Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

[An overview of investments in the development of the Russian Medtech market and the prospects for the impact of digitalization in medicine on the economic performance of companies until 2030].

Today, the topic of digitalization, the introduction of innovations based on Big Data, the complexity of technologies due to the introduction of artificial intelligence in medicine and healthcare is one of the most relevant in this industry, undoubtedly contributing to its rapid development. As a result of this development, there is a huge number of services and applications. Internet resources, not only for health tracking (more than 3,500 applications are available by the end of 2023), but also the development of diagnostic resources, telemedicine, etc. Quite quickly, it was the pandemic and its consequences that changed the format of interaction between doctors, communication in the community of doctors, and their interaction with patients. Saving time when making an appointment with a doctor, visiting him, constant monitoring of the condition of patients, becoming better and more multidirectional day by day, make it possible to provide timely, relevant care to more people. The use of artificial intelligence technologies and digital solutions in the field of Russian healthcare opens up great prospects for both doctors and patients, as well as for many government agencies, since the development of regulatory and legal regulation and state control and management of innovations in the field of medicine and healthcare is important. An important factor is that not only government programs for the development of healthcare, but also investments are extremely important for the development of digital medicine.

Green radiography: Exploring perceptions, practices, and barriers to sustainability.

INTRODUCTION: Previous research has delved into the attitudes and behaviors of diverse professions regarding environmental sustainability. However, there needs to be more research specifically targeting radiographers. This study aims to survey radiographers' perceptions, practices, and barriers to change concerning environmental sustainability in radiology. METHODS: Institutional ethical approval was obtained (IRB-COHS-FAC-110-2024) and data collection was conducted using Google Forms (Google Inc., Mountain View, CA). The survey targeted 104 practicing radiographers across several countries. Questions were structured around five domains to gather insights into demographics, training in global warming and climate change, perceptions of sustainability and climate change, sustainability barriers, and current radiology practices on sustainability. Data analysis utilized descriptive and d inferential statistics. RESULTS: One hundred and four radiographers completed the study. Females had a significantly higher attendance rate in environmental protection campaigns (P = 0.01). The majority of respondents (68%) believe in climate change's knowledge and impact on the natural world. Our survey findings demonstrate that 74% of respondents believe there's a need to improve sustainability practices. The most commonly used strategies to decrease energy consumption and emissions were low-energy lighting (60%), real-time power monitoring tools (41%), and energy-efficient heating systems (32%). A significant concern regarding sustainability emerges among respondents: time (50%) and lack of leadership (48%) are prevalent concerns among the identified barriers. CONCLUSION: Participants are recognising the importance of environmental sustainability in radiology, but lack of leadership, support, authority, and facility limitations hinder their adoption. IMPACT ON PRACTICE: Radiology must prioritize environmental sustainability by providing resources and training for radiographers and collaborating with healthcare professionals, policymakers, and environmental experts to develop comprehensive strategies for a sustainable healthcare system.

Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation.

Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.

Asymmetric lesion detection with geometric patterns and CNN-SVM classification.

In dermoscopic images, which allow visualization of surface skin structures not visible to the naked eye, lesion shape offers vital insights into skin diseases. In clinically practiced methods, asymmetric lesion shape is one of the criteria for diagnosing Melanoma. Initially, we labeled data for a non-annotated dataset with symmetrical information based on clinical assessments. Subsequently, we propose a supporting technique-a supervised learning image processing algorithm-to analyze the geometrical pattern of lesion shape, aiding non-experts in understanding the criteria of an asymmetric lesion. We then utilize a pre-trained convolutional neural network (CNN) to extract shape, color, and texture features from dermoscopic images for training a multiclass support vector machine (SVM) classifier, outperforming state-of-the-art methods from the literature. In the geometry-based experiment, we achieved a 99.00 % detection rate for dermatological asymmetric lesions. In the CNN-based experiment, the best performance is found 94 % Kappa Score, 95 % Macro F1-score, and 97 % weighted F1-score for classifying lesion shapes (Asymmetric, Half-Symmetric, and Symmetric).

Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia and morpholino knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy. Using homology modelling we show that the identified POPDC2 variants are predicted to diminish the ability of POPDC2 to bind cAMP. In in vitro electrophysiological studies we demonstrated that, while co-expression of wild-type POPDC2 with TREK-1 increased TREK-1 current density, POPDC2 variants found in the patients failed to increase TREK-1 current density. While patient muscle biopsy did not show clear myopathic disease, it showed significant reduction of the expression of both POPDC1 and POPDC2, suggesting that stability and/or membrane trafficking of the POPDC1-POPDC2 complex is impaired by pathogenic variants in any of the two proteins. Single-cell RNA sequencing from human hearts demonstrated that co-expression of POPDC1 and 2 was most prevalent in AV node, AV node pacemaker and AV bundle cells. Sinoatrial node cells expressed POPDC2 abundantly, but expression of POPDC1 was sparse. Together, these results concur with predisposition to AV node disease in humans with loss-of-function variants in POPDC1 and POPDC2 and presence of sinus node disease in POPDC2, but not in POPDC1 related disease in human. Using population-level genetic data of more than 1 million individuals we showed that none of the familial variants were associated with clinical outcomes in heterozygous state, suggesting that heterozygous family members are unlikely to develop clinical manifestations and therefore might not necessitate clinical follow-up. Our findings provide evidence for POPDC2 as the cause of a novel Mendelian autosomal recessive cardiac syndrome, consistent with previous work showing that mice and zebrafish deficient in functional POPDC2 display sinus and AV node dysfunction.

Relation between the internal anal sphincter and defecation disorders in patients with anorectal malformations.

OBJECTIVES: To investigate associations between the rectoanal inhibitory reflex (RAIR), type of congenital anorectal malformations (ARMs), type of operation that patients with ARM had undergone, and objectively measured fecal incontinence and defecation problems. METHODS: We retrospectively included 69 pediatric patients with ARM. All underwent anorectal function tests at the University Medical Center of Groningen during the last 10 years. We assessed anorectal physiology using the Rome IV criteria and anorectal function tests. RESULTS: We found the reflex in 67% of patients and all types of ARMs. All patients who had not been operated on, and those who had undergone less extensive surgery possessed the reflex. In contrast, patients who underwent posterior sagittal anorectoplasty, 44% possessed it. We found no difference between mean rectal volumes in patients with and without the reflex (251 mL vs. 325 mL, respectively, p = 0.266). We found that over time, patients without the reflex seemed to develop significantly higher rectal volumes than patients who had it. We did not find a significant difference between the reflex and fecal incontinence; however, it seems that the absence of the reflex, resting anal sphincter pressure, and fecal incontinence are related. CONCLUSION: The RAIR seems present in patients with ARM irrespective of their malformation type. Corrective surgery, however, may impair this reflex. Seemingly, its absence results in constipation with enlarged rectal volumes and fecal incontinence. Every effort should be made to preserve this reflex during surgery and to use extensive surgical procedures as sparingly as possible.

Synthesis, Antimicrobial, Molecular Docking Against Bacterial and Fungal Proteins and In Silico Studies of Glucopyranoside Derivatives as Potent Antimicrobial Agents.

Carbohydrate derivatives play a crucial role in biochemical and medicinal research. Therefore, the present study was designed to explore the synthesis of methyl α-D-glucopyranoside derivatives (1, MDG), focusing on their efficacy against bacterial and fungal infections. The structure of the synthesized compounds was ascertained using spectral and elemental analyses. Antimicrobial screening revealed strong antifungal properties and exhibited MIC values of 16-32 µg/L and MBC 64-128 µg/L. Structure-activity relationship (SAR) analysis indicated that adding nonanoyl and decanoyl groups to ribose moiety enhanced potency against both bacterial and fungal strains. Compounds 6 and 7, presented nonanoyl and decanoyl substituents and demonstrated greater efficacy. In addition, DFT studies identified compound 8 as possessing ideal electronic properties. Molecular docking revealed that compound 8 exhibits exceptional binding affinities to bacterial proteins, conferring potent antibacterial and antifungal activities. In addition, pharmacokinetic optimization via POM analysis highlighted compounds 1 and 2 as promising bioavailable drugs with minimal toxicity. Molecular dynamics simulations confirmed the stability of the 2-S. aureus complex, revealing the therapeutic potential of compounds 2 and 8. The integration of in vitro and in silico methods, including DFT anchoring dynamics and molecular dynamics simulations, provides a solid framework for the advancement of effective anti-infective drugs.

Lake Baikal amphipods and their genomes, great and small.

Endemic amphipods (Crustacea: Amphipoda) of Lake Baikal represent an outstanding example of large species flocks occupying a wide range of ecological niches and originating from a handful of ancestor species. Their development took place at a restricted territory and is thus open for comprehensive research. Such examples provide unique opportunities for studying behavioral, anatomic, or physiological adaptations in multiple combinations of environmental conditions and thus attract considerable attention. The existing taxonomies of this group list over 350 species and subspecies, which, according to the molecular phylogenetic studies of marker genes, full transcriptomes and mitochondrial genomes, originated from at least two introductions into the lake. The studies of allozymes and marker genes have revealed a significant cryptic diversity in Baikal amphipods, as well as a large variance in genetic diversity within some morphological species. Crossing experiments conducted so far for two morphological species suggest that the differences in the mitochondrial marker (cytochrome c oxidase subunit I gene) can potentially be applied for making predictions about reproductive isolation. For about one-tenth of the Baikal amphipod species, nuclear genome sizes and chromosome numbers are known. While genome sizes vary within one order of magnitude, the karyotypes are relatively stable (2n = 52 for most species studied). Moreover, analysis of the diversity of repeated sequences in nuclear genomes showed significant between-species differences. Studies of mitochondrial genomes revealed some unusual features, such as variation in length and gene order, as well as duplications of tRNA genes, some of which also underwent remolding (change in anticodon specificity due to point mutations). The next important steps should be (i) the assembly of whole genomes for different species of Baikal amphipods, which is at the moment hampered by complicated genome structures with high repeat content, and (ii) updating species taxonomy taking into account all the data.

How does a Saccharomyces cerevisiae extract influence the components of isolated rotavirus particles from stool samples collected in a clinical setting from children?

Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x106, 3.0x106, 4.2x106, and 7.5x105 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the S. cerevisiae extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. Saccharomyces cerevisiae extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.

Exploring the Relationship Between Bakhour Use and Respiratory Health: A Cross-Sectional Study in the Jazan Region, Saudi Arabia.

Background: Despite deep cultural traditions, incense burning significantly impacts respiratory health. Effects of Arabian bakhour remain unknown in Saudi Arabia's Jazan region with prevalent use. This cross-sectional study addresses this gap by investigating bakhour exposure and respiratory diseases. Methods: This was descriptive cross-sectional study conducted in Jazan area, Saudi Arabia, from October 2023 to March 2024. A total of 1612 participants age more than 18 years, both gender and resident of Jazan Area were included. Those aged less than 18 years were excluded. SPSS v 26 was used for data analysis. Results: The sample (n=1612) had a mean age of 29±11 years and was 63% female. Bakhour use was nearly universal (98%), especially using coal (73%). Higher bakhour frequency significantly associated with increased cough (p<0.01) and dyspnea (p<0.01). Certain bakhour types linked to greater allergic rhinitis prevalence (p<0.01). Regression analysis revealed cough during bakhour use worsened respiratory health (increased respiratory score) by 3.89 times (95% CI 1.13-6.64; p=0.006) while dyspnea increased the score by 7.48 times (95% CI 4.70-10.25; p<0.001). Conclusion: This study provides valuable insights into the association between Bakhour use and respiratory health in the Jazan region. The findings emphasize the need for further research and public health interventions to mitigate potential respiratory risks associated with Bakhour use.

A novel genus of Pectobacterium bacteriophages display broad host range by targeting several species of Danish soft rot isolates.

The bacterial diseases black leg and soft rot in potatoes cause heavy losses of potatoes worldwide. Bacteria within the genus Pectobacteriaceae are the causative agents of black leg and soft rot. The use of antibiotics in agriculture is heavily regulated and no other effective treatment currently exists, but bacteriophages (phages) have shown promise as potential biocontrol agents. In this study we isolated soft rot bacteria from potato tubers and plant tissue displaying soft rot or black leg symptoms collected in Danish fields. We then used the isolated bacterial strains as hosts for phage isolation. Using organic waste, we isolated phages targeting different species within Pectobacterium. Here we focus on seven of these phages representing a new genus primarily targeting P. brasiliense; phage Ymer, Amona, Sabo, Abuela, Koroua, Taid and Pappous. TEM image of phage Ymer showed siphovirus morphotype, and the proposed Ymer genus belongs to the class Caudoviricetes, with double-stranded DNA genomes varying from 39kb to 43kb. In silico host range prediction using a CRISPR-Cas spacer database suggested both P. brasiliense, P. polaris and P. versatile as natural hosts for phages within the proposed Ymer genus. A following host range experiment, using 47 bacterial isolates from Danish tubers and plants symptomatic with soft rot or black leg disease verified the in silico host range prediction, as the genus as a group were able to infect all three Pectobacterium species. Phages did, however, primarily target P. brasiliense isolates and displayed differences in host range even within the species level. Two of the phages were able to infect two or more Pectobacterium species. Despite no nucleotide similarity with any phages in the NCBI database, the proposed Ymer genus did share some similarity at the protein level, as well as gene synteny, with currently known phages. None of the phages encoded integrases or other genes typically associated with lysogeny. Similarly, no virulence factors nor antimicrobial resistance genes were found, and combined with their ability to infect several soft rot-causing Pectobacterium species from Danish fields, demonstrates their potential as biocontrol agents against soft rot and black leg diseases in potatoes.

Mercury in the Southwestern Atlantic reef-building coral Montastraea cavernosa (Cnidaria, Scleractinia).

Coastal ecosystems, such as coral reefs, are particularly vulnerable to mercury contamination due to direct contact with terrestrial sources. Here, we evaluated, for the first time, the concentration of mercury in coral reefs in the Southwestern Atlantic using the amphi-atlantic scleractinian coral Montastraea cavernosa. Sampling was realized over an extension of 200 km along different coral reefs. Our data show mercury values ranging from 0.01 to 0.27 mg kg-1 in the tissue and 0.001 to 0.06 mg kg-1 in the skeleton and higher values when compared to coral worldwide. The concentration of mercury in the tissue from Todos os Santos Bay was higher than in open sea regions but also higher compared to other coral reefs of the world, while the skeleton concentration did not indicate any differences when compared to the open sea regions. The data presented is of concern as we consider the importance of coral reefs and should be used in future environmental management planning.

Late-onset corneal edema after customized crosslinking for progressive keratoconus.

Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 µm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 µm after epithelial debridement and 375 µm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 µm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 µm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 µm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 µm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.

Response surface methodology and machine learning optimisations comparisons of recycled AA6061-B4C-ZrO2 hybrid metal matrix composites via hot forging forming process.

The optimal conditions of applied factors to reuse Aluminium AA6061 scraps are (450, 500, and 550) °C preheating temperature, (1-15) % Boron Carbide (B4C), and Zirconium (ZrO2) hybrid reinforced particles at 120 min forging time via Hot Forging (HF) process. The response surface methodology (RSM) and machine learning (ML) were established for the optimisations and comparisons towards materials strength structure. The Ultimate Tensile Strength (UTS) strength and Microhardness (MH) were significantly increased by increasing the processed temperature and reinforced particles because of the material dispersion strengthening. The high melting point of particles caused impedance movements of aluminium ceramics dislocations which need higher plastic deformation force and hence increased the material's mechanical and physical properties. But, beyond Al/10 % B4C + 10 % ZrO2 the strength and hardness were decreased due to more particle agglomeration distribution. The optimisation tools of both RSM and ML show high agreement between the reported results of applied parameters towards the materials' strength characterisation. The microstructure analysis of Field Emission Scanning Electron Microscopy (FE-SEM) and Atomic Force Microscope (AFM) provides insights mapping behavioural characterisation supports related to strength and hardness properties. The distribution of different volumes of ceramic particle proportion was highlighted. The environmental impacts were also analysed by employing a life cycle assessment (LCA) to identify energy savings because of its fewer processing steps and produce excellent hybrid materials properties.