Torques in the human upper ankle joint level and their importance in conservative and surgical treatment.

The paper deals with the torques of external muscles acting on the upper ankle joint under weight-bearing conditions and their importance in diagnosing and treating the human foot. Experimental data were collected and calculations were performed. Based on the experiments with the biomechanical model of the foot and upper ankle joint, it was shown how the changes in the force arms of the external muscles of the foot under weight-bearing conditions, change the torque. The real values of muscle forces and torques of the external muscles of the foot were calculated. Taking into account the distance of the lines of muscle action from the axis of rotation of the upper ankle joint the rotational force of the muscles was calculated. The influence of changing the force arm on the rotational efficiency of the muscle balancing the moment of gravity was shown. Knowledge of muscle torque under weight-bearing conditions is crucial for correctly assessing foot biomechanics. It has been shown that torque (gravitational and muscular), not pure force, is crucial when assessing the rotational capacity of the analyzed joint. A change in the approach to diagnostics and treating paresis or weakness of extrinsic foot muscles was proposed through the manipulation of the distance of their action line from the axis of joint rotation.

Reduction in the Free Androgen Index in Overweight Women After Sixty Days of a Low Glycemic Diet.

BACKGROUND: Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including nutritious dietary patterns and physical activity, may influence the clinical manifestation of the disease. This study determined the effect of a low-glycemic index anti-inflammatory diet on testosterone levels and sex hormone-binding globulin (SHBG) and clinical symptoms in hyperandrogenic women at their reproductive age. METHODS: The study included 44 overweight and obese women diagnosed with hyperandrogenism. The anthropometrics (weight, height, body mass index, waist circumference, hip circumference), physical activity, and dietary habits were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was <0.001. Serum testosterone and SHBG levels were measured using automated immunoassay instruments. RESULTS: The intervention based on a low-glycemic index diet with anti-inflammatory elements and slight energy deficit decreased total testosterone levels (p<0.003), increased SHBG levels (p<0.001), and decreased the free androgen index (FAI; p<0.001). Post-intervention, overall well-being was much higher than in the pre-intervention period (p<0.001), and stress was diminished (p<0.001). Western nutritional patterns positively correlate with clinical hyperandrogenism progression, whereas several factors of the low-glycemic index diet with anti-inflammatory elements and slight energy deficit positively associate with reduced clinical hyperandrogenism symptoms. CONCLUSIONS: In overweight and obese women, proper selection of diet, introduction of moderate physical activity, and reduction in weight, stress factors, and alcohol consumption translate into several positive effects, including reduced FAI and symptoms such as acne, hirsutism, menstrual disorders, and infertility.

Data integration through canonical correlation analysis and its application to OMICs research.

The subject of the paper is a review of multidimensional data analysis methods, which is the canonical analysis with its various variants and its use in omics data research. The dynamic development of high-throughput methods, and with them the availability of large and constantly growing data resources, forces the development of new analytical approaches that allow the review of the analyzed processes, taking into account data from various levels of the organization of living organisms. The multidimensional perspective allows for the assessment of the analyzed phenomenon in a more realistic way, as it generally takes into account much more data (including OMICs data). Without omitting the complexity of an organism, the method simplifies the multidimensional view, finally giving the result so that the researcher can draw practical conclusions. This is particularly important in medical sciences, where the study of pathological processes is usually aimed at developing treatment regimens. One of the primary methods for studying biomedical processes in a multidimensional approach is the canonical correlation analysis (CCA) with various variants. The use of CCA unique methodologies for simultaneous analysis of multiset biomolecular data opens up new avenues for studying previously undiscovered processes and interdependencies such as e.g. in the tumor microenvironment (TME) connected to intercellular communication. Because of the huge and still untapped potential of canonical correlation, in this review available implementations of CCA techniques are presented. In particular, the possibility of using the technique of canonical correlation analysis for OMICs data is emphasized.

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma.

Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model (Mus musculus SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.

miRNA Signature of Urine Extracellular Vesicles Shows the Involvement of Inflammatory and Apoptotic Processes in Diabetic Chronic Kidney Disease.

BACKGROUND: The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM). METHODS: UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR. RESULTS: A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR­451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR­503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR­375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways. CONCLUSIONS: This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease.

Dynamic-passive correction of hallux valgus and associated static foot deformities.

PURPOSE: The aim of this paper was the application of a new dynamic-passive method of treatment in correction of hallux valgus and coexisting static deformities of the foot (transverse-plane and plano-valgus foot). METHODS: The study involved 50 patients; 26 with full big toe correction after the passive correction grip (group I) and 24 with big toe correction requiring additional passive abduction (group II). The patients regularly performed exercises using the designed device according to the planned schedule. The progress of the correction was assessed by a medical examination and additional tests. RESULTS: The cross-sectional area [cm2 ] of the abductor hallucis muscle in three-time points among I and II groups of patients with the hallux valgus was measured based on MRI images. The STIR examination showed, among others, the abductor hallucis muscle edema after exercises with the DPc device were carried out. It evidences that exercises with the new device activate the muscle. Alignment of the big toes of both feet in groups I and II were obtained with a statistically significant result ( p < 0.05). The percentage progression of correction for HV and I/II IM was calculated. CONCLUSIONS: Based on the new correction approach the alignment of the big toe phalanges and the remaining toes was obtained. The passive setup of the tendons with their distal inserts at the level of the big toe phalanges to the correct path of their course with the withdrawal of articular subluxations was obtained. Simultaneously, the big toe's passive correction was dynamically consolidated through a specially selected set of exercises.

Muscular Systems and Their Influence on Foot Arches and Toes Alignment-Towards the Proper Diagnosis and Treatment of Hallux Valgus.

(1) Background: Static foot deformities, including hallux valgus, are common deformities. The subject under consideration is the role of extrinsic and intrinsic muscles working within muscular systems that shape the arches of the foot and the alignment of the toes. (2) Methods: Based on a literature review, the muscle systems were analyzed. The systems under consideration were as follows: "tendon stirrup" (system I); muscles complementary to the tendon stirrup (system II); "foot lever" (system III); muscles complementary to system III (system IV); "reins of hallux" (system V), a muscular system having distal inserts on the hallux. The shape of the foot arches was analyzed in this context. (3) Results: The correct arch architecture of the foot stabilized mainly by the extrinsic muscle systems determining the function of the intrinsic muscle systems of the foot is described. The proper function of muscular systems shaping the arches of the foot is a prerequisite for the proper function of muscles directly responsible for the alignment of the big toe (hallux) and other foot toes. (4) Conclusion: The action of muscles should be considered in groups (systems) because the action of the group of muscles results in the creation of a new quality of movement. The analysis of individual muscle-pulling forces, especially the moments of force in the weight-bearing foot, may lead to extremely incorrect conclusions. In pathological cases, the restoration of the correct arches of the foot guarantees the recovery of the correct function of the pulling forces of the foot muscles responsible for the physiological alignment of the hallux. This is especially important concerning conservative and surgical treatment of hallux valgus.

Secondary (Late) Developmental Dysplasia of the Hip with Displacement: From Case Studies to a Proposition for a Modified Diagnostic Path.

(1) Background. This paper presents a case of hip joints that were initially described as either normal or physiologically immature in four successive ultrasound examinations using the static method by Graf; however, the final treatment of the patient involved multiple hip reconstruction surgeries. (2) Case presentation. The patient was born with an Apgar score of 10 and did not exhibit neurological diseases that could deform and lead to pathological dislocation of the right hip joint. The subsequent analysis of medical data revealed that the hip luxation was due to secondary (late) developmental dysplasia of the right hip. (3) Conclusion. The article emphasizes the importance of early diagnosis and treatment standards for developmental dysplasia of the hip (DDH). The development of uniform international medical guidelines for the diagnosis, treatment, and prevention of hip dysplasia, along with the unification of DDH-related terminology, would allow for more effective management of DDH cases and reduce the cost of patient treatment.

The Multi-Component Causes of Late Neonatal Sepsis-Can We Regulate Them?

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

The Role of the Western Diet and Oral Microbiota in Parkinson's Disease.

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson's disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella, Streptococcus, and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

The Role of Single Nucleotide Polymorphisms of Monoamine Oxidase B, Dopamine D2 Receptor, and DOPA Decarboxylase Receptors Among Patients Treated for Parkinson's Disease.

This study aimed to investigate the association between selected variants of genes related to dopamine metabolism pathways and the risk of and progression of Parkinson's disease (PD). This prospective cohort study was conducted in one academic teaching hospital. The study was conducted on 126 patients diagnosed with idiopathic Parkinson's disease. Blood samples were collected to conduct a genotyping of MAOB, DRD1, DRD2, and DDC genes. Genotype and allele frequencies of MAOB (rs1799836) variants were not associated with the course of PD. Genotype and allele frequencies of DRD2 (rs2283265) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DRD2 (rs1076560) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DDC (rs921451) variants were not associated with the course of PD.

Segmental Phase Angle and Body Composition Fluctuation of Elite Ski Jumpers between Summer and Winter FIS Competitions.

(1) Background: The purpose of this study was to observe segmental phase angle (PhA) and body composition fluctuation of elite ski jumpers. (2) Methods: In the study, 12 professional ski jumpers took part. Body composition was estimated with segmental multi-frequency bioelectrical impedance analysis. Repeated ANOVA was used to check the parameters' variability in time. The symmetry between the right and left side of the body was verified with the t-test for dependent samples. Pearson's linear correlation coefficient was calculated. (3) Results: The most stable parameter was body weight. An increase in the visceral fat area was noted, the fat-free mass dropped, and significant changes were noted in the internal and external cell water parameters. Parameters connected with water between the right and left side of the body were symmetrical. Significant correlation between PhA values and body parameters with regard to fat tissue and PhA values of the legs was noticed when PhA was measured at 50 kHz. (4) Conclusions: PhA could be considered as a ski jumper body symmetry monitoring tool. The described relationship may be useful for the assessment of body fat change, which, in the case of jumpers, is crucial. Moreover, our data suggest that segmental PhA evaluation could be a good solution for ski jumpers as a confirmation if lowered body mass and low BMI are still healthy and increase the chance for longer jumps and good performance.

Nucleotide spacing distribution analysis for human genome.

The distribution of nucleotides spacing in human genome was investigated. An analysis of the frequency of occurrence in the human genome of different sequence lengths flanked by one type of nucleotide was carried out showing that the distribution has no self-similar (fractal) structure. The results nevertheless revealed several characteristic features: (i) the distribution for short-range spacing is quite similar to the purely stochastic sequences; (ii) the distribution for long-range spacing essentially deviates from the random sequence distribution, showing strong long-range correlations; (iii) the differences between (A, T) and (C, G) nucleotides are quite significant; (iv) the spacing distribution displays tiny oscillations.

OmicsON - Integration of omics data with molecular networks and statistical procedures.

A huge amount of atomized biological data collected in various databases and the need for a description of their relation by theoretical methods causes the development of data integration methods. The omics data analysis by integration of biological knowledge with mathematical procedures implemented in the OmicsON R library is presented in the paper. OmicsON is a tool for the integration of two sets of data: transcriptomics and metabolomics. In the workflow of the library, the functional grouping and statistical analysis are applied. Subgroups among the transcriptomic and metabolomics sets are created based on the biological knowledge stored in Reactome and String databases. It gives the possibility to analyze such sets of data by multivariate statistical procedures like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). The integration of metabolomic and transcriptomic data based on the methodology contained in OmicsON helps to easily obtain information on the connection of data from two different sets. This information can significantly help in assessing the relationship between gene expression and metabolite concentrations, which in turn facilitates the biological interpretation of the analyzed process.

DNA extraction from FFPE tissue samples - a comparison of three procedures.

AIM OF THE STUDY: One of the critical steps in molecular oncology diagnostics is obtaining high quality genomic DNA. Therefore, it is important to evaluate and compare the techniques used to extract DNA from tissue samples. Since formalin-fixed, paraffin-embedded (FFPE) tissues are routinely used for both retrospective and prospective studies, we compared three commercially available methods of nucleic acid extraction in terms of quantity and quality of isolated DNA. MATERIAL AND METHODS: Slides prepared from 42 FFPE blocks were macro-dissected. Resulting material was divided and processed simultaneously using three extraction kits: QIAamp DNA FFPE Tissue Kit (QIAGEN), Cobas DNA Sample Preparation Kit (Roche Molecular Systems) and Maxwell 16 FFPE Plus LEV DNA Purification Kit (Promega). Subsequently, quantity and quality of obtained DNA samples were analysed spectrophotometrically (NanoDrop 2000, Thermo Scientific). Results of quantitative analysis were confirmed by a fluorometric procedure (Qubit 3.0 Fluorometer, Life Technologies). RESULTS: The results demonstrated that the yields of total DNA extracted using either Maxwell or Cobas methods were significantly higher compared to the QIAamp method (p < 0.001). The Maxwell Extraction Kit delivered DNA samples of the highest quality (p < 0.01). However, the highest total yield of extracted DNA was achieved with the Cobas technique, which may be due to a higher volume of eluate compared to the Maxwell method. CONCLUSIONS: To our knowledge, this is the first paper which directly compares three extraction methods: Cobas, Maxwell and QIAamp. The data herein provide information required for the selection of a protocol that best suits the needs of the overall study design in terms of the quantity and quality of the extracted DNA.

FokI as a genetic factor of intervertebral disc degeneration: A PRISMA-compliant systematic review of overlapping meta-analyses.

The association of FokI (rs2228570), a polymorphism of the vitamin D receptor gene, with intervertebral disc degeneration (IDD) has been investigated in a multitude of studies. However, conflicting results of these studies led to emergence of several meta-analyses over the past few years. Despite the increased statistical power, these meta-analyses have failed to provide uniform and conclusive data on the relationship of FokI with IDD. The aim of this study was to present a comprehensive review based on the most up-to-date meta-analyses on the association of FokI with IDD. A comprehensive search of all major databases was conducted to identify meta-analyses investigating relation between FokI and IDD. No date or language restrictions were applied. The Jadad decision algorithm was utilized to evaluate included meta-analyses and identify the one providing the best evidence. A total of 7 meta-analyses (n = 2580 original patients), that included six to ten case control studies, analyzed the association of FokI polymorphism with IDD. The meta-analysis of the highest quality supported the notion that overall there is no statistically significant association between FokI polymorphism and IDD. However, the authors showed that Caucasians have a reduced risk of IDD and Hispanics have an increased risk of IDD in the dominant and dominant/homozygous/heterozygous models of FokI polymorphism. While currently there is no evidence of an association between FokI polymorphism and IDD in the general population, ethnic predisposition has been shown.

Directional Association Measurement in Contingency Tables: Genomic Case.

Analysis of large data sets is currently a major challenge. Strong efforts are being undertaken to tackle this problem by developing new methods or modifying existing ones. The Z association method is a new method for describing directional association in contingency tables. It allows to arbitrarily group categories for each of the two variables, for which the contingency table is analyzed. The Z coefficient was calculated on a sample data set with gene mutations in different cancer types. Results showed some association with both gene mutations and annotation groups. Detailed results obtained for particular cancer types versus particular genes and annotation groups were in line with well-known facts in cancer genomics. The "MEUSassociation" R library allows to analyze the directional association between two categorical variables, and the mutual relationship is summarized in a contingency table, by means of the Z association coefficient. The method implemented in the library allows to compute the standard Z coefficient and to apply it in a case, where all possible singular coefficients Z(A:B) are computed at the same time, giving information of association between particular rows and columns. Investigating the ranked list of the highest singular coefficients allows to reduce the complexity of a large-scale data set. Both the Z coefficient and its R implementation are important tools in categorical data analysis.

Analysis of Malignant Melanoma Cell Lines Exposed to Hypoxia Reveals the Importance of PFKFB4 Overexpression for Disease Progression.

BACKGROUND/AIM: Most melanomas develop in hypoxic conditions. Since hypoxia via HIF-1 induces glycolysis, a process essential for malignant melanoma growth/survival, the goal of this study was to analyze the influence of hypoxia on the expression of HIF-1 target genes involved in glucose metabolism. MATERIALS AND METHODS: The response of melanoma cell lines to hypoxic conditions was analyzed by RT-PCR and western blotting. A Kaplan-Meier survival analysis for patients with high and low expression level of PFKFB4 was performed. Further analysis of patients' data was performed using the R/Bioconductor environment. RESULTS: Induction of PFKFB4 gene expression can be considered a crucial mechanism behind glycolysis enhancement in hypoxic melanoma cells. Analysis of a publicly available database revealed that high PFKFB4 expression contributes to poor prognosis of melanoma patients. CONCLUSION: Currently available anti-melanoma therapeutic strategies may significantly benefit from agents targeting PFKFB4 activity.

Case report of dysregulation of primary bile acid synthesis in a family with X-linked adrenoleukodystrophy.

RATIONALE: X-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms. PATIENT CONCERNS: We report a case of 37-year-old patient with diagnosis of X-ALD, confirmed based on elevated VLCFA concentrations and genetic testing of ABCD1 gene. The complete clinical picture in the patient indicates AMN phenotype with cerebral involvement. DIAGNOSES: The reduced synthesis of unconjugated cholic and chenodeoxycholic acids, and the reduction to 28% to 29% of peroxisomal beta-oxidation of behenic acid and normal peroxisomal metabolism of pristanic and palmitic acid were observed in the X-ALD patient. Sanger sequencing of major genes involved in primary bile acid (BA) synthesis failed to identify pathogenic mutations of the investigated set of genes. INTERVENTIONS: Plasma concentrations of BAs, VLCFAs, and beta-oxidation of C22:0, C16:0, and pristanic acid were studied in primary skin fibroblasts of the patient. In addition, we performed sequencing of the ABCD1, ABCD3, CYP7A1, CYP7B1, CYP27A1, HSD3B7, AKR1D1, and SLC27A5 genes in the X-ALD family. OUTCOMES: In the Polish family affected with AMN a dysregulation of the primary BA synthesis pathway was found. LESSONS: We have demonstrated the coincidence of the adult form of X-ALD with abnormalities in BA synthesis. We suggest that decreased synthesis of BAs may be an additional dysfunction as a consequence of the ABCD1 c.659T>C, p.(Leu220Pro) mutation and may be further evidence that disturbed cholesterol metabolism is important in the pathology of ALD.

Regularization and grouping -omics data by GCA method: A transcriptomic case.

The paper presents the application of Grade Correspondence Analysis (GCA) and Grade Correspondence Cluster Analysis (GCCA) for ordering and grouping -omics datasets, using transcriptomic data as an example. Based on gene expression data describing 256 patients with Multiple Myeloma it was shown that the GCA method could be used to find regularities in the analyzed collections and to create characteristic gene expression profiles for individual groups of patients. GCA iteratively permutes rows and columns to maximize the tau-Kendall or rho-Spearman coefficients, which makes it possible to arrange rows and columns in such a way that the most similar ones remain in each other's neighbourhood. In this way, the GCA algorithm highlights regularities in the data matrix. The ranked data can then be grouped using the GCCA method, and after that aggregated in clusters, providing a representation that is easier to analyze-especially in the case of large sets of gene expression profiles. Regularization of transcriptomic data, which is presented in this manuscript, has enabled division of the data set into column clusters (representing genes) and row clusters (representing patients). Subsequently, rows were aggregated (based on medians) to visualise the gene expression profiles for patients with Multiple Myeloma in each collection. The presented analysis became the starting point for characterisation of differentiated genes and biochemical processes in which they are involved. GCA analysis may provide an alternative analytical method to support differentiation and analysis of gene expression profiles characterising individual groups of patients.