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Erectile dysfunction in diabetes mellitus
Get PDFIntroduction Erectile dysfunction (ED) is a highly prevalent complication of diabetes mellitus (DM), significantly impairing quality of life and psychosocial well-being. The prevalence of ED is estimated to be over 3.5 times higher in men with diabetes mellitus compared to those without. The aetiology of diabetic ED is multifactorial, stemming from complex diabetes mellitus-related systemic changes. The pathophysiology of diabetic ED involves interacting pathways, including endothelial dysfunction, accelerated atherosclerosis, autonomic and peripheral neuropathy, structural penile changes, hormonal imbalances, and psychological factors. Methods A review of the literature was conducted to examine the pathophysiological mechanisms, genetic associations, and treatment modalities related to diabetic ED. Particular attention was given to studies exploring pharmacogenetics and emerging therapeutic interventions. Results Management is multimodal, including lifestyle changes, counselling, and pharmacological agents (primarily phosphodiesterase type 5 inhibitors (PDE5Is)), but treatment response varies. Genetic studies have identified associations between ED risk/severity and polymorphisms in several candidate genes, including NOS3 (G894T, T786C, VNTR), ARG1/ARG2 (influencing nitric oxide substrate availability), ACE (I/D polymorphism), AR (CAG repeat length affecting androgen sensitivity), and VEGF (promoter polymorphisms). Pharmacogenetic studies suggest that polymorphisms in NOS3, AR, and VEGF may predict response to PDE5Is or testosterone therapy, while ARG1/ARG2 variations might guide future arginase-targeted therapies. Emerging treatments like low-intensity shockwave therapy, platelet-rich plasma, gene therapy, and stem cell therapy show promise but require more robust evidence. Conclusions Diabetic ED is a complex condition driven by multiple pathophysiological mechanisms often influenced by an underlying genetic predisposition. Understanding the interplay between pathophysiology and genetics is crucial for developing personalised treatment strategies. While current therapies offer benefits, variability in response highlights the need for tailored approaches. Further research, especially large-scale pharmacogenetic studies and randomised controlled trials for emerging therapies, is essential to identify reliable biomarkers, optimise treatment selection, and improve outcomes for men with diabetic ED
Phylodynamic inference suggests introductions as main driver of Mpox Clade II outbreak in 2022 in Slovenia
Get PDFThe use of machine learning in the diagnosis of kidney allograft rejection
Get PDFAbstract: Kidney allograft rejection is one of the main limitations to long-term kidney transplant survival. The diagnostic gold standard for detecting rejection is a kidney biopsy, an invasive procedure that can often give imprecise results due to complex diagnostic criteria and high interobserver variability. In recent years, several additional diagnostic approaches to rejection have been investigated, some of them with the aid of machine learning (ML). In this review, we addressed studies that investigated the detection of kidney allograft rejection over the last decade using various ML algorithms. Various ML techniques were used in three main categories: (a) histopathologic assessment of kidney tissue with the aim to improve the diagnostic accuracy of a kidney biopsy, (b) assessment of gene expression in rejected kidney tissue or peripheral blood and the development of diagnostic classifiers based on these data, (c) radiologic assessment of kidney tissue using diffusion-weighted magnetic resonance imaging and the construction of a computer-aided diagnostic system. In histopathology, ML algorithms could serve as a support to the pathologist to avoid misclassifications and overcome interobserver variability. Diagnostic platforms based on biopsy-based transcripts serve as a supplement to a kidney biopsy, especially in cases where histopathologic diagnosis is inconclusive. ML models based on radiologic evaluation or gene signature in peripheral blood may be useful in cases where kidney biopsy is contraindicated in addition to other non-invasive biomarkers. The implementation of ML-based diagnostic methods is usually slow and undertaken with caution considering ethical and legal issues. In summary, the approach to the diagnosis of rejection should be individualized and based on all available diagnostic tools (including ML-based), leaving the responsibility for over- and under-treatment in the hands of the clinician
The quality and detection limits of mitochondrial heteroplasmy by long read nanopore sequencing
Get PDFHeat treatment optimisation of 18 % Ni maraging steel produced by DED-ARC for enhancing mechanical properties
Get PDFThis article deals with the Directed Energy Deposition using Wire and Arc (DED-ARC) for maraging steel cladding. A technology for cladding using Gas Metal Arc Welding (GMAW) has been developed that enables the perfect deposition of maraging steel. The material characterisation was carried out in different material states: in the as-built, solution annealed and aged. The research included visual examinations, optical microscopy, Scanning Electron Microscopy / Energy-dispersive X-ray spectroscopy (SEM/EDS), fractography, hardness testing, tensile testing and impact toughness testing. The as-deposited state exhibited a microstructure with very long crystal grains and microsegregations orientated the direction of the heat sink, consisting of lath martensite. Consequently, a subsequent heat treatment is absolutely necessary in order to obtain a uniform fine-grained microstructure. Two different solution annealing processes were analysed, which allowed us to select the most suitable process for the first step of heat treatment followed by aging. A response surface methodology was used to optimise the aging conditions. The results show that additively manufactured maraging steel reaches a tensile strength of 1947 MPa, a hardness of 657 HV5 and a Charpy impact toughness of 11 J at peak aging condition, which is comparable to conventionally manufactured maraging steel
Assessment of three criteria to establish borrelial infection in suspected lyme neuroborreliosis
Get PDFPurpose: Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. infection. It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. Methods: We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients≥15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. Results: Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15–84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4%), followed by EM (52.9%), and by a positive CSF Borrelia culture (9.6%). Of the 280 patients, 154 (55%) met only one criterion (43.2% ITBAS only, 10.7% EM only, and 1.1% positive CSF culture only), whereas 42.1% met two criteria. Only 2.9% of patients were positive by all three criteria. Conclusion: Although ITBAS was the most frequent criterion for confirmation for Borrelia infection, the presence of EM alone confirmed an additional 10.7% of patients and a positive CSF Borrelia culture alone added another 1.1%
Postopek izdelave slojnatega furnirnega lesa iz bukovine (Fagus sylvatica) na primeru operativne skupine GOFAGUS
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European human granulocytic anaplasmosis is caused by a subcluster of Anaplasma phagocytophilum Ecotype I
Get PDFAnaplasma phagocytophilum causes human granulocytic anaplasmosis. However, despite its ubiquitous presence in animals and ticks, human cases are rarely reported in Europe. We generated genetic data from A. phagocytophilum from patients and compared them with sequences from wild and domestic animals to assess the zoonotic potential of the respective genotypes. The genomic sequence of an A. phagocytophilum isolate obtained from a Slovenian patient was determined. We also sequenced a groEL-gene fragment of eight isolates from human patients from France and Poland. The A. phagocytophilum genome from the Slovenian patient was more closely related to isolates from dogs than from sheep. Using groEL-based typing, isolates from humans were found within a distinct subcluster of A. phagocytophilum Ecotype I. This subcluster was defined as zoonotic. Strains from dogs, horses, cats, foxes, wolves, and wild boar were significantly overrepresented in this branch. Variants outside this subcluster were more abundant and found in a wider variety of domestic and wild animals, most notably ruminants. A similar pattern was observed for the MLST analyses targeting seven housekeeping genes. Human anaplasmosis in Europe is associated with a specific subcluster of A. phagocytophilum Ecotype I, which is not primarily associated with ruminants, but rather with dogs, horses, cats, carnivores, wild boar and hedgehogs. Our findings provide a reasonable explanation for the discrepancy between the omnipresence of A. phagocytophilum in the environment and the limited number of reported human cases. We recommend taking this genetic sub-clustering into account for future risk assessments