case of metastatic disease, palliative chemotherapy employing doxorubicin or a combination of doxorubicin and ifosfamide is utilized. Approximately 25–30% of patients experience clinical improvement after chemotherapy. Looking ahead, advancements in research on molecular biology may lead to the development of inhibitors demonstrating greater efficacy than traditional chemotherapy for MPNST patients. At present, ongoing clinical trials of the therapeutic management of MPNST encompass pembrolizumab, the combination of nivolumab with ipilimumab, pexydartinib (an inhibitor targeting KIT, CSF1R, and FLT3) in conjunction with sirolimus, sapanisertib (a TORC1/2 inhibitor), or LOXO-195 (an inhibitor of neurotrophic tyrosine kinase receptors NTRK type 1, 2, and 3)