A scoping review of scores or grading systems for pelvic venous disorders.

BACKGROUND: Pelvic venous disorders (PeVD) encompass a variety of conditions linked to chronic pelvic pain in women. However, PeVD remain underdiagnosed due to the absence of universally accepted diagnostic criteria. The complexity of PeVD classifications across specialties leads to delays in treatment. This scoping review aims to fill a gap in PeVD diagnosis and management by identifying all existing scoring or grading systems to lay the foundation for standardized clinical scoring tools for PeVD. METHODS: This scoping review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping reviews. Online databases were searched up to April 2023. Studies implementing a scoring or grading system for patients with confirmed or suspected PeVD were included. Scores or grading systems were classified into four main categories based on their use in the study: screening, diagnosis, measure of disease severity, and measure of response to treatment. RESULTS: Of the 2976 unique records identified, 82 were reviewed in full, and 20 were included in this study. The publication dates ranged from 1984 to 2023 (median, 2018; interquartile range, 2003-2022). A total of 21 scores and/or grading systems were identified. Of these 21 scores, 10 (47.6%) were clinical scores, and 10 (47.6%) were scores based on radiological findings; one study included a score that used both clinical and radiological findings. The identified scores were used in various settings. Of the 21 scores, 2 (9.52%) were used for screening in a tertiary care setting; 3 (14.3%) were used to establish the PeVD diagnosis; 8 (38.1%) were used to assess disease severity; and 8 (38.1%) were used as measures of response to treatment. Of the eight scores assessing disease severity, four (50.0%) assessed the degree of dilatation of pelvic veins and four (50%) assessed the severity of reflux. Only three of the scores were validated. CONCLUSIONS: This scoping review identified a range of scoring and grading systems for PeVD. We note a lack of a validated scoring system, both clinical and radiological, for screening and assessment of disease severity. This is an important first step in developing validated disease-specific scoring systems for patient screening, appropriate referral, assessment of symptom severity, and assessment of the response to treatment.

Structural effects of charge destabilization and amino acid substitutions in amyloid fragments of CsgA.

The most studied functional amyloid is the CsgA, major curli subunit protein, which is produced by numerous strains of Enterobacteriaceae. Although CsgA sequences are highly conserved, they exhibit species diversity, which reflects the specific evolutionary and functional adaptability of the major curli subunit. Herein, we performed bioinformatics analyses to uncover the differences in the amyloidogenic properties of the R4 fragments in Escherichia coli and Salmonella enterica and proposed four mutants for more detailed studies: M1, M2, M3, and M4. The mutated sequences were characterized by various experimental techniques, such as circular dichroism, ATR-FTIR, FT-Raman, thioflavin T, transmission electron microscopy and confocal microscopy. Additionally, molecular dynamics simulations were performed to determine the role of buffer ions in the aggregation process. Our results demonstrated that the aggregation kinetics, fibril morphology, and overall structure of the peptide were significantly affected by the positions of charged amino acids within the repeat sequences of CsgA. Notably, substituting glycine with lysine resulted in the formation of distinctive spherically packed globular aggregates. The differences in morphology observed are attributed to the influence of phosphate ions, which disrupt the local electrostatic interaction network of the polypeptide chains. This study provides knowledge on the preferential formation of amyloid fibrils based on charge states within the polypeptide chain.

Identification of outcomes in clinical studies for pelvic venous disorders.

OBJECTIVE: There is increasing recognition that health systems need to measure and improve the value of patient care by measuring outcomes. Chronic pelvic pain secondary to pelvic venous insufficiency can have a significant impact on the quality of life (QOL) of women affected. Despite growing recognition, pelvic venous disorders (PeVDs), an important cause of chronic pelvic pain, remain underdiagnosed. Developing a core outcome set (COS) for benchmarking care delivery enhances the standardization of care. However, there is no consensus regarding a standardized minimum set of outcomes for PeVD. We aimed to generate a list of outcomes reported in previous PeVD treatment studies to lay the foundation for developing a COS for PeVD. METHODS: This scoping review was undertaken according to the PRISMA-ScR guidelines. Initially, screening, full-text review and extraction was conducted on studies published between 2018 and 2023. Subsequently, the search was expanded using 1-year intervals, until, over a 1-year interval, no new outcomes were recorded. Closely related outcomes were classified into domains, and domains into three core areas: disease-specific, treatment-related, and QOL-related outcomes. RESULTS: Of the 1579 records identified, 51 publications were included. From these studies, 108 different outcomes were identified. The median number of outcomes per study was 8 (interquartile range, 6-13). Closely related outcomes were organized into 42 outcome domains, which were then categorized into 3 core outcome areas; 47.6% (20/42) were disease specific, 35.7% (15/42) treatment related, and 16.7% (7/42) were QOL related. Of the 51 included studies, disease-specific outcomes were identified in 96.1% of the studies (49/51), treatment-related outcomes in 94.1% (48/51), and QOL outcomes in only 13.7% (7/51). CONCLUSIONS: There was significant heterogeneity in outcomes reported in PeVD studies. Most PeVD treatment studies evaluated disease-specific and treatment-related outcomes of PeVD, but few reported outcomes that measured the impact on QOL. These findings will inform the next steps in developing a COS for PeVD.

Quantifying the Dynamics of Bacterial Biofilm Formation on the Surface of Soft Contact Lens Materials Using Digital Holographic Tomography to Advance Biofilm Research.

The increase in bacterial resistance to antibiotics in recent years demands innovative strategies for the detection and combating of biofilms, which are notoriously resilient. Biofilms, particularly those on contact lenses, can lead to biofilm-related infections (e.g., conjunctivitis and keratitis), posing a significant risk to patients. Non-destructive and non-contact sensing techniques are essential in addressing this threat. Digital holographic tomography emerges as a promising solution. This allows for the 3D reconstruction of the refractive index distribution in biological samples, enabling label-free visualization and the quantitative analysis of biofilms. This tool provides insight into the dynamics of biofilm formation and maturation on the surface of transparent materials. Applying digital holographic tomography for biofilm examination has the potential to advance our ability to combat the antibiotic bacterial resistance crisis. A recent study focused on characterizing biofilm formation and maturation on six soft contact lens materials (three silicone hydrogels, three hydrogels), with a particular emphasis on Staphylococcus epidermis and Pseudomonas aeruginosa, both common culprits in ocular infections. The results revealed species- and time-dependent variations in the refractive indexes and volumes of biofilms, shedding light on cell dynamics, cell death, and contact lens material-related factors. The use of digital holographic tomography enables the quantitative analysis of biofilm dynamics, providing us with a better understanding and characterization of bacterial biofilms.

Fake-news-free evidence-based communication for proper vein-lymphatic disease management.

Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.

A Systematic Approach: Molecular Dynamics Study and Parametrisation of Gemini Type Cationic Surfactants.

The spreading of antibiotic-resistant bacteria strains is one of the most serious problem in medicine to struggle nowadays. This triggered the development of alternative antimicrobial agents in recent years. One of such group is Gemini surfactants which are massively synthesised in various structural configurations to obtain the most effective antibacterial properties. Unfortunately, the comparison of antimicrobial effectiveness among different types of Gemini agents is unfeasible since various protocols for the determination of Minimum Inhibitory Concentration are used. In this work, we proposed alternative, computational, approach for such comparison. We designed a comprehensive database of 250 Gemini surfactants. Description of structure parameters, for instance spacer type and length, are included in the database. We parametrised modelled molecules to obtain force fields for the entire Gemini database. This was used to conduct in silico studies using the molecular dynamics to investigate the incorporation of these agents into model E. coli inner membrane system. We evaluated the effect of Gemini surfactants on structural, stress and mechanical parameters of the membrane after the agent incorporation. This enabled us to select four most likely membrane properties that could correspond to Gemini's antimicrobial effect. Based on our results we selected several types of Gemini spacers which could demonstrate a particularly strong effect on the bacterial membranes.

Bacteria Single-Cell and Photosensitizer Interaction Revealed by Quantitative Phase Imaging.

Quantifying changes in bacteria cells in the presence of antibacterial treatment is one of the main challenges facing contemporary medicine; it is a challenge that is relevant for tackling issues pertaining to bacterial biofilm formation that substantially decreases susceptibility to biocidal agents. Three-dimensional label-free imaging and quantitative analysis of bacteria-photosensitizer interactions, crucial for antimicrobial photodynamic therapy, is still limited due to the use of conventional imaging techniques. We present a new method for investigating the alterations in living cells and quantitatively analyzing the process of bacteria photodynamic inactivation. Digital holographic tomography (DHT) was used for in situ examination of the response of Escherichia coli and Staphylococcus aureus to the accumulation of the photosensitizers immobilized in the copolymer revealed by the changes in the 3D refractive index distributions of single cells. Obtained results were confirmed by confocal microscopy and statistical analysis. We demonstrated that DHT enables real-time characterization of the subcellular structures, the biophysical processes, and the induced local changes of the intracellular density in a label-free manner and at sub-micrometer spatial resolution.

Biotin-Containing Third Generation Glucoheptoamidated Polyamidoamine Dendrimer for 5-Aminolevulinic Acid Delivery System.

Polyamidoamine PAMAM dendrimer generation 3 (G3) was modified by attachment of biotin via amide bond and glucoheptoamidated by addition of α-D-glucoheptono-1,4-lacton to obtain a series of conjugates with a variable number of biotin residues. The composition of conjugates was determined by detailed 1-D and 2-D NMR spectroscopy to reveal the number of biotin residues, which were 1, 2, 4, 6, or 8, while the number of glucoheptoamide residues substituted most of the remaining primary amine groups of PAMAM G3. The conjugates were then used as host molecules to encapsulate the 5-aminolevulinic acid. The solubility of 5-aminolevulinic acid increased twice in the presence of the 5-mM guest in water. The interaction between host and guest was accompanied by deprotonation of the carboxylic group of 5-aminolevulinic acid and proton transfer into internal ternary nitrogen atoms of the guest as evidenced by a characteristic chemical shift of resonances in the 1H NMR spectrum of associates. The guest molecules were most likely encapsulated inside inner shell voids of the host. The number of guest molecules depended on the number of biotin residues of the host, which was 15 for non-biotin-containing glucoheptoamidated G3 down to 6 for glucoheptoamidated G3 with 8 biotin residues on the host surface. The encapsulates were not cytotoxic against Caco-2 cells up to 200-µM concentration in the dark. All encapsulates were able to deliver 5-aminolevulinic acid to cells but aqueous encapsulates were more active in this regard. Simultaneously, the reactive oxygen species were detected by staining with H2DCFDA in Caco-2 cells incubated with encapsulates. The amount of PpIX was sufficient for induction of reactive oxygen species upon 30-s illumination with a 655-nm laser beam.

Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer.

The tumor microenvironment (TME) consists of numerous biologically relevant elements. One of the most important components of the TME is the extracellular matrix (ECM). The compounds of the ECM create a network that provides structural and biochemical support to surrounding cells. The most important substances involved in the regulation of the ECM degradation process are matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs). The disruption of the physiological balance between MMP activation and deactivation could lead to progression of various diseases such as cardiovascular disease, cancer, fibrosis arthritis, chronic tissue ulcers, pathologies of the nervous system (such as stroke and Alzheimer's disease), periodontitis, and atheroma. MMP-TIMP imbalance results in matrix proteolysis associated with various pathological processes such as tumor invasion. The present review discusses the involvement of two MMPs, MMP-2 and MMP-7, in cancer pathogenesis. These two MMPs have been proven in several studies, conducted mostly on adults, to make an important contribution to cancer development and progression. In the current review, several studies that indicate the importance of MMP-TIMP balance determination for the pediatric population are also highlighted. The authors of this review believe that carrying out biochemical and clinical studies focused on metalloproteinases and their inhibitors in tumors in children will be of great relevance for future patient diagnosis, determination of a prognosis, and monitoring of therapy.

Profound Nanoscale Structural and Biomechanical Changes in DNA Helix upon Treatment with Anthracycline Drugs.

In our study, we describe the outcomes of the intercalation of different anthracycline antibiotics in double-stranded DNA at the nanoscale and single molecule level. Atomic force microscopy analysis revealed that intercalation results in significant elongation and thinning of dsDNA molecules. Additionally, using optical tweezers, we have shown that intercalation decreases the stiffness of DNA molecules, that results in greater susceptibility of dsDNA to break. Using DNA molecules with different GC/AT ratios, we checked whether anthracycline antibiotics show preference for GC-rich or AT-rich DNA fragments. We found that elongation, decrease in height and decrease in stiffness of dsDNA molecules was highest in GC-rich dsDNA, suggesting the preference of anthracycline antibiotics for GC pairs and GC-rich regions of DNA. This is important because such regions of genomes are enriched in DNA regulatory elements. By using three different anthracycline antibiotics, namely doxorubicin (DOX), epirubicin (EPI) and daunorubicin (DAU), we could compare their detrimental effects on DNA. Despite their analogical structure, anthracyclines differ in their effects on DNA molecules and GC-rich region preference. DOX had the strongest overall effect on the DNA topology, causing the largest elongation and decrease in height. On the other hand, EPI has the lowest preference for GC-rich dsDNA. Moreover, we demonstrated that the nanoscale perturbations in dsDNA topology are reflected by changes in the microscale properties of the cell, as even short exposition to doxorubicin resulted in an increase in nuclei stiffness, which can be due to aberration of the chromatin organization, upon intercalation of doxorubicin molecules.

Photoactive Pore Matrix for In Situ Delivery of a Photosensitizer in Vascular Smooth Muscle Cells Selective PDT.

In this study we present the porous silica-based material that can be used for in situ drug delivery, offering effective supply of active compounds regardless its water solubility. To demonstrate usability of this new material, three silica-based materials with different pore size distribution as a matrix for doping with Photolon (Ph) and Protoporphyrin IX (PPIX) photosensitizers, were prepared. These matrices can be used for coating cardiovascular stents used for treatment of the coronary artery disease and enable intravascular photodynamic therapy (PDT), which can modulate the vascular response to injury caused by stent implantation-procedure that should be thought as an alternative for drug eluting stent. The FTIR spectroscopic analysis confirmed that all studied matrices have been successfully functionalized with the target photosensitizers. Atomic force microscopy revealed that resulting photoactive matrices were very smooth, which can limit the implantation damage and reduce the risk of restenosis. No viability loss of human peripheral blood lymphocytes and no erythrocyte hemolysis upon prolonged incubations on matrices indicated good biocompatibility of designed materials. The suitability of photoactive surfaces for PDT was tested in two cell lines relevant to stent implantation: vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMC). It was demonstrated that 2 h incubation on the silica matrices was sufficient for uptake of the encapsulated photosensitizers. Moreover, the amount of the absorbed photosensitizer was sufficient for induction of a phototoxic reaction as shown by a rise of the reactive oxygen species in photosensitized VSMC. On the other hand, limited reactive oxygen species (ROS) induction in HUVECs in our experimental set up suggests that the proposed method of PDT may be less harmful for the endothelial cells and may decrease a risk of the restenosis. Presented data clearly demonstrate that porous silica-based matrices are capable of in situ delivery of photosensitizer for PDT of VSMC.

Application of SPME supported by ionic liquids for the determination of biogenic amines by MEKC in clinical practice.

The analysis of biogenic amines (BAs) and their metabolites is helpful for the diagnosis of central nervous system disorders and other neuroendocrine and cancer disturbances. In the study, a developed micellar electrokinetic chromatography method, coupled with diode array detection (MEKC-DAD), was validated to monitor levels of adrenaline (A), noradrenaline (NA), dopamine (DA), L-Tryptophan (L-Tryp) and L-Tyrosine (L-Tyr) in real human urine samples. These neurotransmitters were isolated from urine samples using solid-phase microextraction (SPME) and methanol containing 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid as the desorption phase. The method was linear for DA, A and L-Tyr in the range of 0.5-20 µg/mL and for NA and L-Tryp in the range of 0.25-20 µg/mL. The good linearity for BAs was confirmed by the correlation coefficient (R2) from 0.9989 for A to 0.9997 for NA and L-Tryp, respectively. The validation assays for accuracy, precision, limit of detection, limit of quantification, absolute recovery, and stability of the analytes were consistent with the requirements recommended by the FDA and ICH guidelines. Next, the validated SPME-MEKC method was successfully used for the quantification of A, NA, DA, L-Tryp and L-Tyr in real human urine samples collected from pediatric patients suffering from neuroblastoma, ganglioneuroblastoma, Wilms' tumor, rhabdoid tumor and lipoblastomatosis, as well as from healthy volunteers. Finally, the levels of BAs in cancer patients were evaluated as to whether they can be used as biomarkers of various health disturbances.

Alterations of biomechanics in cancer and normal cells induced by doxorubicin.

Mechanical properties of biological structures play an important role in regulating cellular activities and are critical for understanding metabolic processes in cancerous cells and the effects of drugs. For some cancers, such as acute myeloid leukaemia, chemotherapy is one of preferential methods. However, due to the lack of selectivity to cancer cells, cytostatic agents cause toxicity to normal tissues. Here, we study the effect of doxorubicin (DOX) on the mechanical properties of DNA molecules, leukemic blast cells and erythrocytes, using optical tweezers. In addition, we controlled the subcellular distribution of the drug by confocal microscopy. Our results indicated that doxorubicin affects mechanical properties of cellular structures. In all cases the drug reduced mechanical strength of examined objects. For the leukemic cells the drug subcellular distribution was predominantly nuclear with some particulate cytoplasmic fluorescence. In erythrocytes, doxorubicin showed fluorescence mainly in cytoplasm and plasma membrane. The lowering of blast cells stiffness may be due to the interaction of doxorubicin with nuclear structures, especially with nucleic acids, as our studies with DNA confirmed. In addition, it is known that DOX inhibits the polymerization of actin and thus cytoskeletal modification may also be important in reducing of cell mechanical strength. In the case of erythrocytes - the non-nucleated cells, a significant effect on the decrease of cell stiffness, besides the cytoskeleton, may have the interaction of the drug with the cell membrane. Experiments with model phospholipid membranes confirmed that observed increase in cell elasticity originates, among other things, from the drug incorporation in the lipid membrane itself. The lowering of mechanical strength of leukemic cells may have an significant impact on the effectiveness of chemotherapy. However, the fact that doxorubicin interacts not only with proliferating cancer cells, but also with the health ones may explains the high toxicity of the drug at the therapeutic concentrations. Our observations also suggest that chemotherapy with doxorubicin may decrease the risk of vascular complications in acute leukemia, due to increasing the cell elasticity.

OXTR polymorphism in depression and completed suicide-A study on a large population sample.

In the light of contradictory results concerning OXTR polymorphism rs53576 and depression, we decided to verify the potential association between the two on 1) a large, ethnically homogenous sample of 1185 individuals who completed the Beck Depression Inventory (BDI), as well as on 2) a sample of 763 suicide victims. In the population sample, AA males showed significantly lower BDI scores (p=0.005, pcor=0.030). Exploratory analyses suggested that this effect was limited to a subgroup within 0-9 BDI score range (p=0.0007, U-Mann Whitney test), whereas no main effect on depressive symptoms (BDI>9) was found. In the suicide sample no association with rs53576 genotype was present. Exploratory analyses in suicides revealed higher blood alcohol concentration (BAC) among AA than GG/GA males (p=0.014, U-Mann Whitney test). Our results show that the OXTR rs53576 variant modulates the mood in male individuals and may positively correlate with alcohol intake among male suicides, but is not associated with suicide or depression. The study adds to the growing knowledge on rs53576 genotype characteristics.

Saphenous vein stripping surgical technique and frequency of saphenous nerve injury.

OBJECTIVES: Saphenous nerve injury is the most common complication after surgical treatment of varicose veins. The aim of this study was to establish its frequency at great saphenous vein long stripping when four methods of surgery were applied. METHODS: Eighty patients were divided into four groups depending on different stripping methods. Sensory transmission in saphenous nerve and sensory perception of shank were examined before surgery and two weeks, three and six months afterwards with clinical neurophysiology methods. RESULTS: In 36% of patients, surgeries caused the injury of saphenous nerve mainly by proximal stripping without invagination (65%, group I). Transmission disturbances ceased completely after three months in patients undergoing distal stripping with invagination (group IV), while in group I they persisted for six months in 35%. Group IV patients were the least injured and group I the most. CONCLUSION: Neurophysiological findings may suggest that distal stripping with vein invagination gives the best saphenous nerve sparing.