The dual nature of the nucleolus.

The nucleolus is best known for housing the highly ordered assembly line that produces ribosomal subunits. The >100 ribosome assembly factors in the nucleolus are thought to cycle between two states: an operative state (when integrated into subunit assembly intermediates) and a latent state (upon release from intermediates). Although it has become commonplace to refer to the nucleolus as "being a multilayered condensate," and this may be accurate for latent factors, there is little reason to think that such assertions pertain to the operative state of assembly factors.

Spatiotemporal genotype replacement of H5N8 avian influenza viruses contributed to H5N1 emergence in 2021/2022 panzootic.

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics.

Saw-box osteotomy versus reamer-box osteotomy in posterior stabilized total knee arthroplasty: a retrospective study of an average five year follow-up.

PURPOSE: The purpose of this study is to compare the difference of results between two methods of femoral box osteotomy adopted by two designs of posterior stabilized total knee prostheses. PATIENTS AND METHODS: Retrospective analysis of the results of two groups of patients operated upon using two primary PS TKA systems, PFC Sigma (DePuy Synthes, Johnson and Johnson®) and Genesis II prosthesis (Smith and Nephew®), with an average of five year follow-up was done. Group 1 included 152 knees in 121 patients and group 2 included 122 knees in 111 patients. The average follow-up period in both groups was five years. The box osteotomy method depends on bone saw in group 1, and bone reamer in group 2. RESULTS: The KSS score of group 2 was better in the first six months postoperatively. Then, no significant differences were seen in the remaining follow-up visits. The risk of periprosthetic fractures was significantly higher in group 1 (p-value 0.040). Survival analysis showed a significantly shorter time for reoperation in group 1 than in group 2 as described by log-rank test, (p < 0.006). CONCLUSION: The method of box cutting has an impact on the function and longevity of posterior stabilized primary knee implants. The risk of periprosthetic fractures can be reduced by proper patient selection, decreasing the box sizes, and development of more "controlled" box osteotomy instruments.

Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies.

Acne vulgaris is a common dermatological condition that can present across different ages but predominantly affects adolescents and young adults. Characterized by various lesion types, the pathogenesis of acne is complex, involving genetic, hormonal, microbial, and inflammatory factors. This review comprehensively addresses current and emerging acne management strategies, emphasizing both topical and systemic treatments, procedural therapies, and dietary modifications. Key topical agents include retinoids, benzoyl peroxide, antibiotics, and other specialized compounds. Systemic options like antibiotics, hormonal therapies, and retinoids offer significant therapeutic benefits, particularly for moderate to severe cases. Procedural treatments such as laser devices, photodynamic therapy, chemical peels, and intralesional injections present viable alternatives for reducing acne symptoms and scarring. Emerging therapies focus on novel biologics, bacteriophages, probiotics, and peptides, providing promising future options. This review underscores the importance of personalized approaches to treatment due to the multifaceted nature of acne, highlighting the potential of innovative therapies for improving patient outcomes.

A novel artificial intelligence approach to detect the breast cancer using KNNet technique with EPM gene profiling.

Women's most frequent type of cancer is breast cancer, second only to lung cancer. This paper summarizes changes in genomics and epigenetics and incremental biological activities. A tumour develops through a series of phases involving a separate abnormal gene. Even though many diseases cause DNA mutations, most treatments are designed to relieve symptoms rather than change the DNA. Clustering short palindromic repeats (CRISPR) or Cas9 is the primary approach for discovering and confirming tumorigenic genomic targets. A Kohonen neural network with an expression programming model was developed for gene selection. The main problem in genetic selection is reducing the number of features chosen while maintaining accuracy. This purpose is accomplished systematically. In the end, the approach method performed better than the existing quantum squirrel-inspired algorithm and the recurrent neural network oppositional call search algorithm for genetic selection. The KNNet-EPM model used an expression programming approach to identify gene biomarkers for breast cancer. This method was achieved with RAE of 42%, sensitivity of 93%, f1 score of 88%, accuracy of 98%, kappa score of 83%, specificity of 92% and MAE of 30%.

Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.

BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up. METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses. RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.

Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021.

The H10 subtypes of avian influenza viruses pose a continual threat to the poultry industry and human health. The sporadic spillover of H10 subtypes viruses from poultry to humans is represented by the H10N8 human cases in 2013 and the recent H10N3 human infection in 2021. However, the genesis and characteristics of the recent reassortment H10N3 viruses have not been systemically investigated. In this study, we characterized 20 H10N3 viruses isolated in live poultry markets during routine nationwide surveillance in China from 2014 to 2021. The viruses in the recent reassortant genotype acquired their hemagglutinin (HA) and neuraminidase (NA) genes from the duck H10 viruses and H7N3 viruses, respectively, whereas the internal genes were derived from chicken H9N2 viruses as early as 2019. Receptor-binding analysis indicated that two of the tested H10N3 viruses had a higher affinity for human-type receptors than for avian-type receptors, highlighting the potential risk of avian-to-human transmission. Animal studies showed that only viruses belonging to the recent reassortant genotype were pathogenic in mice; two tested viruses transmitted via direct contact and one virus transmitted by respiratory droplets in guinea pigs, though with limited efficiency. These findings emphasize the need for enhanced surveillance of H10N3 viruses.

Analysis of gender differences with traditional posterior stabilized versus kinematic designs in total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty (TKA) is a good treatment for end-stage knee osteoarthritis (KOA). Approximately 60% of the patients are females, and 40% are males. This study analyzed pre- and postoperative angle differences in the range of motion (ROM), and the occurrence of complications with traditional posterior stabilization versus kinematic TKA in relation to gender. METHODS: Data from 434 patients with primary cemented total knee arthroplasty from 2018 to 2021 were collected. Alpha and beta angles were determined pre- and postsurgery. The ROM was collected pre- and postoperatively and during follow-up. Additionally, perioperative complications, revision rate, and blood transfusion management were investigated. RESULTS: The pre- and postoperative alpha-angle between men and women was significantly different, as was the level of alpha-angle correction between men and women (p = 0.001; p = 0.003). Same-gender differences in pre- to postoperative alpha-angles between traditional and kinematic TKA were shown (women (w): p = 0.001; men (m); p = 0.042). High postoperative alpha angles led to less ROM in traditional TKA for women (p = 0.008). No significant gender differences in ROM, perioperative complications, or revision surgery and transfusion rates were found. CONCLUSION: Despite high gender differences in pre- and postoperative angles, only female patients with traditional arthroplasty and high postoperative alpha angles showed less ROM in the follow-up. This leads to the assumption that gender-related pre- and postoperative angle differences, and the degree of angle correction, do not influence the ROM or perioperative occurrence of complications. Both designs present safe procedures for both genders with a wide spectrum of axis deformities.

Pedological data for the study of soils developed over a limestone bed in a humid tropical environment.

Lithological characteristics interact with other factors of soil formation to define soil genesis. This becomes more interesting as data on the mineral and elemental oxide components of soils developed from limestone are rarely available in the humid tropical environment. The present study investigated the elemental oxide content, forms of sesquioxides, and clay mineral species in some limestone soils. Soil samples were obtained from three (3) crestal soil profile pits and analyzed for elemental content by the use of an X-ray fluorescence spectrometer, and sesquioxide forms by inductively coupled plasma-mass spectrometer. Analyses were done in triplicates. The mineralogy of the clay fraction was determined on the A, B, and C horizon samples using an X-ray diffraction technique. The occurrence of SiO2 (203-277 g/kg), Al2O3 (65-105 g/kg), and Fe2O3 (14-95 g/kg) in substantial amounts over MnO2, ZrO2, and TiO2 with negligible quantities of CaO suggested comparatively more developed soils in the Agoi Ibami and Mfamosing tropical rainforests. Crystalline form of Fe was dominant over amorphous form, with indications of the co-migration of dithionite Fe with clay to the B horizons of the soils. Quartz, kaolinite, montmorillonite, and chlorite-vermiculite-montmorillonite interlayered minerals dominated the clay mineralogy of the studied soils. Mineral transformation places the soils at the transitory stage from the intermediate to the complete stage of soil development. The expanding clay minerals are most likely to increase plant nutrient adsorption and soil fertility status to accommodate the cultivation of a wider range of crops.

[Complications of percutaneous endoscopic gastrostomy in intensive care patients with dysphagia associated with neurological disorders]. / Oslozhneniya chreskozhnoi endoskopicheskoi gastrostomii u reanimatsionnykh bol'nykh s sindromom disfagii tsentral'nogo geneza.

OBJECTIVE: To develop an effective method for percutaneous endoscopic gastrostomy using gastropexy technology. MATERIAL AND METHODS: We retrospectively analyzed 260 ICU patients with dysphagia associated with neurological disorders between 2010 and 2020. All patients were divided into two groups: the main group (n=50) - percutaneous endoscopic gastrostomy with gastropexy, control group (n=210) - surgery without fixing the anterior wall of the stomach to the abdominal wall. RESULTS. G: Astropexy significantly reduced the incidence of postoperative complications (p=0.045) and severe complications (grade IIIa and higher) (χ2=3.701, p=0.055). Early postoperative complications occurred in 20 (7.7%) patients. Surgery and subsequent treatment were associated with normalization of leukocyte count (p=0.041), C-reactive protein (p=0.024) and serum albumin (p=0.0012). Mortality was similar in both groups. Overall 30-day mortality rate in both groups was 20.8% that was associated with clinical severity of patients. Percutaneous endoscopic gastrostomy was not the direct cause of death in any case. However, complications of endoscopic gastrostomy aggravated the underlying disease in 2.9% of cases. CONCLUSION: Percutaneous endoscopic gastrostomy with gastropexy reduces the incidence of postoperative complications.

Plectin promotes tumor formation by B16 mouse melanoma cells via regulation of Rous sarcoma oncogene activity.

BACKGROUND: Melanoma is a malignant tumor characterized by high proliferation and aggressive metastasis. To address the molecular mechanisms of the proto-oncogene, Rous sarcoma oncogene (Src), which is highly activated and promotes cell proliferation, migration, adhesion, and metastasis in melanoma. Plectin, a cytoskeletal protein, has recently been identified as a Src-binding protein that regulates Src activity in osteoclasts. Plectin is a candidate biomarker of certain tumors because of its high expression and the target of anti-tumor reagents such as ruthenium pyridinecarbothioamide. The molecular mechanisms by which plectin affects melanoma is still unclear. In this study, we examined the role of plectin in melanoma tumor formation. METHODS: We used CRISPR/Cas9 gene editing to knock-out plectin in B16 mouse melanoma cells. Protein levels of plectin and Src activity were examined by western blotting analysis. In vivo tumor formation was assessed by subcutaneous injection of B16 cells into nude mice and histological analysis performed after 2 weeks by Hematoxylin-Eosin (H&E) staining. Cell proliferation was evaluated by direct cell count, cell counting kit-8 assays, cyclin D1 mRNA expression and Ki-67 immunostaining. Cell aggregation and adhesion were examined by spheroid formation, dispase-based dissociation assay and cell adhesion assays. RESULTS: In in vivo tumor formation assays, depletion of plectin resulted in low-density tumors with large intercellular spaces. In vitro experiments revealed that plectin-deficient B16 cells exhibit reduced cell proliferation and reduced cell-to-cell adhesion. Since Src activity is reduced in plectin-deficient melanomas, we examined the relationship between plectin and Src signaling. Src overexpression in plectin knockout B16 cells rescued cell proliferation and improved cell-to-cell adhesion and cell to extracellular matrix adhesion. CONCLUSION: These results suggest that plectin plays critical roles in tumor formation by promoting cell proliferation and cell-to-cell adhesion through Src signaling activity in melanoma cells.

Expression characteristic, immune signature, and prognosis value of EFNA family identified by multi-omics integrative analysis in pan-cancer.

BACKGROUND: EphrinA (EFNA) are Eph receptor ligands that regulate various disease processes. Nonetheless, the expression characteristics of EFNAs in pan-cancer, their relationship with tumor immune microenvironment, and prognostic value landscape remain unknown. METHODS: A comprehensive landscape of EFNAs was created using various statistical data extracted from 33 cancers. Subsequently, we identified differential expression, genetic variations, potential function enrichment, tumor immune-related analysis, and drug sensitivity. Further, we investigated the clinical features and diagnostic prognostic value of EFNAs. RT-qPCR, western blot and immunohistochemistry (IHC) were used to validate the expression level and significant clinical value of EFNA5 in lung adenocarcinoma cell lines and tissues. RESULTS: EFNAs were highly mutated in various cancers. Genomic and epigenetic alterations of EFNAs were observed in various tumors, where an oncogenic mutation in specific cancer types potentially affected EFNA expression. Moreover, tumor-derived EFNAs were significantly related to the tumor immune microenvironment, suggesting that they are promising therapeutic targets. The majority of EFNA family genes were significantly linked to patient prognosis. Eventually, EFNA5 was an independent prognostic factor in lung adenocarcinoma. CONCLUSION: In summary, EFNAs are crucial in tumor immune regulation, and EFNA5 is a prognostic marker in lung adenocarcinoma. Our findings provide new insights into EFNAs from a bioinformatics standpoint and highlight the significance of EFNAs in cancer diagnosis and treatment.

Digital Mapping of Soil Organic Carbon Based on Machine Learning and Regression Kriging.

In the last two decades, machine learning (ML) methods have been widely used in digital soil mapping (DSM), but the regression kriging (RK) model which combines the advantages of the ML and kriging methods has rarely been used in DSM. In addition, due to the limitation of a single-model structure, many ML methods have poor prediction accuracy in undulating terrain areas. In this study, we collected the SOC content of 115 soil samples in a hilly farming area with continuous undulating terrain. According to the theory of soil-forming factors in pedogenesis, we selected 10 topographic indices, 7 vegetation indices, and 2 soil indices as environmental covariates, and according to the law of geographical similarity, we used ML and RK methods to mine the relationship between SOC and environmental covariates to predict the SOC content. Four ensemble models-random forest (RF), Cubist, stochastic gradient boosting (SGB), and Bayesian regularized neural networks (BRNNs)-were used to fit the trend of SOC content, and the simple kriging (SK) method was used to interpolate the residuals of the ensemble models, and then the SOC and residual were superimposed to obtain the RK prediction result. Moreover, the 115 samples were divided into calibration and validation sets at a ratio of 80%, and the tenfold cross-validation method was used to fit the optimal parameters of the model. From the results of four ensemble models: RF performed best in the calibration set (R2c = 0.834) but poorly in the validation set (R2v = 0.362); Cubist had good accuracy and stability in both the calibration and validation sets (R2c = 0.693 and R2v = 0.445); SGB performed poorly (R2c = 0.430 and R2v = 0.336); and BRNN had the lowest accuracy (R2c = 0.323 and R2v = 0.282). The results showed that the R2 of the four RK models in the validation set were 0.718, 0.674, 0.724, and 0.625, respectively. Compared with the ensemble models without superimposed residuals, the prediction accuracy was improved by 0.356, 0.229, 0.388, and 0.343, respectively. In conclusion, Cubist has high prediction accuracy and generalization ability in areas with complex topography, and the RK model can make full use of trends and spatial structural factors that are not easy to mine by ML models, which can effectively improve the prediction accuracy. This provides a reference for soil survey and digital mapping in complex terrain areas.

The Role of Cytoskeletal Proteins in the Formation of a Functional In Vitro Blood-Brain Barrier Model.

The brain capillary endothelium is highly regulatory, maintaining the chemical stability of the brain's microenvironment. The role of cytoskeletal proteins in tethering nanotubules (TENTs) during barrier-genesis was investigated using the established immortalized mouse brain endothelial cell line (bEnd5) as an in vitro blood-brain barrier (BBB) model. The morphology of bEnd5 cells was evaluated using both high-resolution scanning electron microscopy and immunofluorescence to evaluate treatment with depolymerizing agents Cytochalasin D for F-actin filaments and Nocodazole for α-tubulin microtubules. The effects of the depolymerizing agents were investigated on bEnd5 monolayer permeability by measuring the transendothelial electrical resistance (TEER). The data endorsed that during barrier-genesis, F-actin and α-tubulin play a cytoarchitectural role in providing both cell shape dynamics and cytoskeletal structure to TENTs forming across the paracellular space to provide cell-cell engagement. Western blot analysis of the treatments suggested a reduced expression of both proteins, coinciding with a reduction in the rates of cellular proliferation and decreased TEER. The findings endorsed that TENTs provide alignment of the paracellular (PC) spaces and tight junction (TJ) zones to occlude bEnd5 PC spaces. The identification of specific cytoskeletal structures in TENTs endorsed the postulate of their indispensable role in barrier-genesis and the maintenance of regulatory permeability across the BBB.

An Epigenetic LINE-1-Based Mechanism in Cancer.

In the last fifty years, large efforts have been deployed in basic research, clinical oncology, and clinical trials, yielding an enormous amount of information regarding the molecular mechanisms of cancer and the design of effective therapies. The knowledge that has accumulated underpins the complexity, multifactoriality, and heterogeneity of cancer, disclosing novel landscapes in cancer biology with a key role of genome plasticity. Here, we propose that cancer onset and progression are determined by a stress-responsive epigenetic mechanism, resulting from the convergence of upregulation of LINE-1 (long interspersed nuclear element 1), the largest family of human retrotransposons, genome damage, nuclear lamina fragmentation, chromatin remodeling, genome reprogramming, and autophagy activation. The upregulated expression of LINE-1 retrotransposons and their protein products plays a key role in these processes, yielding an increased plasticity of the nuclear architecture with the ensuing reprogramming of global gene expression, including the reactivation of embryonic transcription profiles. Cancer phenotypes would thus emerge as a consequence of the unscheduled reactivation of embryonic gene expression patterns in an inappropriate context, triggering de-differentiation and aberrant proliferation in differentiated cells. Depending on the intensity of the stressing stimuli and the level of LINE-1 response, diverse degrees of malignity would be generated.

Gustav Nikolaus Specht (1860­1940): psychiatric practice, research and teaching during a change of psychiatric paradigm before and after Kraepelin.

Gustav Specht (1860-1940) developed academic psychiatry in Erlangen. After studying medicine in Würzburg, Munich and Berlin, he became assistant medical director in the mental asylum of Erlangen. In 1897 he was appointed extraordinary, and in 1903 ordinary, Professor of Psychiatry. A good clinician and teacher, Specht worked during a time of paradigm change in psychiatry. He was an expert in chronic mania, and introduced the concept of the 'grumbler's delusion'. Paranoia he believed to be the core problem of psychopathology and considered the depressive syndrome as an 'exogenous-type' of reaction. For him, trauma was important in the genesis of mental illness, and his 'hystero-melancholy' anticipated the concept of borderline personality disorder.

Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell.

Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor ß (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Evaluating the "Patella-Friendly" Concept in Total Knee Arthroplasty: A Minimum 15-Year Follow-Up Outcome Study Comparing Constant Radius, Multiradius Cruciate-Retaining, and Nonanatomical Cruciate-Retaining Implants.

BACKGROUND: Patella-friendly femoral components were developed in order to reduce anterior knee pain and patellofemoral complications in total knee arthroplasty (TKA), but their effect on long-term outcome is still unclear. METHODS: We retrospectively evaluated prospectively collected data from 3 groups consisting of 100 patients (100 knees in each). In group A, the constant radius a-MP, in group B the multiradius cruciate-retaining Genesis II, and in group C the nonanatomic, multiradius, cruciate-retaining AGC TKA was implanted. Patients of all groups were matched for age, gender, side, body mass index, and length of follow-up. Preoperative and postoperative clinical outcome data in the form of Knee Society System (KSS), Short Form-12, Western Ontario and McMaster University Osteoarthritis Index, and Oxford Knee Score were available at regular intervals for groups A and B. For patients of group C, KSS score data were available at the same time intervals. In all groups, the patellofemoral compartment was assessed using the Clinical Patella Score scale. Anterior knee pain, secondary patella resurfacing, implant failure, and radiological outcome were assessed in patients of all groups. RESULTS: At 10-year and 15-year follow-up, patients of group A showed statistically significant (s.s.) higher (all P = .000) KSS values as compared to those of groups B and C. At 15-year follow-up, patients of group B showed s.s. higher (P = .001) KSS values as compared to those of group C. At 10-year and 15-year follow up, patients of group A showed s.s. higher (all P = .00) Western Ontario and McMaster University Osteoarthritis Index and Oxford Knee Score values as compared to those of group B. At 15-year follow-up only, patients of group A showed s.s. higher (P = .00) Short Form-12 (physical) values as compared to those of group B. In terms of Clinical Patella Score, patients in group A had s.s. higher values (P = .05) when compared to those of groups B and C. Anterior knee pain was recorded in 4.4% of TKAs in group A, 7.5% in group B, and 17.2% in group C. One (1.1%) patient in group A, 3 (3.25%) in group B, and 7 (8%) in group C underwent secondary resurfacing. CONCLUSION: Anatomical, patella-friendly, constant radius femoral components outperform others in reducing anterior knee pain and patella complications in TKA in which the patellae are left nonresurfaced.

The Involvement of Insulin-Like Growth Factor 1 and Nerve Growth Factor in Alzheimer's Disease-Like Pathology and Survival Role of the Mix of Embryonic Proteoglycans: Electrophysiological Fingerprint, Structural Changes and Regulatory Effects on Neurotrophins.

Alzheimer's disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aß). Among them, Aß (25-35) fragment plays a critical role in the development of neurodegeneration-it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors-the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)-of AD-like neurodegeneration induced by Aß (25-35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex-hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aß (25-35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.

NGS in Hereditary Ataxia: When Rare Becomes Frequent.

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP-based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.